Effects of trimetazidine in nonischemic heart failure: a randomized study.

PubMed

Winter, José Luis; Castro, Pablo F; Quintana, Juan Carlos; Altamirano, Rodrigo; Enriquez, Andres; Verdejo, Hugo E; Jalil, Jorge E; Mellado, Rosemarie; Concepción, Roberto; Sepúlveda, Pablo; Rossel, Victor; Sepúlveda, Luis; Chiong, Mario; García, Lorena; Lavandero, Sergio

2014-03-01

Heart failure (HF) is associated with changes in myocardial metabolism that lead to impairment of contractile function. Trimetazidine (TMZ) modulates cardiac energetic efficiency and improves outcomes in ischemic heart disease. We evaluated the effects of TMZ on left ventricular ejection fraction (LVEF), cardiac metabolism, exercise capacity, O2 uptake, and quality of life in patients with nonischemic HF. Sixty patients with stable nonischemic HF under optimal medical therapy were included in this randomized double-blind study. Patients were randomized to TMZ (35 mg orally twice a day) or placebo for 6 months. LVEF, 6-minute walk test (6MWT), maximum O2 uptake in cardiopulmonary exercise test, different markers of metabolism, oxidative stress, and endothelial function, and quality of life were assessed at baseline and after TMZ treatment. Left ventricular peak glucose uptake was evaluated with the use of the maximum standardized uptake value (SUV) by 18-fluorodeoxyglucose positron emission tomography ((18)FDG-PET). Etiology was idiopathic in 85% and hypertensive in 15%. Both groups were similar in age, functional class, LVEF, and levels of N-terminal pro-B-type natriuretic peptide at baseline. After 6 months of TMZ treatment, no changes were observed in LVEF (31 ± 10% vs 34 ± 8%; P = .8), 6MWT (443 ± 25 m vs 506 ± 79 m; P = .03), maximum O2 uptake (19.1 ± 5.0 mL kg(-1) min(-1) vs 23.0 ± 7.2 mL kg(-1) min(-1); P = .11), functional class (percentages of patients in functional classes I/II/III/IV 10/3753/0 vs 7/40/50/3; P = .14), or quality of life (32 ± 26 points vs 24 ± 18 points; P = .25) in TMZ versus placebo, respectively. In the subgroup of patients evaluated with (18)FDG-PET, no significant differences were observed in SUV between both groups (7.0 ± 3.6 vs 8.2 ± 3.4 respectively; P = .47). In patients with nonischemic HF, the addition of TMZ to optimal medical treatment does not result in significant changes of LVEF, exercise capacity, O2 uptake, or quality of life. Copyright © 2014 Elsevier Inc. All rights reserved.

Soluble ST2 in ambulatory patients with heart failure: Association with functional capacity and long-term outcomes.

PubMed

Felker, G Michael; Fiuzat, Mona; Thompson, Vivian; Shaw, Linda K; Neely, Megan L; Adams, Kirkwood F; Whellan, David J; Donahue, Mark P; Ahmad, Tariq; Kitzman, Dalane W; Piña, Ileana L; Zannad, Faiez; Kraus, William E; O'Connor, Christopher M

2013-11-01

ST2 is involved in cardioprotective signaling in the myocardium and has been identified as a potentially promising biomarker in heart failure (HF). We evaluated ST2 levels and their association with functional capacity and long-term clinical outcomes in a cohort of ambulatory patients with HF enrolled in the Heart Failure: A Controlled Trial Investigating Outcomes of Exercise Training (HF-ACTION) study-a multicenter, randomized study of exercise training in HF. HF-ACTION randomized 2331 patients with left ventricular ejection fraction <0.35 and New York Heart Association class II to IV HF to either exercise training or usual care. ST2 was analyzed in a subset of 910 patients with evaluable plasma samples. Correlations and Cox models were used to assess the relationship among ST2, functional capacity, and long-term outcomes. The median baseline ST2 level was 23.7 ng/mL (interquartile range, 18.6-31.8). ST2 was modestly associated with measures of functional capacity. In univariable analysis, ST2 was significantly associated with death or hospitalization (hazard ratio, 1.48; P<0.0001), cardiovascular death or HF hospitalization (hazard ratio, 2.14; P<0.0001), and all-cause mortality (hazard ratio, 2.33; P<0.0001; all hazard ratios for log2 ng/mL). In multivariable models, ST2 remained independently associated with outcomes after adjustment for clinical variables and amino-terminal pro-B-type natriuretic peptide. However, ST2 did not add significantly to reclassification of risk as assessed by changes in the C statistic, net reclassification improvement, and integrated discrimination improvement. ST2 was modestly associated with functional capacity and was significantly associated with outcomes in a well-treated cohort of ambulatory patients with HF although it did not significantly affect reclassification of risk. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00047437.

Sleep Disturbance, Daytime Symptoms, and Functional Performance in Patients With Stable Heart Failure: A Mediation Analysis.

PubMed

Jeon, Sangchoon; Redeker, Nancy S

2016-01-01

Sleep disturbance is common among patients with heart failure (HF) who also experience symptom burden and poor functional performance. We evaluated the extent to which sleep-related, daytime symptoms (fatigue, excessive daytime sleepiness, and depressive symptoms) mediate the relationship between sleep disturbance and functional performance among patients with stable HF. We recruited patients with stable HF for this secondary analysis of data from a cross-sectional, observational study. Participants completed unattended ambulatory polysomnography from which the Respiratory Disturbance Index was calculated, along with a Six-Minute Walk Test, questionnaires to elicit sleep disturbance (Pittsburgh Sleep Quality Index, Insomnia Symptoms from the Sleep Habits Questionnaire), daytime symptoms (Center for Epidemiologic Studies Depression Scale, Global Fatigue Index, Epworth Sleepiness Scale), and self-reported functional performance (Medical Outcomes Study SF36 V2 Physical Function Scale). We used structural equation modeling with latent variables for the key analysis. Follow-up, exploratory regression analysis with bootstrapped samples was used to examine the extent to which individual daytime symptoms mediated effects of sleep disturbance on functional performance after controlling for clinical and demographic covariates. The sample included 173 New York Heart Association Class I-IV HF patients (n = 60/34.7% women; M = 60.7, SD = 16.07 years of age). Daytime symptoms mediated the relationship between sleep disturbance and functional performance. Fatigue and depression mediated the relationship between insomnia symptoms and self-reported functional performance, whereas fatigue and sleepiness mediated the relationship between sleep quality and functional performance. Sleepiness mediated the relationship between the respiratory index and self-reported functional performance only in people who did not report insomnia. Daytime symptoms explain the relationships between sleep disturbance and functional performance in stable HF.

Predictive value of high sensitivity CRP in patients with diastolic heart failure.

PubMed

Michowitz, Yoav; Arbel, Yaron; Wexler, Dov; Sheps, David; Rogowski, Ori; Shapira, Itzhak; Berliner, Shlomo; Keren, Gad; George, Jacob; Roth, Arie

2008-04-25

C-reactive protein (CRP) has been tested in patients with systolic heart failure (HF) and mixed results have been obtained with regards to its potential predictive value. However, the role of C-reactive protein (CRP) in patients with diastolic HF is not established. We studied the predictive role of high sensitivity CRP (hsCRP) in patients with diastolic HF. HsCRP levels were measured in a cohort of CHF outpatients, 77 patients with diastolic HF and 217 patients with systolic HF. Concentrations were compared to a large cohort of healthy population (n=7701) and associated with the HF admissions and mortality of the patients. Levels of hsCRP did not differ between patients with systolic and diastolic HF and were significantly elevated compared to the cohort of healthy subjects even after adjustment to various clinical parameters (p<0.0001). In patients with diastolic HF, hsCRP levels associated with New York Heart Association functional class (NYHA-FC) (r=0.31 p=0.01). On univariate Cox regression model hsCRP levels independently predicted hospitalizations in patients with systolic but not diastolic HF (p=0.047). HsCRP concentrations are elevated in patients with diastolic HF and correlate with disease severity; their prognostic value in this patient population should be further investigated.

Higher salt preference in heart failure patients.

PubMed

de Souza, Juli Thomaz; Matsubara, Luiz S; Menani, José Vanderlei; Matsubara, Beatriz B; Johnson, Alan Kim; De Gobbi, Juliana Irani Fratucci

2012-02-01

Heart failure (HF) is a complex syndrome that involves changes in behavioral, neural and endocrine regulatory systems. Dietary salt restriction along with pharmacotherapy is considered an essential component in the effective management of symptomatic HF patients. However, it is well recognized that HF patients typically have great difficulty in restricting sodium intake. We hypothesized that under HF altered activity in systems that normally function to regulate body fluid and cardiovascular homeostasis could produce an increased preference for the taste of salt. Therefore, this study was conducted to evaluate the perceived palatability (defined as salt preference) of food with different concentrations of added salt in compensated chronically medicated HF patients and comparable control subjects. Healthy volunteers (n=25) and medicated, clinically stable HF patients (n=38, NYHA functional class II or III) were interviewed and given an evaluation to assess their preferences for different amounts of saltiness. Three salt concentrations (0.58, 0.82, and 1.16 g/100 g) of bean soup were presented to the subjects. Salt preference for each concentration was quantified using an adjective scale (unpleasant, fair or delicious). Healthy volunteers preferred the soup with medium salt concentration (p=0.042), HF patients disliked the low concentration (p<0.001) and preferred the high concentration of salted bean soup (p<0.001). When compared to healthy volunteers, HF patients demonstrated a significantly greater preference for the soup with a high salt concentration (p=0.038). It is concluded that medicated, compensated patients under chronic treatment for HF have an increased preference for salt. Copyright © 2011 Elsevier Ltd. All rights reserved.

Catheter ablation of atrial fibrillation in patients with heart failure and preserved ejection fraction.

PubMed

Black-Maier, Eric; Ren, Xinru; Steinberg, Benjamin A; Green, Cynthia L; Barnett, Adam S; Rosa, Normita Sta; Al-Khatib, Sana M; Atwater, Brett D; Daubert, James P; Frazier-Mills, Camille; Grant, Augustus O; Hegland, Donald D; Jackson, Kevin P; Jackson, Larry R; Koontz, Jason I; Lewis, Robert K; Sun, Albert Y; Thomas, Kevin L; Bahnson, Tristam D; Piccini, Jonathan P

2018-05-01

Few studies have examined outcomes of catheter ablation for atrial fibrillation (AF) in patients with heart failure (HF) with preserved ejection fraction (HFpEF). The purpose of this study was to compare outcomes of AF ablation in patients with HFpEF vs HF with reduced ejection fraction (HFrEF). We performed a retrospective study of 230 patients with HF who underwent AF ablation, including 97 (42.2%) with HFrEF and 133 (57.8%) with HFpEF. Outcomes included adverse events, symptoms (Mayo AF Symptom Inventory [MAFSI]), New York Heart Association (NYHA) functional class, and freedom from recurrent atrial arrhythmia at 12 months. Overall, 150 of 230 patients had nonparoxysmal AF (62.8% HFpEF vs 63.0% HFrEF). Patients with HFpEF had a smaller mean left atrial diameter (4.4 ± 0.8 cm vs 4.7 ± 0.7 cm; P = .013) and were less likely to be taking a beta-blocker at baseline (72.9% vs 85.6%; P = .022). Median (Q1, Q3) procedure times (233 minutes [192, 290] vs 233.5 minutes [193.0, 297.5]; P = .780) and adverse events such as acute HF (3.8% vs 6.2%; P = .395) were similar between HFpEF and HFrEF patients. Freedom from recurrent atrial arrhythmia was not significantly different in HFpEF vs HFrEF patients (33.9% vs 32.6%; adjusted hazard ratio 1.47; 95% confidence interval 0.72-3.01), with similar improvements in NYHA functional class (-0.32 vs -0.19; P = .135) and MAFSI symptom severity (-0.23 vs -0.09; P = .116) after ablation. Catheter ablation of AF seems to have similar effectiveness in patients with HF, regardless of presence of systolic dysfunction. There were no significant differences in procedural characteristics, arrhythmia-free recurrence, or functional improvements between patients with HFpEF and those with HFrEF. Copyright © 2017 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

Salivary Biomarkers, Oral Inflammation, and Functional Status in Patients With Heart Failure.

PubMed

Dekker, Rebecca L; Lennie, Terry A; Moser, Debra K; Miller, Craig S; Ebersole, Jeffrey L; Chung, Misook L; Campbell, Charles L; Bailey, Alison; Tovar, Elizabeth G

2017-03-01

To describe correlations and agreement between salivary and serum B-type natriuretic peptide (BNP), C-reactive protein (CRP), interleukin (IL)-6, and IL-10 and determine which biomarkers predict worse functional class in patients with heart failure (HF). Serum and saliva were collected from 75 hospitalized patients with HF (57 ± 12 years, 43% female, New York Heart Association [NYHA] Classes I [4%], II [43%], and III [53%]). Oral inflammation was rated as good, fair, or poor. Spearman's ρ and Bland-Altman were used to determine correlations and agreement of the salivary and serum forms of each biomarker. Logistic regressions were used to determine which biomarkers predicted worse NYHA functional class, controlling for depression, body mass index, smoking, and oral inflammation. Median biomarker concentrations were as follows: BNP (serum 361 pg/ml, saliva 9 pg/ml), CRP (serum 13 ng/ml, saliva 25.6 ng/ml), IL-6 (serum 19.3 pg/ml, saliva 10.5 pg/ml), and IL-10 (serum 64.1 pg/ml, saliva 4.7 pg/ml). There was a moderate-to-strong correlation for serum-salivary CRP, weak correlation for serum-salivary IL-6, and no correlations for serum-salivary BNP and IL-10. The Bland-Altman test showed good salivary-serum agreement for all biomarkers, but as serum concentrations rose, salivary measures underestimated serum levels. Visible oral inflammation was the only predictor of worse NYHA class.

Design of a multicentre randomized controlled trial to assess the safety and efficacy of dose titration by specialized nurses in patients with heart failure. ETIFIC study protocol

PubMed Central

García‐Garrido, LLuisa; Nebot Margalef, Magdalena; Lekuona, Iñaki; Comin‐Colet, Josep; Manito, Nicolás; Roure, Julia; Ruiz Rodriguez, Pilar; Enjuanes, Cristina; Latorre, Pedro; Torcal Laguna, Jesús; García‐Gutiérrez, Susana

2017-01-01

Abstract Aims Heart failure (HF) is associated with many hospital admissions and relatively high mortality, rates decreasing with administration of beta‐blockers (BBs), angiotensin‐converting‐enzyme inhibitors, angiotensin II receptor blockers, and mineralocorticoid receptor antagonists. The effect is dose dependent, suboptimal doses being common in clinical practice. The 2012 European guidelines recommend close monitoring and dose titration by HF nurses. Our main aim is to compare BB doses achieved by patients after 4 months in intervention (HF nurse‐managed) and control (cardiologist‐managed) groups. Secondary aims include comparing doses of the other aforementioned drugs achieved after 4 months, adverse events, and outcomes at 6 months in the two groups. Methods We have designed a multicentre (20 hospitals) non‐inferiority randomized controlled trial, including patients with new‐onset HF, left ventricular ejection fraction ≤40%, and New York Heart Association class II–III, with no contraindications to BBs. We will also conduct qualitative analysis to explore potential barriers to and facilitators of dose titration by HF nurses. In the intervention group, HF nurses will implement titration as prescribed by cardiologists, following a protocol. In controls, cardiologists will both prescribe and titrate doses. The study variables are doses of each of the drugs after 4 months relative to the target dose (%), New York Heart Association class, left ventricular ejection fraction, N‐terminal pro B‐type natriuretic peptide levels, 6 min walk distance, comorbidities, renal function, readmissions, mortality, quality of life, and psychosocial characteristics. Conclusions The trial seeks to assess whether titration by HF nurses of drugs recommended in practice guidelines is safe and not inferior to direct management by cardiologists. The results could have an impact on clinical practice. PMID:29154427

The mitochondrial-targeted antioxidant, MitoQ, increases liver mitochondrial cardiolipin content in obesogenic diet-fed rats.

PubMed

Fouret, Gilles; Tolika, Evanthia; Lecomte, Jérôme; Bonafos, Béatrice; Aoun, Manar; Murphy, Michael P; Ferreri, Carla; Chatgilialoglu, Chryssostomos; Dubreucq, Eric; Coudray, Charles; Feillet-Coudray, Christine

2015-10-01

Cardiolipin (CL), a unique mitochondrial phospholipid, plays a key role in several processes of mitochondrial bioenergetics as well as in mitochondrial membrane stability and dynamics. The present study was designed to determine the effect of MitoQ, a mitochondrial-targeted antioxidant, on the content of liver mitochondrial membrane phospholipids, in particular CL, and its fatty acid composition in obesogenic diet-fed rats. To do this, twenty-four 6week old male Sprague Dawley rats were randomized into three groups of 8 animals and fed for 8weeks with either a control diet, a high fat diet (HF), or a HF diet with MitoQ (HF+MitoQ). Phospholipid classes and fatty acid composition were assayed by chromatographic methods in liver and liver mitochondria. Mitochondrial bioenergetic function was also evaluated. While MitoQ had no or slight effects on total liver fatty acid composition and phospholipid classes and their fatty acid composition, it had major effects on liver mitochondrial phospholipids and mitochondrial function. Indeed, MitoQ both increased CL synthase gene expression and CL content of liver mitochondria and increased 18:2n-6 (linoleic acid) content of mitochondrial phospholipids by comparison to the HF diet. Moreover, mitochondrial CL content was positively correlated to mitochondrial membrane fluidity, membrane potential and respiration, as well as to ATP synthase activity, while it was negatively correlated to mitochondrial ROS production. These findings suggest that MitoQ may decrease pathogenic alterations to CL content and profiles, thereby preserving mitochondrial function and attenuating the development of some of the features of metabolic syndrome in obesogenic diet-fed rats. Copyright © 2015 Elsevier B.V. All rights reserved.

Comparison of Predictors of Heart Failure-related Hospitalization or Death in Patients with versus without Preserved Left Ventricular Ejection Fraction

PubMed Central

Mangla, Ashvarya; Kane, John; Beaty, Elijah; Richardson, DeJuran; Powell, Lynda H.; Calvin, James E.

2013-01-01

Heart failure with preserved ejection fraction (HFpEF) is recognized as a major cause of cardiovascular morbidity and mortality. An ability to identify patients with HFpEF who are at increased risk for adverse outcome can facilitate their more careful management. We studied the patients having heart failure (HF) using data from the Heart Failure Adherence and Retention Trial (HART). HART enrolled 902 NYHA Class II or III patients who had been recently hospitalized for HF to study the impact of self-management counseling on the primary outcome of death or HF hospitalization. In HART 208 patients had HFpEF and 692 had HFrEF (heart failure with reduced ejection fraction), and were followed for median of 1080 days. Two final multivariate models were developed. In patients having HFpEF, predictors of primary outcome were: male sex (OR 3.45, p=0.004), NYHA class III (OR 3.05, p=0.008), distance covered on 6-minute walk test (6-MWT) of< 620 feet (OR 2.81, p=0.013), and <80% adherence to prescribed medications (OR 2.61, p=0.018). In patients having HFrEF, the predictors were: being on diuretics (OR 3.06, p=0.001), having ≥ 3 comorbidities (OR 2.11, p=0.0001), distance covered on 6-MWT of < 620 feet (OR 1.94, p=0.001), NYHA class III (OR 1.90, p=0.001) and age > 65 years (OR 1.63, p=0.01). In conclusion, indicators of functional status(6-MWT and NYHA class) were common to both HFpEF and HFrEF patients while gender and adherence to prescribed therapy were unique to patients having HFpEF in predicting death or HF hospitalization. PMID:24063842

Clinical and prognostic value of spot urinary creatinine in chronic heart failure-An analysis from GISSI-HF.

PubMed

Ter Maaten, Jozine M; Maggioni, Aldo Pietro; Latini, Roberto; Masson, Serge; Tognoni, Gianni; Tavazzi, Luigi; Signorini, Stefano; Voors, Adriaan A; Damman, Kevin

2017-06-01

This study aimed to identify patient characteristics associated with low urinary creatinine in morning spot urine and investigate its association with clinical outcome. Twenty-four-hour creatinine excretion is an established marker of muscle mass in heart failure and other populations. Spot urine creatinine might be an easy obtainable, cheap marker of muscle wasting and prognosis in heart failure (HF) patients. Spot urine creatinine concentration was measured in 2130 patients included in the GISSI-HF trial. We evaluated the prognostic value of urinary creatinine and its relation with clinical variables. Median spot urinary creatinine was 0.80 (IQR 0.50-1.10) g/L. Lower spot urinary creatinine was associated with older age, smaller height and weight, higher NYHA class, worse renal function and more frequent spironolactone and diuretic use (all P<.02). During a median follow-up of 2.8 years, 655 patients (31%) experienced the combined endpoint of all-cause mortality or HF hospitalization. Lower urinary creatinine was independently associated with an increased risk of all-cause mortality or HF hospitalization (HR, 1.59 [1.21-2.08] per log decrease, P=.001), and all-cause mortality (HR, 1.75 [1.25-2.45] per log decrease, P=.001). Lower urinary creatinine, measured in morning spot urine in patients with chronic HF, is associated with worse renal function, smaller body size, more severe HF and is independently associated with an increased risk of all-cause death and HF hospitalization. Copyright © 2017 Elsevier Inc. All rights reserved.

[The role of oxidative metabolism disturbance in the development of NO-related endothelial dysfunction during chronic hearth failure].

PubMed

Goishvili, N; Kakauridze, N; Sanikidze, T

2005-05-01

The aim of the work was to establish the oxidative metabolism changes and NO data in Chronic Hearth Failure (HF). 52 patients were included in the investigation, among them 37 patients with CHD and chronic HF (II-IV functional class by NIHA) and 17 without it (control group). For revealing of organism redox-status (ceruloplasmine, Fe3+-transfferine, Mn2+, methemoglobine) the blood paramagnetic centers was studied by electron paramagnetic resonance method. For revealing of blood free NO, the diethyldithiocarbamat (SIGMA) was used. In chronic HF the oxidative process intensification and organism compensate reaction reduction with low Fe3+-transferine levels, increased Mn2++, methaemoglobin and inactivation of erythrocytes membranes adrenergic receptors were revealed. In chronic HF the accumulation of reactive oxygen levels provoke NO transformation in peroxynitrote with following decreases of blood free NO and develop the endothelial dysfunction.

Plasma urocortin in human systolic heart failure.

PubMed

Ng, Leong L; Loke, Ian W; O'Brien, Russell J; Squire, Iain B; Davies, Joan E

2004-04-01

Urocortin (UCN), a member of the corticotrophin-releasing factor family, is expressed in heart, brain and gut. UCN has potent cardiostimulatory, cardioprotective, vasodilator and diuretic/natriuretic effects, and cardiac UCN expression is increased in heart failure (HF). In the present study, we investigated plasma levels of UCN in 119 patients with HF and 212 age- and gender-matched controls to clarify its relationship with gender and disease severity. UCN was elevated in HF [normal males, 19.5 (3.9-68.8) pmol/l and HF males, 50.2 (6.9-108.2) pmol/l, P < 0.0005; normal females, 14.2 (3.9-53.5) pmol/l and HF females, 21.8 (3.9-112.5) pmol/l, P < 0.001; values are medians (range)]. The relative increase was greater in males than females ( P < 0.03). UCN fell with increasing age, especially in HF patients ( r(s) = -0.56, P < 0.0005) and with increasing New York Heart Association (NYHA) class ( r(s) = -0.55, P < 0.0005). The fall in UCN levels with increasing NYHA class was reinforced by a significant correlation between UCN and ejection fraction ( r(s) = 0.45, P < 0.0005) in HF patients. Although receiver operating characteristic (ROC) curves for diagnosis of all HF cases yielded an area under the curve (AUC) of 0.76, ROC AUCs for patients with early HF (NYHA class I and II) were better (0.91). ROC AUCs for logistic models incorporating N-terminal probrain natriuretic peptide (N-BNP) and UCN were better than either peptide alone. In conclusion, plasma UCN is elevated in HF, especially in its early stages. Its decline with increasing HF severity may expedite disease progression due to diminished cardioprotective/anti-inflammatory effects. UCN measurement may also complement N-BNP in the diagnosis of early HF.

Association of Central Sleep Apnea with Impaired Heart Structure and Cardiovascular Hemodynamics in Patients with Chronic Heart Failure.

PubMed

Kazimierczak, Anna; Krzesiński, Paweł; Gielerak, Grzegorz; Uziębło-Życzkowska, Beata; Smurzyński, Paweł; Ryczek, Robert; Cwetsch, Andrzej; Skrobowski, Andrzej

2016-08-25

BACKGROUND Advanced heart failure (HF) is commonly accompanied by central sleep apnea (CSA) with Cheyne-Stokes respiration (CSR). The aim of this study was to evaluate the relationship between CSA/CSR and other clinical features of HF, with particular emphasis on cardiovascular hemodynamics. MATERIAL AND METHODS In 161 stable HF patients with left ventricular ejection fraction (LVEF) ≤45% (NYHA class I-III; mean LVEF 32.8%) the clinical evaluation included: LVEF; left and right ventricular end-diastolic diameter (LVDd, RVDd); ratio of early transmitral flow velocity to early diastolic septal mitral annulus velocity (E/e') assessed by echocardiography; stroke index (SI); heart rate (HR); cardiac index (CI); and systemic vascular resistance index (SVRI) assessed by impedance cardiography (ICG). The comparison was performed between 2 subgroups: one with moderate/severe CSA/CSR - CSR_ [+] (n=51), and one with mild or no CSA/CSR - CSR_ [-] (n=110). RESULTS CSR_ [+] patients presented more advanced NYHA class (p<0.001) and more frequently had permanent atrial fibrillation (p=0.018). Moreover, they had: lower LVEF (p<0.0001); higher LVDd (p<0.0001), RVDd (p<0.001), and E/e' (p<0.001); lower SI (p<0.001) and CI (p=0.009); and higher HR (p=0.044) and SVRI (p=0.016). The following predictors of CSR_ [+] were identified: NYHA class (OR=3.34 per class, p<0.001, which was the only independent predictor); atrial fibrillation (OR=2.29, p=0.019); RV enlargement (OR=2.75, p=0.005); LVEF<35% (OR=3.38, p=0.001); E/e' (OR=3.15; p=0.003); and SI<35 ml/m2 (OR=2.96, p=0.003). CONCLUSIONS Presence of CSA/CSR in HF is associated with NYHA class, atrial fibrillation and more advanced impairment of cardiovascular structure and hemodynamics. Patient functional state remains the main determinant of CSR.

Association of Central Sleep Apnea with Impaired Heart Structure and Cardiovascular Hemodynamics in Patients with Chronic Heart Failure

PubMed Central

Kazimierczak, Anna; Krzesiński, Paweł; Gielerak, Grzegorz; Uziebło-Życzkowska, Beata; Smurzyński, Paweł; Ryczek, Robert; Cwetsch, Andrzej; Skrobowski, Andrzej

2016-01-01

Background Advanced heart failure (HF) is commonly accompanied by central sleep apnea (CSA) with Cheyne-Stokes respiration (CSR). The aim of this study was to evaluate the relationship between CSA/CSR and other clinical features of HF, with particular emphasis on cardiovascular hemodynamics. Material/Methods In 161 stable HF patients with left ventricular ejection fraction (LVEF) ≤45% (NYHA class I–III; mean LVEF 32.8%) the clinical evaluation included: LVEF; left and right ventricular end-diastolic diameter (LVDd, RVDd); ratio of early transmitral flow velocity to early diastolic septal mitral annulus velocity (E/e’) assessed by echocardiography; stroke index (SI); heart rate (HR); cardiac index (CI); and systemic vascular resistance index (SVRI) assessed by impedance cardiography (ICG). The comparison was performed between 2 subgroups: one with moderate/severe CSA/CSR - CSR_ [+] (n=51), and one with mild or no CSA/CSR – CSR_ [−] (n=110). Results CSR_ [+] patients presented more advanced NYHA class (p<0.001) and more frequently had permanent atrial fibrillation (p=0.018). Moreover, they had: lower LVEF (p<0.0001); higher LVDd (p<0.0001), RVDd (p<0.001), and E/e’ (p<0.001); lower SI (p<0.001) and CI (p=0.009); and higher HR (p=0.044) and SVRI (p=0.016). The following predictors of CSR_ [+] were identified: NYHA class (OR=3.34 per class, p<0.001, which was the only independent predictor); atrial fibrillation (OR=2.29, p=0.019); RV enlargement (OR=2.75, p=0.005); LVEF<35% (OR=3.38, p=0.001); E/e’ (OR=3.15; p=0.003); and SI<35 ml/m2 (OR=2.96, p=0.003). Conclusions Presence of CSA/CSR in HF is associated with NYHA class, atrial fibrillation and more advanced impairment of cardiovascular structure and hemodynamics. Patient functional state remains the main determinant of CSR. PMID:27558771

Left ventricular chamber stiffness at rest as a determinant of exercise capacity in heart failure subjects with decreased ejection fraction.

PubMed

Meyer, Timothy E; Karamanoglu, Mustafa; Ehsani, Ali A; Kovács, Sándor J

2004-11-01

Impaired exercise tolerance, determined by peak oxygen consumption (VO2 peak), is predictive of mortality and the necessity for cardiac transplantation in patients with chronic heart failure (HF). However, the role of left ventricular (LV) diastolic function at rest, reflected by chamber stiffness assessed echocardiographically, as a determinant of exercise tolerance is unknown. Increased LV chamber stiffness and limitation of VO2 peak are known correlates of HF. Yet, the relationship between chamber stiffness and VO2 peak in subjects with HF has not been fully determined. Forty-one patients with HF New York Heart Association [(NYHA) class 2.4 +/- 0.8, mean +/- SD] had echocardiographic studies and VO2 peak measurements. Transmitral Doppler E waves were analyzed using a previously validated method to determine k, the LV chamber stiffness parameter. Multiple linear regression analysis of VO(2 peak) variance indicated that LV chamber stiffness k (r2 = 0.55) and NYHA classification (r2 = 0.43) were its best independent predictors and when taken together account for 59% of the variability in VO2 peak. We conclude that diastolic function at rest, as manifested by chamber stiffness, is a major determinant of maximal exercise capacity in HF.

Effects of Spinal Cord Stimulation on Cardiac Sympathetic Nerve Activity in Patients with Heart Failure.

PubMed

Naar, Jan; Jaye, Deborah; Linde, Cecilia; Neužil, Petr; Doškář, Petr; Málek, Filip; Braunschweig, Frieder; Lund, Lars H; Mortensen, Lars; Linderoth, Bengt; Lind, Göran; Bone, Dianna; Scholte, Arthur J; Kueffer, Fred; Koehler, Jodi; Shahgaldi, Kambiz; Lang, Otto; Ståhlberg, Marcus

2017-05-01

Spinal cord stimulation (SCS) reduces sympathetic activity in animal models of heart failure with reduced ejection fraction (HF) but limited data exist of SCS in patients with HF. The aim of the present study was to test the primary hypothesis that SCS reduces cardiac sympathetic nerve activity in HF patients. Secondary hypotheses were that SCS improves left ventricular function and dimension, exercise capacity, and clinical variables relevant to HF. HF patients with a SCS device previously participating in the DEFEAT-HF trial were included in this crossover study with 6-week intervention periods (SCS-ON and SCS-OFF). SCS (50 Hz, 210-μs pulse duration, aiming at T2-T4 segments) was delivered for 12 hours daily. Indices of myocardial sympathetic neuronal function (heart-to-mediastinum ratio, HMR) and activity (washout rate, WR) were assessed using 123 I-metaiodobenzylguanidine (MIBG) scintigraphy. Echocardiography, exercise testing, and clinical data collection were also performed. We included 13 patients (65.3 ± 8.0 years, nine males) and MIBG scintigraphy data were available in 10. HMR was not different comparing SCS-ON (1.37 ± 0.16) and SCS-OFF (1.41 ± 0.21, P = 0.46). WR was also unchanged comparing SCS-ON (41.5 ± 5.3) and SCS-OFF (39.1 ± 5.8, P = 0.30). Similarly, average New York Heart Association class (2.4 ± 0.5 vs 2.3 ± 0.6, P = 0.34), quality of life score (24 ± 16 vs 24 ± 16, P = 0.94), and left ventricular dimension and function as well as exercise capacity were all unchanged comparing SCS-ON and SCS-OFF. In patients with HF, SCS (12 hours daily, targeting the T2-T4 segments of the spinal cord) does not appear to influence cardiac sympathetic neuronal activity or function as assessed by MIBG scintigraphy. © 2017 Wiley Periodicals, Inc.

Effects of Statin Treatment on Inflammation and Cardiac Function in Heart Failure: An Adjusted Indirect Comparison Meta-Analysis of Randomized Trials.

PubMed

Bonsu, Kwadwo Osei; Reidpath, Daniel Diamond; Kadirvelu, Amudha

2015-12-01

Statins are known to prevent heart failure (HF). However, it is unclear whether statins as class or type (lipophilic or hydrophilic) improve outcomes of established HF. The current meta-analysis was performed to compare the treatment effects of lipophilic and hydrophilic statins on inflammation and cardiac function in HF. Outcomes were indicators of cardiac function [changes in left ventricular ejection fraction (LVEF) and B-type natriuretic peptide (BNP)] and inflammation [changes in highly sensitive C-reactive protein (hsCRP) and interluekin-6 (IL-6)]. We conducted a search of PubMed, EMBASE, and the Cochrane databases until December 31, 2014 for randomized control trials (RCTs) of statin versus placebo in patients with HF. RCTs with their respective extracted information were dichotomized into statin type evaluated and analyzed separately. Outcomes were pooled with random effect approach, producing standardized mean differences (SMD) for each statin type. Using these pooled estimates, we performed adjusted indirect comparisons for each outcome. Data from 6214 patients from 19 trials were analyzed. Lipophilic statin was superior to hydrophilic statin treatment regarding follow-up LVEF (SMD, 4.54; 95% CI, 4.16-4.91; P < 0.001), BNP (SMD, -1.60; 95% CI, -2.56 to -0.65; P < 0.001), hsCRP (SMD, -1.13; 95% CI, -1.54 to -0.72; P < 0.001), and IL-6 (SMD, -3.75; 95% CI, -4.77 to -0.72; P < 0.001) in HF. Lipophilic statin produces greater treatment effects on cardiac function and inflammation compared with hydrophilic statin in patients with HF. Until data from adequately powered head-to-head trial of the statin types are available, our meta-analysis brings clinicians and researchers a step closer to the quest on which statin--lipophilic or hydrophilic--is associated with better outcomes in HF. © 2015 John Wiley & Sons Ltd.

A Cross-Cultural Comparison of Symptom Reporting and Symptom Clusters in Heart Failure.

PubMed

Park, Jumin; Johantgen, Mary E

2017-07-01

An understanding of symptoms in heart failure (HF) among different cultural groups has become increasingly important. The purpose of this study was to compare symptom reporting and symptom clusters in HF patients between a Western (the United States) and an Eastern Asian sample (China and Taiwan). A secondary analysis of a cross-sectional observational study was conducted. The data were obtained from a matched HF patient sample from the United States and China/Taiwan ( N = 240 in each). Eight selective items related to HF symptoms from the Minnesota Living with Heart Failure Questionnaire were analyzed. Compared with the U.S. sample, HF patients from China/Taiwan reported a lower level of symptom distress. Analysis of two different regional groups did not result in the same number of clusters using latent class approach: the United States (four classes) and China/Taiwan (three classes). The study demonstrated that symptom reporting and identification of symptom clusters might be influenced by cultural factors.

The performance and relationship among range-separated schemes for density functional theory

NASA Astrophysics Data System (ADS)

Nguyen, Kiet A.; Day, Paul N.; Pachter, Ruth

2011-08-01

The performance and relationship among different range-separated (RS) hybrid functional schemes are examined using the Coulomb-attenuating method (CAM) with different values for the fractions of exact Hartree-Fock (HF) exchange (α), long-range HF (β), and a range-separation parameter (μ), where the cases of α + β = 1 and α + β = 0 were designated as CA and CA0, respectively. Attenuated PBE exchange-correlation functionals with α = 0.20 and μ = 0.20 (CA-PBE) and α = 0.25 and μ = 0.11 (CA0-PBE) are closely related to the LRC-ωPBEh and HSE functionals, respectively. Time-dependent density functional theory calculations were carried out for a number of classes of molecules with varying degrees of charge-transfer (CT) character to provide an assessment of the accuracy of excitation energies from the CA functionals and a number of other functionals with different exchange hole models. Functionals that provided reasonable estimates for local and short-range CT transitions were found to give large errors for long-range CT excitations. In contrast, functionals that afforded accurate long-range CT excitation energies significantly overestimated energies for short-range CT and local transitions. The effects of exchange hole models and parameters developed for RS functionals for CT excitations were analyzed in detail. The comparative analysis across compound classes provides a useful benchmark for CT excitations.

Salivary Biomarkers, Oral Inflammation, and Functional Status in Patients With Heart Failure

PubMed Central

Dekker, Rebecca L.; Lennie, Terry A.; Moser, Debra K.; Miller, Craig S.; Ebersole, Jeffrey L.; Chung, Misook L.; Campbell, Charles L.; Bailey, Alison; Tovar, Elizabeth G.

2016-01-01

Aims: To describe correlations and agreement between salivary and serum B-type natriuretic peptide (BNP), C-reactive protein (CRP), interleukin (IL)-6, and IL-10 and determine which biomarkers predict worse functional class in patients with heart failure (HF). Methods: Serum and saliva were collected from 75 hospitalized patients with HF (57 ± 12 years, 43% female, New York Heart Association [NYHA] Classes I [4%], II [43%], and III [53%]). Oral inflammation was rated as good, fair, or poor. Spearman’s ρ and Bland–Altman were used to determine correlations and agreement of the salivary and serum forms of each biomarker. Logistic regressions were used to determine which biomarkers predicted worse NYHA functional class, controlling for depression, body mass index, smoking, and oral inflammation. Results: Median biomarker concentrations were as follows: BNP (serum 361 pg/ml, saliva 9 pg/ml), CRP (serum 13 ng/ml, saliva 25.6 ng/ml), IL-6 (serum 19.3 pg/ml, saliva 10.5 pg/ml), and IL-10 (serum 64.1 pg/ml, saliva 4.7 pg/ml). There was a moderate-to-strong correlation for serum–salivary CRP, weak correlation for serum–salivary IL-6, and no correlations for serum–salivary BNP and IL-10. The Bland–Altman test showed good salivary–serum agreement for all biomarkers, but as serum concentrations rose, salivary measures underestimated serum levels. Visible oral inflammation was the only predictor of worse NYHA class. PMID:27605566

Adherence to 2016 European Society of Cardiology guidelines predicts outcome in a large real-world population of heart failure patients requiring cardiac resynchronization therapy.

PubMed

Stabile, Giuseppe; Pepi, Patrizia; Palmisano, Pietro; D'Onofrio, Antonio; De Simone, Antonio; Caico, Salvatore Ivan; Pecora, Domenico; Rapacciuolo, Antonio; Arena, Giuseppe; Marini, Massimiliano; Pieragnoli, Paolo; Badolati, Sandra; Savarese, Gianluca; Maglia, Gianpiero; Iuliano, Assunta; Botto, Giovanni Luca; Malacrida, Maurizio; Bertaglia, Emanuele

2018-04-14

Professional guidelines are based on the best available evidence. However, patients treated in clinical practice may differ from those included in reference trials. The aim of this study was to evaluate the effects of cardiac resynchronization therapy (CRT) in a large population of patients implanted with a CRT device stratified in accordance with the 2016 European heart failure (HF) guidelines. We collected data on 930 consecutive patients from the Cardiac Resynchronization Therapy MOdular REgistry. The primary end point was a composite of death and HF hospitalization. Five hundred sixty-three (60.5%) patients met class I indications, 145 (15.6%) class IIa, 108 (11.6%) class IIb, and 114 (12.3%) class III. After a median follow-up of 1001 days, 120 patients who had an indication for CRT implantation had died and 71 had been hospitalized for HF. The time to the end point was longer in patients with a class I indication (hazard ratio 0.55; 95% confidence interval 0.39-0.76; P = .0001). After 12 months, left ventricular (LV) end-systolic volume had decreased by ≥15% in 61.5% of patients whereas in 57.5% of patients the absolute LV ejection fraction improvement was ≥5%. Adherence to class I was also associated with an absolute LV ejection fraction increase of >5% (P = .0142) and an LV end-systolic volume decrease of ≥15% (P = .0055). In our population, ∼60% of patients underwent implantation according to the 2016 European HF guidelines class I indication. Adherence to class I was associated with a lower death and HF hospitalization rate and better LV reverse remodeling. Copyright © 2018 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

The arterial baroreflex effectiveness index in risk stratification of chronic heart failure patients who are candidates for cardiac resynchronization therapy.

PubMed

Fernandes Serôdio, João; Martins Oliveira, Mário; Matoso Laranjo, Sérgio; Tavares, Cristiano; Silva Cunha, Pedro; Abreu, Ana; Branco, Luísa; Alves, Sandra; Rocha, Isabel; Cruz Ferreira, Rui

2016-06-01

Baroreflex function is an independent marker of prognosis in heart failure (HF). However, little is known about its relation to response to cardiac resynchronization therapy (CRT). The aim of this study is to assess arterial baroreflex function in HF patients who are candidates for CRT. The study population consisted of 25 patients with indication for CRT, aged 65±10 years, NYHA functional class ≥III in 52%, QRS width 159±15 ms, left ventricular ejection fraction (LVEF) 29±5%, left ventricular end-systolic volume (LVESV) 150±48 ml, B-type natriuretic peptide (BNP) 357±270 pg/ml, and peak oxygen consumption (peak VO2) 18.4±5.0 ml/kg/min. An orthostatic tilt test was performed to assess the baroreflex effectiveness index (BEI) by the sequence method. This group was compared with 15 age-matched healthy individuals. HF patients showed a significantly depressed BEI during tilt (31±12% vs. 49±18%, p=0.001). A lower BEI was associated with higher BNP (p=0.038), lower peak VO2 (p=0.048), and higher LVESV (p=0.031). By applying a cut-off value of 25% for BEI, two clusters of patients were identified: lower risk cluster (BEI >25%) QRS 153 ms, LVESV 129 ml, BNP 146 pg/ml, peak VO2 19.0 ml/kg/min; and higher risk cluster (IEB ≤25%) QRS 167 ms, LVESV 189 ml, BNP 590 pg/ml, peak VO2 16.2 ml/kg/min. Candidates for CRT show depressed arterial baroreflex function. Lower BEI was observed in high-risk HF patients. Baroreflex function correlated closely with other clinical HF parameters. Therefore, BEI may improve risk stratification in HF patients undergoing CRT. Copyright © 2016 Sociedade Portuguesa de Cardiologia. Published by Elsevier España. All rights reserved.

Solution Structure of Enterocin HF, an Antilisterial Bacteriocin Produced by Enterococcus faecium M3K31.

PubMed

Arbulu, Sara; Lohans, Christopher T; van Belkum, Marco J; Cintas, Luis M; Herranz, Carmen; Vederas, John C; Hernández, Pablo E

2015-12-16

The solution structure of enterocin HF (EntHF), a class IIa bacteriocin of 43 amino acids produced by Enterococcus faecium M3K31, was evaluated by CD and NMR spectroscopy. Purified EntHF was unstructured in water, but CD analysis supports that EntHF adopts an α-helical conformation when exposed to increasing concentrations of trifluoroethanol. Furthermore, NMR spectroscopy indicates that this bacteriocin adopts an antiparallel β-sheet structure in the N-terminal region (residues 1-17), followed by a well-defined central α-helix (residues 19-30) and a more disordered C-terminal end (residues 31-43). EntHF could be structurally organized into three flexible regions that might act in a coordinated manner. This is in agreement with the absence of long-range nuclear Overhauser effect signals between the β-sheet domain and the C-terminal end of the bacteriocin. The 3D structure recorded for EntHF fits emerging facts regarding target recognition and mode of action of class IIa bacteriocins.

Psychometric Analysis of the Heart Failure Somatic Perception Scale as a Measure of Patient Symptom Perception.

PubMed

Jurgens, Corrine Y; Lee, Christopher S; Riegel, Barbara

Symptoms are known to predict survival among patients with heart failure (HF), but discrepancies exist between patients' and health providers' perceptions of HF symptom burden. The purpose of this study is to quantify the internal consistency, validity, and prognostic value of patient perception of a broad range of HF symptoms using an HF-specific physical symptom measure, the 18-item HF Somatic Perception Scale v. 3. Factor analysis of the HF Somatic Perception Scale was conducted in a convenience sample of 378 patients with chronic HF. Convergent validity was examined using the Physical Limitation subscale of the Kansas City Cardiomyopathy Questionnaire. Divergent validity was examined using the Self-care of HF Index self-care management score. One-year survival based on HF Somatic Perception Scale scores was quantified using Cox regression controlling for Seattle HF Model scores to account for clinical status, therapeutics, and lab values. The sample was 63% male, 85% white, 67% functionally compromised (New York Heart Association class III-IV) with a mean (SD) age of 63 (12.8) years. Internal consistency of the HF Somatic Perception Scale was α = .90. Convergent (r = -0.54, P < .0001) and divergent (r = 0.18, P > .05) validities were supported. Controlling for Seattle HF scores, HF Somatic Perception Scale was a significant predictor of 1-year survival, with those most symptomatic having worse survival (hazard ratio, 1.012; 95% confidence interval, 1.001-1.024; P = .038). Perception of HF symptom burden as measured by the HF Somatic Perception Scale is a significant predictor of survival, contributing additional prognostic value over and above objective Seattle HF Risk Model scores. This analysis suggests that assessment of a broad range of HF symptoms, or those related to dyspnea or early and subtle symptoms, may be useful in evaluating therapeutic outcomes and predicting event-free survival.

Difference in resource utilization between patients with acute and chronic heart failure from Japanese administrative database.

PubMed

Kuwabara, Kazuaki; Matsuda, Shinya; Anan, Makoto; Fushimi, Kiyohide; Ishikawa, Koichi B; Horiguchi, Hiromasa; Hayashida, Kenshi; Fujimori, Kenji

2010-06-11

Many studies have reported economic evaluation of evolving agents or therapies for patients with heart failure (HF). However, little is known whether the disease progression category (acute or chronic HF) would be considered as a risk adjustment in health service research. This study profiles the difference in resource use or medical care for acute versus chronic HF. This study analyzed 17,912 HF patients treated in 62 academic hospitals and 351 community hospitals. Study variables included demographic variables, comorbid status, physical activity or disease progression at admission, procedures and laboratory tests, type and dose of heart-related medications, length of stay (LOS), and total charges (TC; 1 US$= 100 yen) for acute and chronic HF. The independent contributions of disease progression categories on LOS and TC were identified using multivariate analysis. We identified 9813 chronic and 8099 acute HF patients. Median LOS was 18 days for both chronic and acute HF, whereas TC was US$5731 and US$6447, respectively. Regression analysis revealed that acute HF was associated with a slightly greater TC, whereas performance of procedures was the most prominent factor. As NYHA class was the next most influential factor, class 3 or 4 resulted in longer LOS or greater TC, than did class 1. This study suggests that acute HF increased resource use slightly, whereas use of some practices indicated in critical care was affected more by the procedures performed. Disease progression category should remain an indicator for appropriateness of medical care. Copyright (c) 2008 Elsevier Ireland Ltd. All rights reserved.

Design of a multicentre randomized controlled trial to assess the safety and efficacy of dose titration by specialized nurses in patients with heart failure. ETIFIC study protocol.

PubMed

Oyanguren, Juana; García-Garrido, LLuisa; Nebot Margalef, Magdalena; Lekuona, Iñaki; Comin-Colet, Josep; Manito, Nicolás; Roure, Julia; Ruiz Rodriguez, Pilar; Enjuanes, Cristina; Latorre, Pedro; Torcal Laguna, Jesús; García-Gutiérrez, Susana

2017-11-01

Heart failure (HF) is associated with many hospital admissions and relatively high mortality, rates decreasing with administration of beta-blockers (BBs), angiotensin-converting-enzyme inhibitors, angiotensin II receptor blockers, and mineralocorticoid receptor antagonists. The effect is dose dependent, suboptimal doses being common in clinical practice. The 2012 European guidelines recommend close monitoring and dose titration by HF nurses. Our main aim is to compare BB doses achieved by patients after 4 months in intervention (HF nurse-managed) and control (cardiologist-managed) groups. Secondary aims include comparing doses of the other aforementioned drugs achieved after 4 months, adverse events, and outcomes at 6 months in the two groups. We have designed a multicentre (20 hospitals) non-inferiority randomized controlled trial, including patients with new-onset HF, left ventricular ejection fraction ≤40%, and New York Heart Association class II-III, with no contraindications to BBs. We will also conduct qualitative analysis to explore potential barriers to and facilitators of dose titration by HF nurses. In the intervention group, HF nurses will implement titration as prescribed by cardiologists, following a protocol. In controls, cardiologists will both prescribe and titrate doses. The study variables are doses of each of the drugs after 4 months relative to the target dose (%), New York Heart Association class, left ventricular ejection fraction, N-terminal pro B-type natriuretic peptide levels, 6 min walk distance, comorbidities, renal function, readmissions, mortality, quality of life, and psychosocial characteristics. The trial seeks to assess whether titration by HF nurses of drugs recommended in practice guidelines is safe and not inferior to direct management by cardiologists. The results could have an impact on clinical practice. © 2017 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of the European Society of Cardiology.

COPD predicts mortality in HF: the Norwegian Heart Failure Registry.

PubMed

De Blois, Jonathan; Simard, Serge; Atar, Dan; Agewall, Stefan

2010-03-01

Chronic obstructive pulmonary disease (COPD) and chronic heart failure (HF) are common clinical conditions that share tobacco as a risk factor. Our aim was to evaluate the prognostic impact of COPD on HF patients. The Norwegian Heart Failure Registry was used. The study included 4132 HF patients (COPD, n = 699) from 22 hospitals (mean follow-up, 13.3 months). COPD patients were older, more often smokers and diabetics, less often on beta-blockers and had a higher heart rate. They were more often in New York Heart Association (NYHA) Class III or IV (COPD, 63%; no COPD, 51%), although left ventricular ejection fraction (LVEF) distribution was similar. COPD independently predicted death (adjusted hazard ratio [HR], 1.188; 95% CI: 1.015 to 1.391; P = 0.03) along with age, creatinine, NYHA Class III/IV (HR, 1.464; 95% CI: 1.286 to 1.667) and diabetes. beta-blockers at baseline were associated with improved survival in patients with LVEF < or =40% independently of COPD. COPD is associated with a poorer survival in HF patients. COPD patients are overrated in terms of NYHA class in comparison with patients with similar LVEF. Nonetheless, NYHA class remains the strongest predictor of death in these patients. Copyright (c) 2010 Elsevier Inc. All rights reserved.

A systematic review of mHealth-based heart failure interventions

PubMed Central

Cajita, Maan Isabella; Gleason, Kelly T.; Han, Hae-Ra

2015-01-01

Background The popularity of mobile phones and similar mobile devices makes it an ideal medium for delivering interventions. This is especially true with heart failure (HF) interventions, in which mHealth-based HF interventions are rapidly replacing their telephone-based predecessors. Purpose This systematic review examined the impact of mHealth-based HF management interventions on HF outcomes. The specific aims of the systematic review are to: (1) describe current mHealth-based HF interventions and (2) discuss the impact of these interventions on HF outcomes. Methods PubMed, CINAHL Plus, Embase, PsycINFO, and Scopus were systematically searched for randomized controlled trials or quasi-experimental studies that tested mHealth interventions in people with HF using the terms Heart Failure, Mobile Health, mHealth, Telemedicine, Text Messaging, Texting, Short Message Service, Mobile Applications, and Mobile Apps. Conclusions Ten articles, representing nine studies, were included in this review. Majority of the studies utilized mobile health technology as part of a HF monitoring system, which typically included a blood pressure measuring device, weighing scale, and an ECG recorder. The impact of the mHealth interventions on all-cause mortality, cardiovascular mortality, HF-related hospitalizations, length of stay, NYHA functional class, LVEF, quality of life, and self-care were inconsistent at best. Implications Further research is needed to conclusively determine the impact of mHealth interventions on HF outcomes. The limitations of the current studies (e.g. inadequate sample size, quasi-experimental design, use of older mobile phone models, etc.) should be taken into account when designing future studies. PMID:26544175

A Systematic Review of mHealth-Based Heart Failure Interventions.

PubMed

Cajita, Maan Isabella; Gleason, Kelly T; Han, Hae-Ra

2016-01-01

The popularity of mobile phones and similar mobile devices makes it an ideal medium for delivering interventions. This is especially true with heart failure (HF) interventions, in which mHealth-based HF interventions are rapidly replacing their telephone-based predecessors. This systematic review examined the impact of mHealth-based HF management interventions on HF outcomes. The specific aims of the systematic review are to (1) describe current mHealth-based HF interventions and (2) discuss the impact of these interventions on HF outcomes. PubMed, CINAHL Plus, EMBASE, PsycINFO, and Scopus were systematically searched for randomized controlled trials or quasi-experimental studies that tested mHealth interventions in people with HF using the terms Heart Failure, Mobile Health, mHealth, Telemedicine, Text Messaging, Texting, Short Message Service, Mobile Applications, and Mobile Apps. Ten articles, representing 9 studies, were included in this review. The majority of the studies utilized mobile health technology as part of an HF monitoring system, which typically included a blood pressure-measuring device, weighing scale, and an electrocardiogram recorder. The impact of the mHealth interventions on all-cause mortality, cardiovascular mortality, HF-related hospitalizations, length of stay, New York Heart Association functional class, left ventricular ejection fraction, quality of life, and self-care were inconsistent at best. Further research is needed to conclusively determine the impact of mHealth interventions on HF outcomes. The limitations of the current studies (eg, inadequate sample size, quasi-experimental design, use of older mobile phone models, etc) should be taken into account when designing future studies.

A Low-Normal Free Triiodothyronine Level Is Associated with Adverse Prognosis in Euthyroid Patients with Heart Failure Receiving Cardiac Resynchronization Therapy.

PubMed

Chen, Yu-Yang; Shu, Xiao-Rong; Su, Zi-Zhuo; Lin, Rong-Jie; Zhang, Hai-Feng; Yuan, Wo-Liang; Wang, Jing-Feng; Xie, Shuang-Lun

2017-12-12

Thyroid dysfunction is prevalent in patients with heart failure (HF) and hypothyroidism is related to the adverse prognosis of HF subjects receiving cardiac resynchronization therapy (CRT). We aim to investigate whether low-normal free triiodothyronine (fT3) level is related to CRT response and the prognosis of euthyroid patients with HF after CRT implantation.One hundred and thirteen euthyroid patients who received CRT therapy without previous thyroid disease and any treatment affecting thyroid hormones were enrolled. All of patients were evaluated for cardiac function and thyroid hormones (serum levels of fT3, free thyroxine [fT4] and thyroid-stimulating hormone [TSH]). The end points were overall mortality and hospitalization for HF worsening. During a follow-up period of 39 ± 3 weeks, 36 patients (31.9%) died and 45 patients (39.8%) had hospitalization for HF exacerbation. A higher rate of NYHA III/IV class and a lower fT3 level were both observed in death group and HF event group. Multivariate Cox regression analyses disclosed that a lower-normal fT3 level (HR = 0.648, P = 0.009) and CRT response (HR = 0.441, P = 0.001) were both independent predictors of overall mortality. In addition, they were also both related to HF re-hospitalization event (P < 0.01 for both). Patients with fT3 < 3.00 pmol/L had a significantly higher overall mortality than those with fT3 ≥ 3.00 pmol/L (P = 0.027). Meanwhile, a higher HF hospitalization event rate was also found in patients with fT3 < 3.00 pmol/L (P < 0.001).A lower-normal fT3 level is correlated with a worse cardiac function an adverse prognosis in euthyroid patients with HF after CRT implantation.

Hemodynamic-guided heart-failure management using a wireless implantable sensor: Infrastructure, methods, and results in a community heart failure disease-management program.

PubMed

Jermyn, Rita; Alam, Amit; Kvasic, Jessica; Saeed, Omar; Jorde, Ulrich

2017-03-01

The real-world impact of remote pulmonary artery pressure (PAP) monitoring on New York Heart Association (NYHA) class improvement and heart failure (HF) hospitalization rate is presented here from a single center. METHODS: Seventy-seven previously hospitalized outpatients with NYHA class III HF were offered PAP monitoring via device implantation in a multidisciplinary HF-management program. Prospective effectiveness analyses compared outcomes in 34 hemodynamically monitored patients to a group of similar patients (n = 32) who did not undergo device implantation but received usual care. NYHA class and 6-minute walk testing were assessed at baseline and 90 days. All hospitalizations were collected after 6 months of the implantation date (average follow-up, 15 months) and compared with the number of hospitalizations experienced prior to hemodynamic monitoring. Patients in both groups had similar distributions of age, sex, and ejection fraction. After 90 days, 61.8% of the monitored patients had NYHA class improvement of ≥1, compared with 12.5% in the controls (P < 0.001). Distance walked in 6 minutes increased by 54.5 meters in the monitored group (253.0 ± 25.6 meters to 307.4 ± 26.3 meters; P < 0.005), whereas no change was seen in the usual-care group. After implantation, 19.4% of the monitored group had ≥1 HF hospitalization, compared with 100% who had been hospitalized in the year prior to implantation. The monitored group had a significantly lower HF hospitalization rate (0.16; 95% confidence interval: 0.06-0.35 hospitalizations/patient-year) compared with the year prior (1.0 hospitalizations/patient-year; P < 0.001). Hemodynamic-guided HF management leads to significant improvements in NYHA class and HF hospitalization rate in a real-world setting compared with usual care delivered in a comprehensive disease-management program. © 2016 Wiley Periodicals, Inc.

Predictors of Depressive Symptoms in Caregivers of Patients with Heart Failure

PubMed Central

Chung, Misook L.; Pressler, Susan J.; Dunbar, Sandra B.; Lennie, Terry A.; Moser, Debra K.; Endowed, Gill

2010-01-01

Background Millions of family members deliver informal care and support to patients with heart failure (HF). Caregivers of patients with HF suffer from depressive symptoms, but factors associated with depressive symptoms are unknown. The purposes of this study were (1) to examine differences between caregivers with and without depressive symptoms in patients’ characteristics and caregivers’ functional status, caregiving burden (time devoted to caregiving, difficulty of caregiving tasks, and overall perceived caregiving distress), and perceived control; and (2) to determine predictors of depressive symptoms of caregivers. Method A total of 109 caregivers (mean age of 57 years; spousal caregiver 79%) and patients with HF participated in this study. Depressive symptoms, perceived control, and functional status of both patients and caregivers were assessed using the Beck Depression Inventory-II (BDI-II), the Control Attitudes Scale-Revised, and the Duke Activity Status Index, respectively. Caregivers’ burden (time and difficulty of caregiving tasks and burden) were assessed using the Oberst Caregiving Burden Scale, and the Zarit Burden Interview. Results The 27.5% of HF caregivers with depressive symptoms (BDI-II ≥ 14) had poorer functional status, lower perceived control, higher perceived caregiving distress, experienced more caregiving difficulty and spent more time in caregiving tasks than caregivers without depressive symptoms. Controlling for age and gender in a multiple regression, caregivers’ own functional disability (sβ = -.307, P < .001), perceived control (sβ = -.304, P < .001), and caregiver burden (sβ =.316, P = .002) explained 45% of the variance in caregivers’ depressive symptoms. Patients’ NYHA class and functional status did not predict caregivers’ depressive symptoms. Conclusion Caregivers’ poor functional status, overall perception of caregiving distress, and perceived control were associated with depressive symptoms. Depressed caregivers of patients with HF may benefit from interventions that improve caregivers’ perceived control, address the caregiving burden and improve or assist with caregivers’ functional status. PMID:20714239

Comparative Effectiveness of Low-Volume Time-Efficient Resistance Training Versus Endurance Training in Patients With Heart Failure.

PubMed

Munch, Gregers Winding; Rosenmeier, Jaya Birgitte; Petersen, Morten; Rinnov, Anders Rasmussen; Iepsen, Ulrik Winning; Pedersen, Bente Klarlund; Mortensen, Stefan Peter

2018-05-01

Cardiorespiratory fitness is positively related to heart failure (HF) prognosis, but lack of time and low energy are barriers for adherence to exercise. We, therefore, compared the effect of low-volume time-based resistance exercise training (TRE) with aerobic moderate-intensity cycling (AMC) on maximal and submaximal exercise capacity, health-related quality of life, and vascular function. Twenty-eight HF patients (New York Heart Association class I-II) performed AMC (n = 14) or TRE (n = 14). Maximal and submaximal exercise capacity, health-related quality of life, and vascular function were evaluated before and after a 6-wk training intervention with 3 training sessions per week. The AMC group and the TRE group trained for 45 and 25 min per training session, respectively. During the training sessions, the TRE and AMC groups trained at 60 ± 4% and 59 ± 2% (mean ± standard deviation) of (Equation is included in full-text article.)O2peak, respectively. The energy expenditure was significantly greater in AMC than in TRE (P < .05). The (Equation is included in full-text article.)O2peak and Wattpeak increased in AMC group (P < .001) and TRE group (P = .001), with no differences between groups. Six-minute walk distance also increased in both groups (AMC, P = .006 and TRE, P = .036), with no difference between groups. Health-related quality of life improved equally in the 2 groups, whereas vascular function did not change in either group. These results demonstrate that AMC and TRE equally improved exercise capacity and health-related quality of life in lower New York Heart Association-stage HF patients, despite less time required as well as lower energy expenditure during TRE than during AMC. Therefore, TRE might represent a time-efficient exercise modality for improving adherence to exercise in patients with class I-II HF.

Inflammatory mediators in chronic heart failure in North India.

PubMed

Fedacko, Jan; Singh, Ram B; Gupta, Aditya; Hristova, Krasimira; Toda, Eri; Kumar, Adarsh; Saxena, Manoj; Baby, Anjum; Singh, Ranjana; Toru, Takahashi; Wilson, Douglas W

2014-08-01

Recent evidence shows that pro-inflammatory cytokines may be important in the assessment of severity and prognosis in congestive heart failure (CHF). In the present study, we examine the association of cytokines with causes, grade and prognosis of CHF patients. Of 127 patients with CHF, 11 were excluded and the remaining 116 patients with different aetiologies of CHF, and 250 age- and sex-matched control subjects, were evaluated in this case study. Severity of disease based on the New York Heart Association (NYHA) standards, fell within functional classes II to IV. The diagnosis of HF was based on clinical manifestations as well as on echocardiographic heart enlargement. Cytokines were measured by chemiluminescence. Causes of death were assessed based on death certificates. Multivariate logistic regression analysis was used to determine the risk factors of heart failure. Echocardiographic ejection fraction was 39.1 +/- 8.2% (mean +/- SD) in the study group indicating class II-IV heart failure. Laboratory data showed increase in biomarkers of oxidative stress, among HF patients compared to healthy subjects. Pro-inflammatory cytokines; IL-6 and TNF-alpha were significantly higher among HF patients compared to healthy subjects. TNF-alpha and IL-6, showed significant increase among patients with CHF due to ischaemic heart disease and cardiomyopathy compared to levels among CHF patients with valvular heart disease and hypertensive heart diseases. The levels of the cytokines were significantly higher among patients with class III and IV heart failure and those who died, compared to patients with class II heart failure. Multivariate logistic regression analysis revealed that CAD, cardiomyopathy, and IL-6 were strongly associated--and low ejection fraction and TNF-alpha--weakly associated with HF. Of 116 patients, 20 (17.2%) died during a follow-up of two years, and the deaths were mainly among NYHA class III and IV patients in whom the cause of CHF was CAD (10.9%) and cardiomyopathy (6.9%) which had greater levels of cytokines. The findings indicated that pro-inflammatory cytokines may be important indicators of causes, severity of CHF and prognosis among these patients.

Plasma urotensin in human systolic heart failure.

PubMed

Ng, Leong L; Loke, Ian; O'Brien, Russell J; Squire, Iain B; Davies, Joan E

2002-12-03

Human urotensin II (UTN) has potent vasoactive and cardiostimulatory effects, acting on the G protein-linked receptor GPR14. Myocardial UTN expression is upregulated in heart failure, and UTN stimulates myocardial expression of the natriuretic peptides. We investigated plasma UTN levels in heart failure (HF; left ventricular systolic dysfunction) in comparison with plasma N-terminal pro-brain natriuretic peptide (N-BNP) levels. N-BNP and UTN were measured in plasma from 126 patients with HF and 220 age- and sex-matched controls. Both peptides were elevated in plasma of HF patients and were correlated (r(s)=0.35, P<0.001). In contrast to N-BNP, there was no relationship of plasma UTN with New York Heart Association (NYHA) class. Although plasma N-BNP showed a positive relationship with age and female sex, there was no such age-dependent change in plasma UTN, and control women had lower levels compared with control men. Receiver operating characteristic curves for the diagnosis of HF had areas of 0.90 and 0.86 for N-BNP and UTN, respectively (P<0.001 for both). Receiver operating characteristic curve area for diagnosis of NYHA class I HF with UTN was better than that with N-BNP. Plasma UTN is elevated in HF, which suggests a pathophysiological role for this peptide. Plasma UTN may be a useful alternative to N-BNP in the diagnosis of HF, inasmuch as its levels are elevated irrespective of age, sex, or NYHA class.

Edema index-guided disease management improves 6-month outcomes of patients with acute heart failure.

PubMed

Liu, Min-Hui; Wang, Chao-Hung; Huang, Yu-Yen; Tung, Tao-Hsin; Lee, Chii-Ming; Yang, Ning-I; Wang, Jong-Shyan; Kuo, Li-Tang; Cherng, Wen-Jin

2012-01-01

The efficacy of heart failure (HF) management programs is compromised by the challenge of early identification of patients at imminent risk. Segmental multifrequency bioelectrical impedance analysis can generate an "edema index" (EI) as a surrogate for the body fluid status. In this study, we tested whether integration of EI-guided management improved the 6-month outcomes of HF patients under multidisciplinary care. In total, 159 patients with acute HF were randomized into control, case management (CM), and EI-guided CM (EI) groups (n = 53 in each group). In the EI group, a management algorithm was designed based on the measured EI. The analyzed endpoints included HF-related and all cause-related events during the 6-month follow-up period. In the 6 months, there were 11 (6.9%) deaths, 19 (11.9%) HF-related rehospitalizations, and 45 (28.3%) all-cause-related rehospitalizations. Compared to the control (26.4%) and CM groups (15.1%), the EI group had a lower rate of HF-related death and rehospitalization (3.8%, P = 0.004). Multivariate analysis revealed that EI-guided management was an independent predictor of a lower HF-related event rate (hazard ratio = 0.15, 95%CI = 0.03~0.66, P = 0.012). Patients with a higher pre-discharge EI were older, had lower blood albumin and hemoglobin levels, and had a higher functional class and incidences of diabetes mellitus and chronic kidney disease. An increase in the pre-discharge EI by 0.001 increased the HF-related event rate by 6% (P = 0.002). Use of EI-guided management lowered this risk (P = 0.03). In conclusion, an EI-based HF management program demonstrated an event-lowering effect superior to traditional nurse-led multidisciplinary care in 6 months after an acute HF episode.

Clinical Spectrum and Management of Heart Failure in Hypertrophic Cardiomyopathy.

PubMed

Maron, Barry J; Rowin, Ethan J; Udelson, James E; Maron, Martin S

2018-05-01

Heart failure (HF), characterized by excessive exertional dyspnea, is a common complication within the broad clinical spectrum of hypertrophic cardiomyopathy (HCM). HF has become an increasingly prominent management issue with the reduction in sudden deaths due to use of implantable defibrillators in this disease. Exertional dyspnea ranges in severity from mild to severe (New York Heart Association functional classes II to IV) and not uncommonly becomes refractory to medical management, leading to progressive disability, but largely in the absence of pulmonary congestion and volume overload requiring hospitalization. HCM-related HF is most commonly due to dynamic mechanical impedance to left ventricular outflow produced by mitral valve systolic anterior motion, leading to high intracavity pressures. Surgical septal myectomy with low operative mortality (<1%) produces HF reversal and symptom relief in 90% to 95% of patients, while also conveying a survival benefit. Exercise echocardiography has assumed an important role in the evaluation of patients with HCM, i.e., by identifying candidates for septal reduction therapy with refractory HF when outflow gradients are present only with physiological exercise, distinguishing highly symptomatic nonobstructive patients as heart transplant candidates, and predicting future development of progressive HF. Notably, mortality directly attributable to HF has become exceedingly uncommon in HCM (<0.5%/year) in contrast with HF in non-HCM diseases (by 20-fold). In conclusion, HF in HCM is associated with diverse and complex pathophysiology, but a substantially more favorable prognosis than conventional non-HCM HF, and highly amenable to effective treatment options in the vast majority of patients. Copyright © 2018 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Singing-related neural activity distinguishes two putative pallidal cell types in the songbird basal ganglia: comparison to the primate internal and external pallidal segments

PubMed Central

Goldberg, Jesse H.; Adler, Avital; Bergman, Hagai; Fee, Michale S.

2010-01-01

The songbird area X is a basal ganglia homologue that contains two pallidal cell types—local neurons that project within the basal ganglia and output neurons that project to the thalamus. Based on these projections, it has been proposed that these classes are structurally homologous to the primate external (GPe) and internal (GPi) pallidal segments. To test the hypothesis that the two area X pallidal types are functionally homologous to GPe and GPi neurons, we recorded from neurons in area X of singing juvenile male zebra finches, and directly compare their firing patterns to neurons recorded in the primate pallidus. In area X, we find two cell classes that exhibited high firing (HF) rates (>60Hz) characteristic of pallidal neurons. HF-1 neurons, like most GPe neurons we examined, exhibited large firing rate modulations, including bursts and long pauses. In contrast, HF-2 neurons, like GPi neurons, discharged continuously without bursts or long pauses. To test if HF-2 neurons were the output neurons that project to the thalamus, we next recorded directly from pallidal axon terminals in thalamic nucleus DLM, and found that all terminals exhibited singing-related firing patterns indistinguishable from HF-2 neurons. Our data show that singing-related neural activity distinguishes two putative pallidal cell types in area X: thalamus-projecting neurons that exhibit activity similar to the primate GPi, and non-thalamus-projecting neurons that exhibit activity similar to the primate GPe. These results suggest that song learning in birds and motor learning in mammals employ conserved basal ganglia signaling strategies. PMID:20484651

Impact of sacubitril/valsartan on heart failure admissions: insights from real-world patient prescriptions.

PubMed

Martens, Pieter; Lambeets, Seppe; Lau, Chirikwah; Dupont, Matthias; Mullens, Wilfried

2018-06-17

Sacubitril/valsartan reduced heart failure (HF)-admissions and cardiovascular mortality in the PARADIGM-HF-trial. However, real-world patients are often frailer and less able to tolerate high doses of sacubitril/valsartan. We performed a retrospective analysis of consecutive patients prescribed sacubitril/valsartan in a single tertiary HF-clinic between December 2016 and January 2018. HF-admissions were assessed in a paired fashion, comparing the amount of antecedent HF-episodes with incident HF-episodes after the initiation. Baseline risk for adverse events was assessed by the EMPHASIS-HF-risk-score Results: A total of 201-HF-patients were retrospectively identified (age = 68 ± 11 years, ejection fraction = 29 ± 8%). Real world patients were older, had higher serum creatinine and a higher New-York Heart-Association (NYHA)-class (p < .05 for all) than in the PARADIGM-HF trial. Over a mean duration of 221 ± 114 days after initiation of sacubitril/valsartan a total of 23-individual patients experienced at least one HF-episodes. Over the same time period preceding initiation of sacubitril/valsartan, 51 individual patients experienced a HF-episodes (p < .001). Sacubitril/valsartan significantly reduced the rate of incident vs. antecedent HF-admissions, in patients with low or high baseline NYHA-class (II vs. III and IV; p value = 0.019 respectively p = .004) or patients with an EMPHASIS-HF risk score below or above the mean (p = .002 respectively p = .016). Patients older than 75-years exhibited a trend towards HF-reduction. Higher doses of sacubitril/valsartan were associated with more reduction in incident versus antecedent HF-episodes. Despite being frailer and older, real-world patients exhibit a significant and early reduction in incident HF-hospitalisations following initiation of sacubitril/valsartan. Higher doses might be associated with more reduction in HF-admissions, underscoring the importance of dose uptitration.

Effects of thalidomide treatment in heart failure patients.

PubMed

Orea-Tejeda, Arturo; Arrieta-Rodríguez, Oscar; Castillo-Martínez, Lilia; Rodríguez-Reyna, Tatiana; Asensio-Lafuente, Enrique; Granados-Arriola, Julio; Dorantes-García, Joel

2007-01-01

Several studies have reported a direct association between elevated plasma levels of inflammatory cytokines and worse functional class (New York Heart Association [NYHA]) and cardiac function, measured as left ventricular ejection fraction (LVEF). Thalidomide has recently shown to improve LVEF in chronic heart failure patients, accompanied by a marked decrease in plasma levels of tumor necrosis factor alpha (TNF-alpha). In a randomized prospective open label study of men and women with heart failure (HF) due to ischemic and non-ischemic cardiomyopathy who had systolic dysfunction (LVEF <40%) and NHYA classification, functional classes II and III were assigned to control (without thalidomide, 60 patients) or thalidomide group (20 patients). The initial dose of thalidomide was 100 mg once a day, and it was increased to 100 mg twice a day after a period of 10 days, if the prior dosage was well-tolerated. Demographic characteristics, etiology of HF, prior myocardial infarction, co-morbidities associated were registered and laboratory routine test, TNF-alpha serum levels, and echocardiogram were obtained at the beginning and after 6 months of follow-up. Clinical status (NYHA) at the end of the follow-up period, improved moderately in both groups. TNF-alpha levels were initially of 5.88 +/- 0.9 and 6.49 +/- 1.82 vs. 6.32 +/- 1.6 and 7.94 +/- 3.8 pg/ml during follow-up, for thalidomide and control groups, respectively. There were non-significant differences in echocardiography variables. In conclusion, although there is a large amount of information supporting a direct relationship between TNF-alpha and worsening of symptoms and prognosis in patients with HF and recently, the beneficial effect on thalidomide treatment has been suggested, these preliminary observations should be confirmed in a larger prospective study, specially trying to clarify the action mechanisms. (c) 2007 S. Karger AG, Basel.

Predicting device failure after percutaneous repair of functional mitral regurgitation in advanced heart failure: Implications for patient selection.

PubMed

Stolfo, Davide; De Luca, Antonio; Morea, Gaetano; Merlo, Marco; Vitrella, Giancarlo; Caiffa, Thomas; Barbati, Giulia; Rakar, Serena; Korcova, Renata; Perkan, Andrea; Pinamonti, Bruno; Pappalardo, Aniello; Berardini, Alessandra; Biagini, Elena; Saia, Francesco; Grigioni, Francesco; Rapezzi, Claudio; Sinagra, Gianfranco

2018-04-15

Patients with heart failure (HF) and severe symptomatic functional mitral regurgitation (FMR) may benefit from MitraClip implantation. With increasing numbers of patients being treated the success of procedure becomes a key issue. We sought to investigate the pre-procedural predictors of device failure in patients with advanced HF treated with MitraClip. From April 2012 to November 2016, 76 patients with poor functional class (NYHA class III-IV) and severe left ventricular (LV) remodeling underwent MitraClip implantation at University Hospitals of Trieste and Bologna (Italy). Device failure was assessed according to MVARC criteria. Patients were subsequently followed to additionally assess the patient success after 12months. Mean age was 67±12years, the mean Log-EuroSCORE was 23.4±16.5%, and the mean LV end-diastolic volume index and ejection fraction (EF) were 112±33ml/m 2 and 30.6±8.9%, respectively. At short-term evaluation, device failure was observed in 22 (29%) patients. Univariate predictors of device failure were LVEF, LV and left atrial volumes and anteroposterior mitral annulus diameter. Annulus dimension (OR 1.153, 95% CI 1.002-1.327, p=0.043) and LV end-diastolic volume (OR 1.024, 95% CI 1.000-1.049, p=0.049) were the only variables independently associated with the risk of device failure at the multivariate model. Pre-procedural anteroposterior mitral annulus diameter accurately predicted the risk of device failure after MitraClip in the setting of advanced HF. Its assessment might aid the selection of the best candidates to percutaneous correction of FMR. Copyright © 2018 Elsevier B.V. All rights reserved.

Prevalent digoxin use and subsequent risk of death or hospitalization in ambulatory heart failure patients with a reduced ejection fraction-Findings from the Heart Failure: A Controlled Trial Investigating Outcomes of Exercise Training (HF-ACTION) randomized controlled trial.

PubMed

Ambrosy, Andrew P; Bhatt, Ankeet S; Stebbins, Amanda L; Wruck, Lisa M; Fudim, Marat; Greene, Stephen J; Kraus, William E; O'Connor, Christopher M; Piña, Ileana L; Whellan, David J; Mentz, Robert J

2018-05-01

Despite more than 200 years of clinical experience and a pivotal trial, recently published research has called into question the safety and efficacy of digoxin therapy in heart failure (HF). HF-ACTION (ClinicalTrials.gov Number: NCT00047437) enrolled 2331 outpatients with HF and an EF ≤35% between April 2003 and February 2007 and randomized them to aerobic exercise training versus usual care. Patients were grouped according to prevalent digoxin status at baseline. The association between digoxin therapy and outcomes was assessed using Cox proportional hazard and inverse-probability weighted (IPW) regression models adjusted for demographics, medical history, medications, laboratory values, quality of life, and exercise parameters. The prevalence of digoxin therapy decreased from 52% during the first 6 months of enrollment to 35% at the end of the HF-ACTION trial (P <0.0001). Study participants were 59± 13 years of age, 72% were male, and approximately half had an ischemic etiology of HF. Patients receiving digoxin at baseline tended to be younger and were more likely to report New York Heart Association functional class III/IV symptoms (rather than class II) compared to those not receiving digoxin. Patients taking digoxin had worse baseline exercise capacity as measured by peak VO 2 and 6-min walk test and greater impairments in health status as reflected by the Kansas City Cardiomyopathy Questionnaire. The association between digoxin and the risk of death or hospitalization differed depending on whether Cox proportional hazard (Hazard Ratio 1.03, 95% Confidence Interval 0.92-1.16; P = .62) or IPW regression models (HR 1.08, 95% CI 1.00-1.17; P = .057) were used to adjust for potential confounders. Although digoxin use was associated with high-risk clinical features, the association between digoxin therapy and outcomes was dependent on the statistical methods used for multivariable adjustment. Clinical equipoise exists and additional prospective research is required to clarify the role of digoxin in contemporary clinical practice including its effects on functional capacity, quality of life, and long-term outcomes. Copyright © 2018. Published by Elsevier Inc.

A randomized pilot study of optimization of cardiac resynchronization therapy in sinus rhythm patients using a peak endocardial acceleration sensor vs. standard methods.

PubMed

Ritter, Philippe; Delnoy, Peter Paul H M; Padeletti, Luigi; Lunati, Maurizio; Naegele, Herbert; Borri-Brunetto, Alberto; Silvestre, Jorge

2012-09-01

Non-response rate to cardiac resynchronization therapy (CRT) might be decreased by optimizing device programming. The Clinical Evaluation on Advanced Resynchronization (CLEAR) study aimed to assess the effects of CRT with automatically optimized atrioventricular (AV) and interventricular (VV) delays, based on a Peak Endocardial Acceleration (PEA) signal system. This multicentre, single-blind study randomized patients in a 1 : 1 ratio to CRT optimized either automatically by the PEA-based system, or according to centres' usual practices, mostly by echocardiography. Patients had heart failure (HF) New York Heart Association (NYHA) functional class III/IV, left ventricular ejection fraction (LVEF) <35%, QRS duration >150 or >120 ms with mechanical dyssynchrony. Follow-up was 1 year. The primary endpoint was the proportion of patients who improved their condition at 1 year, based on a composite of all-cause death, HF hospitalizations, NYHA class, and quality of life. In all, 268 patients in sinus rhythm (63% men; mean age: 73.1 ± 9.9 years; mean NYHA: 3.0 ± 0.3; mean LVEF: 27.1 ± 8.1%; and mean QRS duration: 160.1 ± 22.0 ms) were included and 238 patients were randomized, 123 to PEA and 115 to the control group. At 1 year, 76% of patients assigned to PEA were classified as improved, vs. 62% in the control group (P= 0.0285). The percentage of patients with improved NYHA class was significantly (P= 0.0020) higher in the PEA group than in controls. Fatal and non-fatal adverse events were evenly distributed between the groups. PEA-based optimization of CRT in HF patients significantly increased the proportion of patients who improved with therapy, mainly through improved NYHA class, after 1 year of follow-up.

Reduction of lymphocyte G protein-coupled receptor kinase-2 (GRK2) after exercise training predicts survival in patients with heart failure.

PubMed

Rengo, Giuseppe; Galasso, Gennaro; Femminella, Grazia D; Parisi, Valentina; Zincarelli, Carmela; Pagano, Gennaro; De Lucia, Claudio; Cannavo, Alessandro; Liccardo, Daniela; Marciano, Caterina; Vigorito, Carlo; Giallauria, Francesco; Ferrara, Nicola; Furgi, Giuseppe; Filardi, Pasquale Perrone; Koch, Walter J; Leosco, Dario

2014-01-01

Increased cardiac G protein-coupled receptor kinase-2 (GRK2) expression has a pivotal role at inducing heart failure (HF)-related β-adrenergic receptor (βAR) dysfunction. Importantly, abnormalities of βAR signalling in the failing heart, including GRK2 overexpression, are mirrored in circulating lymphocytes and correlate with HF severity. Exercise training has been shown to exert several beneficial effects on the failing heart, including normalization of cardiac βAR function and GRK2 protein levels. In the present study, we evaluated whether lymphocyte GRK2 levels and short-term changes of this kinase after an exercise training programme can predict long-term survival in HF patients. For this purpose, we prospectively studied 193 HF patients who underwent a 3-month exercise training programme. Lymphocyte GRK2 protein levels, plasma N-terminal pro-brain natriuretic peptide, and norepinephrine were measured at baseline and after training along with clinical and functional parameters (left ventricular ejection fraction, NYHA class, and peak-VO2). Cardiac-related mortality was evaluated during a mean follow-up period of 37 ± 20 months. Exercise was associated with a significant reduction of lymphocyte GRK2 protein levels (from 1.29 ± 0.52 to 1.16 ± 0.65 densitometric units, p < 0.0001). Importantly, exercise related changes of GRK2 (delta values) robustly predicted survival in our study population. Interestingly, HF patients who did not show reduced lymphocyte GRK2 protein levels after training presented the poorest outcome. Our data offer the first demonstration that changes of lymphocyte GRK2 after exercise training can strongly predict outcome in advanced HF.

Progression of Renal Impairment and Chronic Kidney Disease in Chronic Heart Failure: An Analysis From GISSI-HF.

PubMed

Damman, Kevin; Masson, Serge; Lucci, Donata; Gorini, Marco; Urso, Renato; Maggioni, Aldo P; Tavazzi, Luigi; Tarantini, Luigi; Tognoni, Gianni; Voors, Adriaan; Latini, Roberto

2017-01-01

Data on the natural change in renal function in patients with chronic heart failure (HF) are limited. Estimated glomerular filtration rate (eGFR) was assessed over 36 months in 6934 patients included in the GISSI-HF study. Associations from baseline, changes in renal function, and occurrence of cardiovascular death or HF hospitalization were assessed. Mean age was 67 years, mainly men (78%), and mean eGFR was 68 mL • min -1  • 1.73 m -2 . Change in eGFR in the 1st year was -1.5 ± 16 mL • min -1  • 1.73 m -2 , and over 36 months it was -3.7 ± 18 mL • min -1  • 1.73 m -2 . Over the latter period, only 25% deteriorated ≥1 Kidney Disease Outcomes Quality Initiatives (KDOQI) class of chronic kidney disease (CKD). Fifteen percent of patients had >15 mL • min -1  • 1.73 m -2 decrease in eGFR in the 1st 12 months. Lower eGFR was associated with outcome: hazard ratio (HR) 1.10, 95% confidence interval (CI) 1.08-1.10 (P < .001) per 10 mL • min -1  • 1.73 m -2 decrease, as well as every 10 mL • min -1  • 1.73 m -2 decrease over the 1st year (HR 1.10, 95% CI 1.04-1.17; P < .001). A deterioration in eGFR >15 mL • min -1  • 1.73 m -2 in the 1st year showed the highest risk of events (HR 1.22, 95% CI 1.10-1.36; P < .001). Mean decrease in renal function over time in patients with chronic HF was modest. Only 25% deteriorated ≥1 KDOQI class of CKD after 3 years. Any decrease in eGFR over time was associated with strongly increased event rates. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Half-Heusler Alloys as Promising Thermoelectric Materials

NASA Astrophysics Data System (ADS)

Page, Alexander A.

This thesis describes Ph.D. research on the half-Heusler class of thermoelectric materials. Half-Heusler alloys are a versatile class of materials that have been studied for use in photovoltaics, phase change memory, and thermoelectric power generation. With respect to thermoelectric power generation, new approaches were recently developed in order to improve the thermoelectric figure of merit, ZT, of half-Heusler alloys. Two of the strategies discussed in this work are adding excess Ni within MNiSn (M = Ti, Zr, or Hf) compounds to form full-Heusler nanostructures and using isoelectronic substitution of Ti, Zr, and Hf in MNiSn compounds to create microscale grain boundaries. This work uses computational simulations based on density functional theory, combined with the cluster expansion method, to predict the stable phases of pseudo-binary and pseudo-ternary composition systems. Statistical mechanics methods were used to calculate temperature-composition phase diagrams that relate the equilibrium phases. It is shown that full-Heusler nanostructures are predicted to remain stable even at high temperatures, and the microscale grain boundaries observed in (Ti,Zr,Hf)NiSn materials are found to be thermodynamically unstable at equilibrium. A new strategy of combining MNiSn materials with ZrNiPb has also recently emerged, and theoretical and experimental work show that a solid solution of the two materials is stable.

Psychometric properties of the Symptom Status Questionnaire-Heart Failure.

PubMed

Heo, Seongkum; Moser, Debra K; Pressler, Susan J; Dunbar, Sandra B; Mudd-Martin, Gia; Lennie, Terry A

2015-01-01

Many patients with heart failure (HF) experience physical symptoms, poor health-related quality of life (HRQOL), and high rates of hospitalization. Physical symptoms are associated with HRQOL and are major antecedents of hospitalization. However, reliable and valid physical symptom instruments have not been established. Therefore, this study examined the psychometric properties of the Symptom Status Questionnaire-Heart Failure (SSQ-HF) in patients with HF. Data on symptoms using the SSQ-HF were collected from 249 patients (aged 61 years, 67% male, 45% in New York Heart Association functional class III/IV). Internal consistency reliability was assessed using Cronbach's α. Item homogeneity was assessed using item-total and interitem correlations. Construct validity was assessed using factor analysis and testing hypotheses on known relationships. Data on depressive symptoms (Beck Depression Inventory II), HRQOL (Minnesota Living With Heart Failure Questionnaire), and event-free survival were collected to test known relationships. Internal consistency reliability was supported: Cronbach's α was .80. Item-total correlation coefficients and interitem correlation coefficients were acceptable. Factor analysis supported the construct validity of the instrument. More severe symptoms were associated with more depressive symptoms, poorer HRQOL, and more risk for hospitalization, emergency department visit, or death, controlling for covariates. The findings of this study support the reliability and validity of the SSQ-HF. Clinicians and researchers can use this instrument to assess physical symptoms in patients with HF.

Tai chi exercise in patients with chronic heart failure: a randomized clinical trial.

PubMed

Yeh, Gloria Y; McCarthy, Ellen P; Wayne, Peter M; Stevenson, Lynne W; Wood, Malissa J; Forman, Daniel; Davis, Roger B; Phillips, Russell S

2011-04-25

Preliminary evidence suggests that meditative exercise may have benefits for patients with chronic systolic heart failure (HF); this has not been rigorously tested in a large clinical sample. We sought to investigate whether tai chi, as an adjunct to standard care, improves functional capacity and quality of life in patients with HF. A single-blind, multisite, parallel-group, randomized controlled trial evaluated 100 outpatients with systolic HF (New York Heart Association class I-III, left ventricular ejection fraction ≤40%) who were recruited between May 1, 2005, and September 30, 2008. A group-based 12-week tai chi exercise program (n = 50) or time-matched education (n = 50, control group) was conducted. Outcome measures included exercise capacity (6- minute walk test and peak oxygen uptake) and disease-specific quality of life (Minnesota Living With Heart Failure Questionnaire). Mean (SD) age of patients was 67 (11) years; baseline values were left ventricular ejection fraction, 29% (8%) and peak oxygen uptake, 13.5 mL/kg/min; the median New York Heart Association class of HF was class II. At completion of the study, there were no significant differences in change in 6-minute walk distance and peak oxygen uptake (median change [first quartile, third quartile], 35 [-2, 51] vs 2 [-7, 54] meters, P = .95; and 1.1 [-1.1, 1.5] vs -0.5 [-1.2, 1.8] mL/kg/min, P = .81) when comparing tai chi and control groups; however, patients in the tai chi group had greater improvements in quality of life (Minnesota Living With Heart Failure Questionnaire, -19 [-23, -3] vs 1 [-16, 3], P = .02). Improvements with tai chi were also seen in exercise self-efficacy (Cardiac Exercise Self-efficacy Instrument, 0.1 [0.1, 0.6] vs -0.3 [-0.5, 0.2], P < .001) and mood (Profile of Mood States total mood disturbance, -6 [-17, 1] vs -1 [-13, 10], P = .01). Tai chi exercise may improve quality of life, mood, and exercise self-efficacy in patients with HF. Trial Registration clinicaltrials.gov Identifier: NCT00110227.

Non-Contact Tabletop Mechanical Testing of Ultra-High Temperature Ceramics

DTIC Science & Technology

2012-05-01

class of refractory materials including transition metal borides , carbides and nitrides e.g. ZrB2l HfB2) ZrC, HfC, TaC, HfN and ZrN. They recently...ike oxidizing atmospheres, at very high temperatures Refractory borides like ZrB2 and HfB2 have extremely high melting temperatures (over 3000°C...But borides are very poor in oxidation resistance, due to the nature of thär oxides Non-protective ZrCfe or Hf02 and volatile liquid B203. Addition

Adverse effects of permanent atrial fibrillation on heart failure in patients with preserved left ventricular function and chronic right apical pacing for complete heart block.

PubMed

Lampe, Brigitte; Hammerstingl, Christoph; Schwab, Jörg Otto; Mellert, Fritz; Stoffel-Wagner, Birgit; Grigull, Andreas; Fimmers, Rolf; Maisch, Bernhard; Nickenig, Georg; Lewalter, Thorsten; Yang, Alexander

2012-10-01

The impact of atrial fibrillation (AF) on heart failure (HF) was evaluated in patients with preserved left ventricular (LV) function and long-term right ventricular (RV) pacing for complete heart block. Clinical, echocardiographic, and laboratory parameters of HF were assessed in 35 patients with established AF who had undergone ablation of the atrioventricular node and pacemaker implantation (Group A) and 31 patients who received dual-chamber pacing for spontaneous complete heart block (Group B). During a follow-up period of 12.7 ± 7.5 years, New York Heart Association (NYHA) functional class increased from 1.3 ± 0.5 to 2.1 ± 0.6 (p < 0.0001) in Group A, and from 1.3 ± 0.4 to 1.6 ± 0.7 (p < 0.01) in Group B. Left ventricular ejection fraction (LVEF) decreased from 59.7 ± 5.1 to 53.0 ± 8.2 (p < 0.0001) in Group A, but remained stable (58.6 ± 4.2 vs. 56.9 ± 7.0 %, p = 0,21) in Group B. At the end of follow-up, markers of LV function were moderately depressed in Group A compared with those in Group B: NYHA class 2.1 ± 0.6 versus 1.6 ± 0.7, p = 0.001; LVEF 53.0 ± 8.2 versus 56.9 ± 7.0 %, p < 0.05; LV diastolic diameter 53.6 ± 5.8 mm versus 50.7 ± 4.9 mm, p < 0.05; N-terminal pro-brain natriuretic peptide (NT-proBNP) 1116.8 ± 883.9 versus 622.9 ± 1059.4 pg/ml, p < 0.05. Progression of paroxysmal AF to permanent AF during follow-up was common, while new onset of AF was rare. Permanent AF was an independent predictor of declining LVEF >10 %, increasing NYHA class ≥1, and NT-proBNP levels >1,000 pg/ml. Permanent AF was associated with adverse effects on LV function and symptoms of HF in patients with long-term RV pacing for complete heart block, and appears to play an important role in the development of HF in this specific patient cohort.

Influence of atrial fibrillation on plasma von willebrand factor, soluble E-selectin, and N-terminal pro B-type natriuretic peptide levels in systolic heart failure.

PubMed

Freestone, Bethan; Gustafsson, Finn; Chong, Aun Yeong; Corell, Pernille; Kistorp, Caroline; Hildebrandt, Per; Lip, Gregory Y H

2008-05-01

Endothelial dysfunction is present in patients with heart failure (HF) due to left ventricular systolic dysfunction, as well as in patients with atrial fibrillation (AF) who have normal cardiac function. It is unknown whether AF influences the degree of endothelial dysfunction in patients with systolic HF. We measured levels of plasma von Willebrand factor (vWF) and E-selectin (as indexes of endothelial damage/dysfunction and endothelial activation, respectively; both enzyme-linked immunosorbent assay) in patients with AF and HF (AF-HF), who were compared to patients with sinus rhythm and HF (SR-HF), as well as in age-matched, healthy, control subjects. We also assessed the relationship of vWF and E-selectin to plasma N-terminal pro B-type natriuretic peptide (NTpro-BNP), a marker for HF severity and prognosis. One hundred ninety patients (73% men; mean age, 69.0 +/- 10.1 years [+/- SD]) with systolic HF were studied, who were compared to 117 healthy control subjects: 52 subjects (27%) were in AF, while 138 subjects (73%) were in sinus rhythm. AF-HF patients were older than SR-HF patients (p = 0.046), but left ventricular ejection fraction and New York Heart Association class were similar. There were significant differences in NT-proBNP (p < 0.0001) and plasma vWF (p = 0.003) between patients and control subjects. On Tukey post hoc analysis, AF-HF patients had significantly increased NT-proBNP (p < 0.001) and vWF (p = 0.0183) but not E-selectin (p = 0.071) levels when compared to SR-HF patients. On multivariate analysis, the presence of AF was related to plasma vWF levels (p = 0.018). Plasma vWF was also significantly correlated with NT-proBNP levels (Spearman r = 0.139; p = 0.017). There is evidence of greater endothelial damage/dysfunction in AF-HF patients when compared to SR-HF patients. The clinical significance of this is unclear but may have prognostic value.

Potential role of biventricular pacing beyond advanced systolic heart failure.

PubMed

Fang, Fang; Sanderson, John E; Yu, Cheuk-Man

2013-01-01

Cardiac resynchronization therapy (CRT) is an effective therapy for advanced heart failure (HF) patients. The indications are well defined in recent guidelines and broadly indicate that CRT is suitable for chronic HF patients with left ventricular ejection fraction (EF) ≤35% and in NYHA class III or IV (Class I), and those with prolonged QRS duration ≥120 ms with left bundle branch block (LBBB) QRS morphology, or QRS duration ≥150 ms irrespective of QRS morphology (Class IIa). For patients with NYHA class II symptoms, CRT is recommended for patients with EF ≤30% and QRS duration ≥130 ms with LBBB QRS morphology (Class I, level of evidence: A), or QRS duration ≥150 ms irrespective of QRS morphology (Class IIa, level of evidence: A). However, CRT may benefit additional patients outside these criteria. In this review, we summarize the role of CRT in some subgroups, including patients with mild and moderate HF, upgrading to CRT from right ventricular (RV) pacing, bradycardia patients with routine pacing indications, congenital heart disease and specific cardiomyopathies. It is possible that CRT can give symptomatic and mortality benefits in some of these subgroups in the future and further clinical trials are warranted.  

One-year follow-up results from AUGMENT-HF: a multicentre randomized controlled clinical trial of the efficacy of left ventricular augmentation with Algisyl in the treatment of heart failure.

PubMed

Mann, Douglas L; Lee, Randall J; Coats, Andrew J S; Neagoe, Gheorghe; Dragomir, Dinu; Pusineri, Enrico; Piredda, Massimo; Bettari, Luca; Kirwan, Bridget-Anne; Dowling, Robert; Volterrani, Maurizio; Solomon, Scott D; Sabbah, Hani N; Hinson, Andy; Anker, Stefan D

2016-03-01

AUGMENT-HF was an international, multicentre, prospective, open-label, randomized, controlled evaluation testing the hypothesis that Algisyl (injectable calcium alginate hydrogel) is superior to standard medical therapy (SMT) for improving functional capacity and clinical outcomes in patients with advanced heart failure (HF). We previously reported results following 6 months of follow-up. This report presents the results from 1 year of extended follow up for this clinical trial. We enrolled 78 patients with advanced HF, randomized (1:1), to Algisyl with SMT or SMT alone as previously reported. Patient inclusion criteria were LVEF ≤35%, peak VO2 of 9.0-14.5 mL/min/kg and LV end-diastolic diameter (LVEDD) index 30-40 mm/m(2) (LVEDD/body surface area). Patients must have been on stable, evidence-based therapy for HF. A total of 58 patients, mean age 62.3 ± 9.6 years, with ischaemic (57.7%) or non-ischaemic (42.3%) HF completed 12 months of follow-up. Treatment with Algisyl was associated with improved peak VO2 at 12 months; treatment effect vs. control of +2.10 mL/kg/min (95% confidence interval 0.96-3.24, P < 0.001). Statistically significant improvements were observed for VO2 at anaerobic threshold, 6-min walk test distance, and NYHA functional class (all P < 0.001). Through 12 months of follow-up there were 4 (10.5%) deaths in the control group and 9 (22.5%) deaths in the Algisyl group. Algisyl in addition to SMT was more effective than SMT alone for providing sustained 1-year benefits in exercise capacity, symptoms, and clinical status for patients with advanced HF. These data support larger clinical evaluations of this novel therapy. © 2015 The Authors European Journal of Heart Failure © 2015 European Society of Cardiology.

The association between atrial fibrillation and cognitive function in patients with heart failure.

PubMed

Yang, Huifeng; Niu, Weihua; Zang, Xiaoying; Lin, Mei; Zhao, Yue

2017-02-01

Atrial fibrillation (AF) is associated with cognitive impairment in heart failure (HF). The purpose of this study was to examine whether AF independently predicted cognitive function in HF patients after controlling for more demographic, medical and psychological characteristics, and whether the timing of AF onset in relation to HF diagnosis independently contributed to cognitive function in HF patients with AF. A total of 188 hospitalized HF patients (62.8% male, age 66.3±10.6 years) completed cognitive function assessment with the Montreal Cognitive Assessment (MoCA). A history of AF, along with other medical characteristics, was ascertained through a review of participants' medical charts. The timing of AF onset in relation to HF diagnosis was categorized into AF occurring prior to HF diagnosis (i.e. prior AF) and AF developing after HF diagnosis (i.e. incident AF). Altogether 72 participants had a positive diagnostic history of AF. Specifically, 41 had prior AF, and 31 developed AF subsequently. In HF patients, AF was associated with poorer performance on cognitive function after controlling for more confounders (β=-0.112, ΔR 2 =0.010, p=0.046). Among HF patients with AF, incident AF independently predicted poorer cognitive function (β=-0.238, ΔR 2 =0.027, p=0.047). AF independently contributes to cognitive function in HF patients after adjusting for more confounding variables. The timing of AF onset in relation to HF diagnosis independently predicts cognitive function in HF patients with AF. Prospective studies are needed to elucidate possible mechanisms for the association between AF and cognitive function in HF populations.

Safety and efficacy of doxazosin as an "add-on" antihypertensive therapy in mild to moderate heart failure patients.

PubMed

Spoladore, Roberto; Roccaforte, Rosa; Fragasso, Gabriele; Gardini, Chiara; Palloshi, Altin; Cuko, Amarild; Arioli, Francesco; Salerno, Anna; Margonato, Alberto

2009-08-01

Doxazosin treatment has been discouraged in hypertensive patients in order to prevent heart failure (HF) development. However, this drug is still prescribed as an "add-on" medication to achieve a better blood pressure (BP) control. The aim of this study was to evaluate the safety and efficacy of doxazosin as an "add-on" medication in HF patients with uncontrolled hypertension. We reviewed our HF clinic files to collect patient variables recorded at baseline and during follow-up visits in patients receiving, or not, doxazosin. We compared HF-related hospitalization rates and all-cause and cardiovascular mortality rates between patients on doxazosin and those not on doxazosin. We constructed cumulative risk curves for time to first event (HF-related hospitalization and/or death) for both groups of patients. Fifty-two HF patients had been prescribed doxazosin. At baseline, several relevant variables were unevenly distributed between patients receiving doxazosin and those not receiving doxazosin (N=122), such as left ventricular ejection fraction (LVEF) and NYHA class. HF-related hospitalization and death rates were similar between patients on doxazosin and those not on doxazosin at the end of the follow-up. Even after adjustment for all potentially confounding variables, doxazosin was not associated with HF-related hospitalization and/or death. Doxazosin significantly reduced BP, but did not affect NYHA class. Doxazosin, "on top" of other antihypertensive treatments was safe and effective, and did not appear to be associated with HF-related hospitalization and mortality rates in our patients with mild/moderate HF.

Diagnostic value of analysis of H-FABP, NT-proBNP, and cTnI in heart function in children with congenital heart disease and pneumonia.

PubMed

Zhou, F-J; Zhou, C-Y; Tian, Y-J; Xiao, A-J; Li, P-L; Wang, Y-H; Jia, J-W

2014-01-01

To analyze the expression of heart-fatty acid-binding protein (H-FABP), N-terminal pro-brain natriuretic peptide (NT-proBNP), and cTnI in children with congenital heart disease (CHD) and pneumonia, and evaluate its diagnostic value in heart failure (HF). The levels of serum H-FABP, NT-proBNP, and cardiac troponin 1 (cTnI) were measured by immunoassays in 22 children with CHD, pneumonia, and HF (group I), 25 children with CHD and pneumonia (group II), and 25 healthy children without CHD or pneumonia (control group). The concentration and positive rate of serum H-FABP, NT-proBNP, and cTnI were significantly higher in group I than those in group II. Compared to control group, these indexes were increased in both group I and group II. There were statistical significant differences in the positive rate of NT-proBNP and cTnI but not H-FABP between groups of patients with different classes of heart function. The levels of H-FABP, NT-proBNP, and cTnI were correlated with heart function, and can be used for the diagnosis of early-stage HF in children with CHD.

Long-Term Survival With Implantable Cardioverter-Defibrillator in Different Symptomatic Functional Classes of Heart Failure.

PubMed

Biton, Yitschak; Rosero, Spencer; Moss, Arthur; Zareba, Wojciech; Kutyifa, Valentina; Baman, Jayson; Barsheshet, Alon; McNitt, Scott; Polonsky, Bronislava; Goldenberg, Ilan

2018-03-01

The ACC/AHA/HRS (American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society) guidelines recommend implantable cardioverter-defibrillator (ICD) therapy primary prevention in all patients with severely reduced left ventricular ejection fraction (≤30%) regardless of New York Heart Association (NYHA) functional class, whereas recent European guidelines limit the indication to those with symptomatic heart failure (NYHA ≥ II). We therefore aimed to evaluate the long-term survival benefit of primary ICD therapy among postmyocardial infarction patients with and without heart failure (HF) symptoms who were enrolled in MADIT-II (Multicenter Automatic Defibrillator Implantation Trial II). We classified 1,164 MADIT-II patient groups according to the baseline NYHA class (NYHA I [n = 442], NYHA II [n = 425], and NYHA III [n = 297]); patients with NYHA IV were excluded. Multivariate Cox proportional hazards regression modeling was performed to compare the mortality reduction with ICD versus non-ICD therapy during 8 years of follow-up between the 3 NYHA groups. The median (interquartile range) follow-up time was 7.6 (3.5 to 9) years. At 8 years of follow-up, the cumulative probability of mortality in the non-ICD treatment arm was 57% for NYHA I, 57% for NYHA II, and 76% for NYHA III (p <0.001). Multivariate models demonstrated similar long-term mortality risk reduction with ICD compared with the non-ICD treatment arm regardless of HF symptoms: NYHA I (HR = 0.63, 0.46 to 0.85, p = 0.003), NYHA II (HR = 0.68, 0.50 to 0.93, p = 0.017), and NYHA III (HR = 0.68, 0.50 to 0.94, p = 0.018); p for NYHA class by treatment arm interaction >0.10. In conclusion, primary ICD therapy provides consistent long-term survival benefit among patients with previous myocardial infarction and severe left ventricular dysfunction, regardless of HF symptoms. Copyright © 2017 Elsevier Inc. All rights reserved.

Practical considerations on the introduction of sacubitril/valsartan in clinical practice: Current evidence and early experience.

PubMed

Farmakis, Dimitrios; Bistola, Vassiliki; Karavidas, Apostolos; Parissis, John

2016-11-15

The combination of neprilysin inhibitor sacubitril with the angiotensin II receptor 1 blocker valsartan is the first agent from the angiotensin receptor neprilysin inhibitors (ARNI) class authorized for clinical use in heart failure (HF) patients with reduced ejection fraction (HFrEF). Sacubitril/valsartan resulted in 20% reduction in the incidence rate of death or HF hospitalization compared to enalapril in symptomatic HFrEF patients in the seminal PARADIGM-HF trial. As a result, the recently updated European and American HF guidelines granted this agent a class IB indication for the treatment of ambulatory/chronic symptomatic HFrEF patients. However, translating the positive results of trials into true clinical benefit is often challenging. This is particularly true in the case of sacubitril/valsartan, as HF is a heterogeneous syndrome including many severely ill patients who are prone to decompensation, while this new agent comes to replace a cornerstone of current evidence-based HF therapy. In the present paper, we address a number of practical issues regarding the introduction of sacubitril/valsartan and propose an algorithm based on available evidence and early clinical experience. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Metabolic disturbances identified in plasma are associated with outcomes in patients with heart failure: diagnostic and prognostic value of metabolomics.

PubMed

Cheng, Mei-Ling; Wang, Chao-Hung; Shiao, Ming-Shi; Liu, Min-Hui; Huang, Yu-Yen; Huang, Cheng-Yu; Mao, Chun-Tai; Lin, Jui-Fen; Ho, Hung-Yao; Yang, Ning-I

2015-04-21

Identification of novel biomarkers is needed to improve the diagnosis and prognosis of heart failure (HF). Metabolic disturbance is remarkable in patients with HF. This study sought to assess the diagnostic and prognostic values of metabolomics in HF. Mass spectrometry-based profiling of plasma metabolites was performed in 515 participants; the discovery phase study enrolled 51 normal control subjects and 183 HF patients, and the validation study enrolled 63 control subjects and 218 patients with stage C HF. Another independent group of 32 patients with stage C HF who recovered to New York Heart Association functional class I at 6 and 12 months was profiled as the "recovery" group. A panel of metabolites, including histidine, phenylalanine, spermidine, and phosphatidylcholine C34:4, has a diagnostic value similar to B-type natriuretic peptide (BNP). In the recovery group, the values of this panel significantly improved at 6 and 12 months. To evaluate the prognostic values, events were defined as the combined endpoints of death or HF-related re-hospitalization. A metabolite panel, which consisted of the asymmetric methylarginine/arginine ratio, butyrylcarnitine, spermidine, and the total amount of essential amino acids, provided significant prognostic values (p < 0.0001) independent of BNP and traditional risk factors. The prognostic value of the metabolite panel was better than that of BNP (area under the curve of 0.85 vs. 0.74 for BNP) and Kaplan-Meier curves (log rank: 17.5 vs. 9.95). These findings were corroborated in the validation study. Metabolomics demonstrate powerful diagnostic value in estimating HF-related metabolic disturbance. The profile of metabolites provides better prognostic value versus conventional biomarkers. Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Correlation between plasma N-terminal pro-brain natriuretic peptide levels and changes in New York Heart Association functional class, left atrial size, left ventricular size and function after mitral and/or aortic valve replacement.

PubMed

Elasfar, Abdelfatah

2012-01-01

Elevated plasma brain natriuretic peptide (BNP) levels have been demonstrated in patients with chronic valvular disease. We designed the present study to assess whether changes in N-terminal pro-brain natriuretic peptide (NT-proBNP) levels after mitral, aortic and double mitral and aortic valve replacement reflect changes in heart failure (HF) symptoms including New York Heart Association (NYHA) class and changes in left atrium (LA) size, left ventricle (LV) size and LV function. A prospective observational nonrandomized study among consecutive patients undergoing mitral and/or aortic valve replacement in our center. The study population consisted of 24 patients (mean [SD] age of 55.3 [16.2] years, 58% were males) who underwent surgical mitral valve replacement (12 patients), aortic valve replacement (8 patients) and combined mitral and aortic valve replacement (4 patients). NT-proBNP measurements, transthoracic echocardiography and NYHA class assessments were performed before and 6 months after surgery. The decrease in NT-proBNP was associated with decrease in left atrial dimension (r = 0.73, P < .002), LV end-diastolic dimension (r=0.65, P=.001), LV end-systolic dimension (r=0.53, P=.036), and increase in ejection fraction (r=-0.65, P=.001) after 6 months postoperatively. Furthermore, a decreasing NT-proBNP was associated with improvement in NYHA class. NT-proBNP levels after mitral, aortic and double valve replacement correlates with changes in HF manifestations as well as changes in LA size and LV dimension and function. Thus, we hypothesize that interval measurement of the NT-proBNP level at clinic visits can allow early detection of any clinical deterioration as well as the possibility of assessment of the long-term outcome of those patients.

Soluble Flt-1 links microvascular disease with heart failure in CKD.

PubMed

Di Marco, Giovana S; Kentrup, Dominik; Reuter, Stefan; Mayer, Anna B; Golle, Lina; Tiemann, Klaus; Fobker, Manfred; Engelbertz, Christiane; Breithardt, Günter; Brand, Eva; Reinecke, Holger; Pavenstädt, Hermann; Brand, Marcus

2015-05-01

Chronic kidney disease (CKD) is associated with an increased risk of heart failure (HF). Elevated plasma concentrations of soluble Flt-1 (sFlt-1) have been linked to cardiovascular disease in CKD patients, but whether sFlt-1 contributes to HF in CKD is still unknown. To provide evidence that concludes a pathophysiological role of sFlt-1 in CKD-associated HF, we measured plasma sFlt-1 concentrations in 586 patients with angiographically documented coronary artery disease and renal function classified according to estimated glomerular filtration rate (eGFR). sFlt-1 concentrations correlated negatively with eGFR and were associated with signs of heart failure, based on New York Heart Association functional class and reduced left ventricular ejection fraction (LVEF), and early mortality. Additionally, rats treated with recombinant sFlt-1 showed a 15 % reduction in LVEF and a 29 % reduction in cardiac output compared with control rats. High sFlt-1 concentrations were associated with a 15 % reduction in heart capillary density (number of vessels/cardiomyocyte) and a 24 % reduction in myocardial blood volume. Electron microscopy and histological analysis revealed mitochondrial damage and interstitial fibrosis in the hearts of sFlt-1-treated, but not control rats. In 5/6-nephrectomised rats, an animal model of CKD, sFlt-1 antagonism with recombinant VEGF121 preserved heart microvasculature and significantly improved heart function. Overall, these findings suggest that a component of cardiovascular risk in CKD patients could be directly attributed to sFlt-1. Assessment of patients with CKD confirmed that sFlt-1 concentrations were inversely correlated with renal function, while studies in rats suggested that sFlt-1 may link microvascular disease with HF in CKD.

Blood pressure dynamics during exercise rehabilitation in heart failure patients.

PubMed

Hecht, Idan; Arad, Michael; Freimark, Dov; Klempfner, Robert

2017-05-01

Background Patients suffering from heart failure (HF) may demonstrate an abnormal blood pressure response to exercise (ABPRE), which may revert to a normal one following medical treatment. It is assumed that this change correlates positively with prognosis and functional aspects. The aim of this study was to characterize patients with ABPRE and assess ABPRE normalization and the correlation with clinical and functional outcomes. Methods In the study, 651 patients with HF who underwent cardiac rehabilitation (CR) were examined. Patients who presented an ABPRE during stress testing were identified and divided into those who corrected their initial ABPRE following CR and those who did not. Results Pre-rehabilitation ABPRE was present in 27% of patients, 68% of whom normalized their ABPRE following CR. Two parameters were independently predictive of failure to normalize the blood pressure response: female gender (odds ratio (OR) 3.5; 95% confidence interval (CI) 1.4-9.0) and decreased systolic function (OR 3.2; 95% CI 1.0-9.4). Patients with hypertrophic cardiomyopathy demonstrated higher rates of ABPRE normalization than patients with other causes of HF (93% vs. 62%, respectively, P = 0.03). The research population exhibited an average improvement in exercise capacity (4.7 to 6.4 metabolic equivalents (METS), P < .001), ejection fraction (35.4% to 37.7%, P < .001) and percentage of patients with New York Heart Association (NYHA) class 3-4 (50% to 43.4%, P = .123). The group who normalized their ABPRE exhibited greater improvement. Conclusions Amongst a population of patients suffering from HF, an ABPRE was normalized following CR in two thirds of patients. Female gender and a reduced systolic function independently predicted the failure to correct the ABPRE, while patients with hypertrophic cardiomyopathy demonstrated exceptionally high rates of normalization.

The pharmacotherapy implications of ventricular assist device in the patient with end-stage heart failure.

PubMed

Von Ruden, Serena A S; Murray, Margaret A; Grice, Jennifer L; Proebstle, Amy K; Kopacek, Karen J

2012-04-01

Advances in mechanical circulatory support, such as the use of ventricular assist devices (VADs), have become a means for prolonging survival in end-stage heart failure (HF). VADs decrease the symptoms of HF and improve quality of life by replacing some of the work of a failing heart. They unload the ventricle to provide improved cardiac output and end-organ perfusion, resulting in improvement in cardiorenal syndromes and New York Heart Association functional class rating. VADs are currently used asa bridge to heart transplantation, a bridge to recovery of cardiac function, or as destination therapy. Complications of VAD include bleeding, infections, arrhythmias, multiple organ failure, right ventricular failure, and neurological dysfunction. Patients with VAD have unique pharmacotherapeutic requirements in terms of anticoagulation, appropriate antibiotic selection, and continuation of HF medications. Pharmacists in acute care and community settings are well prepared to care for the patient with VAD. These patients require thorough counseling and follow-up with regard to prevention and treatment of infections, appropriate levels of anticoagulation, and maintenance of fluid balance. A basic understanding of this unique therapy can assist pharmacists in attending to the needs of patients with VAD.

Signs, symptoms, and treatment patterns across serial ambulatory cardiology visits in patients with heart failure: insights from the NCDR PINNACLE® registry.

PubMed

Allen, Larry A; Tang, Fengming; Jones, Philip; Breeding, Tracie; Ponirakis, Angelo; Turner, Stuart J

2018-05-03

Due to a relative lack of outpatient heart failure (HF) clinical registries, we aimed to describe symptoms, signs, and medication treatment among ambulatory patients with heart failure (HF) over time. Using health records from 234 PINNACLE (Practice Innovation and Clinical Excellence) U.S. cardiology practices (2008-2014), serial visits for patients with HF were characterized. Symptoms, signs, and HF medications (angiotensin-converting enzyme inhibitors [ACEI], angiotensin receptor blockers [ARB], beta blockers [BB], and diuretics) were compared between visits. Among 763,331 patients with HF, 550,581 had ≥2 clinic visits < 1 year apart, with 2,998,444 visit pairs. In the 12 months following an index visit, patients had a mean of 2.5 ± 2.3 additional visits. Recorded index visit symptoms ranged from dyspnea (53.6%) to orthopnea (23.1%); signs ranged from peripheral edema (52.2%) to hepatomegaly (0.6%). Of those with ejection fraction < 40%, ACEI was prescribed in 58.6%, ARB in 18.5%, BB in 85.2%, and diuretics in 70.0%. Between-visit recorded changes were infrequent: dyspnea appeared in 3.8%, resolved in 2.7%; NYHA class increased in 2.9%, decreased in 2.9%; number of signs increased in 6.0%, decreased in 5.1%; ACEI/ARB or BB added in 6.4%, removed in 6.2%; diuretic added in 3.7%, removed in 3.8%. Changes in recorded symptoms were rarely associated with initiation or discontinuation in HF medication classes. Ambulatory HF care in U.S. cardiology practices seldom recorded changes in symptoms, signs, and medication class. Although templated medical records and absence of medication dosing likely underestimated the degree to which clinical changes occur over serial visits for HF, these PINNACLE data suggest opportunities for greater symptom-based and therapy-focused visits.

Determinants of Excessive Daytime Sleepiness and Fatigue in Adults with Heart Failure

PubMed Central

Riegel, Barbara; Ratcliffe, Sarah J.; Sayers, Steven L.; Potashnik, Sheryl; Buck, Harleah; Jurkovitz, Claudine; Fontana, Sarah; Weaver, Terri E.; Weintraub, William S.; Goldberg, Lee R.

2012-01-01

Little is known about excessive daytime sleepiness (EDS) in heart failure (HF). The aim of this cross-sectional descriptive study was to describe the prevalence of EDS and factors associated with it in HF. A secondary purpose was to explore the correlates of fatigue. We enrolled a consecutive sample of 280 adults with a confirmed diagnosis of chronic HF from three outpatient settings in the northeastern US. Patients with major depressive illness were excluded. Clinical, sociodemographic, behavioral, and perceptual factors were explored as possible correlates of EDS. Using an Epworth Sleepiness Scale score >10, the prevalence of EDS was 23.6%. Significant determinants of EDS were worse sleep quality (p=0.048), worse functional class (p=0.004), not taking a diuretic (p=0.005), and lack of physical activity (p=0.04). Only sleep quality was associated with fatigue (p<0.001). Sleep disordered breathing was not significantly associated with EDS or with fatigue. These factors may be amenable to intervention. PMID:21878581

[Heart failure patterns in Djibouti: epidemiologic transition].

PubMed

Massoure, P L; Roche, N C; Lamblin, G; Topin, F; Dehan, C; Kaiser, E; Fourcade, L

2013-05-01

The features of heart failure (HF) in Djibouti have not been well described. We sought to document the current patterns of HF here. We prospectively included Djiboutian adults hospitalized for HF in the French Military Hospital (Djibouti) from August 2008 through December 2010. Of 1688 adults hospitalized in the medical department, 45 (2.7%) had symptomatic HF: 38 (84%) men, mean age 55.8 years (range 27-75). Twenty-five (56%) patients were initially hospitalized for acute pulmonary edema. The underlying diseases included coronary artery disease (CAD) (62%), hypertensive heart disease (18%), rheumatic valvular disease (13%), and primary dilated cardiomyopathy (7%). Their cardiovascular risk factors included tobacco use (53%), hypertension (69%), diabetes (47%), and hypercholesterolemia (51%). Patients in the CAD group were older, and had diabetes more often (p<0.01). All khat chewers (53%) were males and smokers. Mean left ventricular ejection fraction (LVEF) was 39 ± 14%. During follow-up (14.4 ± 9 months), 8 (18%) patients died, 9 (20%) were again hospitalized for HF, and 3 (7%) had ischemic strokes. One month after discharge, the New York Heart Association (NYHA) class was II for 40%, III for 44%, and IV for 16%. Higher NYHA classes and dilated cardiomyopathy were both associated with poorer outcomes (p<0.03). In hospitalized Djiboutians, most HF patterns are similar to those in industrialized countries. CAD is more prevalent than previously reported in African patients with HF.

Sacubitril/valsartan in heart failure: latest evidence and place in therapy

PubMed Central

Kaplinsky, Edgardo

2016-01-01

Despite significant therapeutic advances, patients with chronic heart failure (HF) remain at high risk for HF progression and death. Sacubitril/valsartan (previously known as LCZ696) is a first-in-class medicine that contains a neprilysin (NEP) inhibitor (sacubitril) and an angiotensin II (Ang-II) receptor blocker (valsartan). NEP is an endopeptidase that metabolizes different vasoactive peptides including natriuretic peptides, bradykinin and Ang-II. In consequence, its inhibition increases mainly the levels of both, natriuretic peptides (promoting diuresis, natriuresis and vasodilatation) and Ang-II whose effects are blocked by the angiotensin receptor blocker, valsartan (reducing vasoconstriction and aldosterone release). Results from the 8442 patient PARADIGM-HF study showed in patients with New York Heart Association (NYHA) class II–IV and reduced ejection fraction treated with LCZ696 (versus enalapril), the following benefits: reduction of the risk of death from cardiovascular causes by 20%; reduction of HF hospitalizations by 21%; reduction of the risk of all-cause mortality by 16%. Overall there was a 20% risk reduction on the primary endpoint, composite measure of cardiovascular (CV) death or time to first HF hospitalization. PARADIGM-HF was stopped early after a median follow up of 27 months. Post hoc analyses of PARADIGM-HF as well as the place in therapy of sacubitril/valsartan, including future directions, are included in the present review. PMID:27803793

Six-minute walk test and cardiopulmonary exercise testing in patients with chronic heart failure: a comparative analysis on clinical and prognostic insights.

PubMed

Guazzi, Marco; Dickstein, Kenneth; Vicenzi, Marco; Arena, Ross

2009-11-01

The six-minute walk test (6MWT) and cardiopulmonary exercise testing (CPET) are the 2 testing modalities most broadly used for assessing functional limitation in patients with heart failure (HF). A comprehensive comparison on clinical and prognostic validity of the 2 techniques has not been performed and is the aim of the present investigation. Two hundred fifty-three patients diagnosed with systolic (n=211) or diastolic (n=42) HF (age: 61.9+/-10.1 years; New York Heart Association Class: 2.2+/-0.78) underwent a 6MWT and a symptom-limited CPET evaluation and were prospectively followed up. During the 4-year tracking period, there were 43 cardiac-related deaths with an annual cardiac mortality rate of 8.7%. The 6MWT distance correlated with CPET-derived variables (ie, peak Vo(2), Vo(2) at anaerobic threshold, and Ve/Vco(2) slope) and was significantly reduced in proportion with lower peak Vo(2) and higher Ve/Vco(2) slope classes and presence of an exercise oscillatory breathing (EOB) pattern (P<0.01). However, no significant differences were observed in distance covered between survivors and nonsurvivors (353.2+/-95.8 m versus 338.5+/-76.4 m; P=NS). At univariate and multivariate Cox proportional analyses, the association of the 6MWT distance with survival was not significant either as a continuous or dicotomized variable (< or =300 m). Conversely, CPET-derived variables emerged as prognostic with the strongest association found for EOB (systolic HF) and Ve/Vco(2) slope (entire population with HF and patients with a 6MWT< or =300 m). The 6MWT is confirmed to be a simple and reliable first-line test for quantification of exercise intolerance in patients with HF. However, there is no supportive evidence for its use as a prognostic marker in alternative to or in conjunction with CPET-derived variables.

Sacubitril/valsartan for heart failure with reduced left ventricular ejection fraction : A retrospective cohort study.

PubMed

De Vecchis, R; Ariano, C; Di Biase, G; Noutsias, M

2018-01-19

The combination drug sacubitril/valsartan was reported to be superior to enalapril in reducing all-cause death, cardiovascular mortality, and heart failure (HF) hospitalizations in patients with cardiac insufficiency and reduced left ventricular ejection fraction (HFREF) with NYHA class II-IV. Our retrospective cohort study aimed to assess the effects of sacubitril/valsartan in addition to a beta-blocker and mineral receptor antagonist (MRA) in a group of HFREF patients with NYHA class II-III HF vs. conventional therapy (ACE inhibitor or angiotensin II receptor blocker added to a beta-blocker plus an MRA) administered to a control group of HFREF patients with comparable clinical features. In both groups, treatment was supplemented by a loop diuretic, usually furosemide, at variable doses. The primary outcomes were all-cause death and HF hospitalizations. Safety outcomes were symptomatic hypotension, angioedema, hyperkalemia, and worsening renal function. Mortality at 6 months was 6.8% in patients taking sacubitril/valsartan vs. 34% in those on conventional therapy (odds ratio [OR] = 0.14; 95% CI: 0.04-0.49). Moreover, there was a 4.5% rate of HF hospitalizations in the sacubitril/valsartan group vs. 59% in the control group (OR = 0.03; 95% CI: 0.01-0.14). Safety outcomes were comparable in the two groups, although hypotension (systolic blood pressure < 100 mm Hg) was found in 15.9% of patients in the sacubitril/valsartan group vs. 5.7% in the control group (OR = 3.14; 95% CI: 0.94-10.55). Sacubitril/valsartan offered strong protection against all-cause death and HF hospitalizations at 6 months without any significant side effects. To validate this efficacious molecule, further postmarketing observational studies, focusing mainly on hypotension and angioedema are warranted.

Dietary sodium restriction below 2 gram per day predicted shorter event-free survival in patients with mild heart failure

PubMed Central

Song, Eun Kyeung; Moser, Debra K.; Dunbar, Sandra B.; Pressler, Susan J.; Lennie, Terry A.

2015-01-01

Background Despite a growing recognition that a strict low sodium diet may not be warranted in compensated heart failure (HF) patients, the link between sodium restriction below 2g/day and health outcomes is unknown in patients at different levels of HF severity. Purpose To compare differences in event-free survival among patients with < 2g/day, 2–3g/day, or > 3g/day sodium intake stratified by New York Heart Association (NYHA) class. Method A total of 244 patients with HF completed a four-day food diary to measure daily sodium intake. All-cause hospitalization or death for a median of 365follow-up days and covariates on age, gender, etiology, body mass index, NYHA class, ejection fraction, total comorbidity score, the presence of ankle edema, and prescribed medications were determined by patient interview and medical record review. Hierarchical Cox hazard regression was used to address the purpose. Results In NYHA class I/II (n=134), patients with < 2g/day sodium intake had a 3.7-times higher risk (p = .025), while patients with > 3g/day sodium intake had a 0.4-times lower risk (p = .047) for hospitalization or death than those with 2–3g/day sodium intake after controlling for covariates. In NYHA class III/IV (n=110), > 3g/day sodium intake predicted shorter event-free survival (p = .044), whereas there was no difference in survival curves between patients with < 2g/day and those with 2–3g/day sodium intake. Conclusion Sodium restriction below 2g/day is not warranted in mild HF patients, whereas excessive sodium intake above 3g/day may be harmful in moderate to severe HF patients. PMID:24366983

Safety and feasibility of pulmonary artery pressure-guided heart failure therapy: rationale and design of the prospective CardioMEMS Monitoring Study for Heart Failure (MEMS-HF).

PubMed

Angermann, Christiane E; Assmus, Birgit; Anker, Stefan D; Brachmann, Johannes; Ertl, Georg; Köhler, Friedrich; Rosenkranz, Stephan; Tschöpe, Carsten; Adamson, Philip B; Böhm, Michael

2018-05-19

Wireless monitoring of pulmonary artery (PA) pressures with the CardioMEMS HF™ system is indicated in patients with New York Heart Association (NYHA) class III heart failure (HF). Randomized and observational trials have shown a reduction in HF-related hospitalizations and improved quality of life in patients using this device in the United States. MEMS-HF is a prospective, non-randomized, open-label, multicenter study to characterize safety and feasibility of using remote PA pressure monitoring in a real-world setting in Germany, The Netherlands and Ireland. After informed consent, adult patients with NYHA class III HF and a recent HF-related hospitalization are evaluated for suitability for permanent implantation of a CardioMEMS™ sensor. Participation in MEMS-HF is open to qualifying subjects regardless of left ventricular ejection fraction (LVEF). Patients with reduced ejection fraction must be on stable guideline-directed pharmacotherapy as tolerated. The study will enroll 230 patients in approximately 35 centers. Expected duration is 36 months (24-month enrolment plus ≥ 12-month follow-up). Primary endpoints are freedom from device/system-related complications and freedom from pressure sensor failure at 12-month post-implant. Secondary endpoints include the annualized rate of HF-related hospitalization at 12 months versus the rate over the 12 months preceding implant, and health-related quality of life. Endpoints will be evaluated using data obtained after each subject's 12-month visit. The MEMS-HF study will provide robust evidence on the clinical safety and feasibility of implementing haemodynamic monitoring as a novel disease management tool in routine out-patient care in selected European healthcare systems. ClinicalTrials.gov; NCT02693691.

Effectiveness of a multidimensional home nurse led heart failure disease management program--a French nationwide time-series comparison.

PubMed

Agrinier, Nelly; Altieri, Christelle; Alla, François; Jay, Nicolas; Dobre, Daniela; Thilly, Nathalie; Zannad, Faiez

2013-10-09

The purpose of this study was to assess the effectiveness of a disease management program (DMP) in heart failure (HF) on the incidence of HF hospitalizations and related costs in a real-world population-based setting. Insuffisance CArdiaque en LORraine (ICALOR), a DMP for HF was established in 2006 in the French region of Lorraine. Patients were enrolled after an index HF hospitalization. They received educational and home-visit monitoring programs by HF-trained nurses. General physicians received automatic alerts about patients' significant clinical or biological changes. We used the ICALOR and the national diagnostic related group databases to conduct a comparison of time-series trends in HF hospitalizations in France. The economic impact was obtained using the national scale of costs in France. The median age of the 1222 patients recruited before 2010 was 76 years, and 65% were male. Upon enrollment, patients essentially presented with NYHA class II (n=537, 48%) or class III (n=359, 32%) symptoms. One-year mortality rate was 20.3%. The implementation of the ICALOR program was associated with a reduction in HF hospitalizations in Lorraine estimated by an absolute difference between the number of hospitalizations observed in the Lorraine region and that expected had it been similar to that observed in the whole country of -7.19% in 2010. The estimated annual hospital cost saved by ICALOR was €1,927,648 in 2010. Coordinated DMP of HF might improve outcome cost-effectively when implemented in a real-world population setting, and was associated in Lorraine with a substantial modification of the trend of HF hospitalizations. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Characteristics and in-hospital outcomes of patients with acute coronary syndromes and heart failure in the United Arab Emirates.

PubMed

Shehab, Abdulla; Al-Dabbagh, Bayan; Almahmeed, Wael; Bustani, Nazar; Nagelkerke, Nicolaas; Yusufali, Afzal; Wassef, Adel; Ibrahim, Mohamed; Brek, Azan Bin

2012-09-26

Heart failure (HF) is a serious complication of acute coronary syndromes (ACS), and is associated with high in-hospital mortality and poor long-term survival. The aims of this study were to describe the clinical characteristics, management and in-hospital outcomes of coronary syndrome (ACS) patients with HF in the United Arab Emirates. The study was selected from the Gulf Registry of Acute Coronary Events (Gulf RACE), a prospective multi-national, multicenter registry of patients hospitalized with ACS in six Middle East countries. The present analysis was focused on participants admitted to various hospitals in the UAE with a diagnosis of ACS in 2007 and were analyzed in terms of HF (Killip class II/III and IV) on admission. Of 1691 patients (mean age: 52.6 ± 11.7 years; 210 Females, 1481 Males) with ACS, 356 (21%) had an admission diagnosis of HF (Killip class II/III and IV). HF patients were less frequently males (19.2% vs. 34.3%; P < 0.001). HF was more frequently associated with hypertension (64.3% vs. 43.9%; P < 0.001), hyperlipidemia (49.4% vs. 31.8%; P < 0.001) and diabetes mellitus (DM) (51.1% vs. 36.2%; P < 0.001). HF was significantly associated with in-hospital mortality (OR = 11.821; 95% CI: 5.385-25.948; P < 0.001). In multivariate logistic regression, age, hyperlipidemia, heart rate and DM were associated with higher in-hospital HF. HF is observed in about 1 in 5 patients with ACS in the UAE and is associated with a significant increase in in-hospital mortality and other adverse outcomes.

Severe chronic heart failure in patients considered for heart transplantation in Poland.

PubMed

Korewicki, Jerzy; Leszek, Przemysław; Zieliński, Tomasz; Rywik, Tomasz; Piotrowski, Walerian; Kurjata, Paweł; Kozar-Kamińska, Katarzyna; Kodziszewska, Katarzyna

2012-01-01

Based on the results of clinical trials, the prognosis for patients with severe heart failure (HF) has improved over the last 20 years. However, clinical trials do not reflect 'real life' due to patient selection. Thus, the aim of the POLKARD-HF registry was the analysis of survival of patients with refractory HF referred for orthotopic heart transplantation (OHT). Between 1 November 2003 and 31 October 2007, 983 patients with severe HF, referred for OHT in Poland, were included into the registry. All patients underwent routine clinical and hemodynamic evaluation, with NT-proBNP and hsCRP assessment. Death or an emergency OHT were assumed as the endpoints. The average observation period was 601 days. Kaplan-Meier curves with log-rank and univariate together with multifactor Cox regression model the stepwise variable selection method were used to determine the predictive value of analyzed variables. Among the 983 patients, the probability of surviving for one year was approximately 80%, for two years 70%, and for three years 67%. Etiology of the HF did not significantly influence the prognosis. The patients in NYHA class IV had a three-fold higher risk of death or emergency OHT. The univariate/multifactor Cox regression analysis revealed that NYHA IV class (HR 2.578, p < 0.0001), HFSS score (HR 2.572, p < 0.0001) and NT-proBNP plasma level (HR 1.600, p = 0.0200), proved to influence survival without death or emergency OHT. Despite optimal treatment, the prognosis for patients with refractory HF is still not good. NYHA class IV, NT-proBNP and HFSS score can help define the highest risk group. The results are consistent with the prognosis of patients enrolled into the randomized trials.

A mitochondrial-targeted ubiquinone modulates muscle lipid profile and improves mitochondrial respiration in obesogenic diet-fed rats.

PubMed

Coudray, Charles; Fouret, Gilles; Lambert, Karen; Ferreri, Carla; Rieusset, Jennifer; Blachnio-Zabielska, Agnieszka; Lecomte, Jérôme; Ebabe Elle, Raymond; Badia, Eric; Murphy, Michael P; Feillet-Coudray, Christine

2016-04-14

The prevalence of the metabolic syndrome components including abdominal obesity, dyslipidaemia and insulin resistance is increasing in both developed and developing countries. It is generally accepted that the development of these features is preceded by, or accompanied with, impaired mitochondrial function. The present study was designed to analyse the effects of a mitochondrial-targeted lipophilic ubiquinone (MitoQ) on muscle lipid profile modulation and mitochondrial function in obesogenic diet-fed rats. For this purpose, twenty-four young male Sprague-Dawley rats were divided into three groups and fed one of the following diets: (1) control, (2) high fat (HF) and (3) HF+MitoQ. After 8 weeks, mitochondrial function markers and lipid metabolism/profile modifications in skeletal muscle were measured. The HF diet was effective at inducing the major features of the metabolic syndrome--namely, obesity, hepatic enlargement and glucose intolerance. MitoQ intake prevented the increase in rat body weight, attenuated the increase in adipose tissue and liver weights and partially reversed glucose intolerance. At the muscle level, the HF diet induced moderate TAG accumulation associated with important modifications in the muscle phospholipid classes and in the fatty acid composition of total muscle lipid. These lipid modifications were accompanied with decrease in mitochondrial respiration. MitoQ intake corrected the lipid alterations and restored mitochondrial respiration. These results indicate that MitoQ protected obesogenic diet-fed rats from some features of the metabolic syndrome through its effects on muscle lipid metabolism and mitochondrial activity. These findings suggest that MitoQ is a promising candidate for future human trials in the metabolic syndrome prevention.

The WAP four-disulfide core domain protein HE4: a novel biomarker for heart failure.

PubMed

de Boer, Rudolf A; Cao, Qi; Postmus, Douwe; Damman, Kevin; Voors, Adriaan A; Jaarsma, Tiny; van Veldhuisen, Dirk J; Arnold, William D; Hillege, Hans L; Silljé, Herman H W

2013-04-01

This study investigated clinical determinants and added prognostic value of HE4 as a biomarker not previously described in heart failure (HF). Identification of plasma biomarkers that help to risk stratify HF patients may help to improve treatment. Plasma HE4 levels were determined in 567 participants of the COACH (Coordinating study evaluating outcomes of Advising and Counseling in Heart failure). Patients had been hospitalized for HF and were followed for 18 months. The primary endpoint of this study was a composite of all-cause mortality and HF hospitalization. HE4 showed a strong correlation with HF severity, according to New York Heart Association functional class and brain natriuretic peptide (BNP) levels (p < 0.001). HE4 also showed a positive correlation with GDF15 (p < 0.001) and, in addition, correlated with kidney function (estimated glomerular filtration rate [eGFR]; p < 0.001). Cox regression analysis revealed that a doubling of HE4 levels was associated with a hazard ratio (HR) of 1.73 (95% confidence interval [CI]: 1.53 to 1.95) for the primary outcome (p < 0.001). After correction for age, gender, BNP, and eGFR, the HR was 1.46 (95% CI: 1.23 to 1.72; p < 0.001), and after additional adjustment for GDF15, the HR lowered to 1.30 (95% CI: 1.07 to 1.59; p = 0.009). The area under the curve in the receiver-operating characteristic curve analysis increased from 0.727 to 0.752 when HE4 was included in the clinical evaluation (p = 0.051). The integrated discrimination improvement and net reclassification index for reclassification showed significant improvements when HE4 was added to the clinical model, and this remained significant after BNP inclusion in the model. HE4 plasma levels are correlated with markers of HF severity, show prognostic value, and can improve risk assessment in HF. Copyright © 2013 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Insights into implementation of sacubitril/valsartan into clinical practice.

PubMed

Martens, Pieter; Beliën, Hanne; Dupont, Matthias; Mullens, Wilfried

2018-06-01

Sacubitril/valsartan significantly reduced heart failure hospitalization and mortality in PARADIGM-HF (Prospective Comparison of Angiotensin Receptor-Neprilysin Inhibitor With an Angiotensin-Converting Enzyme Inhibitor to Determine Impact on Global Mortality and Morbidity in Heart Failure). However, real-world data from its use are lacking. We retrospectively assessed all baseline and follow-up data of consecutive heart failure patients with reduced ejection fraction receiving therapy with sacubitril/valsartan for Class I recommendation between December 2016 and July 2017. Baseline characteristics and dose titration of sacubitril/valsartan were compared between patients in clinical practice and in PARADIGM-HF. A total of 120 patients (81% male) were switched from angiotensin-converting enzyme inhibitor or angiotensin receptor blocker to sacubitril/valsartan. A total of 20.1% of patients received dose uptitration. Patients were treated with an equipotential dose of renin-angiotensin system blockers before and after uptitration of sacubitril/valsartan (57 ± 29% vs. 53 ± 29% of target dose indicated by European Society of Cardiology guidelines; P = 0.286). However, they received a lower dose of sacubitril/valsartan in comparison with those in the PARADIGM-HF (219 ± 12 vs. 375 ± 75 mg; P < 0.001). In comparison with the patients receiving sacubitril/valsartan in PARADIGM-HF, patients in clinical practice were older and had a higher serum creatinine, higher New York Heart Association functional classification, and lower left ventricular ejection fraction (all P-value <0.05). Even in comparison with patients who experienced dropout during the run-in phase of PARADIGM-HF, real-world patients exhibited baseline characteristics indicative of more disease severity. Patients were at high absolute baseline risk for adverse outcome as illustrated by the EMPHASIS-HF (Eplerenone in Mild Patients Hospitalization and Survival Study in Heart Failure) risk score of 6 (inter-quartile range 3), in comparison with 5 (inter-quartile range 4) in PARADIGM-HF. After initiation of sacubitril/valsartan, New York Heart Association class significantly improved (P < 0.001), but systolic blood pressure dropped more than was reported in PARADIGM-HF (7.1 ± 8.0 vs. 3.2 ± 0.4 mmHg; P < 0.001). Patients in clinical practice exhibit baseline characteristics associated with more severe disease, which might lead to prescription of lower doses. Nevertheless, patients in clinical practice are at high risk of adverse outcome as illustrated by the EMPHASIS-HF risk score, underscoring the large potential for sacubitril/valsartan therapy to reduce the risk of heart failure hospitalization and all-cause mortality. © 2018 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of the European Society of Cardiology.

Insights into implementation of sacubitril/valsartan into clinical practice

PubMed Central

Martens, Pieter; Beliën, Hanne; Dupont, Matthias

2018-01-01

Abstract Background Sacubitril/valsartan significantly reduced heart failure hospitalization and mortality in PARADIGM‐HF (Prospective Comparison of Angiotensin Receptor‐Neprilysin Inhibitor With an Angiotensin‐Converting Enzyme Inhibitor to Determine Impact on Global Mortality and Morbidity in Heart Failure). However, real‐world data from its use are lacking. Methods and results We retrospectively assessed all baseline and follow‐up data of consecutive heart failure patients with reduced ejection fraction receiving therapy with sacubitril/valsartan for Class I recommendation between December 2016 and July 2017. Baseline characteristics and dose titration of sacubitril/valsartan were compared between patients in clinical practice and in PARADIGM‐HF. A total of 120 patients (81% male) were switched from angiotensin‐converting enzyme inhibitor or angiotensin receptor blocker to sacubitril/valsartan. A total of 20.1% of patients received dose uptitration. Patients were treated with an equipotential dose of renin–angiotensin system blockers before and after uptitration of sacubitril/valsartan (57 ± 29% vs. 53 ± 29% of target dose indicated by European Society of Cardiology guidelines; P = 0.286). However, they received a lower dose of sacubitril/valsartan in comparison with those in the PARADIGM‐HF (219 ± 12 vs. 375 ± 75 mg; P < 0.001). In comparison with the patients receiving sacubitril/valsartan in PARADIGM‐HF, patients in clinical practice were older and had a higher serum creatinine, higher New York Heart Association functional classification, and lower left ventricular ejection fraction (all P‐value <0.05). Even in comparison with patients who experienced dropout during the run‐in phase of PARADIGM‐HF, real‐world patients exhibited baseline characteristics indicative of more disease severity. Patients were at high absolute baseline risk for adverse outcome as illustrated by the EMPHASIS‐HF (Eplerenone in Mild Patients Hospitalization and Survival Study in Heart Failure) risk score of 6 (inter‐quartile range 3), in comparison with 5 (inter‐quartile range 4) in PARADIGM‐HF. After initiation of sacubitril/valsartan, New York Heart Association class significantly improved (P < 0.001), but systolic blood pressure dropped more than was reported in PARADIGM‐HF (7.1 ± 8.0 vs. 3.2 ± 0.4 mmHg; P < 0.001). Conclusions Patients in clinical practice exhibit baseline characteristics associated with more severe disease, which might lead to prescription of lower doses. Nevertheless, patients in clinical practice are at high risk of adverse outcome as illustrated by the EMPHASIS‐HF risk score, underscoring the large potential for sacubitril/valsartan therapy to reduce the risk of heart failure hospitalization and all‐cause mortality. PMID:29464879

Dual angiotensin receptor and neprilysin inhibition as an alternative to angiotensin-converting enzyme inhibition in patients with chronic systolic heart failure: rationale for and design of the Prospective comparison of ARNI with ACEI to Determine Impact on Global Mortality and morbidity in Heart Failure trial (PARADIGM-HF).

PubMed

McMurray, John J V; Packer, Milton; Desai, Akshay S; Gong, Jim; Lefkowitz, Martin P; Rizkala, Adel R; Rouleau, Jean; Shi, Victor C; Solomon, Scott D; Swedberg, Karl; Zile, Michael R

2013-09-01

Although the focus of therapeutic intervention has been on neurohormonal pathways thought to be harmful in heart failure (HF), such as the renin-angiotensin-aldosterone system (RAAS), potentially beneficial counter-regulatory systems are also active in HF. These promote vasodilatation and natriuresis, inhibit abnormal growth, suppress the RAAS and sympathetic nervous system, and augment parasympathetic activity. The best understood of these mediators are the natriuretic peptides which are metabolized by the enzyme neprilysin. LCZ696 belongs to a new class of drugs, the angiotensin receptor neprilysin inhibitors (ARNIs), which both block the RAAS and augment natriuretic peptides. Patients with chronic HF, NYHA class II-IV symptoms, an elevated plasma BNP or NT-proBNP level, and an LVEF of ≤40% were enrolled in the Prospective comparison of ARNI with ACEI to Determine Impact on Global Mortailty and morbidity in Heart Failure trial (PARADIGM-HF). Patients entered a single-blind enalapril run-in period (titrated to 10 mg b.i.d.), followed by an LCZ696 run-in period (100 mg titrated to 200 mg b.i.d.). A total of 8436 patients tolerating both periods were randomized 1:1 to either enalapril 10 mg b.i.d. or LCZ696 200 mg b.i.d. The primary outcome is the composite of cardiovascular death or HF hospitalization, although the trial is powered to detect a 15% relative risk reduction in cardiovascular death. PARADIGM-HF will determine the place of the ARNI LCZ696 as an alternative to enalapril in patients with systolic HF. PARADIGM-HF may change our approach to neurohormonal modulation in HF. NCT01035255.

Dual angiotensin receptor and neprilysin inhibition as an alternative to angiotensin-converting enzyme inhibition in patients with chronic systolic heart failure: rationale for and design of the Prospective comparison of ARNI with ACEI to Determine Impact on Global Mortality and morbidity in Heart Failure trial (PARADIGM-HF)

PubMed Central

McMurray, John J. V.; Packer, Milton; Desai, Akshay S.; Gong, Jim; Lefkowitz, Martin P.; Rizkala, Adel R.; Rouleau, Jean; Shi, Victor C.; Solomon, Scott D.; Swedberg, Karl; Zile, Michael R.

2013-01-01

Aims Although the focus of therapeutic intervention has been on neurohormonal pathways thought to be harmful in heart failure (HF), such as the renin–angiotensin–aldosterone system (RAAS), potentially beneficial counter-regulatory systems are also active in HF. These promote vasodilatation and natriuresis, inhibit abnormal growth, suppress the RAAS and sympathetic nervous system, and augment parasympathetic activity. The best understood of these mediators are the natriuretic peptides which are metabolized by the enzyme neprilysin. LCZ696 belongs to a new class of drugs, the angiotensin receptor neprilysin inhibitors (ARNIs), which both block the RAAS and augment natriuretic peptides. Methods Patients with chronic HF, NYHA class II–IV symptoms, an elevated plasma BNP or NT-proBNP level, and an LVEF of ≤40% were enrolled in the Prospective comparison of ARNI with ACEI to Determine Impact on Global Mortailty and morbidity in Heart Failure trial (PARADIGM-HF). Patients entered a single-blind enalapril run-in period (titrated to 10 mg b.i.d.), followed by an LCZ696 run-in period (100 mg titrated to 200 mg b.i.d.). A total of 8436 patients tolerating both periods were randomized 1:1 to either enalapril 10 mg b.i.d. or LCZ696 200 mg b.i.d. The primary outcome is the composite of cardiovascular death or HF hospitalization, although the trial is powered to detect a 15% relative risk reduction in cardiovascular death. Perspectives PARADIGM-HF will determine the place of the ARNI LCZ696 as an alternative to enalapril in patients with systolic HF. PARADIGM-HF may change our approach to neurohormonal modulation in HF. Trial registration NCT01035255 PMID:23563576

Intrinsic Defect Ferromagnetism: The case of Hafnium Oxide

NASA Astrophysics Data System (ADS)

Das Pemmaraju, Chaitanya

2005-03-01

In view of the recent experimental reports of intrinsic ferromagnetism in Hafnium Oxide (HfO2) thin film systems ootnotetextM. Venkatesan, C. B. Fitzgerald, J. M. D. Coey Nature 430, 630 (2004) Brief Communications, we carried out first principles investigations to look for magnetic structure in HfO2 possibly brought about by the presence of small concentrations of intrinsic point defects. Ab initio electronic structure calculations using Density Functional Theory (DFT) show that isolated cation vacancy sites in HfO2 lead to the formation of high spin defect states which couple ferromagnetically to each other. Interestingly, these high spin states are observed in the low symmetry monoclinic and tetragonal phases while the highly symmetric cubic flourite phase exhibits a non-magnetic ground state. Detailed studies of the electronic structure of cation vacancies in the three crystalline phases of Hafnia show that symmetry leading to orbitally degenerate defect levels is not a pre-requsite for ferromagnetism and that the interplay between Kinetic, Coulomb and Exchange energy together with favourable coupling to the Crystalline environment can lead to high spin ferromagnetic ground states even in extreme low symmetry systems like monoclinic HfO2. These findings open up a much wider class of systems to the possibility of intrinsic defect ferromagnetism.

The vasovagal tonus index as a prognostic indicator in dogs with dilated cardiomyopathy.

PubMed

Pereira, Y Martinez; Woolley, R; Culshaw, G; French, A; Martin, M

2008-11-01

To investigate the prognostic and diagnostic value of heart rate variability (HRV) using the vasovagal tonus index (VVTI) in dogs suffering from idiopathic dilated cardiomyopathy (DCM). Electrocardiographic (ECG) recordings of 369 patients presented to a referral centre between 1993 and 2006 were reviewed. VVTI values were calculated from 132 dogs. Lower VVTI values were found in patients in International Small Animal Cardiac Health Council (ISACHC) heart failure (HF) class 2 and 3 compared with class 1. VVTI was found to be positively correlated with survival time (ST) in class 2 and 3 patients. When a cut-off value of 7.59 for VVTI was used, the test could differentiate patients in ISACHC HF class 1 versus 2 and 3 with a sensitivity of 89 per cent and a specificity of 62.5 per cent. The ST for patients with VVTI values less than 7.59 was significantly lower. The VVTI is a useful index, obtained from a standard ECG recording that estimates HRV in dogs and does not require any specific equipment for its calculation. It can be useful as a diagnostic tool to assess the severity of HF and is a useful prognostic tool in dogs with DCM.

Symptom-Hemodynamic Mismatch and Heart Failure Event Risk

PubMed Central

Lee, Christopher S.; Hiatt, Shirin O.; Denfeld, Quin E.; Mudd, James O.; Chien, Christopher; Gelow, Jill M.

2014-01-01

Background Heart failure (HF) is a heterogeneous condition of both symptoms and hemodynamics. Objective The goal of this study was to identify distinct profiles among integrated data on physical and psychological symptoms and hemodynamics, and quantify differences in 180-day event-risk among observed profiles. Methods A secondary analysis of data collected during two prospective cohort studies by a single group of investigators was performed. Latent class mixture modeling was used to identify distinct symptom-hemodynamic profiles. Cox proportional hazards modeling was used to quantify difference in event-risk (HF emergency visit, hospitalization or death) among profiles. Results The mean age (n=291) was 57±13 years, 38% were female, and 61% had class III/IV HF. Three distinct symptom-hemodynamic profiles were identified. 17.9% of patients had concordant symptoms and hemodynamics (i.e. moderate physical and psychological symptoms matched the comparatively hemodynamic profile), 17.9% had severe symptoms and average hemodynamics, and 64.2% had poor hemodynamics and mild symptoms. Compared to those in the concordant profile, both profiles of symptom-hemodynamic mismatch were associated with a markedly increased event-risk (severe symptoms hazards ratio = 3.38, p=0.033; poor hemodynamics hazards ratio = 3.48, p=0.016). Conclusions A minority of adults with HF have concordant symptoms and hemodynamics. Either profile of symptom-hemodynamic mismatch in HF is associated with a greater risk of healthcare utilization for HF or death. PMID:24988323

One-year mortality outcomes and hospital readmissions of patients admitted with acute heart failure: Data from the Trivandrum Heart Failure Registry in Kerala, India.

PubMed

Harikrishnan, Sivadasanpillai; Sanjay, Ganapathi; Agarwal, Anubha; Kumar, N Pratap; Kumar, K Krishna; Bahuleyan, Charantharayil Gopalan; Vijayaraghavan, Govindan; Viswanathan, Sunitha; Sreedharan, Madhu; Biju, R; Rajalekshmi, N; Nair, Tiny; Suresh, Krishnan; Jeemon, Panniyammakal

2017-07-01

There are sparse data on outcomes of patients with heart failure (HF) from India. The objective was to evaluate hospital readmissions and 1-year mortality outcomes of patients with HF in Kerala, India. We followed 1,205 patients enrolled in the Trivandrum Heart Failure Registry for 1 year. A trained research nurse contacted each participant every 3 months using a structured questionnaire which included hospital readmission and mortality information. The mean (SD) age was 61.2 (13.7) years, and 31% were women. One out of 4 (26%) participants had HF with preserved ejection fraction. Only 25% of patients with HF with reduced ejection fraction received guideline-directed medical therapy at discharge. Cumulative all-cause mortality at 1 year was 30.8% (n = 371), but the greatest risk of mortality was in the first 3 months (18.1%). Most deaths (61%) occurred in patients younger than 70 years. One out of every 3 (30.2%) patients was readmitted at least once over 1 year. The hospital readmission rates were similar between HF with preserved ejection fraction and HF with reduced ejection fraction patients. New York Heart Association functional class IV status and lack of guideline-directed medical treatment after index hospitalization were associated with increased likelihood of readmission. Similarly, older age, lower education status, nonischemic etiology, history of stroke, higher serum creatinine, lack of adherence to guideline-directed medical therapy, and hospital readmissions were associated with increased 1-year mortality. In the Trivandrum Heart Failure Registry, 1 of 3 HF patients died within 1 year of follow-up during their productive life years. Suboptimal adherence to guideline-directed treatment is associated with increased propensity of readmission and death. Quality improvement programs aiming to improve adherence to guideline-based therapy and reducing readmission may result in significant survival benefits in the relatively younger cohort of HF patients in India. Copyright © 2017 Elsevier Inc. All rights reserved.

Humoral immunity in heart failure.

PubMed

Sarkar, Amrita; Rafiq, Khadija

2018-05-17

Cardiovascular disease (CVD) is a class of diseases that involve disorders of heart and blood vessels, including: hypertension, coronary heart disease, cerebrovascular disease, peripheral vascular disease, which finally lead to heart failure (HF). There are several treatments available all over the world, but still CVD and heart failure became the number one problem causing death every year worldwide. Both experimental and clinical studies have shown a role for inflammation in the pathogenesis of heart failure. This seems related to an imbalance between pro-inflammatory and anti-inflammatory cytokines. Cardiac inflammation is major pathophysiological mechanism operating in the failing heart, regardless of HF aetiology. Disturbances of the cellular and humoral immune system are frequently observed in heart failure. This review describes how B-cells play specific role in the heart failure states. There is an urgent need to identify novel therapeutic targets and develop advanced therapeutic strategies to combat the syndrome of HF. Understanding and describing the elements of the humoral immunity function are essential, and may suggest potential new treatment strategies. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

[Efficacy of a multidisciplinary care management program for patients admitted at hospital because of heart failure (ProMIC)].

PubMed

Domingo, Cristina; Aros, Fernando; Otxandategi, Agurtzane; Beistegui, Idoia; Besga, Ariadna; Latorre, Pedro María

2018-02-26

To assess the efficacy of the ProMIC, multidisciplinary program for patients admitted at hospital because of heart failure (HF) programme, in reducing the HF-related readmission rate. Quasi-experimental research with control group. Twelve primary health care centres and 3 hospitals from the Basque Country. Aged 40 years old or above patients admitted for HF with a New York Heart Association functional class II to IV. Patients in the intervention group carried out the ProMIC programme, a structured clinical intervention based on clinical guidelines and on the chronic care model. Control group received usual care. The rate of readmission for HF and health-related quality of life RESULTS: One hundred fifty five patients were included in ProMIC group and 129 in control group. 45 rehospitalisation due to heart failure happened in ProMIC versus 75 in control group (adjusted hazard ratio=0.59, CI 95%: 0.36-0.98; P=.049). There were significant differences in specific quality of life al 6 months. No significant differences were found in rehospitalisation due to all causes, due to cardiovascular causes, visits to emergency room, mortality, the combined variable of these events, the functional capacity or quality of life at 12 months of follow up. ProMIC reduces significantly heart failure rehospitalisation and improve quality of life al 6 months of follow up. No significant differences were found in the rests of variables. Copyright © 2018 The Authors. Publicado por Elsevier España, S.L.U. All rights reserved.

Memory loss and decreased executive function are associated with limited functional capacity in patients with heart failure compared to patients with other medical conditions.

PubMed

Kim, JinShil; Shin, Mi-Seung; Hwang, Seon Young; Park, Eunok; Lim, Young-Hyo; Shim, Jae Lan; Kim, Sun Hwa; Kim, Yeon Hee; An, Minjeong

There is limited evidence on the degree of cognitive impairment and its association with physical functional capacity among patients with heart failure (HF) in Korea. In this study, we compared cognitive impairment between patients with HF and community-dwelling participants with non-HF medical conditions (medical participants) and its association with physical functional capacity. We conducted a cross-sectional comparative study and assessed the neuropsychological cognitive status (Seoul Neuropsychological Screening Battery) and physical functional capacity (Duke Activity Status Index) of patients with HF and medical participants using face-to-face interviews. One hundred and eighteen patients with HF (age, 65.45 ± 9.38 years; men, 57.6%; left ventricular ejection fraction, 34.93 ± 8.72%) and 83 medical participants (age, 66.02 ± 8.28 years; men, 47.0%) were included. Using seventh-percentile medical participant Z-scores as cutoffs, memory and executive function were worse in patients with HF than in medical participants: immediate (35.0% vs. 6.0%) and delayed recall memory (34.5% vs. 8.4%), and executive function (28.6% vs. 6.0%). Independent of age, sex, education, comorbidity, and HF status, executive function was a significant predictor of physical functional capacity (b = 1.82, p = .021). More patients with HF had impaired memory and executive function, which were associated with their physical functional capacities. Copyright © 2017 Elsevier Inc. All rights reserved.

Reconciliation of the excess 176Hf conundrum in meteorites: Recent disturbances of the Lu-Hf and Sm-Nd isotope systematics

NASA Astrophysics Data System (ADS)

Bast, Rebecca; Scherer, Erik E.; Sprung, Peter; Mezger, Klaus; Fischer-Gödde, Mario; Taetz, Stephan; Böhnke, Mischa; Schmid-Beurmann, Hinrich; Münker, Carsten; Kleine, Thorsten; Srinivasan, Gopalan

2017-09-01

The long-lived 176Lu-176Hf and 147Sm-143Nd radioisotope systems are commonly used chronometers, but when applied to meteorites, they can reveal disturbances. Specifically, Lu-Hf isochrons commonly yield dates up to ∼300 Myr older than the solar system and varying initial 176Hf/177Hf values. We investigated this problem by attempting to construct mineral and whole rock isochrons for eucrites and angrites. Meteorites from different parent bodies exhibit similar disturbance features suggesting that a common process is responsible. Minerals scatter away from isochron regressions for both meteorite classes, with low-Hf phases such as plagioclase and olivine typically being most displaced above (or left of) reference isochrons. Relatively Hf-rich pyroxene is less disturbed but still to the point of steepening Lu-Hf errorchrons. Using our Lu-Hf and Sm-Nd data, we tested various Hf and Lu redistribution scenarios and found that decoupling of Lu/Hf from 176Hf/177Hf must postdate the accumulation of significant radiogenic 176Hf. Therefore early irradiation or diffusion cannot explain the excess 176Hf. Instead, disturbed meteorite isochrons are more likely caused by terrestrial weathering, contamination, or common laboratory procedures. The partial dissolution of phosphate minerals may predominantly remove rare earth elements including Lu, leaving relatively immobile and radiogenic Hf behind. Robust Lu-Hf (and improved Sm-Nd) meteorite geochronology will require the development of chemical or physical methods for removing unsupported radiogenic Hf and silicate-hosted terrestrial contaminants without disturbing parent-daughter ratios.

Real-time Specification and Forecasting for HF Links During Disturbed Conditions

NASA Astrophysics Data System (ADS)

Rice, D.; Hunsuker, R. D.; Eccles, J.; Sojka, J. J.

2004-05-01

The HF communications community has long been dependent on climatological ionosphere descriptions to support HF propagation programs. Additionally, these programs include solar zenith angle and frequency-squared variation of HF absorption but do not include space weather effects due to solar x-ray events and sporadic E layers. The usefulness of real-time specification and forecasting of HF links is desired in programs such as Operational Space Environment Network Display (OpSend). The creation of HF illumination maps requires proper specifications of D, E and F regions of the ionosphere. We present results and validation efforts of the Data-Driven D region (DDDR) model of HF absorption for mid-latitude HF paths. The DDDR programs assimilate real-time data such as the NOAA/GOES 12 x-ray measurements to produce space weather related absorption predictions. The data-driven model is being validated with observations from the HF Investigation of D-Region Ionospheric Variation Experiment (HIDIVE). Monitoring of standard time-frequency HF stations has been employed for the past three decades. The passive monitoring technique used in HIDIVE was mainly applied for studies of the high-latitude and equatorial ionosphere, thus long-term, quantitative data on the mid-latitude ionosphere are difficult to find in archival literature. HIDIVE is a careful examination of long-term observations HF absorption to study seasonal variation and space weather events. Simultaneous continuous measurements of NOAA/GOES 12 solar x-ray flux and calibrated HF signal strength were initiated in December 2002 to provide validation data for the DDDR model. Continuous recording of transmissions of standard time-frequency stations (WWV and WWVH) over the range of 2.5 to 20.0 MHz and 5-minute averages of 1.0 to 8.0 nm solar x-ray flux have been studied for 35 solar flares ranging from Class C to Class X from March through August 2003 during the descending phase of solar cycle 23. The monitoring stations are located at Providence, Utah and at Klamath Falls, Oregon and continuous recordings are planned through August 2005. In particular, we will examine the extreme solar events of October-November 2003 as an example of the Societal Impact of Space Weather. This is timely because of renewed interest in the use of HF circuits by the Military and by commercial airlines.

Long-term effects of patiromer for hyperkalaemia treatment in patients with mild heart failure and diabetic nephropathy on angiotensin-converting enzymes/angiotensin receptor blockers: results from AMETHYST-DN.

PubMed

Pitt, Bertram; Bakris, George L; Weir, Matthew R; Freeman, Mason W; Lainscak, Mitja; Mayo, Martha R; Garza, Dahlia; Zawadzki, Rezi; Berman, Lance; Bushinsky, David A

2018-05-16

Chronic kidney disease (CKD) in heart failure (HF) increases the risk of hyperkalaemia (HK), limiting angiotensin-converting enzyme inhibitor (ACE-I) or angiotensin receptor blocker (ARB) use. Patiromer is a sodium-free, non-absorbed potassium binder approved for HK treatment. We retrospectively evaluated patiromer's long-term safety and efficacy in HF patients from AMETHYST-DN. Patients with Type 2 diabetes, CKD, and HK [baseline serum potassium >5.0-5.5 mmol/L (mild) or >5.5-<6.0 mmol/L (moderate)], with or without HF (New York Heart Association Class I and II, by investigator judgement), on ACE-I/ARB, were randomized to patiromer 8.4-33.6 g to start, divided twice daily. Overall, 105/304 (35%) patients had HF (75%, Class II). Mean (standard deviation) ejection fraction (EF) was 44.9% (8.2) (n = 81) in patients with HF; 26 had EF ≤40%. In HF patients, mean serum potassium decreased by Day 3 through Week 52. At Week 4, estimated mean (95% confidence interval) change in serum potassium was -0.64 mmol/L (-0.72, -0.55) in mild and -0.97 mmol/L (-1.14, -0.80) in moderate HK (both P < 0.0001). Most HF patients with mild (>88%) and moderate (≥73%) HK had normokalaemia at each visit from Weeks 12 to 52. Three HF patients were withdrawn because of high (n = 1) or low (n = 2) serum potassium. The most common patiromer-related adverse event was hypomagnesaemia (8.6%). In patients with a clinical diagnosis of HF, diabetes, CKD, and HK on ACE-I/ARB, patiromer was well tolerated and effective for HK treatment over 52 weeks. © 2018 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of the European Society of Cardiology.

Impact of remote telemedical management on mortality and hospitalizations in ambulatory patients with chronic heart failure: the telemedical interventional monitoring in heart failure study.

PubMed

Koehler, Friedrich; Winkler, Sebastian; Schieber, Michael; Sechtem, Udo; Stangl, Karl; Böhm, Michael; Boll, Herbert; Baumann, Gert; Honold, Marcus; Koehler, Kerstin; Gelbrich, Goetz; Kirwan, Bridget-Anne; Anker, Stefan D

2011-05-03

This study was designed to determine whether physician-led remote telemedical management (RTM) compared with usual care would result in reduced mortality in ambulatory patients with chronic heart failure (HF). We enrolled 710 stable chronic HF patients in New York Heart Association functional class II or III with a left ventricular ejection fraction ≤35% and a history of HF decompensation within the previous 2 years or with a left ventricular ejection fraction ≤25%. Patients were randomly assigned (1:1) to RTM or usual care. Remote telemedical management used portable devices for ECG, blood pressure, and body weight measurements connected to a personal digital assistant that sent automated encrypted transmission via cell phones to the telemedical centers. The primary end point was death from any cause. The first secondary end point was a composite of cardiovascular death and hospitalization for HF. Baseline characteristics were similar between the RTM (n=354) and control (n=356) groups. Of the patients assigned to RTM, 287 (81%) were at least 70% compliant with daily data transfers and no break for >30 days (except during hospitalizations). The median follow-up was 26 months (minimum 12), and was 99.9% complete. Compared with usual care, RTM had no significant effect on all-cause mortality (hazard ratio, 0.97; 95% confidence interval, 0.67 to 1.41; P=0.87) or on cardiovascular death or HF hospitalization (hazard ratio, 0.89; 95% confidence interval, 0.67 to 1.19; P=0.44). In ambulatory patients with chronic HF, RTM compared with usual care was not associated with a reduction in all-cause mortality. URL: http://www.ClinicalTrials.gov. Unique identifier: NCT00543881.

Gender-Specific Physical Symptom Biology in Heart Failure.

PubMed

Lee, Christopher S; Hiatt, Shirin O; Denfeld, Quin E; Chien, Christopher V; Mudd, James O; Gelow, Jill M

2015-01-01

There are several gender differences that may help explain the link between biology and symptoms in heart failure (HF). The aim of this study was to examine gender-specific relationships between objective measures of HF severity and physical symptoms. Detailed clinical data, including left ventricular ejection fraction and left ventricular internal end-diastolic diameter, and HF-specific physical symptoms were collected as part of a prospective cohort study. Gender interaction terms were tested in linear regression models of physical symptoms. The sample (101 women and 101 men) averaged 57 years of age and most participants (60%) had class III/IV HF. Larger left ventricle size was associated with better physical symptoms for women and worse physical symptoms for men. Decreased ventricular compliance may result in worse physical HF symptoms for women and dilation of the ventricle may be a greater progenitor of symptoms for men with HF.

Is Mixed Apnea Associated with Non-Rapid Eye Movement Sleep a Reversible Compensatory Sign of Heart Failure?

PubMed Central

Korostovtseva, Lyudmila; Sazonova, Yulia; Zvartau, Nadezhda; Semenov, Andrew; Nepran, Viktoriya; Bochkarev, Mikhail; Nikolaev, German; Mitrofanova, Lyubov; Sviryaev, Yurii; Gordeev, Mikhail; Konradi, Aleksandra

2015-01-01

Patient: Male, 24 Final Diagnosis: Dilated cardiomyopathy Symptoms: Biventricular heart failure • sleep apnea Medication: — Clinical Procedure: Heart transplantation Specialty: Cardiology Objective: Unusual or unexpected effect of treatment Background: Sleep-disordered breathing is common in heart failure (HF), and prolonged circulation time and diminished pulmonary volume are considered the main possible causes of sleep apnea in these patients. However, the impact and interrelation between sleep apnea and HF development are unclear. We report the case of a patient with complete elimination of non-rapid-eye-movement (NREM) sleep-associated mixed apnea in HF after heart transplantation. Case Report: After unsuccessful 12-month conventional treatment with abrupt exacerbation of biventricular HF IV class (according to New York Heart Association Functional Classification), a 26-year-old man was admitted to the hospital. Based on a comprehensive examination including endomyocardial biopsy, dilated cardiomyopathy was diagnosed. Heart transplantation was considered the only possible treatment strategy. Polysomnography showed severe NREM sleep-associated mixed sleep apnea [apnea-hypopnea index 43/h, in rapid eye movement (REM) sleep 3.7/h, in NREM sleep 56.4/h, mean SatO2 93.9%], and periodic breathing. One-month post-transplantation polysomnography did not show sleep-disordered breathing (apnea-hypopnea index 1.0/h; in REM sleep − 2.8/h, in NREM sleep 0.5/h, mean SatO2 97.5%). The patient was discharged from the hospital in improved condition. Conclusions: NREM sleep-associated mixed apnea occurring in severe systolic HF due to dilated cardiomyopathy might be reversible in case of successful HF treatment. We suggest that mixed sleep apnea strongly associated with NREM sleep occurs in HF, when the brain centers regulating ventilation are intact, and successful HF compensation might be highly effective regarding sleep-breathing disorders without non-invasive ventilation. This is important to know, especially with regard to the recently published data of potentially unfavorable effects of adaptive servoventilation in systolic HF, and the lack of other treatment options. PMID:26681187

Cost-Effectiveness of Remote Cardiac Monitoring With the CardioMEMS Heart Failure System.

PubMed

Schmier, Jordana K; Ong, Kevin L; Fonarow, Gregg C

2017-07-01

Heart failure (HF) is a leading cause of cardiovascular mortality in the United States and presents a substantial economic burden. A recently approved implantable wireless pulmonary artery pressure remote monitor, the CardioMEMS HF System, has been shown to be effective in reducing hospitalizations among New York Heart Association (NYHA) class III HF patients. The objective of this study was to estimate the cost-effectiveness of this remote monitoring technology compared to standard of care treatment for HF. A Markov cohort model relying on the CHAMPION (CardioMEMS Heart Sensor Allows Monitoring of Pressure to Improve Outcomes in NYHA Class III Heart Failure Patients) clinical trial for mortality and hospitalization data, published sources for cost data, and a mix of CHAMPION data and published sources for utility data, was developed. The model compares outcomes over 5 years for implanted vs standard of care patients, allowing patients to accrue costs and utilities while they remain alive. Sensitivity analyses explored uncertainty in input parameters. The CardioMEMS HF System was found to be cost-effective, with an incremental cost-effectiveness ratio of $44,832 per quality-adjusted life year (QALY). Sensitivity analysis found the model was sensitive to the device cost and to whether mortality benefits were sustained, although there were no scenarios in which the cost/QALY exceeded $100,000. Compared with standard of care, the CardioMEMS HF System was cost-effective when leveraging trial data to populate the model. © 2017 Wiley Periodicals, Inc.

Antihyperglycemic Medication Use Among Medicare Beneficiaries With Heart Failure, Diabetes Mellitus, and Chronic Kidney Disease.

PubMed

Patel, Priyesh A; Liang, Li; Khazanie, Prateeti; Hammill, Bradley G; Fonarow, Gregg C; Yancy, Clyde W; Bhatt, Deepak L; Curtis, Lesley H; Hernandez, Adrian F

2016-07-01

Diabetes mellitus, heart failure (HF), and chronic kidney disease are common comorbidities, but overall use and safety of antihyperglycemic medications (AHMs) among patients with these comorbidities are poorly understood. Using Get With the Guidelines-Heart Failure and linked Medicare Part D data, we assessed AHM use within 90 days of hospital discharge among HF patients with diabetes mellitus discharged from Get With the Guidelines-Heart Failure hospitals between January 1, 2006, and October 1, 2011. We further summarized use by renal function and assessed renal contraindicated AHM use for patients with estimated glomerular filtration rate <30 mL/min/1.73m(2). Among 8791 patients meeting inclusion criteria, the median age was 77 (interquartile range 71-83), 62.3% were female, median body mass index was 29.7 (interquartile range 25.5-35.3), median hemoglobin A1c was 6.8 (interquartile range 6.2-7.8), and 34% had ejection fraction <40%. 74.9% of patients filled a prescription for an AHM, with insulin (39.5%), sulfonylureas (32.4%), and metformin (17%) being the most commonly used AHMs. Insulin use was higher and sulfonylurea/metformin use was lower among patients with lower renal function classes. Among 1512 patients with estimated glomerular filtration rate <30 mL/min/1.73m(2), 35.4% filled prescriptions for renal contraindicated AHMs per prescribing information, though there was a trend toward lower renal contraindicated AHM use over time (Cochran-Mantel-Haenszel row-mean score test P=0.048). Although use of other AHMs was low overall, thiazolidinediones were used in 6.6% of HF patients, and dipeptidyl peptidase-4 inhibitors were used in 5.1%, with trends for decreasing thiazolidinedione use and increased dipeptidyl peptidase-4 inhibitor use over time (P<0.001). Treatment of diabetes mellitus in patients with HF and chronic kidney disease is complex, and these patients are commonly treated with renal contraindicated AHMs, including over 6% receiving a thiazolidinedione, despite known concerns regarding HF. More research regarding safety and efficacy of various AHMs among HF patients is needed. © 2016 American Heart Association, Inc.

CorVue algorithm efficacy to predict heart failure in real life: Unnecessary and potentially misleading information?

PubMed

Palfy, Julia Anna; Benezet-Mazuecos, Juan; Milla, Juan Martinez; Iglesias, Jose Antonio; de la Vieja, Juan Jose; Sanchez-Borque, Pepa; Miracle, Angel; Rubio, Jose Manuel

2018-06-01

Heart failure (HF) hospitalizations have a negative impact on quality of life and imply important costs. Intrathoracic impedance (ITI) variations detected by cardiac devices have been hypothesized to predict HF hospitalizations. Although Optivol™ algorithm (Medtronic) has been widely studied, CorVue™ algorithm (St. Jude Medical) long term efficacy has not been systematically evaluated in a "real life" cohort. CorVue™ was activated in ICD/CRT-D patients to store information about ITI measures. Clinical events (new episodes of HF requiring treatment and hospitalizations) and CorVue™ data were recorded every three months. Appropriate CorVue™ detection for HF was considered if it occurred in the four prior weeks to the clinical event. 53 ICD/CRT-D (26 ICD and 27 CRT-D) patients (67±1 years-old, 79% male) were included. Device position was subcutaneous in 28 patients. At inclusion, mean LVEF was 25±7% and 27 patients (51%) were in NYHA class I, 18 (34%) class II and 8 (15%) class III. After a mean follow-up of 17±9 months, 105 ITI drops alarms were detected in 32 patients (60%). Only six alarms were appropriate (true positive) and required hospitalization. Eighteen patients (34%) presented 25 clinical episodes (12 hospitalizations and 13 ER/ambulatory treatment modifications). Nineteen of these clinical episodes (76%) remained undetected by the CorVue™ (false negative). Sensitivity of CorVue™ resulted in 24%, specificity was 70%, positive predictive value of 6% and negative predictive value of 93%. CorVue™ showed a low sensitivity to predict HF events. Therefore, routinely activation of this algorithm could generate misleading information. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

[Diuretic therapy in heart failure].

PubMed

Trullàs, Joan Carles; Morales-Rull, José Luís; Formiga, Francesc

2014-02-20

Many of the primary clinical manifestations of heart failure (HF) are due to fluid retention, and treatments targeting congestion play a central role in HF management. Diuretic therapy remains the cornerstone of congestion treatment, and diuretics are prescribed to the majority of HF patients. Despite this ubiquitous use, there is limited evidence from prospective randomized studies to guide the use of diuretics. With the chronic use of diuretic and usually in advanced stages of HF, diuretics may fail to control salt and water retention. This review describes the mechanism of action of available diuretic classes, reviews their clinical use based on scientific evidence and discusses strategies to overcome diuretic resistance. Copyright © 2013 Elsevier España, S.L. All rights reserved.

Coexisting Anxiety and Depressive Symptoms in Patients with Heart Failure

PubMed Central

Dekker, Rebecca L.; Lennie, Terry A.; Doering, Lynn V.; Chung, Misook L.; Wu, Jia-Rong; Moser, Debra K.

2014-01-01

Background Among patients with heart failure (HF), anxiety symptoms may co-exist with depressive symptoms. However, the extent of overlap and risk factors for anxiety symptoms have not been thoroughly described. Purpose To describe the coexistence of anxiety and depressive symptoms, and to determine the predictors of anxiety symptoms in patients with HF. Methods The sample consisted of 556 outpatients with HF (34% female, 62±12 years, 54% NYHA class III/IV) enrolled in a multicenter HF quality of life registry. Anxiety symptoms were assessed with the Brief Symptom Inventory-anxiety subscale. Depressive symptoms were measured with the Beck Depression Inventory-II (BDI). We used a cut-point of 0.35 to categorize patients as having anxiety symptoms or no anxiety symptoms. Logistic regression was used to determine whether age, gender, minority status, educational level, functional status, comorbidities, depressive symptoms, and antidepressant use were predictors of anxiety symptoms. Results One-third of patients had both depressive and anxiety symptoms. There was a dose-response relationship between depressive symptoms and anxiety symptoms; higher levels of depressive symptoms were associated with a higher level of anxiety symptoms. Younger age (OR= 0.97, p = .004, 95% CI 0.95–0.99) and depressive symptoms (OR = 1.25, p < .001, 95% CI 1.19–1.31) were independent predictors of anxiety symptoms. Conclusions Patients with HF and depressive symptoms are at high risk for experiencing anxiety symptoms. Clinicians should assess these patients for comorbid anxiety symptoms. Research is needed to test interventions for both depressive and anxiety symptoms. PMID:24408885

Usefulness of anti-oxidized LDL antibody determination for assessment of clinical control in patients with heart failure.

PubMed

George, Jacob; Wexler, Dov; Roth, Arie; Barak, Tomer; Sheps, David; Keren, Gad

2006-01-01

It has been suggested that oxidative stress may play a role in the pathogenesis of heart failure, this may have potential implications for therapeutic strategies. However, measures of oxidative stress are subject to confounding inaccuracies. IgG antibodies to oxidized LDL reflect exposure to the lipoprotein over an extended period and may thus mirror oxidative stress over a prolonged time frame. Therefore, we tested the hypothesis that anti-oxLDL antibodies correlate with the control of heart failure (HF), as manifested by hospital admissions for cardiac dysfunction. One hundred and two consecutive patients attending the HF clinic with either systolic or diastolic HF were enrolled and the quality of clinical control was evaluated by assessing hospital admissions over the year prior to index determination of the oxidative stress marker. Antibodies to oxLDL were determined by ELISA and pro-BNP levels were also measured. Most patients (mean age 71.5 years) had systolic HF; mean NYHA functional class was 2.7 and mean left ventricular ejection fraction was 39.7%. Anti-oxLDL antibodies, but not pro-BNP, correlated significantly with mean NYHA score (averaged from all clinic visits in the year prior to blood testing), and with hospital admissions over the year prior to blood testing. Mean IgG anti-oxLDL antibody levels in patients with hospital admissions were 3.4 times higher than those in subjects not hospitalized over the previous year. IgG anti-oxLDL antibody levels correlate with the severity of HF.

Coexisting anxiety and depressive symptoms in patients with heart failure.

PubMed

Dekker, Rebecca L; Lennie, Terry A; Doering, Lynn V; Chung, Misook L; Wu, Jia-Rong; Moser, Debra K

2014-04-01

Among patients with heart failure (HF), anxiety symptoms may co-exist with depressive symptoms. However, the extent of overlap and risk factors for anxiety symptoms have not been thoroughly described. The aim of this study was to describe the coexistence of anxiety and depressive symptoms, and to determine the predictors of anxiety symptoms in patients with HF. The sample consisted of 556 outpatients with HF (34% female, 62±12 years, 54% New York Heart Association (NYHA) class III/IV) enrolled in a multicenter HF quality of life registry. Anxiety symptoms were assessed with the Brief Symptom Inventory-anxiety subscale. Depressive symptoms were measured with the Beck Depression Inventory-II (BDI). We used a cut-point of 0.35 to categorize patients as having anxiety symptoms or no anxiety symptoms. Logistic regression was used to determine whether age, gender, minority status, educational level, functional status, comorbidities, depressive symptoms, and antidepressant use were predictors of anxiety symptoms. One-third of patients had both depressive and anxiety symptoms. There was a dose-response relationship between depressive symptoms and anxiety symptoms; higher levels of depressive symptoms were associated with a higher level of anxiety symptoms. Younger age (odds ratio (OR)= 0.97, p=0.004, 95% confidence interval (CI) 0.95-0.99) and depressive symptoms (OR =1.25, p<0.001, 95% CI 1.19-1.31) were independent predictors of anxiety symptoms. Patients with HF and depressive symptoms are at high risk for experiencing anxiety symptoms. Clinicians should assess these patients for comorbid anxiety symptoms. Research is needed to test interventions for both depressive and anxiety symptoms.

Normalization of cardiac substrate utilization and left ventricular hypertrophy precede functional recovery in heart failure regression.

PubMed

Byrne, Nikole J; Levasseur, Jody; Sung, Miranda M; Masson, Grant; Boisvenue, Jamie; Young, Martin E; Dyck, Jason R B

2016-05-15

Impaired cardiac substrate metabolism plays an important role in heart failure (HF) pathogenesis. Since many of these metabolic changes occur at the transcriptional level of metabolic enzymes, it is possible that this loss of metabolic flexibility is permanent and thus contributes to worsening cardiac function and/or prevents the full regression of HF upon treatment. However, despite the importance of cardiac energetics in HF, it remains unclear whether these metabolic changes can be normalized. In the current study, we investigated whether a reversal of an elevated aortic afterload in mice with severe HF would result in the recovery of cardiac function, substrate metabolism, and transcriptional reprogramming as well as determined the temporal relationship of these changes. Male C57Bl/6 mice were subjected to either Sham or transverse aortic constriction (TAC) surgery to induce HF. After HF development, mice with severe HF (% ejection fraction < 30) underwent a second surgery to remove the aortic constriction (debanding, DB). Three weeks following DB, there was a near complete recovery of systolic and diastolic function, and gene expression of several markers for hypertrophy/HF were returned to values observed in healthy controls. Interestingly, pressure-overload-induced left ventricular hypertrophy (LVH) and cardiac substrate metabolism were restored at 1-week post-DB, which preceded functional recovery. The regression of severe HF is associated with early and dramatic improvements in cardiac energy metabolism and LVH normalization that precede restored cardiac function, suggesting that metabolic and structural improvements may be critical determinants for functional recovery. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2016. For permissions please email: journals.permissions@oup.com.

How Do Cognitive Function and Knowledge Affect Heart Failure Self-Care?

ERIC Educational Resources Information Center

Dickson, Victoria Vaughan; Lee, Christopher S.; Riegel, Barbara

2011-01-01

Despite extensive patient education, few heart failure (HF) patients master self-care. Impaired cognitive function may explain why patient education is ineffective. A concurrent triangulation mixed methods design was used to explore how knowledge and cognitive function influence HF self-care. A total of 41 adults with HF participated in interviews…

Association Between Valvular Surgery and Mortality Among Patients With Infective Endocarditis Complicated by Heart Failure

PubMed Central

Kiefer, Todd; Park, Lawrence; Tribouilloy, Christophe; Cortes, Claudia; Casillo, Roberta; Chu, Vivian; Delahaye, Francois; Durante-Mangoni, Emanuele; Edathodu, Jameela; Falces, Carlos; Logar, Mateja; Miró, José M.; Naber, Christophe; Tripodi, Marie Françoise; Murdoch, David R.; Moreillon, Philippe; Utili, Riccardo; Wang, Andrew

2016-01-01

Context Heart failure (HF) is the most common complication of infective endocarditis. However, clinical characteristics of HF in patients with infective endocarditis, use of surgical therapy, and their associations with patient outcome are not well described. Objectives To determine the clinical, echocardiographic, and microbiological variables associated with HF in patients with definite infective endocarditis and to examine variables independently associated with in-hospital and 1-year mortality for patients with infective endocarditis and HF, including the use and association of surgery with outcome. Design, Setting, and Patients The International Collaboration on Endocarditis–Prospective Cohort Study, a prospective, multicenter study enrolling 4166 patients with definite native- or prosthetic-valve infective endocarditis from 61 centers in 28 countries between June 2000 and December 2006. Main Outcome Measures In-hospital and 1-year mortality. Results Of 4075 patients with infective endocarditis and known HF status enrolled, 1359 (33.4% [95% CI, 31.9%–34.8%]) had HF, and 906 (66.7% [95% CI, 64.2%–69.2%]) were classified as having New York Heart Association class III or IV symptom status. Within the subset with HF, 839 (61.7% [95% CI, 59.2%–64.3%]) underwent valvular surgery during the index hospitalization. In-hospital mortality was 29.7% (95% CI, 27.2%–32.1%) for the entire HF cohort, with lower mortality observed in patients undergoing valvular surgery compared with medical therapy alone (20.6% [95% CI, 17.9%–23.4%] vs 44.8% [95% CI, 40.4%–49.0%], respectively; P<.001). One-year mortality was 29.1% (95% CI, 26.0%–32.2%) in patients undergoing valvular surgery vs 58.4% (95% CI, 54.1%–62.6%) in those not undergoing surgery (P<.001). Cox proportional hazards modeling with propensity score adjustment for surgery showed that advanced age, diabetes mellitus, health care–associated infection, causative microorganism (Staphylococcus aureus or fungi), severe HF (New York Heart Association class III or IV), stroke, and paravalvular complications were independently associated with 1-year mortality, whereas valvular surgery during the initial hospitalization was associated with lower mortality. Conclusion In this cohort of patients with infective endocarditis complicated by HF, severity of HF was strongly associated with surgical therapy and subsequent mortality, whereas valvular surgery was associated with lower in-hospital and 1-year mortality. PMID:22110106

Long-Term Adaptive Servo-Ventilator Treatment Prevents Cardiac Death and Improves Clinical Outcome.

PubMed

Imamura, Teruhiko; Kinugawa, Koichiro; Nitta, Daisuke; Komuro, Issei

2016-01-01

Adaptive servo-ventilation (ASV) is a recently developed, noninvasive therapeutic tool for the treatment of heart failure (HF). However, the efficacy of ASV therapy in patients with advanced HF remains uncertain, especially as regards its contribution to freedom from cardiac replacement therapy. A total of 85 patients with advanced HF (New York Heart Association [NYHA] class IV 71%, inotrope infusion-dependent 34%) refractory to guideline-directed medical therapy, received ASV therapy, irrespective of sleep-disordered breathing, at our institute between 2008 and 2014. Among these 85 patients, 46 continued ASV therapy for > 1 month (continued group), whereas 39 discontinued the therapy after < 1 month because of intolerance (discontinued group). There were no significant differences in baseline variables between the two groups. Heart rate indicating sympathetic activity, left ventricular (LV) reverse remodeling assessed by LV diastolic diameter, LV ejection fraction, and the grades of mitral and tricuspid regurgitations, HF severity assessed by NYHA class and plasma level of B-type natriuretic peptide, and end-organ dysfunction, improved significantly at 6 months following the initiation of ASV therapy (P < 0.05 for all). All-cause mortality and cardiac death rate were significantly lower during 2-year follow up in the continued group (P < 0.05 for both). In conclusion, ASV is a novel therapeutic tool prior to cardiac replacement therapy in patients with advanced HF and may prolong the period until cardiac replacement therapy becomes necessary.

Effects of auto-servo ventilation on patients with sleep-disordered breathing, stable systolic heart failure and concomitant diastolic dysfunction: subanalysis of a randomized controlled trial.

PubMed

Birner, Christoph; Series, Frederic; Lewis, Keir; Benjamin, Amit; Wunderlich, Silke; Escourrou, Pierre; Zeman, Florian; Luigart, Ruth; Pfeifer, Michael; Arzt, Michael

2014-01-01

Systolic heart failure (HF) is frequently accompanied by diastolic dysfunction and sleep-disordered breathing (SDB). The objective of this subset analysis was to determine effect sizes of auto-servo ventilation (ASV and biphasic positive airway pressure ASV) on echocardiographic measures of diastolic function in patients with systolic HF and SDB. Thirty-two patients with stable systolic HF, concomitant diastolic dysfunction [age 66 ± 9 years old, left ventricular (LV) ejection fraction: 30 ± 7% and New York Heart Association class II: 72%] and SDB (apnea-hypopnea index, AHI: 48 ± 19/h; 53% had predominantly obstructive sleep apnea) receiving either ASV (n = 19) or optimal medical treatment (control, n = 13) were analyzed in a randomized controlled clinical trial. Polysomnographic and echocardiographic measurements were obtained at baseline and after 12 weeks. AHI significantly improved in the ASV group compared to the control group (-39 ± 18 vs. -0.2 ± 13.2/h, p < 0.001). At baseline, 24 (75%) patients had impaired LV relaxation, and 8 (25%) had a pseudo-normalized filling pattern. At the 12-week control visit, diastolic function assessed by the isovolumetric relaxation time (-10.3 ± 26.1 vs. 9.3 ± 49.1, p = 0.48) and deceleration time (-43.9 ± 88.8 vs. 12.4 ± 68.8, p = 0.40) tended to improve after ASV treatment, but did not reach statistical significance. Likewise, the proportion of patients whose diastolic dysfunction improved was nonsignificantly higher in the ASV than in the control group, respectively (37 vs. 15%, p = 0.25). ASV treatment efficiently abolishes SDB in patients with stable systolic HF and concomitant diastolic dysfunction, and was associated with a statistically nonsignificant improvement in measures of diastolic dysfunction. Thus, these data provide estimates of effect size and justify the evaluation of the effects of ASV on diastolic function in larger randomized controlled trials. Copyright © 2013 S. Karger AG, Basel.

Effect of contraindicated drugs for heart failure on hospitalization among seniors with heart failure

PubMed Central

Girouard, Catherine; Grégoire, Jean-Pierre; Poirier, Paul; Moisan, Jocelyne

2017-01-01

Abstract Little is known about the effect of nonsteroidal anti-inflammatory drugs (NSAIDs), thiazolidinediones (TZDs), nifedipine and nondihydropyridine calcium channel blockers (CCBs) usage on the risk of all-cause hospitalization among seniors with heart failure (HF). We assessed the risk of all-cause hospitalization associated with exposure to each of these drug classes, in a population of seniors with HF. Using the Quebec provincial databases, we conducted a nested case-control study in a population of individuals aged ≥65 with a first HF diagnosis between 2000 and 2009. Patients were considered users of a potentially inappropriate drug class if their date of hospital admission occurred in the interval between the date of the last drug claim and the end date of its days’ supply. The risks of hospitalization were estimated using multivariate conditional logistic regression. Of the 128,853 individuals included in the study population, 101,273 (78.6%) were hospitalized. When compared to nonusers, users of NSAIDs (adjusted odds ratio: 1.16; 95% confidence interval: 1.13–1.20), TZD (1.09; 1.04–1.14), and CCBs (1.03; 1.01–1.05) had an increased risk of all-cause hospitalization, but not the users of nifedipine (1.00; 0.97–1.03). Seniors with HF exposed to a potentially inappropriate drug class are at increased risk of worse health outcomes. Treatment alternatives should be considered, as they are available. PMID:28248890

Heart failure and diabetes: collateral benefit of chronic disease management.

PubMed

Ware, Molly G; Flavell, Carol M; Lewis, Eldrin F; Nohria, Anju; Warner-Stevenson, Lynne; Givertz, Michael M

2006-01-01

To test the hypothesis that a focus on heart failure (HF) care may be associated with inadequate diabetes care, the authors screened 78 patients (aged 64+/-11 years; 69% male) with diabetes enrolled in an HF disease management program for diabetes care as recommended by the American Diabetes Association (ADA). Ninety-five percent of patients had hemoglobin A1c levels measured within 12 months, and 71% monitored their glucose at least once daily. Most patients received counseling regarding diabetic diet and exercise, and approximately 80% reported receiving regular eye and foot examinations. Mean hemoglobin A1c level was 7.8+/-1.9%. There was no relationship between hemoglobin A1c levels and New York Heart Association class or history of HF hospitalizations. Contrary to the authors' hypothesis, patients in an HF disease management program demonstrated levels of diabetic care close to ADA goals. "Collateral benefit" of HF disease management may contribute to improved patient outcomes in diabetic patients with HF.

Sacubitril/Valsartan in an Elderly Patient with Heart Failure: A Case Report.

PubMed

Cameli, Matteo; Pastore, Maria Concetta; Pagliaro, Antonio; Di Tommaso, Cristina; Reccia, Rosanna; Curci, Valeria; Mandoli, Giulia Elena; Mondillo, Sergio

2017-01-01

Sacubitril/valsartan has recently been approved for the treatment of heart failure with reduced ejection fraction. Given its recent introduction in the armamentarium for the treatment of heart failure (HF), "field-practice" evidence is required to deepen the clinical management of sacubitril/valsartan therapy. We report a relevant case of an elderly patient who achieved major clinical benefits after only 3 months of sacubitril/valsartan therapy. Importantly, in our assessment, we employed speckle tracking echocardiography (STE), a recent echocardiography technique that is non-Doppler and not angle dependent, which analyzes deformations of heart chambers from standard images and allows a fast, reliable, and reproducible assessment of heart function. After 3 months of therapy, NHYA class decreased from III to I-II and hypertension was controlled. Echocardiography examination also showed a marked improvement, with a reduction of left ventricular diameter, improved diastolic function (E = 0.39 m/s; A 0.69 m/s; E/A 0.55), normalized diastolic function index (E/E' TDI = 6.93), normalized atrial volume (63 mL), and improved atrial strain (15.44%). This case report documents the fast clinical and symptom improvement with sacubitril/valsartan in an elderly patient with HF; comprehensive echocardiographic assessment, including STE, also revealed a marked functional improvement with this compound. © 2017 S. Karger AG, Basel.

Economic Value and Cost-Effectiveness of Cardiac Resynchronization Therapy Among Patients With Mild Heart Failure: Projections From the REVERSE Long-Term Follow-Up.

PubMed

Gold, Michael R; Padhiar, Amie; Mealing, Stuart; Sidhu, Manpreet K; Tsintzos, Stelios I; Abraham, William T

2017-03-01

This study investigated the cost effectiveness of early cardiac resynchronization therapy (CRT) implantation among patients with mild heart failure (HF). The differential cost effectiveness between CRT using a defibrillator (CRT-Ds) and CRT using a pacemaker (CRT-P) was also assessed. Cardiac resynchronization has been shown to be cost effective in New York Heart Association (NYHA) functional classes III/IV but is less studied in class II HF. The incremental costs of early CRT implementation in mild HF compared with the costs potentially avoided because of delaying disease progression to advanced HF are also unknown. Finally, combined biventricular pacing and defibrillator (CRT-D) devices are more expensive than biventricular pacemakers (CRT-P), but the relative cost effectiveness is controversial. Data from the 5-year follow-up phase of REVERSE (REsynchronization reVErses Remodeling in Systolic Left vEntricular Dysfunction) were used. The economics were evaluated from the U.S. Medicare perspective based on published clinical projections. Probabilistic estimates yielded $8,840/quality-adjusted life year (QALY) gained (95% confidence interval [CI]: $6,705 to $10,804/QALY gained) for CRT-ON versus CRT-OFF (i.e., programmed "ON" or "OFF" at pre-specified post-implantation timings) and $43,678/QALY gained for CRT-D versus CRT-P (95% CI: $35,164 to $53,589/QALY gained) over the patient's lifetime. Results were robust to choice of patient subgroup and alterations of ±10% to key model parameters. An "early" CRT-D class II strategy totaled $95,292 compared with $91,511 for a "late" implantation. An "early" implant offered on average 1.00 year of additional survival for $3,781, resulting in an ICER of $3,795/LY gained. This study demonstrates CRT cost effectiveness in mild HF. The incremental CRT-D costs are justified by the anticipated benefits, despite increased procurement costs and shorter generator longevities. "Early" CRT-D implants have essential cost parity with "late" implants while increasing the patient's survival. (REsynchronization reVErses Remodeling in Systolic Left vEntricular Dysfunction [REVERSE]; NCT00271154). Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

The obesity paradox in elderly patients with heart failure: analysis of nutritional status.

PubMed

Casas-Vara, Antonio; Santolaria, Francisco; Fernández-Bereciartúa, Ainhoa; González-Reimers, Emilio; García-Ochoa, Alfonso; Martínez-Riera, Antonio

2012-06-01

The obesity paradox refers to the improved survival of obese compared with non-obese elderly or diseased patients for reasons that are not clear. To assess the relative roles of fat and other factors in this improved survival, we analyzed the prognostic value of overweight and obesity elderly patients with heart failure (HF), controlling for other nutritional data such as midarm anthropometrics, serum proteins, and muscle strength. Two hundred forty-four patients (83.2 ± 0.5 y old) hospitalized for HF were included. A nutritional survey was performed in all patients. After discharge, the patients were followed up by telephone. Fourteen patients (5.7%) died during hospitalization. The median survival was 984 d. Patients with better nutritional status as assessed by the body mass index (BMI), subjective score, midarm muscle area, triceps skinfold thickness, handgrip, lymphocyte count, and serum albumin, prealbumin, and cholesterol levels showed better short- and long-term prognoses. Obese patients with a BMI above 30 kg/m(2) showed a better long-term prognosis than those with a BMI from 25 to 30 kg/m(2), those with a BMI from 20 to 25 kg/m(2), and those with a BMI lower than 20 kg/m(2). However, survival was not significantly related to a triceps skinfold thickness above the 95th percentile. Obese and overweight patients were younger and had better a nutritional status than those with a normal or decreased BMI as shown by the anthropometrics, subjective score, handgrip, lymphocyte count, hemoglobin, and serum albumin, prealbumin, and cholesterol levels. All the nutritional data correlated closely with each other. New York Heart Association class also correlated with nutrition-derived data: as the HF class increased, the nutritional status deteriorated. On multivariate analysis, to predict long-term survival, neither BMI nor triceps skinfold thickness showed an independent predictive value, whereas a larger midarm muscle area did. The obesity paradox was confirmed in this series of elderly patients with HF. Those with a high BMI and improved survival had a better nutritional status and New York Heart Association functional class than those with a lower BMI, which may explain the differences in survival. Copyright © 2012 Elsevier Inc. All rights reserved.

The effect of Al segregation on Schottky barrier height and effective work function in TiAl/TiN/HfO2 gate stacks

NASA Astrophysics Data System (ADS)

Kim, Geun-Myeong; Oh, Young Jun; Chang, K. J.

2016-07-01

We perform first-principles density functional calculations to investigate the effects of Al incorporation on the p-type Schottky barrier height ≤ft({φ\\text{p}}\\right) and the effective work function for various high-k/metal gate stacks, such as TiN/HfO2 with interface Al impurities, Ti1-x Al x N/HfO2, and TiAl/TiN/HfO2. When Al atoms substitute for the interface Ti atoms at TiN/HfO2 interface, interface dipole fields become stronger, leading to the increase of {φ\\text{p}} and thereby the n-type shift of effective work function. In Ti1-x Al x N/HfO2 interface, {φ\\text{p}} linearly increases with the Al content, attributed to the presence of interface Al atoms. On the other hand, in TiAl/TiN/HfO2 interface, where Al is assumed not to segregate from TiAl to TiN, {φ\\text{p}} is nearly independent of the thickness of TiAl. Our results indicate that Al impurities at the metal/dielectric interface play an important role in controlling the effective work function, and provide a clue to understanding the n-type shift of the effective work function observed in TiAl/TiN/HfO2 gate stacks fabricated by using thegate-last process.

Evaluation of autonomic functions of patients with multiple system atrophy and Parkinson's disease by head-up tilt test.

PubMed

Watano, Chikako; Shiota, Yuri; Onoda, Keiichi; Sheikh, Abdullah Md; Mishima, Seiji; Nitta, Eri; Yano, Shozo; Yamaguchi, Shuhei; Nagai, Atsushi

2018-02-01

The aim of this study was to evaluate the autonomic neural function in Parkinson's disease (PD) and multiple system atrophy (MSA) with head-up tilt test and spectral analysis of cardiovascular parameters. This study included 15 patients with MSA, 15 patients with PD, and 29 healthy control (HC) subjects. High frequency power of the RR interval (RR-HF), the ratio of low frequency power of RR interval to RR-HF (RR-LF/HF) and LF power of systolic BP were used to evaluate parasympathetic, cardiac sympathetic and vasomotor sympathetic functions, respectively. Both patients with PD and MSA showed orthostatic hypotension and lower parasympathetic function (RR-HF) at tilt position as compared to HC subjects. Cardiac sympathetic function (RR-LF/HF) was significantly high in patients with PD than MSA at supine position. RR-LF/HF tended to increase in MSA and HC, but decreased in PD by tilting. Consequently, the change of the ratio due to tilting (ΔRR-LF/HF) was significantly lower in patients with PD than in HC subjects. Further analysis showed that compared to mild stage of PD, RR-LF/HF at the supine position was significantly higher in advanced stage. By tilting, it was increased in mild stage and decreased in the advanced stage of PD, causing ΔRR-LF/HF to decrease significantly in the advanced stage. Thus, we demonstrated that spectral analysis of cardiovascular parameters is useful to identify sympathetic and parasympathetic disorders in MSA and PD. High cardiac sympathetic function at the supine position, and its reduction by tilting might be a characteristic feature of PD, especially in the advanced stage.

[Type B natriuretic peptide in the diagnosis of heart failure with preserved systolic function].

PubMed

Castro, A; Dias, P; Pereira, M; Pimenta, J; Friões, F; Rodrigues, R; Ferreira, A; Bettencourt, P

2001-11-01

Heart failure (HF) with preserved left ventricular systolic function (LVSF) is observed in up to 50% patients with HF. There is no consensus on non-invasive diagnosis of this entity. Evaluation of B-type natriuretic peptide (BNP) in the diagnosis of HF with preserved left ventricular systolic function. Prospective study. One hundred and seventy-six consecutive patients with suspected HF were evaluated. Patients were classified as having HF with preserved LVSF, if they had symptoms and signs of HF, an ejection fraction greater than 40% and an abnormal Doppler pattern of the mitral inflow or atrial fibrilation and no other causes for the symptoms. All patients had a 12-lead EKG, chest roentgenogram, simple spirometry, M-mode and 2D echocardiogram with pulsed Doppler study of transmitral inflow and determination of plasma BNP levels. Of the 176 patients, 65 had ejection fraction greater than 40%. Of these patients 46 were classified as having HF with preserved LVSF and 19 as not having HF. Patients with HF and preserved LVSF were older, had a higher systolic blood pressure (SBP), less pathologic Q waves on ECG and higher left ventricular ejection fraction and plasma BNP than patients without HF. Multivariate analysis revealed that BNP and SBP were independently associated with the diagnosis of HF. The accuracy of BNP in the diagnosis of HF with preserved LVSF evaluated by the area under the receiver operating characteristic curve was 0.94. These results suggest that the measurement of BNP levels can help clinicians in the diagnosis of HF with preserved LVSF. Whether BNP levels might be used in clinical practice as a test for the diagnosis of HF with preserved LVSF is a question that merits further studies.

Role of point defects and HfO2/TiN interface stoichiometry on effective work function modulation in ultra-scaled complementary metal-oxide-semiconductor devices

NASA Astrophysics Data System (ADS)

Pandey, R. K.; Sathiyanarayanan, Rajesh; Kwon, Unoh; Narayanan, Vijay; Murali, K. V. R. M.

2013-07-01

We investigate the physical properties of a portion of the gate stack of an ultra-scaled complementary metal-oxide-semiconductor (CMOS) device. The effects of point defects, such as oxygen vacancy, oxygen, and aluminum interstitials at the HfO2/TiN interface, on the effective work function of TiN are explored using density functional theory. We compute the diffusion barriers of such point defects in the bulk TiN and across the HfO2/TiN interface. Diffusion of these point defects across the HfO2/TiN interface occurs during the device integration process. This results in variation of the effective work function and hence in the threshold voltage variation in the devices. Further, we simulate the effects of varying the HfO2/TiN interface stoichiometry on the effective work function modulation in these extremely-scaled CMOS devices. Our results show that the interface rich in nitrogen gives higher effective work function, whereas the interface rich in titanium gives lower effective work function, compared to a stoichiometric HfO2/TiN interface. This theoretical prediction is confirmed by the experiment, demonstrating over 700 meV modulation in the effective work function.

Renal denervation improves cardiac function in rats with chronic heart failure: Effects on expression of β-adrenoceptors

PubMed Central

Zheng, Hong; Liu, Xuefei; Sharma, Neeru M.

2016-01-01

Chronic activation of the sympathetic drive contributes to cardiac remodeling and dysfunction during chronic heart failure (HF). The present study was undertaken to assess whether renal denervation (RDN) would abrogate the sympathoexcitation in HF and ameliorate the adrenergic dysfunction and cardiac damage. Ligation of the left coronary artery was used to induce HF in Sprague-Dawley rats. Four weeks after surgery, RDN was performed, 1 wk before the final measurements. At the end of the protocol, cardiac function was assessed by measuring ventricular hemodynamics. Rats with HF had an average infarct area >30% of the left ventricle and left ventricular end-diastolic pressure (LVEDP) >20 mmHg. β1- and β2-adrenoceptor proteins in the left ventricle were reduced by 37 and 49%, respectively, in the rats with HF. RDN lowered elevated levels of urinary excretion of norepinephrine and brain natriuretic peptide levels in the hearts of rats with HF. RDN also decreased LVEDP to 10 mmHg and improved basal dP/dt to within the normal range in rats with HF. RDN blunted loss of β1-adrenoceptor (by 47%) and β2-adrenoceptor (by 100%) protein expression and improved isoproterenol (0.5 μg/kg)-induced increase in +dP/dt (by 71%) and −dP/dt (by 62%) in rats with HF. RDN also attenuated the increase in collagen 1 expression in the left ventricles of rats with HF. These findings demonstrate that RDN initiated in chronic HF condition improves cardiac function mediated by adrenergic agonist and blunts β-adrenoceptor expression loss, providing mechanistic insights for RDN-induced improvements in cardiac function in the HF condition. PMID:27288440

Structure and properties of a model conductive filament/host oxide interface in HfO2-based ReRAM

NASA Astrophysics Data System (ADS)

Padilha, A. C. M.; McKenna, K. P.

2018-04-01

Resistive random-access memory (ReRAM) is a promising class of nonvolatile memory capable of storing information via its resistance state. In the case of hafnium oxide-based devices, experimental evidence shows that a conductive oxygen-deficient filament is formed and broken inside of the device by oxygen migration, leading to switching of its resistance state. However, little is known about the nature of this conductive phase, its interface with the host oxide, or the associated interdiffusion of oxygen, presenting a challenge to understanding the switching mechanism and device properties. To address these problems, we present atomic-scale first-principles simulations of a prototypical conductive phase (HfO), the electronic properties of its interface with HfO2, as well as stability with respect to oxygen diffusion across the interface. We show that the conduction-band offset between HfO and HfO2 is 1.3 eV, smaller than typical electrode-HfO2 band offsets, suggesting that positive charging and band bending should occur at the conductive filament-HfO2 interface. We also show that transfer of oxygen across the interface, from HfO2 into HfO, costs around 1.2 eV per atom and leads to a gradual opening of the HfO band gap, and hence disruption of the electrical conductivity. These results provide invaluable insights into understanding the switching mechanism for HfO2-based ReRAM.

Influence of Prior Heart Failure Hospitalization on Cardiovascular Events in Patients with Reduced and Preserved Ejection Fraction

PubMed Central

Bello, Natalie A.; Claggett, Brian; Desai, Akshay S.; McMurray, John J.V.; Granger, Christopher B.; Yusuf, Salim; Swedberg, Karl; Pfeffer, Marc A.; Solomon, Scott D.

2014-01-01

Background Hospitalization for acute heart failure (HF) is associated with high rates of subsequent mortality and readmission. We assessed the influence of the time interval between prior HF hospitalization and randomization in the CHARM trials on clinical outcomes in patients with both reduced and preserved ejection fraction. Methods and Results CHARM enrolled 7,599 patients with NYHA class II-IV heart failure, of whom 5,426 had a history of prior HF hospitalization. Cox proportional hazards regression models were utilized to assess the association between time from prior HF hospitalization and randomization and the primary outcome of cardiovascular death or unplanned admission to hospital for the management of worsening HF over a median of 36.6 months. For patients with HF and reduced (HFrEF) or preserved (HFpEF) ejection fraction, rates of CV mortality and HF hospitalization were higher among patients with prior HF hospitalization than those without. The risk for mortality and hospitalization varied inversely with the time interval between hospitalization and randomization. Rates were higher for HFrEF patients within each category. Event rates for those with HFpEF and a HF hospitalization in the 6 months prior to randomization were comparable to the rate in HFrEF patients with no prior HF hospitalization. Conclusions Rates of CV death or HF hospitalization are greatest in those who have been previously hospitalized for HF. Independent of EF, rates of death and readmission decline as time from HF hospitalization to trial enrollment increased. Recent HF hospitalization identifies a high risk population for future clinical trials in HFrEF and HFpEF. Clinical Trial Registration URL: http://www.ClinicalTrials.gov. Unique identifier: NCT00634400. PMID:24874200

Heart failure in pregnant women with cardiac disease: data from the ROPAC.

PubMed

Ruys, Titia P E; Roos-Hesselink, Jolien W; Hall, Roger; Subirana-Domènech, Maria T; Grando-Ting, Jennifer; Estensen, Mette; Crepaz, Roberto; Fesslova, Vlasta; Gurvitz, Michelle; De Backer, Julie; Johnson, Mark R; Pieper, Petronella G

2014-02-01

Heart failure (HF) is one of the most important complications in pregnant women with heart disease, causing maternal and fetal mortality and morbidity. This is an international observational registry of patients with structural heart disease during pregnancy. Sixty hospitals in 28 countries enrolled 1321 women between 2007 and 2011. Pregnant women with valvular heart disease, congenital heart disease, ischaemic heart disease, or cardiomyopathy could be included. Main outcome measures were onset and predictors of HF and maternal and fetal death. In total, 173 (13.1%) of the 1321 patients developed HF, making HF the most common major cardiovascular complication during pregnancy. Baseline parameters associated with HF were New York Heart Association class ≥ 3, signs of HF, WHO category ≥ 3, cardiomyopathy or pulmonary hypertension. HF occurred at a median time of 31 weeks gestation (IQR 23-40) with the highest incidence at the end of the second trimester (34%) or peripartum (31%). Maternal mortality was higher in patients with HF (4.8% in patients with HF and 0.5% in those without HF p<0.001). Pre-eclampsia was strongly related to HF (OR 7.1, 95% CI 3.9 to 13.2, p<0.001). Fetal death and the incidence of preterm birth were higher in women with HF compared to women without HF (4.6% vs 1.2%, p=0.001; and 30% vs 13%, p=0.001). HF was the most common complication during pregnancy, and occurred typically at the end of the second trimester, or after birth. It was most common in women with cardiomyopathy or pulmonary hypertension and was strongly associated with pre-eclampsia and an adverse maternal and perinatal outcome.

Impact of worsening renal function related to medication in heart failure.

PubMed

Brunner-La Rocca, Hans-Peter; Knackstedt, Christian; Eurlings, Luc; Rolny, Vinzent; Krause, Friedemann; Pfisterer, Matthias E; Tobler, Daniel; Rickenbacher, Peter; Maeder, Micha T

2015-02-01

Renal failure is a major challenge in treating heart failure (HF) patients. HF medication may deteriorate renal function, but the impact thereof on outcome is unknown. We investigated the effects of HF medication on worsening renal function (WRF) and the relationship to outcome. This post-hoc analysis of TIME-CHF (NT-proBNP-guided vs. symptom-guided management in chronic HF) included patients with LVEF ≤45% and ≥1 follow-up visit (n = 462). WRF III was defined as a rise in serum creatinine ≥0.5 mg/dL (i.e. 44.2 µmol/L) at any time during the first 6 months. Four classes of medication were considered: loop diuretics, beta-blockers, renin-angiotensin system (RAS)-blockers, and spironolactone. Functional principal component analysis of daily doses was used to comprehend medication over time. All-cause mortality after 18 months was the primary outcome. Interactions between WRF, medication, and outcome were tested. Patients with WRF III received on average higher loop diuretic doses (P = 0.0002) and more spironolactone (P = 0.02), whereas beta-blockers (P = 0.69) did not differ and lower doses of RAS-blockers were given (P = 0.09). There were significant interactions between WRF III, medicationn and outcome. Thus, WRF III was associated with poor prognosis if high loop diuretic doses were given (P = 0.001), but not with low doses (P = 0.29). The opposite was found for spironolactone (poor prognosis in the case of WRF III with no spironolactone, P <0.0001; but not with spironolactone, P = 0.31). Beta-blockers were protective in all patients (P <0.001), but most in those with WRF III (P <0.05 for interaction). RAS-blockade was associated with improved outcome (P = 0.006), irrespective of WRF III. Based on this analysis, it may be hypothesized that high doses of loop diuretics might have detrimental effects, particularly in combination with significant WRF, whereas spironolactone and beta-blockers might be protective in patients with WRF. © 2014 The Authors. European Journal of Heart Failure © 2014 European Society of Cardiology.

The Caregiver Burden Questionnaire for Heart Failure (CBQ-HF): face and content validity

PubMed Central

2013-01-01

Background A new caregiver burden questionnaire for heart failure (CBQ-HF v1.0) was developed based on previously conducted qualitative interviews with HF caregivers and with input from HF clinical experts. Version 1.0 of the CBQ-HF included 41 items measuring the burden associated with caregiving in the following domains: physical, emotional/psychological, social, and impact on caregiver’s life. Following initial development, the next stage was to evaluate caregivers’ understanding of the questionnaire items and their conceptual relevance. Methods To evaluate the face and content validity of the new questionnaire, cognitive interviews were conducted with caregivers of heart failure patients. The cognitive interviews included a “think aloud” exercise as the patient completed the CBQ-HF, followed by more specific probing questions to better understand caregivers’ understanding, interpretation and the relevance of the instructions, items, response scales and recall period. Results Eighteen caregivers of heart failure patients were recruited. The mean age of the caregivers was 50 years (SD = 10.2). Eighty-three percent of caregivers were female and most commonly the patient was either a spouse (44%) or a parent (28%). Among the patients 55% were NYHA Class 2 and 45% were NYHA Class 3 or 4. The caregiver cognitive interviews demonstrated that the CBQ-HF was well understood, relevant and consistently interpreted. From the initial 41 item questionnaire, fifteen items were deleted due to conceptual overlap and/or item redundancy. The final 26-item CBQ-HF (v3.0) uses a 5-point Likert severity scale, assessing 4 domains of physical, emotional/psychological, social and lifestyle burdens using a 4-week recall period. Conclusions The CBQ-HF (v3.0) is a comprehensive and relevant measure of subjective caregiver burden with strong content validity. This study has established that the CBQ-HF (v3.0) has strong face and content validity and should be valuable as an outcomes measure to help understand and monitor the relationship between patient heart failure severity and caregiver burden. A Translatability AssessmentSM of the measure has since been performed confirming the cultural appropriateness of the measure and psychometric validation is planned for the future to further explore the reliability, and validity of the new questionnaire in a larger caregiver sample. PMID:23706131

Efficacy and safety of sacubitril/valsartan (LCZ696) in Japanese patients with chronic heart failure and reduced ejection fraction: Rationale for and design of the randomized, double-blind PARALLEL-HF study.

PubMed

Tsutsui, Hiroyuki; Momomura, Shinichi; Saito, Yoshihiko; Ito, Hiroshi; Yamamoto, Kazuhiro; Ohishi, Tomomi; Okino, Naoko; Guo, Weinong

2017-09-01

The prognosis of heart failure patients with reduced ejection fraction (HFrEF) in Japan remains poor, although there is growing evidence for increasing use of evidence-based pharmacotherapies in Japanese real-world HF registries. Sacubitril/valsartan (LCZ696) is a first-in-class angiotensin receptor neprilysin inhibitor shown to reduce mortality and morbidity in the recently completed largest outcome trial in patients with HFrEF (PARADIGM-HF trial). The prospectively designed phase III PARALLEL-HF (Prospective comparison of ARNI with ACE inhibitor to determine the noveL beneficiaL trEatment vaLue in Japanese Heart Failure patients) study aims to assess the clinical efficacy and safety of LCZ696 in Japanese HFrEF patients, and show similar improvements in clinical outcomes as the PARADIGM-HF study enabling the registration of LCZ696 in Japan. This is a multicenter, randomized, double-blind, parallel-group, active controlled study of 220 Japanese HFrEF patients. Eligibility criteria include a diagnosis of chronic HF (New York Heart Association Class II-IV) and reduced ejection fraction (left ventricular ejection fraction ≤35%) and increased plasma concentrations of natriuretic peptides [N-terminal pro B-type natriuretic peptide (NT-proBNP) ≥600pg/mL, or NT-proBNP ≥400pg/mL for those who had a hospitalization for HF within the last 12 months] at the screening visit. The study consists of three phases: (i) screening, (ii) single-blind active LCZ696 run-in, and (iii) double-blind randomized treatment. Patients tolerating LCZ696 50mg bid during the treatment run-in are randomized (1:1) to receive LCZ696 100mg bid or enalapril 5mg bid for 4 weeks followed by up-titration to target doses of LCZ696 200mg bid or enalapril 10mg bid in a double-blind manner. The primary outcome is the composite of cardiovascular death or HF hospitalization and the study is an event-driven trial. The design of the PARALLEL-HF study is aligned with the PARADIGM-HF study and aims to assess the efficacy and safety of LCZ696 in Japanese HFrEF patients. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Left Ventricular Reverse Remodeling With Biventricular Versus Right Ventricular Pacing in Patients With Atrioventricular Block and Heart Failure in the BLOCK HF Trial.

PubMed

St John Sutton, Martin; Plappert, Ted; Adamson, Philip B; Li, Pei; Christman, Shelly A; Chung, Eugene S; Curtis, Anne B

2015-05-01

Biventricular pacing in heart failure (HF) improves survival, relieves symptoms, and attenuates left ventricular (LV) remodeling. However, little is known about biventricular pacing in HF patients with atrioventricular block because they are typically excluded from biventricular trials. The Biventricular versus Right Ventricular Pacing in Heart Failure Patients with Atrioventricular Block (BLOCK HF) trial randomized patients with atrioventricular block, New York Heart Association symptom classes I to III HF, and LV ejection fraction ≤50% to biventricular or right ventricular pacing. Doppler echocardiograms were obtained at randomization (after 30 to 60 days of right ventricular pacing postimplant) and every 6 months through 24 months. Data analysis comparing changes in 10 prespecified echo parameters over time was conducted using a Bayesian design. LV end systolic volume index was also evaluated as a predictor of mortality/morbidity. Of 691 randomized subjects, 624 had paired Doppler echocardiogram data for ≥1 analyses at 6, 12, 18, or 24 months. Biventricular pacing significantly reduced LV volume indices and intraventricular mechanical delay, and improved LV ejection fraction, consistent with LV reverse remodeling. These parameters showed little change with right ventricular pacing alone, indicating no systematic reverse remodeling with right ventricular pacing. LV end systolic volume index was predictive of mortality/morbidity; the estimated risk increased up to 1% for every 1 mL/m(2) increase in LV end systolic volume index. LV end systolic volume index is a significant predictor of mortality/morbidity in this population. Cardiac structure and function are improved with biventricular pacing for patients with atrioventricular block and LV systolic dysfunction. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00267098. © 2015 American Heart Association, Inc.

Ethnic differences in macrovascular and microvascular function in systolic heart failure.

PubMed

Shantsila, Eduard; Wrigley, Benjamin; Shantsila, Alena; Tapp, Luke D; Blann, Andrew D; Gill, Paramjit S; Lip, Gregory Y H

2011-11-01

Endothelial dysfunction is implicated in the pathophysiological features of heart failure (HF), and ethnic differences in the presentation of cardiovascular disease are evident, with an excess seen among South Asians (SAs). However, data on ethnic differences in endothelial function in HF are limited. In a cross-sectional study, we recruited 128 subjects with systolic HF: 50 SAs, 50 whites, and 28 African Caribbeans (ACs). In addition, SAs with systolic HF were compared with 40 SAs with coronary artery disease without HF ("disease controls") and 40 SA healthy controls. Macrovascular endothelial function was assessed by measurement of flow-mediated dilation (FMD) in response to hyperemia, arterial stiffness was assessed by the pulse-wave velocity, and microvascular endothelial function was assessed by forearm laser Doppler flowmetry. CD144-expressing endothelial microparticles were measured by flow cytometry. When compared with disease controls and healthy controls, SAs with HF had an impaired microvascular response to acetylcholine (P=0.001) and reduced FMD (P<0.001). In comparing ethnic groups, SAs with HF had an impaired response to acetylcholine (123±95.5%) compared with whites (258±156%) and ACs (286±173%, P<0.001 for both). Whites had a higher FMD (8.49±4.63%) than SAs (4.76±4.78%, P<0.001) and ACs (4.55±3.56%, P=0.01). No difference in endothelial-independent response was observed between study groups or in pulse-wave velocity. Ethnicity remained associated with microvascular endothelial function even after adjustment for age, presence of hypertension and diabetes mellitus, blood pressure, and glucose levels (P=0.003). There were no differences in numbers of endothelial microparticles. The SAs with HF have impaired microvascular and macrovascular endothelial function but preserved arterial elastic properties. Significant ethnic differences in endothelial function are evident in subjects with HF, with ethnicity being associated with microvascular endothelial dysfunction in this disorder.

Hydrotherapy in advanced heart failure: the cardio-HKT pilot study.

PubMed

Municinó, Annamaria; Nicolino, Annamaria; Milanese, Manlio; Gronda, Edoardo; Andreuzzi, Bruno; Oliva, Fabrizio; Chiarella, Francesco

2006-12-01

In-water exercise, hydrotherapy, may offer an attractive alternative to conventional training in markedly compromised patients with advanced HF. This Pilot Study evaluates the safety and efficacy of Cardio-Hydrokinesitherapy (Cardio-HKT) in patients with advanced HF on optimal medical therapy. Cardio-HKT is a novel rehabilitation program that includes training sessions in warm water (31 degrees C), integrated by educational and psycho-behavioural sessions to promote healthy life style modifications. We studied 18 adult patients with advanced HF, LVEF < 35%, NYHA functional class > II and peak oxygen uptake (peak VO2) < 18 ml/kg/min. Cardio-HKT consisted of a 3 weeks daily in-water training, combined to educational and psycho-behavioural sessions. Patients underwent a six-minute-walking-test (6mWT), a cardiopulmonary exercise test at baseline and after 3 weeks of Cardio-HKT. Quality of life was assessed with the Minnesota Living with Heart Failure Questionnaire (MLHF). All patients completed the Cardio-HKT rehabilitation program without complications. The 6mWT improved from 453 +/- 172 m to 571 +/- 120 m (p < 0.01), peak VO2 from 13.0 +/- 3.1 to 14.5 +/- 2.9 ml/kg/min (p = 0.03), whereas VE/ CO2 slope declined from 37 +/- 10 to 33 +/- 9 (p = 0.01). MLHF markedly improved from 56 (68-27) to 18 (40-7) (p < 0.01). Our results support the safety and efficacy of the innovative Cardio-HKT rehabilitation program in patients with advanced HF.

Lipophilic versus hydrophilic statin therapy for heart failure: a protocol for an adjusted indirect comparison meta-analysis

PubMed Central

2013-01-01

Background Statins are known to reduce cardiovascular morbidity and mortality in primary and secondary prevention studies. Subsequently, a number of nonrandomised studies have shown statins improve clinical outcomes in patients with heart failure (HF). Small randomised controlled trials (RCT) also show improved cardiac function, reduced inflammation and mortality with statins in HF. However, the findings of two large RCTs do not support the evidence provided by previous studies and suggest statins lack beneficial effects in HF. Two meta-analyses have shown statins do not improve survival, whereas two others showed improved cardiac function and reduced inflammation in HF. It appears lipophilic statins produce better survival and other outcome benefits compared to hydrophilic statins. But the two types have not been compared in direct comparison trials in HF. Methods/design We will conduct a systematic review and meta-analysis of lipophilic and hydrophilic statin therapy in patients with HF. Our objectives are: 1. To determine the effects of lipophilic statins on (1) mortality, (2) hospitalisation for worsening HF, (3) cardiac function and (4) inflammation. 2. To determine the effects of hydrophilic statins on (1) mortality, (2) hospitalisation for worsening HF, (3) cardiac function and (4) inflammation. 3. To compare the efficacy of lipophilic and hydrophilic statins on HF outcomes with an adjusted indirect comparison meta-analysis. We will conduct an electronic search of databases for RCTs that evaluate statins in patients with HF. The reference lists of all identified studies will be reviewed. Two independent reviewers will conduct the search. The inclusion criteria include: 1. RCTs comparing statins with placebo or no statin in patients with symptomatic HF. 2. RCTs that employed the intention-to-treat (ITT) principle in data analysis. 3. Symptomatic HF patients of all aetiologies and on standard treatment. 4. Statin of any dose as intervention. 5. Placebo or no statin arm as control. The exclusion criteria include: 1. RCTs involving cerivastatin in HF patients. 2. RCTs with less than 4 weeks of follow-up. Discussion We will perform an adjusted indirect comparison meta-analysis of lipophilic versus hydrophilic statins in patients with HF using placebo or no statin arm as common comparator. PMID:23618535

Fatigue With Systolic Heart Failure

PubMed Central

Fink, Anne M.; Sullivan, Shawna L.; Zerwic, Julie J.; Piano, Mariann R.

2010-01-01

Background and Research Objective Fatigue is one of the most prevalent symptoms in persons with systolic heart failure (HF). There remains insufficient information about the physiological and psychosocial underpinnings of fatigue in HF. The specific aims of this study were to (1) determine the psychometric properties of 2 fatigue questionnaires in patients with HF, (2) compare fatigue in patients with HF to published scores of healthy adults and patients with cancer undergoing treatment, and (3) identify the physiological (eg, hemoglobin, B-type natriuretic peptide, body mass index, and ejection fraction) and psychosocial (eg, depressed mood) correlates of fatigue in HF. Subjects and Methods A convenience sample of 87 HF outpatients was recruited from 2 urban medical centers. Patients completed the Fatigue Symptom Inventory, Profile of Mood States, and Short Form-36 Health Survey. Results and Conclusions Patients with HF and patients with cancer reported similar levels of fatigue, and both patient groups reported significantly more fatigue than did healthy adults. Physical functioning and hemoglobin categories explained 30% of the variance in Fatigue Symptom Inventory-Interference Scale scores, whereas depressed mood and physical functioning explained 47% of the variance in Profile of Mood States Fatigue subscale scores. Patients with HF experienced substantial fatigue that is comparable with cancer-related fatigue. Low physical functioning, depressed mood, and low hemoglobin level were associated with HF-related fatigue. PMID:19707101

Electronic and thermodynamic properties of layered Hf2Sfrom first-principles calculations

NASA Astrophysics Data System (ADS)

Nandadasa, Chandani; Yoon, Mina; Kim, Seong-Gon; Erwin, Steve; Kim, Sungho; Kim, Sung Wng; Lee, Kimoon

Theoretically we explored two stable phases of inorganic fullerene-like structure of the layered dihafnium sulfide (Hf2 S) . We investigated structural and electronic properties of the two phases of Hf2 S by using first-principles calculations. Our calculation identifies experimentally observed anti-NbS2 structure of Hf2 S . Our electronic calculation results indicate that the density of states of anti- NbS2 structure of Hf2 S at fermi level is less than that of the other phase of Hf2 S . To study the relative stability of different phases at finite temperature Helmholtz free energies of two phases are obtained using density functional theory and density functional perturbation theory. The free energy of the anti-NbS2 structure of Hf2 S always lies below the free energy of the other phase by confirming the most stable structure of Hf2 S . The phonon dispersion, phonon density of states including partial density of states and total density of states are obtained within density functional perturbation theory. Our calculated zero-pressure phonon dispersion curves confirm that the thermodynamic stability of Hf2 S structures. For further investigation of thermodynamic properties, the temperature dependency of thermal expansion, heat capacities at constant pressure and volume are evaluated within the quasiharmonic approximations (QHA).

Preliminary Results From the C-Pulse OPTIONS HF European Multicenter Post-Market Study.

PubMed

Schulz, Antonia; Krabatsch, Thomas; Schmitto, Jan D; Hetzer, Roland; Seidel, Mirko; Dohmen, Pascal M; Hotz, Holger

2016-02-18

BACKGROUND The C-Pulse System is an extra-aortic balloon counterpulsation device. It is used to treat patients with heart failure disease in NYHA functional class III or ambulatory class IV. MATERIAL AND METHODS We present preliminary site-reported 6-month data from 3 centers in Germany as part of the prospective observational post-market OPTIONS HF study. RESULTS Between May 2013 and March 2014, the C-Pulse System was implanted in 8 patients (7 male) with a mean age of 61.6±9.3 years. Four had ischemic and 4 had non-ischemic cardiomyopathy. No stroke, myocardial infarction, major bleeding, or major infection due to the device were reported. One patient developed non-device-related refractory tachycardia with worsening heart failure 12 h after surgery and underwent left ventricular assist device implantation. Within 6 months of observation, functional status improved from NYHA III to II in 5 patients, and 2 remained in NYHA III. Mean left ventricular ejection fraction increased from 24.3±7.9% to 44.5±4.5% (p<0.0001). Mean Kansas City Cardiomyopathy Questionnaire overall score improved from 28.6±19.1 to 59.1±22.5 (p=0.0183). Six-minute walk test was performed in 6 out of 7 patients at follow-up. The mean distance improved from 252.0±85.1 m to 279.2±87.5 m (p>0.05). One patient was weaned off the device after 6 months of support. CONCLUSIONS The C-Pulse System provides a therapeutic option for patients with moderate-to-severe heart failure and seems to improve quality of life and cardiac function over time.

Heart failure with recovered ejection fraction: clinical characteristics, determinants and prognosis. CARDIOCHUS-CHOP registry.

PubMed

Agra Bermejo, Rosa; Gonzalez Babarro, Eva; López Canoa, J Nicolás; Varela Román, Alfonso; Gómez Otero, Inés; Oro Ayude, Marcos; Parada Vazquez, Pablo; Gómez Rodríguez, Isabel; Díaz Castro, Oscar; González Juanatey, Jose Ramón

2017-10-05

The magnitude and the prognostic impact of recovering left ventricular ejection fraction (LVEF) in patients with heart failure (HF) and systolic dysfunction is unclear. The aim of this study was to evaluate the clinical characteristics and prognosis of patients with HFrecEF in an HF population. 449 consecutive patients were selected with the diagnosis of HF and an evaluation of LVEF in the 6 months prior to selection who were referred to two HF units. Patients with systolic dysfunction were only considered if a second echocardiogram was performed during the follow-up. At the time of diagnosis, 207 patients had LVEF > 40% (HFpEF) and 242 had LVEF ≤ 40% (HFrEF). After 1 year, the LVEF was re-evaluated in all 242 patients with a LVEF ≤ 40%: in 126 (52%), the second LVEF was > 40% (HFrecEF), and the remaining 116 (48%) had LVEF ≤ 40% (HFrEF). After 1800 ± 900 days of follow-up patients with recovered LVEF had a significantly lower mortality rate (HFpEF vs. HFrecEF: hazard ratio (HR) = 2.286, 95% confidence interval (95% CI) 1.264-4.145, p = 0.019; HFrEF vs. HFrecEF: HR = 2.222, 95% CI 1.189-4.186, p < 0.001) and hospitalization rate (HFpEF vs. HFrecEF: HR = 1.411, 95% CI 1.046-1.903, p = 0.024; HFrEF vs. HFrecEF: HR = 1.388, 95% CI 1.002-1.924, p = 0.049). The following are predictors of LVEF recovery: younger age, lower functional class, treatment with renin-angiotensin-aldosterone system inhibitors and beta-blockers, absence of defibrillator use, and non-ischemic aetiology. Patients with HF and reduced LVEF who were re-evaluated after 1 year, had significant improvement in their LVEF and had a more favourable prognosis than HF with preserved and reduced ejection fraction.

Bloodstream Amyloid-beta (1-40) Peptide, Cognition, and Outcomes in Heart Failure.

PubMed

Bayes-Genis, Antoni; Barallat, Jaume; de Antonio, Marta; Domingo, Mar; Zamora, Elisabet; Vila, Joan; Subirana, Isaac; Gastelurrutia, Paloma; Pastor, M Cruz; Januzzi, James L; Lupón, Josep

2017-11-01

In the brain, amyloid-beta generation participates in the pathophysiology of cognitive disorders; in the bloodstream, the role of amyloid-beta is uncertain but may be linked to sterile inflammation and senescence. We explored the relationship between blood levels of amyloid-beta 1-40 peptide (Aβ40), cognition, and mortality (all-cause, cardiovascular, and heart failure [HF]-related) in ambulatory patients with HF. Bloodstream Aβ40 was measured in 939 consecutive patients with HF. Cognition was evaluated with the Pfeiffer questionnaire (adjusted for educational level) at baseline and during follow-up. Multivariate Cox regression analyses and measurements of performance (discrimination, calibration, and reclassification) were used, with competing risk for specific causes of death. Over 5.1 ± 2.9 years, 471 patients died (all-cause): 250 from cardiovascular causes and 131 HF-related. The median Aβ40 concentration was 519.1 pg/mL [Q1-Q3: 361.8-749.9 pg/mL]. The Aβ40 concentration correlated with age, body mass index, renal dysfunction, and New York Heart Association functional class (all P < .001). There were no differences in Aβ40 in patients with and without cognitive impairment at baseline (P = .97) or during follow-up (P = .20). In multivariable analysis, including relevant clinical predictors and N-terminal pro-B-type natriuretic peptide, Aβ40 remained significantly associated with all-cause death (HR, 1.22; 95%CI, 1.10-1.35; P < .001) and cardiovascular death (HR, 1.18; 95%CI, 1.03-1.36; P = .02), but not with HF-related death (HR, 1.13; 95%CI, 0.93-1.37; P = .22). Circulating Aβ40 improved calibration and patient reclassification. Blood levels of Aβ40 are not associated with cognitive decline in HF. Circulating Aβ40 was predictive of mortality and may indicate systemic aging. Copyright © 2017 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.

Educational level and self-care behaviour in patients with heart failure before and after nurse educational intervention.

PubMed

González, Beatriz; Lupón, Josep; Domingo, Maria del Mar; Cano, Lucía; Cabanes, Roser; de Antonio, Marta; Arenas, Miquel; Crespo, Eva; Rodríguez, Margarita; Bayes-Genis, Antoni

2014-10-01

Self-care is important for heart failure (HF) management and may be influenced by the patient's educational level. We assessed the relationship of educational level with baseline self-care behaviour and changes one year after a nursing intervention in HF outpatients attending a HF unit. Three hundred and thirty-five HF patients were studied, with a median age of 67 years (P(25-75) 57-75) and a median HF duration of six months (P(25-75) 1-36). HF aetiology was mainly ischaemic heart disease (53.4%). Median ejection fraction was 30% (P(25-75) 24-37%). The functional class was mainly II (66.3%) and III (25.7%). Educational levels were: very low 17.3%; low 62.1%; medium-high 20.6%. Patients were evaluated at the first visit (baseline) and one year after the educational intervention with the nine-item European Heart Failure Self-care Behaviour Scale. Median patient scores differed in the baseline (19 (P(25-75) 15-26) vs. 16 (P(25-75) 13-21) vs. 15 (P(25-75) 12.5-15.5)) and the one-year evaluation (15 (P(25-75) 13-17) vs. 13 (P(25-75) 11-15) vs. 12 (P(25-75) 10-14)) for the three educational levels, respectively, with statistically significant differences between levels (p=0.007 to p<0.001) except between low and medium-high education at one year (p=0.057). In the one-year evaluation, self-care behaviour significantly improved in the three educational groups (p<0.001), with a similar, albeit not statistically significant, magnitude of improvement in all groups. Self-care behaviour at baseline and one year after a nursing intervention was better in patients with a higher education, although the improvement with the intervention was similar irrespective of the educational level. © The European Society of Cardiology 2013.

A phenomenological study of day-to-day experiences of living with heart failure: do cultural differences matter?

PubMed

Chiaranai, Chantira

2014-07-01

Although there is a significant body of literature addressing heart failure (HF) epidemiology, physiology, and treatment, little is known about the experiences of Thai patients living with this chronic condition. The primary goal of this study was to gain a better understanding of how Thai patients with HF live with chronic and debilitating illness. A phenomenological approach was chosen to investigate the experience of living with HF. Fifteen Thai men and women with HF in New York Heart Association classes I to III, aged between 47 and 75 years, were interviewed with open-ended questions. Data were analyzed using qualitative inductive content analysis. Three themes emerged from the data analysis: identifying losses or changes in their lives, accepting the losses, and regaining some control. Unlike their western counterparts, the Thai patients with HF incorporated their karma, a Buddhist belief system, as a tool to rationalize the occurrence of their HF experience. The participants of this study used kreng jai as a cultural desire not to disrupt the happiness of others, even at the expense of efficiency, or to burden others, which might affect their own quality of life. The Thai patients with HF faced many limitations. The Thai patients with HF use religion and traditional culture to overcome their life situations. To support Thai patients with HF, healthcare providers must have an understanding of cultural differences.

Cognitive deficits are associated with poorer simulated driving in older adults with heart failure

PubMed Central

2013-01-01

Background Cognitive impairment is prevalent in older adults with heart failure (HF) and associated with reduced functional independence. HF patients appear at risk for reduced driving ability, as past work in other medical samples has shown cognitive dysfunction to be an important contributor to driving performance. The current study examined whether cognitive dysfunction was independently associated with reduced driving simulation performance in a sample of HF patients. Methods 18 persons with HF (67.72; SD = 8.56 year) completed echocardiogram and a brief neuropsychological test battery assessing global cognitive function, attention/executive function, memory and motor function. All participants then completed the Kent Multidimensional Assessment Driving Simulation (K-MADS), a driving simulator scenario with good psychometric properties. Results The sample exhibited an average Mini Mental State Examination (MMSE) score of 27.83 (SD = 2.09). Independent sample t-tests showed that HF patients performed worse than healthy adults on the driving simulation scenario. Finally, partial correlations showed worse attention/executive and motor function were independently associated with poorer driving simulation performance across several indices reflective of driving ability (i.e., centerline crossings, number of collisions, % of time over the speed limit, among others). Conclusion The current findings showed that reduced cognitive function was associated with poor simulated driving performance in older adults with HF. If replicated using behind-the-wheel testing, HF patients may be at elevated risk for unsafe driving and routine driving evaluations in this population may be warranted. PMID:24499466

Liver Stiffness Reflecting Right-Sided Filling Pressure Can Predict Adverse Outcomes in Patients With Heart Failure.

PubMed

Taniguchi, Tatsunori; Ohtani, Tomohito; Kioka, Hidetaka; Tsukamoto, Yasumasa; Onishi, Toshinari; Nakamoto, Kei; Katsimichas, Themistoklis; Sengoku, Kaoruko; Chimura, Misato; Hashimoto, Haruko; Yamaguchi, Osamu; Sawa, Yoshiki; Sakata, Yasushi

2018-01-12

This study sought to investigate whether elevated liver stiffness (LS) values at discharge reflect residual liver congestion and are associated with worse outcomes in patients with heart failure (HF). Transient elastography is a newly developed, noninvasive method for assessing LS, which can be highly reflective of right-sided filling pressure associated with passive liver congestion in patients with HF. LS values were determined for 171 hospitalized patients with HF before discharge using a Fibroscan device. The median LS value was 5.6 kPa (interquartile range: 4.4 to 8.1; range 2.4 to 39.7) and that of right-sided filling pressure, which was estimated based on LS, was 5.7 mm Hg (interquartile range: 4.1 to 8.2 mm Hg; range 0.1 to 18.9 mm Hg). The patients in the highest LS tertile (>6.9 kPa, corresponding to an estimated right-sided filling pressure of >7.1 mm Hg) had advanced New York Heart Association functional class, high prevalence of jugular venous distention and moderate/severe tricuspid regurgitation, large inferior vena cava (IVC) diameter, low hemoglobin and hematocrit levels, high serum direct bilirubin level, and a similar left ventricular ejection fraction compared with the lower tertiles. During follow-up periods (median: 203 days), 8 (5%) deaths and 33 (19%) hospitalizations for HF were observed. The patients in the highest LS group had a significantly higher mortality rate and HF rehospitalization (hazard ratio: 3.57; 95% confidence interval: 1.93 to 6.83; p < 0.001) compared with the other tertiles. Although LS correlated with IVC diameter and serum direct bilirubin and brain natriuretic peptide levels, LS values were predictive of worse outcomes, even after adjustment for these indices. These data suggest that LS is a useful index for assessing systemic volume status and predicting the severity of HF, and that the presence of liver congestion at discharge is associated with worse outcomes in patients with HF. Copyright © 2018 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Serum bicarbonate and structural and functional cardiac abnormalities in CKD - A report from the CRIC study

PubMed Central

Dobre, Mirela; Roy, Jason; Tao, Kaixiang (Kelvin); Anderson, Amanda; Bansal, Nisha; Chen, Jing; Deo, Raj; Drawz, Paul; Feldman, Harold; Hamm, LL; Hostetter, Thomas; Kusek, John W; Lora, Claudia; Ojo, Akinlolu; Sharma, Kumar; Rahman, Mahboob

2016-01-01

Background Heart failure (HF) is a frequent occurrence in chronic kidney disease (CKD) patients and predicts poor survival. Serum bicarbonate is associated with increased rates of HF in CKD; however, the mechanisms leading to this association are incompletely understood. This study aims to assess whether serum bicarbonate is independently associated with structural and functional cardiac abnormalities in CKD. Methods The association between serum bicarbonate and left ventricular hypertrophy (LVH), LV mass indexed to height2.7, LV geometry, ejection fraction and diastolic dysfunction were assessed in 3483 participants without NYHA class III/IV HF, enrolled in the Chronic Renal Insufficiency Cohort (CRIC) study. Results The mean eGFR was 42.5±17ml/min per 1.73m2. The overall prevalence of LVH was 51.2%, with 57.8%, 50.9% and 47.7% for bicarbonate categories <22, 22-26, and >26mmol/L, respectively. Participants with low bicarbonate were more likely to have LVH and abnormal LV geometry (OR 1.32; 95%CI 1.07–1.64, and 1.57; 95%CI 1.14–2.16, respectively). However, the association was not statistically significant after adjustment for demographics, traditional cardiovascular risk factors, medications and kidney function (OR1.07; 95%CI 0.66–1.72, and 1.27; 95%CI 0.64–2.51, respectively). No association was found between bicarbonate and systolic or diastolic dysfunction. During follow-up no significant changes in LV mass or EF were observed in any bicarbonate strata. Conclusions In a large CKD study, serum bicarbonate was associated with LV mass and concentric LVH; however, this association was attenuated after adjustment for clinical factors suggesting that the observed cardiac effects are mediated through yet unknown mechanisms. PMID:27241893

Submaximal oxygen uptake kinetics, functional mobility, and physical activity in older adults with heart failure and reduced ejection fraction

PubMed Central

Hummel, Scott L; Herald, John; Alpert, Craig; Gretebeck, Kimberlee A; Champoux, Wendy S; Dengel, Donald R; Vaitkevicius, Peter V; Alexander, Neil B

2016-01-01

Background Submaximal oxygen uptake measures are more feasible and may better predict clinical cardiac outcomes than maximal tests in older adults with heart failure (HF). We examined relationships between maximal oxygen uptake, submaximal oxygen kinetics, functional mobility, and physical activity in older adults with HF and reduced ejection fraction. Methods Older adults with HF and reduced ejection fraction (n = 25, age 75 ± 7 years) were compared to 25 healthy age- and gender-matched controls. Assessments included a maximal treadmill test for peak oxygen uptake (VO2peak), oxygen uptake kinetics at onset of and on recovery from a submaximal treadmill test, functional mobility testing [Get Up and Go (GUG), Comfortable Gait Speed (CGS), Unipedal Stance (US)], and self-reported physical activity (PA). Results Compared to controls, HF had worse performance on GUG, CGS, and US, greater delays in submaximal oxygen uptake kinetics, and lower PA. In controls, VO2peak was more strongly associated with functional mobility and PA than submaximal oxygen uptake kinetics. In HF patients, submaximal oxygen uptake kinetics were similarly associated with GUG and CGS as VO2peak, but weakly associated with PA. Conclusions Based on their mobility performance, older HF patients with reduced ejection fraction are at risk for adverse functional outcomes. In this population, submaximal oxygen uptake measures may be equivalent to VO2 peak in predicting functional mobility, and in addition to being more feasible, may provide better insight into how aerobic function relates to mobility in older adults with HF. PMID:27594875

Submaximal oxygen uptake kinetics, functional mobility, and physical activity in older adults with heart failure and reduced ejection fraction.

PubMed

Hummel, Scott L; Herald, John; Alpert, Craig; Gretebeck, Kimberlee A; Champoux, Wendy S; Dengel, Donald R; Vaitkevicius, Peter V; Alexander, Neil B

2016-07-01

Submaximal oxygen uptake measures are more feasible and may better predict clinical cardiac outcomes than maximal tests in older adults with heart failure (HF). We examined relationships between maximal oxygen uptake, submaximal oxygen kinetics, functional mobility, and physical activity in older adults with HF and reduced ejection fraction. Older adults with HF and reduced ejection fraction (n = 25, age 75 ± 7 years) were compared to 25 healthy age- and gender-matched controls. Assessments included a maximal treadmill test for peak oxygen uptake (VO2peak), oxygen uptake kinetics at onset of and on recovery from a submaximal treadmill test, functional mobility testing [Get Up and Go (GUG), Comfortable Gait Speed (CGS), Unipedal Stance (US)], and self-reported physical activity (PA). Compared to controls, HF had worse performance on GUG, CGS, and US, greater delays in submaximal oxygen uptake kinetics, and lower PA. In controls, VO2peak was more strongly associated with functional mobility and PA than submaximal oxygen uptake kinetics. In HF patients, submaximal oxygen uptake kinetics were similarly associated with GUG and CGS as VO2peak, but weakly associated with PA. Based on their mobility performance, older HF patients with reduced ejection fraction are at risk for adverse functional outcomes. In this population, submaximal oxygen uptake measures may be equivalent to VO2 peak in predicting functional mobility, and in addition to being more feasible, may provide better insight into how aerobic function relates to mobility in older adults with HF.

Adaptive servo-ventilation to treat central sleep apnea in heart failure with reduced ejection fraction: the Bad Oeynhausen prospective ASV registry.

PubMed

Oldenburg, Olaf; Wellmann, Birgit; Bitter, Thomas; Fox, Henrik; Buchholz, Anika; Freiwald, Eric; Horstkotte, Dieter; Wegscheider, Karl

2018-04-13

Central sleep apnea (CSA) is highly prevalent in heart failure patients with reduced left ventricular ejection fraction (HF-REF). The Bad Oeynhausen Adaptive Servo-ventilation (ASV) registry (NCT01657188) was designed to investigate whether treatment of CSA with ASV improved survival in HF-REF patients; the effects of ASV on symptoms and cardiopulmonary performance were also investigated. From January 2004 to October 2013, the registry prospectively enrolled HF-REF patients [NYHA class ≥ II, left ventricular ejection fraction (LVEF) ≤ 45%] with moderate to severe predominant CSA [apnea-hypopnea index (AHI) ≥ 15/h]. ASV-treated patients were followed up at 3, 6, 12 and 24 months, including natriuretic peptide concentrations, blood gas analyses, echocardiography, 6-min walk distance (6MWD), and cardiopulmonary exercise (CPX) testing. 550 patients were included [age 67.7 ± 10 years, 90% male, 52% in NYHA class ≥ III, LVEF 29.9 ± 8%, AHI 35.4 ± 13.6/h, and time with nocturnal oxygen saturation < 90% (T < 90%) 58 ± 73 min]; ASV was prescribed to 224 patients. Over a median follow-up of 6.6 years, 109 (48.7%) ASV-treated patients and 191 (58.6%) controls died (adjusted Cox modelling hazard ratio of 0.95, 95% confidence interval 0.68-1.24; p = 0.740); older age, lower LVEF, impaired renal function, low sodium concentration, and nocturnal hypoxemia were significant predictors of mortality. Patient reported NYHA functional class improved in the ASV group, but LVEF, CPX, 6MWD, natriuretic peptides and blood gases remained unchanged. Long-term ASV treatment of predominant CSA in HF-REF patients included in our registry had no statistically significant effect on survival. ASV improved HF symptoms, but had no significant effects on exercise capacity, LVEF, natriuretic peptide concentrations or blood gases during follow-up as compared to control patients.

β1-Adrenergic blocker bisoprolol reverses down-regulated ion channels in sinoatrial node of heart failure rats.

PubMed

Du, Yuan; Zhang, Junbo; Xi, Yutao; Wu, Geru; Han, Ke; Huang, Xin; Ma, Aiqun; Wang, Tingzhong

2016-06-01

Bisoprolol, an antagonist of β1-adrenergic receptors, is effective in reducing the morbidity and mortality in patients with heart failure (HF). It has been found that HF is accompanied with dysfunction of the sinoatrial node (SAN). However, whether bisoprolol reverses the decreased SAN function in HF and how the relevant ion channels in SAN change were relatively less studied. SAN function and messenger RNA (mRNA) expression of sodium channels and hyperpolarization-activated cyclic nucleotide-gated (HCN) channel subunits were assessed in sham-operated rats, abdominal arterio-venous shunt (volume overload)-induced HF rats, and bisoprolol- treated HF rats. SAN cells of rats were isolated by laser capture microdissection. Quantitative real-time PCR analysis was used to quantify mRNA expression of sodium channels and HCN channel subunits in SAN. Intrinsic heart rate declined and sinus node recovery time prolonged in HF rats, indicating the suppressed SAN function, which could be improved by bisoprolol treatment. Nav1.1, Nav1.6, and HCN4 mRNA expressions were reduced in SAN in HF rats compared with that in control rats. Treatment with bisoprolol could reverse both the SAN function and the Nav1.1, Nav1.6, and HCN4 mRNA expression partially. These data indicated that bisoprolol is effective in HF treatment partially due to improved SAN function by reversing the down-regulation of sodium channels (Nav1.1 and Nav1.6) and HCN channel (HCN4) subunits in SAN in failing hearts.

Exact exchange and Wilson-Levy correlation: a pragmatic device for studying complex weakly-bonded systems.

PubMed

Walsh, T R

2005-02-07

The Wilson-Levy (WL) correlation functional is used together with Hartree-Fock (HF) theory to evaluate interaction energies at intermediate separations (i.e. around equilibrium separation) for several weakly-bonded systems. The HF+WL approach reproduces binding trends for all complexes studied: selected rare-gas dimers, isomers of the methane dimer, benzene dimer and naphthalene dimer, and base-pair stacking structures for pyrimidine, cytosine, uracil and guanine dimers. These HF+WL data are contrasted against results obtained from some popular functionals (including B3LYP and PBE), as well as two newly-developed functionals, X3LYP and xPBE. The utility of HF+WL, with reference to exact-exchange (EXX) density-functional theory, is discussed in terms of a suggested EXXWL exchange-correlation functional.

Synergistic effect of combined HMG-CoA reductase inhibitor and angiotensin-II receptor blocker therapy in patients with chronic heart failure: the HF-COSTAR trial.

PubMed

Maejima, Yasuhiro; Nobori, Kiyoshi; Ono, Yuichi; Adachi, Susumu; Suzuki, Jun-Ichi; Hirao, Kenzo; Isobe, Mitsuaki; Ito, Hiroshi

2011-01-01

It is known that HMG-CoA reductase inhibitors (statins) may have a therapeutic benefit in patients with heart failure (HF). However, no studies have yet evaluated the possible interaction of statins and angiotensin-II receptor blockers (ARBs) on left ventricular (LV) function in patients with HF. We hypothesized that statins might alter the effect of ARBs on cardiac function in patients with HF. We prospectively randomized patients with chronic HF who received the ARB, losartan (LOS group), or the statin, simvastatin (SIM), in combination with LOS (SIM+LOS group) at our hospitals and assessed before and after treatment for 6 months. Although no significant improvement of HF symptoms as evaluated by the New York Heart Association (NYHA) classification was observed in the LOS group, HF symptoms in the SIM+LOS group significantly improved. The percent increase of LV ejection fraction after treatment in the SIM+LOS group was significantly larger than in the LOS group. Furthermore, the plasma brain natriuretic peptide level was significantly lower after treatment in the SIM+LOS group than in the LOS group. Combined statin and ARB therapy significantly improves both symptoms and LV function over time in patients with HF. Thus, the combination of an ARB with a statin may be a useful therapeutic strategy for HF.

Lung function and airway obstruction: associations with circulating markers of cardiac function and incident heart failure in older men—the British Regional Heart Study

PubMed Central

Wannamethee, S Goya; Shaper, A Gerald; Papacosta, Olia; Lennon, Lucy; Welsh, Paul; Whincup, Peter H

2016-01-01

Aims The association between lung function and cardiac markers and heart failure (HF) has been little studied in the general older population. We have examined the association between lung function and airway obstruction with cardiac markers N-terminal pro-brain natriuretic peptide (NT-proBNP) and cardiac troponin T (cTnT) and risk of incident HF in older men. Methods and results Prospective study of 3242 men aged 60–79 years without prevalent HF or myocardial infarction followed up for an average period of 13 years, in whom 211 incident HF cases occurred. Incident HF was examined in relation to % predicted FEV1 and FVC. The Global Initiative on Obstructive Lung Diseases spirometry criteria were used to define airway obstruction. Reduced FEV1, but not FVC in the normal range, was significantly associated with increased risk of HF after adjustment for established HF risk factors including inflammation. The adjusted HRs comparing men in the 6–24th percentile with the highest quartile were 1.91 (1.24 to 2.94) and 1.30 (0.86 to 1.96) for FEV1 and FVC, respectively. FEV1 and FVC were inversely associated with NT-proBNP and cTnT, although the association between FEV1 and incident HF remained after adjustment for NT-proBNP and cTnT. Compared with normal subjects (FEV1/FVC ≥0.70 and FVC≥80%), moderate or severe (FEV1/FVC <0.70 and FEV1 <80%) airflow obstruction was independently associated with HF ((adjusted relative risk 1.59 (1.08 to 2.33)). Airflow restriction (FEV1/FVC ≥0.70 and FVC <80%) was not independently associated with HF. Conclusions Reduced FEV1 reflecting airflow obstruction is associated with cardiac dysfunction and increased risk of incident HF in older men. PMID:26811343

Effectiveness of implementation strategies in improving physician adherence to guideline recommendations in heart failure: a systematic review protocol.

PubMed

Van Spall, Harriette G C; Shanbhag, Deepti; Gabizon, Itzhak; Ibrahim, Quazi; Graham, Ian D; Harlos, Karen; Haynes, R Brian; Connolly, Stuart J

2016-03-31

The uptake of Clinical Practice Guideline (CPG) recommendations that improve outcomes in heart failure (HF) remains suboptimal. We will conduct a systematic review to identify implementation strategies that improve physician adherence to class I recommendations, those with clear evidence that benefits outweigh the risks. We will use American, Canadian and European HF guidelines as our reference. We will conduct a literature search in the databases of MEDLINE, EMBASE, HEALTHSTAR, CINAHL, Cochrane Library, Campbell Collaboration, Joanna Briggs Institute Evidence Based Practice, Centre for Reviews and Dissemination and Evidence Based Practice Centres. We will include prospective studies evaluating implementation interventions aimed at improving uptake of class I CPG recommendations in HF. We will extract data in duplicate. We will classify interventions according to their level of application (ie, provider, organisation, systems level) and common underlying characteristics (eg, education, decision-support, financial incentives) using the Cochrane Effective Practice and Organisation of Care Taxonomy. We will assess the impact of the intervention on adherence to the CPGs. Outcomes will include proportion of eligible patients who were: prescribed a CPG-recommended pharmacological treatment; referred for device consideration; provided self-care education at discharge; and provided left ventricular function assessment. We will include clinical outcomes such as hospitalisations, readmissions and mortality, if data is available. We will identify the common elements of successful and failing interventions, and examine the context in which they were applied, using the Process Redesign contextual framework. We will synthesise the results narratively and, if appropriate, will pool results for meta-analysis. In this review, we will assess the impact of implementation strategies and contextual factors on physician adherence to HF CPGs. We will explore why some interventions may succeed in one setting and fail in another. We will disseminate our findings through briefing reports, publications and presentations. CRD42015017155. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Lateralized Resting-State Functional Brain Network Organization Changes in Heart Failure

PubMed Central

Park, Bumhee; Roy, Bhaswati; Woo, Mary A.; Palomares, Jose A.; Fonarow, Gregg C.; Harper, Ronald M.; Kumar, Rajesh

2016-01-01

Heart failure (HF) patients show brain injury in autonomic, affective, and cognitive sites, which can change resting-state functional connectivity (FC), potentially altering overall functional brain network organization. However, the status of such connectivity or functional organization is unknown in HF. Determination of that status was the aim here, and we examined region-to-region FC and brain network topological properties across the whole-brain in 27 HF patients compared to 53 controls with resting-state functional MRI procedures. Decreased FC in HF appeared between the caudate and cerebellar regions, olfactory and cerebellar sites, vermis and medial frontal regions, and precentral gyri and cerebellar areas. However, increased FC emerged between the middle frontal gyrus and sensorimotor areas, superior parietal gyrus and orbito/medial frontal regions, inferior temporal gyrus and lingual gyrus/cerebellar lobe/pallidum, fusiform gyrus and superior orbitofrontal gyrus and cerebellar sites, and within vermis and cerebellar areas; these connections were largely in the right hemisphere (p<0.005; 10,000 permutations). The topology of functional integration and specialized characteristics in HF are significantly changed in regions showing altered FC, an outcome which would interfere with brain network organization (p<0.05; 10,000 permutations). Brain dysfunction in HF extends to resting conditions, and autonomic, cognitive, and affective deficits may stem from altered FC and brain network organization that may contribute to higher morbidity and mortality in the condition. Our findings likely result from the prominent axonal and nuclear structural changes reported earlier in HF; protecting neural tissue may improve FC integrity, and thus, increase quality of life and reduce morbidity and mortality. PMID:27203600

Self-Efficacy as a Marker of Cardiac Function and Predictor of Heart Failure Hospitalization and Mortality in Patients With Stable Coronary Heart Disease: Findings From the Heart and Soul Study

PubMed Central

Sarkar, Urmimala; Ali, Sadia; Whooley, Mary A.

2009-01-01

Objective The authors sought to evaluate the association of self-efficacy with objective measures of cardiac function, subsequent hospitalization for heart failure (HF), and all-cause mortality. Design Observational cohort of ambulatory patients with stable CHD. The authors measured self-efficacy using a published, validated, 5-item summative scale, the Sullivan Self-Efficacy to Maintain Function Scale. The authors also performed a cardiac assessment, including an exercise treadmill test with stress echocardiography. Main Outcome Measures Hospitalizations for HF, as determined by blinded review of medical records, and all-cause mortality, with adjustment for demographics, medical history, medication use, depressive symptoms, and social support. Results Of the 1,024 predominately male, older CHD patients, 1013 (99%) were available for follow-up, 124 (12%) were hospitalized for HF, and 235 (23%) died during 4.3 years of follow-up. Mean cardiac self-efficacy score was 9.7 (SD 4.5, range 0–20), corresponding to responses between “not at all confident” and “somewhat confident” for ability to maintain function. Lower self-efficacy predicted subsequent HF hospitalization (OR per SD decrease = 1.4, p = 0006), and all-cause mortality (OR per SD decrease = 1.4, p < .0001). After adjustment, the association of cardiac self-efficacy with both HF hospitalization and mortality was explained by worse baseline cardiac function. Conclusion Among patients with CHD, self-efficacy was a reasonable proxy for predicting HF hospitalizations. The increased risk of HF associated with lower baseline self-efficacy was explained by worse cardiac function. These findings indicate that measuring cardiac self-efficacy provides a rapid and potentially useful assessment of cardiac function among outpatients with CHD. PMID:19290708

Plasma Serotonin in Heart Failure: Possible Marker and Potential Treatment Target.

PubMed

Selim, Ahmed M; Sarswat, Nitasha; Kelesidis, Iosif; Iqbal, Muhammad; Chandra, Ramesh; Zolty, Ronald

2017-05-01

The relationship between heart failure (HF) and the serotonergic system has been established in animal studies. However, data on human plasma serotonin level in HF and its significance over the course of the disease is lacking. Serotonin levels were measured in 173 patients (108 males, 65 females), 116 were stable HF and 40 were acute decompensated HF patients. The normal control group included 17 healthy volunteers with no known medical or psychiatric conditions. Patients receiving medications affecting serotonin receptors and those with pulmonary hypertension were excluded. All patients, except for those in the decompensated group, were on stable doses of HF medications. Plasma serotonin levels were significantly elevated in decompensated HF patients compared with stable patients (P=0.002). Higher plasma serotonin levels were associated with worse HF symptoms (NYHA class) and the presence of systolic dysfunction, and was borderline associated with low peak oxygen consumption during cardiopulmonary exercise testing (P=0.055). These results were independent of age, gender, race, hypertension, diabetes, renal failure, weight, coronary artery disease (CAD), atrial fibrillation and medication use. Serotonin is a marker for decompensation in patients with chronic heart failure. Higher serotonin levels were associated with worse HF symptoms and systolic dysfunction. Copyright © 2016 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). Published by Elsevier B.V. All rights reserved.

Dietary sodium modulation of aldosterone activation and renal function during the progression of experimental heart failure.

PubMed

Miller, Wayne L; Borgeson, Daniel D; Grantham, J Aaron; Luchner, Andreas; Redfield, Margaret M; Burnett, John C

2015-02-01

Aldosterone activation is central to the sodium–fluid retention that marks the progression of heart failure (HF). The actions of dietary sodium restriction, a mainstay in HF management, on cardiorenal and neuroendocrine adaptations during the progression of HF are poorly understood. The study aim was to assess the role of dietary sodium during the progression of experimental HF. Experimental HF was produced in a canine model by rapid right ventricular pacing which evolves from early mild HF to overt, severe HF. Dogs were fed one of three diets: (i) high sodium [250 mEq (5.8 g) per day, n =6]; (ii) standard sodium [58 mEq (1.3 g) per day, n =6]; and (iii) sodium restriction [11 mEq (0.25 g) per day, n =6]. During the 38-day study, haemodynamics, renal function, plasma renin activity (PRA), and aldosterone were measured. Changes in haemodynamics at 38 days were similar in all three groups, as were changes in renal function. Aldosterone activation was demonstrated in all three groups; however, dietary sodium restriction, in contrast to high sodium, resulted in early (10 days) activation of PRA and aldosterone. High sodium demonstrated significant suppression of aldosterone activation over the course of HF progression. Excessive dietary sodium restriction particularly in early stage HF results in early aldosterone activation, while normal and excess sodium intake are associated with delayed or suppressed activation. These findings warrant evaluation in humans to determine if dietary sodium manipulation, particularly during early stage HF, may have a significant impact on neuroendocrine disease progression.

Renal impairment and heart failure with preserved ejection fraction early post-myocardial infarction

PubMed Central

Jorapur, Vinod; Lamas, Gervasio A; Sadowski, Zygmunt P; Reynolds, Harmony R; Carvalho, Antonio C; Buller, Christopher E; Rankin, James M; Renkin, Jean; Steg, Philippe Gabriel; White, Harvey D; Vozzi, Carlos; Balcells, Eduardo; Ragosta, Michael; Martin, C Edwin; Srinivas, Vankeepuram S; Wharton III, William W; Abramsky, Staci; Mon, Ana C; Kronsberg, Shari S; Hochman, Judith S

2010-01-01

AIM: To study if impaired renal function is associated with increased risk of peri-infarct heart failure (HF) in patients with preserved ejection fraction (EF). METHODS: Patients with occluded infarct-related arteries (IRAs) between 1 to 28 d after myocardial infarction (MI) were grouped into chronic kidney disease (CKD) stages based on estimated glomerular filtration rate (eGFR). Rates of early post-MI HF were compared among eGFR groups. Logistic regression was used to explore independent predictors of HF. RESULTS: Reduced eGFR was present in 71.1% of 2160 patients, with significant renal impairment (eGFR < 60 mL/min every 1.73 m2) in 14.8%. The prevalence of HF was higher with worsening renal function: 15.5%, 17.8% and 29.4% in patients with CKD stages 1, 2 and 3 or 4, respectively (P < 0.0001), despite a small absolute difference in mean EF across eGFR groups: 48.2 ± 10.0, 47.9 ± 11.3 and 46.2 ± 12.1, respectively (P = 0.02). The prevalence of HF was again higher with worsening renal function among patients with preserved EF: 10.1%, 13.6% and 23.6% (P < 0.0001), but this relationship was not significant among patients with depressed EF: 27.1%, 26.2% and 37.9% (P = 0.071). Moreover, eGFR was an independent correlate of HF in patients with preserved EF (P = 0.003) but not in patients with depressed EF (P = 0.181). CONCLUSION: A significant proportion of post-MI patients with occluded IRAs have impaired renal function. Impaired renal function was associated with an increased rate of early post-MI HF, the association being strongest in patients with preserved EF. These findings have implications for management of peri-infarct HF. PMID:20885993

An Acuity Tool for Heart Failure Case Management: Quantifying Workload, Service Utilization, and Disease Severity.

PubMed

Kilgore, Matthew D

The cardiology service line director at a health maintenance organization (HMO) in Washington State required a valid, reliable, and practical means for measuring workloads and other productivity factors for six heart failure (HF) registered nurse case managers located across three geographical regions. The Kilgore Heart Failure Case Management (KHFCM) Acuity Tool was systematically designed, developed, and validated to measure workload as a dependent function of the number of heart failure case management (HFCM) services rendered and the duration of times spent on various care duties. Research and development occurred at various HMO-affiliated internal medicine and cardiology offices throughout Western Washington. The concepts, methods, and principles used to develop the KHFCM Acuity Tool are applicable for any type of health care professional aiming to quantify workload using a high-quality objective tool. The content matter, scaling, and language on the KHFCM Acuity Tool are specific to HFCM settings. The content matter and numeric scales for the KHFCM Acuity Tool were developed and validated using a mixed-method participant action research method applied to a group of six outpatient HF case managers and their respective caseloads. The participant action research method was selected, because the application of this method requires research participants to become directly involved in the diagnosis of research problems, the planning and execution of actions taken to address those problems, and the implementation of progressive strategies throughout the course of the study, as necessary, to produce the most credible and practical practice improvements (; ; ; ). Heart failure case managers served clients with New York Heart Association Functional Class III-IV HF (), and encounters were conducted primarily by telephone or in-office consultation. A mix of qualitative and quantitative results demonstrated a variety of quality improvement outcomes achieved by the design and practice application of the KHFCM Acuity Tool. Quality improvement outcomes included a more valid reflection of encounter times and demonstration of the KHFCM Acuity Tool as a reliable, practical, credible, and satisfying tool for reflecting HF case manager workloads and HF disease severity. The KHFCM Acuity Tool defines workload simply as a function of the number of HFCM services performed and the duration of time spent on a client encounter. The design of the tool facilitates the measure of workload, service utilization, and HF disease characteristics, independently from the overall measure of acuity, so that differences in individual case manager practice, as well as client characteristics within sites, across sites, and potentially throughout annual seasons, can be demonstrated. Data produced from long-term applications of the KHFCM Acuity Tool, across all regions, could serve as a driver for establishing systemwide HFCM productivity benchmarks or standards of practice for HF case managers. Data produced from localized applications could serve as a reference for coordinating staffing resources or developing HFCM productivity benchmarks within individual regions or sites.

Blood flow dynamics in heart failure

NASA Technical Reports Server (NTRS)

Shoemaker, J. K.; Naylor, H. L.; Hogeman, C. S.; Sinoway, L. I.

1999-01-01

BACKGROUND: Exercise intolerance in heart failure (HF) may be due to inadequate vasodilation, augmented vasoconstriction, and/or altered muscle metabolic responses that lead to fatigue. METHODS AND RESULTS: Vascular and metabolic responses to rhythmic forearm exercise were tested in 9 HF patients and 9 control subjects (CTL) during 2 protocols designed to examine the effect of HF on the time course of oxygen delivery versus uptake (protocol 1) and on vasoconstriction during exercise with 50 mm Hg pressure about the forearm to evoke a metaboreflex (protocol 2). In protocol 1, venous lactate and H+ were greater at 4 minutes of exercise in HF versus CTL (P<0.05) despite similar blood flow and oxygen uptake responses. In protocol 2, mean arterial pressure increased similarly in each group during ischemic exercise. In CTL, forearm blood flow and vascular conductance were similar at the end of ischemic and ambient exercise. In HF, forearm blood flow and vascular conductance were reduced during ischemic exercise compared with the ambient trial. CONCLUSIONS: Intrinsic differences in skeletal muscle metabolism, not vasodilatory dynamics, must account for the augmented glycolytic metabolic responses to moderate-intensity exercise in class II and III HF. The inability to increase forearm vascular conductance during ischemic handgrip exercise, despite a normal pressor response, suggests that enhanced vasoconstriction of strenuously exercising skeletal muscle contributes to exertional fatigue in HF.

A novel ventricular restraint device (ASD) repetitively deliver Salvia miltiorrhiza to epicardium have good curative effects in heart failure management.

PubMed

Naveed, Muhammad; Wenhua, Li; Gang, Wang; Mohammad, Imran Shair; Abbas, Muhammad; Liao, Xiaoqian; Yang, Mengqi; Zhang, Li; Liu, Xiaolin; Qi, Xiaoming; Chen, Yineng; Jiadi, Lv; Ye, Linlan; Zhijie, Wang; Ding, Chen Ding; Feng, Yu; Xiaohui, Zhou

2017-11-01

A novel ventricular restraint is the non-transplant surgical option for the management of an end-stage dilated heart failure (HF). To expand the therapeutic techniques we design a novel ventricular restraint device (ASD) which has the ability to deliver a therapeutic drug directly to the heart. We deliver a Traditional Chinese Medicine (TCM) Salvia miltiorrhiza (Danshen Zhusheye) through active hydraulic ventricular support drug delivery system (ASD) and we hypothesize that it will show better results in HF management than the restraint device and drug alone. SD rats were selected and divided into five groups (n=6), Normal, HF, HF+SM (IV), HF+ASD, HF+ASD+SM groups respectively. Post myocardial infarction (MI), electrocardiography (ECG) showed abnormal heart function in all groups and HF+ASD+SM group showed a significant therapeutic improvement with respect to other treatment HF, HF+ASD, and HF+SM (IV) groups on day 30. The mechanical functions of the heart such as heart rate, LVEDP, and LVSP were brought to normal when treated with ASD+SM and show significant (P value<0.01) compared to other groups. BNP significantly declines in HF+ASD+SM group animals compared with other treatment groups. Masson's Trichrome staining was used to study histopathology of cardiac myocytes and quantification of fibrosis was assessed. The large blue fibrotic area was observed in HF, HF+ASD, and HF+SM (IV) groups while HF+ASD+SM showed negligible fibrotic myocyte at the end of study period (30days). This study proves that novel ASD device augments the therapeutic effect of the drug and delivers Salvia miltiorrhiza to the cardiomyocytes significantly as well as provides additional support to the dilated ventricle by the heart failure. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Design for the sacubitril/valsartan (LCZ696) compared with enalapril study of pediatric patients with heart failure due to systemic left ventricle systolic dysfunction (PANORAMA-HF study).

PubMed

Shaddy, Robert; Canter, Charles; Halnon, Nancy; Kochilas, Lazaros; Rossano, Joseph; Bonnet, Damien; Bush, Christopher; Zhao, Ziqiang; Kantor, Paul; Burch, Michael; Chen, Fabian

2017-11-01

Sacubitril/valsartan (LCZ696) is an angiotensin receptor neprilysin inhibitor approved for the treatment of adult heart failure (HF); however, the benefit of sacubitril/valsartan in pediatric HF patients is unknown. This global multi-center study will use an adaptive, seamless two-part design. Part 1 will assess the pharmacokinetics/pharmacodynamics of single ascending doses of sacubitril/valsartan in pediatric (1 month to <18 years) HF patients with systemic left ventricle and reduced left ventricular systolic function stratified into 3 age groups (Group 1: 6 to <18 years; Group 2: 1 to <6 years; Group 3: 1 month to <1 year). Part 2 is a 52-week, efficacy and safety study where 360 eligible patients will be randomized to sacubitril/valsartan or enalapril. A novel global rank primary endpoint derived by ranking patients (worst-to-best outcome) based on clinical events such as death, initiation of mechanical life support, listing for urgent heart transplant, worsening HF, measures of functional capacity (NYHA/Ross scores), and patient-reported HF symptoms will be used to assess efficacy. The PANORAMA-HF study, which will be the largest prospective pediatric HF trial conducted to date and the first to use a global rank primary endpoint, will determine whether sacubitril/valsartan is superior to enalapril for treatment of pediatric HF patients with reduced systemic left ventricular systolic function. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Biological Therapies: Effects of Proinflammatory Pathways and their Inhibition on the Myocardium of Rheumatoid Athritis Patients.

PubMed

Obermair, Florian; Pieringer, Herwig

2015-01-01

The elevated risk of heart failure (HF) in rheumatoid arthritis (RA) is considered to be partly caused by the chronic low-grade systemic inflammation. As potent suppressors of inflammation, biologics were expected to influence HF development in RA. Unfortunately, case reports of HF in RA patients and non-RA HF studies have suggested that these drugs may even increase HF rates in RA. With this review we want to provide insight into the molecular mechanisms by which elevated cytokines, immune cell alterations and biologics influence myocardial function in RA patients. Beside preclinical data, clinical studies that assess the influence of biologics on HF development are reviewed. Preclinical studies suggest a bidirectional role of the investigated cytokines (TNF-alpha, IL- 1, IL-6) on myocardial function. Common mechanisms of immune cell alterations in HF and RA have been observed in preclinical studies. High doses of infliximab in non-RA patients with HF were found to be harmful. The vast majority of retrospective studies suggest that TNF-alpha inhibitors do not increase the risk of HF development in RA patients. Nevertheless randomized controlled trials are missing and TNF-alpha inhibitors are contraindicated in RA patients with HF NYHA III/IV and should be used with caution in RA patients with HF NYHA I/II based on non-RA HF studies. Due to rare adverse events of HF, rituximab is contraindicated in RA patients with HF NYHA IV. Cytokines seem to have a bidirectional influence on HF development in RA. According to the published evidence it is unlikely that TNFalpha inhibitors substantially increase the risk of HF development in an RA population. Nevertheless they are contraindicated in RA patients with HF NYHA III/IV and should be used with caution in RA patients with HF NYHA I/II. The influence of anakinra, tocilizumab, rituximab and abatacept needs to be investigated in future studies.

Factors Associated With Inadequate Effectiveness of a Multidisciplinary Disease Management Program in Heart Failure Patients Stratified by Galectin 3 Level.

PubMed

Liu, Min-Hui; Wang, Chao-Hung; Chiou, Ai-Fu; Yang, Ning-I; Kuo, Li-Tang

2016-07-21

This study investigated whether multidisciplinary disease management programs (MDPs) exert the same effects in heart failure (HF) patients across risk levels stratified by galectin-3 (Gal-3) level and what factors are associated with inadequate effectiveness of MDP. We used a longitudinal follow-up design based on a previous randomized trial. A total of 355 stabilized hospitalized HF patients were enrolled. The effects of MDP on death and HF-related rehospitalization were analyzed according to Gal-3 levels. During the 4-year follow-up, Gal-3 levels predicted mortality and composite events (p < .001). Multivariable analysis demonstrated the event-lowering effect of MDP (hazard ratio [HR] = 0.49, p = .001 for death and HR = 0.50, p < .001 for composite events). However, the effect of MDP was inadequate for those with high Gal-3 levels (≥17.9 ng/ml), whose 4-year composite event rate was 43% in the MDP arm. Further analysis showed that, in patients with Gal-3 ≥ 17.9 ng/ml, the independent factors associated with a high composite event rate were no MDP, older age, worse New York Heart Association functional class, no angiotensin-converting enzyme inhibitor or angiotensin II receptor blocker use, higher predischarge natriuretic peptide levels, and wider QRS complexes. The effectiveness of MDP for HF patients at high risk was inadequate. Our findings identified the characteristics of these MDP nonresponders. Better integration of advanced care plans based on strategies guided by Gal-3 level is needed to improve care quality. © The Author(s) 2016.

Influence of exercise on oxidative stress in patients with heart failure.

PubMed

Sties, Sabrina Weiss; Andreato, Leonardo Vidal; de Carvalho, Tales; Gonzáles, Ana Inês; Angarten, Vitor Giatte; Ulbrich, Anderson Zampier; de Mara, Lourenço Sampaio; Netto, Almir Schmitt; da Silva, Edson Luiz; Andrade, Alexandro

2018-03-01

Reactive oxygen species play an important role in the pathophysiology of heart failure (HF). In contrast, regular physical exercise can promote adaptations to reactive oxygen species that are beneficial for patients with HF. We completed a systematic review of randomized controlled trials that evaluate the influence of exercise on oxidative stress in patients with HF. Articles were searched in the PubMed, Cochrane, SciELO, and LILACS databases. The search was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The quality of the included studies was assessed using the Physiotherapy Evidence Database scale. We selected 12 studies with a total of 353 participants. The included patients had a left ventricle ejection fraction of < 52% and New York Heart Association functional class II or III disease. A significant increase was observed in peak oxygen consumption (between 10 and 46%) in the group that underwent training (TG). There was an improvement in the oxidative capacity of skeletal muscles in the TG, related to the positive activity of mitochondrial cytochrome c oxidase (between 27 and 41%). An increase in the expression of the enzymes glutathione peroxidase (41%), catalase (between 14 and 42%), and superoxide dismutase (74.5%), and a decrease in lipid peroxidation (between 28.8 and 58.5%) were observed in the TG. Physical training positively influenced the cardiorespiratory capacity and enhanced the benefits of oxidant and antioxidant biomarkers in patients with HF. High-intensity training promoted a 15% increase in the plasma total antioxidant capacity, whereas moderate training had no effect.

Characterization and prediction of adverse events from intensive chronic heart failure management and effect on quality of life: results from the pro-B-type natriuretic peptide outpatient-tailored chronic heart failure therapy (PROTECT) study.

PubMed

Gandhi, Parul U; Szymonifka, Jackie; Motiwala, Shweta R; Belcher, Arianna M; Januzzi, James L; Gaggin, Hanna K

2015-01-01

Serious adverse events (SAEs) from heart failure (HF) therapy are frequent; however, techniques to identify at-risk patients are inadequate. Furthermore, the relationship between SAEs, quality of life (QOL), and cardiac structure are unknown. 151 symptomatic patients with systolic HF were followed for a mean of 10 months. In this post hoc analysis, treatment-related SAEs included acute renal failure, dizziness, hypo/hyperkalemia, hypotension, and syncope. At 1 year, 21 treatment-related SAEs occurred. No difference in SAEs existed between the N-terminal pro-B-type natriuretic peptide (NT-proBNP)-guided arm and the standard of care arm (P = .20). At baseline, patients who suffered SAEs were less likely to be receiving beta-blockers (85.7% vs 97.7%; P = .009) and had worse functional class and lower chloride levels. Patients who experienced SAEs had less improvement in their Minnesota Living With Heart Failure Questionnaire scores and had a trend toward reduced echocardiographic reverse remodeling over the follow-up period. Univariable and multivariable analyses were conducted to develop a risk score for SAE prediction; patients in the highest risk quartile had the shortest time to first cardiovascular event (P = 0.01). NT-proBNP-guided HF care is safe. Experiencing treatment-related SAEs is associated with worse QOL and potentially reduced reverse remodeling. A risk score to prospectively predict SAEs in aggressive HF management was developed. Copyright © 2015 Elsevier Inc. All rights reserved.

Prognostic significance of anaemia in patients with heart failure with preserved and reduced ejection fraction: results from the MAGGIC individual patient data meta-analysis.

PubMed

Berry, C; Poppe, K K; Gamble, G D; Earle, N J; Ezekowitz, J A; Squire, I B; McMurray, J J V; McAlister, F A; Komajda, M; Swedberg, K; Maggioni, A P; Ahmed, A; Whalley, G A; Doughty, R N; Tarantini, L

2016-06-01

Anaemia is common among patients with heart failure (HF) and is an important prognostic marker. We sought to determine the prognostic importance of anaemia in a large multinational pooled dataset of prospectively enrolled HF patients, with the specific aim to determine the prognostic role of anaemia in HF with preserved and reduced ejection fraction (HF-PEF and HF-REF, respectively). Individual person data meta-analysis. Patients with haemoglobin (Hb) data from the MAGGIC dataset were used. Anaemia was defined as Hb < 120 g/l in women and <130 g/l in men. HF-PEF was defined as EF ≥ 50%; HF-REF was EF < 50%. Cox proportional hazard modelling, with adjustment for clinically relevant variables, was undertaken to investigate factors associated with 3-year all-cause mortality. Thirteen thousand two hundred and ninety-five patients with HF from 19 studies (9887 with HF-REF and 3408 with HF-PEF). The prevalence of anaemia was similar among those with HF-REF and HF-PEF (42.8 and 41.6% respectively). Compared with patients with normal Hb values, those with anaemia were older, were more likely to have diabetes, ischaemic aetiology, New York Heart Association class IV symptoms, lower estimated glomerular filtration rate and were more likely to be taking diuretic and less likely to be taking a beta-blocker. Patients with anaemia had higher all-cause mortality (adjusted hazard ratio [aHR] 1.38, 95% confidence interval [CI] 1.25-1.51), independent of EF group: aHR 1.67 (1.39-1.99) in HF-PEF and aHR 2.49 (2.13-2.90) in HF-REF. Anaemia is an adverse prognostic factor in HF irrespective of EF. The prognostic importance of anaemia was greatest in patients with HF-REF. © The Author 2015. Published by Oxford University Press on behalf of the Association of Physicians. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

PROspective MEmory Training to improve HEart failUre Self-care (PROMETHEUS): study protocol for a randomised controlled trial.

PubMed

Cameron, Jan; Rendell, Peter G; Ski, Chantal F; Kure, Christina E; McLennan, Skye N; Rose, Nathan S; Prior, David L; Thompson, David R

2015-04-29

Cognitive impairment is seen in up to three quarters of heart failure (HF) patients and has a significant negative impact on patients' health outcomes. Prospective memory, which is defined as memory to carry out future intentions, is important for functional independence in older adults and involves application of multiple cognitive processes that are often impaired in HF patients. The objective of this study is to examine the effects of prospective memory training on patients' engagement in HF self-care and health outcomes, carer strain and quality of life. The proposed study is a randomised, controlled trial in which 200 patients diagnosed with HF, and their carers will be recruited from 3 major hospitals across Melbourne. Eligible patients with HF will be randomised to receive either: 1) The Virtual Week Training Program - a computerised prospective memory (PM) training program (intervention) or 2) non-adaptive computer-based word puzzles (active control). HF patients' baseline cognitive function will be compared to a healthy control group (n = 60) living independently in the community. Patients will undergo a comprehensive assessment of PM, neuropsychological functioning, self-care, physical, and emotional functioning. Assessments will take place at baseline, 4 weeks and 12 months following intervention. Carers will complete measures assessing quality of life, strain, perceived control in the management of the patients' HF symptoms, and ratings of the patients' level of engagement in HF self-care behaviours. If the Virtual Week Training Program is effective in improving: 1) prospective memory; 2) self-care behaviours, and 3) wellbeing in HF patients, this study will enhance our understanding of impaired cognitive processes in HF and potentially is a mechanism to reduce healthcare costs. Australian New Zealand Clinical Trials Registry #366376; 27 May 2014. https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=366376&isClinicalTrial=False .

Personal growth, symptoms, and uncertainty in community-residing adults with heart failure.

PubMed

Overbaugh, Kristen J; Parshall, Mark B

Personal growth has not been studied extensively in heart failure (HF). To characterize personal growth in HF and its relationships with symptom burden, uncertainty, and demographic and clinical factors. Associations among personal growth, uncertainty, symptom burden, and clinical and demographic variables were examined in adult outpatients with HF using bivariate correlations and multiple regressions. Participants (N = 103; 76% male, mean age = 74 years, 97% New York Heart Association classes II and III) reported moderate levels of personal growth, uncertainty, and symptom burden. Personal growth was weakly correlated with age and symptom burden but not with other study variables. In a regression model, age, sex, ethnicity, disease severity, time since diagnosis, symptom burden, and uncertainty were not significant independent correlates of personal growth. Community-residing patients with HF report moderate personal growth that is not explained by uncertainty, symptom burden, or demographic and clinical variables. Copyright © 2016 Elsevier Inc. All rights reserved.

The Effects of Mitral Valve Repair on Memory Performance, Executive Function, and Psychological Measures in Patients With Heart Failure.

PubMed

Nikendei, Christoph; Schäfer, Hannah; Weisbrod, Matthias; Huber, Julia; Geis, Nicolas; Katus, Hugo A; Bekeredjian, Raffi; Herzog, Wolfgang; Pleger, Sven T; Schultz, Jobst-Hendrik

2016-05-01

Heart failure (HF) is a prevalent disease that remains costly and associated with a high mortality rate. HF is also associated with poor neurocognitive functioning. For the treatment for HF patients with severe mitral regurgitation, the MitraClip device has emerged as a promising interventional tool that reduces the mitral valve leakage and thus increases cardiac output. Currently, there is only limited knowledge on changes in cognitive and psychosocial functioning before and after the MitraClip intervention. Cognitive function (memory and executive function) and psychosocial measures (depression, anxiety, and quality of life) were assessed before and after the MitraClip intervention in 24 HF patients and 23 healthy participants (comparison group). MitraClip intervention in HF patients was followed by improvements in figural long-term memory (p = .003) and executive function (planning ability, p < .001) relative to the comparison group. In addition, the intervention resulted in a significant improvement in depression (p = .002), anxiety (p = .003) and quality of life scores (physical p = .017, mental p = .013) as well as improved 6-minute walk test results over time (p = .002). The presented data provide evidence of a significant improvement in memory and executive function as well as in depression, anxiety, and quality of life scores in patients with chronic HF after MitraClip intervention. Further research is needed to shed light on the long-term development of cognitive function, psychosocial well-being, and clinical parameters after MitraClip intervention and how these factors depend on one another.

Absolute iron deficiency without anaemia in patients with chronic systolic heart failure is associated with poorer functional capacity.

PubMed

Pozzo, Joffrey; Fournier, Pauline; Delmas, Clément; Vervueren, Paul-Louis; Roncalli, Jérôme; Elbaz, Meyer; Galinier, Michel; Lairez, Olivier

2017-02-01

Functional status is one of the main concerns in the management of heart failure (HF). Recently, the FAIR-HF and CONFIRM-HF trials showed that correcting anaemia using intravenous iron supplementation improved functional variables in patients with absolute or relative iron deficiency. Relative iron deficiency is supposed to be a marker of HF severity, as ferritin concentration increases with advanced stages of HF, but little is known about the impact of absolute iron deficiency (AID). To study the impact of AID on functional variables and survival in patients with chronic systolic HF. One hundred and thirty-eight non-anaemic patients with chronic systolic HF were included retrospectively. Patients were divided into two groups according to iron status: the AID group, defined by a ferritin concentration<100μg/L and the non-AID group, defined by a ferritin concentration≥100μg/L. Functional, morphological and biological variables were collected, and survival was assessed. Patients in the AID group had a poorer 6-minute walking test (342 vs. 387m; P=0.03) and poorer peak exercise oxygen consumption (13.8 vs. 16.0mL/min/kg; P=0.01). By multivariable analysis, ferritin<100μg/L was associated with impaired capacity of effort, assessed by peak exercise oxygen consumption. By multivariable analysis, there was no difference in total mortality between groups, with a mean follow-up of 5.1±1.1 years. The poorer functional evaluations in iron-deficient patients previously reported are not caused by the merging of two different populations (i.e. patients with absolute or relative iron deficiency). Our study has confirmed that non-anaemic HF patients with AID have poorer peak oxygen consumption. However, AID has no impact on the survival of these patients. Copyright © 2017. Published by Elsevier Masson SAS.

Assessing the role of Hartree-Fock exchange, correlation energy and long range corrections in evaluating ionization potential, and electron affinity in density functional theory.

PubMed

Vikramaditya, Talapunur; Lin, Shiang-Tai

2017-06-05

Accurate determination of ionization potentials (IPs), electron affinities (EAs), fundamental gaps (FGs), and HOMO, LUMO energy levels of organic molecules play an important role in modeling and predicting the efficiencies of organic photovoltaics, OLEDs etc. In this work, we investigate the effects of Hartree Fock (HF) Exchange, correlation energy, and long range corrections in predicting IP and EA in Hybrid Functionals. We observe increase in percentage of HF exchange results in increase of IPs and decrease in EAs. Contrary to the general expectations inclusion of both HF exchange and correlation energy (from the second order perturbation theory MP2) leads to poor prediction. Range separated Hybrid Functionals are found to be more reliable among various DFT Functionals investigated. DFT Functionals predict accurate IPs whereas post HF methods predict accurate EAs. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

A study of nitrogen behavior in the formation of Ta/TaN and Ti/TaN alloyed metal electrodes on SiO2 and HfO2 dielectrics

NASA Astrophysics Data System (ADS)

Gassilloud, R.; Maunoury, C.; Leroux, C.; Piallat, F.; Saidi, B.; Martin, F.; Maitrejean, S.

2014-04-01

We studied Ta, TaN, and sub-stoichiometric TaNx electrodes (obtained by nitrogen redistribution in Ta/TaN or Ti/TaN bilayers) deposited on thermal SiO2 and HfO2/IL (0.8 nm SiO2 IL, i.e., interlayer) stacks. Effective work-functions (WF) were extracted on MOS capacitor structures on SiO2 bevelled insulator of 4.2 eV for pure Ta, 4.6 eV for TaN, and 4.3 eV for sub-stoichiometric TaNx. This intermediate WF value is explained by TaN nitrogen redistribution with reactive Ta or Ti elements shifting the gate work-function toward the Si conduction band. The same electrodes deposited on an HfO2/IL dielectric showed different behavior: First, the Ta/HfO2/IL stack shows a +200 meV WF increase (towards the Si valence band) compared to the SiO2 dielectric stack. This increase is explained by the well-known HfO2/IL dipole formation. Second, in contrast to electrodes deposited on SiO2, sub-stoichiometric TaNx/HfO2 is found to have a lower WF (4.3 eV), than pure Ta on HfO2 (4.4 eV). This inversion in work-function behavior measured on SiO2 vs. HfO2 is explained by the nitrogen redistribution in Ta/TaN bilayer together with diffusion of nitrogen through the HfO2 layer, leading to Si-N formation which prevents dipole formation at the HfO2/IL interface.

Rural patients' knowledge about heart failure.

PubMed

Dracup, Kathleen; Moser, Debra K; Pelter, Michele M; Nesbitt, Thomas; Southard, Jeffrey; Paul, Steven M; Robinson, Susan; Hemsey, Jessica Zègre; Cooper, Lawton

2014-01-01

Heart failure (HF) is a potentially disabling condition requiring significant patient knowledge to manage the requirements of self-care. The need for self-care is important for all patients but particularly for those living in rural areas that are geographically remote from healthcare services. The aim of this study was to identify the level of knowledge of rural patients with HF and the clinical and demographic characteristics associated with low levels of HF knowledge. Baseline data from 612 patients with HF enrolled in the Rural Education to Improve Outcomes in Heart Failure trial were analyzed using the Heart Failure Knowledge Scale, the Short Test of Functional Health Literacy in Adults, and the anxiety subscale of the Brief Symptom Inventory. Multiple linear regression was used to explore the contribution of sociodemographic and clinical variables to levels of HF knowledge. The mean (SD) age was 66 (13) years; 59% were men, and 50.5% had an ejection fraction of less than 40%. The mean (SD) percent correct on the Heart Failure Knowledge Scale was 69.5% (13%; range, 25%-100%), with the most frequent incorrect items related to symptoms of HF and the need for daily weights. The men and the older patients scored significantly lower in HF knowledge than did the women and the younger patients (P = 0.002 and 0.011, respectively). The patients with preserved systolic function also scored significantly lower than those with systolic HF (P = 0.030). Patients who are at risk for poor self-care because of low levels of HF knowledge can be identified. Older patients, men, and, patients with HF with preserved systolic function may require special educational strategies to gain the knowledge required for effective self-care.

Dietary Sodium Modulation of Aldosterone Activation and Renal Function During the Progression of Experimental Heart Failure Miller: Dietary Sodium and Early Heart Failure

PubMed Central

Miller, Wayne L.; Borgeson, Daniel D.; Grantham, J. Aaron; Luchner, Andreas; Redfield, Margaret M.; Burnett, John C.

2015-01-01

Aims Aldosterone activation is central to the sodium-fluid retention that marks the progression of heart failure (HF). The actions of dietary sodium restriction, a mainstay in HF management, on cardiorenal and neuroendocrine adaptations during the progression of HF are poorly understood. The study aim was to assess the role of dietary sodium during the progression of experimental HF. Methods and Results Experimental HF was produced in a canine model by rapid right ventricular pacing which evolves from early mild HF to overt, severe HF. Dogs were fed one of three diets: 1) high sodium [250 mEq (5.8 grams) per day, n=6]; 2) standard sodium [58 mEq (1.3 grams) per day, n=6]; and 3) sodium restriction [11 mEq (0.25 grams) per day, n=6]. During the 38 day study hemodynamics, renal function, renin activity (PRA), and aldosterone were measured. Changes in hemodynamics at 38 days were similar in all three groups, as were changes in renal function. Aldosterone activation was demonstrated in all three groups, however, dietary sodium restriction, in contrast to high sodium, resulted in early (10 days) activation of PRA and aldosterone. High sodium demonstrated significant suppression of aldosterone activation over the course of HF progression. Conclusions Excessive dietary sodium restriction particularly in early stage HF results in early aldosterone activation, while normal and excess sodium intake are associated with delayed or suppressed activation. These findings warrant evaluation in humans to determine if dietary sodium manipulation, particularly during early stage HF, may have a significant impact on neuroendocrine disease progression. PMID:25823360

Functional Class in Children with Idiopathic Dilated Cardiomyopathy. A pilot Study

PubMed Central

Tavares, Aline Cristina; Bocchi, Edimar Alcides; Guimarães, Guilherme Veiga

2016-01-01

Background Idiopathic dilated cardiomyopathy (IDCM), most common cardiac cause of pediatric deaths, mortality descriptor: a low left ventricular ejection fraction (LVEF) and low functional capacity (FC). FC is never self reported by children. Objective The aims of this study were (i) To evaluate whether functional classifications according to the children, parents and medical staff were associated. (iv) To evaluate whether there was correlation between VO2 max and Weber's classification. Method Prepubertal children with IDCM and HF (by previous IDCM and preserved LVEF) were selected, evaluated and compared. All children were assessed by testing, CPET and functional class classification. Results Chi-square test showed association between a CFm and CFp (1, n = 31) = 20.6; p = 0.002. There was no significant association between CFp and CFc (1, n = 31) = 6.7; p = 0.4. CFm and CFc were not associated as well (1, n = 31) = 1.7; p = 0.8. Weber's classification was associated to CFm (1, n = 19) = 11.8; p = 0.003, to CFp (1, n = 19) = 20.4; p = 0.0001and CFc (1, n = 19) = 6.4; p = 0.04). Conclusion Drawing were helpful for children's self NYHA classification, which were associated to Weber's stratification. PMID:27168472

Interests in high-functioning autism are more intense, interfering, and idiosyncratic, but not more circumscribed, than those in neurotypical development

PubMed Central

Anthony, Laura Gutermuth; Kenworthy, Lauren; Yerys, Benjamin E.; Jankowski, Kathryn F.; James, Joette D.; Harms, Madeline B.; Martin, Alex; Wallace, Gregory L.

2015-01-01

Though circumscribed interests are pathognomonic with autism, how these interests differ from those expressed during neutotypical (NT) development remains unknown. Using a novel measure, the Interests Scale (IS), this study compares interests between 76 NT individuals and 109 individuals with high-functioning autism spectrum disorder (HF-ASD) matched group-wise on age, IQ and gender ratio. Participants and their parents/caregivers completed diagnostic measures (Autism Diagnostic Interview-Revised [ADI-R], Autism Diagnostic Observation Schedule [ADOS]; HF-ASD only), cognitive tests (Wechsler IQ Scales), and questionnaires (the Repetitive Behavior Scale-Revised [RBS-R], the Behavior Rating Inventory of Executive Function [BRIEF], and the Social Responsiveness Scale [SRS]), in addition to the IS. HF-ASD and NT individuals did not differ in number of interest areas, but the types of interests differed considerably. HF-ASD individuals had significantly more intense and interfering interests than NT individuals. Using only the intensity score, 77.5% of individuals were correctly classified (NT or HF-ASD) in a discriminant function analysis. Among individuals with HF-ASD, IS scores were significantly related to ADOS, BRIEF, RBS-R and SRS scores, but not to ADI-R scores, IQ, gender, age or psychotropic medication use. The type and intensity, but not the number, of interests distinguish high-functioning children with ASD from NT children. PMID:23880382

Visual assessment of brain magnetic resonance imaging detects injury to cognitive regulatory sites in patients with heart failure.

PubMed

Pan, Alan; Kumar, Rajesh; Macey, Paul M; Fonarow, Gregg C; Harper, Ronald M; Woo, Mary A

2013-02-01

Heart failure (HF) patients exhibit depression and executive function impairments that contribute to HF mortality. Using specialized magnetic resonance imaging (MRI) analysis procedures, brain changes appear in areas regulating these functions (mammillary bodies, hippocampi, and frontal cortex). However, specialized MRI procedures are not part of standard clinical assessment for HF (which is usually a visual evaluation), and it is unclear whether visual MRI examination can detect changes in these structures. Using brain MRI, we visually examined the mammillary bodies and frontal cortex for global and hippocampi for global and regional tissue changes in 17 HF and 50 control subjects. Significantly global changes emerged in the right mammillary body (HF 1.18 ± 1.13 vs control 0.52 ± 0.74; P = .024), right hippocampus (HF 1.53 ± 0.94 vs control 0.80 ± 0.86; P = .005), and left frontal cortex (HF 1.76 ± 1.03 vs control 1.24 ± 0.77; P = .034). Comparison of the visual method with specialized MRI techniques corroborates right hippocampal and left frontal cortical, but not mammillary body, tissue changes. Visual examination of brain MRI can detect damage in HF in areas regulating depression and executive function, including the right hippocampus and left frontal cortex. Visual MRI assessment in HF may facilitate evaluation of injury to these structures and the assessment of the impact of potential treatments for this damage. Copyright © 2013 Elsevier Inc. All rights reserved.

The association between metabolic syndrome and its components and heart failure in patients referred to a primary care facility.

PubMed

Coelho, Flávio Augusto Colucci; Moutinho, Marco Aurélio Espósito; Miranda, Verônica Alcooforado de; Tavares, Leandro Reis; Rachid, Maurício; Rosa, Maria Luiza Garcia; Mesquita, Evandro Tinoco

2007-07-01

Metabolic syndrome (MS) is characterized by a collection of risk factors that are associated with elevated rates of cardiovascular events and the risk of developing heart failure (HF). In our field, the association of MS in stable chronic HF patients has not been established. To determine the prevalence of MS in relation to gender and HF type in patients treated at a Primary Care Facility. Between January 2005 and August 2006, 144 patients were included in a cross sectional study. An echocardiogram, using the modified criteria of the EPICA study, was performed to determine whether or not the patient had HF, and of which type. Statistical analysis was conducted using the software SAS System, version 6.04, and statistical significance was established as 5%. MS was observed in 111 patients (77%), of which 73 (66%) were females: odds ratio (OR) 0.195--(confidence interval--CI = 0.08 - 0.46) and p< 0.0001. HF was identified in 102 patients (71%) with a great correlation between females and the presence of MS: 51 patients (65%); OR 0.116 (CI = 0.36- 0.37) and p < 0.0001. Among the HF patients, 61 (42%) presented HF with preserved systolic function and 41 (29%) with systolic dysfunction; p = ns. HF with preserved systolic function was associated with the presence of MS in 53 (87%) of the 61 patients, p = 0.022. In our community, MS is closely related to HF with preserved systolic function and to the female gender.

Mobile Technologies for Managing Heart Failure: A Systematic Review and Meta-analysis.

PubMed

Carbo, Anisleidy; Gupta, Manish; Tamariz, Leonardo; Palacio, Ana; Levis, Silvina; Nemeth, Zsuzsanna; Dang, Stuti

2018-04-02

Randomized clinical trials (RCTs) conducted among heart failure (HF) patients have reported that mobile technologies can improve HF-related outcomes. Our aim was to conduct a meta-analysis to evaluate m-Health's impact on healthcare services utilization, mortality, and cost. We searched MEDLINE, Cochrane, CINAHL, and EMBASE for studies published between 1966 and May-2017. We included studies that compared the use of m-Health in HF patients to usual care. m-Health is defined as the use of mobile computing and communication technologies to record and transmit data. The outcomes were HF-related and all-cause hospital days, cost, admissions, and mortality. Our search strategy resulted in 1,494 articles. We included 10 RCTs and 1 quasi-experimental study, which represented 3,109 patients in North America and Europe. Patient average age range was 53-80 years, New York Heart Association (NYHA) class III, and Left Ventricular Ejection Fraction <50%. Patients were mostly monitored daily and followed for an average of 6 months. A reduction was seen in HF-related hospital days. Nonsignificant reductions were seen in HF-related cost, admissions, and mortality and total mortality. We found no significant differences for all-cause hospital days and admissions, and an increase in total cost. m-Health reduced HF-related hospital days, showed reduction trends in total mortality and HF-related admissions, mortality and cost, and increased total costs related to more clinic visits and implementation of new technologies. More studies reporting consistent quality outcomes are warranted to give conclusive information about the effectiveness and cost-effectiveness of m-Health interventions for HF.

Within-Site Variation in Feather Stable Hydrogen Isotope (δ2Hf) Values of Boreal Songbirds: Implications for Assignment to Molt Origin.

PubMed

Nordell, Cameron J; Haché, Samuel; Bayne, Erin M; Sólymos, Péter; Foster, Kenneth R; Godwin, Christine M; Krikun, Richard; Pyle, Peter; Hobson, Keith A

2016-01-01

Understanding bird migration and dispersal is important to inform full life-cycle conservation planning. Stable hydrogen isotope ratios from feathers (δ2Hf) can be linked to amount-weighted long-term, growing season precipitation δ2H (δ2Hp) surfaces to create δ2Hf isoscapes for assignment to molt origin. However, transfer functions linking δ2Hp with δ2Hf are influenced by physiological and environmental processes. A better understanding of the causes and consequences of variation in δ2Hf values among individuals and species will improve the predictive ability of geographic assignment tests. We tested for effects of species, land cover, forage substrate, nest substrate, diet composition, body mass, sex, and phylogenetic relatedness on δ2Hf from individuals at least two years old of 21 songbird species captured during the same breeding season at a site in northeastern Alberta, Canada. For four species, we also tested for a year × species interaction effect on δ2Hf. A model including species as single predictor received the most support (AIC weight = 0.74) in explaining variation in δ2Hf. A species-specific variance parameter was part of all best-ranked models, suggesting variation in δ2Hf was not consistent among species. The second best-ranked model included a forage substrate × diet interaction term (AIC weight = 0.16). There was a significant year × species interaction effect on δ2Hf suggesting that interspecific differences in δ2Hf can differ among years. Our results suggest that within- and among-year interspecific variation in δ2Hf is the most important source of variance typically not being explicitly quantified in geographic assignment tests using non-specific transfer functions to convert δ2Hp into δ2Hf. However, this source of variation is consistent with the range of variation from the transfer functions most commonly being propagated in assignment tests of geographic origins for passerines breeding in North America.

High Fat Diet Augments Amphetamine Sensitization in Mice: Role of Feeding Pattern, Obesity, and Dopamine Terminal Changes

PubMed Central

Fordahl, Steve C.; Locke, Jason L.; Jones, Sara R.

2016-01-01

High fat (HF) diet-induced obesity has been shown to augment behavioral responses to psychostimulants that target the dopamine system. The purpose of this study was to characterize dopamine terminal changes induced by a HF diet that correspond with enhanced locomotor sensitization to amphetamine. C57BL/6J mice had limited (2hr 3d/week) or extended (24h 7d/week) access to a HF diet or standard chow for six weeks. Mice were then repeatedly exposed to amphetamine (AMPH), and their locomotor responses to an amphetamine challenge were measured. Fast scan cyclic voltammetry was used to identify changes in dopamine terminal function after AMPH exposure. Exposure to a HF diet reduced dopamine uptake and increased locomotor responses to acute, high-dose AMPH administration compared to chow fed mice. Microdialysis showed elevated extracellular dopamine in the nucleus accumbens (NAc) coincided with enhanced locomotion after acute AMPH in HF-fed mice. All mice exhibited locomotor sensitization to amphetamine, but both extended and limited access to a HF diet augmented this response. Neither HF-fed group showed the robust amphetamine sensitization-induced increases in dopamine release, reuptake, and amphetamine potency observed in chow fed animals. However, the potency of amphetamine as an uptake inhibitor was significantly elevated after sensitization in mice with extended (but not limited) access to HF. Conversely, after amphetamine sensitization, mice with limited (but not extended) access to HF displayed reduced autoreceptor sensitivity to the D2/D3 agonist quinpirole. Additionally, we observed reduced membrane dopamine transporter (DAT) levels after HF, and a shift in DAT localization to the cytosol was detected with limited access to HF. This study showed that different patterns of HF exposure produced distinct dopamine terminal adaptations to repeated AMPH, which differed from chow fed mice, and enhanced sensitization to AMPH. Locomotor sensitization in chow fed mice coincided with elevated DAT function and increased AMPH potency; however, the enhanced behavioral response to AMPH after HF exposure was unique in that it coincided with reduced DAT function and diet pattern-specific adaptations. PMID:27267686

Differential Effects of Left and Right Prefrontal High-Frequency Repetitive Transcranial Magnetic Stimulation on Resting-State Functional Magnetic Resonance Imaging in Healthy Individuals.

PubMed

Schluter, Renée S; Jansen, Jochem M; van Holst, Ruth J; van den Brink, Wim; Goudriaan, Anna E

2018-03-01

High-frequency repetitive transcranial magnetic stimulation (HF-rTMS) has gained great interest in multiple clinical and research fields and is believed to accomplish its effect by influencing neuronal networks. The dorsolateral prefrontal cortex (dlPFC) is frequently chosen as the cortical target for HF-rTMS. However, very little is known about the differential effect of HF-rTMS over the left and right dlPFC on intrinsic functional connectivity networks in patients or in healthy individuals. The current study assessed the differential effects of left or right HF-rTMS (corrected for sham) on intrinsic independent component analysis (ICA)-defined functional connectivity networks in a sample of 45 healthy individuals. All subjects had a first scanning session in which baseline functional connectivity was assessed. During the second session, individuals received one session of left, right, or sham dlPFC HF-rTMS (60 5-sec trains of 10 Hz at 110% motor threshold). The sham condition was used to correct for time and placebo effects. ICAs were performed to assess baseline differences and stimulation effects on within- and between-network functional connectivity. Stimulation of the left dlPFC resulted in decreased functional connectivity in the salience network, whereas right dlPFC stimulation resulted in increased functional connectivity within this network. No differences between left or right dlPFC stimulation were found in between-network connectivity. These results suggest that left and right HF-rTMS may have differential effects, and more research is needed on the clinical consequences.

The Health and Functioning ICF-60: Development and Psychometric Properties

PubMed Central

Tutelyan, V A; Chatterji, S; Baturin, A K; Pogozheva, A V; Kishko, O N; Akolzina, S E

2014-01-01

Background This paper describes the development and psychometric properties of the Health and Functioning ICF-60 (HF-ICF-60) measure, based on the World Health Organization (WHO) ‘International Classification of Functioning, Disability and Health: ICF’ (2001). The aims of the present study were to test psychometric properties of the HF-ICF-60, developed as a measure that would be responsive to change in functioning through changes in health and nutritional status, as a prospective measure to monitor health and nutritional status of populations and to explore the relationship of the HF-ICF-60 with quality of life measures such as the World Health Organization WHOQOL-BREF quality of life assessment in relation to non-communicable diseases. Methods The HF-ICF-60 measure consists of 60 items selected from the ICF by an expert panel, which included 18 items that cover Body Functions, 21 items that cover Activities and Participation, rated on five-point scales, and 21 items that cover Environmental Factors (seven items cover Individual Environmental Factors and 14 items cover Societal Environmental Factors), rated on nine-point scales. The HF-ICF-60 measure was administered to the Russian nationally representative sample within the Russian National Population Quality of Life, Health and Nutrition Survey, in 2004 (n = 9807) and 2005 (n = 9560), as part of the two waves of the Russian Longitudinal Monitoring Survey (RLMS). The statistical analyses were carried out with the use of both classical and modern psychometric methods, such as factor analysis, and based on Item Response Theory, respectively. Results The HF-ICF-60 questionnaire is a new measure derived directly from the ICF and covers the ICF components as follows: Body Functions, Activities and Participation, and Environmental Factors (Individual Environmental Factors and Societal Environmental Factors). The results from the factor analyses (both Exploratory Factor Analyses and Confirmatory Factor Analyses) show good support for the proposed structure together with an overall higher-order factor for each scale of the measure. The measure has good reliability and validity, and sensitivity to change in the health and nutritional status of respondents over time. Normative values were developed for the Russian adult population. Conclusions The HF-ICF-60 has shown good psychometric properties in the two waves of the nationally representative RLMS, which provided considerable support to using the HF-ICF-60 data as the normative health and functioning values for the Russian population. Similarly, the administration of the WHOQOL-BREF in the same two waves of the nationally representative RLMS has allowed the normative quality of life values for the Russian population to be obtained. Therefore, the objective assessment of health and functioning of the HF-ICF-60 could be mapped onto the subjective evaluation of quality of life of the WHOQOL-BREF to increase the potential usefulness of the surveys in relation to non-communicable diseases. © 2014 The Authors. Clinical Psychology & Psychotherapy. Published by John Wiley & Sons, Ltd. Key Practitioner Message The HF-ICF-60 offers a new perspective in measuring change in functioning through changes in lifestyle and diet. The HF-ICF-60 can be combined with the WHOQOL-BREF to map the objective assessment of health and functioning onto the subjective evaluation of quality of life. Combined use of the HF-ICF-60 and the WHOQOL-BREF can be especially useful for national and global monitoring and surveillance of implementation of measures to reduce risk factors of non-communicable diseases and to promote healthy lifestyles and healthy diets. PMID:24931300

Modulation of RAAS-natriuretic peptides in the treatment of HF: Old guys and newcomers.

PubMed

Mollace, Vincenzo; Gliozzi, Micaela; Capuano, Annalisa; Rossi, Francesco

2017-01-01

The use of renin-angiotensin-aldosterone system (RAAS) inhibitors in the treatment of chronic heart failure (HF) and arterial hypertension is recommended by the European Society of Cardiology Guidelines on the basis of consolidated evidence supporting their efficacy in the development of such a disease. However, the high incidence of re-hospitalization and mortality in patients undergoing chronic HF, leads to the need for the development of novel RAAS inhibitors possessing a better pharmacokinetic/pharmacodynamics profile in approaching hemodynamic imbalance and myocardial dysfunction associated with the development of chronic HF. Here we summarize some of the recent advances in the area of RAAS-modulators, including novel renin inhibitors, mineralcorticoid receptor antagonists and novel AT1 and AT2-receptor modulators. In addition, the pharmacology of a new class of compounds which display both AT1-receptor blocking properties combined with inhibition of neprilysin, the vasopeptidase enzyme degradating natriuretic peptide (ARNi), will be reviewed, alongside with their impact in the pathophysiology of chronic HF. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

‘Engage me in taking care of my heart’: a grounded theory study on patient–cardiologist relationship in the hospital management of heart failure

PubMed Central

Barello, Serena; Graffigna, Guendalina; Vegni, Elena; Savarese, Mariarosaria; Lombardi, Federico; Bosio, A Claudio

2015-01-01

Objective In approaching the study and practice of heart failure (HF) management, authors recognise that the patient–doctor relationship has a central role in engaging patients in their care. This study aims at identifying the features and the levers of HF patient engagement and suggestions for orienting clinical encounters. Design Using a grounded theory approach, we conducted 22 in-depth interviews (13 patients with HF, 5 physicians and 4 caregivers). Data were collected and analysed using open, axial and selective coding procedures according to the grounded theory principles. Settings All interviews were conducted in an office in a university hospital located in a metropolitan area of Milan, Italy. Participants The data comprised a total of 22 patient, hospital cardiologist and caregiver interviews. Patients aged ≥18 years with New York Heart Association (NYHA) Functional Class of II or III were eligible to take part. Patients were recruited primarily through their referral cardiologist. Results The HF patient engagement process develops in four main phases that are characterised by different patients’ emotional, cognitive and behavioural dynamics that contribute to shape the process of a patient's meaning making towards health and illness regarding their care. The emerging model illustrates that HF patient engagement entails a meaning-making process enacted by the patient after the critical event. This implies patients’ ability to give sense to their care experience and to their disease, symptomatology and treatments, and their changes along their illness course. Doctors are recognised as crucial in fostering patients’ engagement along all the phases of the process as they contribute to providing patients with self-continuity and give new meaning to their illness experience. Conclusions This study identifies the core experiential domains and the main levers involved in driving patients with HF to effectively engage in their disease management. The model emerging from this study may help clinicians think in a fresh way about encounters with patients and their role in fostering their patients’ health engagement. PMID:25776041

Sleep-Disordered Breathing Exacerbates Muscle Vasoconstriction and Sympathetic Neural Activation in Patients with Systolic Heart Failure.

PubMed

Lobo, Denise M L; Trevizan, Patricia F; Toschi-Dias, Edgar; Oliveira, Patricia A; Piveta, Rafael B; Almeida, Dirceu R; Mady, Charles; Bocchi, Edimar A; Lorenzi-Filho, Geraldo; Middlekauff, Holly R; Negrão, Carlos E

2016-11-01

Sleep-disordered breathing (SDB) is common in patients with heart failure (HF), and hypoxia and hypercapnia episodes activate chemoreceptors stimulating autonomic reflex responses. We tested the hypothesis that muscle vasoconstriction and muscle sympathetic nerve activity (MSNA) in response to hypoxia and hypercapnia would be more pronounced in patients with HF and SDB than in patients with HF without SDB (NoSBD). Ninety consecutive patients with HF, New York Heart Association functional class II-III, and left ventricular ejection fraction ≤40% were screened for the study. Forty-one patients were enrolled: NoSDB (n=13, 46 [39-53] years) and SDB (n=28, 57 [54-61] years). SDB was characterized by apnea-hypopnea index ≥15 events per hour (polysomnography). Peripheral (10% O 2 and 90% N 2 , with CO 2 titrated) and central (7% CO 2 and 93% O 2 ) chemoreceptors were stimulated for 3 minutes. Forearm and calf blood flow were evaluated by venous occlusion plethysmography, MSNA by microneurography, and blood pressure by beat-to-beat noninvasive technique. Baseline forearm blood flow, forearm vascular conductance, calf blood flow, and calf vascular conductance were similar between groups. MSNA was higher in the SDB group. During hypoxia, the vascular responses (forearm blood flow, forearm vascular conductance, calf blood flow, and calf vascular conductance) were significantly lower in the SDB group compared with the NoSDB group (P<0.01 to all comparisons). Similarly, during hypercapnia, the vascular responses (forearm blood flow, forearm vascular conductance, calf blood flow, and calf vascular conductance) were significantly lower in the SDB group compared with the NoSDB group (P<0.001 to all comparisons). MSNA were higher in response to hypoxia (P=0.024) and tended to be higher to hypercapnia (P=0.066) in the SDB group. Patients with HF and SDB have more severe muscle vasoconstriction during hypoxia and hypercapnia than HF patients without SDB, which seems to be associated with endothelial dysfunction and, in part, increased MSNA response. © 2016 American Heart Association, Inc.

Sympathetic Response and Outcomes Following Renal Denervation in Patients With Chronic Heart Failure: 12-Month Outcomes From the Symplicity HF Feasibility Study.

PubMed

Hopper, Ingrid; Gronda, Edoardo; Hoppe, Uta C; Rundqvist, Bengt; Marwick, Thomas H; Shetty, Sharad; Hayward, Christopher; Lambert, Thomas; Hering, Dagmara; Esler, Murray; Schlaich, Markus; Walton, Antony; Airoldi, Flavio; Brandt, Mathias C; Cohen, Sidney A; Reiters, Pascalle; Krum, Henry

2017-09-01

Heart failure (HF) is associated with chronic sympathetic activation. Renal denervation (RDN) aims to reduce sympathetic activity by ablating the renal sympathetic nerves. We investigated the effect of RDN in patients with chronic HF and concurrent renal dysfunction in a prospective, multicenter, single-arm feasibility study. Thirty-nine patients with chronic systolic HF (left ventricular ejection fraction [LVEF] <40%, New York Heart Association class II-III,) and renal impairment (estimated glomerular filtration rate [eGFR; assessed with the use of the Modification of Diet in Renal Disease equation] < 75 mL • min -1  • 1.73 m -2 ) on stable medical therapy were enrolled. Mean age was 65 ± 11 years; 62% had ischemic HF. The average number of ablations per patient was 13 ± 3. No protocol-defined safety events were associated with the procedure. One subject experienced a renal artery occlusion that was possibly related to the denervation procedure. Statistically significant reductions in N-terminal pro-B-type natriuretic peptide (NT-proBNP; 1530 ± 1228 vs 1428 ± 1844 ng/mL; P = .006) and 120-minute glucose tolerance test (11.2 ± 5.1 vs 9.9 ± 3.6; P = .026) were seen at 12 months, but there was no significant change in LVEF (28 ± 9% vs 29 ± 11%; P= .536), 6-minute walk test (384 ± 96 vs 391 ± 97 m; P= .584), or eGFR (52.6 ± 15.3 vs 52.3 ± 18.5 mL • min -1  • 1.73 m -2 ; P= .700). RDN was associated with reductions in NT-proBNP and 120-minute glucose tolerance test in HF patients 12 months after RDN treatment. There was no deterioration in other indices of cardiac and renal function in this small feasibility study. Copyright © 2017 Elsevier Inc. All rights reserved.

Nutritional status and its effects on muscle wasting in patients with chronic heart failure: insights from Studies Investigating Co-morbidities Aggravating Heart Failure.

PubMed

Saitoh, Masakazu; Dos Santos, Marcelo Rodrigues; Ebner, Nicole; Emami, Amir; Konishi, Masaaki; Ishida, Junichi; Valentova, Miroslava; Sandek, Anja; Doehner, Wolfram; Anker, Stefan D; von Haehling, Stephan

2016-12-01

Inadequate nutritional status has been linked to poor outcomes in patients with heart failure (HF). Skeletal muscle wasting affects about 20% of ambulatory patients with HF. The impact of nutritional intake and appetite on skeletal muscle wasting has not been investigated so far. We sought to investigate the impact of nutritional status on muscle wasting and mortality in ambulatory patients with HF. We studied 130 ambulatory patients with HF who were recruited as a part of the Studies Investigating Co-morbidities Aggravating Heart Failure (SICA-HF) program. Muscle wasting was defined according to criteria of sarcopenia, i.e., appendicular skeletal muscle mass two standard deviations below the mean of a healthy reference group aged 18-40 years. Nutritional status was evaluated using the Mini-Nutritional Assessment-Short Form (MNA-SF). Functional capacity was assessed as peak oxygen consumption (peak VO 2 ) by cardiopulmonary exercise testing, 6‑minute walk testing, and the Short Physical Performance Battery (SPPB). At baseline, 19 patients (15%) presented with muscle wasting. Patients with muscle wasting had significantly lower values of peak VO 2 , 6‑minute walk distance, SPPB, and MNA-SF score than patients without (all p < 0.05). In multivariate analysis, MNA-SF remained an independent predictor of muscle wasting after adjustment for age and New York Heart Association class (odds ratio [OR] 0.66; confidence interval [CI] 0.50-0.88; p < 0.01). A total of 16 (12%) patients died during a mean follow-up of 21 months. In Cox regression analysis, MNA-SF (OR 0.80, CI 0.64-0.99, p = 0.04), left ventricular ejection fraction (OR 0.93, CI 0.86-0.99, p = 0.05), and peak VO 2 (OR 0.78, CI 0.65-0.94, p = 0.008) were predictors of death. MNA-SF is an independent predictor of muscle wasting and mortality in ambulatory patients with HF. Nutritional screening should be included as a fundamental part of the overall assessment of these patients.

Prognostic value of indeterminable anaerobic threshold in heart failure.

PubMed

Agostoni, Piergiuseppe; Corrà, Ugo; Cattadori, Gaia; Veglia, Fabrizio; Battaia, Elisa; La Gioia, Rocco; Scardovi, Angela B; Emdin, Michele; Metra, Marco; Sinagra, Gianfranco; Limongelli, Giuseppe; Raimondo, Rosa; Re, Federica; Guazzi, Marco; Belardinelli, Romualdo; Parati, Gianfranco; Magrì, Damiano; Fiorentini, Cesare; Cicoira, Mariantonietta; Salvioni, Elisabetta; Giovannardi, Marta; Mezzani, Alessandro; Scrutinio, Domenico; Di Lenarda, Andrea; Mantegazza, Valentina; Ricci, Roberto; Apostolo, Anna; Iorio, Annamaria; Paolillo, Stefania; Palermo, Pietro; Contini, Mauro; Vassanelli, Corrado; Passino, Claudio; Piepoli, Massimo F

2013-09-01

In patients with heart failure (HF), during maximal cardiopulmonary exercise test, anaerobic threshold (AT) is not always identified. We evaluated whether this finding has a prognostic meaning. We recruited and prospectively followed up, in 14 dedicated HF units, 3058 patients with systolic (left ventricular ejection fraction <40%) HF in stable clinical conditions, New York Heart Association class I to III, who underwent clinical, laboratory, echocardiographic, and cardiopulmonary exercise test investigations at study enrollment. We excluded 921 patients who did not perform a maximal exercise, based on lack of achievement of anaerobic metabolism (peak respiratory quotient ≤1.05). Primary study end point was a composite of cardiovascular death and urgent cardiac transplant, and secondary end point was all-cause death. Median follow-up was 3.01 (1.39-4.98) years. AT was identified in 1935 out of 2137 patients (90.54%). At multivariable logistic analysis, failure in detecting AT resulted significantly in reduced peak oxygen uptake and higher metabolic exercise and cardiac and kidney index score value, a powerful prognostic composite HF index (P<0.001). At multivariable analysis, the following variables were significantly associated with primary study end point: peak oxygen uptake (% pred; P<0.001; hazard ratio [HR]=0.977; confidence interval [CI]=0.97-0.98), ventilatory efficiency slope (P=0.01; HR=1.02; CI=1.01-1.03), hemoglobin (P<0.05; HR=0.931; CI=0.87-1.00), left ventricular ejection fraction (P<0.001; HR=0.948; CI=0.94-0.96), renal function (modification of diet in renal disease; P<0.001; HR=0.990; CI=0.98-0.99), sodium (P<0.05; HR=0.967; CI=0.94-0.99), and AT nonidentification (P<0.05; HR=1.41; CI=1.06-1.89). Nonidentification of AT remained associated to prognosis also when compared with metabolic exercise and cardiac and kidney index score (P<0.01; HR=1.459; CI=1.09-1.10). Similar results were obtained for the secondary study end point. The inability to identify AT most often occurs in patients with severe HF, and it has an independent prognostic role in HF.

'Engage me in taking care of my heart': a grounded theory study on patient-cardiologist relationship in the hospital management of heart failure.

PubMed

Barello, Serena; Graffigna, Guendalina; Vegni, Elena; Savarese, Mariarosaria; Lombardi, Federico; Bosio, A Claudio

2015-03-16

In approaching the study and practice of heart failure (HF) management, authors recognise that the patient-doctor relationship has a central role in engaging patients in their care. This study aims at identifying the features and the levers of HF patient engagement and suggestions for orienting clinical encounters. Using a grounded theory approach, we conducted 22 in-depth interviews (13 patients with HF, 5 physicians and 4 caregivers). Data were collected and analysed using open, axial and selective coding procedures according to the grounded theory principles. All interviews were conducted in an office in a university hospital located in a metropolitan area of Milan, Italy. The data comprised a total of 22 patient, hospital cardiologist and caregiver interviews. Patients aged ≥18 years with New York Heart Association (NYHA) Functional Class of II or III were eligible to take part. Patients were recruited primarily through their referral cardiologist. The HF patient engagement process develops in four main phases that are characterised by different patients' emotional, cognitive and behavioural dynamics that contribute to shape the process of a patient's meaning making towards health and illness regarding their care. The emerging model illustrates that HF patient engagement entails a meaning-making process enacted by the patient after the critical event. This implies patients' ability to give sense to their care experience and to their disease, symptomatology and treatments, and their changes along their illness course. Doctors are recognised as crucial in fostering patients' engagement along all the phases of the process as they contribute to providing patients with self-continuity and give new meaning to their illness experience. This study identifies the core experiential domains and the main levers involved in driving patients with HF to effectively engage in their disease management. The model emerging from this study may help clinicians think in a fresh way about encounters with patients and their role in fostering their patients' health engagement. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Mortality in Advanced Chronic Obstructive Pulmonary Disease and Heart Failure Following Cardiopulmonary Rehabilitation.

PubMed

Kang, Youjeong; Steele, Bonnie G; Burr, Robert L; Dougherty, Cynthia M

2018-07-01

Cardiopulmonary rehabilitation (CR) improves physical function and quality of life (QoL) in chronic obstructive pulmonary disease (COPD) and heart failure (HF), but it is unknown if CR improves outcomes in very severe disease. This study's purpose was to describe functional capacity (6-min walk distance [6MWD], steps/day), symptoms (dyspnea, depression), QoL (Short-Form Health Survey-Veterans [SF-36 V]) and cardiopulmonary function ( N-terminal pro-brain natriuretic peptide [NT-proBNP], forced expiratory volume in 1 s [FEV 1 ]), and derive predictors of mortality among patients with severe COPD and HF who participated in CR. In this secondary analysis of a randomized controlled trial comparing two CR methods in severe COPD and HF, 90 (COPD = 63, HF = 27) male veterans, mean age 66 ± 9.24 years, 79% Caucasian, and body mass index 31 kg/m 2 , were followed for 12 months after CR. The COPD group had greater functional decline than the HF group (6MWD, p = .006). Dyspnea was lower ( p = .001) and QoL higher ( p = .006) in the HF group. Mean NT-proBNP was higher in the HF group at all time points. FEV 1 improved over 12 months in both groups ( p = .01). Mortality was 8.9%, 16.7%, and 37.8% at 12, 24, and 60 months, respectively. One-year predictors of mortality were baseline total steps (<3,000/day), 6MWD (<229 meters), and NT-proBNP level (>2,000 mg/pg). In very severe COPD and HF, risks of mortality over 12 months can predict patients unlikely to benefit from CR and should be considered at initial referral.

Maternal high-fat diet impairs glucose metabolism, β-cell function and proliferation in the second generation of offspring rats.

PubMed

Huang, Yan-Hong; Ye, Ting-Ting; Liu, Chong-Xiao; Wang, Lei; Chen, Yuan-Wen; Dong, Yan

2017-01-01

This study aimed to assess the impact of perinatal high-fat (HF) diet in female Sprague-Dawley rats (F0) on glucose metabolism and islet function in their early life of second-generation of offspring (F2). F0 rats were fed with a standard chow (SC) or HF diet for 8 weeks before mating, up to termination of lactation for their first-generation of offspring (F1-SC and F1-HF). F1 females were mated with normal males at the age of week 11, and producing F2 offspring (F2-SC, F2-HF). All the offspring were fed SC diet after weaning for 3 weeks. The glucose level and islet function of F2 offspring were assessed at the age of week 3 and 12. The F2-HF offspring had a high birth weight and maintained a higher body mass at the age of week 3 and 12, along with an impaired glucose tolerance and lower serum insulin levels compared with the F2-SC. β-cell proliferation was also impaired in the islets of F2-HF rats at the age of week 3 and 12. The pancreatic and duodenal homeobox factor-1 (Pdx1) and Neurogenic differentiation 1 (NeuroD1) expressions were decreased in the islet of F2-HF rats at the age of week 12. Maternal HF diet during pre-gestation, gestation, and lactation in rats could result in the increased body weight and glucose intolerance in their early life of F2 offspring due to impaired β-cell function and proliferation.

Low-intensity interval exercise training attenuates coronary vascular dysfunction and preserves Ca²⁺-sensitive K⁺ current in miniature swine with LV hypertrophy.

PubMed

Emter, Craig A; Tharp, Darla L; Ivey, Jan R; Ganjam, Venkataseshu K; Bowles, Douglas K

2011-10-01

Coronary vascular dysfunction has been observed in several models of heart failure (HF). Recent evidence indicates that exercise training is beneficial for patients with HF, but the precise intensity and underlying mechanisms are unknown. Left ventricular (LV) hypertrophy can play a significant role in the development of HF; therefore, the purpose of this study was to assess the effects of low-intensity interval exercise training on coronary vascular function in sedentary (HF) and exercise trained (HF-TR) aortic-banded miniature swine displaying LV hypertrophy. Six months postsurgery, in vivo coronary vascular responses to endothelin-1 (ET-1) and adenosine were measured in the left anterior descending coronary artery. Baseline and maximal coronary vascular conductance were similar between all groups. ET-1-induced reductions in coronary vascular conductance (P < 0.05) were greater in HF vs. sedentary control and HF-TR groups. Pretreatment with the ET type A (ET(A)) receptor blocker BQ-123 prevented ET-1 hypersensitivity in HF animals. Whole cell voltage clamp was used to characterize composite K(+) currents (I(K(+))) in coronary smooth muscle cells. Raising internal Ca(2+) from 200 to 500 nM increased Ca(2+)-sensitive K(+) current in HF-TR and control, but not HF animals. In conclusion, an ET(A)-receptor-mediated hypersensitivity to ET-1, elevated resting LV wall tension, and decreased coronary smooth muscle cell Ca(2+)-sensitive I(K(+)) was found in sedentary animals with LV hypertrophy. Low-intensity interval exercise training preserved normal coronary vascular function and smooth muscle cell Ca(2+)-sensitive I(K(+)), illustrating a potential mechanism underlying coronary vascular dysfunction in a large-animal model of LV hypertrophy. Our results demonstrate the potential clinical impact of exercise on coronary vascular function in HF patients displaying pathological LV hypertrophy.

Low-intensity interval exercise training attenuates coronary vascular dysfunction and preserves Ca2+-sensitive K+ current in miniature swine with LV hypertrophy

PubMed Central

Tharp, Darla L.; Ivey, Jan R.; Ganjam, Venkataseshu K.; Bowles, Douglas K.

2011-01-01

Coronary vascular dysfunction has been observed in several models of heart failure (HF). Recent evidence indicates that exercise training is beneficial for patients with HF, but the precise intensity and underlying mechanisms are unknown. Left ventricular (LV) hypertrophy can play a significant role in the development of HF; therefore, the purpose of this study was to assess the effects of low-intensity interval exercise training on coronary vascular function in sedentary (HF) and exercise trained (HF-TR) aortic-banded miniature swine displaying LV hypertrophy. Six months postsurgery, in vivo coronary vascular responses to endothelin-1 (ET-1) and adenosine were measured in the left anterior descending coronary artery. Baseline and maximal coronary vascular conductance were similar between all groups. ET-1-induced reductions in coronary vascular conductance (P < 0.05) were greater in HF vs. sedentary control and HF-TR groups. Pretreatment with the ET type A (ETA) receptor blocker BQ-123 prevented ET-1 hypersensitivity in HF animals. Whole cell voltage clamp was used to characterize composite K+ currents (IK+) in coronary smooth muscle cells. Raising internal Ca2+ from 200 to 500 nM increased Ca2+-sensitive K+ current in HF-TR and control, but not HF animals. In conclusion, an ETA-receptor-mediated hypersensitivity to ET-1, elevated resting LV wall tension, and decreased coronary smooth muscle cell Ca2+-sensitive IK+ was found in sedentary animals with LV hypertrophy. Low-intensity interval exercise training preserved normal coronary vascular function and smooth muscle cell Ca2+-sensitive IK+, illustrating a potential mechanism underlying coronary vascular dysfunction in a large-animal model of LV hypertrophy. Our results demonstrate the potential clinical impact of exercise on coronary vascular function in HF patients displaying pathological LV hypertrophy. PMID:21841018

The Vascular Marker Soluble Fms-like Tyrosine Kinase 1 is Associated with Disease Severity and Adverse Outcomes in Chronic Heart Failure

PubMed Central

Ky, Bonnie; French, Benjamin; Ruparel, Kosha; Sweitzer, Nancy K.; Fang, James C.; Levy, Wayne C.; Sawyer, Douglas B.; Cappola, Thomas P.

2011-01-01

Objectives We sought to evaluate placental growth factor (PlGF) and soluble fms-like tyrosine kinase 1 (sFlt-1) as clinical biomarkers in chronic heart failure (HF). Background Vascular remodeling is a crucial compensatory mechanism in chronic HF. The angiogenic ligand PlGF and its target receptor fms-like tyrosine kinase 1 (Flt-1) modulate vascular growth and function, but their relevance in human HF is undefined. Methods We measured plasma PlGF and sFlt-1 in 1,403 patients from the Penn Heart Failure Study, a multi-center cohort of chronic systolic HF. Subjects were followed for death, cardiac transplantation, or ventricular assist device placement over a median follow-up of 2 years. Results sFlt-1 was independently associated with measures of HF severity, including NYHA Class (p<0.01) and BNP (p<0.01). Patients in the 4th quartile of sFlt-1 (>379pg/ml) had a 6.17-fold increased risk of adverse outcomes (p<0.01). This association was robust, even after adjustment for the Seattle Failure Model (HR 2.54, 95%CI 1.76–2.27, p<0.01) and clinical confounders including heart failure etiology (HR 1.67, 95%CI 1.06–2.63, p=0.03). Combined assessment of sFlt-1 and BNP exhibited high predictive accuracy at 1-year (AUC 0.791, 95%CI 0.752–0.831), that was greater than either marker alone (p<0.01 and p=0.03, respectively). In contrast, PlGF was not an independent marker of disease severity or outcomes. Conclusions Our findings support a role for sFlt-1 in the biology of human heart failure. With additional study, circulating sFlt-1 may emerge as a clinically useful biomarker to assess the influence of vascular remodeling on clinical outcomes. PMID:21757116

Clinical presentation, management, in-hospital and 90-day outcomes of heart failure patients in Trivandrum, Kerala, India: the Trivandrum Heart Failure Registry.

PubMed

Harikrishnan, Sivadasanpillai; Sanjay, Ganapathi; Anees, Thajudeen; Viswanathan, Sunitha; Vijayaraghavan, Govindan; Bahuleyan, Charantharayil G; Sreedharan, Madhu; Biju, Ramabhadran; Nair, Tiny; Suresh, Krishnan; Rao, Ashok C; Dalus, Dae; Huffman, Mark D; Jeemon, Panniyammakal

2015-08-01

To evaluate the presentation, management, and outcomes of patients hospitalized for heart failure (HF) in Trivandrum, India. The Trivandrum Heart Failure Registry (THFR) enrolled consecutive admissions from 13 urban and five rural hospitals in Trivandrum with a primary diagnosis of HF from January to December 2013. Clinical characteristics at presentation, treatment, in-hospital outcomes, and 90-day mortality data were collected. 'Guideline-based' medical treatment was defined as the combination of beta-blockers, angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, and aldosterone receptor blockers in patients with left ventricular systolic dysfunction (LVSD). We enrolled 1205 cases (834 men, 69%) into the registry. Mean (standard deviation) age was 61.2 (13.7) years. The most common HF aetiology was ischaemic heart disease (IHD) (72%). Heart failure with preserved ejection fraction (≥45%) constituted 26% of the population. The median hospital stay was 6 days (interquartile range = 4-9 days) with an in-hospital mortality rate of 8.5% (95% confidence interval 6.9-10.0). The 90-day all-cause mortality rate was 2.43 deaths per 1000 person-days (95% confidence interval 2.11-2.78). Guideline-based medical treatment was given to 19% and 25% of patients with LVSD during hospital admission and at discharge, respectively. Older age, lower education, poor ejection fraction, higher serum creatinine, New York Heart Association functional class IV, and suboptimal medical treatment were associated with higher risk of 90-day mortality. Patients hospitalized with HF in the THFR were younger, more likely to be men, had a higher prevalence of IHD, reported longer length of hospital stay, and higher mortality compared with published data from other registries. We also identified key areas for improving hospital-based HF medical care in Trivandrum. © 2015 The Authors. European Journal of Heart Failure © 2015 European Society of Cardiology.

Mind the Gap: Mismatches Between Clinicians and Patients in Heart Failure Medication Management.

PubMed

Chin, Ken Lee; Skiba, Marina; Reid, Christopher M; Tonkin, Andrew; Hopper, Ingrid; Mariani, Justin A; Liew, Danny

2018-02-01

Previous studies on the 'treatment gap' in patients with heart failure (HF) have focused either on prescribing or patients' adherence to prescribed treatment. This study sought to determine whether or not recent initiatives to close the gap have also minimised any mismatches between physicians' expectation of their patients' medications, medications in the patients' possession and their actual medication use. A cross-sectional observational survey was conducted from December 2015 to June 2016 in The Alfred Hospital HF clinic in Melbourne, Australia. Patients were invited to participate if they had chronic HF (NYHA class II to IV), were aged ≥ 60 years, had no history of HF related hospitalisation within the past 6 months and were prescribed at least two HF medications. Of 123 eligible patients, 102 were recruited into the study. Beta-blockers, mineralocorticoid receptor antagonists, loop diuretics and statins were associated with the highest rates of mismatches of drugs and doses, ranging from 10 to 17%. Discrepancy of total daily doses was the most common type of mismatch. Overall, only 23.5% of the patients were taking the right drugs at the right doses as expected by their cardiologists/HF specialists. Despite improved prescribers' adherence to guideline-directed medical therapy, there remain considerable mismatches between prescribers' expectation of patients' HF medications, medications in patients' possession and their actual medication use. Initiatives to improve this situation are urgently needed.

Baseline characteristics of patients in the Reduction of Events with Darbepoetin alfa in Heart Failure trial (RED-HF).

PubMed

McMurray, John J V; Anand, Inder S; Diaz, Rafael; Maggioni, Aldo P; O'Connor, Christopher; Pfeffer, Marc A; Solomon, Scott D; Tendera, Michal; van Veldhuisen, Dirk J; Albizem, Moetaz; Cheng, Sunfa; Scarlata, Debra; Swedberg, Karl; Young, James B

2013-03-01

This report describes the baseline characteristics of patients in the Reduction of Events with Darbepoetin alfa in Heart Failure trial (RED-HF) which is testing the hypothesis that anaemia correction with darbepoetin alfa will reduce the composite endpoint of death from any cause or hospital admission for worsening heart failure, and improve other outcomes. Key demographic, clinical, and laboratory findings, along with baseline treatment, are reported and compared with those of patients in other recent clinical trials in heart failure. Compared with other recent trials, RED-HF enrolled more elderly [mean age 70 (SD 11.4) years], female (41%), and black (9%) patients. RED-HF patients more often had diabetes (46%) and renal impairment (72% had an estimated glomerular filtration rate < 60 mL/min/1.73 m2). Patients in RED-HF had heart failure of longer duration [5.3 (5.4) years], worse NYHA class (35% II, 63% III, and 2% IV), and more signs of congestion. Mean EF was 30% (6.8%). RED-HF patients were well treated at randomization, and pharmacological therapy at baseline was broadly similar to that of other recent trials, taking account of study-specific inclusion/exclusion criteria. Median (interquartile range) haemoglobin at baseline was 112 (106-117) g/L. The anaemic patients enrolled in RED-HF were older, moderately to markedly symptomatic, and had extensive co-morbidity.

The impact of non-alcoholic fatty liver disease fibrosis score on cardiac prognosis in patients with chronic heart failure.

PubMed

Takahashi, Tetsuya; Watanabe, Tetsu; Shishido, Tetsuro; Watanabe, Ken; Sugai, Takayuki; Toshima, Taku; Kinoshita, Daisuke; Yokoyama, Miyuki; Tamura, Harutoshi; Nishiyama, Satoshi; Arimoto, Takanori; Takahashi, Hiroki; Yamanaka, Tamon; Miyamoto, Takuya; Kubota, Isao

2018-07-01

Liver abnormalities have a strong impact on clinical outcomes in patients with heart failure (HF), and are known as cardio-hepatic syndrome. The non-alcoholic fatty liver disease (NAFLD) fibrosis score (NFS) has been developed to identify liver fibrosis in patients with NAFLD. It remains to be determined whether NFS is associated with cardiovascular prognosis in patients with chronic heart failure (CHF). We calculated NFS in 516 patients with CHF admitted to our hospital. The clinical endpoints were deaths due to progressive HF, myocardial infarction, stroke, and sudden cardiac death, and rehospitalization for worsening HF. There were 173 cardiovascular events noted during a median follow-up of 464 days. Patients with cardiovascular events showed a higher NFS as compared with those without. We divided the patients into four groups according to quartiles of NFS. The proportion of New York Heart Association functional class III/IV and serum brain natriuretic peptide levels were increased with increasing NFS. Kaplan-Meier analysis revealed that cardiovascular event rate was increased with increasing NFS in patients with CHF. In multivariate Cox proportional hazards analysis, NFS was independently associated with cardiovascular events after adjustment for confounding factors. Elevated NFS was associated with unfavorable outcomes in patients with CHF. Liver fibrosis assessed by NFS may provide valuable prognostic information in patients with CHF.

A peripheral blood transcriptome biomarker test to diagnose functional recovery potential in advanced heart failure.

PubMed

Deng, Mario C

2018-05-08

Heart failure (HF) is a complex clinical syndrome that causes systemic hypoperfusion and failure to meet the body's metabolic demands. In an attempt to compensate, chronic upregulation of the sympathetic nervous system and renin-angiotensin-aldosterone leads to further myocardial injury, HF progression and reduced O 2 delivery. This triggers progressive organ dysfunction, immune system activation and profound metabolic derangements, creating a milieu similar to other chronic systemic diseases and presenting as advanced HF with severely limited prognosis. We hypothesize that 1-year survival in advanced HF is linked to functional recovery potential (FRP), a novel clinical composite parameter that includes HF severity, secondary organ dysfunction, co-morbidities, frailty, disabilities as well as chronological age and that can be diagnosed by a molecular biomarker.

Serum levels of NT- pro ANP, BNP, NT-pro BNP and function of the left atrium in patients with heart failure and preserved ejection fraction after myocardial infarction

NASA Astrophysics Data System (ADS)

Shurupov, V.; Suslova, T.; Ryabov, V.

2015-11-01

The objective of our study was to evaluate the levels of natriuretic peptides in patients (pts) with heart failure with preserved ejection fraction (HFpEF) in 12 month after ST elevation myocardial infarction (STEMI) with a focus on the function of left atrium (LA) and left ventricular (LV) filling pressure. 55 pts were included in the study. 6-minute walk test was performed. Echo exam was performed by the diagnostic system VIVID 7. BNP in whole blood was determined using the Triage ® Meter BNP test. The serum levels of NT-pro BNP, NT-pro ANP («Biomedica», Austria) were determined in blood samples by enzyme-linked immune-sorbent assay (ELISA). LA volume index were differences (16.03±3.39 ml/m2; 25.36±8.26 ml/m2; 29.41±9.46 ml/m2 accordingly I, II, III class) depending on severity of HF. Well as E/E' ratio were differences (7.5±1.4; 9.8±5.1; 13.5±7.6 accordingly I, II, III class) depending on severity of HF. The LA volume index correlated with levels of NT-pro ANP (R=0.29; p=0.04), levels of NT-pro BNP (R=0.37; p=0.01), levels of BNP (R=0.51; p=0.0001). The LV filling pressure correlated with levels of NT-pro ANP (R=0.45; p=0.002), levels of NT-pro BNP (R=0.49; p=0.001), levels of BNP (R=0.37; p=0.01).

Heart Failure Increases the Risk of Adverse Renal Outcomes in Patients With Normal Kidney Function.

PubMed

George, Lekha K; Koshy, Santhosh K G; Molnar, Miklos Z; Thomas, Fridtjof; Lu, Jun L; Kalantar-Zadeh, Kamyar; Kovesdy, Csaba P

2017-08-01

Heart failure (HF) is associated with poor cardiac outcomes and mortality. It is not known whether HF leads to poor renal outcomes in patients with normal kidney function. We hypothesized that HF is associated with worse long-term renal outcomes. Among 3 570 865 US veterans with estimated glomerular filtration rate (eGFR) ≥60 mL min -1 1.73 m -2 during October 1, 2004 to September 30, 2006, we identified 156 743 with an International Classification of Diseases , Ninth Revision , diagnosis of HF. We examined the association of HF with incident chronic kidney disease (CKD), the composite of incident CKD or mortality, and rapid rate of eGFR decline (slopes steeper than -5 mL min -1 1.73 m -2 y -1 ) using Cox proportional hazard analyses and logistic regression. Adjustments were made for various confounders. The mean±standard deviation baseline age and eGFR of HF patients were 68±11 years and 78±14 mL min -1 1.73 m -2 and in patients without HF were 59±14 years and 84±16 mL min -1 1.73 m -2 , respectively. HF patients had higher prevalence of hypertension, diabetes mellitus, cardiac, peripheral vascular and chronic lung diseases, stroke, and dementia. Incidence of CKD was 69.0/1000 patient-years in HF patients versus 14.5/1000 patient-years in patients without HF, and 22% of patients with HF had rapid decline in eGFR compared with 8.5% in patients without HF. HF patients had a 2.12-, 2.06-, and 2.13-fold higher multivariable-adjusted risk of incident CKD, composite of CKD or mortality, and rapid eGFR decline, respectively. HF is associated with significantly higher risk of incident CKD, incident CKD or mortality, and rapid eGFR decline. Early diagnosis and management of HF could help reduce the risk of long-term renal complications. © 2017 American Heart Association, Inc.

Protective effect of anti-oxidants on endothelial function in young Korean-Asians compared to Caucasians.

PubMed

Yim, Jongeun; Petrofsky, Jerrold; Berk, Lee; Daher, Noha; Lohman, Everett; Moss, Abigail; Cavalcanti, Paula

2012-08-01

Previous studies show that Asians have an impaired blood flow response (BFR) to occlusion after a single high fat (HF) meal. The mechanism is believed to be the presence and susceptibility to high free radicals in their blood. The free radical concentration after a HF meal has not been examined in Asians. Further the BFR to heat after a single HF meal in Koreans has not been measured. This study evaluated postprandial endothelial function by measuring the BFR to vascular occlusion and local heat before and after a HF meal and the interventional effects of anti-oxidant vitamins on improving endothelial function in young Korean-Asians (K) compared to Caucasians (C) with these assessments. Ten C and ten K participated in the study (mean age 25.3±3.6 years old). BFR to vascular occlusion and local heat and oxidative stress were assessed after a single low fat (LF) and HF meal at 2 hours compared to baseline. After administration of vitamins (1000 mg of vitamin C, 800 IU of vitamin E, and 300 mg of Coenzyme Q-10) for 14 days, the same measurements were made. This study showed that the skin BFR to vascular occlusion and local heat following a HF meal significantly decreased and free radicals significantly increased at 2 hours compared to baseline in K (p<.001), but not in C. When vitamins were given, the BFR to vascular occlusion and local heat before and after HF meal were not significantly different in K and C. These findings suggest that even a single HF meal can reduce endothelial response to stress through an oxidative stress mechanism but can be blocked by antioxidants, probably through scavenging free radicals in K. Since endothelial function improved even before a HF meal in K, endothelial damage from an Americanized diet may be reduced in K by antioxidants.

Protective effect of anti-oxidants on endothelial function in young Korean-Asians compared to Caucasians

PubMed Central

Yim, Jongeun; Petrofsky, Jerrold; Berk, Lee; Daher, Noha; Lohman, Everett; Moss, Abigail; Cavalcanti, Paula

2012-01-01

Summary Background Previous studies show that Asians have an impaired blood flow response (BFR) to occlusion after a single high fat (HF) meal. The mechanism is believed to be the presence and susceptibility to high free radicals in their blood. The free radical concentration after a HF meal has not been examined in Asians. Further the BFR to heat after a single HF meal in Koreans has not been measured. Material/Methods This study evaluated postprandial endothelial function by measuring the BFR to vascular occlusion and local heat before and after a HF meal and the interventional effects of anti-oxidant vitamins on improving endothelial function in young Korean-Asians (K) compared to Caucasians (C) with these assessments. Ten C and ten K participated in the study (mean age 25.3±3.6 years old). BFR to vascular occlusion and local heat and oxidative stress were assessed after a single low fat (LF) and HF meal at 2 hours compared to baseline. After administration of vitamins (1000 mg of vitamin C, 800 IU of vitamin E, and 300 mg of Coenzyme Q-10) for 14 days, the same measurements were made. Results This study showed that the skin BFR to vascular occlusion and local heat following a HF meal significantly decreased and free radicals significantly increased at 2 hours compared to baseline in K (p<.001), but not in C. When vitamins were given, the BFR to vascular occlusion and local heat before and after HF meal were not significantly different in K and C. Conclusions These findings suggest that even a single HF meal can reduce endothelial response to stress through an oxidative stress mechanism but can be blocked by antioxidants, probably through scavenging free radicals in K. Since endothelial function improved even before a HF meal in K, endothelial damage from an Americanized diet may be reduced in K by antioxidants. PMID:22847195

Heart and brain interaction in patients with heart failure: overview and proposal for a taxonomy. A position paper from the Study Group on Heart and Brain Interaction of the Heart Failure Association.

PubMed

Doehner, Wolfram; Ural, Dilek; Haeusler, Karl Georg; Čelutkienė, Jelena; Bestetti, Reinaldo; Cavusoglu, Yuksel; Peña-Duque, Marco A; Glavas, Duska; Iacoviello, Massimo; Laufs, Ulrich; Alvear, Ricardo Marmol; Mbakwem, Amam; Piepoli, Massimo F; Rosen, Stuart D; Tsivgoulis, Georgios; Vitale, Cristiana; Yilmaz, M Birhan; Anker, Stefan D; Filippatos, Gerasimos; Seferovic, Petar; Coats, Andrew J S; Ruschitzka, Frank

2018-02-01

Heart failure (HF) is a complex clinical syndrome with multiple interactions between the failing myocardium and cerebral (dys-)functions. Bi-directional feedback interactions between the heart and the brain are inherent in the pathophysiology of HF: (i) the impaired cardiac function affects cerebral structure and functional capacity, and (ii) neuronal signals impact on the cardiovascular continuum. These interactions contribute to the symptomatic presentation of HF patients and affect many co-morbidities of HF. Moreover, neuro-cardiac feedback signals significantly promote aggravation and further progression of HF and are causal in the poor prognosis of HF. The diversity and complexity of heart and brain interactions make it difficult to develop a comprehensive overview. In this paper a systematic approach is proposed to develop a comprehensive atlas of related conditions, signals and disease mechanisms of the interactions between the heart and the brain in HF. The proposed taxonomy is based on pathophysiological principles. Impaired perfusion of the brain may represent one major category, with acute (cardio-embolic) or chronic (haemodynamic failure) low perfusion being sub-categories with mostly different consequences (i.e. ischaemic stroke or cognitive impairment, respectively). Further categories include impairment of higher cortical function (mood, cognition), of brain stem function (sympathetic over-activation, neuro-cardiac reflexes). Treatment-related interactions could be categorized as medical, interventional and device-related interactions. Also interactions due to specific diseases are categorized. A methodical approach to categorize the interdependency of heart and brain may help to integrate individual research areas into an overall picture. © 2017 The Authors. European Journal of Heart Failure © 2017 European Society of Cardiology.

Rehabilitation Therapy in Older Acute Heart Failure Patients (REHAB-HF) Trial: Design and Rationale

PubMed Central

Reeves, Gordon R.; Whellan, David J.; Duncan, Pamela; O’Connor, Christopher M.; Pastva, Amy M.; Eggebeen, Joel D; Hewston, Leigh Ann; Morgan, Timothy M.; Reed, Shelby D.; Rejeski, W. Jack; Mentz, Robert J.; Rosenberg, Paul B.; Kitzman, Dalane W.

2017-01-01

Background Acute decompensated heart failure (ADHF) is a leading cause of hospitalization in older persons in the United States. Reduced physical function and frailty are major determinants of adverse outcomes in older patients with hospitalized ADHF. However, these are not addressed by current heart failure (HF) management strategies and there has been little study of exercise training in older, frail HF patients with recent ADHF. Hypothesis Targeting physical frailty with a multi-domain structured physical rehabilitation intervention will improve physical function and reduce adverse outcomes among older patients experiencing a HF hospitalization. Study Design Rehabilitation Therapy in Older Acute Heart Failure Patients (REHAB-HF) is a multi-center clinical trial in which 360 patients ≥ 60 years hospitalized with ADHF will be randomized either to a novel 12-week multi-domain physical rehabilitation intervention or to attention control. The goal of the intervention is to improve balance, mobility, strength and endurance utilizing reproducible, targeted exercises administered by a multi-disciplinary team with specific milestones for progression. The primary study aim is to assess the efficacy of the REHAB-HF intervention on physical function measured by total Short Physical Performance Battery score. The secondary outcome is 6-month all-cause rehospitalization. Additional outcome measures include quality of life and costs. Conclusions REHAB-HF is the first randomized trial of a physical function intervention in older patients with hospitalized ADHF designed to determine if addressing deficits in balance, mobility, strength and endurance improves physical function and reduces rehospitalizations. It will address key evidence gaps concerning the role of physical rehabilitation in the care of older patients, those with ADHF, frailty, and multiple comorbidities. PMID:28267466

A machine learning system to improve heart failure patient assistance.

PubMed

Guidi, Gabriele; Pettenati, Maria Chiara; Melillo, Paolo; Iadanza, Ernesto

2014-11-01

In this paper, we present a clinical decision support system (CDSS) for the analysis of heart failure (HF) patients, providing various outputs such as an HF severity evaluation, HF-type prediction, as well as a management interface that compares the different patients' follow-ups. The whole system is composed of a part of intelligent core and of an HF special-purpose management tool also providing the function to act as interface for the artificial intelligence training and use. To implement the smart intelligent functions, we adopted a machine learning approach. In this paper, we compare the performance of a neural network (NN), a support vector machine, a system with fuzzy rules genetically produced, and a classification and regression tree and its direct evolution, which is the random forest, in analyzing our database. Best performances in both HF severity evaluation and HF-type prediction functions are obtained by using the random forest algorithm. The management tool allows the cardiologist to populate a "supervised database" suitable for machine learning during his or her regular outpatient consultations. The idea comes from the fact that in literature there are a few databases of this type, and they are not scalable to our case.

Accuracy of Hartree-Fock wave functions for electron-H/sub 2/ scattering calculations

DOE Office of Scientific and Technical Information (OSTI.GOV)

Feldt, A.N.

1988-05-01

Recent papers on electron-N/sub 2/ scattering by Rumble, Stevens, and Truhlar (J. Phys. B 17, 3151 (1984)) and Weatherford, Brown, and Temkin (Phys. Rev. A 35, 4561 (1987)) have suggested that Hartree-Fock (HF) wave functions may not be accurate for calculating potentials for use in studying electron-molecule collisions. A comparison of results for electron-H/sub 2/ scattering using both correlated and HF wave functions is presented. It is found that for both elastic and inelastic collisions and for all energies considered (up to 10 eV) the HF wave functions yield results in excellent agreement with those obtained from the more accuratemore » wave functions.« less

Relationships Among Cognitive Function and Cerebral Blood Flow, Oxidative Stress, and Inflammation in Older Heart Failure Patients.

PubMed

Kure, Christina E; Rosenfeldt, Franklin L; Scholey, Andrew B; Pipingas, Andrew; Kaye, David M; Bergin, Peter J; Croft, Kevin D; Wesnes, Keith A; Myers, Stephen P; Stough, Con

2016-07-01

The mechanisms for cognitive impairment in heart failure (HF) are unclear. We investigated the relative contributions of cerebral blood flow velocity (BFV), oxidative stress, and inflammation to HF-associated cognitive impairment. Thirty-six HF patients (≥60 years) and 40 healthy controls (68 ± 7 vs 67 ± 5 years, P > .05; 69% vs 50% male, P > .05) completed the Cognitive Drug Research computerized assessment battery and Stroop tasks. Common carotid (CCA) and middle cerebral arterial BFV were obtained by transcranial Doppler. Blood samples were collected for oxidant (diacron-reactive oxygen metabolites; F2-isoprostanes), antioxidant (coenzyme Q10; CoQ10), and inflammatory markers (high-sensitivity C-reactive protein). Compared with controls, patients exhibited impaired attention (Cognitive Drug Research's Power of Attention domain, congruent Stroop) and executive function (incongruent Stroop). Multiple regression modeling showed that CCA-BFV and CoQ10 but not group predicted performance on attention and executive function. Additionally, in HF patients, CCA-BFV and CoQ10 (β = -0.34 vs β = -0.35) were significant predictors of attention, and CCA-BFV (β = -0.34) was a predictor of executive function. Power of Attention and executive function is impaired in older HF patients, and reduced CCA-BFV and CoQ10 are associated with worse cognition. Interventions addressing these mechanisms may improve cognition in older HF patients. Copyright © 2016 Elsevier Inc. All rights reserved.

Role of gender in heart failure with normal left ventricular ejection fraction.

PubMed

Regitz-Zagrosek, Vera; Brokat, Sebastian; Tschope, Carsten

2007-01-01

Heart failure with normal ejection fraction (HF-NEF) is frequently believed to be more common in women than in men. However, the interaction of gender and age has rarely been analyzed in detail, and knowledge of the distinction between pre- and postmenopausal women is lacking. Some of the studies that have described a higher prevalence of HF-NEF in women relied on clinical diagnoses of HF together with normal systolic function and did not measure diastolic function. This applies to the analysis of patients hospitalized for HF and some epidemiological investigations that agree on the greater prevalence of HF-NEF in women. Population-based studies with echocardiographic determination of diastolic function have suggested equal or greater prevalence of diastolic dysfunction in men. Major risk factors for HF-NEF include hypertension, aging, obesity, diabetes, and ischemia. Hypertension is more frequent in women and can contribute to left ventricular and arterial stiffening in a gender-specific way. Aging, obesity, and diabetes affect myocardial and vascular stiffness differently and lead to different forms of myocardial hypertrophy in women and men. In contrast, ischemia may play a greater role in men. Gender differences in ventricular diastolic distensibility, in vascular stiffness and ventricular/vascular coupling, in skeletal muscle adaptation to HF, and in the perception of symptoms may contribute to a greater rate of HF-NEF in women. The underlying molecular mechanisms include gender differences in calcium handling, in the NO system, and in natriuretic peptides. Estrogen affects collagen synthesis and degradation and inhibits the renin-angiotensin system. Effects of estrogen may provide benefit to premenopausal women, and the loss of its protective mechanisms may render the heart of postmenopausal women more vulnerable. Thus, a number of molecular mechanisms can contribute to the gender differences in HF-NEF.

Additional predictive value of nutritional status in the prognostic assessment of heart failure patients.

PubMed

La Rovere, M T; Maestri, R; Olmetti, F; Paganini, V; Riccardi, G; Riccardi, R; Pinna, G D; Traversi, E

2017-03-01

Nutritional status (NS) is not routinely assessed in HF. We sought to evaluate whether NS may be additive to a comprehensive pre-discharge evaluation based on a clinical score that includes BMI (MAGGIC) and on an index of functional capacity (six minute walking test, 6mWT) in HF patients. The CONUT (Controlling Nutritional Status) score (including serum albumin level, total cholesterol and lymphocyte count) was computed in 466 consecutive patients (mean age 61 ± 11 years, NYHA class 2.6 ± 0.6, LVEF 34 ± 11%, BMI 27.2 ± 4.5) who had pre-discharge MAGGIC and 6MWT. The endpoint was all-cause mortality. Mild or moderate undernourishment was present in 54% of patients with no differences across BMI strata. The 12-month event rate was 7.7%. Deceased patients had a more compromised NS (CONUT 2.8 ± 1.5 vs 1.7 ± 1.3, p < 0.0001), and a more advanced HF (MAGGIC 28.2 ± 6.0 vs 22.0 ± 6.6, p < 0.0001; 6MWT 311.1 ± 102.2 vs. 408.9 ± 95.9 m, p < 0.0001). The 12-month mortality rate varied from 4% for well-nourished to 11% for undernourished patients (p = 0.008). At univariate analysis, the CONUT was predictive for all-cause mortality with a Hazard Ratio of 1.701 [95% CI 1.363-2.122], p < 0.0001. Multivariable analysis showed that the CONUT significantly added to the combination of MAGGIC and 6MWT and improved predictive discrimination and risk classification (c-index 0.82 [95% CI 0.75-0.88], integrated discrimination improvement 0.028 [95% CI 0.015-0.081]). In HF patients assessment of NS, significantly improves prediction of 12-month mortality on top of the information provided by clinical evaluation and functional capacity and should be incorporated in the overall assessment of HF patients. Copyright © 2016 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.

Galectin-3 in ambulatory patients with heart failure: results from the HF-ACTION study.

PubMed

Felker, G Michael; Fiuzat, Mona; Shaw, Linda K; Clare, Robert; Whellan, David J; Bettari, Luca; Shirolkar, Shailesh C; Donahue, Mark; Kitzman, Dalane W; Zannad, Faiez; Piña, Ileana L; O'Connor, Christopher M

2012-01-01

Galectin-3 is a soluble ß-galactoside-binding lectin released by activated cardiac macrophages. Elevated levels of galectin-3 have been found to be associated with adverse outcomes in patients with heart failure. We evaluated the association between galectin-3 and long-term clinical outcomes in ambulatory heart failure patients enrolled in the HF-ACTION study. HF-ACTION was a randomized, controlled trial of exercise training in patients with chronic heart failure caused by left ventricular systolic dysfunction. Galectin-3 was assessed at baseline in a cohort of 895 HF-ACTION subjects with stored plasma samples available. The association between galectin-3 and clinical outcomes was assessed using a series of Cox proportional hazards models. Higher galectin-3 levels were associated with other measures of heart failure severity, including higher New York Heart Association class, lower systolic blood pressure, higher creatinine, higher amino-terminal proB-type natriuretic peptide (NTproBNP), and lower maximal oxygen consumption. In unadjusted analysis, there was a significant association between elevated galectin-3 levels and hospitalization-free survival (unadjusted hazard ratio, 1.14 per 3-ng/mL increase in galectin-3; P<0.0001). In multivariable modeling, the prognostic impact of galectin-3 was significantly attenuated by the inclusion of other known predictors, and galectin-3 was no longer a significant predictor after the inclusion of NTproBNP. Galectin-3 is elevated in ambulatory heart failure patients and is associated with poor functional capacity and other known measures of heart failure severity. In univariate analysis, galectin-3 was significantly predictive of long-term outcomes, but this association did not persist after adjustment for other predictors, especially NTproBNP. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00047437.

Galectin-3 in Ambulatory Patients with Heart Failure: Results from the HF-ACTION Study

PubMed Central

Felker, G. Michael; Fiuzat, Mona; Shaw, Linda K.; Clare, Robert; Whellan, David J.; Bettari, Luca; Shirolkar, Shailesh C.; Donahue, Mark; Kitzman, Dalane W.; Zannad, Faiez; Piña, Ileana L.; O’Connor, Christopher M.

2011-01-01

Background Galectin-3 is a soluble ß-galactoside-binding lectin released by activated cardiac macrophages. Elevated levels of galectin-3 have been found to be associated with adverse outcomes in patients with heart failure. We evaluated the association between galectin-3 and long-term clinical outcomes in ambulatory heart failure patients enrolled in the HF-ACTION study. Methods and Results HF-ACTION was a randomized controlled trial of exercise training in patients with chronic heart failure due to left ventricular (LV) systolic dysfunction. Galectin-3 was assessed at baseline in a cohort of 895 HF-ACTION subjects with stored plasma samples available. The association between galectin-3 and clinical outcomes was assessed using a series of Cox proportional hazards models. Higher galectin-3 levels were associated with other measures of heart failure severity, including higher NYHA class, lower systolic blood pressure, higher creatinine, higher NTproBNP, and lower maximal oxygen consumption. In unadjusted analysis, there was a significant association between elevated galectin-3 levels and hospitalization-free survival (unadjusted hazard ratio = 1.14 per 3 ng/mL increase in galectin-3, P<0.0001). In multivariable modeling, the prognostic impact of galectin-3 was significantly attenuated by the inclusion of other known predictors and galectin-3 was no longer a significant predictor after the inclusion of NTproBNP. Conclusions Galectin-3 is elevated in ambulatory heart failure patients and is associated with poor functional capacity and other known measures of heart failure severity. In univariate analysis, galectin-3 was significantly predictive of long-term outcomes, but this association did not persist after adjustment for other predictors, especially NTproBNP. PMID:22016505

Self-Care and All-Cause Mortality in Patients With Chronic Heart Failure.

PubMed

Kessing, Dionne; Denollet, Johan; Widdershoven, Jos; Kupper, Nina

2016-03-01

This study examined the association of self-care with all-cause mortality in a cohort of patients with chronic heart failure (HF). Although self-care is crucial to maintain health in patients with chronic HF, studies examining an association with clinical outcomes are scarce. Consecutive patients with chronic HF (n = 559, mean age 66.3 ± 9.5 years, 78% men) completed the 9-item European Heart Failure Self-care Behaviour scale. Our endpoint was all-cause mortality. Associations between self-care and all-cause mortality were assessed with Kaplan-Meier analyses and multivariable Cox regression accounting for standard sociodemographic and clinical covariates, psychological distress, and self-rated health. After a median follow-up of 5.5 ± 2.4 years (range 16 weeks to 9.9 years), 221 deaths (40%) from any cause were recorded. There was no evidence of a mortality benefit in patients high over those low in global self-care (p = 0.71). In post hoc analyses, low self-reported sodium intake was associated with increased mortality (adjusted hazard ratio: 1.47; 95% confidence interval: 1.10 to 1.96; p = 0.01). Other significant predictors of mortality were: male sex, lack of a partner, New York Heart Association functional class III to IV, and increasing comorbid conditions. Global self-care was not associated with long-term mortality whereas low self-reported sodium intake independently predicted increased all-cause mortality beyond parameters of disease severity. Replication of findings is needed as well as studies examining the correspondence of subjectively and objectively measured sodium intake and its effects on long-term prognosis in patients with chronic HF. Copyright © 2016 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Efficacy and safety of LCZ696 (sacubitril-valsartan) according to age: insights from PARADIGM-HF

PubMed Central

Jhund, Pardeep S.; Fu, Michael; Bayram, Edmundo; Chen, Chen-Huan; Negrusz-Kawecka, Marta; Rosenthal, Arvo; Desai, Akshay S.; Lefkowitz, Martin P.; Rizkala, Adel R.; Rouleau, Jean L.; Shi, Victor C.; Solomon, Scott D.; Swedberg, Karl; Zile, Michael R.; McMurray, John J.V.; Packer, Milton

2015-01-01

Background The age at which heart failure develops varies widely between countries and drug tolerance and outcomes also vary by age. We have examined the efficacy and safety of LCZ696 according to age in the Prospective comparison of angiotensin receptor neprilysin inhibitor with angiotensin converting enzyme inhibitor to Determine Impact on Global Mortality and Morbidity in Heart Failure trial (PARADIGM-HF). Methods In PARADIGM-HF, 8399 patients aged 18–96 years and in New York Heart Association functional class II–IV with an LVEF ≤40% were randomized to either enalapril or LCZ696. We examined the pre-specified efficacy and safety outcomes according to age category (years): <55 (n = 1624), 55–64 (n = 2655), 65–74 (n = 2557), and ≥75 (n = 1563). Findings The rate (per 100 patient-years) of the primary outcome of cardiovascular (CV) death or heart failure hospitalization (HFH) increased from 13.4 to 14.8 across the age categories. The LCZ696:enalapril hazard ratio (HR) was <1.0 in all categories (P for interaction between age category and treatment = 0.94) with an overall HR of 0.80 (0.73, 0.87), P < 0.001. The findings for HFH were similar for CV and all-cause mortality and the age category by treatment interactions were not significant. The pre-specified safety outcomes of hypotension, renal impairment and hyperkalaemia increased in both treatment groups with age, although the differences between treatment (more hypotension but less renal impairment and hyperkalaemia with LCZ696) were consistent across age categories. Interpretation LCZ696 was more beneficial than enalapril across the spectrum of age in PARADIGM-HF with a favourable benefit–risk profile in all age groups. PMID:26231885

Prognostic indicators for dogs with dilated cardiomyopathy.

PubMed

Borgarelli, Michele; Santilli, Roberto A; Chiavegato, David; D'Agnolo, Gino; Zanatta, Renato; Mannelli, Alessandro; Tarducci, Alberto

2006-01-01

The purpose of this study was to investigate the prognostic value of various clinical, ECG, echocardiographic, and Doppler echocardiographic variables in dogs with dilated cardiomyopathy. The relationship to survival of 11 variables was evaluated in 63 dogs. Studied variables were age at time of diagnosis, class of heart failure (HF), dyspnea, ascites, atrial fibrillation (AF), ejection fraction (EF), E-point septal separation, end-diastolic volume index, end-systolic volume index (ESV-I), and restrictive or nonrestrictive transmitral flow (TMF) pattern. Median survival time was 671 days (lower 95% confidence limit, 350 days). Survival curves showed that severity of HF, ascites, ESV-I greater than 140 mL/m2, EF less than 25%, and restrictive TMF pattern had a significant negative relation to survival time. Thirty-nine dogs with both sinus rhythm and AF presented adequate TMF recordings; in these dogs, after stratification by TMF pattern, the restrictive TMF pattern was the most important negative prognostic indicator. We conclude that in dogs with dilated cardiomyopathy the restrictive TMF pattern appears to represent a useful prognostic indicator. Class of HF, ascites, ESV-I, and EF are also useful indexes if an adequate TMF pattern is not recorded.

Ginsenoside Rb1 inhibits autophagy through regulation of Rho/ROCK and PI3K/mTOR pathways in a pressure-overload heart failure rat model.

PubMed

Yang, Tianrui; Miao, Yunbo; Zhang, Tong; Mu, Ninghui; Ruan, Libo; Duan, Jinlan; Zhu, Ying; Zhang, Rongping

2018-06-01

This study was designed to explore the relationship between ginsenoside Rb1 (Grb1) and high-load heart failure (HF) in rats. The parameters of cardiac systolic function (left ventricular posterior wall thickness (LVPWT), left ventricular internal diastolic diameter (LVID), fraction shortening (FS) and mitral valves (MVs)) of rat hearts in each group were inspected by echocardiogram. The expressions of rat myocardial contractile proteins, autophagy-related proteins and the activation of Rho/ROCK and PI3K/mTOR pathways were detected by Western blot. LVPWT, FS, MVs and the expression of myocardial contractile proteins α-MHC, apoptosis-related proteins Bcl-2 and signalling pathway involved proteins pAkt and mTOR were significantly reduced in the HF, HF+5 mg/kg Grb1 (HF+Grb1-5) and HF+Grb1+arachidonic acid (AA) groups with LVID, β-MHC, cell apoptosis, cell autophagy and Rho/ROCK significantly increased compared with the control group, of which the tendency was contrary to the HF+20 mg/kg Grb1 (HF+Grb1-20) group compared with the HF group (P < 0.05). In the HF+Grb1+AA group, there was no significant change in the above indexes compared with the HF group. The results indicated that Grb1 can exert anti-HF function by inhibiting cardiomyocyte autophagy of rats through regulation of Rho/ROCK and PI3K/mTOR pathways. © 2018 Royal Pharmaceutical Society.

Cardiovascular function in male and female JCR:LA-cp rats: effect of high-fat/high-sucrose diet.

PubMed

Hunter, Ian; Soler, Amanda; Joseph, Gregory; Hutcheson, Brenda; Bradford, Chastity; Zhang, Frank Fan; Potter, Barry; Proctor, Spencer; Rocic, Petra

2017-04-01

Thirty percent of the world population is diagnosed with metabolic syndrome. High-fat/high-sucrose (HF/HS) diet (Western diet) correlates with metabolic syndrome prevalence. We characterized effects of the HF/HS diet on vascular (arterial stiffness, vasoreactivity, and coronary collateral development) and cardiac (echocardiography) function, oxidative stress, and inflammation in a rat model of metabolic syndrome (JCR rats). Furthermore, we determined whether male versus female animals were affected differentially by the Western diet. Cardiovascular function in JCR male rats was impaired versus normal Sprague-Dawley (SD) rats. HF/HS diet compromised cardiovascular (dys)function in JCR but not SD male rats. In contrast, cardiovascular function was minimally impaired in JCR female rats on normal chow. However, cardiovascular function in JCR female rats on the HF/HS diet deteriorated to levels comparable to JCR male rats on the HF/HS diet. Similarly, oxidative stress was markedly increased in male but not female JCR rats on normal chow but was equally exacerbated by the HF/HS diet in male and female JCR rats. These results indicate that the Western diet enhances oxidative stress and cardiovascular dysfunction in metabolic syndrome and eliminates the protective effect of female sex on cardiovascular function, implying that both males and females with metabolic syndrome are at equal risk for cardiovascular disease. NEW & NOTEWORTHY Western diet abolished protective effect of sex against cardiovascular disease (CVD) development in premenopausal animals with metabolic syndrome. Western diet accelerates progression of CVD in male and female animals with preexisting metabolic syndrome but not normal animals. Exacerbation of baseline oxidative stress correlates with accelerated progression of CVD in metabolic syndrome animals on Western diet. Copyright © 2017 the American Physiological Society.

Cardiovascular function in male and female JCR:LA-cp rats: effect of high-fat/high-sucrose diet

PubMed Central

Hunter, Ian; Soler, Amanda; Joseph, Gregory; Hutcheson, Brenda; Bradford, Chastity; Zhang, Frank Fan; Potter, Barry; Proctor, Spencer

2017-01-01

Thirty percent of the world population is diagnosed with metabolic syndrome. High-fat/high-sucrose (HF/HS) diet (Western diet) correlates with metabolic syndrome prevalence. We characterized effects of the HF/HS diet on vascular (arterial stiffness, vasoreactivity, and coronary collateral development) and cardiac (echocardiography) function, oxidative stress, and inflammation in a rat model of metabolic syndrome (JCR rats). Furthermore, we determined whether male versus female animals were affected differentially by the Western diet. Cardiovascular function in JCR male rats was impaired versus normal Sprague-Dawley (SD) rats. HF/HS diet compromised cardiovascular (dys)function in JCR but not SD male rats. In contrast, cardiovascular function was minimally impaired in JCR female rats on normal chow. However, cardiovascular function in JCR female rats on the HF/HS diet deteriorated to levels comparable to JCR male rats on the HF/HS diet. Similarly, oxidative stress was markedly increased in male but not female JCR rats on normal chow but was equally exacerbated by the HF/HS diet in male and female JCR rats. These results indicate that the Western diet enhances oxidative stress and cardiovascular dysfunction in metabolic syndrome and eliminates the protective effect of female sex on cardiovascular function, implying that both males and females with metabolic syndrome are at equal risk for cardiovascular disease. NEW & NOTEWORTHY Western diet abolished protective effect of sex against cardiovascular disease (CVD) development in premenopausal animals with metabolic syndrome. Western diet accelerates progression of CVD in male and female animals with preexisting metabolic syndrome but not normal animals. Exacerbation of baseline oxidative stress correlates with accelerated progression of CVD in metabolic syndrome animals on Western diet. PMID:28087518

Brain metabolites in autonomic regulatory insular sites in heart failure.

PubMed

Woo, Mary A; Yadav, Santosh K; Macey, Paul M; Fonarow, Gregg C; Harper, Ronald M; Kumar, Rajesh

2014-11-15

Autonomic, pain, and neuropsychologic comorbidities appear in heart failure (HF), likely resulting from brain changes, indicated as loss of structural integrity and functional deficits. Among affected brain sites, the anterior insulae are prominent in serving major regulatory roles in many of the disrupted functions commonly seen in HF. Metabolite levels, including N-acetylaspartate (NAA), creatine (Cr), choline (Cho), and myo-inositol (MI), could indicate the nature of anterior insula tissue injury in HF. The study aim was to assess anterior insular metabolites to determine processes mediating autonomic, pain, and neuropsychologic disruptions in HF. We performed magnetic resonance spectroscopy in bilateral anterior insulae in 11 HF and 53 controls, using a 3.0-Tesla magnetic resonance imaging scanner. Peaks for NAA at 2.02 ppm, Cr at 3.02 ppm, Cho at 3.2 ppm, and MI at 3.56 ppm were assigned, peak areas were calculated, and metabolites were expressed as ratios, including NAA/Cr, Cho/Cr, and MI/Cr. HF patients showed significantly increased Cho/Cr ratios, indicative of glial proliferation or injury, on the left anterior insula, and reduced NAA/Cr levels, suggesting neuronal loss/dysfunction, on the right anterior insula over controls. No differences in MI/Cr ratios appeared between groups. Right anterior insular neuronal loss and left glial alterations may contribute to distorted autonomic, pain, and neuropsychologic functions found in HF. Copyright © 2014 Elsevier B.V. All rights reserved.

Brain Metabolites in Autonomic Regulatory Insular Sites in Heart Failure

PubMed Central

Woo, Mary A.; Yadav, Santosh K.; Macey, Paul M.; Fonarow, Gregg C.; Harper, Ronald M.; Kumar, Rajesh

2014-01-01

Autonomic, pain, and neuropsychologic comorbidities appear in heart failure (HF), likely resulting from brain changes, indicated as loss of structural integrity and functional deficits. Among affected brain sites, the anterior insulae are prominent in serving major regulatory roles in many of the disrupted functions commonly seen in HF. Metabolite levels, including N-acetylaspartate (NAA), creatine (Cr), choline (Cho), and myo-inositol (MI), could indicate the nature of anterior insula tissue injury in HF. The study aim was to assess anterior insular metabolites to determine processes mediating autonomic, pain, and neuropsychologic disruptions in HF. We performed magnetic resonance spectroscopy in bilateral anterior insulae in 11 HF and 53 controls, using a 3.0-Tesla magnetic resonance imaging scanner. Peaks for NAA at 2.02ppm, Cr at 3.02ppm, Cho at 3.2ppm, and MI at 3.56ppm were assigned, peak areas calculated, and metabolites expressed as ratios, including NAA/Cr, Cho/Cr, and MI/Cr. HF patients showed significantly increased Cho/Cr ratios, indicative of glial proliferation or injury, on the left anterior insula, and reduced NAA/Cr levels, suggesting neuronal loss/dysfunction, on the right anterior insula over controls. No differences in MI/Cr ratios appeared between groups. Right anterior insular neuronal loss and left glial alterations may contribute to distorted autonomic, pain, and neuropsychologic functions found in HF. PMID:25248953

Effect of Switching from Cilnidipine to Azelnidipine on Cardiac Sympathetic Nerve Function in Patients with Heart Failure Preserved Ejection Fraction.

PubMed

Kiuchi, Shunsuke; Hisatake, Shinji; Kabuki, Takayuki; Oka, Takashi; Dobashi, Shintaro; Fujii, Takahiro; Ikeda, Takanori

2018-01-27

Cardiac sympathetic nerve activity is known to play a key role in the development and progression of heart failure (HF). Azelnidipine, an L-type calcium channel blocker (CCB), inhibits the sympathetic nerve activity of the central system. In contrast, cilnidipine, an N-type CCB, inhibits the sympathetic nerve activity of the peripheral system. CCBs are recommended as class IIa in patients with HF preserved ejection fraction (HFpEF); however, there are no comparative data on the difference in effect of cilnidipine and azelnidipine in patients with HFpEF and hypertension. We investigated the difference in effect of azelnidipine compared with cilnidipine in patients with HFpEF. Twenty-four consecutive HF patients who received angiotensin II type1a receptor blocker and beta blocker from April 2013 to January 2015 were enrolled. Cilnidipine was switched to azelnidipine during the follow-up period. Blood pressures, heart rate, blood tests, echocardiography, and 123 I-metaiodobenzylguanidine (MIBG) cardiac-scintigraphy were measured before and after 6 months from azelnidipine administration. B-type natriuretic peptide tended to decrease after switching to azelnidipine; however, there were no significant differences between the pre-state and post-state (pre-state: 118.5 pg/mL and post-state: 78.4 pg/mL, P = 0.137). Other laboratory findings, including catecholamine, also did not change significantly. In echocardiography, there were no significant differences in systolic and diastolic functions at the pre-state and post-state. As for MIBG, there were no significant changes in heart/mediastinum ratio. However, washout rate was significantly reduced (pre-state: 42.9 and post-state: 39.6, P = 0.030). Azelnidipine improved the dysfunction of cardiac sympathetic nerve activity compared with cilnidipine in patients with HFpEF.

Work function tuning at Au-HfO{sub 2} interfaces using organophosphonate monolayers

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kwan, Matthew; Cardinal, Thomas; Ramanath, Ganpati, E-mail: Ramanath@rpi.edu

2016-05-09

We show that introducing organophosphonate nanomolecular monolayers (NMLs) at Au-HfO{sub 2} interfaces shift the effective work function by 0.2 eV ≥ ΔΦ{sub eff} ≥ −0.6 eV, due to NML body and bonding dipoles. Electron spectroscopy of NML-Au, NML-HfO{sub 2,} and Au-NML-HfO{sub 2} structures indicate that the Au-NML bond strength is the major factor. Au-NML covalent bonding yields ΔΦ{sub eff} ∼ − 0.2 eV, while weak bonding yields ΔΦ{sub eff} ∼ 0.6 eV. In contrast, NMLs on HfO{sub 2} decrease Φ{sub eff} by ∼0.4 eV due to competing contributions from NML-HfO{sub 2} bonding strength and NML orientation. These findings are relevant for nanomolecularly tailoring the electronic properties of metal–ceramic interfaces for applications.

Choline supplementation protects against liver damage by normalizing cholesterol metabolism in Pemt/Ldlr knockout mice fed a high-fat diet.

PubMed

Al Rajabi, Ala; Castro, Gabriela S F; da Silva, Robin P; Nelson, Randy C; Thiesen, Aducio; Vannucchi, Helio; Vine, Donna F; Proctor, Spencer D; Field, Catherine J; Curtis, Jonathan M; Jacobs, René L

2014-03-01

Dietary choline is required for proper structure and dynamics of cell membranes, lipoprotein synthesis, and methyl-group metabolism. In mammals, choline is synthesized via phosphatidylethanolamine N-methyltransferase (Pemt), which converts phosphatidylethanolamine to phosphatidylcholine. Pemt(-/-) mice have impaired VLDL secretion and developed fatty liver when fed a high-fat (HF) diet. Because of the reduction in plasma lipids, Pemt(-/-)/low-density lipoprotein receptor knockout (Ldlr(-/-)) mice are protected from atherosclerosis. The goal of this study was to investigate the importance of dietary choline in the metabolic phenotype of Pemt(-/-)/Ldlr(-/-) male mice. At 10-12 wk of age, Pemt(+/+)/Ldlr(-/-) (HF(+/+)) and half of the Pemt(-/-)/Ldlr(-/-) (HF(-/-)) mice were fed an HF diet with normal (1.3 g/kg) choline. The remaining Pemt(-/-)/Ldlr(-/-) mice were fed an HF diet supplemented (5 g/kg) with choline (HFCS(-/-) mice). The HF diet contained 60% of calories from fat and 1% cholesterol, and the mice were fed for 16 d. HF(-/-) mice lost weight and developed hepatomegaly, steatohepatitis, and liver damage. Hepatic concentrations of free cholesterol, cholesterol-esters, and triglyceride (TG) were elevated by 30%, 1.1-fold and 3.1-fold, respectively, in HF(-/-) compared with HF(+/+) mice. Choline supplementation normalized hepatic cholesterol, but not TG, and dramatically improved liver function. The expression of genes involved in cholesterol transport and esterification increased by 50% to 5.6-fold in HF(-/-) mice when compared with HF(+/+) mice. Markers of macrophages, oxidative stress, and fibrosis were elevated in the HF(-/-) mice. Choline supplementation normalized the expression of these genes. In conclusion, HF(-/-) mice develop liver failure associated with altered cholesterol metabolism when fed an HF/normal choline diet. Choline supplementation normalized cholesterol metabolism, which was sufficient to prevent nonalcoholic steatohepatitis development and improve liver function. Our data suggest that choline can promote liver health by maintaining cholesterol homeostasis.

Health literacy and global cognitive function predict e-mail but not internet use in heart failure patients.

PubMed

Schprechman, Jared P; Gathright, Emily C; Goldstein, Carly M; Guerini, Kate A; Dolansky, Mary A; Redle, Joseph; Hughes, Joel W

2013-01-01

Background. The internet offers a potential for improving patient knowledge, and e-mail may be used in patient communication with providers. However, barriers to internet and e-mail use, such as low health literacy and cognitive impairment, may prevent patients from using technological resources. Purpose. We investigated whether health literacy, heart failure knowledge, and cognitive function were related to internet and e-mail use in older adults with heart failure (HF). Methods. Older adults (N = 119) with heart failure (69.84 ± 9.09 years) completed measures of health literacy, heart failure knowledge, cognitive functioning, and internet use in a cross-sectional study. Results. Internet and e-mail use were reported in 78.2% and 71.4% of this sample of patients with HF, respectively. Controlling for age and education, logistic regression analyses indicated that higher health literacy predicted e-mail (P < .05) but not internet use. Global cognitive function predicted e-mail (P < .05) but not internet use. Only 45% used the Internet to obtain information on HF and internet use was not associated with greater HF knowledge. Conclusions. The majority of HF patients use the internet and e-mail, but poor health literacy and cognitive impairment may prevent some patients from accessing these resources. Future studies that examine specific internet and email interventions to increase HF knowledge are needed.

Serum myostatin levels are independently associated with skeletal muscle wasting in patients with heart failure.

PubMed

Furihata, Takaaki; Kinugawa, Shintaro; Fukushima, Arata; Takada, Shingo; Homma, Tsuneaki; Masaki, Yoshihiro; Abe, Takahiro; Yokota, Takashi; Oba, Koji; Okita, Koichi; Tsutsui, Hiroyuki

2016-10-01

It has been reported that skeletal muscle mass and strength are decreased in patients with heart failure (HF), and HF is associated with both reduced exercise capacity and adverse clinical outcomes. Myostatin has been known as a negative regulator of muscle growth, follistatin as the myostatin antagonist, maintaining tissue homeostasis. We thus determined serum myostatin levels in HF patients and whether they are associated with skeletal muscle wasting. Forty one consecutive HF patients (58±15years old, New York Heart Association class I-III) and 30 age-matched healthy subjects as controls (53±8years old) were studied. Serum myostatin levels were significantly lower in HF patients than controls (18.7±7.4 vs. 23.6±5.2ng/mL, P<0.001). Circumference of the thickest part of the right thigh was significantly small (468±72 vs. 559±37mm, P=0.001) and lower extremity muscular strength was lower in patients with HF (129±55 vs. 219±52N×m, P<0.001). Fourteen HF patients (34%) had muscle wasting. By univariate analysis, higher age, higher serum follistatin, and lower serum myostatin were significantly associated with the presence of muscle wasting. By multivariate analysis, serum myostatin levels were independently associated with muscle wasting (OR=0.77, 95% CI [0.58, 0.93], P=0.02). Serum myostatin levels were significantly decreased in HF patients and associated with lower extremity muscle wasting, suggesting that myostatin may be an important factor for maintaining skeletal muscle mass and strength in HF. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

The Immediate Effect of Sildenafil on Right Ventricular Function in Patients with Heart Failure Measured by Cardiac Magnetic Resonance: A Randomized Control Trial

PubMed Central

Durães, André Rodrigues; Borges, Sirlene Mendes; Aras, Roque

2015-01-01

Background Studies have demonstrated that phosphodiesterase 5 (PDE5) inhibition is associated with right ventricle (RV) functional improvement in patients with primary pulmonary hypertension. This study aims to demonstrate the immediate impact of Sildenafil, a PDE5 inhibitor, on RV function, measured by cardiovascular magnetic resonance (CMR), in patients with heart failure (HF). Methods We conducted a randomized double-blind controlled trial. Inclusion criteria: diagnosis of HF functional class I-III; left ventricle ejection fraction < 35%. Patients underwent CMR evaluation and were then equally randomly assigned to either 50 mg of Sildenafil or Placebo groups. One hour following drug administration, they were submitted to a second scan examination. Results 26 patients were recruited from a tertiary reference center in Brazil and 13 were allocated to each study group. The median age was 61.5 years (50–66.5 years). Except for the increase in RV fractional area change following the administration of sildenafil (Sildenafil [before vs. after]: 34.3 [25.2–43.6]% vs. 42.9 [28.5–46.7]%, p = 0.04; Placebo [before vs. after]: 28.1 [9.2–34.8]% vs. 29.2 [22.5–38.8]%, p = 0.86), there was no statistically significant change in parameters. There was no improvement in left ventricular parameters or in the fractional area change of the pulmonary artery. Conclusion This study demonstrated that a single dose of Sildenafil did not significantly improve RV function as measured by the CMR. Trial Registration ClinicalTrials.gov NCT01936350 PMID:25793988

Synthesis of Hf 8O 7, a new binary hafnium oxide, at high pressures and high temperatures

DOE PAGES

Bayarjargal, L.; Morgenroth, W.; Schrodt, N.; ...

2017-01-23

In this paper, two binary phases in the system Hf-O have been synthesized at pressures between 12 and 34 GPa and at temperatures up to 3000 K by reacting Hf with HfO 2 using a laser-heated diamond anvil cell. In situ X-ray diffraction in conjunction with density functional theory calculations has been employed to characterize a previously unreported tetragonal Hf 8O 7 phase. This phase has a structure which is based on an fcc Hf packing with oxygen atoms occupying octahedral interstitial positions. Its predicted bulk modulus is 223(1) GPa. The second phase has a composition close to Hf 6O,more » where oxygen atoms occupy octahedral interstitial sites in an hcp Hf packing. Its experimentally determined bulk modulus is 128(30) GPa. Finally, the phase diagram of Hf metal was further constrained at high pressures and temperatures, where we show that α-Hf transforms to β-Hf around 2160(150) K and 18.2 GPa and β-Hf remains stable up to at least 2800 K at this pressure.« less

Wideband pulse amplifiers for the NECTAr chip

NASA Astrophysics Data System (ADS)

Sanuy, A.; Delagnes, E.; Gascon, D.; Sieiro, X.; Bolmont, J.; Corona, P.; Feinstein, F.; Glicenstein, J.-F.; Naumann, C. L.; Nayman, P.; Ribó, M.; Tavernet, J.-P.; Toussenel, F.; Vincent, P.; Vorobiov, S.

2012-12-01

The NECTAr collaboration's FE option for the camera of the CTA is a 16 bits and 1-3 GS/s sampling chip based on analog memories including most of the readout functions. This works describes the input amplifiers of the NECTAr ASIC. A fully differential wideband amplifier, with voltage gain up to 20 V/V and a BW of 400 MHz. As it is impossible to design a fully differential OpAmp with an 8 GHz GBW product in a 0.35 CMOS technology, an alternative implementation based on HF linearized transconductors is explored. The output buffer is a class AB miller operational amplifier, with special non-linear current boost.

Insufficient Hartree–Fock Exchange in Hybrid DFT Functionals Produces Bent Alkynyl Radical Structures

DOE Office of Scientific and Technical Information (OSTI.GOV)

Oyeyemi, Victor B.; Keith, John A.; Pavone, Michele

2012-01-11

Density functional theory (DFT) is often used to determine the electronic and geometric structures of molecules. While studying alkynyl radicals, we discovered that DFT exchange-correlation (XC) functionals containing less than ~22% Hartree–Fock (HF) exchange led to qualitatively different structures than those predicted from ab initio HF and post-HF calculations or DFT XCs containing 25% or more HF exchange. We attribute this discrepancy to rehybridization at the radical center due to electron delocalization across the triple bonds of the alkynyl groups, which itself is an artifact of self-interaction and delocalization errors. Inclusion of sufficient exact exchange reduces these errors and suppressesmore » this erroneous delocalization; we find that a threshold amount is needed for accurate structure determinations. Finally, below this threshold, significant errors in predicted alkyne thermochemistry emerge as a consequence.« less

Is plasma N-BNP a good indicator of the functional reserve of failing hearts? The FRESH-BNP study.

PubMed

Williams, Simon G; Ng, Leong L; O'Brien, Russell J; Taylor, Steve; Wright, D Jay; Tan, Lip-Bun

2004-12-01

Whether plasma N-terminal brain natriuretic peptide (N-BNP) is useful in the diagnosis of heart failure (HF) depends traditionally on whether it is as good as the putative 'gold-standard', left ventricular ejection fraction (LVEF), in indicating cardiac dysfunction. However, since HF is primarily an impairment of function of the cardiac pump, we explored the relationship between N-BNP and direct and indirect indicators of cardiac pump dysfunction. Eighty-six HF patients (mean age 56 years) with a range of LVEF's (mean 36.9+/-15.2%, range 15-66%) and 10 age-matched healthy controls were recruited into the study and had resting N-BNP measured. Cardiopulmonary exercise testing was performed to assess peak oxygen consumption (Vo(2)). A subgroup of 23 subjects underwent further exercise haemodynamic assessment to evaluate peak cardiac power output (CPO). The CHF group had significantly higher N-BNP (median [interquartile range]) levels (299 [705] fmol/ml) than the control group (7 [51] fmol/ml, P<0.005). Significant correlations between N-BNP and peak Vo(2), and N-BNP and peak CPO were observed (R> or =0.5, P<0.005). Although significant correlation was observed between N-BNP and LVEF (R=0.34, P=0.01), the correlations between LVEF and peak Vo(2) or peak CPO (all R<0.3, P>0.3) were not significant. Multivariate analysis identified plasma N-BNP and NYHA class, but not LVEF, as independent predictors of peak Vo(2). We have found that N-BNP was surprisingly good as a simple indicator of cardiac pump dysfunction. Since heart failure is an inadequacy of function, these results strongly support the notion that N-BNP is a useful blood test in estimating the extent of cardiac pump dysfunction and helpful in establishing positive diagnosis of heart failure.

Serum Bicarbonate and Structural and Functional Cardiac Abnormalities in Chronic Kidney Disease - A Report from the Chronic Renal Insufficiency Cohort Study.

PubMed

Dobre, Mirela; Roy, Jason; Tao, Kaixiang; Anderson, Amanda H; Bansal, Nisha; Chen, Jing; Deo, Rajat; Drawz, Paul; Feldman, Harold I; Hamm, L Lee; Hostetter, Thomas; Kusek, John W; Lora, Claudia; Ojo, Akinlolu O; Shrama, Kumar; Rahman, Mahboob

2016-01-01

Heart failure (HF) is a frequent occurrence in chronic kidney disease (CKD) patients and predicts poor survival. Serum bicarbonate is associated with increased rates of HF in CKD; however, the mechanisms leading to this association are incompletely understood. This study aims to assess whether serum bicarbonate is independently associated with structural and functional cardiac abnormalities in CKD. The association between serum bicarbonate and left ventricular (LV) hypertrophy (LVH), LV mass indexed to height2.7, LV geometry, ejection fraction (EF) and diastolic dysfunction was assessed in 3,483 participants without NYHA class III/IV HF, enrolled in the Chronic Renal Insufficiency Cohort study. The mean estimated glomerular filtration rate was 42.5 ± 17 ml/min/1.73 m2. The overall prevalence of LVH was 51.2%, with 57.8, 50.9 and 47.7% for bicarbonate categories <22, 22-26 and >26 mmol/l, respectively. Participants with low bicarbonate were more likely to have LVH and abnormal LV geometry (OR 1.32; 95% CI 1.07-1.64, and OR 1.57; 95% CI 1.14-2.16, respectively). However, the association was not statistically significant after adjustment for demographics, traditional cardiovascular risk factors, medications and kidney function (OR 1.07; 95% CI 0.66-1.72, and OR 1.27; 95% CI 0.64-2.51, respectively). No association was found between bicarbonate and systolic or diastolic dysfunction. During follow-up, no significant changes in LV mass or EF were observed in any bicarbonate strata. In a large CKD study, serum bicarbonate was associated with LV mass and concentric LVH; however, this association was attenuated after adjustment for clinical factors suggesting that the observed cardiac effects are mediated through yet unknown mechanisms. © 2016 Published by S. Karger AG, Basel.

Heart failure in women and men during acute coronary syndrome and long-term cardiovascular mortality (the ABC-3* Study on Heart Disease) (*Adria, Bassano, Conegliano, and Padova Hospitals).

PubMed

Berton, Giuseppe; Cordiano, Rocco; Cavuto, Fiorella; Bagato, Francesco; Pellegrinet, Marco; Cati, Arianna

2016-10-01

We investigated the gender-based differences in the association between heart failure (HF) during acute coronary syndrome (ACS) and post-discharge, long-term cardiovascular (CV) mortality. The present study included 557 patients enrolled in three intensive coronary care units and discharged alive. HF during ACS was evaluated by Killip class and left ventricular ejection fraction (LVEF). Interaction between gender and HF after 15years of follow up was studied using Cox models including a formal interaction term. Median age was 67 (interquartile range [IQR], 59-75) years, 29% were females, 37% had non-ST elevation myocardial infarction and 32% Killip class>1, and median LVEF was 53% (IQR 46-61). All but five patients were followed up to 15years, representing 5332 person-years. Of these, 40.2% died of CV-related causes. Crude CV mortality rate was higher among women (52.2%) than men (35.3%; P<0.0001). At a univariable level, a negative interaction between female gender and Killip class for CV mortality was found [hazard ratio (HR)=0.51 (0.34-0.77), P=0.002]. In five multivariable models after controlling for age, main CV risk factors, clinical features, post-discharge medical treatment, and mechanical coronary reperfusion, the interaction was significant across all models [HR=0.63 (0.42-0.95), P=0.02 in the fully adjusted model]. LVEF showed no significant hazard associated with female gender on univariable analysis [HR=1.4 (0.9-0.2.0), P=0.11] but did so in all adjusted models [HR=1.7 (1.2-2.5), P=0.005 in the fully adjusted model]. Gender is a consistent, independent effect modifier in the association between HF and long-term CV mortality after ACS. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Depressive symptoms and outcomes in patients with heart failure: data from the COACH study.

PubMed

Lesman-Leegte, Ivonne; van Veldhuisen, Dirk J; Hillege, Hans L; Moser, Debra; Sanderman, Robbert; Jaarsma, Tiny

2009-12-01

To study the prognostic value of depressive symptoms on heart failure (HF) readmission and mortality, in a large and clinically relevant population of hospitalized HF patients adjusted for disease severity by B-type natriuretic peptide (BNP) level. We studied 958 patients enrolled after hospitalization for HF; 37% female; mean age 71 +/- 11 years; New York Heart Association class II (51%) or III/IV (49%). Left ventricular ejection fraction: 33% +/- 14%, and median BNP level: 454 pg/mL (75% CI, 195-876 pg/mL). In total, 377 patients (39%) had depressive symptoms [Centre for Epidemiological Studies Depression Scale (CES-D) score >or=16] and 200 (21%) had severe depressive symptoms (score >or=24). During 18 months of follow-up, 386 (40%) patients reached the primary endpoint of death or readmission for HF. In multivariate analyses, CES-D was significantly associated with the primary endpoint [hazard ratio (HR) 1.13, P = 0.02], and also with both individual components of the primary endpoint [HF readmission (HR 1.165, P = 0.02) and mortality (HR 1.169, P = 0.02)]. Patients with severe depressive symptoms had a >40% higher risk for HF readmission or death. In patients with HF, depression is independently associated with poor outcomes. These findings highlight the need for continued exploration of whether improvements in depression lead to better cardiovascular outcomes. The study was registered at clinical trial (www.trialregister.nl): NCT 98675639.

Intrauterine Growth Retardation Increases the Susceptibility of Pigs to High-Fat Diet-Induced Mitochondrial Dysfunction in Skeletal Muscle

PubMed Central

Liu, Jingbo; Chen, Daiwen; Yao, Ying; Yu, Bing; Mao, Xiangbing; He, Jun; Huang, Zhiqing; Zheng, Ping

2012-01-01

It has been recognized that there is a relationship between prenatal growth restriction and the development of metabolic-related diseases in later life, a process involved in mitochondrial dysfunction. In addition, intrauterine growth retardation (IUGR) increases the susceptibility of offspring to high-fat (HF) diet-induced metabolic syndrome. Recent findings suggested that HF feeding decreased mitochondrial oxidative capacity and impaired mitochondrial function in skeletal muscle. Therefore, we hypothesized that the long-term consequences of IUGR on mitochondrial biogenesis and function make the offspring more susceptible to HF diet-induced mitochondrial dysfunction. Normal birth weight (NBW), and IUGR pigs were allotted to control or HF diet in a completely randomized design, individually. After 4 weeks of feeding, growth performance and molecular pathways related to mitochondrial function were determined. The results showed that IUGR decreased growth performance and plasma insulin concentrations. In offspring fed a HF diet, IUGR was associated with enhanced plasma leptin levels, increased concentrations of triglyceride and malondialdehyde (MDA), and reduced glycogen and ATP contents in skeletal muscle. High fat diet-fed IUGR offspring exhibited decreased activities of lactate dehydrogenase (LDH) and glucose-6-phosphate dehydrogenase (G6PD). These alterations in metabolic traits of IUGR pigs were accompanied by impaired mitochondrial respiration function, reduced mitochondrial DNA (mtDNA) contents, and down-regulated mRNA expression levels of genes responsible for mitochondrial biogenesis and function. In conclusion, our results suggest that IUGR make the offspring more susceptible to HF diet-induced mitochondrial dysfunction. PMID:22523560

Dissociation energies of the hydrogen-bonded dimers RCN-HF (R = CH3, HCC) determined by rotational spectroscopy

NASA Astrophysics Data System (ADS)

Legon, A. C.; Millen, D. J.; North, Hazel M.

1987-03-01

The zero-point and equilibrium dissociation energies (D0 and De) of the hydrogen-bonded dimers CH3CN-HF and HCCCN-HF are determined experimentally on the basis of absolute intensity measurements of selected rotational transitions. A Stark-modulated microwave spectrometer is employed with the cooled absorption cell described by Legon et al. (1980). The results are presented in tables and analyzed. Energies determined are D0 = 26.1(0.6) kJ/mol and De = 29.0(0.9) kJ/mol for CH3CN-HF and D0 = 20.4(0.7) kJ/mol and De = 23.4(0.9) kJ/mol for HCCCN-HF. Theoretical De values calculated using the Morse potential function are found to be in much better agreement with the experimental results than those calculated with the Lennard-Jones potential function.

HF/H2O2 treated graphite felt as the positive electrode for vanadium redox flow battery

NASA Astrophysics Data System (ADS)

He, Zhangxing; Jiang, Yingqiao; Meng, Wei; Jiang, Fengyun; Zhou, Huizhu; Li, Yuehua; Zhu, Jing; Wang, Ling; Dai, Lei

2017-11-01

In order to improve the electrochemical performance of the positive graphite felt electrode in vanadium flow redox battery, a novel method is developed to effectively modify the graphite felt by combination of etching of HF and oxidation of H2O2. After the etching of HF for the graphite felt at ambient temperature, abundant oxygen-containing functional groups were further introduced on the surface of graphite felt by hydrothermal treatment using H2O2 as oxidant. Benefiting from the surface etching and introduction of functional groups, mass transfer and electrode process can be improved significantly on the surface of graphite felt. VO2+/VO2+ redox reaction on the graphite felt modified by HF and H2O2 jointly (denote: GF-HF/H2O2) exhibits superior electrochemical kinetics in comparison with the graphite felt modified by single HF or H2O2 treatment. The cell using GF-HF/H2O2 as the positive electrode was assembled and its electrochemical properties were evaluated. The increase of energy efficiency of 4.1% for GF-HF/H2O2 at a current density of 50 mA cm-2 was obtained compared with the pristine graphite felt. The cell using GF-HF/H2O2 also demonstrated higher discharge capacity. Our study revealed that HF/H2O2 treatment is an efficient method to enhance the electrochemical performance of graphite felt, further improving the comprehensive energy storage performance of the vanadium flow redox battery.

Cognitive behavioral therapy for insomnia in stable heart failure: Protocol for a randomized controlled trial.

PubMed

Redeker, Nancy S; Knies, Andrea K; Hollenbeak, Christopher; Klar Yaggi, H; Cline, John; Andrews, Laura; Jacoby, Daniel; Sullivan, Anna; O'Connell, Meghan; Iennaco, Joanne; Finoia, Lisa; Jeon, Sangchoon

2017-04-01

Chronic insomnia is associated with disabling symptoms and decrements in functional performance. It may contribute to the development of heart failure (HF) and incident mortality. In our previous work, cognitive-behavioral therapy for insomnia (CBT-I), compared to HF self-management education, provided as an attention control condition, was feasible, acceptable, and had large effects on insomnia and fatigue among HF patients. The purpose of this randomized controlled trial (RCT) is to evaluate the sustained effects of group CBT-I compared with HF self-management education (attention control) on insomnia severity, sleep characteristics, daytime symptoms, symptom clusters, functional performance, and health care utilization among patients with stable HF. We will estimate the cost-effectiveness of CBT-I and explore the effects of CBT-I on event-free survival (EFS). Two hundred participants will be randomized in clusters to a single center parallel group (CBT-I vs. attention control) RCT. Wrist actigraphy and self-report will elicit insomnia, sleep characteristics, symptoms, and functional performance. We will use the psychomotor vigilance test to evaluate sleep loss effects and the Six Minute Walk Test to evaluate effects on daytime function. Medical record review and interviews will elicit health care utilization and EFS. Statistical methods will include general linear mixed models and latent transition analysis. Stochastic cost-effectiveness analysis with a competing risk approach will be employed to conduct the cost-effectiveness analysis. The results will be generalizable to HF patients with chronic comorbid insomnia and pave the way for future research focused on the dissemination and translation of CBT-I into HF settings. Copyright © 2017 Elsevier Inc. All rights reserved.

Regulatory T Cells in Skin Facilitate Epithelial Stem Cell Differentiation.

PubMed

Ali, Niwa; Zirak, Bahar; Rodriguez, Robert Sanchez; Pauli, Mariela L; Truong, Hong-An; Lai, Kevin; Ahn, Richard; Corbin, Kaitlin; Lowe, Margaret M; Scharschmidt, Tiffany C; Taravati, Keyon; Tan, Madeleine R; Ricardo-Gonzalez, Roberto R; Nosbaum, Audrey; Bertolini, Marta; Liao, Wilson; Nestle, Frank O; Paus, Ralf; Cotsarelis, George; Abbas, Abul K; Rosenblum, Michael D

2017-06-01

The maintenance of tissue homeostasis is critically dependent on the function of tissue-resident immune cells and the differentiation capacity of tissue-resident stem cells (SCs). How immune cells influence the function of SCs is largely unknown. Regulatory T cells (Tregs) in skin preferentially localize to hair follicles (HFs), which house a major subset of skin SCs (HFSCs). Here, we mechanistically dissect the role of Tregs in HF and HFSC biology. Lineage-specific cell depletion revealed that Tregs promote HF regeneration by augmenting HFSC proliferation and differentiation. Transcriptional and phenotypic profiling of T regs and HFSCs revealed that skin-resident Tregs preferentially express high levels of the Notch ligand family member, Jagged 1 (Jag1). Expression of Jag1 on Tregs facilitated HFSC function and efficient HF regeneration. Taken together, our work demonstrates that Tregs in skin play a major role in HF biology by promoting the function of HFSCs. Copyright © 2017 Elsevier Inc. All rights reserved.

Altered thermoregulatory responses in heart failure patients exercising in the heat.

PubMed

Balmain, Bryce N; Jay, Ollie; Sabapathy, Surendran; Royston, Danielle; Stewart, Glenn M; Jayasinghe, Rohan; Morris, Norman R

2016-11-01

Heart failure (HF) patients appear to exhibit impaired thermoregulatory capacity during passive heating, as evidenced by diminished vascular conductance. Although some preliminary studies have described the thermoregulatory response to passive heating in HF, responses during exercise in the heat remain to be described. Therefore, the aim of this study was to compare thermoregulatory responses in HF and controls (CON) during exercise in the heat. Ten HF (NYHA classes I-II) and eight CON were included. Core temperature (T c ), skin temperature (T sk ), and cutaneous vascular conductance (CVC) were assessed at rest and during 1 h of exercise at 60% of maximal oxygen uptake. Metabolic heat production (H prod ) and the evaporative requirements for heat balance (E req ) were also calculated. Whole-body sweat rate was determined from pre-post nude body mass corrected for fluid intake. While H prod (HF: 3.9 ± 0.9; CON: 6.4 ± 1.5 W/kg) and E req (HF: 3.3 ± 0.9; CON: 5.6 ± 1.4 W/kg) were lower (P < 0.01) for HF compared to CON, both groups demonstrated a similar rise in T c (HF: 0.9 ± 0.4; CON: 1.0 ± 0.3°C). Despite this similar rise in T c , T sk (HF: 1.6 ± 0.7; CON: 2.7 ± 1.2°C), and the elevation in CVC (HF: 1.4 ± 1.0; CON: 3.0 ± 1.2 au/mmHg) was lower (P < 0.05) in HF compared to CON Additionally, whole-body sweat rate (HF: 0.36 ± 0.15; CON: 0.81 ± 0.39 L/h) was lower (P = 0.02) in HF compared to CON Patients with HF appear to be limited in their ability to manage a thermal load and distribute heat content to the body surface (i.e., skin), secondary to impaired circulation to the periphery. © 2016 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.

Advances in the management of heart failure: the role of ivabradine

PubMed Central

Müller-Werdan, Ursula; Stöckl, Georg; Werdan, Karl

2016-01-01

A high resting heart rate (≥70–75 b.p.m.) is a risk factor for patients with heart failure (HF) with reduced ejection fraction (EF), probably in the sense of accelerated atherosclerosis, with an increased morbidity and mortality. Beta-blockers not only reduce heart rate but also have negative inotropic and blood pressure-lowering effects, and therefore, in many patients, they cannot be given in the recommended dose. Ivabradine specifically inhibits the pacemaker current (funny current, If) of the sinoatrial node cells, resulting in therapeutic heart rate lowering without any negative inotropic and blood pressure-lowering effect. According to the European Society of Cardiology guidelines, ivabradine should be considered to reduce the risk of HF hospitalization and cardiovascular death in symptomatic patients with a reduced left ventricular EF ≤35% and sinus rhythm ≥70 b.p.m. despite treatment with an evidence-based dose of beta-blocker or a dose below the recommended dose (recommendation class “IIa” = weight of evidence/opinion is in favor of usefulness/efficacy: “should be considered”; level of evidence “B” = data derived from a single randomized clinical trial or large nonrandomized studies). Using a heart rate cutoff of ≥ 75 b.p.m., as licensed by the European Medicines Agency, treatment with ivabradine 5–7.5 mg b.i.d. reduces cardiovascular mortality by 17%, HF mortality by 39% and HF hospitalization rate by 30%. A high resting heart rate is not only a risk factor in HF with reduced EF but also at least a risk marker in HF with preserved EF, in acute HF and also in special forms of HF. In this review, we discuss the proven role of ivabradine in the validated indication “HF with reduced EF” together with interesting preliminary findings, and the potential role of ivabradine in further, specific forms of HF. PMID:27895488

Profile of sacubitril/valsartan in the treatment of heart failure: patient selection and perspectives

PubMed Central

Yandrapalli, Srikanth; Andries, Gabriela; Biswas, Medha; Khera, Sahil

2017-01-01

With an estimated prevalence of 5.8 million in the USA and over 23 million people worldwide, heart failure (HF) is growing in epidemic proportions. Despite the use of guideline-directed medical therapies such as angiotensin-converting enzyme inhibitors, beta-adrenergic blockers, angiotensin receptor blockers, and mineralocorticoid receptor antagonists for chronic systolic HF for almost two decades, HF remains a leading cause of morbidity, mortality, and health care expenditures. The Prospective Comparison of Angiotensin Receptor-Neprilysin Inhibitor with Angiotensin-Converting Enzyme Inhibitor to Determine Impact on Global Mortality and Morbidity in Heart Failure (PARADIGM-HF) trial provided compelling evidence for the cardiovascular and mortality benefit of sacubitril/valsartan when compared to enalapril in patients with heart failure and reduced ejection fraction (HFrEF). Sacubitril/valsartan performed better than enalapril across various HFrEF patient characteristics and showed substantial benefit in patients with other common comorbidities. Following the trial, the US Food and Drug Administration approved this drug for the treatment of HF. Various international HF consensus guidelines endorse sacubitril/valsartan as a class I recommendation for the management of symptomatic HFrEF. Although this high-quality clinical study is the largest and the most globally represented trial in HFrEF patients, concerns have been raised regarding the generalizability of the trial results in real-world HF population. The gaps in US Food and Drug Administration labeling and guideline recommendations might lead to this medication being used in a larger population than it was studied in. In this review, we will discuss the current role of sacubitril/valsartan in the management of HF, concerns related to PARADIGM-HF and answers, shortcomings of this novel drug, effects on patient characteristics, real-world eligibility, and the role of ongoing and further investigations to clarify the profile of sacubitril/valsartan in the management of HF. PMID:29042791

Profile of sacubitril/valsartan in the treatment of heart failure: patient selection and perspectives.

PubMed

Yandrapalli, Srikanth; Andries, Gabriela; Biswas, Medha; Khera, Sahil

2017-01-01

With an estimated prevalence of 5.8 million in the USA and over 23 million people worldwide, heart failure (HF) is growing in epidemic proportions. Despite the use of guideline-directed medical therapies such as angiotensin-converting enzyme inhibitors, beta-adrenergic blockers, angiotensin receptor blockers, and mineralocorticoid receptor antagonists for chronic systolic HF for almost two decades, HF remains a leading cause of morbidity, mortality, and health care expenditures. The Prospective Comparison of Angiotensin Receptor-Neprilysin Inhibitor with Angiotensin-Converting Enzyme Inhibitor to Determine Impact on Global Mortality and Morbidity in Heart Failure (PARADIGM-HF) trial provided compelling evidence for the cardiovascular and mortality benefit of sacubitril/valsartan when compared to enalapril in patients with heart failure and reduced ejection fraction (HFrEF). Sacubitril/valsartan performed better than enalapril across various HFrEF patient characteristics and showed substantial benefit in patients with other common comorbidities. Following the trial, the US Food and Drug Administration approved this drug for the treatment of HF. Various international HF consensus guidelines endorse sacubitril/valsartan as a class I recommendation for the management of symptomatic HFrEF. Although this high-quality clinical study is the largest and the most globally represented trial in HFrEF patients, concerns have been raised regarding the generalizability of the trial results in real-world HF population. The gaps in US Food and Drug Administration labeling and guideline recommendations might lead to this medication being used in a larger population than it was studied in. In this review, we will discuss the current role of sacubitril/valsartan in the management of HF, concerns related to PARADIGM-HF and answers, shortcomings of this novel drug, effects on patient characteristics, real-world eligibility, and the role of ongoing and further investigations to clarify the profile of sacubitril/valsartan in the management of HF.

Predictors of a Change and Correlation in Activities of Daily Living after Hip Fracture in Elderly Patients in a Community Hospital in Poland: A Six-Month Prospective Cohort Study

PubMed Central

Ganczak, Maria; Chrobrowski, Krzysztof

2018-01-01

Objectives: The consequences of hip fractures (HFs) in elderly persons include a deterioration in functional capacity to perform activities that enable independent living. Since prior research into this issue in Central Europe is rather scant, this study sought to assess the change in activities and instrumental activities of daily living (ADL/IADL) after HF surgery among Polish patients, to study predictors of regaining pre-fracture functional status three and six months later, and to evaluate the correlation between ADL and IADL limitations over time. Methods: A prospective study was conducted between 2011 and 2013 in a tertiary hospital in Western Poland. ADL/IADL were evaluated using the Katz index and Lawton scale, respectively. Results: About half (50.8%) of 120 patients (mean age 80.1 ± SD 7.59) had cognitive impairment (CI). Patients with CI were older (p = 0.002) and had lower scores for pre-fracture ADL/IADL (p = 0.001 and p < 0.001, respectively). Six months after HF, 33.3% of patients failed to return to their pre-fracture ADL and 62.5% failed to return to pre-fracture IADL; 20% of those who could walk before HF were unable to walk after six months. The pre-fracture Spearman correlation coefficient between ADL and IADL summary scores was 0.46; it increased to 0.70 at three months after HF surgery and 0.77 at six months (p < 0.0001). Regaining ADL after six months was more likely in patients with pre-fracture intact intellectual function and independence in pre-fracture ADL; regaining IADL, in younger patients and those with higher pre-fracture IADL scores. Conclusions: Impairment in functional performance is common after HF surgery. ADL and IADL were strongly correlated in these patients, with this increasing over time. Functional outcomes after HF were more dependent on patient characteristics than treatment-related factors. Therefore, more emphasis should be directed towards the pre-fracture period and, in particular, maintaining cognitive function and preserving functional capacity in older persons at high risk of HF. PMID:29316721

Soluble ST2 protein in the short-term prognosis after hospitalisation in chronic systolic heart failure.

PubMed

Wojtczak-Soska, Karolina; Sakowicz, Agata; Pietrucha, Tadeusz; Lelonek, Małgorzata

2014-01-01

The prognosis in patients with chronic heart failure (CHF) is poor. ST2 protein is a promising prognostic biomarker for CHF. ST2 belongs to the cardioprotective signalling pathway involving interleukin-33 and its concentration in the serum depends on the biomechanical stress of cardiomyocytes (biomechanical strain). To determine the prognostic value of ST2 in short term follow-up after hospitalisation among patients with CHF. The study included 167 patients (mean age 62 years, 83% men) in stable NYHA class I-III with left ventricular ejection fraction (LVEF) of ≤ 45% (average 29.65%, ranges 13-45%). We analysed 58 variables including: demographics, co-morbidities, resting ECG, echocardiographic and coronary arteriography data, basic laboratory tests including N-terminal prohormone B-type natriuretic peptide (NT-proBNP), serum concentration of soluble form of ST2 (sST2) using quantitative ELISA test ST2 Kit (Medical and Biological Laboratories; Japan) and adverse cardiovascular events during a one year observation. In the study, the primary endpoint (death) and the composite endpoint (hospitalisation for HF worsening, worsening in NYHA functional class, the need to increase the dose of diuretics, and/or death in a one year observation) were determined. Patients who died (n = 24; 14.55%) were in more advanced NYHA class, had prolonged QRS duration, higher levels of sST2, NT-proBNP, and lower estimated glomerular filtration rate. From multivariate analysis, the independent variable for the primary endpoint was NT-proBNP (OR = 1.00012; 95% CI 1.00002-1.00022; p = 0.018). 93 (56%) patients reached the composite endpoint. Multivariate analysis revealed that fasting glucose (OR = 1.343; 95% CI 1.041-1.732; p = 0.023) and sST2 (OR = 3.593; 95% CI 1.427-9.05; p = 0.007) independently enhanced the risk of composite endpoint occurrence in a one year observation. In patients with CHF with LVEF ≤ 45%, the prognostic value of sST2 protein in a short-term observation of one year was confirmed. sST2 protein was an independent variable for the composite endpoint, which consisted of worsening NYHA functional class, hospitalisation for worsening of HF, the need to increase the dose of diuretics, and/or death.

Appropriateness and acceptability of a Tele-Yoga intervention for people with heart failure and chronic obstructive pulmonary disease: qualitative findings from a controlled pilot study.

PubMed

Selman, Lucy; McDermott, Kelly; Donesky, DorAnne; Citron, Tracie; Howie-Esquivel, Jill

2015-02-07

Heart failure (HF) and chronic obstructive pulmonary disease (COPD) are highly prevalent and associated with a large symptom burden, that is compounded in a dual HF-COPD diagnosis. Yoga has potential benefit for symptom relief; however functional impairment hinders access to usual yoga classes. We developed a Tele-Yoga intervention and evaluated it in a controlled pilot trial. This paper reports on the appropriateness and acceptability of the intervention and the evaluation design. A controlled, non-randomised trial was conducted of an 8-week Tele-Yoga intervention versus an educational control (information leaflets mailed to participants with one phone call a week). Biweekly one-hour Tele-Yoga classes were implemented via multipoint videoconferencing that connected participants to live classes via an Internet connection to their televisions. Semi-structured qualitative interviews were conducted with participants post study exit to explore reasons for and experiences of participating, including views of study outcome measures and physiological tests. Transcribed interviews were analysed using thematic content analysis. Fifteen people participated in the pilot study (7 in the intervention group, 8 in the control). Of these, 12 participants were interviewed, 6 in each group, mean age 71.2 years (SD 10.09); 3 were male. Themes are reported in the following categories: acceptability and appropriateness of the intervention, potential active ingredients of the intervention, acceptability and appropriateness of the control, participation in the research, and acceptability of the testing procedures. The intervention was acceptable and appropriate: the intervention group reported enjoying yoga and valuing the home-based aspect and participants described a high symptom burden and social isolation. However, technological problems resulted in poor video-streaming quality for some participants. Potential active ingredients included physical postures, breathing exercises and guidance in relaxation and meditation. The educational control intervention was acceptable and appropriate, with participants reporting little effect on their well-being and no impact on mechanisms hypothesised to explain yoga's effectiveness. The questionnaires and home physiological testing were acceptable to participants. Tele-Yoga is an acceptable and appropriate intervention in people with HF and COPD and further research is warranted to refine the technology used in its delivery. Findings provide guidance for researchers working in tele-interventions, yoga, and similar populations. ClinicalTrials.gov Identifier: NCT02078739 (4 March 2014).

Enhancing fatty acid utilization ameliorates mitochondrial fragmentation and cardiac dysfunction via rebalancing optic atrophy 1 processing in the failing heart.

PubMed

Guo, Yongzheng; Wang, Zhen; Qin, Xinghua; Xu, Jie; Hou, Zuoxu; Yang, Hongyan; Mao, Xuechao; Xing, Wenjuan; Li, Xiaoliang; Zhang, Xing; Gao, Feng

2018-06-01

Heart failure (HF) is characterized by reduced fatty acid (FA) utilization associated with mitochondrial dysfunction. Recent evidence has shown that enhancing FA utilization may provide cardioprotection against HF. Our aim was to investigate the effects and the underlying mechanisms of cardiac FA utilization on cardiac function in response to pressure overload. Transverse aortic constriction (TAC) was used in C57 mice to establish pressure overload-induced HF. TAC mice fed on a high fat diet (HFD) exhibited increased cardiac FA utilization and improved cardiac function and survival compared with those on control diet. Such cardioprotection could also be provided by cardiac-specific overexpression of CD36. Notably, both HFD and CD36 overexpression attenuated mitochondrial fragmentation and improved mitochondrial function in the failing heart. Pressure overload decreased ATP-dependent metalloprotease (YME1L) expression and induced the proteolytic cleavage of the dynamin-like guanosine triphosphatase OPA1 as a result of suppressed FA utilization. Enhancing FA utilization upregulated YME1L expression and subsequently rebalanced OPA1 processing, resulting in restoration of mitochondrial morphology in the failing heart. In addition, cardiac-specific overexpression of YME1L exerted similar cardioprotective effects against HF to those provided by HFD or CD36 overexpression. These findings demonstrate that enhancing FA utilization ameliorates mitochondrial fragmentation and cardiac dysfunction via rebalancing OPA1 processing in pressure overload-induced HF, suggesting a unique metabolic intervention approach to improving cardiac functions in HF.

A thermodynamic model for the solubility of HfO2(am) in the aqueous K +– HCO 3 -– CO 3 2-–O -–H 2O system

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rai, Dhanpat; Kitamura, Akira; Rosso, Kevin M.

Solubility of HfO2(am) was determined as a function of KHCO3 concentrations ranging from 0.001 mol·kg-1 to 0.1 mol·kg-1. The solubility of HfO2(am) increased dramatically with the increase in KHCO3 concentrations, indicating that Hf(IV) makes strong complexes with carbonate. Thermodynamic equilibrium constants for the formation of Hf-carbonate complexes were determined using both the Pitzer and SIT models. The dramatic increase in Hf concentrations with the increase in KHCO3 concentrations can best be described by the formation of Hf(OH-)2(CO3)22- and Hf(CO3)56-. The log10 K0 values for the reactions [Hf4++2CO32-+2OH-⇌Hf(OH)2(CO3)22-] and [Hf4++5CO32-⇌Hf(CO3)56-], based on the SIT model, were determined to be 44.53±0.46 andmore » 41.53±0.46, respectively, and based on the Pitzer model they were 44.56±0.48 and 40.20±0.48, respectively.« less

Future Perspectives for Management of Stage A Heart Failure.

PubMed

Tanaka, Hidekazu

2018-05-07

Patients with Stage A heart failure (HF) show no HF symptoms but have related comorbid diseases with a high risk of progressing to HF. Screening for comorbid diseases warrants closer attention because of the growing interest in addressing Stage A HF as the best means of preventing eventual progression to overt HF such as Stages C and D. The identification of individuals of Stage A HF is potentially useful for the implementation of HF-prevention strategies; however, not all Stage A HF patients develop left ventricular (LV) structural heart disease or symptomatic HF, which lead to advanced HF stages. Therefore, Stage A HF requires management with the long-term goal of avoiding HF development; likewise, Stage B HF patients are ideal targets for HF prevention. Although the early detection of subclinical LV dysfunction is, thus, essential for delaying the progression to HF, the assessment of subclinical LV dysfunction can be challenging. Global longitudinal strain (GLS) as assessed by speckle-tracking echocardiography has recently been reported to be a sensitive marker of early subtle LV myocardial abnormalities, helpful for the prediction of the outcomes for various cardiac diseases, and superior to conventional echocardiographic indices. GLS reflects LV longitudinal myocardial systolic function, and can be assessed usually by means of two-dimensional speckle-tracking. This article reviews the importance of the assessment of subclinical LV dysfunction in Stage A HF patients by means of GLS, and its current potential to prevent progression to later stage HF.

The large-scale placebo-controlled beta-blocker studies in systolic heart failure revisited: results from CIBIS-II, COPERNICUS and SENIORS-SHF compared with stratified subsets from MERIT-HF.

PubMed

Wikstrand, J; Wedel, H; Castagno, D; McMurray, J J V

2014-02-01

The four pivotal beta-blocker trials in heart failure (HF) had different inclusion criteria, making comparison difficult without patient stratifying. The aim of this study was to compare, in similar patients, the effects of bisoprolol, metoprolol controlled release/extended release (CR/XL), carvedilol and nebivolol on (i) total mortality, (ii) all-cause mortality or hospitalization due to cardiovascular causes (time to first event), (iii) all-cause mortality or hospitalization because of HF and (iv) tolerability, defined as discontinuation of randomized treatment. We compared stratified (s ) subsets in MERIT-HF with patients in CIBIS-II [New York Heart Association (NYHA) class III/IV and ejection fraction (EF) ≤ 35%] and COPERNICUS (NYHA III/IV and EF <25%) and in patients with systolic HF in SENIORS-SHF (age ≥ 70 years and EF ≤ 35%). The annual mortality rates in the placebo and beta-blocker arms were: (i) CIBIS-II (n = 2647), 13.2% vs. 8.8% (relative risk reduction 34%, 95% CI: 19-46, P < 0.0001) and MERIT-HFs (n = 2002), 14.8% vs. 8.6% (relative risk reduction 42%, 95% CI: 24-56, P < 0.0001); (ii) COPERNICUS (n = 2289), 19.7% vs. 12.8% (relative risk reduction 35%, 95% CI: 19-48, P = 0.0014) and MERIT-HFs (n = 795), 19.1% vs. 11.7% (relative risk reduction 39%; 95% CI: 11-58, P = 0.0086); (iii) SENIORS-SHF (n = 1359), 11.3% vs. 9.7% (relative risk reduction 16%, NS) and MERIT-HFs (n = 985), 14.8% vs. 10.1% (relative risk reduction 32%, 95% CI: 2-53, P = 0.038). The effects on the other outcomes assessed were similar. Analyses indicated fewer discontinuations from randomized treatment on beta-blockers compared with placebo in COPERNICUS and the MERIT-HFs subsets. The efficacy and tolerability of bisoprolol, carvedilol and metoprolol CR/XL are similar in patients with systolic HF, irrespective of NYHA class or ejection fraction. Nebivolol is less effective and not better tolerated. © 2013 The Association for the Publication of the Journal of Internal Medicine.

Effects of discontinuing a high-fat diet on mitochondrial proteins and 6-hydroxydopamine-induced dopamine depletion in rats.

PubMed

Ma, Delin; Shuler, Jeffrey M; Raider, Kayla D; Rogers, Robert S; Wheatley, Joshua L; Geiger, Paige C; Stanford, John A

2015-07-10

Diet-induced obesity can increase the risk for developing age-related neurodegenerative diseases including Parkinson's disease (PD). Increasing evidence suggests that mitochondrial and proteasomal mechanisms are involved in both insulin resistance and PD. The goal of this study was to determine whether diet intervention could influence mitochondrial or proteasomal protein expression and vulnerability to 6-Hydroxydopamine (6-OHDA)-induced nigrostriatal dopamine (DA) depletion in rats' nigrostriatal system. After a 3 month high-fat diet regimen, we switched one group of rats to a low-fat diet for 3 months (HF-LF group), while the other half continued with the high-fat diet (HF group). A chow group was included as a control. Three weeks after unilateral 6-OHDA lesions, HF rats had higher fasting insulin levels and higher Homeostasis model assessment of insulin resistance (HOMA-IR), indicating insulin resistance. HOMA-IR was significantly lower in HF-LF rats than HF rats, indicating that insulin resistance was reversed by switching to a low-fat diet. Compared to the Chow group, the HF group exhibited significantly greater DA depletion in the substantia nigra but not in the striatum. DA depletion did not differ between the HF-LF and HF group. Proteins related to mitochondrial function (such as AMPK, PGC-1α), and to proteasomal function (such as TCF11/Nrf1) were influenced by diet intervention, or by 6-OHDA lesion. Our findings suggest that switching to a low-fat diet reverses the effects of a high-fat diet on systemic insulin resistance, and mitochondrial and proteasomal function in the striatum. Conversely, they suggest that the effects of the high-fat diet on nigrostriatal vulnerability to 6-OHDA-induced DA depletion persist. Copyright © 2015 Elsevier B.V. All rights reserved.

Studies of dispersion energy in hydrogen-bonded systems. H2O-HOH, H2O-HF, H3N-HF, HF-HF

NASA Astrophysics Data System (ADS)

Szcześniak, M. M.; Scheiner, Steve

1984-02-01

Dispersion energy is calculated in the systems H2O-HOH, H2O-HF, H3N-HF, and HF-HF as a function of the intermolecular separation using a variety of methods. M≂ller-Plesset perturbation theory to second and third orders is applied in conjunction with polarized basis sets of 6-311G** type and with an extended basis set including a second set of polarization functions (DZ+2P). These results are compared to a multipole expansion of the dispersion energy, based on the Unsöld approximation, carried out to the inverse tenth power of the intermolecular distance. Pairwise evaluation is also carried out using both atom-atom and bond-bond formulations. The MP3/6-311G** results are in generally excellent accord with the leading R-6 term of the multipole expansion. This expansion, if carried out to the R-10 term, reproduces extremely well previously reported dispersion energies calculated via variation-perturbation theory. Little damping of the expansion is required for intermolecular distances equal to or greater than the equilibrium separation. Although the asymptotic behavior of the MP2 dispersion energy is somewhat different than that of the other methods, augmentation of the basis set by a second diffuse set of d functions leads to quite good agreement in the vicinity of the minima. Both the atom-atom and bond-bond parametrization schemes are in good qualitative agreement with the other methods tested. All approaches produce similar dependence of the dispersion energy upon the angular orientation between the two molecules involved in the H bond.

The Structure of Liquid and Amorphous Hafnia.

PubMed

Gallington, Leighanne C; Ghadar, Yasaman; Skinner, Lawrie B; Weber, J K Richard; Ushakov, Sergey V; Navrotsky, Alexandra; Vazquez-Mayagoitia, Alvaro; Neuefeind, Joerg C; Stan, Marius; Low, John J; Benmore, Chris J

2017-11-10

Understanding the atomic structure of amorphous solids is important in predicting and tuning their macroscopic behavior. Here, we use a combination of high-energy X-ray diffraction, neutron diffraction, and molecular dynamics simulations to benchmark the atomic interactions in the high temperature stable liquid and low-density amorphous solid states of hafnia. The diffraction results reveal an average Hf-O coordination number of ~7 exists in both the liquid and amorphous nanoparticle forms studied. The measured pair distribution functions are compared to those generated from several simulation models in the literature. We have also performed ab initio and classical molecular dynamics simulations that show density has a strong effect on the polyhedral connectivity. The liquid shows a broad distribution of Hf-Hf interactions, while the formation of low-density amorphous nanoclusters can reproduce the sharp split peak in the Hf-Hf partial pair distribution function observed in experiment. The agglomeration of amorphous nanoparticles condensed from the gas phase is associated with the formation of both edge-sharing and corner-sharing HfO 6,7 polyhedra resembling that observed in the monoclinic phase.

Processing, Structure and High Temperature Oxidation Properties of Polymer-Derived and Hafnium Oxide Based Ceramic Systems

NASA Astrophysics Data System (ADS)

Terauds, Kalvis

Demands for hypersonic aircraft are driving the development of ultra-high temperature structural materials. These aircraft, envisioned to sustain Mach 5+, are expected to experience continuous temperatures of 1200--1800°C on the aircraft surface and temperatures as high as 2800°C in combustion zones. Breakthroughs in the development of fiber based ceramic matrix composites (CMCs) are opening the door to a new class of high-tech UHT structures for aerospace applications. One limitation with current carbon fiber or silicon carbide fiber based CMC technology is the inherent problem of material oxidation, requiring new approaches for protective environmental barrier coatings (EBC) in extreme environments. This thesis focuses on the development and characterization of SiCN-HfO2 based ceramic composite EBC systems to be used as a protective layer for silicon carbide fiber based CMCs. The presented work covers three main architectures for protection (i) multilayer films, (ii) polymer-derived HfSiCNO, and (iii) composite SiCN-HfO 2 infiltration. The scope of this thesis covers processing development, material characterization, and high temperature oxidation behavior of these three SiCN-HfO2 based systems. This work shows that the SiCN-HfO 2 composite materials react upon oxidation to form HfSiO4, offering a stable EBC in streaming air and water vapor at 1600°C.

Fluid status monitoring with a wireless network to reduce cardiovascular-related hospitalizations and mortality in heart failure: rationale and design of the OptiLink HF Study (Optimization of Heart Failure Management using OptiVol Fluid Status Monitoring and CareLink).

PubMed

Brachmann, Johannes; Böhm, Michael; Rybak, Karin; Klein, Gunnar; Butter, Christian; Klemm, Hanno; Schomburg, Rolf; Siebermair, Johannes; Israel, Carsten; Sinha, Anil-Martin; Drexler, Helmut

2011-07-01

The Optimization of Heart Failure Management using OptiVol Fluid Status Monitoring and CareLink (OptiLink HF) study is designed to investigate whether OptiVol fluid status monitoring with an automatically generated wireless CareAlert notification via the CareLink Network can reduce all-cause death and cardiovascular hospitalizations in an HF population, compared with standard clinical assessment. Methods Patients with newly implanted or replacement cardioverter-defibrillator devices with or without cardiac resynchronization therapy, who have chronic HF in New York Heart Association class II or III and a left ventricular ejection fraction ≤35% will be eligible to participate. Following device implantation, patients are randomized to either OptiVol fluid status monitoring through CareAlert notification or regular care (OptiLink 'on' vs. 'off'). The primary endpoint is a composite of all-cause death or cardiovascular hospitalization. It is estimated that 1000 patients will be required to demonstrate superiority of the intervention group to reduce the primary outcome by 30% with 80% power. The OptiLink HF study is designed to investigate whether early detection of congestion reduces mortality and cardiovascular hospitalization in patients with chronic HF. The study is expected to close recruitment in September 2012 and to report first results in May 2014.

Structural stability and electronic structure of transition metal compound: HfN

NASA Astrophysics Data System (ADS)

Sarwan, Madhu; Shukoor, V. Abdul; Singh, Sadhna

2018-05-01

The structural stability of transition metal nitride (HfN) has been investigated using density functional theory (DFT) with the help of Quantum-espresso codes. Our calculations confirm that the hafnium nitride (HfN) is stable in zinc-blende (B3) and rock-salt (B1) type structure. We have also reported the structural and electronic properties of HfN compound. These structural properties have been compared with experimental and theoretical data available on this compound.

Prognostic Value of Lymphocyte G Protein-Coupled Receptor Kinase-2 Protein Levels in Patients With Heart Failure

PubMed Central

Rengo, Giuseppe; Pagano, Gennaro; Filardi, Pasquale Perrone; Femminella, Grazia Daniela; Parisi, Valentina; Cannavo, Alessandro; Liccardo, Daniela; Komici, Klara; Gambino, Giuseppina; D’Amico, Maria Loreta; de Lucia, Claudio; Paolillo, Stefania; Trimarco, Bruno; Vitale, Dino Franco; Ferrara, Nicola; Koch, Walter J; Leosco, Dario

2016-01-01

Rationale Sympathetic nervous system (SNS) hyperactivity is associated with poor prognosis in patients with HF, yet routine assessment of SNS activation is not recommended for clinical practice. Myocardial G protein-coupled receptor kinase 2 (GRK2) is up-regulated in heart failure (HF) patients, causing dysfunctional β-adrenergic receptor signaling. Importantly, myocardial GRK2 levels correlate with levels found in peripheral lymphocytes of HF patients. Objective The independent prognostic value of blood GRK2 measurements in HF patients has never been investigated, thus, the purpose of the present study was to evaluate whether lymphocyte GRK2 levels predict clinical outcome in HF patients. Methods and Results We prospectively studied 257 HF patients with mean left ventricular ejection fraction (LVEF) of 31.4±8.5%. At the time of enrollment, plasma norepinephrine, serum NT-proBNP and lymphocyte GRK2 levels, as well as clinical and instrumental variables were measured. The prognostic value of GRK2 to predict cardiovascular (CV) death and all-cause mortality was assessed using the Cox proportional hazard model including demographic, clinical, instrumental and laboratory data. Over a mean follow-up period of 37.5±20.2 months (range: 3–60 months) there were 102 CV deaths. Age, LVEF, NYHA class, Chronic Obstructive Pulmonary Disease, Chronic Kidney Disease, N-terminal-pro Brain Natriuretic Peptide, and lymphocyte GRK2 protein levels were independent predictors of CV mortality in HF patients. GRK2 levels showed an additional prognostic and clinical value over demographic and clinical variables. The independent prognostic value of lymphocyte GRK2 levels was also confirmed for all-cause mortality. Conclusion Lymphocyte GRK2 protein levels can independently predict prognosis in patients with HF. PMID:26884616

Self-Reported Sleep Duration, Napping, and Incident Heart Failure: Prospective Associations in the British Regional Heart Study.

PubMed

Wannamethee, S Goya; Papacosta, Olia; Lennon, Lucy; Whincup, Peter H

2016-09-01

To examine the associations between self-reported nighttime sleep duration and daytime sleep and incident heart failure (HF) in men with and without preexisting cardiovascular disease (CVD). Population-based prospective study. General practices in 24 British towns. Men aged 60-79 without prevalent HF followed for 9 years (N = 3,723). Information on incident HF cases was obtained from primary care records. Assessment of sleep was based on self-reported sleep duration at night and daytime napping. Self-reported short nighttime sleep duration and daytime sleep of longer than 1 hour were associated with preexisting CVD, breathlessness, depression, poor health, physical inactivity, and manual social class. In all men, self-reported daytime sleep of longer than 1 hour duration was associated with significantly greater risk of HF after adjustment for potential confounders (adjusted hazard ratio (aHR) = 1.69, 95% CI = 1.06-2.71) than in those who reported no daytime napping. Self-reported nighttime sleep duration was not associated with HF risk except in men with preexisting CVD (<6 hours: aHR = 2.91, 95% CI = 1.31-6.45; 6 hours: aHR = 1.89, 95% CI = 0.89-4.03; 8 hours: aHR = 1.29, 95% CI = 0.61-2.71; ≥9 hours: aHR = 1.80, 905% CI = 0.71-4.61 vs nighttime sleep of 7 hours). Snoring was not associated with HF risk. Self-reported daytime napping of longer than 1 hour is associated with greater risk of HF in older men. Self-reported short sleep (<6 hours) in men with CVD is associated with particularly high risk of developing HF. © 2016 The Authors. The Journal of the American Geriatrics Society published by Wiley Periodicals, Inc. on behalf of The American Geriatrics Society.

Heart Failure in Africa, Asia, the Middle East and South America: The INTER-CHF study.

PubMed

Dokainish, Hisham; Teo, Koon; Zhu, Jun; Roy, Ambuj; AlHabib, Khalid F; ElSayed, Ahmed; Palileo-Villaneuva, Lia; Lopez-Jaramillo, Patricio; Karaye, Kamilu; Yusoff, Khalid; Orlandini, Andres; Sliwa, Karen; Mondo, Charles; Lanas, Fernando; Prabhakaran, Dorairaj; Badr, Amr; Elmaghawry, Mohamed; Damasceno, Albertino; Tibazarwa, Kemi; Belley-Cote, Emilie; Balasubramanian, Kumar; Yacoub, Magdi H; Huffman, Mark D; Harkness, Karen; Grinvalds, Alex; McKelvie, Robert; Yusuf, Salim

2016-02-01

There are few data on heart failure (HF) patients from Africa, Asia, the Middle East and South America. INTER-CHF is a prospective study that enrolled HF patients in 108 centers in 16 countries from 2012 to 2014. Consecutive ambulatory or hospitalized adult patients with HF were enrolled. Baseline data were recorded on sociodemographics, clinical characteristics, HF etiology and treatments. Age- and sex-adjusted results are reported. We recruited 5813 HF patients: mean(SE) age=59(0.2)years, 39% female, 65% outpatients, 31% from rural areas, 26% with HF with preserved ejection fraction, with 1294 from Africa, 2661 from Asia, 1000 from the Middle-East, and 858 from South America. Participants from Africa-closely followed by Asians-were younger, had lower literacy levels, and were less likely to have health or medication insurance or be on beta-blockers compared with participants from other regions, but were most likely to be in NYHA class IV. Participants from South America were older, had higher insurance and literacy levels, and, along with Middle Eastern participants, were more likely to be on beta-blockers, but had the lowest proportion in NYHA IV. Ischemic heart disease was the most common HF etiology in all regions except Africa where hypertensive heart disease was most common. INTER-CHF describes significant regional variability in socioeconomic and clinical factors, etiologies and treatments in HF patients from Africa, Asia, the Middle East and South America. Opportunities exist for improvement in health/medication insurance rates and proportions of patients on beta blockers, particularly in Africa and Asia. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Structural and functional alterations in the atrioventricular node and atrioventricular ring tissue in ischaemia-induced heart failure.

PubMed

Yanni, Joseph; Maczewski, Michal; Mackiewicz, Urszula; Siew, Samuel; Fedorenko, Olga; Atkinson, Andrew; Price, Marcus; Beresewicz, Andrzej; Anderson, Robert H; Boyett, Mark R; Dobrzynski, Halina

2014-07-01

Heart failure (HF) causes dysfunction of the atrioventricular node (AVN) - first or second-degree heart block is a risk factor for sudden cardiac death in HF patients. The aim of the study was to determine if HF causes remodelling of the AVN and right atrioventricular ring (RAVR). HF was induced in rats (n=4) by ligation of the proximal left coronary artery, which resulted in a large infarct of the left ventricle. Sham-operated rats (n=4) were used as controls. Eight weeks after surgery, functional experiments were performed and the hearts were frozen. The body weight of HF rats was similar to control rats, but the mean heart weight of HF rats was significantly enlarged. In HF rats compared to controls, the left ventricle was dilated, left ventricular end-diastolic pressure elevated (21.0 ± 0.6 and 5.4 ± 0.2 mm Hg), left ventricular ejection fraction reduced (0.2 ± 0.02 and 0.5 ± 0.02) and left ventricular end-systolic pressure reduced (102 ± 4.2 and 127 ± 3.1 mm Hg). In HF rats, the in vivo and in vitro PR intervals were increased (41% and 20%), as was the Wenckebach cycle length, indicative of AVN dysfunction. The collagen content was significantly increased in the AVN and RAVR indicating fibrosis. Immunolabelling of caveolin3 (cell membrane marker) showed that there was hypertrophy in HF (cell diameter was increased by 63%, 39% in AVN, RAVR). The TUNEL assay showed that the myocytes of the AVN and RAVR in HF undergo apoptotic cell death. Immunolabelling showed that expression of HCN4 was significantly decreased in the AVN and RAVR (43% and 47%) in HF. We conclude that in HF there is remodelling of the AVN and RAVR and this remodelling may explain the AVN dysfunction.

Assessment of Quantum Mechanical Methods for Copper and Iron Complexes by Photoelectron Spectroscopy.

PubMed

Niu, Shuqiang; Huang, Dao-Ling; Dau, Phuong D; Liu, Hong-Tao; Wang, Lai-Sheng; Ichiye, Toshiko

2014-03-11

Broken-symmetry density functional theory (BS-DFT) calculations are assessed for redox energetics [Cu(SCH 3 ) 2 ] 1-/0 , [Cu(NCS) 2 ] 1-/0 , [FeCl 4 ] 1-/0 , and [Fe(SCH 3 ) 4 ] 1-/0 against vertical detachment energies (VDE) from valence photoelectron spectroscopy (PES), as a prelude to studies of metalloprotein analogs. The M06 and B3LYP hybrid functionals give VDE that agree with the PES VDE for the Fe complexes, but both underestimate it by ∼400 meV for the Cu complexes; other hybrid functionals give VDEs that are an increasing function of the amount of Hartree-Fock (HF) exchange and so cannot show good agreement for both Cu and Fe complexes. Range-separated (RS) functionals appear to give a better distribution of HF exchange since the negative HOMO energy is approximately equal to the VDEs but also give VDEs dependent on the amount of HF exchange, sometimes leading to ground states with incorrect electron configurations; the LRC- ω PBEh functional reduced to 10% HF exchange at short-range give somewhat better values for both, although still ∼150 meV too low for the Cu complexes and ∼50 meV too high for the Fe complexes. Overall, the results indicate that while HF exchange compensates for self-interaction error in DFT calculations of both Cu and Fe complexes, too much may lead to more sensitivity to nondynamical correlation in the spin-polarized Fe complexes.

Assessment of Quantum Mechanical Methods for Copper and Iron Complexes by Photoelectron Spectroscopy

PubMed Central

2015-01-01

Broken-symmetry density functional theory (BS-DFT) calculations are assessed for redox energetics [Cu(SCH3)2]1–/0, [Cu(NCS)2]1–/0, [FeCl4]1–/0, and [Fe(SCH3)4]1–/0 against vertical detachment energies (VDE) from valence photoelectron spectroscopy (PES), as a prelude to studies of metalloprotein analogs. The M06 and B3LYP hybrid functionals give VDE that agree with the PES VDE for the Fe complexes, but both underestimate it by ∼400 meV for the Cu complexes; other hybrid functionals give VDEs that are an increasing function of the amount of Hartree–Fock (HF) exchange and so cannot show good agreement for both Cu and Fe complexes. Range-separated (RS) functionals appear to give a better distribution of HF exchange since the negative HOMO energy is approximately equal to the VDEs but also give VDEs dependent on the amount of HF exchange, sometimes leading to ground states with incorrect electron configurations; the LRC-ωPBEh functional reduced to 10% HF exchange at short-range give somewhat better values for both, although still ∼150 meV too low for the Cu complexes and ∼50 meV too high for the Fe complexes. Overall, the results indicate that while HF exchange compensates for self-interaction error in DFT calculations of both Cu and Fe complexes, too much may lead to more sensitivity to nondynamical correlation in the spin-polarized Fe complexes. PMID:24803858

Isoenergetic feeding of low carbohydrate-high fat diets does not increase brown adipose tissue thermogenic capacity in rats.

PubMed

Betz, Matthias J; Bielohuby, Maximilian; Mauracher, Brigitte; Abplanalp, William; Müller, Hans-Helge; Pieper, Korbinian; Ramisch, Juliane; Tschöp, Matthias H; Beuschlein, Felix; Bidlingmaier, Martin; Slawik, Marc

2012-01-01

Low-carbohydrate, high-fat (LC-HF) diets are popular for inducing weight loss in overweighed adults. Adaptive thermogenesis increased by specific effects of macronutrients on energy expenditure has been postulated to induce this weight loss. We studied brown adipose tissue (BAT) morphology and function following exposure to different LC-HF diets. Male Wistar rats were fed a standard control diet ad libitum or pair-fed isoenergetic amounts of three experimental diets for 4 weeks. The diets had the following macronutrient composition (% metabolizable energy: carbohydrates, fat, protein): control (64.3/16.7/19), LC-HF-low protein (LC-HF-LP, 1.7/92.8/5.5), LC-HF-normal-protein (LC-HF-NP, 2.2/78.7/19.1), and a high fat diet with carbohydrates ("high fat", 19.4/61.9/18.7). Body weight gain was reduced in all pair-fed experimental groups as compared to rats fed the control diet, with more pronounced effect in rats on LC-HF diets than on the high fat diet with carbohydrates. High fat diets increased expression of PGC1α and ADRB3 in BAT indicating higher SNS outflow. However, UCP1 mRNA expression and expression of UCP1 assessed by immunohistochemistry was not different between diet groups. In accordance, analysis of mitochondrial function in-vitro by extracellular flux analyser (Seahorse Bioscience) and measurement of inducible thermogenesis in vivo (primary endpoint), explored by indirect calorimetry following norepinephrine injection, did not show significant differences between groups. Histology of BAT revealed increased lipid droplet size in rats fed the high-fat diet and both LC-HF diets. All experimental diets upregulated expression of genes which are indicative for increased BAT activity. However, the functional measurements in vivo revealed no increase of inducible BAT thermogenesis. This indicates that lower body weight gain with LC-HF diets and a high fat diet in a pair-feeding setting is not caused by increased adaptive thermogenesis in BAT.

Nature, nurture or nutrition? Impact of maternal nutrition on maternal care, offspring development and reproductive function

PubMed Central

Connor, K L; Vickers, M H; Beltrand, J; Meaney, M J; Sloboda, D M

2012-01-01

We have previously reported that offspring of mothers fed a high fat (HF) diet during pregnancy and lactation enter puberty early and are hyperleptinaemic, hyperinsulinaemic and obese as adults. Poor maternal care and bonding can also impact offspring development and disease risk. We therefore hypothesized that prenatal nutrition would affect maternal care and that an interaction may exist between a maternal HF diet and maternal care, subsequently impacting on offspring phenotype. Wistar rats were mated and randomized to control dams fed a control diet (CON) or dams fed a HF diet from conception until the end of lactation (HF). Maternal care was assessed by observing maternal licking and grooming of pups between postnatal day (P)3 and P8. Postweaning (P22), offspring were fed a control (–con) or HF (–hf) diet. From P27, pubertal onset was assessed. At ∼P105 oestrous cyclicity was investigated. Maternal HF diet reduced maternal care; HF-fed mothers licked and groomed pups less than CON dams. Maternal fat:lean ratio was higher in HF dams at weaning and was associated with higher maternal plasma leptin and insulin concentrations, but there was no effect of maternal care on fat:lean ratio or maternal hormone levels. Both female and male offspring of HF dams were lighter from birth to P11 than offspring of CON dams, but by P19, HF offspring were heavier than controls. Prepubertal retroperitoneal fat mass was greater in pups from HF-fed dams compared to CON and was associated with elevated circulating leptin concentrations in females only, but there was neither an effect of maternal care, nor an interaction between maternal diet and care on prepubertal fat mass. Pups from HF-fed dams went into puberty early and this effect was exacerbated by a postweaning HF diet. Maternal and postweaning HF diets independently altered oestrous cyclicity in females: female offspring of HF-fed mothers were more likely to have prolonged or persistent oestrus, whilst female offspring fed a HF diet postweaning were more likely to have irregular oestrous cycles and were more likely to have prolonged or persistent oestrus. These data indicate that maternal HF nutrition during pregnancy and lactation results in a maternal obese phenotype and has significant impact on maternal care during lactation. Maternal and postweaning nutritional signals, independent of maternal care, alter offspring body fat pre-puberty and female reproductive function in adulthood, which may be associated with advanced ovarian ageing and altered fertility. PMID:22411006

Cost-effectiveness of telephonic disease management in heart failure.

PubMed

Smith, Brad; Hughes-Cromwick, Paul F; Forkner, Emma; Galbreath, Autumn Dawn

2008-02-01

To evaluate the cost-effectiveness of a telephonic disease management (DM) intervention in heart failure (HF). Randomized controlled trial of telephonic DM among 1069 community-dwelling patients with systolic HF (SHF) and diastolic HF performed between 1999 and 2003. The enrollment period was 18 months per subject. Bootstrap-resampled incremental cost-effectiveness ratios (ICERs) were computed and compared across groups. Direct medical costs were obtained from a medical record review that collected records from 92% of patients; 66% of records requested were obtained. Disease management produced statistically significant survival advantages among all patients (17.4 days, P = .04), among patients with New York Heart Association (NYHA) class III/IV symptoms (47.7 days, P = .02), and among patients with SHF (24.2 days, P = .01). Analyses of direct medical and intervention costs showed no cost savings associated with the intervention. For all patients and considering all-cause medical care, the ICER was $146 870 per quality-adjusted life-year (QALY) gained, while for patients with NYHA class III/IV symptoms and patients with SHF, the ICERs were $67 784 and $95 721 per QALY gained, respectively. Costs per QALY gained were $101 120 for all patients, $72 501 for patients with SHF, and $41 348 for patients with NYHA class III/IV symptoms. The intervention was effective but costly to implement and did not reduce utilization. It may not be cost-effective in other broadly representative samples of patients. However, with program cost reductions and proper targeting, this program may produce life-span increases at costs that are less than $100 000 per QALY gained.

Baroreflex activation therapy for the treatment of heart failure with a reduced ejection fraction: safety and efficacy in patients with and without cardiac resynchronization therapy.

PubMed

Zile, Michael R; Abraham, William T; Weaver, Fred A; Butter, Christian; Ducharme, Anique; Halbach, Marcel; Klug, Didier; Lovett, Eric G; Müller-Ehmsen, Jochen; Schafer, Jill E; Senni, Michele; Swarup, Vijay; Wachter, Rolf; Little, William C

2015-10-01

Increased sympathetic and decreased parasympathetic activity contribute to heart failure (HF) symptoms and disease progression. Carotid baroreceptor stimulation (baroreflex activation therapy, BAT) results in centrally mediated reduction of sympathetic and increase in parasympathetic activity. Because patients treated with cardiac resynchronization therapy (CRT) may have less sympathetic/parasympathetic imbalance, we hypothesized that there would be differences in the response to BAT in patients with CRT vs. those without CRT. New York Heart Association (NYHA) Class III patients with an ejection fraction (EF) ≤35% were randomized (1 : 1) to ongoing guideline-directed medical and device therapy (GDMT, control) or ongoing GDMT plus BAT. Safety endpoint was system-/procedure-related major adverse neurological and cardiovascular events (MANCE). Efficacy endpoints were Minnesota Living with Heart Failure Quality of Life (QoL), 6-min hall walk distance (6MHWD), N-terminal pro-brain natriuretic peptide (NT-proBNP), left ventricular ejection fraction (LVEF), and HF hospitalization rate. In this sample, 146 patients were randomized (70 control; 76 BAT) and were 140 activated (45 with CRT and 95 without CRT). MANCE-free rate at 6 months was 100% in CRT and 96% in no-CRT group. At 6 months, in the no-CRT group, QoL score, 6MHWD, LVEF, NT-proBNP and HF hospitalizations were significantly improved in BAT patients compared with controls. Changes in efficacy endpoints in the CRT group favoured BAT; however, the improvements were less than in the no-CRT group and were not statistically different from control. BAT is safe and significantly improved QoL, exercise capacity, NTpro-BNP, EF, and rate of HF hospitalizations in GDMT-treated NYHA Class III HF patients. These effects were most pronounced in patients not treated with CRT. © 2015 The Authors European Journal of Heart Failure © 2015 European Society of Cardiology.

Clinical trials update from the Heart Failure Society of America Meeting 2009: FAST, IMPROVE-HF, COACH galectin-3 substudy, HF-ACTION nuclear substudy, DAD-HF, and MARVEL-1.

PubMed

Lainscak, Mitja; Coletta, Alison P; Sherwi, Nasser; Cleland, John G F

2010-02-01

This article presents findings and a commentary on late-breaking trials presented during the meeting of the Heart Failure Society of America in September 2009. Unpublished reports should be considered as preliminary, since analyses may change in the final publication. The FAST trial showed somewhat better performance of intrathoracic impedance for prediction of deterioration in patients with heart failure (HF) when compared with daily weighing. The IMPROVE-HF study reported the benefits of education on the management of patients with systolic HF. Galectin-3 appeared a useful method for improving risk stratification of patients with chronic HF in a substudy of the COACH trial. A nuclear substudy of the HF-ACTION trial failed to demonstrate that resting myocardial perfusion imaging, a measure of myocardial scar and viability, was clinically useful. A small randomized controlled trial (DAD-HF) suggested that the use of low-dose dopamine in patients with acutely decompensated HF was associated with less deterioration in renal function and less hypokalaemia. The MARVEL-1 trial raises further concerns about the safety of myoblast transplantation in ischaemic HF.

The effect of the hydrogen fluoride chain on the aromaticity of C6H6 in the C6H6...(HF)1-4 complexes

NASA Astrophysics Data System (ADS)

Jouypazadeh, Hamidreza; Farrokhpour, Hossein; Solimannejad, Mohammad

2018-02-01

The effect of the hydrogen fluoride chain ((HF)n) on the aromaticity and π character of C-C bonds of C6H6 in the C6H6...(HF)n (n = 1-4) complexes were investigated using density functional theory employing RM05 functional. It was found that the binding energy between C6H6 and different (HF)n chains showed a maximum at n = 3 (C6H6...(HF)3). Also, the π-hydrogen interaction (πHI) and the bifurcated fluorine interaction (BFI) increased and decreased the π character of the C-C bond of C6H6, respectively. In addition, the change of aromaticity of the C6H6 due to the interaction with the HF chains was also studied using three different aspects such as aromatic fluctuation index (FLU), average two centre index (ATI) and proton nuclear magnetic resonance (HNMR) spectrum. The most change in the aromaticity happens when the C6H6 interacts with (HF)3 chain. The variation of aromaticity with the binding energy and the summation of two-body terms were investigated and very good linear correlations were observed.

Density-functional theory molecular dynamics simulations of a-HfO2/a-SiO2/SiGe and a-HfO2/a-SiO2/Ge with a-SiO2 and a-SiO suboxide interfacial layers

NASA Astrophysics Data System (ADS)

Chagarov, Evgueni A.; Kavrik, Mahmut S.; Fang, Ziwei; Tsai, Wilman; Kummel, Andrew C.

2018-06-01

Comprehensive Density-Functional Theory (DFT) Molecular Dynamics (MD) simulations were performed to investigate interfaces between a-HfO2 and SiGe or Ge semiconductors with fully-stoichiometric a-SiO2 or sub-oxide SiO interlayers. The electronic structure of the selected stacks was calculated with a HSE06 hybrid functional. Simulations were performed before and after hydrogen passivation of residual interlayer defects. For the SiGe substrate with Ge termination prior to H passivation, the stacks with a-SiO suboxide interlayer (a-HfO2/a-SiO/SiGe) demonstrate superior electronic properties and wider band-gaps than the stacks with fully coordinated a-SiO2 interlayers (a-HfO2/a-SiO2/SiGe). After H passivation, most of the a-HfO2/a-SiO2/SiGe defects are passivated. To investigate effect of random placement of Si and Ge atoms additional simulations with a randomized SiGe slab were performed demonstrating improvement of electronic structure. For Ge substrates, before H passivation, the stacks with a SiO suboxide interlayer (a-HfO2/a-SiO/Ge) also demonstrate wider band-gaps than the stacks with fully coordinated a-SiO2 interlayers (a-HfO2/a-SiO2/Ge). However, even for a-HfO2/a-SiO/Ge, the Fermi level is shifted close to the conduction band edge (CBM) consistent with Fermi level pinning. Again, after H passivation, most of the a-HfO2/a-SiO2/Ge defects are passivated. The stacks with fully coordinated a-SiO2 interlayers have much stronger deformation and irregularity in the semiconductor (SiGe or Ge) upper layers leading to multiple under-coordinated atoms which create band-edge states and decrease the band-gap prior to H passivation.

Synthesis of High-Frequency Ground Motion Using Information Extracted from Low-Frequency Ground Motion

NASA Astrophysics Data System (ADS)

Iwaki, A.; Fujiwara, H.

2012-12-01

Broadband ground motion computations of scenario earthquakes are often based on hybrid methods that are the combinations of deterministic approach in lower frequency band and stochastic approach in higher frequency band. Typical computation methods for low-frequency and high-frequency (LF and HF, respectively) ground motions are the numerical simulations, such as finite-difference and finite-element methods based on three-dimensional velocity structure model, and the stochastic Green's function method, respectively. In such hybrid methods, LF and HF wave fields are generated through two different methods that are completely independent of each other, and are combined at the matching frequency. However, LF and HF wave fields are essentially not independent as long as they are from the same event. In this study, we focus on the relation among acceleration envelopes at different frequency bands, and attempt to synthesize HF ground motion using the information extracted from LF ground motion, aiming to propose a new method for broad-band strong motion prediction. Our study area is Kanto area, Japan. We use the K-NET and KiK-net surface acceleration data and compute RMS envelope at four frequency bands: 0.5-1.0 Hz, 1.0-2.0 Hz, 2.0-4.0 Hz, .0-8.0 Hz, and 8.0-16.0 Hz. Taking the ratio of the envelopes of adjacent bands, we find that the envelope ratios have stable shapes at each site. The empirical envelope-ratio characteristics are combined with low-frequency envelope of the target earthquake to synthesize HF ground motion. We have applied the method to M5-class earthquakes and a M7 target earthquake that occurred in the vicinity of Kanto area, and successfully reproduced the observed HF ground motion of the target earthquake. The method can be applied to a broad band ground motion simulation for a scenario earthquake by combining numerically-computed low-frequency (~1 Hz) ground motion with the empirical envelope ratio characteristics to generate broadband ground motion. The strengths of the proposed method are that: 1) it is based on observed ground motion characteristics, 2) it takes full advantage of precise velocity structure model, and 3) it is simple and easy to apply.

The effect of androgen excess on maternal metabolism, placental function and fetal growth in obese dams.

PubMed

Fornes, Romina; Maliqueo, Manuel; Hu, Min; Hadi, Laila; Jimenez-Andrade, Juan M; Ebefors, Kerstin; Nyström, Jenny; Labrie, Fernand; Jansson, Thomas; Benrick, Anna; Stener-Victorin, Elisabet

2017-08-14

Pregnant women with polycystic ovary syndrome (PCOS) are often overweight or obese. To study the effects of maternal androgen excess in obese dams on metabolism, placental function and fetal growth, female C57Bl6J mice were fed a control (CD) or a high fat/high sucrose (HF/HS) diet for 4-10 weeks, and then mated. On gestational day (GD) 15.5-17.5, dams were injected with dihydrotestosterone (CD-DHT, HF/HS-DHT) or a vehicle (CD-Veh, HF/HS-Veh). HF/HS dams had higher fat content, both before mating and on GD18.5, with no difference in glucose homeostasis, whereas the insulin sensitivity was higher in DHT-exposed dams. Compared to the CD groups, the livers from HF/HS dams weighed more on GD18.5, the triglyceride content was higher, and there was a dysregulation of liver enzymes related to lipogenesis and higher mRNA expression of Fitm1. Fetuses from HF/HS-Veh dams had lower liver triglyceride content and mRNA expression of Srebf1c. Maternal DHT exposure, regardless of diet, decreased fetal liver Pparg mRNA expression and increased placental androgen receptor protein expression. Maternal diet-induced obesity, together with androgen excess, affects maternal and fetal liver function as demonstrated by increased triglyceride content and dysfunctional expression of enzymes and transcription factors involved in de novo lipogenesis and fat storage.

Translating and testing the ENABLE: CHF-PC concurrent palliative care model for older adults with heart failure and their family caregivers.

PubMed

Dionne-Odom, J Nicholas; Kono, Alan; Frost, Jennifer; Jackson, Lisa; Ellis, Daphne; Ahmed, Ali; Azuero, Andres; Bakitas, Marie

2014-09-01

Heart failure (HF) and palliative care (PC) organizations recommend early PC to improve the quality of life of patients living with HF. We conducted a two-phase formative evaluation study to translate a cancer-focused concurrent PC intervention into one that would be appropriate for rural-dwelling adults with New York Heart Association Class III-IV HF and their primary caregivers. Phase I: We tailored the intervention for an HF population via literature review, expert consultation, and clinician (N=15) small group interviews. Phase II: We enrolled 11 patient/caregiver dyads to assess intervention feasibility and satisfaction. We assessed participants' experiences and satisfaction after session/week three and session/week six via digitally recorded interviews. Clinician and participant interviews were transcribed and content analyzed. Outcome measures were evaluated for completion rates and effect sizes. Phase I: Clinicians described barriers to initiating PC in HF, triggers for initiating PC, and suggestions for intervention improvement. Phase II: Participants were able to complete the majority of study sessions, measures, and interviews. Satisfaction interviews revealed the content to be relevant and comprehensive in addressing HF patient and caregiver primary concerns; however, participants unanimously suggested making the intervention available earlier in the illness trajectory. Efficacy measures demonstrated small to medium effect sizes. We tailored and demonstrated feasibility of providing an early, concurrent palliative care intervention to patients with advanced HF and their caregivers. Based on this experience we are now conducting an efficacy trial in a racially diverse sample.

Short-term outcomes in heart failure patients with chronic obstructive pulmonary disease in the community

PubMed Central

O’Kelly, Noel; Robertson, William; Smith, Jude; Dexter, Jonathan; Carroll-Hawkins, Collette; Ghosh, Sudip

2012-01-01

AIM: To establish the short term outcomes of heart failure (HF) patients in the community who have concurrent chronic obstructive pulmonary disease (COPD). METHODS: We evaluated 783 patients (27.2%) with left ventricular systolic dysfunction under the care of a regional nurse-led community HF team between June 2007 and June 2010 through a database analysis. RESULTS: One hundred and one patients (12.9%) also had a diagnosis of COPD; 94% of patients were treated with loop diuretics, 83% with angiotensin converting enzyme inhibitors, 74% with β-blockers; 10.6% with bronchodilators; and 42% with aldosterone antagonists. The mean age of the patients was 77.9 ± 5.7 years; 43% were female and mean New York Heart Association class was 2.3 ± 0.6. The mean follow-up was 28.2 ± 2.9 mo. β-blocker utilization was markedly lower in patients receiving bronchodilators compared with those not taking bronchodilators (overall 21.7% vs 81%, P < 0.001). The 24-mo survival was 93% in patients with HF alone and 89% in those with both comorbidities (P = not significant). The presence of COPD was associated with increased risk of HF hospitalization [hazard ratio (HR): 1.56; 95% CI: 1.4-2.1; P < 0.001] and major adverse cardiovascular events (HR: 1.23; 95% CI: 1.03-1.75; P < 0.001). CONCLUSION: COPD is a common comorbidity in ambulatory HF patients in the community and is a powerful predictor of worsening HF. It does not however appear to affect short-term mortality in ambulatory HF patients. PMID:22451854

Interactive Digital e-Health Game for Heart Failure Self-Management: A Feasibility Study.

PubMed

Radhakrishnan, Kavita; Toprac, Paul; O'Hair, Matt; Bias, Randolph; Kim, Miyong T; Bradley, Paul; Mackert, Michael

2016-12-01

To develop and test the prototype of a serious digital game for improving community-dwelling older adults' heart failure (HF) knowledge and self-management behaviors. The serious game innovatively incorporates evidence-based HF guidelines with contemporary game technology. The study included three phases: development of the game prototype, its usability assessment, and evaluation of the game's functionality. Usability testing included researchers' usability assessment, followed by research personnel's observations of participants playing the game, and participants' completion of a usability survey. Next, in a pretest-post-test design, validated instruments-the Atlanta Heart Failure Knowledge Test and the Self Care for Heart Failure Index-were used to measure improvement in HF self-management knowledge and behaviors related to HF self-maintenance, self-management, and self-efficacy, respectively. A postgame survey assessed participants' perceptions of the game. During usability testing, with seven participants, 100%, 100%, and 86% found the game easy to play, enjoyable, and helpful for learning about HF, respectively. In the subsequent functionality testing, with 19 participants, 89% found the game interesting, enjoyable, and easy to play. Playing the game resulted in a significant improvement in HF self-management knowledge, a nonsignificant improvement in self-reported behaviors related to HF self-maintenance, and no difference in HF self-efficacy scores. Participants with lower education level and age preferred games to any other medium for receiving information. It is feasible to develop a serious digital game that community-dwelling older adults with HF find both satisfying and acceptable and that can improve their self-management knowledge.

Interactive Digital e-Health Game for Heart Failure Self-Management: A Feasibility Study

PubMed Central

Toprac, Paul; O'Hair, Matt; Bias, Randolph; Kim, Miyong T.; Bradley, Paul; Mackert, Michael

2016-01-01

Abstract Objective: To develop and test the prototype of a serious digital game for improving community-dwelling older adults' heart failure (HF) knowledge and self-management behaviors. The serious game innovatively incorporates evidence-based HF guidelines with contemporary game technology. Materials and Methods: The study included three phases: development of the game prototype, its usability assessment, and evaluation of the game's functionality. Usability testing included researchers' usability assessment, followed by research personnel's observations of participants playing the game, and participants' completion of a usability survey. Next, in a pretest–post-test design, validated instruments—the Atlanta Heart Failure Knowledge Test and the Self Care for Heart Failure Index—were used to measure improvement in HF self-management knowledge and behaviors related to HF self-maintenance, self-management, and self-efficacy, respectively. A postgame survey assessed participants' perceptions of the game. Results: During usability testing, with seven participants, 100%, 100%, and 86% found the game easy to play, enjoyable, and helpful for learning about HF, respectively. In the subsequent functionality testing, with 19 participants, 89% found the game interesting, enjoyable, and easy to play. Playing the game resulted in a significant improvement in HF self-management knowledge, a nonsignificant improvement in self-reported behaviors related to HF self-maintenance, and no difference in HF self-efficacy scores. Participants with lower education level and age preferred games to any other medium for receiving information. Conclusion: It is feasible to develop a serious digital game that community-dwelling older adults with HF find both satisfying and acceptable and that can improve their self-management knowledge. PMID:27976955

Functional anatomy of the hair follicle: The Secondary Hair Germ.

PubMed

Panteleyev, Andrey A

2018-07-01

The secondary hair germ (SHG)-a transitory structure in the lower portion of the mouse telogen hair follicle (HF)-is directly involved in anagen induction and eventual HF regrowth. Some crucial aspects of SHG functioning and ontogenetic relations with other HF parts, however, remain undefined. According to recent evidence (in contrast to previous bulge-centric views), the SHG is the primary target of anagen-inducing signalling and a source of both the outer root sheath (ORS) and ascending HF layers during the initial (morphogenetic) anagen subphase. The SHG is comprised of two functionally distinct cell populations. Its lower portion (originating from lower HF cells that survived catagen) forms all ascending HF layers, while the upper SHG (formed by bulge-derived cells) builds up the ORS. The predetermination of SHG cells to a specific morphogenetic fate contradicts their attribution to the "stem cell" category and supports SHG designation as a "germinative" or a "founder" cell population. The mechanisms of this predetermination driving transition of the SHG from "refractory" to the "competent" state during the telogen remain unknown. Functionally, the SHG serves as a barrier, protecting the quiescent bulge stem cell niche from the extensive follicular papilla/SHG signalling milieu. The formation of the SHG is a prerequisite for efficient "precommitment" of these cells and provides for easier sensing and a faster response to anagen-inducing signals. In general, the formation of the SHG is an evolutionary adaptation, which allowed the ancestors of modern Muridae to acquire a specific, highly synchronized pattern of hair cycling. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

A minireview of E4BP4/NFIL3 in heart failure.

PubMed

Velmurugan, Bharath Kumar; Chang, Ruey-Lin; Marthandam Asokan, Shibu; Chang, Chih-Fen; Day, Cecilia-Hsuan; Lin, Yueh-Min; Lin, Yuan-Chuan; Kuo, Wei-Wen; Huang, Chih-Yang

2018-06-01

Heart failure (HF) remains a major cause of morbidity and mortality worldwide. The primary cause identified for HF is impaired left ventricular myocardial function, and clinical manifestations may lead to severe conditions like pulmonary congestion, splanchnic congestion, and peripheral edema. Development of new therapeutic strategies remains the need of the hour for controlling the problem of HF worldwide. Deeper insights into the molecular mechanisms involved in etiopathology of HF indicate the significant role of calcium signaling, autocrine signaling pathways, and insulin-like growth factor-1 signaling that regulates the physiologic functions of heart growth and development such as contraction, metabolism, hypertrophy, cytokine signaling, and apoptosis. In view of these facts, a transcription factor (TF) regulating the myriad of these signaling pathways may prove as a lead candidate for development of therapeutics. Adenovirus E4 promoter-binding protein (E4BP4), also known as nuclear-factor, interleukin 3 regulated (NFIL3), a type of basic leucine zipper TF, is known to regulate the signaling processes involved in the functioning of heart. The current review discusses about the expression, structure, and functional role of E4BP4 in signaling processes with emphasis on calcium signaling mechanisms, autocrine signaling, and insulin-like growth factor II receptor-mediated processes regulated by E4BP4 that may regulate the pathogenesis of HF. We propose that E4BP4, being the critical component for the regulation of the above signaling processes, may serve as a novel therapeutic target for HF, and scientific investigations are merited in this direction. © 2018 Wiley Periodicals, Inc.

Resting sympathetic arousal moderates the association between parasympathetic reactivity and working memory performance in adults reporting high levels of life stress.

PubMed

Giuliano, Ryan J; Gatzke-Kopp, Lisa M; Roos, Leslie E; Skowron, Elizabeth A

2017-08-01

The neurovisceral integration model stipulates that autonomic function plays a critical role in the regulation of higher-order cognitive processes, yet most work to date has examined parasympathetic function in isolation from sympathetic function. Furthermore, the majority of work has been conducted on normative samples, which typically demonstrate parasympathetic withdrawal to increase arousal needed to complete cognitive tasks. Little is known about how autonomic regulation supports cognitive function in populations exposed to high levels of stress, which is critical given that chronic stress exposure alters autonomic function. To address this, we sought to characterize how parasympathetic (high-frequency heart rate variability, HF-HRV) and sympathetic (preejection period, PEP) measures of cardiac function contribute to individual differences in working memory (WM) capacity in a sample of high-risk women. HF-HRV and PEP were measured at rest and during a visual change detection measure of WM. Multilevel modeling was used to examine within-person fluctuations in WM performance throughout the task concurrently with HF-HRV and PEP, as well as between-person differences as a function of resting HF-HRV and PEP levels. Results indicate that resting PEP moderated the association between HF-HRV reactivity and WM capacity. Increases in WM capacity across the task were associated with increases in parasympathetic activity, but only among individuals with longer resting PEP (lower sympathetic arousal). Follow-up analyses showed that shorter resting PEP was associated with greater cumulative risk exposure. These results support the autonomic space framework, in that the relationship between behavior and parasympathetic function appears dependent on resting sympathetic activation. © 2017 Society for Psychophysiological Research.

Resting sympathetic arousal moderates the association between parasympathetic reactivity and working memory performance in adults reporting high levels of life stress

PubMed Central

Giuliano, Ryan J.; Gatzke-Kopp, Lisa M.; Roos, Leslie E.; Skowron, Elizabeth A.

2017-01-01

The neurovisceral integration model stipulates that autonomic function plays a critical role in the regulation of higher-order cognitive processes, yet most work to date has examined parasympathetic function in isolation from sympathetic function. Furthermore, the majority of work has been conducted on normative samples, which typically demonstrate parasympathetic withdrawal to increase arousal needed to complete cognitive tasks. Little is known about how autonomic regulation supports cognitive function in populations exposed to high levels of stress, which is critical given that chronic stress exposure alters autonomic function. To address this, we sought to characterize how parasympathetic (high-frequency heart rate variability, HF-HRV) and sympathetic (preejection period, PEP) measures of cardiac function contribute to individual differences in working memory (WM) capacity in a sample of high-risk women. HF-HRV and PEP were measured at rest and during a visual change detection measure of WM. Multilevel modeling was used to examine within-person fluctuations in WM performance throughout the task concurrently with HF-HRV and PEP, as well as between-person differences as a function of resting HF-HRV and PEP levels. Results indicate that resting PEP moderated the association between HF-HRV reactivity and WM capacity. Increases in WM capacity across the task were associated with increases in parasympathetic activity, but only among individuals with longer resting PEP (lower sympathetic arousal). Follow-up analyses showed that shorter resting PEP was associated with greater cumulative risk exposure. These results support the autonomic space framework, in that the relationship between behavior and parasympathetic function appears dependent on resting sympathetic activation. PMID:28449242

A study of the neuropsychological correlates in adults with high functioning autism spectrum disorders.

PubMed

Fried, Ronna; Joshi, Gagan; Bhide, Pradeep; Pope, Amanda; Galdo, Maribel; Koster, Ariana; Chan, James; Faraone, Stephen V; Biederman, Joseph

2016-10-01

To examine the unique neuropsychological presentation in adults with high functioning autism spectrum disorders (HF-ASD) by comparison with adults with attention deficit hyperactivity disorder (ADHD). Adults with ASD referred to a specialty clinic (n=26) were compared to two non-ASD groups with (n=52) and without (n=52) ADHD of similar age and sex. No differences in IQ were found. Subjects with HF-ASD were significantly more impaired than both comparison groups in processing speed, cognitive flexibility and sight words. Subjects with HF-ASD were more impaired than controls in working memory, but not the ADHD group. These findings suggest that there may be specific neuropsychological correlates of HF-ASD differing from ADHD that could have significant implications for identifying individuals at risk for ASD.

Ultralow-voltage design of graphene PN junction quantum reflective switch transistor

NASA Astrophysics Data System (ADS)

Sohier, Thibault; Yu, Bin

2011-05-01

We propose the concept of a graphene-based quantum reflective switch (QRS) for low-power logic application. With the unique electronic properties of graphene, a tilted PN junction is used to implement logic switch function with 103 ON/OFF ratio. Carriers are reflected on an electrostatically induced potential step with strong incidence-angle-dependency due to the widening of classically forbidden energies. Optimized design of the device for ultralow-voltage operating has been conducted. The device is constantly ON with a turning-off gate voltage around 180 mV using thin HfO2 as the gate dielectric. The results suggest a class of logic switch devices operating with micropower dissipation.

High early event rates in patients with questionable eligibility for advanced heart failure therapies: Results from the Medical Arm of Mechanically Assisted Circulatory Support (Medamacs) Registry.

PubMed

Ambardekar, Amrut V; Forde-McLean, Rhondalyn C; Kittleson, Michelle M; Stewart, Garrick C; Palardy, Maryse; Thibodeau, Jennifer T; DeVore, Adam D; Mountis, Maria M; Cadaret, Linda; Teuteberg, Jeffrey J; Pamboukian, Salpy V; Cantor, Ryan S; Lindenfeld, JoAnn

2016-06-01

The prognosis of ambulatory patients with advanced heart failure (HF) who are not yet inotrope dependent and implications for evaluation and timing for transplant or destination therapy with a left ventricular assist device (DT-LVAD) are unknown. We hypothesized that the characteristics defining eligibility for advanced HF therapies would be a primary determinant of outcomes in these patients. Ambulatory patients with advanced HF (New York Heart Association class III-IV, Interagency Registry for Mechanically Assisted Circulatory Support profiles 4-7) were enrolled across 11 centers from May 2013 to February 2015. Patients were stratified into 3 groups: likely transplant eligible, DT-LVAD eligible, and ineligible for both transplant and DT-LVAD. Clinical characteristics were collected, and patients were prospectively followed for death, transplant, and left ventricular assist device implantation. The study enrolled 144 patients with a mean follow-up of 10 ± 6 months. Patients in the ineligible cohort (n = 43) had worse congestion, renal function, and anemia compared with transplant (n = 51) and DT-LVAD (n = 50) eligible patients. Ineligible patients had higher mortality (23.3% vs 8.0% in DT-LVAD group and 5.9% in transplant group, p = 0.02). The differences in mortality were related to lower rates of transplantation (11.8% in transplant group vs 2.0% in DT-LVAD group and 0% in ineligible group, p = 0.02) and left ventricular assist device implantation (15.7% in transplant group vs 2.0% in DT-LVAD group and 0% in ineligible group, p < 0.01). Ambulatory patients with advanced HF who were deemed ineligible for transplant and DT-LVAD had markers of greater HF severity and a higher rate of mortality compared with patients eligible for transplant or DT-LVAD. The high early event rate in this group emphasizes the need for timely evaluation and decision making regarding lifesaving therapies. Copyright © 2016 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

Serum magnesium and risk of new onset heart failure in men: the Kuopio Ischemic Heart Disease Study.

PubMed

Kunutsor, Setor K; Khan, Hassan; Laukkanen, Jari A

2016-10-01

Serum magnesium is an essential intracellular cation involved in processes that regulate cardiovascular function and has been linked to the risk of several cardiovascular disease outcomes. We aimed to investigate the association of serum magnesium concentrations with risk of incident heart failure (HF). We studied 2181 middle-aged men without prevalent HF (aged 42-61 years) enrolled in the finnish Kuopio Ischemic Heart Disease prospective cohort study with serum magnesium measurements made at baseline. Hazard ratios (95 % confidence intervals [CI]) for HF were assessed. During a median follow-up of 24.8 years, 278 HF events occurred. Baseline serum magnesium was weakly and inversely associated with several clinical markers and was continuously associated with risk of HF. The age-adjusted HR (95 % CIs) for HF per 1 standard deviation (SD) higher serum magnesium levels was 0.86 (0.76-0.97). The HR (95 % CIs) was 0.87 (0.76-0.98) after controlling for measures of adiposity, socio-economic variables, medical history, blood pressure, renal function, alcohol consumption, and lipids. These findings remained consistent in analyses accounting for incident coronary heart disease. The results were comparable across several clinically relevant subgroups and analyses with atrial fibrillation as a competing risk yielded similar results. Serum magnesium was continuously, inversely and independently associated with future risk of HF. Further research is needed to assess any potential relevance of serum magnesium in HF prevention.

Postural muscle atrophy prevention and recovery and bone remodelling through high frequency proprioception for astronauts

NASA Astrophysics Data System (ADS)

Riva, Dario; Rossitto, Franco; Battocchio, Luciano

2009-09-01

The difficulty in applying active exercises during space flights increases the importance of passive countermeasures, but coupling load and instability remains indispensable for generating high frequency (HF) proprioceptive flows and preventing muscle atrophy and osteoporosis. The present study, in microgravity conditions during a parabolic flight, verified whether an electronic system, composed of a rocking board, a postural reader and a bungee-cord loading apparatus creates HF postural instability comparable to that reachable on the Earth. Tracking the subject, in single stance, to real-time visual signals is necessary to obtain HF instability situations. The bungee-cord loading apparatus allowed the subject to manage the 81.5% body weight load (100% could easily be exceeded). A preliminary training programme schedule on the Earth and in space is suggested. Comparison with a pathological muscle atrophy is presented. The possibility of generating HF proprioceptive flows could complement current countermeasures for the prevention and recovery of muscle atrophy and osteoporosis in terrestrial and space environments. These exercises combine massive activation of spindles and joint receptors, applying simultaneously HF variations of pressure to different areas of the sole of the foot. This class of exercises could improve the effectiveness of current countermeasures, reducing working time and fatigue.

Heart failure and endothelial nitric oxide synthase G894T gene polymorphism frequency variations within ancestries.

PubMed

Oliveira, Romulo V M; Albuquerque, Felipe N; Duque, Gustavo S; Freitas, Rossana G A; Carvalho, Elizeu F; Brandão, Andrea A; Silva, Dayse A; Mourilhe-Rocha, Ricardo; Albuquerque, Denilson C

2018-02-28

The G894T polymorphism in endothelial nitric oxide synthase enzyme gene plays an important role in heart failure (HF) and its frequency varies among populations. We investigated this association in highly admixed samples in terms of ancestry. The cohort included 210 HF patients and 106 healthy individuals. Self-reported race and NYHA class were analyzed for HF patients. G894T polymorphism was analyzed by polymerase chain reaction (PCR) and by restriction fragment length polymorphism technique. Ancestry was estimated using a PCR reaction containing 46 autosomal ancestry informative markers and an analysis by capillary electrophoresis. The GG homozygous genotype had a higher frequency in HF patients (63.8%) than in healthy individuals (48.1%), showing an increased chance (odds ratio 1.90, 95% confidence interval 1.18-3.05). The ancestry profiles in patients and controls were similar, with a major European contribution (57.1% and 63.2%), followed by African (30.2% and 24.0%) and Native American (12.7% and 12.8%), without a significant difference between both samples (p = 0.28). The GG genotype is associated to HF prognosis, and this association remains present in highly admixed sample groups. Copyright © 2017 Elsevier Inc. All rights reserved.

Changing the treatment of heart failure with reduced ejection fraction: clinical use of sacubitril-valsartan combination

PubMed Central

Kaplinsky, Edgardo

2016-01-01

Despite significant therapeutic advances, patients with chronic heart failure (HF) remain at high risk of morbidity and mortality. Sacubitril valsartan (previously known as LCZ696) is a new oral agent approved for the treatment of symptomatic chronic heart failure in adults with reduced ejection fraction. It is described as the first in class angiotensin receptor neprilysin inhibitor (ARNI) since it incorporates the neprilysin inhibitor, sacubitril and the angiotensin II receptor antagonist, valsartan. Neprilysin is an endopeptidase that breaks down several vasoactive peptides including natriuretic peptides (NPs), bradykinin, endothelin and angiotensin II (Ang-II). Therefore, a natural consequence of its inhibition is an increase of plasmatic levels of both, NPs and Ang-II (with opposite biological actions). So, a combined inhibition of these both systems (Sacubitril / valsartan) may enhance the benefits of NPs effects in HF (natriuresis, diuresis, etc) while Ang-II receptor is inhibited (reducing vasoconstriction and aldosterone release). In a large clinical trial (PARADIGM-HF with 8442 patients), this new agent was found to significantly reduce cardiovascular and all cause mortality as well as hospitalizations due to HF (compared to enalapril). This manuscript reviews clinical evidence for sacubitril valsartan, dosing and cautions, future directions and its considered place in the therapy of HF with reduced ejection fraction. PMID:28133468

Hair follicle is a target of stress hormone and autoimmune reactions.

PubMed

Ito, Taisuke

2010-11-01

Interest in the hair follicle (HF) has recently increased, yet the detailed mechanisms of HF function and immune privilege (IP) have not yet been elucidated. This review discusses the critical points of immunobiology and hormonal aspects of HFs. The HF is a unique mini-organ because it has its own immune system and hormonal milieu. In addition, the HF immune and hormonal systems may greatly affect skin immunobiology. Therefore, knowledge of HF immunobiology and hormonal aspects will lead to a better understanding of skin biology. The HF has a unique hair cycle (anagen, catagen and telogen) and contains stem cells in the bulge area. The HF is closely related to sebaceous glands and the nervous system. This article reviews the interaction between the endocrine/immune system and HFs, including the pathogenesis of alopecia areata associated with stress. Copyright © 2010 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.

Efficient method of evaluation for Gaussian Hartree-Fock exchange operator for Gau-PBE functional

NASA Astrophysics Data System (ADS)

Song, Jong-Won; Hirao, Kimihiko

2015-07-01

We previously developed an efficient screened hybrid functional called Gaussian-Perdew-Burke-Ernzerhof (Gau-PBE) [Song et al., J. Chem. Phys. 135, 071103 (2011)] for large molecules and extended systems, which is characterized by the usage of a Gaussian function as a modified Coulomb potential for the Hartree-Fock (HF) exchange. We found that the adoption of a Gaussian HF exchange operator considerably decreases the calculation time cost of periodic systems while improving the reproducibility of the bandgaps of semiconductors. We present a distance-based screening scheme here that is tailored for the Gaussian HF exchange integral that utilizes multipole expansion for the Gaussian two-electron integrals. We found a new multipole screening scheme helps to save the time cost for the HF exchange integration by efficiently decreasing the number of integrals of, specifically, the near field region without incurring substantial changes in total energy. In our assessment on the periodic systems of seven semiconductors, the Gau-PBE hybrid functional with a new screening scheme has 1.56 times the time cost of a pure functional while the previous Gau-PBE was 1.84 times and HSE06 was 3.34 times.

Efficient method of evaluation for Gaussian Hartree-Fock exchange operator for Gau-PBE functional

DOE Office of Scientific and Technical Information (OSTI.GOV)

Song, Jong-Won; Hirao, Kimihiko, E-mail: hirao@riken.jp

2015-07-14

We previously developed an efficient screened hybrid functional called Gaussian-Perdew–Burke–Ernzerhof (Gau-PBE) [Song et al., J. Chem. Phys. 135, 071103 (2011)] for large molecules and extended systems, which is characterized by the usage of a Gaussian function as a modified Coulomb potential for the Hartree-Fock (HF) exchange. We found that the adoption of a Gaussian HF exchange operator considerably decreases the calculation time cost of periodic systems while improving the reproducibility of the bandgaps of semiconductors. We present a distance-based screening scheme here that is tailored for the Gaussian HF exchange integral that utilizes multipole expansion for the Gaussian two-electron integrals.more » We found a new multipole screening scheme helps to save the time cost for the HF exchange integration by efficiently decreasing the number of integrals of, specifically, the near field region without incurring substantial changes in total energy. In our assessment on the periodic systems of seven semiconductors, the Gau-PBE hybrid functional with a new screening scheme has 1.56 times the time cost of a pure functional while the previous Gau-PBE was 1.84 times and HSE06 was 3.34 times.« less

Effectiveness of Housing First with Intensive Case Management in an Ethnically Diverse Sample of Homeless Adults with Mental Illness: A Randomized Controlled Trial.

PubMed

Stergiopoulos, Vicky; Gozdzik, Agnes; Misir, Vachan; Skosireva, Anna; Connelly, Jo; Sarang, Aseefa; Whisler, Adam; Hwang, Stephen W; O'Campo, Patricia; McKenzie, Kwame

2015-01-01

Housing First (HF) is being widely disseminated in efforts to end homelessness among homeless adults with psychiatric disabilities. This study evaluates the effectiveness of HF with Intensive Case Management (ICM) among ethnically diverse homeless adults in an urban setting. 378 participants were randomized to HF with ICM or treatment-as-usual (TAU) in Toronto (Canada), and followed for 24 months. Measures of effectiveness included housing stability, physical (EQ5D-VAS) and mental (CSI, GAIN-SS) health, social functioning (MCAS), quality of life (QoLI20), and health service use. Two-thirds of the sample (63%) was from racialized groups and half (50%) were born outside Canada. Over the 24 months of follow-up, HF participants spent a significantly greater percentage of time in stable residences compared to TAU participants (75.1% 95% CI 70.5 to 79.7 vs. 39.3% 95% CI 34.3 to 44.2, respectively). Similarly, community functioning (MCAS) improved significantly from baseline in HF compared to TAU participants (change in mean difference = +1.67 95% CI 0.04 to 3.30). There was a significant reduction in the number of days spent experiencing alcohol problems among the HF compared to TAU participants at 24 months (ratio of rate ratios = 0.47 95% CI 0.22 to 0.99) relative to baseline, a reduction of 53%. Although the number of emergency department visits and days in hospital over 24 months did not differ significantly between HF and TAU participants, fewer HF participants compared to TAU participants had 1 or more hospitalizations during this period (70.4% vs. 81.1%, respectively; P=0.044). Compared to non-racialized HF participants, racialized HF participants saw an increase in the amount of money spent on alcohol (change in mean difference = $112.90 95% CI 5.84 to 219.96) and a reduction in physical community integration (ratio of rate ratios = 0.67 95% CI 0.47 to 0.96) from baseline to 24 months. Secondary analyses found a significant reduction in the number of days experiencing problems due to alcohol use among foreign-born (vs. Canadian-born) HF participants at 24 months (ratio of rate ratios = 0.19 95% 0.04 to 0.88), relative to baseline. Compared to usual care, HF with ICM can improve housing stability and community functioning and reduce the days of alcohol related problems in an ethnically diverse sample of homeless adults with mental illness within 2-years. Controlled-Trials.com ISRCTN42520374.

Effectiveness of Housing First with Intensive Case Management in an Ethnically Diverse Sample of Homeless Adults with Mental Illness: A Randomized Controlled Trial

PubMed Central

Stergiopoulos, Vicky; Gozdzik, Agnes; Misir, Vachan; Skosireva, Anna; Connelly, Jo; Sarang, Aseefa; Whisler, Adam; Hwang, Stephen W.; O’Campo, Patricia; McKenzie, Kwame

2015-01-01

Housing First (HF) is being widely disseminated in efforts to end homelessness among homeless adults with psychiatric disabilities. This study evaluates the effectiveness of HF with Intensive Case Management (ICM) among ethnically diverse homeless adults in an urban setting. 378 participants were randomized to HF with ICM or treatment-as-usual (TAU) in Toronto (Canada), and followed for 24 months. Measures of effectiveness included housing stability, physical (EQ5D-VAS) and mental (CSI, GAIN-SS) health, social functioning (MCAS), quality of life (QoLI20), and health service use. Two-thirds of the sample (63%) was from racialized groups and half (50%) were born outside Canada. Over the 24 months of follow-up, HF participants spent a significantly greater percentage of time in stable residences compared to TAU participants (75.1% 95% CI 70.5 to 79.7 vs. 39.3% 95% CI 34.3 to 44.2, respectively). Similarly, community functioning (MCAS) improved significantly from baseline in HF compared to TAU participants (change in mean difference = +1.67 95% CI 0.04 to 3.30). There was a significant reduction in the number of days spent experiencing alcohol problems among the HF compared to TAU participants at 24 months (ratio of rate ratios = 0.47 95% CI 0.22 to 0.99) relative to baseline, a reduction of 53%. Although the number of emergency department visits and days in hospital over 24 months did not differ significantly between HF and TAU participants, fewer HF participants compared to TAU participants had 1 or more hospitalizations during this period (70.4% vs. 81.1%, respectively; P=0.044). Compared to non-racialized HF participants, racialized HF participants saw an increase in the amount of money spent on alcohol (change in mean difference = $112.90 95% CI 5.84 to 219.96) and a reduction in physical community integration (ratio of rate ratios = 0.67 95% CI 0.47 to 0.96) from baseline to 24 months. Secondary analyses found a significant reduction in the number of days experiencing problems due to alcohol use among foreign-born (vs. Canadian-born) HF participants at 24 months (ratio of rate ratios = 0.19 95% 0.04 to 0.88), relative to baseline. Compared to usual care, HF with ICM can improve housing stability and community functioning and reduce the days of alcohol related problems in an ethnically diverse sample of homeless adults with mental illness within 2-years. Trial Registration Controlled-Trials.com ISRCTN42520374. PMID:26176621

Highly Functional TNTs with Superb Photocatalytic, Optical, and Electronic Performance Achieving Record PV Efficiency of 10.1% for 1D-Based DSSCs.

PubMed

Qadir, Muhammad Bilal; Li, Yuewen; Sahito, Iftikhar Ali; Arbab, Alvira Ayoub; Sun, Kyung Chul; Mengal, Naveed; Memon, Anam Ali; Jeong, Sung Hoon

2016-09-01

Different nanostructures of TiO2 play an important role in the photocatalytic and photoelectronic applications. TiO2 nanotubes (TNTs) have received increasing attention for these applications due to their unique physicochemical properties. Focusing on highly functional TNTs (HF-TNTs) for photocatalytic and photoelectronic applications, this study describes the facile hydrothermal synthesis of HF-TNTs by using commercial and cheaper materials for cost-effective manufacturing. To prove the functionality and applicability, these TNTs are used as scattering structure in dye-sensitized solar cells (DSSCs). Photocatalytic, optical, Brunauer-Emmett-Teller (BET), electrochemical impedance spectrum, incident-photon-to-current efficiency, and intensity-modulated photocurrent spectroscopy/intensity-modulated photovoltage spectroscopy characterizations are proving the functionality of HF-TNTs for DSSCs. HF-TNTs show 50% higher photocatalytic degradation rate and also 68% higher dye loading ability than conventional TNTs (C-TNTs). The DSSCs having HF-TNT and its composite-based multifunctional overlayer show effective light absorption, outstanding light scattering, lower interfacial resistance, longer electron lifetime, rapid electron transfer, and improved diffusion length, and consequently, J SC , quantum efficiency, and record photoconversion efficiency of 10.1% using commercial N-719 dye is achieved, for 1D-based DSSCs. These new and highly functional TNTs will be a concrete fundamental background toward the development of more functional applications in fuel cells, dye-sensitized solar cells, Li-ion batteries, photocatalysis process, ion-exchange/adsorption process, and photoelectrochemical devices. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Computational studies of molecular charge transfer complexes of heterocyclic 4-methylepyridine-2-azomethine-p-benzene derivatives with picric acid and m-dinitrobenzene.

PubMed

Al-Harbi, L M; El-Mossalamy, E H; Obaid, A Y; Al-Jedaani, A H

2014-01-01

Charge transfer complexes of substituted aryl Schiff bases as donors with picric acid and m-dinitrobenzene as acceptors were investigated by using computational analysis calculated by Configuration Interaction Singles Hartree-Fock (CIS-HF) at standard 6-31G∗ basis set and Time-Dependent Density-Functional Theory (TD-DFT) levels of theory at standard 6-31G∗∗ basis set, infrared spectra, visible and nuclear magnetic resonance spectra are investigated. The optimized geometries and vibrational frequencies were evaluated. The energy and oscillator strength were calculated by Configuration Interaction Singles Hartree-Fock method (CIS-HF) and the Time-Dependent Density-Functional Theory (TD-DFT) results. Electronic properties, such as HOMO and LUMO energies and band gaps of CTCs set, were studied by the Time-Dependent density functional theory with Becke-Lee-Young-Parr (B3LYP) composite exchange correlation functional and by Configuration Interaction Singles Hartree-Fock method (CIS-HF). The ionization potential Ip and electron affinity EA were calculated by PM3, HF and DFT methods. The columbic force was calculated theoretically by using (CIS-HF and TD-DFT) methods. This study confirms that the theoretical calculation of vibrational frequencies for (aryl Schiff bases--(m-dinitrobenzene and picric acid)) complexes are quite useful for the vibrational assignment and for predicting new vibrational frequencies. Copyright © 2013 Elsevier B.V. All rights reserved.

Antibodies to oxidized LDL as predictors of morbidity and mortality in patients with chronic heart failure.

PubMed

Charach, Gideon; George, Jacob; Afek, Arnon; Wexler, Dov; Sheps, David; Keren, Gad; Rubinstein, Ardon

2009-11-01

Oxidative stress appears to play a significant role in the pathogenesis of heart failure (HF). Antibodies to oxidized low-density lipoprotein (Ox LDL Abs) reflect an immune response to LDL over a prolonged period and may thus represent oxidative stress over an extended time. Ox LDL Abs have been shown to correlate with clinical control in HF patients. We evaluated the predictive power of Ox LDL Abs on the outcome in patients with HF. Baseline levels of Ox LDL Abs were determined by enzyme-linked immunosorbent assay in 284 consecutive outpatients with severe chronic HF who were being treated in the cardiology services of our medical center. Their mean New York Heart Association (NYHA) Class was 2.8. The mean follow-up for the group was 3.7 years, during which 107 (37%) died. The mean time from symptom onset to first hospital admission from HF was 25.8 months. Ox LDL Abs were found to predict morbidity and mortality as evaluated by a Cox multivariate regression analysis with a hazard ration of 1.013 (P < .013), whereas N-terminal pro-B-type natriuretic peptide (NT pro-BNP) levels achieved a HR of 1.028 (P < .099). Ox LDL Abs level maybe a useful parameter for monitoring and planning better management of patients with HF. It was superior to pro-BNP as a predictor of clinical course as expressed by time to hospitalization.

The pro-apoptotic serum activity is an independent mortality predictor of patients with heart failure.

PubMed

Rössig, Lothar; Fichtlscherer, Stephan; Heeschen, Christopher; Berger, Jürgen; Dimmeler, Stefanie; Zeiher, Andreas M

2004-09-01

Systemic inflammation with elevated serum levels of circulating pro-inflammatory cytokines is a major determinant of prognosis in heart failure (HF). Since serum of patients with HF induces apoptosis of endothelial cells (EC), we aimed to determine whether the pro-apoptotic activity in the serum may predict prognosis of patients with HF. We measured the pro-apoptotic activity in the serum of 48 patients with HF of different aetiology by an ex vivo cell culture assay and subsequently monitored these patients for the single endpoint all-cause mortality. During follow-up, 16 patients died and 11 patients received a heart transplant. Survivors had a lower pro-apoptotic serum activity (P=0.007). By univariate analysis, pro-apoptotic serum activity, NYHA class, pro-BNP, low blood pressure, and creatinine levels were significantly associated with mortality. In a multivariable stepwise Cox-regression model, the pro-apoptotic serum activity (adjusted hazard ratio, HR=1.85 per %, P=0.008), elevated pro-BNP levels (HR=9.35 per log[pro-BNP], P=0.001), and low blood pressure (HR=0.96 per mmHg, P=0.041) remained as independent predictors of death. In this exploratory study, the pro-apoptotic serum capacity is independently associated with a worse prognosis in patients with HF, suggesting that the assessment of serum-induced EC apoptosis could provide an integrative estimate of the deleterious effects of various pro-inflammatory cytokines and other cytotoxic factors in HF.

Fluid status monitoring with a wireless network to reduce cardiovascular-related hospitalizations and mortality in heart failure: rationale and design of the OptiLink HF Study (Optimization of Heart Failure Management using OptiVol Fluid Status Monitoring and CareLink)

PubMed Central

Brachmann, Johannes; Böhm, Michael; Rybak, Karin; Klein, Gunnar; Butter, Christian; Klemm, Hanno; Schomburg, Rolf; Siebermair, Johannes; Israel, Carsten; Sinha, Anil-Martin; Drexler, Helmut

2011-01-01

Aims The Optimization of Heart Failure Management using OptiVol Fluid Status Monitoring and CareLink (OptiLink HF) study is designed to investigate whether OptiVol fluid status monitoring with an automatically generated wireless CareAlert notification via the CareLink Network can reduce all-cause death and cardiovascular hospitalizations in an HF population, compared with standard clinical assessment. Methods Patients with newly implanted or replacement cardioverter-defibrillator devices with or without cardiac resynchronization therapy, who have chronic HF in New York Heart Association class II or III and a left ventricular ejection fraction ≤35% will be eligible to participate. Following device implantation, patients are randomized to either OptiVol fluid status monitoring through CareAlert notification or regular care (OptiLink ‘on' vs. ‘off'). The primary endpoint is a composite of all-cause death or cardiovascular hospitalization. It is estimated that 1000 patients will be required to demonstrate superiority of the intervention group to reduce the primary outcome by 30% with 80% power. Conclusion The OptiLink HF study is designed to investigate whether early detection of congestion reduces mortality and cardiovascular hospitalization in patients with chronic HF. The study is expected to close recruitment in September 2012 and to report first results in May 2014. ClinicalTrials.gov Identifier: NCT00769457 PMID:21555324

Interrelationship between diabetes mellitus and heart failure: the role of peroxisome proliferator-activated receptors in left ventricle performance.

PubMed

Oikonomou, Evangelos; Mourouzis, Konstantinos; Fountoulakis, Petros; Papamikroulis, Georgios Angelos; Siasos, Gerasimos; Antonopoulos, Alexis; Vogiatzi, Georgia; Tsalamadris, Sotiris; Vavuranakis, Manolis; Tousoulis, Dimitris

2018-05-01

Heart failure (HF) is a common cardiac syndrome, whose pathophysiology involves complex mechanisms, some of which remain unknown. Diabetes mellitus (DM) constitutes not only a glucose metabolic disorder accompanied by insulin resistance but also a risk factor for cardiovascular disease and HF. During the last years though emerging data set up, a bidirectional interrelationship between these two entities. In the case of DM impaired calcium homeostasis, free fatty acid metabolism, redox state, and advance glycation end products may accelerate cardiac dysfunction. On the other hand, when HF exists, hypoperfusion of the liver and pancreas, b-blocker and diuretic treatment, and autonomic nervous system dysfunction may cause impairment of glucose metabolism. These molecular pathways may be used as therapeutic targets for novel antidiabetic agents. Peroxisome proliferator-activated receptors (PPARs) not only improve insulin resistance and glucose and lipid metabolism but also manifest a diversity of actions directly or indirectly associated with systolic or diastolic performance of left ventricle and symptoms of HF. Interestingly, they may beneficially affect remodeling of the left ventricle, fibrosis, and diastolic performance but they may cause impaired water handing, sodium retention, and decompensation of HF which should be taken into consideration in the management of patients with DM. In this review article, we present the pathophysiological data linking HF with DM and we focus on the molecular mechanisms of PPARs agonists in left ventricle systolic and diastolic performance providing useful insights in the molecular mechanism of this class of metabolically active regiments.

Influence of LVAD function on mechanical unloading and electromechanical delay: a simulation study.

PubMed

Heikhmakhtiar, Aulia Khamas; Ryu, Ah Jin; Shim, Eun Bo; Song, Kwang-Soup; Trayanova, Natalia A; Lim, Ki Moo

2018-05-01

This study hypothesized that a left ventricular assist device (LVAD) shortens the electromechanical delay (EMD) by mechanical unloading. The goal of this study is to examine, by computational modeling, the influence of LVAD on EMD for four heart failure (HF) cases ranging from mild HF to severe HF. We constructed an integrated model of an LVAD-implanted cardiovascular system, then we altered the Ca 2+ transient magnitude, with scaling factors 1, 0.9, 0.8, and 0.7 representing HF1, HF2, HF3, and HF4, respectively, in order of increasing HF severity. The four HF conditions are classified into two groups. Group one is the four HF conditions without LVAD, and group two is the conditions treated with continuous LVAD pump. The single-cell mechanical responses showed that EMD was prolonged with the higher load. The findings indicated that in group one, the HF-induced Ca2 + transient remodeling prolonged the mechanical activation time (MAT) and decreased the contractile tension, which reduced the left ventricle (LV) pressure, and increased the end-diastolic strain. In group two, LVAD shortened MAT of the ventricles. Furthermore, LVAD reduced the contractile tension, and end-diastolic strain, but increased the aortic pressure. The computational study demonstrated that LVAD shortens EMD by mechanical unloading of the ventricle.

Effects of High-Intensity Interval Training versus Continuous Training on Physical Fitness, Cardiovascular Function and Quality of Life in Heart Failure Patients.

PubMed

Benda, Nathalie M M; Seeger, Joost P H; Stevens, Guus G C F; Hijmans-Kersten, Bregina T P; van Dijk, Arie P J; Bellersen, Louise; Lamfers, Evert J P; Hopman, Maria T E; Thijssen, Dick H J

2015-01-01

Physical fitness is an important prognostic factor in heart failure (HF). To improve fitness, different types of exercise have been explored, with recent focus on high-intensity interval training (HIT). We comprehensively compared effects of HIT versus continuous training (CT) in HF patients NYHA II-III on physical fitness, cardiovascular function and structure, and quality of life, and hypothesize that HIT leads to superior improvements compared to CT. Twenty HF patients (male:female 19:1, 64±8 yrs, ejection fraction 38±6%) were allocated to 12-weeks of HIT (10*1-minute at 90% maximal workload-alternated by 2.5 minutes at 30% maximal workload) or CT (30 minutes at 60-75% of maximal workload). Before and after intervention, we examined physical fitness (incremental cycling test), cardiac function and structure (echocardiography), vascular function and structure (ultrasound) and quality of life (SF-36, Minnesota living with HF questionnaire (MLHFQ)). Training improved maximal workload, peak oxygen uptake (VO2peak) related to the predicted VO2peak, oxygen uptake at the anaerobic threshold, and maximal oxygen pulse (all P<0.05), whilst no differences were present between HIT and CT (N.S.). We found no major changes in resting cardiovascular function and structure. SF-36 physical function score improved after training (P<0.05), whilst SF-36 total score and MLHFQ did not change after training (N.S.). Training induced significant improvements in parameters of physical fitness, although no evidence for superiority of HIT over CT was demonstrated. No major effect of training was found on cardiovascular structure and function or quality of life in HF patients NYHA II-III. Nederlands Trial Register NTR3671.

Interaction of Body Mass Index on the Association Between N-Terminal-Pro-b-Type Natriuretic Peptide and Morbidity and Mortality in Patients With Acute Heart Failure: Findings From ASCEND-HF (Acute Study of Clinical Effectiveness of Nesiritide in Decompensated Heart Failure).

PubMed

Bhatt, Ankeet S; Cooper, Lauren B; Ambrosy, Andrew P; Clare, Robert M; Coles, Adrian; Joyce, Emer; Krishnamoorthy, Arun; Butler, Javed; Felker, G Michael; Ezekowitz, Justin A; Armstrong, Paul W; Hernandez, Adrian F; O'Connor, Christopher M; Mentz, Robert J

2018-02-03

Higher body mass index (BMI) is associated with lower circulating levels of N-terminal-pro-b-type natriuretic peptide (NT-proBNP). The Interaction between BMI and NT-proBNP with respect to clinical outcomes is not well characterized in patients with acute heart failure. A total of 686 patients from the biomarker substudy of the ASCEND-HF (Acute Study of Clinical Effectiveness of Nesiritide in Decompensated HF ) clinical trial with documented NT-proBNP levels at baseline were included in the present analysis. Patients were classified by the World Health Organization obesity classification (nonobese: BMI <30 kg/m 2 , Class I obesity: BMI 30-34.9 kg/m 2 , Class II obesity BMI 35-39.9 kg/m 2 , and Class III obesity BMI ≥40 kg/m 2 ). We assessed baseline characteristics and 30- and 180-day outcomes by BMI class and explored the interaction between BMI and NT-proBNP for these outcomes. Study participants had a median age of 67 years (55, 78) and 71% were female. NT-proBNP levels were inversely correlated with BMI ( P <0.001). Higher NT-proBNP levels were associated with higher 180-day mortality (adjusted hazard ratio for each doubling of NT-proBNP, 1.40; 95% confidence interval, 1.16, 1.71; P <0.001), but not 30-day outcomes. The effect of NT-proBNP on 180-day death was not modified by BMI class (interaction P =0.24). The prognostic value of NT-proBNP was not modified by BMI in this acute heart failure population. NT-proBNP remains a useful prognostic indicator of long-term mortality in acute heart failure even in the obese patient. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00475852. © 2018 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

Therapeutic effects of selective atrioventricular node vagal stimulation in atrial fibrillation and heart failure.

PubMed

Zhang, Youhua; Popović, Zoran B; Kusunose, Kenya; Mazgalev, Todor N

2013-01-01

Atrial fibrillation (AF) and heart failure (HF) frequently coexist. We have previously demonstrated that selective atrioventricular node (AVN) vagal stimulation (AVN-VS) can be used to control ventricular rate during AF. Due to withdrawal of vagal activity in HF, the therapeutic effects of AVN-VS may be compromised in the combined condition of AF and HF. Accordingly, this study was designed to evaluate the therapeutic effects of AVN-VS to control ventricular rate in AF and HF. A combined model of AF and HF was created by implanting a dual chamber pacemaker in 24 dogs. A newly designed bipolar electrode was inserted into the ganglionic AVN fat pad and connected to a nerve stimulator for delivering AVN-VS. In all dogs, HF was induced by high rate ventricular pacing at 220 bpm for 4 weeks. AF was then induced and maintained by rapid atrial pacing at 600 bpm after discontinuation of ventricular pacing. These HF + AF dogs were randomized into control (n = 9) and AVN-VS (n = 15) groups. In the latter group, vagal stimulation (310 μs, 20 Hz, 3-7 mA) was delivered continuously for 6 months. Compared with the control, AVN-VS had a consistent effect on ventricular rate slowing (by >50 bpm, all P < 0.001) during the entire 6-month observation period that was associated with left ventricular functional improvement. Moreover, AVN-VS was well tolerated by the treated animals. AVN-VS achieved consistent rate slowing, which was associated with improved ventricular function in a canine AF and HF model. Thus, AVN-VS may be a novel, effective therapeutic option in the combined condition of AF and HF. © 2012 Wiley Periodicals, Inc.

Autonomic Recovery Is Delayed in Chinese Compared with Caucasian following Treadmill Exercise.

PubMed

Sun, Peng; Yan, Huimin; Ranadive, Sushant M; Lane, Abbi D; Kappus, Rebecca M; Bunsawat, Kanokwan; Baynard, Tracy; Hu, Min; Li, Shichang; Fernhall, Bo

2016-01-01

Caucasian populations have a higher prevalence of cardiovascular disease (CVD) when compared with their Chinese counterparts and CVD is associated with autonomic function. It is unknown whether autonomic function during exercise recovery differs between Caucasians and Chinese. The present study investigated autonomic recovery following an acute bout of treadmill exercise in healthy Caucasians and Chinese. Sixty-two participants (30 Caucasian and 32 Chinese, 50% male) performed an acute bout of treadmill exercise at 70% of heart rate reserve. Heart rate variability (HRV) and baroreflex sensitivity (BRS) were obtained during 5-min epochs at pre-exercise, 30-min, and 60-min post-exercise. HRV was assessed using frequency [natural logarithm of high (LnHF) and low frequency (LnLF) powers, normalized high (nHF) and low frequency (nLF) powers, and LF/HF ratio] and time domains [Root mean square of successive differences (RMSSD), natural logarithm of RMSSD (LnRMSSD) and R-R interval (RRI)]. Spontaneous BRS included both up-up and down-down sequences. At pre-exercise, no group differences were observed for any HR, HRV and BRS parameters. During exercise recovery, significant race-by-time interactions were observed for LnHF, nHF, nLF, LF/HF, LnRMSSD, RRI, HR, and BRS (up-up). The declines in LnHF, nHF, RMSSD, RRI and BRS (up-up) and the increases in LF/HF, nLF and HR were blunted in Chinese when compared to Caucasians from pre-exercise to 30-min to 60-min post-exercise. Chinese exhibited delayed autonomic recovery following an acute bout of treadmill exercise. This delayed autonomic recovery may result from greater sympathetic dominance and extended vagal withdrawal in Chinese. Chinese Clinical Trial Register ChiCTR-IPR-15006684.

Autonomic Recovery Is Delayed in Chinese Compared with Caucasian following Treadmill Exercise

PubMed Central

Sun, Peng; Yan, Huimin; Ranadive, Sushant M.; Lane, Abbi D.; Kappus, Rebecca M.; Bunsawat, Kanokwan; Baynard, Tracy; Hu, Min; Li, Shichang; Fernhall, Bo

2016-01-01

Caucasian populations have a higher prevalence of cardiovascular disease (CVD) when compared with their Chinese counterparts and CVD is associated with autonomic function. It is unknown whether autonomic function during exercise recovery differs between Caucasians and Chinese. The present study investigated autonomic recovery following an acute bout of treadmill exercise in healthy Caucasians and Chinese. Sixty-two participants (30 Caucasian and 32 Chinese, 50% male) performed an acute bout of treadmill exercise at 70% of heart rate reserve. Heart rate variability (HRV) and baroreflex sensitivity (BRS) were obtained during 5-min epochs at pre-exercise, 30-min, and 60-min post-exercise. HRV was assessed using frequency [natural logarithm of high (LnHF) and low frequency (LnLF) powers, normalized high (nHF) and low frequency (nLF) powers, and LF/HF ratio] and time domains [Root mean square of successive differences (RMSSD), natural logarithm of RMSSD (LnRMSSD) and R–R interval (RRI)]. Spontaneous BRS included both up-up and down-down sequences. At pre-exercise, no group differences were observed for any HR, HRV and BRS parameters. During exercise recovery, significant race-by-time interactions were observed for LnHF, nHF, nLF, LF/HF, LnRMSSD, RRI, HR, and BRS (up-up). The declines in LnHF, nHF, RMSSD, RRI and BRS (up-up) and the increases in LF/HF, nLF and HR were blunted in Chinese when compared to Caucasians from pre-exercise to 30-min to 60-min post-exercise. Chinese exhibited delayed autonomic recovery following an acute bout of treadmill exercise. This delayed autonomic recovery may result from greater sympathetic dominance and extended vagal withdrawal in Chinese. Trial Registration: Chinese Clinical Trial Register ChiCTR-IPR-15006684 PMID:26784109

Novel Wearable Seismocardiography and Machine Learning Algorithms Can Assess Clinical Status of Heart Failure Patients.

PubMed

Inan, Omer T; Baran Pouyan, Maziyar; Javaid, Abdul Q; Dowling, Sean; Etemadi, Mozziyar; Dorier, Alexis; Heller, J Alex; Bicen, A Ozan; Roy, Shuvo; De Marco, Teresa; Klein, Liviu

2018-01-01

Remote monitoring of patients with heart failure (HF) using wearable devices can allow patient-specific adjustments to treatments and thereby potentially reduce hospitalizations. We aimed to assess HF state using wearable measurements of electrical and mechanical aspects of cardiac function in the context of exercise. Patients with compensated (outpatient) and decompensated (hospitalized) HF were fitted with a wearable ECG and seismocardiogram sensing patch. Patients stood at rest for an initial recording, performed a 6-minute walk test, and then stood at rest for 5 minutes of recovery. The protocol was performed at the time of outpatient visit or at 2 time points (admission and discharge) during an HF hospitalization. To assess patient state, we devised a method based on comparing the similarity of the structure of seismocardiogram signals after exercise compared with rest using graph mining (graph similarity score). We found that graph similarity score can assess HF patient state and correlates to clinical improvement in 45 patients (13 decompensated, 32 compensated). A significant difference was found between the groups in the graph similarity score metric (44.4±4.9 [decompensated HF] versus 35.2±10.5 [compensated HF]; P <0.001). In the 6 decompensated patients with longitudinal data, we found a significant change in graph similarity score from admission (decompensated) to discharge (compensated; 44±4.1 [admitted] versus 35±3.9 [discharged]; P <0.05). Wearable technologies recording cardiac function and machine learning algorithms can assess compensated and decompensated HF states by analyzing cardiac response to submaximal exercise. These techniques can be tested in the future to track the clinical status of outpatients with HF and their response to pharmacological interventions. © 2018 American Heart Association, Inc.

The Effect of Massage Therapy on Autonomic Activity in Critically Ill Children

PubMed Central

Guan, Ling; Yuskiv, Nataliya; Skippen, Peter; Brant, Rollin; Kissoon, Niranjan

2014-01-01

Objectives. Our main objective was to describe the effect of foot and hand (F&H) massage on the autonomic nervous system (ANS) activity in children hospitalized in a pediatric intensive care unit (PICU); the secondary objectives were to assess the relationship between ANS function and the clinical severity and to explore the effects of repeated massage sessions on the ANS. Methods. Design was a descriptive experimental study. Intervention was single or six session(s) of F&H massage. ANS function was assessed through the frequency-domain analysis of heart rate variability. Main metrics included high and low frequency power (HF and LF), HF + LF, and LF/HF ratio. Results. Eighteen children participated in the study. A strong Spearman's correlation (ρ = −0.77) was observed between HF + LF and clinical severity. During massage, the parasympathetic activity (measured by HF) increased significantly from baseline (P = 0.04) with a mean percentage increase of 75% (95% CI: 20%∼130%). LF increased by 56% (95% CI: 20%∼92%) (P = 0.026). Repeated sessions were associated with a persistent effect on HF and LF which peaked at the second session and remained stable thereafter. Conclusions. HF + LF is positively correlated with clinical severity. F&H massage can improve the ANS activity and the effect persists when repeated sessions are offered. PMID:25587344

E- and P-cadherin expression during murine hair follicle morphogenesis and cycling.

PubMed

Müller-Röver, S; Tokura, Y; Welker, P; Furukawa, F; Wakita, H; Takigawa, M; Paus, R

1999-08-01

The role of adhesion molecules in the control of hair follicle (HF) morphogenesis, regression and cycling is still rather enigmatic. Since the adhesion molecules E- and P-cadherin (Ecad and Pcad) are functionally important, e.g. during embryonic pattern formation, we have studied their expression patterns during neonatal HF morphogenesis and cycling in C57/BL6 mice by immunohistology and semi-quantitative RT-PCR. The expression of both cadherins was strikingly hair cycle-dependent and restricted to distinct anatomical HF compartments. During HF morphogenesis, hair bud keratinocytes displayed strong Ecad and Pcad immunoreactivity (IR). While neonatal epidermis showed Ecad IR in all epidermal layers, Pcad IR was restricted to the basal layer. During later stages of HF morphogenesis and during anagen IV-VI of the adolescent murine hair cycle, the outer root sheath showed strong E- and Pcad IR. Instead, the outermost portion of the hair matrix and the inner root sheath displayed isolated Ecad IR, while the innermost portion of the hair matrix exhibited isolated Pcad IR. During telogen, all epidermal and follicular keratinocytes showed strong Ecad IR. This is in contrast to Pcad, whose IR was stringently restricted to matrix and secondary hair germ keratinocytes which are in closest proximity to the dermal papilla. These findings suggest that isolated or combined E- and/or Pcad expression is involved in follicular pattern formation by segregating HF keratinocytes into functionally distinct subpopulations; most notably, isolated Pcad expression may segregate those hair matrix keratinocytes into one functional epithelial tissue unit, which is particularly susceptible to growth control by dermal papilla-derived morphogens. The next challenge is to define which secreted agents implicated in hair growth control modulate these follicular cadherin expression patterns, and to define how these basic parameters of HF topobiology are altered during common hair growth disorders.

Resting state connectivity of the medial prefrontal cortex covaries with individual differences in high-frequency heart rate variability.

PubMed

Jennings, J Richard; Sheu, Lei K; Kuan, Dora C-H; Manuck, Stephen B; Gianaros, Peter J

2016-04-01

Resting high-frequency heart rate variability (HF-HRV) relates to cardiac vagal control and predicts individual differences in health and longevity, but its functional neural correlates are not well defined. The medial prefrontal cortex (mPFC) encompasses visceral control regions that are components of intrinsic networks of the brain, particularly the default mode network (DMN) and the salience network (SN). Might individual differences in resting HF-HRV covary with resting state neural activity in the DMN and SN, particularly within the mPFC? This question was addressed using fMRI data from an eyes-open, 5-min rest period during which echoplanar brain imaging yielded BOLD time series. Independent component analysis yielded functional connectivity estimates defining the DMN and SN. HF-HRV was measured in a rest period outside of the scanner. Midlife (52% female) adults were assessed in two studies (Study 1, N = 107; Study 2, N = 112). Neither overall DMN nor SN connectivity strength was related to HF-HRV. However, HF-HRV related to connectivity of one region within mPFC shared by the DMN and SN, namely, the perigenual anterior cingulate cortex, an area with connectivity to other regions involved in autonomic control. In sum, HF-HRV does not seem directly related to global resting state activity of intrinsic brain networks, but rather to more localized connectivity. A mPFC region was of particular interest as connectivity related to HF-HRV was shared by the DMN and SN. These findings may indicate a functional basis for the coordination of autonomic cardiac control with engagement and disengagement from the environment. © 2015 Society for Psychophysiological Research.

Microdomain-Specific Modulation of L-Type Calcium Channels Leads to Triggered Ventricular Arrhythmia in Heart Failure

PubMed Central

Sanchez-Alonso, Jose L.; Bhargava, Anamika; O’Hara, Thomas; Glukhov, Alexey V.; Schobesberger, Sophie; Bhogal, Navneet; Sikkel, Markus B.; Mansfield, Catherine; Korchev, Yuri E.; Lyon, Alexander R.; Punjabi, Prakash P.; Nikolaev, Viacheslav O.; Trayanova, Natalia A.

2016-01-01

Rationale: Disruption in subcellular targeting of Ca2+ signaling complexes secondary to changes in cardiac myocyte structure may contribute to the pathophysiology of a variety of cardiac diseases, including heart failure (HF) and certain arrhythmias. Objective: To explore microdomain-targeted remodeling of ventricular L-type Ca2+ channels (LTCCs) in HF. Methods and Results: Super-resolution scanning patch-clamp, confocal and fluorescence microscopy were used to explore the distribution of single LTCCs in different membrane microdomains of nonfailing and failing human and rat ventricular myocytes. Disruption of membrane structure in both species led to the redistribution of functional LTCCs from their canonical location in transversal tubules (T-tubules) to the non-native crest of the sarcolemma, where their open probability was dramatically increased (0.034±0.011 versus 0.154±0.027, P<0.001). High open probability was linked to enhance calcium–calmodulin kinase II–mediated phosphorylation in non-native microdomains and resulted in an elevated ICa,L window current, which contributed to the development of early afterdepolarizations. A novel model of LTCC function in HF was developed; after its validation with experimental data, the model was used to ascertain how HF-induced T-tubule loss led to altered LTCC function and early afterdepolarizations. The HF myocyte model was then implemented in a 3-dimensional left ventricle model, demonstrating that such early afterdepolarizations can propagate and initiate reentrant arrhythmias. Conclusions: Microdomain-targeted remodeling of LTCC properties is an important event in pathways that may contribute to ventricular arrhythmogenesis in the settings of HF-associated remodeling. This extends beyond the classical concept of electric remodeling in HF and adds a new dimension to cardiovascular disease. PMID:27572487

Association of time to reperfusion with left ventricular function and heart failure in patients with acute myocardial infarction treated with primary percutaneous coronary intervention: a systematic review.

PubMed

Goel, Kashish; Pinto, Duane S; Gibson, C Michael

2013-04-01

Shorter time to reperfusion is associated with a significant reduction in mortality; however, its association with heart failure (HF) is not clearly documented. We conducted a systematic review to examine the association between time to reperfusion and incident HF and/or left ventricular dysfunction. MEDLINE/OVID, EMBASE, Cochrane Library, and Web of Science databases were searched from January 1974 to May 2012 for studies that reported the association between time to reperfusion and incident HF or left ventricular ejection fraction (LVEF) in patients undergoing primary percutaneous coronary intervention. Of 362 nonduplicate abstracts, 71 studies were selected for full-text review. Thirty-three studies were included in the final review, of which 16 were single-center studies, 7 were population-based studies, 7 were subanalyses from randomized controlled trials, and 3 were based on national samples. The pooled data demonstrate that every 1-hour delay in time to reperfusion is associated with a 4% to 12% increased risk of new-onset HF and a 4% relative increase in the risk of incident HF during follow-up. Early reperfusion was associated with a 2% to 8% greater LVEF before discharge and a 3% to 12% larger improvement in absolute LVEF at follow-up compared with the index admission. This systematic review presents evidence that longer time to reperfusion is not only associated with worsened left ventricular systolic function and new-onset HF at the time of index admission, but also with increased risk of HF and reduced improvement in left ventricular systolic function during follow-up. Copyright © 2013 Mosby, Inc. All rights reserved.

Performance of wave function and density functional methods for water hydrogen bond spin-spin coupling constants.

PubMed

García de la Vega, J M; Omar, S; San Fabián, J

2017-04-01

Spin-spin coupling constants in water monomer and dimer have been calculated using several wave function and density functional-based methods. CCSD, MCSCF, and SOPPA wave functions methods yield similar results, specially when an additive approach is used with the MCSCF. Several functionals have been used to analyze their performance with the Jacob's ladder and a set of functionals with different HF exchange were tested. Functionals with large HF exchange appropriately predict 1 J O H , 2 J H H and 2h J O O couplings, while 1h J O H is better calculated with functionals that include a reduced fraction of HF exchange. Accurate functionals for 1 J O H and 2 J H H have been tested in a tetramer water model. The hydrogen bond effects on these intramolecular couplings are additive when they are calculated by SOPPA(CCSD) wave function and DFT methods. Graphical Abstract Evaluation of the additive effect of the hydrogen bond on spin-spin coupling constants of water using WF and DFT methods.

Top-Down and Bottom-Up Visual Information Processing of Non-Social Stimuli in High-Functioning Autism Spectrum Disorder

ERIC Educational Resources Information Center

Maekawa, Toshihiko; Tobimatsu, Shozo; Inada, Naoko; Oribe, Naoya; Onitsuka, Toshiaki; Kanba, Shigenobu; Kamio, Yoko

2011-01-01

Individuals with high-functioning autism spectrum disorder (HF-ASD) often show superior performance in simple visual tasks, despite difficulties in the perception of socially important information such as facial expression. The neural basis of visual perception abnormalities associated with HF-ASD is currently unclear. We sought to elucidate the…

About Cardiac Arrest

MedlinePlus

... Options for Heart Failure Living With HF and Advanced HF High Blood Pressure ... Updated:Mar 10,2017 What is cardiac arrest? Cardiac arrest is the abrupt loss of heart function in a person who may or may not ...

Left atrial function measured by cardiac magnetic resonance imaging in patients with heart failure: clinical associations and prognostic value.

PubMed

Pellicori, Pierpaolo; Zhang, Jufen; Lukaschuk, Elena; Joseph, Anil C; Bourantas, Christos V; Loh, Huan; Bragadeesh, Thanjavur; Clark, Andrew L; Cleland, John G F

2015-03-21

Left atrial (LA) volume is an important marker of cardiac dysfunction and cardiovascular outcome in heart failure (HF), but LA function is rarely measured. Left atrial emptying function (LAEF), its clinical associations and prognostic value was studied in outpatients referred with suspected HF who were in sinus rhythm and had cardiac magnetic resonance imaging (CMRI). Heart failure was defined as relevant symptoms and signs with either a left ventricular ejection fraction (LVEF) <50% or amino-terminal pro-B-type natriuretic peptide (NTproBNP) >400 pg/mL (or >125 pg/mL if taking loop diuretics). Of 982 patients, 664 fulfilled the HF criteria and were in sinus rhythm. The median (interquartile range, IQR) LAEF was 42 (31-51)% and 55 (48-61)% in patients with and without HF (P < 0.001). Patients with HF in the lowest quartile of LAEF (23%; IQR: 17-28%) had lower LV and right ventricular (RV) EF, and greater LV and RV mass and higher plasma NTproBNP than those in the highest quartile of LAEF (56%; IQR: 53-61%). Log[LAEF] and log[NTproBNP] were inversely correlated (r = -0.410, P < 0.001). During a median follow-up of 883 (IQR: 469-1626) days, 394 (59%) patients with HF died or were admitted with HF and 101 (15%) developed atrial fibrillation (AF). In a multivariable Cox model, increasing LAEF, but not LVEF, was independently associated with survival (HR for 10% change: 0.81 (95%CI: 0.73-0.90), P = <0.001). Increasing age and decreasing LAEF predicted incident AF. In patients with HF, LAEF predicts adverse outcome independently of other measures of cardiac dysfunction. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2014. For permissions please email: journals.permissions@oup.com.

The significance of serum urea and renal function in patients with heart failure.

PubMed

Gotsman, Israel; Zwas, Donna; Planer, David; Admon, Dan; Lotan, Chaim; Keren, Andre

2010-07-01

Renal function and urea are frequently abnormal in patients with heart failure (HF) and are predictive of increased mortality. The relative importance of each parameter is less clear. We prospectively compared the predictive value of renal function and serum urea on clinical outcome in patients with HF. Patients hospitalized with definite clinical diagnosis of HF (n = 355) were followed for short-term (1 yr) and long-term (mean, 6.5 yr) survival and HF rehospitalization. Increasing tertiles of discharge estimated glomerular filtration rate (eGFR) were an independent predictor of increased long-term survival (hazard ratio [HR], 0.65; 95% confidence interval [CI], 0.47-0.91; p = 0.01) but not short-term survival. Admission and discharge serum urea and blood urea nitrogen (BUN)/creatinine ratio were predictors of reduced short- and long-term survival on multivariate Cox regression analysis. Increasing tertiles of discharge urea were a predictor of reduced 1-year survival (HR, 2.13; 95% CI, 1.21-3.73; p = 0.009) and long-term survival (HR, 1.93; 95% CI, 1.37-2.71; p < 0.0001). Multivariate analysis including discharge eGFR and serum urea demonstrated that only serum urea remained a significant predictor of long-term survival; however, eGFR and BUN/creatinine ratio were both independently predictive of survival. Urea was more discriminative than eGFR in predicting long-term survival by area under the receiver operating characteristic curve (0.803 vs. 0.787; p = 0.01). Increasing tertiles of discharge serum urea and BUN/creatinine were independent predictors of HF rehospitalization and combined death and HF rehospitalization. This study suggests that serum urea is a more powerful predictor of survival than eGFR in patients with HF. This may be due to urea's relation to key biological parameters including renal, hemodynamic, and neurohormonal parameters pertaining to the overall clinical status of the patient with chronic HF.

Increase in parasympathetic tone by pyridostigmine prevents ventricular dysfunction during the onset of heart failure.

PubMed

Lataro, Renata M; Silva, Carlos A A; Fazan, Rubens; Rossi, Marcos A; Prado, Cibele M; Godinho, Rosely O; Salgado, Helio C

2013-10-15

Heart failure (HF) is characterized by elevated sympathetic activity and reduced parasympathetic control of the heart. Experimental evidence suggests that the increase in parasympathetic function can be a therapeutic alternative to slow HF evolution. The parasympathetic neurotransmission can be improved by acetylcholinesterase inhibition. We investigated the long-term (4 wk) effects of the acetylcholinesterase inhibitor pyridostigmine on sympathovagal balance, cardiac remodeling, and cardiac function in the onset of HF following myocardial infarction. Myocardial infarction was elicited in adult male Wistar rats. After 4 wk of pyridostigmine administration, per os, methylatropine and propranolol were used to evaluate the cardiac sympathovagal balance. The tachycardic response caused by methylatropine was considered to be the vagal tone, whereas the bradycardic response caused by propranolol was considered to be the sympathetic tone. In conscious HF rats, pyridostigmine reduced the basal heart rate, increased vagal, and reduced sympathetic control of heart rate. Pyridostigmine reduced the myocyte diameter and collagen density of the surviving left ventricle. Pyridostigmine also increased vascular endothelial growth factor protein in the left ventricle, suggesting myocardial angiogenesis. Cardiac function was assessed by means of the pressure-volume conductance catheter system. HF rats treated with pyridostigmine exhibited a higher stroke volume, ejection fraction, cardiac output, and contractility of the left ventricle. It was demonstrated that the long-term administration of pyridostigmine started right after coronary artery ligation augmented cardiac vagal and reduced sympathetic tone, attenuating cardiac remodeling and left ventricular dysfunction during the progression of HF in rats.

Respiratory muscle training improves hemodynamics, autonomic function, baroreceptor sensitivity, and respiratory mechanics in rats with heart failure

PubMed Central

Jaenisch, Rodrigo B.; Hentschke, Vítor S.; Quagliotto, Edson; Cavinato, Paulo R.; Schmeing, Letiane A.; Xavier, Léder L.

2011-01-01

Respiratory muscle training (RMT) improves functional capacity in chronic heart-failure (HF) patients, but the basis for this improvement remains unclear. We evaluate the effects of RMT on the hemodynamic and autonomic function, arterial baroreflex sensitivity (BRS), and respiratory mechanics in rats with HF. Rats were assigned to one of four groups: sedentary sham (n = 8), trained sham (n = 8), sedentary HF (n = 8), or trained HF (n = 8). Trained animals underwent a RMT protocol (30 min/day, 5 day/wk, 6 wk of breathing through a resistor), whereas sedentary animals did not. In HF rats, RMT had significant effects on several parameters. It reduced left ventricular (LV) end-diastolic pressure (P < 0.01), increased LV systolic pressure (P < 0.01), and reduced right ventricular hypertrophy (P < 0.01) and pulmonary (P < 0.001) and hepatic (P < 0.001) congestion. It also decreased resting heart rate (HR; P < 0.05), indicating a decrease in the sympathetic and an increase in the vagal modulation of HR. There was also an increase in baroreflex gain (P < 0.05). The respiratory system resistance was reduced (P < 0.001), which was associated with the reduction in tissue resistance after RMT (P < 0.01). The respiratory system and tissue elastance (Est) were also reduced by RMT (P < 0.01 and P < 0.05, respectively). Additionally, the quasistatic Est was reduced after RMT (P < 0.01). These findings show that a 6-wk RMT protocol in HF rats promotes an improvement in hemodynamic function, sympathetic and vagal heart modulation, arterial BRS, and respiratory mechanics, all of which are benefits associated with improvements in cardiopulmonary interaction. PMID:21903877

Isoenergetic Feeding of Low Carbohydrate-High Fat Diets Does Not Increase Brown Adipose Tissue Thermogenic Capacity in Rats

PubMed Central

Mauracher, Brigitte; Abplanalp, William; Müller, Hans-Helge; Pieper, Korbinian; Ramisch, Juliane; Tschöp, Matthias H.; Beuschlein, Felix; Bidlingmaier, Martin; Slawik, Marc

2012-01-01

Low-carbohydrate, high-fat (LC-HF) diets are popular for inducing weight loss in overweighed adults. Adaptive thermogenesis increased by specific effects of macronutrients on energy expenditure has been postulated to induce this weight loss. We studied brown adipose tissue (BAT) morphology and function following exposure to different LC-HF diets. Methods Male Wistar rats were fed a standard control diet ad libitum or pair-fed isoenergetic amounts of three experimental diets for 4 weeks. The diets had the following macronutrient composition (% metabolizable energy: carbohydrates, fat, protein): control (64.3/16.7/19), LC-HF-low protein (LC-HF-LP, 1.7/92.8/5.5), LC-HF-normal-protein (LC-HF-NP, 2.2/78.7/19.1), and a high fat diet with carbohydrates (“high fat”, 19.4/61.9/18.7). Results Body weight gain was reduced in all pair-fed experimental groups as compared to rats fed the control diet, with more pronounced effect in rats on LC-HF diets than on the high fat diet with carbohydrates. High fat diets increased expression of PGC1α and ADRB3 in BAT indicating higher SNS outflow. However, UCP1 mRNA expression and expression of UCP1 assessed by immunohistochemistry was not different between diet groups. In accordance, analysis of mitochondrial function in-vitro by extracellular flux analyser (Seahorse Bioscience) and measurement of inducible thermogenesis in vivo (primary endpoint), explored by indirect calorimetry following norepinephrine injection, did not show significant differences between groups. Histology of BAT revealed increased lipid droplet size in rats fed the high-fat diet and both LC-HF diets. Conclusion All experimental diets upregulated expression of genes which are indicative for increased BAT activity. However, the functional measurements in vivo revealed no increase of inducible BAT thermogenesis. This indicates that lower body weight gain with LC-HF diets and a high fat diet in a pair-feeding setting is not caused by increased adaptive thermogenesis in BAT. PMID:22720011

Aldosterone Does Not Predict Cardiovascular Events Following Acute Coronary Syndrome in Patients Initially Without Heart Failure.

PubMed

Pitts, Reynaria; Gunzburger, Elise; Ballantyne, Christie M; Barter, Philip J; Kallend, David; Leiter, Lawrence A; Leitersdorf, Eran; Nicholls, Stephen J; Shah, Prediman K; Tardif, Jean-Claude; Olsson, Anders G; McMurray, John J V; Kittelson, John; Schwartz, Gregory G

2017-01-10

Aldosterone may have adverse effects in the myocardium and vasculature. Treatment with an aldosterone antagonist reduces cardiovascular risk in patients with acute myocardial infarction complicated by heart failure (HF) and left ventricular systolic dysfunction. However, most patients with acute coronary syndrome do not have advanced HF. Among such patients, it is unknown whether aldosterone predicts cardiovascular risk. To address this question, we examined data from the dal-OUTCOMES trial that compared the cholesteryl ester transfer protein inhibitor dalcetrapib with placebo, beginning 4 to 12 weeks after an index acute coronary syndrome. Patients with New York Heart Association class II (with LVEF <40%), III, or IV HF were excluded. Aldosterone was measured at randomization in 4073 patients. The primary outcome was a composite of coronary heart disease death, nonfatal myocardial infarction, stroke, hospitalization for unstable angina, or resuscitated cardiac arrest. Hospitalization for HF was a secondary endpoint. Over a median follow-up of 37 months, the primary outcome occurred in 366 patients (9.0%), and hospitalization for HF occurred in 72 patients (1.8%). There was no association between aldosterone and either the time to first occurrence of a primary outcome (hazard ratio for doubling of aldosterone 0.92, 95% confidence interval 0.78-1.09, P=0.34) or hospitalization for HF (hazard ratio 1.38, 95% CI 0.96-1.99, P=0.08) in Cox regression models adjusted for covariates. In patients with recent acute coronary syndrome but without advanced HF, aldosterone does not predict major cardiovascular events. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00658515. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

Rationale and design of the CONFIRM-HF study: a double-blind, randomized, placebo-controlled study to assess the effects of intravenous ferric carboxymaltose on functional capacity in patients with chronic heart failure and iron deficiency.

PubMed

Ponikowski, Piotr; van Veldhuisen, Dirk J; Comin-Colet, Josep; Ertl, Georg; Komajda, Michel; Mareev, Viacheslav; McDonagh, Theresa A; Parkhomenko, Alexander; Tavazzi, Luigi; Levesque, Victoria; Mori, Claudio; Roubert, Bernard; Filippatos, Gerasimos; Ruschitzka, Frank; Anker, Stefan D

2014-09-01

Iron deficiency (ID) is a common co-morbidity associated with chronic heart failure (CHF), which has unfavourable clinical and prognostic consequences. In Ferinject Assessment in Patients with IRon Deficiency and Chronic Heart Failure (FAIR-HF), the treatment with i.v. ferric carboxymaltose (FCM) improved symptoms and quality of life over a 24 week period. Ferric CarboxymaltOse evaluatioN on perFormance in patients with IRon deficiency in coMbination with chronic Heart Failure (CONFIRM-HF) was designed to test a simplifieddosage scheme of FCM during a longer follow-up period. CONFIRM-HF, a double-blind, multi-centre, prospective, randomized, two-arm study, enrolled ambulatory patients with symptomatic CHF [New York Heart Association (NYHA) class II/III] with left ventricular ejection fraction ≤45%, BNP >100 pg/mL, or NT-proBNP >400 pg/mL, presence of ID [defined as ferritin <100 ng/mL, or ferritin 100-300 ng/mL if transferrin saturation (TSAT) <20%], and haemoglobin (Hb) <15 g/dL. Patients were randomized 1:1 to treatment with FCM or placebo for 52 weeks. Primary endpoint is change in 6-minute walk test (6MWT) distance from baseline to Week 24. Secondary endpoints are: change in 6MWT from baseline to Weeks 6, 12, 36, and 52; Patient Global Assessment score at Weeks 6, 12, 24, 36, and 52; and change from baseline to Weeks 6, 12, 24, 36, and 52 in NYHA class, fatigue score, and quality of life. Safety endpoints include overall safety over the treatment period of 52 weeks. Study medication was administered in single doses as undiluted bolus injection of up to 1000 mg of iron or normal saline at Day 0 and Week 6 up to iron repletion. Further doses of study medication could be administered at Weeks 12, 24, and 36 if a patient still had ID. Overall, 304 patients were recruited in 41 centres in nine countries. This study will provide further information on the efficacy and safety of iron therapy with i.v. FCM in CHF patients with ID over a 1 year period using a simplified dosing scheme. © 2014 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of the European Society of Cardiology.

[Incidence, associated factors, and follow-up of hospital heart failure complicating acute anterior myocardial infarction successfully treated by primary angioplasty].

PubMed

Meimoun, P; M'barek, D; Dragomir, C; Luycx-Bore, A; Elmkies, F; Boulanger, J; Zemir, H; Martis, S; Neykova, A; Tzvetkov, B; Clerc, J

2013-11-01

Heart failure (HF) complicating acute myocardial infarction (AMI) is of poor prognosis and is often associated with patient's characteristics and success of reperfusion strategies. However, few data is available regarding the high-risk subgroup of patients with anterior AMI treated successfully by primary angioplasty. The aim of the study was to assess the incidence, associated factors, and the future of HF occurring during hospitalisation, in the setting of anterior AMI treated successfully by primary angioplasty. Eighty-five consecutive patients with anterior AMI treated successfully by primary angioplasty (final angiographic TIMI flow grade=3, without residual stenosis) were included. Clinical, biochemical, angiographic, and echocardiographic data were prospectively collected and compared between patients with (Killip 2 and 3) and without HF during hospitalisation. Fifteen patients had HF (18%) during hospitalisation and 70 did not. By comparison to patients without HF, patients with HF were more frequently diabetics, had troponin peak and CPK, leucocytes count, and fasting glucose higher, LVEF and wall motion score index in the left anterior descending territory (WMSi-lad) poorer, and a lower non-invasive coronary flow reserve (CFR) in the LAD 24hours after angioplasty (all, P<0.05). In multivariate analysis, fasting glucose, leucocytes count after angioplasty, CFR and WMSi-lad were independently associated with HF, even after adjusting with angiographic variables (all, P<0.05). At 6months, patients with HF had less recovery of LV function and higher frequency of adverse LV remodelling (58% versus 20%, P<0.01) by comparison to patients without HF. In conclusion, HF is not uncommon even after successful primary angioplasty for anterior AMI (nearly one patient out of 5), is associated with hyperglycaemia and inflammation, a poor microvascular reperfusion, and left ventricular systolic function, and is more frequently complicated by adverse LV remodelling and lack of LV recovery. Copyright © 2013. Published by Elsevier SAS.

The concerns of patients under palliative care and a heart failure clinic are not being met.

PubMed

Anderson, H; Ward, C; Eardley, A; Gomm, S A; Connolly, M; Coppinger, T; Corgie, D; Williams, J L; Makin, W P

2001-07-01

Patients with a terminal illness, identified by palliative care teams working in Manchester, and patients attending a heart failure clinic, were asked to participate in a prospective survey to determine their main concerns. Data were collected from 213 palliative care (PC) patients (mostly with cancer) and 66 patients with heart failure (HF). The median ages of the two patient groups were similar, but the HF patients were more likely to be male and living with a partner; 13% of PC and 7% of HF patients reported that they had no carer. The PC patients had more district nurse, hospice, social work and physiotherapy input. The most frequently reported troublesome problems for PC patients were pain (49%), loss of independence (30%) and difficulty walking (27%). HF patients reported dyspnoea (55%), angina (32%) and tiredness (27%) as the most troublesome problems. From a checklist of symptoms, the frequency of tiredness (PC = 77%, HF = 82%) and difficulty getting about (PC = 71%, HF = 65%) were high in each group. Psychological problems were reported by 61% of PC and 41% of HF patients. Cardiac patients reported more breathlessness and cough than PC patients (83% vs 49% and 44% vs 26%, respectively). Reduced libido was more common in cardiac patients (42% vs 21%). Patient disclosure of troublesome problems to professional carers was high (>87% in both PC and HF patients). Documented action was greater for physical than social or psychological problems. For PC patients, documented action was recorded for 83% physical, 43% social/functional and 52% psychological problems. For HF patients documented action was recorded for 74% cardiac, 60% physical - non-cardiac, 30% social/functional and 28% psychological problems. Clearly many patients' troublesome problems were not being addressed. As a result of this study, specific action by health care professionals was taken in 50% of PC patients and 71% of HF patients. We plan to target specific educational events on the treatment of physical problems, psychological assessment and social service provision.

Randomized double-blind trial of darbepoetin alfa in patients with symptomatic heart failure and anemia.

PubMed

Ghali, Jalal K; Anand, Inder S; Abraham, William T; Fonarow, Gregg C; Greenberg, Barry; Krum, Henry; Massie, Barry M; Wasserman, Scott M; Trotman, Marie-Louise; Sun, Yan; Knusel, Beat; Armstrong, Paul

2008-01-29

Substantial evidence suggests that anemia is an independent risk factor for worse outcomes in patients with heart failure (HF). The Study of Anemia in Heart Failure Trial (STAMINA-HeFT) is the largest multicenter, randomized, double-blind, placebo-controlled trial to date evaluating the effect of treating anemia in HF. Patients (N=319) with symptomatic HF, left ventricular ejection fraction < or = 40%, and hemoglobin > or = 9.0 g/dL and < or = 12.5 g/dL were randomized (double-blind) to placebo (N=157) or darbepoetin alfa (N=162) subcutaneously every 2 weeks for 1 year (target hemoglobin, 14.0+/-1.0 g/dL). The primary end point was change from baseline to week 27 in treadmill exercise time. Secondary end points were change from baseline in New York Heart Association class and quality of life at week 27. An additional prespecified efficacy analysis included the time to death by any cause or first HF-related hospitalization by 1 year. At baseline, the median (interquartile range) hemoglobin was 11.4 (10.9, 12.0) g/dL. At week 27, darbepoetin alfa treatment increased median (interquartile range) hemoglobin by 1.8 (1.1, 2.5) g/dL (placebo, 0.3 [-0.2, 1.0] g/dL; P<0.001). Of the patients treated with darbepoetin alfa, 85% achieved 2 consecutive hemoglobin levels of 14.0+/-1.0 g/dL during the study and experienced a hemoglobin increase of > or = 1.0 g/dL from baseline. By intent-to-treat analysis, darbepoetin alfa treatment did not significantly improve exercise duration, New York Heart Association class, or quality of life score compared with placebo. A nonsignificant trend was observed toward a lower risk of all-cause mortality or first HF hospitalization in darbepoetin alfa-treated patients compared with placebo (hazard ratio, 0.68; 95% CI, 0.43, 1.08; P=0.10). Occurrences of adverse events were similar in both treatment groups. In this study of patients with symptomatic HF and anemia, treatment with darbepoetin alfa was not associated with significant clinical benefits. Darbepoetin alfa treatment was well tolerated and effectively raised hemoglobin. A trend of lower risk of morbidity and mortality was observed.

Evidence of Microvascular Dysfunction in Heart Failure with Preserved Ejection Fraction

PubMed Central

Lee, Joshua F.; Barrett-O’Keefe, Zachary; Garten, Ryan S.; Nelson, Ashley D.; Ryan, John J.; Nativi, Jose N.; Richardson, Russell S.; Wray, D. Walter

2015-01-01

Objective While vascular dysfunction is well-defined in HF patients with reduced ejection fraction (HFrEF), disease-related alterations in the peripheral vasculature of HF patients with preserved ejection fraction (HFpEF) are not well characterized. Thus, we sought test the hypothesis that HFpEF patients would demonstrate reduced vascular function, at both the conduit artery and microvascular levels, compared to controls. Methods We examined both conduit artery function via brachial artery flow-mediated dilation (FMD) and microvascular function via reactive hyperemia (RH) following 5 min of ischemia in 24 Class II–IV HFpEF patients and 24 healthy controls matched for age, sex, and brachial artery diameter. Results FMD was reduced in HFpEF patients compared to controls (HFpEF: 3.1 ± 0.7%; Controls: 5.1 ± 0.5%; P = 0.03). However, shear rate at time of peak brachial artery dilation was lower in HFpEF patients compared to controls (HFpEF: 42,070 ± 4,018 s−1; Controls: 69,018 ± 9,509 s−1; P = 0.01), and when brachial artery FMD was normalized for the shear stimulus, cumulative area-under-the-curve (AUC) at peak dilation, the between-group differences were eliminated (HFpEF: 0.11 ± 0.03 %/AUC; Controls: 0.09 ± 0.01 %/AUC; P = 0.58). RH, assessed as AUC, was lower in HFpEF patients (HFpEF: 454 ± 35 mL; Controls: 660 ± 63 mL; P < 0.01). Conclusions Collectively, these data suggest that maladaptations at the microvascular level contribute to the pathophysiology of HFpEF, while conduit artery vascular function is not diminished beyond that which occurs with healthy aging. PMID:26567228

Study of {sup 179}Hf{sup m2} excitation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Vishnevsky, I. N.; Zheltonozhsky, V. A., E-mail: zhelton@kinr.kiev.ua; Savrasov, A. N.

Isomeric ratios of {sup 179}Hf{sup m2,g} yields in the (γ, n) reaction and the cross section for the {sup 179}Hf{sup m2} population in the (α, p) reaction are measured for the first time at the end-point energies of 15.1 and 17.5 MeV for bremsstrahlung photons and 26 MeV for alpha particles. The results are σ = (1.1 ± 0.11) × 10{sup −27} cm{sup 2} for the {sup 176}Lu(α, p){sup 179}Hf{sup m2} reaction and Y{sub m2}/Y{sub g} = (6.1 ± 0.3) × 10{sup −6} and (3.7 ± 0.2) × 10{sup −6} for the {sup 180}Hf(γ, n){sup 179}Hf{sup m22} reaction at E{submore » ep} =15.1 and 17.5 MeV, respectively. The experimental data on the relative {sup 179}Hf{sup m2} yield indicate a single-humped shape of the excitation function for the {sup 180}Hf(γ, n){sup 179}Hf{sup m2} reaction. Simulation is performed using the TALYS-1.4 and EMPIRE-3.2 codes.« less

QishenYiqi Dripping Pill Improves Heart Failure by Up-Regulation of β2-Adrenergic Receptor Expression.

PubMed

Sun, Junfeng; Qian, Hua; Li, Xiaoguang; Tang, Xianling

2017-03-01

QishenYiqi Dripping Pill (QYDP) is a Chinese herbal medicine that originally was used for the treatment of coronary artery disease. Recently, QYDP was used as a complementary treatment for heart failure (HF) in China. An HF rat model was used to clarify the possible therapeutic effects of QYDP on HF. The HF rats were allocated to two groups, HF and HF+QYDP, while normal rats served as a negative control. Cardiac functions were evaluated echocardiographically and hemodynamically. Cardiac apoptosis and the expression of β-adrenergic receptors were also investigated. Compared to the HF group, rats in the HF+QYDP group had a significantly higher fraction shortening (p<0.05), ejection fraction (p<0.05), left ventricular systolic pressure (p<0.05), maximum positive derivatives of left ventricular pressure (p<0.05), maximum negative derivatives of left ventricular pressure (p<0.05), and β2-adrenergic receptor expression (p<0.05), and lower left ventricular end-diastolic pressure (p<0.05) and apoptotic index (p<0.05). The study results indicated that QYDP could efficiently improve HF, possibly by an inhibition of cardiac apoptosis via the β2-adrenergic receptor signaling pathway. Hence, QYDP might be a promising candidate drug for HF therapy.

Differentiation of hepatocytes from induced pluripotent stem cells derived from human hair follicle mesenchymal stem cells.

PubMed

Shi, Xu; Lv, Shuang; He, Xia; Liu, Xiaomei; Sun, Meiyu; Li, Meiying; Chi, Guangfan; Li, Yulin

2016-10-01

Due to the limitations of organ donors and immune rejection in severe liver diseases, stem cell-based therapy presents a promising application for tissue repair and regeneration. As a novel cell source, mesenchymal stem cells separated from human hair follicles (HF-MSCs) are convenient to obtain and have no age limit. To date, the differentiation of HF-MSCs into hepatocytes has not been reported. In this study, we explored whether HF-MSCs and HF-MSC-derived-induced pluripotent stem cells (HF-iPS) could differentiate into hepatocytes in vitro. Flow cytometry, Oil Red O stain and Alizarin Red stain were used to identify the characteristics of HF-MSCs. The expression of liver-specific gene was detected by immunofluorescence and Quantitative Polymerase Chain Reaction. Periodic Acid-Schiff stain, Indocyanine Green stain and Low-Density Lipoprotein stain were performed to evaluate the functions of induced hepatocyte-like cells (HLCs). HF-MSCs were unable to differentiate into HLCs using previously reported procedures for MSCs from other tissues. However, HF-iPS efficiently induced the generation of HLCs that expressed hepatocyte markers and drug metabolism-related genes. HF-iPS can be used as novel and alternative cellular tools for inducing hepatocytes in vitro, simultaneously benefiting from utilizing HF-MSCs as a noninvasive and convenient cell source for reprogramming.

The Palliative Care in Heart Failure (PAL-HF) Trial: Rationale and Design

PubMed Central

Mentz, Robert J.; Tulsky, James A.; Granger, Bradi B.; Anstrom, Kevin J.; Adams, Patricia A.; Dodson, Gwen C.; Fiuzat, Mona; Johnson, Kimberly S.; Patel, Chetan B.; Steinhauser, Karen E.; Taylor, Donald H.; O’Connor, Christopher M.; Rogers, Joseph G.

2014-01-01

Background The progressive nature of heart failure (HF) coupled with high mortality and poor quality of life mandates greater attention to palliative care as a routine component of advanced HF management. Limited evidence exists from randomized, controlled trials supporting the use of interdisciplinary palliative care in HF. Methods The Palliative Care in Heart Failure trial (PAL-HF) is a prospective, controlled, unblinded, single-center study of an interdisciplinary palliative care intervention in 200 patients with advanced HF estimated to have a high likelihood of mortality or re-hospitalization in the ensuing 6 months. The 6-month PAL-HF intervention focuses on physical and psychosocial symptom relief, attention to spiritual concerns and advanced care planning. The primary endpoint is health-related quality of life measured by the Kansas City Cardiomyopathy Questionnaire and the Functional Assessment of Chronic Illness Therapy with Palliative Care Subscale score at 6 months. Secondary endpoints include changes in anxiety/depression, spiritual well-being, caregiver satisfaction, cost and resource utilization, and a composite of death, HF hospitalization and quality of life. Conclusions PAL-HF is a randomized, controlled clinical trial that will help evaluate the efficacy and cost-effectiveness of palliative care in advanced HF using a patient-centered outcome as well as clinical and economic endpoints. PMID:25440791

Heart failure in patients with kidney disease.

PubMed

Tuegel, Courtney; Bansal, Nisha

2017-12-01

Heart failure (HF) is a leading cause of morbidity and mortality in patients with chronic kidney disease (CKD), and the population of CKD patients with concurrent HF continues to grow. The accurate diagnosis of HF is challenging in patients with CKD in part due to a lack of validated imaging and biomarkers specifically in this population. The pathophysiology between the heart and the kidneys is complex and bidirectional. Patients with CKD have greater prevalence of traditional HF risk factors as well as unique kidney-specific risk factors including malnutrition, acid-base alterations, uraemic toxins, bone mineral changes, anemia and myocardial stunning. These risk factors also contribute to the decline of kidney function seen in patients with subclinical and clinical HF. More targeted HF therapies may improve outcomes in patients with kidney disease as current HF therapies are underutilised in this population. Further work is also needed to develop novel HF therapies for the CKD population. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Mechanisms of LiCoO2 Cathode Degradation by Reaction with HF and Protection by Thin Oxide Coatings.

PubMed

Tebbe, Jonathon L; Holder, Aaron M; Musgrave, Charles B

2015-11-04

Reactions of HF with uncoated and Al and Zn oxide-coated surfaces of LiCoO2 cathodes were studied using density functional theory. Cathode degradation caused by reaction of HF with the hydroxylated (101̅4) LiCoO2 surface is dominated by formation of H2O and a LiF precipitate via a barrierless reaction that is exothermic by 1.53 eV. We present a detailed mechanism where HF reacts at the alumina coating to create a partially fluorinated alumina surface rather than forming AlF3 and H2O and thus alumina films reduce cathode degradation by scavenging HF and avoiding H2O formation. In contrast, we find that HF etches monolayer zinc oxide coatings, which thus fail to prevent capacity fading. However, thicker zinc oxide films mitigate capacity loss by reacting with HF to form a partially fluorinated zinc oxide surface. Metal oxide coatings that react with HF to form hydroxyl groups over H2O, like the alumina monolayer, will significantly reduce cathode degradation.

Influence of Ejection Fraction on Outcomes and Efficacy of Sacubitril/Valsartan (LCZ696) in Heart Failure with Reduced Ejection Fraction: The Prospective Comparison of ARNI with ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure (PARADIGM-HF) Trial.

PubMed

Solomon, Scott D; Claggett, Brian; Desai, Akshay S; Packer, Milton; Zile, Michael; Swedberg, Karl; Rouleau, Jean L; Shi, Victor C; Starling, Randall C; Kozan, Ömer; Dukat, Andrej; Lefkowitz, Martin P; McMurray, John J V

2016-03-01

The angiotensin receptor neprilysin inhibitor sacubitril/valsartan (LCZ696) reduced cardiovascular morbidity and mortality compared with enalapril in patients with heart failure (HF) and reduced ejection fraction (EF) in the Prospective Comparison of ARNI with ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure (PARADIGM-HF) trial. We evaluated the influence of EF on clinical outcomes and on the effectiveness of sacubitril/valsartan compared with enalapril. Eight thousand three hundred ninety-nine patients with New York Heart Association class II to IV HF with reduced EF [left ventricular EF (LVEF) ≤40%] were randomized to sacubitril/valsartan 97/103 mg twice daily versus enalapril 10 mg twice daily and followed for a median of 27 months. The primary study end point was cardiovascular death or HF hospitalization. LVEF was assessed at the sites and recorded on case report forms. We related LVEF to study outcomes and assessed the effectiveness of sacubitril/valsartan across the LVEF spectrum. The mean LVEF in PARADIGM-HF, reported by sites, was 29.5 (interquartile range, 25-34). The risk of all outcomes increased with decreasing LVEF. Each 5-point reduction in LVEF was associated with a 9% increased risk of cardiovascular death or HF hospitalization (hazard ratio, 1.09; 95% confidence interval, 1.05-1.13; P<0.001), a 9% increased risk for CV death (hazard ratio, 1.09; 95% confidence interval, 1.04-1.14), a 9% increased risk in HF hospitalization (hazard ratio, 1.09; 95% confidence interval, 1.04-1.14) and a 7% increased risk in all-cause mortality (hazard ratio, 1.07; 95% confidence interval, 1.03-1.12) in adjusted analyses. Sacubitril/valsartan was effective across the LVEF spectrum, with no evidence of heterogeneity, when modeled either in tertiles (P interaction=0.87) or continuously (P interaction=0.95). In patients with HF and reduced EF enrolled in PARADIGM-HF, LVEF was a significant and independent predictor of all outcomes. Sacubitril/valsartan was effective at reducing cardiovascular death and HF hospitalization throughout the LVEF spectrum. URL: http://www.clinicaltrials.gov. Unique identifier: NCT01035255. © 2016 American Heart Association, Inc.

Density functional theory study of HfCl4, ZrCl4, and Al(CH3)3 decomposition on hydroxylated SiO2: Initial stage of high-k atomic layer deposition

NASA Astrophysics Data System (ADS)

Jeloaica, L.; Estève, A.; Djafari Rouhani, M.; Estève, D.

2003-07-01

The initial stage of atomic layer deposition of HfO2, ZrO2, and Al2O3 high-k films, i.e., the decomposition of HfCl4, ZrCl4, and Al(CH3)3 precursor molecules on an OH-terminated SiO2 surface, is investigated within density functional theory. The energy barriers are determined using artificial activation of vibrational normal modes. For all precursors, reaction proceeds through the formation of intermediate complexes that have equivalent formation energies (˜-0.45 eV), and results in HCl and CH4 formation with activation energies of 0.88, 0.91, and 1.04 eV for Hf, Zr, and Al based precursors, respectively. The reaction product of Al(CH3)3 decomposition is found to be more stable (by -1.45 eV) than the chemisorbed intermediate complex compared to the endothermic decomposition of HfCl4 and ZrCl4 chemisorbed precursors (0.26 and 0.29 eV, respectively).

What is your patient’s cognitive profile? Three distinct subgroups of cognitive function in persons with heart failure

PubMed Central

Hawkins, Misty A.W.; Schaefer, Julie T.; Gunstad, John; Dolansky, Mary A.; Redle, Joseph D.; Josephson, Richard; Moore, Shirley M.; Hughes, Joel W.

2014-01-01

Purpose To determine whether patients with heart failure (HF) have distinct profiles of cognitive impairment. Background Cognitive impairment is common in HF. Recent work found three cognitive profiles in HF patients— (1) intact, (2) impaired, and (3) memory-impaired. We examined the reproducibility of these profiles and clarified mechanisms. Methods HF patients (68.6±9.7years; N=329) completed neuropsychological testing. Composite scores were created for cognitive domains and used to identify clusters via agglomerative-hierarchical cluster analysis. Results A 3-cluster solution emerged. Cluster 1 (n=109) had intact cognition. Cluster 2 (n=123) was impaired across all domains. Cluster 3 (n=97) had impaired memory only. Clusters differed in age, race, education, SES, IQ, BMI, and diabetes (ps ≤.026) but not in mood, anxiety, cardiovascular, or pulmonary disease (ps≥.118). Conclusions We replicated three distinct patterns of cognitive function in persons with HF. These profiles may help providers offer tailored care to patients with different cognitive and clinical needs. PMID:25510559

Xanthine-oxidase inhibitors and statins in chronic heart failure: effects on vascular and functional parameters.

PubMed

Greig, Douglas; Alcaino, Hernan; Castro, Pablo F; Garcia, Lorena; Verdejo, Hugo E; Navarro, Mario; López, Rafael; Mellado, Rosemarie; Tapia, Fabiola; Gabrielli, Luigi A; Nogerol, Camilo; Chiong, Mario; Godoy, Ivan; Lavandero, Sergio

2011-04-01

Increased oxidative stress in heart failure (HF) leads to inflammation and endothelial dysfunction (ED). Both statins and allopurinol have known anti-oxidant properties, but their utility in HF has not been fully assessed. This investigation was a prospective, double-blind, double-dummy study, performed between March 2007 and June 2009. Seventy-four HF patients, with New York Heart Association (NYHA) Class II or III status and left ventricular ejection fraction (LVEF) <40%, were included. Patients received placebo during 4 weeks and were then randomized to receive 4 weeks of either atorvastatin 20 mg/day plus placebo (ATV+PLA group) or atorvastatin 20 mg/day orally plus allopurinol 300 mg/day orally (ATV+ALLO group). Malondialdehyde (MDA), extracellular superoxide dismutase (ecSOD) activity and uric acid (UA) levels, among others, were determined at baseline and after 4 weeks of treatment. ED was assessed by flow-dependent endothelial-mediated vasodilation (FDD), and functional capacity by 6-minute walk test (6MWT). Thirty-two patients were randomized to ATV+PLA and 38 to ATV+ALLO. Mean age was 59 ± 2 years, 82% were male, and 22% had an ischemic etiology. Hypertension was present in 60% and diabetes in 15% of those studied. No significant differences were observed between baseline measurements and after placebo. After 4 weeks of treatment, both groups showed a significant decrease on MDA (0.9 ± 0.1 to 0.8 ± 0.1 and 1.0 ± 0.5 to 0.9 ± 0.1 μmol/liter, p = 0.88), UA (7.4 ± 0.4 to 6.8 ± 0.3 and 7.2 ± 0.4 to 5.0 ± 0.3 mg/dl, p < 0.01) and FDD (3.9 ± 0.2% to 5.6 ± 0.4% and 4.6 ± 0.3% to 7.1 ± 0.5%, p = 0.07) with increased ecSOD activity (109 ± 11 to 173 ± 13 and 98 ± 10 to 202 ± 16, U/ml/min, p = 0.41) and improved 6MWT (447 ± 18 to 487 ± 19 and 438 ± 17 to 481 ± 21 m, p = 0.83), with all values for ATV+PLA and ATV+ALLO, respectively; p-values are for comparison between groups after treatment. Short-term ATV treatment in heart failure (HF) patients reduces oxidative stress and improves FDD and functional capacity. These beneficial effects are not strengthened by the addition of allopurinol. Copyright © 2011 International Society of Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

Effect of Instant Cooked Giant Embryonic Rice on Body Fat Weight and Plasma Lipid Profile in High Fat-Fed Mice

PubMed Central

Chung, Soo Im; Kim, Tae Hyeong; Rico, Catherine W.; Kang, Mi Young

2014-01-01

The comparative effects of instant cooked rice made from giant embryo mutant or ordinary normal rice on body weight and lipid profile in high fat-fed mice were investigated. The animals were given experimental diets for seven weeks: normal control (NC), high fat (HF), and HF supplemented with instant normal white (HF-NW), normal brown (HF-NB), giant embryonic white (HF-GW), or giant embryonic brown (HF-GB) rice. The HF group showed markedly higher body weight, body fat, plasma and hepatic triglyceride and cholesterol concentrations, and atherogenic index relative to NC group. However, instant rice supplementation counteracted this high fat-induced hyperlipidemia through regulation of lipogenesis and adipokine production. The GB rice exhibited greater hypolipidemic and body fat-lowering effects than the GW or NB rice. These findings illustrate that the giant embryo mutant may be useful as functional biomaterial for the development of instant rice with strong preventive action against high fat diet-induced hyperlipidemia and obesity. PMID:24932656

Thermoelectric properties of doped BaHfO{sub 3}

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dixit, Chandra Kr., E-mail: ckparadise@gmail.com, E-mail: sharmarameshfgiet@gmail.com; Bhamu, K. C.; Sharma, Ramesh, E-mail: ckparadise@gmail.com, E-mail: sharmarameshfgiet@gmail.com

2016-05-06

We have studied the structural stability, electronic structure, optical properties and thermoelectric properties of doped BaHfO{sub 3} by full potential linearized augmented plane wave (FP-LAPW) method. The electronic structure of BaHfO{sub 3} doped with Sr shows enhances the indirect band gaps of 3.53 eV, 3.58 eV. The charge density plots show strong ionic bonding in Ba-Hf, and ionic and covalent bonding between Hf and O. Calculations of the optical spectra, viz., the dielectric function, refractive index and extinction coefficient are performed for the energy range are calculated and analyzed. Thermoelectric properties of semi conducting are also reported first time. Themore » doped BaHfO{sub 3} is approximately wide band gap semiconductor with the large p-type Seebeck coefficient. The power factor of BaHfO{sub 3} is increased with Sr doping, decreases because of low electrical resistivity and thermal conductivity.« less

Has the Time Come to Be More Aggressive With Bariatric Surgery in Obese Patients With Chronic Systolic Heart Failure?

PubMed

Vest, Amanda R

2018-06-01

Obesity is a strong risk factor for the development of heart failure (HF). Diet, exercise, and weight-loss pharmacotherapies have limited potential to achieve significant and sustainable weight loss, especially in patients with symptomatic systolic HF. This review seeks to determine the role of bariatric surgery for patients with systolic HF and obesity. Bariatric surgeries such as the laparoscopic sleeve gastrectomy (LSG) and Roux-en-Y gastric bypass (RYGB) represent the most successful long-term strategy for achieving weight loss and diabetes and hypertension remission in the general obese population. These benefits translate to reductions in cardiovascular events and mortality, as well as improvements in myocardial structure and function. There is also now data supporting the safety of LSG or RYGB in patients with systolic dysfunction and a reduction in HF admissions post-operatively. Current literature and clinical experience suggest that the most appropriate bariatric surgery candidates with HF are patients aged < 50-60 years, with severely depressed systolic function and NYHA II-III symptoms, who have failed non-surgical strategies and have a high likelihood of future cardiac transplantation candidacy after weight loss. This review seeks to determine the role of bariatric surgery for patients with systolic HF and obesity.

Experimental Evidences Supporting the Benefits of Exercise Training in Heart Failure.

PubMed

Ichige, Marcelo H A; Pereira, Marcelo G; Brum, Patrícia C; Michelini, Lisete C

2017-01-01

Heart Failure (HF), a common end point for many cardiovascular diseases, is a syndrome with a very poor prognosis. Although clinical trials in HF have achieved important outcomes in reducing mortality, little is known about functional mechanisms conditioning health improvement in HF patients. In parallel with clinical studies, basic science has been providing important discoveries to understand the mechanisms underlying the pathophysiology of HF, as well as to identify potential targets for the treatment of this syndrome. In spite of being the end-point of cardiovascular derangements caused by different etiologies, autonomic dysfunction, sympathetic hyperactivity, oxidative stress, inflammation and hormonal activation are common factors involved in the progression of this syndrome. Together these causal factors create a closed link between three important organs: brain, heart and the skeletal muscle. In the past few years, we and other groups have studied the beneficial effects of aerobic exercise training as a safe therapy to avoid the progression of HF. As summarized in this chapter, exercise training, a non-pharmacological tool without side effects, corrects most of the HF-induced neurohormonal and local dysfunctions within the brain, heart and skeletal muscles. These adaptive responses reverse oxidative stress, reduce inflammation, ameliorate neurohormonal control and improve both cardiovascular and skeletal muscle function, thus increasing the quality of life and reducing patients' morbimortality.

Educational needs for improving self-care in heart failure patients with diabetes.

PubMed

Cha, EunSeok; Clark, Patricia C; Reilly, Carolyn Miller; Higgins, Melinda; Lobb, Maureen; Smith, Andrew L; Dunbar, Sandra B

2012-01-01

To explore the need for self-monitoring and self-care education in heart failure patients with diabetes (HF- DM patients) by describing cognitive and affective factors to provide guidance in developing effective self-management education. A cross-sectional correlation design was employed using baseline patient data from a study testing a 12-week patient and family dyad intervention to improve dietary and medication-taking self-management behaviors in HF patients. Data from 116 participants recruited from metropolitan Atlanta area were used. Demographic and comorbidities, physical function, psychological distress, relationship with health care provider, self-efficacy (medication taking and low sodium diet), and behavioral outcomes (medications, dietary habits) were assessed. Descriptive statistics and a series of chi-square tests, t tests, or Mann-Whitney tests were performed to compare HF patients with and without DM. HF-DM patients were older and heavier, had more comorbidities, and took more daily medications than HF patients. High self-efficacy on medication and low-sodium diet was reported in both groups with no significant difference. Although HF-DM patients took more daily medications than HF, both groups exhibited high HF medication-taking behaviors. The HF-DM patients consumed significantly lower total sugar than HF patients but clinically higher levels of sodium. Diabetes educators need to be aware of potential conflicts of treatment regimens to manage 2 chronic diseases. Special and integrated diabetes self-management education programs that incorporate principles of HF self-management should be developed to improve self-management behavior in HF-DM patients.

A human factors methodology for real-time support applications

NASA Technical Reports Server (NTRS)

Murphy, E. D.; Vanbalen, P. M.; Mitchell, C. M.

1983-01-01

A general approach to the human factors (HF) analysis of new or existing projects at NASA/Goddard is delineated. Because the methodology evolved from HF evaluations of the Mission Planning Terminal (MPT) and the Earth Radiation Budget Satellite Mission Operations Room (ERBS MOR), it is directed specifically to the HF analysis of real-time support applications. Major topics included for discussion are the process of establishing a working relationship between the Human Factors Group (HFG) and the project, orientation of HF analysts to the project, human factors analysis and review, and coordination with major cycles of system development. Sub-topics include specific areas for analysis and appropriate HF tools. Management support functions are outlined. References provide a guide to sources of further information.

Atomic layer deposition of hafnium oxide: A detailed reaction mechanism from first principles

NASA Astrophysics Data System (ADS)

Widjaja, Yuniarto; Musgrave, Charles B.

2002-08-01

Atomic layer deposition (ALD) of hafnium oxide (HfO2) using HfCl4 and H2O as precursors is studied using density functional theory. The mechanism consists of two deposition half-reactions: (1) HfCl4 with Hf-OH sites, and (2) H2O with Hf-Cl sites. Both half-reactions exhibit stable intermediates with energies lower than those of the final products. We show that increasing the temperature reduces the stability of the complex. However, increasing temperature also increases the dissociation free-energy barrier, which in turn results in increased desorption of adsorbed precursors. Both half-reactions are qualitatively similar to the corresponding reactions of ZrO2 ALD using ZrCl4 and H2O.

Hydrogen fluoride capture by imidazolium acetate ionic liquid

NASA Astrophysics Data System (ADS)

Chaban, Vitaly

2015-04-01

Extraction of hydrofluoric acid (HF) from oils is a drastically important problem in petroleum industry, since HF causes quick corrosion of pipe lines and brings severe health problems to humanity. Some ionic liquids (ILs) constitute promising scavenger agents thanks to strong binding to polar compounds and tunability. PM7-MD simulations and hybrid density functional theory are employed here to consider HF capture ability of ILs. Discussing the effects and impacts of the cation and the anion separately and together, we evaluate performance of imidazolium acetate and outline systematic search guidelines for efficient adsorption and extraction of HF.

Nutritional Status and Energy Intake as Predictors of Functional Status After Cardiac Rehabilitation in Elderly Inpatients With Heart Failure　- A Retrospective Cohort Study.

PubMed

Katano, Satoshi; Hashimoto, Akiyoshi; Ohori, Katsuhiko; Watanabe, Ayako; Honma, Remi; Yanase, Rimi; Ishigo, Tomoyuki; Fujito, Takefumi; Ohnishi, Hirofumi; Tsuchihashi, Kazufumi; Ishiai, Sumio; Miura, Tetsuji

2018-05-25

Whether the short-term effect of cardiac rehabilitation (CR) in elderly patients with heart failure (HF) is influenced by nutritional status is uncertain, so the present study investigated the effect of nutritional status on functional recovery after CR in elderly HF inpatients.Methods and Results:We enrolled 145 patients admitted for treatment of HF who were aged ≥65 years and had a low functional status defined as a Barthel index (BI) score ≤85 points at the commencement of CR. Nutritional status was assessed by the Mini Nutritional Assessment Short Form (MNA-SF) and total energy intake per day. The primary endpoint was functional status determined by the BI score at discharge. The median CR period was 20 days (interquartile range: 14-34 days), and 87 patients (60%) were functionally dependent (BI score ≤85) at discharge. Multivariate logistic regression analysis showed that MNA-SF score (odds ratio [OR]: 0.76, P=0.02) and total energy intake at the commencement of CR (OR: 0.91, P=0.02) were independent predictors of functional dependence after CR. MNA-SF score ≤7 and total energy intake ≤24.5 kcal/kg/day predicted functional dependence at discharge with moderate sensitivity and specificity. MNA-SF score and total energy intake at the commencement of CR are novel predictors of the extent of functional recovery of elderly HF inpatients after in-hospital CR.

Upregulation of adenosine A1 receptors facilitates sinoatrial node dysfunction in chronic canine heart failure by exacerbating nodal conduction abnormalities revealed by novel dual-sided intramural optical mapping.

PubMed

Lou, Qing; Hansen, Brian J; Fedorenko, Olga; Csepe, Thomas A; Kalyanasundaram, Anuradha; Li, Ning; Hage, Lori T; Glukhov, Alexey V; Billman, George E; Weiss, Raul; Mohler, Peter J; Györke, Sándor; Biesiadecki, Brandon J; Carnes, Cynthia A; Fedorov, Vadim V

2014-07-22

Although sinoatrial node (SAN) dysfunction is a hallmark of human heart failure (HF), the underlying mechanisms remain poorly understood. We aimed to examine the role of adenosine in SAN dysfunction and tachy-brady arrhythmias in chronic HF. We applied multiple approaches to characterize SAN structure, SAN function, and adenosine A1 receptor expression in control (n=17) and 4-month tachypacing-induced chronic HF (n=18) dogs. Novel intramural optical mapping of coronary-perfused right atrial preparations revealed that adenosine (10 μmol/L) markedly prolonged postpacing SAN conduction time in HF by 206 ± 99 milliseconds (versus 66 ± 21 milliseconds in controls; P=0.02). Adenosine induced SAN intranodal conduction block or microreentry in 6 of 8 dogs with HF versus 0 of 7 controls (P=0.007). Adenosine-induced SAN conduction abnormalities and automaticity depression caused postpacing atrial pauses in HF versus control dogs (17.1 ± 28.9 versus 1.5 ± 1.3 seconds; P<0.001). Furthermore, 10 μmol/L adenosine shortened atrial repolarization and led to pacing-induced atrial fibrillation in 6 of 7 HF versus 0 of 7 control dogs (P=0.002). Adenosine-induced SAN dysfunction and atrial fibrillation were abolished or prevented by adenosine A1 receptor antagonists (50 μmol/L theophylline/1 μmol/L 8-cyclopentyl-1,3-dipropylxanthine). Adenosine A1 receptor protein expression was significantly upregulated during HF in the SAN (by 47 ± 19%) and surrounding atrial myocardium (by 90 ± 40%). Interstitial fibrosis was significantly increased within the SAN in HF versus control dogs (38 ± 4% versus 23 ± 4%; P<0.001). In chronic HF, adenosine A1 receptor upregulation in SAN pacemaker and atrial cardiomyocytes may increase cardiac sensitivity to adenosine. This effect may exacerbate conduction abnormalities in the structurally impaired SAN, leading to SAN dysfunction, and potentiate atrial repolarization shortening, thereby facilitating atrial fibrillation. Atrial fibrillation may further depress SAN function and lead to tachy-brady arrhythmias in HF. © 2014 American Heart Association, Inc.

Impaired compensatory beta-cell function and growth in response to high-fat diet in LDL receptor knockout mice

PubMed Central

Oliveira, Ricardo B d; Carvalho, Carolina P d F; Polo, Carla C; Dorighello, Gabriel d G; Boschero, Antônio C; Oliveira, Helena C F d; Collares-Buzato, Carla B

2014-01-01

In this study, we investigated the effect of low density lipoprotein receptor (LDLr) deficiency on gap junctional connexin 36 (Cx36) islet content and on the functional and growth response of pancreatic beta-cells in C57BL/6 mice fed a high-fat (HF) diet. After 60 days on regular or HF diet, the metabolic state and morphometric islet parameters of wild-type (WT) and LDLr−/− mice were assessed. HF diet-fed WT animals became obese and hypercholesterolaemic as well as hyperglycaemic, hyperinsulinaemic, glucose intolerant and insulin resistant, characterizing them as prediabetic. Also they showed a significant decrease in beta-cell secretory response to glucose. Overall, LDLr−/− mice displayed greater susceptibility to HF diet as judged by their marked cholesterolaemia, intolerance to glucose and pronounced decrease in glucose-stimulated insulin secretion. HF diet induced similarly in WT and LDLr−/− mice, a significant decrease in Cx36 beta-cell content as revealed by immunoblotting. Prediabetic WT mice displayed marked increase in beta-cell mass mainly due to beta-cell hypertrophy/replication. Nevertheless, HF diet-fed LDLr−/− mice showed no significant changes in beta-cell mass, but lower islet–duct association (neogenesis) and higher beta-cell apoptosis index were seen as compared to controls. The higher metabolic susceptibility to HF diet of LDLr−/− mice may be explained by a deficiency in insulin secretory response to glucose associated with lack of compensatory beta-cell expansion. PMID:24853046

Real-world heart failure management in 10,910 patients with chronic heart failure in the Netherlands : Design and rationale of the Chronic Heart failure ESC guideline-based Cardiology practice Quality project (CHECK-HF) registry.

PubMed

Brugts, J J; Linssen, G C M; Hoes, A W; Brunner-La Rocca, H P

2018-05-01

Data from patient registries give insight into the management of patients with heart failure (HF), but actual data from unselected real-world HF patients are scarce. Therefore, we performed a cross sectional study of current HF care in the period 2013-2016 among more than 10,000 unselected HF patients at HF outpatient clinics in the Netherlands. In 34 participating centres, all 10,910 patients with chronic HF treated at cardiology centres were included in the CHECK-HF registry. Of these, most (96%) were managed at a specific HF outpatient clinic. Heart failure was typically diagnosed according to the ESC guidelines 2012, based on signs, symptoms and structural and/or functional cardiac abnormalities. Information on diagnostics, treatment and co-morbidities were recorded, with specific focus on drug therapy and devices. In our cohort, the mean age was 73 years (SD 12) and 60% were male. Frequent co-morbidities reported in the patient records were diabetes mellitus 30%, hypertension 43%, COPD 19%, and renal insufficiency 58%. In 47% of the patients, ischaemia was the origin of HF. In our registry, the prevalence of HF with preserved ejection fraction was 21%. The CHECK-HF registry will provide insight into the current, real world management of patient with chronic HF, including HF with reduced ejection fraction, preserved ejection fraction and mid-range ejection fraction, that will help define ways to improve quality of care. Drug and device therapy and guideline adherence as well as interactions with age, gender and co-morbidities will receive specific attention.

First-principles modeling of hafnia-based nanotubes.

PubMed

Evarestov, Robert A; Bandura, Andrei V; Porsev, Vitaly V; Kovalenko, Alexey V

2017-09-15

Hybrid density functional theory calculations were performed for the first time on structure, stability, phonon frequencies, and thermodynamic functions of hafnia-based single-wall nanotubes. The nanotubes were rolled up from the thin free layers of cubic and tetragonal phases of HfO 2 . It was shown that the most stable HfO 2 single-wall nanotubes can be obtained from hexagonal (111) layer of the cubic phase. Phonon frequencies have been calculated for different HfO 2 nanolayers and nanotubes to prove the local stability and to find the thermal contributions to their thermodynamic functions. The role of phonons in stability of nanotubes seems to be negligible for the internal energy and noticeable for the Helmholtz free energy. Zone folding approach has been applied to estimate the connection between phonon modes of the layer and nanotubes and to approximate the nanotube thermodynamic properties. It is found that the zone-folding approximation is sufficiently accurate for heat capacity, but less accurate for entropy. The comparison has been done between the properties of TiO 2 , ZrO 2 , and HfO 2 . © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Hair Follicle-Derived Smooth Muscle Cells and Small Intestinal Submucosa for Engineering Mechanically Robust and Vasoreactive Vascular Media

PubMed Central

Peng, Hao-Fan; Liu, Jin Yu

2011-01-01

Our laboratory recently reported a new source of smooth muscle cells (SMCs) derived from hair follicle (HF) mesenchymal stem cells. HF-SMCs demonstrated high proliferation and clonogenic potential as well as contractile function. In this study, we aimed at engineering the vascular media using HF-SMCs and a natural biomaterial, namely small intestinal submucosa (SIS). Engineering functional vascular constructs required application of mechanical force, resulting in actin reorganization and cellular alignment. In turn, cell alignment was necessary for development of receptor- and nonreceptor-mediated contractility as soon as 24 h after cell seeding. Within 2 weeks in culture, the cells migrated into SIS and secreted collagen and elastin, the two major extracellular matrix components of the vessel wall. At 2 weeks, vascular reactivity increased significantly up to three- to fivefold and mechanical properties were similar to those of native ovine arteries. Taken together, our data demonstrate that the combination of HF-SMCs with SIS resulted in mechanically strong, biologically functional vascular media with potential for arterial implantation. PMID:21083418

Prediction of core level binding energies in density functional theory: Rigorous definition of initial and final state contributions and implications on the physical meaning of Kohn-Sham energies.

PubMed

Pueyo Bellafont, Noèlia; Bagus, Paul S; Illas, Francesc

2015-06-07

A systematic study of the N(1s) core level binding energies (BE's) in a broad series of molecules is presented employing Hartree-Fock (HF) and the B3LYP, PBE0, and LC-BPBE density functional theory (DFT) based methods with a near HF basis set. The results show that all these methods give reasonably accurate BE's with B3LYP being slightly better than HF but with both PBE0 and LCBPBE being poorer than HF. A rigorous and general decomposition of core level binding energy values into initial and final state contributions to the BE's is proposed that can be used within either HF or DFT methods. The results show that Koopmans' theorem does not hold for the Kohn-Sham eigenvalues. Consequently, Kohn-Sham orbital energies of core orbitals do not provide estimates of the initial state contribution to core level BE's; hence, they cannot be used to decompose initial and final state contributions to BE's. However, when the initial state contribution to DFT BE's is properly defined, the decompositions of initial and final state contributions given by DFT, with several different functionals, are very similar to those obtained with HF. Furthermore, it is shown that the differences of Kohn-Sham orbital energies taken with respect to a common reference do follow the trend of the properly calculated initial state contributions. These conclusions are especially important for condensed phase systems where our results validate the use of band structure calculations to determine initial state contributions to BE shifts.

Segmental arterial stiffness in relation to B-type natriuretic peptide with preserved systolic heart function.

PubMed

Yen, Chih-Hsuan; Hung, Chung-Lieh; Lee, Ping-Ying; Tsai, Jui-Peng; Lai, Yau-Huei; Su, Cheng-Huang; Yeh, Hung-I; Hou, Charles Jia-Yin; Chien, Kuo-Liong

2017-01-01

Central arterial stiffness has been shown to play a key role in cardiovascular disease. However, evidence regarding such arterial stiffness from various arterial segments in relation to B-type natriuretic peptide (BNP) remains elusive. A total of 1255 participants (47.8% men; mean age: 62.6 ± 12.3 [SD] years) with preserved left ventricular function (ejection fraction ≥50%) and ≥1 risk factors were consecutively studied. Arterial pulse wave velocity (PWV) by automatic device (VP-2000; Omron Healthcare) for heart-femoral (hf-PWV), brachial-ankle (ba-PWV), and heart-carotid (hc-PWV) segments were obtained and related to BNP concentrations (Abbott Diagnostics, Abbott Park, IL, USA). Subjects in the highest hf-PWV quartile were older and had worse renal function and higher blood pressure (all P < 0.05). Elevated PWV (m/s) was correlated with elevated BNP (pg/ml) (beta coefficient = 19.3, 12.4, 5.9 for hf-PWV, ba-PWV, hc-PWV respectively, all p < 0.05). After accounting for clinical co-variates and left ventricle mass index (LVMI), both hf-PWV and ba-PWV were correlated with higher BNP (beta coefficient = 8.3, 6.4 respectively, P < 0.01 for each). Adding both hf-PWV and ba-PWV to LVMI significantly expanded ROC in predicting abnormal BNP>100 pg/ml (both P < 0.01), but only hf-PWV presented significant integrated discrimination improvement to predict risk for BNP concentrations (0.7%, P = 0.029). A significant segmental PWV associated with biomarker BNP concentrations suggests that arterial stiffness is associated with myocardial damage.

Segmental arterial stiffness in relation to B-type natriuretic peptide with preserved systolic heart function

PubMed Central

Yen, Chih-Hsuan; Hung, Chung-Lieh; Lee, Ping-Ying; Tsai, Jui-Peng; Lai, Yau-Huei; Su, Cheng-Huang; Yeh, Hung-I; Hou, Charles Jia-Yin

2017-01-01

Background Central arterial stiffness has been shown to play a key role in cardiovascular disease. However, evidence regarding such arterial stiffness from various arterial segments in relation to B-type natriuretic peptide (BNP) remains elusive. Methods A total of 1255 participants (47.8% men; mean age: 62.6 ± 12.3 [SD] years) with preserved left ventricular function (ejection fraction ≥50%) and ≥1 risk factors were consecutively studied. Arterial pulse wave velocity (PWV) by automatic device (VP-2000; Omron Healthcare) for heart-femoral (hf-PWV), brachial-ankle (ba-PWV), and heart-carotid (hc-PWV) segments were obtained and related to BNP concentrations (Abbott Diagnostics, Abbott Park, IL, USA). Results Subjects in the highest hf-PWV quartile were older and had worse renal function and higher blood pressure (all P < 0.05). Elevated PWV (m/s) was correlated with elevated BNP (pg/ml) (beta coefficient = 19.3, 12.4, 5.9 for hf-PWV, ba-PWV, hc-PWV respectively, all p < 0.05). After accounting for clinical co-variates and left ventricle mass index (LVMI), both hf-PWV and ba-PWV were correlated with higher BNP (beta coefficient = 8.3, 6.4 respectively, P < 0.01 for each). Adding both hf-PWV and ba-PWV to LVMI significantly expanded ROC in predicting abnormal BNP>100 pg/ml (both P < 0.01), but only hf-PWV presented significant integrated discrimination improvement to predict risk for BNP concentrations (0.7%, P = 0.029). Conclusion A significant segmental PWV associated with biomarker BNP concentrations suggests that arterial stiffness is associated with myocardial damage. PMID:28922407

Spatiotemporal Variability in Hydraulic Fracturing Water Use and Water Produced with Shale Gas in the U.S.

NASA Astrophysics Data System (ADS)

Nicot, J. P.; Scanlon, B. R.; Reedy, R. C.

2016-12-01

Longer time series and increasing data availability allows more comprehensive assessment of spatiotemporal variability in hydraulic fracturing (HF) water use and flowback/produced (FP) water generation in shale plays in the U.S. In this analysis we quantified HF and FP water volumes for seven major shale gas plays in the U.S. using detailed well by well analyses through 2015. Well count ranges from 1,500 (Utica) to 20,200 (Barnett) with total cumulative? HF water use ranging from 12 billion gallons (bgal) (Utica) to 65 bgal (Barnett). HF water use/well has been increasing over time in many plays and currently ranges from 4.5 mgal/well (Fayetteville) to 10 mgal/well (Utica) (2015). Normalizing by lateral length results in a range of 900 gal/ft (Fayetteville) to 15,600 gal/ft (Marcellus) (2015). FP water volumes are also highly variable, lowest in the Utica and highest in the Barnett. Management of FP water is mostly through disposal into Class II salt water injection wells, with the exception of the Marcellus where >90% of the FP water is reused/recycled. Along the dramatic domestic gas production increase, electricity generation from natural gas has almost doubled since 2000. It is important to consider the water use for HF in terms of the lifecycle of natural gas with HF water consumption. It is equivalent to <10% of the water consumed in natural gas-fired power plants that usually require less water than coal-fired power plants, resulting in net water savings.

Effects of carvedilol therapy in patients with heart failure with preserved ejection fraction - Results from the Croatian heart failure (CRO-HF) registry.

PubMed

Domagoj, Markovic; Branka, Jurcevic Zidar; Jelena, Macanovic; Davor, Milicic; Duska, Glavas

2018-04-17

According to recent guidelines, the best approach for treatment of heart failure patients with preserved ejection function is still not defined. The aim of this study was to investigate how carvedilol therapy influences the survival rate, ejection fraction and NYHA class in these patients. We conducted study on heart failure patients with preserved systolic function from the Croatian heart failure registry who were hospitalized in the period between 2005 and 2010. We enrolled patients with carvedilol listed as treatment on their discharge letters and patients who had been using carvedilol for at least 4 years, while for the control group we selected patients with no beta-blockers on their discharge letters (113 vs 204 respectively). The primary outcome was the overall survival rate and the secondary outcome was the change in ejection fraction of the left ventricle and NYHA class during the study. Patients in the carvedilol group had a higher overall survival rate compared to patients in the control group (chi-square=14.1, P<0.001). Patients in the carvedilol group in two measurements had a significantly higher ejection fraction compared to the control group (F=148.04, P<0.001). Also, patients in the carvedilol group showed improvement in NYHA class (chi-square=29.768, P<0.001). Long term carvedilol therapy appears to be associated with a higher overall survival rate, improvement in ejection fraction and NYHA class in heart failure patients with preserved ejection fraction. Copyright © 2018 Elsevier España, S.L.U. All rights reserved.

Multiple frequency radar observations of high-latitude E region irregularities in the HF modified ionosphere

NASA Technical Reports Server (NTRS)

Noble, S. T.; Gordon, W. E.; Djuth, F. T.; Jost, R. J.; Hedberg, A.

1987-01-01

This paper discusses the results of the September 1983 observations of artificial field-aligned irregularities (AFAIs) in the Tromso, Norway region, made by backscatter radars operating at 46.9, 143.8, 21.4, and 140.0 MHz. Four classes of resonant instability processes at work in the E and F regions are examined in detail: (1) the coupling of parametric decay instability waves across geomagnetic field lines, (2) thermal parametric instability, (3) four-wave interaction thermal parametric instability, and (4) the resonance instability. The characteristics of the AFAI scatter are described, with special attention given to the growth and decay time constants, functional dependence on the heater power and polarization, and the scattering cross sections of the irregularities.

Behavioral in-effectiveness of high frequency electromagnetic field in mice.

PubMed

Salunke, Balwant P; Umathe, Sudhir N; Chavan, Jagatpalsingh G

2015-03-01

The present investigation was carried out with an objective to study the influence of high frequency electromagnetic field (HF-EMF) on anxiety, obsessive compulsive disorder (OCD) and depression-like behavior. For exposure to HF-EMF, non-magnetic material was used to fabricate the housing. Mice were exposed to HF-EMF (2.45GHz), 60min/day for 7 or 30 or 60 or 90 or 120days. The exposure was carried out by switching-on inbuilt class-I BLUETOOTH device that operates on 2.45GHz frequency in file transfer mode at a peak density of 100mW. Mice were subjected to the assessment of anxiety, OCD and depression-like behavior for 7 or 30 or 60 or 90 or 120days of exposure. The anxiety-like behavior was assessed by elevated plus maze, open field test and social interaction test. OCD-like behavior was assessed by marble burying behavior, whereas depression-like behavior was assessed by forced swim test and tail suspension test. The present experiment demonstrates that up to 120days of exposure to HF-EMF does not produce anxiety, OCD and depression-like behavior in mice. Copyright © 2014 Elsevier Inc. All rights reserved.

Cluster analysis differentiates high and low community functioning in schizophrenia: Subgroups differ on working memory but not other neurocognitive domains.

PubMed

Alden, Eva C; Cobia, Derin J; Reilly, James L; Smith, Matthew J

2015-10-01

Schizophrenia is characterized by impairment in multiple aspects of community functioning. Available literature suggests that community functioning may be enhanced through cognitive remediation, however, evidence is limited regarding whether specific neurocognitive domains may be treatment targets. We characterized schizophrenia subjects based on their level of community functioning through cluster analysis in an effort to identify whether specific neurocognitive domains were associated with variation in functioning. Schizophrenia (SCZ, n=60) and control (CON, n=45) subjects completed a functional capacity task, social competence role-play, functional attainment interview, and a neuropsychological battery. Multiple cluster analytic techniques were used on the measures of functioning in the schizophrenia subjects to generate functionally-defined subgroups. MANOVA evaluated between-group differences in neurocognition. The cluster analysis revealed two distinct groups, consisting of 36 SCZ characterized by high levels of community functioning (HF-SCZ) and 24 SCZ with low levels of community functioning (LF-SCZ). There was a main group effect for neurocognitive performance (p<0.001) with CON outperforming both SCZ groups in all neurocognitive domains. Post-hoc tests revealed that HF-SCZ had higher verbal working memory compared to LF-SCZ (p≤0.05, Cohen's d=0.78) but the two groups did not differ in remaining domains. The cluster analysis classified schizophrenia subjects in HF-SCZ and LF-SCZ using a multidimensional assessment of community functioning. Moreover, HF-SCZ demonstrated rather preserved verbal working memory relative to LF-SCZ. The results suggest that verbal working memory may play a critical role in community functioning, and is a potential cognitive treatment target for schizophrenia subjects. Copyright © 2015 Elsevier B.V. All rights reserved.

A High Fat Diet during Adolescence in Male Rats Negatively Programs Reproductive and Metabolic Function Which Is Partially Ameliorated by Exercise

PubMed Central

Ibáñez, Carlos A.; Erthal, Rafaela P.; Ogo, Fernanda M.; Peres, Maria N. C.; Vieira, Henrique R.; Conejo, Camila; Tófolo, Laize P.; Francisco, Flávio A.; da Silva Silveira, Sandra; Malta, Ananda; Pavanello, Audrei; Martins, Isabela P.; da Silva, Paulo H. O.; Jacinto Saavedra, Lucas Paulo; Gonçalves, Gessica D.; Moreira, Veridiana M.; Alves, Vander S.; da Silva Franco, Claudinéia C.; Previate, Carina; Gomes, Rodrigo M.; de Oliveira Venci, Renan; Dias, Francielle R. S.; Armitage, James A.; Zambrano, Elena; Mathias, Paulo C. F.; Fernandes, Glaura S. A.; Palma-Rigo, Kesia

2017-01-01

An interaction between obesity, impaired glucose metabolism and sperm function in adults has been observed but it is not known whether exposure to a diet high in fat during the peri-pubertal period can have longstanding programmed effects on reproductive function and gonadal structure. This study examined metabolic and reproductive function in obese rats programmed by exposure to a high fat (HF) diet during adolescence. The effect of physical training (Ex) in ameliorating this phenotype was also assessed. Thirty-day-old male Wistar rats were fed a HF diet (35% lard w/w) for 30 days then subsequently fed a normal fat diet (NF) for a 40-day recovery period. Control animals were fed a NF diet throughout life. At 70 days of life, animals started a low frequency moderate exercise training that lasted 30 days. Control animals remained sedentary (Se). At 100 days of life, biometric, metabolic and reproductive parameters were evaluated. Animals exposed to HF diet showed greater body weight, glucose intolerance, increased fat tissue deposition, reduced VO2max and reduced energy expenditure. Consumption of the HF diet led to an increase in the number of abnormal seminiferous tubule and a reduction in seminiferous epithelium height and seminiferous tubular diameter, which was reversed by moderate exercise. Compared with the NF-Se group, a high fat diet decreased the number of seminiferous tubules in stages VII-VIII and the NF-Ex group showed an increase in stages XI-XIII. HF-Se and NF-Ex animals showed a decreased number of spermatozoa in the cauda epididymis compared with animals from the NF-Se group. Animals exposed to both treatments (HF and Ex) were similar to all the other groups, thus these alterations induced by HF or Ex alone were partially prevented. Physical training reduced fat pad deposition and restored altered reproductive parameters. HF diet consumption during the peri-pubertal period induces long-term changes on metabolism and the reproductive system, but moderate and low frequency physical training is able to recover adipose tissue deposition and reproductive system alterations induced by high fat diet. This study highlights the importance of a balanced diet and continued physical activity during adolescence, with regard to metabolic and reproductive health. PMID:29163186

A High Fat Diet during Adolescence in Male Rats Negatively Programs Reproductive and Metabolic Function Which Is Partially Ameliorated by Exercise.

PubMed

Ibáñez, Carlos A; Erthal, Rafaela P; Ogo, Fernanda M; Peres, Maria N C; Vieira, Henrique R; Conejo, Camila; Tófolo, Laize P; Francisco, Flávio A; da Silva Silveira, Sandra; Malta, Ananda; Pavanello, Audrei; Martins, Isabela P; da Silva, Paulo H O; Jacinto Saavedra, Lucas Paulo; Gonçalves, Gessica D; Moreira, Veridiana M; Alves, Vander S; da Silva Franco, Claudinéia C; Previate, Carina; Gomes, Rodrigo M; de Oliveira Venci, Renan; Dias, Francielle R S; Armitage, James A; Zambrano, Elena; Mathias, Paulo C F; Fernandes, Glaura S A; Palma-Rigo, Kesia

2017-01-01

An interaction between obesity, impaired glucose metabolism and sperm function in adults has been observed but it is not known whether exposure to a diet high in fat during the peri-pubertal period can have longstanding programmed effects on reproductive function and gonadal structure. This study examined metabolic and reproductive function in obese rats programmed by exposure to a high fat (HF) diet during adolescence. The effect of physical training (Ex) in ameliorating this phenotype was also assessed. Thirty-day-old male Wistar rats were fed a HF diet (35% lard w/w) for 30 days then subsequently fed a normal fat diet (NF) for a 40-day recovery period. Control animals were fed a NF diet throughout life. At 70 days of life, animals started a low frequency moderate exercise training that lasted 30 days. Control animals remained sedentary (Se). At 100 days of life, biometric, metabolic and reproductive parameters were evaluated. Animals exposed to HF diet showed greater body weight, glucose intolerance, increased fat tissue deposition, reduced VO 2max and reduced energy expenditure. Consumption of the HF diet led to an increase in the number of abnormal seminiferous tubule and a reduction in seminiferous epithelium height and seminiferous tubular diameter, which was reversed by moderate exercise. Compared with the NF-Se group, a high fat diet decreased the number of seminiferous tubules in stages VII-VIII and the NF-Ex group showed an increase in stages XI-XIII. HF-Se and NF-Ex animals showed a decreased number of spermatozoa in the cauda epididymis compared with animals from the NF-Se group. Animals exposed to both treatments (HF and Ex) were similar to all the other groups, thus these alterations induced by HF or Ex alone were partially prevented. Physical training reduced fat pad deposition and restored altered reproductive parameters. HF diet consumption during the peri-pubertal period induces long-term changes on metabolism and the reproductive system, but moderate and low frequency physical training is able to recover adipose tissue deposition and reproductive system alterations induced by high fat diet. This study highlights the importance of a balanced diet and continued physical activity during adolescence, with regard to metabolic and reproductive health.

Oxidation Resitant HfC-TaC Rocket Thruster for High Performance Propellants

NASA Technical Reports Server (NTRS)

Patterson, Mark

1999-01-01

The purpose of this reasearch effort was to develop high temperature, oxidation resistant thrusters which would lessen the thruster cooling requirements, resulting in increased performance and longer life for onboard propulsion systems for spacecraft. This research effort focussed on developing ceramic matrix composites (CMCs) for this application, and specifically investigated the use of HfC stabilized with TaC. This material composition can potentially operate in a stoichiometric oxygen to hydrogen ratio at a temperature of 5000 deg F (2760 deg C) in a radiatively cooled mode. Various compositions of Hafnium Carbide (HfC) and Tantalum Carbide (TaC) were deposited by chemical vapor deposition (CVD) and tested, in an attempt to identify the composition which offered the best oxidation resistance. Although it was identified that small amounts of TaC appeared to offer improved oxidation resistance over HfC alone, an optimal composition was not identified. A 251bf thruster was fabricated from a novel CMC sandwich construction with a HfC-TaC matrix, and survived two test firings, each of 5 seconds before a failure in the injector caused the run to be aborted. It was not possible to control the relative stoichiometry of the HfC and TaC composition throughout the reactor due to the large difference in the thermodynamics of the HfC and TaC formation from their respective chlorides. This also resulted in an inability to infiltrate TaC into the preform under the experimental conditions investigated. Other material compositions were fabricated and tested and two material systems; HfC-SiC functionally graded to C(sub f)/C and Re functionally graded to C(sub f)/C were selected for further testing. These functionally graded composites have use in a number of propulsion applications presently of interest to NASA and the defense industry. Their ability to withstand extremely hostile thermal environments and the light-weight and high-strength exhibited from the C(sub f)/C composite make these materials particularly suited for these applications. In the Phase III which is presently underway, Re functionally graded to C(sub f)/C is being further developed and tested for application in the thrust cells for the Linear Aerospike Engine for the X33 and RLV.

High-Entropy Metal Diborides: A New Class of High-Entropy Materials and a New Type of Ultrahigh Temperature Ceramics

NASA Astrophysics Data System (ADS)

Gild, Joshua; Zhang, Yuanyao; Harrington, Tyler; Jiang, Sicong; Hu, Tao; Quinn, Matthew C.; Mellor, William M.; Zhou, Naixie; Vecchio, Kenneth; Luo, Jian

2016-11-01

Seven equimolar, five-component, metal diborides were fabricated via high-energy ball milling and spark plasma sintering. Six of them, including (Hf0.2Zr0.2Ta0.2Nb0.2Ti0.2)B2, (Hf0.2Zr0.2Ta0.2Mo0.2Ti0.2)B2, (Hf0.2Zr0.2Mo0.2Nb0.2Ti0.2)B2, (Hf0.2Mo0.2Ta0.2Nb0.2Ti0.2)B2, (Mo0.2Zr0.2Ta0.2Nb0.2Ti0.2)B2, and (Hf0.2Zr0.2Ta0.2Cr0.2Ti0.2)B2, possess virtually one solid-solution boride phase of the hexagonal AlB2 structure. Revised Hume-Rothery size-difference factors are used to rationalize the formation of high-entropy solid solutions in these metal diborides. Greater than 92% of the theoretical densities have been generally achieved with largely uniform compositions from nanoscale to microscale. Aberration-corrected scanning transmission electron microscopy (AC STEM), with high-angle annular dark-field and annular bright-field (HAADF and ABF) imaging and nanoscale compositional mapping, has been conducted to confirm the formation of 2-D high-entropy metal layers, separated by rigid 2-D boron nets, without any detectable layered segregation along the c-axis. These materials represent a new type of ultra-high temperature ceramics (UHTCs) as well as a new class of high-entropy materials, which not only exemplify the first high-entropy non-oxide ceramics (borides) fabricated but also possess a unique non-cubic (hexagonal) and layered (quasi-2D) high-entropy crystal structure that markedly differs from all those reported in prior studies. Initial property assessments show that both the hardness and the oxidation resistance of these high-entropy metal diborides are generally higher/better than the average performances of five individual metal diborides made by identical fabrication processing.

Resveratrol improves exercise performance and skeletal muscle oxidative capacity in heart failure.

PubMed

Sung, Miranda M; Byrne, Nikole J; Robertson, Ian M; Kim, Ty T; Samokhvalov, Victor; Levasseur, Jody; Soltys, Carrie-Lynn; Fung, David; Tyreman, Neil; Denou, Emmanuel; Jones, Kelvin E; Seubert, John M; Schertzer, Jonathan D; Dyck, Jason R B

2017-04-01

We investigated whether treatment of mice with established pressure overload-induced heart failure (HF) with the naturally occurring polyphenol resveratrol could improve functional symptoms of clinical HF such as fatigue and exercise intolerance. C57Bl/6N mice were subjected to either sham or transverse aortic constriction surgery to induce HF. Three weeks postsurgery, a cohort of mice with established HF (%ejection fraction <45) was administered resveratrol (~450 mg·kg -1 ·day -1 ) or vehicle for 2 wk. Although the percent ejection fraction was similar between both groups of HF mice, those mice treated with resveratrol had increased total physical activity levels and exercise capacity. Resveratrol treatment was associated with altered gut microbiota composition, increased skeletal muscle insulin sensitivity, a switch toward greater whole body glucose utilization, and increased basal metabolic rates. Although muscle mass and strength were not different between groups, mice with HF had significant declines in basal and ADP-stimulated O 2 consumption in isolated skeletal muscle fibers compared with sham mice, which was completely normalized by resveratrol treatment. Overall, resveratrol treatment of mice with established HF enhances exercise performance, which is associated with alterations in whole body and skeletal muscle energy metabolism. Thus, our preclinical data suggest that resveratrol supplementation may effectively improve fatigue and exercise intolerance in HF patients. NEW & NOTEWORTHY Resveratrol treatment of mice with heart failure leads to enhanced exercise performance that is associated with altered gut microbiota composition, increased whole body glucose utilization, and enhanced skeletal muscle metabolism and function. Together, these preclinical data suggest that resveratrol supplementation may effectively improve fatigue and exercise intolerance in heart failure via these mechanisms. Copyright © 2017 the American Physiological Society.

Corrosion resistant surface for vanadium nitride and hafnium nitride layers as function of grain size

NASA Astrophysics Data System (ADS)

Escobar, C. A.; Caicedo, J. C.; Aperador, W.

2014-01-01

In this research it was studied vanadium nitride (VN) and hafnium nitride (HfN) film, which were deposited onto silicon (Si (100)) and AISI 4140 steel substrates via r.f. magnetron sputtering technique in Ar/N2 atmosphere with purity at 99.99% for both V and Hf metallic targets. Both films were approximately 1.2±0.1 μm thick. The crystallography structures that were evaluated via X-ray diffraction analysis (XRD) showed preferential orientations in the Bragg planes VN (200) and HfN (111). The chemical compositions for both films were characterized by EDX. Atomic Force Microscopy (AFM) was used to study the morphology; the results reveal grain sizes of 78±2 nm for VN and 58±2 nm for HfN and roughness values of 4.2±0.1 nm for VN and 1.5±0.1 nm for HfN films. The electrochemical performance in VN and HfN films deposited onto steel 4140 were studied by Tafel polarization curves and impedance spectroscopy methods (EIS) under contact with sodium chloride at 3.5 wt% solution, therefore, it was found that the corrosion rate decreased about 95% in VN and 99% for HfN films in relation to uncoated 4140 steel, thus demonstrating, the protecting effect of VN and HfN films under a corrosive environment as function of morphological characteristics (grain size). VN(grain size)=78±2.0 nm, VN(roughness)=4.2±0.1 nm, VN(corrosion rate)=40.87 μmy. HfN(grain size)=58±2.0 nm, HfN(roughness)=1.5±0.1 nm, HfN(corrosion rate)=0.205 μmy. It was possible to analyze that films with larger grain size, can be observed smaller grain boundary thus generating a higher corrosion rate, therefore, in this work it was found that the HfN layer has better corrosion resistance (low corrosion rate) in relation to VN film which presents a larger grain size, indicating that the low grain boundary in (VN films) does not restrict movement of the Cl- ion and in this way the corrosion rate increases dramatically.

Effect of Ferric Carboxymaltose on Exercise Capacity in Patients With Chronic Heart Failure and Iron Deficiency.

PubMed

van Veldhuisen, Dirk J; Ponikowski, Piotr; van der Meer, Peter; Metra, Marco; Böhm, Michael; Doletsky, Artem; Voors, Adriaan A; Macdougall, Iain C; Anker, Stefan D; Roubert, Bernard; Zakin, Lorraine; Cohen-Solal, Alain

2017-10-10

Iron deficiency is common in patients with heart failure (HF) and is associated with reduced exercise capacity and poor outcomes. Whether correction of iron deficiency with (intravenous) ferric carboxymaltose (FCM) affects peak oxygen consumption [peak VO 2 ], an objective measure of exercise intolerance in HF, has not been examined. We studied patients with systolic HF (left ventricular ejection fraction ≤45%) and mild to moderate symptoms despite optimal HF medication. Patients were randomized 1:1 to treatment with FCM for 24 weeks or standard of care. The primary end point was the change in peak VO 2 from baseline to 24 weeks. Secondary end points included the effect on hematinic and cardiac biomarkers, quality of life, and safety. For the primary analysis, patients who died had a value of 0 imputed for 24-week peak VO 2 . Additional sensitivity analyses were performed to determine the impact of imputation of missing peak VO 2 data. A total of 172 patients with HF were studied and received FCM (n=86) or standard of care (control group, n=86). At baseline, the groups were well matched; mean age was 64 years, 75% were male, mean left ventricular ejection fraction was 32%, and peak VO 2 was 13.5 mL/min/kg. FCM significantly increased serum ferritin and transferrin saturation. At 24 weeks, peak VO 2 had decreased in the control group (least square means -1.19±0.389 mL/min/kg) but was maintained on FCM (-0.16±0.387 mL/min/kg; P =0.020 between groups). In a sensitivity analysis, in which missing data were not imputed, peak VO 2 at 24 weeks decreased by -0.63±0.375 mL/min/kg in the control group and by -0.16±0.373 mL/min/kg in the FCM group; P =0.23 between groups). Patients' global assessment and functional class as assessed by the New York Heart Association improved on FCM versus standard of care. Treatment with intravenous FCM in patients with HF and iron deficiency improves iron stores. Although a favorable effect on peak VO 2 was observed on FCM, compared with standard of care in the primary analysis, this effect was highly sensitive to the imputation strategy for peak VO 2 among patients who died. Whether FCM is associated with an improved outcome in these high-risk patients needs further study. URL: http://www.clinicaltrials.gov. Unique identifier: NCT01394562. © 2017 The Authors.

Effect of Ferric Carboxymaltose on Exercise Capacity in Patients With Chronic Heart Failure and Iron Deficiency

PubMed Central

Ponikowski, Piotr; van der Meer, Peter; Metra, Marco; Böhm, Michael; Doletsky, Artem; Voors, Adriaan A.; Macdougall, Iain C.; Anker, Stefan D.; Roubert, Bernard; Zakin, Lorraine; Cohen-Solal, Alain

2017-01-01

Background: Iron deficiency is common in patients with heart failure (HF) and is associated with reduced exercise capacity and poor outcomes. Whether correction of iron deficiency with (intravenous) ferric carboxymaltose (FCM) affects peak oxygen consumption [peak VO2], an objective measure of exercise intolerance in HF, has not been examined. Methods: We studied patients with systolic HF (left ventricular ejection fraction ≤45%) and mild to moderate symptoms despite optimal HF medication. Patients were randomized 1:1 to treatment with FCM for 24 weeks or standard of care. The primary end point was the change in peak VO2 from baseline to 24 weeks. Secondary end points included the effect on hematinic and cardiac biomarkers, quality of life, and safety. For the primary analysis, patients who died had a value of 0 imputed for 24-week peak VO2. Additional sensitivity analyses were performed to determine the impact of imputation of missing peak VO2 data. Results: A total of 172 patients with HF were studied and received FCM (n=86) or standard of care (control group, n=86). At baseline, the groups were well matched; mean age was 64 years, 75% were male, mean left ventricular ejection fraction was 32%, and peak VO2 was 13.5 mL/min/kg. FCM significantly increased serum ferritin and transferrin saturation. At 24 weeks, peak VO2 had decreased in the control group (least square means −1.19±0.389 mL/min/kg) but was maintained on FCM (−0.16±0.387 mL/min/kg; P=0.020 between groups). In a sensitivity analysis, in which missing data were not imputed, peak VO2 at 24 weeks decreased by −0.63±0.375 mL/min/kg in the control group and by −0.16±0.373 mL/min/kg in the FCM group; P=0.23 between groups). Patients’ global assessment and functional class as assessed by the New York Heart Association improved on FCM versus standard of care. Conclusions: Treatment with intravenous FCM in patients with HF and iron deficiency improves iron stores. Although a favorable effect on peak VO2 was observed on FCM, compared with standard of care in the primary analysis, this effect was highly sensitive to the imputation strategy for peak VO2 among patients who died. Whether FCM is associated with an improved outcome in these high-risk patients needs further study. Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01394562. PMID:28701470

Use of Home Telemonitoring to Support Multidisciplinary Care of Heart Failure Patients in Finland: Randomized Controlled Trial

PubMed Central

Leppänen, Juha; Kaijanranta, Hannu; Kulju, Minna; Heliö, Tiina; van Gils, Mark; Lähteenmäki, Jaakko

2014-01-01

Background Heart failure (HF) patients suffer from frequent and repeated hospitalizations, causing a substantial economic burden on society. Hospitalizations can be reduced considerably by better compliance with self-care. Home telemonitoring has the potential to boost patients’ compliance with self-care, although the results are still contradictory. Objective A randomized controlled trial was conducted in order to study whether the multidisciplinary care of heart failure patients promoted with telemonitoring leads to decreased HF-related hospitalization. Methods HF patients were eligible whose left ventricular ejection fraction was lower than 35%, NYHA functional class ≥2, and who needed regular follow-up. Patients in the telemonitoring group (n=47) measured their body weight, blood pressure, and pulse and answered symptom-related questions on a weekly basis, reporting their values to the heart failure nurse using a mobile phone app. The heart failure nurse followed the status of patients weekly and if necessary contacted the patient. The primary outcome was the number of HF-related hospital days. Control patients (n=47) received multidisciplinary treatment according to standard practices. Patients’ clinical status, use of health care resources, adherence, and user experience from the patients’ and the health care professionals’ perspective were studied. Results Adherence, calculated as a proportion of weekly submitted self-measurements, was close to 90%. No difference was found in the number of HF-related hospital days (incidence rate ratio [IRR]=0.812, P=.351), which was the primary outcome. The intervention group used more health care resources: they paid an increased number of visits to the nurse (IRR=1.73, P<.001), spent more time at the nurse reception (mean difference of 48.7 minutes, P<.001), and there was a greater number of telephone contacts between the nurse and intervention patients (IRR=3.82, P<.001 for nurse-induced contacts and IRR=1.63, P=.049 for patient-induced contacts). There were no statistically significant differences in patients’ clinical health status or in their self-care behavior. The technology received excellent feedback from the patient and professional side with a high adherence rate throughout the study. Conclusions Home telemonitoring did not reduce the number of patients’ HF-related hospital days and did not improve the patients’ clinical condition. Patients in the telemonitoring group contacted the Cardiology Outpatient Clinic more frequently, and on this way increased the use of health care resources. Trial Registration Clinicaltrials.gov NCT01759368; http://clinicaltrials.gov/show/NCT01759368 (Archived by WebCite at http://www.webcitation.org/6UFxiCk8Z). PMID:25498992

The effects and possible mechanism of β2AR gene expression in cardiocytes of canines with heart failure.

PubMed

Gong, Haibin; San, Yu; Wang, Lei; Lv, Qian; Chen, Libin

2017-07-01

The objective of the present study was to observe the changes of β 2 -adrenergic receptor (β 2 AR) protein expression in a canine model of heart failure (HF), and the function of cardiocytes after transfection with Adv-β 2 AR. The canine model of chronic HF was induced by rapid right ventricular pacing and cardiocytes were isolated with collagenase II. Cardiocytes were transfected with Adv-β 2 AR to observe contractile function with a motion edge-detection system of single cells. Expression of β 2 AR protein in cardiocytes was measured by immunoblotting and the levels of intracellular cAMP were measured by ELISA. Compared with the control group (the sham group), the expression of β 2 AR protein in HF cardiocytes did not change, but the basal (1 mM Ca 2+ ) contraction amplitude percentage (1.809±0.922 vs. 1.120±0.432%, P<0.05), the maximum contraction amplitude percentage (14.855±2.377 vs. 10.784±2.675%, P<0.01) and the basal levels of intracellular cAMP (9.39±2.54 vs. 5.26±0.95 pmol/ml, n=6, P<0.05) of HF cardiocytes were significantly decreased. However, when HF cardiocytes were transfected with Adv-β 2 AR and cultured for 48 h, compared with the non-transfected group, the basal contraction amplitude percentage (0.851±0.324 vs. 1.629±0.522%, P<0.05), the maximum contraction amplitude percentage (9.260±2.208% vs. 12.205±1.437%, P<0.01) and the basal levels of intracellular cAMP (5.26±0.95 vs. 9.03±1.03 pmol/ml, n=6, P<0.05) of cardiocytes in the transfected group were significantly increased. In conclusion, the expression of β 2 AR protein in HF cardiocytes did not change, but contraction function was impaired. The moderate overexpression of β 2 AR gene in the HF cardiocytes increased the levels of intracellular cAMP and improved contraction function.

Evaluation of Quality of Life in Patients with and without Heart Failure in Primary Care.

PubMed

Jorge, Antonio José Lagoeiro; Rosa, Maria Luiza Garcia; Correia, Dayse Mary da Silva; Martins, Wolney de Andrade; Ceron, Diana Maria Martinez; Coelho, Leonardo Chaves Ferreira; Soussume, William Shinji Nobre; Kang, Hye Chung; Moscavitch, Samuel Datum; Mesquita, Evandro Tinoco

2017-09-01

Heart failure (HF) is a major public health issue with implications on health-related quality of life (HRQL). To compare HRQL, estimated by the Short-Form Health Survey (SF-36), in patients with and without HF in the community. Cross-sectional study including 633 consecutive individuals aged 45 years or older, registered in primary care. The subjects were selected from a random sample representative of the population studied. They were divided into two groups: group I, HF patients (n = 59); and group II, patients without HF (n = 574). The HF group was divided into HF with preserved ejection fraction (HFpEF - n = 35) and HF with reduced ejection fraction (HFrEF - n = 24). Patients without HF had a mean SF-36 score significantly greater than those with HF (499.8 ± 139.1 vs 445.4 ± 123.8; p = 0.008). Functional capacity - ability and difficulty to perform common activities of everyday life - was significantly worse (p < 0.0001) in patients with HF independently of sex and age. There was no difference between HFpEF and HFrEF. Patients with HF had low quality of life regardless of the syndrome presentation (HFpEF or HFrEF phenotype). Quality of life evaluation in primary care could help identify patients who would benefit from a proactive care program with more emphasis on multidisciplinary and social support. (Arq Bras Cardiol. 2017; [online].ahead print, PP.0-0).

The palliative care in heart failure trial: rationale and design.

PubMed

Mentz, Robert J; Tulsky, James A; Granger, Bradi B; Anstrom, Kevin J; Adams, Patricia A; Dodson, Gwen C; Fiuzat, Mona; Johnson, Kimberly S; Patel, Chetan B; Steinhauser, Karen E; Taylor, Donald H; O'Connor, Christopher M; Rogers, Joseph G

2014-11-01

The progressive nature of heart failure (HF) coupled with high mortality and poor quality of life mandates greater attention to palliative care as a routine component of advanced HF management. Limited evidence exists from randomized, controlled trials supporting the use of interdisciplinary palliative care in HF. PAL-HF is a prospective, controlled, unblinded, single-center study of an interdisciplinary palliative care intervention in 200 patients with advanced HF estimated to have a high likelihood of mortality or rehospitalization in the ensuing 6 months. The 6-month PAL-HF intervention focuses on physical and psychosocial symptom relief, attention to spiritual concerns, and advanced care planning. The primary end point is health-related quality of life measured by the Kansas City Cardiomyopathy Questionnaire and the Functional Assessment of Chronic Illness Therapy with Palliative Care Subscale score at 6 months. Secondary end points include changes in anxiety/depression, spiritual well-being, caregiver satisfaction, cost and resource utilization, and a composite of death, HF hospitalization, and quality of life. PAL-HF is a randomized, controlled clinical trial that will help evaluate the efficacy and cost effectiveness of palliative care in advanced HF using a patient-centered outcome as well as clinical and economic end points. Copyright © 2014 Elsevier Inc. All rights reserved.

Educational Needs for Improving Self-care in Heart Failure Patients with Diabetes

PubMed Central

Cha, Eun Seok; Clark, Patricia C.; Reilly, Carolyn Miller; Higgins, Melinda; Lobb, Maureen; Smith, Andrew L.; Dunbar, Sandra B.

2013-01-01

Purpose To explore the need for self-monitoring and self-care education in heart failure patients with diabetes (HF-DM patients) by describing cognitive and affective factors to provide guidance in developing effective self- management education. Method A cross-sectional correlation design was employed using baseline patient data from a study testing a 12 week patient and family dyad intervention to improve dietary and medication-taking self-management behaviors in HF patients. Data from 116 participants recruited from metropolitan Atlanta area were used. Demographic and co-morbidities, physical function, psychological distress, relationship with health care provider, self-efficacy (medication taking and low sodium diet), and behavioral outcomes (medications, dietary habits) were assessed. Descriptive statistics and a series of chi-square tests, t-tests or Mann Whitney tests were performed to compare HF patients with and without DM. Results HF-DM patients were older, heavier, had more co- morbidities, and took more daily medications than HF patients. High self-efficacy on medication and low sodium diet was reported in both groups with no significant difference. Although HF-DM patients took more daily medications than HF, both groups exhibited high HF medication taking behaviors. The HF-DM patients consumed significantly lower total sugar than HF patients, but clinically higher levels of sodium. Conclusions Diabetes educators need to be aware of potential conflicts of treatment regimens to manage two chronic diseases. Special and integrated diabetes self-management education programs which incorporate principles of HF self-management should be developed to improve self-management behavior in HF-DM patients. PMID:22722611

Glucose Homeostasis, Pancreatic Endocrine Function, and Outcomes in Advanced Heart Failure.

PubMed

Melenovsky, Vojtech; Benes, Jan; Franekova, Janka; Kovar, Jan; Borlaug, Barry A; Segetova, Marketa; Tura, Andrea; Pelikanova, Tereza

2017-08-07

The mechanisms and relevance of impaired glucose homeostasis in advanced heart failure (HF) are poorly understood. The study goals were to examine glucose regulation, pancreatic endocrine function, and metabolic factors related to prognosis in patients with nondiabetic advanced HF. In total, 140 advanced HF patients without known diabetes mellitus and 21 sex-, age-, and body mass index-matched controls underwent body composition assessment, oral glucose tolerance testing, and measurement of glucose-regulating hormones to model pancreatic β-cell secretory response. Compared with controls, HF patients had similar fasting glucose and insulin levels but higher levels after oral glucose tolerance testing. Insulin secretion was not impaired, but with increasing HF severity, there was a reduction in glucose, insulin, and insulin/glucagon ratio-a signature of starvation. The insulin/C-peptide ratio was decreased in HF, indicating enhanced insulin clearance, and this was correlated with lower cardiac output, hepatic insufficiency, right ventricular dysfunction, and body wasting. After a median of 449 days, 41% of patients experienced an adverse event (death, urgent transplant, or assist device). Increased glucagon and, paradoxically, low fasting plasma glucose displayed the strongest relations to outcome ( P =0.01). Patients in the lowest quartile of fasting plasma glucose (3.8-5.1 mmol·L -1 , 68-101 mg·dL -1 ) had 3-times higher event risk than in the top quartile (6.0-7.9 mmol·L -1 , 108-142 mg·dL -1 ; relative risk: 3.05 [95% confidence interval, 1.46-6.77]; P =0.002). Low fasting plasma glucose and increased glucagon are robust metabolic predictors of adverse events in advanced HF. Pancreatic insulin secretion is preserved in advanced HF, but levels decrease with increasing HF severity due to enhanced insulin clearance that is coupled with right heart failure and cardiac cachexia. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

Body mass index and mortality in acutely decompensated heart failure across the world: a global obesity paradox.

PubMed

Shah, Ravi; Gayat, Etienne; Januzzi, James L; Sato, Naoki; Cohen-Solal, Alain; diSomma, Salvatore; Fairman, Enrique; Harjola, Veli-Pekka; Ishihara, Shiro; Lassus, Johan; Maggioni, Aldo; Metra, Marco; Mueller, Christian; Mueller, Thomas; Parenica, Jiri; Pascual-Figal, Domingo; Peacock, William Frank; Spinar, Jindrich; van Kimmenade, Roland; Mebazaa, Alexandre

2014-03-04

This study sought to define the relationship between body mass index (BMI) and mortality in heart failure (HF) across the world and to identify specific groups in whom BMI may differentially mediate risk. Obesity is associated with incident HF, but it is paradoxically associated with better prognosis during chronic HF. We studied 6,142 patients with acute decompensated HF from 12 prospective observational cohorts followed-up across 4 continents. Primary outcome was all-cause mortality. Cox proportional hazards models and net reclassification index described associations of BMI with all-cause mortality. Normal-weight patients (BMI 18.5 to 25 kg/m(2)) were older with more advanced HF and lower cardiometabolic risk. Despite worldwide heterogeneity in clinical features across obesity categories, a higher BMI remained associated with decreased 30-day and 1-year mortality (11% decrease at 30 days; 9% decrease at 1 year per 5 kg/m(2); p < 0.05), after adjustment for clinical risk. The BMI obtained at index admission provided effective 1-year risk reclassification beyond current markers of clinical risk (net reclassification index 0.119, p < 0.001). Notably, the "protective" association of BMI with mortality was confined to persons with older age (>75 years; hazard ratio [HR]: 0.82; p = 0.006), decreased cardiac function (ejection fraction <50%; HR: 0.85; p < 0.001), no diabetes (HR: 0.86; p < 0.001), and de novo HF (HR: 0.89; p = 0.004). A lower BMI is associated with age, disease severity, and a higher risk of death in acute decompensated HF. The "obesity paradox" is confined to older persons, with decreased cardiac function, less cardiometabolic illness, and recent-onset HF, suggesting that aging, HF severity/chronicity, and metabolism may explain the obesity paradox. Copyright © 2014 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Left ventricular systolic dysfunction, heart failure, and the risk of stroke and systemic embolism in patients with atrial fibrillation: insights from the ARISTOTLE trial.

PubMed

McMurray, John J V; Ezekowitz, Justin A; Lewis, Basil S; Gersh, Bernard J; van Diepen, Sean; Amerena, John; Bartunek, Jozef; Commerford, Patrick; Oh, Byung-Hee; Harjola, Veli-Pekka; Al-Khatib, Sana M; Hanna, Michael; Alexander, John H; Lopes, Renato D; Wojdyla, Daniel M; Wallentin, Lars; Granger, Christopher B

2013-05-01

We examined the risk of stroke or systemic embolism (SSE) conferred by heart failure (HF) and left ventricular systolic dysfunction (LVSD) in the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation Trial (ARISTOTLE), as well as the effect of apixaban versus warfarin. The risk of a number of outcomes, including the composite of SSE or death (to take account of competing risks) and composite of SSE, major bleeding, or death (net clinical benefit) were calculated in 3 patient groups: (1) no HF/no LVSD (n=8728), (2) HF/no LVSD (n=3207), and (3) LVSD with/without symptomatic HF (n=2736). The rate of both outcomes was highest in patients with LVSD (SSE or death 8.06; SSE, major bleeding, or death 10.46 per 100 patient-years), intermediate for HF but preserved LV systolic function (5.32; 7.24), and lowest in patients without HF or LVSD (1.54; 5.27); each comparison P<0.0001. Each outcome was less frequent in patients treated with apixaban: in all ARISTOTLE patients, the apixaban/warfarin hazard ratio for SSE or death was 0.89 (95% confidence interval, 0.81-0.98; P=0.02); for SSE, major bleed, or death it was 0.85 (0.78-0.92; P<0.001). There was no heterogeneity of treatment effect across the 3 groups. Patients with LVSD (with/without HF) had a higher risk of SSE or death (but similar rate of SSE) compared with patients with HF but preserved LV systolic function; both had a greater risk than patients without either HF or LVSD. Apixaban reduced the risk of both outcomes more than warfarin in all 3 patient groups. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00412984.

Cardio-adipose tissue cross-talk: relationship between adiponectin, plasma pro brain natriuretic peptide and incident heart failure.

PubMed

Lindberg, Søren; Jensen, Jan Skov; Bjerre, Mette; Pedersen, Sune H; Frystyk, Jan; Flyvbjerg, Allan; Mogelvang, Rasmus

2014-06-01

There is increasing evidence of cross-talk between the heart, body metabolism, and adipose tissue, but the precise mechanisms are poorly understood. Natriuretic peptides (NPs) have recently emerged as the prime candidate for a mediator. In patients with heart failure (HF), infusion of NPs increases adiponectin secretion, indicating that NPs may improve adipose tissue function and in this way function as a cardio-protective agent in HF. Accordingly we investigated the interplay between plasma adiponectin, plasma proBNP, and development of HF. We prospectively followed 5574 randomly selected men and women from the community without ischaemic heart disease or HF. Plasma adiponectin and proBNP were measured at study entry. Median follow-up time was 8.5 years (interquartile range 8.0-9.1 years). During follow-up 271 participants developed symptomatic HF. Plasma adiponectin and proBNP were strongly associated (P < 0.001). Participants with increasing adiponectin had increased risk of incident HF (P < 0.001). After adjustment for confounding risk factors (including age, gender, smoking status, body mass ratio, waist-hip ratio, glucose, glycated haemoglobin, systolic and diastolic blood pressure, lipid profile, high sensitivity C-reactive protein, estimated glomerular filtration rate, and physical activity) by Cox regression analysis, adiponectin remained an independent predictor of HF: the hazard ratio (HR) per 1 standard deviation (SD) increase in adiponectin was 1.20 [95% confidence interval (CI) 1.06-1.30; P = 0.003]. However, the association vanished when plasma proBNP was included in the analysis, HR 1.08 (95% CI 0.95-1.23; P = 0.26). In conclusion, plasma adiponectin and proBNP are strongly associated. Increasing plasma adiponectin is associated with increased risk of HF. However, concomitantly elevated proBNP levels appear to explain the positive association between adiponectin and risk of HF. © 2014 The Authors. European Journal of Heart Failure © 2014 European Society of Cardiology.

Developmental conditioning of endothelium-derived hyperpolarizing factor-mediated vasorelaxation

PubMed Central

Stead, Rebecca; Musa, Moji G.; Bryant, Claire L.; Lanham, Stuart A.; Johnston, David A.; Reynolds, Richard; Torrens, Christopher; Fraser, Paul A.; Clough, Geraldine F.

2016-01-01

Objectives: The endothelium maintains vascular homeostasis through the release of endothelium-derived relaxing factors (EDRF) and endothelium-derived hyperpolarization (EDH). The balance in EDH : EDRF is disturbed in cardiovascular disease and may also be susceptible to developmental conditioning through exposure to an adverse uterine environment to predispose to later risk of hypertension and vascular disease. Methods: Developmentally conditioned changes in EDH : EDRF signalling pathways were investigated in cremaster arterioles (18–32 μm diameter) and third-order mesenteric arteries of adult male mice offspring of dams fed either a fat-rich (high fat, HF, 45% energy from fat) or control (C, 10% energy from fat) diet. After weaning, offspring either continued on high fat or were placed on control diets to give four dietary groups (C/C, HF/C, C/HF, and HF/HF) and studied at 15 weeks of age. Results: EDH via intermediate (IKCa) and small (SKca) conductance calcium-activated potassium channels contributed less than 10% to arteriolar acetylcholine-induced relaxation in in-situ conditioned HF/C offspring compared with ∼60% in C/C (P < 0.01). The conditioned reduction in EDH signalling in HF/C offspring was reversed in offspring exposed to a high-fat diet both before and after weaning (HF/HF, 55%, P < 0.01 vs. HF/C). EDH signalling was unaffected in arterioles from C/HF offspring. The changes in EDH : EDRF were associated with altered endothelial cell expression and localization of IKCa channels. Conclusion: This is the first evidence that EDH-mediated microvascular relaxation is susceptible to an adverse developmental environment through down-regulation of the IKCa signalling pathway. Conditioned offspring exposed to a ‘second hit’ (HF/HF) exhibit adaptive vascular mechanisms to preserve dilator function. PMID:26682783

Developmental conditioning of endothelium-derived hyperpolarizing factor-mediated vasorelaxation.

PubMed

Stead, Rebecca; Musa, Moji G; Bryant, Claire L; Lanham, Stuart A; Johnston, David A; Reynolds, Richard; Torrens, Christopher; Fraser, Paul A; Clough, Geraldine F

2016-03-01

The endothelium maintains vascular homeostasis through the release of endothelium-derived relaxing factors (EDRF) and endothelium-derived hyperpolarization (EDH). The balance in EDH : EDRF is disturbed in cardiovascular disease and may also be susceptible to developmental conditioning through exposure to an adverse uterine environment to predispose to later risk of hypertension and vascular disease. Developmentally conditioned changes in EDH : EDRF signalling pathways were investigated in cremaster arterioles (18-32  μm diameter) and third-order mesenteric arteries of adult male mice offspring of dams fed either a fat-rich (high fat, HF, 45% energy from fat) or control (C, 10% energy from fat) diet. After weaning, offspring either continued on high fat or were placed on control diets to give four dietary groups (C/C, HF/C, C/HF, and HF/HF) and studied at 15 weeks of age. EDH via intermediate (IKCa) and small (SKca) conductance calcium-activated potassium channels contributed less than 10% to arteriolar acetylcholine-induced relaxation in in-situ conditioned HF/C offspring compared with ∼60% in C/C (P < 0.01). The conditioned reduction in EDH signalling in HF/C offspring was reversed in offspring exposed to a high-fat diet both before and after weaning (HF/HF, 55%, P < 0.01 vs. HF/C). EDH signalling was unaffected in arterioles from C/HF offspring. The changes in EDH : EDRF were associated with altered endothelial cell expression and localization of IKCa channels. This is the first evidence that EDH-mediated microvascular relaxation is susceptible to an adverse developmental environment through down-regulation of the IKCa signalling pathway. Conditioned offspring exposed to a 'second hit' (HF/HF) exhibit adaptive vascular mechanisms to preserve dilator function.

Clinical Usefulness of a Mobile Application for the Appropriate Selection of the Antiarrhythmic Device in Heart Failure.

PubMed

Curcio, Antonio; DE Rosa, Salvatore; Sabatino, Jolanda; DE Luca, Simona; Bochicchio, Angela; Polimeni, Alberto; Santarpia, Giuseppe; Ricci, Pietrantonio; Indolfi, Ciro

2016-07-01

Appropriate selection of implantable cardioverter defibrillator (ICD) or cardiac resynchronization therapy (CRT) device can be challenging in patients with left ventricular (LV) dysfunction. In this setting, limited information exists about the role of medical applications in helping physicians to choose the most useful device. We developed a medical application that provides guidelines-based algorithms for helping doctors in decision process using the Apache Cordova application programming interface. e-CRTD App was tested in 36 consecutive patients (age 66.4 ± 8.5 years, 31 males) with diagnosis of heart failure (HF) addressed to electrophysiology laboratory for evaluation of ICD (N = 18) or CRT with defibrillator device (CRT-D; N = 18) implantation. Two separate teams evaluated each patient independently: expert electrophysiologists (Group A); cardiologists in training using the App (Group B). The outcomes of the clinical evaluation performed by Groups A and B were similar in 100% of patients in terms of classes of recommendations to device (Class I in eight cases, Class IIa in seven cases, Class III in the remaining 21). Surprisingly, the majority of indications from the general practitioners to cardiac device were inappropriate (N = 17 ICD, and N = 4 CRT-D, Class III); nevertheless, e-CRTD App helped Group B (nonexpert cardiologists) in excluding all these cases. This study describes and validates a mobile application realized to help the decision-making process in HF patients candidate to ICD/CRT-D. This application supports physicians to assess the eligibility for ICD or CRT-D according to current guidelines in patients with LV dysfunction. © 2016 Wiley Periodicals, Inc.

The Potential of Clinical Phenotyping of Heart Failure With Imaging Biomarkers for Guiding Therapies: A Focused Update.

PubMed

Sengupta, Partho P; Kramer, Christopher M; Narula, Jagat; Dilsizian, Vasken

2017-09-01

The need for noninvasive assessment of cardiac volumes and ejection fraction (EF) ushered in the use of cardiac imaging techniques in heart failure (HF) trials that investigated the roles of pharmacological and device-based therapies. However, in contrast to HF with reduced EF (HFrEF), modern HF pharmacotherapy has not improved outcomes in HF with preserved EF (HFpEF), largely attributed to patient heterogeneity and incomplete understanding of pathophysiological insights underlying the clinical presentations of HFpEF. Modern cardiac imaging methods offer insights into many sets of changes in cardiac tissue structure and function that can precisely link cause with cardiac remodeling at organ and tissue levels to clinical presentations in HF. This has inspired investigators to seek a more comprehensive understanding of HF presentations using imaging techniques. This article summarizes the available evidence regarding the role of cardiac imaging in HF. Furthermore, we discuss the value of cardiac imaging techniques in identifying HF patient subtypes who share similar causes and mechanistic pathways that can be targeted using specific HF therapies. Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

The role of micronutrients and macronutrients in patients hospitalized for heart failure.

PubMed

Trippel, Tobias D; Anker, Stefan D; von Haehling, Stephan

2013-07-01

The detrimental pathophysiology of heart failure (HF) leaves room for physiologic and metabolomic concepts that include supplementation of micronutrients and macronutrients in these patients. Hence myocardial energetics and nutrient metabolism may represent relevant treatment targets in HF. This review focuses on the role of nutritive compounds such as lipids, amino acids, antioxidants, and other trace elements in the setting of HF. Supplementation of ferric carboxymaltose improves iron status, functional capacity, and quality of life in HF patients. To close the current gap in evidence further interventional studies investigating the role of micro- and macronutrients are needed in this setting. Copyright © 2013 Elsevier Inc. All rights reserved.

Orientation Dependence of Functional Properties in Heterophase Single Crystals of the Ti36.5Ni51.0Hf12.5 and Ti48.5Ni51.5 Alloys

NASA Astrophysics Data System (ADS)

Panchenko, E. Yu.; Chumlyakov, Yu. I.; Surikov, N. Yu.; Tagiltsev, A. I.; Vetoshkina, N. G.; Osipovich, K. S.; Maier, H.; Sehitoglu, H.

2016-03-01

The features of orientation dependence of stress-induced thermoelastic B2-( R)- B19'-martensitic transformations in single crystals of the Ti48.5Ni51.5 and Ni51.0Ti36.5Hf12.5 (at.%) alloys, which contain disperse particles of the Ti3Ni4 and H-phase, respectively, are revealed along with those of their shape-memory effects (SME) and superelasticity (SE). It is experimentally demonstrated that irrespective of the crystal structure of disperse particles measuring more than 100 nm, for their volume fraction f > 16% there is a weaker orientation dependence of the reversible strain in the cases of manifestation of SME and SE. In the orientations of Class I, wherein martensitic detwinning introduces a considerable contribution into transformation strain, the values of SME |ɛ SME | and SE |ɛ SE | decrease by over a factor of two compared to the theoretical lattice strain value |ɛ tr0 | for a B2- B19'-transformation and the experimental values of reversible strain for quenched TiNi crystals. In the orientations of Class 2, wherein detwinning of the martensite is suppressed as is the case in quenched single-phase single crystals, the reversible strain is maintained close to its theoretical value |ɛ tr0 |. Micromechanical models of interaction between the martensite and the disperse particles are proposed, which account for the weaker orientation dependence of |ɛ SME | and |ɛ SE | due to suppression of detwinning of the B19'-martensite crystals by the particles and a transition from a single-variant evolution of the stress-induced martensitic transformations to a multiple-variant evolution of transformations in the cases of increased size of the particles and their larger volume fractions.

Chronic high-fat diet-induced obesity decreased survival and increased hypertrophy of rats with experimental eccentric hypertrophy from chronic aortic regurgitation.

PubMed

Dhahri, Wahiba; Drolet, Marie-Claude; Roussel, Elise; Couet, Jacques; Arsenault, Marie

2014-09-24

The composition of a diet can influence myocardial metabolism and development of left ventricular hypertrophy (LVH). The impact of a high-fat diet in chronic left ventricular volume overload (VO) causing eccentric LVH is unknown. This study examined the effects of chronic ingestion of a high-fat diet in rats with chronic VO caused by severe aortic valve regurgitation (AR) on LVH, function and on myocardial energetics and survival. Male Wistar rats were divided in four groups: Shams on control or high-fat (HF) diet (15 rats/group) and AR rats fed with the same diets (ARC (n = 56) and ARHF (n = 32)). HF diet was started one week before AR induction and the protocol was stopped 30 weeks later. As expected, AR caused significant LV dilation and hypertrophy and this was exacerbated in the ARHF group. Moreover, survival in the ARHF group was significantly decreased compared the ARC group. Although the sham animals on HF also developed significant obesity compared to those on control diet, this was not associated with heart hypertrophy. The HF diet in AR rats partially countered the expected shift in myocardial energy substrate preference usually observed in heart hypertrophy (from fatty acids towards glucose). Systolic function was decreased in AR rats but HF diet had no impact on this parameter. The response to HF diet of different fatty acid oxidation markers as well as the increase in glucose transporter-4 translocation to the plasma membrane compared to ARC was blunted in AR animals compared to those on control diet. HF diet for 30 weeks decreased survival of AR rats and worsened eccentric hypertrophy without affecting systolic function. The expected adaptation of myocardial energetics to volume-overload left ventricle hypertrophy in AR animals seemed to be impaired by the high-fat diet suggesting less metabolic flexibility.

Resistance training alters skeletal muscle structure and function in human heart failure: effects at the tissue, cellular and molecular levels

PubMed Central

Toth, Michael J; Miller, Mark S; VanBuren, Peter; Bedrin, Nicholas G; LeWinter, Martin M; Ades, Philip A; Palmer, Bradley M

2012-01-01

Reduced skeletal muscle function in heart failure (HF) patients may be partially explained by altered myofilament protein content and function. Resistance training increases muscle function, although whether these improvements are achieved by correction of myofilament deficits is not known. To address this question, we examined 10 HF patients and 14 controls prior to and following an 18 week high-intensity resistance training programme. Evaluations of whole muscle size and strength, single muscle fibre size, ultrastructure and tension and myosin–actin cross-bridge mechanics and kinetics were performed. Training improved whole muscle isometric torque in both groups, although there were no alterations in whole muscle size or single fibre cross-sectional area or isometric tension. Unexpectedly, training reduced the myofibril fractional area of muscle fibres in both groups. This structural change manifested functionally as a reduction in the number of strongly bound myosin–actin cross-bridges during Ca2+ activation. When post-training single fibre tension data were corrected for the loss of myofibril fractional area, we observed an increase in tension with resistance training. Additionally, training corrected alterations in cross-bridge kinetics (e.g. myosin attachment time) in HF patients back to levels observed in untrained controls. Collectively, our results indicate that improvements in myofilament function in sedentary elderly with and without HF may contribute to increased whole muscle function with resistance training. More broadly, these data highlight novel cellular and molecular adaptations in muscle structure and function that contribute to the resistance-trained phenotype. PMID:22199163

New developments in high field electron paramagnetic resonance with applications in structural biology

NASA Astrophysics Data System (ADS)

Bennati, Marina; Prisner, Thomas F.

2005-02-01

Recent developments in microwave technologies have led to a renaissance of electron paramagnetic resonance (EPR) due to the implementation of new spectrometers operating at frequencies >=90 GHz. EPR at high fields and high frequencies (HF-EPR) has been established up to THz (very high frequency (VHF) EPR) in continuous wave (cw) operation and up to about 300 GHz in pulsed operation. To date, its most prominent application field is structural biology. This review article first gives an overview of the theoretical basics and the technical aspects of HF-EPR methodologies, such as cw and pulsed HF-EPR, as well as electron nuclear double resonance at high fields (HF-ENDOR). In the second part, the article illustrates different application areas of HF-EPR in studies of protein structure and function. In particular, HF-EPR has delivered essential contributions to disentangling complex spectra of radical cofactors or reaction intermediates in photosynthetic reaction centres, radical enzymes (such as ribonucleotide reductase) and in metalloproteins. Furthermore, HF-EPR combined with site-directed spin labelling in membranes and soluble proteins provides new methods of investigating complex molecular dynamics and intermolecular distances.

Judicial Perceptions of Media Portrayals of Offenders with High Functioning Autistic Spectrum Disorders.

PubMed

Berryessa, Colleen M

In recent years, sensational media reporting focusing on crimes committed by those diagnosed with or thought to have High Functioning Autistic Spectrum Disorders (hfASDs) has caused societal speculation that there is a link between the disorder and violent criminality. No research exists on how and if the judiciary understands and is affected by this coverage. Therefore this study aims to examine how judges perceive and are influenced by media attention surrounding hfASDs and criminality. Semi-structured interviews were conducted with 21 California Superior Court Judges, including questions on media portrayal. Judges perceived general media portrayals of hfASDs in both positive and negative ways. However, almost all judges who had experienced media coverage surrounding hfASDs and criminality identified it as misleading and harmful to public perceptions of the disorder. These findings suggest judges are not exempt from media attention surrounding violence and hfASDs, and they recognize the potential adverse effects of this negative coverage. Although judges' report their opinions are not affected, the results demonstrate that judges are worried that the public and potentially other criminal justice actors are adversely affected and will continue to be moving forward.

Concise Review: Mending a Broken Heart: The Evolution of Biological Therapeutics.

PubMed

Chen, Caressa; Termglinchan, Vittavat; Karakikes, Ioannis

2017-05-01

Heart failure (HF), a common sequela of cardiovascular diseases, remains a staggering clinical problem, associated with high rates of morbidity and mortality worldwide. Advances in pharmacological, interventional, and operative management have improved patient care, but these interventions are insufficient to halt the progression of HF, particularly the end-stage irreversible loss of functional cardiomyocytes. Innovative therapies that could prevent HF progression and improve the function of the failing heart are urgently needed. Following successful preclinical studies, two main strategies have emerged as potential solutions: cardiac gene therapy and cardiac regeneration through stem and precursor cell transplantation. Many potential gene- and cell-based therapies have entered into clinical studies, intending to ameliorate cardiac dysfunction in patients with advanced HF. In this review, we focus on the recent advances in cell- and gene-based therapies in the context of cardiovascular disease, emphasizing the most advanced therapies. The principles and mechanisms of action of gene and cell therapies for HF are discussed along with the limitations of current approaches. Finally, we highlight the emerging technologies that hold promise to revolutionize the biological therapies for cardiovascular diseases. Stem Cells 2017;35:1131-1140. © 2017 AlphaMed Press.

Judicial Perceptions of Media Portrayals of Offenders with High Functioning Autistic Spectrum Disorders

PubMed Central

Berryessa, Colleen M.

2015-01-01

In recent years, sensational media reporting focusing on crimes committed by those diagnosed with or thought to have High Functioning Autistic Spectrum Disorders (hfASDs) has caused societal speculation that there is a link between the disorder and violent criminality. No research exists on how and if the judiciary understands and is affected by this coverage. Therefore this study aims to examine how judges perceive and are influenced by media attention surrounding hfASDs and criminality. Semi-structured interviews were conducted with 21 California Superior Court Judges, including questions on media portrayal. Judges perceived general media portrayals of hfASDs in both positive and negative ways. However, almost all judges who had experienced media coverage surrounding hfASDs and criminality identified it as misleading and harmful to public perceptions of the disorder. These findings suggest judges are not exempt from media attention surrounding violence and hfASDs, and they recognize the potential adverse effects of this negative coverage. Although judges’ report their opinions are not affected, the results demonstrate that judges are worried that the public and potentially other criminal justice actors are adversely affected and will continue to be moving forward. PMID:25722757

Impact of Psychiatric Information on Potential Jurors in Evaluating High-Functioning Autism Spectrum Disorder (hfASD)

PubMed Central

Berryessa, Colleen M.; Milner, Lauren C.; Garrison, Nanibaa' A.; Cho, Mildred K.

2015-01-01

During a trial involving an offender with a mental disorder, jurors are often required to evaluate information on the disorder and its characteristics. This evaluation relies on how jurors understand and synthesize psychiatric and other evidence on the disorder and this information's impact on the case, an offender's culpability, and the rendered verdict. The importance of this evaluation is further highlighted when jurors are faced with evaluating a disorder that may be associated with criminal actions of diagnosed offenders, such as high-functioning autism spectrum disorder (hfASD). We designed a three-part survey to assess potential jurors' attitudes concerning an offender's diagnosis with hfASD in terms of perceptions and decisions surrounding legal and moral responsibility, personal characteristics of the offender, the introduction of psychiatric and genetic information, and the condition's influence on the facts of the case. A sample of 623 jury-eligible U.S. adults completed the survey. We found the majority of participants were influenced by the information provided on hfASD. Most respondents indicated that hfASD diagnosis should generally not affect the legal responsibility of an offender, but many reported the disorder as a mitigating factor when evaluating moral responsibility and legal consequences for criminal actions. Respondents reported favorable and sympathetic perceptions of individuals with autism and associated characteristics but were unsure, even after the presentation of psychiatric information on hfASD, if these disorders should be classified as “mental illness.” Further, the majority reported their views were in some way influenced by the fact that hfASD has potential genetic origins. PMID:26843900

Short-term effects of β2-AR blocker ICI 118,551 on sarcoplasmic reticulum SERCA2a and cardiac function of rats with heart failure.

PubMed

Gong, Haibin; Li, Yanfei; Wang, Lei; Lv, Qian; Wang, Xiuli

2016-09-01

The study was conducted to examine the effects of ICI 118,551 on the systolic function of cardiac muscle cells of rats in heart failure and determine the molecular mechanism of selective β2-adrenergic receptor (β2-AR) antagonist on these cells. The chronic heart failure model for rats was prepared through abdominal aortic constriction and separate cardiac muscle cells using the collagenase digestion method. The rats were then divided into Sham, HF and HF+ICI 50 nM goups and cultivated for 48 h. β2-AR, Gi/Gs and sarcoplasmic reticulum Ca 2+ -ATPase (SERCA2a) protein expression levels in the cardiac muscle cells were evaluated by western blotting and changes in the systolic function of cardiac muscle cells based on the boundary detection system of contraction dynamics for individual cells was measured. The results showed that compared with the Sham group, the survival rate, percentage of basic contraction and maximum contraction amplitude percentage of cardiac muscle cells with heart failure decreased, Gi protein expression increased while Gs and SERCA2a protein expression decreased. Compared with the HF group, the maximum contraction amplitude percentage of cardiac muscle cells in group HF+ICI 50 nM decreased, the Gi protein expression level increased while the SERCA2a protein expression level decreased. Following the stimulation of Ca 2+ and ISO, the maximum contraction amplitude percentage of cardiac muscle cells in the HF+ICI 50 nM group was lower than that in group HF. This indicated that ICI 118,551 has negative inotropic effects on cardiac muscle cells with heart failure, which may be related to Gi protein. Systolic function of cardiac muscle cells with heart failure can therefore be reduced by increasing Gi protein expression and lowering SERCA2a protein expression.

Adipose tissue uncoupling protein 1 levels and function are increased in a mouse model of developmental obesity induced by maternal exposure to high-fat diet.

PubMed

Bytautiene Prewit, E; Porter, C; La Rosa, M; Bhattarai, N; Yin, H; Gamble, P; Kechichian, T; Sidossis, L S

2018-05-17

With brown adipose tissue (BAT) becoming a possible therapeutic target to counteract obesity, the prenatal environment could represent a critical window to modify BAT function and browning of white AT. We investigated if levels of uncoupling protein 1 (UCP1) and UCP1-mediated thermogenesis are altered in offspring exposed to prenatal obesity. Female CD-1 mice were fed a high-fat (HF) or standard-fat (SF) diet for 3 months before breeding. After weaning, all pups were placed on SF. UCP1 mRNA and protein levels were quantified using quantitative real-time PCR and Western blot analysis, respectively, in brown (BAT), subcutaneous (SAT) and visceral (VAT) adipose tissues at 6 months of age. Total and UCP1-dependent mitochondrial respiration were determined by high-resolution respirometry. A Student's t-test and Mann-Whitney test were used (significance: P<0.05). UCP1 mRNA levels were not different between the HF and SF offspring. UCP1 protein levels, total mitochondrial respiration and UCP1-dependent respiration were significantly higher in BAT from HF males (P=0.02, P=0.04, P=0.005, respectively) and females (P=0.01, P=0.04, P=0.02, respectively). In SAT, the UCP1 protein was significantly lower in HF females (P=0.03), and the UCP1-dependent thermogenesis was significantly lower from HF males (P=0.04). In VAT, UCP1 protein levels and UCP1-dependent respiration were significantly lower only in HF females (P=0.03, P=0.04, respectively). There were no differences in total respiration in SAT and VAT. Prenatal exposure to maternal obesity leads to significant increases in UCP1 levels and function in BAT in offspring with little impact on UCP1 levels and function in SAT and VAT.

Myocardial Adeno-Associated Virus Serotype 6–βARKct Gene Therapy Improves Cardiac Function and Normalizes the Neurohormonal Axis in Chronic Heart Failure

PubMed Central

Rengo, Giuseppe; Lymperopoulos, Anastasios; Zincarelli, Carmela; Donniacuo, Maria; Soltys, Stephen; Rabinowitz, Joseph E.; Koch, Walter J.

2009-01-01

Background The upregulation of G protein–coupled receptor kinase 2 in failing myocardium appears to contribute to dysfunctional β-adrenergic receptor (βAR) signaling and cardiac function. The peptide βARKct, which can inhibit the activation of G protein–coupled receptor kinase 2 and improve βAR signaling, has been shown in transgenic models and short-term gene transfer experiments to rescue heart failure (HF). This study was designed to evaluate long-term βARKct expression in HF with the use of stable myocardial gene delivery with adeno-associated virus serotype 6 (AAV6). Methods and Results In HF rats, we delivered βARKct or green fluorescent protein as a control via AAV6-mediated direct intramyocardial injection. We also treated groups with concurrent administration of the β-blocker metoprolol. We found robust and long-term transgene expression in the left ventricle at least 12 weeks after delivery. βARKct significantly improved cardiac contractility and reversed left ventricular remodeling, which was accompanied by a normalization of the neurohormonal (catecholamines and aldosterone) status of the chronic HF animals, including normalization of cardiac βAR signaling. Addition of metoprolol neither enhanced nor decreased βARKct-mediated beneficial effects, although metoprolol alone, despite not improving contractility, prevented further deterioration of the left ventricle. Conclusions Long-term cardiac AAV6-βARKct gene therapy in HF results in sustained improvement of global cardiac function and reversal of remodeling at least in part as a result of a normalization of the neurohormonal signaling axis. In addition, βARKct alone improves outcomes more than a β-blocker alone, whereas both treatments are compatible. These findings show that βARKct gene therapy can be of long-term therapeutic value in HF. PMID:19103992

Dose-Dependent Effects of the Myosin Activator Omecamtiv Mecarbil on Cross-Bridge Behavior and Force Generation in Failing Human Myocardium.

PubMed

Mamidi, Ranganath; Li, Jiayang; Gresham, Kenneth S; Verma, Sujeet; Doh, Chang Yoon; Li, Amy; Lal, Sean; Dos Remedios, Cristobal G; Stelzer, Julian E

2017-10-01

Omecamtiv mecarbil (OM) enhances systolic function in vivo by directly binding the myosin cross-bridges (XBs) in the sarcomere. However, the mechanistic details governing OM-induced modulation of XB behavior in failing human myocardium are unclear. The effects of OM on steady state and dynamic XB behavior were measured in chemically skinned myocardial preparations isolated from human donor and heart failure (HF) left ventricle. HF myocardium exhibited impaired contractile function as evidenced by reduced maximal force, magnitude of XB recruitment ( P df ), and a slowed rate of XB detachment ( k rel ) at submaximal Ca 2+ activations. Ca 2+ sensitivity of force generation (pCa 50 ) was higher in HF myocardium when compared with donor myocardium, both prior to and after OM incubations. OM incubation (0.5 and 1.0 μmol/L) enhanced force generation at submaximal Ca 2+ activations in a dose-dependent manner. Notably, OM induced a slowing in k rel with 1.0 μmol/L OM but not with 0.5 μmol/L OM in HF myocardium. Additionally, OM exerted other differential effects on XB behavior in HF myocardium as evidenced by a greater enhancement in P df and slowing in the time course of cooperative XB recruitment ( T rec ), which collectively prolonged achievement of peak force development ( T pk ), compared with donor myocardium. Our findings demonstrate that OM augments force generation but also prolongs the time course of XB transitions to force-bearing states in remodeled HF myocardium, which may extend the systolic ejection time in vivo. Optimal OM dosing is critical for eliciting enhanced systolic function without excessive prolongation of systolic ejection time, which may compromise diastolic filling. © 2017 American Heart Association, Inc.

Autonomic regulation therapy to enhance myocardial function in heart failure patients: the ANTHEM‐HFpEF study

PubMed Central

DiCarlo, Lorenzo A.; Libbus, Imad; Kumar, H. Uday; Mittal, Sanjay; Premchand, Rajendra K.; Amurthur, Badri; KenKnight, Bruce H.; Ardell, Jeffrey L.

2017-01-01

Abstract Background Approximately half of the patients presenting with new‐onset heart failure (HF) have HF with preserved left ventricular ejection fraction (HFpEF) and HF with mid‐range left ventricular ejection fraction (HFmrEF). These patients have neurohormonal activation like that of HF with reduced ejection fraction; however, beta‐blockers and angiotensin‐converting enzyme inhibitors have not been shown to improve their outcomes, and current treatment for these patients is symptom based and empiric. Sympathoinhibition using parasympathetic stimulation has been shown to improve central and peripheral aspects of the cardiac nervous system, reflex control, induce myocyte cardioprotection, and can lead to regression of left ventricular hypertrophy. Beneficial effects of autonomic regulation therapy (ART) using vagus nerve stimulation (VNS) have also been observed in several animal models of HFpEF, suggesting a potential role for ART in patients with this disease. Methods The Autonomic Neural Regulation Therapy to Enhance Myocardial Function in Patients with Heart Failure and Preserved Ejection Fraction (ANTHEM‐HFpEF) study is designed to evaluate the feasibility, tolerability, and safety of ART using right cervical VNS in patients with chronic, stable HFpEF and HFmrEF. Patients with symptomatic HF and HFpEF or HFmrEF fulfilling the enrolment criteria will receive chronic ART with a subcutaneous VNS system attached to the right cervical vagus nerve. Safety parameters will be continuously monitored, and cardiac function and HF symptoms will be assessed every 3 months during a post‐titration follow‐up period of at least 12 months. Conclusions The ANTHEM‐HFpEF study is likely to provide valuable information intended to expand our understanding of the potential role of ART in patients with chronic symptomatic HFpEF and HFmrEF. PMID:29283224

Induction of MHC Class I Expression on Immature Thymocytes in HIV-1-Infected SCID-hu Thy/Liv Mice: Evidence of Indirect Mechanisms1

PubMed Central

Kovalev, Grigoriy; Duus, Karen; Wang, Liping; Lee, Robert; Bonyhadi, Mark; Ho, David; McCune, Joseph M.; Kaneshima, Hideto; Su, Lishan

2015-01-01

The SCID-hu Thy/Liv mouse and human fetal thymic organ culture (HF-TOC) models have been used to explore the pathophysiologic mechanisms of HIV-1 infection in the thymus. We report here that HIV-1 infection of the SCID-hu Thy/Liv mouse leads to the induction of MHC class I (MHCI) expression on CD4+CD8+ (DP) thymocytes, which normally express low levels of MHCI. Induction of MHCI on DP thymocytes in HIV-1-infected Thy/Liv organs precedes their depletion and correlates with the pathogenic activity of the HIV-1 isolates. Both MHCI protein and mRNA are induced in thymocytes from HIV-1-infected Thy/Liv organs, indicating induction of MHCI gene expression. Indirect mechanisms are involved, because only a fraction (<10%) of the DP thymocytes were directly infected by HIV-1, although the majority of DP thymocytes are induced to express high levels of MHCI. We further demonstrate that IL-10 is induced in HIV-1-infected thymus organs. Similar HIV-1-mediated induction of MHCI expression was observed in HF-TOC assays. Exogenous IL-10 in HF-TOC induces MHCI expression on DP thymocytes. Therefore, HIV-1 infection of the thymus organ leads to induction of MHCI expression on immature thymocytes via indirect mechanisms involving IL-10. Overexpression of MHCI on DP thymocytes can interfere with thymocyte maturation and may contribute to HIV-1-induced thymocyte depletion. PMID:10358212

PARADIGM - HF: The Rise of the Arnis.

PubMed

Guha, Kaushik; Varkey, Sneha; Sharma, Rakesh

2016-01-01

Heart failure remains a widespread commonly encountered clinical condition. It is responsible for increased healthcare expenditure, driven by frequent and often prolonged hospital admissions associated with an increased mortality. A clinically useful classification of the syndrome is, patients with left ventricular systolic impairment (Heart Failure and reduced ejection fraction, HFREF) and patients with preserved left ventricular systolic function (HFPEF). The pharmacological treatment for patients with HFREF has evolved over the last twenty five years, focusing on modulation of the neurohormonal activation which represents a hallmark of this condition. This has led to the development of a stepwise treatment algorithm predominately based on inhibition of the renin angiotensin aldosterone pathway and counteracting sympathetic over-activation. In particular since the early trials in chronic heart failure (CHF) demonstrated a significant mortality benefit with ACE-inhibitors, subsequent studies have been conducted in conjunction with these drugs. The rationale being that it would be unethical to trial any new agent without the concomitant use of ACE-inhibitors. The recent publication of the PARADIGM -HF study has challenged this convention by trialling a novel pharmacological agent against an ACE-inhibitor in a landmark trial. The review sets out the current pharmacological treatment for patients with heart failure and discusses the recent findings with this novel class of medication.

"We are all there for the same purpose": Support for an integrated community exercise program for older adults with HF and COPD.

PubMed

Desveaux, Laura; Harrison, Samantha; Lee, Annemarie; Mathur, Sunita; Goldstein, Roger; Brooks, Dina

Despite well-established improvements following rehabilitation, functional gains often diminish following discharge. To explore the attitudes of older adults with HF and COPD, who have completed rehabilitation, toward community-based exercise maintenance. Semi-structured interviews were conducted with 11 individuals with HF or COPD. Deductive thematic analysis uncovered three themes: 1) transitioning to community exercise is challenging, highlighting participants' struggle with unstructured maintenance and a lack of appropriate programs; 2) a structured, group-based program tailored to functional ability facilitates adherence, describing participants views on the importance of routine, and accountability; and 3) "We are all there for the same purpose" - participant support for integrated exercise, including the benefit of multiple perspectives and sustainability. A motivating program leader and access to appropriate facilities are key features to support adherence to prescribed activity. Tailored programs can be delivered consecutively to older adults with HF and COPD. Copyright © 2017 Elsevier Inc. All rights reserved.

Accumulation of 5-oxoproline in myocardial dysfunction and the protective effects of OPLAH.

PubMed

van der Pol, Atze; Gil, Andres; Silljé, Herman H W; Tromp, Jasper; Ovchinnikova, Ekaterina S; Vreeswijk-Baudoin, Inge; Hoes, Martijn; Domian, Ibrahim J; van de Sluis, Bart; van Deursen, Jan M; Voors, Adriaan A; van Veldhuisen, Dirk J; van Gilst, Wiek H; Berezikov, Eugene; van der Harst, Pim; de Boer, Rudolf A; Bischoff, Rainer; van der Meer, Peter

2017-11-08

In response to heart failure (HF), the heart reacts by repressing adult genes and expressing fetal genes, thereby returning to a more fetal-like gene profile. To identify genes involved in this process, we carried out transcriptional analysis on murine hearts at different stages of development and on hearts from adult mice with HF. Our screen identified Oplah , encoding for 5-oxoprolinase, a member of the γ-glutamyl cycle that functions by scavenging 5-oxoproline. OPLAH depletion occurred as a result of cardiac injury, leading to elevated 5-oxoproline and oxidative stress, whereas OPLAH overexpression improved cardiac function after ischemic injury. In HF patients, we observed elevated plasma 5-oxoproline, which was associated with a worse clinical outcome. Understanding and modulating fetal-like genes in the failing heart may lead to potential diagnostic, prognostic, and therapeutic options in HF. Copyright © 2017 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

Renal dysfunction in patients with heart failure with preserved versus reduced ejection fraction: impact of the new Chronic Kidney Disease-Epidemiology Collaboration Group formula.

PubMed

McAlister, Finlay A; Ezekowitz, Justin; Tarantini, Luigi; Squire, Iain; Komajda, Michel; Bayes-Genis, Antoni; Gotsman, Israel; Whalley, Gillian; Earle, Nikki; Poppe, Katrina K; Doughty, Robert N

2012-05-01

Prior studies in heart failure (HF) have used the Modification of Diet in Renal Disease (MDRD) equation to calculate estimated glomerular filtration rate (eGFR). The Chronic Kidney Disease-Epidemiology Collaboration Group (CKD-EPI) equation provides a more-accurate eGFR than the MDRD when compared against the radionuclide gold standard. The prevalence and prognostic import of renal dysfunction in HF if the CKD-EPI equation is used rather than the MDRD is uncertain. We used individual patient data from 25 prospective studies to stratify patients with HF by eGFR using the CKD-EPI and the MDRD equations and examined survival across eGFR strata. In 20 754 patients (15 962 with HF with reduced ejection fraction [HF-REF] and 4792 with HF with preserved ejection fraction [HF-PEF]; mean age, 68 years; deaths per 1000 patient-years, 151; 95% CI, 146-155), 10 589 (51%) and 11 422 (55%) had an eGFR <60 mL/min using the MDRD and CKD-EPI equations, respectively. Use of the CKD-EPI equation resulted in 3760 (18%) patients being reclassified into different eGFR risk strata; 3089 (82%) were placed in a lower eGFR category and exhibited higher all-cause mortality rates (net reclassification improvement with CKD-EPI, 3.7%; 95% CI, 1.5%-5.9%). Reduced eGFR was a stronger predictor of all-cause mortality in HF-REF than in HF-PEF. Use of the CKD-EPI rather than the MDRD equation to calculate eGFR leads to higher estimates of renal dysfunction in HF and a more-accurate categorization of mortality risk. Renal function is more closely related to outcomes in HF-REF than in HF-PEF.

Parallel evolution of circulating FABP4 and NT-proBNP in heart failure patients

PubMed Central

2013-01-01

Background Circulating adipocyte fatty acid-binding protein (FABP4) levels are considered to be a link between obesity, insulin resistance, diabetes, and cardiovascular (CV) diseases. In vitro, FABP4 has exhibited cardiodepressant activity by suppressing cardiomyocyte contraction. We have explored the relationship between FABP4 and the N-terminal fragment of pro-B-type natriuretic peptide (NT-proBNP) as a clinical parameter of heart failure (HF). Methods We included 179 stable HF patients who were referred to a specialized HF unit, 108 of whom were prospectively followed for up to 6 months. A group of 163 non-HF patients attending a CV risk unit was used as the non-HF control group for the FABP4 comparisons. Results In the HF patients, FABP4 and NT-proBNP were assayed, along with a clinical and functional assessment of the heart at baseline and after 6 months of specialized monitoring. The FABP4 levels were higher in the patients with HF than in the non-HF high CV risk control group (p<0.001). The FABP4 levels were associated with the NT-proBNP levels in patients with HF (r=0.601, p<0.001), and this association was stronger in the diabetic patients. FABP4 was also associated with heart rate and the results of the 6-minute walk test. After the follow-up period, FABP4 decreased in parallel to NT-proBNP and to the clinical parameters of HF. Conclusions FABP4 is associated with the clinical manifestations and biomarkers of HF. It exhibits a parallel evolution with the circulating levels of NT-proBNP in HF patients. PMID:23642261

Parallel evolution of circulating FABP4 and NT-proBNP in heart failure patients.

PubMed

Cabré, Anna; Valdovinos, Pilar; Lázaro, Iolanda; Bonet, Gil; Bardají, Alfredo; Masana, Lluís

2013-05-04

Circulating adipocyte fatty acid-binding protein (FABP4) levels are considered to be a link between obesity, insulin resistance, diabetes, and cardiovascular (CV) diseases. In vitro, FABP4 has exhibited cardiodepressant activity by suppressing cardiomyocyte contraction. We have explored the relationship between FABP4 and the N-terminal fragment of pro-B-type natriuretic peptide (NT-proBNP) as a clinical parameter of heart failure (HF). We included 179 stable HF patients who were referred to a specialized HF unit, 108 of whom were prospectively followed for up to 6 months. A group of 163 non-HF patients attending a CV risk unit was used as the non-HF control group for the FABP4 comparisons. In the HF patients, FABP4 and NT-proBNP were assayed, along with a clinical and functional assessment of the heart at baseline and after 6 months of specialized monitoring. The FABP4 levels were higher in the patients with HF than in the non-HF high CV risk control group (p<0.001). The FABP4 levels were associated with the NT-proBNP levels in patients with HF (r=0.601, p<0.001), and this association was stronger in the diabetic patients. FABP4 was also associated with heart rate and the results of the 6-minute walk test. After the follow-up period, FABP4 decreased in parallel to NT-proBNP and to the clinical parameters of HF. FABP4 is associated with the clinical manifestations and biomarkers of HF. It exhibits a parallel evolution with the circulating levels of NT-proBNP in HF patients.

Renal handling of galectin-3 in the general population, chronic heart failure, and hemodialysis.

PubMed

Meijers, Wouter C; van der Velde, A Rogier; Ruifrok, Willem P; Schroten, Nicolas F; Dokter, Martin M; Damman, Kevin; Assa, Solmaz; Franssen, Casper F; Gansevoort, Ron T; van Gilst, Wiek H; Silljé, Herman H; de Boer, Rudolf A

2014-09-18

Galectin-3 is a biomarker for prognostication and risk stratification of patients with heart failure (HF). It has been suggested that renal function strongly relates to galectin-3 levels. We aimed to describe galectin-3 renal handling in HF. In Sprague-Dawley rats, we infused galectin-3 and studied distribution and renal clearance. Furthermore, galectin-3 was measured in urine and plasma of healthy controls, HF patients and hemodialysis patients. To mimic the human situation, we measured galectin-3 before and after the artificial kidney. Infusion in rats resulted in a clear increase in plasma and urine galectin-3. Plasma galectin-3 in HF patients (n=101; mean age 64 years; 93% male) was significantly higher compared to control subjects (n=20; mean age 58 years; 75% male) (16.6 ng/mL versus 9.7 ng/mL, P<0.001), while urinary galectin-3 in HF patients was comparable (28.1 ng/mL versus 35.1 ng/mL, P=0.830). The calculated galectin-3 excretion rate was lower in HF patient (2.3 mL/min [1.5 to 3.4] versus 3.9 mL/min [2.3 to 6.4] in control subjects; P=0.005). This corresponded with a significantly lower fractional excretion of galectin-3 in HF patients (2.4% [1.7 to 3.7] versus 3.0% [1.9 to 5.5]; P=0.018). These differences, however, were no longer significant after correction for age, gender, diabetes, and smoking. HF patients who received diuretics (49%) showed significantly higher aldosterone and galectin-3 levels. Hemodialysis patients (n=105; mean age 63 years; 65% male), without urinary galectin-3 excretion, had strongly increased median plasma galectin-3 levels (70.6 ng/mL). In this small cross-sectional study, we report that urine levels of galectin-3 are not increased in HF patients, despite substantially increased plasma galectin-3 levels. The impaired renal handling of galectin-3 in patients with HF may explain the described relation between renal function and galectin-3 and may account for the elevated plasma galectin-3 in HF. © 2014 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

Detection and Characterization of Traveling Ionospheric Disturbances (TIDs) with GPS and HF sensors

NASA Astrophysics Data System (ADS)

Groves, K. M.; Paznukhov, V.; Bullett, T. W.; Mackenzie, E.

2014-12-01

Recently there has been increasing interest and awareness in the coupling between the neutral atmosphere and the ionosphere and specifically in processes that cause wave-like non-stationary perturbations in the bottom-side of the F-region. A class of these perturbations having periods greater than about five minutes and wavelengths greater than a kilometer or so are believed to occur routinely and propagate throughout the ionosphere; they are known as traveling ionospheric disturbances (TIDs). In this study we investigate ground-based techniques for detecting and characterizing TIDs with periods ranging from 30-90 minutes and wavelengths of 10s of km or more. These waves are believed to affect the Doppler and propagation angles of high frequency (HF) radio waves refracting through the affected regions. Wave-like perturbations are also commonly observed in GPS total electron content (TEC) data. In the current study we monitor a number of different commercial HF broadcast transmitters from a station in Wallops Island, VA and collect GPS TEC data from numerous stations along the path between the HF receiver at Wallops and specific HF transmitters. The objective is to understand the relationship between TID signatures on HF and GPS sensors and to possibly characterize TIDs using such observations, including propagation velocity, amplitude, wavelength and potentially source. Given that GPS TEC data are now relatively abundant around the globe, establishing a reliable technique for quantifying TIDs with these measurements would yield an important new technique towards developing a global TID monitoring capability that could support ionosphere-thermosphere coupling science as well as potential monitoring capabilities for natural disasters (e.g., earthquakes, tsunamis, volcanic eruptions) with significant TID signatures.

Risk stratification for death and all-cause hospitalization in heart failure clinic outpatients.

PubMed

Hummel, Scott L; Ghalib, Hussam H; Ratz, David; Koelling, Todd M

2013-11-01

Most heart failure (HF) risk stratification models were developed for inpatient use, and available outpatient models use a complex set of variables. We hypothesized that routinely collected clinical data could predict the 6-month risk of death and all-cause medical hospitalization in HF clinic outpatients. Using a quality improvement database and multivariable Cox modeling, we derived the Heart Failure Patient Severity Index (HFPSI) in the University of Michigan HF clinic (UM cohort, n = 1,536; 314 reached primary outcome). We externally validated the HFPSI in the Ann Arbor Veterans' Affairs HF clinic (VA cohort, n = 445; 106 outcomes) and explored "real-time" HFPSI use (VA-RT cohort, n = 486; 141 outcomes) by tracking VA patients for 6 months from their most recently calculated HFPSI, rather than using an arbitrary start date for the cohort. The HFPSI model included blood urea nitrogen, B-type natriuretic peptide, New York Heart Association class, diabetes status, history of atrial fibrillation/flutter, and all-cause hospitalization within the prior 1 and 2 to 6 months. The concordance c statistics in the UM/VA/VA-RT cohorts were 0.71/0.68/0.74. Kaplan-Meier curves and log-rank testing demonstrated excellent risk stratification, particularly between a large, low-risk group (40% of patients, 6-month event rates in the UM/VA/VA-RT cohorts 8%/12%/12%) and a small, high-risk group (10% of patients, 6-month event rates in the UM/VA/VA-RT cohorts 57%/58%/79%). The HFPSI uses readily available data to predict the 6-month risk of death and/or all-cause medical hospitalization in HF clinic outpatients and could potentially help allocate specialized HF resources within health systems. © 2013.

Sacubitril/valsartan: An important piece in the therapeutic puzzle of heart failure.

PubMed

Marques da Silva, Pedro; Aguiar, Carlos

2017-09-01

Sacubitril/valsartan (LCZ696), a supramolecular sodium salt complex of the neprilysin inhibitor prodrug sacubitril and the angiotensin receptor blocker (ARB) valsartan, was recently approved in the EU and the USA for the treatment of chronic heart failure (HF) with reduced ejection fraction (HFrEF) (NYHA class II-IV). Inhibition of chronically activated neurohormonal pathways (the renin-angiotensin-aldosterone system [RAAS] and sympathetic nervous system [SNS]) is central to the treatment of chronic HFrEF. Furthermore, enhancement of the natriuretic peptide (NP) system, with favorable cardiovascular (CV) and renal effects in HF, is a desirable therapeutic goal to complement RAAS and SNS blockade. Sacubitril/valsartan represents a novel pharmacological approach that acts by enhancing the NP system via inhibition of neprilysin (an enzyme that degrades NPs) and by suppressing the RAAS via AT1 receptor blockade, thereby producing more effective neurohormonal modulation than can be achieved with RAAS inhibition alone. In the large, randomized, double-blind PARADIGM-HF trial, replacement of an angiotensin-converting enzyme inhibitor (ACEI) (enalapril) with sacubitril/valsartan resulted in a significant improvement in morbidity and mortality in patients with HFrEF. Sacubitril/valsartan was superior to enalapril in reducing the risk of CV death or HF hospitalization (composite primary endpoint) and all-cause death, and in limiting progression of HF. Sacubitril/valsartan was generally well tolerated, with a comparable safety profile to enalapril; symptomatic hypotension was more common with sacubitril/valsartan, whereas renal dysfunction, hyperkalemia and cough were less common compared with enalapril. In summary, sacubitril/valsartan is a superior alternative to ACEIs/ARBs in the treatment of HFrEF, a recommendation that is reflected in many HF guidelines. Copyright © 2017 Sociedade Portuguesa de Cardiologia. Publicado por Elsevier España, S.L.U. All rights reserved.

Depression as an independent prognostic factor for all-cause mortality after a hospital admission for worsening heart failure.

PubMed

Sokoreli, I; de Vries, J J G; Riistama, J M; Pauws, S C; Steyerberg, E W; Tesanovic, A; Geleijnse, G; Goode, K M; Crundall-Goode, A; Kazmi, S; Cleland, J G; Clark, A L

2016-10-01

Depression is associated with increased mortality amongst patients with chronic heart failure (HF). Whether depression is an independent predictor of outcome in patients admitted for worsening of HF is unclear. OPERA-HF is an observational study enrolling patients hospitalized with worsening HF. Depression was assessed by the Hospital Anxiety and Depression Scale (HADS-D) questionnaire. Comorbidity was assessed by the Charlson Comorbidity Index (CCI). Kaplan-Meier and Cox regression analyses were used to estimate the association between depression and all-cause mortality. Of 242 patients who completed the HADS-D questionnaire, 153, 54 and 35 patients had no (score 0-7), mild (score 8-10) or moderate-to-severe (score 11-21) depression, respectively. During follow-up, 35 patients died, with a median time follow-up of 360days amongst survivors (interquartile range, IQR 217-574days). In univariable analysis, moderate-to-severe depression was associated with an increased risk of death (HR: 4.9; 95% CI: 2.3 to 10.2; P<0.001) compared to no depression. Moderate-to-severe depression also predicted all-cause mortality after controlling for age, CCI score, NYHA class IV, NT-proBNP and treatment with mineralocorticoid receptor antagonist, beta-blocker and diuretics (HR: 3.0; 95% CI: 1.3 to 7.0; P<0.05). Depression is strongly associated with an adverse outcome in the year following discharge after an admission to hospital for worsening HF. The association is only partly explained by the severity of HF or comorbidity. Further research is required to demonstrate whether recognition and treatment of depression improves patient outcomes. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Reduced long-term overall mortality in heart failure patients with prolonged QRS treated with CRT combined with ICD vs. heart failure patients with narrow QRS treated with ICD only.

PubMed

Palmisano, Pietro; Accogli, Michele; Pisanò, Ennio Carmine Luigi; Zaccaria, Maria; De Blasi, Sergio; Ponzetta, Maria Antonietta; Valsecchi, Sergio; Milanese, Giovanni; Lauretti, Maurelio; Magliari, Francesco

2016-09-01

It is not known whether heart failure (HF) patients with prolonged QRS who undergo cardiac resynchronization therapy combined with a defibrillator (CRT-D) have a prognostic advantage over HF patients with narrow QRS (therefore without indication for CRT) treated with an implantable cardioverter defibrillator (ICD) only. The aim of this study was to compare the long-term mortality of a group of HF patients with prolonged QRS receiving CRT-D with that of a similar group of patients with narrow QRS receiving ICD only. A total of 312 patients (mean age 66 ± 13 years; 84% male, mean left ventricular ejection fraction 25 ± 4%, mean New York Heart Association class 2.6 ± 0.5) were included in the analysis. Of these, 138 with a QRS complex duration ≥120 ms received a CRT-D. During follow-up, the time and cause of death were assessed. During a median follow-up of 46 months, CRT-D patients showed significantly lower overall mortality (P = 0.038). Compared with patients receiving ICD only, CRT-D patients showed lower HF mortality (P = 0.003). Coronary mortality, non-cardiac mortality, and sudden mortality were similar in both groups (all P > 0.05). A positive response to CRT was an independent predictor of reduced mortality on multivariate analysis (hazard ratio: 0.27; P = 0.047). In HF patients treated with ICD, the subgroup of patients with prolonged QRS who receive CRT-D displays better long-term survival than narrow QRS ICD recipients, owing to their reduced HF mortality. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.

A randomized trial of heart failure disease management in skilled nursing facilities: design and rationale.

PubMed

Boxer, Rebecca S; Dolansky, Mary A; Bodnar, Christine A; Singer, Mendel E; Albert, Jeffery M; Gravenstein, Stefan

2013-09-01

Heart failure (HF) disease management can improve health outcomes for older community dwelling patients with heart failure. HF disease management has not been studied in skilled nursing facilities, a major site of transitional care for older adults. The objective of this trial is to investigate if a HF- disease management program (HF-DMP) in skilled nursing facilities (SNF)s will decrease all-cause rehospitalizations for the first 60 days post-SNF admission. The trial is a randomized cluster trial to be conducted in 12 for-profit SNF in the greater Cleveland area. The study population is inclusive of patients with HF regardless of ejection fraction but excludes those patients on dialysis and with a life expectancy of 6 months or less. The HF-DMP includes 7 elements considered standard of care for patients with HF documentation of left ventricular function, tracking of weight and symptoms, medication titration, discharge instructions, 7-day follow-up appointment post-SNF discharge, and patient education. The HF-DMP is conducted by a research nurse tasked with adhering to each element of the program and regularly audited to maintain fidelity of the program. Additional outcomes include health status, self-care management, and discharge destination. The SNF-Connect Trial is the first trial of its kind to assess if a HF-DMP will improve outcomes for patients in SNFs. This trial will provide evidence on the effectiveness of HF-DMP to improve outcomes for older frail HF patients undergoing postacute rehabilitation. Copyright © 2013 American Medical Directors Association, Inc. Published by Elsevier Inc. All rights reserved.

First-principles evaluation of electronic and optical properties of (Mo, C) codoped BaHfO3 for applications in photocatalysis

NASA Astrophysics Data System (ADS)

Akhtar, Shaheen; Alay-e-Abbas, Syed Muhammad; Abbas, Syed Muhammad Ghulam; Arshad, Muhammad Imran; Batool, Javaria; Amin, Nasir

2018-04-01

In this paper, we report first-principles spin-polarized density functional theory calculations for exploring the effect of aliovalent Mo and C dopants on the electronic properties and photocatalysis potential of doped modifications of wide-bandgap cubic perovskite oxide BaHfO3 for water splitting. The structural and thermodynamic properties are computed by using the generalized gradient approximation, whereas the modified Becke-Johnson local density approximation is used to calculate the electronic structures of pristine, cation (Mo), and anion (C) monodoped and cation-anion (Mo, C) codoped BaHfO3. The spin-polarized calculations reveal that substitutional dopants CO and MoHf in the BaHfO3 lattice are thermodynamically stable. The incorporation of C in the O site reduces the bandgap of BaHfO3 and acts as a double-acceptor system, whereas a metallic character is obtained when Mo is doped into the Hf site giving rise to a double-donor system. We show that the acceptor and donor states of the C- and Mo-monodoped BaHfO3 can be passivated by (Mo, C) codoping at nearest-neighbor Hf and O sites of the BaHfO3 lattice, respectively. Analysis of the calculated electronic structure and optical absorption of (Mo, C) codoped BaHfO3 with reference to the H2O oxidation and reduction potentials reveals that this system is a suitable candidate for efficient splitting of water through photocatalysis in the visible region of the electromagnetic spectrum.

Pregnancy in women with hypertrophic cardiomyopathy: data from the European Society of Cardiology initiated Registry of Pregnancy and Cardiac disease (ROPAC).

PubMed

Goland, S; van Hagen, I M; Elbaz-Greener, G; Elkayam, U; Shotan, A; Merz, W M; Enar, S C; Gaisin, I R; Pieper, P G; Johnson, M R; Hall, R; Blatt, A; Roos-Hesselink, J W

2017-09-14

We report the maternal and foetal outcomes at birth and after 6 months in a cohort of pregnant women with hypertrophic cardiomyopathy (HCM). Although most women with HCM tolerate pregnancy well, there is an increased risk of obstetric and cardiovascular complications. All pregnant women with HCM entered into the prospective worldwide Registry of Pregnancy and Cardiac disease (ROPAC) were included in this analysis. The primary endpoint was a major adverse cardiovascular event (MACE), which included death, heart failure (HF), thrombo-embolic event, and arrhythmia. Baseline and outcome data were analysed and compared for patients with MACE vs. without MACE and for patients with obstructive HCM vs. non-obstructive HCM. Sixty pregnant women (mean age 30.4 ± 6.0 years) with HCM (41.7% obstructive) were included. No maternal mortality occurred in this cohort. In 14 (23%) patients at least one MACE occurred: 9 (15.0%) HF and 7 (12%) an arrhythmia (6 ventricular and 1 atrial fibrillation). MACE occurred most commonly during the 3rd trimester and postpartum period. In total, 3 (5.0%) women experienced foetal loss. Women with MACE had a higher rate of emergency Caesarean delivery for cardiac reasons (21.4% vs. 0%, P = 0.01). No significant differences in pregnancy outcome were found between women with obstructive and non-obstructive HCM. NYHA functional class of ≥II and signs of HF before pregnancy, were associated with MACE. Although most women with HCM tolerated pregnancy well, cardiovascular complications were not uncommon and predicted by pre-pregnancy status facilitating pre-pregnancy counselling and targeted antenatal care. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2017. For permissions, please email: journals.permissions@oup.com.

Taurine supplementation has anti-atherogenic and anti-inflammatory effects before and after incremental exercise in heart failure.

PubMed

Ahmadian, Mehdi; Roshan, Valiollah Dabidi; Aslani, Elaheh; Stannard, Stephen R

2017-07-01

The purpose of this study was to examine the anti-atherogenic and anti-inflammatory effect of supplemental taurine prior to and following incremental exercise in patients with heart failure (HF). Patients with HF and left ventricle ejection fraction less than 50%, and placed in functional class II or III according to the New York Heart Association classification, were randomly assigned to two groups: (1) taurine supplementation; or (2) placebo. The taurine group received oral taurine (500 mg) 3 times a day for 2 weeks, and performed exercise before and after the supplementation period. The placebo group followed the same protocol, but with a starch supplement (500 mg) rather than taurine. The incremental multilevel treadmill test was done using a modified Bruce protocol. Our results indicate that inflammatory indices [C-reactive protein (CRP), platelets] decreased in the taurine group in pre-exercise, post-supplementation and post-exercise, post-supplementation as compared with pre-exercise, pre-supplementation ( p < 0.05) whereas these indices increased in pre-exercise, post-supplementation and post-exercise, post-supplementation as compared with pre-exercise, pre-supplementation in the placebo group ( p < 0.05). Our results also show that atherogenic indices [Castelli's Risk Index-I (CRI-I), Castelli's Risk Index-II (CRI-II) and Atherogenic Coefficient (AC)] decreased in the taurine group in pre-exercise, post-supplementation and post-exercise, post-supplementation as compared with pre-exercise, pre-supplementation ( p < 0.05). No such changes were noted in the placebo group ( p > 0.05). our results suggest that 2 weeks of oral taurine supplementation increases the taurine levels and has anti-atherogenic and anti-inflammatory effects prior to and following incremental exercise in HF patients.

Relation of Natriuretic Peptide Concentrations to Central Sleep Apnea in Patients With Heart Failure

PubMed Central

Calvin, Andrew D.; Somers, Virend K.; van der Walt, Christelle; Scott, Christopher G.

2011-01-01

Background: Central sleep apnea (CSA) is frequent among patients with heart failure (HF) and associated with increased morbidity and mortality. Elevated cardiac filling pressures promote CSA and atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) secretion. We hypothesized that circulating natriuretic peptide concentrations predict CSA. Methods: Consecutive patients with HF (n = 44) with left ventricular ejection fraction (LVEF) ≤ 35% underwent polysomnography for detection of CSA. CSA was defined as an apnea-hypopnea index ≥ 15 with ≥ 50% central apneic events. The relation of natriuretic peptide concentrations to CSA was evaluated by estimation of ORs and receiver operator characteristics (ROCs). Results: Twenty-seven subjects (61%) had CSA, with men more frequently affected than women (73% vs 27%; OR, 7.1; P = .01); given that only three women had CSA, further analysis was restricted to men. Subjects with CSA had higher mean ANP (4,336 pg/mL vs 2,510 pg/mL, P = .03) and BNP concentrations (746 pg/mL vs 379 pg/mL, P = .05). ANP and BNP concentrations were significantly related to CSA (OR, 3.7 per 3,000 pg/mL, P = .03 and OR, 1.5 per 200 pg/mL, P = .04, respectively), whereas age, LVEF, and New York Heart Association functional class were not. Concentrations of ANP and BNP were predictive of CSA as ROC demonstrated areas under the curve of 0.75 and 0.73, respectively. Conclusions: Risk of CSA is related to severity of HF. ANP and BNP concentrations performed similarly for detection of CSA; low concentrations appear associated with low risk for CSA in men. PMID:21636668

Variability of NT‐proBNP plasma and urine levels in patients with stable heart failure: a 2‐year follow‐up study

PubMed Central

Cortés, Raquel; Rivera, Miguel; Salvador, Antonio; Bertomeu, Vicente; de Burgos, Fernando García; Roselló‐Lletí, Esther; Portolés, Manuel; Payá, Rafael; Martínez‐Dolz, Luis; Climent, Vicente

2007-01-01

Objectives To examine N‐terminal pro‐brain natriuretic peptide (NT‐proBNP) variability in plasma and urine samples of patients with stable heart failure (HF) during a 24‐month follow‐up. Design Prospective study. Setting Teaching hospital based study. Patients 74 clinically and functionally stable patients (NYHA class 2±0.5) out of 114 patients diagnosed with HF were followed up, and NT‐proBNP plasma and urine levels were measured at baseline, 12 and 24 months. Results Significant differences in mean urinary levels (p<0.01) were found during follow‐up, but no changes were found in plasma. Bland–Altman plots showed few variations in plasma percentages in the three intervals (stage I–basal; stage II–stage I; stage II–basal) with a coefficient of reproducibility (CR) of 22%, 21% and 25%, respectively. Changes in NT‐proBNP urinary levels had a CR of 7.1%, 6.8% and 9.4% at the three intervals, respectively. A good correlation was found between plasma and urinary levels of NT‐proBNP (p<0.001) and between the different NT‐proBNP plasma (p<0.001) and urine measurements (p<0.001). Conclusions NT‐proBNP plasma and urine levels show good stability in a 24‐month follow‐up of patients with stable heart failure. Thus, assessment of urinary and plasma NT‐proBNP concentrations may be a useful tool for monitoring patients with HF during follow‐up. The results suggest that variations in peptide concentrations exceeding 22% in plasma and 7% in urine in a 12‐month follow‐up and 25% and 9% in a 24‐month follow‐up may indicate pathophysiological changes. PMID:17488774

Performance of the Automated Neuropsychological Assessment Metrics (ANAM) in detecting cognitive impairment in heart failure patients.

PubMed

Xie, Susan S; Goldstein, Carly M; Gathright, Emily C; Gunstad, John; Dolansky, Mary A; Redle, Joseph; Hughes, Joel W

2015-01-01

Evaluate capacity of the Automated Neuropsychological Assessment Metrics (ANAM) to detect cognitive impairment (CI) in heart failure (HF) patients. CI is a key prognostic marker in HF. Though the most widely used cognitive screen in HF, the Mini-Mental State Examination (MMSE) is insufficiently sensitive. The ANAM has demonstrated sensitivity to cognitive domains affected by HF, but has not been assessed in this population. Investigators administered the ANAM and MMSE to 57 HF patients, compared against a composite model of cognitive function. ANAM efficiency (p < .05) and accuracy scores (p < .001) successfully differentiated CI and non-CI. ANAM efficiency and accuracy scores classified 97.7% and 93.0% of non-CI patients, and 14.3% and 21.4% with CI, respectively. The ANAM is more effective than the MMSE for detecting CI, but further research is needed to develop a more optimal cognitive screen for routine use in HF patients. Copyright © 2015 Elsevier Inc. All rights reserved.

Self-Efficacy and Health-Related Quality of Life Among Heart Failure Patients in Singapore: A Descriptive Correlational Study.

PubMed

Suresh, Rajasekaram; Wang, Wenru; Koh, Karen W L; Shorey, Shefaly; Lopez, Violeta

2018-07-01

Heart failure (HF) accounts for 30% of all global deaths and Asians are likely to suffer from HF 10 years earlier than their Western counterparts. Low self-efficacy and poor health-related quality of life (HRQoL) have been reported in patients with HF. A descriptive correlational design was adopted to investigate the associations between self-efficacy and HRQoL in 91 patients with HF in Singapore. Patients with HF demonstrated moderately good self-efficacy ( M = 3.05, SD = 0.61) and HRQoL ( M = 22.48, SD = 18.99). Significant differences were found between total self-efficacy scores and education levels ( p = .05), and between overall HRQoL and smoking status ( p < .05). Self-efficacy was not significantly correlated to HRQoL. Smoking status, HF classification, and self-efficacy in maintaining function predicted HRQoL. Health care professionals should assess each patient's demographics, smoking status, and clinical condition before delivering individualized education to enhance their self-efficacy and, in turn, overall HRQoL.

Exercise training in heart failure.

PubMed

Abela, Mark

2018-05-04

Exercise training (ET) in heart failure (HF) has long been established as an important part of HF care. ET is known to improve quality of life and functional capacity in a number of ways. Despite its proposed benefits, evidence supporting its routine inclusion in standard rehabilitation programme is at times conflicting, partly because of the significant heterogeneity present in available randomised controlled trials. There is lack of evidence with regard to the duration of the overall benefit, the optimal exercise regimen and whether certain types of HF aetiologies benefit more than others. The aim of this review is to provide an update to date literature review of the positive and negative evidence surrounding ET in HF, while proposing an efficient novel in-hospital exercise-based rehabilitation programme for patients with HF in addition to a pre-existing HF clinic. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

The innate immune system in chronic cardiomyopathy: a European Society of Cardiology (ESC) scientific statement from the Working Group on Myocardial Function of the ESC

PubMed Central

Falcao‐Pires, Ines; Balligand, Jean‐Luc; Bauersachs, Johann; Brutsaert, Dirk; Ciccarelli, Michele; Dawson, Dana; de Windt, Leon J.; Giacca, Mauro; Hamdani, Nazha; Hilfiker‐Kleiner, Denise; Hirsch, Emilio; Leite‐Moreira, Adelino; Mayr, Manuel; Thum, Thomas; Tocchetti, Carlo G.; van der Velden, Jolanda; Varricchi, Gilda; Heymans, Stephane

2018-01-01

Activation of the immune system in heart failure (HF) has been recognized for over 20 years. Initially, experimental studies demonstrated a maladaptive role of the immune system. However, several phase III trials failed to show beneficial effects in HF with therapies directed against an immune activation. Preclinical studies today describe positive and negative effects of immune activation in HF. These different effects depend on timing and aetiology of HF. Therefore, herein we give a detailed review on immune mechanisms and their importance for the development of HF with a special focus on commonalities and differences between different forms of cardiomyopathies. The role of the immune system in ischaemic, hypertensive, diabetic, toxic, viral, genetic, peripartum, and autoimmune cardiomyopathy is discussed in depth. Overall, initial damage to the heart leads to disease specific activation of the immune system whereas in the chronic phase of HF overlapping mechanisms occur in different aetiologies. PMID:29333691

Activation cross-sections of proton induced reactions on natHf in the 38-65 MeV energy range: Production of 172Lu and of 169Yb

NASA Astrophysics Data System (ADS)

Tárkányi, F.; Hermanne, A.; Ditrói, F.; Takács, S.; Ignatyuk, A. V.

2018-07-01

In the frame of a systematical study of light ion induced nuclear reactions on hafnium, activation cross sections for proton induced reactions were investigated. Excitation functions were measured in the 38-65 MeV energy range for the natHf(p,xn)180g,177,176,175,173Ta, natHf(p,x)180m,179m,175,173,172,171Hf, 177g,173,172,171,170,169Lu and natHf(p,x)169Yb reactions by using the activation method, combining stacked foil irradiation and off line gamma ray spectroscopy. The experimental results are compared with earlier results in the overlapping energy range, and with the theoretical predictions of the ALICE IPPE and EMPIRE theoretical codes and of the TALYS code reported in the TENDL-2015 and TENDL-2017 libraries. The production routes of 172Lu (and its parent 172Hf) and of 169Yb are reviewed.

Electron-beam-evaporated thin films of hafnium dioxide for fabricating electronic devices

DOE PAGES

Xiao, Zhigang; Kisslinger, Kim

2015-06-17

Thin films of hafnium dioxide (HfO 2) are widely used as the gate oxide in fabricating integrated circuits because of their high dielectric constants. In this paper, the authors report the growth of thin films of HfO 2 using e-beam evaporation, and the fabrication of complementary metal-oxide semiconductor (CMOS) integrated circuits using this HfO 2 thin film as the gate oxide. The authors analyzed the thin films using high-resolution transmission electron microscopy and electron diffraction, thereby demonstrating that the e-beam-evaporation-grown HfO 2 film has a polycrystalline structure and forms an excellent interface with silicon. Accordingly, we fabricated 31-stage CMOS ringmore » oscillator to test the quality of the HfO 2 thin film as the gate oxide, and obtained excellent rail-to-rail oscillation waveforms from it, denoting that the HfO 2 thin film functioned very well as the gate oxide.« less

Hemoglobin Regulates the Metabolic, Synthetic, Detoxification, and Biotransformation Functions of Hepatoma Cells Cultured in a Hollow Fiber Bioreactor

PubMed Central

Chen, Guo

2010-01-01

Hepatic hollow fiber (HF) bioreactors constitute one type of extracorporeal bioartificial liver assist device (BLAD). Ideally, cultured hepatocytes in a BLAD should closely mimic the in vivo oxygenation environment of the liver sinusoid to yield a device with optimal performance. However, most BLADs, including hepatic HF bioreactors, suffer from O2 limited transport toward cultured hepatocytes, which reduces their performance. We hypothesize that supplementation of hemoglobin-based O2 carriers into the circulating cell culture medium of hepatic HF bioreactors is a feasible and effective strategy to improve bioreactor oxygenation and performance. We examined the effect of bovine hemoglobin (BvHb) supplementation (15 g/L) in the circulating cell culture medium of hepatic HF bioreactors on hepatocyte proliferation, metabolism, and varied liver functions, including biosynthesis, detoxification, and biotransformation. It was observed that BvHb supplementation supported the maintenance of a higher cell mass in the extracapillary space, improved hepatocyte metabolic efficiency (i.e., hepatocytes consumed much less glucose), improved hepatocyte capacity for drug metabolism, and conserved both albumin synthesis and ammonia detoxification functions compared to controls (no BvHb supplementation) under the same experimental conditions. PMID:20528678

Loss of ovarian function in the VCD mouse-model of menopause leads to insulin resistance and a rapid progression into the metabolic syndrome.

PubMed

Romero-Aleshire, Melissa J; Diamond-Stanic, Maggie K; Hasty, Alyssa H; Hoyer, Patricia B; Brooks, Heddwen L

2009-09-01

Factors comprising the metabolic syndrome occur with increased incidence in postmenopausal women. To investigate the effects of ovarian failure on the progression of the metabolic syndrome, female B(6)C(3)F(1) mice were treated with 4-vinylcyclohexene diepoxide (VCD) and fed a high-fat (HF) diet for 16 wk. VCD destroys preantral follicles, causing early ovarian failure and is a well-characterized model for the gradual onset of menopause. After 12 wk on a HF diet, VCD-treated mice had developed an impaired glucose tolerance, whereas cycling controls were unaffected [12 wk AUC HF mice 13,455 +/- 643 vs. HF/VCD 17,378 +/- 1140 mg/dl/min, P < 0.05]. After 16 wk on a HF diet, VCD-treated mice had significantly higher fasting insulin levels (HF 5.4 +/- 1.3 vs. HF/VCD 10.1 +/- 1.4 ng/ml, P < 0.05) and were significantly more insulin resistant (HOMA-IR) than cycling controls on a HF diet (HF 56.2 +/- 16.7 vs. HF/VCD 113.1 +/- 19.6 mg/dl x microU/ml, P < 0.05). All mice on a HF diet gained more weight than mice on a standard diet, and weight gain in HF/VCD mice was significantly increased compared with HF cycling controls. Interestingly, even without a HF diet, progression into VCD-induced menopause caused a significant increase in cholesterol and free fatty acids. Furthermore, in mice fed a standard diet (6% fat), insulin resistance developed 4 mo after VCD-induced ovarian failure. Insulin resistance following ovarian failure (menopause) was prevented by estrogen replacement. Studies here demonstrate that ovarian failure (menopause) accelerates progression into the metabolic syndrome and that estrogen replacement prevents the onset of insulin resistance in VCD-treated mice. Thus, the VCD model of menopause provides a physiologically relevant means of studying how sex hormones influence the progression of the metabolic syndrome.

Saxagliptin and Tadalafil Differentially Alter Cyclic Guanosine Monophosphate (cGMP) Signaling and Left Ventricular Function in Aortic-Banded Mini-Swine.

PubMed

Hiemstra, Jessica A; Lee, Dong I; Chakir, Khalid; Gutiérrez-Aguilar, Manuel; Marshall, Kurt D; Zgoda, Pamela J; Cruz Rivera, Noelany; Dozier, Daniel G; Ferguson, Brian S; Heublein, Denise M; Burnett, John C; Scherf, Carolin; Ivey, Jan R; Minervini, Gianmaria; McDonald, Kerry S; Baines, Christopher P; Krenz, Maike; Domeier, Timothy L; Emter, Craig A

2016-04-20

Cyclic guanosine monophosphate-protein kinase G-phosphodiesterase 5 signaling may be disturbed in heart failure (HF) with preserved ejection fraction, contributing to cardiac remodeling and dysfunction. The purpose of this study was to manipulate cyclic guanosine monophosphate signaling using the dipeptidyl-peptidase 4 inhibitor saxagliptin and phosphodiesterase 5 inhibitor tadalafil. We hypothesized that preservation of cyclic guanosine monophosphate cGMP signaling would attenuate pathological cardiac remodeling and improve left ventricular (LV) function. We assessed LV hypertrophy and function at the organ and cellular level in aortic-banded pigs. Concentric hypertrophy was equal in all groups, but LV collagen deposition was increased in only HF animals. Prevention of fibrotic remodeling by saxagliptin and tadalafil was correlated with neuropeptide Y plasma levels. Saxagliptin better preserved integrated LV systolic and diastolic function by maintaining normal LV chamber volumes and contractility (end-systolic pressure-volume relationship, preload recruitable SW) while preventing changes to early/late diastolic longitudinal strain rate. Function was similar to the HF group in tadalafil-treated animals including increased LV contractility, reduced chamber volume, and decreased longitudinal, circumferential, and radial mechanics. Saxagliptin and tadalafil prevented a negative cardiomyocyte shortening-frequency relationship observed in HF animals. Saxagliptin increased phosphodiesterase 5 activity while tadalafil increased cyclic guanosine monophosphate levels; however, neither drug increased downstream PKG activity. Early mitochondrial dysfunction, evident as decreased calcium-retention capacity and Complex II-dependent respiratory control, was present in both HF and tadalafil-treated animals. Both saxagliptin and tadalafil prevented increased LV collagen deposition in a manner related to the attenuation of increased plasma neuropeptide Y levels. Saxagliptin appears superior for treating heart failure with preserved ejection fraction, considering its comprehensive effects on integrated LV systolic and diastolic function. © 2016 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

Catheter ablation for premature ventricular contractions and ventricular tachycardia in patients with heart failure.

PubMed

Kumar, Saurabh; Stevenson, William G; John, Roy M

2014-09-01

Ventricular arrhythmias (VA) are a significant contributor to morbidity and mortality in patients with heart failure (HF). Implantable cardioverter defibrillators are effective in reducing mortality, but do not prevent arrhythmia recurrence. There is increasing recognition that frequent premature ventricular contractions or repetitive ventricular tachycardia may also lead to new onset ventricular dysfunction or deterioration of ventricular function in patients with pre-existing HF. Suppression of the arrhythmia may lead to recovery of ventricular function. Catheter ablation has emerged as a safe and effective treatment option for reducing arrhythmia recurrence and for suppression of PVCs but its efficacy is governed by the nature of the arrhythmias, the underlying HF substrate and the accessibility of the arrhythmia substrates to ablation.

HMGB1 is an independent predictor of death and heart transplantation in heart failure.

PubMed

Volz, H C; Laohachewin, D; Schellberg, D; Wienbrandt, A R; Nelles, M; Zugck, C; Kaya, Z; Katus, H A; Andrassy, M

2012-06-01

High-Mobility-Group Box 1 (HMGB1) has been established as an important mediator of myocardial inflammation and associated with progression of heart failure (HF). The aim of this study was to analyze the prognostic value of systemic HMGB1 levels in HF patients with ischemic and non-ischemic cardiomyopathy. We conducted an analysis (median follow-up time 2.5 years) of HMGB1 plasma concentration in 154 patients with systolic HF and correlated the results with disease severity and prognosis. HMGB1 in HF patients with severe symptoms (NYHA III/IV; 5.35 ng/ml; interquartile range (IQR) = 3.48-8.42 ng/ml) was significantly elevated compared with that in patients with mild symptoms (NYHA I/II; 3.37 ng/ml, IQR = 2.31-5.22 ng/ml, p < 0.0001) and with controls (3.25 ng/ml, IQR = 3.04-3.67 ng/ml, p < 0.0001). HMGB1 levels correlated with other markers of heart failure indicating an association of HMGB1 with disease severity in HF. In a univariate cox regression model for the combined endpoint of death and heart transplantation, HMGB1 proved to be a predictor at cut-off values based on HMGB1 terciles of either 3.4 or 6.1 ng/ml (p = 0.001 and p < 0.0001, respectively). In a multivariate cox regression model, which included NT-proBNP, creatinine, age, NYHA class, white blood cell count, anemia, and age, HMGB1 remained an independent predictor of the combined endpoint (hazard ratio (HR) = 2.48, 95% confidence interval (CI) = 1.06-5.83, p = 0.037 and HR = 2.48, 95% CI = 1.31-4.71, p = 0.005, respectively). Our findings demonstrate that HMGB1 plasma concentration is elevated in HF and correlates with disease severity and that is an independent predictor of the combined endpoint death and heart transplantation in HF patients.

Management and Long-Term Outcome of Acute Coronary Syndrome Patients Presenting with Heart Failure in a Contemporary New Zealand Cohort (ANZACS-QI 4).

PubMed

Kueh, Shaw Hua Anthony; Devlin, Gerry; Lee, Mildred; Doughty, Rob N; Kerr, Andrew J

2016-08-01

Acute heart failure (HF) associated with an acute coronary syndrome (ACS) predicts adverse outcome. There have been important recent improvements in ACS management. Our aim was to describe the management and outcomes in those with and without HF in a contemporary ACS cohort. Consecutive patients presenting with ACS between 2007 and 2011 were enrolled in the All New Zealand Acute Coronary Syndrome Quality Improvement (ANZACS-QI) registry. Outcomes and medication dispensing were obtained using anonymised linkage to national data sets. A summary pharmacotherapy measure of "quadruple therapy" was defined as dispensing of at least one agent from each of the four evidence-based classes - anti-platelet, statin, angiotensin converting enzyme inhibitor/angiotensin receptor blocker and beta blocker. Of 3743 ACS patients 14% had acute HF. Acute heart failure patients were older (69.2±12.6 vs 62.3±12.8 years, p<0.001), less likely to have coronary angiography (66% vs 86%, p<0.001) and revascularisation (46% vs 62%, p<0.001). Immediate post-discharge quadruple therapy was higher for those with than without HF (61% vs 55%, p=0.02) but fell to similar levels by one-year (45% vs 53%, p=0.55). At four years follow-up nearly half of those presenting with ACS and HF had died. After adjustment, HF remained a strong predictor of death within 28 days (OR 2.9, 95%CI 1.5 - 5.5) and beyond 28 days (HR 1.8, 95%CI 1.5 - 2.3). Acute heart failure complicating ACS is associated with heightened risk of short-term and long-term mortality. One in three ACS patients with HF did not have coronary angiography and less than half received quadruple therapy a year after presentation. Copyright © 2016. Published by Elsevier B.V.

Extraction chromatographic separations of tantalum and tungsten from hafnium and complex matrix constituents

DOE Office of Scientific and Technical Information (OSTI.GOV)

Snow, Mathew S.; Finck, Martha R.; Carney, Kevin P.

2017-02-01

Ta, Hf, and W analyses from complex matrices (including environmental samples) require high purification of these analytes from each other and major/trace matrix constituents, however, current state-of-the-art Ta/Hf/W separations rely on traditional anion exchange approaches that suffer from relatively similar distribution coefficient (Kd) values for these analytes. This work reports assessment of three commercially available extraction chromatographic resins (TEVA, TRU, and UTEVA) for Ta/Hf/W separations. Batch contact studies show differences in Ta/W,Hf Kd values of up to 106, representing an improvement of a factor of 100 and 300 in Ta/Hf and Ta/W Kd values (respectively) over AG1x4 resin. Variations inmore » the Kd values as a function of HCl concentration for TRU resin show that this resin is well suited for Ta/Hf/W separations, with Ta/Hf, Ta/W, and W/Hf Kd value improvements of 10, 200, and 30 (respectively) over AG1x4 resin. Finally, analyses of digested soil samples (NIST 2710a) using TRU resin and tandem TEVA-TRU columns demonstrate the ability to achieve extremely high purification (>99%) of Ta and W from each other and Hf, as well as enabling very high purification of Ta and W from the major and trace elemental constituents present in soils, using a single chromatographic step.« less

Health Literacy and Heart Failure

PubMed Central

Cajita, Maan Isabella; Cajita, Tara Rafaela; Han, Hae-Ra

2015-01-01

Background Low health literacy affects millions of Americans, putting those who are affected at a disadvantage and at risk for poorer health outcomes. Low health literacy can act as a barrier to effective disease self-management; this is especially true for chronic diseases such as heart failure (HF) that require complicated self-care regimens. Purpose This systematic review examined quantitative research literature published between 1999 and 2014 to explore the role of health literacy among HF patients. The specific aims of the systematic review are to (1) describe the prevalence of low health literacy among HF patients, (2) explore the predictors of low health literacy among HF patients, and (3) discuss the relationship between health literacy and HF self-care and common HF outcomes. Methods A systematic search of the following databases was conducted, PubMed, CINAHL Plus, Embase, PsycINFO, and Scopus, using relevant keywords and clear inclusion and exclusion criteria. Conclusions An average of 39% of HF patients have low health literacy. Age, race/ethnicity, years of education, and cognitive function are predictors of health literacy. In addition, adequate health literacy is consistently correlated with higher HF knowledge and higher salt knowledge. Clinical Implications Considering the prevalence of low health literacy among in the HF population, nurses and healthcare professionals need to recognize the consequences of low health literacy and adopt strategies that could minimize its detrimental effect on the patient's health outcomes. PMID:25569150

Extraction chromatographic separations of tantalum and tungsten from hafnium and complex matrix constituents

DOE PAGES

Snow, Mathew S.; Finck, Martha R.; Carney, Kevin P.; ...

2017-01-08

Ta, Hf, and W analyses from complex matrices (including environmental samples) require high purification of these analytes from each other and major/trace matrix constituents, but, current state-of-the-art Ta/Hf/W separations rely on traditional anion exchange approaches that suffer from relatively similar distribution coefficient (Kd) values for these analytes. Our work reports assessment of three commercially available extraction chromatographic resins (TEVA, TRU, and UTEVA) for Ta/Hf/W separations. Batch contact studies show differences in Ta/W,Hf Kd values of up to 10 6, representing an improvement of a factor of 100 and 300 in Ta/Hf and Ta/W Kd values (respectively) over AG1x4 resin. Furthermore,more » variations in the Kd values as a function of HCl concentration for TRU resin show that this resin is well suited for Ta/Hf/W separations, with Ta/Hf, Ta/W, and W/Hf Kd value improvements of 10, 200, and 30 (respectively) over AG1x4 resin. Finally, analyses of digested soil samples (NIST 2710a) using TRU resin and tandem TEVA-TRU columns demonstrate the ability to achieve extremely high purification (>99%) of Ta and W from each other and Hf, as well as enabling very high purification of Ta and W from the major and trace elemental constituents present in soils, using a single chromatographic step.« less

Hartree-Fock implementation using a Laguerre-based wave function for the ground state and correlation energies of two-electron atoms.

PubMed

King, Andrew W; Baskerville, Adam L; Cox, Hazel

2018-03-13

An implementation of the Hartree-Fock (HF) method using a Laguerre-based wave function is described and used to accurately study the ground state of two-electron atoms in the fixed nucleus approximation, and by comparison with fully correlated (FC) energies, used to determine accurate electron correlation energies. A variational parameter A is included in the wave function and is shown to rapidly increase the convergence of the energy. The one-electron integrals are solved by series solution and an analytical form is found for the two-electron integrals. This methodology is used to produce accurate wave functions, energies and expectation values for the helium isoelectronic sequence, including at low nuclear charge just prior to electron detachment. Additionally, the critical nuclear charge for binding two electrons within the HF approach is calculated and determined to be Z HF C =1.031 177 528.This article is part of the theme issue 'Modern theoretical chemistry'. © 2018 The Author(s).

Family partnership and education interventions to reduce dietary sodium by patients with heart failure differ by family functioning.

PubMed

Dunbar, Sandra B; Clark, Patricia C; Stamp, Kelly D; Reilly, Carolyn M; Gary, Rebecca A; Higgins, Melinda; Kaslow, Nadine

2016-01-01

Determine if family functioning influences response to family-focused interventions aimed at reducing dietary sodium by heart failure (HF) patients. Lowering dietary sodium by HF patients often occurs within the home and family context. Secondary analysis of 117 dyads randomized to patient and family education (PFE), family partnership intervention (FPI) or usual care (UC). Dietary sodium measures were obtained from 3-day food record and 24-h urine samples. In the poor family functioning groups, FPI and PFE had lower mean urine sodium than UC (p < .05) at 4 months, and FPI remained lower than UC at 8 months (p < .05). For good family functioning groups, FPI and PFE had lower mean sodium levels by 3-day food record at 4 and 8 months compared to the UC group. Optimizing family-focused interventions into HF clinical care maybe indicated. Copyright © 2016 Elsevier Inc. All rights reserved.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Song, Jong-Won; Hirao, Kimihiko

Long-range corrected density functional theory (LC-DFT) attracts many chemists’ attentions as a quantum chemical method to be applied to large molecular system and its property calculations. However, the expensive time cost to evaluate the long-range HF exchange is a big obstacle to be overcome to be applied to the large molecular systems and the solid state materials. Upon this problem, we propose a linear-scaling method of the HF exchange integration, in particular, for the LC-DFT hybrid functional.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Berdova, Maria; Liu, Xuwen; Franssila, Sami, E-mail: sami.franssila@aalto.fi

The investigation of mechanical properties of atomic layer deposition HfO{sub 2} films is important for implementing these layers in microdevices. The mechanical properties of films change as a function of composition and structure, which accordingly vary with deposition temperature and post-annealing. This work describes elastic modulus, hardness, and wear resistance of as-grown and annealed HfO{sub 2}. From nanoindentation measurements, the elastic modulus and hardness remained relatively stable in the range of 163–165 GPa and 8.3–9.7 GPa as a function of deposition temperature. The annealing of HfO{sub 2} caused significant increase in hardness up to 14.4 GPa due to film crystallization and densification. Themore » structural change also caused increase in the elastic modulus up to 197 GPa. Wear resistance did not change as a function of deposition temperature, but improved upon annealing.« less

Heart failure patient adherence: epidemiology, cause, and treatment.

PubMed

Corotto, Paul S; McCarey, Melissa M; Adams, Suzanne; Khazanie, Prateeti; Whellan, David J

2013-01-01

Poor adherence to therapeutic regimens is a significant impediment to improving clinical outcomes in the HF population. Typical rates of adherence to prescribed medications, low-sodium diets, and aerobic exercise programs remain lower than that needed to decrease morbidity and mortality associated with HF. Factors contributing to poor adherence include multiple comorbidities, clinical depression, and decreased cognitive functioning. HF education and programs to enhance self-management skills have improved patient quality of life but have yet to decrease mortality or rehospitalization rates significantly. Telemonitoring to improve adherence behaviors and self-management interventions within broader HF management programs have demonstrated significant clinical improvements in this population. Copyright © 2013 Elsevier Inc. All rights reserved.

Merits of Non-Invasive Rat Models of Left Ventricular Heart Failure

EPA Science Inventory

Heart failure (HF) is defined primarily by the impairment of cardiac function and consequent inability of the heart to supply tissues with ample oxygen. To study HF etiology, investigators have applied many different techniques to elicit this condition in animals, with varying de...

Plasma matrix metalloproteinase-9 better predicts outcome than N-terminal protype-B natriuretic peptide in patients with systolic heart failure and a high prevalence of coronary artery disease.

PubMed

Dini, Frank Lloyd; Buralli, Simona; Bajraktari, Gani; Elezi, Shpend; Duranti, Emiliano; Metelli, Maria Rita; Carpi, Angelo; Taddei, Stefano

2010-05-01

Metalloproteinases have been proposed as biochemical markers of left ventricular (LV) remodeling in systolic heart failure (HF). However, their role in the prognostic stratification of these patients remains controversial. In the present study, we aimed at investigating the value of plasma metalloproteinases-3 and -9 in comparison with N-terminal protype-B natriuretic peptide in patients with systolic HF. One hundred and 27 consecutive patients hospitalized for systolic HF (LV ejection fraction < 45%) were enrolled. Coronary artery disease (CAD) was the aetiology in 67% of the study patients. Plasma metalloproteinases-3 and -9 and N-terminal protype-B natriuretic peptide levels were assessed. A complete echocardiographic and Doppler examination was also performed. Follow-up period was 24-15 months. On univariate analysis, a number of measurements predicted cardiac events in the following order of power: NYHA class >2, LV ejection fraction < 25%, metalloproteinases-9 > 238 ng/ml, mitral E wave deceleration time < 150 ms, N-terminal protype-B natriuretic peptide > 1586 pg/ml and metalloproteinases-3 > 15 ng/ml. However, on multivariate analysis the only independent variables of cardiac events were NYHA class (OR=2.26, p=0.059) and plasma metalloproteinases-9 (OR=2.00, p=0.029). On Kaplan-Meier survival analysis, patients with elevated levels of metalloproteinases-9 exhibited a significantly worse event free-survival at 45 months than those without (21% vs. 54%, log-rank: 13.93, p=0.0002). A worse survival was also observed in patients with elevated N-terminal protype-B natriuretic peptide levels with respect to those without (18% vs. 46%, log-rank: 9.11, p=0.025). Our results demonstrated the value of plasma metalloproteinases-9 levels for prognostication of patients with systolic HF and a high prevalence of CAD. 2009. Published by Elsevier SAS.

Rationale and design of the comParIson Of sacubitril/valsartaN versus Enalapril on Effect on nt-pRo-bnp in patients stabilized from an acute Heart Failure episode (PIONEER-HF) trial.

PubMed

Velazquez, Eric J; Morrow, David A; DeVore, Adam D; Ambrosy, Andrew P; Duffy, Carol I; McCague, Kevin; Hernandez, Adrian F; Rocha, Ricardo A; Braunwald, Eugene

2018-04-01

The objective is to assess the safety, tolerability, and efficacy of sacubitril/valsartan compared with enalapril in patients with heart failure (HF) with a reduced ejection fraction (EF) stabilized during hospitalization for acute decompensated HF. Sacubitril/valsartan, a first-in-class angiotensin receptor-neprilysin inhibitor, improves survival among ambulatory HF patients with a reduced EF. However, there is very limited experience with the in-hospital initiation of sacubitril/valsartan in patients who have been stabilized following hospitalization for acute decompensated HF. PIONEER-HF is a 12-week, prospective, multicenter, double-blind, randomized controlled trial enrolling a planned 882 patients at more than 100 participating sites in the United States. Medically stable patients >18 years of age with an EF <40% and an amino terminal-pro b-type natriuretic peptide >1600 pg/mL or b-type natriuretic peptide >400 pg/mL are eligible for participation no earlier than 24 hours and up to 10 days from initial presentation while still hospitalized. Patients are randomly assigned 1:1 to in-hospital initiation of sacubitril/valsartan titrated to 97/103 mg by mouth twice daily versus enalapril titrated to 10 mg by mouth twice daily for 8 weeks. All patients receive open-label treatment with sacubitril/valsartan for the remaining 4 weeks of the study. The primary efficacy end point is the time-averaged proportional change in amino terminal-pro b-type natriuretic peptide from baseline through weeks 4 and 8. Secondary and exploratory end points include serum and urinary biomarkers as well as clinical outcomes. Safety end points include the incidence of angioedema, hypotension, renal insufficiency, and hyperkalemia. The PIONEER-HF trial will inform clinical practice by providing evidence on the safety, tolerability, and efficacy of in-hospital initiation of sacubitril/valsartan among patients who have been stabilized following an admission for acute decompensated HF with a reduced EF. Copyright © 2018 Elsevier Inc. All rights reserved.

Open access to an outpatient intravenous diuresis program in a systolic heart failure disease management program.

PubMed

Hebert, Kathy; Dias, Andre; Franco, Emiliana; Tamariz, Leonardo; Steen, Dylan; Arcement, Lee M

2011-01-01

In order to provide efficient utilization of resources in an outpatient setting for acute exacerbation of heart failure (HF), the authors piloted an open-access outpatient intravenous (IV) diuretic program (IVDP) to evaluate utilization in an HF disease management program (HFDMP), patient characteristics for users of the program, and safety. An outpatient HFDMP at Jackson Memorial Hospital in Miami, Florida, enrolling 577 patients 18 years and older with an ejection fraction ≤40% was implemented. For symptoms or weight gain ≥5 pounds, patients were eligible to use an open-access IVDP during clinic hours. A total of 130 HFDM patients (22.5%) used the IVDP. IVDP users were more likely to be diabetic, with lower body mass indices than non-IVDP users. New York Heart Association class IV patients and previously hospitalized patients were more likely to use the IVDP. There were no documented adverse reactions for patients receiving treatment and no difference in mortality between groups. This open-access outpatient IVDP model for patients with HF was readily utilized by the HFDMP participants and appears safe for use in this population. This unique model may provide alternative access for acute HF treatment. Congest Heart Fail. © 2011 Wiley Periodicals, Inc.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Song, Jong-Won; Hirao, Kimihiko, E-mail: hirao@riken.jp

Since the advent of hybrid functional in 1993, it has become a main quantum chemical tool for the calculation of energies and properties of molecular systems. Following the introduction of long-range corrected hybrid scheme for density functional theory a decade later, the applicability of the hybrid functional has been further amplified due to the resulting increased performance on orbital energy, excitation energy, non-linear optical property, barrier height, and so on. Nevertheless, the high cost associated with the evaluation of Hartree-Fock (HF) exchange integrals remains a bottleneck for the broader and more active applications of hybrid functionals to large molecular andmore » periodic systems. Here, we propose a very simple yet efficient method for the computation of long-range corrected hybrid scheme. It uses a modified two-Gaussian attenuating operator instead of the error function for the long-range HF exchange integral. As a result, the two-Gaussian HF operator, which mimics the shape of the error function operator, reduces computational time dramatically (e.g., about 14 times acceleration in C diamond calculation using periodic boundary condition) and enables lower scaling with system size, while maintaining the improved features of the long-range corrected density functional theory.« less

Sacubitril/Valsartan in Clinical Practice: A Report of 2 Cases.

PubMed

Cosentino, Eugenio

Following the results of the PARADIGM-HF trial, the European Society of Cardiology (ESC) guidelines recommend sacubitril/valsartan to replace ACE inhibitors in ambulatory patients with heart failure with reduced ejection fraction (HFrEF) who remain symptomatic despite optimal therapy and who fit trial criteria. However, the optimal use of sacubitril/valsartan in clinical practice needs further investigation. We report here the cases of 2 patients with HFrEH successfully treated with sacubitril/valsartan in our daily practice. Both subjects presented multiple comorbidities and received an implantable cardioverter defibrillator in primary prevention. In both patients, therapy with sacubitril/valsartan led to prompt (30 days) amelioration of heart function, with a corresponding decrease in NHYA class and without any relevant safety issue. © 2017 S. Karger AG, Basel.

Insulin resistance and carotid intima-media thickness mediate the association between resting-state heart rate variability and executive function: A path modelling study.

PubMed

Kemp, Andrew H; López, Santiago Rodríguez; Passos, Valeria M A; Bittencourt, Marcio S; Dantas, Eduardo M; Mill, José G; Ribeiro, Antonio L P; Thayer, Julian F; Bensenor, Isabela M; Lotufo, Paulo A

2016-05-01

Research has linked high-frequency heart rate variability (HF-HRV) to cognitive function. The present study adopts a modern path modelling approach to understand potential causal pathways that may underpin this relationship. Here we examine the association between resting-state HF-HRV and executive function in a large sample of civil servants from Brazil (N=8114) recruited for the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil). HF-HRV was calculated from 10-min resting-state electrocardiograms. Executive function was assessed using the trail-making test (version B). Insulin resistance (a marker of type 2 diabetes mellitus) and carotid intima-media thickness (subclinical atherosclerosis) mediated the relationship between HRV and executive function in seriatim. A limitation of the present study is its cross-sectional design; therefore, conclusions must be confirmed in longitudinal study. Nevertheless, findings support that possibility that HRV provides a 'spark' that initiates a cascade of adverse downstream effects that subsequently leads to cognitive impairment. Copyright © 2016 Elsevier B.V. All rights reserved.

Anorexia, functional capacity, and clinical outcome in patients with chronic heart failure: results from the Studies Investigating Co‐morbidities Aggravating Heart Failure (SICA‐HF)

PubMed Central

Saitoh, Masakazu; dos Santos, Marcelo R.; Emami, Amir; Ishida, Junichi; Ebner, Nicole; Valentova, Miroslava; Bekfani, Tarek; Sandek, Anja; Lainscak, Mitja; Doehner, Wolfram; Anker, Stefan D.

2017-01-01

Abstract Aims We aimed to assess determinants of anorexia, that is loss of appetite in patients with heart failure (HF) and aimed to further elucidate the association between anorexia, functional capacity, and outcomes in affected patients. Methods and results We assessed anorexia status among 166 patients with HF (25 female, 66 ± 12 years) who participated in the Studies Investigating Co‐morbidities Aggravating HF. Anorexia was assessed by a 6‐point Likert scale (ranging from 0 to 5), wherein values ≥1 indicate anorexia. Functional capacity was assessed as peak oxygen uptake (peak VO2), 6 min walk test, and short physical performance battery test. A total of 57 patients (34%) reported any anorexia, and these patients showed lower values of peak VO2, 6 min walk distance, and short physical performance battery score (all P < 0.05). Using multivariate analysis adjusting for clinically important factors, only high‐sensitivity C‐reactive protein [odds ratio (OR) 1.24, P = 0.04], use of loop diuretics (OR 5.76, P = 0.03), and the presence of cachexia (OR 2.53, P = 0.04) remained independent predictors of anorexia. A total of 22 patients (13%) died during a mean follow‐up of 22.5 ± 5.1 months. Kaplan‐Meier curves for cumulative survival showed that those patients with anorexia presented higher mortality (Log‐rank test P = 0.03). Conclusions Inflammation, use of loop diuretics, and cachexia are associated with an increased likelihood of anorexia in patients with HF, and patients with anorexia showed impaired functional capacity and poor outcomes. PMID:28960880

A new twist on an old idea part 2: cyclosporine preserves normal mitochondrial but not cardiomyocyte function in mini‐swine with compensated heart failure

PubMed Central

Hiemstra, Jessica A.; Gutiérrez‐Aguilar, Manuel; Marshall, Kurt D.; McCommis, Kyle S.; Zgoda, Pamela J.; Cruz‐Rivera, Noelany; Jenkins, Nathan T.; Krenz, Maike; Domeier, Timothy L.; Baines, Christopher P.; Emter, Craig A.

2014-01-01

Abstract We recently developed a clinically relevant mini‐swine model of heart failure with preserved ejection fraction (HFpEF), in which diastolic dysfunction was associated with increased mitochondrial permeability transition (MPT). Early diastolic function is ATP and Ca2+‐dependent, thus, we hypothesized chronic low doses of cyclosporine (CsA) would preserve mitochondrial function via inhibition of MPT and subsequently maintain normal cardiomyocyte Ca2+ handling and contractile characteristics. Left ventricular cardiomyocytes were isolated from aortic‐banded Yucatan mini‐swine divided into three groups; control nonbanded (CON), HFpEF nontreated (HF), and HFpEF treated with CsA (HF‐CsA). CsA mitigated the deterioration of mitochondrial function observed in HF animals, including functional uncoupling of Complex I‐dependent mitochondrial respiration and increased susceptibility to MPT. Attenuation of mitochondrial dysfunction in the HF‐CsA group was not associated with commensurate improvement in cardiomyocyte Ca2+ handling or contractility. Ca2+ transient amplitude was reduced and transient time to peak and recovery (tau) prolonged in HF and HF‐CsA groups compared to CON. Alterations in Ca2+ transient parameters observed in the HF and HF‐CsA groups were associated with decreased cardiomyocyte shortening and shortening rate. Cellular function was consistent with impaired in vivo systolic and diastolic whole heart function. A significant systemic hypertensive response to CsA was observed in HF‐CsA animals, and may have played a role in the accelerated the development of heart failure at both the whole heart and cellular levels. Given the significant detriment to cardiac function observed in response to CsA, our findings suggest chronic CsA treatment is not a viable therapeutic option for HFpEF. PMID:24963034

Nutraceuticals and Dietary Supplements to Improve Quality of Life and Outcomes in Heart Failure Patients.

PubMed

Cicero, Arrigo F G; Colletti, Alessandro

2017-01-01

Heart failure (HF) is a complex clinical syndrome that can result from any structural or functional cardiac disorder that impairs the ability of the ventricle to fill or eject blood. It represents a major public health issue, with a prevalence of over 23 million worldwide. The lifetime risk of developing HF is one in five and the most important risk factors identified are ischemic heart disease, hypertension, smoking, obesity and diabetes. Preventive approaches are based on improvements of lifestyle, associated with pharmacological therapy. Several nutraceuticals have shown interesting clinical results in prevention of HF as well as in the treatment of the early stages of the disease, alone or in association with pharmacological therapy. The aim of this review is to resume the available clinical evidence on phytochemicals effect on HF prevention and/or treatment. A systematic search strategy was developed to identify trials in PubMed (January 1980 to April 2016). The terms 'nutraceuticals', 'dietary supplements', 'herbal drug' and 'heart failure' were incorporated into an electronic search strategy. Clinical trials reported that the intake of some nutraceuticals (hawthorn, coenzyme Q10, L-carnitine, Dribose, Carnosine, Vitamin D, Some probiotics, Omega-3 PUFAs, Beet nitrates) is associated with improvements in functional parameters such as ejection fraction, stroke volume and cardiac output in HF patients, with minimal side effects. These findings were sometimes reinforced by subsequent meta-analyses, which further concluded that benefits tended to be greater in earlier stage HF. The main mechanisms involved are antioxidant, antinflammatory, anti-ischemic and antiaggregant effects. Evidence suggests that the supplementation with nutraceuticals may be a useful option for effective management of HF, with the advantage of excellent clinical tolerance. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Effect of low-carbohydrate diets high in either fat or protein on thyroid function, plasma insulin, glucose, and triglycerides in healthy young adults.

PubMed

Ullrich, I H; Peters, P J; Albrink, M J

1985-01-01

A low-carbohydrate diet, frequently used for treatment of reactive hypoglycemia, hypertriglyceridemia, and obesity may affect thyroid function. We studied the effects of replacing the deleted carbohydrate with either fat or protein in seven healthy young adults. Subjects were randomly assigned to receive seven days of each of two isocaloric liquid-formula, low-carbohydrate diets consecutively. One diet was high in polyunsaturated fat (HF), with 10%, 55%, and 35% of total calories derived from protein, fat, and carbohydrate, respectively. The other was high in protein (HP) with 35%, 30%, and 35% of total calories derived from protein, fat, and carbohydrate. Fasting blood samples were obtained at baseline and on day 8 of each diet. A meal tolerance test representative of each diet was given on day 7. The triiodothyronine (T3) declined more (P less than .05) following the HF diet than the HP diet (baseline 198 micrograms/dl, HP 138, HF 113). Thyroxine (T4) and reverse T3 (rT3) did not change significantly. Thyroid-stimulating hormone (TSH) declined equally after both diets. The insulin level was significantly higher 30 minutes after the HP meal (148 microU/ml) than after the HF meal (90 microU/ml). The two-hour glucose level for the HP meal was less, 85 mg/dl, than after the HF meal (103 mg/dl). Serum triglycerides decreased more after the HF diet (HF 52 mg/dl, HP 67 mg/dl). Apparent benefits of replacing carbohydrate with polyunsaturated fat rather than protein are less insulin response and less postpeak decrease in blood glucose and lower triglycerides. The significance of the lower T3 level is unknown.

Aerobic Exercise Training Prevents Heart Failure-Induced Skeletal Muscle Atrophy by Anti-Catabolic, but Not Anabolic Actions

PubMed Central

Souza, Rodrigo W. A.; Piedade, Warlen P.; Soares, Luana C.; Souza, Paula A. T.; Aguiar, Andreo F.; Vechetti-Júnior, Ivan J.; Campos, Dijon H. S.; Fernandes, Ana A. H.; Okoshi, Katashi; Carvalho, Robson F.; Cicogna, Antonio C.; Dal-Pai-Silva, Maeli

2014-01-01

Background Heart failure (HF) is associated with cachexia and consequent exercise intolerance. Given the beneficial effects of aerobic exercise training (ET) in HF, the aim of this study was to determine if the ET performed during the transition from cardiac dysfunction to HF would alter the expression of anabolic and catabolic factors, thus preventing skeletal muscle wasting. Methods and Results We employed ascending aortic stenosis (AS) inducing HF in Wistar male rats. Controls were sham-operated animals. At 18 weeks after surgery, rats with cardiac dysfunction were randomized to 10 weeks of aerobic ET (AS-ET) or to an untrained group (AS-UN). At 28 weeks, the AS-UN group presented HF signs in conjunction with high TNF-α serum levels; soleus and plantaris muscle atrophy; and an increase in the expression of TNF-α, NFκB (p65), MAFbx, MuRF1, FoxO1, and myostatin catabolic factors. However, in the AS-ET group, the deterioration of cardiac function was prevented, as well as muscle wasting, and the atrophy promoters were decreased. Interestingly, changes in anabolic factor expression (IGF-I, AKT, and mTOR) were not observed. Nevertheless, in the plantaris muscle, ET maintained high PGC1α levels. Conclusions Thus, the ET capability to attenuate cardiac function during the transition from cardiac dysfunction to HF was accompanied by a prevention of skeletal muscle atrophy that did not occur via an increase in anabolic factors, but through anti-catabolic activity, presumably caused by PGC1α action. These findings indicate the therapeutic potential of aerobic ET to block HF-induced muscle atrophy by counteracting the increased catabolic state. PMID:25330387

Cardiac support device (ASD) delivers bone marrow stem cells repetitively to epicardium has promising curative effects in advanced heart failure.

PubMed

Yue, Shizhong; Naveed, Muhammad; Gang, Wang; Chen, Dingding; Wang, Zhijie; Yu, Feng; Zhou, Xiaohui

2018-05-12

Ventricular restraint therapy is a non-transplant surgical option for the management of advanced heart failure (HF). To augment the therapeutic applications, it is hypothesized that ASD shows remarkable capabilities not only in delivering stem cells but also in dilated ventricles. Male SD rats were divided into four groups (n = 6): normal, HF, HF + ASD, and HF + ASD-BMSCs respectively. HF was developed by left anterior descending (LAD) coronary artery ligation in all groups except normal group. Post-infarcted electrocardiography (ECG) and brain natriuretic peptide (BNP) showed abnormal heart function in all model groups and HF + ASD-BMSCs group showed significant improvement as compared to other HF, HF + ASD groups on day 30. Masson's trichrome staining was used to study the histology, and a large blue fibrotic area has been observed in HF and HF + ASD groups and quantification of fibrosis was assessed. ASD-treated rats showed normal heart rhythm, demonstrated by smooth -ST and asymmetrical T-wave. The mechanical function of the heart such as left ventricular systolic pressure (LVSP), left ventricular end-diastolic pressure (LVEDP) and heart rate was brought to normal when treated with ASD-BMSCs. This effect was more prominent than that of ASD therapy alone. In comparison to HF group, the SD rats in HF + ASD-BMBCs group showed a significant decline in BNP levels. So ASD can deliver BMSCs to the cardiomyocytes successfully and broaden the therapeutic efficacy, in comparison to the restraint device alone. An effective methodology to manage the end-stage HF has been proved.

Central versus peripheral impact of estradiol on the impaired glucose metabolism in ovariectomized mice on a high-fat diet.

PubMed

Yonezawa, Rika; Wada, Tsutomu; Matsumoto, Natsumi; Morita, Mayuko; Sawakawa, Kanae; Ishii, Yoko; Sasahara, Masakiyo; Tsuneki, Hiroshi; Saito, Shigeru; Sasaoka, Toshiyasu

2012-08-15

Age-related loss of ovarian function promotes adiposity and insulin resistance in women. Estrogen (E(2)) directly enhances insulin sensitivity and suppresses lipogenesis in peripheral tissues. Recently, the central actions of E(2) in the regulation of energy homeostasis are becoming clearer; however, the functional relevance and degree of contribution of the central vs. peripheral actions of E(2) are currently unknown. Therefore, we prepared and analyzed four groups of mice. 1) CONTROL: sham-operated mice fed a regular diet, 2) OVX-HF: ovariectomized (OVX) mice fed a 60% high-fat diet (HF), 3) E2-SC: OVX-HF mice subcutaneously treated with E(2), and 4) E2-ICV: OVX-HF mice treated with E(2) intracerebroventricularly. OVX-HF mice showed increased body weight with both visceral and subcutaneous fat volume enlargement, glucose intolerance, and insulin resistance. Both E2-SC and E2-ICV equally ameliorated these abnormalities. Although the size of adipocytes and number of CD11c-positive macrophages in perigonadal fat in OVX-HF were reduced by both E(2) treatments, peripherally administered E(2) decreased the expression of TNFα, lipoprotein lipase, and fatty acid synthase in the white adipose tissue (WAT) of OVX-HF. In contrast, centrally administered E(2) increased hormone-sensitive lipase in WAT, decreased the hepatic expression of gluconeogenic enzymes, and elevated core body temperature and energy expenditure with marked upregulation of uncoupling proteins in the brown adipose tissue. These results suggest that central and peripheral actions of E(2) regulate insulin sensitivity and glucose metabolism via different mechanisms, and their coordinated effects may be important to prevent the development of obesity and insulin resistance in postmenopausal women.

First principles study of structural, electronic and optical properties of perovskites CaZrO3 and CaHfO3 in cubic phase

NASA Astrophysics Data System (ADS)

Hoat, D. M.; Silva, J. F. Rivas; Blas, A. Méndez

2018-07-01

In this work, we present the first principles calculations for structural, electronic and optical properties of perovskites CaZrO3 and CaHfO3 using the full-potential linearized augmented plane wave method (FP-LAPW) within the framework of density functional theory (DFT) as implemented in WIEN2k package. The exchange-correlation potential is treated with local density approximation (LDA) and generalized gradient approximation (GGA-PBE and PBESol). Additionally, the Tran Blaha modified Becke-Johnson exchange potential (mBJ) also is employed for electronic and optical calculations due to that it gives very accurate band gap of solids. Our obtained structural parameters are in good agreement with experimental datas and other theoretical results. The energy band gap obtained with mBJ is 4.56 eV for CaZrO3 and 5.27 eV for CaHfO3. The hybridization of states of O atom with those of Zr and Hf atoms in CaZrO3 and CaHfO3, respectively, is observed. The spin-orbit coupling effect on electronic properties of considered compounds also is investigated. Finally, the linear optical properties of CaZrO3 and CaHfO3 are derived from their complex dielectric function calculated with mBJ potential for wide energy range up to 45 eV, and all of them analyzed in details.

Tubular damage and worsening renal function in chronic heart failure.

PubMed

Damman, Kevin; Masson, Serge; Hillege, Hans L; Voors, Adriaan A; van Veldhuisen, Dirk J; Rossignol, Patrick; Proietti, Gianni; Barbuzzi, Savino; Nicolosi, Gian Luigi; Tavazzi, Luigi; Maggioni, Aldo P; Latini, Roberto

2013-10-01

This study sought to investigate the relationship between tubular damage and worsening renal function (WRF) in chronic heart failure (HF) BACKGROUND: WRF is associated with poor outcome in chronic HF. It is unclear whether urinary tubular markers may identify patients at risk for WRF. In 2,011 patients with chronic HF, we evaluated the ability of urinary tubular markers (N-acetyl-beta-d-glucosaminidase (NAG), kidney injury molecule (KIM)-1, and neutrophil gelatinase-associated lipocalin (NGAL) to predict WRF. Finally, we assessed the prognostic importance of WRF. A total of 290 patients (14.4%) experienced WRF during follow-up, and WRF was a strong and independent predictor of all-cause mortality and HF hospitalizations (hazard ratio [HR]: 2.87; 95% CI: 2.40 to 3.43; p < 0.001). Patients with WRF had lower baseline glomerular filtration rate and higher KIM-1, NAG, and NGAL levels. In a multivariable-adjusted model, KIM-1 was the strongest independent predictor of WRF (HR: 1.23; 95% CI: 1.09 to 1.39 per log increase; p = 0.001). WRF was associated with strongly impaired outcome in patients with chronic HF. Increased level of urinary KIM-1 was the strongest independent predictor of WRF and could therefore be used to identify patients at risk for WRF and poor clinical outcome. (GISSI-HF-Effects of n-3 PUFA and Rosuvastatin on Mortality-Morbidity of Patients With Symptomatic CHF; NCT00336336). Copyright © 2013 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Direct mapping between exchange potentials of Hartree-Fock and Kohn-Sham schemes as origin of orbital proximity

NASA Astrophysics Data System (ADS)

Cinal, M.

2010-01-01

It is found that for closed-l-shell atoms, the exact local exchange potential vx(r) calculated in the exchange-only Kohn-Sham (KS) scheme of the density functional theory (DFT) is very well represented within the region of every atomic shell by each of the suitably shifted potentials obtained with the nonlocal Fock exchange operator for the individual Hartree-Fock (HF) orbitals belonging to this shell. This newly revealed property is not related to the well-known steplike shell structure in the response part of vx(r), but it results from specific relations satisfied by the HF orbital exchange potentials. These relations explain the outstanding proximity of the occupied HF and exchange-only KS orbitals as well as the high quality of the Krieger-Li-Iafrate and localized HF (or, equivalently, common-energy-denominator) approximations to the DFT exchange potential vx(r). Another highly accurate representation of vx(r) is given by the continuous piecewise function built of shell-specific exchange potentials, each defined as the weighted average of the shifted orbital exchange potentials corresponding to a given shell. The constant shifts added to the HF orbital exchange potentials, to map them onto vx(r), are nearly equal to the differences between the energies of the corresponding KS and HF orbitals. It is discussed why these differences are positive and grow when the respective orbital energies become lower for inner orbitals.

Obesity and Heart Failure: Focus on the Obesity Paradox.

PubMed

Carbone, Salvatore; Lavie, Carl J; Arena, Ross

2017-02-01

The escalating prevalence of obesity has been linked to substantial increases in both metabolic and cardiovascular disease. Nevertheless, the direct effects of obesity on cardiovascular health and function require further exploration. In particular, the relationship between obesity and cardiac function has received intense scrutiny. Although obesity increases the risk for development of heart failure (HF), it appears to exert a protective effect in patients in whom HF has already been diagnosed (the "obesity paradox"). The protective effects of obesity in patients with previously diagnosed HF are the focus of particularly intense research. Several explanations have been proposed, but most studies are limited by the use of body mass index to classify obesity. Because body mass index does not distinguish between fat mass, fat-free mass, and lean mass, individuals with similar body mass indices may have vastly different body composition. This article discusses the roles of body composition, diet, cardiorespiratory fitness, and weight loss in the development of cardiac dysfunction and HF and the potential protective role that body composition compartments might play in improving HF prognosis. Based on an intensive literature search (Pubmed, Google Scholar) and critical review of the literature, we also discuss how a multidisciplinary approach including a nutritional intervention targeted to reduce systemic inflammation and lean mass-targeted exercise training could potentially exert beneficial effects for patients with HF. Copyright © 2016 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.

Mitochondrial ROS Drive Sudden Cardiac Death and Chronic Proteome Remodeling in Heart Failure.

PubMed

Dey, Swati; DeMazumder, Deeptankar; Sidor, Agnieszka; Foster, D B; O'Rourke, Brian

2018-06-13

Rationale: Despite increasing prevalence and incidence of heart failure (HF), therapeutic options remain limited. In early stages of HF, sudden cardiac death (SCD) from ventricular arrhythmias claims many lives. Reactive oxygen species (ROS) have been implicated in both arrhythmias and contractile dysfunction. However, little is known about how ROS in specific subcellular compartments contribute to HF or SCD pathophysiology. The role of ROS in chronic proteome remodeling has not been explored. Objective: We will test the hypothesis that elevated mitochondrial ROS (mROS) is a principal source of oxidative stress in HF and in vivo reduction of mROS mitigates SCD. Methods and Results: Using a unique guinea pig model of non-ischemic HF that recapitulates important features of human HF, including prolonged QT interval and high incidence of spontaneous arrhythmic SCD. Compartment-specific ROS sensors revealed increased mROS in resting and contracting left ventricular (LV) myocytes in failing hearts. Importantly, mitochondrially-targeted antioxidant (MitoTEMPO) normalized global cellular ROS. Further, in vivo MitoTEMPO treatment of HF animals prevented and reversed HF; eliminated SCD by decreasing dispersion of repolarization and ventricular arrhythmias; suppressed chronic HF-induced remodeling of the expression proteome; and prevented specific phosphoproteome alterations. Pathway analysis of mROS-sensitive networks indicated that increased mROS in HF disrupts the normal coupling between cytosolic signals and nuclear gene programs driving mitochondrial function, antioxidant enzymes, Ca2+ handling and action potential repolarization, suggesting new targets for therapeutic intervention. Conclusions: mROS drive both acute emergent events, such as electrical instability responsibly for SCD, and those that mediate chronic HF remodeling, characterized by suppression or altered phosphorylation of metabolic, antioxidant and ion transport protein networks. In vivo reduction of mROS prevents and reverses electrical instability, SCD and HF. Our findings support the feasibility of targeting the mitochondria as a potential new therapy for HF and SCD while identifying new mROS-sensitive protein modifications.

Kansas City Cardiomyopathy Questionnaire Score Is Associated With Incident Heart Failure Hospitalization in Patients With Chronic Kidney Disease Without Previously Diagnosed Heart Failure: Chronic Renal Insufficiency Cohort Study.

PubMed

Mishra, Rakesh K; Yang, Wei; Roy, Jason; Anderson, Amanda H; Bansal, Nisha; Chen, Jing; DeFilippi, Christopher; Delafontaine, Patrice; Feldman, Harold I; Kallem, Radhakrishna; Kusek, John W; Lora, Claudia M; Rosas, Sylvia E; Go, Alan S; Shlipak, Michael G

2015-07-01

Chronic kidney disease is a risk factor for heart failure (HF). Patients with chronic kidney disease without diagnosed HF have an increased burden of symptoms characteristic of HF. It is not known whether these symptoms are associated with occurrence of new onset HF. We studied the association of a modified Kansas City Cardiomyopathy Questionnaire with newly identified cases of hospitalized HF among 3093 participants enrolled in the Chronic Renal Insufficiency Cohort (CRIC) Study who did not report HF at baseline. The annually updated Kansas City Cardiomyopathy Questionnaire score was categorized into quartiles (Q1-4) with the lower scores representing the worse symptoms. Multivariable-adjusted repeated measure logistic regression models were adjusted for demographic characteristics, clinical risk factors for HF, N-terminal probrain natriuretic peptide level and left ventricular hypertrophy, left ventricular systolic and diastolic dysfunction. Over a mean (±SD) follow-up period of 4.3±1.6 years, there were 211 new cases of HF hospitalizations. The risk of HF hospitalization increased with increasing symptom quartiles; 2.62, 1.85, 1.14, and 0.74 events per 100 person-years, respectively. The median number of annual Kansas City Cardiomyopathy Questionnaire assessments per participant was 5 (interquartile range, 3-6). The annually updated Kansas City Cardiomyopathy Questionnaire score was independently associated with higher risk of incident HF hospitalization in multivariable-adjusted models (odds ratio, 3.30 [1.66-6.52]; P=0.001 for Q1 compared with Q4). Symptoms characteristic of HF are common in patients with chronic kidney disease and are associated with higher short-term risk for new hospitalization for HF, independent of level of kidney function, and other known HF risk factors. © 2015 American Heart Association, Inc.

Effects of nitrogen incorporation in HfO(2) grown on InP by atomic layer deposition: an evolution in structural, chemical, and electrical characteristics.

PubMed

Kang, Yu-Seon; Kim, Dae-Kyoung; Kang, Hang-Kyu; Jeong, Kwang-Sik; Cho, Mann-Ho; Ko, Dae-Hong; Kim, Hyoungsub; Seo, Jung-Hye; Kim, Dong-Chan

2014-03-26

We investigated the effects of postnitridation on the structural characteristics and interfacial reactions of HfO2 thin films grown on InP by atomic layer deposition (ALD) as a function of film thickness. By postdeposition annealing under NH3 vapor (PDN) at 600 °C, an InN layer formed at the HfO2/InP interface, and ionized NHx was incorporated in the HfO2 film. We demonstrate that structural changes resulting from nitridation of HfO2/InP depend on the film thickness (i.e., a single-crystal interfacial layer of h-InN formed at thin (2 nm) HfO2/InP interfaces, whereas an amorphous InN layer formed at thick (>6 nm) HfO2/InP interfaces). Consequently, the tetragonal structure of HfO2 transformed into a mixture structure of tetragonal and monoclinic because the interfacial InN layer relieved interfacial strain between HfO2 and InP. During postdeposition annealing (PDA) in HfO2/InP at 600 °C, large numbers of oxidation states were generated as a result of interfacial reactions between interdiffused oxygen impurities and out-diffused InP substrate elements. However, in the case of the PDN of HfO2/InP structures at 600 °C, nitrogen incorporation in the HfO2 film effectively blocked the out-diffusion of atomic In and P, thus suppressing the formation of oxidation states. Accordingly, the number of interfacial defect states (Dit) within the band gap of InP was significantly reduced, which was also supported by DFT calculations. Interfacial InN in HfO2/InP increased the electron-barrier height to ∼0.6 eV, which led to low-leakage-current density in the gate voltage region over 2 V.

Potential Protective Mechanism in the Cardiac Microvascular Injury.

PubMed

Li, Xiuchuan; Hou, Juanni; Du, Jin; Feng, Jian; Yang, Yi; Shen, Yang; Chen, Sha; Feng, Juan; Yang, Dachun; Li, De; Pei, Haifeng; Yang, Yongjian

2018-05-07

Cardiac microvascular injury often occurs in patients with type 2 diabetes mellitus (T2DM) who develop hyperglycemia and hyperlipidemia. However, besides reported contradictory roles in cardiac diseases, the function of TRPV1 (transient receptor potential vanilloid 1) in cardiac microvessels is not well defined. This study was performed to determine the detailed role of TRPV1 in cardiac microvascular endothelial cells (CMECs) in T2DM. T2DM mice were established by multiple injections of low-dose streptozotocin and high-fat feeding. CMECs were cultured separately in mediums of normal glucose, high glucose (HG), high fatty acid (HF), and HG plus HF (HG-HF). HG-HF inhibited TRPV1 expression in CMECs, reducing cellular Ca 2+ content ([Ca 2+ ] i ). T2DM impaired cardiac function, disturbed glucose uptake, and damaged microvascular barrier, which were further aggravated by TRPV1 -/- Exposure to HG-HF, particularly in TRPV1 -/- CMECs, led to a higher level of apoptosis and a lower level of nitric oxide production in viable CMECs. HG-HF markedly enhanced generation of reactive oxygen species and nitrotyrosine, especially in the absence of TRPV1. H 2 O 2 administration reduced TRPV1 expression in CMECs. HG-HF significantly depressed expression of PGC-1α (peroxisome proliferator-activated receptor-γ coactivator-1α) and OPA1 (optic atrophy 1) by reducing [Ca 2+ ] i , whereas OPA1 supplementation partly reversed those detrimental effects induced by TRPV1 -/- Furthermore, capsaicin treatment not only attenuated CMECs injury induced by HG-HF but also mitigated cardiac microvascular injury induced by T2DM. Collectively, T2DM leads to cardiac microvascular injury by exacerbating the vicious circle of TRPV1 blockage and reactive oxygen species overload. Long-term capsaicin can protect cardiac microvessels against T2DM via suppressing oxidative/nitrative stress mediated by TRPV1/Ca 2+ /PGC-1α/OPA1 pathway in CMECs. © 2018 American Heart Association, Inc.

Brief exposure to obesogenic diet disrupts brain dopamine networks

PubMed Central

Williams, Jason M.; Siuta, Michael A.; Tantawy, Mohammed N.; Speed, Nicole K.; Saunders, Christine; Galli, Aurelio; Niswender, Kevin D.; Avison, Malcolm J.

2018-01-01

Objective We have previously demonstrated that insulin signaling, through the downstream signaling kinase Akt, is a potent modulator of dopamine transporter (DAT) activity, which fine-tunes dopamine (DA) signaling at the synapse. This suggests a mechanism by which impaired neuronal insulin receptor signaling, a hallmark of diet-induced obesity, may contribute to impaired DA transmission. We tested whether a short-term (two-week) obesogenic high-fat (HF) diet could reduce striatal Akt activity, a marker of central insulin, receptor signaling and blunt striatal and dopaminergic network responsiveness to amphetamine (AMPH). Methods We examined the effects of a two-week HF diet on striatal DAT activity in rats, using AMPH as a probe in a functional magnetic resonance imaging (fMRI) assay, and mapped the disruption in AMPH-evoked functional connectivity between key dopaminergic targets and their projection areas using correlation and permutation analyses. We used phosphorylation of the Akt substrate GSK3α in striatal extracts as a measure of insulin receptor signaling. Finally, we confirmed the impact of HF diet on striatal DA D2 receptor (D2R) availability using [18F]fallypride positron emission tomography (PET). Results We found that rats fed a HF diet for only two weeks have reductions in striatal Akt activity, a marker of decreased striatal insulin receptor signaling and blunted striatal responsiveness to AMPH. HF feeding also reduced interactions between elements of the mesolimbic (nucleus accumbens–anterior cingulate) and sensorimotor circuits (caudate/putamen–thalamus–sensorimotor cortex) implicated in hedonic feeding. D2R availability was reduced in HF-fed animals. Conclusion These studies support the hypothesis that central insulin signaling and dopaminergic neurotransmission are already altered after short-term HF feeding. Because AMPH induces DA efflux and brain activation, in large part via DAT, these findings suggest that blunted central nervous system insulin receptor signaling through a HF diet can impair DA homeostasis, thereby disrupting cognitive and reward circuitry involved in the regulation of hedonic feeding. PMID:29698491

The Relationship between Serum Zinc Level and Heart Failure: A Meta-Analysis

PubMed Central

Yu, Xuefang; Huang, Lei; Zhao, Jinyan; Wang, Zhuoqun; Yao, Wei; Wu, Xianming; Huang, Jingjing

2018-01-01

Zinc is essential for the maintenance of normal cellular structure and functions. Zinc dyshomeostasis can lead to many diseases, such as cardiovascular disease. However, there are conflicting reports on the relationship between serum zinc levels and heart failure (HF). The purpose of the present study is to explore the relationship between serum zinc levels and HF by using a meta-analysis approach. PubMed, Web of Science, and OVID databases were searched for reports on the association between serum zinc levels and HF until June 2016. 12 reports with 1453 subjects from 27 case-control studies were chosen for the meta-analysis. Overall, the pooled analysis indicated that patients with HF had lower zinc levels than the control subjects. Further subgroup analysis stratified by different geographic locations also showed that HF patients had lower zinc levels than the control subjects. In addition, subgroup analysis stratified by HF subgroups found that patients with idiopathic dilated cardiomyopathy (IDCM) had lower zinc levels than the control subjects, except for patients with ischemic cardiomyopathy (ICM). In conclusion, the results of the meta-analysis indicate that there is a significant association between low serum zinc levels and HF. PMID:29682528

Hydraulic fracture height limits and fault interactions in tight oil and gas formations

NASA Astrophysics Data System (ADS)

Flewelling, Samuel A.; Tymchak, Matthew P.; Warpinski, Norm

2013-07-01

widespread use of hydraulic fracturing (HF) has raised concerns about potential upward migration of HF fluid and brine via induced fractures and faults. We developed a relationship that predicts maximum fracture height as a function of HF fluid volume. These predictions generally bound the vertical extent of microseismicity from over 12,000 HF stimulations across North America. All microseismic events were less than 600 m above well perforations, although most were much closer. Areas of shear displacement (including faults) estimated from microseismic data were comparatively small (radii on the order of 10 m or less). These findings suggest that fracture heights are limited by HF fluid volume regardless of whether the fluid interacts with faults. Direct hydraulic communication between tight formations and shallow groundwater via induced fractures and faults is not a realistic expectation based on the limitations on fracture height growth and potential fault slip.

Polymorphic SVA retrotransposons at four loci and their association with classical HLA class I alleles in Japanese, Caucasians and African Americans.

PubMed

Kulski, Jerzy K; Shigenari, Atsuko; Inoko, Hidetoshi

2010-04-01

Polymorphic insertion frequencies of the retrotransposons known as the "SVA" elements were investigated at four loci in the MHC class I genomic region to determine their allele and haplotype frequencies and associations with the HLA-A, -B or -C genes for 100 Japanese, 100 African Americans, 174 Australian Caucasians and 66 reference cell lines obtained from different ethnic groups. The SVA insertions representing different subfamily members varied in frequency between none for SVA-HF in Japanese and 65% for SVA-HB in Caucasians or African Americans with significant differences in frequencies between the three populations at least at three loci. The SVA loci were in Hardy-Weinberg equilibrium except for the SVA-HA locus which deviated significantly in African Americans and Caucasians possibly because of a genomic deletion of this locus in individuals with the HLA-A*24 allele. Strong linkage disequilibria and high percentage associations between the human leucocyte antigen (HLA) class I gene alleles and some of the SVA insertions were detected in all three populations in spite of significant frequency differences for the SVA and HLA class I alleles between the three populations. The highest percentage associations (>86%) were between SVA-HB and HLA-B*08, -B*27, -B*37 to -B*41, -B*52 and -B*53; SVA-HC and HLA-B*07; SVA-HA and HLA-A*03, -A*11 and -A*30; and SVA-HF and HLA-A*03 and HLA-B*47. From pairwise associations in the three populations and the homozygous cell line results, it was possible to deduce the SVA and HLA class I allelic combinations (haplotypes), population differences and the identity by descent of several common HLA-A allelic lineages.

Update on SGLT2 Inhibitors-New Data Released at the American Diabetes Association.

PubMed

Lee, Sara

2017-09-01

Sodium-glucose cotransporter 2 (SGLT2) inhibitors are one of the newer classes of antiglycemic agents approved for the management of patients with type 2 diabetes mellitus. Due to their unique mechanism of action, SGLT2 inhibitors have shown to be beneficial beyond glucose control. The improvement in cardiovascular (CV) outcomes was first observed in the landmark EMPA-REG OUTCOMES study. Following these results, numerous CV outcome trials were designed to identify whether the beneficial CV and renal effects observed with empagliflozin are unique or a drug class effect. The benefit of SGLT2 inhibition was confirmed by the CANagliflozin cardioVascular Assessment Study (CANVAS) Program, presented at the American Diabetes Association 77th Scientific Sessions. With over 10,000 patients, the CANVAS Program integrated data from two large CV outcome studies. Canagliflozin achieved a 14% reduction in the composite endpoint of CV mortality, nonfatal myocardial infarction (MI), or nonfatal stroke, and a 33% reduction in the risk of hospitalization for heart failure (HF) compared with placebo. Potential renal protective effects were also observed with canagliflozin; however, an increased risk of amputation with canagliflozin was seen in both CANVAS studies. The class effect of SGLT2 inhibitors was also confirmed in new analyses of the The Comparative Effectiveness of Cardiovascular Outcomes (CVD-REAL) study, which aimed to evaluate SGLT2 inhibitors (dapagliflozin, canagliflozin, and empagliflozin) in broader patient populations with type 2 diabetes mellitus. In patients who were new to SGLT2 inhibitors, significant reductions in rates of CV death and hospitalization for HF were observed compared with any other glucose-lowering agents. SGLT2 inhibitors were also associated with lower rates in hospitalization for HF in patients with and without CV disease. In addition, substudies of the EMPA-REG OUTCOME trial further provided insight on the efficacy of empagliflozin across categories of adjusted control of blood pressure, low-density lipoprotein cholesterol, and hemoglobin A1c (HbA1c) over time.

Halofuginone alleviates acute viral myocarditis in suckling BALB/c mice by inhibiting TGF-β1

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sun, Xiao-Hua; Fu, Jia; Sun, Da-Qing, E-mail: daqingsuncd@163.com

2016-04-29

Viral myocarditis (VMC) is an inflammation of heart muscle in infants and young adolescents. This study explored the function of halofuginone (HF) in Coxsackievirus B3 (CVB3) -treated suckling mice. HF-treated animal exhibited higher survival rate, lower heart/body weight, and more decreased blood sugar concentration than CVB3 group. HF also reduced the expressions of interleukin(IL)-17 and IL-23 and the numbers of Th17 cells. Moreover, HF downregulated pro-inflammatory cytokine levels and increased anti-inflammatory cytokine levels. The expressions of transforming growth factor(TGF-β1) and nuclear factor kappa-light-chain-enhancer of activated B (NF-κB) p65/ tumor necrosis factor-α (TNF-α) proteins were decreased by HF as well. Finally,more » the overexpression of TGF-β1 counteracted the protection effect of HF in CVB3-treated suckling mice. In summary, our study suggests HF increases the survival of CVB3 suckling mice, reduces the Th17 cells and pro-inflammatory cytokine levels, and may through downregulation of the TGF-β1-mediated expression of NF-κB p65/TNF-α pathway proteins. These results offer a potential therapeutic strategy for the treatment of VMC. - Highlights: • Halofuginone (HF) increases the survival of suckling BALB/c mice infected with acute CVB3. • HF reduces the expression of Th17 cell markers (IL-17 and IL-23) and the number of CD4{sup +} IL17{sup +} cells. • Pro-inflammatory cytokines levels associated with myocarditis were reduced by HF in CVB3-treated suckling mice. • HF alleviates VMC via inhibition of TGF-β1-mediated NF-κB p65/TNF-α pathway.« less

Contemporary strategies in the diagnosis and management of heart failure.

PubMed

Dunlay, Shannon M; Pereira, Naveen L; Kushwaha, Sudhir S

2014-05-01

Heart failure (HF) is an important public health problem, and strategies are needed to improve outcomes and decrease health care resource utilization and costs. Its prevalence has increased as the population ages, and HF continues to be associated with a high mortality rate and frequent need for hospitalization. The total cost of care for patients with HF was $30.7 billion in 2012, and it is estimated to more than double to $69.8 billion by 2030. Given this reality, there has been recent investigation into ways of identifying and preventing HF in patients at risk (stage A HF) and those with cardiac structural and functional abnormalities but no clinical HF symptoms (stage B). For patients who have symptoms of HF (stage C), there has been important research into the most effective ways to decongest patients hospitalized with acute decompensated HF and prevent future hospital readmissions. Successful strategies to treat patients with HF and preserved ejection fraction, which has increased in prevalence, continue to be sought. We are in the midst of a rapid evolution in our ability to care for patients with end-stage HF (stage D) because of the introduction of and improvements in mechanical circulatory support. Left ventricular assist devices used as destination therapy offer an important therapeutic option to patients who do not qualify for heart transplant because of advanced age or excessive comorbidity. This review provides a thorough update on contemporary strategies in the diagnosis and management of HF by stage (A to D) that have emerged during the past several years. Copyright © 2014 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.

Aquapheresis Versus Intravenous Diuretics and Hospitalizations for Heart Failure.

PubMed

Costanzo, Maria Rosa; Negoianu, Daniel; Jaski, Brian E; Bart, Bradley A; Heywood, James T; Anand, Inder S; Smelser, James M; Kaneshige, Alan M; Chomsky, Don B; Adler, Eric D; Haas, Garrie J; Watts, James A; Nabut, Jose L; Schollmeyer, Michael P; Fonarow, Gregg C

2016-02-01

The AVOID-HF (Aquapheresis versus Intravenous Diuretics and Hospitalization for Heart Failure) trial tested the hypothesis that patients hospitalized for HF treated with adjustable ultrafiltration (AUF) would have a longer time to first HF event within 90 days after hospital discharge than those receiving adjustable intravenous loop diuretics (ALD). Congestion in hospitalized heart failure (HF) patients portends unfavorable outcomes. The AVOID-HF trial, designed as a multicenter, 1-to-1 randomized study of 810 hospitalized HF patients, was terminated unilaterally and prematurely by the sponsor (Baxter Healthcare, Deerfield, Illinois) after enrollment of 224 patients (27.5%). Aquadex FlexFlow System (Baxter Healthcare) was used for AUF. A Clinical Events Committee, blinded to the randomized treatment, adjudicated whether 90-day events were due to HF. A total of 110 patients were randomized to AUF and 114 to ALD. Baseline characteristics were similar. Estimated days to first HF event for the AUF and ALD group were, respectively, 62 and 34 (p = 0.106). At 30 days, compared with the ALD group, the AUF group had fewer HF and cardiovascular events. Renal function changes were similar. More AUF patients experienced an adverse effect of special interest (p = 0.018) and a serious study product-related adverse event (p = 0.026). The 90-day mortality was similar. Compared with the ALD group, the AUF group trended toward a longer time to first HF event within 90 days and fewer HF and cardiovascular events. More patients in the AUF group experienced special interest or serious product-related adverse event. Due to the trial's untimely termination, additional AUF investigation is warranted. Copyright © 2016 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Effects of High-Frequency Repetitive Transcranial Magnetic Stimulation Combined with Task-Oriented Mirror Therapy Training on Hand Rehabilitation of Acute Stroke Patients.

PubMed

Kim, Jinhong; Yim, Jongeun

2018-02-06

BACKGROUND Impairments of hand function make it difficult to perform daily life activities and to return to work. The aim of this study was to investigate the effect of high-frequency repetitive transcranial magnetic stimulation (HF-rTMS) combined with task-oriented mirror therapy (TOMT) on hand rehabilitation in acute stroke patients. MATERIAL AND METHODS Twenty subacute stroke patients in the initial stages (<3 months) participated in the study. Subjects were allocated to 2 groups: the experimental group received HF-rTMS + TOMT and the control group received HF-rTMS. TOMT training was conducted in 10 sessions over 2 weeks for 30 min. rTMS was applied at a 20 Hz frequency over the hand motor area in the cortex of the affected hemisphere for 15 min. Outcomes, including motor-evoked potential (MEP), pinch grip, hand grip, and box and block test, were measured before and after training. RESULTS Significant improvements in the MEP and hand function variables were observed in both groups (p<0.05). In particular, hand functions (pinch grip and box and block test) were significantly different between the 2 groups (p<0.05). CONCLUSIONS HF-rTMS combined with TOMT had a positive effect on hand function and can be used for the rehabilitation of precise hand movements in acute stroke patients.

Left-Hemispheric Microstructural Abnormalities in Children With High Functioning Autism Spectrum Disorder

PubMed Central

Peterson, Daniel; Mahajan, Rajneesh; Crocetti, Deana; Mejia, Amanda; Mostofsky, Stewart

2014-01-01

Current theories of the neurobiological basis of Autism Spectrum Disorder (ASD) posit an altered pattern of connectivity in large-scale brain networks. Here we used Diffusion Tensor Imaging to investigate the microstructural properties of the white matter that mediates inter-regional connectivity in 36 high-functioning children with ASD (HF-ASD), as compared to 37 controls. By employing an atlas-based analysis using LDDMM registration, a widespread, but left-lateralized pattern of abnormalities was revealed. The Mean Diffusivity (MD) of water in the white matter of HF-ASD children was significantly elevated throughout the left hemisphere, particularly in the outer-zone cortical white matter. Across diagnostic groups there was a significant effect of age on left hemisphere MD, with a similar reduction in MD during childhood in both TD and HF-ASD children. The increased MD in children with HF-ASD suggests hypomyelination, and may reflect increased short-range cortico-cortical connections subsequent to early white matter overgrowth. These findings also highlight left hemispheric connectivity as relevant to the pathophysiology of ASD, and indicate that the spatial distribution of microstructural abnormalities in HF-ASD is widespread, and left-lateralized. This altered left-hemispheric connectivity may contribute to deficits in communication and praxis observed in ASD. PMID:25256103

Mediterranean Diet and Other Dietary Patterns in Primary Prevention of Heart Failure and Changes in Cardiac Function Markers: A Systematic Review.

PubMed

Sanches Machado d'Almeida, Karina; Ronchi Spillere, Stefanny; Zuchinali, Priccila; Corrêa Souza, Gabriela

2018-01-10

Heart failure (HF) is a complex syndrome and is recognized as the ultimate pathway of cardiovascular disease (CVD). Studies using nutritional strategies based on dietary patterns have proved to be effective for the prevention and treatment of CVD. Although there are studies that support the protective effect of these diets, their effects on the prevention of HF are not clear yet. We searched the Medline, Embase, and Cochrane databases for studies that examined dietary patterns, such as dietary approaches to stop hypertension (DASH diet), paleolithic, vegetarian, low-carb and low-fat diets and prevention of HF. No limitations were used during the search in the databases. A total of 1119 studies were identified, 14 met the inclusion criteria. Studies regarding the Mediterranean, DASH, vegetarian, and Paleolithic diets were found. The Mediterranean and DASH diets showed a protective effect on the incidence of HF and/or worsening of cardiac function parameters, with a significant difference in relation to patients who did not adhere to these dietary patterns. It is observed that the adoption of Mediterranean or DASH-type dietary patterns may contribute to the prevention of HF, but these results need to be analyzed with caution due to the low quality of evidence.

Bilateral Renal Denervation Ameliorates Isoproterenol-Induced Heart Failure through Downregulation of the Brain Renin-Angiotensin System and Inflammation in Rat

PubMed Central

Li, Jian-Dong; Cheng, Ai-Yuan; Huo, Yan-Li; Fan, Jie; Zhang, Yu-Ping; Fang, Zhi-Qin; Sun, Hong-Sheng; Peng, Wei; Zhang, Jin-Shun

2016-01-01

Heart failure (HF) is characterized by cardiac dysfunction along with autonomic unbalance that is associated with increased renin-angiotensin system (RAS) activity and elevated levels of proinflammatory cytokines (PICs). Renal denervation (RD) has been shown to improve cardiac function in HF, but the protective mechanisms remain unclear. The present study tested the hypothesis that RD ameliorates isoproterenol- (ISO-) induced HF through regulation of brain RAS and PICs. Chronic ISO infusion resulted in remarked decrease in blood pressure (BP) and increase in heart rate and cardiac dysfunction, which was accompanied by increased BP variability and decreased baroreflex sensitivity and HR variability. Most of these adverse effects of ISO on cardiac and autonomic function were reversed by RD. Furthermore, ISO upregulated mRNA and protein expressions of several components of the RAS and PICs in the lamina terminalis and hypothalamic paraventricular nucleus, two forebrain nuclei involved in cardiovascular regulations. RD significantly inhibited the upregulation of these genes. Either intracerebroventricular AT1-R antagonist, irbesartan, or TNF-α inhibitor, etanercept, mimicked the beneficial actions of RD in the ISO-induced HF. The results suggest that the RD restores autonomic balance and ameliorates ISO-induced HF and that the downregulated RAS and PICs in the brain contribute to these beneficial effects of RD. PMID:27746855

Metabolic remodeling of substrate utilization during heart failure progression.

PubMed

Chen, Liang; Song, Jiangping; Hu, Shengshou

2018-05-23

Heart failure (HF) is a clinical syndrome caused by a decline in cardiac systolic or diastolic function, which leaves the heart unable to pump enough blood to meet the normal physiological requirements of the human body. It is a serious disease burden worldwide affecting nearly 23 million patients. The concept that heart failure is "an engine out of fuel" has been generally accepted and metabolic remodeling has been recognized as an important aspect of this condition; it is characterized by defects in energy production and changes in metabolic pathways involved in the regulation of essential cellular functions such as the process of substrate utilization, the tricarboxylic acid cycle, oxidative phosphorylation, and high-energy phosphate metabolism. Advances in second-generation sequencing, proteomics, and metabolomics have made it possible to perform comprehensive tests on genes and metabolites that are crucial in the process of HF, thereby providing a clearer and comprehensive understanding of metabolic remodeling during HF. In recent years, new metabolic changes such as ketone bodies and branched-chain amino acids were demonstrated as alternative substrates in end-stage HF. This systematic review focuses on changes in metabolic substrate utilization during the progression of HF and the underlying regulatory mechanisms. Accordingly, the conventional concepts of metabolic remodeling characteristics are reviewed, and the latest developments, particularly multi-omics studies, are compiled.

Mediterranean Diet and Other Dietary Patterns in Primary Prevention of Heart Failure and Changes in Cardiac Function Markers: A Systematic Review

PubMed Central

Sanches Machado d’Almeida, Karina; Ronchi Spillere, Stefanny; Zuchinali, Priccila; Corrêa Souza, Gabriela

2018-01-01

Background: Heart failure (HF) is a complex syndrome and is recognized as the ultimate pathway of cardiovascular disease (CVD). Studies using nutritional strategies based on dietary patterns have proved to be effective for the prevention and treatment of CVD. Although there are studies that support the protective effect of these diets, their effects on the prevention of HF are not clear yet. Methods: We searched the Medline, Embase, and Cochrane databases for studies that examined dietary patterns, such as dietary approaches to stop hypertension (DASH diet), paleolithic, vegetarian, low-carb and low-fat diets and prevention of HF. No limitations were used during the search in the databases. Results: A total of 1119 studies were identified, 14 met the inclusion criteria. Studies regarding the Mediterranean, DASH, vegetarian, and Paleolithic diets were found. The Mediterranean and DASH diets showed a protective effect on the incidence of HF and/or worsening of cardiac function parameters, with a significant difference in relation to patients who did not adhere to these dietary patterns. Conclusions: It is observed that the adoption of Mediterranean or DASH-type dietary patterns may contribute to the prevention of HF, but these results need to be analyzed with caution due to the low quality of evidence. PMID:29320401

Increasing exercise capacity and quality of life of patients with heart failure through Wii gaming: the rationale, design and methodology of the HF-Wii study; a multicentre randomized controlled trial.

PubMed

Jaarsma, Tiny; Klompstra, Leonie; Ben Gal, Tuvia; Boyne, Josiane; Vellone, Ercole; Bäck, Maria; Dickstein, Kenneth; Fridlund, Bengt; Hoes, Arno; Piepoli, Massimo F; Chialà, Oronzo; Mårtensson, Jan; Strömberg, Anna

2015-07-01

Exercise is known to be beneficial for patients with heart failure (HF), and these patients should therefore be routinely advised to exercise and to be or to become physically active. Despite the beneficial effects of exercise such as improved functional capacity and favourable clinical outcomes, the level of daily physical activity in most patients with HF is low. Exergaming may be a promising new approach to increase the physical activity of patients with HF at home. The aim of this study is to determine the effectiveness of the structured introduction and access to a Wii game computer in patients with HF to improve exercise capacity and level of daily physical activity, to decrease healthcare resource use, and to improve self-care and health-related quality of life. A multicentre randomized controlled study with two treatment groups will include 600 patients with HF. In each centre, patients will be randomized to either motivational support only (control) or structured access to a Wii game computer (Wii). Patients in the control group will receive advice on physical activity and will be contacted by four telephone calls. Patients in the Wii group also will receive advice on physical activity along with a Wii game computer, with instructions and training. The primary endpoint will be exercise capacity at 3 months as measured by the 6 min walk test. Secondary endpoints include exercise capacity at 6 and 12 months, level of daily physical activity, muscle function, health-related quality of life, and hospitalization or death during the 12 months follow-up. The HF-Wii study is a randomized study that will evaluate the effect of exergaming in patients with HF. The findings can be useful to healthcare professionals and improve our understanding of the potential role of exergaming in the treatment and management of patients with HF. NCT01785121. © 2015 The Authors. European Journal of Heart Failure © 2015 European Society of Cardiology.

Music Improves Subjective Feelings Leading to Cardiac Autonomic Nervous Modulation: A Pilot Study

PubMed Central

Kume, Satoshi; Nishimura, Yukako; Mizuno, Kei; Sakimoto, Nae; Hori, Hiroshi; Tamura, Yasuhisa; Yamato, Masanori; Mitsuhashi, Rika; Akiba, Keigo; Koizumi, Jun-ichi; Watanabe, Yasuyoshi; Kataoka, Yosky

2017-01-01

It is widely accepted that listening to music improves subjective feelings and reduces fatigue sensations, and different kinds of music lead to different activations of these feelings. Recently, cardiac autonomic nervous modulation has been proposed as a useful objective indicator of fatigue. However, scientific considerations of the relation between feelings of fatigue and cardiac autonomic nervous modulation while listening to music are still lacking. In this study, we examined which subjective feelings of fatigue are related to participants' cardiac autonomic nervous function while they listen to music. We used an album of comfortable and relaxing environmental music, with blended sounds from a piano and violin as well as natural sound sources. We performed a crossover trial of environmental music and silent sessions for 20 healthy subjects, 12 females, and 8 males, after their daily work shift. We measured changes in eight types of subjective feelings, including healing, fatigue, sleepiness, relaxation, and refreshment, using the KOKORO scale, a subjective mood measurement system for self-reported feelings. Further, we obtained measures of cardiac autonomic nervous function on the basis of heart rate variability before and after the sessions. During the music session, subjective feelings significantly shifted toward healing and a secure/relaxed feeling and these changes were greater than those in the silent session. Heart rates (ΔHR) in the music session significantly decreased compared with those in the silent session. Other cardiac autonomic parameters such as high-frequency (HF) component and the ratio of low-frequency (LF) and HF components (LF/HF) were similar in the two sessions. In the linear regression analysis of the feelings with ΔHR and changes in LF/HF (ΔLF/HF), increases and decreases in ΔHR were correlated to the feeling axes of Fatigue-Healing and Anxiety/Tension–Security/Relaxation, whereas those in ΔLF/HF were related to the feeling axes of Sleepiness–Wakefulness and Gloomy–Refreshed. This indicated that listening to music improved the participants' feelings of fatigue and decreased their heart rates. However, it did not reduce the cardiac LF/HF, suggesting that cardiac LF/HF might show a delayed response to fatigue. Thus, we demonstrated changes in cardiac autonomic nervous functions based on feelings of fatigue. PMID:28344545

Music Improves Subjective Feelings Leading to Cardiac Autonomic Nervous Modulation: A Pilot Study.

PubMed

Kume, Satoshi; Nishimura, Yukako; Mizuno, Kei; Sakimoto, Nae; Hori, Hiroshi; Tamura, Yasuhisa; Yamato, Masanori; Mitsuhashi, Rika; Akiba, Keigo; Koizumi, Jun-Ichi; Watanabe, Yasuyoshi; Kataoka, Yosky

2017-01-01

It is widely accepted that listening to music improves subjective feelings and reduces fatigue sensations, and different kinds of music lead to different activations of these feelings. Recently, cardiac autonomic nervous modulation has been proposed as a useful objective indicator of fatigue. However, scientific considerations of the relation between feelings of fatigue and cardiac autonomic nervous modulation while listening to music are still lacking. In this study, we examined which subjective feelings of fatigue are related to participants' cardiac autonomic nervous function while they listen to music. We used an album of comfortable and relaxing environmental music, with blended sounds from a piano and violin as well as natural sound sources. We performed a crossover trial of environmental music and silent sessions for 20 healthy subjects, 12 females, and 8 males, after their daily work shift. We measured changes in eight types of subjective feelings, including healing, fatigue, sleepiness, relaxation, and refreshment, using the KOKORO scale, a subjective mood measurement system for self-reported feelings. Further, we obtained measures of cardiac autonomic nervous function on the basis of heart rate variability before and after the sessions. During the music session, subjective feelings significantly shifted toward healing and a secure/relaxed feeling and these changes were greater than those in the silent session. Heart rates (ΔHR) in the music session significantly decreased compared with those in the silent session. Other cardiac autonomic parameters such as high-frequency (HF) component and the ratio of low-frequency (LF) and HF components (LF/HF) were similar in the two sessions. In the linear regression analysis of the feelings with ΔHR and changes in LF/HF (ΔLF/HF), increases and decreases in ΔHR were correlated to the feeling axes of Fatigue-Healing and Anxiety/Tension-Security/Relaxation, whereas those in ΔLF/HF were related to the feeling axes of Sleepiness-Wakefulness and Gloomy-Refreshed. This indicated that listening to music improved the participants' feelings of fatigue and decreased their heart rates. However, it did not reduce the cardiac LF/HF, suggesting that cardiac LF/HF might show a delayed response to fatigue. Thus, we demonstrated changes in cardiac autonomic nervous functions based on feelings of fatigue.

Schematic and realistic biological motion identification in children with high-functioning autism spectrum disorder

PubMed Central

Wright, Kristyn; Kelley, Elizabeth; Poulin-Dubois, Diane

2014-01-01

Research investigating biological motion perception in children with ASD has revealed conflicting findings concerning whether impairments in biological motion perception exist. The current study investigated how children with high-functioning ASD (HF-ASD) performed on two tasks of biological motion identification: a novel schematic motion identification task and a point-light biological motion identification task. Twenty-two HFASD children were matched with 21 TD children on gender, non-verbal mental, and chronological, age (M years = 6.72). On both tasks, HF-ASD children performed with similar accuracy as TD children. Across groups, children performed better on animate than on inanimate trials of both tasks. These findings suggest that HF-ASD children's identification of both realistic and schematic biological motion identification is unimpaired. PMID:25395988

Iron deficiency and heart failure: diagnostic dilemmas and therapeutic perspectives

PubMed Central

Jankowska, Ewa A.; von Haehling, Stephan; Anker, Stefan D.; Macdougall, Iain C.; Ponikowski, Piotr

2013-01-01

Iron is a micronutrient essential for cellular energy and metabolism, necessary for maintaining body homoeostasis. Iron deficiency is an important co-morbidity in patients with heart failure (HF). A major factor in the pathogenesis of anaemia, it is also a separate condition with serious clinical consequences (e.g. impaired exercise capacity) and poor prognosis in HF patients. Experimental evidence suggests that iron therapy in iron-deficient animals may activate molecular pathways that can be cardio-protective. Clinical studies have demonstrated favourable effects of i.v. iron on the functional status, quality of life, and exercise capacity in HF patients. It is hypothesized that i.v. iron supplementation may become a novel therapy in HF patients with iron deficiency. PMID:23100285

Cardiac autonomic activity has a circadian rhythm in summer but not in winter in non-lactating pregnant dairy cows.

PubMed

Kovács, Levente; Kézér, Fruzsina Luca; Ruff, Ferenc; Szenci, Ottó

2016-03-01

This investigation was conducted to examine circadian and seasonal rhythms of heart rate and heart rate variability (HRV) by means of hour-by-hour recordings over 24h in a large population of non-lactating Holstein-Friesian pregnant cows [N=56, summer (June-July); N=61, winter (November-December)]. Data were collected during a 5-day period from each animal. Besides parameters of cardiac autonomic function [the high-frequency (HF) component of HRV and the ratio between the low-frequency (LF) and the HF components (LF/HF ratio)], the RR triangular index and Lmax were calculated. A clear circadian profile was observed for every parameter in summer. Heart rate elevated gradually with the course of the day from 7:00 to 17:00 o'clock and then slightly decreased from 18:00 to 6:00. Sympathovagal balance shifted towards sympathetic dominance during the daytime (increased LF/HF ratio), whereas parasympathetic activity was predominant during the night (increased HF). Lmax reflected a chaotic behavior of heart rate fluctuations during the afternoon in summer. Decreased values of RR triangular index indicated a sensitive period for cows between 14:00 and 16:00 o'clock in summer. During winter, except for the RR triangular (RRtri) index reflecting a high overall variability in R-R intervals between 12:00 and 23:00 o'clock, heart rate and HRV showed no periodicity over the 24-h period. The results suggest an impaired cardiac autonomic function during daytime in summer. HF, Lmax and RRtri index showed seasonal differences for both daytime and nighttime. Heart rate was higher in summer than in winter during the daytime, whereas the LF/HF ratio was higher in winter during the nighttime. Circadian and seasonal rhythms of cardiovascular function are presumably related to the differing temperature, and animal activity associated with summer and winter. As all of the investigated parameters are commonly used in bovine HRV research, these findings have practical implications for behavioral, physiological and welfare studies on dairy cattle. Copyright © 2015 Elsevier Inc. All rights reserved.

The prognostic role of exercise echocardiography in heart failure.

PubMed

Rubiś, Paweł; Drabik, Leszek; Kopeć, Grzegorz; Olszowska, Maria; Płazak, Wojciech; Podolec, Piotr

2011-01-01

Gradual impairment of exercise tolerance is the commonest sign of heart failure (HF). Little is known as to which cardiac contributors of poor exercise capacity carry an independent prognostic information in HF. We investigated the prognostic role of exercise echocardiography (ex-echo) in HF patients. We studied 85 consecutive, symptomatic HF patients (66 males, mean age 62.5 ± 11.8 [range 21-83] years, mean left ventricular ejection fraction [LVEF] 27.2 ± 9.5%). The end-point was all-cause mortality. During the follow-up period (mean 43 ± 21 months) 21 patients died. Resting echocardiography and ex-echo, with the simultaneous measurement of peak oxygen uptake (VO(2peak)), was performed in each patient using a semi-supine ergometer (20 W, 2-min increments). Apart from conventional assessment of systolic and diastolic function (EF, E/A, DT, IVRT) or right ventricular systolic pressure (RVSP), tissue Doppler imaging was used for the assessment of LV and RV peak velocity (IVV) as well as acceleration during isovolumic contraction (IVA), peak velocity during ejection phase (S'), peak early diastolic velocity (E'), peak late diastolic velocity (A'), and ratio of early diastolic mitral/tricuspid velocity to peak early diastolic velocity (E/E'). Patients who died were significantly older, had lower exercise capacity, more advanced HF, greater impairment of baseline systolic function, higher baseline pulmonary artery systolic pressure, and most importantly a lack of improvement in EF, diastolic function, and further increase of RVSP during exercise. Out of all echocardiographic parameters, only peak stress EF (x(2) 6.1; p = 0.01), baseline and peak exercise RVSP (x(2) 12.5 and c(2) 18.7; p 〈 0.001; respectively), and mitral E/E' ratio (x(2) 8.9; p 〈 0.01) were univariate predictors of prognosis and remained independently prognostic when adjusted for age and sex but were eliminated from the model by NT-proBNP. During exercise, more severe systolic and diastolic dysfunction with the elevation of pulmonary arterial pressure is more prevalent in HF patients who have a poorer outcome. The estimation of common parameters such as EF, RVSP and E/E' using ex-echo, provides prognostic information in HF.

Long-range corrected density functional theory with accelerated Hartree-Fock exchange integration using a two-Gaussian operator [LC-ωPBE(2Gau)].

PubMed

Song, Jong-Won; Hirao, Kimihiko

2015-10-14

Since the advent of hybrid functional in 1993, it has become a main quantum chemical tool for the calculation of energies and properties of molecular systems. Following the introduction of long-range corrected hybrid scheme for density functional theory a decade later, the applicability of the hybrid functional has been further amplified due to the resulting increased performance on orbital energy, excitation energy, non-linear optical property, barrier height, and so on. Nevertheless, the high cost associated with the evaluation of Hartree-Fock (HF) exchange integrals remains a bottleneck for the broader and more active applications of hybrid functionals to large molecular and periodic systems. Here, we propose a very simple yet efficient method for the computation of long-range corrected hybrid scheme. It uses a modified two-Gaussian attenuating operator instead of the error function for the long-range HF exchange integral. As a result, the two-Gaussian HF operator, which mimics the shape of the error function operator, reduces computational time dramatically (e.g., about 14 times acceleration in C diamond calculation using periodic boundary condition) and enables lower scaling with system size, while maintaining the improved features of the long-range corrected density functional theory.

The innate immune system in chronic cardiomyopathy: a European Society of Cardiology (ESC) scientific statement from the Working Group on Myocardial Function of the ESC.

PubMed

Frantz, Stefan; Falcao-Pires, Ines; Balligand, Jean-Luc; Bauersachs, Johann; Brutsaert, Dirk; Ciccarelli, Michele; Dawson, Dana; de Windt, Leon J; Giacca, Mauro; Hamdani, Nazha; Hilfiker-Kleiner, Denise; Hirsch, Emilio; Leite-Moreira, Adelino; Mayr, Manuel; Thum, Thomas; Tocchetti, Carlo G; van der Velden, Jolanda; Varricchi, Gilda; Heymans, Stephane

2018-03-01

Activation of the immune system in heart failure (HF) has been recognized for over 20 years. Initially, experimental studies demonstrated a maladaptive role of the immune system. However, several phase III trials failed to show beneficial effects in HF with therapies directed against an immune activation. Preclinical studies today describe positive and negative effects of immune activation in HF. These different effects depend on timing and aetiology of HF. Therefore, herein we give a detailed review on immune mechanisms and their importance for the development of HF with a special focus on commonalities and differences between different forms of cardiomyopathies. The role of the immune system in ischaemic, hypertensive, diabetic, toxic, viral, genetic, peripartum, and autoimmune cardiomyopathy is discussed in depth. Overall, initial damage to the heart leads to disease specific activation of the immune system whereas in the chronic phase of HF overlapping mechanisms occur in different aetiologies. © 2018 The Authors. European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.

Acute hemodynamic effects of adaptive servo-ventilation in patients with heart failure.

PubMed

Yamada, Shiro; Sakakibara, Mamoru; Yokota, Takashi; Kamiya, Kiwamu; Asakawa, Naoya; Iwano, Hiroyuki; Yamada, Satoshi; Oba, Koji; Tsutsui, Hiroyuki

2013-01-01

Adaptive servo-ventilation (ASV) improves cardiac function in patients with heart failure (HF). We compared the hemodynamics of control and HF patients, and identified the predictors for acute effects of ASV in HF. We performed baseline echocardiographic measurements and hemodynamic measurements at baseline and after 15 min of ASV during cardiac catheterization in 11 control and 34 HF patients. Heart rate and blood pressure did not change after ASV in either the control or HF group. Stroke volume index (SVI) decreased from 49.3±7.6 to 41.3±7.6 ml/m2 in controls (P<0.0001) but did not change in the HF patients (from 34.8±11.5 to 32.8±8.9 ml/m2, P=0.148). In the univariate analysis, pulmonary capillary wedge pressure (PCWP), mitral regurgitation (MR)/left atrial (LA) area, E/A, E/e', and the sphericity index defined by the ratio between the short-axis and long-axis dimensions of the left ventricle significantly correlated with % change of SVI from baseline during ASV. PCWP and MR/LA area were independent predictors by multivariate analysis. Moreover, responders (15 of 34 HF patients; 44%) categorized by an increase in SVI showed significantly higher PCWP, MR, and sphericity index. Left ventricular structure and MR, as well as PCWP, could predict acute favorable effects on hemodynamics by ASV therapy in HF patients. 

Cost-effectiveness of eplerenone in patients with systolic heart failure and mild symptoms.

PubMed

Lee, Dawn; Wilson, Koo; Akehurst, Ron; Cowie, Martin R; Zannad, Faiez; Krum, Henry; van Veldhuisen, Dirk J; Vincent, John; Pitt, Bertram; McMurray, John J V

2014-11-01

In the Eplerenone in Mild Patients Hospitalization and Survival Study in Heart Failure (EMPHASIS-HF), aldosterone blockade with eplerenone decreased mortality and hospitalisation in patients with mild symptoms (New York Heart Association class II) and chronic systolic heart failure (HF). The present study evaluated the cost-effectiveness of eplerenone in the treatment of these patients in the UK and Spain. Results from the EMPHASIS-HF trial were used to develop a discrete-event simulation model estimating lifetime direct costs and effects (life years and quality-adjusted life years (QALYs) gained) of the addition of eplerenone to standard care among patients with chronic systolic HF and mild symptoms. Eplerenone plus standard care compared with standard care alone increased lifetime direct costs per patient by £4284 for the UK and €7358 for Spain, with additional quality-adjusted life expectancy of 1.22 QALYs for the UK and 1.33 QALYs for Spain. Mean lifetime costs were £3520 per QALY in the UK and €5532 per QALY in Spain. Probabilistic sensitivity analysis suggested a 100% likelihood of eplerenone being regarded as cost-effective at a willingness-to-pay threshold of £20 000 per QALY (UK) or €30 000 per QALY (Spain). By currently accepted standards of value for money, the addition of eplerenone to optimal medical therapy for patients with chronic systolic HF and mild symptoms is likely to be cost-effective. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

The Effect of Vitamin D on Aldosterone and Health Status in Patients with Heart Failure

PubMed Central

Boxer, Rebecca S.; Hoit, Brian D.; Schmotzer, Brian J.; Stefano, Gregory T.; Gomes, Amanda; Negrea, Lavinia

2014-01-01

Background: Vitamin D deficiency is associated with HF events and in animal models vitamin D down-regulates RAAS hormones. Methods: Patients with NYHA II-IV HF and a 25OHD level ≤ 37.5 ng/mL received weekly vitamin D3 50,000 IU (n=31) or placebo (n=33) for 6 months. Serum aldosterone, renin, echocardiography and health status were collected at baseline and 6 months. Results: Mean age of participants 65.9±10.4 years, women 48%, AA 64%, mean EF 37.6±13.9, NYHA class III 36 %, II 64%. The vitamin D group increased serum 25OHD (19.1± 9.3 to 61.7±20.3 ng/ml) and not in the placebo group (17.8±9.0 to 17.4±9.8 ng/ml). Aldosterone decreased in the vitamin D group (10.0±11.9 to 6.2±11.6 ng/dl) and not in the placebo group 8.9±8.6 to 9.0±12.4 ng/dl) (p=.02). There was no difference between groups in renin, echocardiographic measures or health status from baseline to 6 months. Modeling indicated that variables which predicted change in aldosterone included receiving vitamin D, increasing age, AA race, and lower GFR. Conclusions: Vitamin D3 repletion decreases aldosterone in patients with HF and low serum vitamin D. Vitamin D may be an important adjunct to standard HF therapy. Further will assess if vitamin D provides long-term benefit for patients with HF. PMID:24508026

Home telemonitoring in heart failure patients: the HHH study (Home or Hospital in Heart Failure)

PubMed Central

Mortara, Andrea; Pinna, Gian Domenico; Johnson, Paul; Maestri, Roberto; Capomolla, Soccorso; La Rovere, Maria Teresa; Ponikowski, Piotr; Tavazzi, Luigi; Sleight, Peter

2009-01-01

Aims The Home or Hospital in Heart failure (HHH) study was a European Community-funded, multinational, randomized controlled clinical trial, conducted in the UK, Poland, and Italy, to assess the feasibility of a new system of home telemonitoring (HT). The HT system was used to monitor clinical and physiological parameters, and its effectiveness (compared with usual care) in reducing cardiac events in heart failure (HF) patients was evaluated. Measurements were patient-managed. Methods and results From 2002 to 2004, 461 HF patients (age 60 ± 11 years, New York Heart Association class 2.4 ± 0.6, left ventricular ejection fraction 29 ± 7%) were enrolled at 11 centres and randomized (1:2) to either usual outpatient care or HT administered as three randomized strategies: (i) monthly telephone contact; (ii) strategy 1 plus weekly transmission of vital signs; and (iii) strategy 2 plus monthly 24 h recording of cardiorespiratory activity. Patients completed 81% of vital signs transmissions, as well as 92% of cardiorespiratory recordings. Over a 12-month follow-up, there was no significant effect of HT in reducing bed-days occupancy for HF or cardiac death plus HF hospitalization. Post hoc analysis revealed a heterogeneous effect of HT in the three countries with a trend towards a reduction of events in Italy. Conclusion Home or Hospital in Heart failure indicates that self-managed HT of clinical and physiological parameters is feasible in HF patients, with surprisingly high compliance. Whether HT contributes to a reduction of cardiac events requires further investigation. PMID:19228800

Quality of life questionnaire predicts poor exercise capacity only in HFpEF and not in HFrEF.

PubMed

Ahmeti, Artan; Henein, Michael Y; Ibrahimi, Pranvera; Elezi, Shpend; Haliti, Edmond; Poniku, Afrim; Batalli, Arlind; Bajraktari, Gani

2017-10-17

The Minnesota Living with Heart Failure Questionnaire (MLHFQ) is the most widely used measure of quality of life (QoL) in HF patients. This prospective study aimed to assess the relationship between QoL and exercise capacity in HF patients. The study subjects were 118 consecutive patients with chronic HF (62 ± 10 years, 57 females, in NYHA I-III). Patients answered a MLHFQ questionnaire in the same day of complete clinical, biochemical and echocardiographic assessment. They also underwent a 5 min walk test (6-MWT), in the same day, which grouped them into; Group I: ≤ 300 m and Group II: >300 m. In addition, left ventricular (LV) ejection fraction (EF), divided them into: Group A, with preserved EF (HFpEF) and Group B with reduced EF (HFrEF). The mean MLHFQ total scale score was 48 (±17). The total scale, and the physical and emotional functional MLHFQ scores did not differ between HFpEF and HFpEF. Group I patients were older (p = 0.003), had higher NYHA functional class (p = 0.002), faster baseline heart rate (p = 0.006), higher prevalence of smoking (p = 0.015), higher global, physical and emotional MLHFQ scores (p < 0.001, for all), larger left atrial (LA) diameter (p = 0.001), shorter LV filling time (p = 0.027), higher E/e' ratio (0.02), shorter isovolumic relaxation time (p = 0.028), lower septal a' (p = 0.019) and s' (p = 0.023), compared to Group II. Independent predictors of 6-MWT distance for the group as a whole were increased MLHFQ total score (p = 0.005), older age (p = 0.035), and diabetes (p = 0.045), in HFpEF were total MLHFQ (p = 0.007) and diabetes (p = 0.045) but in HFrEF were only LA enlargement (p = 0.005) and age (p = 0.013. A total MLHFQ score of 48.5 had a sensitivity of 67% and specificity of 63% (AUC on ROC analysis of 72%) for limited exercise performance in HF patients. Quality of life, assessment by MLHFQ, is the best correlate of exercise capacity measured by 6-MWT, particularly in HFpEF patients. Despite worse ejection fraction in HFrEF, signs of raised LA pressure independently determine exercise capacity in these patients.

The mechanical, optoelectronic and thermoelectric properties of NiYSn (Y = Zr and Hf) alloys

NASA Astrophysics Data System (ADS)

Hamioud, Farida; Mubarak, A. A.

2017-09-01

First-principle calculations are performed using DFT as implemented in Wien2k code to compute the mechanical, electronic, optical and thermoelectric properties of NiYSn (Y = Zr and Hf) alloys. The computed lattice constants, bulk modulus and cohesive energy of these alloys at 0 K and 0 GPa are performed. NiZrSn and NiHfSn are found to be anisotropic and elastically stable. Furthermore, both alloys are confirmed to be thermodynamically stable by the calculated values of the standard enthalpy of formation. The Young’s and shear moduli values show that NiZrSn seems to be stiffer than NiHfSn. The optical properties are performed using the dielectric function. Some beneficial optoelectronic applications are found as exposed in the optical spectra. Moreover, the alloys are classified as good insulators for solar heating. The thermoelectric properties as a function of temperature are computed utilizing BoltzTrap code. The major charge carriers are found to be electrons and the alloys are classified as p-type doping alloys.

Prognostic impact of intestinal wall thickening in hospitalized patients with heart failure.

PubMed

Ikeda, Yuki; Ishii, Shunsuke; Fujita, Teppei; Iida, Yuichiro; Kaida, Toyoji; Nabeta, Takeru; Maekawa, Emi; Yanagisawa, Tomoyoshi; Koitabashi, Toshimi; Takeuchi, Ichiro; Inomata, Takayuki; Ako, Junya

2017-03-01

Intestine-cardiovascular relationship has been increasingly recognized as a key factor in patients with heart disease. We aimed to identify the relationships among intestinal wall edema, cardiac function, and adverse clinical events in hospitalized heart failure (HF) patients. Abdominal computed tomographic images of 168 hospitalized HF patients were retrospectively investigated for identification of average colon wall thickness (CWT) from the ascending to sigmoid colon. Relationships between average CWT and echocardiographic parameters, blood sampling data, and primary outcomes including readmission for deteriorated HF and all-cause mortality were evaluated. Among the echocardiographic parameters, lower left ventricular diastolic function was correlated with higher average CWT. In multivariate analysis, higher logarithmic C-reactive protein level, lower estimated glomerular filtration rate, lower peripheral blood lymphocyte count, higher E/E' ratio, and extremely higher/lower defecation frequency were independently correlated with higher average CWT. Multivariate Cox-hazard analysis demonstrated that higher average CWT was independently related to higher incidence of primary outcomes. In hospitalized HF patients, increased CWT was associated with lower cardiac performance, and predicted poorer long-term clinical outcomes. Copyright © 2016. Published by Elsevier B.V.

A novel experimental model of erectile dysfunction in rats with heart failure using volume overload

PubMed Central

Silva, Fábio Henrique; Veiga, Frederico José Reis; Mora, Aline Gonçalves; Heck, Rodrigo Sader; De Oliveira, Caroline Candida; Gambero, Alessandra; Franco-Penteado, Carla Fernanda; Antunes, Edson; Gardner, Jason D.; Priviero, Fernanda Bruschi Marinho

2017-01-01

Background Patients with heart failure (HF) display erectile dysfunction (ED). However, the pathophysiology of ED during HF remains poorly investigated. Objective This study aimed to characterize the aortocaval fistula (ACF) rat model associated with HF as a novel experimental model of ED. We have undertaken molecular and functional studies to evaluate the alterations of the nitric oxide (NO) pathway, autonomic nervous system and oxidative stress in the penis. Methods Male rats were submitted to ACF for HF induction. Intracavernosal pressure in anesthetized rats was evaluated. Concentration-response curves to contractile (phenylephrine) and relaxant agents (sodium nitroprusside; SNP), as well as to electrical field stimulation (EFS), were obtained in the cavernosal smooth muscle (CSM) strips from sham and HF rats. Protein expression of endothelial NO synthase (eNOS) and neuronal NO synthase (nNOS) and phosphodiestarese-5 in CSM were evaluated, as well as NOX2 (gp91phox) and superoxide dismutase (SOD) mRNA expression. SOD activity and thiobarbituric acid reactive substances (TBARs) were also performed in plasma. Results HF rats display erectile dysfunction represented by decreased ICP responses compared to sham rats. The neurogenic contractile responses elicited by EFS were greater in CSM from the HF group. Likewise, phenylephrine-induced contractions were greater in CSM from HF rats. Nitrergic response induced by EFS were decreased in the cavernosal tissue, along with lower eNOS, nNOS and phosphodiestarese-5 protein expressions. An increase of NOX2 and SOD mRNA expression in CSM and plasma TBARs of HF group were detected. Plasma SOD activity was decreased in HF rats. Conclusion ED in HF rats is associated with decreased NO bioavailability in erectile tissue due to eNOS/nNOS dowregulation and NOX2 upregulation, as well as hypercontractility of the penis. This rat model of ACF could be a useful tool to evaluate the molecular alterations of ED associated with HF. PMID:29095897

Evidence for a hyper-reductive redox in a sub-set of heart failure patients.

PubMed

Sairam, Thiagarajan; Patel, Amit N; Subrahmanian, Meenu; Gopalan, Rajendiran; Pogwizd, Steven M; Ramalingam, Sudha; Sankaran, Ramalingam; Rajasekaran, Namakkal Soorapan

2018-05-18

Oxidative stress has been linked to heart failure (HF) in humans. Antioxidant-based treatments are often ineffective. Therefore, we hypothesize that some of the HF patients might have a reductive stress (RS) condition. Investigating RS-related mechanisms will aid in personalized optimization of redox homeostasis for better outcomes among HF patients. Blood samples were collected from HF patients (n = 54) and healthy controls (n = 42) and serum was immediately preserved in - 80 °C for redox analysis. Malondialdehyde (MDA; lipid peroxidation) levels by HPLC, reduced glutathione (GSH) and its redox ratio (GSH/GSSG) using enzymatic-recycling assay in the serum of HF patients were measured. Further, the activities of key antioxidant enzymes were analyzed by UV-Vis spectrophotometry. Non-invasive echocardiography was used to relate circulating redox status with cardiac function and remodeling. The circulatory redox state (GSH/MDA ratio) was used to stratify the HF patients into normal redox (NR), hyper-oxidative (HO), and hyper-reductive (HR) groups. While the majority of the HF patients exhibited the HO (42%), 41% of them had a normal redox (NR) state. Surprisingly, a subset of HF patients (17%) belonged to the hyper-reductive group, suggesting a strong implication for RS in the progression of HF. In all the groups of HF patients, SOD, GPx and catalase were significantly increased while GR activity was significantly reduced relative to healthy controls. Furthermore, echocardiography analyses revealed that 55% of HO patients had higher systolic dysfunction while 62.5% of the hyper-reductive patients had higher diastolic dysfunction. These results suggest that RS may be associated with HF pathogenesis for a subset of cardiac patients. Thus, stratification of HF patients based on their circulating redox status may serve as a useful prognostic tool to guide clinicians designing personalized antioxidant therapies.

A novel experimental model of erectile dysfunction in rats with heart failure using volume overload.

PubMed

Silva, Fábio Henrique; Veiga, Frederico José Reis; Mora, Aline Gonçalves; Heck, Rodrigo Sader; De Oliveira, Caroline Candida; Gambero, Alessandra; Franco-Penteado, Carla Fernanda; Antunes, Edson; Gardner, Jason D; Priviero, Fernanda Bruschi Marinho; Claudino, Mário Angelo

2017-01-01

Patients with heart failure (HF) display erectile dysfunction (ED). However, the pathophysiology of ED during HF remains poorly investigated. This study aimed to characterize the aortocaval fistula (ACF) rat model associated with HF as a novel experimental model of ED. We have undertaken molecular and functional studies to evaluate the alterations of the nitric oxide (NO) pathway, autonomic nervous system and oxidative stress in the penis. Male rats were submitted to ACF for HF induction. Intracavernosal pressure in anesthetized rats was evaluated. Concentration-response curves to contractile (phenylephrine) and relaxant agents (sodium nitroprusside; SNP), as well as to electrical field stimulation (EFS), were obtained in the cavernosal smooth muscle (CSM) strips from sham and HF rats. Protein expression of endothelial NO synthase (eNOS) and neuronal NO synthase (nNOS) and phosphodiestarese-5 in CSM were evaluated, as well as NOX2 (gp91phox) and superoxide dismutase (SOD) mRNA expression. SOD activity and thiobarbituric acid reactive substances (TBARs) were also performed in plasma. HF rats display erectile dysfunction represented by decreased ICP responses compared to sham rats. The neurogenic contractile responses elicited by EFS were greater in CSM from the HF group. Likewise, phenylephrine-induced contractions were greater in CSM from HF rats. Nitrergic response induced by EFS were decreased in the cavernosal tissue, along with lower eNOS, nNOS and phosphodiestarese-5 protein expressions. An increase of NOX2 and SOD mRNA expression in CSM and plasma TBARs of HF group were detected. Plasma SOD activity was decreased in HF rats. ED in HF rats is associated with decreased NO bioavailability in erectile tissue due to eNOS/nNOS dowregulation and NOX2 upregulation, as well as hypercontractility of the penis. This rat model of ACF could be a useful tool to evaluate the molecular alterations of ED associated with HF.

VLF and HF Plasma Waves Associated with Spread-F Plasma Depletions Observed on the C/NOFS Satellite

NASA Technical Reports Server (NTRS)

Pfaff, Robert; Freudenreich, H.; Schuck, P.; Klenzing, J.

2011-01-01

The C/NOFS spacecraft frequently encounters structured plasma depletions associated with equatorial spread-F along its trajectory that varies between 401 km perigee and 867 km apogee in the low latitude ionosphere. We report two classes of plasma waves detected with the Vector Electric Field Investigation (VEFI) that appear when the plasma frequency is less than the electron gyro frequency, as is common in spread-F depletions where the plasma number density typically decreases below 10(exp 4)/cu cm. In these conditions, both broadband VLF waves with a clear cutoff at the lower hybrid frequency and broadband HF waves with a clear cutoff at the plasma frequency are observed. We interpret these waves as "hiss-type" emissions possibly associated with the flow of suprathermal electrons within the inter-hemispherical magnetic flux tubes. We also report evidence of enhanced wave "transients" sometimes embedded in the broader band emissions that are associated with lightning sferics detected within the depleted plasma regions that appear in both the VLF and HF data. Theoretical implications of these observations are discussed.

Does permanent atrial fibrillation modify response to cardiac resynchronization therapy in heart failure patients?

PubMed

Abreu, Ana; Oliveira, Mário; Silva Cunha, Pedro; Santa Clara, Helena; Portugal, Guilherme; Gonçalves Rodrigues, Inês; Santos, Vanessa; Morais, Luís; Selas, Mafalda; Soares, Rui; Branco, Luísa; Ferreira, Rui; Mota Carmo, Miguel

2017-10-01

The benefits of cardiac resynchronization therapy (CRT) documented in heart failure (HF) may be influenced by atrial fibrillation (AF). We aimed to compare CRT response in patients in AF and in sinus rhythm (SR). We prospectively studied 101 HF patients treated by CRT. Rates of clinical, echocardiographic and functional response, baseline NYHA class and variation, left ventricular ejection fraction, volumes and mass, atrial volumes, cardiopulmonary exercise test (CPET) duration (CPET dur), peak oxygen consumption (VO 2 max) and ventilatory efficiency (VE/VCO 2 slope) were compared between AF and SR patients, before and at three and six months after implantation of a CRT device. All patients achieved ≥95% biventricular pacing, and 5.7% underwent atrioventricular junction ablation. Patients were divided into AF (n=35) and SR (n=66) groups; AF patients were older, with larger atrial volumes and lower CPET dur and VO 2 max before CRT. The percentages of clinical and echocardiographic responders were similar in the two groups, but there were more functional responders in the AF group (71% vs. 39% in SR patients; p=0.012). In SR patients, left atrial volume and left ventricular mass were significantly reduced (p=0.015 and p=0.021, respectively), whereas in AF patients, CPET dur (p=0.003) and VO 2 max (p=0.001; 0.083 age-adjusted) showed larger increases. Clinical and echocardiographic response rates were similar in SR and AF patients, with a better functional response in AF. Improvement in left ventricular function and volumes occurred in both groups, but left ventricular mass reduction and left atrial reverse remodeling were seen exclusively in SR patients (ClinicalTrials.gov identifier: NCT02413151; FCT code: PTDC/DES/120249/2010). Copyright © 2017 Sociedade Portuguesa de Cardiologia. Publicado por Elsevier España, S.L.U. All rights reserved.

Empowering human cardiac progenitor cells by P2Y14 nucleotide receptor overexpression.

PubMed

Khalafalla, Farid G; Kayani, Waqas; Kassab, Arwa; Ilves, Kelli; Monsanto, Megan M; Alvarez, Roberto; Chavarria, Monica; Norman, Benjamin; Dembitsky, Walter P; Sussman, Mark A

2017-12-01

Autologous cardiac progenitor cell (CPC) therapy is a promising approach for treatment of heart failure (HF). There is an unmet need to identify inherent deficits in aged/diseased human CPCs (hCPCs) derived from HF patients in the attempts to augment their regenerative capacity prior to use in the clinical setting. Here we report significant functional correlations between phenotypic properties of hCPCs isolated from cardiac biopsies of HF patients, clinical parameters of patients and expression of the P2Y 14 purinergic receptor (P2Y 14 R), a crucial detector for extracellular UDP-sugars released during injury/stress. P2Y 14 R is downregulated in hCPCs derived from HF patients with lower ejection fraction or diagnosed with diabetes. Augmenting P2Y 14 R expression levels in aged/diseased hCPCs antagonizes senescence and improves functional responses. This study introduces purinergic signalling modulation as a potential strategy to rejuvenate and improve phenotypic characteristics of aged/functionally compromised hCPCs prior to transplantation in HF patients. Autologous cardiac progenitor cell therapy is a promising alternative approach to current inefficient therapies for heart failure (HF). However, ex vivo expansion and pharmacological/genetic modification of human cardiac progenitor cells (hCPCs) are necessary interventions to rejuvenate aged/diseased cells and improve their regenerative capacities. This study was designed to assess the potential of improving hCPC functional capacity by targeting the P2Y 14 purinergic receptor (P2Y 14 R), which has been previously reported to induce regenerative and anti-senescence responses in a variety of experimental models. c-Kit + hCPCs were isolated from cardiac biopsies of multiple HF patients undergoing left ventricular assist device implantation surgery. Significant correlations existed between the expression of P2Y 14 R in hCPCs and clinical parameters of HF patients. P2Y 14 R was downregulated in hCPCs derived from patients with a relatively lower ejection fraction and patients diagnosed with diabetes. hCPC lines with lower P2Y 14 R expression did not respond to P2Y 14 R agonist UDP-glucose (UDP-Glu) while hCPCs with higher P2Y 14 R expression showed enhanced proliferation in response to UDP-Glu stimulation. Mechanistically, UDP-Glu stimulation enhanced the activation of canonical growth signalling pathways ERK1/2 and AKT. Restoring P2Y 14 R expression levels in functionally compromised hCPCs via lentiviral-mediated overexpression improved proliferation, migration and survival under stress stimuli. Additionally, P2Y 14 R overexpression reversed senescence-associated morphology and reduced levels of molecular markers of senescence p16 INK4a , p53, p21 and mitochondrial reactive oxygen species. Findings from this study unveil novel biological roles of the UDP-sugar receptor P2Y 14 in hCPCs and suggest purinergic signalling modulation as a promising strategy to improve phenotypic properties of functionally impaired hCPCs. © 2017 The Authors. The Journal of Physiology © 2017 The Physiological Society.

Judiciary views on criminal behaviour and intention of offenders with high-functioning autism

PubMed Central

Berryessa, Colleen M.

2015-01-01

Purpose The purpose of this paper is to explore how judges perceive High Functioning Autistic Spectrum Disorders (hfASDs) and the disorders’ effects on an offender’s ability to formulate criminal intent and control behaviour. Design/methodology/approach Semi-structured interviews on topics related to offenders with hfASDs were conducted with 21 California Superior Court Judges. A coding scheme was developed and an iterative qualitative coding process was used for analysis. Findings Analysis yielded three major themes on how an hfASD diagnosis affects an offender’s ability to regulate actions and criminal behaviour. Interviewed judges reported beliefs that hfASD offenders view the world in a different way and that much of their behaviour is not under their direct control. Judges reported these perceptions likely affect how they criminally process and make legal decisions regarding offenders with hfASDs. Research limitations/implications The sample size was small and therefore no statistical significance can be drawn from results; findings cannot be applied to perceptions or experiences of the entire California Superior Court Judge population. Originality/value Past academic research reports that individuals with hfASDs that offend often do so because of specific symptoms associated with the disorder. This presents a complex dilemma for the criminal justice system regarding how best to understand the disorder and process these offenders. This study and its findings aim to shed light on issues judges encounter in determining these offenders’ responsibility and sentencing, in what ways this information might be integrated into judicial decision making, and areas where future research is needed. PMID:25866642