Heart transplantation for adults with congenital heart disease: current status and future prospects.

PubMed

Matsuda, Hikaru; Ichikawa, Hajime; Ueno, Takayoshi; Sawa, Yoshiki

2017-06-01

Increased survival rates after corrective or palliative surgery for complex congenital heart disease (CHD) in infancy and childhood are now being coupled with increased numbers of patients who survive to adulthood with various residual lesions or sequelae. These patients are likely to deteriorate in cardiac function or end-organ function, eventually requiring lifesaving treatment including heart transplantation. Although early and late outcomes of heart transplantation have been improving for adult survivors of CHD, outcomes and pretransplant management could still be improved. Survivors of Fontan procedures are a vulnerable cohort, particularly when single ventricle physiology fails, mostly with protein-losing enteropathy and hepatic dysfunction. Therefore, we reviewed single-institution and larger database analyses of adults who underwent heart transplantation for CHD, to enable risk stratification by identifying the indications and outcomes. As the results, despite relatively high early mortality, long-term results were encouraging after heart transplantation. However, further investigations are needed to improve the indication criteria for complex CHD, especially for failed Fontan. In addition, the current system of status criteria and donor heart allocation system in heart transplantation should be arranged as suitable for adults with complex CHD. Furthermore, there is a strong need to develop ventricular assist devices as a bridge to transplantation or destination therapy, especially where right-sided circulatory support is needed.

Impact of pharmaceutical care on the quality of life of patients with Chagas disease and heart failure: randomized clinical trial

PubMed Central

2012-01-01

Background Pharmaceutical care is the direct interaction between pharmacist and patient, in order to improve therapeutic compliance, promote adequate pharmacotherapeutic follow-up, and improve quality of life. Pharmaceutical care may be effective in reducing complications and in improving the quality of life of patients with chronic diseases, like Chagas heart disease, while bringing a positive impact on health system costs. The morbidity and mortality indexes for patients with Chagas heart disease are high, especially if this heart disease is complicated by heart failure. In this setting, we hypothesize that pharmaceutical care might be an important tool for the clinical management of these patients by improving their quality of life, as a better compliance to their treatment and the avoidance and prompt correction of drug-related problems will minimize their symptoms, improve their functional class, and decrease the number of hospital admissions. Therefore, the aim of this trial is to evaluate the contribution of pharmaceutical care to clinical treatment of patients with Chagas heart disease complicated by heart failure. Methods/design A prospective, single-center randomized clinical trial will be conducted in patients with Chagas heart disease complicated by heart failure. A total of 88 patients will be randomly assigned into two parallel groups: an intervention group will receive standard care and pharmaceutical care, and a control group will receive only standard care. Both groups will be subjected to a follow-up period of 12 months. The primary outcome of this trial is the evaluation of quality of life, measured by the 36-item short-form and the Minnesota Living with Heart Failure Questionnaire. Secondary outcomes include drug-related problems, exercise tolerance as measured by the standard six-minute-walk test, and compliance. Discussion Patients with Chagas heart disease complicated by heart failure under pharmaceutical care are expected to improve their quality of life, present with a lower incidence of drug-related problems, improve their functional capacity, and improve in their compliance to treatment. Trial registration ClinicalTrials.gov Identifier: NCT01566617 PMID:23270509

Impact of pharmaceutical care on the quality of life of patients with Chagas disease and heart failure: randomized clinical trial.

PubMed

Sperandio da Silva, Gilberto M; Chambela, Mayara C; Sousa, Andrea S; Sangenis, Luiz Henrique C; Xavier, Sergio S; Costa, Andréa R; Brasil, Pedro Emmanuel A A; Hasslocher-Moreno, Alejandro M; Saraiva, Roberto M

2012-12-27

Pharmaceutical care is the direct interaction between pharmacist and patient, in order to improve therapeutic compliance, promote adequate pharmacotherapeutic follow-up, and improve quality of life. Pharmaceutical care may be effective in reducing complications and in improving the quality of life of patients with chronic diseases, like Chagas heart disease, while bringing a positive impact on health system costs. The morbidity and mortality indexes for patients with Chagas heart disease are high, especially if this heart disease is complicated by heart failure. In this setting, we hypothesize that pharmaceutical care might be an important tool for the clinical management of these patients by improving their quality of life, as a better compliance to their treatment and the avoidance and prompt correction of drug-related problems will minimize their symptoms, improve their functional class, and decrease the number of hospital admissions. Therefore, the aim of this trial is to evaluate the contribution of pharmaceutical care to clinical treatment of patients with Chagas heart disease complicated by heart failure. A prospective, single-center randomized clinical trial will be conducted in patients with Chagas heart disease complicated by heart failure. A total of 88 patients will be randomly assigned into two parallel groups: an intervention group will receive standard care and pharmaceutical care, and a control group will receive only standard care. Both groups will be subjected to a follow-up period of 12 months. The primary outcome of this trial is the evaluation of quality of life, measured by the 36-item short-form and the Minnesota Living with Heart Failure Questionnaire. Secondary outcomes include drug-related problems, exercise tolerance as measured by the standard six-minute-walk test, and compliance. Patients with Chagas heart disease complicated by heart failure under pharmaceutical care are expected to improve their quality of life, present with a lower incidence of drug-related problems, improve their functional capacity, and improve in their compliance to treatment. ClinicalTrials.gov Identifier: NCT01566617.

The treatment with pyridostigmine improves the cardiocirculatory function in rats with chronic heart failure.

PubMed

Sabino, João Paulo J; da Silva, Carlos Alberto Aguiar; de Melo, Rubens Fernando; Fazan, Rubens; Salgado, Helio C

2013-01-01

Sympathetic hyperactivity and its outcome in heart failure have been thoroughly investigated to determine the focus of pharmacologic approaches targeting the sympathetic nervous system in the treatment of this pathophysiological condition. On the other hand, therapeutic approaches aiming to protect the reduced cardiac parasympathetic function have not received much attention. The present study evaluated rats with chronic heart failure (six to seven weeks after coronary artery ligation) and the effects of an increased parasympathetic function by pyridostigmine (an acetylcholinesterase inhibitor) on the following aspects: arterial pressure (AP), heart rate (HR), baroreceptor and Bezold-Jarisch reflex, pulse interval (PI) and AP variability, cardiac sympathetic and parasympathetic tonus, intrinsic heart rate (i-HR) and cardiac function. Conscious rats with heart failure exhibited no change in HR, Bezold-Jarisch reflex, PI variability and cardiac sympathetic tonus. On the other hand, these animals presented hypotension and reduced baroreflex sensitivity, power in the low frequency (LF) band of the systolic AP spectrum, cardiac parasympathetic tonus and i-HR, while anesthetized rats exhibited reduced cardiac performance. Pyridostigmine prevented the attenuation of all the parameters examined, except basal AP and cardiac performance. In conclusion, the blockade of acetylcholinesterase with pyridostigmine was revealed to be an important pharmacological approach, which could be used to increase parasympathetic function and to improve a number of cardiocirculatory parameters in rats with heart failure. Copyright © 2012 Elsevier B.V. All rights reserved.

Effects of short-term continuous positive airway pressure on myocardial sympathetic nerve function and energetics in patients with heart failure and obstructive sleep apnea: a randomized study.

PubMed

Hall, Allison B; Ziadi, Maria C; Leech, Judith A; Chen, Shin-Yee; Burwash, Ian G; Renaud, Jennifer; deKemp, Robert A; Haddad, Haissam; Mielniczuk, Lisa M; Yoshinaga, Keiichiro; Guo, Ann; Chen, Li; Walter, Olga; Garrard, Linda; DaSilva, Jean N; Floras, John S; Beanlands, Rob S B

2014-09-09

Heart failure with reduced ejection fraction and obstructive sleep apnea (OSA), 2 states of increased metabolic demand and sympathetic nervous system activation, often coexist. Continuous positive airway pressure (CPAP), which alleviates OSA, can improve ventricular function. It is unknown whether this is due to altered oxidative metabolism or presynaptic sympathetic nerve function. We hypothesized that short-term (6-8 weeks) CPAP in patients with OSA and heart failure with reduced ejection fraction would improve myocardial sympathetic nerve function and energetics. Forty-five patients with OSA and heart failure with reduced ejection fraction (left ventricular ejection fraction 35.8±9.7% [mean±SD]) were evaluated with the use of echocardiography and 11C-acetate and 11C-hydroxyephedrine positron emission tomography before and ≈6 to 8 weeks after randomization to receive short-term CPAP (n=22) or no CPAP (n=23). Work metabolic index, an estimate of myocardial efficiency, was calculated as follows: (stroke volume index×heart rate×systolic blood pressure÷Kmono), where Kmono is the monoexponential function fit to the myocardial 11C-acetate time-activity data, reflecting oxidative metabolism. Presynaptic sympathetic nerve function was measured with the use of the 11C-hydroxyephedrine retention index. CPAP significantly increased hydroxyephedrine retention versus no CPAP (Δretention: +0.012 [0.002, 0.021] versus -0.006 [-0.013, 0.005] min(-1); P=0.003). There was no significant change in work metabolic index between groups. However, in those with more severe OSA (apnea-hypopnea index>20 events per hour), CPAP significantly increased both work metabolic index and systolic blood pressure (P<0.05). In patients with heart failure with reduced ejection fraction and OSA, short-term CPAP increased hydroxyephedrine retention, indicating improved myocardial sympathetic nerve function, but overall did not affect energetics. In those with more severe OSA, CPAP may improve cardiac efficiency. Further outcome-based investigation of the consequences of CPAP is warranted. http://www.clinicaltrials.gov. Unique identifier: NCT00756366. © 2014 American Heart Association, Inc.

Effect of exercise on diastolic function in heart failure patients: a systematic review and meta-analysis.

PubMed

Pearson, M J; Mungovan, S F; Smart, N A

2017-03-01

Diastolic dysfunction contributes to the development and progression of heart failure. Conventional echocardiography and tissue Doppler imaging are widely utilised in clinical research providing a number of indices of diastolic function valuable in the diagnosis and prognosis of heart failure patients. The aim of this meta-analysis was to quantify the effect of exercise training on diastolic function in patients with heart failure. Exercise training studies that investigate different indices of diastolic function in patients with heart failure have reported that exercise training improves diastolic function in these patients. We sought to add to the current literature by quantifying, where possible, the effect of exercise training on diastolic function. We conducted database searches (PubMed, EBSCO, EMBASE, and Cochrane Trials Register to 31 July 2016) for exercise based rehabilitation trials in heart failure, using the search terms 'exercise training, diastolic function and diastolic dysfunction'. Data from six studies, with a total of 266 heart failure with reduced ejection fraction (HFrEF) participants, 144 in intervention groups and 122 in control groups, indicated a significant reduction in the ratio of early diastolic transmitral velocity (E) to early diastolic tissue velocity (E') (E/E' ratio) with exercise training, exercise vs. control mean difference (MD) of -2.85 (95% CI -3.66 to -2.04, p < 0.00001). Data from five studies in heart failure with preserved ejection fraction (HFpEF) patients, with a total of 204 participants, 115 in intervention groups and 89 in control groups, also demonstrated a significant improvement in E/E' in exercise vs. control MD of -2.38 (95% CI -3.47 to -1.28, p < 0.0001).

Drug Does Not Improve Set of Cardiovascular Outcomes for Diastolic Heart Failure

MedlinePlus

... preserved systolic function, is a common heart condition accounting for about half of all heart failure cases. ... study showed that participants enrolled via elevated BNP measurements who received spironolactone fared better in the composite ...

Exercise Training for Heart Failure Patients with and without Systolic Dysfunction: An Evidence-Based Analysis of How Patients Benefit

PubMed Central

Smart, Neil

2011-01-01

Significant benefits can be derived by heart failure patients from exercise training. This paper provides an evidence-based assessment of expected clinical benefits of exercise training for heart failure patients. Meta-analyses and randomized, controlled trials of exercise training in heart failure patients were reviewed from a search of PubMed, Cochrane Controlled Trial Registry (CCTR), CINAHL, and EMBASE. Exercise training improves functional capacity, quality of life, hospitalization, and systolic and diastolic function in heart failure patients. Heart failure patients with preserved systolic function (HFnEF) participating in exercise training studies are more likely to be women and are 5–7 years older than their systolic heart failure (CHF) counterparts. All patients exhibit low functional capacities, although in HFnEF patients this may be age related, therefore subtle differences in exercise prescriptions are required. Published works report that exercise training is beneficial for heart failure patients with and without systolic dysfunction. PMID:20953365

Cardiorenal syndrome: new developments in the understanding and pharmacologic management.

PubMed

House, Andrew A

2013-10-01

Cardiorenal syndromes (CRSs) with bidirectional heart-kidney signaling are increasingly being recognized for their association with increased morbidity and mortality. In acute CRS, recognition of the importance of worsening kidney function complicating management of acute decompensated heart failure has led to the examination of this specific outcome in the context of acute heart failure clinical trials. In particular, the role of fluid overload and venous congestion has focused interest in the most effective use of diuretic therapy to relieve symptoms of heart failure while at the same time preserving kidney function. Additionally, many novel vasoactive therapies have been studied in recent years with the hopes of augmenting cardiac function, improving symptoms and patient outcomes, while maintaining or improving kidney function. Similarly, recent advances in our understanding of the pathophysiology of chronic CRS have led to reanalysis of kidney outcomes in pivotal trials in chronic congestive heart failure, and newer trials are including changes in kidney function as well as kidney injury biomarkers as prospectively monitored and adjudicated outcomes. This paper provides an overview of some new developments in the pharmacologic management of acute and chronic CRS, examines several reports that illustrate a key management principle for each subtype, and discusses opportunities for future research.

Studying the Microanatomy of the Heart in Three Dimensions: A Practical Update

PubMed Central

Jarvis, Jonathan C.; Stephenson, Robert

2013-01-01

The structure and function of the heart needs to be understood in three dimensions. We give a brief historical summary of the methods by which such an understanding has been sought, and some practical details of the relatively new technique of micro-CT with iodine contrast enhancement in samples from rat and rabbit. We discuss how the improved anatomical detail available in fixed cadaveric hearts will enhance our ability to model and to understand the integrated function of the cardiomyocytes, conducting tissues, and fibrous supporting structures that generate the pumping function of the heart. PMID:24400272

Protective effects of hydroalcoholic extract from rhizomes of Cynodon dactylon (L.) Pers. on compensated right heart failure in rats.

PubMed

Garjani, Alireza; Afrooziyan, Arash; Nazemiyeh, Hossein; Najafi, Moslem; Kharazmkia, Ali; Maleki-Dizaji, Nasrin

2009-08-05

The rhizomes of Cynodon dactylon are used for the treatment of heart failure in folk medicine. In the present study, we investigated the effects of hydroalcoholic extract of C. dactylon rhizomes on cardiac contractility in normal hearts and on cardiac functions in right-heart failure in rats. Right-heart failure was induced by intraperitoneal injection of monocrotaline (50 mg/kg). Two weeks later, the animals were treated orally with different doses of the extract for fifteen days. At the end of the experiments cardiac functions and markers of myocardial hypertrophy were measured. The treated rats showed very less signs of fatigue, peripheral cyanosis and dyspnea. The survival rate was high in the extract treated groups (90%). Administration of C. dactylon in monocrotaline-injected rats led to profound improvement in cardiac functions as demonstrated by decreased right ventricular end diastolic pressure (RVEDP) and elevated mean arterial pressure. RVdP/dtmax, and RVdP/dt/P as indices of myocardial contractility were also markedly (p < 0.001; using one way ANOVA) increased by the extract. The extract reduced heart and lung congestion by decreasing tissue wet/dry and wet/body weight ratios (p < 0.01). In the isolated rat hearts, the extract produced a remarkable (P < 0.001) positive inotropic effect concomitant with a parallel decrease in LVEDP. The results of this study indicated that C. dactylon exerted a strong protective effect on right heart failure, in part by positive inotropic action and improving cardiac functions.

Berberine promotes ischemia-induced angiogenesis in mice heart via upregulation of microRNA-29b.

PubMed

Zhu, Mo-Li; Yin, Ya-Ling; Ping, Song; Yu, Hai-Ya; Wan, Guang-Rui; Jian, Xu; Li, Peng

2017-01-01

Berberine has several preventive effects on cardiovascular diseases. Increased expression of miR-29b has been reported to attenuate cardiac remodeling after myocardial infarction (MI). We hypothesized that berberine via an miR-29b-dependent mechanism promotes angiogenesis and improves heart functions in mice after MI. The MI model was established in mice by ligation of left anterior descending coronary artery. The expression of miR-29b was examined by RT-qPCR. Angiogenesis was assessed by immunohistochemistry. Berberine increased miR-29b expression and promoted cell proliferations and migrations in cultured endothelial cells, which were abolished by miR-29b antagomir or AMP-activated protein kinase inhibitor compound C. In mice following MI, administration of berberine significantly increased miR-29b expressional level, promoted angiogenesis, reduced infarct size, and improved heart functions after 14 postoperative days. Importantly, these in vivo effects of berberine were ablated by antagonism of miR-29b. Berberine via upregulation of miR-29b promotes ischemia-induced angiogenesis and improves heart functions.

[Improvement in functional capacity after levothyroxine treatment in patients with chronic heart failure and subclinical hypothyroidism].

PubMed

Curotto Grasiosi, Jorge; Peressotti, Bruno; Machado, Rogelio A; Filipini, Eduardo C; Angel, Adriana; Delgado, Jorge; Cortez Quiroga, Gustavo A; Rus Mansilla, Carmen; Martínez Quesada, María del Mar; Degregorio, Alejandro; Cordero, Diego J; Dak, Marcelo; Izurieta, Carlos; Esper, Ricardo J

2013-10-01

To assess whether levothyroxine treatment improves functional capacity in patients with chronic heart failure (New York Heart Association class i-iii) and subclinical hypothyroidism. One hundred and sixty-three outpatients with stable chronic heart failure followed up for at least 6 months were enrolled. A physical examination was performed, and laboratory tests including thyroid hormone levels, Doppler echocardiogram, radionuclide ventriculography, and Holter monitoring were requested. Functional capacity was assessed by of the 6-min walk test. Patients with subclinical hypothyroidism were detected and, after undergoing the s6-min walk test, were given replacement therapy. When they reached normal thyrotropin (TSH) levels, the 6-min walk test was performed again. The distance walked in both tests was recorded, and the difference in meters covered by each patient was analyzed. Prevalence of subclinical hypothyroidism in patients with heart failure was 13%. These patients walked 292±63m while they were hypothyroid and 350±76m when TSH levels returned to normal, a difference of 58±11m (P<.011). Patients with normal baseline TSH levels showed no significant difference between the 2 6-min walk tests. Patients with chronic heart failure and subclinical hypothyroidism significantly improved their physical performance when normal TSH levels were reached. Copyright © 2012 SEEN. Published by Elsevier Espana. All rights reserved.

Mitochondria and heart failure.

PubMed

Murray, Andrew J; Edwards, Lindsay M; Clarke, Kieran

2007-11-01

Energetic abnormalities in cardiac and skeletal muscle occur in heart failure and correlate with clinical symptoms and mortality. It is likely that the cellular mechanism leading to energetic failure involves mitochondrial dysfunction. Therefore, it is crucial to elucidate the causes of mitochondrial myopathy, in order to improve cardiac and skeletal muscle function, and hence quality of life, in heart failure patients. Recent studies identified several potential stresses that lead to mitochondrial dysfunction in heart failure. Chronically elevated plasma free fatty acid levels in heart failure are associated with decreased metabolic efficiency and cellular insulin resistance. Tissue hypoxia, resulting from low cardiac output and endothelial impairment, can lead to oxidative stress and mitochondrial DNA damage, which in turn causes dysfunction and loss of mitochondrial mass. Therapies aimed at protecting mitochondrial function have shown promise in patients and animal models with heart failure. Despite current therapies, which provide substantial benefit to patients, heart failure remains a relentlessly progressive disease, and new approaches to treatment are necessary. Novel pharmacological agents are needed that optimize substrate metabolism and maintain mitochondrial integrity, improve oxidative capacity in heart and skeletal muscle, and alleviate many of the clinical symptoms associated with heart failure.

People with heart failure and home health care resource use and outcomes.

PubMed

Madigan, Elizabeth A

2008-04-01

Patients with heart failure represent a common patient population in home health care, yet little is known about their outcomes. Patients with heart failure, regardless of site of care, experience substantial numbers of rehospitalisations in the United States. Home health care is a common postacute care service for patients with heart failure. Retrospective analysis. The study employed a large administrative data base from 2003 - the Outcomes and Assessment Information Set, which is required for all US Medicare and Medicaid patients receiving home health care. There were 145 191 patients with a primary diagnosis of heart failure represented in the data set. The outcomes of interest were the trajectory of care (point of entry and discharge from home health care), hospitalisation, length of stay and change in functional status. Almost three-quarters (73.9%) of patients entered home health care following a hospital stay. Nearly two-thirds (64%) remained at home at discharge from home health care. Approximately 15% of patients are hospitalised during the home health care episode, most often for symptoms consistent with exacerbation of the heart failure, if a reason could be identified. The average length of stay in home health care was 44 days. There was only a small improvement in functional status: 0.50 points for activities of daily living and 0.57 points for instrumental activities of daily living. Similar small improvement occurred in depressive symptoms, 0.68. There may be room for improvement in these outcomes with more recent evidence that suggests strategies for reducing hospitalisation and improving patient functional status abilities. Yet, the chronic progressive nature of heart failure may also provide a limiting factor in the outcomes that can be attained.

Role of B-type natriuretic peptide in epoxyeicosatrienoic acid-mediated improved post-ischaemic recovery of heart contractile function

PubMed Central

Chaudhary, Ketul R.; Batchu, Sri Nagarjun; Das, Dipankar; Suresh, Mavanur R.; Falck, John R.; Graves, Joan P.; Zeldin, Darryl C.; Seubert, John M.

2009-01-01

Aims This study examined the functional role of B-type natriuretic peptide (BNP) in epoxyeicosatrienoic acid (EET)-mediated cardioprotection in mice with targeted disruption of the sEH or Ephx2 gene (sEH null). Methods and results Isolated mouse hearts were perfused in the Langendorff mode and subjected to global no-flow ischaemia followed by reperfusion. Hearts were analysed for recovery of left ventricular developed pressure (LVDP), mRNA levels, and protein expression. Naïve hearts from sEH null mice had similar expression of preproBNP (Nppb) mRNA compared with wild-type (WT) hearts. However, significant increases in Nppb mRNA and BNP protein expression occurred during post-ischaemic reperfusion and correlated with improved post-ischaemic recovery of LVDP. Perfusion with the putative EET receptor antagonist 14,15-epoxyeicosa-5(Z)-enoic acid prior to ischaemia reduced the preproBNP mRNA in sEH null hearts. Inhibitor studies demonstrated that perfusion with the natriuretic peptide receptor type-A (NPR-A) antagonist, A71915, limited the improved recovery in recombinant full-length mouse BNP (rBNP)- and 11,12-EET-perfused hearts as well as in sEH null mice. Increased expression of phosphorylated protein kinase C ε and Akt were found in WT hearts perfused with either 11,12-EET or rBNP, while mitochondrial glycogen synthase kinase-3β was significantly lower in the same samples. Furthermore, treatment with the phosphoinositide 3-kinase (PI3K) inhibitor wortmannin abolished improved LVDP recovery in 11,12-EET-treated hearts but not did significantly inhibit recovery of rBNP-treated hearts. Conclusion Taken together, these data indicate that EET-mediated cardioprotection involves BNP and PI3K signalling events. PMID:19401302

[MR tomography of the heart].

PubMed

Hahn, D; Beer, M; Sandstede, J

2000-10-01

The introduction of magnetic resonance (MR) tomography has fundamentally changed radiological diagnosis for many diseases. Invasive digital subtraction angiography has already been widely replaced by noninvasive MR angiography for most of the vascular diseases. The rapid technical development of MR imaging in recent years has opened new functional imaging techniques. MR imaging of the heart allows simultaneous measurement of morphological and functional parameters in a single noninvasive examination without any radiation exposure. Because of the high spatial resolution and the reproducibility cine MR imaging is now the gold standard for functional analysis. With the improvement of myocardial perfusion and viability studies many diseases of the heart can be diagnosed in a single examination. MR spectroscopy is the only method which allows a view of the metabolism of the heart. New examinations for vascular imaging and flow quantification complete the goal of "one-stop-shop" imaging of the heart. MR imaging is the only diagnostic modality which allows a complete evaluation of many diseases of the heart with one technique, basic examination as well as follow-up studies. The very rapid improvement in MRI will overcome most of the limitations in the near future, especially concerning MR coronary angiography.

Echocardiographic predictors of change in renal function with intravenous diuresis for decompensated heart failure.

PubMed

Gannon, Stephen A; Mukamal, Kenneth J; Chang, James D

2018-06-14

The aim of this study was to identify echocardiographic predictors of improved or worsening renal function during intravenous diuresis for decompensated heart failure. Secondary aim included defining the incidence and clinical risk factors for acute changes in renal function with decongestion. A retrospective review of 363 patients admitted to a single centre for decompensated heart failure who underwent intravenous diuresis and transthoracic echocardiography was conducted. Clinical, echocardiographic, and renal function data were retrospectively collected. A multinomial logistic regression model was created to determine relative risk ratios for improved renal function (IRF) or worsening renal function (WRF). Within this cohort, 36% of patients experienced WRF, 35% had stable renal function, and 29% had IRF. Patients with WRF were more likely to have a preserved left ventricular ejection fraction compared with those with stable renal function or IRF (P = 0.02). Patients with IRF were more likely to have a dilated, hypokinetic right ventricle compared with those with stable renal function or WRF (P ≤ 0.01), although this was not significant after adjustment for baseline characteristics. Left atrial size, left ventricular linear dimensions, and diastolic function did not significantly predict change in renal function. An acute change in renal function occurred in 65% of patients admitted with decompensated heart failure. WRF was statistically more likely in patients with a preserved left ventricular ejection fraction. A trend towards IRF was noted in patients with global right ventricular dysfunction. © 2018 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of the European Society of Cardiology.

Cardiorenal Syndrome: New Developments in the Understanding and Pharmacologic Management

PubMed Central

2013-01-01

Summary Cardiorenal syndromes (CRSs) with bidirectional heart-kidney signaling are increasingly being recognized for their association with increased morbidity and mortality. In acute CRS, recognition of the importance of worsening kidney function complicating management of acute decompensated heart failure has led to the examination of this specific outcome in the context of acute heart failure clinical trials. In particular, the role of fluid overload and venous congestion has focused interest in the most effective use of diuretic therapy to relieve symptoms of heart failure while at the same time preserving kidney function. Additionally, many novel vasoactive therapies have been studied in recent years with the hopes of augmenting cardiac function, improving symptoms and patient outcomes, while maintaining or improving kidney function. Similarly, recent advances in our understanding of the pathophysiology of chronic CRS have led to reanalysis of kidney outcomes in pivotal trials in chronic congestive heart failure, and newer trials are including changes in kidney function as well as kidney injury biomarkers as prospectively monitored and adjudicated outcomes. This paper provides an overview of some new developments in the pharmacologic management of acute and chronic CRS, examines several reports that illustrate a key management principle for each subtype, and discusses opportunities for future research. PMID:23929925

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

Hu Shunying; Chen Yundai; Li Libing

Purpose: Irradiation to the heart may lead to late cardiovascular complications. The purpose of this study was to investigate whether adenovirus-mediated delivery of the human hepatocyte growth factor gene could reduce post-irradiation damage of the rat heart and improve heart function. Methods and Materials: Twenty rats received single-dose irradiation of 20 Gy gamma ray locally to the heart and were randomized into two groups. Two weeks after irradiation, these two groups of rats received Ad-HGF or mock adenovirus vector intramyocardial injection, respectively. Another 10 rats served as sham-irradiated controls. At post-irradiation Day 120, myocardial perfusion was tested by myocardial contrastmore » echocardiography with contrast agent injected intravenously. At post-irradiation Day 180, cardiac function was assessed using the Langendorff technique with an isolated working heart model, after which heart samples were collected for histological evaluation. Results: Myocardial blood flow was significantly improved in HGF-treated animals as measured by myocardial contrast echocardiography at post-irradiation Day 120 . At post-irradiation Day 180, cardiac function was significantly improved in the HGF group compared with mock vector group, as measured by left ventricular peak systolic pressure (58.80 +- 9.01 vs. 41.94 +- 6.65 mm Hg, p < 0.05), the maximum dP/dt (5634 +- 1303 vs. 1667 +- 304 mm Hg/s, p < 0.01), and the minimum dP/dt (3477 +- 1084 vs. 1566 +- 499 mm Hg/s, p < 0.05). Picrosirius red staining analysis also revealed a significant reduction of fibrosis in the HGF group. Conclusion: Based on the study findings, hepatocyte growth factor gene transfer can attenuate radiation-induced cardiac injury and can preserve cardiac function.« less

Persufflation (gaseous oxygen perfusion) as a method of heart preservation.

PubMed

Suszynski, Thomas M; Rizzari, Michael D; Scott, William E; Eckman, Peter M; Fonger, James D; John, Ranjit; Chronos, Nicolas; Tempelman, Linda A; Sutherland, David E R; Papas, Klearchos K

2013-04-22

Persufflation (PSF; gaseous oxygen perfusion) is an organ preservation technique with a potential for use in donor heart preservation. Improved heart preservation with PSF may improve outcomes by maintaining cardiac tissue quality in the setting of longer cold ischemia times and possibly increasing the number of donor hearts available for allotransplant. Published data suggests that PSF is able to extend the cold storage times for porcine hearts up to 14 hours without compromising viability and function, and has been shown to resuscitate porcine hearts following donation after cardiac death. This review summarizes key published work on heart PSF, including prospective implications and future directions for PSF in heart transplantation. We emphasize the potential impact of extending preservation times and expanding donor selection criteria in heart allotransplant. Additionally, the key issues that need to be addressed before PSF were to become a widely utilized preservation strategy prior to clinical heart transplantation are summarized and discussed.

Heart Valve Biomechanics and Underlying Mechanobiology

PubMed Central

Ayoub, Salma; Ferrari, Giovanni; Gorman, Robert C.; Gorman, Joseph H.; Schoen, Frederick J.; Sacks, Michael S.

2017-01-01

Heart valves control unidirectional blood flow within the heart during the cardiac cycle. They have a remarkable ability to withstand the demanding mechanical environment of the heart, achieving lifetime durability by processes involving the ongoing remodeling of the extracellular matrix. The focus of this review is on heart valve functional physiology, with insights into the link between disease-induced alterations in valve geometry, tissue stress, and the subsequent cell mechanobiological responses and tissue remodeling. We begin with an overview of the fundamentals of heart valve physiology and the characteristics and functions of valve interstitial cells (VICs). We then provide an overview of current experimental and computational approaches that connect VIC mechanobiological response to organ- and tissue-level deformations and improve our understanding of the underlying functional physiology of heart valves. We conclude with a summary of future trends and offer an outlook for the future of heart valve mechanobiology, specifically, multiscale modeling approaches, and the potential directions and possible challenges of research development. PMID:27783858

Renal Function Recovery with Total Artificial Heart Support.

PubMed

Quader, Mohammed A; Goodreau, Adam M; Shah, Keyur B; Katlaps, Gundars; Cooke, Richard; Smallfield, Melissa C; Tchoukina, Inna F; Wolfe, Luke G; Kasirajan, Vigneshwar

2016-01-01

Heart failure patients requiring total artificial heart (TAH) support often have concomitant renal insufficiency (RI). We sought to quantify renal function recovery in patients supported with TAH at our institution. Renal function data at 30, 90, and 180 days after TAH implantation were analyzed for patients with RI, defined as hemodialysis supported or an estimated glomerular filtration rate (eGFR) less than 60 ml/min/1.73 m. Between January 2008 and December 2013, 20 of the 46 (43.5%) TAH recipients (age 51 ± 9 years, 85% men) had RI, mean preoperative eGFR of 48 ± 7 ml/min/1.73 m. Renal function recovery was noted at each follow-up interval: increment in eGFR (ml/min/1.73 m) at 30, 90, and 180 days was 21 ± 35 (p = 0.1), 16.5 ± 18 (p = 0.05), and 10 ± 9 (p = 0.1), respectively. Six patients (30%) required preoperative dialysis. Of these, four recovered renal function, one remained on dialysis, and one died. Six patients (30%) required new-onset dialysis. Of these, three recovered renal function and three died. Overall, 75% (15 of 20) of patients' renal function improved with TAH support. Total artificial heart support improved renal function in 75% of patients with pre-existing significant RI, including those who required preoperative dialysis.

First permanent implant of the Jarvik 2000 Heart.

PubMed

Westaby, S; Banning, A P; Jarvik, R; Frazier, O H; Pigott, D W; Jin, X Y; Catarino, P A; Saito, S; Robson, D; Freeland, A; Myers, T J; Poole-Wilson, P A

2000-09-09

Heart failure is a major public-health concern. Quality and duration of life on maximum medical therapy are poor. The availability of donor hearts is severely limited, therefore an alternative approach is necessary. We have explored the use of a new type of left-ventricular assist device intended as a long-term solution to end-stage heart failure. As part of a prospective clinical trial, we implanted the first permanent Jarvik 2000 Heart--an intraventricular device with an innovative power delivery system--into a 61-year-old man (New York Heart Association functional class IV) with dilated cardiomyopathy. We assessed the effect of this left-ventricular assist device on both native heart function and the symptoms and systemic characteristics of heart failure. The Jarvik 2000 Heart sustained the patient's circulation, and was practical and user-friendly. After 6 weeks, exercise tolerance, myocardial function, and end-organ function improved. Symptoms of heart failure have resolved, and continuous decreased pulse-pressure perfusion has had no adverse effects in the short term. There has been no significant haemolysis and no device-related complications. The skull-mounted pedestal is unobtrusive and has healed well. The initial success of this procedure raises the possibility of a new treatment for end-stage heart failure. In the longer term, its role will be determined by mechanical reliability.

Protective effects of hydroalcoholic extract from rhizomes of Cynodon dactylon (L.) Pers. on compensated right heart failure in rats

PubMed Central

Garjani, Alireza; Afrooziyan, Arash; Nazemiyeh, Hossein; Najafi, Moslem; Kharazmkia, Ali; Maleki-Dizaji, Nasrin

2009-01-01

Background The rhizomes of Cynodon dactylon are used for the treatment of heart failure in folk medicine. In the present study, we investigated the effects of hydroalcoholic extract of C. dactylon rhizomes on cardiac contractility in normal hearts and on cardiac functions in right-heart failure in rats. Methods Right-heart failure was induced by intraperitoneal injection of monocrotaline (50 mg/kg). Two weeks later, the animals were treated orally with different doses of the extract for fifteen days. At the end of the experiments cardiac functions and markers of myocardial hypertrophy were measured. Results The treated rats showed very less signs of fatigue, peripheral cyanosis and dyspnea. The survival rate was high in the extract treated groups (90%). Administration of C. dactylon in monocrotaline-injected rats led to profound improvement in cardiac functions as demonstrated by decreased right ventricular end diastolic pressure (RVEDP) and elevated mean arterial pressure. RVdP/dtmax, and RVdP/dt/P as indices of myocardial contractility were also markedly (p < 0.001; using one way ANOVA) increased by the extract. The extract reduced heart and lung congestion by decreasing tissue wet/dry and wet/body weight ratios (p < 0.01). In the isolated rat hearts, the extract produced a remarkable (P < 0.001) positive inotropic effect concomitant with a parallel decrease in LVEDP. Conclusion The results of this study indicated that C. dactylon exerted a strong protective effect on right heart failure, in part by positive inotropic action and improving cardiac functions. PMID:19653918

Promoting PGC-1α-driven mitochondrial biogenesis is detrimental in pressure-overloaded mouse hearts

PubMed Central

Karamanlidis, Georgios; Garcia-Menendez, Lorena; Kolwicz, Stephen C.; Lee, Chi Fung

2014-01-01

Mitochondrial dysfunction in animal models of heart failure is associated with downregulation of the peroxisome proliferator-activated receptor-γ coactivator (PGC)-1α pathway. To test whether PGC-1α is an appropriate therapeutic target for increasing mitochondrial biogenesis and improving function in heart failure, we used a transgenic (TG) mouse model of moderate overexpression of PGC-1α (∼3-fold) in the heart. TG mice had small increases in citrate synthase activity and mitochondria size in the heart without alterations in myocardial energetics or cardiac function at baseline. In vivo dobutamine stress increased fractional shortening in wild-type mice, but this increase was attenuated in TG mice, whereas ex vivo isolated perfused TG hearts demonstrated normal functional and energetic response to high workload challenge. When subjected to pressure overload by transverse aortic constriction (TAC), TG mice displayed a significantly greater acute mortality for both male and female mice; however, long-term survival up to 8 wk was similar between the two groups. TG mice also showed a greater decrease in fractional shortening and a greater increase in left ventricular chamber dimension in response to TAC. Mitochondrial gene expression and citrate synthase activity were mildly increased in TG mice compared with wild-type mice, and this difference was also maintained after TAC. Our data suggest that a moderate level of PGC-1α overexpression in the heart compromises acute survival and does not improve cardiac function during chronic pressure overload in mice. PMID:25172896

[Combined heart-kidney transplantation in Mexic].

PubMed

Careaga-Reyna, Guillermo; Zetina-Tun, Hugo Jesús; Lezama-Urtecho, Carlos Alberto; Hernández-Domínguez, José Mariano; Santos-Caballero, Marlene

In our country, heart and kidney transplantation is a novel option for treatment of combined terminal heart and kidney failure. This program began in 2012 for selected patients with documented terminal heart failure and structural kidney damage with renal failure. Description of cases: Between January 1, 2012 and April 30, 2016, we made 92 orthotopic heart transplantations. In five of these cases the heart transplantation was combined with kidney transplantation. There were three male and two female patients with a mean age 25.6 ± 5.2 years (range, 17-29). The patients improved their renal function and the heart transplantation was successful with an improved quality of life. One patient died from abdominal sepsis. The other patients are doing well. The combined heart-kidney transplantation is a safe and efficient procedure for patients with structural kidney and heart damage as a cause of terminal failure.

Improving Patient Outcomes With Oral Heart Failure Medications.

PubMed

Sherrod, Melissa M; Cheek, Dennis J; Seale, Ashlie

2016-05-01

Hospitals are under immense pressure to reduce heart failure readmissions that occur within 30 days of discharge, and to improve the quality of care for these patients. Penalties mandated by the Affordable Care Act decrease hospital reimbursement and ultimately the overall cost of caring for these patients increases if they are not well managed. Approximately 25% of patients hospitalized for heart failure are at high risk for readmission and these rates have not changed over the past decade. As a result of an aging population, the incidence of heart failure is expected to increase to one in five Americans over the age of 65. Pharmacologic management can reduce the risk of death and help prevent unnecessary hospitalizations. Healthcare providers who have knowledge of heart failure medications and drug interactions and share this information with their patients contribute to improved long-term survival and physical functioning as well as fewer hospitalizations and a delay of progressive worsening of heart failure.

The effect of ivabradine on functional capacity in patients with chronic obstructive pulmonary disease.

PubMed

Mahmoud, Kareem; Kassem, Hussien Heshmat; Baligh, Essam; ElGameel, Usama; Akl, Yosri; Kandil, Hossam

2016-10-01

Increased sympathetic tone and use of bronchodilators increase heart rate and this may worsen functional capacity in patients with chronic obstructive pulmonary disease (COPD). The aim of this study was to look at the short-term effect of the heart rate lowering drug ivabradine on clinical status in COPD patients.We randomised 80 COPD patients with sinus heart rate ≥90 bpm into either taking ivabradine 7.5 mg twice per day or placebo for two weeks. We assessed all patients using the modified Borg scale and 6-minute walk test at baseline and then again 2 weeks after randomisation.There were no significant differences in age, sex, severity of airway obstruction (measured using forceful exhalation), severity of diastolic dysfunction or pulmonary artery systolic pressure between the two groups. The ivabradine group showed significant improvement in 6-minute walk distance (from 192.6±108.8 m at baseline to 285.1±88.9 m at the end of the study) compared with the control group (230.6±68.4 at baseline and 250.4±65.8 m at the end of study) (p<0.001). This improvement in the drug group was associated with significant improvement of dyspnea on modified Borg scale (p=0.007).Lowering heart rate with ivabradine can improve exercise capacity and functional class in COPD patients with resting heart rate >90 bpm. © Royal College of Physicians 2016. All rights reserved.

Cardiovascular progenitor-derived extracellular vesicles recapitulate the beneficial effects of their parent cells in the treatment of chronic heart failure.

PubMed

Kervadec, Anaïs; Bellamy, Valérie; El Harane, Nadia; Arakélian, Lousineh; Vanneaux, Valérie; Cacciapuoti, Isabelle; Nemetalla, Hany; Périer, Marie-Cécile; Toeg, Hadi D; Richart, Adèle; Lemitre, Mathilde; Yin, Min; Loyer, Xavier; Larghero, Jérôme; Hagège, Albert; Ruel, Marc; Boulanger, Chantal M; Silvestre, Jean-Sébastien; Menasché, Philippe; Renault, Nisa K E

2016-06-01

Cell-based therapies are being explored as a therapeutic option for patients with chronic heart failure following myocardial infarction. Extracellular vesicles (EV), including exosomes and microparticles, secreted by transplanted cells may orchestrate their paracrine therapeutic effects. We assessed whether post-infarction administration of EV released by human embryonic stem cell-derived cardiovascular progenitors (hESC-Pg) can provide equivalent benefits to administered hESC-Pg and whether hESC-Pg and EV treatments activate similar endogenous pathways. Mice underwent surgical occlusion of their left coronary arteries. After 2-3 weeks, 95 mice included in the study were treated with hESC-Pg, EV, or Minimal Essential Medium Alpha Medium (alpha-MEM; vehicle control) delivered by percutaneous injections under echocardiographic guidance into the peri-infarct myocardium. functional and histologic end-points were blindly assessed 6 weeks later, and hearts were processed for gene profiling. Genes differentially expressed between control hearts and hESC-Pg-treated and EV-treated hearts were clustered into functionally relevant pathways. At 6 weeks after hESC-Pg administration, treated mice had significantly reduced left ventricular end-systolic (-4.20 ± 0.96 µl or -7.5%, p = 0.0007) and end-diastolic (-4.48 ± 1.47 µl or -4.4%, p = 0.009) volumes compared with baseline values despite the absence of any transplanted hESC-Pg or human embryonic stem cell-derived cardiomyocytes in the treated mouse hearts. Equal benefits were seen with the injection of hESC-Pg-derived EV, whereas animals injected with alpha-MEM (vehicle control) did not improve significantly. Histologic examination suggested a slight reduction in infarct size in hESC-Pg-treated animals and EV-treated animals compared with alpha-MEM-treated control animals. In the hESC-Pg-treated and EV-treated groups, heart gene profiling identified 927 genes that were similarly upregulated compared with the control group. Among the 49 enriched pathways associated with these up-regulated genes that could be related to cardiac function or regeneration, 78% were predicted to improve cardiac function through increased cell survival and/or proliferation or DNA repair as well as pathways related to decreased fibrosis and heart failure. In this post-infarct heart failure model, either hESC-Pg or their secreted EV enhance recovery of cardiac function and similarly affect cardiac gene expression patterns that could be related to this recovery. Although the mechanisms by which EV improve cardiac function remain to be determined, these results support the idea that a paracrine mechanism is sufficient to effect functional recovery in cell-based therapies for post-infarction-related chronic heart failure. Copyright © 2016 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

Cardiac rehabilitation improves coronary endothelial function in patients with heart failure due to dilated cardiomyopathy: A positron emission tomography study.

PubMed

Legallois, Damien; Belin, Annette; Nesterov, Sergey V; Milliez, Paul; Parienti, J-J; Knuuti, Juhani; Abbas, Ahmed; Tirel, Olivier; Agostini, Denis; Manrique, Alain

2016-01-01

Endothelial dysfunction is common in patients with heart failure and is associated with poor clinical outcome. Cardiac rehabilitation is able to enhance peripheral endothelial function but its impact on coronary vasomotion remains unknown. We aimed to evaluate the effect of cardiac rehabilitation on coronary vasomotion in patients with heart failure. We prospectively enrolled 29 clinically stable heart failure patients from non-ischaemic dilated cardiomyopathy and without coronary risk factors. Myocardial blood flow was quantified using (15)-O water positron emission tomography at rest and during a cold pressor test, before and after 12 weeks of cardiac rehabilitation and optimization of medical therapy. Rest myocardial blood flow was significantly improved after the completion of rehabilitation compared to baseline (1.31 ± 0.38 mL/min/g vs. 1.16 ± 0.41 mL/min/g, p = 0.04). The endothelium-related change in myocardial blood flow from rest to cold pressor test and the percentage of myocardial blood flow increase during the cold pressor test were both significantly improved after cardiac rehabilitation (respectively from -0.03 ± 0.22 mL/min/g to 0.19 ± 0.22 mL/min/g, p < 0.001 and from 101.5 ± 16.5% to 118.3 ± 24.4%, p < 0.001). Left ventricular ejection fraction, plasma levels of brain natriuretic peptide, maximal oxygen consumption and the Minnesota Living with Heart Failure Questionnaire score were also significantly improved. The improvement was not related to uptitration of medical therapy. Coronary endothelial function is altered in patients with heart failure due to non-ischaemic dilated cardiomyopathy. In these patients, cardiac rehabilitation significantly improves coronary vasomotion. © The European Society of Cardiology 2014.

Muscle electrical stimulation improves neurovascular control and exercise tolerance in hospitalised advanced heart failure patients.

PubMed

Groehs, Raphaela V; Antunes-Correa, Ligia M; Nobre, Thais S; Alves, Maria-Janieire Nn; Rondon, Maria Urbana Pb; Barreto, Antônio Carlos Pereira; Negrão, Carlos E

2016-10-01

We investigated the effects of muscle functional electrical stimulation on muscle sympathetic nerve activity and muscle blood flow, and, in addition, exercise tolerance in hospitalised patients for stabilisation of heart failure. Thirty patients hospitalised for treatment of decompensated heart failure, class IV New York Heart Association and ejection fraction ≤ 30% were consecutively randomly assigned into two groups: functional electrical stimulation (n = 15; 54 ± 2 years) and control (n = 15; 49 ± 2 years). Muscle sympathetic nerve activity was directly recorded via microneurography and blood flow by venous occlusion plethysmography. Heart rate and blood pressure were evaluated on a beat-to-beat basis (Finometer), exercise tolerance by 6-minute walk test, quadriceps muscle strength by a dynamometer and quality of life by Minnesota questionnaire. Functional electrical stimulation consisted of stimulating the lower limbs at 10 Hz frequency, 150 ms pulse width and 70 mA intensity for 60 minutes/day for 8-10 consecutive days. The control group underwent electrical stimulation at an intensity of < 20 mA. Baseline characteristics were similar between groups, except age that was higher and C-reactive protein and forearm blood flow that were smaller in the functional electrical stimulation group. Functional electrical stimulation significantly decreased muscle sympathetic nerve activity and increased muscle blood flow and muscle strength. No changes were found in the control group. Walking distance and quality of life increased in both groups. However, these changes were greater in the functional electrical stimulation group. Functional electrical stimulation improves muscle sympathetic nerve activity and vasoconstriction and increases exercise tolerance, muscle strength and quality of life in hospitalised heart failure patients. These findings suggest that functional electrical stimulation may be useful to hospitalised patients with decompensated chronic heart failure. © The European Society of Cardiology 2016.

THE EFFECT OF RIGHT VENTRICULAR PACEMAKER LEAD POSITION ON FUNCTIONAL STATUS IN PATIENTS WITH PRESERVED LEFT VENTRICULAR EJECTION FRACTION.

PubMed

Mitov, Vladimir M; Perisic, Zoran; Jolic, Aleksandar; Kostic, Tomislav; Aleksic, Aleksandar; Aleksic, Zeljka

2016-07-01

The study was aimed at assessing the difference between the right ventricle apex versus the right ventricular outflow tract lead position in functional capacity in the patients with the preserved left ventricular ejection fraction after 12 months of pacemaker stimulation. This was a prospective, randomized, follow-up study, which lasted for 12 months. The study sample included 132 consecutive patients who were implanted with permanent anti-bradicardiac pacemaker. Regarding the right ventricular lead position the patients were divided into two groups: the right ventricle apex group consisting of 61 patients with right ventricular apex lead position. The right ventricular outflow tract group included 71 patients with right ventricular outflow tract lead position. Functional capacity was assessed by Minnesota Living With Heart Failure score, New York Heart Association class and Six Minute Walk Test. Left ventricular ejection fraction was assessed by echocardiography. Minnesota Living With Heart Failure score and New York Heart Association class had a statistically significant improvement in both study groups. The patients from right ventricle apex group walked 20.95% (p=O.03) more in comparison to starting values. The patients from right ventricular outflow tract group walked only 13.63% (p=0.09) longer distance than the startingoneConclusion. Analysis of tests of functional status New York Heart Association class and Minnesota Living With Heart Failure questionnaire showed an even improvement in the right ventricle apex and right ventricular outflow tract groups. Analysis of 6 minute walk test showed that only the patients with the preserved left ventricular ejection fraction from the right ventricle apex group had a significant improvement after 12 months of pacemaker stimulation..

Folic acid prevents cardiac dysfunction and reduces myocardial fibrosis in a mouse model of high-fat diet-induced obesity.

PubMed

Li, Wei; Tang, Renqiao; Ouyang, Shengrong; Ma, Feifei; Liu, Zhuo; Wu, Jianxin

2017-01-01

Folic acid (FA) is an antioxidant that can reduce reactive oxygen species generation and can blunt cardiac dysfunction during ischemia. We hypothesized that FA supplementation prevents cardiac fibrosis and cardiac dysfunction induced by obesity. Six-week-old C57BL6/J mice were fed a high-fat diet (HFD), normal diet (ND), or an HFD supplemented with folic acid (FAD) for 14 weeks. Cardiac function was measured using a transthoracic echocardiographic exam. Phenotypic analysis included measurements of body and heart weight, blood glucose and tissue homocysteine (Hcy) content, and heart oxidative stress status. HFD consumption elevated fasting blood glucose levels and caused obesity and heart enlargement. FA supplementation in HFD-fed mice resulted in reduced fasting blood glucose, heart weight, and heart tissue Hcy content. We also observed a significant cardiac systolic dysfunction when mice were subjected to HFD feeding as indicated by a reduction in the left ventricular ejection fraction and fractional shortening. However, FAD treatment improved cardiac function. FA supplementation protected against cardiac fibrosis induced by HFD. In addition, HFD increased malondialdehyde concentration of the heart tissue and reduced the levels of antioxidant enzyme, glutathione, and catalase. HFD consumption induced myocardial oxidant stress with amelioration by FA treatment. FA supplementation significantly lowers blood glucose levels and heart tissue Hcy content and reverses cardiac dysfunction induced by HFD in mice. These functional improvements of the heart may be mediated by the alleviation of oxidative stress and myocardial fibrosis.

[Comorbidities of heart failure: sleep apnea].

PubMed

Woehrle, H; Oldenburg, O; Stadler, S; Arzt, M

2018-05-01

Since sleep apnea often occurs in heart failure, physicians regularly need to decide whether further diagnostic procedures and/or treatment are required. Which types of sleep apnea occur in heart failure patients? When is treatment needed? Which treatments and treatment goals are appropriate? Clinical trials and guidelines as well as their implementation in clinical practice are discussed. At least 40% of patients with heart failure, both with reduced and preserved left ventricular ejection fraction (HFrEF and HFpEF, respectively), suffer from relevant sleep apnea. In heart failure patients both obstructive and central sleep apnea are associated with increased mortality. In HFrEF as well as in HFpEF patients with obstructive sleep apnea, treatment with continuous positive airway pressure (CPAP) achieves symptomatic and functional improvements. In patients with HFpEF, positive airway pressure treatment of central sleep apnea may be beneficial. In patients with HFrEF and left ventricular ejection fraction ≤45%, adaptive servoventilation is contraindicated. Sleep apnea is highly prevalent in heart failure patients and its treatment in specific patient groups can improve symptoms and functional outcomes. Thus, testing for sleep apnea is recommended.

Stem Cell Therapy in Acute Myocardial Infarction: A Pot of Gold or Pandora's Box

PubMed Central

Shah, V. K.; Shalia, K. K.

2011-01-01

Stem cell therapy for conditions characterized by myocyte loss in myocardial infarction and heart failure is intuitively appealing. Stem cells from various sources, including heart itself in preclinical and animal studies, have shown the potential to improve the function of ventricular muscle after ischaemic injury. The clinical experience from worldwide studies have indicated the safety profile but with modest benefits. The predominant mechanisms of transplanted cells for improving cardiac function have pointed towards paracrine effects rather than transdifferentiation into cardiomyocytes. Thus, further investigations should be encouraged towards bench side and bedside to resolve various issues for ensuring the correct type and dosing of cells, time, and method of delivery and identify correct mechanism of functional improvement. An interdisciplinary effort at the scientific, clinical, and the government front will bring successful realization of this therapy for healing the heart and may convert what seems now a Pandora's Box into a Pot of Gold. PMID:21804827

Effects of nocturnal oxygen therapy on heart function in SDB patients undergoing dialysis.

PubMed

Nakajima, Fumitaka; Furumatsu, Yoshiyuki; Yurugi, Takatomi; Amari, Yoshifumi; Iida, Takeshi; Uehara, Mitsuru; Fukunaga, Megumu

2015-06-01

There is a close relationship between sleep disordered breathing (SDB) and heart failure. We performed home oxygen therapy (HOT) in patients with SAS undergoing dialysis, and investigated its effects on the heart function. The subjects were 10 SDB patients on dialysis. On retiring at night, oxygen was transnasally administered at 1.0 L/min. The human atrial natriuretic peptide (hANP), brain natriuretic peptide (BNP), total protein, Alb, cholesterol and phosphorus levels were measured before the start of oxygen therapy and after 6 weeks. The mean SpO2 increased from 93.5% [91.5, 97.0] to 96.3% [94.8, 97.4] (median [interquartile range]) (p = 0.015). The hANP (p = 0.0039), BNP (p = 0.0098) and serum Alb (p = 0.015) levels significantly improved. There were no significant changes in the cholesterol, phosphorus or total protein levels. These results suggest that nocturnal oxygen therapy improves indices of heart failure, contributing to the prevention and treatment of heart failure in dialysis patients with SDB.

The effect of massage on heart rate variability in preterm infants.

PubMed

Smith, S L; Lux, R; Haley, S; Slater, H; Beachy, J; Beechy, J; Moyer-Mileur, L J

2013-01-01

To test the hypothesis that massage would improve autonomic nervous system (ANS) function as measured by heart rate variability (HRV) in preterm infants. Medically stable, 29- to 32-week preterm infants (17 massage, 20 control) were enrolled in a masked, randomized longitudinal study. Licensed massage therapists provided the massage or control condition twice a day for 4 weeks. Weekly HRV, a measure of ANS development and function, was analyzed using SPSS generalized estimating equations. Infant characteristics were similar between groups. HRV improved in massaged infants but not in the control infants (P<0.05). Massaged males had a greater improvement in HRV than females (P<0.05). HRV in massaged infants was on a trajectory comparable to term-born infants by study completion. Massage-improved HRV in a homogeneous sample of hospitalized, medically stable, preterm male infants and may improve infant response to exogenous stressors. We speculate that massage improves ANS function in these infants.

Active inhibitor-1 maintains protein hyper-phosphorylation in aging hearts and halts remodeling in failing hearts.

PubMed

Pritchard, Tracy J; Kawase, Yoshiaki; Haghighi, Kobra; Anjak, Ahmad; Cai, Wenfeng; Jiang, Min; Nicolaou, Persoulla; Pylar, George; Karakikes, Ioannis; Rapti, Kleopatra; Rubinstein, Jack; Hajjar, Roger J; Kranias, Evangelia G

2013-01-01

Impaired sarcoplasmic reticulum calcium cycling and depressed contractility are key characteristics in heart failure. Defects in sarcoplasmic reticulum function are characterized by decreased SERCA2a Ca-transport that is partially attributable to dephosphorylation of its regulator phospholamban by increased protein phosphatase 1 activity. Inhibition of protein phosphatase 1 through activation of its endogenous inhibitor-1 has been shown to enhance cardiac Ca-handling and contractility as well as protect from pathological stress remodeling in young mice. In this study, we assessed the long-term effects of inducible expression of constitutively active inhibitor-1 in the adult heart and followed function and remodeling through the aging process, up to 20 months. Mice with inhibitor-1 had normal survival and similar function to WTs. There was no overt remodeling as evidenced by measures of left ventricular end-systolic and diastolic diameters and posterior wall dimensions, heart weight to tibia length ratio, and histology. Higher phosphorylation of phospholamban at both Ser16 and Thr17 was maintained in aged hearts with active inhibitor-1, potentially offsetting the effects of elevated Ser2815-phosphorylation in ryanodine receptor, as there were no increases in arrhythmias under stress conditions in 20-month old mice. Furthermore, long-term expression of active inhibitor-1 via recombinant adeno-associated virus type 9 gene transfer in rats with pressure-overload induced heart failure improved function and prevented remodeling, associated with increased phosphorylation of phospholamban at Ser16 and Thr17. Thus, chronic inhibition of protein phosphatase 1, through increases in active inhibitor-1, does not accelerate age-related cardiomyopathy and gene transfer of this molecule in vivo improves function and halts remodeling in the long term.

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.

Intravenous Milrinone in Treatment of Advanced Congestive Heart Failure

PubMed Central

Zewail, Aly M.; Nawar, Mohammad; Vrtovec, Bojan; Eastwood, Cathy; Kar, Biswajit; Delgado, Reynolds M.

2003-01-01

Phosphodiesterase inhibitors such as milrinone can relieve symptoms and improve hemodynamics in patients with advanced congestive heart failure. We retrospectively evaluated the hemodynamic and clinical outcomes of long-term combination therapy with intravenous milrinone and oral β-blockers in 65 patients with severe congestive heart failure (New York Heart Association class IV function and ejection fraction <25%) refractory to oral medical therapy. Fifty-one patients successfully began β-blocker therapy while on intravenous milrinone. Oral medical therapy was maximized when possible. The mean duration of milrinone treatment in this combination-treatment group was 269 days (range, 14–1,026 days). Functional class improved from IV to II–III with milrinone therapy. Twenty-four such patients tolerated β-blocker up-titration and were successfully weaned from milrinone. Sixteen patients (31%) died while receiving combination therapy; one died of sudden cardiac death (on treatment day 116); the other 15 died of progressive heart failure or other complications. Hospital admissions during the previous 6 months and admissions within 6 months after milrinone initiation stayed the same. Meanwhile, the total number of hospital days decreased from 450 to 380 (a 15.6% reduction), and the mean length of stay decreased by 1.4 days (a 14.7% reduction). We conclude that 1) milrinone plus β-blocker combination therapy is an effective treatment for heart failure even with β-blocker up-titration, 2) weaning from milrinone may be possible once medications are maximized, 3) patients' functional status improves on the combination regimen, and 4) treatment-related sudden death is relatively infrequent during the combination regimen. (Tex Heart Inst J 2003;30:109–13) PMID:12809251

Improvement of Automated Identification of the Heart Wall in Echocardiography by Suppressing Clutter Component

NASA Astrophysics Data System (ADS)

Takahashi, Hiroki; Hasegawa, Hideyuki; Kanai, Hiroshi

2013-07-01

For the facilitation of analysis and elimination of the operator dependence in estimating the myocardial function in echocardiography, we have previously developed a method for automated identification of the heart wall. However, there are misclassified regions because the magnitude-squared coherence (MSC) function of echo signals, which is one of the features in the previous method, is sensitively affected by the clutter components such as multiple reflection and off-axis echo from external tissue or the nearby myocardium. The objective of the present study is to improve the performance of automated identification of the heart wall. For this purpose, we proposed a method to suppress the effect of the clutter components on the MSC of echo signals by applying an adaptive moving target indicator (MTI) filter to echo signals. In vivo experimental results showed that the misclassified regions were significantly reduced using our proposed method in the longitudinal axis view of the heart.

What can we learn about treating heart failure from the heart's response to acute exercise? Focus on the coronary microcirculation.

PubMed

Heinonen, Ilkka; Sorop, Oana; de Beer, Vincent J; Duncker, Dirk J; Merkus, Daphne

2015-10-15

Coronary microvascular function and cardiac function are closely related in that proper cardiac function requires adequate oxygen delivery through the coronary microvasculature. Because of the close proximity of cardiomyocytes and coronary microvascular endothelium, cardiomyocytes not only communicate their metabolic needs to the coronary microvasculature, but endothelium-derived factors also directly modulate cardiac function. This review summarizes evidence that the myocardial oxygen balance is disturbed in the failing heart because of increased extravascular compressive forces and coronary microvascular dysfunction. The perturbations in myocardial oxygen balance are exaggerated during exercise and are due to alterations in neurohumoral influences, endothelial function, and oxidative stress. Although there is some evidence from animal studies that the myocardial oxygen balance can partly be restored by exercise training, it is largely unknown to what extent the beneficial effects of exercise training include improvements in endothelial function and/or oxidative stress in the coronary microvasculature and how these improvements are impacted by risk factors such as diabetes, obesity, and hypercholesterolemia. Copyright © 2015 the American Physiological Society.

Neuregulin-1/erbB-activation improves cardiac function and survival in models of ischemic, dilated, and viral cardiomyopathy.

PubMed

Liu, Xifu; Gu, Xinhua; Li, Zhaoming; Li, Xinyan; Li, Hui; Chang, Jianjie; Chen, Ping; Jin, Jing; Xi, Bing; Chen, Denghong; Lai, Donna; Graham, Robert M; Zhou, Mingdong

2006-10-03

We evaluated the therapeutic potential of a recombinant 61-residue neuregulin-1 (beta2a isoform) receptor-active peptide (rhNRG-1) in multiple animal models of heart disease. Activation of the erbB family of receptor tyrosine kinases by rhNRG-1 could provide a treatment option for heart failure, because neuregulin-stimulated erbB2/erbB4 heterodimerization is not only critical for myocardium formation in early heart development but prevents severe dysfunction of the adult heart and premature death. Disabled erbB-signaling is also implicated in the transition from compensatory hypertrophy to failure, whereas erbB receptor-activation promotes myocardial cell growth and survival and protects against anthracycline-induced cardiomyopathy. rhNRG-1 was administered IV to animal models of ischemic, dilated, and viral cardiomyopathy, and cardiac function and survival were evaluated. Short-term intravenous administration of rhNRG-1 to normal dogs and rats did not alter hemodynamics or cardiac contractility. In contrast, rhNRG-1 improved cardiac performance, attenuated pathological changes, and prolonged survival in rodent models of ischemic, dilated, and viral cardiomyopathy, with the survival benefits in the ischemic model being additive to those of angiotensin-converting enzyme inhibitor therapy. In addition, despite continued pacing, rhNRG-1 produced global improvements in cardiac function in a canine model of pacing-induced heart failure. These beneficial effects make rhNRG-1 promising as a broad-spectrum therapeutic for the treatment of heart failure due to a variety of common cardiac diseases.

Combined aerobic and resistance exercise program improves task performance in patients with heart failure.

PubMed

Gary, Rebecca A; Cress, M Elaine; Higgins, Melinda K; Smith, Andrew L; Dunbar, Sandra B

2011-09-01

To assess the effects of a home-based aerobic and resistance training program on the physical function of adults with New York Heart Association (NYHA) class II and III patients and systolic heart failure (HF). Randomized controlled trial. Home based. Stable patients (N=24; mean age, 60 ± 10 y; left ventricular ejection fraction, 25% ± 9%; 50% white; 50% women) with New York Heart Association (NYHA) classes II and III (NYHA class III, 58%) systolic heart failure (HF). A 12-week progressive home-based program of moderate-intensity aerobic and resistance exercise. Attention control wait list participants performed light stretching and flexibility exercises. A 10-item performance-based physical function measure, the Continuous Scale Physical Functional Performance test (CS-PFP10), was the major outcome variable and included specific physical activities measured in time to complete a task, weight carried during a task, and distance walked. Other measures included muscle strength, HRQOL (Minnesota Living With Heart Failure Questionnaire, Epworth Sleepiness Scale), functional capacity (Duke Activity Status Index), and disease severity (brain natriuretic peptide) levels. After the exercise intervention, 9 of 10 specific task activities were performed more rapidly, with increased weight carried by exercise participants compared with the attention control wait list group. Exercise participants also showed significant improvements in CS-PFP10 total score (P<.025), upper and lower muscle strength, and HRQOL (P<.001) compared with the attention control wait list group. Adherence rates were 83% and 99% for the aerobic and resistance training, respectively. Patients with stable HF who participate in a moderate-intensity combined aerobic and resistance exercise program may improve performance of routine physical activities of daily living by using a home-based exercise approach. Performance-based measures such as the CS-PFP10 may provide additional insights into physical function in patients with HF that more commonly used exercise tests may not identify. Early detection of subtle changes that may signal declining physical function that are amenable to intervention potentially may slow further loss of function in this patient population. Copyright © 2011 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

Treatment of Heart Failure With Associated Functional Mitral Regurgitation Using the ARTO System: Initial Results of the First-in-Human MAVERIC Trial (Mitral Valve Repair Clinical Trial).

PubMed

Rogers, Jason H; Thomas, Martyn; Morice, Marie-Claude; Narbute, Inga; Zabunova, Milana; Hovasse, Thomas; Poupineau, Mathieu; Rudzitis, Ainars; Kamzola, Ginta; Zvaigzne, Ligita; Greene, Samantha; Erglis, Andrejs

2015-07-01

MAVERIC (Mitral Valve Repair Clinical Trial) reports the safety and efficacy of the ARTO system in patients with symptomatic heart failure and functional mitral regurgitation (FMR). The ARTO system percutaneously modifies the mitral annulus to improve leaflet coaptation in FMR. The MAVERIC trial is a prospective, nonrandomized first-in-human study. Key inclusion criteria were systolic heart failure New York Heart Association functional classes II to IV, FMR grade ≥2+, left ventricular (LV) ejection fraction ≤40%, LV end-diastolic diameter >50 mm and ≤75 mm. Exclusion criteria were clinical variables that precluded feasibility of the ARTO procedure. Primary outcomes were safety (30-day major adverse events) and efficacy (MR reduction, LV volumes, and functional status). Eleven patients received the ARTO system, and there were no procedural adverse events. From baseline to 30 days, there were meaningful improvements. Effective regurgitant orifice area decreased from 30.3 ± 11.1 mm(2) to 13.5 ± 7.1 mm(2) and regurgitant volumes from 45.4 ± 15.0 ml to 19.5 ± 10.2 ml. LV end-systolic volume index improved from 77.5 ± 24.3 ml/m(2) to 68.5 ± 21.4 ml/m(2), and LV end-diastolic volume index 118.7 ± 28.6 ml/m(2) to 103.9 ± 21.2 ml/m(2). Mitral annular anteroposterior diameter decreased from 45.0 ± 3.3 mm to 38.7 ± 3.0 mm. Functional status was 81.8% New York Heart Association functional class III/IV improving to 54.6% functional class I/II. At 30 days, there were 2 adverse events: 1 pericardial effusion requiring surgical drainage; and 1 asymptomatic device dislodgement. The ARTO system is a novel transcatheter device that can be used safely with meaningful efficacy in the treatment of FMR. (Mitral Valve Repair Clinical Trial [MAVERIC]; NCT02302872). Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

An intervention to promote physical activity and self-management in people with stable chronic heart failure The Home-Heart-Walk study: study protocol for a randomized controlled trial

PubMed Central

2011-01-01

Background Chronic heart failure (CHF) is a chronic debilitating condition with economic consequences, mostly because of frequent hospitalisations. Physical activity and adequate self-management capacity are important risk reduction strategies in the management of CHF. The Home-Heart-Walk is a self-monitoring intervention. This model of intervention has adapted the 6-minute walk test as a home-based activity that is self-administered and can be used for monitoring physical functional capacity in people with CHF. The aim of the Home-Heart-Walk program is to promote adherence to physical activity recommendations and improving self-management in people with CHF. Methods/Design A randomised controlled trial is being conducted in English speaking people with CHF in four hospitals in Sydney, Australia. Individuals diagnosed with CHF, in New York Heart Association Functional Class II or III, with a previous admission to hospital for CHF are eligible to participate. Based on a previous CHF study and a loss to follow-up of 10%, 166 participants are required to be able to detect a 12-point difference in the study primary endpoint (SF-36 physical function domain). All enrolled participant receive an information session with a cardiovascular nurse. This information session covers key self-management components of CHF: daily weight; diet (salt reduction); medication adherence; and physical activity. Participants are randomised to either intervention or control group through the study randomisation centre after baseline questionnaires and assessment are completed. For people in the intervention group, the research nurse also explains the weekly Home-Heart-Walk protocol. All participants receive monthly phone calls from a research coordinator for six months, and outcome measures are conducted at one, three and six months. The primary outcome of the trial is the physical functioning domain of quality of life, measured by the physical functioning subscale of the Medical Outcome Study Short Form -36. Secondary outcomes include physical functional capacity measured by the standard six minute walk test, self-management capacity, health related quality of life measured by Medical Outcome Study Short Form -36 and Minnesota Living With Heart Failure Questionnaire, self-efficacy and self-care behaviour. Discussion A self-monitoring intervention that can improve individual's exercise self-efficacy, self-management capacity could have potential significance in improving the management of people with chronic heart failure in community settings. Trial Registration Australian New Zealand Clinical Trial Registry 12609000437268 PMID:21366927

An intervention to promote physical activity and self-management in people with stable chronic heart failure The Home-Heart-Walk study: study protocol for a randomized controlled trial.

PubMed

Du, Hui Y; Newton, Phillip J; Zecchin, Robert; Denniss, Robert; Salamonson, Yenna; Everett, Bronwyn; Currow, David C; Macdonald, Peter S; Davidson, Patricia M

2011-03-02

Chronic heart failure (CHF) is a chronic debilitating condition with economic consequences, mostly because of frequent hospitalisations. Physical activity and adequate self-management capacity are important risk reduction strategies in the management of CHF. The Home-Heart-Walk is a self-monitoring intervention. This model of intervention has adapted the 6-minute walk test as a home-based activity that is self-administered and can be used for monitoring physical functional capacity in people with CHF. The aim of the Home-Heart-Walk program is to promote adherence to physical activity recommendations and improving self-management in people with CHF. A randomised controlled trial is being conducted in English speaking people with CHF in four hospitals in Sydney, Australia. Individuals diagnosed with CHF, in New York Heart Association Functional Class II or III, with a previous admission to hospital for CHF are eligible to participate. Based on a previous CHF study and a loss to follow-up of 10%, 166 participants are required to be able to detect a 12-point difference in the study primary endpoint (SF-36 physical function domain).All enrolled participant receive an information session with a cardiovascular nurse. This information session covers key self-management components of CHF: daily weight; diet (salt reduction); medication adherence; and physical activity. Participants are randomised to either intervention or control group through the study randomisation centre after baseline questionnaires and assessment are completed. For people in the intervention group, the research nurse also explains the weekly Home-Heart-Walk protocol. All participants receive monthly phone calls from a research coordinator for six months, and outcome measures are conducted at one, three and six months. The primary outcome of the trial is the physical functioning domain of quality of life, measured by the physical functioning subscale of the Medical Outcome Study Short Form -36. Secondary outcomes include physical functional capacity measured by the standard six minute walk test, self-management capacity, health related quality of life measured by Medical Outcome Study Short Form -36 and Minnesota Living With Heart Failure Questionnaire, self-efficacy and self-care behaviour. A self-monitoring intervention that can improve individual's exercise self-efficacy, self-management capacity could have potential significance in improving the management of people with chronic heart failure in community settings. Australian New Zealand Clinical Trial Registry 12609000437268.

Overcoming the Roadblocks to Cardiac Cell Therapy Using Tissue Engineering.

PubMed

Yanamandala, Mounica; Zhu, Wuqiang; Garry, Daniel J; Kamp, Timothy J; Hare, Joshua M; Jun, Ho-Wook; Yoon, Young-Sup; Bursac, Nenad; Prabhu, Sumanth D; Dorn, Gerald W; Bolli, Roberto; Kitsis, Richard N; Zhang, Jianyi

2017-08-08

Transplantations of various stem cells or their progeny have repeatedly improved cardiac performance in animal models of myocardial injury; however, the benefits observed in clinical trials have been generally less consistent. Some of the recognized challenges are poor engraftment of implanted cells and, in the case of human cardiomyocytes, functional immaturity and lack of electrical integration, leading to limited contribution to the heart's contractile activity and increased arrhythmogenic risks. Advances in tissue and genetic engineering techniques are expected to improve the survival and integration of transplanted cells, and to support structural, functional, and bioenergetic recovery of the recipient hearts. Specifically, application of a prefabricated cardiac tissue patch to prevent dilation and to improve pumping efficiency of the infarcted heart offers a promising strategy for making stem cell therapy a clinical reality. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Educational level and the quality of life of heart failure patients: a longitudinal study.

PubMed

Barbareschi, Giorgio; Sanderman, Robbert; Leegte, Ivonne Lesman; van Veldhuisen, Dirk J; Jaarsma, Tiny

2011-01-01

Lower education in heart failure (HF) patients is associated with high levels of anxiety, limited physical functioning, and an increased risk of hospitalization. We examined whether educational level is related to longitudinal differences in quality of life (QoL) in HF patients. This research is a substudy of the Coordinating study evaluating Outcomes of Advising and Counselling in Heart failure (COACH). QoL of 553 HF patients (mean age 69, 38% female, mean left ventricular ejection fraction 33%) was assessed during their hospitalization and at 4 follow-up measurements after discharge. In total 32% of the patients had very low, 24% low, 32% medium, and 12% high education. Patients with low educational levels reported the worst QoL. Significant differences between educational groups (P < .05) were only reported in physical functioning, social functioning, energy/fatigue, pain, and limitations in role functioning related to emotional problems. Longitudinal results show that a significantly higher proportion of high-educated patients improved in functional limitations related to emotional problems over time compared with lower-educated patients (P < .05). Patients with low educational levels reported the worst physical and functional condition. High-educated patients improved more than the other patients in functional limitations related to emotional problems over time. Low-educated patients may require different levels of intervention to improve their physical and functional condition. Copyright © 2011 Elsevier Inc. All rights reserved.

[Effect of formula of removing both phlegm and blood stasis in improving cardiac function of Chinese mini-swine with coronary heart disease of phlegm-stasis cementation syndrome].

PubMed

Li, Lei; Lin, Cheng-Ren; Ren, Jian-Xun; Miao, Lan; Yao, Ming-Jiang; Li, Dan; Shi, Yue; Ma, Yan-Lei; Fu, Jian-Hua; Liu, Jian-Xun

2014-02-01

To evaluate that the effect of formula of removing both phlegm and blood stasis in improving cardiac function of Chinese mini-swine with coronary heart disease of phlegm-stasis cementation syndrome. Totally 36 Chinese mini-swine were randomly divided to six groups: the normal control group, the model group, the Danlou tablet group, and Tanyu Tonzhi Fang(TYTZ) groups with doses of 2. 0, 1. 0 and 0. 5 g kg-1, with six in each group. Except for the normal control group, all of other groups were fed with high-fat diet for 2 weeks. Interventional balloons are adopted to injure their left anterior descending artery endothelium. After the operation, they were fed with high-fat diet for 8 weeks to prepare the coronary heart disease model of phlegm-stasis cementation syndrome. After the operation, they were administered with drugs for 8 weeks. The changes in the myocardial ischemia were observed. The changes in the cardiac function and structure were detected by cardiac ultrasound and noninvasive hemodynamic method. Compared with the normal control group, the model group showed significant increase in myocardial ischemia and SVR and obvious decrease in CO, SV and LCW in noninvasive hemodynamic parameters (P <0.05 or P <0.01). The ultrasonic cardiogram indicated notable decrease in IVSd, LVPWs, EF and FS, and remarkable increase in LVIDs (P<0. 05 orP<0.01). Compared with the model group, TYTZ could reduce the myocardial ischemia, strengthen cardiac function, and improve the abnormal cardiac structure and function induced by ischemia (P <0. 05 or P <0. 01). TYTZ shows a significant effect in improving cardiac function of Chinese mini-swine with coronary heart disease of phlegm-stasis cementation syndrome. The clinical cardiac function detection method could be adopted to correctly evaluate the changes in the post-myocardial ischemia cardiac function, and narrow the gap between clinical application and basic experimental studies.

[Systemic sclerosis: Efficacy of intravenous immunoglobulins in severe cardiac involvement?

PubMed

Cacciatore, C; Riviere, S; Cohen, A; Gatfosse, M; Ederhy, S; Fain, O; Mekinian, A

2018-07-01

The heart involvement in systemic sclerosis is frequent and can touch various sites. The prognosis in the presence of heart disease is poor, but few data are available about its management. We report the case of 48 years old woman with systemic sclerosis which presented severe heart involvement. She has severe heart failure, supraventricular arrhythmias and symptomatic pericarditis, which required surgical intervention and immunosuppressive drugs (steroids with rituximab). Despite this treatment, she has persistent severe heart impaired function and intravenous immunoglobulins have been initiated. She experienced progressively the improvement of dyspnea, of heart systolic ejection fraction and decrease of Rodnan scale. Our case illustrates a severe heart involvement in systemic sclerosis which have been improved by intravenous immunoglobulins. Copyright © 2018 Société Nationale Française de Médecine Interne (SNFMI). Published by Elsevier Masson SAS. All rights reserved.

TRPV2 is critical for the maintenance of cardiac structure and function in mice

PubMed Central

Katanosaka, Yuki; Iwasaki, Keiichiro; Ujihara, Yoshihiro; Takatsu, Satomi; Nishitsuji, Koki; Kanagawa, Motoi; Sudo, Atsushi; Toda, Tatsushi; Katanosaka, Kimiaki; Mohri, Satoshi; Naruse, Keiji

2014-01-01

The heart has a dynamic compensatory mechanism for haemodynamic stress. However, the molecular details of how mechanical forces are transduced in the heart are unclear. Here we show that the transient receptor potential, vanilloid family type 2 (TRPV2) cation channel is critical for the maintenance of cardiac structure and function. Within 4 days of eliminating TRPV2 from hearts of the adult mice, cardiac function declines severely, with disorganization of the intercalated discs that support mechanical coupling with neighbouring myocytes and myocardial conduction defects. After 9 days, cell shortening and Ca2+ handling by single myocytes are impaired in TRPV2-deficient hearts. TRPV2-deficient neonatal cardiomyocytes form no intercalated discs and show no extracellular Ca2+-dependent intracellular Ca2+ increase and insulin-like growth factor (IGF-1) secretion in response to stretch stimulation. We further demonstrate that IGF-1 receptor/PI3K/Akt pathway signalling is significantly downregulated in TRPV2-deficient hearts, and that IGF-1 administration partially prevents chamber dilation and impairment in cardiac pump function in these hearts. Our results improve our understanding of the molecular processes underlying the maintenance of cardiac structure and function. PMID:24874017

TRPV2 is critical for the maintenance of cardiac structure and function in mice.

PubMed

Katanosaka, Yuki; Iwasaki, Keiichiro; Ujihara, Yoshihiro; Takatsu, Satomi; Nishitsuji, Koki; Kanagawa, Motoi; Sudo, Atsushi; Toda, Tatsushi; Katanosaka, Kimiaki; Mohri, Satoshi; Naruse, Keiji

2014-05-29

The heart has a dynamic compensatory mechanism for haemodynamic stress. However, the molecular details of how mechanical forces are transduced in the heart are unclear. Here we show that the transient receptor potential, vanilloid family type 2 (TRPV2) cation channel is critical for the maintenance of cardiac structure and function. Within 4 days of eliminating TRPV2 from hearts of the adult mice, cardiac function declines severely, with disorganization of the intercalated discs that support mechanical coupling with neighbouring myocytes and myocardial conduction defects. After 9 days, cell shortening and Ca(2+) handling by single myocytes are impaired in TRPV2-deficient hearts. TRPV2-deficient neonatal cardiomyocytes form no intercalated discs and show no extracellular Ca(2+)-dependent intracellular Ca(2+) increase and insulin-like growth factor (IGF-1) secretion in response to stretch stimulation. We further demonstrate that IGF-1 receptor/PI3K/Akt pathway signalling is significantly downregulated in TRPV2-deficient hearts, and that IGF-1 administration partially prevents chamber dilation and impairment in cardiac pump function in these hearts. Our results improve our understanding of the molecular processes underlying the maintenance of cardiac structure and function.

Iloprost improves ventricular function in the hypertrophic and functionally impaired right heart by direct stimulation.

PubMed

Holmboe, Sarah; Andersen, Asger; Vildbrad, Mads D; Nielsen, Jan M; Ringgaard, Steffen; Nielsen-Kudsk, Jens E

2013-12-01

Right heart function is an important predictor of morbidity and mortality in patients suffering from pulmonary arterial hypertension and congenital heart diseases. We investigated whether the prostacyclin analog iloprost has a direct inotropic effect in the pressure-overloaded hypertrophic and dysfunctional right ventricle (RV). Rats were randomized to monocrotaline injection (60 mg/kg; [Formula: see text]), pulmonary trunk banding (PTB; [Formula: see text]), or a sham operation ([Formula: see text]). RV function was evaluated with magnetic resonance imaging, echocardiography, and invasive pressure measurements at baseline, after intravenous administration of placebo, iloprost 10 ng/kg/min, or iloprost 100 ng/kg/min (Ilo100). Infusion of Ilo100 induced a [Formula: see text] ([Formula: see text]) increase in stroke volume in the sham group and a [Formula: see text] ([Formula: see text]) increase in the PTB group. RV [Formula: see text] was elevated by [Formula: see text] ([Formula: see text]) in the sham group and by [Formula: see text] ([Formula: see text]) in the PTB group. An elevation in cardiac output of [Formula: see text] ([Formula: see text]) and an [Formula: see text] ([Formula: see text]) increase in RV systolic pressure were found in the PTB group. Iloprost caused a decrease in mean arterial blood pressure (MAP) in all groups of animals. An equal reduction in MAP induced by the arterial vasodilator nitroprusside did not improve any of the measured parameters of RV function. We conclude that iloprost has inotropic properties directly improving ventricular function in the hypertrophic and dysfunctional right heart of the rat.

Intermittent levosimendan infusions in advanced heart failure: favourable effects on left ventricular function, neurohormonal balance, and one-year survival.

PubMed

Malfatto, Gabriella; Della Rosa, Francesco; Villani, Alessandra; Rella, Valeria; Branzi, Giovanna; Facchini, Mario; Parati, Gianfranco

2012-11-01

The role of repeated infusions of Levosimendan (LEVO) in patients with chronic advanced heart failure is still unclear. Thirty-three patients with chronic heart failure presenting clinical deterioration were randomized 2:1 to receive monthly infusions of LEVO (n = 22) or Furosemide (Controls, n = 11). At the first drug's administration, noninvasive hemodynamic evaluation was performed; before and after each infusion, we assessed NYHA class, systolic and diastolic function, functional mitral regurgitation, and brain natriuretic peptide (BNP) levels. Noninvasive hemodynamic in the LEVO group showed vasodilation and decrease in thoracic conductance (index of pulmonary congestion), whereas in Controls, only a reduced thoracic conductance was observed. In the LEVO group, systolic and diastolic function, ventricular volumes, severity of mitral regurgitation, and BNP levels improved over time from baseline and persisted 4 weeks after the last infusion (P < 0.01). In Controls, no change developed over time in cardiac function and BNP levels. In LEVO-treated patients, 1-year mortality tended to be lower than in those treated with Furosemide. In conclusion, serial LEVO infusions in advanced heart failure improved ventricular performance and favorably modulated neurohormonal activation. Multicenter randomized studies are warranted to test the effect of LEVO on long-term outcome.

[Effects of integrated disease management program on the outcome of patients with heart failure].

PubMed

Fan, Hui-hua; Shi, Hao-ying; Jin, Wei; Zhu, Ya-juan; Huang, Dai-ni; Yan, Yi-wen; Zhu, Feng; Li, Hong-li; Liu, Jian; Liu, Shao-wen

2010-07-01

To investigate the feasibility and efficacy on the outcome of patients with heart failure of integrated disease management program with heart failure clinic, patient education and telephone follow-up. A total of 145 hospitalized patients with chronic heart failure and LVEF ≤ 45% or patients with LVEF > 45% and NT-proBNP > 1500 ng/L were divided into conventional group (n = 71) and interventional group (n = 74). Patients were followed for 10 to 12 months. Baseline clinical characteristics, LVEF and dose of evidence-based medicine were similar between the 2 groups. During follow-up, the NYHA functional class was higher in conventional group than interventional group (3.2 ± 0.5 vs 1.4 ± 0.5, P < 0.05), and the LVEF deteriorated in the conventional group and improved from 34% to 40%in the interventional group. The proportions of self-monitoring of weight, blood pressure and pulse rate in the interventional group were significantly higher than those of conventional group (P < 0.05). Among patients with systolic heart failure, 40% patients in the interventional group and 11% patients in the conventional group achieved the target doses of β-blockers (P < 0.05). Cardiovascular event rate of conventional group and interventional group is 91.5% and 27.0% respectively (P < 0.05). Integrated disease management program with heart failure clinic, patient education and telephone follow-up can improve patient compliance to heart failure treatment, improve cardiac function and reduce cardiovascular event rate.

Adaptive servo ventilation improves cardiac dysfunction and prognosis in chronic heart failure patients with Cheyne-Stokes respiration.

PubMed

Yoshihisa, Akiomi; Shimizu, Takeshi; Owada, Takashi; Nakamura, Yuichi; Iwaya, Shoji; Yamauchi, Hiroyuki; Miyata, Makiko; Hoshino, Yasuto; Sato, Takamasa; Suzuki, Satoshi; Sugimoto, Koichi; Yamaki, Takayoshi; Kunii, Hiroyuki; Nakazato, Kazuhiko; Suzuki, Hitoshi; Saitoh, Shu-ichi; Takeishi, Yasuchika

2011-01-01

Cheyne-Stokes respiration (CSR) is often observed in patients with chronic heart failure (CHF). Although adaptive servo ventilation (ASV) is effective for CSR, it remains unclear whether ASV improves the cardiac function and prognosis of patients with CHF and CSR.Sixty patients with CHF and CSR (mean left ventricular ejection fraction 38.7%, mean apnea hypopnea index 36.8 times/hour, mean central apnea index 19.1 times/hour) were enrolled in this study. Patients were divided into two groups: 23 patients treated with ASV (ASV group) and 37 patients treated without ASV (Non-ASV group). Measurement of plasma B-type natriuretic peptide (BNP) levels and echocardiography were performed before, 3 and 6 months after treatments in each group. Patients were followed-up for cardiac events (cardiac death and re-hospitalization) after discharge. In the ASV group, NYHA functional class, BNP levels, cardiac systolic and diastolic function were significantly improved with ASV treatment for 6 months. In contrast, none of these parameters changed in the Non-ASV group. Importantly, Kaplan-Meier analysis clearly demonstrated that the event-free rate was significantly higher in the ASV group than in the Non-ASV group.Adaptive servo ventilation improves cardiac function and prognosis in patients with chronic heart failure and Cheyne-Stokes respiration.

Loss of stearoyl-CoA desaturase 1 rescues cardiac function in obese leptin-deficient mice.

PubMed

Dobrzyn, Pawel; Dobrzyn, Agnieszka; Miyazaki, Makoto; Ntambi, James M

2010-08-01

The heart of leptin-deficient ob/ob mice is characterized by pathologic left ventricular hypertrophy along with elevated triglyceride (TG) content, increased stearoyl-CoA desaturase (SCD) activity, and increased myocyte apoptosis. In the present study, using an ob/ob;SCD1(-/-) mouse model, we tested the hypothesis that lack of SCD1 could improve steatosis and left ventricle (LV) function in leptin deficiency. We show that disruption of the SCD1 gene improves cardiac function in ob/ob mice by correcting systolic and diastolic dysfunction without affecting levels of plasma TG and FFA. The improvement is associated with reduced expression of genes involved in FA transport and lipid synthesis in the heart, as well as reduction in cardiac FFA, diacylglycerol, TG, and ceramide levels. The rate of FA beta-oxidation is also significantly lower in the heart of ob/ob;SCD1(-/-) mice compared with ob/ob controls. Moreover, SCD1 deficiency reduces cardiac apoptosis in ob/ob mice due to increased expression of antiapoptotic factor Bcl-2 and inhibition of inducible nitric oxide synthase and caspase-3 activities. Reduction in myocardial lipid accumulation and inhibition of apoptosis appear to be one of the main mechanisms responsible for improved LV function in ob/ob mice caused by SCD1 deficiency.

Aerobic training in adults after atrial switch procedure for transposition of the great arteries improves exercise capacity without impairing systemic right ventricular function.

PubMed

Westhoff-Bleck, Mechthild; Schieffer, Bernhard; Tegtbur, Uwe; Meyer, Gerd Peter; Hoy, Ludwig; Schaefer, Arnd; Tallone, Ezequiel Marcello; Tutarel, Oktay; Mertins, Ramona; Wilmink, Lena Mara; Anker, Stefan D; Bauersachs, Johann; Roentgen, Philipp

2013-12-05

Exercise training safely and efficiently improves symptoms in patients with heart failure due to left ventricular dysfunction. However, studies in congenital heart disease with systemic right ventricle are scarce and results are controversial. In a randomised controlled study we investigated the effect of aerobic exercise training on exercise capacity and systemic right ventricular function in adults with d-transposition of the great arteries after atrial redirection surgery (28.2 ± 3.0 years after Mustard procedure). 48 patients (31 male, age 29.3 ± 3.4 years) were randomly allocated to 24 weeks of structured exercise training or usual care. Primary endpoint was the change in maximum oxygen uptake (peak VO2). Secondary endpoints were systemic right ventricular diameters determined by cardiac magnetic resonance imaging (CMR). Data were analysed per intention to treat analysis. At baseline peak VO2 was 25.5 ± 4.7 ml/kg/min in control and 24.0 ± 5 ml/kg/min in the training group (p=0.3). Training significantly improved exercise capacity (treatment effect for peak VO2 3.8 ml/kg/min, 95% CI: 1.8 to 5.7; p=0.001), work load (p=0.002), maximum exercise time (p=0.002), and NYHA class (p=0.046). Systemic ventricular function and volumes determined by CMR remained unchanged. None of the patients developed signs of cardiac decompensation or arrhythmias while on exercise training. Aerobic exercise training did not detrimentally affect systemic right ventricular function, but significantly improved exercise capacity and heart failure symptoms. Aerobic exercise training can be recommended for patients following atrial redirection surgery to improve exercise capacity and to lessen or prevent heart failure symptoms. ( ClinicalTrials.gov #NCT00837603). © 2013.

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

Global Intracoronary Infusion of Allogeneic Cardiosphere-Derived Cells Improves Ventricular Function and Stimulates Endogenous Myocyte Regeneration throughout the Heart in Swine with Hibernating Myocardium

PubMed Central

Suzuki, Gen; Weil, Brian R.; Leiker, Merced M.; Ribbeck, Amanda E.; Young, Rebeccah F.; Cimato, Thomas R.; Canty, John M.

2014-01-01

Background Cardiosphere-derived cells (CDCs) improve ventricular function and reduce fibrotic volume when administered via an infarct-related artery using the “stop-flow” technique. Unfortunately, myocyte loss and dysfunction occur globally in many patients with ischemic and non-ischemic cardiomyopathy, necessitating an approach to distribute CDCs throughout the entire heart. We therefore determined whether global intracoronary infusion of CDCs under continuous flow improves contractile function and stimulates new myocyte formation. Methods and Results Swine with hibernating myocardium from a chronic LAD occlusion were studied 3-months after instrumentation (n = 25). CDCs isolated from myocardial biopsies were infused into each major coronary artery (∼33×106 icCDCs). Global icCDC infusion was safe and while ∼3% of injected CDCs were retained, they did not affect ventricular function or myocyte proliferation in normal animals. In contrast, four-weeks after icCDCs were administered to animals with hibernating myocardium, %LADWT increased from 23±6 to 51±5% (p<0.01). In diseased hearts, myocyte proliferation (phospho-histone-H3) increased in hibernating and remote regions with a concomitant increase in myocyte nuclear density. These effects were accompanied by reductions in myocyte diameter consistent with new myocyte formation. Only rare myocytes arose from sex-mismatched donor CDCs. Conclusions Global icCDC infusion under continuous flow is feasible and improves contractile function, regresses myocyte cellular hypertrophy and increases myocyte proliferation in diseased but not normal hearts. New myocytes arising via differentiation of injected cells are rare, implicating stimulation of endogenous myocyte regeneration as the primary mechanism of repair. PMID:25402428

Heart failure—potential new targets for therapy

PubMed Central

Nabeebaccus, Adam; Zheng, Sean; Shah, Ajay M.

2016-01-01

Abstract Introduction/background Heart failure is a major cause of cardiovascular morbidity and mortality. This review covers current heart failure treatment guidelines, emerging therapies that are undergoing clinical trial, and potential new therapeutic targets arising from basic science advances. Sources of data A non-systematic search of MEDLINE was carried out. International guidelines and relevant reviews were searched for additional articles. Areas of agreement Angiotensin-converting enzyme inhibitors and beta-blockers are first line treatments for chronic heart failure with reduced left ventricular function. Areas of controversy Treatment strategies to improve mortality in heart failure with preserved left ventricular function are unclear. Growing points Many novel therapies are being tested for clinical efficacy in heart failure, including those that target natriuretic peptides and myosin activators. A large number of completely novel targets are also emerging from laboratory-based research. Better understanding of pathophysiological mechanisms driving heart failure in different settings (e.g. hypertension, post-myocardial infarction, metabolic dysfunction) may allow for targeted therapies. Areas timely for developing research Therapeutic targets directed towards modifying the extracellular environment, angiogenesis, cell viability, contractile function and microRNA-based therapies. PMID:27365454

Traditional and new composite endpoints in heart failure clinical trials: facilitating comprehensive efficacy assessments and improving trial efficiency.

PubMed

Anker, Stefan D; Schroeder, Stefan; Atar, Dan; Bax, Jeroen J; Ceconi, Claudio; Cowie, Martin R; Crisp, Adam; Dominjon, Fabienne; Ford, Ian; Ghofrani, Hossein-Ardeschir; Gropper, Savion; Hindricks, Gerhard; Hlatky, Mark A; Holcomb, Richard; Honarpour, Narimon; Jukema, J Wouter; Kim, Albert M; Kunz, Michael; Lefkowitz, Martin; Le Floch, Chantal; Landmesser, Ulf; McDonagh, Theresa A; McMurray, John J; Merkely, Bela; Packer, Milton; Prasad, Krishna; Revkin, James; Rosano, Giuseppe M C; Somaratne, Ransi; Stough, Wendy Gattis; Voors, Adriaan A; Ruschitzka, Frank

2016-05-01

Composite endpoints are commonly used as the primary measure of efficacy in heart failure clinical trials to assess the overall treatment effect and to increase the efficiency of trials. Clinical trials still must enrol large numbers of patients to accrue a sufficient number of outcome events and have adequate power to draw conclusions about the efficacy and safety of new treatments for heart failure. Additionally, the societal and health system perspectives on heart failure have raised interest in ascertaining the effects of therapy on outcomes such as repeat hospitalization and the patient's burden of disease. Thus, novel methods for using composite endpoints in clinical trials (e.g. clinical status composite endpoints, recurrent event analyses) are being applied in current and planned trials. Endpoints that measure functional status or reflect the patient experience are important but used cautiously because heart failure treatments may improve function yet have adverse effects on mortality. This paper discusses the use of traditional and new composite endpoints, identifies qualities of robust composites, and outlines opportunities for future research. © 2016 The Authors. European Journal of Heart Failure © 2016 European Society of Cardiology.

Parental overprotection and heart-focused anxiety in adults with congenital heart disease.

PubMed

Ong, Lephuong; Nolan, Robert P; Irvine, Jane; Kovacs, Adrienne H

2011-09-01

The care of adult patients with congenital heart disease (CHD) is challenging from a mental health perspective, as these patients continue to face a variety of biopsychosocial issues that may impact emotional functioning. Despite these issues, there are limited data on the psychosocial functioning of adults with CHD, and there are no data on the impact of parental overprotection on heart-focused anxiety in this patient population. The aim of this study was to examine the relationships between patient recollections of parental overprotection and current heart-focused anxiety in adults with CHD. A cross-sectional sample of 190 adult patients with CHD (51% male; mean age = 32.28, SD = 11.86 years) completed validated measures of perceived parental overprotection (Parental Bonding Instrument) and heart-focused anxiety (Cardiac Anxiety Questionnaire). The results indicated that perceived parental overprotection (β = 0.19, p = 0.02) and heart defect complexity (β = 0.17, p = 0.03) were significantly related to heart-focused anxiety. Contrary to hypotheses, perceived parental overprotection did not vary as a function of heart defect complexity (F (2, 169) = 0.02, p = 0.98). Perceived parental overprotection and heart defect complexity are associated with heart-focused anxiety in adults with congenital heart disease. These results can inform the development of clinical interventions aimed at improving the psychosocial adjustment of this patient population.

Heart repair by reprogramming non-myocytes with cardiac transcription factors

PubMed Central

Song, Kunhua; Nam, Young-Jae; Luo, Xiang; Qi, Xiaoxia; Tan, Wei; Huang, Guo N.; Acharya, Asha; Smith, Christopher L.; Tallquist, Michelle D.; Neilson, Eric G.; Hill, Joseph A.; Bassel-Duby, Rhonda; Olson, Eric N.

2012-01-01

The adult mammalian heart possesses little regenerative potential following injury. Fibrosis due to activation of cardiac fibroblasts impedes cardiac regeneration and contributes to loss of contractile function, pathological remodeling and susceptibility to arrhythmias. Cardiac fibroblasts account for a majority of cells in the heart and represent a potential cellular source for restoration of cardiac function following injury through phenotypic reprogramming to a myocardial cell fate. Here we show that four transcription factors, GATA4, Hand2, MEF2C and Tbx5 can cooperatively reprogram adult mouse tail-tip and cardiac fibroblasts into beating cardiac-like myocytes in vitro. Forced expression of these factors in dividing non-cardiomyocytes in mice reprograms these cells into functional cardiac-like myocytes, improves cardiac function and reduces adverse ventricular remodeling following myocardial infarction. Our results suggest a strategy for cardiac repair through reprogramming fibroblasts resident in the heart with cardiogenic transcription factors or other molecules. PMID:22660318

Changes in collagen metabolism account for ventricular functional recovery following beta-blocker therapy in patients with chronic heart failure.

PubMed

Fukui, Miho; Goda, Akiko; Komamura, Kazuo; Nakabo, Ayumi; Masaki, Mitsuru; Yoshida, Chikako; Hirotani, Shinichi; Lee-Kawabata, Masaaki; Tsujino, Takeshi; Mano, Toshiaki; Masuyama, Tohru

2016-02-01

While beta blockade improves left ventricular (LV) function in patients with chronic heart failure (CHF), the mechanisms are not well known. This study aimed to examine whether changes in myocardial collagen metabolism account for LV functional recovery following beta-blocker therapy in 62 CHF patients with reduced ejection fraction (EF). LV function was echocardiographically measured at baseline and 1, 6, and 12 months after bisoprolol therapy along with serum markers of collagen metabolism including C-terminal telopeptide of collagen type I (CITP) and matrix metalloproteinase (MMP)-2. Deceleration time of mitral early velocity (DcT) increased even in the early phase, but LVEF gradually improved throughout the study period. Heart rate (HR) was reduced from the early stage, and CITP gradually decreased. LVEF and DcT increased more so in patients with the larger decreases in CITP (r = -0.33, p < 0.05; r = -0.28, p < 0.05, respectively), and HR (r = -0.31, p < 0.05; r = -0.38, p < 0.05, respectively). In addition, there were greater decreases in CITP, MMP-2 and HR from baseline to 1, 6, or 12 months in patients with above-average improvement in LVEF than in those with below-average improvement in LVEF. Similar results were obtained in terms of DcT. There was no significant correlation between the changes in HR and CITP. In conclusion, improvement in LV systolic/diastolic function was greatest in patients with the larger inhibition of collagen degradation. Changes in myocardial collagen metabolism are closely related to LV functional recovery somewhat independently from HR reduction.

Can the Nerve Growth Factor promote the reinnervation of the transplanted heart?

PubMed

Galli, Alessio

2014-02-01

The activity of the heart is widely regulated by the autonomous nervous system. This important mechanism of control may be impaired in chronic diseases such as heart failure or lost in those patients who undergo heart transplantation, owing to the surgical interruption of cardiac nerves in the transplanted heart. It has been demonstrated that spontaneous reinnervation can occur in transplanted hearts and is associated with an improvement in cardiac function. However, this process may require many years and the restoration of a proper cardiac innervation and functioning during exercise is never complete. In this perspective, the Nerve Growth Factor (NGF) and other neurotrophic hormones might ameliorate cardiac innervation in the transplanted heart and should be tried in animal models. Endothelial cells engineered with a viral vector to overexpress the NGF might be engrafted in the heart and integrate into cardiac small vessels, thus providing a source of neurotrophic factors which might promote and direct regrowth and axonal sprouting of cardiac nerves. Copyright © 2013 Elsevier Ltd. All rights reserved.

Heart-lung transplantation for cystic fibrosis and subsequent domino heart transplantation.

PubMed

Yacoub, M H; Banner, N R; Khaghani, A; Fitzgerald, M; Madden, B; Tsang, V; Radley-Smith, R; Hodson, M

1990-01-01

Between September 1984 and October 1988, 27 patients underwent combined heart-lung transplantation for treatment of end-stage respiratory disease caused by cystic fibrosis. The actuarial patient survival was 78% at 1 year and 72% at 2 years. Bacterial respiratory infections were common in the early postoperative period and necessitated vigorous medical therapy. The dose of cyclosporine required in these patients was higher than in conventional transplant recipients, and this contributed to an increased cost of postoperative care. Lung function was greatly improved after transplantation, and long-term survivors achieved an excellent quality of life. Lymphoproliferative disorders developed in two patients; these disorders regressed after a reduction in immunosuppression. Two patients required retransplantation: one because of obliterative bronchiolitis and the other because of recurrent respiratory infections associated with a moderate tracheal stenosis and severe deterioration in lung function. A modification of the technique used for heart-lung transplantation allowed 20 hearts from cystic fibrosis patients to be used for subsequent heart transplantation. Immediate heart function was satisfactory in all cases. The actuarial survival of the recipients of these domino heart transplants was 75% at 1 year. No coronary artery disease was present in the 12 patients who have undergone coronary angiography at 1 year.

Self-care and quality of life of heart failure patients at a multidisciplinary heart function clinic.

PubMed

Seto, Emily; Leonard, Kevin J; Cafazzo, Joseph A; Masino, Caterina; Barnsley, Jan; Ross, Heather J

2011-01-01

Multidisciplinary heart function clinics aim to improve self-care through patient education and to provide clinical management. The objectives of the present study were to investigate the self-care and quality of life of patients attending a multidisciplinary heart function clinic and to explore the relationship between self-care and quality of life. One hundred outpatients attending a multidisciplinary heart function clinic were asked to complete a questionnaire. The questionnaire included the Self-care of Heart Failure Index (SCHFI) and the Minnesota Living With Heart Failure Questionnaire, which were used to assess self-care behavior and quality of life, respectively. Self-care practices and perceived barriers were also assessed through semistructured interviews with each patient. : The returned questionnaires (n = 94) were used to compute the following SCHFI maintenance, management, and confidence scores: 60.8 (SD, 19.3), 62.0 (SD, 20.7), and 55.9 (SD, 19.7), respectively. Higher SCHFI scores indicate better self-care. None of the self-care dimensions reached the self-care adequacy cut point of 70. The average score on the Minnesota Living With Heart Failure Questionnaire was 49.9 (SD, 25.4), indicating a moderate health-related quality of life. Lower ejection fraction, older age, and better quality of life were associated with better self-care. Determinants of better quality of life were older age, better functional capacity, higher self-care confidence, and fewer comorbidities. The patient interviews revealed that better quality of life is associated with higher self-care confidence and barriers to self-care caused anxiety to the patients. The self-care barriers were found to include lack of self-care education, financial constraints, lack of perceived benefit, and low self-efficacy. Patients attending a large multidisciplinary Canadian heart failure clinic do not perform adequate self-care as measured with the SCHFI and report only a moderate quality of life. Increasing self-care through education and tools that target self-care barriers are required and may help improve quality of life.

The effect of massage on heart rate variability in preterm infants

PubMed Central

Smith, SL.; Lux, R.; Haley, S.; Slater, H.; Beechy, J.; Moyer-Mileur, LJ.

2012-01-01

Objective To test the hypothesis that massage would improve autonomic nervous system (ANS) function as measured by heart rate variability (HRV) in preterm infants. Study Design Medically stable, 29- to 32-week preterm infants (17 massage, 20 control) were enrolled in a masked, randomized longitudinal study. Licensed massage therapists provided the massage or control condition twice a day for 4 weeks. Weekly HRV, a measure of ANS development and function, was analyzed using SPSS generalized estimating equations. Results Infant characteristics were similar between groups. HRV improved in massaged infants but not in the control infants (P<0.05). Massaged males had a greater improvement in HRV than females (P<0.05). HRV in massaged infants was on a trajectory comparable to term-born infants by study completion. Conclusion Massage-improved HRV in a homogeneous sample of hospitalized, medically stable, preterm male infants and may improve infant response to exogenous stressors. We speculate that massage improves ANS function in these infants. PMID:22538325

Effect of renal function status on the prognostic value of heart rate in acute ischemic stroke patients.

PubMed

Zhu, Zhengbao; Zhong, Chongke; Xu, Tian; Wang, Aili; Peng, Yanbo; Xu, Tan; Peng, Hao; Chen, Chung-Shiuan; Wang, Jinchao; Ju, Zhong; Li, Qunwei; Geng, Deqin; Sun, Yingxian; Du, Qingjuan; Li, Yongqiu; Chen, Jing; Zhang, Yonghong; He, Jiang

2017-08-01

The association between heart rate and prognosis of ischemic stroke remains debatable, and whether renal function status influences the relationship between them is still not elucidated. A total of 3923 ischemic stroke patients were included in this prospective multicenter study from the China Antihypertensive Trial in Acute Ischemic Stroke (CATIS). The primary outcome was a combination of death and major disability (modified Rankin Scale score ≥3) at 3 months after stroke. Secondary outcomes were, separately, death and major disability. The association between heart rate tertiles and primary outcome was appreciably modified by renal function status (p interaction  = 0.037). After multivariate adjustment, high heart rate was associated with increased risk of primary outcome in patients with abnormal renal function (odds ratio, 1.61; 95% confidence interval, 1.02-2.54; p trend  = 0.039) but not in patients with normal renal function (odds ratio, 0.96; 95% confidence interval, 0.75-1.23; p trend  = 0.741), when two extreme tertiles were compared. Each 10 bpm increase of heart rate was associated with 21% (95% CI: 1%-44%) increased risk of primary outcome, and a linear association between heart rate and risk of primary outcome was observed among patients with abnormal renal function (p for linearity = 0.002). High heart rate may be merely a strong predictor of poor prognosis in acute ischemic stroke patients with abnormal renal function, suggesting that heart rate reduction should be applied to ischemic stroke patients with abnormal renal function to improve their prognosis. Copyright © 2017 Elsevier B.V. All rights reserved.

A prospective study on the impact of heart rate control achieved with metoprolol on cardiac performance, motor function and quality of life in Chinese chronic heart failure patients.

PubMed

Meng, Yong; Liu, Xuelu; Liu, Juan; Cheng, Xianliang

2017-01-15

To prospectively evaluate the impact of metoprolol achieved heart rate (HR) on cardiac-motor function and quality of life (QoL) in chronic heart failure (CHF) patients. Between February 2013 to April 2016, association of HR reduction with haemodynamic indices, motor function and QoL in CHF patients with HR>80bpm receiving metoprolol 23.75mg or 47.5mgq.d was studied. Overall, 154 patients (median age, 66.39years; males, n=101; females, n=53) were enrolled, whose average resting HR decreased significantly from baseline value of 82.72±6.73 to 69.38±3.57, 67.72±2.61, 66.50±3.14 and 64.86±3.21bpm in the 1st, 3rd, 6th and 12th months post metoprolol intervention, respectively (P<0.0001). Similarly, the ejection fraction (r=-0.6461, P<0.0001), cardiac output (r=-0.5238, P<0.0001), cardiac index (r=-0.5378, P<0.0001) and veterans specific activity questionnaire scores (r=-0.4088, P<0.0001) were significantly associated with the reduction in HR after 12months. The improvement in 6-min walk test was independent of HR reduction (P=0.005). Similarly, QoL as measured by short form-8 questionnaire (SF-8) but not Minnesota Living with Heart Failure was significantly improved at the 12th-month. However, this was not associated with the reductions in HR. Metoprolol achieved HR control was associated with improvement in cardiac performance and motor function but not QoL in patients with CHF. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

THYROID HORMONE REVERSES AGING-INDUCED MYOCARDIAL FATTY ACID OXIDATION DEFECTS AND IMPROVES THE RESPONSE TO ACUTELY INCREASED AFTERLOAD

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

Ledee, Dolena; Portman, Michael A.; Kajimoto, Masaki

Background: Subclinical hypothyroidism occurs during aging in humans and mice and may contribute to development of heart failure. Aging also impairs myocardial fatty acid oxidation, causing increased reliance on flux through pyruvate dehydrogenase (PDH) to maintain function. We hypothesize that the metabolic changes in aged hearts make them less tolerant to acutely increased work and that thyroid hormone reverses these defects. Methods: Studies were performed on young (Young, 4-6 months) and aged (Old, 22-24 months) C57/BL6 mice at standard (50 mmHg) and high afterload (80 mmHg). Another aged group received thyroid hormone for 3 weeks (Old-TH, high afterload only). Functionmore » was measured in isolated working hearts along with substrate fractional contributions (Fc) to the citric acid cycle (CAC) using perfusate with 13C labeled lactate, pyruvate, glucose and unlabeled palmitate and insulin. Results: Cardiac function was similar between Young and Old mice at standard afterload. Palmitate Fc was reduced but no individual carbohydrate contributions differed. CAC and individual substrate fluxes decreased in aged. At high afterload, -dP/dT was decreased in Old versus Young. Similar to low afterload, palmitate Fc was decreased in Old. Thyroid hormone reversed aging-induced changes in palmitate Fc and flux while significantly improving cardiac function. Conclusion: The aged heart shows diminished ability to increase cardiac work due to substrate limitations, primarily impaired fatty acid oxidation. The heart accommodates slightly by increasing efficiency through oxidation of carbohydrate substrates. Thyroid hormone supplementation in aged mice significantly improves cardiac function potentially through restoration of fatty acid oxidation.« less

Assessment of the physiologic contribution of right atrial function to total right heart function in patients with and without pulmonary arterial hypertension.

PubMed

Sivak, Joseph A; Raina, Amresh; Forfia, Paul R

2016-09-01

Total right heart function requires normal function of both the right ventricle and the right atrium. However, the degree to which right atrial (RA) function and right ventricular (RV) function each contribute to total right heart function has not been quantified. In this study, we aimed to quantify the contribution of RA function to total right heart function in a group of pulmonary arterial hypertension (PAH) patients compared to a cohort of normal controls without cardiovascular disease. The normal cohort comprised 35 subjects with normal clinical echocardiograms, while the PAH cohort included 37 patients, of whom 31 had echocardiograms before and after initiation of PAH-specific therapy. Total right heart function was measured via tricuspid annular plane excursion (TAPSE). TAPSE was broken down into two components, the excursion occurring during RA contraction (TAPSERA) and that occurring before RA contraction (TAPSERV). RA fractional area change (RA-FAC) was also compared between the two groups. In the PAH cohort, more than half of the total TAPSE occurred during atrial systole, compared to less than one-third in the normal cohort (51.0% vs. 32.1%; P < 0.0001). There was a significant correlation between RA-FAC and TAPSE in the PAH cohort but not in the normal cohort. TAPSE improved significantly in the posttreatment cohort (1.7 vs. 2.1 cm), but TAPSERA continued to account for about half of the total TAPSE after treatment. RA function accounts for a significantly greater proportion of total right heart function in patients with PAH than in normal subjects.

Assessment of the physiologic contribution of right atrial function to total right heart function in patients with and without pulmonary arterial hypertension

PubMed Central

Sivak, Joseph A.; Raina, Amresh

2016-01-01

Abstract Total right heart function requires normal function of both the right ventricle and the right atrium. However, the degree to which right atrial (RA) function and right ventricular (RV) function each contribute to total right heart function has not been quantified. In this study, we aimed to quantify the contribution of RA function to total right heart function in a group of pulmonary arterial hypertension (PAH) patients compared to a cohort of normal controls without cardiovascular disease. The normal cohort comprised 35 subjects with normal clinical echocardiograms, while the PAH cohort included 37 patients, of whom 31 had echocardiograms before and after initiation of PAH-specific therapy. Total right heart function was measured via tricuspid annular plane excursion (TAPSE). TAPSE was broken down into two components, the excursion occurring during RA contraction (TAPSERA) and that occurring before RA contraction (TAPSERV). RA fractional area change (RA-FAC) was also compared between the two groups. In the PAH cohort, more than half of the total TAPSE occurred during atrial systole, compared to less than one-third in the normal cohort (51.0% vs. 32.1%; P < 0.0001). There was a significant correlation between RA-FAC and TAPSE in the PAH cohort but not in the normal cohort. TAPSE improved significantly in the posttreatment cohort (1.7 vs. 2.1 cm), but TAPSERA continued to account for about half of the total TAPSE after treatment. RA function accounts for a significantly greater proportion of total right heart function in patients with PAH than in normal subjects. PMID:27683609

Neurocognitive functions after beating heart mitral valve replacement without cross-clamping the aorta.

PubMed

Cicekcioglu, Ferit; Ozen, Anil; Tuluce, Hicran; Tutun, Ufuk; Parlar, Ali Ihsan; Kervan, Umit; Karakas, Sirel; Katircioglu, Salih Fehmi

2008-01-01

Although neurologic outcome after cardiac surgery is well-established, neurocognitive functions after beating heart mitral valve replacement still needs to be elucidated. The aim of this study was to compare preoperative and postoperative neurocognitive functions in patients who underwent beating heart mitral valve replacement on cardiopulmonary bypass without cross-clamping the aorta. The prospective study included 25 consecutive patients who underwent mitral valve replacement. The operations were carried out on a beating heart method using normothermic cardiopulmonary bypass without cross-clamping the aorta. All patients were evaluated preoperatively (E1) and postoperatively (at sixth day [E2] and second month [E3]) for neurocognitive functions. Neurologic deficit was not observed in the postoperative period. Comparison of the neurocognitive test results, between the preoperative and postoperative assessment for both hemispheric cognitive functions, demonstrated that no deterioration occurred. In the three subsets of left hemispheric cognitive function test evaluation, total verbal learning, delayed recall, and recognition, significant improvements were detected at the postoperative second month (E3) compared to the preoperative results (p = 0.005, 0.01, and 0.047, respectively). Immediate recall and retention were significantly improved within the first postoperative week (E2) when compared to the preoperative results (p = 0.05 and 0.05, respectively). The technique of mitral valve replacement with normothermic cardiopulmonary bypass without cross-clamping of the aorta may be safely used for majority of patients requiring mitral valve replacement without causing deterioration in neurocognitive functions.

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.

MicroRNA-133a engineered mesenchymal stem cells augment cardiac function and cell survival in the infarct heart.

PubMed

Dakhlallah, Duaa; Zhang, Jianying; Yu, Lianbo; Marsh, Clay B; Angelos, Mark G; Khan, Mahmood

2015-03-01

: Cardiovascular disease is the number 1 cause of morbidity and mortality in the United States. The most common manifestation of cardiovascular disease is myocardial infarction (MI), which can ultimately lead to congestive heart failure. Cell therapy (cardiomyoplasty) is a new potential therapeutic treatment alternative for the damaged heart. Recent preclinical and clinical studies have shown that mesenchymal stem cells (MSCs) are a promising cell type for cardiomyoplasty applications. However, a major limitation is the poor survival rate of transplanted stem cells in the infarcted heart. miR-133a is an abundantly expressed microRNA (miRNA) in the cardiac muscle and is downregulated in patients with MI. We hypothesized that reprogramming MSCs using miRNA mimics (double-stranded oligonucleotides) will improve survival of stem cells in the damaged heart. MSCs were transfected with miR-133a mimic and antagomirs, and the levels of miR-133a were measured by quantitative real-time polymerase chain reaction. Rat hearts were subjected to MI and MSCs transfected with miR-133a mimic or antagomir were implanted in the ischemic hearts. Four weeks after MI, cardiac function, cardiac fibrosis, miR-133a levels, and apoptosis-related genes (Apaf-1, Caspase-9, and Caspase-3) were measured in the heart. We found that transfecting MSCs with miR-133a mimic improves survival of MSCs as determined by the MTT assay. Similarly, transplantation of miR-133a mimic transfected MSCs in rat hearts subjected to MI led to a significant increase in cell engraftment, cardiac function, and decreased fibrosis when compared with MSCs only or MI groups. At the molecular level, quantitative real-time polymerase chain reaction data demonstrated a significant decrease in expression of the proapoptotic genes; Apaf-1, caspase-9, and caspase-3 in the miR-133a mimic transplanted group. Furthermore, luciferase reporter assay confirmed that miR-133a is a direct target for Apaf-1. Overall, bioengineering of stem cells through miRNAs manipulation could potentially improve the therapeutic outcome of patients undergoing stem cell transplantation for MI.

β-Arrestin2 Improves Post-Myocardial Infarction Heart Failure via Sarco(endo)plasmic Reticulum Ca2+-ATPase-Dependent Positive Inotropy in Cardiomyocytes.

PubMed

McCrink, Katie A; Maning, Jennifer; Vu, Angela; Jafferjee, Malika; Marrero, Christine; Brill, Ava; Bathgate-Siryk, Ashley; Dabul, Samalia; Koch, Walter J; Lymperopoulos, Anastasios

2017-11-01

Heart failure is the leading cause of death in the Western world, and new and innovative treatments are needed. The GPCR (G protein-coupled receptor) adapter proteins βarr (β-arrestin)-1 and βarr-2 are functionally distinct in the heart. βarr1 is cardiotoxic, decreasing contractility by opposing β 1 AR (adrenergic receptor) signaling and promoting apoptosis/inflammation post-myocardial infarction (MI). Conversely, βarr2 inhibits apoptosis/inflammation post-MI but its effects on cardiac function are not well understood. Herein, we sought to investigate whether βarr2 actually increases cardiac contractility. Via proteomic investigations in transgenic mouse hearts and in H9c2 rat cardiomyocytes, we have uncovered that βarr2 directly interacts with SERCA2a (sarco[endo]plasmic reticulum Ca 2+ -ATPase) in vivo and in vitro in a β 1 AR-dependent manner. This interaction causes acute SERCA2a SUMO (small ubiquitin-like modifier)-ylation, increasing SERCA2a activity and thus, cardiac contractility. βarr1 lacks this effect. Moreover, βarr2 does not desensitize β 1 AR cAMP-dependent procontractile signaling in cardiomyocytes, again contrary to βarr1. In vivo, post-MI heart failure mice overexpressing cardiac βarr2 have markedly improved cardiac function, apoptosis, inflammation, and adverse remodeling markers, as well as increased SERCA2a SUMOylation, levels, and activity, compared with control animals. Notably, βarr2 is capable of ameliorating cardiac function and remodeling post-MI despite not increasing cardiac βAR number or cAMP levels in vivo. In conclusion, enhancement of cardiac βarr2 levels/signaling via cardiac-specific gene transfer augments cardiac function safely, that is, while attenuating post-MI remodeling. Thus, cardiac βarr2 gene transfer might be a novel, safe positive inotropic therapy for both acute and chronic post-MI heart failure. © 2017 American Heart Association, Inc.

Allopurinol improves endothelial dysfunction in chronic heart failure.

PubMed

Farquharson, Colin A J; Butler, Robert; Hill, Alexander; Belch, Jill J F; Struthers, Allan D

2002-07-09

Increased oxidative stress in chronic heart failure is thought to contribute to endothelial dysfunction. Xanthine oxidase produces oxidative stress and therefore we examined whether allopurinol improved endothelial dysfunction in chronic heart failure. We performed a randomized, placebo-controlled, double-blind crossover study on 11 patients with New York Heart Association class II-III chronic heart failure, comparing 300 mg allopurinol daily (1 month) versus placebo. Endothelial function was assessed by standard forearm venous occlusion plethysmography with acetylcholine, nitroprusside, and verapamil. Plasma malondialdehyde levels were also compared to assess significant changes in oxidative stress. Allopurinol significantly increased the forearm blood flow response to acetylcholine (percentage change in forearm blood flow [mean+/-SEM]: 181+/-19% versus 120+/-22% allopurinol versus placebo; P=0.003). There were no significant differences in the forearm blood flow changes between the placebo and allopurinol treatment arms with regard to sodium nitroprusside or verapamil. Plasma malondialdehyde was significantly reduced with allopurinol treatment (346+/-128 nmol/L versus 461+/-101 nmol/L, allopurinol versus placebo; P=0.03), consistent with reduced oxidative stress with allopurinol therapy. We have shown that allopurinol improves endothelial dysfunction in chronic heart failure. This raises the distinct possibility that allopurinol might reduce cardiovascular events and even improve exercise capacity in chronic heart failure.

Psychosocial functioning in pediatric heart transplant recipients and their families.

PubMed

Cousino, Melissa K; Schumacher, Kurt R; Rea, Kelly E; Eder, Sally; Zamberlan, Mary; Jordan, Jessica; Fredericks, Emily M

2018-03-01

Across pediatric organ transplant populations, patient and family psychosocial functioning is associated with important health-related outcomes. Research has suggested that pediatric heart transplant recipients and their families are at increased risk for adverse psychosocial outcomes; however, recent investigation of psychosocial functioning in this population is lacking. This study aimed to provide a contemporary characterization of psychosocial functioning in pediatric heart transplant recipients and their families. Associations between psychosocial function, demographic variables, and transplant-related variables were investigated. Fifty-six parents/guardians of pediatric heart transplant recipients completed a comprehensive psychosocial screening measure during transplant follow-up clinic visits. Descriptive statistics, correlational analyses, and independent samples t tests were performed. Forty percent of pediatric heart transplant recipients and their families endorsed clinically meaningful levels of total psychosocial risk. One-third of patients presented with clinically significant psychological problems per parent report. Psychosocial risk was unassociated with demographic or transplant-related factors. Despite notable improvements in the survival of pediatric heart transplant recipients over the past decade, patients and families present with sustained psychosocial risks well beyond the immediate post-transplant period, necessitating mental health intervention to mitigate adverse impact on health-related outcomes. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Repeated daclizumab administration to delay the introduction of calcineurin inhibitors in heart transplant patients with postoperative renal dysfunction.

PubMed

Sánchez Lázaro, Ignacio J; Almenar Bonet, Luis; Martínez Dolz, Luis; Buendía Fuentes, Francisco; Navarro Manchón, Josep; Agüero Ramón-Llin, Jaime; Vicente Sánchez, José Luis; Salvador Sanz, Antonio

2011-03-01

Daclizumab is an interleukin-2 receptor antagonist which is used for induction therapy in heart transplant patients. It has few side effects and is associated with a low infection rate. Postoperative renal failure after heart transplantation is common and potentially fatal. The administration of calcineurin inhibitors in the postoperative period can aggravate the situation. We report the cases of six patients who underwent heart transplantation and developed acute renal failure in the immediate postoperative period. All were administered daclizumab weekly to avoid the introduction of calcineurin inhibitors and to facilitate recovery of renal function. Calcineurin inhibitors were introduced only once renal function had improved. Renal function recovered in all cases and there was a low complication rate. The administration of repeated doses of daclizumab to patients who experience acute postoperative renal failure after heart transplantation may provide an alternative therapeutic approach that enables calcineurin inhibitors to be avoided and, consequently, renal function to recover. Copyright © 2010 Sociedad Española de Cardiología. Published by Elsevier Espana. All rights reserved.

Yoga respiratory training improves respiratory function and cardiac sympathovagal balance in elderly subjects: a randomised controlled trial

PubMed Central

Santaella, Danilo F; Devesa, Cesar R S; Rojo, Marcos R; Amato, Marcelo B P; Drager, Luciano F; Casali, Karina R; Montano, Nicola

2011-01-01

Objectives Since ageing is associated with a decline in pulmonary function, heart rate variability and spontaneous baroreflex, and recent studies suggest that yoga respiratory exercises may improve respiratory and cardiovascular function, we hypothesised that yoga respiratory training may improve respiratory function and cardiac autonomic modulation in healthy elderly subjects. Design 76 healthy elderly subjects were enrolled in a randomised control trial in Brazil and 29 completed the study (age 68±6 years, 34% males, body mass index 25±3 kg/m2). Subjects were randomised into a 4-month training program (2 classes/week plus home exercises) of either stretching (control, n=14) or respiratory exercises (yoga, n=15). Yoga respiratory exercises (Bhastrika) consisted of rapid forced expirations followed by inspiration through the right nostril, inspiratory apnoea with generation of intrathoracic negative pressure, and expiration through the left nostril. Pulmonary function, maximum expiratory and inspiratory pressures (PEmax and PImax, respectively), heart rate variability and blood pressure variability for spontaneous baroreflex determination were determined at baseline and after 4 months. Results Subjects in both groups had similar demographic parameters. Physiological variables did not change after 4 months in the control group. However, in the yoga group, there were significant increases in PEmax (34%, p<0.0001) and PImax (26%, p<0.0001) and a significant decrease in the low frequency component (a marker of cardiac sympathetic modulation) and low frequency/high frequency ratio (marker of sympathovagal balance) of heart rate variability (40%, p<0.001). Spontaneous baroreflex did not change, and quality of life only marginally increased in the yoga group. Conclusion Respiratory yoga training may be beneficial for the elderly healthy population by improving respiratory function and sympathovagal balance. Trial Registration CinicalTrials.gov identifier: NCT00969345; trial registry name: Effects of respiratory yoga training (Bhastrika) on heart rate variability and baroreflex, and quality of life of healthy elderly subjects. PMID:22021757

Acute Responses of a Physical Training Session with a Nintendo Wii on Hemodynamic Variables of an Individual with Multiple Sclerosis.

PubMed

Monteiro Junior, Renato Sobral; Dantas, Aretha; de Souza, Cíntia Pereira; da Silva, Elirez Bezerra

2012-12-01

Multiple sclerosis is a neurological illness that decreases motor functions. This disease can cause weakness of cardiorespiratory muscles and impaired functional capacity and quality of life. Therefore it requires preventive treatments. This study investigated the acute responses of a virtual physical training session with the Nintendo(®) (Kyoto, Japan) Wii™ on hemodynamic variables of an individual with multiple sclerosis (relapsing-remitting). A 34-year-old man with multiple sclerosis with previous experience in aerobic, strength, and functional training (2 years) was tested. His Expanded Disability Status Scale was 2.5. We compared the heart rate, blood pressure, and double product obtained at rest and during (heart rate) and after the Nintendo Wii games "Boxing" and "Sword Play." In rest, the variables were measured in the supine position. Our results showed positive hemodynamic alterations after execution of both games. The peak of heart rate was 121 beats per minute (65% of maximal heart rate) and 104 beats per minute (56% of maximal heart rate) for "Boxing" and "Sword Play," respectively. The training session with "Boxing" was able to stimulate the heart rate to achieve the recommended values for the maintenance of physical fitness in accordance with the American College of Sports Medicine guidelines. We conclude that an exercise training program with the Nintendo Wii may improve physical fitness in people with multiple sclerosis. Moreover, these activities could improve affective status and perhaps maintain the individual engaged at treatment program.

TGF-β improves myocardial function and prevents apoptosis induced by anoxia-reoxygenation, through the reduction of endoplasmic reticulum stress.

PubMed

Wang, Yufeng; Zong, Ligeng; Wang, Xiaolei

2016-01-01

Transforming growth factor-β (TGF-β) is known for its role in ventricular remodeling, inflammatory response, cell survival, and apoptosis. However, its role in improving myocardial function in rat hearts subjected to ischemia-reperfusion (I/R) and protecting against apoptosis induced in cardiomyocytes by anoxia-reoxygenation (A/R) has not been elucidated. This study investigated the protective effects and molecular mechanisms of TGF-β on myocardial function and cardiomyocyte apoptosis. We used TUNEL staining, we tested cell viability, and we measured mitochondrial membrane potential and levels of mitochondrial ROS after 6 h of simulated anoxia together with various durations of simulated reoxygenation in H9c2 cells. We further observed the contractile function in rat hearts after they were subjected to 30 min global ischemia and 180 min reperfusion. Pretreatment with TGF-β markedly inhibited apoptosis in H9c2 cells, as evidenced by increased cell viability and decreased numbers of TUNEL-positive cells, maintained mitochondrial membrane potential, and diminished mitochondrial production of reactive oxygen species (ROS). These changes were associated with the inhibition of endoplasmic reticulum (ER) stress-dependent markers of apoptosis (GRP78, CHOP, caspase-12, and JNK), and the modulation of the expression of Bcl2/Bax. Furthermore, TGF-β improved I/R-induced myocardial contractile dysfunction. All of these protective effects were concentration-dependent. Our results show that TGF-β prevents A/R-induced apoptosis of cardiomyocytes and improves myocardial function in rat hearts injured by I/R.

Safety and Efficacy of the Intravenous Infusion of Umbilical Cord Mesenchymal Stem Cells in Patients With Heart Failure: A Phase 1/2 Randomized Controlled Trial (RIMECARD Trial [Randomized Clinical Trial of Intravenous Infusion Umbilical Cord Mesenchymal Stem Cells on Cardiopathy]).

PubMed

Bartolucci, Jorge; Verdugo, Fernando J; González, Paz L; Larrea, Ricardo E; Abarzua, Ema; Goset, Carlos; Rojo, Pamela; Palma, Ivan; Lamich, Ruben; Pedreros, Pablo A; Valdivia, Gloria; Lopez, Valentina M; Nazzal, Carolina; Alcayaga-Miranda, Francisca; Cuenca, Jimena; Brobeck, Matthew J; Patel, Amit N; Figueroa, Fernando E; Khoury, Maroun

2017-10-27

Umbilical cord-derived mesenchymal stem cells (UC-MSC) are easily accessible and expanded in vitro, possess distinct properties, and improve myocardial remodeling and function in experimental models of cardiovascular disease. Although bone marrow-derived mesenchymal stem cells have been previously assessed for their therapeutic potential in individuals with heart failure and reduced ejection fraction, no clinical trial has evaluated intravenous infusion of UC-MSCs in these patients. Evaluate the safety and efficacy of the intravenous infusion of UC-MSC in patients with chronic stable heart failure and reduced ejection fraction. Patients with heart failure and reduced ejection fraction under optimal medical treatment were randomized to intravenous infusion of allogenic UC-MSCs (Cellistem, Cells for Cells S.A., Santiago, Chile; 1×10 6 cells/kg) or placebo (n=15 per group). UC-MSCs in vitro, compared with bone marrow-derived mesenchymal stem cells, displayed a 55-fold increase in the expression of hepatocyte growth factor, known to be involved in myogenesis, cell migration, and immunoregulation. UC-MSC-treated patients presented no adverse events related to the cell infusion, and none of the patients tested at 0, 15, and 90 days presented alloantibodies to the UC-MSCs (n=7). Only the UC-MSC-treated group exhibited significant improvements in left ventricular ejection fraction at 3, 6, and 12 months of follow-up assessed both through transthoracic echocardiography ( P =0.0167 versus baseline) and cardiac MRI ( P =0.025 versus baseline). Echocardiographic left ventricular ejection fraction change from baseline to month 12 differed significantly between groups (+7.07±6.22% versus +1.85±5.60%; P =0.028). In addition, at all follow-up time points, UC-MSC-treated patients displayed improvements of New York Heart Association functional class ( P =0.0167 versus baseline) and Minnesota Living with Heart Failure Questionnaire ( P <0.05 versus baseline). At study completion, groups did not differ in mortality, heart failure admissions, arrhythmias, or incident malignancy. Intravenous infusion of UC-MSC was safe in this group of patients with stable heart failure and reduced ejection fraction under optimal medical treatment. Improvements in left ventricular function, functional status, and quality of life were observed in patients treated with UC-MSCs. URL: https://www.clinicaltrials.gov/ct2/show/NCT01739777. Unique identifier: NCT01739777. © 2017 The Authors.

Three good reasons for heart surgeons to understand cardiac metabolism.

PubMed

Doenst, Torsten; Bugger, Heiko; Schwarzer, Michael; Faerber, Gloria; Borger, Michael A; Mohr, Friedrich W

2008-05-01

It is the principal goal of cardiac surgeons to improve or reinstate contractile function with, through or after a surgical procedure on the heart. Uninterrupted contractile function of the heart is irrevocably linked to the uninterrupted supply of energy in the form of ATP. Thus, it would appear natural that clinicians interested in myocardial contractile function are interested in the way the heart generates ATP, i.e. the processes generally referred to as energy metabolism. Yet, it may appear that the relevance of energy metabolism in cardiac surgery is limited to the area of cardioplegia, which is a declining research interest. It is the goal of this review to change this trend and to illustrate the role and the therapeutic potential of metabolism and metabolic interventions for management. We present three compelling reasons why cardiac metabolism is of direct, practical interest to the cardiac surgeon and why a better understanding of energy metabolism might indeed result in improved surgical outcomes: (1) To understand cardioplegic arrest, ischemia and reperfusion, one needs a working knowledge of metabolism; (2) hyperglycemia is an underestimated and modifiable risk factor; (3) acute metabolic interventions can be effective in patients undergoing cardiac surgery.

Effects of whole-body vibration on heart rate variability: acute responses and training adaptations.

PubMed

Wong, Alexei; Figueroa, Arturo

2018-05-18

Heart rate variability (HRV) is a noninvasive and practical measure of cardiac autonomic nervous system function, mainly the sympathetic and parasympathetic modulations of heart rate. A low HRV has been shown to be indicative of compromised cardiovascular health. Interventions that enhance HRV are therefore beneficial to cardiovascular health. Whole-body vibration (WBV) training has been proposed as an alternative time-efficient exercise intervention for the improvement of cardiovascular health. In this review, we discuss the effect of WBV both acute and after training on HRV. WBV training appears to be a useful therapeutic intervention to improve cardiac autonomic function in different populations, mainly through decreases in sympathovagal balance. Although the mechanisms by which WBV training improves symphathovagal balance are not yet well understood; enhancement of baroreflex sensitivity, nitric oxide bioavailability and angiotensin II levels seem to play an important role. © 2018 Scandinavian Society of Clinical Physiology and Nuclear Medicine. Published by John Wiley & Sons Ltd.

Medical application and clinical validation for reliable and trustworthy physiological monitoring using functional textiles: experience from the HeartCycle and MyHeart project.

PubMed

Reiter, Harald; Muehlsteff, Jens; Sipilä, Auli

2011-01-01

Functional textiles are seen as promising technology to enable healthcare services and medical care outside hospitals due to their ability to integrate textile-based sensing and monitoring technologies into the daily life. In the past much effort has been spent onto basic functional textile research already showing that reliable monitoring solutions can be realized. The challenge remains to find and develop suited medical application and to fulfil the boundary conditions for medical endorsement and exploitation. The HeartCycle vest described in this abstract will serve as an example for a functional textile carefully developed according to the requirements of a specific medical application, its clinical validation, the related certification aspects and the next improvement steps towards exploitation.

Liver failure in total artificial heart therapy.

PubMed

Dimitriou, Alexandros Merkourios; Dapunt, Otto; Knez, Igor; Wasler, Andrae; Oberwalder, Peter; Koerfer, Reiner; Tenderich, Gero; Spiliopoulos, Sotirios

2016-07-01

Congestive hepatopathy (CH) and acute liver failure (ALF) are common among biventricular heart failure patients. We sought to evaluate the impact of total artificial heart (TAH) therapy on hepatic function and associated clinical outcomes. A total of 31 patients received a Syncardia Total Artificial Heart. Preoperatively 17 patients exhibited normal liver function or mild hepatic derangements that were clinically insignificant and did not qualify as acute or chronic liver failure, 5 patients exhibited ALF and 9 various hepatic derangements owing to CH. Liver associated mortality and postoperative course of liver values were prospectively documented and retrospectively analyzed. Liver associated mortality in normal liver function, ALF and CH cases was 0%, 20% (P=0.03) and 44.4% (P=0.0008) respectively. 1/17 (5.8%) patients with a normal liver function developed an ALF, 4/5 (80%) patients with an ALF experienced a markedly improvement of hepatic function and 6/9 (66.6%) patients with CH a significant deterioration. TAH therapy results in recovery of hepatic function in ALF cases. Patients with CH prior to surgery form a high risk group with increased liver associated mortality.

Over-expression of mitochondrial creatine kinase in the murine heart improves functional recovery and protects against injury following ischaemia-reperfusion.

PubMed

Whittington, Hannah J; Ostrowski, Philip J; McAndrew, Debra J; Cao, Fang; Shaw, Andrew; Eykyn, Thomas R; Lake, Hannah; Tyler, Jack; Schneider, Jurgen E; Neubauer, Stefan; Zervou, Sevasti; Lygate, Craig A

2018-03-02

Mitochondrial creatine kinase (MtCK) couples ATP production via oxidative phosphorylation to phosphocreatine in the cytosol, which acts as a mobile energy store available for regeneration of ATP at times of high demand. We hypothesised that elevating MtCK would be beneficial in ischaemia-reperfusion (I/R) injury. Mice were created overexpressing the sarcomeric MtCK gene with αMHC promoter at the Rosa26 locus (MtCK-OE) and compared with wild-type (WT) littermates. MtCK activity was 27% higher than WT, with no change in other CK isoenzymes or creatine levels. Electron microscopy confirmed normal mitochondrial cell density and mitochondrial localisation of transgenic protein. Respiration in isolated mitochondria was unaltered and metabolomic analysis by 1H-NMR suggests that cellular metabolism was not grossly affected by transgene expression. There were no significant differences in cardiac structure or function under baseline conditions by cine-MRI or LV haemodynamics. In Langendorff-perfused hearts subjected to 20min ischaemia and 30 min reperfusion, MtCK-OE exhibited less ischaemic contracture and improved functional recovery (Rate pressure product 58% above WT; P < 0.001). These hearts had reduced myocardial infarct size, which was confirmed in vivo: 55±4% in WT vs 29±4% in MtCK-OE; P < 0.0001). Isolated cardiomyocytes from MtCK-OE hearts exhibited delayed opening of the mitochondrial permeability transition pore (mPTP) compared to WT, which was confirmed by reduced mitochondrial swelling in response to calcium. There was no detectable change in the structural integrity of the mitochondrial membrane. Modest elevation of MtCK activity in the heart does not adversely affect cellular metabolism, mitochondrial or in vivo cardiac function, but modifies mPTP opening to protect against I/R injury and improve functional recovery. Our findings support MtCK as a prime therapeutic target in myocardial ischaemia.

Neovascularization of Ischemic Myocardium by Newly Isolated Tannins Prevents Cardiomyocyte Apoptosis and Improves Cardiac Function

PubMed Central

Gu, Xuemei; Cheng, Lei; Chueng, Winghong L; Yao, Xinsheng; Liu, Hongwei; Qi, Guoqing; Li, Ming

2006-01-01

During remodeling progress post myocardial infarction, the contribution of neoangiogenesis to the infarct-bed capillary is insufficient to support the greater demands of the hypertrophied but viable myocardium resulting in further ischemic injury to the viable cardiomyocytes at risk. Here we reported the bio-assay-guided identification and isolation of angiogenic tannins (angio-T) from Geum japonicum that induced rapid revascularization of infarcted myocardium and promoted survival potential of the viable cardiomyocytes at risk after myocardial infarction. Our results demonstrated that angio-T displayed potent dual effects on up-regulating expression of angiogenic factors, which would contribute to the early revascularization and protection of the cardiomyocytes against further ischemic injury, and inducing antiapoptotic protein expression, which inhibited apoptotic death of cardiomyocytes in the infarcted hearts and limited infarct size. Echocardiographic studies demonstrated that angio-T-induced therapeutic effects on acute infarcted myocardium were accompanied by significant functional improvement by 2 days after infarction. This improvement was sustained for 14 days. These therapeutic properties of angio-T to induce early reconstitution of a blood supply network, prevent apoptotic death of cardiomyocytes at risk, and improve heart function post infarction appear entirely novel and may provide a new dimension for therapeutic angiogenesis medicine for the treatment of ischemic heart diseases. PMID:17380192

The successful implantation of continuous-flow left ventricular assist device as a destination therapy in Korea: echocardiographic assessment.

PubMed

Lee, Ga Yeon; Park, Sung-Ji; Kim, Sujin; Choi, Namgyung; Jeong, Dong Seop; Jeon, Eun-Seok; Lee, Young Tak

2014-01-01

Left ventricular assist device (LVAD) is a good treatment option for the patients ineligible for cardiac transplantation. Several studies have demonstrated that a ventricular assist device improves the quality of life and prognosis of the patients with end-stage heart failure. A 75-yr-old man debilitated with New York Heart Association (NYHA) functional class III-IV due to severe left ventricular systolic dysfunction received LVAD implantation as a destination therapy. The patient was discharged with improved functional status (NYHA functional class II) after appropriate cardiac rehabilitation and education about how to manage the device and potential emergency situations. This is the first case of successful continuous-flow LVAD implantation as a destination therapy in Korea.

Exercise for Those with Chronic Heart Failure: Matching Programs to Patients.

ERIC Educational Resources Information Center

Braith, Randy W.

2002-01-01

Exercise training increases functional capacity and improves symptoms in selected patients with chronic heart failure and moderate-to-severe left ventricular systolic dysfunction. Aerobic training forms the basis of such a program. This paper describes contributors to exercise intolerance, responses to exercise training, favorable outcomes with…

Hippo pathway deficiency reverses systolic heart failure after infarction.

PubMed

Leach, John P; Heallen, Todd; Zhang, Min; Rahmani, Mahdis; Morikawa, Yuka; Hill, Matthew C; Segura, Ana; Willerson, James T; Martin, James F

2017-10-12

Mammalian organs vary widely in regenerative capacity. Poorly regenerative organs, such as the heart are particularly vulnerable to organ failure. Once established, heart failure commonly results in mortality. The Hippo pathway, a kinase cascade that prevents adult cardiomyocyte proliferation and regeneration, is upregulated in human heart failure. Here we show that deletion of the Hippo pathway component Salvador (Salv) in mouse hearts with established ischaemic heart failure after myocardial infarction induces a reparative genetic program with increased scar border vascularity, reduced fibrosis, and recovery of pumping function compared with controls. Using translating ribosomal affinity purification, we isolate cardiomyocyte-specific translating messenger RNA. Hippo-deficient cardiomyocytes have increased expression of proliferative genes and stress response genes, such as the mitochondrial quality control gene, Park2. Genetic studies indicate that Park2 is essential for heart repair, suggesting a requirement for mitochondrial quality control in regenerating myocardium. Gene therapy with a virus encoding Salv short hairpin RNA improves heart function when delivered at the time of infarct or after ischaemic heart failure following myocardial infarction was established. Our findings indicate that the failing heart has a previously unrecognized reparative capacity involving more than cardiomyocyte renewal.

B lymphocytes trigger monocyte mobilization and impair heart function after acute myocardial infarction.

PubMed

Zouggari, Yasmine; Ait-Oufella, Hafid; Bonnin, Philippe; Simon, Tabassome; Sage, Andrew P; Guérin, Coralie; Vilar, José; Caligiuri, Giuseppina; Tsiantoulas, Dimitrios; Laurans, Ludivine; Dumeau, Edouard; Kotti, Salma; Bruneval, Patrick; Charo, Israel F; Binder, Christoph J; Danchin, Nicolas; Tedgui, Alain; Tedder, Thomas F; Silvestre, Jean-Sébastien; Mallat, Ziad

2013-10-01

Acute myocardial infarction is a severe ischemic disease responsible for heart failure and sudden death. Here, we show that after acute myocardial infarction in mice, mature B lymphocytes selectively produce Ccl7 and induce Ly6C(hi) monocyte mobilization and recruitment to the heart, leading to enhanced tissue injury and deterioration of myocardial function. Genetic (Baff receptor deficiency) or antibody-mediated (CD20- or Baff-specific antibody) depletion of mature B lymphocytes impeded Ccl7 production and monocyte mobilization, limited myocardial injury and improved heart function. These effects were recapitulated in mice with B cell-selective Ccl7 deficiency. We also show that high circulating concentrations of CCL7 and BAFF in patients with acute myocardial infarction predict increased risk of death or recurrent myocardial infarction. This work identifies a crucial interaction between mature B lymphocytes and monocytes after acute myocardial ischemia and identifies new therapeutic targets for acute myocardial infarction.

B lymphocytes trigger monocyte mobilization and impair heart function after acute myocardial infarction

PubMed Central

Zouggari, Yasmine; Ait-Oufella, Hafid; Bonnin, Philippe; Simon, Tabassome; Sage, Andrew P; Guérin, Coralie; Vilar, José; Caligiuri, Giuseppina; Tsiantoulas, Dimitrios; Laurans, Ludivine; Dumeau, Edouard; Kotti, Salma; Bruneval, Patrick; Charo, Israel F; Binder, Christoph J; Danchin, Nicolas; Tedgui, Alain; Tedder, Thomas F; Silvestre, Jean-Sébastien; Mallat, Ziad

2014-01-01

Acute myocardial infarction is a severe ischemic disease responsible for heart failure and sudden death. Here, we show that after acute myocardial infarction in mice, mature B lymphocytes selectively produce Ccl7 and induce Ly6Chi monocyte mobilization and recruitment to the heart, leading to enhanced tissue injury and deterioration of myocardial function. Genetic (Baff receptor deficiency) or antibody-mediated (CD20- or Baff-specific antibody) depletion of mature B lymphocytes impeded Ccl7 production and monocyte mobilization, limited myocardial injury and improved heart function. These effects were recapitulated in mice with B cell–selective Ccl7 deficiency. We also show that high circulating concentrations of CCL7 and BAFF in patients with acute myocardial infarction predict increased risk of death or recurrent myocardial infarction. This work identifies a crucial interaction between mature B lymphocytes and monocytes after acute myocardial ischemia and identifies new therapeutic targets for acute myocardial infarction. PMID:24037091

Estimating energy expenditure from heart rate in older adults: a case for calibration.

PubMed

Schrack, Jennifer A; Zipunnikov, Vadim; Goldsmith, Jeff; Bandeen-Roche, Karen; Crainiceanu, Ciprian M; Ferrucci, Luigi

2014-01-01

Accurate measurement of free-living energy expenditure is vital to understanding changes in energy metabolism with aging. The efficacy of heart rate as a surrogate for energy expenditure is rooted in the assumption of a linear function between heart rate and energy expenditure, but its validity and reliability in older adults remains unclear. To assess the validity and reliability of the linear function between heart rate and energy expenditure in older adults using different levels of calibration. Heart rate and energy expenditure were assessed across five levels of exertion in 290 adults participating in the Baltimore Longitudinal Study of Aging. Correlation and random effects regression analyses assessed the linearity of the relationship between heart rate and energy expenditure and cross-validation models assessed predictive performance. Heart rate and energy expenditure were highly correlated (r=0.98) and linear regardless of age or sex. Intra-person variability was low but inter-person variability was high, with substantial heterogeneity of the random intercept (s.d. =0.372) despite similar slopes. Cross-validation models indicated individual calibration data substantially improves accuracy predictions of energy expenditure from heart rate, reducing the potential for considerable measurement bias. Although using five calibration measures provided the greatest reduction in the standard deviation of prediction errors (1.08 kcals/min), substantial improvement was also noted with two (0.75 kcals/min). These findings indicate standard regression equations may be used to make population-level inferences when estimating energy expenditure from heart rate in older adults but caution should be exercised when making inferences at the individual level without proper calibration.

Cardiac Ablation of Rheb1 Induces Impaired Heart Growth, Endoplasmic Reticulum-Associated Apoptosis and Heart Failure in Infant Mice

PubMed Central

Cao, Yunshan; Tao, Lichan; Shen, Shutong; Xiao, Junjie; Wu, Hang; Li, Beibei; Wu, Xiangqi; Luo, Wen; Xiao, Qi; Hu, Xiaoshan; Liu, Hailang; Nie, Junwei; Lu, Shuangshuang; Yuan, Baiyin; Han, Zhonglin; Xiao, Bo; Yang, Zhongzhou; Li, Xinli

2013-01-01

Ras homologue enriched in brain 1 (Rheb1) plays an important role in a variety of cellular processes. In this study, we investigate the role of Rheb1 in the post-natal heart. We found that deletion of the gene responsible for production of Rheb1 from cardiomyocytes of post-natal mice resulted in malignant arrhythmias, heart failure, and premature death of these mice. In addition, heart growth impairment, aberrant metabolism relative gene expression, and increased cardiomyocyte apoptosis were observed in Rheb1-knockout mice prior to the development of heart failure and arrhythmias. Also, protein kinase B (PKB/Akt) signaling was enhanced in Rheb1-knockout mice, and removal of phosphatase and tensin homolog (Pten) significantly prolonged the survival of Rheb1-knockouts. Furthermore, signaling via the mammalian target of rapamycin complex 1 (mTORC1) was abolished and C/EBP homologous protein (CHOP) and phosphorylation levels of c-Jun N-terminal kinase (JNK) were increased in Rheb1 mutant mice. In conclusion, this study demonstrates that Rheb1 is important for maintaining cardiac function in post-natal mice via regulation of mTORC1 activity and stress on the endoplasmic reticulum. Moreover, activation of Akt signaling helps to improve the survival of mice with advanced heart failure. Thus, this study provides direct evidence that Rheb1 performs multiple important functions in the heart of the post-natal mouse. Enhancing Akt activity improves the survival of infant mice with advanced heart failure. PMID:24351823

Physical Functioning, Physical Activity, Exercise Self-Efficacy, and Quality of Life Among Individuals With Chronic Heart Failure in Korea: A Cross-Sectional Descriptive Study.

PubMed

Lee, Haejung; Boo, Sunjoo; Yu, Jihyoung; Suh, Soon-Rim; Chun, Kook Jin; Kim, Jong Hyun

2017-04-01

Both the beneficial relationship between exercise and quality of life and the important role played by exercise self-efficacy in maintaining an exercise regimen among individuals with chronic heart failure are well known. However, most nursing interventions for Korean patients with chronic heart failure focus only on providing education related to risk factors and symptoms. Little information is available regarding the influence of physical functions, physical activity, and exercise self-efficacy on quality of life. This study was conducted to examine the impact of physical functioning, physical activity, and exercise self-efficacy on quality of life among individuals with chronic heart failure. This study used a cross-sectional descriptive design. Data were collected from 116 outpatients with chronic heart failure in Korea. Left ventricular ejection fraction and New York Heart Association classifications were chart reviewed. Information pertaining to levels of physical activity, exercise self-efficacy, and quality of life were collected using self-administered questionnaires. Data were analyzed using descriptive statistics, t tests, analyses of variance, correlations, and hierarchical multiple regressions. About 60% of participants were physically inactive, and most showed relatively low exercise self-efficacy. The mean quality-of-life score was 80.09. The significant correlates for quality of life were poverty, functional status, physical inactivity, and exercise self-efficacy. Collectively, these four variables accounted for 50% of the observed total variance in quality of life. Approaches that focus on enhancing exercise self-efficacy may improve patient-centered outcomes in those with chronic heart failure. In light of the low level of exercise self-efficacy reported and the demonstrated ability of this factor to predict quality of life, the development of effective strategies to enhance exercise self-efficacy offers a novel and effective approach to improving the quality of life of patients with chronic heart failure. Nurses should be proactive in advising patients with chronic heart failure to be more physically active and to enhance their self-confidence in diverse ways.

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

Reduced Collagen Deposition in Infarcted Myocardium Facilitates Induced Pluripotent Stem Cell Engraftment and Angiomyogenesis for Improvement of Left Ventricular Function

PubMed Central

Dai, Bo; Huang, Wei; Xu, Meifeng; Millard, Ronald W.; Gao, Mei Hua; Hammond, H. Kirk; Menick, Donald R.; Ashraf, Muhammad; Wang, Yigang

2012-01-01

Objectives The purpose of this study was to assess the effect of scar tissue composition on engraftment of progenitor cells into infarcted myocardium. Background Scar tissue formation after myocardial infarction creates a barrier that severely compromises tissue regeneration, limiting potential functional recovery. Methods In vitro: A tricell patch (Tri-P) was created from peritoneum seeded and cultured with induced pluripotent stem cell–derived cardiomyocytes, endothelial cells, and mouse embryonic fibroblasts. The expression of fibrosis-related molecules from mouse embryonic fibroblasts and infarcted heart was measured by Western blot and quantitative reverse transcriptase polymerase chain reaction. In vivo: A Tri-P was affixed over the entire infarcted area 7 days after myocardial infarction in mice overexpressing adenylyl cyclase 6 (AC6). Engraftment efficiency of progenitor cells in hearts of AC6 mice was compared with that of control wild-type (WT) mice using a combination of in vivo bioluminescence imaging, post-mortem ex vivo tissue analysis, and the number of green fluorescent protein–positive cells. Echocardiography of left ventricular (LV) function was performed weekly. Hearts were harvested for analysis 4 weeks after Tri-P application. Mouse embryonic fibroblasts were stimulated with forskolin before an anoxia/reoxygenation protocol. Fibrosis-related molecules were analyzed. Results In AC6 mice, infarcted hearts treated with Tri-P showed significantly higher bioluminescence imaging intensity and numbers of green fluorescent protein–positive cells than in WT mice. LV function improved progressively in AC6 mice from weeks 2 to 4 and was associated with reduced LV fibrosis. Conclusions Application of a Tri-P in AC6 mice resulted in significantly higher induced pluripotent stem cell engraftment accompanied by angiomyogenesis in the infarcted area and improvement in LV function. PMID:22051336

Adverse Effects on β-Adrenergic Receptor Coupling: Ischemic Postconditioning Failed to Preserve Long-Term Cardiac Function.

PubMed

Schreckenberg, Rolf; Bencsik, Péter; Weber, Martin; Abdallah, Yaser; Csonka, Csaba; Gömöri, Kamilla; Kiss, Krisztina; Pálóczi, János; Pipis, Judit; Sárközy, Márta; Ferdinandy, Péter; Schulz, Rainer; Schlüter, Klaus-Dieter

2017-12-22

Ischemic preconditioning (IPC) and ischemic postconditioning (IPoC) are currently among the most efficient strategies protecting the heart against ischemia/reperfusion injury. However, the effect of IPC and IPoC on functional recovery following ischemia/reperfusion is less clear, particularly with regard to the specific receptor-mediated signaling of the postischemic heart. The current article examines the effect of IPC or IPoC on the regulation and coupling of β-adrenergic receptors and their effects on postischemic left ventricular function. The β-adrenergic signal transduction was analyzed in 3-month-old Wistar rats for each of the intervention strategies (Sham, ischemia/reperfusion, IPC, IPoC) immediately and 7 days after myocardial infarction. Directly after the infarction a cardioprotective potential was demonstrated for both IPC and IPoC: the infarct size was reduced, apoptosis and production of reactive oxygen species were lowered, and the myocardial tissue was preserved. Seven days after myocardial ischemia, only IPC hearts showed significant functional improvement. Along with a deterioration in fractional shortening, IPoC hearts no longer responded adequately to β-adrenergic stimulation. The stabilization of β-adrenergic receptor kinase-2 via increased phosphorylation of Mdm2 (an E3-ubiquitin ligase) was responsible for desensitization of β-adrenergic receptors and identified as a characteristic specific to IPoC hearts. Immediately after myocardial infarction, rapid and transient activation of β-adrenergic receptor kinase-2 may be an appropriate means to protect the injured heart from excessive stress. In the long term, however, induction and stabilization of β-adrenergic receptor kinase-2, with the resultant loss of positive inotropic function, leads to the functional picture of heart failure. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

Reduced Gray Matter Volume Is Associated With Poorer Instrumental Activities of Daily Living Performance in Heart Failure.

PubMed

Alosco, Michael L; Brickman, Adam M; Spitznagel, Mary Beth; Narkhede, Atul; Griffith, Erica Y; Cohen, Ronald; Sweet, Lawrence H; Josephson, Richard; Hughes, Joel; Gunstad, John

2016-01-01

Heart failure patients require assistance with instrumental activities of daily living in part because of the high rates of cognitive impairment in this population. Structural brain insult (eg, reduced gray matter volume) is theorized to underlie cognitive dysfunction in heart failure, although no study has examined the association among gray matter, cognition, and instrumental activities of daily living in heart failure. The aim of this study was to investigate the associations among gray matter volume, cognitive function, and functional ability in heart failure. A total of 81 heart failure patients completed a cognitive test battery and the Lawton-Brody self-report questionnaire to assess instrumental activities of daily living. Participants underwent magnetic resonance imaging to quantify total gray matter and subcortical gray matter volume. Impairments in instrumental activities of daily living were common in this sample of HF patients. Regression analyses controlling for demographic and medical confounders showed that smaller total gray matter volume predicted decreased scores on the instrumental activities of daily living composite, with specific associations noted for medication management and independence in driving. Interaction analyses showed that reduced total gray matter volume interacted with worse attention/executive function and memory to negatively impact instrumental activities of daily living. Smaller gray matter volume is associated with greater impairment in instrumental activities of daily living in persons with heart failure, possibly via cognitive dysfunction. Prospective studies are needed to clarify the utility of clinical correlates of gray matter volume (eg, cognitive dysfunction) in identifying heart failure patients at risk for functional decline and determine whether interventions that target improved brain and cognitive function can preserve functional independence in this high-risk population.

Chronic heat improves mechanical and metabolic response of trained rat heart on ischemia and reperfusion.

PubMed

Levy, E; Hasin, Y; Navon, G; Horowitz, M

1997-05-01

Cardiac mechanics and metabolic performance were studied in isolated perfused hearts of rats subjected to a combined chronic stress of heat acclimation and swimming training (EXAC) or swimming training alone (EX). Diastolic (DP) and systolic pressures (SP), coronary flow (CF), and oxygen consumption were measured during normoperfusion (80 mmHg), and the appearance of ischemic contracture (IC), DP, and SP were measured during progressive graded ischemia, total ischemia (TI), and reperfusion insults. ATP, phosphocreatine, and intracellular pH were measured during TI and reperfusion with 31P nuclear magnetic resonance spectroscopy. During normoperfusion, SP and cardiac efficiency (derived from rate-pressure product-oxygen consumption relationships) were the highest in the 2-mo EXAC hearts (P < 0.0001). During progressive graded ischemia, the development of IC (percentage of total hearts) was similar in both EXAC and EX hearts; the only significant difference was confined to the 1- vs. 2-mo groups. The onset of IC was delayed in the EXAC hearts and, on reperfusion, recovery, particularly of DP, was significantly improved in the latter. After TI, EXAC hearts retained 30% of the ATP pool and there was a delayed decline in intracellular pH. On reperfusion, these hearts also displayed improved ATP and phosphocreatine recovery, the 2-mo EXAC heart demonstrating significantly faster high-energy phosphate salvage, improved diastolic function, and pulse pressure recovery. The data attest to the beneficial effects of heat acclimation on cardiac mechanics of trained rats during normoperfusion and cardiac protection on ischemia and reperfusion. Possibly, energy sparing, lesser acidosis, and shorter duration of IC on ischemia and improved energy salvage on reperfusion contribute synergistically to this potent beneficial effect.

Outcomes of HeartWare Ventricular Assist System support in 141 patients: a single-centre experience.

PubMed

Wu, Long; Weng, Yu-Guo; Dong, Nian-Guo; Krabatsch, Thomas; Stepanenko, Alexander; Hennig, Ewald; Hetzer, Roland

2013-07-01

A third-generation ventricular assist device, the HeartWare Ventricular Assist System, has demonstrated its reliability and durability in animal models and clinical experience. However, studies of a large series of applications are still lacking. We evaluate the safety and efficacy of the HeartWare pump in 141 patients with end-stage heart failure at a single centre. A total of 141 patients (116 men and 25 women with a mean age of 52 years) in New York Heart Association (NYHA) Class IV received implantation of the HeartWare Ventricular Assist System between August 2009 and April 2011 at the Deutsches Herzzentrum Berlin. The outcomes were measured in terms of laboratory data, adverse events, NYHA functional class and survival during device support. The HeartWare system provided an adequate haemodynamic support for patients both inside and outside the hospital. NYHA class improved to I-II. Organ function and pulmonary vascular resistance improved significantly. In this cohort of patients, 14 patients underwent heart transplantation, one had had the device explanted following myocardial recovery, one had changed to another assist device, 81 were on ongoing support and 44 died. The overall actuarial survival rates at 6 and 12 months were 70 and 67%, respectively, and the 3-, 6- and 12-month survival rates on a left ventricular assist device (LVAD) support for bridge to transplantation patients were 82, 81 and 79%, respectively. Infection and bleeding were the main adverse events. Four patients underwent an LVAD exchange for pump thrombosis. The HeartWare system provides a safe and effective circulatory support in a population with a wide range of body surface areas, with a satisfactory actuarial survival time and an improved quality of life. It can be used for univentricular or biventricular support, being implanted into the pericardial space with simplified surgical techniques.

Bone-Derived Stem Cells Repair the Heart after Myocardial Infarction Through Transdifferentiation and Paracrine Signaling Mechanisms

PubMed Central

Duran, Jason M.; Makarewich, Catherine A.; Sharp, Thomas E.; Starosta, Timothy; Fang, Zhu; Hoffman, Nicholas E.; Chiba, Yumi; Madesh, Muniswamy; Berretta, Remus M.; Kubo, Hajime; Houser, Steven R.

2013-01-01

Rationale Autologous bone marrow- or cardiac-derived stem cell therapy for heart disease has demonstrated safety and efficacy in clinical trials but functional improvements have been limited. Finding the optimal stem cell type best suited for cardiac regeneration is key toward improving clinical outcomes. Objective To determine the mechanism by which novel bone-derived stem cells support the injured heart. Methods and Results Cortical bone stem cells (CBSCs) and cardiac-derived stem cells (CDCs) were isolated from EGFP+ transgenic mice and were shown to express c-kit and Sca-1 as well as 8 paracrine factors involved in cardioprotection, angiogenesis and stem cell function. Wild-type C57BL/6 mice underwent sham operation (n=21) or myocardial infarction (MI) with injection of CBSCs (n=67), CDCs (n=36) or saline (n=60). Cardiac function was monitored using echocardiography. Only 2/8 paracrine factors were detected in EGFP+ CBSCs in vivo (basic fibroblast growth factor and vascular endothelial growth factor) and this expression was associated with increased neovascularization of the infarct border zone. CBSC therapy improved survival, cardiac function, regional strain, attenuated remodeling, and decreased infarct size relative to CDC- or saline-treated MI controls. By 6 weeks, EGFP+ cardiomyocytes, vascular smooth muscle and endothelial cells could be identified in CBSC- but not in CDC-treated animals. EGFP+ CBSC-derived isolated myocytes were smaller and more frequently mononucleated, but were functionally indistinguishable from EGFP- myocytes. Conclusions CBSCs improve survival, cardiac function, and attenuate remodeling through two mechanisms:1) secretion of pro-angiogenic factors that stimulate endogenous neovascularization, and 2) differentiation into functional adult myocytes and vascular cells. PMID:23801066

New strategies for improving stem cell therapy in ischemic heart disease.

PubMed

Huang, Peisen; Tian, Xiaqiu; Li, Qing; Yang, Yuejin

2016-11-01

Stem cell therapy is a promising approach to the treatment of ischemic heart disease via replenishing cell loss after myocardial infarction. Both preclinical studies and clinical trials have indicated that cardiac function improved consistently, but very modestly after cell-based therapy. This mainly attributed to low cell survival rate, engraftment and functional integration, which became the major challenges to regenerative medicine. In recent years, several new cell types have been developed to regenerate cardiomyocytes and novel delivery approaches helped to increase local cell retention. New strategies, such as cell pretreatment, gene-based therapy, tissue engineering, extracellular vesicles application and immunologic regulation, have surged and brought about improved cell survival and functional integration leading to better therapeutic effects after cell transplantation. In this review, we summarize these new strategies targeting at challenges of cardiac regenerative medicine and discuss recent evidences that may hint their effectiveness in the future clinical settings.

Structural and Functional Phenotyping of the Failing Heart: Is the Left Ventricular Ejection Fraction Obsolete?

PubMed

Bristow, Michael R; Kao, David P; Breathett, Khadijah K; Altman, Natasha L; Gorcsan, John; Gill, Edward A; Lowes, Brian D; Gilbert, Edward M; Quaife, Robert A; Mann, Douglas L

2017-11-01

Diagnosis, prognosis, treatment, and development of new therapies for diseases or syndromes depend on a reliable means of identifying phenotypes associated with distinct predictive probabilities for these various objectives. Left ventricular ejection fraction (LVEF) provides the current basis for combined functional and structural phenotyping in heart failure by classifying patients as those with heart failure with reduced ejection fraction (HFrEF) and those with heart failure with preserved ejection fraction (HFpEF). Recently the utility of LVEF as the major phenotypic determinant of heart failure has been challenged based on its load dependency and measurement variability. We review the history of the development and adoption of LVEF as a critical measurement of LV function and structure and demonstrate that, in chronic heart failure, load dependency is not an important practical issue, and we provide hemodynamic and molecular biomarker evidence that LVEF is superior or equal to more unwieldy methods of identifying phenotypes of ventricular remodeling. We conclude that, because it reliably measures both left ventricular function and structure, LVEF remains the best current method of assessing pathologic remodeling in heart failure in both individual clinical and multicenter group settings. Because of the present and future importance of left ventricular phenotyping in heart failure, LVEF should be measured by using the most accurate technology and methodologic refinements available, and improved characterization methods should continue to be sought. Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

VEGF improves survival of mesenchymal stem cells in infarcted hearts

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

Pons, Jennifer; Huang Yu; Arakawa-Hoyt, Janice

2008-11-14

Bone marrow-derived mesenchymal stem cells (MSC) are a promising source for cell-based treatment of myocardial infarction (MI), but existing strategies are restricted by low cell survival and engraftment. We examined whether vascular endothelial growth factor (VEGF) improve MSC viability in infracted hearts. We found long-term culture increased MSC-cellular stress: expressing more cell cycle inhibitors, p16{sup INK}, p21 and p19{sup ARF}. VEGF treatment reduced cellular stress, increased pro-survival factors, phosphorylated-Akt and Bcl-xL expression and cell proliferation. Co-injection of MSCs with VEGF to MI hearts increased cell engraftment and resulted in better improvement of cardiac function than that injected with MSCs ormore » VEGF alone. In conclusion, VEGF protects MSCs from culture-induce cellular stress and improves their viability in ischemic myocardium, which results in improvements of their therapeutic effect for the treatment of MI.« less

Divergent Requirements for EZH1 in Heart Development Versus Regeneration.

PubMed

Ai, Shanshan; Yu, Xianhong; Li, Yumei; Peng, Yong; Li, Chen; Yue, Yanzhu; Tao, Ge; Li, Chuanyun; Pu, William T; He, Aibin

2017-07-07

Polycomb repressive complex 2 is a major epigenetic repressor that deposits methylation on histone H3 on lysine 27 (H3K27me) and controls differentiation and function of many cells, including cardiac myocytes. EZH1 and EZH2 are 2 alternative catalytic subunits with partial functional redundancy. The relative roles of EZH1 and EZH2 in heart development and regeneration are unknown. We compared the roles of EZH1 versus EZH2 in heart development and neonatal heart regeneration. Heart development was normal in Ezh1 -/- ( Ezh 1 knockout) and Ezh2 f/f ::cTNT -Cre ( Ezh 2 knockout) embryos. Ablation of both genes in Ezh1 -/- ::Ezh2 f/f ::cTNT -Cre embryos caused lethal heart malformations, including hypertrabeculation, compact myocardial hypoplasia, and ventricular septal defect. Epigenome and transcriptome profiling showed that derepressed genes were upregulated in a manner consistent with total EZH dose. In neonatal heart regeneration, Ezh1 was required, but Ezh2 was dispensable. This finding was further supported by rescue experiments: cardiac myocyte-restricted re-expression of EZH1 but not EZH2 restored neonatal heart regeneration in Ezh 1 knockout. In myocardial infarction performed outside of the neonatal regenerative window, EZH1 but not EZH2 likewise improved heart function and stimulated cardiac myocyte proliferation. Mechanistically, EZH1 occupied and activated genes related to cardiac growth. Our work unravels divergent mechanisms of EZH1 in heart development and regeneration, which will empower efforts to overcome epigenetic barriers to heart regeneration. © 2017 American Heart Association, Inc.

Effects of a dance-based aquatic exercise program in obese postmenopausal women with knee osteoarthritis: a randomized controlled trial.

PubMed

Casilda-López, Jesús; Valenza, Marie Carmen; Cabrera-Martos, Irene; Díaz-Pelegrina, Ana; Moreno-Ramírez, Maria Paz; Valenza-Demet, Gerald

2017-07-01

To evaluate the effects of a dance-based aquatic exercise program on functionality, cardiorespiratory capacity, postexercise heart rate, and fatigue in obese postmenopausal women with knee osteoarthritis. A randomized controlled trial was performed. In all, 34 obese women diagnosed with knee osteoarthritis participated. Women were randomly allocated to an experimental group (n = 17) or a control group (n = 17). Participants in the experimental group were included in an 8-week dance-based aquatic exercise program conducted in community swimming pools. Those in the control group underwent a global aquatic exercise program. The primary outcome measure was functionality assessed with the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). Secondary outcomes were cardiorespiratory capacity evaluated with the 6-minute walk test, and postexercise heart rate and fatigue assessed using a visual analog scale. Variables were measured at baseline, after the intervention, and at 3-month follow-up. A between-group analysis showed significant postintervention differences in functionality (aggregate postintervention WOMAC score of 37.30 ± 16.61 vs 41.83 ± 13.69; P = 0.048) in favor of the experimental group. In addition, significant between-group differences were found after the 8 weeks in cardiorespiratory capacity, postexercise heart rate, and fatigue. Follow-up continued to show significant differences between groups in function (aggregate WOMAC score of 38.60 ± 13.61 vs 42.60 ± 9.05; P = 0.038), postexercise heart rate, and fatigue. An 8-week dance-based exercise program significantly improved function and cardiorespiratory capacity, and decreased postexercise heart rate and fatigue. Most of these improvements were maintained at 3-month follow-up in obese postmenopausal women.

Use of venoarterial extracorporeal membrane oxygenation in fulminant chagasic myocarditis as a bridge to heart transplant

PubMed Central

Durães, André Rodrigues; Figueira, Fernando Augusto Marinho dos Santos; Lafayette, André Rabelo; Martins, Juliana de Castro Solano; Juliano Cavalcante de, Sá

2015-01-01

A 17-year-old Brazilian male presented with progressive dyspnea for 15 days, worsening in the last 24 hours, and was admitted in respiratory failure and cardiogenic shock, with multiple organ dysfunctions. Echocardiography showed a left ventricle ejection fraction of 11%, severe diffuse hypokinesia, and a systolic pulmonary artery pressure of 50mmHg, resulting in the need for hemodynamic support with dobutamine (20mcg/kg/min) and noradrenaline (1.7mcg/kg/min). After 48 hours with no clinical or hemodynamic improvement, an extracorporeal membrane oxygenation was implanted. The patient presented with hemodynamic, systemic perfusion and renal and liver function improvements; however, his cardiac function did not recover after 72 hours, and he was transfer to another hospital. Air transport was conducted from Salvador to Recife in Brazil. A heart transplant was performed with rapid recovery of both liver and kidney functions, as well as good graft function. Histopathology of the explanted heart showed chronic active myocarditis and amastigotes of Trypanosoma cruzi. The estimated global prevalence of T. cruzi infections declined from 18 million in 1991, when the first regional control initiative began, to 5.7 million in 2010. Myocarditis is an inflammatory disease due to infectious or non-infectious conditions. Clinical manifestation is variable, ranging from subclinical presentation to refractory heart failure and cardiogenic shock. Several reports suggest that the use of extracorporeal membrane oxygenation in patients presenting with severe refractory myocarditis is a potential bridging therapy to heart transplant when there is no spontaneous recovery of ventricular function. In a 6-month follow-up outpatient consult, the patient presented well and was asymptomatic. PMID:26761479

Restoring heart function and electrical integrity: closing the circuit

NASA Astrophysics Data System (ADS)

Monteiro, Luís Miguel; Vasques-Nóvoa, Francisco; Ferreira, Lino; Pinto-do-Ó, Perpétua; Nascimento, Diana Santos

2017-04-01

Cardiovascular diseases are the main cause of death in the world and are often associated with the occurrence of arrhythmias due to disruption of myocardial electrical integrity. Pathologies involving dysfunction of the specialized cardiac excitatory/conductive tissue are also common and constitute an added source of morbidity and mortality since current standard therapies withstand a great number of limitations. As electrical integrity is essential for a well-functioning heart, innovative strategies have been bioengineered to improve heart conduction and/or promote myocardial repair, based on: (1) gene and/or cell delivery; or (2) conductive biomaterials as tools for cardiac tissue engineering. Herein we aim to review the state-of-art in the area, while briefly describing the biological principles underlying the heart electrical/conduction system and how this system can be disrupted in heart disease. Suggestions regarding targets for future studies are also presented.

Recognition and Management of Sleep-Disordered Breathing in Chronic Heart Failure

PubMed Central

Kikta, Donald; Khayat, Rami

2013-01-01

It is increasingly recognized that sleep-disordered breathing (SDB) is a common modifiable risk factor for cardiovascular disease with significant impact on morbidity and potentially mortality. SDB is highly prevalent in patients with systolic or diastolic heart failure. A high index of suspicion is necessary to diagnose SDB in patients with heart failure because the vast majority of affected patients do not report daytime symptoms. Recent clinical trials have demonstrated improvement in heart function, exercise tolerance, and quality of life after treatment of SDB in patients with heart failure. Accumulating evidence suggests that treatment of SDB should complement the established pharmacologic therapy for chronic heart failure. However, mortality benefit has yet to be demonstrated. PMID:21086079

Embryonic Heart Progenitors and Cardiogenesis

PubMed Central

Brade, Thomas; Pane, Luna S.; Moretti, Alessandra; Chien, Kenneth R.; Laugwitz, Karl-Ludwig

2013-01-01

The mammalian heart is a highly specialized organ, comprised of many different cell types arising from distinct embryonic progenitor populations during cardiogenesis. Three precursor populations have been identified to contribute to different myocytic and nonmyocytic cell lineages of the heart: cardiogenic mesoderm cells (CMC), the proepicardium (PE), and cardiac neural crest cells (CNCCs). This review will focus on molecular cues necessary for proper induction, expansion, and lineage-specific differentiation of these progenitor populations during cardiac development in vivo. Moreover, we will briefly discuss how the knowledge gained on embryonic heart progenitor biology can be used to develop novel therapeutic strategies for the management of congenital heart disease as well as for improvement of cardiac function in ischemic heart disease. PMID:24086063

Effects of renin-angiotensin-aldosterone system inhibitors on mortality, hospitalization, and diastolic function in patients with HFpEF. A meta-analysis of 13 randomized controlled trials.

PubMed

Zhang, Q; Chen, Y; Liu, Q; Shan, Q

2016-02-01

The purpose of this meta-analysis was to evaluate the effects of renin-angiotensin-aldosterone system (RAAS) inhibitors on mortality, hospitalization, diastolic function, and exercise capacity in heart failure with preserved ejection fraction (HFpEF). Thirteen randomized controlled trials (RCTs), totaling 12,532 patients with HFpEF, were selected. All-cause and cardiovascular mortality, all-cause and heart failure-related hospitalization, diastolic function, and the 6-min walk distance were assessed. The risk ratios (RR) of the dichotomous data, weighted mean difference (WMD) of continuous data, and 95 % confidence intervals (CI) were calculated to assess the effects of RAAS inhibitors. RAAS inhibitors significantly decreased heart failure-related hospitalization (RR 0.89; 95 % CI 0.82-0.97; p = 0.01) and improved the diastolic function, as reflected in a reduced E/e' index (MD -1.38; 95 % CI -2.01 to -0.74; p < 0.0001). However, there were no beneficial effects on all-cause cardiovascular mortality and all-cause hospitalization. Other diastolic parameters had few changes compared with the controls. The 6-min walk distance was not improved by the use of RAAS inhibitors. In patients with HFpEF, RAAS inhibitors decreased heart-failure hospitalization and the E/e' index without affecting mortality, all-cause hospitalization, other diastolic function parameters, and the 6-min walk distance.

Physiological Implications of Myocardial Scar Structure

PubMed Central

Richardson, WJ; Clarke, SA; Quinn, TA; Holmes, JW

2016-01-01

Once myocardium dies during a heart attack, it is replaced by scar tissue over the course of several weeks. The size, location, composition, structure and mechanical properties of the healing scar are all critical determinants of the fate of patients who survive the initial infarction. While the central importance of scar structure in determining pump function and remodeling has long been recognized, it has proven remarkably difficult to design therapies that improve heart function or limit remodeling by modifying scar structure. Many exciting new therapies are under development, but predicting their long-term effects requires a detailed understanding of how infarct scar forms, how its properties impact left ventricular function and remodeling, and how changes in scar structure and properties feed back to affect not only heart mechanics but also electrical conduction, reflex hemodynamic compensations, and the ongoing process of scar formation itself. In this article, we outline the scar formation process following an MI, discuss interpretation of standard measures of heart function in the setting of a healing infarct, then present implications of infarct scar geometry and structure for both mechanical and electrical function of the heart and summarize experiences to date with therapeutic interventions that aim to modify scar geometry and structure. One important conclusion that emerges from the studies reviewed here is that computational modeling is an essential tool for integrating the wealth of information required to understand this complex system and predict the impact of novel therapies on scar healing, heart function, and remodeling following myocardial infarction. PMID:26426470

Regular physical exercise improves endothelial function in heart transplant recipients.

PubMed

Schmidt, Alice; Pleiner, Johannes; Bayerle-Eder, Michaela; Wiesinger, Günther F; Rödler, Suzanne; Quittan, Michael; Mayer, Gert; Wolzt, Michael

2002-04-01

Impaired endothelial function is detectable in heart transplant (HTX) recipients and regarded as risk factor for coronary artery disease. We have studied whether endothelial function can be improved in HTX patients participating in a regular physical training program as demonstrated in patients with chronic heart failure, hypertension and coronary artery disease. Male HTX patients and healthy, age-matched controls were studied. Seven HTX patients (age: 60 +/- 6 yr; 6 +/- 2 yr of HTX) participated in an outpatient training program, six HTX patients (age: 63 +/- 8 yr; 7 +/- 1 yr of HTX) maintained a sedentary lifestyle without regular physical exercise since transplantation. A healthy control group comprised six subjects (age: 62 +/- 6 yr). Vascular function was assessed by flow-mediated dilation of the brachial artery (FMD). Systemic haemodynamic responses to intravenous infusion of the endothelium independent vasodilator sodium nitroprusside (SNP) and to NG-monomethyl-L-arginine (L-NMMA), an inhibitor of constitutive nitric oxide synthase, were also measured. Resting heart rate was significantly lower (p < 0.05) in healthy controls (66 +/- 13) than in the HTX training group (83 +/- 11) and in non-training HTX patients (91 +/- 9), baseline blood pressure also tended to be lower in healthy subjects and in the training HTX patients. FMD was significantly higher (p < 0.05) in the control group (8.4 +/- 2.2%) and in the training group (7.1 +/- 2.4%), compared with non-training HTX patients (1.4 +/- 0.8%). The response of systolic blood pressure (p = 0.08) and heart rate (p < 0.05) to L-NMMA was reduced in sedentary HTX patients compared with healthy controls and heart rate response to SNP was also impaired in sedentary HTX patients. Regular aerobic physical training restores vascular function in HTX patients, who are at considerable risk for developing vascular complications. This effect is demonstrable in conduit and systemic resistance arteries.

The effectiveness of telehealth care on caregiver burden, mastery of stress, and family function among family caregivers of heart failure patients: a quasi-experimental study.

PubMed

Chiang, Li-Chi; Chen, Wan-Chou; Dai, Yu-Tzu; Ho, Yi-Lwun

2012-10-01

Telehealth care was developed to provide home-based monitoring and support for patients with chronic disease. The positive effects on physical outcome have been reported; however, more evidence is required concerning the effects on family caregivers and family function for heart failure patients transitioning from the hospital to home. To evaluate the effectiveness of nursing-led transitional care combining discharge plans and telehealth care on family caregiver burden, stress mastery and family function in family caregivers of heart failure patients compared to those receiving traditional discharge planning only. This is a quasi-experimental study design. Sixty-three patients with heart failure were assessed for eligibility and invited to participate in either telehealth care or standard care in a medical centre from May to October 2010. Three families refused to participate in data collection. Thirty families who chose telehealth care after discharge from the hospital to home comprised the experimental group; the others families receiving discharge planning only comprised the comparison group. Telenursing specialist provided the necessary family nursing interventions by 24-h remote monitoring of patients' health condition and counselling by telephone, helping the family caregivers successfully transition from hospital to home. Data on caregiver burden, stress mastery and family function were collected before discharge from the hospital and one month later at home. Effects of group, time, and group×time interaction were analysed using Mixed Model in SPSS (17.0). Family caregivers in both groups had significantly lower burden, higher stress mastery, and better family function at one-month follow-up compared to before discharge. The total score of caregiver burden, stress mastery and family function was significantly improved for the family caregivers in the experimental group compared to the comparison group at posttest. Two subscales of family function-Relationships between family and subsystems and Relationships between family and society were improved in the experimental group compared to the comparison group, but Relationships between family and family members was not different. The results provide evidence that telehealth care combined with discharge planning could reduce family caregiver burden, improve stress mastery, and improve family function during the first 30 days at home after heart failure patients are discharged from the hospital. Telenursing specialists cared caregivers with the concepts of providing transitional care to help them successful cross the critical transition stage. Copyright © 2012 Elsevier Ltd. All rights reserved.

Improved Accuracy of Automated Estimation of Cardiac Output Using Circulation Time in Patients with Heart Failure.

PubMed

Dajani, Hilmi R; Hosokawa, Kazuya; Ando, Shin-Ichi

2016-11-01

Lung-to-finger circulation time of oxygenated blood during nocturnal periodic breathing in heart failure patients measured using polysomnography correlates negatively with cardiac function but possesses limited accuracy for cardiac output (CO) estimation. CO was recalculated from lung-to-finger circulation time using a multivariable linear model with information on age and average overnight heart rate in 25 patients who underwent evaluation of heart failure. The multivariable model decreased the percentage error to 22.3% relative to invasive CO measured during cardiac catheterization. This improved automated noninvasive CO estimation using multiple variables meets a recently proposed performance criterion for clinical acceptability of noninvasive CO estimation, and compares very favorably with other available methods. Copyright © 2016 Elsevier Inc. All rights reserved.

Chocolate: A Heart-healthy Food? Show Me the Science!

PubMed

Hannum, Sandra M.; Schmitz, Harold H.; Keen, Carl L.

2002-01-01

Cocoa and chocolate foods produced by appropriate methods can contribute significant amounts of heart-healthy flavanols to the diet. These flavanols may enhance cardiovascular health by delaying blood clotting, improving vascular endothelial function, and helping to moderate inflammation. The benefits of chocolate can be enjoyed without guilt as part of a healthful balanced diet.

[EFFICIENCY OF COMBINATION OF ROFLUMILAST AND QUERCETIN FOR CORRECTION OXYGEN- INDEPENDENT MECHANISMS AND PHAGOCYTIC ACTIVITY OF MACROPHAGE CELLS OF PATIENTS WITH ACUTE EXACERBATION OF CHRONIC OBSTRUCTIVE PULMONARY DISEASE WHEN COMBINED WITH CORONARY HEART DISEASE].

PubMed

Gerych, P; Yatsyshyn, R

2015-01-01

Studied oxygen independent reaction and phagocytic activity of macrophage cells of patients with chronic obstructive pulmonary disease (COPD) II-III stage when combined with coronary heart disease (CHD). The increasing oxygen independent reactions monocytes and neutrophils and a decrease of the parameters that characterize the functional state of phagocytic cells, indicating a decrease in the functional capacity of macrophage phagocytic system (MPS) in patients with acute exacerbation of COPD, which runs as its own or in combination with stable coronary heart disease angina I-II. FC. Severity immunodeficiency state in terms of cellular component of nonspecific immunity in patients with acute exacerbation of COPD II-III stage in conjunction with the accompanying CHD increases with the progression of heart failure. Inclusion of basic therapy of COPD exacerbation and standard treatment of coronary artery disease and drug combinations Roflumilastand quercetin causes normalization of phagocytic indices MFS, indicating improved immune status and improves myocardial perfusion in terms of daily ECG monitoring.

Dual effects of VEGF-B on activating cardiomyocytes and cardiac stem cells to protect the heart against short- and long-term ischemia-reperfusion injury.

PubMed

Li, Guo-Hua; Luo, Bin; Lv, Yan-Xia; Zheng, Fei; Wang, Lu; Wei, Meng-Xi; Li, Xian-Yu; Zhang, Lei; Wang, Jia-Ning; Chen, Shi-You; Tang, Jun-Ming; He, Xiaohua

2016-05-04

To investigate whether vascular endothelial growth factor B (VEGF-B) improves myocardial survival and cardiac stem cell (CSC) function in the ischemia-reperfusion (I/R) heart and promotes CSC mobilization and angiogenesis. One hour after myocardial ischemia and infarction, rats were treated with recombinant human VEGF-B protein following 24 h or 7 days of myocardial reperfusion. Twenty-four hours after myocardial I/R, VEGF-B increased pAkt and Bcl-2 levels, reduced p-p38MAPK, LC3-II/I, beclin-1, CK, CK-MB and cTnt levels, triggered cardiomyocyte protection against I/R-induced autophagy and apoptosis, and contributed to the decrease of infarction size and the improvement of heart function during I/R. Simultaneously, an in vitro hypoxia-reoxygenation (H/R)-induced H9c2 cardiomyocyte injury model was used to mimic I/R injury model in vivo; in this model, VEGF-B decreased LDH release, blocked H/R-induced apoptosis by inhibiting cell autophagy, and these special effects could be abolished by the autophagy inducer, rapamycin. Mechanistically, VEGF-B markedly activated the Akt signaling pathway while slightly inhibiting p38MAPK, leading to the blockade of cell autophagy and thus protecting cardiomyocyte from H/R-induced activation of the intrinsic apoptotic pathway. Seven days after I/R, VEGF-B induced the expression of SDF-1α and HGF, resulting in the massive mobilization and homing of c-Kit positive cells, triggering further angiogenesis and vasculogenesis in the infracted heart and contributing to the improvement of I/R heart function. VEGF-B could contribute to a favorable short- and long-term prognosis for I/R via the dual manipulation of cardiomyocytes and CSCs.

Echocardiographic findings in stable outpatients with properly functioning HeartMate II left ventricular assist devices.

PubMed

Topilsky, Yan; Oh, Jae K; Atchison, Fawn W; Shah, Dipesh K; Bichara, Valentina M; Schirger, John A; Kushwaha, Sudhir S; Pereira, Naveen L; Park, Soon J

2011-02-01

Continuous-flow left ventricular assist devices (LVADs) have become part of the standard of care for the treatment of advanced heart failure. However, knowledge of normal values for transthoracic echocardiographic examination and measurements in these patients are lacking. All transthoracic echocardiographic examinations in 63 consecutive patients, performed 90 and 180 days after surgery with the implantation of a HeartMate II continuous-flow LVAD between February 2007 and January 2010, were retrospectively analyzed. All patients had to be outpatients at 3 and 6 months after surgery and considered stable on LVAD therapy (New York Heart Association class I or II and no need for inotropes, intravenous furosemide, or hospitalization). End-diastolic and end-systolic diameters and left ventricular mass decreased considerably compared with baseline measurements before LVAD implantation. Mitral inflow deceleration time increased (188 ± 70 vs 132.5 ± 27 msec, P = .009) and left atrial volume (84.1 ± 33 vs 141.7 ± 62 mL, P = .003) and E/e' ratio decreased (20.3 ± 9 vs 26 ± 11, P = .01), all consistent with decreased left ventricular filling pressure. Estimated right ventricular (RV) and right atrial pressure decreased significantly (34.1 ± 10 vs 51.7 ± 14 mm Hg and 9.5 ± 5 vs 14.4 ± 5 mm Hg, respectively, P < .0001 for both). Quantitatively estimated RV function (P = .02), RV fractional area change (27.9 ± 10% vs 37.4 ± 10.9%, P < .0001), and the RV index of myocardial performance (0.32 ± 0.1 vs 0.65 ± 0.2 vs 0.32 ± .01, P < .0001) improved, suggesting improved RV efficiency. LVAD therapy resulted in significant decreases in the severity of mitral regurgitation. Tricuspid regurgitation improved in patients who had concurrent tricuspid surgical correction and was unchanged otherwise. Aortic regurgitation severity increased 3 months after LVAD implantation. There were no significant differences in any of the echocardiographic parameters in the 6-month evaluation compared with the 3-month evaluation. This is the first report of selected typical echocardiographic values in a group of stable patients with normally functioning HeartMate II continuous-flow LVADs. A stable functioning continuous LVAD is associated with evidence of efficient unloading of the left ventricle, improved RV function, significant improvement in mitral regurgitation, improvement in tricuspid regurgitation only in patients undergoing repair, and increased aortic regurgitation. These normal data provide a basis for future echocardiographic studies after LVAD implantation. Copyright © 2011 American Society of Echocardiography. Published by Mosby, Inc. All rights reserved.

Cardiac I-1c overexpression with reengineered AAV improves cardiac function in swine ischemic heart failure.

PubMed

Ishikawa, Kiyotake; Fish, Kenneth M; Tilemann, Lisa; Rapti, Kleopatra; Aguero, Jaume; Santos-Gallego, Carlos G; Lee, Ahyoung; Karakikes, Ioannis; Xie, Chaoqin; Akar, Fadi G; Shimada, Yuichi J; Gwathmey, Judith K; Asokan, Aravind; McPhee, Scott; Samulski, Jade; Samulski, Richard Jude; Sigg, Daniel C; Weber, Thomas; Kranias, Evangelia G; Hajjar, Roger J

2014-12-01

Cardiac gene therapy has emerged as a promising option to treat advanced heart failure (HF). Advances in molecular biology and gene targeting approaches are offering further novel options for genetic manipulation of the cardiovascular system. The aim of this study was to improve cardiac function in chronic HF by overexpressing constitutively active inhibitor-1 (I-1c) using a novel cardiotropic vector generated by capsid reengineering of adeno-associated virus (BNP116). One month after a large anterior myocardial infarction, 20 Yorkshire pigs randomly received intracoronary injection of either high-dose BNP116.I-1c (1.0 × 10(13) vector genomes (vg), n = 7), low-dose BNP116.I-1c (3.0 × 10(12) vg, n = 7), or saline (n = 6). Compared to baseline, mean left ventricular ejection fraction increased by 5.7% in the high-dose group, and by 5.2% in the low-dose group, whereas it decreased by 7% in the saline group. Additionally, preload-recruitable stroke work obtained from pressure-volume analysis demonstrated significantly higher cardiac performance in the high-dose group. Likewise, other hemodynamic parameters, including stroke volume and contractility index indicated improved cardiac function after the I-1c gene transfer. Furthermore, BNP116 showed a favorable gene expression pattern for targeting the heart. In summary, I-1c overexpression using BNP116 improves cardiac function in a clinically relevant model of ischemic HF.

Cardiac I-1c Overexpression With Reengineered AAV Improves Cardiac Function in Swine Ischemic Heart Failure

PubMed Central

Ishikawa, Kiyotake; Fish, Kenneth M; Tilemann, Lisa; Rapti, Kleopatra; Aguero, Jaume; Santos-Gallego, Carlos G; Lee, Ahyoung; Karakikes, Ioannis; Xie, Chaoqin; Akar, Fadi G; Shimada, Yuichi J; Gwathmey, Judith K; Asokan, Aravind; McPhee, Scott; Samulski, Jade; Samulski, Richard Jude; Sigg, Daniel C; Weber, Thomas; Kranias, Evangelia G; Hajjar, Roger J

2014-01-01

Cardiac gene therapy has emerged as a promising option to treat advanced heart failure (HF). Advances in molecular biology and gene targeting approaches are offering further novel options for genetic manipulation of the cardiovascular system. The aim of this study was to improve cardiac function in chronic HF by overexpressing constitutively active inhibitor-1 (I-1c) using a novel cardiotropic vector generated by capsid reengineering of adeno-associated virus (BNP116). One month after a large anterior myocardial infarction, 20 Yorkshire pigs randomly received intracoronary injection of either high-dose BNP116.I-1c (1.0 × 1013 vector genomes (vg), n = 7), low-dose BNP116.I-1c (3.0 × 1012 vg, n = 7), or saline (n = 6). Compared to baseline, mean left ventricular ejection fraction increased by 5.7% in the high-dose group, and by 5.2% in the low-dose group, whereas it decreased by 7% in the saline group. Additionally, preload-recruitable stroke work obtained from pressure–volume analysis demonstrated significantly higher cardiac performance in the high-dose group. Likewise, other hemodynamic parameters, including stroke volume and contractility index indicated improved cardiac function after the I-1c gene transfer. Furthermore, BNP116 showed a favorable gene expression pattern for targeting the heart. In summary, I-1c overexpression using BNP116 improves cardiac function in a clinically relevant model of ischemic HF. PMID:25023328

Supplementation of l-Alanyl-l-Glutamine and Fish Oil Improves Body Composition and Quality of Life in Patients With Chronic Heart Failure.

PubMed

Wu, Christina; Kato, Tomoko S; Ji, Ruiping; Zizola, Cynthia; Brunjes, Danielle L; Deng, Yue; Akashi, Hirokazu; Armstrong, Hilary F; Kennel, Peter J; Thomas, Tiffany; Forman, Daniel E; Hall, Jennifer; Chokshi, Aalap; Bartels, Matthew N; Mancini, Donna; Seres, David; Schulze, P Christian

2015-11-01

Skeletal muscle dysfunction and exercise intolerance are clinical hallmarks of patients with heart failure. These have been linked to a progressive catabolic state, skeletal muscle inflammation, and impaired oxidative metabolism. Previous studies suggest beneficial effects of ω-3 polyunsaturated fatty acids and glutamine on exercise performance and muscle protein balance. In a randomized double-blind, placebo-controlled trial, 31 patients with heart failure were randomized to either l-alanyl-l-glutamine (8 g/d) and polyunsaturated fatty acid (6.5 g/d) or placebo (safflower oil and milk powder) for 3 months. Cardiopulmonary exercise testing, dual-energy x-ray absorptiometry, 6-minute walk test, hand grip strength, functional muscle testing, echocardiography, and quality of life and lateral quadriceps muscle biopsy were performed at baseline and at follow-up. Oxidative capacity and metabolic gene expression were analyzed on muscle biopsies. No differences in muscle function, echocardiography, 6-minute walk test, or hand grip strength and a nonsignificant increase in peak VO2 in the treatment group were found. Lean body mass increased and quality of life improved in the active treatment group. Molecular analysis revealed no differences in muscle fiber composition, fiber cross-sectional area, gene expression of metabolic marker genes (PGC1α, CPT1, PDK4, and GLUT4), and skeletal muscle oxidative capacity. The combined supplementation of l-alanyl-l-glutamine and polyunsaturated fatty acid did not improve exercise performance or muscle function but increased lean body mass and quality of life in patients with chronic stable heart failure. These findings suggest potentially beneficial effects of high-dose nutritional polyunsaturated fatty acids and amino acid supplementations in patients with chronic stable heart failure. URL: http://www.clinicaltrials.gov. Unique identifier: NCT01534663. © 2015 American Heart Association, Inc.

Effect of shilajit on the heart of Daphnia: A preliminary study.

PubMed

Gaikwad, N S; Panat, A V; Deshpande, M S; Ramya, K; Khalid, P U; Augustine, P

2012-01-01

Shilajit is a mineral-rich complex organic compound used in the traditional system of Ayurvedic medicine for treating hypertension and improving the cardiac function with many herbomineral preparations. However, very little experimental evidence is available about its effect on the cardiac function. We used Daphnia as a model organism for observing the effect of shilajit on its heart due to its myogenic properties and its response to number of cardioactive drugs that are known to affect human heart function. Genome of Daphnia shows the strongest homology with the human genome. These characteristics of Daphnia make it an ideal organism for biomedical research. Our results suggest that this complex organic compound lowers the heart beats as its concentration increases from 1.0 to 100 ppm. The beats come to near normal condition at 1000 ppm. Above 1000 ppm, the beats are very fast and impossible to count. These results indicate a negative chronotropic effect on the Daphnia heart at low concentrations and a positive chronotropic effect to arrhythmia and finally failure at increasing higher concentrations of shilajit.

Effect of shilajit on the heart of Daphnia: A preliminary study

PubMed Central

Gaikwad, N. S.; Panat, A. V.; Deshpande, M. S.; Ramya, K.; Khalid, P. U.; Augustine, P.

2012-01-01

Shilajit is a mineral-rich complex organic compound used in the traditional system of Ayurvedic medicine for treating hypertension and improving the cardiac function with many herbomineral preparations. However, very little experimental evidence is available about its effect on the cardiac function. We used Daphnia as a model organism for observing the effect of shilajit on its heart due to its myogenic properties and its response to number of cardioactive drugs that are known to affect human heart function. Genome of Daphnia shows the strongest homology with the human genome. These characteristics of Daphnia make it an ideal organism for biomedical research. Our results suggest that this complex organic compound lowers the heart beats as its concentration increases from 1.0 to 100 ppm. The beats come to near normal condition at 1000 ppm. Above 1000 ppm, the beats are very fast and impossible to count. These results indicate a negative chronotropic effect on the Daphnia heart at low concentrations and a positive chronotropic effect to arrhythmia and finally failure at increasing higher concentrations of shilajit. PMID:22529672

Clinical effects of carvedilol and trimetazidine for the treatmentof alcoholic myocardiopathy.

PubMed

Li, Hui; Liu, Fu-Yuan; Li, Xiao-Lan; Li, Xiao-Mei; Zhu, Lei

2016-08-01

The aim of the study was to compare the clinical effects of carvedilol and trimetazidine for the treatment of alcoholic cardiomyopathy. A total of 60 patients diagnosed with alcoholic cardiomyopathy were enrolled in the study. The patients were randomly divided into the carvedilol (n=20), trimetazidine (n=20) and control (n=20) groups. The patients in the control, carvedilol and trimetazidine groups were treated with conventional drugs, conventional drugs + carvedil and conventional drugs + trimetazidine respectively, for 12 weeks. The patients were compared for their heart functions [left ventricular ejection fraction (LVEF), C-reactive protein (CRP) and 6 min walking], heart rate, blood pressure and heart enlargement (cardiothoracic proportion and left ventricular diameter) before and after treatment. The parameters studied for heart functions, heart rate, blood pressure, heart enlargement, clinical effects before and after treatment were statistically insignificant (p>0.05). After treatment, the carvedilol and trimetazidine groups showed higher LVEF and CRP, longer walking distance in 6 min, as well as lower heart rate and blood pressure (both systolic and diastolic) compared to the control group. Similarly, the cardiothoracic proportion and left ventricular internal diameter for the carvedilol and trimetazidine groups was lower than those of the control group, with better clinical effects (p<0.05). In conclusion, the curative effects of the carvedilol and trimetazidine groups of alcoholic myocardiopathy similar. Both are safe agents that may improve the cardiac function and heart expansion of patients.

Overview of implantable cardioverter defibrillator and cardiac resynchronisation therapy in heart failure management

PubMed Central

Chia, Pow-Li; Foo, David

2016-01-01

Clinical trials have established the benefits of implantable cardioverter defibrillators (ICDs) and cardiac resynchronisation therapy (CRT) in the treatment of heart failure patients. As adjuncts to guideline-directed medical therapy, ICDs confer mortality benefits from sudden cardiac arrest, while CRT reduces mortality, hospitalisation rates and improves functional capacity. This review discusses the use of ICDs and CRT devices in heart failure management, outlining the evidence supporting their use, indications and contraindications. PMID:27440409

High-throughput screening identifies microRNAs that target Nox2 and improve function after acute myocardial infarction.

PubMed

Yang, Junyu; Brown, Milton E; Zhang, Hanshuo; Martinez, Mario; Zhao, Zhihua; Bhutani, Srishti; Yin, Shenyi; Trac, David; Xi, Jianzhong Jeff; Davis, Michael E

2017-05-01

Myocardial infarction (MI) is the most common cause of heart failure. Excessive production of ROS plays a key role in the pathogenesis of cardiac remodeling after MI. NADPH with NADPH oxidase (Nox)2 as the catalytic subunit is a major source of superoxide production, and expression is significantly increased in the infarcted myocardium, especially by infiltrating macrophages. While microRNAs (miRNAs) are potent regulators of gene expression and play an important role in heart disease, there still lacks efficient ways to identify miRNAs that target important pathological genes for treating MI. Thus, the overall objective was to establish a miRNA screening and delivery system for improving heart function after MI using Nox2 as a critical target. With the use of the miRNA-target screening system composed of a self-assembled cell microarray (SAMcell), three miRNAs, miR-106b, miR-148b, and miR-204, were identified that could regulate Nox2 expression and its downstream products in both human and mouse macrophages. Each of these miRNAs were encapsulated into polyketal (PK3) nanoparticles that could effectively deliver miRNAs into macrophages. Both in vitro and in vivo studies in mice confirmed that PK3-miRNAs particles could inhibit Nox2 expression and activity and significantly improve infarct size and acute cardiac function after MI. In conclusion, our results show that miR-106b, miR-148b, and miR-204 were able to improve heart function after myocardial infarction in mice by targeting Nox2 and possibly altering inflammatory cytokine production. This screening system and delivery method could have broader implications for miRNA-mediated therapeutics for cardiovascular and other diseases. NEW & NOTEWORTHY NADPH oxidase (Nox)2 is a promising target for treating cardiovascular disease, but there are no specific inhibitors. Finding endogenous signals that can target Nox2 and other inflammatory molecules is of great interest. In this study, we used high-throughput screening to identify microRNAs that target Nox2 and improve cardiac function after infarction. Copyright © 2017 the American Physiological Society.

Activation of PPAR-α in the early stage of heart failure maintained myocardial function and energetics in pressure-overload heart failure.

PubMed

Kaimoto, Satoshi; Hoshino, Atsushi; Ariyoshi, Makoto; Okawa, Yoshifumi; Tateishi, Shuhei; Ono, Kazunori; Uchihashi, Motoki; Fukai, Kuniyoshi; Iwai-Kanai, Eri; Matoba, Satoaki

2017-02-01

Failing heart loses its metabolic flexibility, relying increasingly on glucose as its preferential substrate and decreasing fatty acid oxidation (FAO). Peroxisome proliferator-activated receptor α (PPAR-α) is a key regulator of this substrate shift. However, its role during heart failure is complex and remains unclear. Recent studies reported that heart failure develops in the heart of myosin heavy chain-PPAR-α transgenic mice in a manner similar to that of diabetic cardiomyopathy, whereas cardiac dysfunction is enhanced in PPAR-α knockout mice in response to chronic pressure overload. We created a pressure-overload heart failure model in mice through transverse aortic constriction (TAC) and activated PPAR-α during heart failure using an inducible transgenic model. After 8 wk of TAC, left ventricular (LV) function had decreased with the reduction of PPAR-α expression in wild-type mice. We examined the effect of PPAR-α induction during heart failure using the Tet-Off system. Eight weeks after the TAC operation, LV construction was preserved significantly by PPAR-α induction with an increase in PPAR-α-targeted genes related to fatty acid metabolism. The increase of expression of fibrosis-related genes was significantly attenuated by PPAR-α induction. Metabolic rates measured by isolated heart perfusions showed a reduction in FAO and glucose oxidation in TAC hearts, but the rate of FAO preserved significantly owing to the induction of PPAR-α. Myocardial high-energy phosphates were significantly preserved by PPAR-α induction. These results suggest that PPAR-α activation during pressure-overloaded heart failure improved myocardial function and energetics. Thus activating PPAR-α and modulation of FAO could be a promising therapeutic strategy for heart failure. NEW & NOTEWORTHY The present study demonstrates the role of PPAR-α activation in the early stage of heart failure using an inducible transgenic mouse model. Induction of PPAR-α preserved heart function, and myocardial energetics. Activating PPAR-α and modulation of fatty acid oxidation could be a promising therapeutic strategy for heart failure. Copyright © 2017 the American Physiological Society.

A protocol to study ex vivo mouse working heart at human-like heart rate.

PubMed

Feng, Han-Zhong; Jin, Jian-Ping

2018-01-01

Genetically modified mice are widely used as experimental models to study human heart function and diseases. However, the fast rate of normal mouse heart at 400-600bpm limits its capacity of assessing kinetic parameters that are important for the physiology and pathophysiology of human heart that beats at a much slower rate (75-180bpm). To extend the value of mouse models, we established a protocol to study ex vivo mouse working hearts at a human-like heart rate. In the presence of 300μM lidocaine to lower pacemaker and conductive activities and prevent arrhythmia, a stable rate of 120-130bpm at 37°C is achieved for ex vivo mouse working hearts. The negative effects of decreased heart rate on force-frequency dependence and lidocaine as a myocardial depressant on intracellular calcium can be compensated by using a higher but still physiological level of calcium (2.75mM) in the perfusion media. Multiple parameters were studied to compare the function at the human-like heart rate with that of ex vivo mouse working hearts at the standard rate of 480bpm. The results showed that the conditions for slower heart rate in the presence of 300μM lidocaine did not have depressing effect on left ventricular pressure development, systolic and diastolic velocities and stroke volume with maintained positive inotropic and lusitropic responses to β-adrenergic stimulation. Compared with that at 480bpm, the human-like heart rate increased ventricular filling and end diastolic volume with enhanced Frank-Starling responses. Coronary perfusion was increased from longer relaxation time and interval between beats whereas cardiac efficiency was significantly improved. Although the intrinsic differences between mouse and human heart remain, this methodology for ex vivo mouse hearts to work at human-like heart rate extends the value of using genetically modified mouse models to study cardiac function and human heart diseases. Copyright © 2017 Elsevier Ltd. All rights reserved.

The Prognostic Importance of Changes in Renal Function during Treatment for Acute Heart Failure Depends on Admission Renal Function

PubMed Central

Reid, Ryan; Ezekowitz, Justin A.; Brown, Paul M.; McAlister, Finlay A.; Rowe, Brian H.; Braam, Branko

2015-01-01

Background Worsening and improving renal function during acute heart failure have been associated with adverse outcomes but few studies have considered the admission level of renal function upon which these changes are superimposed. Objectives The objective of this study was to evaluate definitions that incorporate both admission renal function and change in renal function. Methods 696 patients with acute heart failure with calculable eGFR were classified by admission renal function (Reduced [R, eGFR<45 ml/min] or Preserved [P, eGFR≥45 ml/min]) and change over hospital admission (worsening [WRF]: eGFR ≥20% decline; stable [SRF]; and improving [IRF]: eGFR ≥20% increase). The primary outcome was all-cause mortality. The prevalence of Pres and Red renal function was 47.8% and 52.2%. The frequency of R-WRF, R-SRF, and R-IRF was 11.4%, 28.7%, and 12.1%, respectively; the incidence of P-WRF, P-SRF, and P-IRF was 5.7%, 35.3%, and 6.8%, respectively. Survival was shorter for patients with R-WRF compared to R-IRF (median survival times 13.9 months (95%CI 7.7–24.9) and 32.5 months (95%CI 18.8–56.1), respectively), resulting in an acceleration factor of 2.3 (p = 0.016). Thus, an increase compared with a decrease in renal function was associated with greater than two times longer survival among patients with Reduced renal function. PMID:26380982

Shenfu Formula reduces cardiomyocyte apoptosis in heart failure rats by regulating microRNAs.

PubMed

Yan, Xu; Wu, Hongjin; Ren, Jianxun; Liu, Yuna; Wang, Shengqi; Yang, Jiyuan; Qin, Shuyan; Wu, Delin

2018-05-07

Shenfu decoction consists of the water extract from the dried root or rootstalk of Panax ginseng C. A. Mey (Asian ginseng) and the lateral root of Aconitum carmichaeli Debx (Fuzi, Heishunpian in Chinese). Shenfu Formula has been used as a folk Chinese medicine for thousands of years. Recent studies have shown that Shenfu injection can enhance cardiac function and regulate arrhythmia. Shenfu Formula plays an important role in the treatment of heart failure. However, its microRNA-mediated mechanisms are still not fully understood. Thus, we established a heart failure model in rats to investigate the microRNA mechanism of Shenfu Formula in cardiac function and apoptosis. The heart failure animal model was established via left-anterior descending coronary artery ligation in rats. Seven days after surgery, Shenfu Formula was given to the heart failure rats, which were selected by echocardiography with an LVEF<45%. After Shenfu Formula was given intragastrically for 30 days, blood samples were drawn, the heart was excised after echocardiography, and echocardiographic parameters and apoptosis-related proteins were further examined. Fas/Fas-L and Bcl-2/Bax proteins were analyzed by Western blot, and microRNAs were evaluated using Affymetrix GeneChip miRNA arrays. Shenfu Formula increased the left ventricular ejection fraction, improved the hemodynamic index of heart failure rats, and decreased serum brain natriuretic peptide (BNP) levels. Shenfu Formula also decreased the positive rate of myocardial cells as detected by the TUNEL method and significantly suppressed caspase 3 expression. Moreover, we found that Shenfu formula can regulate the initiative factors Fas/Fas-L in the intrinsic pathway and Bcl-2/Bax in the extrinsic apoptosis pathway to suppress apoptosis in heart failure rats. Finally, Shenfu formula potentially alters the balance of microRNAs involved in activating and inhibiting apoptosis, ultimately suppressing apoptosis; this leads to changes in the gene expression profiles of microRNAs targets. Shenfu Granule can effectively improve cardiac function in heart failure rats, and the anti-apoptosis effects of Shenfu Formula are potential mechanisms for inhibiting heart failure. Copyright © 2018. Published by Elsevier B.V.

Response of the oxygen uptake efficiency slope to orthotopic heart transplantation: lack of correlation with changes in central hemodynamic parameters and resting lung function.

PubMed

Van Laethem, Christophe; Goethals, Marc; Verstreken, Sofie; Walravens, Maarten; Wellens, Francis; De Proft, Margot; Bartunek, Jozef; Vanderheyden, Marc

2007-09-01

Recently, a new linear measure of ventilatory response to exercise, the oxygen uptake efficiency slope (OUES), was proposed in the evaluation of heart failure patients. No data are available on the response of the OUES after orthotopic heart transplantation (HTx). Thirty patients who underwent HTx between 1999 and 2003 were included in the study. Data from maximal cardiopulmonary exercise test, resting pulmonary function and hemodynamic assessment were collected before the transplant at time of screening and 1 year after HTx. During the first year after HTx, OUES and normalized OUES for body weight (OUES/kg) increased significantly from 15.6 +/- 4.9 to 19.7 +/- 4.8 (p < 0.05). Changes in OUES/kg were significantly correlated with changes in peak VO2, VAT and peak VE, and inversely to changes in peak VD/VT, but not to changes in VE/VCO2 slope (all p < 0.05). Changes in OUES or OUES/kg did not correlate with any changes in measures of resting lung volumes or capacities and measures of central hemodynamic function after HTx. OUES improved significantly after HTx, but, similar to other exercise parameters, remained considerably impaired. The changes in OUES were highly correlated with the improvements in other exercise variables, but did not correlate with marked improvements in central hemodynamics or resting lung function.

Clinical-Physiological Considerations in Patients Undergoing Staged Palliation for a Functionally Single Ventricle.

PubMed

Penny, Daniel J; Krishnamurthy, Rajesh

2016-08-01

The objectives of this review are to discuss the pathophysiology of the circulation with a functionally univentricular heart, with a focus on the unique physiologic characteristics, which provide the underpinnings for the management of these complex patients. MEDLINE and PubMed. The circulation of the patient with a functionally univentricular heart displays unique physiologic characteristics, which are quite different from those of the normal biventricular circulation. There are profound differences within the heart itself in terms of ventricular function, interventricular interactions, and myocardial architecture, which are likely to have significant implications for the efficiency of ventricular ejection and metabolism. The coupling between the systemic ventricle and the aorta also displays unique features. The 3D orientation of the Fontan anastomosis itself can profoundly impact cardiac output, although the "portal" pulmonary arterial bed is a crucial determinant of overall cardiovascular function. As a result, disease-specific approaches to improve cardiovascular function are required at all stages during the care of these complex patients.

Inhibition of Oct 3/4 mitigates the cardiac progenitor-derived myocardial repair in infarcted myocardium.

PubMed

Zhao, Yu Tina; Du, Jianfeng; Chen, Youfang; Tang, Yaoliang; Qin, Gangjian; Lv, Guorong; Zhuang, Shougang; Zhao, Ting C

2015-12-24

Recent evidence has demonstrated that cardiac progenitor cells play an essential role in the induction of angiomyogenesis in infarcted myocardium. We and others have shown that engraftment of c-kit(+) cardiac stem cells (CSCs) into infarcted hearts led to myocardium regeneration and neovascularization, which was associated with an improvement of ventricular function. The purpose of this study is aimed at investigating the functional role of transcription factor (TF) Oct3/4 in facilitating CSCs to promote myocardium regeneration and preserve cardiac performance in the post-MI heart. c-kit(+) CSCs were isolated from adult hearts and re-introduced into the infarcted myocardium in which the mouse MI model was created by permanent ligation of the left anterior descending artery (LAD). The Oct3/4 of CSCs was inhibited by transfection of Oct3/4 siRNA, and transfection of CSCs with control siRNA serves as control groups. Myocardial functions were evaluated by echocardiographic measurement. Histological analysis was employed to assess newly formed cardiogenesis, neovascularization, and cell proliferations. Terminal deoxynucleotidyltransferase (TdT) nick-end labeling (TUNEL) was carried out to assess apoptotic cardiomyocytes. Real time polymerase chain reaction and Western blot were carried out to evaluate the level of Oct 3/4 in CSCs. Two weeks after engraftment, CSCs increased ventricular functional recovery as shown by a serial echocardiographic measurement, which is concomitant with the suppression of cardiac hypertrophy and attenuation of myocardial interstitial fibrosis. Suppression of Oct 3/4 of CSCs abrogated functional improvements and mitigated the hypertrophic response and cardiac remodeling. Transplantation of c-kit(+) CSCs into MI hearts promoted cardiac regeneration and neovascularization, which were abolished with the knockdown of Oct3/4. Additionally, suppression of Oct3/4 abrogated myocyte proliferation in the CSC-engrafted myocardium. Our results indicate that CSCs-derived cardiac regeneration improves the restoration of cardiac function and is mediated through Oct 3/4.

Potential benefits of weight loss in coronary heart disease.

PubMed

Ades, Philip A; Savage, Patrick D

2014-01-01

The prevalence of overweight, obesity and insulin resistance in patients with coronary heart disease (CHD) exceeds that of the general population. Obesity is associated with a constellation of coronary risk factors that predispose to the development and progression of CHD. Intentional weight loss, accomplished through behavioral weight loss and exercise, improves insulin sensitivity and associated cardio-metabolic risk factors such as lipid measures, blood pressure, measures of inflammation and vascular function both in healthy individuals and patients with CHD. Additionally, physical fitness, physical function and quality of life all improve. There is evidence that intentional weight loss prevents the onset of CHD in high risk overweight individuals. While weight loss associated improvements in insulin resistance, fitness and related risk factors strongly supports favorable prognostic effects in individuals with established CHD, further study is needed to determine if long-term clinical outcomes are improved. © 2014.

Effect of beta blockers (carvedilol or metoprolol XL) in patients with transposition of great arteries and dysfunction of the systemic right ventricle.

PubMed

Doughan, Abdul Rahman K; McConnell, Michael E; Book, Wendy M

2007-03-01

This study evaluated the effects of beta blockers (carvedilol and metoprolol XL) on New York Heart Association functional class and systemic right ventricular (RV) function in patients with complete transposition of the great arteries who had systemic RV dysfunction late after atrial inflow correction. A significant improvement in New York Heart Association functional class was found after 4 months of therapy with beta blockers. Functional recovery was significant mostly in those patients with pacemakers who received higher maintenance doses of carvedilol. RV end-diastolic area was significantly greater in untreated patients at the end of the follow-up period, whereas it was unchanged in treated patients. In conclusion, beta blockers prevent RV remodeling, with a concomitant improvement in exercise tolerance in patients with complete transposition of the great arteries and systemic RV dysfunction.

Physical Function and Health Status in Aging Puerto Rican Adults: The Boston Puerto Rican Health Study

PubMed Central

Castaneda-Sceppa, Carmen; Price, Lori Lyn; Noel, Sabrina E.; Midle, Jennifer Bassett; Falcon, Luis M.; Tucker, Katherine L.

2015-01-01

Objectives This article describes physical function in Puerto Rican older adults and examines associations between health status and physical function. It also assesses relationships between physical function and disability. Method This study uses a cross-sectional study of Puerto Ricans 45 to 75 years in Boston (N = 1,357). Measures included performance-based physical function (handgrip strength, walking speed, balance, chair stands, foot tapping), health conditions (obesity, diabetes, depressive symptomatology, history of heart disease, heart attack, stroke, and arthritis), and self-reported disability (activities of daily living, instrumental activities of daily living). Results Older women (60-75 years) had the poorest physical function. Poor physical function was associated with obesity, diabetes, depression, history of heart attack, stroke, and arthritis, after adjusting for age, sex, education, income, and lifestyle (p < .05). Physical function and disability were correlated (p < .01). Discussion Health status among Puerto Ricans appears to contribute to poor physical function. Targeted interventions to improve strength, endurance, and balance are needed to combat physical frailty and its consequences in this population. PMID:20495158

Low-dose β-blocker in combination with milrinone safely improves cardiac function and eliminates pulsus alternans in patients with acute decompensated heart failure.

PubMed

Kobayashi, Shigeki; Susa, Takehisa; Tanaka, Takeo; Murakami, Wakako; Fukuta, Seiko; Okuda, Shinichi; Doi, Masahiro; Wada, Yasuaki; Nao, Tomoko; Yamada, Jutaro; Okamura, Takayuki; Yano, Masafumi; Matsuzaki, Masunori

2012-01-01

The purpose of this study was to determine whether a low-dose β-blocker, in combination with milrinone, improves cardiac function in acute decompensated heart failure (ADHF) with tachycardia. Twenty ADHF patients (New York Heart Association classification III, n=1, and IV, n=19; heart rate [HR], 107±12 beats/min; left ventricular ejection fraction, 24±7%; cardiac index [CI], 2.2±0.6 L·min(-1)·m(-2); pulmonary capillary wedge pressure [PCWP], 26±8 mmHg) were enrolled in this study. The patients first underwent conventional therapy with milrinone, vasodilators and diuretics; landiolol (1.5-6.0 µg·kg(-1)·min(-1); i.v.), which is an ultra-short-acting β(1)-selective blocker, was then added to the treatment regimen to study its effect on hemodynamics. Low-dose landiolol (1.5 µg·kg(-1)·min(-1)) significantly reduced HR by 11% without changing blood pressure (BP) and CI, whereas higher doses (≥3.0 µg·kg(-1)·min(-1)) tended to decrease BP and CI while increasing PCWP and systemic vascular resistance. After treatment with landiolol (1.5 µg·kg(-1)·min(-1)), hemodynamic parameters such as PCWP, stroke volume index, SvO(2), rate pressure product, filling time/RR, E/e', and Tei index were significantly improved. A low-dose β-blocker in combination with milrinone improved cardiac function in ADHF patients with tachycardia; therefore, it may be considered as an adjunct therapy for use when standard therapy with milrinone is not effective at slowing HR.

Chronically elevated bilirubin protects from cardiac reperfusion injury in the male Gunn rat.

PubMed

Bakrania, B; Du Toit, E F; Ashton, K J; Wagner, K-H; Headrick, J P; Bulmer, A C

2017-08-01

Bilirubin is associated with reduced risk of cardiovascular disease, as evidenced in conditions of mild hyperbilirubinaemia (Gilbert's Syndrome). Little is known regarding myocardial stress resistance in hyperbilirubinaemic conditions or whether life-long exposure modifies cardiac function, which might contribute to protection from cardiovascular disease. Hyperbilirubinaemic rats and littermate controls underwent echocardiography at 3, 6 and 12 months of age, with hearts subsequently assessed for resistance to 30 min of ischaemia. Heart tissue was then collected for assessment of bilirubin content. No difference in baseline cardiac function was evident until 6 months onwards, where Gunn rats demonstrated aortic dilatation and reduced peak ejection velocities. Additionally, duration of ventricular ejection increased progressively, indicating a negative inotropic effect of bilirubin in vivo. Ex vivo analysis of baseline function revealed reduced left ventricular pressure development (LVDP) and contractility in hyperbilirubinaemic rats. Furthermore, stress resistance was improved in Gunn hearts: post-ischaemic recoveries of LVDP (76 ± 22% vs. 29 ± 17% Control, P < 0.01) and coronary flow (96 ± 9% vs. 86 ± 16% Control, P < 0.01) were improved in Gunn hearts, accompanied by reduced infarct area (21 ± 5% vs. 47 ± 15% Control, P < 0.01), and ventricular malondialdehyde and protein carbonyl content. Expression of myocardial nitric oxide-regulating genes including Nos1 and Noa1 were not significantly different. These data reveal life-long hyperbilirubinaemia induces age-dependent hypocontractility in male Gunn rats, and improved stress resistance. In addition, bilirubin exerts sex-independent effects on vascular structure, myocardial function and ischaemic tolerance, the latter likely mediated via bilirubin's antioxidant properties. © 2017 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd.

The pharmacists' role in improving guideline compliance for thyroid function testing in patients with heart failure.

PubMed

Ziman, Melanie E; Bui, Hien T; Smith, Craig S; Tsukiji, Lori A; Asmatey, Veda M; Chu, Steven B; Miano, John S

2012-04-01

This single-center retrospective pilot program's objective was to utilize outpatient pharmacists to improve laboratory test adherence in chronic heart failure (CHF) patients overdue for thyroid function testing, thereby demonstrating the value of the outpatient pharmacist and justifying possible clinical role expansion. Thyroid disorders may contribute to CHF development, progression, and exacerbation. Testing is the standard of care in CHF patients per American Heart Association's 2009 Guidelines. Delinquency was defined as labs not conducted within 1 year in patients with euthyroid history, within 6 months in patients with thyroid dysfunction, abnormal labs at any time without follow-up, or lab absence after thyroid medication initiation, adjustment, or discontinuation. Targeted 80 nonpregnant adult CHF patients with delinquent thyroid function tests were counseled to get thyroid labs at point of sale, via telephone, e-mail, or letter. In collaboration with physicians, pharmacists ordered thyroid-stimulating hormone (TSH) and free T4 (FT4) labs. For patients with abnormal laboratory results, pharmacists coordinated drug therapy and follow-up labs. Data were collected from November 1, 2009 to March 30, 2010. Seventy-two patients (90%) previously delinquent for thyroid function testing received relevant thyroid labs. Ten patients (12.5%) with abnormal thyroid function tests not on prior drug therapy received treatment.

[Levosimendan as a treatment for acute renal failure associated with cardiogenic shock after hip fracture].

PubMed

Hinojosa, Fabiola Quinteros; Revelo, Margarita; Salazar, Alexander; Maggi, Genaro; Schiraldi, Renato; Brogly, Nicolas; Gilsanz, Fernando

Inotropic drugs are part of the treatment of heart failure; however, inotropic treatment has been largely debated due to the increased incidence of adverse effects and increased mortality. Recently levosimendan, an inotropic positive agent, has been proved to be effective in acute heart failure, reducing the mortality and improving cardiac and renal performance. We report the case of a 75-year-old woman with history of heart and renal failure and hip fracture. Levosimendan was used in preoperative preparation as an adjuvant therapy, to improve cardiac and renal function and to allow surgery. Copyright © 2014 Sociedade Brasileira de Anestesiologia. Publicado por Elsevier Editora Ltda. All rights reserved.

Levosimendan as a treatment for acute renal failure associated with cardiogenic shock after hip fracture.

PubMed

Hinojosa, Fabiola Quinteros; Revelo, Margarita; Salazar, Alexander; Maggi, Genaro; Schiraldi, Renato; Brogly, Nicolas; Gilsanz, Fernando

Inotropic drugs are part of the treatment of heart failure; however, inotropic treatment has been largely debated due to the increased incidence of adverse effects and increased mortality. Recently levosimendan, an inotropic positive agent, has been proved to be effective in acute heart failure, reducing the mortality and improving cardiac and renal performance. We report the case of a 75-year-old woman with history of heart and renal failure and hip fracture. Levosimendan was used in preoperative preparation as an adjuvant therapy, to improve cardiac and renal function and to allow surgery. Copyright © 2014 Sociedade Brasileira de Anestesiologia. Published by Elsevier Editora Ltda. All rights reserved.

Relative adrenal insufficiency in severe congestive heart failure with preserved systolic function: a case report.

PubMed

Lovelock, Joshua D; Coslet, Sandra; Johnson, Marie; Rich, Stuart; Gomberg-Maitland, Mardi

2007-09-01

Relative adrenal insufficiency in critically ill patients is an important syndrome in septic shock. The insufficient stress response of the hypothalamic-pituitary-adrenal axis in acute illness contributes to hemodynamic instability. Treatment of this state in septic shock improves patient outcomes. In this report, we describe the case of a patient with severe diastolic dysfunction who presented in cardiogenic shock associated with relative adrenal insufficiency and had a complete recovery with corticosteroid replacement. Alteration of the hypothalamic-pituitary-adrenal axis may be more prevalent than suspected in end-stage heart failure, and the diagnosis and treatment of this syndrome may ultimately improve outcomes in a subgroup of heart failure patients.

Normalization of NAD+ Redox Balance as a Therapy for Heart Failure.

PubMed

Lee, Chi Fung; Chavez, Juan D; Garcia-Menendez, Lorena; Choi, Yongseon; Roe, Nathan D; Chiao, Ying Ann; Edgar, John S; Goo, Young Ah; Goodlett, David R; Bruce, James E; Tian, Rong

2016-09-20

Impairments of mitochondrial function in the heart are linked intricately to the development of heart failure, but there is no therapy for mitochondrial dysfunction. We assessed the reduced/oxidized ratio of nicotinamide adenine dinucleotide (NADH/NAD(+) ratio) and protein acetylation in the failing heart. Proteome and acetylome analyses were followed by docking calculation, mutagenesis, and mitochondrial calcium uptake assays to determine the functional role of specific acetylation sites. The therapeutic effects of normalizing mitochondrial protein acetylation by expanding the NAD(+) pool also were tested. Increased NADH/NAD(+) and protein hyperacetylation, previously observed in genetic models of defective mitochondrial function, also are present in human failing hearts as well as in mouse hearts with pathologic hypertrophy. Elevation of NAD(+) levels by stimulating the NAD(+) salvage pathway suppressed mitochondrial protein hyperacetylation and cardiac hypertrophy, and improved cardiac function in responses to stresses. Acetylome analysis identified a subpopulation of mitochondrial proteins that was sensitive to changes in the NADH/NAD(+) ratio. Hyperacetylation of mitochondrial malate-aspartate shuttle proteins impaired the transport and oxidation of cytosolic NADH in the mitochondria, resulting in altered cytosolic redox state and energy deficiency. Furthermore, acetylation of oligomycin-sensitive conferring protein at lysine-70 in adenosine triphosphate synthase complex promoted its interaction with cyclophilin D, and sensitized the opening of mitochondrial permeability transition pore. Both could be alleviated by normalizing the NAD(+) redox balance either genetically or pharmacologically. We show that mitochondrial protein hyperacetylation due to NAD(+) redox imbalance contributes to the pathologic remodeling of the heart via 2 distinct mechanisms. Our preclinical data demonstrate a clear benefit of normalizing NADH/NAD(+) imbalance in the failing hearts. These findings have a high translational potential as the pharmacologic strategy of increasing NAD(+) precursors are feasible in humans. © 2016 American Heart Association, Inc.

Incretin-related drug therapy in heart failure.

PubMed

Vest, Amanda R

2015-02-01

The new pharmacological classes of GLP-1 agonists and DPP-4 inhibitors are now widely used in diabetes and have been postulated as beneficial in heart failure. These proposed benefits arise from the inter-related pathophysiologies of diabetes and heart failure (diabetes increases the risk of heart failure, and heart failure can induce insulin resistance) and also in light of the dysfunctional myocardial energetics seen in heart failure. The normal heart utilizes predominantly fatty acids for energy production, but there is some evidence to suggest that increased myocardial glucose uptake may be beneficial for the failing heart. Thus, GLP-1 agonists, which stimulate glucose-dependent insulin release and enhance myocardial glucose uptake, have become a focus of investigation in both animal models and humans with heart failure. Limited pilot data for GLP-1 agonists shows potential improvements in systolic function, hemodynamics, and quality of life, forming the basis for current phase II trials.

Orexin: a Missing Link Between Sleep Disorders and Heart Failure?

PubMed

Pan, Stephen; Cabral, Carolina S; Ashley, Euan A; Perez, Marco V

2017-04-01

Sleep disorders represent a significant comorbidity in the heart failure population, and there is mounting evidence that treatment of sleep disorders such as obstructive sleep apnea can significantly improve cardiac function. However, the link between these two disorders is still not entirely clear. Recently, a novel neurohormonal pathway has been elucidated involving signaling molecules now collectively known as the orexins, which have been implicated in regulating autonomic function during sleep/wake cycles. Further evidence has mounted that orexin signaling is deeply perturbed in the setting of sleep disorders, and furthermore that abnormal orexin signaling may be implicated in the pathology of heart failure. The orexin signaling pathway represents an enticing novel target for both the treatment of sleep disorders as well as heart failure, and may represent one facet of the "missing link" between these two prevalent and often comorbid diseases.

Age-associated Pro-inflammatory Remodeling and Functional Phenotype in the Heart and Large Arteries

PubMed Central

Wang, Mingyi; Shah, Ajay M

2015-01-01

The aging population is increasing dramatically. Aging–associated stress simultaneously drives proinflammatory remodeling, involving angiotensin II and other factors, in both the heart and large arteries. The structural remodeling and functional changes that occur with aging include cardiac and vascular wall stiffening, systolic hypertension and suboptimal ventricular-arterial coupling, features that are often clinically silent and thus termed a silent syndrome. These age-related effects are the result of responses initiated by cardiovascular proinflammatory cells. Local proinflammatory signals are coupled between the heart and arteries due to common mechanical and humoral messengers within a closed circulating system. Thus, targeting proinflammatory signaling molecules would be a promising approach to improve age-associated suboptimal ventricular-arterial coupling, a major predisposing factor for the pathogenesis of clinical cardiovascular events such as heart failure. PMID:25665458

Pulmonary vasodilation in acute and chronic heart failure: empiricism and evidence.

PubMed

Guglin, Maya

2011-09-01

Pulmonary hypertension in heart failure is associated with exercise intolerance and adverse outcomes. With the availability of multiple drugs that cause pulmonary vasodilation and decrease pulmonary arterial pressure, pulmonary hypertension becomes an attractive therapeutic target. Out of several classes of medications, oral phosphodiesterase inhibitors emerge as the most promising in terms of symptomatic improvement, hemodynamic benefits, reverse cardiac remodeling, and functional capacity. Future trials will show whether the use of these drugs translates to decreased morbidity and mortality in heart failure.

A serving of blueberry (V. corymbosum) acutely improves peripheral arterial dysfunction in young smokers and non-smokers: two randomized, controlled, crossover pilot studies.

PubMed

Del Bo', Cristian; Deon, Valeria; Campolo, Jonica; Lanti, Claudia; Parolini, Marina; Porrini, Marisa; Klimis-Zacas, Dorothy; Riso, Patrizia

2017-11-15

Several studies have documented the important role of polyphenol-rich foods in the modulation of vascular remodelling and function. This study aimed to evaluate the capacity of a single portion of blueberry (V. corymbosum) to acutely improve peripheral arterial dysfunction in a group of young volunteers. Twenty-four healthy males (12 non-smokers and 12 smokers) were recruited for two different randomized, controlled, crossover pilot acute studies. In the first study, non-smokers were exposed to a control treatment (C; 300 mL of water with sugar) and a blueberry treatment (BB; 300 g of blueberry). In the second study, smokers underwent 3 different protocols: (1) - smoking treatment (S); (2) - control treatment (CS; 300 mL of water with sugar + smoking); (3) - blueberry treatment (BS; 300 g of blueberry + smoking). Each treatment (1 day long) was separated by a one week washout period. Blood pressure, peripheral arterial function (reactive hyperemia index, RHI, a marker of endothelial function) and arterial stiffness (digital augmentation index, dAix and dAix normalized by considering a heart rate of 75 bpm, dAix@75) were measured before and after each treatment. In the first study, the consumption of blueberry and control treatment acutely increased peripheral arterial function in the group of non-smokers. The improvement in RHI was higher and significantly different after blueberry treatment compared to the control treatment (54.8 ± 8.4% BB vs. 28.2 ± 8.3% C; p = 0.01). No effects were observed for markers of arterial stiffness, blood pressure and heart rate. Acute cigarette smoke significantly increased blood pressure and heart rate, while no significant effect was registered in peripheral arterial function and stiffness. The intake of blueberry and control treatment before a cigarette did not counteract the increase in blood pressure and heart rate, while it significantly improved peripheral arterial function. In particular, a significant increase was observed following BS (35.2 ± 7.5% RHI; p = 0.02) and CS treatments (34.6 ± 11.9% RHI; p = 0.02) when compared to only smoking treatment. No difference between BS and CS was detected. In conclusion, the intake of blueberry and control treatments acutely improved peripheral arterial dysfunction both in smoker and in non-smoker subjects. Further studies should be performed to confirm the results obtained and reveal the potential mechanisms of blueberry in the improvement of endothelial function.

Improved graft mesenchymal stem cell survival in ischemic heart with a hypoxia-regulated heme oxygenase-1 vector.

PubMed

Tang, Yao Liang; Tang, Yi; Zhang, Y Clare; Qian, Keping; Shen, Leping; Phillips, M Ian

2005-10-04

The goal of this study was to modify mesenchymal stem cells (MSCs) cells with a hypoxia-regulated heme oxygenase-1 (HO-1) plasmid to enhance the survival of MSCs in acute myocardial infarction (MI) heart. Although stem cells are being tested clinically for cardiac repair, graft cells die in the ischemic heart because of the effects of hypoxia/reoxygenation, inflammatory cytokines, and proapoptotic factors. Heme oxygenase-1 is a key component in inhibiting most of these factors. Mesenchymal stem cells from bone marrow were transfected with either HO-1 or LacZ plasmids. Cell apoptosis was assayed in vitro after hypoxia-reoxygen treatment. In vivo, 1 x 10(6) of male MSC(HO-1), MSC(LacZ), MSCs, or medium was injected into mouse hearts 1 h after MI (n = 16/group). Cell survival was assessed in a gender-mismatched transplantation model. Apoptosis, left ventricular remodeling, and cardiac function were tested in a gender-matched model. In the ischemic myocardium, the MSC(HO-1) group had greater expression of HO-1 and a 2-fold reduction in the number of terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate in situ nick end labeling-positive cells compared with the MSC(LacZ) group. At seven days after implantation, the survival MSC(HO-1) was five-fold greater than the MSC(LacZ) group; MSC(HO-1) also attenuated left ventricular remodeling and enhanced the functional recovery of infarcted hearts two weeks after MI. A hypoxia-regulated HO-1 vector modification of MSCs enhances the tolerance of engrafted MSCs to hypoxia-reoxygen injury in vitro and improves their viability in ischemic hearts. This demonstration is the first showing that a physiologically inducible vector expressing of HO-1 genes improves the survival of stem cells in myocardial ischemia.

Effects of propranolol treatment on left ventricular function and intracellular calcium regulation in rats with postinfarction heart failure

PubMed Central

Litwin, Sheldon E; Katz, Sarah E; Morgan, James P; Douglas, Pamela S

1999-01-01

Chronic treatment with beta-adrenergic blocking agents can improve survival in patients with heart failure. The mechanisms underlying the beneficial effects and whether these effects are generalizable to ischaemic heart failure are unresolved.We performed echocardiographic-Doppler examinations in rats (n=28) 1 and 6 weeks after myocardial infarction (MI) or sham surgery. Rats were randomized to no treatment or propranolol (500 mg/l in drinking water) after the first echocardiogram. Isometric contractions and intracellular Ca transients were recorded simultaneously in noninfarcted left ventricular (LV) papillary muscles.Untreated MI rats had significant LV dilatation (10.6±0.4* vs 8.9±0.3 mm, MI vs control), impaired systolic function (fractional shortening=11±2* vs 38±2%), and a restrictive LV diastolic filling pattern. MI rats receiving propranolol had similar LV chamber sizes (10.6±0.5 mm) and systolic function (13±2%). The propranolol treated animals had higher LV end-diastolic pressures (27±2* vs 20±3 mmHg) and a more restricted LV diastolic filling pattern (increased ratio of early to late filling velocities and more rapid E wave deceleration rate). Contractility of papillary muscles from untreated MI rats was depressed (1.6±0.3 vs 2.4±0.5 g mm−2). In addition, Ca transients were prolonged and the inotropic response to isoproterenol was blunted. Propranolol treatment did not improve force development (1.6±0.3 g mm−2) or the duration of Ca transients during isoproterenol stimulation.Chronic propranolol treatment in rats with postinfarction heart failure did not improve LV remodeling or systolic function. LV diastolic pressures and filling patterns were worsened by propranolol. Treatment also did not produce appreciable improvement in contractility, intracellular Ca regulation or beta-adrenergic responsiveness in the noninfarcted myocardium. PMID:10455325

Naturally Engineered Maturation of Cardiomyocytes

PubMed Central

Scuderi, Gaetano J.; Butcher, Jonathan

2017-01-01

Ischemic heart disease remains one of the most prominent causes of mortalities worldwide with heart transplantation being the gold-standard treatment option. However, due to the major limitations associated with heart transplants, such as an inadequate supply and heart rejection, there remains a significant clinical need for a viable cardiac regenerative therapy to restore native myocardial function. Over the course of the previous several decades, researchers have made prominent advances in the field of cardiac regeneration with the creation of in vitro human pluripotent stem cell-derived cardiomyocyte tissue engineered constructs. However, these engineered constructs exhibit a functionally immature, disorganized, fetal-like phenotype that is not equivalent physiologically to native adult cardiac tissue. Due to this major limitation, many recent studies have investigated approaches to improve pluripotent stem cell-derived cardiomyocyte maturation to close this large functionality gap between engineered and native cardiac tissue. This review integrates the natural developmental mechanisms of cardiomyocyte structural and functional maturation. The variety of ways researchers have attempted to improve cardiomyocyte maturation in vitro by mimicking natural development, known as natural engineering, is readily discussed. The main focus of this review involves the synergistic role of electrical and mechanical stimulation, extracellular matrix interactions, and non-cardiomyocyte interactions in facilitating cardiomyocyte maturation. Overall, even with these current natural engineering approaches, pluripotent stem cell-derived cardiomyocytes within three-dimensional engineered heart tissue still remain mostly within the early to late fetal stages of cardiomyocyte maturity. Therefore, although the end goal is to achieve adult phenotypic maturity, more emphasis must be placed on elucidating how the in vivo fetal microenvironment drives cardiomyocyte maturation. This information can then be utilized to develop natural engineering approaches that can emulate this fetal microenvironment and thus make prominent progress in pluripotent stem cell-derived maturity toward a more clinically relevant model for cardiac regeneration. PMID:28529939

Low-dose copper infusion into the coronary circulation induces acute heart failure in diabetic rats: New mechanism of heart disease.

PubMed

Cheung, Carlos Chun Ho; Soon, Choong Yee; Chuang, Chia-Lin; Phillips, Anthony R J; Zhang, Shaoping; Cooper, Garth J S

2015-09-01

Diabetes impairs copper (Cu) regulation, causing elevated serum Cu and urinary Cu excretion in patients with established cardiovascular disease; it also causes cardiomyopathy and chronic cardiac impairment linked to defective Cu homeostasis in rats. However, the mechanisms that link impaired Cu regulation to cardiac dysfunction in diabetes are incompletely understood. Chronic treatment with triethylenetetramine (TETA), a Cu²⁺-selective chelator, improves cardiac function in diabetic patients, and in rats with heart disease; the latter displayed ∼3-fold elevations in free Cu²⁺ in the coronary effluent when TETA was infused into their coronary arteries. To further study the nature of defective cardiac Cu regulation in diabetes, we employed an isolated-perfused, working-heart model in which we infused micromolar doses of Cu²⁺ into the coronary arteries and measured acute effects on cardiac function in diabetic and non-diabetic-control rats. Infusion of CuCl₂ solutions caused acute dose-dependent cardiac dysfunction in normal hearts. Several measures of baseline cardiac function were impaired in diabetic hearts, and these defects were exacerbated by low-micromolar Cu²⁺ infusion. The response to infused Cu²⁺ was augmented in diabetic hearts, which became defective at lower infusion levels and underwent complete pump failure (cardiac output = 0 ml/min) more often (P < 0.0001) at concentrations that only moderately impaired function of control hearts. To our knowledge, this is the first report describing the acute effects on cardiac function of pathophysiological elevations in coronary Cu²⁺. The effects of Cu²⁺ infusion occur within minutes in both control and diabetic hearts, which suggests that they are not due to remodelling. Heightened sensitivity to the acute effects of small elevations in Cu²⁺ could contribute substantively to impaired cardiac function in patients with diabetes and is thus identified as a new mechanism of heart disease. Copyright © 2015 Elsevier Inc. All rights reserved.

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

Inhibition of Let-7 microRNA attenuates myocardial remodeling and improves cardiac function postinfarction in mice

PubMed Central

Tolonen, Anna-Maria; Magga, Johanna; Szabó, Zoltán; Viitala, Pirkko; Gao, Erhe; Moilanen, Anne-Mari; Ohukainen, Pauli; Vainio, Laura; Koch, Walter J; Kerkelä, Risto; Ruskoaho, Heikki; Serpi, Raisa

2014-01-01

The members of lethal-7 (Let-7) microRNA (miRNA) family are involved in regulation of cell differentiation and reprogramming of somatic cells into induced pluripotent stem cells. However, their function in the heart is not known. In this study, we examined the effect of inhibiting the function of Let-7c miRNA on the progression of postinfarction left ventricular (LV) remodeling in mice. Myocardial infarction was induced with permanent ligation of left anterior descending coronary artery with a 4-week follow-up period. Let-7c miRNA was inhibited with a specific antagomir administered intravenously. The inhibition of Let-7c miRNA downregulated the levels of mature Let-7c miRNA and its other closely related members of Let-7 family in the heart and resulted in increased expression of pluripotency-associated genes Oct4 and Sox2 in cardiac fibroblasts in vitro and in adult mouse heart in vivo. Importantly, Let-7c inhibitor prevented the deterioration of cardiac function postinfarction, as demonstrated by preserved LV ejection fraction and elevated cardiac output. Improvement in cardiac function by Let-7c inhibitor postinfarction was associated with decreased apoptosis, reduced fibrosis, and reduction in the number of discoidin domain receptor 2–positive fibroblasts, while the number of c-kit+ cardiac stem cells and Ki-67+ proliferating cells remained unaltered. In conclusion, inhibition of Let-7 miRNA may be beneficial for the prevention of postinfarction LV remodeling and progression of heart failure. PMID:25505600

Patient-reported outcomes and associations with pleural effusion in outpatients with heart failure: an observational cohort study

PubMed Central

Gundersen, Guri H; Norekvål, Tone M; Graven, Torbjørn; Haug, Hilde H; Skjetne, Kyrre; Kleinau, Jens O; Gustad, Lise T; Dalen, Håvard

2017-01-01

Objectives We aimed to study whether patient-reported outcomes, measured by quality of life (QoL) and functional class, are sensitive to pleural effusion (PLE) in patients with heart failure (HF), and to study changes in QoL and functional class during follow-up of PLE. Methods A cohort of 62 patients from an outpatient HF clinic was included. The amount of PLE was quantified using a pocket-sized ultrasound imaging device. Self-reports of QoL and functional class were collected using the Minnesota Living with Heart Failure Questionnaire (MLHFQ) and the New York Heart Association (NYHA) functional classification. Results At baseline, 26 (42%) patients had PLE of which 19 (31%) patients had moderate to severe amounts of PLE. Patients with no to mild PLE had a lower MLHFQ score (mean 42, SD 21) compared with patients with a moderate to severe amount of PLE (mean 55, SD 24), p=0.03. For 28 patients (45%) with follow-up data, we observed a linear improvement of the MLHFQ-score (3.2, 95% CI 1.2 to 5.1) with each centimetre reduction of PLE. Correspondingly, patient-reported NYHA-class followed the same pattern as the MLHFQ-score. Conclusions Our study indicates that patient-reported outcome measures as MLHFQ may be sensitive tools to identify patients with HF at highest risk of symptomatic PLE and that treatment targeting reduction of PLE during follow-up is essential to improvement of QoL and functional capacity of outpatients with HF. Trial registration number NCT01794715; Results PMID:28320791

Abnormal cardiovascular response to exercise in hypertension: contribution of neural factors.

PubMed

Mitchell, Jere H

2017-06-01

During both dynamic (e.g., endurance) and static (e.g., strength) exercise there are exaggerated cardiovascular responses in hypertension. This includes greater increases in blood pressure, heart rate, and efferent sympathetic nerve activity than in normal controls. Two of the known neural factors that contribute to this abnormal cardiovascular response are the exercise pressor reflex (EPR) and functional sympatholysis. The EPR originates in contracting skeletal muscle and reflexly increases sympathetic efferent nerve activity to the heart and blood vessels as well as decreases parasympathetic efferent nerve activity to the heart. These changes in autonomic nerve activity cause an increase in blood pressure, heart rate, left ventricular contractility, and vasoconstriction in the arterial tree. However, arterial vessels in the contracting skeletal muscle have a markedly diminished vasoconstrictor response. The markedly diminished vasoconstriction in contracting skeletal muscle has been termed functional sympatholysis. It has been shown in hypertension that there is an enhanced EPR, including both its mechanoreflex and metaboreflex components, and an impaired functional sympatholysis. These conditions set up a positive feedback or vicious cycle situation that causes a progressively greater decrease in the blood flow to the exercising muscle. Thus these two neural mechanisms contribute significantly to the abnormal cardiovascular response to exercise in hypertension. In addition, exercise training in hypertension decreases the enhanced EPR, including both mechanoreflex and metaboreflex function, and improves the impaired functional sympatholysis. These two changes, caused by exercise training, improve the muscle blood flow to exercising muscle and cause a more normal cardiovascular response to exercise in hypertension. Copyright © 2017 the American Physiological Society.

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.

Direct Cardiac Reprogramming as a Novel Therapeutic Strategy for Treatment of Myocardial Infarction.

PubMed

Ma, Hong; Wang, Li; Liu, Jiandong; Qian, Li

2017-01-01

Direct reprogramming of fibroblasts into induced cardiomyocytes (iCMs) holds great promise as a novel therapy for the treatment of heart failure, a common and morbid disease that is usually caused by irreversible loss of functional cardiomyocytes (CMs). Recently, we and others showed that in a murine model of acute myocardial infarction, delivery of three transcription factors, Gata4, Mef2c, and Tbx5 converted endogenous cardiac fibroblasts into functional iCMs. These iCMs integrated electrically and mechanically with surrounding myocardium, resulting in a reduction in scar size and an improvement in heart function. Our findings suggest that iCM reprogramming may be a means of regenerating functional CMs in vivo for patients with heart disease. However, because relatively little is known about the factors that regulate iCM reprogramming, the applicability of iCM reprogramming is currently limited to the experimental settings in which it has been attempted. Specific hurdles include the relatively low conversion rate of iCMs and the need for reprogramming to occur in the context of acute injury. Therefore, before this treatment can become a viable therapy for human heart disease, the optimal condition for efficient iCM generation must be determined. Here, we provide a detailed protocol for both in vitro and in vivo iCM generation that has been optimized so far in our lab. We hope that this protocol will lay a foundation for future further improvement of iCM generation and provide a platform for mechanistic studies.

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

Anti-inflammatory γ- and δ-tocotrienols improve cardiovascular, liver and metabolic function in diet-induced obese rats.

PubMed

Wong, Weng-Yew; Ward, Leigh C; Fong, Chee Wai; Yap, Wei Ney; Brown, Lindsay

2017-02-01

This study tested the hypothesis that γ- and δ-tocotrienols are more effective than α-tocotrienol and α-tocopherol in attenuating the signs of diet-induced metabolic syndrome in rats. Five groups of rats were fed a corn starch-rich (C) diet containing 68 % carbohydrates as polysaccharides, while the other five groups were fed a diet (H) high in simple carbohydrates (fructose and sucrose in food, 25 % fructose in drinking water, total 68 %) and fats (beef tallow, total 24 %) for 16 weeks. Separate groups from each diet were supplemented with either α-, γ-, δ-tocotrienol or α-tocopherol (85 mg/kg/day) for the final 8 of the 16 weeks. H rats developed visceral obesity, hypertension, insulin resistance, cardiovascular remodelling and fatty liver. α-Tocopherol, α-, γ- and δ-tocotrienols reduced collagen deposition and inflammatory cell infiltration in the heart. Only γ- and δ-tocotrienols improved cardiovascular function and normalised systolic blood pressure compared to H rats. Further, δ-tocotrienol improved glucose tolerance, insulin sensitivity, lipid profile and abdominal adiposity. In the liver, these interventions reduced lipid accumulation, inflammatory infiltrates and plasma liver enzyme activities. Tocotrienols were measured in heart, liver and adipose tissue showing that chronic oral dosage delivered tocotrienols to these organs despite low or no detection of tocotrienols in plasma. In rats, δ-tocotrienol improved inflammation, heart structure and function, and liver structure and function, while γ-tocotrienol produced more modest improvements, with minimal changes with α-tocotrienol and α-tocopherol. The most important mechanism of action is likely to be reduction in organ inflammation.

Robust detection of heart beats in multimodal records using slope- and peak-sensitive band-pass filters.

PubMed

Pangerc, Urška; Jager, Franc

2015-08-01

In this work, we present the development, architecture and evaluation of a new and robust heart beat detector in multimodal records. The detector uses electrocardiogram (ECG) signals, and/or pulsatile (P) signals, such as: blood pressure, artery blood pressure and pulmonary artery pressure, if present. The base approach behind the architecture of the detector is collecting signal energy (differentiating and low-pass filtering, squaring, integrating). To calculate the detection and noise functions, simple and fast slope- and peak-sensitive band-pass digital filters were designed. By using morphological smoothing, the detection functions were further improved and noise intervals were estimated. The detector looks for possible pacemaker heart rate patterns and repairs the ECG signals and detection functions. Heart beats are detected in each of the ECG and P signals in two steps: a repetitive learning phase and a follow-up detecting phase. The detected heart beat positions from the ECG signals are merged into a single stream of detected ECG heart beat positions. The merged ECG heart beat positions and detected heart beat positions from the P signals are verified for their regularity regarding the expected heart rate. The detected heart beat positions of a P signal with the best match to the merged ECG heart beat positions are selected for mapping into the noise and no-signal intervals of the record. The overall evaluation scores in terms of average sensitivity and positive predictive values obtained on databases that are freely available on the Physionet website were as follows: the MIT-BIH Arrhythmia database (99.91%), the MGH/MF Waveform database (95.14%), the augmented training set of the follow-up phase of the PhysioNet/Computing in Cardiology Challenge 2014 (97.67%), and the Challenge test set (93.64%).

Adaptive servo-ventilation therapy for patients with chronic heart failure in a confirmatory, multicenter, randomized, controlled study.

PubMed

Momomura, Shin-Ichi; Seino, Yoshihiko; Kihara, Yasuki; Adachi, Hitoshi; Yasumura, Yoshio; Yokoyama, Hiroyuki; Wada, Hiroshi; Ise, Takayuki; Tanaka, Koichi

2015-01-01

Adaptive servo-ventilation (ASV) therapy is expected to be novel nonpharmacotherapy with hemodynamic effects on patients with chronic heart failure (CHF), but sufficient evidence has not been obtained. A 24-week, open-label, randomized, controlled study was performed to confirm the cardiac function-improving effect of ASV therapy on CHF patients. At 39 institutions, 213 outpatients with CHF, whose left ventricular ejection fraction (LVEF) was <40% and who had mild to severe symptoms [New York Heart Association (NYHA) class: ≥II], were enrolled. After excluding 8 patients, 102 and 103 underwent ASV plus guideline-directed medical therapy (GDMT) [ASV group] and GDMT only [control group], respectively. The primary endpoint was LVEF, and the secondary endpoints were HF deterioration, B-type natriuretic peptide (BNP), and clinical composite response (CCR: NYHA class+HF deterioration). LVEF and BNP improved significantly at completion against the baseline values in the 2 groups. However, no significant difference was found between these groups. HF deterioration tended to be suppressed. The ASV group showed a significant improvement in CCR corroborated by significant improvements in NYHA class and ADL against the control group. Under the present study's conditions, ASV therapy was not superior to GDMT in the cardiac function-improving effect but showed a clinical status-improving effect, thus indicating a given level of clinical benefit.

Impaired Right Ventricular-Pulmonary Arterial Coupling and Effect of Sildenafil in Heart Failure With Preserved Ejection Fraction: An Ancillary Analysis From the Phosphodiesterase-5 Inhibition to Improve Clinical Status And Exercise Capacity in Diastolic Heart Failure (RELAX) Trial.

PubMed

Hussain, Imad; Mohammed, Selma F; Forfia, Paul R; Lewis, Gregory D; Borlaug, Barry A; Gallup, Dianne S; Redfield, Margaret M

2016-04-01

Right ventricular (RV) dysfunction (RVD) is a poor prognostic factor in heart failure with preserved ejection fraction (HFpEF). The physiological perturbations associated with RVD or RV function indexed to load (RV-pulmonary arterial [PA] coupling) in HFpEF have not been defined. HFpEF patients with marked impairment in RV-PA coupling may be uniquely sensitive to sildenafil. In a subset of HFpEF patients enrolled in the Phosphodiesteas-5 Inhibition to Improve Clinical Status And Exercise Capacity in Diastolic Heart Failure (RELAX) trial, physiological variables and therapeutic effect of sildenafil were examined relative to the severity of RVD (tricuspid annular plane systolic excursion [TAPSE]) and according to impairment in RV-PA coupling (TAPSE/pulmonary artery systolic pressure) ratio. The prevalence of atrial fibrillation and diuretic use, n-terminal probrain natriuretic peptide levels, renal dysfunction, neurohumoral activation, myocardial necrosis and fibrosis biomarkers, and the severity of diastolic dysfunction all increased with severity of RVD. Peak oxygen consumption decreased and ventilatory inefficiency (VE/VCO2 slope) increased with increasing severity of RVD. Many but not all physiological derangements were more closely associated with the TAPSE/pulmonary artery systolic pressure ratio. Compared with placebo, at 24 weeks, TAPSE decreased, and peak oxygen consumption and VE/CO2 slope were unchanged with sildenafil. There was no interaction between RV-PA coupling and treatment effect, and sildenafil did not improve TAPSE, peak oxygen consumption, or VE/VCO2 in patients with pulmonary hypertension and RVD. HFpEF patients with RVD and impaired RV-PA coupling have more advanced heart failure. In RELAX patients with RVD and impaired RV-PA coupling, sildenafil did not improve RV function, exercise capacity, or ventilatory efficiency. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00763867. © 2016 American Heart Association, Inc.

Functional electrical stimulation for chronic heart failure: a meta-analysis.

PubMed

Smart, Neil A; Dieberg, Gudrun; Giallauria, Francesco

2013-07-15

We conducted a meta-analysis of randomized, controlled trials of combined electrical stimulation versus conventional exercise training or placebo control in heart failure patients. A systematic search was conducted of Medline (Ovid) (1950-September 2011), Embase.com (1974-September 2011), Cochrane Central Register of Controlled Trials and CINAHL (1981-September 2011). The search strategy included a mix of MeSH and free text terms for the key concepts heart failure, exercise training and functional electrical stimulation (FES). FES produced inferior improvements in peak VO2 when compared to cycle training: mean difference (MD) -0.32 ml.kg(-1).min(-1) (95% C.I. -0.63 to -0.02 ml.kg(-1).min(-1), p=0.04), however FES elicited superior improvements in peak VO2: MD 2.30 ml.kg(-1).min(-1) (95% C.I. 1.98 to 2.62 ml.kg(-1).min(-1), p<0.00001); and six minute walk distance to sedentary care or sham FES; MD 46.9 m (95% C.I. 22.5 to 71.3m, p=0.0002). There was no difference in change in quality of life between cycling and FES, but FES elicited significantly larger improvements in Minnesota Living with Heart Failure score than placebo or sham treatment; MD 1.15 (95% C.I. 0.69 to 1.61, p<0.00001). Moreover, the total FES intervention hours were strongly correlated with change in peak VO2, (r=0.80, p=0.02). Passive or active exercise is beneficial for patients with moderate to severe heart failure, but active cycling, or other aerobic/resistance activity is preferred in patients with heart failure who are able to exercise, and FES is the preferred modality in those unable to actively exercise. The benefits of FES may however, be smaller than those observed in conventional exercise training. Aggregate hours of electrical stimulation therapy were associated with larger improvements in cardio-respiratory fitness. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Effects of inspiratory muscle training on autonomic activity, endothelial vasodilator function, and N-terminal pro-brain natriuretic peptide levels in chronic heart failure.

PubMed

Laoutaris, Ioannis D; Dritsas, Athanasios; Brown, Margaret D; Manginas, Athanassios; Kallistratos, Manolis S; Chaidaroglou, Antigoni; Degiannis, Dimitrios; Alivizatos, Peter A; Cokkinos, Dennis V

2008-01-01

To assess the effects of inspiratory muscle training (IMT) on autonomic activity, endothelial function, and N-terminal pro-brain natriuretic peptide (NT-proBNP) levels in patients with chronic heart failure. Using age- and sex-matched controlled study, 23 patients (mean left ventricular ejection fraction 29 +/- 2%) were assigned to either a high-intensity training group (n = 14), New York Heart Association (NYHA) class II (n = 9)/III (n = 5), or a low-intensity training group (n = 9), NYHA class II (n = 6)/III (n = 3), exercising at 60% and 15% of sustained maximum inspiratory pressure (SPImax), respectively, 3 times per week for 10 weeks. Before and following IMT, patients underwent cardiopulmonary exercise testing and dyspnea evaluation on exertion. Sympathovagal balance was assessed by heart rate variability (HRV) from 24-hour electrocardiogram and endothelial function, using venous occlusion plethysmography. Serum levels of NT-proBNP were determined. High-intensity training group improved maximum inspiratory pressure (PImax, 105.4 +/- 5.3 vs 79.1 +/- 5 cm H2O, P = .001), SPImax (511 +/- 42 vs 308 +/- 28 cm H2O/sec/10, P = .001), peak oxygen consumption (19 +/- 1.2 vs 17.1 +/- 0.7 mL.kgmin, P = .01) and dyspnea (17.6 +/- 0.2 vs 18.1 +/- 0.1, P = .02). Endothelium-dependent vasodilation, HRV, and NT-proBNP levels were not altered. Low-intensity training group increased only the PImax (97.6 +/- 11.3 vs 84.2 +/- 8.7 cm H2O, P = .03). Improvement in dyspnea and exercise tolerance after IMT were not associated with changes in markers of HRV, endothelial function, and NT-proBNP in patients with mild to moderate chronic heart failure. Further studies on the effects of IMT in advanced heart failure would be worthwhile.

Assessment of sustained effects of levosimendan and dobutamine on left ventricular systolic functions by using novel tissue Doppler derived indices in patients with advanced heart failure.

PubMed

Oner, Ender; Erturk, Mehmet; Birant, Ali; Kurtar Mansıroglu, Aslı; Akturk, Ibrahim Faruk; Karakurt, Huseyin; Yalcin, Ahmet Arif; Uzun, Fatih; Somuncu, Mustafa Umut; Yildirim, Aydin

2015-01-01

Previous studies comparing levosimendan vs. dobutamine have revealed that levosimendan is better in relieving symptoms. Echocardiographic studies have been done using second measurements immediately following a dobutamine infusion or while it was still being administered. The aim of our study was assessment of sustained effects of 24 h levosimendan and dobutamine infusions on left ventricular systolic functions. A total of 61 patients with acutely decompensated heart failure with New York Heart Association (NYHA) class III or IV symptoms were randomized to receive either levosimendan or dobutamine 2:1 in an open label fashion. Before and 5 days after the initiation of infusions, functional class was assessed, N-terminal prohormone of B-type natriuretic peptide (NT-proBNP) levels and left ventricular ejection fraction (LVEF), mitral inflow peak E and A wave velocity, and E/A ratios were measured; using tissue Doppler imaging, isovolumic myocardial acceleration (IVA), peak myocardial velocity during isovolumic contraction (IVV), peak systolic velocity during ejection period (Sa), early (E') and late (A') diastolic velocities, and E'/A' and E/E' ratios were measured. The NYHA class improved in both groups, but improvements were prominent in the levosimendan group. NT-proBNP levels were significantly reduced in the levosimendan group. Improvements in LVEF and diastolic indices were significant in the levosimendan group. Tissue Doppler-derived systolic indices of IVV and IVA increased significantly in the levosimendan group. Improvements in left ventricular systolic and diastolic functions continue after a levosimendan infusion.

Sildenafil ameliorates left ventricular T-tubule remodeling in a pressure overload-induced murine heart failure model

PubMed Central

Huang, Chun-kai; Chen, Bi-yi; Guo, Ang; Chen, Rong; Zhu, Yan-qi; Kutschke, William; Hong, Jiang; Song, Long-sheng

2016-01-01

Aim: Sildenafil, a phosphodiesterase 5 (PDE5) inhibitor, has been shown to exert beneficial effects in heart failure. The purpose of this study was to test whether sildenafil suppressed transverse-tubule (T-tubule) remodeling in left ventricular (LV) failure and thereby providing the therapeutic benefits. Methods: A pressure overload-induced murine heart failure model was established in mice by thoracic aortic banding (TAB). One day after TAB, the mice received sildenafil (100 mg·kg−1·d−1, sc) or saline for 5 weeks. At the end of treatment, echocardiography was used to examine LV function. Then the intact hearts were dissected out and placed in Langendorff-perfusion chamber for in situ confocal imaging of T-tubule ultrastructure from epicardial myocytes. Results: TAB surgery resulted in heart failure accompanied by remarkable T-tubule remodeling. Sildenafil treatment significantly attenuated TAB-induced cardiac hypertrophy and congestive heart failure, improved LV contractile function, and preserved T-tubule integrity in LV cardiomyocytes. But sildenafil treatment did not significantly affect the chamber dilation. The integrity of LV T-tubule structure was correlated with cardiac hypertrophy (R2=0.74, P<0.01) and global LV function (R2=0.47, P<0.01). Conclusion: Sildenafil effectively ameliorates LV T-tubule remodeling in TAB mice, revealing a novel mechanism underlying the therapeutic benefits of sildenafil in heart failure. PMID:26972492

[CARDIOREABILITATION PECULIARITIES AND CORRECTION OF VIOLATIONS OF SISTOLIC, DIASOLIC FUNCTION AND HEART RATE VARIABILITY IN PATIENTS WITH ACUTE CORONARY SYNDROME AND CORONARY ARTERY REVASCULARIZATION].

PubMed

Shved, M; Tsuglevych, L; Kyrychok, I; Levytska, L; Boiko, T; Kitsak, Ya

2017-04-01

In patients with acute coronary syndrome (ACS) who underwent coronary arteries revascularization, violations of hemodynamics, metabolism and heart rate variability often develop in the postoperative period, therefore, the goal of the study was to establish the features of disturbances and the effectiveness of correction of left ventricular systolic and diastolic dysfunction and heart rate variability in stages of cardiorehabilitation in patients with acute coronary syndrome who underwent coronary arteries revascularization. The experimental group included 40 patients with ACS in the postoperative period who underwent balloon angioplasty and stenting of the coronary arteries (25 patients with ST-segment elevation ACS and 15 patients without ST-segment elevation ACS). The age of examined patients was 37 to 74 years, an average of 52.6±6.7 years. The control group consisted of 20 patients, comparable in age and clinico-laboratory manifestations of ACS, who underwent drug treatment with direct anticoagulants, double antiplatelet therapy, β-blockers, ACE inhibitors and statins. Clinical efficacy of cardiorespiratory process in patients of both groups was assessed by the dynamics of general clinical symptoms and parameters of natriuretic propeptide, systolic and diastolic function of the left ventricle and heart rate variability. In the initial state, clinical and laboratory-instrumental signs of myocardial ischemia disappear in patients with ACS undergoing surgical revascularization of the coronary arteries, but clinical and subclinical manifestations of heart failure were diagnosed. The use of the accelerated program of cardiac rehabilitation already during the first month of studies leads to a decreasement of the signs of systolic and diastolic dysfunction, the level of NT-proBNP and improve in the variability of the heart rhythm wich significantly improves the life quality of patients with ACS. To monitor the effectiveness and safety of cardiac rehabilitation in patients with ACS who underwent coronary arteries revascularization, in addition to the generally accepted methods (determination of heart rate, blood pressure, a 6-minute test), it is advisable to diagnose the subclinical stage of heart failure by determining the level of NT-proBNP, Doppler echocardiogram, parameters of the left ventricular systolic and diastolic function and heart rate variability.

Variability in Cadence During Forced Cycling Predicts Motor Improvement in Individuals With Parkinson’s Disease

PubMed Central

Ridgel, Angela L.; Abdar, Hassan Mohammadi; Alberts, Jay L.; Discenzo, Fred M.; Loparo, Kenneth A.

2014-01-01

Variability in severity and progression of Parkinson’s disease symptoms makes it challenging to design therapy interventions that provide maximal benefit. Previous studies showed that forced cycling, at greater pedaling rates, results in greater improvements in motor function than voluntary cycling. The precise mechanism for differences in function following exercise is unknown. We examined the complexity of biomechanical and physiological features of forced and voluntary cycling and correlated these features to improvements in motor function as measured by the Unified Parkinson’s Disease Rating Scale (UPDRS). Heart rate, cadence, and power were analyzed using entropy signal processing techniques. Pattern variability in heart rate and power were greater in the voluntary group when compared to forced group. In contrast, variability in cadence was higher during forced cycling. UPDRS Motor III scores predicted from the pattern variability data were highly correlated to measured scores in the forced group. This study shows how time series analysis methods of biomechanical and physiological parameters of exercise can be used to predict improvements in motor function. This knowledge will be important in the development of optimal exercise-based rehabilitation programs for Parkinson’s disease. PMID:23144045

The Effectiveness of Aerobic Exercise in Improving Peripheral Nerve Functions in Type 2 Diabetes Mellitus: An Evidence Based Case Report.

PubMed

Mirtha, Listya Tresnanti; Permatahati, Viandini

2018-01-01

peripheral neuropathy is known as one of most common complication in diabetes mellitus type 2 patient. This complication is caused by uncontrolled condition of blood glucose level in long periode. Regular physical activity in moderate to high intensity is beneficial in management of diabetes mellitus. This report aimed to know the effectiveness of aerobic exercise in causing improved peripheral functions in type 2 diabetes mellitus. literature searching using several related keywords in Medline®, Pubmed®, and Cochrane library, following inclusion and exclusion criteria. Dixit et al suggested that a heart rate intensity of 40-60% aerobic exercise of 30-45 min duration per session for eight weeks suggest an important impact in controlling diabetic peripheral neuropathy. Kluding PM et al suggested that significantly improved selected measures of peripheral nerve function ("worst" pain levels and MNSI score), glycemic control (HbA1c), and resting heart rate. the studies showed significant benefit of aerobic exercise, despite the short duration of exercise being used as intervention towards improvement in peripheral nerve function. However, further studies with large samples and longer duration of intervention are needed to confirm the finding.

Self-care confidence may be the key: A cross-sectional study on the association between cognition and self-care behaviors in adults with heart failure.

PubMed

Vellone, Ercole; Fida, Roberta; D'Agostino, Fabio; Mottola, Antonella; Juarez-Vela, Raul; Alvaro, Rosaria; Riegel, Barbara

2015-11-01

Self-care, a key element of heart failure care, is challenging for patients with impaired cognition. Mechanisms through which cognitive impairment affects self-care are not currently well defined but evidence from other patient populations suggests that self-efficacy, or task-specific confidence, mediates the relationship between cognitive functioning and patient behaviors such as self-care. The aim of this study was to test the mediating role of self-care confidence in the relationship between cognition and self-care behaviors. A secondary analysis of data from a cross-sectional study. Outpatient heart failure clinics in 28 Italian provinces. 628 Italian heart failure patients. We used the Self-Care of Heart Failure Index v.6.2 to measure self-care maintenance, self-care management, and self-care confidence. Cognition was assessed with the Mini Mental State Examination. Structural equation modeling was used to analyze the data. Participants were 73 years old on average (SD=11), mostly (58%) male and mostly (77%) in New York Heart Association functional classes II and III. The mediation model showed excellent fit (comparative fit index=1.0; root mean square error of approximation=0.02): Self-care confidence totally mediated the relationship between cognition and self-care maintenance and management. Cognition affects self-care behaviors indirectly, through self-care confidence. Interventions aimed at improving self-care confidence may improve self-care, even in heart failure patients with impaired cognition. Copyright © 2015 Elsevier Ltd. All rights reserved.

Long-term outcomes and management of the heart transplant recipient.

PubMed

McCartney, Sharon L; Patel, Chetan; Del Rio, J Mauricio

2017-06-01

Cardiac transplantation remains the gold standard in the treatment of advanced heart failure. With advances in immunosuppression, long-term outcomes continue to improve despite older and higher risk recipients. The median survival of the adult after heart transplantation is currently 10.7 years. While early graft failure and multiorgan system dysfunction are the most important causes of early mortality, malignancy, rejection, infection, and cardiac allograft vasculopathy contribute to late mortality. Chronic renal dysfunction is common after heart transplantation and occurs in up to 68% of patients by year 10, with 6.2% of patients requiring dialysis and 3.7% undergoing renal transplant. Functional outcomes after heart transplantation remain an area for improvement, with only 26% of patients working at 1-year post-transplantation, and are likely related to the high incidence of depression after cardiac transplantation. Areas of future research include understanding and managing primary graft dysfunction and reducing immunosuppression-related complications. Copyright © 2017 Elsevier Ltd. All rights reserved.

Choosing Between MRI and CT Imaging in the Adult with Congenital Heart Disease.

PubMed

Bonnichsen, Crystal; Ammash, Naser

2016-05-01

Improvements in the outcomes of surgical and catheter-based interventions and medical therapy have led to a growing population of adult patients with congenital heart disease. Adult patients with previously undiagnosed congenital heart disease or those previously palliated or repaired may have challenging echocardiographic examinations. Understanding the distinct anatomic and hemodynamic features of the congenital anomaly and quantifying ventricular function and valvular dysfunction plays an important role in the management of these patients. Rapid advances in imaging technology with magnetic resonance imaging (MRI) and computed tomography angiography (CTA) allow for improved visualization of complex cardiac anatomy in the evaluation of this unique patient population. Although echocardiography remains the most widely used imaging tool to evaluate congenital heart disease, alternative and, at times, complimentary imaging modalities should be considered. When caring for adults with congenital heart disease, it is important to choose the proper imaging study that can answer the clinical question with the highest quality images, lowest risk to the patient, and in a cost-efficient manner.

Atrial fibrillation driver mechanisms: Insight from the isolated human heart.

PubMed

Csepe, Thomas A; Hansen, Brian J; Fedorov, Vadim V

2017-01-01

Although there have been great technological advances in the treatment of atrial fibrillation (AF), current therapies remain limited due to a narrow understanding of AF mechanisms in the human heart. This review will highlight our recent studies on explanted human hearts where we developed and employed a novel functional-structural mapping approach by integrating high-resolution simultaneous endo-epicardial and panoramic optical mapping with 3D gadolinium-enhanced MRI to define the spatiotemporal characteristics of AF drivers and their structural substrates. The results allow us to postulate that the primary mechanism of AF maintenance in human hearts is a limited number of localized intramural microanatomic reentrant AF drivers anchored to heart-specific 3D fibrotically insulated myobundle tracks, which may remain hidden to clinical single-surface electrode mapping. We suggest that ex vivo human heart studies, by using an integrated 3D functional and structural mapping approach, will help to reveal defining features of AF drivers as well as validate and improve clinical approaches to detect and target these AF drivers in patients with cardiac diseases. Copyright © 2016 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.

HeartWare HVAD for Biventricular Support in Children and Adolescents: The Stanford Experience.

PubMed

Stein, Mary Lyn; Yeh, Justin; Reinhartz, Olaf; Rosenthal, David N; Kaufman, Beth D; Almond, Chris S; Hollander, Seth A; Maeda, Katsuhide

2016-01-01

Despite increasing use of mechanical circulatory support in children, experience with biventricular device implantation remains limited. We describe our experience using the HeartWare HVAD to provide biventricular support to three patients and compare these patients with five patients supported with HeartWare left ventricular assist device (LVAD). At the end of the study period, all three biventricular assist device (BiVAD) patients had been transplanted and were alive. LVAD patients were out of bed and ambulating a median of 10.5 days postimplantation. The BiVAD patients were out of bed a median of 31 days postimplantation. Pediatric patients with both left ventricular and biventricular heart failure can be successfully bridged to transplantation with the HeartWare HVAD. Rapid improvement in functional status following HVAD implantation for isolated left ventricular support is seen. Patients supported with BiVAD also demonstrate functional recovery, albeit more modestly. In the absence of infection, systemic inflammatory response raises concern for inadequate support.

Organ dysfunction, injury and failure in acute heart failure: from pathophysiology to diagnosis and management. A review on behalf of the Acute Heart Failure Committee of the Heart Failure Association (HFA) of the European Society of Cardiology (ESC).

PubMed

Harjola, Veli-Pekka; Mullens, Wilfried; Banaszewski, Marek; Bauersachs, Johann; Brunner-La Rocca, Hans-Peter; Chioncel, Ovidiu; Collins, Sean P; Doehner, Wolfram; Filippatos, Gerasimos S; Flammer, Andreas J; Fuhrmann, Valentin; Lainscak, Mitja; Lassus, Johan; Legrand, Matthieu; Masip, Josep; Mueller, Christian; Papp, Zoltán; Parissis, John; Platz, Elke; Rudiger, Alain; Ruschitzka, Frank; Schäfer, Andreas; Seferovic, Petar M; Skouri, Hadi; Yilmaz, Mehmet Birhan; Mebazaa, Alexandre

2017-07-01

Organ injury and impairment are commonly observed in patients with acute heart failure (AHF), and congestion is an essential pathophysiological mechanism of impaired organ function. Congestion is the predominant clinical profile in most patients with AHF; a smaller proportion presents with peripheral hypoperfusion or cardiogenic shock. Hypoperfusion further deteriorates organ function. The injury and dysfunction of target organs (i.e. heart, lungs, kidneys, liver, intestine, brain) in the setting of AHF are associated with increased risk for mortality. Improvement in organ function after decongestive therapies has been associated with a lower risk for post-discharge mortality. Thus, the prevention and correction of organ dysfunction represent a therapeutic target of interest in AHF and should be evaluated in clinical trials. Treatment strategies that specifically prevent, reduce or reverse organ dysfunction remain to be identified and evaluated to determine if such interventions impact mortality, morbidity and patient-centred outcomes. This paper reflects current understanding among experts of the presentation and management of organ impairment in AHF and suggests priorities for future research to advance the field. © 2017 The Authors. European Journal of Heart Failure © 2017 European Society of Cardiology.

Heart regeneration.

PubMed

Breckwoldt, Kaja; Weinberger, Florian; Eschenhagen, Thomas

2016-07-01

Regenerating an injured heart holds great promise for millions of patients suffering from heart diseases. Since the human heart has very limited regenerative capacity, this is a challenging task. Numerous strategies aiming to improve heart function have been developed. In this review we focus on approaches intending to replace damaged heart muscle by new cardiomyocytes. Different strategies for the production of cardiomyocytes from human embryonic stem cells or human induced pluripotent stem cells, by direct reprogramming and induction of cardiomyocyte proliferation are discussed regarding their therapeutic potential and respective advantages and disadvantages. Furthermore, different methods for the transplantation of pluripotent stem cell-derived cardiomyocytes are described and their clinical perspectives are discussed. This article is part of a Special Issue entitled: Cardiomyocyte Biology: Integration of Developmental and Environmental Cues in the Heart edited by Marcus Schaub and Hughes Abriel. Copyright © 2015 Elsevier B.V. All rights reserved.

Benefit-Risk Assessment of Crataegus Extract WS 1442: An Evidence-Based Review.

PubMed

Holubarsch, Christian J F; Colucci, Wilson S; Eha, Jaan

2018-02-01

Preparations from Crataegus (hawthorn) have a long history in the treatment of heart failure. WS 1442 is a dry extract from hawthorn leaves with flowers (4-6.6:1), extraction solvent of ethanol 45% (w/w), adjusted to 17.3-20.1% of oligomeric procyanidins. Nonclinical studies show that WS 1442 has positive inotropic and antiarrhythmic properties and protects the myocardium from ischemic damage, reperfusion injury, and hypertension-related hypertrophy, improves endothelial functions such as NO synthesis, and delays endothelial senescence. Randomized, controlled trials in patients with heart failure have demonstrated that the herbal medicinal product increases functional capacity, alleviates disabling symptoms, and improves health-related quality of life, all of which have become important targets of heart failure therapy according to current disease management guidelines. Clinical trials (including a 2-year mortality study with polypharmacy and > 1300 patients exposed) and post-marketing surveillance studies have shown that WS 1442 has a very favorable safety profile both as monotherapy and as add-on therapy, where no drug interactions have been observed. No specific adverse reactions to WS 1442 are known to date. WS 1442 may thus help to close the therapeutic gap between systolic and diastolic heart failure for which evidence of efficacy for other cardioactive drugs is sparse. Scientific evidence shows that WS 1442 is safe and has a beneficial effect in patients with heart failure corresponding to New York Heart Association classes II or III. The benefit-risk assessment for WS 1442 is therefore positive.

[Obesity and the prognosis of heart failure: the obesity paradox, myth or reality?].

PubMed

Bounhoure, Jean-Paul; Galinier, Michel; Roncalli, Jerôme; Massabuau, Pierre

2014-01-01

Obesity has now reached epidemic proportions worldwide. Obesity is associated with numerous comorbidities, including hypertension, lipid disorders and type II diabetes, and is also a major cause of cardiovascular disease, coronary disease, heart failure, atrial fibrillation, and sudden death. Obesity is the main cause of heart failure in respectively 11% and 14% of cases in men and women. The Framingham study showed that, after correction for other risk factors, each point increase in the body mass index raises the risk of heart failure by 5% in men and 7% in women. Obesity increases the heart workload, causes left ventricular hypertrophy, and impairs both diastolic and systolic function. The most common form of heart failure is diastolic dysfunction, and heart failure in obese individuals is associated with preserved systolic function. Despite these comorbidities and the severity of heart failure, numerous studies have revealed an "obesity paradox" in which overweight and obese individuals with heart failure appear to have a better prognosis than non overweight subjects. This review summarizes the adverse cardiac effects of this nutritional disease, the results of some studies supporting the obesity paradox, the better survival rate of obese patients with heart failure. Potential explanations for these surprising data include the possibility that a number of obese patients may simply not have heart failure, as well as methodological bias, and protective effects of adipose tissue. Further studies of large populations are needed to determine how obesity may improve the prognosis of heart failure.

Effect of granulocyte colony stimulating EPC on cardiac function and myocardial energy expenditure in patients with heart failure after myocardial infarction.

PubMed

Zhao, Zilin; Luo, Jianchun; Ma, Lixian; Luo, Xia; Huang, Liangyan

2015-01-01

To study the changes of cardiac function and myocardial energy expenditure following treatment with granulocyte colony stimulating factor (G-CSF) in patients with heart failure after myocardial infarction. Thirty-eight patients with heart failure after myocardial infarction were randomized into G-CSF treatment group and control group. All the patients received conventional treatment (medication and interventional therapy), and the patients in treatment group were given additional G-CSF (600 μg/day) for 7 consecutive days. The plasma level of brain-type natriuretic peptide (BNP) and the number of endothelial progenitor cells (EPC) in the peripheral blood were detected before and at 7 days and 4 months after the treatment. The cardiac functions (LVEF, FS, LVIDs, PWTs, EDV, SV, ET) was evaluated by ultrasonic imaging before and at 2 weeks and 4 months after the treatment. The MEE and circumferential end-systolic wall stress (cESS) were calculated by correlation formula. The number of EPC was significantly higher in the treatment group than in the control group after the treatment especially at 7 days (P<0.01). In both groups, BNP level was lowered significantly after the treatment to recover the normal level (P<0.01). The cardiac functions and myocardial energy expenditure were improved in all the patients at 2 weeks and 4 months after the treatment, and the improvement was more obvious in the treatment group (P<0.05), especially in terms of the MEE and cESS was significantly lowered in the treatment group than in the control group after the treatment at 2 weeks (P<0.01), the LVEF and FS was significantly increased in the treatment group than in the control group after the treatment at 4 months (P<0.01). EPC mobilization by G-CSF can effectively improve the cardiac functions, lessen ventricular remodeling and reduce myocardial energy expenditure in patients with heart failure after myocardial infarction.

Nitroxyl Improves Cellular Heart Function by Directly Enhancing Cardiac Sarcoplasmic Reticulum Ca2+ Cycling

PubMed Central

Tocchetti, Carlo G.; Wang, Wang; Froehlich, Jeffrey P.; Huke, Sabine; Aon, Miguel A.; Wilson, Gerald M.; Benedetto, Giulietta Di; O’Rourke, Brian; Gao, Wei Dong; Wink, David A.; Toscano, John P.; Zaccolo, Manuela; Bers, Donald M.; Valdivia, Hector H.; Cheng, Heping; Kass, David A.; Paolocci, Nazareno

2009-01-01

Heart failure remains a leading cause of morbidity and mortality worldwide. Although depressed pump function is common, development of effective therapies to stimulate contraction has proven difficult. This is thought to be attributable to their frequent reliance on cAMP stimulation to increase activator Ca2+. A potential alternative is nitroxyl (HNO), the 1-electron reduction product of nitric oxide (NO) that improves contraction and relaxation in normal and failing hearts in vivo. The mechanism for myocyte effects remains unknown. Here, we show that this activity results from a direct interaction of HNO with the sarcoplasmic reticulum Ca2+ pump and the ryanodine receptor 2, leading to increased Ca2+ uptake and release from the sarcoplasmic reticulum. HNO increases the open probability of isolated ryanodine-sensitive Ca2+-release channels and accelerates Ca2+ reuptake into isolated sarcoplasmic reticulum by stimulating ATP-dependent Ca2+ transport. Contraction improves with no net rise in diastolic calcium. These changes are not induced by NO, are fully reversible by addition of reducing agents (redox sensitive), and independent of both cAMP/protein kinase A and cGMP/protein kinase G signaling. Rather, the data support HNO/thiolate interactions that enhance the activity of intracellular Ca2+ cycling proteins. These findings suggest HNO donors are attractive candidates for the pharmacological treatment of heart failure. PMID:17138943

Biomechanical Behavior of Bioprosthetic Heart Valve Heterograft Tissues: Characterization, Simulation, and Performance

PubMed Central

Soares, Joao S.; Feaver, Kristen R.; Zhang, Will; Kamensky, David; Aggarwal, Ankush; Sacks, Michael S.

2017-01-01

The use of replacement heart valves continues to grow due to the increased prevalence of valvular heart disease resulting from an ageing population. Since bioprosthetic heart valves (BHVs) continue to be the preferred replacement valve, there continues to be a strong need to develop better and more reliable BHVs through and improved the general understanding of BHV failure mechanisms. The major technological hurdle for the lifespan of the BHV implant continues to be the durability of the constituent leaflet biomaterials, which if improved can lead to substantial clinical impact. In order to develop improved solutions for BHV biomaterials, it is critical to have a better understanding of the inherent biomechanical behaviors of the leaflet biomaterials, including chemical treatment technologies, the impact of repetitive mechanical loading, and the inherent failure modes. This review seeks to provide a comprehensive overview of these issues, with a focus on developing insight on the mechanisms of BHV function and failure. Additionally, this review provides a detailed summary of the computational biomechanical simulations that have been used to inform and develop a higher level of understanding of BHV tissues and their failure modes. Collectively, this information should serve as a tool not only to infer reliable and dependable prosthesis function, but also to instigate and facilitate the design of future bioprosthetic valves and clinically impact cardiology. PMID:27507280

Systemic pretreatment with dimethyloxalylglycine increases myocardial HIF-1α and VEGF production and improves functional recovery after acute ischemia/reperfusion.

PubMed

Poynter, Jeffrey A; Manukyan, Mariuxi C; Wang, Yue; Brewster, Benjamin D; Herrmann, Jeremy L; Weil, Brent R; Abarbanell, Aaron M; Meldrum, Daniel R

2011-08-01

Stem cells protect the heart from ischemic damage in part by the release of cytoprotective growth factors, particularly vascular endothelial growth factor (VEGF). Production of VEGF is regulated in part by levels of the transcription factor hypoxia inducible factor 1-α (HIF-1α). Dimethyloxalylglycine (DMOG) prevents the deactivation of HIF-1α and increases VEGF production. However, the effects of systemic DMOG treatment on myocardial tolerance for ischemia are unknown. We hypothesized that systemic pretreatment with DMOG would improve myocardial ischemic tolerance. To study this hypothesis, adult male rats were randomly given an intraperitoneal injection of DMOG (40 mg/kg in 1 mL saline, n = 5) or saline (1 mL, n = 6) 24 h before cardiectomy and isolated heart perfusion. All hearts were subjected to 15 min equilibration, 25 min ischemia and 40 min reperfusion. Myocardial function was continuously monitored. Following reperfusion, myocardial homogenates were analyzed for HIF-1α and VEGF production. We observed that hearts in the DMOG group exhibited greater recovery of left ventricular developed pressure LVDP, +dP/dt and -dP/dt. Myocardial HIF-1α and VEGF levels were increased by DMOG therapy. In conclusion, systemic pretreatment with DMOG augments post-ischemic myocardial functional recovery through increased HIF-1α levels and greater VEGF production. Copyright © 2011 Mosby, Inc. All rights reserved.

Long-term low dose dietary resveratrol supplement reduces cardiovascular structural and functional deterioration in chronic heart failure in rats.

PubMed

Ahmet, Ismayil; Tae, Hyun-Jin; Lakatta, Edward G; Talan, Mark

2017-03-01

A short-term exposure to resveratrol at high dosages exerts a remarkable cardioprotective effect. Whether a long-term exposure to resveratrol at low dosages that can be obtained through consumption of a resveratrol-rich diet is beneficial to heart diseases is unknown. We tested the effects of a resveratrol-enriched diet on cardiovascular remodeling of chronic heart failure (CHF) in rats resulting from permanent ligation of left coronary artery. Two weeks after surgery, rats were started on either a resveratrol-enriched (R; 5 mg/kg per day; n = 23) or normal (Control; n = 23) diet for next 10 months. Serial echocardiography in Control showed a significant decline in LV ejection fraction, increases in LV end-systolic and end-diastolic volumes, and expansion in myocardial infarct from pre-treatment values. In R, compared with Control, there were substantial improvements in those parameters. End-point LV pressure-volume loop analysis showed a significantly improved LV systolic function and AV-coupling, an index of energy transfer efficacy between the heart and aortic tree, in R compared with Control (p < 0.05). Aortic pulse wave velocity, a measure of arterial stiffness, was significantly lower in R (389 ± 15 cm/s; p < 0.05) compared with Control (489 ± 38 cm/s). These results demonstrated that long-term dietary resveratrol supplement reduces cardiovascular structural and functional deterioration in CHF.

An exploratory study on the efficacy and safety of a BCAA preparation used in combination with cardiac rehabilitation for patients with chronic heart failure.

PubMed

Takata, Munenori; Amiya, Eisuke; Watanabe, Masafumi; Hosoya, Yumiko; Nakayama, Atsuko; Fujiwara, Takayuki; Taya, Masanobu; Oguri, Gaku; Hyodo, Kanako; Takayama, Naoko; Takano, Nami; Mashiko, Tomoe; Uemura, Yukari; Komuro, Issei

2017-07-27

Sarcopenia is generally complicated with patients with chronic heart failure (CHF) and its presence negatively affects the course of heart failure, however effective nutritional intervention had not been elucidated yet. The primary objective of this study is to explore whether the addition of a branched-chain amino acid (BCAA) preparation for cardiac rehabilitation (CR) of patients with CHF further improves cardiopulmonary functions, skeletal muscle functions, and metabolism in comparison with conventional CR. This is a randomized, parallel-group comparative study. The elderly patients that were participated in CR and complicated with left ventricular systolic or diastolic dysfunction are randomized into two groups, CR + BCAA and CR. 20 weeks later, the second randomization is performed, which divide subjects into two groups with and without BCAA intervention without CR. Primary outcome measure is the rate of change of the anaerobic threshold workload from baseline to post-intervention. Secondary outcome include parameters of exercise capacity, cardiac function and psychological status. In the current study the effect of a promising new intervention, BCAA, will be assessed to determine whether its addition to CR improve exercise capacity in patients with heart failure, who are generally complicated with sarcopenia. This clinical trial was registered with the University Hospital Medical Information Network-Clinical Trials Registry (UMIN-CTR; JPRN-UMIN R000022440 ).

Zebrafish heart failure models: opportunities and challenges.

PubMed

Shi, Xingjuan; Chen, Ru; Zhang, Yu; Yun, Junghwa; Brand-Arzamendi, Koroboshka; Liu, Xiangdong; Wen, Xiao-Yan

2018-05-03

Heart failure is a complex pathophysiological syndrome of pumping functional failure that results from injury, infection or toxin-induced damage on the myocardium, as well as genetic influence. Gene mutations associated with cardiomyopathies can lead to various pathologies of heart failure. In recent years, zebrafish, Danio rerio, has emerged as an excellent model to study human cardiovascular diseases such as congenital heart defects, cardiomyopathy, and preclinical development of drugs targeting these diseases. In this review, we will first summarize zebrafish genetic models of heart failure arose from cardiomyopathy, which is caused by mutations in sarcomere, calcium or mitochondrial-associated genes. Moreover, we outline zebrafish heart failure models triggered by chemical compounds. Elucidation of these models will improve the understanding of the mechanism of pathogenesis and provide potential targets for novel therapies.

Construct validity of the Heart Failure Screening Tool (Heart-FaST) to identify heart failure patients at risk of poor self-care: Rasch analysis.

PubMed

Reynolds, Nicholas A; Ski, Chantal F; McEvedy, Samantha M; Thompson, David R; Cameron, Jan

2018-02-14

The aim of this study was to psychometrically evaluate the Heart Failure Screening Tool (Heart-FaST) via: (1) examination of internal construct validity; (2) testing of scale function in accordance with design; and (3) recommendation for change/s, if items are not well adjusted, to improve psychometric credential. Self-care is vital to the management of heart failure. The Heart-FaST may provide a prospective assessment of risk, regarding the likelihood that patients with heart failure will engage in self-care. Psychometric validation of the Heart-FaST using Rasch analysis. The Heart-FaST was administered to 135 patients (median age = 68, IQR = 59-78 years; 105 males) enrolled in a multidisciplinary heart failure management program. The Heart-FaST is a nurse-administered tool for screening patients with HF at risk of poor self-care. A Rasch analysis of responses was conducted which tested data against Rasch model expectations, including whether items serve as unbiased, non-redundant indicators of risk and measure a single construct and that rating scales operate as intended. The results showed that data met Rasch model expectations after rescoring or deleting items due to poor discrimination, disordered thresholds, differential item functioning, or response dependence. There was no evidence of multidimensionality which supports the use of total scores from Heart-FaST as indicators of risk. Aggregate scores from this modified screening tool rank heart failure patients according to their "risk of poor self-care" demonstrating that the Heart-FaST items constitute a meaningful scale to identify heart failure patients at risk of poor engagement in heart failure self-care. © 2018 John Wiley & Sons Ltd.

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.

Heart failure: when form fails to follow function.

PubMed

Katz, Arnold M; Rolett, Ellis L

2016-02-01

Cardiac performance is normally determined by architectural, cellular, and molecular structures that determine the heart's form, and by physiological and biochemical mechanisms that regulate the function of these structures. Impaired adaptation of form to function in failing hearts contributes to two syndromes initially called systolic heart failure (SHF) and diastolic heart failure (DHF). In SHF, characterized by high end-diastolic volume (EDV), the left ventricle (LV) cannot eject a normal stroke volume (SV); in DHF, with normal or low EDV, the LV cannot accept a normal venous return. These syndromes are now generally defined in terms of ejection fraction (EF): SHF became 'heart failure with reduced ejection fraction' (HFrEF) while DHF became 'heart failure with normal or preserved ejection fraction' (HFnEF or HFpEF). However, EF is a chimeric index because it is the ratio between SV--which measures function, and EDV--which measures form. In SHF the LV dilates when sarcomere addition in series increases cardiac myocyte length, whereas sarcomere addition in parallel can cause concentric hypertrophy in DHF by increasing myocyte thickness. Although dilatation in SHF allows the LV to accept a greater venous return, it increases the energy cost of ejection and initiates a vicious cycle that contributes to progressive dilatation. In contrast, concentric hypertrophy in DHF facilitates ejection but impairs filling and can cause heart muscle to deteriorate. Differences in the molecular signals that initiate dilatation and concentric hypertrophy can explain why many drugs that improve prognosis in SHF have little if any benefit in DHF. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.

Reversal of subcellular remodelling by losartan in heart failure due to myocardial infarction

PubMed Central

Babick, Andrea; Chapman, Donald; Zieroth, Shelley; Elimban, Vijayan; Dhalla, Naranjan S

2012-01-01

This study tested the reversal of subcellular remodelling in heart failure due to myocardial infarction (MI) upon treatment with losartan, an angiotensin II receptor antagonist. Twelve weeks after inducing MI, rats were treated with or without losartan (20 mg/kg; daily) for 8 weeks and assessed for cardiac function, cardiac remodelling, subcellular alterations and plasma catecholamines. Cardiac hypertrophy and lung congestion in 20 weeks MI-induced heart failure were associated with increases in plasma catecholamine levels. Haemodynamic examination revealed depressed cardiac function, whereas echocardiographic analysis showed impaired cardiac performance and marked increases in left ventricle wall thickness and chamber dilatation at 20 weeks of inducing MI. These changes in cardiac function, cardiac remodelling and plasma dopamine levels in heart failure were partially or fully reversed by losartan. Sarcoplasmic reticular (SR) Ca2+-pump activity and protein expression, protein and gene expression for phospholamban, as well as myofibrillar (MF) Ca2+-stimulated ATPase activity and α-myosin heavy chain mRNA levels were depressed, whereas β-myosin heavy chain expression was increased in failing hearts; these alterations were partially reversed by losartan. Although SR Ca2+-release activity and mRNA levels for SR Ca2+-pump were decreased in failing heart, these changes were not reversed upon losartan treatment; no changes in mRNA levels for SR Ca2+-release channels were observed in untreated or treated heart failure. These results suggest that the partial improvement of cardiac performance in heart failure due to MI by losartan treatment is associated with partial reversal of cardiac remodelling as well as partial recovery of SR and MF functions. PMID:22947202

Use of extracorporeal life support in patients with congenital heart disease.

PubMed

Delius, R E; Bove, E L; Meliones, J N; Custer, J R; Moler, F W; Crowley, D; Amirikia, A; Behrendt, D M; Bartlett, R H

1992-09-01

To review a large experience with extracorporeal life support in patients with congenital heart disease. To determine the major causes of mortality and morbidity in order to improve the results of using this technology in this patient population. Retrospective chart review. Twenty-five patients between the ages of 1 day and 8 yrs. These patients had congenital heart disease and were clinically felt to be at high risk for death caused by cardiac failure or by respiratory failure complicated by congenital heart disease. All patients in this report were placed on extracorporeal life support to allow recovery of myocardial or pulmonary function. Of these 25 patients, 52% were weaned from bypass support and 40% survived to discharge. Patients who were not weaned from extracorporeal life support characteristically suffered from irreversible neurologic injury, multiple organ failure, or bleeding complications. Only one patient died of irreversible cardiac failure. Extracorporeal life support can be useful in supporting patients with congenital heart disease with life-threatening cardiac or pulmonary failure. Improvements in limiting neurologic and bleeding complications may lead to improvements in the use of extracorporeal life support for this indication. However, prospective, randomized studies are needed to appreciate the role of extracorporeal life support in these patients.

MELAS syndrome and cardiomyopathy: linking mitochondrial function to heart failure pathogenesis.

PubMed

Hsu, Ying-Han R; Yogasundaram, Haran; Parajuli, Nirmal; Valtuille, Lucas; Sergi, Consolato; Oudit, Gavin Y

2016-01-01

Heart failure remains an important clinical burden, and mitochondrial dysfunction plays a key role in its pathogenesis. The heart has a high metabolic demand, and mitochondrial function is a key determinant of myocardial performance. In mitochondrial disorders, hypertrophic remodeling is the early pattern of cardiomyopathy with progression to dilated cardiomyopathy, conduction defects and ventricular pre-excitation occurring in a significant proportion of patients. Cardiac dysfunction occurs in approximately a third of patients with mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS) syndrome, a stereotypical example of a mitochondrial disorder leading to a cardiomyopathy. We performed unique comparative ultrastructural and gene expression in a MELAS heart compared with non-failing controls. Our results showed a remarkable increase in mitochondrial inclusions and increased abnormal mitochondria in MELAS cardiomyopathy coupled with variable sarcomere thickening, heterogeneous distribution of affected cardiomyocytes and a greater elevation in the expression of disease markers. Investigation and management of patients with mitochondrial cardiomyopathy should follow the well-described contemporary heart failure clinical practice guidelines and include an important role of medical and device therapies. Directed metabolic therapy is lacking, but current research strategies are dedicated toward improving mitochondrial function in patients with mitochondrial disorders.

A patient with heart failure and worsening kidney function.

PubMed

Sarnak, Mark J

2014-10-07

There is high prevalence of CKD, defined by reduced GFR, in patients with heart failure. Reduced kidney function is associated with increased morbidity and mortality in this patient population. The cardiorenal syndrome (CRS) involves a bidirectional relationship between the heart and kidneys whereby dysfunction in either may exacerbate the function of the other, but this syndrome has been difficult to precisely define because it has many complex physiologic, biochemical, and hormonal abnormalities. The pathophysiology of CRS is not completely understood, but potential mechanisms include reduced kidney perfusion due to decreased forward flow, increased right ventricular and venous pressure, and neurohormonal adaptations. Treatment options include inotropic medications; diuretics; ultrafiltration; and medications, such as β-blockers, inhibitors of the renin-angiotensin-aldosterone system, and more novel treatments that focus on unique aspects of the pathophysiology. Recent observational studies suggest that treatments that result in a decrease in venous pressure and lead to hemoconcentration may be associated with improved outcomes. Patients with CRS that is not responsive to medical interventions should be considered for ventricular assist devices, heart transplantation, or combined heart and kidney transplantation. Copyright © 2014 by the American Society of Nephrology.

[The effectiveness of comprehensive rehabilitation of the patients presenting with coronary heart disease with the application of underwater shower massage and electrical stimulation].

PubMed

Rykov, S V; Lebedeva, O D; L'vova, N V; Tupitsina, Iu Iu

2014-01-01

The underwater shower massage and electrical stimulation were applied to treat 120 patients presenting with coronary heart disease. The estimation of the effectiveness of this treatment with the use of functional diagnostic methods revealed its psychocorrective effect manifested in the form of reduced frequency and duration of painful and painless angina seizures, restricted sympathetic influences on the heart as well as normalized sympathovagal balance, lipid status, antioxidative system, central and peripheral hemodynamics, improved systolic and diastolic function of the myocardium, enhanced tolerability of mental, emotional, and physical workload. The study allowed the predictors of the effectiveness of therapeutic and health-promoting measures to be identified.

Paraoxonase 2 prevents the development of heart failure.

PubMed

Li, Wei; Kennedy, David; Shao, Zhili; Wang, Xi; Kamdar, Andre Klaassen; Weber, Malory; Mislick, Kayla; Kiefer, Kathryn; Morales, Rommel; Agatisa-Boyle, Brendan; Shih, Diana M; Reddy, Srinivasa T; Moravec, Christine S; Tang, W H Wilson

2018-05-02

Mitochondrial oxidation is a major source of reactive oxygen species (ROS) and mitochondrial dysfunction plays a central role in development of heart failure (HF). Paraoxonase 2 deficient (PON2-def) mitochondria are impaired in function. In this study, we tested whether PON2-def aggravates HF progression. Using qPCR, immunoblotting and lactonase activity assay, we demonstrate that PON2 activity was significantly decreased in failing hearts despite increased PON2 expression. To determine the cardiac-specific function of PON2, we performed heart transplantations in which PON2-def and wild type (WT) donor hearts were implanted into WT recipient mice. Beating scores of the donor hearts, assessed at 4 weeks post-transplantation, were significantly decreased in PON2-def hearts when compared to WT donor hearts. By using a transverse aortic constriction (TAC) model, we found PON2 deficiency significantly exacerbated left ventricular remodeling and cardiac fibrosis post-TAC. We further demonstrated PON2 deficiency significantly enhanced ROS generation in heart tissues post-TAC. ROS generation was measured through dihydroethidium (DHE) using high-pressure liquid chromatography (HPLC) with a fluorescent detector. By using neonatal cardiomyocytes treated with CoCl 2 to mimic hypoxia, we found PON2 deficiency dramatically increased ROS generation in the cardiomyocytes upon CoCl 2 treatment. In response to a short CoCl 2 exposure, cell viability and succinate dehydrogenase (SDH) activity assessed by MTT assay were significantly diminished in PON2-def cardiomyocytes compared to those in WT cardiomyocytes. PON2-def cardiomyocytes also had lower baseline SDH activity. By using adult mouse cardiomyocytes and mitochondrial ToxGlo assay, we found impaired cellular ATP generation in PON2-def cells compared to that in WT cells, suggesting that PON2 is necessary for proper mitochondrial function. Our study suggests a cardioprotective role for PON2 in both experimental and human heart failure, which may be associated with the ability of PON2 to improve mitochondrial function and diminish ROS generation. Copyright © 2018 Elsevier Inc. All rights reserved.

Factors associated with health-related quality of life in stable ambulatory congestive heart failure patients: Systematic review.

PubMed

Baert, Anneleen; De Smedt, Delphine; De Sutter, Johan; De Bacquer, Dirk; Puddu, Paolo Emilio; Clays, Els; Pardaens, Sofie

2018-03-01

Background Since improved treatment of congestive heart failure has resulted in decreased mortality and hospitalisation rates, increasing self-perceived health-related quality of life (HRQoL) has become a major goal of congestive heart failure treatment. However, an overview on predictieve factors of HRQoL is currently lacking in literature. Purpose The aim of this study was to identify key factors associated with HRQoL in stable ambulatory patients with congestive heart failure. Methods A systematic review was performed. MEDLINE, Web of Science and Embase were searched for the following combination of terms: heart failure, quality of life, health perception or functional status between the period 2000 and February 2017. Literature screening was done by two independent reviewers. Results Thirty-five studies out of 8374 titles were included for quality appraisal, of which 29 were selected for further data extraction. Four distinct categories grouping different types of variables were identified: socio-demographic characteristics, clinical characteristics, health and health behaviour, and care provider characteristics. Within the above-mentioned categories the presence of depressive symptoms was most consistently related to a worse HRQoL, followed by a higher New York Heart Association functional class, younger age and female gender. Conclusion Through a systematic literature search, factors associated with HRQoL among congestive heart failure patients were investigated. Age, gender, New York Heart Association functional class and depressive symptoms are the most consistent variables explaining the variance in HRQoL in patients with congestive heart failure. These findings are partly in line with previous research on predictors for hard endpoints in patients with congestive heart failure.

Changes in functional health status of older women with heart disease: evaluation of a program based on self-regulation.

PubMed

Clark, N M; Janz, N K; Dodge, J A; Schork, M A; Fingerlin, T E; Wheeler, J R; Liang, J; Keteyian, S J; Santinga, J T

2000-03-01

This study involving 570 women aged 60 years or older with heart disease, assessed the effects of a disease management program on physical functioning, symptom experience, and psychosocial status. Women were randomly assigned to control or program groups. Six to eight women met weekly with a health educator and peer leader over 4 weeks to learn self-regulation skills with physical activity as the focus. Evaluative data were collected through telephone interviews, physical assessments, and medical records at baseline and 4 and 12 months post baseline. At 12 months, compared with controls, program women were less symptomatic (p < .01), scored better on the physical dimension of the Sickness Impact Profile (SIP; p < 0.05), had improved ambulation as measured by the 6-minute walk (p < 0.01), and lost more body weight (p < .001). No differences related to psychosocial factors as measured by the SIP were noted. A self-regulation-based program that was provided to older women with heart disease and that focused on physical activity and disease management problems salient to them, improved their physical functioning and symptom experience. Psychosocial benefit was not evident and may be a result of measurement error or due to insufficient program time spent on psychosocial aspects of functioning.

Association Between Echocardiography Laboratory Accreditation and the Quality of Imaging and Reporting for Valvular Heart Disease.

PubMed

Thaden, Jeremy J; Tsang, Michael Y; Ayoub, Chadi; Padang, Ratnasari; Nkomo, Vuyisile T; Tucker, Stephen F; Cassidy, Cynthia S; Bremer, Merri; Kane, Garvan C; Pellikka, Patricia A

2017-08-01

It is presumed that echocardiographic laboratory accreditation leads to improved quality, but there are few data. We sought to compare the quality of echocardiographic examinations performed at accredited versus nonaccredited laboratories for the evaluation of valvular heart disease. We enrolled 335 consecutive valvular heart disease subjects who underwent echocardiography at our institution and an external accredited or nonaccredited institution within 6 months. Completeness and quality of echocardiographic reports and images were assessed by investigators blinded to the external laboratory accreditation status and echocardiographic results. Compared with nonaccredited laboratories, accredited sites more frequently reported patient sex (94% versus 78%; P <0.001), height and weight (96% versus 63%; P <0.001), blood pressure (86% versus 39%; P <0.001), left ventricular size (96% versus 83%; P <0.001), right ventricular size (94% versus 80%; P =0.001), and right ventricular function (87% versus 73%; P =0.006). Accredited laboratories had higher rates of complete and diagnostic color (58% versus 35%; P =0.002) and spectral Doppler imaging (45% versus 21%; P <0.0001). Concordance between external and internal grading of external studies was improved when diagnostic quantification was performed (85% versus 69%; P =0.003), and in patients with mitral regurgitation, reproducibility was improved with higher quality color Doppler imaging. Accredited echocardiographic laboratories had more complete reporting and better image quality, while echocardiographic quantification and color Doppler image quality were associated with improved concordance in grading valvular heart disease. Future quality improvement initiatives should highlight the importance of high-quality color Doppler imaging and echocardiographic quantification to improve the accuracy, reproducibility, and quality of echocardiographic studies for valvular heart disease. © 2017 American Heart Association, Inc.

Functional Assays to Screen and Dissect Genomic Hits: Doubling Down on the National Investment in Genomic Research.

PubMed

Musunuru, Kiran; Bernstein, Daniel; Cole, F Sessions; Khokha, Mustafa K; Lee, Frank S; Lin, Shin; McDonald, Thomas V; Moskowitz, Ivan P; Quertermous, Thomas; Sankaran, Vijay G; Schwartz, David A; Silverman, Edwin K; Zhou, Xiaobo; Hasan, Ahmed A K; Luo, Xiao-Zhong James

2018-04-01

The National Institutes of Health have made substantial investments in genomic studies and technologies to identify DNA sequence variants associated with human disease phenotypes. The National Heart, Lung, and Blood Institute has been at the forefront of these commitments to ascertain genetic variation associated with heart, lung, blood, and sleep diseases and related clinical traits. Genome-wide association studies, exome- and genome-sequencing studies, and exome-genotyping studies of the National Heart, Lung, and Blood Institute-funded epidemiological and clinical case-control studies are identifying large numbers of genetic variants associated with heart, lung, blood, and sleep phenotypes. However, investigators face challenges in identification of genomic variants that are functionally disruptive among the myriad of computationally implicated variants. Studies to define mechanisms of genetic disruption encoded by computationally identified genomic variants require reproducible, adaptable, and inexpensive methods to screen candidate variant and gene function. High-throughput strategies will permit a tiered variant discovery and genetic mechanism approach that begins with rapid functional screening of a large number of computationally implicated variants and genes for discovery of those that merit mechanistic investigation. As such, improved variant-to-gene and gene-to-function screens-and adequate support for such studies-are critical to accelerating the translation of genomic findings. In this White Paper, we outline the variety of novel technologies, assays, and model systems that are making such screens faster, cheaper, and more accurate, referencing published work and ongoing work supported by the National Heart, Lung, and Blood Institute's R21/R33 Functional Assays to Screen Genomic Hits program. We discuss priorities that can accelerate the impressive but incomplete progress represented by big data genomic research. © 2018 American Heart Association, Inc.

Cardiac Alpha1-Adrenergic Receptors: Novel Aspects of Expression, Signaling Mechanisms, Physiologic Function, and Clinical Importance

PubMed Central

O’Connell, Timothy D.; Jensen, Brian C.; Baker, Anthony J.

2014-01-01

Adrenergic receptors (AR) are G-protein-coupled receptors (GPCRs) that have a crucial role in cardiac physiology in health and disease. Alpha1-ARs signal through Gαq, and signaling through Gq, for example, by endothelin and angiotensin receptors, is thought to be detrimental to the heart. In contrast, cardiac alpha1-ARs mediate important protective and adaptive functions in the heart, although alpha1-ARs are only a minor fraction of total cardiac ARs. Cardiac alpha1-ARs activate pleiotropic downstream signaling to prevent pathologic remodeling in heart failure. Mechanisms defined in animal and cell models include activation of adaptive hypertrophy, prevention of cardiac myocyte death, augmentation of contractility, and induction of ischemic preconditioning. Surprisingly, at the molecular level, alpha1-ARs localize to and signal at the nucleus in cardiac myocytes, and, unlike most GPCRs, activate “inside-out” signaling to cause cardioprotection. Contrary to past opinion, human cardiac alpha1-AR expression is similar to that in the mouse, where alpha1-AR effects are seen most convincingly in knockout models. Human clinical studies show that alpha1-blockade worsens heart failure in hypertension and does not improve outcomes in heart failure, implying a cardioprotective role for human alpha1-ARs. In summary, these findings identify novel functional and mechanistic aspects of cardiac alpha1-AR function and suggest that activation of cardiac alpha1-AR might be a viable therapeutic strategy in heart failure. PMID:24368739

An automatic method to calculate heart rate from zebrafish larval cardiac videos.

PubMed

Kang, Chia-Pin; Tu, Hung-Chi; Fu, Tzu-Fun; Wu, Jhe-Ming; Chu, Po-Hsun; Chang, Darby Tien-Hao

2018-05-09

Zebrafish is a widely used model organism for studying heart development and cardiac-related pathogenesis. With the ability of surviving without a functional circulation at larval stages, strong genetic similarity between zebrafish and mammals, prolific reproduction and optically transparent embryos, zebrafish is powerful in modeling mammalian cardiac physiology and pathology as well as in large-scale high throughput screening. However, an economical and convenient tool for rapid evaluation of fish cardiac function is still in need. There have been several image analysis methods to assess cardiac functions in zebrafish embryos/larvae, but they are still improvable to reduce manual intervention in the entire process. This work developed a fully automatic method to calculate heart rate, an important parameter to analyze cardiac function, from videos. It contains several filters to identify the heart region, to reduce video noise and to calculate heart rates. The proposed method was evaluated with 32 zebrafish larval cardiac videos that were recording at three-day post-fertilization. The heart rate measured by the proposed method was comparable to that determined by manual counting. The experimental results show that the proposed method does not lose accuracy while largely reducing the labor cost and uncertainty of manual counting. With the proposed method, researchers do not have to manually select a region of interest before analyzing videos. Moreover, filters designed to reduce video noise can alleviate background fluctuations during the video recording stage (e.g. shifting), which makes recorders generate usable videos easily and therefore reduce manual efforts while recording.

miRNAs as therapeutic targets in ischemic heart disease.

PubMed

Frost, Robert J A; van Rooij, Eva

2010-06-01

Ischemic heart disease is a form of congestive heart failure that is caused by insufficient blood supply to the heart, resulting in a loss of viable tissue. In response to the injury, the non-ischemic myocardium displays signs of secondary remodeling, like interstitial fibrosis and hypertrophy of cardiac myocytes. This remodeling process further deteriorates pump function and increases susceptibility to arrhythmias. MicroRNAs (miRNAs) are small, non-coding RNAs that regulate gene expression in a sequence-dependent manner. Recently, several groups identified miRNAs as crucial gene regulators in response to myocardial infarction (MI) and during post-MI remodeling. In this review, we discuss how modulation of these miRNAs represents a promising new therapeutic strategy to improve the clinical outcome in ischemic heart disease.

Autophagy-Inflammasome Interplay in Heart Failure: A Systematic Review on Basics, Pathways, and Therapeutic Perspectives.

PubMed

Chiu, Bonnie; Jantuan, Eugeniu; Shen, Fan; Chiu, Brian; Sergi, Consolato

2017-05-01

Aging of the population contributes to the increasing prevalence of heart failure. Autophagy is an evolutionarily conserved process aiming to degrade both long-lived proteins and damaged or excessive cyto-organelles via the lysosomal-mediated pathway. Although autophagy is involved in the normal homeostasis of cardiovascular cells, upregulation of autophagy and its abnormal modulation by inflammation may lead to cardiovascular functional decline and heart failure. Despite major improvements in the prevention, diagnosis, and treatment of cardiovascular diseases, heart failure remains one of the major diagnostic and therapeutic challenges. Here, we review the cardiovascular autophagy and its interplay with inflammation which may lead to heart failure exploring some potential treatment options. © 2017 by the Association of Clinical Scientists, Inc.

Reducing RBM20 activity improves diastolic dysfunction and cardiac atrophy.

PubMed

Hinze, Florian; Dieterich, Christoph; Radke, Michael H; Granzier, Henk; Gotthardt, Michael

2016-12-01

Impaired diastolic filling is a main contributor to heart failure with preserved ejection fraction (HFpEF), a syndrome with increasing prevalence and no treatment. Both collagen and the giant sarcomeric protein titin determine diastolic function. Since titin's elastic properties can be adjusted physiologically, we evaluated titin-based stiffness as a therapeutic target. We adjusted RBM20-dependent cardiac isoform expression in the titin N2B knockout mouse with increased ventricular stiffness. A ~50 % reduction of RBM20 activity does not only maintain cardiac filling in diastole but also ameliorates cardiac atrophy and thus improves cardiac function in the N2B-deficient heart. Reduced RBM20 activity partially normalized gene expression related to muscle development and fatty acid metabolism. The adaptation of cardiac growth was related to hypertrophy signaling via four-and-a-half lim-domain proteins (FHLs) that translate mechanical input into hypertrophy signals. We provide a novel link between cardiac isoform expression and trophic signaling via FHLs and suggest cardiac splicing as a therapeutic target in diastolic dysfunction. Increasing the length of titin isoforms improves ventricular filling in heart disease. FHL proteins are regulated via RBM20 and adapt cardiac growth. RBM20 is a therapeutic target in diastolic dysfunction.

Improvement of tricuspid regurgitation after transcatheter ASD closure in older patients.

PubMed

Chen, L; Shen, J; Shan, X; Wang, F; Kan, T; Tang, X; Zhao, X; Qin, Y

2017-07-19

Adult patients with undiagnosed atrial septal defect (ASD) may have right heart cavity enlargement and functional tricuspid valve insufficiency. Moderate or more severe tricuspid regurgitation has been associated with a worse prognosis, and more serious complications are typically seen in older patients. This study aimed to evaluate the improvement in functional tricuspid regurgitation and heart geometry after transcatheter ASD closure in older patients. The data of 111 patients over 60 years of age with moderate or severe tricuspid regurgitation before ASD closure were analyzed. At the 1‑month and 6‑month follow-up after closure, both tricuspid regurgitation jet area and right atrial volume decreased significantly. Right ventricular volume decreased 1 month after closure, showing a further decrease at the end of the 6‑month follow-up. However, 24 patients (21.6%) still had persistent severe tricuspid regurgitation after the procedure. Multivariate analysis revealed that patient age at ASD closure and pulmonary artery systolic pressure determined by echocardiography before closure were predictors of persistent tricuspid regurgitation after closure. Transcatheter ASD closure in older patients could significantly decrease tricuspid regurgitation and improve right heart geometry.

Exercise training modalities in chronic heart failure: does high intensity aerobic interval training make the difference?

PubMed

Giallauria, Francesco; Smart, Neil Andrew; Cittadini, Antonio; Vigorito, Carlo

2016-10-14

Exercise training (ET) is strongly recommended in patients with chronic heart failure (CHF). Moderate-intensity aerobic continuous ET is the best established training modality in CHF patients. In the last decade, however, high-intensity interval exercise training (HIIT) has aroused considerable interest in cardiac rehabilitation community. Basically, HIIT consists of repeated bouts of high-intensity exercise alternated with recovery periods. In CHF patients, HIIT exerts larger improvements in exercise capacity compared to moderate-continuous ET. These results are intriguing, mostly considering that better functional capacity translates into an improvement of symptoms and quality of life. Notably, HIIT did not reveal major safety issues; although CHF patients should be clinically stable, have had recent exposure to at least regular moderate-intensity exercise, and appropriate supervision and monitoring during and after the exercise session are mandatory. The impact of HIIT on cardiac dimensions and function and on endothelial function remains uncertain. HIIT should not replace other training modalities in heart failure but should rather complement them. Combining and tailoring different ET modalities according to each patient's baseline clinical characteristics (i.e. exercise capacity, personal needs, preferences and goals) seem the most astute approach to exercise prescription.

Role of Copper and Homocysteine in Pressure Overload Heart Failure

PubMed Central

Hughes, William M.; Rodriguez, Walter E.; Rosenberger, Dorothea; Chen, Jing; Sen, Utpal; Tyagi, Neetu; Moshal, Karni S.; Vacek, Thomas; Kang, Y. James

2009-01-01

Elevated levels of homocysteine (Hcy) (known as hyperhomocysteinemia HHcy) are involved in dilated cardiomyopathy. Hcy chelates copper and impairs copper-dependent enzymes. Copper deficiency has been linked to cardiovascular disease. We tested the hypothesis that copper supplement regresses left ventricular hypertrophy (LVH), fibrosis and endothelial dysfunction in pressure overload DCM mice hearts. The mice were grouped as sham, sham + Cu, aortic constriction (AC), and AC + Cu. Aortic constriction was performed by transverse aortic constriction. The mice were treated with or without 20 mg/kg copper supplement in the diet for 12 weeks. The cardiac function was assessed by echocardiography and electrocardiography. The matrix remodeling was assessed by measuring matrix metalloproteinase (MMP), tissue inhibitor of metalloproteinases (TIMPs), and lysyl oxidase (LOX) by Western blot analyses. The results suggest that in AC mice, cardiac function was improved with copper supplement. TIMP-1 levels decreased in AC and were normalized in AC + Cu. Although MMP-9, TIMP-3, and LOX activity increased in AC and returned to baseline value in AC + Cu, copper supplement showed no significant effect on TIMP-4 activity after pressure overload. In conclusion, our data suggest that copper supplement helps improve cardiac function in a pressure overload dilated cardiomyopathic heart. PMID:18679830

Engineering the heart: Evaluation of conductive nanomaterials for improving implant integration and cardiac function

PubMed Central

Zhou, Jin; Chen, Jun; Sun, Hongyu; Qiu, Xiaozhong; Mou, Yongchao; Liu, Zhiqiang; Zhao, Yuwei; Li, Xia; Han, Yao; Duan, Cuimi; Tang, Rongyu; Wang, Chunlan; Zhong, Wen; Liu, Jie; Luo, Ying; (Mengqiu) Xing, Malcolm; Wang, Changyong

2014-01-01

Recently, carbon nanotubes together with other types of conductive materials have been used to enhance the viability and function of cardiomyocytes in vitro. Here we demonstrated a paradigm to construct ECTs for cardiac repair using conductive nanomaterials. Single walled carbon nanotubes (SWNTs) were incorporated into gelatin hydrogel scaffolds to construct three-dimensional ECTs. We found that SWNTs could provide cellular microenvironment in vitro favorable for cardiac contraction and the expression of electrochemical associated proteins. Upon implantation into the infarct hearts in rats, ECTs structurally integrated with the host myocardium, with different types of cells observed to mutually invade into implants and host tissues. The functional measurements showed that SWNTs were essential to improve the performance of ECTs in inhibiting pathological deterioration of myocardium. This work suggested that conductive nanomaterials hold therapeutic potential in engineering cardiac tissues to repair myocardial infarction. PMID:24429673

Current trends in cardiac rehabilitation

PubMed Central

Dafoe, W; Huston, P

1997-01-01

Cardiac rehabilitation can reduce mortality and morbidity for patients with many types of cardiac disease cost-effectively, yet is generally underutilized. Rehabilitation is helpful not only for patients who have had a myocardial infarction but also for those with stable angina or congestive heart failure or those who have undergone myocardial revascularization procedures, a heart transplant or heart valve surgery. The beneficial effects of rehabilitation include a reduction in the rate of death from cardiovascular disease, improved exercise tolerance, fewer cardiac symptoms, improved lipid levels, decreased cigarette smoking, improvement in psychosocial well-being and increased likelihood of return to work. Rehabilitation involves a multidisciplinary team that focuses on education, individually tailored exercise, risk-factor modification and the optimization of functional status and mental health. Current research trends in this area include the evaluation of new secondary-prevention modalities and alternative program options, such as home-based rehabilitation. PMID:9054823

Cocoa, Blood Pressure, and Vascular Function

PubMed Central

Ludovici, Valeria; Barthelmes, Jens; Nägele, Matthias P.; Enseleit, Frank; Ferri, Claudio; Flammer, Andreas J.; Ruschitzka, Frank; Sudano, Isabella

2017-01-01

Cardiovascular disease (CVD) represents the most common cause of death worldwide. The consumption of natural polyphenol-rich foods, and cocoa in particular, has been related to a reduced risk of CVD, including coronary heart disease and stroke. Intervention studies strongly suggest that cocoa exerts a beneficial impact on cardiovascular health, through the reduction of blood pressure (BP), improvement of vascular function, modulation of lipid and glucose metabolism, and reduction of platelet aggregation. These potentially beneficial effects have been shown in healthy subjects as well as in patients with risk factors (arterial hypertension, diabetes, and smoking) or established CVD (coronary heart disease or heart failure). Several potential mechanisms are supposed to be responsible for the positive effect of cocoa; among them activation of nitric oxide (NO) synthase, increased bioavailability of NO as well as antioxidant, and anti-inflammatory properties. It is the aim of this review to summarize the findings of cocoa and chocolate on BP and vascular function. PMID:28824916

Ribose in the heart.

PubMed

Herrick, James; St Cyr, John

2008-01-01

Every cell needs energy, i.e., adenosine triphosphate (ATP), to carry out its function. Decreased oxygen levels, decreased blood flow, and other stressful conditions can drastically effect the intracellular concentrations of these energy compounds. Skeletal muscle, unlike the heart, can address this drop in ATP by employing the myokinase reaction, ultimately producing ATP with a subsequent elevation in adenosine monophosphate (AMP). Ribose, a naturally occurring 5-carbon monosaccharide, is a key component of RNA, DNA (which has deoxyribose), acetyl coenzyme A, and ATP. Each cell produces its own ribose, involved in the pentose phosphate pathway (PPP), to aid in ATP production. States of ischemia and/or hypoxia can severely lower levels of cellular energy compounds in the heart, with an associated compromise in cellular processes, ultimately reflected in altered function. Ribose appears to provide a solution to the problem in replenishing the depressed ATP levels and improving functional status of patients afflicted with cardiovascular diseases.

[The characteristics of the geroprotective action of magnetotherapy in elderly patients with combined cardiovascular pathology].

PubMed

Abramovich, S G; Fedotchenko, A A; Koriakina, A V; Pogodin, K V; Smirnov, S N

1999-01-01

Central hemodynamics, diastolic and pumping functions of the heart, myocardial reactivity, microcirculation and biological age of cardiovascular system were studied in 66 elderly patients suffering from hypertension and ischemic heart disease. The patients received systemic magnetotherapy which produced a geroprotective effect as shown by improved microcirculation, myocardial reactivity, central hemodynamics reducing biological age of cardiovascular system and inhibiting its ageing.

The effect of matrix stiffness of injectable hydrogels on the preservation of cardiac function after a heart attack.

PubMed

Plotkin, Marian; Vaibavi, Srirangam Ramanujam; Rufaihah, Abdul Jalil; Nithya, Venkateswaran; Wang, Jing; Shachaf, Yonatan; Kofidis, Theo; Seliktar, Dror

2014-02-01

This study compares the effect of four injectable hydrogels with different mechanical properties on the post-myocardial infarction left ventricle (LV) remodeling process. The bioactive hydrogels were synthesized from Tetronic-fibrinogen (TF) and PEG-fibrinogen (PF) conjugates; each hydrogel was supplemented with two levels of additional cross-linker to increase the matrix stiffness as measured by the shear storage modulus (G'). Infarcts created by ligating the left anterior descending coronary artery in a rodent model were treated with the hydrogels, and all four treatment groups showed an increase in wall thickness, arterial density, and viable cardiac tissue in the peri-infarct areas of the LV. Echocardiography and hemodynamics data of the PF/TF treated groups showed significant improvement of heart function associated with the attenuated effects of the remodeling process. Multi-factorial regression analysis indicated that the group with the highest modulus exhibited the best rescue of heart function and highest neovascularization. The results of this study demonstrate that multiple properties of an injectable bioactive biomaterial, and notably the matrix stiffness, provide the multifaceted stimulation necessary to preserve cardiac function and prevent adverse remodeling following a heart attack. Copyright © 2013 Elsevier Ltd. All rights reserved.

Transplantation of Epigenetically Modified Adult Cardiac c-Kit+ Cells Retards Remodeling and Improves Cardiac Function in Ischemic Heart Failure Model

PubMed Central

Zakharova, Liudmila; Nural-Guvener, Hikmet; Feehery, Lorraine; Popovic-Sljukic, Snjezana

2015-01-01

Cardiac c-Kit+ cells have a modest cardiogenic potential that could limit their efficacy in heart disease treatment. The present study was designed to augment the cardiogenic potential of cardiac c-Kit+ cells through class I histone deacetylase (HDAC) inhibition and evaluate their therapeutic potency in the chronic heart failure (CHF) animal model. Myocardial infarction (MI) was created by coronary artery occlusion in rats. c-Kit+ cells were treated with mocetinostat (MOCE), a specific class I HDAC inhibitor. At 3 weeks after MI, CHF animals were retrogradely infused with untreated (control) or MOCE-treated c-Kit+ cells (MOCE/c-Kit+ cells) and evaluated at 3 weeks after cell infusion. We found that class I HDAC inhibition in c-Kit+ cells elevated the level of acetylated histone H3 (AcH3) and increased AcH3 levels in the promoter regions of pluripotent and cardiac-specific genes. Epigenetic changes were accompanied by increased expression of cardiac-specific markers. Transplantation of CHF rats with either control or MOCE/c-Kit+ cells resulted in an improvement in cardiac function, retardation of CHF remodeling made evident by increased vascularization and scar size, and cardiomyocyte hypertrophy reduction. Compared with CHF infused with control cells, infusion of MOCE/c-Kit+ cells resulted in a further reduction in left ventricle end-diastolic pressure and total collagen and an increase in interleukin-6 expression. The low engraftment of infused cells suggests that paracrine effects might account for the beneficial effects of c-Kit+ cells in CHF. In conclusion, selective inhibition of class I HDACs induced expression of cardiac markers in c-Kit+ cells and partially augmented the efficacy of these cells for CHF repair. Significance The study has shown that selective class 1 histone deacetylase inhibition is sufficient to redirect c-Kit+ cells toward a cardiac fate. Epigenetically modified c-Kit+ cells improved contractile function and retarded remodeling of the congestive heart failure heart. This study provides new insights into the efficacy of cardiac c-Kit+ cells in the ischemic heart failure model. PMID:26240433

Macrophage Colony-Stimulating Factor Improves Cardiac Function after Ischemic Injury by Inducing Vascular Endothelial Growth Factor Production and Survival of Cardiomyocytes

PubMed Central

Okazaki, Tatsuma; Ebihara, Satoru; Asada, Masanori; Yamanda, Shinsuke; Saijo, Yoshifumi; Shiraishi, Yasuyuki; Ebihara, Takae; Niu, Kaijun; Mei, He; Arai, Hiroyuki; Yambe, Tomoyuki

2007-01-01

Macrophage colony-stimulating factor (M-CSF), known as a hematopoietic growth factor, induces vascular endothelial growth factor (VEGF) production from skeletal muscles. However, the effects of M-CSF on cardiomyocytes have not been reported. Here, we show M-CSF increases VEGF production from cardiomyocytes, protects cardiomyocytes and myotubes from cell death, and improves cardiac function after ischemic injury. In mice, M-CSF increased VEGF production in hearts and in freshly isolated cardiomyocytes, which showed M-CSF receptor expression. In rat cell line H9c2 cardiomyocytes and myotubes, M-CSF induced VEGF production via the Akt signaling pathway, and M-CSF pretreatment protected these cells from H2O2-induced cell death. M-CSF activated Akt and extracellular signal-regulated kinase signaling pathways and up-regulated downstream anti-apoptotic Bcl-xL expression in these cells. Using goats as a large animal model of myocardial infarction, we found that M-CSF treatment after the onset of myocardial infarction by permanent coronary artery ligation promoted angiogenesis in ischemic hearts but did not reduce the infarct area. M-CSF pretreatment of the goat myocardial infarction model by coronary artery occlusion-reperfusion improved cardiac function, as assessed by hemodynamic parameters and echocardiography. These results suggest M-CSF might be a novel therapeutic agent for ischemic heart disease. PMID:17717142

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.

Macrophage Migration Inhibitory Factor (MIF) Deficiency Exacerbates Aging-Induced Cardiac Remodeling and Dysfunction Despite Improved Inflammation: Role of Autophagy Regulation.

PubMed

Xu, Xihui; Pang, Jiaojiao; Chen, Yuguo; Bucala, Richard; Zhang, Yingmei; Ren, Jun

2016-03-04

Aging leads to unfavorable geometric and functional sequelae in the heart. The proinflammatory cytokine macrophage migration inhibitory factor (MIF) plays a role in the maintenance of cardiac homeostasis under stress conditions although its impact in cardiac aging remains elusive. This study was designed to evaluate the role of MIF in aging-induced cardiac anomalies and the underlying mechanism involved. Cardiac geometry, contractile and intracellular Ca(2+) properties were examined in young (3-4 mo) or old (24 mo) wild type and MIF knockout (MIF(-/-)) mice. Our data revealed that MIF knockout exacerbated aging-induced unfavorable structural and functional changes in the heart. The detrimental effect of MIF knockout was associated with accentuated loss in cardiac autophagy with aging. Aging promoted cardiac inflammation, the effect was attenuated by MIF knockout. Intriguingly, aging-induced unfavorable responses were reversed by treatment with the autophagy inducer rapamycin, with improved myocardial ATP availability in aged WT and MIF(-/-) mice. Using an in vitro model of senescence, MIF knockdown exacerbated doxorubicin-induced premature senescence in H9C2 myoblasts, the effect was ablated by MIF replenishment. Our data indicated that MIF knockout exacerbates aging-induced cardiac remodeling and functional anomalies despite improved inflammation, probably through attenuating loss of autophagy and ATP availability in the heart.

[Is iron important in heart failure?].

PubMed

Murín, Ján; Pernický, Miroslav

2015-01-01

Iron deficiency is a frequent comorbidity in a patient with chronic heart failure, and it associates with a worse pro-gnosis of that patient. Mainly worse quality of life and more rehospitalizations are in these iron deficient patients. Iron metabolism is rather complex and there is some new information concerning this complexity in heart failure. We distinquish an absolute and a functional iron deficiency in heart failure. It is this deficit which is important and not as much is anemia important here. Prevalence of anaemia in heart failure is about 30-50 %, higher it is in patients suffering more frequently heart failure decompensations. Treatment of iron deficiency is important and it improves prognosis of these patients. Most experiences there are with i.v. iron treatment (FERRIC HF, FAIR HF and CONFIRM HF studies), less so with per oral treatment. There are no clinical trials which analysed mortality influences. heart failure - iron metabolism in heart failure - prevalence of iron deficit - treatment of iron deficiency in heart failure.

Patient-reported outcomes and associations with pleural effusion in outpatients with heart failure: an observational cohort study.

PubMed

Gundersen, Guri H; Norekvål, Tone M; Graven, Torbjørn; Haug, Hilde H; Skjetne, Kyrre; Kleinau, Jens O; Gustad, Lise T; Dalen, Håvard

2017-03-20

We aimed to study whether patient-reported outcomes, measured by quality of life (QoL) and functional class, are sensitive to pleural effusion (PLE) in patients with heart failure (HF), and to study changes in QoL and functional class during follow-up of PLE. A cohort of 62 patients from an outpatient HF clinic was included. The amount of PLE was quantified using a pocket-sized ultrasound imaging device. Self-reports of QoL and functional class were collected using the Minnesota Living with Heart Failure Questionnaire (MLHFQ) and the New York Heart Association (NYHA) functional classification. At baseline, 26 (42%) patients had PLE of which 19 (31%) patients had moderate to severe amounts of PLE. Patients with no to mild PLE had a lower MLHFQ score (mean 42, SD 21) compared with patients with a moderate to severe amount of PLE (mean 55, SD 24), p=0.03. For 28 patients (45%) with follow-up data, we observed a linear improvement of the MLHFQ-score (3.2, 95% CI 1.2 to 5.1) with each centimetre reduction of PLE. Correspondingly, patient-reported NYHA-class followed the same pattern as the MLHFQ-score. Our study indicates that patient-reported outcome measures as MLHFQ may be sensitive tools to identify patients with HF at highest risk of symptomatic PLE and that treatment targeting reduction of PLE during follow-up is essential to improvement of QoL and functional capacity of outpatients with HF. NCT01794715; Results. 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/.

Impact of High-Intensity-NIV on the heart in stable COPD: a randomised cross-over pilot study.

PubMed

Duiverman, Marieke Leontine; Maagh, Petra; Magnet, Friederike Sophie; Schmoor, Claudia; Arellano-Maric, Maria Paola; Meissner, Axel; Storre, Jan Hendrik; Wijkstra, Peter Jan; Windisch, Wolfram; Callegari, Jens

2017-05-02

Although high-intensity non-invasive ventilation has been shown to improve outcomes in stable COPD, it may adversely affect cardiac performance. Therefore, the aims of the present pilot study were to compare cardiac and pulmonary effects of 6 weeks of low-intensity non-invasive ventilation and 6 weeks of high-intensity non-invasive ventilation in stable COPD patients. In a randomised crossover pilot feasibility study, the change in cardiac output after 6 weeks of each NIV mode compared to baseline was assessed with echocardiography in 14 severe stable COPD patients. Furthermore, CO during NIV, gas exchange, lung function, and health-related quality of life were investigated. Three patients dropped out: two deteriorated on low-intensity non-invasive ventilation, and one presented with decompensated heart failure while on high-intensity non-invasive ventilation. Eleven patients were included in the analysis. In general, cardiac output and NTproBNP did not change, although individual effects were noticed, depending on the pressures applied and/or the co-existence of heart failure. High-intensity non-invasive ventilation tended to be more effective in improving gas exchange, but both modes improved lung function and the health-related quality of life. Long-term non-invasive ventilation with adequate pressure to improve gas exchange and health-related quality of life did not have an overall adverse effect on cardiac performance. Nevertheless, in patients with pre-existing heart failure, the application of very high inspiratory pressures might reduce cardiac output. The trial was registered in the Deutsches Register Klinischer Studien (DRKS-ID: DRKS00007977 ).

Muscle wasting and sarcopenia in heart failure and beyond: update 2017.

PubMed

Springer, Jochen; Springer, Joshua-I; Anker, Stefan D

2017-11-01

Sarcopenia (loss of muscle mass and muscle function) is a strong predictor of frailty, disability and mortality in older persons and may also occur in obese subjects. The prevalence of sarcopenia is increased in patients suffering from chronic heart failure. However, there are currently few therapy options. The main intervention is resistance exercise, either alone or in combination with nutritional support, which seems to enhance the beneficial effects of training. Also, testosterone has been shown to increased muscle power and function; however, a possible limitation is the side effects of testosterone. Other investigational drugs include selective androgen receptor modulators, growth hormone, IGF-1, compounds targeting myostatin signaling, which have their own set of side effects. There are abundant prospective targets for improving muscle function in the elderly with or without chronic heart failure, and the continuing development of new treatment strategies and compounds for sarcopenia and cardiac cachexia makes this field an exciting one. © 2017 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of the European Society of Cardiology.

[Structural and functional changes of myocardium in Chernobyl disaster clean-up workers with atrial fibrillation].

PubMed

Khomaziuk, I M; Habulavichene, Zh M; Khomaziuk, V A

2011-01-01

Particularities and clinical importance of the structural and functional changes of myocardium were estimated in Chernobyl disaster clean-up workers with atrial fibrillation (AF). We examined 122 men with AF, which was associated with ischemic heart disease and arterial hypertension. Paroxysmal AF was diagnosed in 42 patients, 80 patients had permanent AE Control group comprised 80 men without AF. Echocardiography and Doppler studies were performed using ultrasound scanner Aloka SSD-630 (Japan). Significant structural and functional changes of the heart were revealed already in paroxysmal AF and became more pronounced in permanent AF. Increased left atrial size, its ratio to left ventricular end diastolic diameter, diastolic dysfunction were important echocardiographic predictors of AF. Heart walls thickening was accompanied by disorders of myocardial relaxation, increase in myocardial mass led to ischemia, and together they promoted overload, dysfunction of atrium and development of AF. Obligatory echocardiographic examination of the Chernobyl disaster clean-up workers with ischemic heart disease and arterial hypertension is necessary for predicting AF early, ordering adequate therapy in proper time and improving prognosis.

Effect of a 24-week physical training programme (in water and on land) on pain, functional capacity, body composition and quality of life in women with fibromyalgia.

PubMed

Latorre, Pedro Ángel; Santos, María Aparecida; Heredia-Jiménez, Jose Maria; Delgado-Fernández, Manuel; Soto, Víctor Manuel; Mañas, Alfonso; Carbonell-Baeza, Ana

2013-01-01

To analyse the effect of a 24-week physical training programme in water and on land on women with fibromyalgia. A controlled study was conducted from December 2009 to May 2010. Seventy-two women with fibromyalgia (age: 51.79±7.87 years) were assigned to an exercise group (3 sessions/week, 2 sessions in water, 1 session on land) (n=42) and to a control group (n=30). The variables analysed were: number of tender points, visual analogue scale (VAS) of pain, algometer score, functional capacity (leg strength, hand-grip dynamometry, flexibility, agility, balance, aerobic endurance, heart response), body composition (body mass index, fat mass index, skeletal muscle mass index and percentage of body fat) and psychological variables (Fibromyalgia Impact Questionnaire [FIQ] and Short Form Health Survey 36 [SF-36]). The exercise group improved in the algometer score (p<0.001), positive tender points (p=0.005), VAS (p<0.001) and FIQ (p<0.001). Improvements were also detected in functional capacity (leg strength, p=0.001; hand-grip dynamometry, p=0.001; flexibility, p<0.001; balance, p=0.006; 6-minute walk test, p<0.001; mean heart rate, p=0.031; maximum heart rate, p<0.001 and VO2 max, p<0.001). There was a decrease in the percentage of body fat (p=0.040). There was also an improvement in the subscales of the SF-36; vitality (p=0.004), mental health (p=0.001) social role functioning (p=0.020) and general health functioning (p=0.002). The findings of this study show that a 24-week physical training programme (3 sessions/week, of which 2 sessions are in water and 1 session is on land) reduces pain and disease impact and improves functional capacity in women with fibromyalgia.

Impact of aerobic interval training and continuous training on left ventricular geometry and function: a SAINTEX-CAD substudy.

PubMed

Van De Heyning, Caroline M; De Maeyer, Catherine; Pattyn, Nele; Beckers, Paul J; Cornelissen, Véronique A; Goetschalckx, Kaatje; Possemiers, Nadine; Van Craenenbroeck, Emeline M; Voigt, Jens-Uwe; Vanhees, Luc; Shivalkar, Bharati

2018-04-15

Increase of exercise capacity (peak VO 2 ) after cardiac rehabilitation improves outcome in patients with coronary artery disease (CAD). Systolic and diastolic function have been associated with peak VO 2 , but their role towards improvement of exercise capacity remains unclear. It is unknown which exercise intensity has the most beneficial impact on left ventricular (LV) geometry and function in CAD patients without heart failure. 200 stable CAD patients without heart failure were randomized to 3months of aerobic interval training (AIT) or aerobic continuous training (ACT). Cardiopulmonary exercise test and transthoracic echocardiography were scheduled before and after 3months of training. At baseline, a higher peak VO 2 correlated with lower LV posterior wall thickness (p=0.002), higher LV ejection fraction (p=0.008), better LV global longitudinal strain (p=0.043) and lower E/e' (0=0.001). After multivariate stepwise regression analysis only E/é remained an independent predictor of peak VO 2 (p=0.042). Improvement of peak VO 2 after 3months of training correlated with reverse remodeling of the interventricular septum (p=0.005), enlargement of LV diastolic volume (p=0.007) and increase of LV stroke volume (p=0.018) but not with other indices of systolic or diastolic function. Significant reduction of the interventricular septum thickness after cardiac rehabilitation was observed (p=0.012), with a trend towards more reverse remodeling after ACT compared to AIT (p=0.054). In contrast, there were no changes in other parameters of LV geometry, diastolic or systolic function. Systolic and diastolic function are determinants of baseline exercise capacity in CAD patients without heart failure, but do not seem to mediate improvement of peak VO 2 after either AIT or ACT. Copyright © 2017 Elsevier B.V. All rights reserved.

Design and Rationale of the Cognitive Intervention to Improve Memory in Heart Failure Patients Study.

PubMed

Pressler, Susan J; Giordani, Bruno; Titler, Marita; Gradus-Pizlo, Irmina; Smith, Dean; Dorsey, Susan G; Gao, Sujuan; Jung, Miyeon

Memory loss is an independent predictor of mortality among heart failure patients. Twenty-three percent to 50% of heart failure patients have comorbid memory loss, but few interventions are available to treat the memory loss. The aims of this 3-arm randomized controlled trial were to (1) evaluate efficacy of computerized cognitive training intervention using BrainHQ to improve primary outcomes of memory and serum brain-derived neurotrophic factor levels and secondary outcomes of working memory, instrumental activities of daily living, and health-related quality of life among heart failure patients; (2) evaluate incremental cost-effectiveness of BrainHQ; and (3) examine depressive symptoms and genomic moderators of BrainHQ effect. A sample of 264 heart failure patients within 4 equal-sized blocks (normal/low baseline cognitive function and gender) will be randomly assigned to (1) BrainHQ, (2) active control computer-based crossword puzzles, and (3) usual care control groups. BrainHQ is an 8-week, 40-hour program individualized to each patient's performance. Data collection will be completed at baseline and at 10 weeks and 4 and 8 months. Descriptive statistics, mixed model analyses, and cost-utility analysis using intent-to-treat approach will be computed. This research will provide new knowledge about the efficacy of BrainHQ to improve memory and increase serum brain-derived neurotrophic factor levels in heart failure. If efficacious, the intervention will provide a new therapeutic approach that is easy to disseminate to treat a serious comorbid condition of heart failure.

Donor Preconditioning After the Onset of Brain Death With Dopamine Derivate n-Octanoyl Dopamine Improves Early Posttransplant Graft Function in the Rat.

PubMed

Li, S; Korkmaz-Icöz, S; Radovits, T; Ruppert, M; Spindler, R; Loganathan, S; Hegedűs, P; Brlecic, P; Theisinger, B; Theisinger, S; Höger, S; Brune, M; Lasitschka, F; Karck, M; Yard, B; Szabó, G

2017-07-01

Heart transplantation is the therapy of choice for end-stage heart failure. However, hemodynamic instability, which has been demonstrated in brain-dead donors (BDD), could also affect the posttransplant graft function. We tested the hypothesis that treatment of the BDD with the dopamine derivate n-octanoyl-dopamine (NOD) improves donor cardiac and graft function after transplantation. Donor rats were given a continuous intravenous infusion of either NOD (0.882 mg/kg/h, BDD+NOD, n = 6) or a physiological saline vehicle (BDD, n = 9) for 5 h after the induction of brain death by inflation of a subdural balloon catheter. Controls were sham-operated (n = 9). In BDD, decreased left-ventricular contractility (ejection fraction; maximum rate of rise of left-ventricular pressure; preload recruitable stroke work), relaxation (maximum rate of fall of left-ventricular pressure; Tau), and increased end-diastolic stiffness were significantly improved after the NOD treatment. Following the transplantation, the NOD-treatment of BDD improved impaired systolic function and ventricular relaxation. Additionally, after transplantation increased interleukin-6, tumor necrosis factor TNF-α, NF-kappaB-p65, and nuclear factor (NF)-kappaB-p105 gene expression, and increased caspase-3, TNF-α and NF-kappaB protein expression could be significantly downregulated by the NOD treatment compared to BDD. BDD postconditioning with NOD through downregulation of the pro-apoptotic factor caspase-3, pro-inflammatory cytokines, and NF-kappaB may protect the heart against the myocardial injuries associated with brain death and ischemia/reperfusion. © 2017 The American Society of Transplantation and the American Society of Transplant Surgeons.

Encouraging effects of a short-term, adapted Nordic diet intervention on skin microvascular function and skin oxygen tension in younger and older adults.

PubMed

Rogerson, David; McNeill, Scott; Könönen, Heidi; Klonizakis, Markos

2018-05-01

The microvascular benefits of regional diets appear in the literature; however, little is known about Nordic-type diets. We investigated the effects of a short-term, adapted, Nordic diet on microvascular function in younger and older individuals at rest and during activity. Thirteen young (mean age: 28 y; standard deviation: 5 y) and 15 older (mean age: 68 y; standard deviation: 6 y) participants consumed a modified Nordic diet for 4 wk. Laser Doppler flowmetry and transcutaneous oxygen monitoring were used to assess cutaneous microvascular function and oxygen tension pre- and postintervention; blood pressure, body mass, body fat percentage, ratings of perceived exertion, and peak heart rate during activity were examined concurrently. Axon-mediated vasodilation improved in older participants (1.17 [0.30] to 1.30 [0.30]; P < 0.05). Improvements in endothelium-dependent vasodilation were noted in both young (1.67 [0.50] to 2.03 [0.62]; P < 0.05) and older participants (1.49 [0.37] to 1.63 [0.39]; P < 0.05). Reduced peak heart rate during activity was noted in older participants only (36.5 [8.9] to 35.3 [8.5]; P < 0.05) and reduced body fat percentage in young participants only (young = 27.2 [8.3] to 25.2 [8.8]; P < 0.05). No other variables reached statistical significance; however, trends were observed. We observed statistically significant improvements in microvascular function, peak heart rate, and body composition. An adapted Nordic diet might improve microvascular health. Copyright © 2017 Elsevier Inc. All rights reserved.

A Randomized Trial of Heart Failure Disease Management in Skilled Nursing Facilities: Design and Rationale

PubMed Central

Boxer, Rebecca S.; Dolansky, Mary A.; Bodnar, Christine A.; Singer, Mendel E.; Albert, Jeffery M.; Gravenstein, Stefan

2013-01-01

Background Heart failure disease management can improve health outcomes for older community dwelling patients with heart failure. Heart failure disease management has not been studied in skilled nursing facilities, a major site of transitional care for older adults. Methods and Anticipated Results The objective of this trial is to investigate if a heart failure disease management program (HF-DMP) in skilled nursing facilities (SNF) 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 heart failure 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 heart failure: documentation of left ventricular function, tracking of weight and symptoms, medication titration, discharge instructions, 7 day follow up appointment post SNF discharge, 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. Conclusion 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 heart failure patients undergoing post-acute rehabilitation. PMID:23871475

A controlled clinical trial of vitamin E supplementation in patients with congestive heart failure.

PubMed

Keith, M E; Jeejeebhoy, K N; Langer, A; Kurian, R; Barr, A; O'Kelly, B; Sole, M J

2001-02-01

Oxidative stress is increased in patients with congestive heart failure and can contribute to the progressive deterioration observed in these patients. Increased oxidative stress is the result of either an increased production of free radicals or a depletion of endogenous antioxidants, such as vitamin E. We aimed to determine whether vitamin E supplementation of patients with advanced heart failure would modify levels of oxidative stress, thereby preventing or delaying the deterioration associated with free radical injury. Fifty-six outpatients with advanced heart failure (New York Heart Association functional class III or IV) were enrolled in a double-blind randomized controlled trial for 12 wk. At a baseline visit and at 2 follow-up visits, blood and breath samples were collected for the measurement of indexes of heart function and disease state, including malondialdehyde, isoprostanes, and breath pentane and ethane. Quality of life was also assessed at baseline and after 12 wk of treatment. Vitamin E treatment significantly increased plasma concentrations of alpha-tocopherol in the treatment group but failed to significantly affect any other marker of oxidative stress or quality of life. In addition, concentrations of atrial natriuretic peptide (a humoral marker of ventricular dysfunction), neurohormonal-cytokine markers of prognosis, tumor necrosis factor, epinephrine, and norepinephrine were unchanged with treatment and were not significantly different from those in the control group. Supplementation with vitamin E did not result in any significant improvements in prognostic or functional indexes of heart failure or in the quality of life of patients with advanced heart failure.

Cell and gene therapy for severe heart failure patients: The time and place for Pim-1 Kinase

PubMed Central

Siddiqi, Sailay; Sussman, Mark A

2014-01-01

Regenerative therapy in severe heart failure patients presents a challenging set of circumstances including a damaged myocardial environment that accelerates senescence in myocytes and cardiac progenitor cells. Failing myocardium suffers from deterioration of contractile function coupled with impaired regenerative potential that drives the heart toward decompensation. Efficacious regenerative cell therapy for severe heart failure requires disruption of this vicious circle that can be accomplished by alteration of the compromised myocyte phenotype and rejuvenation of progenitor cells. This review focuses upon potential for Pim-1 kinase to mitigate chronic heart failure by improving myocyte quality through preservation of mitochondrial integrity, prevention of hypertrophy and inhibition of apoptosis. In addition, cardiac progenitors engineered with Pim-1 possess enhanced regenerative potential, making Pim-1 an important player in future treatment of severe heart failure. PMID:23984924

"From right to left": The role of right heart catheterization in the diagnosis and management of left heart diseases.

PubMed

Kałużna-Oleksy, Marta; Araszkiewicz, Aleksander; Migaj, Jacek; Lesiak, Maciej; Straburzyńska-Migaj, Ewa

2017-01-01

Pulmonary hypertension (PH), second only to left heart diseases (LHD), is a frequent problem in clinical practice. At the same time, left heart diseases represent the most common cause of pulmonary hypertension, and the occurrence of PH in patients with chronic heart failure is usually associated with worse functional class, and prognosis. Right heart catheterization (RHC) is the "gold standard" in the diagnosis and differentiation of PH. It is also essential in the process of qualifying for a heart transplantation. Therefore, right heart catheterization should be performed in expert centers by experienced operators and according to a strict protocol to ensure the reliability and reproducibility of results. Recommendations for pulmonary hypertension due to left heart disease are based on the European Society of Cardiology (ESC) guidelines designed in cooperation with the European Respiratory Society (ERS) and the International Society for Heart and Lung Transplantation (ISHL). The new ESC guidelines for pulmonary hypertension published in 2015 have improved the diagnostic and therapeutic process in patients with left heart diseases.

In Vivo Functional Selection Identifies Cardiotrophin-1 as a Cardiac Engraftment Factor for Mesenchymal Stromal Cells.

PubMed

Bortolotti, Francesca; Ruozi, Giulia; Falcione, Antonella; Doimo, Sara; Dal Ferro, Matteo; Lesizza, Pierluigi; Zentilin, Lorena; Banks, Lawrence; Zacchigna, Serena; Giacca, Mauro

2017-10-17

Transplantation of cells into the infarcted heart has significant potential to improve myocardial recovery; however, low efficacy of cell engraftment still limits therapeutic benefit. Here, we describe a method for the unbiased, in vivo selection of cytokines that improve mesenchymal stromal cell engraftment into the heart both in normal conditions and after myocardial infarction. An arrayed library of 80 secreted factors, including most of the currently known interleukins and chemokines, were individually cloned into adeno-associated viral vectors. Pools from this library were then used for the batch transduction of bone marrow-derived mesenchymal stromal cells ex vivo, followed by intramyocardial cell administration in normal and infarcted mice. Three weeks after injection, vector genomes were recovered from the few persisting cells and identified by sequencing DNA barcodes uniquely labeling each of the tested cytokines. The most effective molecule identified by this competitive engraftment screening was cardiotrophin-1, a member of the interleukin-6 family. Intracardiac injection of mesenchymal stromal cells transiently preconditioned with cardiotrophin-1 preserved cardiac function and reduced infarct size, parallel to the persistence of the transplanted cells in the healing hearts for at least 2 months after injection. Engraftment of cardiotrophin-1-treated mesenchymal stromal cells was consequent to signal transducer and activator of transcription 3-mediated activation of the focal adhesion kinase and its associated focal adhesion complex and the consequent acquisition of adhesive properties by the cells. These results support the feasibility of selecting molecules in vivo for their functional properties with adeno-associated viral vector libraries and identify cardiotrophin-1 as a powerful cytokine promoting cell engraftment and thus improving cell therapy of the infarcted myocardium. © 2017 American Heart Association, Inc.

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

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.

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.

Sleep in heart failure.

PubMed

Naughton, Matthew T; Lorenzi-Filho, Geraldo

2009-01-01

Sleep plays a large role in patients with heart failure. In normal subjects, sleep is usually in a supine position with reduced sympathetic drive, elevated vagal tone and as such a relatively lower cardiac output and minute ventilation, allowing for recuperation. Patients with heart failure may not experience the same degree of autonomic activity change and the supine position may place a large strain on the pulmonary system. More than half of all heart failure patients have one of two types of sleep apnea: either obstructive or central sleep apnea. Some patients have both types. Obstructive sleep apnea is likely to be a cause of heart failure due to large negative intrathoracic pressures, apnea related hypoxemia and hypercapnia, terminated by an arousal and surge in systemic blood pressure associated with endothelial damage and resultant premature atherosclerosis. Reversal of obstructive sleep apnea improves blood pressure, systolic contraction and autonomic dysfunction however mortality studies are lacking. Central sleep apnea with Cheyne Stokes pattern of respiration (CSA-CSR) occurs as a result of increased central controller (brainstem driving ventilation) and plant (ventilation driving CO2) gain in the setting of a delayed feed back (i.e., low cardiac output). It is thought this type of apnea is a result of moderately to severely impaired cardiac function and is possibly indicative of high mortality. Treatment of CSA-CSR is best undertaken by treating the underlying cardiac condition which may include with medications, pacemakers, transplantation or continuous positive airway pressure (CPAP). In such patients CPAP exerts unique effects to assist cardiac function and reduce pulmonary edema. Whether CPAP improves survival in this heart failure population remains to be determined.

Long-term changes of renal function in relation to ace inhibitor/angiotensin receptor blocker dosing in patients with heart failure and chronic kidney disease.

PubMed

Fröhlich, Hanna; Nelges, Christoph; Täger, Tobias; Schwenger, Vedat; Cebola, Rita; Schnorbach, Johannes; Goode, Kevin M; Kazmi, Syed; Katus, Hugo A; Cleland, John G F; Clark, Andrew L; Frankenstein, Lutz

2016-08-01

Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) have become cornerstones of therapy for chronic heart failure (CHF). Guidelines advise high target doses for ACEIs/ARBs, but fear of worsening renal function may limit dose titration in patients with concomitant chronic kidney disease (CKD). In this retrospective observational study, we identified 722 consecutive patients with systolic CHF, stable CKD stage III/IV (estimated glomerular filtration rate [eGFR] 15-60 mL min(-1) 1.73 m(-2)) and chronic ACEI/ARB treatment from the outpatient heart failure clinics at the Universities of Hull, UK, and Heidelberg, Germany. Change of renal function, worsening CHF, and hyperkalemia at 12-month follow-up were analyzed as a function of both baseline ACEI/ARB dose and dose change from baseline. ΔeGFR was not related to baseline dose of ACEI/ARB (P = .58), or to relative (P = .18) or absolute change of ACEI/ARB dose (P = .21) during follow-up. Expressing change of renal function as a categorical variable (improved/stable/decreased) as well as subgroup analyses with respect to age, sex, New York Heart Association functional class, left ventricular ejection fraction, diabetes, concomitant aldosterone antagonists, CKD stage, hypertension, ACEI vs ARB, and congestion status yielded similar results. There was no association of dose/dose change with incidence of either worsening CHF or hyperkalemia. In patients with systolic CHF and stable CKD stage III/IV, neither continuation of high doses of ACEI/ARB nor up-titration was related to adverse changes in longer-term renal function. Conversely, down-titration was not associated with improvement in eGFR. Use of high doses of ACEI/ARB and their up-titration in patients with CHF and CKD III/IV may be appropriate provided that the patient is adequately monitored. Copyright © 2016 Elsevier Inc. All rights reserved.

Estradiol improves cardiac and hepatic function after trauma-hemorrhage: role of enhanced heat shock protein expression.

PubMed

Szalay, László; Shimizu, Tomoharu; Suzuki, Takao; Yu, Huang-Ping; Choudhry, Mashkoor A; Schwacha, Martin G; Rue, Loring W; Bland, Kirby I; Chaudry, Irshad H

2006-03-01

Although studies indicate that 17beta-estradiol administration after trauma-hemorrhage (T-H) improves cardiac and hepatic functions, the underlying mechanisms remain unclear. Because the induction of heat shock proteins (HSPs) can protect cardiac and hepatic functions, we hypothesized that these proteins contribute to the salutary effects of estradiol after T-H. To test this hypothesis, male Sprague-Dawley rats ( approximately 300 g) underwent laparotomy and hemorrhagic shock (35-40 mmHg for approximately 90 min) followed by resuscitation with four times the shed blood volume in the form of Ringer lactate. 17beta-estradiol (1 mg/kg body wt) was administered at the end of the resuscitation. Five hours after T-H and resuscitation there was a significant decrease in cardiac output, positive and negative maximal rate of left ventricular pressure. Liver function as determined by bile production and indocyanine green clearance was also compromised after T-H and resuscitation. This was accompanied by an increase in plasma alanine aminotransferase (ALT) levels and liver perfusate lactic dehydrogenase levels. Furthermore, circulating levels of TNF-alpha, IL-6, and IL-10 were also increased. In addition to decreased cardiac and hepatic function, there was an increase in cardiac HSP32 expression and a reduction in HSP60 expression after T-H. In the liver, HSP32 and HSP70 were increased after T-H. There was no change in heart HSP70 and liver HSP60 after T-H and resuscitation. Estradiol administration at the end of T-H and resuscitation increased heart/liver HSPs expression, ameliorated the impairment of heart/liver functions, and significantly prevented the increase in plasma levels of ALT, TNF-alpha, and IL-6. The ability of estradiol to induce HSPs expression in the heart and the liver suggests that HSPs, in part, mediate the salutary effects of 17beta-estradiol on organ functions after T-H.

Review and Analysis of Existing Mobile Phone Apps to Support Heart Failure Symptom Monitoring and Self-Care Management Using the Mobile Application Rating Scale (MARS).

PubMed

Masterson Creber, Ruth M; Maurer, Mathew S; Reading, Meghan; Hiraldo, Grenny; Hickey, Kathleen T; Iribarren, Sarah

2016-06-14

Heart failure is the most common cause of hospital readmissions among Medicare beneficiaries and these hospitalizations are often driven by exacerbations in common heart failure symptoms. Patient collaboration with health care providers and decision making is a core component of increasing symptom monitoring and decreasing hospital use. Mobile phone apps offer a potentially cost-effective solution for symptom monitoring and self-care management at the point of need. The purpose of this review of commercially available apps was to identify and assess the functionalities of patient-facing mobile health apps targeted toward supporting heart failure symptom monitoring and self-care management. We searched 3 Web-based mobile app stores using multiple terms and combinations (eg, "heart failure," "cardiology," "heart failure and self-management"). Apps meeting inclusion criteria were evaluated using the Mobile Application Rating Scale (MARS), IMS Institute for Healthcare Informatics functionality scores, and Heart Failure Society of America (HFSA) guidelines for nonpharmacologic management. Apps were downloaded and assessed independently by 2-4 reviewers, interclass correlations between reviewers were calculated, and consensus was met by discussion. Of 3636 potentially relevant apps searched, 34 met inclusion criteria. Most apps were excluded because they were unrelated to heart failure, not in English or Spanish, or were games. Interrater reliability between reviewers was high. AskMD app had the highest average MARS total (4.9/5). More than half of the apps (23/34, 68%) had acceptable MARS scores (>3.0). Heart Failure Health Storylines (4.6) and AskMD (4.5) had the highest scores for behavior change. Factoring MARS, functionality, and HFSA guideline scores, the highest performing apps included Heart Failure Health Storylines, Symple, ContinuousCare Health App, WebMD, and AskMD. Peer-reviewed publications were identified for only 3 of the 34 apps. This review suggests that few apps meet prespecified criteria for quality, content, or functionality, highlighting the need for further refinement and mapping to evidence-based guidelines and room for overall quality improvement in heart failure symptom monitoring and self-care related apps.

Family Partner Intervention Influences Self-Care Confidence and Treatment Self-Regulation in Patients with Heart Failure

PubMed Central

Stamp, Kelly D.; Dunbar, Sandra B.; Clark, Patricia C.; Reilly, Carolyn M.; Gary, Rebecca A.; Higgins, Melinda; Ryan, Richard M

2015-01-01

Background Heart failure self-care requires confidence in one’s ability and motivation to perform a recommended behavior. Most self-care occurs within a family context, yet little is known about the influence of family on heart failure self-care or motivating factors. Aims To examine the association of family functioning and the self-care antecedents of confidence and motivation among heart failure participants and determine if a family partnership intervention would promote higher levels of perceived confidence and treatment self-regulation (motivation) at four and eight months compared to patient-family education or usual care groups. Methods Heart failure patients (N = 117) and a family member were randomized to a family partnership intervention, patient-family education or usual care groups. Measures of patient’s perceived family functioning, confidence, motivation for medications and following a low-sodium diet were analyzed. Data were collected at baseline, four and eight months. Results Family functioning was related to self-care confidence for diet (p=.02) and autonomous motivation for adhering to their medications (p=.05 and diet p=0.2). The family partnership intervention group significantly improved confidence (p=.05) and motivation (medications (p=.004; diet p=.012) at four months whereas patient-family education group and usual care did not change. Conclusion Perceived confidence and motivation for self-care was enhanced by family partnership intervention, regardless of family functioning. Poor family functioning at baseline contributed to lower confidence. Family functioning should be assessed to guide tailored family-patient interventions for better outcomes. PMID:25673525

Cardioankle vascular index evaluations revealed that cotreatment of ARB Antihypertension medication with traditional Chinese medicine improved arterial functionality.

PubMed

Xu, Yan; Yan, Hua; Yao, Min J; Ma, Jie; Jia, Jun M; Ruan, Fen X; Yao, Zeng C; Huang, Hua M; Zheng, Jing; Chen, Ting; Lv, Hua; Endler, Alexander M

2013-05-01

Qian Yang He Ji (QYHJ) is a traditional Chinese medicine composed of Digitalis purpurea, Uncaria gambir, Fructus tribuli terrestris, and Ligustrum lucidum. Here, we explored whether combining an antihypertensive angiotensin II receptor blocker (ARB) therapy with QYHJ can improve the arterial functionality of hypertensive patients. One hundred and eight hypertensive patients were randomized into 2 groups; 1 group (n = 53) was treated with ARB and the other group (n = 55) was treated with ARB combined with QYHJ. Each of the 2 groups included 3 subgroups (pure hypertension, hypertension with diabetes, and hypertension with coronary heart disease) and was further divided into patients with and without complications. The cardioankle vascular index and intima-media thickness and pulse pressure were the outcome evaluation parameter. Combined QYHJ and ARB treatment reduced the values of cardioankle vascular index, systolic blood pressure, diastolic blood pressure, and pulse pressure to significantly lower levels than ARB treatment alone did in hypertension patients after 6 months of treatment. ARB improves hypertension, but a combined QYHJ treatment can additionally ameliorate the arterial functionality not only in solely hypertensive patients but also in hypertensive patients with diabetes and coronary heart disease complications. QYHJ coapplication might be a choice to further improve the arterial functionality during an ARB hypertension treatment.

Cardiac consequences to skeletal muscle-centric therapeutics for Duchenne muscular dystrophy.

PubMed

Townsend, DeWayne; Yasuda, Soichiro; Chamberlain, Jeffrey; Metzger, Joseph M

2009-02-01

Duchenne muscular dystrophy (DMD) is a fatal disease of muscle deterioration. Duchenne muscular dystrophy affects all striated muscles in the body, including the heart. Recent advances in palliative care, largely directed at improving respiratory function, have extended life but paradoxically further unmasked emergent heart disease in DMD patients. New experimental strategies have shown promise in restoring dystrophin in the skeletal muscles of dystrophin- deficient animals. These strategies often have little or no capacity for restitution of dystrophin in the hearts of these animals. This article draws on both clinical data and recent experimental data to posit that effective skeletal muscle restricted therapies for DMD will paradoxically heighten cardiomyopathy and heart failure in these patients.

Heart-rate reduction by If-channel inhibition with ivabradine restores collateral artery growth in hypercholesterolemic atherosclerosis.

PubMed

Schirmer, Stephan H; Degen, Achim; Baumhäkel, Magnus; Custodis, Florian; Schuh, Lisa; Kohlhaas, Michael; Friedrich, Erik; Bahlmann, Ferdinand; Kappl, Reinhard; Maack, Christoph; Böhm, Michael; Laufs, Ulrich

2012-05-01

Collateral arteries protect tissue from ischaemia. Heart rate correlates with vascular events in patients with arterial obstructive disease. Here, we tested the effect of heart-rate reduction (HRR) on collateral artery growth. The I(f)-channel inhibitor ivabradine reduced heart rate by 11% in wild-type and 15% in apolipoprotein E (ApoE)(-/-) mice and restored endothelium-dependent relaxation in aortic rings of ApoE(-/-) mice. Microsphere perfusion and angiographies demonstrated that ivabradine did not change hindlimb perfusion in wild-type mice but improved perfusion in ApoE(-/-) mice from 40.5 ± 15.8-60.2 ± 18.5% ligated/unligated hindlimb. Heart rate reduction (13%) with metoprolol failed to improve endothelial function and perfusion. Protein expression of endothelial nitric oxide synthase (eNOS), phosphorylated eNOS, and eNOS activity were increased in collateral tissue following ivabradine treatment of ApoE(-/-) mice. Co-treatment with nitric oxide-inhibitor N (G)-nitro-L-arginine methyl ester abolished the effects of ivabradine on arteriogenesis. Following ivabradine, classical inflammatory cytokine expression was lowered in ApoE(-/-) circulating mononuclear cells and in plasma, but unaltered in collateral-containing hindlimb tissue, where numbers of perivascular macrophages also remained unchanged. However, ivabradine reduced expression of anti-arteriogenic cytokines CXCL10and CXCL11 and of smooth muscle cell markers smoothelin and desmin in ApoE(-/-) hindlimb tissue. Endothelial nitric oxide synthase and inflammatory cytokine expression were unchanged in wild-type mice. Ivabradine did not affect cytokine production in HUVECs and THP1 mononuclear cells and had no effect on the membrane potential of HUVECs in patch-clamp experiments. Ivabradine-induced HRR stimulates adaptive collateral artery growth. Important contributing mechanisms include improved endothelial function, eNOS activity, and modulation of inflammatory cytokine gene expression.

Home inotropic therapy in advanced heart failure: cost analysis and clinical outcomes.

PubMed

Harjai, K J; Mehra, M R; Ventura, H O; Lapeyre, Y M; Murgo, J P; Stapleton, D D; Smart, F W

1997-11-05

This study was conducted to assess cost savings and clinical outcomes associated with the use of home i.v. inotropic therapy in patients with advanced (New York Heart Association [NYHA] class IV) heart failure. Retrospective analysis. Tertiary care referral center. Twenty-four patients (13 men, 11 women; age, 61+/-12 years) with left ventricular ejection fraction <30% and heart failure refractory to oral agents required home i.v. inotropic therapy for at least 4 consecutive weeks between May 1994 and April 1996. Inotropic agents used included dobutamine (n=20; dose, 5.0+/-2.2 microg/kg/min) or milrinone (n=7; dose, 0.53+/-0.05 microg/kg/min). Cost of care and clinical outcomes (hospital admissions, length of hospital stay, NYHA functional class) were compared during the period of inotropic therapy (study period) and the immediate preceding period of equal duration (control period). In comparison to the control period, the study period (3.9+/-2.7 months) was associated with a 16% reduction in cost, amounting to a calculated savings of $5,700 per patient or $1,465 per patient per month. Concomitantly, a decrease in the number of hospital admissions from 2.7+/-2.6 to 1.3+/-1.3 (p=0.056) and length of hospital stay from 20.9+/-12.7 to 5.5+/-5.4 days (p=0.0004) was observed with improvement in NYHA functional class from 4.0+/-0.0 to 2.7+/-0.9 (p<0.0001). Eight patients (38%) died after 2.8+/-1.7 months of home i.v. inotropic therapy. Home i.v. inotropic therapy reduces hospital admissions, length of stay, and cost of care and improves functional class in patients with advanced (NYHA class IV) heart failure.

Cardio-protection of ultrafine granular powder for Salvia miltiorrhiza Bunge against myocardial infarction.

PubMed

Wang, Linlin; Li, Yuanmin; Deng, Wen; Dong, Zhihui; Li, Xue; Liu, Dan; Zhao, Lijie; Fu, Weiguo; Cho, Kenka; Niu, Huaying; Guo, Dean; Cheng, Jinle; Jiang, Baohong

2018-08-10

Myocardial infarction (MI) is considered as the major inducer to the morbidity and mortality related to coronary occlusion. Salvia miltiorrhiza Bunge is widely applied in the clinic for the prevention and treatment of heart diseases. The preparation of traditional herb decoction (THD) is not only time consuming but also difficult to keep uniform for every time. New usage form of Salvia miltiorrhiza Bunge with characteristics of convenience, uniform and efficiency is needed. The aims of present study were to investigate the cardio-protection of ultrafine granular powder (UGP) of Salvia miltiorrhiza Bunge; and further compare the characteristics of UGP with THD. MI was induced by ligation of the left anterior descending coronary artery near the main pulmonary artery. Cardio-protection of UGP or THD was evaluated based on two sets of experiments, one was acute myocardial infarction (AMI) through 7 days preventive administration, and the other one was chronic cardiac remodeling through 28 days therapeutic administration. Hemodynamic measurement was conducted to evaluate heart function and histopathological detection was used to evaluate heart structure. No significant improvement of heart structure and function was detected for preventive administration of UGP or THD on AMI rats. While, more significant improvements on left ventricular systolic and diastolic function were detected with therapeutic treatment with 0.81 g/kg UGP than same dose of THD on rats against chronic cardiac remodeling. Both UGP and THD showed the protective effects on heart structure, especially against fibrosis with long-term therapeutic treatment. As a new usage form of Salvia miltiorrhiza Bunge, UGP showed significant cardio-protection against myocardial remodeling with therapeutic treatment. Comparing with THD, UGP also holds the advantages of uniform, convenience and efficiency. Copyright © 2018 Elsevier B.V. All rights reserved.

The evaluation of clinical therapy effects of oral western medicine combined with magnetic pulse acupoint stimulation in treating elderly patients with coronary heart disease.

PubMed

Fu, Xin; Guo, Li; Jiang, Zheng-Ming; Xu, Ai-Guo

2015-01-01

Treat the patients suffered from coronary heart disease with oral western medicine, combining with magnetic pulse acupoint stimulation, and observe the therapeutic effects of such combination therapy method. 56 old people with coronary heart disease are randomly divided into a treatment group and a control group. Both groups of patients are treated by the routine drugs, in addition, the patients of the treatment group are treated by magnetic pulse therapy additionally. Compare clinical symptoms, blood lipid and blood rheological indexes of the patients in the two groups when they are selected and after 30 days' treatment. after 30 days' treatment, it is found that clinical symptoms, blood lipid and blood rheological indexes of the patients in the treatment group are significantly improved compared with those when they are selected and those of the control group (P<0.05). patients with coronary heart disease, treated by pulsed magnetic therapy and the conventional drug intervention, had relieved synptom, improve blood lipid and heart blood supply function.

The evaluation of clinical therapy effects of oral western medicine combined with magnetic pulse acupoint stimulation in treating elderly patients with coronary heart disease

PubMed Central

Fu, Xin; Guo, Li; Jiang, Zheng-Ming; Xu, Ai-Guo

2015-01-01

Objective: Treat the patients suffered from coronary heart disease with oral western medicine, combining with magnetic pulse acupoint stimulation, and observe the therapeutic effects of such combination therapy method. Methods: 56 old people with coronary heart disease are randomly divided into a treatment group and a control group. Both groups of patients are treated by the routine drugs, in addition, the patients of the treatment group are treated by magnetic pulse therapy additionally. Compare clinical symptoms, blood lipid and blood rheological indexes of the patients in the two groups when they are selected and after 30 days’ treatment. Results: after 30 days’ treatment, it is found that clinical symptoms, blood lipid and blood rheological indexes of the patients in the treatment group are significantly improved compared with those when they are selected and those of the control group (P<0.05). Conclusion: patients with coronary heart disease, treated by pulsed magnetic therapy and the conventional drug intervention, had relieved synptom, improve blood lipid and heart blood supply function. PMID:26309664

An Implantable Extracardiac Soft Robotic Device for the Failing Heart: Mechanical Coupling and Synchronization.

PubMed

Payne, Christopher J; Wamala, Isaac; Abah, Colette; Thalhofer, Thomas; Saeed, Mossab; Bautista-Salinas, Daniel; Horvath, Markus A; Vasilyev, Nikolay V; Roche, Ellen T; Pigula, Frank A; Walsh, Conor J

2017-09-01

Soft robotic devices have significant potential for medical device applications that warrant safe synergistic interaction with humans. This article describes the optimization of an implantable soft robotic system for heart failure whereby soft actuators wrapped around the ventricles are programmed to contract and relax in synchrony with the beating heart. Elastic elements integrated into the soft actuators provide recoiling function so as to aid refilling during the diastolic phase of the cardiac cycle. Improved synchronization with the biological system is achieved by incorporating the native ventricular pressure into the control system to trigger assistance and synchronize the device with the heart. A three-state electro-pneumatic valve configuration allows the actuators to contract at different rates to vary contraction patterns. An in vivo study was performed to test three hypotheses relating to mechanical coupling and temporal synchronization of the actuators and heart. First, that adhesion of the actuators to the ventricles improves cardiac output. Second, that there is a contraction-relaxation ratio of the actuators which generates optimal cardiac output. Third, that the rate of actuator contraction is a factor in cardiac output.

[Heart transplantation for the treatment of isolated left ventricular myocardial noncompaction. First case in Mexico].

PubMed

Zetina-Tun, Hugo Jesús; Careaga-Reyna, Guillermo; Galván-Díaz, José; Sánchez-Uribe, Magdalena

Myocardial noncompaction of the left ventricle is a congenital cardiomyopathy characterised by left ventricular hypertrabeculation and prominent intertrabecular recesses. The incidence ranges from 0.15% to 2.2%. Clinical manifestations include heart failure, arrhythmias, and stroke. Prognosis is fatal in most cases. Heart transplantation is a therapeutic option for this cardiomyopathy, and few had been made worldwide. The case is presented of a 20 year-old male with noncompacted myocardium of the left ventricle, who had clinical signs of heart failure. His functional class was IV on the New York Heart Association scale. He was successfully transplanted. Its survival to 15 months is optimal in class I New York Heart Association, and endomyocardial biopsies have been reported without evidence of acute rejection. It is concluded that heart transplantation modified the natural history and improved survival in patients with this congenital heart disease. Copyright © 2016 Academia Mexicana de Cirugía A.C. Publicado por Masson Doyma México S.A. All rights reserved.

Exercise training in Tgαq*44 mice during the progression of chronic heart failure: cardiac vs. peripheral (soleus muscle) impairments to oxidative metabolism.

PubMed

Grassi, Bruno; Majerczak, Joanna; Bardi, Eleonora; Buso, Alessia; Comelli, Marina; Chlopicki, Stefan; Guzik, Magdalena; Mavelli, Irene; Nieckarz, Zenon; Salvadego, Desy; Tyrankiewicz, Urszula; Skórka, Tomasz; Bottinelli, Roberto; Zoladz, Jerzy A; Pellegrino, Maria Antonietta

2017-08-01

Cardiac function, skeletal (soleus) muscle oxidative metabolism, and the effects of exercise training were evaluated in a transgenic murine model (Tgα q *44) of chronic heart failure during the critical period between the occurrence of an impairment of cardiac function and the stage at which overt cardiac failure ensues (i.e., from 10 to 12 mo of age). Forty-eight Tgα q *44 mice and 43 wild-type FVB controls were randomly assigned to control groups and to groups undergoing 2 mo of intense exercise training (spontaneous running on an instrumented wheel). In mice evaluated at the beginning and at the end of training we determined: exercise performance (mean distance covered daily on the wheel); cardiac function in vivo (by magnetic resonance imaging); soleus mitochondrial respiration ex vivo (by high-resolution respirometry); muscle phenotype [myosin heavy chain (MHC) isoform content; citrate synthase (CS) activity]; and variables related to the energy status of muscle fibers [ratio of phosphorylated 5'-AMP-activated protein kinase (AMPK) to unphosphorylated AMPK] and mitochondrial biogenesis and function [peroxisome proliferative-activated receptor-γ coactivator-α (PGC-1α)]. In the untrained Tgα q *44 mice functional impairments of exercise performance, cardiac function, and soleus muscle mitochondrial respiration were observed. The impairment of mitochondrial respiration was related to the function of complex I of the respiratory chain, and it was not associated with differences in CS activity, MHC isoforms, p-AMPK/AMPK, and PGC-1α levels. Exercise training improved exercise performance and cardiac function, but it did not affect mitochondrial respiration, even in the presence of an increased percentage of type 1 MHC isoforms. Factors "upstream" of mitochondria were likely mainly responsible for the improved exercise performance. NEW & NOTEWORTHY Functional impairments in exercise performance, cardiac function, and soleus muscle mitochondrial respiration were observed in transgenic chronic heart failure mice, evaluated in the critical period between the occurrence of an impairment of cardiac function and the terminal stage of the disease. Exercise training improved exercise performance and cardiac function, but it did not affect the impaired mitochondrial respiration. Factors "upstream" of mitochondria, including an enhanced cardiovascular O 2 delivery, were mainly responsible for the functional improvement. Copyright © 2017 the American Physiological Society.

A concentrated parameter model for the human cardiovascular system including heart valve dynamics and atrioventricular interaction.

PubMed

Korakianitis, Theodosios; Shi, Yubing

2006-09-01

Numerical modeling of the human cardiovascular system has always been an active research direction since the 19th century. In the past, various simulation models of different complexities were proposed for different research purposes. In this paper, an improved numerical model to study the dynamic function of the human circulation system is proposed. In the development of the mathematical model, the heart chambers are described with a variable elastance model. The systemic and pulmonary loops are described based on the resistance-compliance-inertia concept by considering local effects of flow friction, elasticity of blood vessels and inertia of blood in different segments of the blood vessels. As an advancement from previous models, heart valve dynamics and atrioventricular interaction, including atrial contraction and motion of the annulus fibrosus, are specifically modeled. With these improvements the developed model can predict several important features that were missing in previous numerical models, including regurgitant flow on heart valve closure, the value of E/A velocity ratio in mitral flow, the motion of the annulus fibrosus (called the KG diaphragm pumping action), etc. These features have important clinical meaning and their changes are often related to cardiovascular diseases. Successful simulation of these features enhances the accuracy of simulations of cardiovascular dynamics, and helps in clinical studies of cardiac function.

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.

Telerehabilitation for patients with heart failure.

PubMed

Tousignant, Michel; Mampuya, Warner Mbuila

2015-02-01

Heart failure is a chronic and progressive condition that is associated with high morbidity and mortality rates. Even though cardiac rehabilitation (CR) has been shown to be beneficial to heart failure patients, only a very small proportion of them will actually be referred and eventually participate. The low participation rate is due in part to accessibility and travel difficulties. Telerehabilitation is a new approach in the rehabilitation field that allows patients to receive a complete rehabilitation program at home in a safe manner and under adequate supervision. We believe that by increasing accessibility to CR, telerehabilitation programs will significantly improve heart failure patients' functional capacity and quality of life. However, it is crucial to provide policy makers with evidence-based data on cardiac telerehabilitation if we want to see its successful implementation in heart failure patients.

Adaptive servo ventilation improves Cheyne-Stokes respiration, cardiac function, and prognosis in chronic heart failure patients with cardiac resynchronization therapy.

PubMed

Miyata, Makiko; Yoshihisa, Akiomi; Suzuki, Satoshi; Yamada, Shinya; Kamioka, Masashi; Kamiyama, Yoshiyuki; Yamaki, Takayoshi; Sugimoto, Koichi; Kunii, Hiroyuki; Nakazato, Kazuhiko; Suzuki, Hitoshi; Saitoh, Shu-ichi; Takeishi, Yasuchika

2012-09-01

Cheyne-Stokes respiration (CSR-CSA) is often observed in patients with chronic heart failure (CHF). Although cardiac resynchronization therapy (CRT) is effective for CHF patients with left ventricular dyssynchrony, it is still unclear whether adaptive servo ventilation (ASV) improves cardiac function and prognosis of CHF patients with CSR-CSA after CRT. Twenty two patients with CHF and CSR-CSA after CRT defibrillator (CRTD) implantation were enrolled in the present study and randomly assigned into two groups: 11 patients treated with ASV (ASV group) and 11 patients treated without ASV (non-ASV group). Measurement of plasma B-type natriuretic peptide (BNP) levels (before 3, and 6 months later) and echocardiography (before and 6 months) were performed in each group. Patients were followed up to register cardiac events (cardiac death and re-hospitalization) after discharge. In the ASV group, indices for apnea-hypopnea, central apnea, and oxyhemoglobin saturation were improved on ASV. BNP levels, cardiac systolic and diastolic function were improved with ASV treatment for 6 months. Importantly, the event-free rate was significantly higher in the ASV group than in the non-ASV group. ASV improves CSR-CSA, cardiac function, and prognosis in CHF patients with CRTD. Patients with CSR-CSA and post CRTD implantation would get benefits by treatment with ASV. Copyright © 2012 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.

Cannabinoid receptor 1 inhibition improves cardiac function and remodelling after myocardial infarction and in experimental metabolic syndrome.

PubMed

Slavic, Svetlana; Lauer, Dilyara; Sommerfeld, Manuela; Kemnitz, Ulrich Rudolf; Grzesiak, Aleksandra; Trappiel, Manuela; Thöne-Reineke, Christa; Baulmann, Johannes; Paulis, Ludovit; Kappert, Kai; Kintscher, Ulrich; Unger, Thomas; Kaschina, Elena

2013-07-01

The cannabinoid receptors, CB1 and CB2, are expressed in the heart, but their role under pathological conditions remains controversial. This study examined the effect of CB1 receptor blockade on cardiovascular functions after experimental MI and in experimental metabolic syndrome. MI was induced in Wistar rats by permanent ligation of the left coronary artery. Treatment with the CB1 receptor antagonist rimonabant (10 mg/kg i.p. daily) started 7 days before or 6 h after MI and continued for 6 weeks. Haemodynamic parameters were measured via echocardiography and intracardiac Samba catheter. CB1 blockade improved systolic and diastolic heart function, decreased cardiac collagen and hydroxyproline content and down-regulated TGF-β1. Additionally, rimonabant decreased arterial stiffness, normalised QRS complex duration and reduced brain natriuretic peptide levels in serum. In primary cardiac fibroblasts, rimonabant decreased MMP-9 activity and TGF-β1 expression. Furthermore, rimonabant improved depressed systolic function of spontaneously hypertensive obese rats and reduced weight gain. Blocking of CB1 receptor with rimonabant improves cardiac functions in the early and late stages after MI, decreases arterial stiffness and reduces cardiac remodelling. Rimonabant also has cardioprotective actions in rats characterised by the metabolic syndrome. Inhibition of proteolysis and TGF-β1 expression and reduced collagen content by rimonabant may attenuate destruction of the extracellular matrix and decrease fibrosis after MI.

Cardiac myofibrillar contractile properties during the progression from hypertension to decompensated heart failure.

PubMed

Hanft, Laurin M; Emter, Craig A; McDonald, Kerry S

2017-07-01

Heart failure arises, in part, from a constellation of changes in cardiac myocytes including remodeling, energetics, Ca 2+ handling, and myofibrillar function. However, little is known about the changes in myofibrillar contractile properties during the progression from hypertension to decompensated heart failure. The aim of the present study was to provide a comprehensive assessment of myofibrillar functional properties from health to heart disease. A rodent model of uncontrolled hypertension was used to test the hypothesis that myocytes in compensated hearts exhibit increased force, higher rates of force development, faster loaded shortening, and greater power output; however, with progression to overt heart failure, we predicted marked depression in these contractile properties. We assessed contractile properties in skinned cardiac myocyte preparations from left ventricles of Wistar-Kyoto control rats and spontaneous hypertensive heart failure (SHHF) rats at ~3, ~12, and >20 mo of age to evaluate the time course of myofilament properties associated with normal aging processes compared with myofilaments from rats with a predisposition to heart failure. In control rats, the myofilament contractile properties were virtually unchanged throughout the aging process. Conversely, in SHHF rats, the rate of force development, loaded shortening velocity, and power all increased at ~12 mo and then significantly fell at the >20-mo time point, which coincided with a decrease in left ventricular fractional shortening. Furthermore, these changes occurred independent of changes in β-myosin heavy chain but were associated with depressed phosphorylation of myofibrillar proteins, and the fall in loaded shortening and peak power output corresponded with the onset of clinical signs of heart failure. NEW & NOTEWORTHY This novel study systematically examined the power-generating capacity of cardiac myofilaments during the progression from hypertension to heart disease. Previously undiscovered changes in myofibrillar power output were found and were associated with alterations in myofilament proteins, providing potential new targets to exploit for improved ventricular pump function in heart failure. Copyright © 2017 the American Physiological Society.

Making Better Scar: Emerging Approaches for Modifying Mechanical and Electrical Properties Following Infarction and Ablation

PubMed Central

Holmes, Jeffrey W.; Laksman, Zachary; Gepstein, Lior

2015-01-01

Following myocardial infarction (MI), damaged myocytes are replaced by collagenous scar tissue, which serves an important mechanical function – maintaining integrity of the heart wall against enormous mechanical forces – but also disrupts electrical function as structural and electrical remodeling in the infarct and borderzone predispose to re-entry and ventricular tachycardia. Novel emerging regenerative approaches aim to replace this scar tissue with viable myocytes. Yet an alternative strategy of therapeutically modifying selected scar properties may also prove important, and in some cases may offer similar benefits with lower risk or regulatory complexity. Here, we review potential goals for such modifications as well as recent proof-of-concept studies employing specific modifications, including gene therapy to locally increase conduction velocity or prolong the refractory period in and around the infarct scar, and modification of scar anisotropy to improve regional mechanics and pump function. Another advantage of scar modification techniques is that they have applications well beyond MI. In particular, ablation treats electrical abnormalities of the heart by intentionally generating scar to block aberrant conduction pathways. Yet in diseases such as atrial fibrillation (AF) where ablation can be extensive, treating the electrical disorder can significantly impair mechanical function. Creating smaller, denser scars that more effectively block conduction, and choosing the location of those lesions by balancing their electrical and mechanical impacts, could significantly improve outcomes for AF patients. We review some recent advances in this area, including the use of computational models to predict the mechanical effects of specific lesion sets and gene therapy for functional ablation. Overall, emerging techniques for modifying scar properties represents a potentially important important set of tools for improving patient outcomes across a range of heart diseases, whether used in place of or as an adjunct to regenerative approaches. PMID:26615948

Psychoeducational support to post cardiac surgery heart failure patients and their partners--a randomised pilot study.

PubMed

Ågren, Susanna; Berg, Sören; Svedjeholm, Rolf; Strömberg, Anna

2015-02-01

Postoperative heart failure is a serious complication that changes the lives of both the person who is critically ill and family in many ways. The purpose of this study was to evaluate the effects of an intervention in postoperative heart failure patient-partner dyads regarding health, symptoms of depression and perceived control. Pilot study with a randomised controlled design evaluating psychosocial support and education from an interdisciplinary team. Patients with postoperative heart failure and their partners. SF-36, Beck Depression Inventory, Perceived Control at baseline, 3 and 12 months. A total of 42 patient-partner completed baseline assessment. Partners in the intervention group increased health in the role emotional and mental health dimensions and patients increased health in vitality, social function and mental health dimensions compared with the control group. Patients' perceived control improved significantly in the intervention group over time. Psychoeducational support to post cardiac surgery heart failure dyads improved health in both patients and partners at short term follow-up and improved patients' perceived control at both short and long-term follow-up. Psychoeducational support appears to be a promising intervention but the results need to be confirmed in larger studies. Copyright © 2014 Elsevier Ltd. All rights reserved.

Transjugular intrahepatic portosystemic shunt: impact on systemic hemodynamics and renal and cardiac function in patients with cirrhosis.

PubMed

Busk, Troels M; Bendtsen, Flemming; Poulsen, Jørgen H; Clemmesen, Jens O; Larsen, Fin S; Goetze, Jens P; Iversen, Jens S; Jensen, Magnus T; Møgelvang, Rasmus; Pedersen, Erling B; Bech, Jesper N; Møller, Søren

2018-02-01

Transjugular intrahepatic portosystemic shunt (TIPS) alleviates portal hypertension and possibly increases central blood volume (CBV). Moreover, renal function often improves; however, its effects on cardiac function are unclear. The aims of our study were to examine the effects of TIPS on hemodynamics and renal and cardiac function in patients with cirrhosis. In 25 cirrhotic patients, we analyzed systemic, cardiac, and splanchnic hemodynamics by catheterization of the liver veins and right heart chambers before and 1 wk after TIPS. Additionally, we measured renal and cardiac markers and performed advanced echocardiography before, 1 wk after, and 4 mo after TIPS. CBV increased significantly after TIPS (+4.6%, P < 0.05). Cardiac output (CO) increased (+15.3%, P < 0.005) due to an increase in stroke volume (SV) (+11.1%, P < 0.005), whereas heart rate (HR) was initially unchanged. Cardiopulmonary pressures increased after TIPS, whereas copeptin, a marker of vasopressin, decreased (-18%, P < 0.005) and proatrial natriuretic peptide increased (+52%, P < 0.0005) 1 wk after TIPS and returned to baseline 4 mo after TIPS. Plasma neutrophil gelatinase-associated lipocalin, renin, aldosterone, and serum creatinine decreased after TIPS (-36%, P < 0.005; -65%, P < 0.05; -90%, P < 0.005; and -13%, P < 0.005, respectively). Echocardiography revealed subtle changes in cardiac function after TIPS, although these were within the normal range. TIPS increases CBV by increasing CO and SV, whereas HR is initially unaltered. These results indicate an inability to increase the heart rate in response to a hemodynamic challenge that only partially increases CBV after TIPS. These changes, however, are sufficient for improving renal function. NEW & NOTEWORTHY For the first time, we have combined advanced techniques to study the integrated effects of transjugular intrahepatic portosystemic shunt (TIPS) in cirrhosis. We showed that TIPS increases central blood volume (CBV) through improved cardiac inotropy. Advanced echocardiography demonstrated that myocardial function was unaffected by the dramatic increase in preload after TIPS. Finally, renal function improved due to the increase in CBV. Recognition of these physiological changes significantly contributes to our clinical understanding of TIPS.

Remote monitoring of heart failure: benefits for therapeutic decision making.

PubMed

Martirosyan, Mihran; Caliskan, Kadir; Theuns, Dominic A M J; Szili-Torok, Tamas

2017-07-01

Chronic heart failure is a cardiovascular disorder with high prevalence and incidence worldwide. The course of heart failure is characterized by periods of stability and instability. Decompensation of heart failure is associated with frequent and prolonged hospitalizations and it worsens the prognosis for the disease and increases cardiovascular mortality among affected patients. It is therefore important to monitor these patients carefully to reveal changes in their condition. Remote monitoring has been designed to facilitate an early detection of adverse events and to minimize regular follow-up visits for heart failure patients. Several new devices have been developed and introduced to the daily practice of cardiology departments worldwide. Areas covered: Currently, special tools and techniques are available to perform remote monitoring. Concurrently there are a number of modern cardiac implantable electronic devices that incorporate a remote monitoring function. All the techniques that have a remote monitoring function are discussed in this paper in detail. All the major studies on this subject have been selected for review of the recent data on remote monitoring of HF patients and demonstrate the role of remote monitoring in the therapeutic decision making for heart failure patients. Expert commentary: Remote monitoring represents a novel intensified follow-up strategy of heart failure management. Overall, theoretically, remote monitoring may play a crucial role in the early detection of heart failure progression and may improve the outcome of patients.

Effects of a novel immune modulation therapy in patients with advanced chronic heart failure: results of a randomized, controlled, phase II trial.

PubMed

Torre-Amione, Guillermo; Sestier, François; Radovancevic, Branislav; Young, James

2004-09-15

We sought to determine whether a novel, non-pharmacological form of immune modulation therapy (IMT), shown experimentally to reduce inflammatory and increase anti-inflammatory cytokines, improved outcomes in patients with advanced heart failure (HF). Immune activation contributes to the progression of HF, but treatments directed against inflammation have been largely unsuccessful. Seventy-five HF patients (New York Heart Association [NYHA] functional class III to IV) were randomized to receive either IMT (n = 38) or placebo (n = 37) in a double-blind trial for six months, with continuation of standard HF therapy. Patients were evaluated using the 6-min walk test, changes in NYHA functional class, cardiac function, and quality of life assessments, as well as occurrence of death and hospitalization. There was no between-group difference in 6-min walk test, but 15 IMT patients (compared with 9 placebo) improved NYHA functional classification by at least one class (p = 0.140). The Kaplan-Meier survival analysis showed that IMT significantly reduced the risk of death (p = 0.022) and hospitalization (p = 0.008). Analysis of a clinical composite score demonstrated a significant between-group difference (p = 0.006). There was no difference in left ventricular ejection fraction, but there was a trend toward improved quality of life (p = 0.110). These preliminary findings are consistent with the hypothesis that immune activation is important in the pathogenesis of HF and establish the basis for a phase III trial to define the benefit of IMT in chronic HF.

Does quantitative left ventricular regional wall motion change after fibrous tissue resection in endomyocardial fibrosis?

PubMed

Salemi, Vera Maria Cury; Fernandes, Fabio; Sirvente, Raquel; Nastari, Luciano; Rosa, Leonardo Vieira; Ferreira, Cristiano A; Pena, José Luiz Barros; Picard, Michael H; Mady, Charles

2009-01-01

We compared left ventricular regional wall motion, the global left ventricular ejection fraction, and the New York Heart Association functional class pre- and postoperatively. Endomyocardial fibrosis is characterized by fibrous tissue deposition in the endomyocardium of the apex and/or inflow tract of one or both ventricles. Although left ventricular global systolic function is preserved, patients exhibit wall motion abnormalities in the apical and inferoapical regions. Fibrous tissue resection in New York Heart Association FC III and IV endomyocardial fibrosis patients has been shown to decrease morbidity and mortality. We prospectively studied 30 patients (20 female, 30+/-10 years) before and 5+/-8 months after surgery. The left ventricular ejection fraction was determined using the area-length method. Regional left ventricular motion was measured by the centerline method. Five left ventricular segments were analyzed pre- and postoperatively. Abnormality was expressed in units of standard deviation from the mean motion in a normal reference population. Left ventricular wall motion in the five regions did not differ between pre- and postoperative measurements. Additionally, the left ventricular ejection fraction did not change after surgery (0.45+/-0.13% x 0.43+/-0.12% pre- and postoperatively, respectively). The New York Heart Association functional class improved to class I in 40% and class II in 43% of patients postoperatively (p<0.05). Although endomyocardial fibrosis patients have improved clinical symptoms after surgery, the global left ventricular ejection fraction and regional wall motion in these patients do not change. This finding suggests that other explanations, such as improvements in diastolic function, may be operational.

Cardioprotective Effect of Intermittent Fasting is Associated with an Elevation of Adiponectin Levels in Rats

PubMed Central

Wan, Ruiqian; Ahmet, Ismayil; Brown, Martin; Cheng, Aiwu; Kamimura, Naomi; Talan, Mark; Mattson, Mark P.

2009-01-01

It has been reported that dietary energy restriction, including intermittent fasting (IF), can protect heart and brain cells against injury and improve functional outcome in animal models of myocardial infarction and stroke. Here we report that IF improves glycemic control and protects the myocardium against ischemia-induced cell damage and inflammation in rats. Echocardiographic analysis of heart structural and functional variables revealed that IF attenuates the growth-related increase in posterior ventricular wall thickness, , end systolic and diastolic volumes, and reduces the ejection fraction. The size of the ischemic infarct 24 hours following permanent ligation of a coronary artery was significantly smaller, and markers of inflammation (infiltration of leukocytes in the area at risk and plasma IL-6 levels) were less, in IF rats compared to rats on the control diet. IF resulted in increased levels of circulating adiponectin prior to and after myocardial infarction. Because recent studies have shown that adiponectin can protect the heart against ischemic injury, our findings suggest a potential role for adiponectin as a mediator of the cardioprotective effect of IF. PMID:19423320

Therapeutic Strategies for Sleep Apnea in Hypertension and Heart Failure

PubMed Central

Noda, Akiko; Miyata, Seiko; Yasuda, Yoshinari

2013-01-01

Sleep-disordered breathing (SDB) causes hypoxemia, negative intrathoracic pressure, and frequent arousal, contributing to increased cardiovascular disease mortality and morbidity. Obstructive sleep apnea syndrome (OSAS) is linked to hypertension, ischemic heart disease, and cardiac arrhythmias. Successful continuous positive airway pressure (CPAP) treatment has a beneficial effect on hypertension and improves the survival rate of patients with cardiovascular disease. Thus, long-term compliance with CPAP treatment may result in substantial blood pressure reduction in patients with resistant hypertension suffering from OSAS. Central sleep apnea and Cheyne-Stokes respiration occur in 30–50% of patients with heart failure (HF). Intermittent hypoxemia, nocturnal surges in sympathetic activity, and increased left ventricular preload and afterload due to negative intrathoracic pressure all lead to impaired cardiac function and poor life prognosis. SDB-related HF has been considered the potential therapeutic target. CPAP, nocturnal O2 therapy, and adaptive servoventilation minimize the effects of sleep apnea, thereby improving cardiac function, prognosis, and quality of life. Early diagnosis and treatment of SDB will yield better therapeutic outcomes for hypertension and HF. PMID:23509623

The Mitochondria in Diabetic Heart Failure: From Pathogenesis to Therapeutic Promise

PubMed Central

2015-01-01

Abstract Significance: Diabetes is an important risk factor for the development of heart failure (HF). Given the increasing prevalence of diabetes in the population, strategies are needed to reduce the burden of HF in these patients. Recent Advances: Diabetes is associated with several pathologic findings in the heart including dysregulated metabolism, lipid accumulation, oxidative stress, and inflammation. Emerging evidence suggests that mitochondrial dysfunction may be a central mediator of these pathologic responses. The development of therapeutic approaches targeting mitochondrial biology holds promise for the management of HF in diabetic patients. Critical Issues: Despite significant data implicating mitochondrial pathology in diabetic cardiomyopathy, the optimal pharmacologic approach to improve mitochondrial function remains undefined. Future Directions: Detailed mechanistic studies coupled with more robust clinical phenotyping will be necessary to develop novel approaches to improve cardiac function in diabetes. Moreover, understanding the interplay between diabetes and other cardiac stressors (hypertension, ischemia, and valvular disease) will be of the utmost importance for clinical translation of scientific discoveries made in this field. Antioxid. Redox Signal. 22, 1515–1526. PMID:25761843

Swimming exercise reverses aging-related contractile abnormalities of female heart by improving structural alterations.

PubMed

Ozturk, Nihal; Olgar, Yusuf; Er, Hakan; Kucuk, Murathan; Ozdemir, Semir

2017-01-01

The objective of this study was to examine the effect of swimming exercise on aging-related Ca2+ handling alterations and structural abnormalities of female rat heart. For this purpose, 4-month and 24-month old female rats were used and divided into three following groups: sedentary young (SY), sedentary old (SO), and exercised old (Ex-O). Swimming exercise was performed for 8 weeks (60 min/day, 5 days/week). Myocyte shortening, L-type Ca2+ currents and associated Ca2+ transients were measured from ventricular myocytes at 36 ± 1°C. NOX-4 levels, aconitase activity, glutathione measurements and ultrastructural examination by electron microscopy were conducted in heart tissue. Swimming exercise reversed the reduced shortening and slowed kinetics of aged cardiomyocytes. Although the current density was similar for all groups, Ca2+ transients were higher in SO and Ex-O myocytes with respect to the SY group. Caffeine-induced Ca2+ transients and the integrated NCX current were lower in cardiomyocytes of SY rats compared with other groups, suggesting an increased sarcoplasmic reticulum Ca2+ content in an aged heart. Aging led to upregulated cardiac NOX-4 along with declined aconitase activity. Although it did not reverse these oxidative parameters, swimming exercise achieved a significant increase in glutathione levels and improved structural alterations of old rats' hearts. We conclude that swimming exercise upregulates antioxidant defense capacity and improves structural abnormalities of senescent female rat heart, although it does not change Ca2+ handling alterations further. Thereby, it improves contractile function of aged myocardium by mitigating detrimental effects of oxidative stress.

The small-molecule fast skeletal troponin activator, CK-2127107, improves exercise tolerance in a rat model of heart failure.

PubMed

Hwee, Darren T; Kennedy, Adam R; Hartman, James J; Ryans, Julie; Durham, Nickie; Malik, Fady I; Jasper, Jeffrey R

2015-04-01

Heart failure-mediated skeletal myopathy, which is characterized by muscle atrophy and muscle metabolism dysfunction, often manifests as dyspnea and limb muscle fatigue. We have previously demonstrated that increasing Ca(2+) sensitivity of the sarcomere by a small-molecule fast skeletal troponin activator improves skeletal muscle force and exercise performance in healthy rats and models of neuromuscular disease. The objective of this study was to investigate the effect of a novel fast skeletal troponin activator, CK-2127107 (2-aminoalkyl-5-N-heteroarylpyrimidine), on skeletal muscle function and exercise performance in rats exhibiting heart failure-mediated skeletal myopathy. Rats underwent a left anterior descending coronary artery ligation, resulting in myocardial infarction and a progressive decline in cardiac function [left anterior descending coronary artery heart failure (LAD-HF)]. Compared with sham-operated control rats, LAD-HF rat hindlimb and diaphragm muscles exhibited significant muscle atrophy. Fatigability was increased during repeated in situ isokinetic plantar flexor muscle contractions. CK-2127107 produced a leftward shift in the force-Ca(2+) relationship of skinned, single diaphragm, and extensor digitorum longus fibers. Exercise performance, which was assessed by rotarod running, was lower in vehicle-treated LAD-HF rats than in sham controls (116 ± 22 versus 193 ± 31 seconds, respectively; mean ± S.E.M.; P = 0.04). In the LAD-HF rats, a single oral dose of CK-2127107 (10 mg/kg p.o.) increased running time compared with vehicle treatment (283 ± 47 versus 116 ± 22 seconds; P = 0.0004). In summary, CK-2127107 substantially increases exercise performance in this heart failure model, suggesting that modulation of skeletal muscle function by a fast skeletal troponin activator may be a useful therapeutic in heart failure-associated exercise intolerance. Copyright © 2015 by The American Society for Pharmacology and Experimental Therapeutics.

Comprehensive Functional Assessment of Right-Sided Heart Using Speckle Tracking Strain for Patients with Pulmonary Hypertension.

PubMed

Fukuda, Yuko; Tanaka, Hidekazu; Ryo-Koriyama, Keiko; Motoji, Yoshiki; Sano, Hiroyuki; Shimoura, Hiroyuki; Ooka, Junichi; Toki, Hiromi; Sawa, Takuma; Mochizuki, Yasuhide; Matsumoto, Kensuke; Emoto, Noriaki; Hirata, Ken-Ichi

2016-07-01

Right ventricular (RV) systolic function is one of the most important determinants of outcome for pulmonary hypertension (PH) patients, but the factors influencing prognosis vary widely. Elevated right atrial (RA) pressure is reported to be one of these prognostic factors, but its functional importance has scarcely been assessed. Eighty-two PH patients, all of whom underwent echocardiography and right heart catheterization, were recruited. RV function was assessed by two-dimensional speckle tracking longitudinal strain from RV-focused apical four-chamber view and calculated by averaging the three regional peak strains from the RV free wall (RV-free). RA function was determined as the sum of three peak strain values comprising reservoir, conduit, and contractile function (sum of RA strain). Sum of RA strain correlated significantly with hemodynamic parameters such as mean right atrial pressure (r = -0.35, P = 0.002) and end-diastolic RV pressure (r = -0.29, P = 0.008). Patients with sum of RA strain ≥30.2% experienced more favorable outcomes than those with sum of RA strain <30.2% (log-rank P = 0.001). Furthermore, patients with impaired RV systolic function (RV-free <20%) and RA function (sum of RA strain <30.2%) showed the worst outcome (P = 0.001). A sequential Cox model based on clinical variables (χ(2) = 5.8) was improved by addition of RV-free (χ(2) = 8.7; P < 0.05) and further improved by addition of sum of RA strain (χ(2) = 12.0; P < 0.01). Right atrial strain appears to be a valuable additive factor for predicting outcomes for PH patients, and comprehensive functional assessment of right-sided heart using speckle tracking strain may have potential clinical implications for better management of PH patients. © 2016, Wiley Periodicals, Inc.

Randomized Clinical Trials of Gene Transfer for Heart Failure with Reduced Ejection Fraction.

PubMed

Penny, William F; Hammond, H Kirk

2017-05-01

Despite improvements in drug and device therapy for heart failure, hospitalization rates and mortality have changed little in the past decade. Randomized clinical trials using gene transfer to improve function of the failing heart are the focus of this review. Four randomized clinical trials of gene transfer in heart failure with reduced ejection fraction (HFrEF) have been published. Each enrolled patients with stable symptomatic HFrEF and used either intracoronary delivery of a virus vector or endocardial injection of a plasmid. The initial CUPID trial randomized 14 subjects to placebo and 25 subjects to escalating doses of adeno-associated virus type 1 encoding sarcoplasmic reticulum calcium ATPase (AAV1.SERCA2a). AAV1.SERCA2a was well tolerated, and the high-dose group met a 6 month composite endpoint. In the subsequent CUPID-2 study, 243 subjects received either placebo or the high dose of AAV1.SERCA2a. AAV1.SERCA2a administration, while safe, failed to meet the primary or any secondary endpoints. STOP-HF used plasmid endocardial injection of stromal cell-derived factor-1 to promote stem-cell recruitment. In a 93-subject trial of patients with ischemic etiology heart failure, the primary endpoint (symptoms and 6 min walk distance) failed, but subgroup analyses showed improvements in subjects with the lowest ejection fractions. A fourth trial randomized 14 subjects to placebo and 42 subjects to escalating doses of adenovirus-5 encoding adenylyl cyclase 6 (Ad5.hAC6). There were no safety concerns, and patients in the two highest dose groups (combined) showed improvements in left ventricular function (left ventricular ejection fraction and -dP/dt). The safety data from four randomized clinical trials of gene transfer in patients with symptomatic HFrEF suggest that this approach can be conducted with acceptable risk, despite invasive delivery techniques in a high-risk population. Additional trials are necessary before the approach can be endorsed for clinical practice.

Early Effects of Prolonged Cardiac Arrest and Ischemic Postconditioning during Cardiopulmonary Resuscitation on Cardiac and Brain Mitochondrial Function in Pigs.

PubMed

Matsuura, Timothy R; Bartos, Jason A; Tsangaris, Adamantios; Shekar, Kadambari Chandra; Olson, Matthew D; Riess, Matthias L; Bienengraeber, Martin; Aufderheide, Tom P; Neumar, Robert W; Rees, Jennifer N; McKnite, Scott H; Dikalova, Anna E; Dikalov, Sergey I; Douglas, Hunter F; Yannopoulos, Demetris

2017-07-01

Out-of-hospital cardiac arrest (CA) is a prevalent medical crisis resulting in severe injury to the heart and brain and an overall survival of less than 10%. Mitochondrial dysfunction is predicted to be a key determinant of poor outcomes following prolonged CA. However, the onset and severity of mitochondrial dysfunction during CA and cardiopulmonary resuscitation (CPR) is not fully understood. Ischemic postconditioning (IPC), controlled pauses during the initiation of CPR, has been shown to improve cardiac function and neurologically favorable outcomes after 15min of CA. We tested the hypothesis that mitochondrial dysfunction develops during prolonged CA and can be rescued with IPC during CPR (IPC-CPR). A total of 63 swine were randomized to no ischemia (Naïve), 19min of ventricular fibrillation (VF) CA without CPR (Untreated VF), or 15min of CA with 4min of reperfusion with either standard CPR (S-CPR) or IPC-CPR. Mitochondria were isolated from the heart and brain to quantify respiration, rate of ATP synthesis, and calcium retention capacity (CRC). Reactive oxygen species (ROS) production was quantified from fresh frozen heart and brain tissue. Compared to Naïve, Untreated VF induced cardiac and brain ROS overproduction concurrent with decreased mitochondrial respiratory coupling and CRC, as well as decreased cardiac ATP synthesis. Compared to Untreated VF, S-CPR attenuated brain ROS overproduction but had no other effect on mitochondrial function in the heart or brain. Compared to Untreated VF, IPC-CPR improved cardiac mitochondrial respiratory coupling and rate of ATP synthesis, and decreased ROS overproduction in the heart and brain. Fifteen minutes of VF CA results in diminished mitochondrial respiration, ATP synthesis, CRC, and increased ROS production in the heart and brain. IPC-CPR attenuates cardiac mitochondrial dysfunction caused by prolonged VF CA after only 4min of reperfusion, suggesting that IPC-CPR is an effective intervention to reduce cardiac injury. However, reperfusion with both CPR methods had limited effect on mitochondrial function in the brain, emphasizing an important physiological divergence in post-arrest recovery between those two vital organs. Copyright © 2017 Elsevier B.V. All rights reserved.

Adenosine triphosphate-sensitive potassium channel blocking agent ameliorates, but the opening agent aggravates, ischemia/reperfusion-induced injury. Heart function studies in nonfibrillating isolated hearts.

PubMed

Tosaki, A; Hellegouarch, A

1994-02-01

This study was conducted to elucidate the role of the adenosine triphosphate (ATP)-sensitive potassium channel blocking agent glibenclamide and the opener cromakalim in the mechanism of reperfusion-induced injury. Recently, ATP-sensitive potassium channel openers have been proposed to reduce ischemia/reperfusion-induced injury, including arrhythmias and heart function. Thus, one might hypothesize that pharmacologic agents that enhance the loss of potassium ions in the myocardium through ATP-sensitive potassium channels would be arrhythmogenic, and agents that interfere with tissue potassium ion loss would be antiarrhythmic. Isolated "working" guinea pig hearts and phosphorus-31 nuclear magnetic resonance spectroscopy were used to study the recovery of myocardial function and phosphorus compounds after 30, 40 and 50 min of normothermic global ischemia followed by reperfusion in untreated control and glibenclamide- and cromakalim-treated groups. After 30 min of ischemia, 1, 3, 10 and 30 mumol/liter of glibenclamide dose-dependently reduced the incidence of reperfusion-induced ventricular fibrillation (total) from its control value of 92% to 75%, 33% (p < 0.05), 33% (p < 0.05) and 42% (p < 0.05), respectively. The incidence of ventricular tachycardia followed the same pattern. A reduction of arrhythmias was also observed after 40 and 50 min of ischemia followed by reperfusion in the glibenclamide-treated hearts. Cromakalim, at the same concentrations, did not reduce the incidence of reperfusion-induced arrhythmias. During reperfusion, glibenclamide (3 and 10 mumol/liter) improved the recovery of coronary blood flow, aortic flow, myocardial contractility and tissue ATP and creatine phosphate content, but cromakalim failed to ameliorate the recovery of postischemic myocardium compared with that in the drug-free control hearts. The preservation of myocardial potassium ions and phosphorus compounds by glibenclamide can improve the recovery of postischemic function, but the use of ATP-sensitive potassium channel openers as antihypertensive or antiarrhythmic agents may be of particular concern in those postinfarction patients who are known to be at high risk for sudden cardiac death.

[Endurance training and cardial adaptation (athlete's heart)].

PubMed

Dickhuth, Hans-Hermann; Röcker, Kai; Mayer, Frank; König, Daniel; Korsten-Reck, Ulrike

2004-06-01

One essential function of the cardiovascular system is to provide an adequate blood supply to all organs, including the skeletal muscles at rest and during exercise. Adaptation to chronic exercise proceeds mainly via the autonomic nervous system. On the one hand, peripheral muscles influence the autonomic reactions through "feedback" control via ergoreceptors, in particular, mechano- and chemoreceptors. On the other hand, there is central control in the sense of a "feed forward" regulation, e. g., the reaction of an athlete before competition. Along with other influential factors, such as circulatory presso-, chemo-, and volume receptors, the incoming impulses are processed in vegetative centers.A cardiovascular reaction, then, is the result of nerval and humoral sympathetic and parasympathetic activity. At rest, the parasympathetic tone dominates. It reduces heart frequency and conduction velocity. The high vagal tone is initially reduced with increasing physical exertion and switches at higher intensity to increasingly sympathetic activation. This mechanism of reaction to exercise is supported by inverse central and peripheral transmissions.Chronic endurance training leads to an improved local aerobic capacity of the exercised musculature. At rest, it augments parasympathetic activity when the muscle mass is sufficiently large, i. e., 20-30% of the skeletal musculature. The extent of the adaptation depends on individual factors, such as scope, intensity of training, and type of muscle fiber. A higher vagal tone delays the increase in the sympathetic tone during physical exertion. The regulatory range of heart rate, contractility, diastolic function, and blood pressure is increased. In addition, adaptation results in functional and structural changes in the vascular system. Cardiocirculatory work is economized, and maximum performance and oxygen uptake are improved. Endurance training exceeding an individual limit causes harmonic enlargement and hypertrophy of the heart. The thickness of both, the septum and posterior wall increases to the same extent as the interior volume. The mass/volume ratio, and therefore the maximum systolic wall stress, remains constant in contrast to pathologic forms of hypertrophy. Adaptations, including function and size of the heart, show a regression in healthy inactive persons without any structural heart disease.

Efficacy of nasal bi-level positive airway pressure in congestive heart failure patients with cheyne-stokes respiration and central sleep apnea.

PubMed

Kasai, Takatoshi; Narui, Koji; Dohi, Tomotaka; Ishiwata, Sugao; Yoshimura, Kunihiko; Nishiyama, Shin-Ichiro; Yamaguchi, Tetsu; Momomura, Shin-Ichi

2005-08-01

Cheyne - Stokes respiration with central sleep apnea (CSR-CSA) contributes to the poor prognosis in patients with congestive heart failure (CHF). Bi-level positive airway pressure (bi-level PAP) may be an effective alternative for treating CSR-CSA and CHF. Fourteen patients with CSR-CSA were divided into 2 groups, a control group that included 7 patients who decided to receive only conventional medications and a group of 7 patients that received bi-level PAP. Left ventricular ejection fraction (LVEF), mitral regurgitation (MR) area, plasma brain natriuretic peptide (BNP) concentration and the New York Heart Association (NYHA) functional class were evaluated initially (baseline) and 3 months later. In the control group, there were no significant changes in cardiac function during the study period. In contrast, in the group that received bi-level PAP, there were significant improvements in LVEF (from 36.3+/-2.9% to 46.0+/-4.0%, p = 0.02), MR area (from 30.4+/-7.6% to 20.0+/-5.1%, p = 0.02), BNP (from 993.6+/-332.0 pg/ml to 474.0+/-257.6 pg/ml, p = 0.02) and NYHA functional class (from 3.1+/-0.1 to 2.1+/-0.1, p = 0.03). Treatment with bi-level PAP improved cardiac functions in CHF patients with CSR-CSA.

Swim-exercised mice show a decreased level of protein O-GlcNAcylation and expression of O-GlcNAc transferase in heart.

PubMed

Belke, Darrell D

2011-07-01

Swim-training exercise in mice leads to cardiac remodeling associated with an improvement in contractile function. Protein O-linked N-acetylglucosamine (O-GlcNAcylation) is a posttranslational modification of serine and threonine residues capable of altering protein-protein interactions affecting gene transcription, cell signaling pathways, and general cell physiology. Increased levels of protein O-GlcNAcylation in the heart have been associated with pathological conditions such as diabetes, ischemia, and hypertrophic heart failure. In contrast, the impact of physiological exercise on protein O-GlcNAcylation in the heart is currently unknown. Swim-training exercise in mice was associated with the development of a physiological hypertrophy characterized by an improvement in contractile function relative to sedentary mice. General protein O-GlcNAcylation was significantly decreased in swim-exercised mice. This effect was mirrored in the level of O-GlcNAcylation of individual proteins such as SP1. The decrease in protein O-GlcNAcylation was associated with a decrease in the expression of O-GlcNAc transferase (OGT) and glutamine-fructose amidotransferase (GFAT) 2 mRNA. O-GlcNAcase (OGA) activity was actually lower in swim-trained than sedentary hearts, suggesting that it did not contribute to the decreased protein O-GlcNAcylation. Thus it appears that exercise-induced physiological hypertrophy is associated with a decrease in protein O-GlcNAcylation, which could potentially contribute to changes in gene expression and other physiological changes associated with exercise.

Understanding the C-pulse device and its potential to treat heart failure.

PubMed

Sales, Virna L; McCarthy, Patrick M

2010-03-01

The Sunshine Heart C-Pulse (C-Pulse; Sunshine Heart Inc., Tustin, CA) device is an extra-aortic implantable counterpulsation pump designed as a non-blood contacting ambulatory heart assist device, which may provide relief from symptoms for class II-III congestive heart failure patients. It has a comparable hemodynamic augmentation to intra-aortic balloon counterpulsation devices. The C-Pulse cuff is implanted through a median sternotomy, secured around the ascending aorta, and pneumatically driven by an external system controller. Pre-clinical studies in the acute pig model, and initial temporary clinical studies in patients undergoing off-pump coronary bypass surgery have shown substantial increase in diastolic perfusion of the coronary vessels, which translated to a favorable improvement in ventricular function. A U.S. prospective multi-center trial to evaluate the safety and efficacy of the C-Pulse in class III patients with moderate heart failure is now in progress.

ECG Based Heart Arrhythmia Detection Using Wavelet Coherence and Bat Algorithm

NASA Astrophysics Data System (ADS)

Kora, Padmavathi; Sri Rama Krishna, K.

2016-12-01

Atrial fibrillation (AF) is a type of heart abnormality, during the AF electrical discharges in the atrium are rapid, results in abnormal heart beat. The morphology of ECG changes due to the abnormalities in the heart. This paper consists of three major steps for the detection of heart diseases: signal pre-processing, feature extraction and classification. Feature extraction is the key process in detecting the heart abnormality. Most of the ECG detection systems depend on the time domain features for cardiac signal classification. In this paper we proposed a wavelet coherence (WTC) technique for ECG signal analysis. The WTC calculates the similarity between two waveforms in frequency domain. Parameters extracted from WTC function is used as the features of the ECG signal. These features are optimized using Bat algorithm. The Levenberg Marquardt neural network classifier is used to classify the optimized features. The performance of the classifier can be improved with the optimized features.

Potential benefits of exercise on blood pressure and vascular function.

PubMed

Pal, Sebely; Radavelli-Bagatini, Simone; Ho, Suleen

2013-01-01

Physical activity seems to enhance cardiovascular fitness during the course of the lifecycle, improve blood pressure, and is associated with decreased prevalence of hypertension and coronary heart disease. It may also delay or prevent age-related increases in arterial stiffness. It is unclear if specific exercise types (aerobic, resistance, or combination) have a better effect on blood pressure and vascular function. This review was written based on previous original articles, systematic reviews, and meta-analyses indexed on PubMed from years 1975 to 2012 to identify studies on different types of exercise and the associations or effects on blood pressure and vascular function. In summary, aerobic exercise (30 to 40 minutes of training at 60% to 85% of predicted maximal heart rate, most days of the week) appears to significantly improve blood pressure and reduce augmentation index. Resistance training (three to four sets of eight to 12 repetitions at 10 repetition maximum, 3 days a week) appears to significantly improve blood pressure, whereas combination exercise training (15 minutes of aerobic and 15 minutes of resistance, 5 days a week) is beneficial to vascular function, but at a lower scale. Aerobic exercise seems to better benefit blood pressure and vascular function. Copyright © 2013 American Society of Hypertension. Published by 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.

Evolution of Cognitive Function After Transcatheter Aortic Valve Implantation.

PubMed

Schoenenberger, Andreas W; Zuber, Chantal; Moser, André; Zwahlen, Marcel; Wenaweser, Peter; Windecker, Stephan; Carrel, Thierry; Stuck, Andreas E; Stortecky, Stefan

2016-10-01

This study aimed to assess the evolution of cognitive function after transcatheter aortic valve implantation (TAVI). Previous smaller studies reported conflicting results on the evolution of cognitive function after TAVI. In this prospective cohort, cognitive function was measured in 229 patients ≥70 years using the Mini Mental State Examination before and 6 months after TAVI. Cognitive deterioration or improvement was defined as change of ≥3 points decrease or increase in the Mini Mental State Examination score between baseline and follow-up. Cognitive deterioration was found in 29 patients (12.7%). Predictive analysis using logistic regression did not identify any statistically significant predictor of cognitive deterioration. A review of individual medical records in 8 patients with a major Mini Mental State Examination score decrease of ≥5 points revealed specific causes in 6 cases (postinterventional delirium in 2; postinterventional stroke, progressive renal failure, progressive heart failure, or combination of preexisting cerebrovascular disease and mild cognitive impairment in 1 each). Among 48 patients with impaired baseline cognition (Mini Mental State Examination score <26 points), 18 patients (37.5%) cognitively improved. The preinterventional aortic valve area was lower in patients who cognitively improved (median aortic valve area 0.60 cm 2 ) as compared with patients who did not improve (median aortic valve area 0.70 cm 2 ; P=0.01). This is the first study providing evidence that TAVI results in cognitive improvement among patients who had impaired preprocedural cognitive function, possibly related to hemodynamic improvement in patients with severe aortic stenosis. Our results confirm that some patients experience cognitive deterioration after TAVI. © 2016 American Heart Association, Inc.

Snf1-related kinase improves cardiac mitochondrial efficiency and decreases mitochondrial uncoupling

PubMed Central

Rines, Amy K.; Chang, Hsiang-Chun; Wu, Rongxue; Sato, Tatsuya; Khechaduri, Arineh; Kouzu, Hidemichi; Shapiro, Jason; Shang, Meng; Burke, Michael A.; Abdelwahid, Eltyeb; Jiang, Xinghang; Chen, Chunlei; Rawlings, Tenley A.; Lopaschuk, Gary D.; Schumacker, Paul T.; Abel, E. Dale; Ardehali, Hossein

2017-01-01

Ischaemic heart disease limits oxygen and metabolic substrate availability to the heart, resulting in tissue death. Here, we demonstrate that the AMP-activated protein kinase (AMPK)-related protein Snf1-related kinase (SNRK) decreases cardiac metabolic substrate usage and mitochondrial uncoupling, and protects against ischaemia/reperfusion. Hearts from transgenic mice overexpressing SNRK have decreased glucose and palmitate metabolism and oxygen consumption, but maintained power and function. They also exhibit decreased uncoupling protein 3 (UCP3) and mitochondrial uncoupling. Conversely, Snrk knockout mouse hearts have increased glucose and palmitate oxidation and UCP3. SNRK knockdown in cardiac cells decreases mitochondrial efficiency, which is abolished with UCP3 knockdown. We show that Tribbles homologue 3 (Trib3) binds to SNRK, and downregulates UCP3 through PPARα. Finally, SNRK is increased in cardiomyopathy patients, and SNRK reduces infarct size after ischaemia/reperfusion. SNRK also decreases cardiac cell death in a UCP3-dependent manner. Our results suggest that SNRK improves cardiac mitochondrial efficiency and ischaemic protection. PMID:28117339

Exercise training improves cardiac function in infarcted rabbits: involvement of autophagic function and fatty acid utilization.

PubMed

Chen, Ching-Yi; Hsu, Hsiu-Ching; Lee, Bai-Chin; Lin, Hung-Ju; Chen, Ying-Hsien; Huang, Hui-Chun; Ho, Yi-Lwun; Chen, Ming-Fong

2010-04-01

To explore whether exercise can improve cardiac function in a post-myocardial infarction (MI) rabbit model and to determine contributing factors in the left ventricle (LV). Adult male New Zealand White rabbits (2.5-3 kg) underwent MI by ligation of the left anterior descending coronary artery. For 8 weeks after surgery, sham-operated, and post-MI rabbits were housed under sedentary conditions or assigned to a 4-week treadmill exercise protocol at a speed of 1.0 km/h for 30 min 5 days per week, then sacrificed. The non-infarcted region of the LV was harvested for further analysis. MI decreased left ventricular ejection fraction (LVEF) and increased thiobarbituric acid reactive substances (TBARS) generation in the LV. Exercise improved the cardiac function of MI rabbits. Left ventricular LC3II/LC3I (microtubule-associated protein light chain 3) in the MI group was 2.1-fold higher than that of the sham group, exercise significantly decreased LC3II/LC3I in the MI group. MI down-regulated the expression of heart-type fatty acid binding protein (h-FABP), and exercise up-regulated h-FABP. In addition, LVEF had a significantly positive correlation with h-FABP and a negative correlation with LC3II/LC3I. Exercise induced change in autophagic function and fatty acid utilization may contribute to the improvement in ventricular function in the infarcted heart.

Consensus Document of the Spanish Society of Cardiology and the Spanish Society of Internal Medicine on the diagnosis and treatment of iron deficiency in heart failure.

PubMed

Manito, N; Cerqueiro, J M; Comín-Colet, J; García-Pinilla, J M; González-Franco, A; Grau-Amorós, J; Peraira, J R; Manzano, L

Iron deficiency in patients with heart failure is a medical problem of recent particular interest. This interest has resulted from the publication of several clinical trials that demonstrated that the administration of intravenous iron to such patients improved their functional capacity and even reduced the number of hospitalisations for heart failure decompensation. However, applying the evidence from these studies in clinical practice is still controversial, both in terms of the diagnostic criteria for iron deficiency (absolute and functional) and the optimal method for iron replenishment. This article is a consensus document that integrates the recommendations of the Spanish Society of Internal Medicine and the Spanish Society of Cardiology. The article reviews the scientific evidence and proposes a diagnostic and therapeutic performance protocol for iron deficiency in heart failure. Copyright © 2016 Elsevier España, S.L.U. and Sociedad Española de Medicina Interna (SEMI). All rights reserved.

A Randomized Controlled Trial to Evaluate the Safety and Efficacy of Cardiac Contractility Modulation.

PubMed

Abraham, William T; Kuck, Karl-Heinz; Goldsmith, Rochelle L; Lindenfeld, JoAnn; Reddy, Vivek Y; Carson, Peter E; Mann, Douglas L; Saville, Benjamin; Parise, Helen; Chan, Rodrigo; Wiegn, Phi; Hastings, Jeffrey L; Kaplan, Andrew J; Edelmann, Frank; Luthje, Lars; Kahwash, Rami; Tomassoni, Gery F; Gutterman, David D; Stagg, Angela; Burkhoff, Daniel; Hasenfuß, Gerd

2018-05-05

The authors sought to confirm a subgroup analysis of the prior FIX-HF-5 (Evaluate Safety and Efficacy of the OPTIMIZER System in Subjects With Moderate-to-Severe Heart Failure) study showing that cardiac contractility modulation (CCM) improved exercise tolerance (ET) and quality of life in patients with ejection fractions between 25% and 45%. CCM therapy for New York Heart Association (NYHA) functional class III and IV heart failure (HF) patients consists of nonexcitatory electrical signals delivered to the heart during the absolute refractory period. A total of 160 patients with NYHA functional class III or IV symptoms, QRS duration <130 ms, and ejection fraction ≥25% and ≤45% were randomized to continued medical therapy (control, n = 86) or CCM (treatment, n = 74, unblinded) for 24 weeks. Peak VO 2 (primary endpoint), Minnesota Living With Heart Failure questionnaire, NYHA functional class, and 6-min hall walk were measured at baseline and at 12 and 24 weeks. Bayesian repeated measures linear modeling was used for the primary endpoint analysis with 30% borrowing from the FIX-HF-5 subgroup. Safety was assessed by the percentage of patients free of device-related adverse events with a pre-specified lower bound of 70%. The difference in peak VO 2 between groups was 0.84 (95% Bayesian credible interval: 0.123 to 1.552) ml O 2 /kg/min, satisfying the primary endpoint. Minnesota Living With Heart Failure questionnaire (p < 0.001), NYHA functional class (p < 0.001), and 6-min hall walk (p = 0.02) were all better in the treatment versus control group. There were 7 device-related events, yielding a lower bound of 80% of patients free of events, satisfying the primary safety endpoint. The composite of cardiovascular death and HF hospitalizations was reduced from 10.8% to 2.9% (p = 0.048). CCM is safe, improves exercise tolerance and quality of life in the specified group of HF patients, and leads to fewer HF hospitalizations. (Evaluate Safety and Efficacy of the OPTIMIZER System in Subjects With Moderate-to-Severe Heart Failure; NCT01381172). Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

Selenite-Releasing Bone Mineral Nanoparticles Retard Bone Tumor Growth and Improve Healthy Tissue Functions In Vivo.

PubMed

Wang, Yanhua; Hao, Hang; Liu, Haoming; Wang, Yifan; Li, Yan; Yang, Gaojie; Ma, Jun; Mao, Chuanbin; Zhang, Shengmin

2015-08-26

Selenite-doped bone mineral nanoparticles can retard the growth of osteosarcoma in a nude mice model, through sustained release of selenite ions. The selenite ions released from the nanoparticles through a degradation-mediated fashion inhibit tumor metastasis. Blood routine analysis indicates that selenite ions can also improve the functions of liver, kidney, and heart. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Micro-encapsulated sensors for in vivo assessment of the oxidative stress in aquatic organisms

NASA Astrophysics Data System (ADS)

Sadovoy, Anton; Teh, Cathleen; Escobar, Marco; Meglinski, Igor; Korzh, Vladimir

2011-10-01

Oxidative stress results from an imbalance between the production and detoxification of reactive oxygen spices (ROS). ROS are natural byproducts of normal metabolism of oxygen and have important roles in cell signaling and homeostasis. Many heart related diseases like heart failure and myocardial infarction develop as a result of oxidative stress. Current treatment cannot improve the progressive decline in heart function experienced by all patients. Therefore heart failure is the cause of around 25% of all deaths in the Asia Pacific region. Thus any step taken to address the oxidative stress problem is essential for enhancing human health and improve their quality of life. Current approach is dedicated to develop micron-size oxidation stress-sensor for in-vivo measuring level of ROS in KillerRed expressing transgenic zebrafish larvae. Central to our investigation is the light-inducible heart failure animal model we developed in zebrafish that expressed KillerRed in the heart. By utilizing the photosensitizer properties of KillerRed to produce ROS upon green light illumination, heart failure can be repeatedly induced in a non-invasive manner. Importantly, the use of this biological platform permits the development of physiologically sensitive ROS sensor and identifies efficient antioxidants that improve heart contractility. The biosensor approach is based on utilizing biocompatible polyelectrolyte microcapsules as a carry of fluorescent dyes sensitive to amount of reactive oxygen spices. Microcapsule prevents dye diffusion in tissue that makes use toxic dyes possible. Microcapsule's wall is permeable for environment with size less than 500 Da. The oxidation stress-sensors are injected directly in zebrafish pericardium with further circulation along blood system. Detecting of ROS is obtained by using laser scanning microscopy by illuminating oxidation stress-sensors and detecting changing excitation signal from the fluorescent dye.

Micro-encapsulated sensors for in vivo assessment of the oxidative stress in aquatic organisms

NASA Astrophysics Data System (ADS)

Sadovoy, Anton; Teh, Cathleen; Escobar, Marco; Meglinski, Igor; Korzh, Vladimir

2012-03-01

Oxidative stress results from an imbalance between the production and detoxification of reactive oxygen spices (ROS). ROS are natural byproducts of normal metabolism of oxygen and have important roles in cell signaling and homeostasis. Many heart related diseases like heart failure and myocardial infarction develop as a result of oxidative stress. Current treatment cannot improve the progressive decline in heart function experienced by all patients. Therefore heart failure is the cause of around 25% of all deaths in the Asia Pacific region. Thus any step taken to address the oxidative stress problem is essential for enhancing human health and improve their quality of life. Current approach is dedicated to develop micron-size oxidation stress-sensor for in-vivo measuring level of ROS in KillerRed expressing transgenic zebrafish larvae. Central to our investigation is the light-inducible heart failure animal model we developed in zebrafish that expressed KillerRed in the heart. By utilizing the photosensitizer properties of KillerRed to produce ROS upon green light illumination, heart failure can be repeatedly induced in a non-invasive manner. Importantly, the use of this biological platform permits the development of physiologically sensitive ROS sensor and identifies efficient antioxidants that improve heart contractility. The biosensor approach is based on utilizing biocompatible polyelectrolyte microcapsules as a carry of fluorescent dyes sensitive to amount of reactive oxygen spices. Microcapsule prevents dye diffusion in tissue that makes use toxic dyes possible. Microcapsule's wall is permeable for environment with size less than 500 Da. The oxidation stress-sensors are injected directly in zebrafish pericardium with further circulation along blood system. Detecting of ROS is obtained by using laser scanning microscopy by illuminating oxidation stress-sensors and detecting changing excitation signal from the fluorescent dye.

Methylene Blue Partially Rescues Heart Defects in a Drosophila Model of Huntington's Disease.

PubMed

Heidari, Raheleh; Monnier, Véronique; Martin, Elodie; Tricoire, Hervé

2015-01-01

Huntington's disease (HD) is a Polyglutamine disease caused by the presence of CAG repeats in the first exon of Huntingtin (Htt), a large protein with multiple functions. In addition to neurodegeneration of specific brain regions, notably the striatum, HD also shows alterations in peripheral tissues, such as the heart, skeletal muscles or peripheral endocrine glands. Mutant Huntingtin (mHtt)-driven mitochondrial impairment may underlie some of the CNS and peripheral tissues dysfunctions, especially in tissues with high energy demand such as the heart. The aim of this study is to characterize two new inducible Drosophila HD heart models and to assay the therapeutic potential of methylene blue in these HD models. We report the construction of inducible Drosophila HD heart models, expressing two Nter fragments of the protein encompassing either exon 1 or the first 171 amino acids and the characterization of heart phenotypes in vivo. We show that both mHtt fragments are able to impair fly cardiac function with different characteristics. Additionally, expression of mHtt, which was limited to adulthood only, leads to mild heart impairment, as opposed to a strong and age-dependent phenotype observed when mHtt expression was driven during both developmental and adult stages. We report that treatment with methylene blue (MB), a protective compound in mitochondria-related diseases, partially protects the fly's heart against mHtt-induced toxicity, but does not rescue neuronal or glial phenotypes in other fly models of HD. This may be linked to its low penetration through the fly's blood-brain barrier. Our data suggest that improvement of mitochondrial function by MB, or related compounds, could be an efficient therapeutic strategy to prevent cardiac failure in HD patients.

Embryonic Stem Cell Therapy of Heart Failure in Genetic Cardiomyopathy

PubMed Central

Yamada, Satsuki; Nelson, Timothy J.; Crespo-Diaz, Ruben J.; Perez-Terzic, Carmen; Liu, Xiao-Ke; Miki, Takashi; Seino, Susumu; Behfar, Atta; Terzic, Andre

2009-01-01

Pathogenic causes underlying nonischemic cardiomyopathies are increasingly being resolved, yet repair therapies for these commonly heritable forms of heart failure are lacking. A case in point is human dilated cardiomyopathy 10 (CMD10; Online Mendelian Inheritance in Man #608569), a progressive organ dysfunction syndrome refractory to conventional therapies and linked to mutations in cardiac ATP-sensitive K+ (KATP) channel sub-units. Embryonic stem cell therapy demonstrates benefit in ischemic heart disease, but the reparative capacity of this allogeneic regenerative cell source has not been tested in inherited cardiomyopathy. Here, in a Kir6.2-knockout model lacking functional KATP channels, we recapitulated under the imposed stress of pressure overload the gene-environment substrate of CMD10. Salient features of the human malignant heart failure phenotype were reproduced, including compromised contractility, ventricular dilatation, and poor survival. Embryonic stem cells were delivered through the epicardial route into the left ventricular wall of cardiomyopathic stressed Kir6.2-null mutants. At 1 month of therapy, transplantation of 200,000 cells per heart achieved teratoma-free reversal of systolic dysfunction and electrical synchronization and halted maladaptive remodeling, thereby preventing end-stage organ failure. Tracked using the lacZ reporter transgene, stem cells engrafted into host heart. Beyond formation of cardiac tissue positive for Kir6.2, transplantation induced cell cycle activation and halved fibrotic zones, normalizing sarcomeric and gap junction organization within remuscularized hearts. Improved systemic function induced by stem cell therapy translated into increased stamina, absence of anasarca, and benefit to overall survivorship. Embryonic stem cells thus achieve functional repair in nonischemic genetic cardiomyopathy, expanding indications to the therapy of heritable heart failure. PMID:18669912

Embryonic stem cell therapy of heart failure in genetic cardiomyopathy.

PubMed

Yamada, Satsuki; Nelson, Timothy J; Crespo-Diaz, Ruben J; Perez-Terzic, Carmen; Liu, Xiao-Ke; Miki, Takashi; Seino, Susumu; Behfar, Atta; Terzic, Andre

2008-10-01

Pathogenic causes underlying nonischemic cardiomyopathies are increasingly being resolved, yet repair therapies for these commonly heritable forms of heart failure are lacking. A case in point is human dilated cardiomyopathy 10 (CMD10; Online Mendelian Inheritance in Man #608569), a progressive organ dysfunction syndrome refractory to conventional therapies and linked to mutations in cardiac ATP-sensitive K(+) (K(ATP)) channel subunits. Embryonic stem cell therapy demonstrates benefit in ischemic heart disease, but the reparative capacity of this allogeneic regenerative cell source has not been tested in inherited cardiomyopathy. Here, in a Kir6.2-knockout model lacking functional K(ATP) channels, we recapitulated under the imposed stress of pressure overload the gene-environment substrate of CMD10. Salient features of the human malignant heart failure phenotype were reproduced, including compromised contractility, ventricular dilatation, and poor survival. Embryonic stem cells were delivered through the epicardial route into the left ventricular wall of cardiomyopathic stressed Kir6.2-null mutants. At 1 month of therapy, transplantation of 200,000 cells per heart achieved teratoma-free reversal of systolic dysfunction and electrical synchronization and halted maladaptive remodeling, thereby preventing end-stage organ failure. Tracked using the lacZ reporter transgene, stem cells engrafted into host heart. Beyond formation of cardiac tissue positive for Kir6.2, transplantation induced cell cycle activation and halved fibrotic zones, normalizing sarcomeric and gap junction organization within remuscularized hearts. Improved systemic function induced by stem cell therapy translated into increased stamina, absence of anasarca, and benefit to overall survivorship. Embryonic stem cells thus achieve functional repair in nonischemic genetic cardiomyopathy, expanding indications to the therapy of heritable heart failure. Disclosure of potential conflicts of interest is found at the end of this article.

Resolution of mitochondrial oxidant stress improves aged-cardiovascular performance

PubMed Central

Owada, Takashi; Yamauchi, Hiroyuki; Miura, Shunsuke; Machii, Hirofumi; Takeishi, Yasuchika

2017-01-01

Background Senescence is a major factor that increases oxidative stress in mitochondria, which contributes toward the pathogenesis of heart disease. However, the effect of antioxidant therapy on cardiac mitochondria in aged-cardiac performance remains elusive. Objectives We postulated that the mitochondrial targeting of superoxide scavenging would have benefits in the aged heart. Methods and results Generation of superoxide in the mitochondria and nicotinamide adenine dinucleotide phosphate oxidase activity increased in the heart of old mice compared with that in young mice. In old mice treated with a mitochondria-targeted antioxidant MitoTEMPO (180 µg/kg/day, 28 days) co-infusion using a subcutaneously implanted minipump, levels of superoxide in the mitochondria and nicotinamide adenine dinucleotide phosphate oxidase activity as well as hydrogen peroxide decreased markedly in cardiomyocytes. Treatment with MitoTEMPO in old mice improved the systolic and diastolic function assessed by echocardiography. Endothelium-dependent vasodilation in isolated coronary arteries and endothelial nitric-oxide synthase phosphorylation were impaired in old mice compared with that in young mice and were improved by MitoTEMPO treatment. Mitochondria from the old mice myocardium showed lower rates of complex I-dependent and II-dependent respiration compared with that from young mice. Supplementation of MitoTEMPO in old mice improved the respiration rates and efficiency of ATP generation in mitochondria to a level similar to that of young mice. Conclusion Resolution of oxidative stress in mitochondria by MitoTEMPO in old mice restored cardiac function and the capacity of coronary vasodilation to the same magnitude observed in young mice. An antioxidant strategy targeting mitochondria could have a therapeutic benefit in heart disease with senescence. PMID:27740971

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.

The impact of an emotional self-management skills course on psychosocial functioning and autonomic recovery to stress in middle school children.

PubMed

McCraty, R; Atkinson, M; Tomasino, D; Goelitz, J; Mayrovitz, H N

1999-01-01

Unmanaged emotional reactions to stress not only lead to behavior problems in young people but also create physiological conditions that inhibit learning and potentially increase the risk of disease later in life. For these reasons, the integration of emotional self-management skills training programs has become an increased priority in some schools. In this study, middle school students enrolled in a course in emotional competence skills learned techniques designed to intercept stressful responses during emotionally challenging situations. Behavioral outcomes were assessed using the Achievement Inventory Measure and autonomic function was measured by heart rate variability (HRV) analysis during and after a stressful interview. Following the program, students exhibited significant improvements in areas including stress and anger management, risky behavior, work management and focus, and relationships with family, peers and teachers. These improvements were sustained over the following six months. Students using the skills taught in the course to recover from acute emotional stress were also able to positively modulate their physiological stress responses. As compared to a control group, trained students demonstrated significantly increased HRV and more rhythmic, sine wave-like heart rhythm patterns during recovery. This response pattern reflects increased parasympathetic activity, heart rhythm coherence, and entrainment of other biological oscillatory systems to the primary heart rhythm frequency. Increased physiological coherence is associated with improved cognitive performance, emotional balance, mental clarity and health outcomes. These physiological shifts could promote the sustained psychological and behavioral improvements associated with the use of emotional management skills. It is suggested that learning emotional competence skills in childhood establishes healthier physiological response patterns which can benefit learning and long-term health. Results provide support for the integration in school curricula of courses designed to teach effective self-management skills to children.

Rejuvenation of human cardiac progenitor cells with Pim-1 kinase.

PubMed

Mohsin, Sadia; Khan, Mohsin; Nguyen, Jonathan; Alkatib, Monique; Siddiqi, Sailay; Hariharan, Nirmala; Wallach, Kathleen; Monsanto, Megan; Gude, Natalie; Dembitsky, Walter; Sussman, Mark A

2013-10-25

Myocardial function is enhanced by adoptive transfer of human cardiac progenitor cells (hCPCs) into a pathologically challenged heart. However, advanced age, comorbidities, and myocardial injury in patients with heart failure constrain the proliferation, survival, and regenerative capacity of hCPCs. Rejuvenation of senescent hCPCs will improve the outcome of regenerative therapy for a substantial patient population possessing functionally impaired stem cells. Reverse phenotypic and functional senescence of hCPCs by ex vivo modification with Pim-1. C-kit-positive hCPCs were isolated from heart biopsy samples of patients undergoing left ventricular assist device implantation. Growth kinetics, telomere lengths, and expression of cell cycle regulators showed significant variation between hCPC isolated from multiple patients. Telomere length was significantly decreased in hCPC with slow-growth kinetics concomitant with decreased proliferation and upregulation of senescent markers compared with hCPC with fast-growth kinetics. Desirable youthful characteristics were conferred on hCPCs by genetic modification using Pim-1 kinase, including increases in proliferation, telomere length, survival, and decreased expression of senescence markers. Senescence characteristics of hCPCs are ameliorated by Pim-1 kinase resulting in rejuvenation of phenotypic and functional properties. hCPCs show improved cellular properties resulting from Pim-1 modification, but benefits were more pronounced in hCPC with slow-growth kinetics relative to hCPC with fast-growth kinetics. With the majority of patients with heart failure presenting advanced age, infirmity, and impaired regenerative capacity, the use of Pim-1 modification should be incorporated into cell-based therapeutic approaches to broaden inclusion criteria and address limitations associated with the senescent phenotype of aged hCPC.

Rejuvenation of Human Cardiac Progenitor Cells With Pim-1 Kinase

PubMed Central

Mohsin, Sadia; Khan, Mohsin; Nguyen, Jonathan; Alkatib, Monique; Siddiqi, Sailay; Hariharan, Nirmala; Wallach, Kathleen; Monsanto, Megan; Gude, Natalie; Dembitsky, Walter; Sussman, Mark A.

2014-01-01

Rationale Myocardial function is enhanced by adoptive transfer of human cardiac progenitor cells (hCPCs) into a pathologically challenged heart. However, advanced age, comorbidities, and myocardial injury in patients with heart failure constrain the proliferation, survival, and regenerative capacity of hCPCs. Rejuvenation of senescent hCPCs will improve the outcome of regenerative therapy for a substantial patient population possessing functionally impaired stem cells. Objective Reverse phenotypic and functional senescence of hCPCs by ex vivo modification with Pim-1. Methods and Results C-kit–positive hCPCs were isolated from heart biopsy samples of patients undergoing left ventricular assist device implantation. Growth kinetics, telomere lengths, and expression of cell cycle regulators showed significant variation between hCPC isolated from multiple patients. Telomere length was significantly decreased in hCPC with slow-growth kinetics concomitant with decreased proliferation and upregulation of senescent markers compared with hCPC with fast-growth kinetics. Desirable youthful characteristics were conferred on hCPCs by genetic modification using Pim-1 kinase, including increases in proliferation, telomere length, survival, and decreased expression of senescence markers. Conclusions Senescence characteristics of hCPCs are ameliorated by Pim-1 kinase resulting in rejuvenation of phenotypic and functional properties. hCPCs show improved cellular properties resulting from Pim-1 modification, but benefits were more pronounced in hCPC with slow-growth kinetics relative to hCPC with fast-growth kinetics. With the majority of patients with heart failure presenting advanced age, infirmity, and impaired regenerative capacity, the use of Pim-1 modification should be incorporated into cell-based therapeutic approaches to broaden inclusion criteria and address limitations associated with the senescent phenotype of aged hCPC. PMID:24044948

Cardiac Expression of Microsomal Triglyceride Transfer Protein Is Increased in Obesity and Serves to Attenuate Cardiac Triglyceride Accumulation

PubMed Central

Bartels, Emil D.; Nielsen, Jan M.; Hellgren, Lars I.; Ploug, Thorkil; Nielsen, Lars B.

2009-01-01

Obesity causes lipid accumulation in the heart and may lead to lipotoxic heart disease. Traditionally, the size of the cardiac triglyceride pool is thought to reflect the balance between uptake and β-oxidation of fatty acids. However, triglycerides can also be exported from cardiomyocytes via secretion of apolipoproteinB-containing (apoB) lipoproteins. Lipoprotein formation depends on expression of microsomal triglyceride transfer protein (MTP); the mouse expresses two isoforms of MTP, A and B. Since many aspects of the link between obesity-induced cardiac disease and cardiac lipid metabolism remain unknown, we investigated how cardiac lipoprotein synthesis affects cardiac expression of triglyceride metabolism-controlling genes, insulin sensitivity, and function in obese mice. Heart-specific ablation of MTP-A in mice using Cre-loxP technology impaired upregulation of MTP expression in response to increased fatty acid availability during fasting and fat feeding. This resulted in cardiac triglyceride accumulation but unaffected cardiac insulin-stimulated glucose uptake. Long-term fat-feeding of male C57Bl/6 mice increased cardiac triglycerides, induced cardiac expression of triglyceride metabolism-controlling genes and attenuated heart function. Abolishing cardiac triglyceride accumulation in fat-fed mice by overexpression of an apoB transgene in the heart prevented the induction of triglyceride metabolism-controlling genes and improved heart function. The results suggest that in obesity, the physiological increase of cardiac MTP expression serves to attenuate cardiac triglyceride accumulation albeit without major effects on cardiac insulin sensitivity. Nevertheless, the data suggest that genetically increased lipoprotein secretion prevents development of obesity-induced lipotoxic heart disease. PMID:19390571

Echocardiographic assessment of right ventricular function in routine practice: Which parameters are useful to predict one-year outcome in advanced heart failure patients with dilated cardiomyopathy?

PubMed

Kawata, Takayuki; Daimon, Masao; Kimura, Koichi; Nakao, Tomoko; Lee, Seitetsu L; Hirokawa, Megumi; Kato, Tomoko S; Watanabe, Masafumi; Yatomi, Yutaka; Komuro, Issei

2017-10-01

Right ventricular (RV) function has recently gained attention as a prognostic predictor of outcome even in patients who have left-sided heart failure. Since several conventional echocardiographic parameters of RV systolic function have been proposed, our aim was to determine if any of these parameters (tricuspid annular plane systolic excursion: TAPSE, tissue Doppler derived systolic tricuspid annular motion velocity: S', fractional area change: FAC) are associated with outcome in advanced heart failure patients with dilated cardiomyopathy (DCM). We retrospectively enrolled 68 DCM patients, who were New York Heart Association (NYHA) Class III or IV and had a left ventricular (LV) ejection fraction <35%. All patients were undergoing evaluation for heart transplantation or management of heart failure. Primary outcomes were defined as LV assist device implantation or cardiac death within one year. Thirty-nine events occurred (5 deaths, 32 LV assist devices implanted). Univariate analysis showed that age, systolic blood pressure, heart rate, NYHA functional class IV, plasma brain natriuretic peptide concentration, intravenous inotrope use, left atrial volume index, and FAC were associated with outcome, whereas TAPSE and S' were not. Receiver-operating characteristic curve analysis showed that the optimal FAC cut-off value to identify patients with an event was <26.7% (area under the curve=0.74). The event-free rate determined by Kaplan-Meier analysis was significantly higher in patients with FAC≥26.7% than in those with FAC<26.7% (log-lank, p=0.0003). Moreover, the addition of FAC<26.7% improved the prognostic utility of a model containing clinical variables and conventional echocardiographic indexes. FAC may provide better prognostic information than TAPSE or S' in advanced heart failure patients with DCM. Copyright © 2017 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.

Acute effects of febuxostat, a nonpurine selective inhibitor of xanthine oxidase, in pacing induced heart failure.

PubMed

Hou, Mingxiao; Hu, Qingsong; Chen, Yingjie; Zhao, Lin; Zhang, Jianyi; Bache, Robert J

2006-11-01

We investigated whether xanthine oxidase inhibition with febuxostat enhances left ventricular (LV) function and improves myocardial high energy phosphates (HEP) in dogs with pacing-induced heart failure (CHF). Febuxostat (2.2 mg/kg over 10 minutes followed by 0.06 mg/kg/min) caused no change of LV function or myocardial oxygen consumption (MVO2) at rest or during treadmill exercise in normal dogs. In dogs with CHF, febuxostat increased LV dP/dtmax at rest and during heavy exercise (P < 0.05), indicating improved LV function with no change of MVO2. Myocardial adenosine triphosphate (ATP) and phosphocreatine (PCr) were examined using 31P nuclear magnetic resonance spectroscopy in the open chest state. In normal dogs, febuxostat increased PCr/ATP during basal conditions and during high workload produced by dobutamine + dopamine (P < 0.05). PCr/ATP was decreased in animals with CHF; in these animals, febuxostat (given after completing basal and high workload measurements with vehicle) tended to increase PCr/ATP during basal conditions with no effect during catecholamine stimulation. Thus, febuxostat improved LV performance in awake dogs with CHF, but caused only a trend toward increased PCr/ATP in the open chest state. It is possible that the antecedent high workload condition prior to drug administration blunted the effect of febuxostat on HEP in the CHF animals. Alternatively, beneficial effects of febuxostat on LV performance in the failing heart may not involve HEP.

Different Roles for Contracture and Calpain in Calcium Paradox-Induced Heart Injury

PubMed Central

Zhang, Jian-Ying; Bi, Sheng-Hui; Xu, Ming; Jin, Zhen-Xiao; Yang, Yang; Jiang, Xiao-Fan; Zhou, Jing-Jun

2012-01-01

The Ca2+ paradox represents a good model to study Ca2+ overload injury in ischemic heart diseases. We and others have demonstrated that contracture and calpain are involved in the Ca2+ paradox-induced injury. This study aimed to elucidate their roles in this model. The Ca2+ paradox was elicited by perfusing isolated rat hearts with Ca2+-free KH media for 3 min or 5 min followed by 30 min of Ca2+ repletion. The LVDP was measured to reflect contractile function, and the LVEDP was measured to indicate contracture. TTC staining and the quantification of LDH release were used to define cell death. Calpain activity and troponin I release were measured after Ca2+ repletion. Ca2+ repletion of the once 3-min Ca2+ depleted hearts resulted in almost no viable tissues and the disappearance of contractile function. Compared to the effects of the calpain inhibitor MDL28170, KB-R7943, an inhibitor of the Na+/Ca2+ exchanger, reduced the LVEDP level to a greater extent, which was well correlated with improved contractile function recovery and tissue survival. The depletion of Ca2+ for 5 min had the same effects on injury as the 3-min Ca2+ depletion, except that the LVEDP in the 5-min Ca2+ depletion group was lower than the level in the 3-min Ca2+ depletion group. KB-R7943 failed to reduce the level of LVEDP, with no improvement in the LVDP recovery in the hearts subjected to the 5-min Ca2+ depletion treatment; however, KB-R7943 preserved its protective effects in surviving tissue. Both KB-R7943 and MDL28170 attenuated the Ca2+ repletion-induced increase in calpain activity in 3 min or 5 min Ca2+ depleted hearts. However, only KB-R7943 reduced the release of troponin I from the Ca2+ paradoxic heart. These results provide evidence suggesting that contracture is the main cause for contractile dysfunction, while activation of calpain mediates cell death in the Ca2+ paradox. PMID:23284963

Protease Activated Receptor-2 Contributes to Heart Failure

PubMed Central

Antoniak, Silvio; Sparkenbaugh, Erica M.; Tencati, Michael; Rojas, Mauricio; Mackman, Nigel; Pawlinski, Rafal

2013-01-01

Heart failure is a major clinical problem worldwide. Previous studies have demonstrated an important role for G protein-coupled receptors, including protease-activated receptors (PARs), in the pathology of heart hypertrophy and failure. Activation of PAR-2 on cardiomyocytes has been shown to induce hypertrophic growth in vitro. PAR-2 also contributes to myocardial infarction and heart remodeling after ischemia/reperfusion injury. In this study, we found that PAR-2 induced hypertrophic growth of cultured rat neonatal cardiomyocytes in a MEK1/2 and p38 dependent manner. In addition, PAR-2 activation on mouse cardiomyocytes increased expression of the pro-fibrotic chemokine MCP-1. Furthermore, cardiomyocyte-specific overexpression of PAR-2 in mice induced heart hypertrophy, cardiac fibrosis, inflammation and heart failure. Finally, in a mouse model of myocardial infarction induced by permanent ligation of the left anterior descending coronary artery, PAR-2 deficiency attenuated heart remodeling and improved heart function independently of its contribution to the size of the initial infarct. Taken together, our data indicate that PAR-2 signaling contributes to the pathogenesis of hypertrophy and heart failure. PMID:24312345

Continuous Flow Left Ventricular Assist Device Implant Significantly Improves Pulmonary Hypertension, Right Ventricular Contractility, and Tricuspid Valve Competence

PubMed Central

Atluri, Pavan; Fairman, Alexander S.; MacArthur, John W.; Goldstone, Andrew B.; Cohen, Jeffrey E.; Howard, Jessica L.; Zalewski, Christyna M.; Shudo, Yasuhiro; Woo, Y. Joseph

2014-01-01

Background Continuous flow left ventricular assist devices (CF LVAD) are being implanted with increasing frequency for end-stage heart failure. At the time of LVAD implant, a large proportion of patients have pulmonary hypertension, right ventricular (RV) dysfunction, and tricuspid regurgitation (TR). RV dysfunction and TR can exacerbate renal dysfunction, hepatic dysfunction, coagulopathy, edema, and even prohibit isolated LVAD implant. Repairing TR mandates increased cardiopulmonary bypass time and bicaval cannulation, which should be reserved for the time of orthotopic heart transplantation. We hypothesized that CF LVAD implant would improve pulmonary artery pressures, enhance RV function, and minimize TR, obviating need for surgical tricuspid repair. Methods One hundred fourteen continuous flow LVADs implanted from 2005 through 2011 at a single center, with medical management of functional TR, were retrospectively analyzed. Pulmonary artery pressures were measured immediately prior to and following LVAD implant. RV function and TR were graded according to standard echocardiographic criteria, prior to, immediately following, and long-term following LVAD. Results There was a significant improvement in post-VAD mean pulmonary arterial pressures (26.6 ± 4.9 vs. 30.2 ± 7.4 mmHg, p = 0.008) with equivalent loading pressures (CVP = 12.0 ± 4.0 vs. 12.1 ± 5.1 p = NS). RV function significantly improved, as noted by right ventricular stroke work index (7.04 ± 2.60 vs. 6.05 ± 2.54, p = 0.02). There was an immediate improvement in TR grade and RV function following LVAD implant, which was sustained long term. Conclusion Continuous flow LVAD implant improves pulmonary hypertension, RV function, and tricuspid regurgitation. TR may be managed nonoperatively during CF LVAD implant. PMID:24118109

Heart transplantation in adult congenital heart disease.

PubMed

Burchill, Luke J

2016-12-01

Heart failure (HF) in adult congenital heart disease (ACHD) is vastly different to that observed in acquired heart disease. Unlike acquired HF in which pharmacological strategies are the cornerstone for protecting and improving ventricular function, ACHD-related HF relies heavily upon structural and other interventions to achieve these aims. patients with ACHD constitute a small percentage of the total adult heart transplant population (∼3%), although the number of ACHD heart transplant recipients is growing rapidly with a 40% increase over the last two decades. The worldwide experience to date has confirmed heart transplantation as an effective life-extending treatment option in carefully selected patients with ACHD with end-stage cardiac disease. Opportunities for improving outcomes in patients with ACHD-related HF include (i) earlier recognition and referral to centres with combined expertise in ACHD and HF, (ii) increased awareness of arrhythmia and sudden cardiac death risk in this population, (iii) greater collaboration between HF and ACHD specialists at the time of heart transplant assessment, (iv) expert surgical planning to reduce ischaemic time and bleeding risk at the time of transplant, (v) tailored immunosuppression in the post-transplant period and (vi) development and validation of ACHD-specific risk scores to predict mortality and guide patient selection. The purpose of this article is to review current approaches to diagnosing and treating advanced HF in patients with ACHD including indications, contraindications and clinical outcomes after heart transplantation. 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/.

Mode of action and effects of standardized collaborative disease management on mortality and morbidity in patients with systolic heart failure: the Interdisciplinary Network for Heart Failure (INH) study.

PubMed

Angermann, Christiane E; Störk, Stefan; Gelbrich, Götz; Faller, Hermann; Jahns, Roland; Frantz, Stefan; Loeffler, Markus; Ertl, Georg

2012-01-01

Trials investigating efficacy of disease management programs (DMP) in heart failure reported contradictory results. Features rendering specific interventions successful are often ill defined. We evaluated the mode of action and effects of a nurse-coordinated DMP (HeartNetCare-HF, HNC). Patients hospitalized for systolic heart failure were randomly assigned to HNC or usual care (UC). Besides telephone-based monitoring and education, HNC addressed individual problems raised by patients, pursued networking of health care providers and provided training for caregivers. End points were time to death or rehospitalization (combined primary), heart failure symptoms, and quality of life (SF-36). Of 1007 consecutive patients, 715 were randomly assigned (HNC: n=352; UC: n=363; age, 69±12 years; 29% female; 40% New York Heart Association class III-IV). Within 180 days, 130 HNC and 137 UC patients reached the primary end point (hazard ratio, 1.02; 95% confidence interval, 0.81-1.30; P=0.89), since more HNC patients were readmitted. Overall, 32 HNC and 52 UC patients died (1 UC patient and 4 HNC patients after dropout); thus, uncensored hazard ratio was 0.62 (0.40-0.96; P=0.03). HNC patients improved more regarding New York Heart Association class (P=0.05), physical functioning (P=0.03), and physical health component (P=0.03). Except for HNC, health care utilization was comparable between groups. However, HNC patients requested counseling for noncardiac problems even more frequently than for cardiovascular or heart-failure-related issues. The primary end point of this study was neutral. However, mortality risk and surrogates of well-being improved significantly. Quantitative assessment of patient requirements suggested that besides (tele)monitoring individualized care considering also noncardiac problems should be integrated in efforts to achieve more sustainable improvement in heart failure outcomes. URL: http://www.controlled-trials.com. Unique identifier: ISRCTN23325295.

Keeping the heart empty and beating: an alternative technique to preserve hypertrophied hearts during valvular surgery.

PubMed

Liu, Shangdian; Liu, Zonghong; Li, Lulu; Liu, Pengfei; Liu, Hongyu

2015-05-13

To determine whether keeping the heart empty and beating is an effective technique to preserve hypertrophied pig hearts, and to investigate the underlying mechanism. Ten Bama Miniature pigs with hypertrophied hearts were divided into 2 groups (n = 5 in each group). One group underwent normothermic normokalemic simultaneous perfusion (NNSP). The other group was subjected to normothermic hypermokalemic simultaneous perfusion (NHSP) and used as controls. Cardiac contractive function, myocardial energy metabolism and myocardial perfusion were assessed using magnetic resonance imaging. Western blot analysis was carried out to determine the expression of Troponin I (cTnI), Troponin T (cTnT), SM-MHC, Casapase-3 and PARP4. TUNEL assay was used to detect apoptotic cardiomyocytes. Keeping the heart empty and beating with NNSP improved the preservation of contractile function in comparison with cardioplegic arrest using NHSP. No significant differences existed in the effects of NNSP and NHSP in maintaining myocardial energy metabolism. 13 % perfusion defects areas were found in one heart in the NHSP group, whereas none was found in all other hearts in both groups. The expressions of cTnI, cTnT, Casapase-3 and PARP4 in NHSP group were abundantly increased compared to NNSP group as measured by Western blotting. Conversely, the expression of SM-MHC in NHSP group was reduced compared with NNSP group. The number of TUNEL positive nuclei per mm(2) area was significantly increased in NHSP group compared with NNSP group. Keeping the heart beating with NNSP is an alternative technique to preserve hypertrophied hearts during valvular surgery.

Exercise physiology, testing, and training in patients supported by a left ventricular assist device.

PubMed

Loyaga-Rendon, Renzo Y; Plaisance, Eric P; Arena, Ross; Shah, Keyur

2015-08-01

The left ventricular assist device (LVAD) is an accepted treatment alternative for the management of end-stage heart failure. As we move toward implantation of LVADs in less severe cases of HF, scrutiny of functional capacity and quality of life becomes more important. Patients demonstrate improvements in exercise capacity after LVAD implantation, but the effect is less than predicted. Exercise training produces multiple beneficial effects in heart failure patients, which would be expected to improve quality of life. In this review, we describe factors that are thought to participate in the persistent exercise impairment in LVAD-supported patients, summarize current knowledge about the effect of exercise training in LVAD-supported patients, and suggest areas for future research. Copyright © 2015 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

Multiphysics and multiscale modelling, data-model fusion and integration of organ physiology in the clinic: ventricular cardiac mechanics.

PubMed

Chabiniok, Radomir; Wang, Vicky Y; Hadjicharalambous, Myrianthi; Asner, Liya; Lee, Jack; Sermesant, Maxime; Kuhl, Ellen; Young, Alistair A; Moireau, Philippe; Nash, Martyn P; Chapelle, Dominique; Nordsletten, David A

2016-04-06

With heart and cardiovascular diseases continually challenging healthcare systems worldwide, translating basic research on cardiac (patho)physiology into clinical care is essential. Exacerbating this already extensive challenge is the complexity of the heart, relying on its hierarchical structure and function to maintain cardiovascular flow. Computational modelling has been proposed and actively pursued as a tool for accelerating research and translation. Allowing exploration of the relationships between physics, multiscale mechanisms and function, computational modelling provides a platform for improving our understanding of the heart. Further integration of experimental and clinical data through data assimilation and parameter estimation techniques is bringing computational models closer to use in routine clinical practice. This article reviews developments in computational cardiac modelling and how their integration with medical imaging data is providing new pathways for translational cardiac modelling.

Micro and nanotechnologies in heart valve tissue engineering.

PubMed

Hasan, Anwarul; Saliba, John; Pezeshgi Modarres, Hassan; Bakhaty, Ahmed; Nasajpour, Amir; Mofrad, Mohammad R K; Sanati-Nezhad, Amir

2016-10-01

Due to the increased morbidity and mortality resulting from heart valve diseases, there is a growing demand for off-the-shelf implantable tissue engineered heart valves (TEHVs). Despite the significant progress in recent years in improving the design and performance of TEHV constructs, viable and functional human implantable TEHV constructs have remained elusive. The recent advances in micro and nanoscale technologies including the microfabrication, nano-microfiber based scaffolds preparation, 3D cell encapsulated hydrogels preparation, microfluidic, micro-bioreactors, nano-microscale biosensors as well as the computational methods and models for simulation of biological tissues have increased the potential for realizing viable, functional and implantable TEHV constructs. In this review, we aim to present an overview of the importance and recent advances in micro and nano-scale technologies for the development of TEHV constructs. Copyright © 2016 Elsevier Ltd. All rights reserved.

Thinking, Feeling, Intuiting and Sensing: Using the Four Psychological Functions as a Model to Empower Student Writers.

ERIC Educational Resources Information Center

Miller, Lori Ann

Writing is an act of self construction. Considering how students process information can improve the quality of instruction in composing courses, but only if quantifiable, verified models of cognitive functions are taken to heart and applied to teaching methods in the classroom. C. G. Jung's model of the four functions (thinking, sensation,…

Strategy to recognize and initiate treatment of chronic heart failure in primary care (STRETCH): a cluster randomized trial.

PubMed

van Riet, Evelien E S; Hoes, Arno W; Limburg, Alexander; van der Hoeven, Henk; Landman, Marcel A J; Rutten, Frans H

2014-01-08

Most patients with heart failure are diagnosed and managed in primary care, however, underdiagnosis and undertreatment are common. We assessed whether implementation of a diagnostic-therapeutic strategy improves functionality, health-related quality of life, and uptake of heart failure medication in primary care. A selective screening study followed by a single-blind cluster randomized trial in primary care. The study population consists of patients aged 65 years or over who presented themselves to the general practitioner in the previous 12 months with shortness of breath on exertion. Patients already known with established heart failure, confirmed by echocardiography, are excluded. Diagnostic investigations include history taking, physical examination, electrocardiography, and serum N-terminal pro B-type natriuretic peptide levels. Only participants with an abnormal electrocardiogram or an N-terminal pro B-type natriuretic peptide level exceeding the exclusionary cutpoint for non-acute onset heart failure (> 15 pmol/L (≈ 125 pg/ml)) will undergo open-access echocardiography. The diagnosis of heart failure (with reduced or preserved ejection fraction) is established by an expert panel consisting of two cardiologists and a general practitioner, according to the criteria of the European Society of Cardiology guidelines.Patients with newly established heart failure are allocated to either the 'care as usual' group or the 'intervention' group. Randomization is at the level of the general practitioner. In the intervention group general practitioners receive a single half-day training in heart failure management and the use of a structured up-titration scheme. All participants fill out quality of life questionnaires at baseline and after six months of follow-up. A six-minute walking test will be performed in patients with heart failure. Information on medication and hospitalization rates is extracted from the electronic medical files of the general practitioners. This study will provide information on the prevalence of unrecognized heart failure in elderly with shortness of breath on exertion, and the randomized comparison will reveal whether management based on a half-day training of general practitioners in the practical application of an up-titration scheme results in improvements in functionality, health-related quality of life, and uptake of heart failure medication in heart failure patients compared to care as usual. ClinicalTrials.gov NCT01202006.

How do cardiorespiratory fitness improvements vary with physical training modality in heart failure patients? A quantitative guide

PubMed Central

Smart, Neil A

2013-01-01

BACKGROUND: Peak oxygen consumption (VO2) is the gold standard measure of cardiorespiratory fitness and a reliable predictor of survival in chronic heart failure patients. Furthermore, any form of physical training usually improves cardiorespiratory fitness, although the magnitude of improvement in peak VO2 may vary across different training prescriptions. OBJECTIVE: To quantify, and subsequently rank, the magnitude of improvement in peak VO2 for different physical training prescriptions using data from published meta-analyses and randomized controlled trials. METHODS: Prospective randomized controlled parallel trials and meta-analyses of exercise training in chronic heart failure patients that provided data on change in peak VO2 for nine a priori comparative analyses were examined. RESULTS: All forms of physical training were beneficial, although the improvement in peak VO2 varied with modality. High-intensity interval exercise yielded the largest increase in peak VO2, followed in descending order by moderate-intensity aerobic exercise, functional electrical stimulation, inspiratory muscle training, combined aerobic and resistance training, and isolated resistance training. With regard to setting, the present study was unable to determine whether outpatient or unsupervised home exercise provided greater benefits in terms of peak VO2 improvment. CONCLUSIONS: Interval exercise is not suitable for all patients, especially the high-intensity variety; however, when indicated, this form of exercise should be adopted to optimize peak VO2 adaptations. Other forms of activity, such as functional electrical stimulation, may be more appropriate for patients who are not capable of high-intensity interval training, especially for severely deconditioned patients who are initially unable to exercise. PMID:24294043

Cardiac Fibroblasts Adopt Osteogenic Fates and Can Be Targeted to Attenuate Pathological Heart Calcification.

PubMed

Pillai, Indulekha C L; Li, Shen; Romay, Milagros; Lam, Larry; Lu, Yan; Huang, Jie; Dillard, Nathaniel; Zemanova, Marketa; Rubbi, Liudmilla; Wang, Yibin; Lee, Jason; Xia, Ming; Liang, Owen; Xie, Ya-Hong; Pellegrini, Matteo; Lusis, Aldons J; Deb, Arjun

2017-02-02

Mammalian tissues calcify with age and injury. Analogous to bone formation, osteogenic cells are thought to be recruited to the affected tissue and induce mineralization. In the heart, calcification of cardiac muscle leads to conduction system disturbances and is one of the most common pathologies underlying heart blocks. However the cell identity and mechanisms contributing to pathological heart muscle calcification remain unknown. Using lineage tracing, murine models of heart calcification and in vivo transplantation assays, we show that cardiac fibroblasts (CFs) adopt an osteoblast cell-like fate and contribute directly to heart muscle calcification. Small-molecule inhibition of ENPP1, an enzyme that is induced upon injury and regulates bone mineralization, significantly attenuated cardiac calcification. Inhibitors of bone mineralization completely prevented ectopic cardiac calcification and improved post injury heart function. Taken together, these findings highlight the plasticity of fibroblasts in contributing to ectopic calcification and identify pharmacological targets for therapeutic development. Copyright © 2017 Elsevier Inc. All rights reserved.

Reconstitution of coronary vasculature by an active fraction of Geum japonicum in ischemic hearts

NASA Astrophysics Data System (ADS)

Chen, Hao; Cheng, Lei; Lin, Xiaoli; Zhou, Xiaping; Cai, Zhiming; Li, Ming

2014-02-01

Chronic coronary heart disease (cCHD) is characterized by atherosclerosis, which progressively narrows the coronary artery lumen and impairs myocardial blood flow. Restoration of occluded coronary vessels with newly formed collaterals remains an ideal therapeutic approach due to the need for redirecting blood flow into the ischemic heart. In this study, we investigated the effect of an active fraction isolated from Geum joponicum (AFGJ) on angiogenesis in cCHD hearts. Our results demonstrated that AFGJ not only enhanced capillary tube formation of endothelial cells, but also promoted the growth of new coronary collaterals (at the diameter 0.021-0.21 mm) in the ischemic region of hearts in rat cCHD model. Our study also indicated that the growth of new collaterals in ischemic hearts resulted in improved functional recovery of the cCHD hearts as demonstrated by ECG and echocardiography analyses. These data suggest that AFGJ may provide a novel therapeutic method for effective treatment of cCHD.

DCDS: A Real-time Data Capture and Personalized Decision Support System for Heart Failure Patients in Skilled Nursing Facilities.

PubMed

Zhu, Wei; Luo, Lingyun; Jain, Tarun; Boxer, Rebecca S; Cui, Licong; Zhang, Guo-Qiang

2016-01-01

Heart disease is the leading cause of death in the United States. Heart failure disease management can improve health outcomes for elderly community dwelling patients with heart failure. This paper describes DCDS, a real-time data capture and personalized decision support system for a Randomized Controlled Trial Investigating the Effect of a Heart Failure Disease Management Program (HF-DMP) in Skilled Nursing Facilities (SNF). SNF is a study funded by the NIH National Heart, Lung, and Blood Institute (NHLBI). The HF-DMP involves proactive weekly monitoring, evaluation, and management, following National HF Guidelines. DCDS collects a wide variety of data including 7 elements considered standard of care for patients with heart failure: 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. We present the design and implementation of DCDS and describe our preliminary testing results.

Diagnosis and management of heart failure in the elderly.

PubMed

King, D

1996-10-01

Heart failure is common in the elderly and is associated with a significant morbidity and mortality. It accounts for about 5% of adult medical admissions and the expenditure of 1% of the total National Health Service budget. Clinical presentation in old age may be with the classical symptoms of heart failure but often, due to multiple pathology and low functional ability, presentation is atypical. Both nonspecific symptoms and signs of heart failure, are often a delayed presentation in this population, make diagnosis difficult. Treatment of the failing heart in an older person is similar to the young however, diligence is required when prescribing due to age-related pharmacokinetic changes and co-existent morbidity. This may result in polypharmacy and an increase in drug interactions which themselves may have deleterious consequences. However, knowledge of the aetiology of heart failure in old age and the possible atypical presentation as well as available treatments, will result in better management and improved quality of life and reduced mortality in the elderly heart failure population.

Diagnosis and management of heart failure in the elderly.

PubMed Central

King, D.

1996-01-01

Heart failure is common in the elderly and is associated with a significant morbidity and mortality. It accounts for about 5% of adult medical admissions and the expenditure of 1% of the total National Health Service budget. Clinical presentation in old age may be with the classical symptoms of heart failure but often, due to multiple pathology and low functional ability, presentation is atypical. Both nonspecific symptoms and signs of heart failure, are often a delayed presentation in this population, make diagnosis difficult. Treatment of the failing heart in an older person is similar to the young however, diligence is required when prescribing due to age-related pharmacokinetic changes and co-existent morbidity. This may result in polypharmacy and an increase in drug interactions which themselves may have deleterious consequences. However, knowledge of the aetiology of heart failure in old age and the possible atypical presentation as well as available treatments, will result in better management and improved quality of life and reduced mortality in the elderly heart failure population. PMID:8977936

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.

Modeling and Representation of Human Hearts for Volumetric Measurement

PubMed Central

Guan, Qiu; Wang, Wanliang; Wu, Guang

2012-01-01

This paper investigates automatic construction of a three-dimensional heart model from a set of medical images, represents it in a deformable shape, and uses it to perform volumetric measurements. This not only significantly improves its reliability and accuracy but also makes it possible to derive valuable novel information, like various assessment and dynamic volumetric measurements. The method is based on a flexible model trained from hundreds of patient image sets by a genetic algorithm, which takes advantage of complete segmentation of the heart shape to form a geometrical heart model. For an image set of a new patient, an interpretation scheme is used to obtain its shape and evaluate some important parameters. Apart from automatic evaluation of traditional heart functions, some new information of cardiovascular diseases may be recognized from the volumetric analysis. PMID:22162723

Radionuclide Imaging of Neurohormonal System of the Heart

PubMed Central

Chen, Xinyu; Werner, Rudolf A.; Javadi, Mehrbod S.; Maya, Yoshifumi; Decker, Michael; Lapa, Constantin; Herrmann, Ken; Higuchi, Takahiro

2015-01-01

Heart failure is one of the growing causes of death especially in developed countries due to longer life expectancy. Although many pharmacological and instrumental therapeutic approaches have been introduced for prevention and treatment of heart failure, there are still limitations and challenges. Nuclear cardiology has experienced rapid growth in the last few decades, in particular the application of single photon emission computed tomography (SPECT) and positron emission tomography (PET), which allow non-invasive functional assessment of cardiac condition including neurohormonal systems involved in heart failure; its application has dramatically improved the capacity for fundamental research and clinical diagnosis. In this article, we review the current status of applying radionuclide technology in non-invasive imaging of neurohormonal system in the heart, especially focusing on the tracers that are currently available. A short discussion about disadvantages and perspectives is also included. PMID:25825596

Evaluation of athletes with complex congenital heart disease.

PubMed

Bates, Benjamin A; Richards, Camille; Hall, Michael; Kerut, Edmund K; Campbell, William; McMullan, Michael R

2017-06-01

As a result of improvements in congenital heart surgery, there are more adults alive today with congenital heart disease (CHD) than children. Individuals with cardiac birth defects may be able to participate in physical activities but require proper cardiovascular evaluation. The American Heart Association and American College of Cardiology released guidelines in 2015 for athletes with cardiovascular abnormalities. The guidelines express that although restriction from competitive athletics may be indicated for some, the majority of individuals with CHD can and should engage in some form of physical activity. This case study demonstrates the importance of combining all aspects of history, physical examination, ECG, and imaging modalities to evaluate cardiac anatomy and function in young athletes with complex CHD. © 2017, Wiley Periodicals, Inc.

Nkx2.5 enhances the efficacy of mesenchymal stem cells transplantation in treatment heart failure in rats.

PubMed

Deng, Bo; Wang, Jin Xin; Hu, Xing Xing; Duan, Peng; Wang, Lin; Li, Yang; Zhu, Qing Lei

2017-08-01

The aim of this study is to determine whether Nkx2.5 transfection of transplanted bone marrow mesenchymal stem cells (MSCs) improves the efficacy of treatment of adriamycin-induced heart failure in a rat model. Nkx2.5 was transfected in MSCs by lentiviral vector transduction. The expressions of Nkx2.5 and cardiac specific genes in MSCs and Nkx2.5 transfected mesenchymal stem cells (MSCs-Nkx2.5) were analyzed with quantitative real-time PCR and Western blot in vitro. Heart failure models of rats were induced by adriamycin and were then randomly divided into 3 groups: injected saline, MSCs or MSCs-Nkx2.5 via the femoral vein respectively. Four weeks after injection, the cardiac function, expressions of cardiac specific gene, fibrosis formation and collagen volume fraction in the myocardium as well as the expressions of GATA4 and MEF2 in rats were analyzed with echocardiography, immunohistochemistry, Masson staining, quantitative real-time PCR and Western blot, respectively. Nkx2.5 enhanced cardiac specific gene expressions including α-MHC, TNI, CKMB, connexin-43 in MSCs-Nkx2.5 in vitro. Both MSCs and MSCs-Nkx2.5 improved cardiac function, promoted the differentiation of transplanted MSCs into cardiomyocyte-like cells, decreased fibrosis formation and collagen volume fraction in the myocardium, as well as increased the expressions of GATA4 and MEF2 in adriamycin-induced rat heart failure models. Moreover, the effect was much more remarkable in MSCs-Nkx2.5 than in MSCs group. This study has found that Nkx2.5 enhances the efficacy of MSCs transplantation in treatment adriamycin-induced heart failure in rats. Nkx2.5 transfected to transplanted MSCs provides a potential effective approach to heart failure. Copyright © 2017 Elsevier Inc. All rights reserved.

Improvement in Creatinine Clearance after Open Heart Surgery in Infants as an Early Indicator of Surgical Success.

PubMed

Dagan, Amit; Dagan, Ovadia

2016-12-01

Early surgical correction of congenital heart malformations in neonates and small infants may be complicated by acute kidney injury (AKI), which is associated with higher morbidity and mortality rates, especially in patients who require dialysis. Glomerular filtration rate (GFR) is considered the best measurement of renal function which, in neonates and infants, is highly dependent on heart function. To determine whether measurements of creatinine clearance after open heart surgery in neonates and young infants can serve as an early indicator of surgical success or AKI. We conducted a prospective observational study in 19 neonates and small infants (body weight < 5 kg) scheduled for open heart surgery with cardiopulmonary bypass. Urine collection measurement of creatinine clearance and albumin excretion was performed before and during surgery and four times during 48 hours after surgery. Mean creatinine clearance was lowest during surgery (25.2 ± 4. ml/min/1.73 m2) and increased significantly in the first 16 hours post-surgery (45.7 ± 6.3 ml/min/1.73 m2). A similar pattern was noted for urine albumin which was highest during surgery (203 ± 31 µg/min) and lowest (93 ± 20 µg/min) 48 hours post-surgery. AKI occurred in four patients, and two patients even required dialysis. All six showed a decline in creatinine clearance and an increase in urine albumin between 8 and 16 hours post-surgery. In neonates and small infants undergoing open heart surgery, a significant improvement in creatinine clearance in the first 16 hours postoperatively is indicative of a good surgical outcome. This finding has important implications for the early evaluation and treatment of patients in the intensive care unit on the first day post-surgery.

Kinin B1 receptor blockade and ACE inhibition attenuate cardiac postinfarction remodeling and heart failure in rats

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

Lin, Xinchun

Introduction: The aim of the present study was to evaluate the effects of the novel kinin B1 receptor antagonist BI113823 on postinfarction cardiac remodeling and heart failure, and to determine whether B1 receptor blockade alters the cardiovascular effects of an angiotensin 1 converting enzyme (ACE) inhibitor in rats. Methods and results: Sprague Dawley rats were subjected to permanent occlusion of the left coronary artery. Cardiovascular function was determined at 6 weeks postinfarction. Treatment with either B1 receptor antagonist (BI113823) or an ACE inhibitor (lisinopril) alone or in combination significantly reduced the heart weight-to-body weight and lung weight-to-body weight ratios, andmore » improved postinfarction cardiac function as evidenced by greater cardiac output, the maximum rate of left ventricular pressure rise (± dP/dtmax), left ventricle ejection fraction, fractional shorting, better wall motion, and attenuation of elevated left ventricular end diastolic pressure (LVEDP). Furthermore, all three treatment groups exhibited significant reduction in cardiac interstitial fibrosis, collagen deposition, CD68 positive macrophages, neutrophils, and proinflammatory cytokine production (TNF-α and IL-1β), compared to vehicle controls. Conclusion: The present study shows that treatment with the novel kinin B1 receptor antagonist, BI113823, reduces postinfarction cardiac remodeling and heart failure, and does not influence the cardiovascular effects of the ACE inhibitor. - Highlights: • We examined the role of kinin B1 receptors in the development of heart failure. • Kinin B1 receptor blockade attenuates post-infarction cardiac remodeling. • Kinin B1 receptor blockade improves dysfunction, and prevented heart failure. • B1 receptor blockade does not affect the cardio-protection of an ACE inhibitor.« less

Strategies for regeneration of heart muscle.

PubMed

Guyette, Jacques P; Cohen, Ira S; Gaudette, Glenn R

2010-01-01

Regenerative medicine has emerged to the forefront of cardiac research, marrying discoveries in both basic science and engineering to develop viable therapeutic approaches for treating the diseased heart. Signifi cant advancements in gene therapy, stem cell biology, and cardiomyoplasty provide new optimism for regenerating damaged myocardium. Exciting new strategies for endogenous and exogenous regeneration have been proposed. However, questions remain as to whether these approaches can provide enough new myocyte mass to sufficiently restore mechanical function to the heart. In this article, we consider the mechanisms of endogenous cardiomyocyte regeneration and exogenous cell differentiation (with respect to myoblasts, stem cells, and induced pluripotent cells being researched for cell therapies). We begin by reviewing some of the cues that are being harnessed in strategies of gene/cell therapy for regenerating myocardium. We also consider some of the technical challenges that remain in determining new myocyte generation, tracking delivered cells in vivo, and correlating new myocyte contractility with cardiac function. Strategies for regenerating the heart are being realized as both animal and clinical trials suggest that these new approaches provide short-term improvement of cardiac function. However, a more complete understanding of the underlying mechanisms and applications is necessary to sustain longer-term therapeutic success.

Modeling the effects of functional performance and post-transplant comorbidities on health-related quality of life after heart transplantation.

PubMed

Butler, Javed; McCoin, Nicole S; Feurer, Irene D; Speroff, Theodore; Davis, Stacy F; Chomsky, Don B; Wilson, John R; Merrill, Walter H; Drinkwater, Davis C; Pierson, Richard N; Pinson, C Wright

2003-10-01

Health-related quality of life and functional performance are important outcome measures following heart transplantation. This study investigates the impact of pre-transplant functional performance and post-transplant rejection episodes, obesity and osteopenia on post-transplant health-related quality of life and functional performance. Functional performance and health-related quality of life were measured in 70 adult heart transplant recipients. A composite health-related quality of life outcome measure was computed via principal component analysis. Iterative, multiple regression-based path analysis was used to develop an integrated model of variables that affect post-transplant functional performance and health-related quality of life. Functional performance, as measured by the Karnofsky scale, improved markedly during the first 6 months post-transplant and was then sustained for up to 3 years. Rejection Grade > or =2 was negatively associated with health-related quality of life, measured by Short Form-36 and reversed Psychosocial Adjustment to Illness Scale scores. Patients with osteopenia had lower Short Form-36 physical scores and obese patients had lower functional performance. Path analysis demonstrated a negative direct effect of obesity (beta = - 0.28, p < 0.05) on post-transplant functional performance. Post-transplant functional performance had a positive direct effect on the health-related quality of life composite score (beta = 0.48, p < 0.001), and prior rejection episodes grade > or =2 had a negative direct effect on this measure (beta = -0.29, p < 0.05). Either directly or through effects mediated by functional performance, moderate-to-severe rejection, obesity and osteopenia negatively impact health-related quality of life. These findings indicate that efforts should be made to devise immunosuppressive regimens that reduce the incidence of acute rejection, weight gain and osteopenia after heart transplantation.

Muscle wasting and sarcopenia in heart failure and beyond: update 2017

PubMed Central

Springer, Joshua‐I.; Anker, Stefan D.

2017-01-01

Abstract Sarcopenia (loss of muscle mass and muscle function) is a strong predictor of frailty, disability and mortality in older persons and may also occur in obese subjects. The prevalence of sarcopenia is increased in patients suffering from chronic heart failure. However, there are currently few therapy options. The main intervention is resistance exercise, either alone or in combination with nutritional support, which seems to enhance the beneficial effects of training. Also, testosterone has been shown to increased muscle power and function; however, a possible limitation is the side effects of testosterone. Other investigational drugs include selective androgen receptor modulators, growth hormone, IGF‐1, compounds targeting myostatin signaling, which have their own set of side effects. There are abundant prospective targets for improving muscle function in the elderly with or without chronic heart failure, and the continuing development of new treatment strategies and compounds for sarcopenia and cardiac cachexia makes this field an exciting one. PMID:29154428

How best to assess right ventricular function by echocardiography*

PubMed Central

DiLorenzo, Michael P.; Bhatt, Shivani M.; Mercer-Rosa, Laura

2016-01-01

Right ventricular function is a crucial determinant of long-term outcomes of children with heart disease. Quantification of right ventricular systolic and diastolic performance by echocardiography is of paramount importance, given the prevalence of children with heart disease, particularly those with involvement of the right heart, such as single or systemic right ventricles, tetralogy of Fallot, and pulmonary arterial hypertension. Identification of poor right ventricular performance can provide an opportunity to intervene. In this review, we will go through the different systolic and diastolic indices, as well as their application in practice. Quantification of right ventricular function is possible and should be routinely performed using a combination of different measures, taking into account each disease state. Quantification is extremely useful for individual patient follow-up. Laboratories should continue to strive to optimise reproducibility through quality improvement and quality assurance efforts in addition to investing in technology and training for new, promising techniques, such as three-dimensional echocardiography. PMID:26675593

Percutaneous transvenous mitral commissurotomy in patients with mitral stenosis and coexistent hyperthyroidism.

PubMed

Wang, P W; Hung, J S; Fu, M; Yeh, K H; Wu, J J

1996-01-01

Percutaneous transvenous mitral commissurotomy (PTMC) was performed successfully without complications in 3 patients with severe mitral stenosis and hyperthyroidism. All 3 patients had pliable, noncalcified mitral valves. One patient who had been treated with methimazole for 6 months was still in a hyperthyroid state when she presented with intractable congestive heart failure and was found to have severe mitral stenosis. The heart failure improved immediately after PTMC, but the patient remained in New York Heart Association functional class 2 until a euthyroid state was achieved with I131 therapy. In the other 2 patients, hyperthyroidism was unsuspected at the time of PTMC. Unexpectedly suboptimal symptom improvement led to the diagnosis of hyperthyroidism 1 month after the intervention. In all 3 patients, PTMC resulted in an immediate hemodynamic and clinical improvement. However, complete clinical improvement occurred only when euthyroid state was achieved after antithyroid treatment. The present study suggests that PTMC is a safe and effective intervention modality in patients with coexisting hyperthyroidism and severe mitral stenosis. The procedure may be considered a therapeutic option in patients with hyperthyroidism and severe mitral stenosis.

Effect of functional electrical stimulation on cardiovascular outcomes in patients with chronic heart failure.

PubMed

Kadoglou, Nikolaos Pe; Mandila, Christina; Karavidas, Apostolos; Farmakis, Dimitrios; Matzaraki, Vasiliki; Varounis, Christos; Arapi, Sofia; Perpinia, Anastasia; Parissis, John

2017-05-01

Background/design Functional electrical stimulation of lower limb muscles is an alternative method of training in patients with chronic heart failure (CHF). Although it improves exercise capacity in CHF, we performed a randomised, placebo-controlled study to investigate its effects on long-term clinical outcomes. Methods We randomly assigned 120 patients, aged 71 ± 8 years, with stable CHF (New York Heart Association (NYHA) class II/III (63%/37%), mean left ventricular ejection fraction 28 ± 5%), to either a 6-week functional electrical stimulation training programme or placebo. Patients were followed for up to 19 months for death and/or hospitalisation due to CHF decompensation. Results At baseline, there were no significant differences in demographic parameters, CHF severity and medications between groups. During a median follow-up of 383 days, 14 patients died (11 cardiac, three non-cardiac deaths), while 40 patients were hospitalised for CHF decompensation. Mortality did not differ between groups (log rank test P = 0.680), while the heart failure-related hospitalisation rate was significantly lower in the functional electrical stimulation group (hazard ratio (HR) 0.40, 95% confidence interval (CI) 0.21-0.78, P = 0.007). The latter difference remained significant after adjustment for prognostic factors: age, gender, baseline NYHA class and left ventricular ejection fraction (HR 0.22, 95% CI 0.10-0.46, P < 0.001). Compared to placebo, functional electrical stimulation training was associated with a lower occurrence of the composite endpoint (death or heart failure-related hospitalisation) after adjustment for the above-mentioned prognostic factors (HR 0.21, 95% CI 0.103-0.435, P < 0.001). However, that effect was mostly driven by the favourable change in hospitalisation rates. Conclusions In CHF patients, 6 weeks functional electrical stimulation training reduced the risk of heart failure-related hospitalisations, without affecting the mortality rate. The beneficial long-term effects of this alternative method of training require further investigation.

Coronary Microvascular Function and Beyond: The Crosstalk between Hormones, Cytokines, and Neurotransmitters

PubMed Central

Dal Lin, Carlo; Tona, Francesco

2015-01-01

Beyond its hemodynamic function, the heart also acts as a neuroendocrine and immunoregulatory organ. A dynamic communication between the heart and other organs takes place constantly to maintain cardiovascular homeostasis. The current understanding highlights the importance of the endocrine, immune, and nervous factors to fine-tune the crosstalk of the cardiovascular system with the entire body. Once disrupted, this complex interorgan communication may promote the onset and the progression of cardiovascular diseases. Thus, expanding our knowledge on how these factors influence the cardiovascular system can lead to novel therapeutic strategies to improve patient care. In the present paper, we review novel concepts on the role of endocrine, immune, and nervous factors in the modulation of microvascular coronary function. PMID:26124827

Cognitive Performance in Older Adults with Stable Heart Failure: Longitudinal Evidence for Stability and Improvement

PubMed Central

Alosco, Michael L.; Garcia, Sarah; Spitznagel, Mary Beth; van Dulmen, Manfred; Cohen, Ronald; Sweet, Lawrence H.; Josephson, Richard; Hughes, Joel; Rosneck, Jim; Gunstad, John

2013-01-01

Cognitive impairment is prevalent in heart failure (HF), though substantial variability in the pattern of cognitive impairment is found across studies. To clarify the nature of cognitive impairment in HF, we examined longitudinal trajectories across multiple domains of cognition in HF patients using latent growth class modeling. 115 HF patients completed a neuropsychological battery at baseline, 3-months and 12-months. Participants also completed the Beck Depression Inventory-II (BDI-II). Latent class growth analyses revealed a three-class model for attention/executive function, four-class model for memory, and a three-class model for language. The slope for attention/executive function and language remained stable, while improvements were noted in memory performance. Education and BDI-II significantly predicted the intercept for attention/executive function and language abilities. The BDI-II also predicted baseline memory. The current findings suggest that multiple performance-based classes of neuropsychological test performance exist within cognitive domains, though case-controlled prospective studies with extended follow-ups are needed to fully elucidate changes and predictors of cognitive function in HF. PMID:23906182

The Visible Heart® project and free-access website 'Atlas of Human Cardiac Anatomy'.

PubMed

Iaizzo, Paul A

2016-12-01

Pre- and post-evaluations of implantable cardiac devices require innovative and critical testing in all phases of the design process. The Visible Heart ® Project was successfully launched in 1997 and 3 years later the Atlas of Human Cardiac Anatomy website was online. The Visible Heart ® methodologies and Atlas website can be used to better understand human cardiac anatomy, disease states and/or to improve cardiac device design throughout the development process. To date, Visible ® Heart methodologies have been used to reanimate 75 human hearts, all considered non-viable for transplantation. The Atlas is a unique free-access website featuring novel images of functional and fixed human cardiac anatomies from >400 human heart specimens. Furthermore, this website includes education tutorials on anatomy, physiology, congenital heart disease and various imaging modalities. For instance, the Device Tutorial provides examples of commonly deployed devices that were present at the time of in vitro reanimation or were subsequently delivered, including: leads, catheters, valves, annuloplasty rings, leadless pacemakers and stents. Another section of the website displays 3D models of vasculature, blood volumes, and/or tissue volumes reconstructed from computed tomography (CT) and magnetic resonance images (MRI) of various heart specimens. A new section allows the user to interact with various heart models. Visible Heart ® methodologies have enabled our laboratory to reanimate 75 human hearts and visualize functional cardiac anatomies and device/tissue interfaces. The website freely shares all images, video clips and CT/MRI DICOM files in honour of the generous gifts received from donors and their families. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2016. For Permissions, please email: journals.permissions@oup.com.

Changes of heart rate variability and prefrontal oxygenation during Tai Chi practice versus arm ergometer cycling.

PubMed

Lu, Xi; Hui-Chan, Christina Wan-Ying; Tsang, William Wai-Nam

2016-11-01

[Purpose] Exercise has been shown to improve cardiovascular fitness and cognitive function. Whether the inclusion of mind over exercise would increase parasympathetic control of the heart and brain activities more than general exercise at a similar intensity is not known. The aim of this study was to compare the effects of Tai Chi (mind-body exercise) versus arm ergometer cycling (body-focused exercise) on the heart rate variability and prefrontal oxygenation level. [Subjects and Methods] A Tai Chi master was invited to perform Tai Chi and arm ergometer cycling with similar exercise intensity on two separate days. Heart rate variability and prefrontal oxyhemoglobin levels were measured continuously by a RR recorder and near-infrared spectroscopy, respectively. [Results] During Tai Chi exercise, spectral analysis of heart rate variability demonstrated a higher high-frequency power as well as a lower low-frequency/high-frequency ratio than during ergometer cycling, suggesting increased parasympathetic and decreased sympathetic control of the heart. Also, prefrontal oxyhemoglobin and total hemoglobin levels were higher than those during arm ergometer exercise. [Conclusion] These findings suggest that increased parasympathetic control of the heart and prefrontal activities may be associated with Tai Chi practice. Having a "mind" component in Tai Chi could be more beneficial for older adults' cardiac health and cognitive function than body-focused ergometer cycling.

Cardioprotective abilities of white wine.

PubMed

Cui, Jianhua; Tosaki, Arpad; Cordis, Gerald A; Bertelli, Alberto A E; Bertelli, Aldo; Maulik, Nilanjana; Das, Dipak K

2002-05-01

To study if white wines, like red wine, can also protect the heart from ischemia reperfusion injury, ethanol-free extracts of three different white wines (WW1, WW2 and WW3) (100 mg/100 g body weight) were given orally to Sprague Dawley rats (200 g body weight) for three weeks. Control rats were given water only for the same period of time. After three weeks, rats were anesthetized and sacrificed, and the hearts excised for the preparation of isolated working rat heart. All hearts were subjected to 30 min global ischemia followed by two hours of reperfusion. The results demonstrated that among the three different white wines, only WW2 showed cardioprotection as evidenced by improved post-ischemic ventricular recovery compared to control. The amount of malonaldehyde production in white wine-fed rat hearts were lower compared to that found in control hearts indicating reduced formation of the reactive oxygen species. In vitro studies using chemiluminescence technique revealed that these white wines scavenged both superoxide anions and hydroxyl radicals. The results of our study demonstrated that only WW2 white wine provided cardioprotection as evidenced by the improved the post-ischemic contractile recovery and reduced myocardial infarct size. The cardioprotective effect of this white wine may be attributed, at least in part, from its ability to function as an in vivo antioxidant.

A randomized comparison of 5 versus 12 hours per day of cardiac contractility modulation treatment for heart failure patients: A preliminary report.

PubMed

Kloppe, Axel; Mijic, Dejan; Schiedat, Fabian; Bogossian, Harilaos; Mügge, Andreas; Rousso, Benny; Lemke, Bernd

2016-01-01

Cardiac contractility modulation (CCM) signals are non-excitatory electrical signals delivered during the absolute refractory period intended to improve contraction and cardiac function. Clinical trials have shown that CCM treatment significantly improves exercise tolerance and quality of life in symptomatic heart failure patients. Studies with CCM therapy typically include CCM delivery for 3, 5 or 7 h per day, although other configurations are also commonly used. Each has been associated with improved outcomes in heart failure, but it is not clear whether different application durations are associated with the various degrees of benefit. The purpose of the current pilot evaluation study was to evaluate the quality of life, exercise tolerance, and cardiac function, over a 6-month period when CCM was delivered for 5 h/day vs. 12 h/day. Increasing the daily CCM therapy duration is safe and as good as the standard CCM periods of application per day. This single center pilot evaluation study involved 19 medically refractory symptomatic patients with heart failure and reduced left ventricular function who underwent implantation of an Optimizer™ system (Impulse Dynamics, Orangeburg, NY, USA). Patients were randomized into one of two treatment groups; 5 h/day CCM treatment or 12 h/day CCM treatment. Subjects and evaluating physicians were blinded to the study group. Subjects returned to the hospital after 12 and 24 weeks. Efficacy evaluations included changes from baseline to 24 weeks in Minnesota Living With Heart Failure Questionnaire score (MLWHFQ), maximal oxygen consumption in the cardio-pulmonary stress test (peak VO2), New York Heart Association classification (NYHA), 6-min walk distance (6MWD), and ejection fraction (EF). At the end of 24 weeks, clinical improvement was observed in the entire cohort in all efficacy measures (mean change from baseline of -17.1 in MLWHFQ, -0.86 in NYHA, and improvement trend of 1.48 mL O2/kg/min in peak VO2, 31.3 m in 6MWD, and 2.25% in EF). There were no significant differences, either clinically or statistically, between the groups receiving CCM for 5 h/day vs. 12 h/day. Three subjects were voluntarily withdrawn before completing the study. One subject died from pneumonia after 125 days, and 6 serious adverse events were reported, none of which was classified as related to either the device or the procedure. Together with previously reported experience with CCM, delivery of CCM therapy is equally safe and appears similarly effective over the range of shorter (5 h) to longer (12 h) daily periods of application. Given the small sample size, further studies are warranted.

Current progress in tissue engineering of heart valves: multiscale problems, multiscale solutions.

PubMed

Cheung, Daniel Y; Duan, Bin; Butcher, Jonathan T

2015-01-01

Heart valve disease is an increasingly prevalent and clinically serious condition. There are no clinically effective biological diagnostics or treatment strategies. The only recourse available is replacement with a prosthetic valve, but the inability of these devices to grow or respond biologically to their environments necessitates multiple resizing surgeries and life-long coagulation treatment, especially in children. Tissue engineering has a unique opportunity to impact heart valve disease by providing a living valve conduit, capable of growth and biological integration. This review will cover current tissue engineering strategies in fabricating heart valves and their progress towards the clinic, including molded scaffolds using naturally derived or synthetic polymers, decellularization, electrospinning, 3D bioprinting, hybrid techniques, and in vivo engineering. Whereas much progress has been made to create functional living heart valves, a clinically viable product is not yet realized. The next leap in engineered living heart valves will require a deeper understanding of how the natural multi-scale structural and biological heterogeneity of the tissue ensures its efficient function. Related, improved fabrication strategies must be developed that can replicate this de novo complexity, which is likely instructive for appropriate cell differentiation and remodeling whether seeded with autologous stem cells in vitro or endogenously recruited cells.

[Effects of xenon preconditioning against ischemia/reperfusion injury and oxidative stress in immature heart].

PubMed

Li, Qian; Lian, Chun-Wei; Fang, Li-Qun; Liu, Bin; Yang, Bo

2014-09-01

To investigate whether xenon preconditioning (PC) could protect immature myocardium against ischemia-reperfusion (I/R) injury in a dose-dependent manner and clarify the role of xenon PC on oxidative stress. Forty-eight isolated perfused immature rabbit hearts were randomly divided into four groups (n = 12): The sham group had the hearts perfused continuously for 300 min. In I/R group, the hearts were subjected to 60 min perfusion followed by 60 min ischemia and 180 min reperfusion. In 1 minimum alveolar concentration (MAC) and 0.5 MAC xenon PC groups, the hearts were preconditioned with 1 MAC or 0.5 MAC xenon respectively, following 60 min ischemia and 180 min reperfusion. The cardiac function, myocardial infarct size, mitochondrial structure, superoxide dismutase (SOD) activity and malondialdehyde (MDA) level in each group were determined after reperfusion. Compared with I/R group, both 1 MAC and 0. 5 MAC xenon preconditioning significantly improved cardiac function (P < 0.01), reduced myocardial infarct size (P < 0.01) and mitochondrial damage, increased SOD activity and decreased MDA level (P < 0.01). There were no differences between 1 MAC group and 0.5 MAC xenon group (P > 0.05). Xenon preconditioning at 0. 5 and 1 MAC produce similar cardioprotective effects against I/R injury in isolated perfused immature heart.

Current Progress in Tissue Engineering of Heart Valves: Multiscale Problems, Multiscale Solutions

PubMed Central

Cheung, Daniel Y; Duan, Bin; Butcher, Jonathan T.

2016-01-01

Introduction Heart valve disease is an increasingly prevalent and clinically serious condition. There are no clinically effective biological diagnostics or treatment strategies. The only recourse available is replacement with a prosthetic valve, but the inability of these devices to grow or respond biologically to their environments necessitates multiple resizing surgeries and life-long coagulation treatment, especially in children. Tissue engineering has a unique opportunity to impact heart valve disease by providing a living valve conduit, capable of growth and biological integration. Areas covered This review will cover current tissue engineering strategies in fabricating heart valves and their progress towards the clinic, including molded scaffolds using naturally-derived or synthetic polymers, decellularization, electrospinning, 3D bioprinting, hybrid techniques, and in vivo engineering. Expert opinion While much progress has been made to create functional living heart valves, a clinically viable product is not yet realized. The next leap in engineered living heart valves will require a deeper understanding of how the natural multi-scale structural and biological heterogeneity of the tissue ensures its efficient function. Related, improved fabrication strategies must be developed that can replicate this de novo complexity, which is likely instructive for appropriate cell differentiation and remodeling whether seeded with autologous stem cells in vitro or endogenously recruited cells. PMID:26027436

Employing Extracellular Volume Cardiovascular Magnetic Resonance Measures of Myocardial Fibrosis to Foster Novel Therapeutics.

PubMed

Schelbert, Erik B; Sabbah, Hani N; Butler, Javed; Gheorghiade, Mihai

2017-06-01

Quantifying myocardial fibrosis (MF) with myocardial extracellular volume measures acquired during cardiovascular magnetic resonance promises to transform clinical care by advancing pathophysiologic understanding and fostering novel therapeutics. Extracellular volume quantifies MF by measuring the extracellular compartment depicted by the myocardial uptake of contrast relative to plasma. MF is a key domain of dysfunctional but viable myocardium among others (eg, microvascular dysfunction and cardiomyocyte/mitochondrial dysfunction). Although anatomically distinct, these domains may functionally interact. MF represents pathological remodeling in the heart associated with cardiac dysfunction and adverse outcomes likely mediated by interactions with the microvasculature and the cardiomyocyte. Reversal of MF improves key measures of cardiac dysfunction, so reversal of MF represents a likely mechanism for improved outcomes. Instead of characterizing the myocardium as homogenous tissue and using important yet still generic descriptors, such as thickness (hypertrophy) and function (diastolic or systolic), which lack mechanistic specificity, paradigms of cardiac disease have evolved to conceptualize myocardial disease and patient vulnerability based on the extent of disease involving its various compartments. Specifying myocardial compartmental involvement may then implicate cellular/molecular disease pathways for treatment and targeted pharmaceutical development and above all highlight the role of the cardiac-specific pathology in heart failure among myriad other changes in the heart and beyond. The cardiology community now requires phase 2 and 3 clinical trials to examine strategies for the regression/prevention of MF and eventually biomarkers to identify MF without reliance on cardiovascular magnetic resonance. It seems likely that efficacious antifibrotic therapy will improve outcomes, but definitive data are needed. © 2017 American Heart Association, Inc.

[Cardiac resynchronization therapy for heart failure - from experimental pacing to evidence-based therapy].

PubMed

Götze, S; Butter, C; Fleck, E

2006-01-01

Within the last decade, cardiac resynchronization therapy (CRT) has become an evidence-based cornerstone for a subset of patients with chronic heart failure. For those, who suffer from ischemic or non-ischemic cardiomyopathies at NYHA III or IV, have sinus rhythm, a left bundle branch block and a left ventricular ejection fraction below 35%, CRT has evolved as an important treatment option with promising results. Numerous studies have shown that in these patients pacemaker-mediated correction of intra- and interventicular conduction disturbances can improve not only clinical symptoms, exercise tolerance and the frequency of hospitalizations, but even more important the overall mortality. These clinical results are due to several functional aspects. In the failing heart characteristic intra- and interventricular alterations in electrical conduction result in mechanical asynchrony that leads to an abnormal contraction of the left ventricle with delayed activation of the lateral wall, a paradoxical septal movement, a reduced diastolic filling and a mitral regurgitation due to dyssynchrony of papillary muscle activation. It is conceivable that these functional changes have fatal consequences for the failing heart. AV-optimized left- or biventricular stimulation by modern pacemakers can correct the pathological dyssynchrony, thereby improving cardiac function and clinical outcome in these patients. Although tremendous progress in cardiac resynchronization therapy has been made during the last decade, a couple of questions still need to be resolved. Critical issues are the identification of patients, who will predictably benefit from CRT, the value of CRT-pacemakers versus CRT-ICDs, and the usefullness of CRT in patients with atrial fibrillation.

[Apathetic hyperthyroidism with heart failure in an elderly patient with Plummer's disease].

PubMed

Narisawa, Manabu; Okada, Yosuke; Arao, Tadashi; Kuno, Fumi; Tanaka, Yoshiya

2014-12-01

We report a case of apathetic hyperthyroidism associated with unrecognized slowly growing functional thyroid adenoma (Plummer's disease), atrial fibrillation and heart failure. An 81-year-old woman with worsening thyroid dysfunction was admitted to our hospital for the treatment of heart failure. The patient had developed heart failure associated with chronic atrial fibrillation at 76 years of age, and one year later was found to have asymptomatic hyperthyroidism. Anti-thyroid autoantibodies were negative, but thyroid echography showed a 32-mm tumor devoid of internal blood flow in the left lower lobe. Free thyroxine 4 (FT4) decreased from 3.30 to 2.60 ng/dl without treatment. The patient was diagnosed with transient thyroiditis and was followed-up without treatment. However, a repeat thyroid echography showed growth of the tumor to 41 mm in 4 years. Thyroid scintigraphy showed uptake that matched the thyroid mass. Based on these findings, the established diagnosis was Plummer's disease complicated with heart failure. The patient was treated with anti-thyroid drugs, which resulted in improvement of FT4 and reduced the severity of heart failure. In this rare case of an elderly patient, Plummer's disease was associated with a slowly-growing functional thyroid adenoma, apathetic hyperthyroidism, repeated episodes of atrial fibrillation and heart failure. Since symptoms of thyrotoxicosis are likely to be missed in the elderly, it is necessary to include hyperthyroidism in the pathoetiology of heart failure and atrial fibrillation in this population.

Autonomic nervous system function, child behavior, and maternal sensitivity in three-year-old children with surgically corrected transposition.

PubMed

Harrison, Tondi M

2013-01-01

Explore relationships among autonomic nervous system (ANS) function, child behavior, and maternal sensitivity in three-year-old children with surgically corrected transposition of the great arteries (TGA) and in children healthy at birth. Children surviving complex congenital heart defects are at risk for behavior problems. ANS function is associated with behavior and with maternal sensitivity. Child ANS function (heart rate variability) and maternal sensitivity (Parent-Child Early Relational Assessment) were measured during a challenging task. Mother completed the Child Behavior Checklist. Data were analyzed descriptively and graphically. Children with TGA had less responsive autonomic function and more behavior problems than healthy children. Autonomic function improved with more maternal sensitivity. Alterations in ANS function may continue years after surgical correction in children with TGA, potentially impacting behavioral regulation. Maternal sensitivity may be associated with ANS function in this population. Continued research on relationships among ANS function, child behavior, and maternal sensitivity is warranted. Copyright © 2013 Elsevier Inc. All rights reserved.

Endothelial function is unaffected by changing between carvedilol and metoprolol in patients with heart failure-a randomized study

PubMed Central

2011-01-01

Background Carvedilol has been shown to be superior to metoprolol tartrate to improve clinical outcomes in patients with heart failure (HF), yet the mechanisms responsible for these differences remain unclear. We examined if there were differences in endothelial function, insulin stimulated endothelial function, 24 hour ambulatory blood pressure and heart rate during treatment with carvedilol, metoprolol tartrate and metoprolol succinate in patients with HF. Methods Twenty-seven patients with mild HF, all initially treated with carvedilol, were randomized to a two-month treatment with carvedilol, metoprolol tartrate or metoprolol succinate. Venous occlusion plethysmography, 24-hour blood pressure and heart rate measurements were done before and after a two-month treatment period. Results Endothelium-dependent vasodilatation was not affected by changing from carvedilol to either metoprolol tartrate or metoprolol succinate. The relative forearm blood flow at the highest dose of serotonin was 2.42 ± 0.33 in the carvedilol group at baseline and 2.14 ± 0.24 after two months continuation of carvedilol (P = 0.34); 2.57 ± 0.33 before metoprolol tartrate treatment and 2.42 ± 0.55 after treatment (p = 0.74) and in the metoprolol succinate group 1.82 ± 0.29 and 2.10 ± 0.37 before and after treatment, respectively (p = 0.27). Diurnal blood pressures as well as heart rate were also unchanged by changing from carvedilol to metoprolol tartrate or metoprolol succinate. Conclusion Endothelial function remained unchanged when switching the beta blocker treatment from carvedilol to either metoprolol tartrate or metoprolol succinate in this study, where blood pressure and heart rate also remained unchanged in patients with mild HF. Trial registration Current Controlled Trials NCT00497003 PMID:21999413

Glucose Regulation of Load‐Induced mTOR Signaling and ER Stress in Mammalian Heart

PubMed Central

Sen, Shiraj; Kundu, Bijoy K.; Wu, Henry Cheng‐Ju; Hashmi, S. Shahrukh; Guthrie, Patrick; Locke, Landon W.; Roy, R. Jack; Matherne, G. Paul; Berr, Stuart S.; Terwelp, Matthew; Scott, Brian; Carranza, Sylvia; Frazier, O. Howard; Glover, David K.; Dillmann, Wolfgang H.; Gambello, Michael J.; Entman, Mark L.; Taegtmeyer, Heinrich

2013-01-01

Background Changes in energy substrate metabolism are first responders to hemodynamic stress in the heart. We have previously shown that hexose‐6‐phosphate levels regulate mammalian target of rapamycin (mTOR) activation in response to insulin. We now tested the hypothesis that inotropic stimulation and increased afterload also regulate mTOR activation via glucose 6‐phosphate (G6P) accumulation. Methods and Results We subjected the working rat heart ex vivo to a high workload in the presence of different energy‐providing substrates including glucose, glucose analogues, and noncarbohydrate substrates. We observed an association between G6P accumulation, mTOR activation, endoplasmic reticulum (ER) stress, and impaired contractile function, all of which were prevented by pretreating animals with rapamycin (mTOR inhibition) or metformin (AMPK activation). The histone deacetylase inhibitor 4‐phenylbutyrate, which relieves ER stress, also improved contractile function. In contrast, adding the glucose analogue 2‐deoxy‐d‐glucose, which is phosphorylated but not further metabolized, to the perfusate resulted in mTOR activation and contractile dysfunction. Next we tested our hypothesis in vivo by transverse aortic constriction in mice. Using a micro‐PET system, we observed enhanced glucose tracer analog uptake and contractile dysfunction preceding dilatation of the left ventricle. In contrast, in hearts overexpressing SERCA2a, ER stress was reduced and contractile function was preserved with hypertrophy. Finally, we examined failing human hearts and found that mechanical unloading decreased G6P levels and ER stress markers. Conclusions We propose that glucose metabolic changes precede and regulate functional (and possibly also structural) remodeling of the heart. We implicate a critical role for G6P in load‐induced mTOR activation and ER stress. PMID:23686371

Loss of Intralipid®- but Not Sevoflurane-Mediated Cardioprotection in Early Type-2 Diabetic Hearts of Fructose-Fed Rats: Importance of ROS Signaling

PubMed Central

Zhang, Liyan; Affolter, Andreas; Gandhi, Manoj; Hersberger, Martin; Warren, Blair E.; Lemieux, Hélène; Sobhi, Hany F.; Clanachan, Alexander S.; Zaugg, Michael

2014-01-01

Background Insulin resistance and early type-2 diabetes are highly prevalent. However, it is unknown whether Intralipid® and sevoflurane protect the early diabetic heart against ischemia-reperfusion injury. Methods Early type-2 diabetic hearts from Sprague-Dawley rats fed for 6 weeks with fructose were exposed to 15 min of ischemia and 30 min of reperfusion. Intralipid® (1%) was administered at the onset of reperfusion. Peri-ischemic sevoflurane (2 vol.-%) served as alternative protection strategy. Recovery of left ventricular function was recorded and the activation of Akt and ERK 1/2 was monitored. Mitochondrial function was assessed by high-resolution respirometry and mitochondrial ROS production was measured by Amplex Red and aconitase activity assays. Acylcarnitine tissue content was measured and concentration-response curves of complex IV inhibition by palmitoylcarnitine were obtained. Results Intralipid® did not exert protection in early diabetic hearts, while sevoflurane improved functional recovery. Sevoflurane protection was abolished by concomitant administration of the ROS scavenger N-2-mercaptopropionyl glycine. Sevoflurane, but not Intralipid® produced protective ROS during reperfusion, which activated Akt. Intralipid® failed to inhibit respiratory complex IV, while sevoflurane inhibited complex I. Early diabetic hearts exhibited reduced carnitine-palmitoyl-transferase-1 activity, but palmitoylcarnitine could not rescue protection and enhance postischemic functional recovery. Cardiac mitochondria from early diabetic rats exhibited an increased content of subunit IV-2 of respiratory complex IV and of uncoupling protein-3. Conclusions Early type-2 diabetic hearts lose complex IV-mediated protection by Intralipid® potentially due to a switch in complex IV subunit expression and increased mitochondrial uncoupling, but are amenable to complex I-mediated sevoflurane protection. PMID:25127027

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.

Triptolide improves systolic function and myocardial energy metabolism of diabetic cardiomyopathy in streptozotocin-induced diabetic rats.

PubMed

Liang, Zhongshu; Leo, Sunnar; Wen, Helin; Ouyang, Mao; Jiang, Weihong; Yang, Kan

2015-05-13

Triptolide treatment leads to an improvement in Diabetic Cardiomyopathy (DCM) in streptozotocin-induced diabetic rat model. DCM is characterized by abnormal cardiac energy metabolism. We hypothesized that triptolide ameliorated cardiac metabolic abnormalities in DCM. We proposed (31)P nuclear magnetic resonance ((31)P NMR) spectrometry method for assessing cardiac energy metabolism in vivo and evaluating the effect of triptolide treatment in DCM rats. Six weeks triptolide treatment was conducted on streptozotocin-induced diabetic rats with dose of 100, 200 or 400 μg/kg/day respectively. Sex- and age-matched non-diabetic rats were used as control group. Cardiac chamber dimension and function were determined with echocardiography. Whole heart preparations were perfused with Krebs-Henseleit buffer and (31)P NMR spectroscopy was performed. Cardiac p38 Mitogen Activating Protein Kinase (MAPK) was measured using real time PCR and western blot analysis. In diabetic rats, cardiac mass index was significantly higher, where as cardiac EF was lower than control group. (31)P NMR spectroscopy showed that ATP and pCr concentrations in diabetic groups were also remarkably lower than control group. Compared to non-treated diabetic rats, triptolide-treated diabetic groups showed remarkable lower cardiac mass index and higher EF, ATP, pCr concentrations, and P38 MAPK expressions. Best improvement was seen in group treated with Triptolide with dose 200 μg/kg/day. (31)P NMR spectroscopy enables assessment of cardiac energy metabolism in whole heart preparations. It detects energy metabolic abnormalities in DCM hearts. Triptolide therapy improves cardiac function and increases cardiac energy metabolism at least partly through upregulation of MAPK signaling transduction.

Cardiovascular actions of the ghrelin gene-derived peptides and growth hormone-releasing hormone.

PubMed

Granata, Riccarda; Isgaard, Jörgen; Alloatti, Giuseppe; Ghigo, Ezio

2011-05-01

In 1976, small peptide growth hormone secretagogues (GHSs) were discovered and found to promote growth hormone (GH) release from the pituitary. The GHS receptor (GHS-R) was subsequently cloned, and its endogenous ligand ghrelin was later isolated from the stomach. Ghrelin is a 28-amino acid peptide, whose acylation is essential for binding to GHS-R type 1a and for the endocrine functions, including stimulation of GH secretion and subsequent food intake. Unacylated ghrelin, the other ghrelin form, although devoid of GHS-R binding is an active peptide, sharing many peripheral effects with acylated ghrelin (AG). The ghrelin system is broadly expressed in myocardial tissues, where it exerts different functions. Indeed, ghrelin inhibits cardiomyocyte and endothelial cell apoptosis, and improves left ventricular (LV) function during ischemia-reperfusion (I/R) injury. In rats with heart failure (HF), ghrelin improves LV dysfunction and attenuates the development of cardiac cachexia. Similarly, ghrelin exerts vasodilatory effects in humans, improves cardiac function and decreases systemic vascular resistance in patients with chronic HF. Obestatin is a recently identified ghrelin gene peptide. The physiological role of obestatin and its binding to the putative GPR39 receptor are still unclear, although protective effects have been demonstrated in the pancreas and heart. Similarly to AG, the hypothalamic peptide growth hormone-releasing hormone (GHRH) stimulates GH release from the pituitary, through binding to the GHRH-receptor. Besides its proliferative effects in different cell types, at the cardiovascular level GHRH inhibits cardiomyocyte apoptosis, and reduces infarct size in both isolated rat heart after I/R and in vivo after myocardial infarction. Therefore, both ghrelin and GHRH exert cardioprotective effects, which make them candidate targets for therapeutic intervention in cardiovascular dysfunctions.

Effect of coenzyme Q10 supplementation on heart failure: a meta-analysis123

PubMed Central

Thompson-Paul, Angela M; Bazzano, Lydia A

2013-01-01

Background: Coenzyme Q10 (CoQ10; also called ubiquinone) is an antioxidant that has been postulated to improve functional status in congestive heart failure (CHF). Several randomized controlled trials have examined the effects of CoQ10 on CHF with inconclusive results. Objective: The objective of this meta-analysis was to evaluate the impact of CoQ10 supplementation on the ejection fraction (EF) and New York Heart Association (NYHA) functional classification in patients with CHF. Design: A systematic review of the literature was conducted by using databases including MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, and manual examination of references from selected studies. Studies included were randomized controlled trials of CoQ10 supplementation that reported the EF or NYHA functional class as a primary outcome. Information on participant characteristics, trial design and duration, treatment, dose, control, EF, and NYHA classification were extracted by using a standardized protocol. Results: Supplementation with CoQ10 resulted in a pooled mean net change of 3.67% (95% CI: 1.60%, 5.74%) in the EF and −0.30 (95% CI: −0.66, 0.06) in the NYHA functional class. Subgroup analyses showed significant improvement in EF for crossover trials, trials with treatment duration ≤12 wk in length, studies published before 1994, and studies with a dose ≤100 mg CoQ10/d and in patients with less severe CHF. These subgroup analyses should be interpreted cautiously because of the small number of studies and patients included in each subgroup. Conclusions: Pooled analyses of available randomized controlled trials suggest that CoQ10 may improve the EF in patients with CHF. Additional well-designed studies that include more diverse populations are needed. PMID:23221577

Skeletal Myoblast Cell Sheet Implantation Ameliorates Both Systolic and Diastolic Cardiac Performance in Canine Dilated Cardiomyopathy Model.

PubMed

Shirasaka, Tomonori; Miyagawa, Shigeru; Fukushima, Satsuki; Kawaguchi, Naomasa; Nakatani, Satoshi; Daimon, Takashi; Okita, Yutaka; Sawa, Yoshiki

2016-02-01

Improving both systolic and diastolic function may be the most important factor in treating heart failure. In this study, we hypothesized that cell-sheet transplantation could improve these function in the damaged heart. We generated a dilated cardiomyopathy model in beagles by continuous ventricle pacing at 240 beats per minute. After 4 weeks, the beagles underwent skeletal myoblast cell sheet transplantation (SMCST) or a sham operation, and rapid ventricle pacing continued for an additional 4 weeks. Six of the e8 beagles treated by SMCST were still alive 4 weeks after the procedure. We evaluated SMCST's cardiotherapeutic effects by comparing beagles treated by SMCST with beagles that underwent a sham operation (control, n = 5). Diastolic function, as well as systolic function improved significantly in the SMCST group as compared with the sham group (control vs SMCST group, median [interquartile range]: E/E', 16 [0.9] vs 11 [1.0]; P < 0.001; tau, 47 [6.0] vs 36 [4.4] ms: P = 0.005. Ejection fraction, 22 (6.0) versus 46 (7.5) %, P < 0.001; end-systolic elastance, 2.5 (0.4) versus 8.2 (3.5) mm Hg/ml, P = 0.001). Histological examination revealed that the volume of collagen I and the collagen I/III ratio in the myocardium were significantly higher in the control than that in the SMCST group (collagen I, 6.0 [0.8] vs 2.6 [1.3]; P = 0.006; collagen I/III ratio, 4.8 [1.7] vs 1.2 [0.4]; P = 0.010). The potential of SMCST to ameliorate both systolic and diastolic performance was proven. The SMCST may be an alternative therapy of conventional medical treatment in the dilated cardiomyopathy heart.

Intermedin improves cardiac function and sympathetic neural remodeling in a rat model of post myocardial infarction heart failure

PubMed Central

Xu, Bin; Xu, Hao; Cao, Heng; Liu, Xiaoxiao; Qin, Chunhuan; Zhao, Yanzhou; Han, Xiaolin; Li, Hongli

2017-01-01

Emerging evidence has suggested that intermedin (IMD), a novel member of the calcitonin gene-related peptide (CGRP) family, has a wide range of cardioprotective effects. The present study investigated the effects of long-term administration of IMD on cardiac function and sympathetic neural remodeling in heart failure (HF) rats, and studied potential underlying mechanism. HF was induced in rats by myocardial infarction (MI). Male Sprague Dawley rats were randomly assigned to either saline or IMD (0.6 µg/kg/h) treatment groups for 4 weeks post-MI. Another group of sham-operated rats served as controls. Cardiac function was assessed by echocardiography, cardiac catheterization and plasma level of B-type natriuretic peptide (BNP). Cardiac sympathetic neural remodeling was assessed by immunohistochemistical study of tyrosine hydroxylase (TH) and growth associated protein 43 (GAP43) immunoreactive nerve fibers. The protein expression levels of nerve growth factor (NGF), TH and GAP43 in the ventricular myocardium were studied by western blotting. Ventricular fibrillation threshold (VFT) was determined to evaluate the incidence of ventricular arrhythmia. Oxidative stress was assessed by detecting the activity of superoxide dismutase and the level of malondialdehyde. Compared with rats administrated with saline, IMD significantly improved cardiac function, decreased the plasma BNP level, attenuated sympathetic neural remodeling, increased VFT and suppressed oxidative stress. In conclusion, these results indicated that IMD prevents ventricle remodeling and improves the performance of a failing heart. In addition, IMD attenuated sympathetic neural remodeling and reduced the incidence of ventricular arrhythmia, which may contribute to its anti-oxidative property. These results implicate IMD as a potential therapeutic agent for the treatment of HF. PMID:28627670

Skeletal Myoblast Cell Sheet Implantation Ameliorates Both Systolic and Diastolic Cardiac Performance in Canine Dilated Cardiomyopathy Model

PubMed Central

Shirasaka, Tomonori; Miyagawa, Shigeru; Fukushima, Satsuki; Kawaguchi, Naomasa; Nakatani, Satoshi; Daimon, Takashi; Okita, Yutaka; Sawa, Yoshiki

2016-01-01

Background Improving both systolic and diastolic function may be the most important factor in treating heart failure. In this study, we hypothesized that cell-sheet transplantation could improve these function in the damaged heart. Methods We generated a dilated cardiomyopathy model in beagles by continuous ventricle pacing at 240 beats per minute. After 4 weeks, the beagles underwent skeletal myoblast cell sheet transplantation (SMCST) or a sham operation, and rapid ventricle pacing continued for an additional 4 weeks. Six of the e8 beagles treated by SMCST were still alive 4 weeks after the procedure. We evaluated SMCST's cardiotherapeutic effects by comparing beagles treated by SMCST with beagles that underwent a sham operation (control, n = 5). Results Diastolic function, as well as systolic function improved significantly in the SMCST group as compared with the sham group (control vs SMCST group, median [interquartile range]: E/E', 16 [0.9] vs 11 [1.0]; P < 0.001; tau, 47 [6.0] vs 36 [4.4] ms: P = 0.005. Ejection fraction, 22 (6.0) versus 46 (7.5) %, P < 0.001; end-systolic elastance, 2.5 (0.4) versus 8.2 (3.5) mm Hg/ml, P = 0.001). Histological examination revealed that the volume of collagen I and the collagen I/III ratio in the myocardium were significantly higher in the control than that in the SMCST group (collagen I, 6.0 [0.8] vs 2.6 [1.3]; P = 0.006; collagen I/III ratio, 4.8 [1.7] vs 1.2 [0.4]; P = 0.010). Conclusions The potential of SMCST to ameliorate both systolic and diastolic performance was proven. The SMCST may be an alternative therapy of conventional medical treatment in the dilated cardiomyopathy heart. PMID:26636739

Experimental Evolution and Heart Function in Drosophila.

PubMed

Shahrestani, Parvin; Burke, Molly K; Birse, Ryan; Kezos, James N; Ocorr, Karen; Mueller, Laurence D; Rose, Michael R; Bodmer, Rolf

Drosophila melanogaster is a good model species for the study of heart function. However, most previous work on D. melanogaster heart function has focused on the effects of large-effect genetic variants. We compare heart function among 18 D. melanogaster populations that have been selected for altered development time, aging, or stress resistance. We find that populations with faster development and faster aging have increased heart dysfunction, measured as percentage heart failure after electrical pacing. Experimental evolution of different triglyceride levels, by contrast, has little effect on heart function. Evolved differences in heart function correlate with allele frequency changes at many loci of small effect. Genomic analysis of these populations produces a list of candidate loci that might affect cardiac function at the intersection of development, aging, and metabolic control mechanisms.

Building a comprehensive team for the longitudinal care of single ventricle heart defects: Building blocks and initial results.

PubMed

Texter, Karen; Davis, Jo Ann M; Phelps, Christina; Cheatham, Sharon; Cheatham, John; Galantowicz, Mark; Feltes, Timothy F

2017-07-01

With increasing survival of children with HLHS and other single ventricle lesions, the complexity of medical care for these patients is substantial. Establishing and adhering to best practice models may improve outcome, but requires careful coordination and monitoring. In 2013 our Heart Center began a process to build a comprehensive Single Ventricle Team designed to target these difficult issues. Comprehensive Single Ventricle Team in 2014 was begun, to standardize care for children with single ventricle heart defects from diagnosis to adulthood within our institution. The team is a multidisciplinary group of providers committed to improving outcomes and quality of life for children with single ventricle heart defects, all functioning within the medical home of our heart center. Standards of care were developed and implemented in five target areas to standardize medical management and patient and family support. Under the team 100 patients have been cared for. Since 2014 a decrease in interstage mortality for HLHS were seen. Using a team approach and the tools of Quality Improvement they have been successful in reaching high protocol compliance for each of these areas. This article describes the process of building a successful Single Ventricle team, our initial results, and lessons learned. Additional study is ongoing to demonstrate the effects of these interventions on patient outcomes. © 2017 Wiley Periodicals, Inc.

Effects of combined mesenchymal stem cells and heme oxygenase-1 therapy on cardiac performance.

PubMed

Zeng, Bin; Chen, Honglei; Zhu, Chengang; Ren, Xiaofeng; Lin, Guosheng; Cao, Feng

2008-10-01

Bone marrow mesenchymal stem cells (MSCs) have the potential to repair the infarcted myocardium and improve cardiac function. However, this approach is limited by its poor viability after transplantation, and controversy still exists over the mechanism by which MSCs contribute to the tissue repair. The human heme oxygenase-1 (hHO-1) was transfected into cultured MSCs using an adenoviral vector. 1 x 10(6) Ad-hHO-1-transfected MSCs (HO-1-MSCs) or Ad-Null-transfected MSCs (Null-MSCs) or PBS only (PBS group) were injected intramyocardially into rat hearts 1h after myocardial infarction. HO-1-MSCs survived in the infarcted myocardium, and expressed hHO-1 mRNA. The expression of basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF) was significantly enhanced in HO-1-MSCs-treated hearts. At the same time, there were significant reduction of TNF-alpha, IL-1-beta and IL-6 mRNA, and marked increase of IL-10 mRNA in HO-1-MSCs-treated hearts. Moreover, a further downregulation of proapoptotic protein, Bax, and a marked increase in microvessel density were observed in HO-1-MSCs-treated hearts. The infarct size and cardiac performance were also significantly improved in HO-1-MSCs-treated hearts. The combined approach improves MSCs survival and is superior to MSCs injection alone.

Roselle Polyphenols Exert Potent Negative Inotropic Effects via Modulation of Intracellular Calcium Regulatory Channels in Isolated Rat Heart.

PubMed

Lim, Yi-Cheng; Budin, Siti Balkis; Othman, Faizah; Latip, Jalifah; Zainalabidin, Satirah

2017-07-01

Roselle (Hibiscus sabdariffa Linn.) calyces have demonstrated propitious cardioprotective effects in animal and clinical studies; however, little is known about its action on cardiac mechanical function. This study was undertaken to investigate direct action of roselle polyphenols (RP) on cardiac function in Langendorff-perfused rat hearts. We utilized RP extract which consists of 12 flavonoids and seven phenolic acids (as shown by HPLC profiling) and has a safe concentration range between 125 and 500 μg/ml in this study. Direct perfusion of RP in concentration-dependent manner lowered systolic function of the heart as shown by lowered LVDP and dP/dt max , suggesting a negative inotropic effect. RP also reduced heart rate (negative chronotropic action) while simultaneously increasing maximal velocity of relaxation (positive lusitropic action). Conversely, RP perfusion increased coronary pressure, an indicator for improvement in coronary blood flow. Inotropic responses elicited by pharmacological agonists for L-type Ca 2+ channel [(±)-Bay K 8644], ryanodine receptor (4-chloro-m-cresol), β-adrenergic receptor (isoproterenol) and SERCA blocker (thapsigargin) were all abolished by RP. In conclusion, RP elicits negative inotropic, negative chronotropic and positive lusitropic responses by possibly modulating calcium entry, release and reuptake in the heart. Our findings have shown the potential use of RP as a therapeutic agent to treat conditions like arrhythmia.

Research and Implementation of Heart Sound Denoising

NASA Astrophysics Data System (ADS)

Liu, Feng; Wang, Yutai; Wang, Yanxiang

Heart sound is one of the most important signals. However, the process of getting heart sound signal can be interfered with many factors outside. Heart sound is weak electric signal and even weak external noise may lead to the misjudgment of pathological and physiological information in this signal, thus causing the misjudgment of disease diagnosis. As a result, it is a key to remove the noise which is mixed with heart sound. In this paper, a more systematic research and analysis which is involved in heart sound denoising based on matlab has been made. The study of heart sound denoising based on matlab firstly use the powerful image processing function of matlab to transform heart sound signals with noise into the wavelet domain through wavelet transform and decomposition these signals in muli-level. Then for the detail coefficient, soft thresholding is made using wavelet transform thresholding to eliminate noise, so that a signal denoising is significantly improved. The reconstructed signals are gained with stepwise coefficient reconstruction for the processed detail coefficient. Lastly, 50HZ power frequency and 35 Hz mechanical and electrical interference signals are eliminated using a notch filter.

Clinical Utility of Exercise Training in Heart Failure with Reduced and Preserved Ejection Fraction

PubMed Central

Asrar Ul Haq, Muhammad; Goh, Cheng Yee; Levinger, Itamar; Wong, Chiew; Hare, David L

2015-01-01

Reduced exercise tolerance is an independent predictor of hospital readmission and mortality in patients with heart failure (HF). Exercise training for HF patients is well established as an adjunct therapy, and there is sufficient evidence to support the favorable role of exercise training programs for HF patients over and above the optimal medical therapy. Some of the documented benefits include improved functional capacity, quality of life (QoL), fatigue, and dyspnea. Major trials to assess exercise training in HF have, however, focused on heart failure with reduced ejection fraction (HFREF). At least half of the patients presenting with HF have heart failure with preserved ejection fraction (HFPEF) and experience similar symptoms of exercise intolerance, dyspnea, and early fatigue, and similar mortality risk and rehospitalization rates. The role of exercise training in the management of HFPEF remains less clear. This article provides a brief overview of pathophysiology of reduced exercise tolerance in HFREF and heart failure with preserved ejection fraction (HFPEF), and summarizes the evidence and mechanisms by which exercise training can improve symptoms and HF. Clinical and practical aspects of exercise training prescription are also discussed. PMID:25698883

Methylene blue improves mitochondrial respiration and decreases oxidative stress in a substrate-dependent manner in diabetic rat hearts.

PubMed

Duicu, Oana M; Privistirescu, Andreea; Wolf, Adrian; Petruş, Alexandra; Dănilă, Maria D; Raţiu, Corina D; Muntean, Danina M; Sturza, Adrian

2017-11-01

Diabetic cardiomyopathy has been systematically associated with compromised mitochondrial energetics and increased generation of reactive oxygen species (ROS) that underlie its progression to heart failure. Methylene blue is a redox drug with reported protective effects mainly on brain mitochondria. The purpose of the present study was to characterize the effects of acute administration of methylene blue on mitochondrial respiration, H 2 O 2 production, and calcium sensitivity in rat heart mitochondria isolated from healthy and 2 months (streptozotocin-induced) diabetic rats. Mitochondrial respiratory function was assessed by high-resolution respirometry. H 2 O 2 production and calcium retention capacity were measured spectrofluorimetrically. The addition of methylene blue (0.1 μmol·L -1 ) elicited an increase in oxygen consumption of mitochondria energized with complex I and II substrates in both normal and diseased mitochondria. Interestingly, methylene blue elicited a significant increase in H 2 O 2 release in the presence of complex I substrates (glutamate and malate), but had an opposite effect in mitochondria energized with complex II substrate (succinate). No changes in the calcium retention capacity of healthy or diabetic mitochondria were found in the presence of methylene blue. In conclusion, in cardiac mitochondria isolated from diabetic and nondiabetic rat hearts, methylene blue improved respiratory function and elicited a dichotomic, substrate-dependent effect on ROS production.

Cardio-pulmonary fitness test by ultra-short heart rate variability.

PubMed

Aslani, Arsalan; Aslani, Amir; Kheirkhah, Jalal; Sobhani, Vahid

2011-10-01

It is known that exercise induces cardio-respiratory autonomic modulation. The aim of this study was to assess the cardio-pulmonary fitness by ultra-short heart rate variability. Study population was divided into 3 groups: Group-1 (n = 40) consisted of military sports man. Group-2 (n = 40) were healthy age-matched sedentary male subjects with normal body mass index [BMI = 19 - 25 kg/m(2)). Group-3 (n = 40) were healthy age-matched obese male subjects [BMI > 29 kg/m(2)). Standard deviation of normal-to-normal QRS intervals (SDNN) was recorded over 15 minutes. Bruce protocol treadmill test was used; and, maximum oxygen consumption (VO(2)max) was calculated. WHEN THE STUDY POPULATION WAS DIVIDED INTO QUARTILES OF SDNN (FIRST QUARTILE: < 60 msec; second quartile: > 60 and < 100 msec; third quartile: > 100 and <140 msec; and fourth quartile: >140 msec), progressive increase was found in VO(2)max; and, SDNN was significantly linked with estimated VO(2)max. In conclusion, the results of this study demonstrate that exercise training improves cardio-respiratory autonomic function (and increases heart rate variability). Improvement in cardio-respiratory autonomic function seems to translate into a lower rate of long term mortality. Ultra-short heart rate variability is a simple cardio-pulmonary fitness test which just requires 15 minutes, and involves no exercise such as in the treadmill or cycle test.

Aging and CaMKII alter intracellular Ca2+ transients and heart rhythm in Drosophila melanogaster.

PubMed

Santalla, Manuela; Valverde, Carlos A; Harnichar, Ezequiel; Lacunza, Ezequiel; Aguilar-Fuentes, Javier; Mattiazzi, Alicia; Ferrero, Paola

2014-01-01

Aging is associated to disrupted contractility and rhythmicity, among other cardiovascular alterations. Drosophila melanogaster shows a pattern of aging similar to human beings and recapitulates the arrhythmogenic conditions found in the human heart. Moreover, the kinase CaMKII has been characterized as an important regulator of heart function and an arrhythmogenic molecule that participate in Ca2+ handling. Using a genetically engineered expressed Ca2+ indicator, we report changes in cardiac Ca2+ handling at two different ages. Aging prolonged relaxation, reduced spontaneous heart rate (HR) and increased the occurrence of arrhythmias, ectopic beats and asystoles. Alignment between Drosophila melanogaster and human CaMKII showed a high degree of conservation and indicates that relevant phosphorylation sites in humans are also present in the fruit fly. Inhibition of CaMKII by KN-93 (CaMKII-specific inhibitor), reduced HR without significant changes in other parameters. By contrast, overexpression of CaMKII increased HR and reduced arrhythmias. Moreover, it increased fluorescence amplitude, maximal rate of rise of fluorescence and reduced time to peak fluorescence. These results suggest that CaMKII in Drosophila melanogaster acts directly on heart function and that increasing CaMKII expression levels could be beneficial to improve contractility.

Knockout of Eva1a leads to rapid development of heart failure by impairing autophagy

PubMed Central

Zhang, Shu; Lin, Xin; Li, Ge; Shen, Xue; Niu, Di; Lu, Guang; Fu, Xin; Chen, Yingyu; Cui, Ming; Bai, Yun

2017-01-01

EVA1A (Eva-1 homologue A) is a novel lysosome and endoplasmic reticulum-associated protein that can regulate cell autophagy and apoptosis. Eva1a is expressed in the myocardium, but its function in myocytes has not yet been investigated. Therefore, we generated inducible, cardiomyocyte-specific Eva1a knockout mice with an aim to determine the role of Eva1a in cardiac remodelling in the adult heart. Data from experiments showed that loss of Eva1a in the adult heart increased cardiac fibrosis, promoted cardiac hypertrophy, and led to cardiomyopathy and death. Further investigation suggested that this effect was associated with impaired autophagy and increased apoptosis in Eva1a knockout hearts. Moreover, knockout of Eva1a activated Mtor signalling and the subsequent inhibition of autophagy. In addition, Eva1a knockout hearts showed disorganized sarcomere structure and mitochondrial misalignment and aggregation, leading to the lack of ATP generation. Collectively, these data demonstrated that Eva1a improves cardiac function and inhibits cardiac hypertrophy and fibrosis by increasing autophagy. In conclusion, our results demonstrated that Eva1a may have an important role in maintaining cardiac homeostasis. PMID:28151473

Ischemic preconditioning fails to confer additional protection against ischemia-reperfusion injury in the hypothyroid rat heart.

PubMed

Mourouzis, I; Dimopoulos, A; Saranteas, T; Tsinarakis, N; Livadarou, E; Spanou, D; Kokkinos, A D; Xinaris, C; Pantos, C; Cokkinos, D V

2009-01-01

There is accumulating evidence showing that ischemic preconditioning (PC) may lose its cardioprotective effect in the diseased states. The present study investigated whether PC can be effective in hypothyroidism, a clinical condition which is common and often accompanies cardiac diseases such as heart failure and myocardial infarction. Hypothyroidism was induced in rats by 3-week administration of 6n-propyl-2-thiouracil in water (0.05 %). Normal and hypothyroid hearts (HYPO) were perfused in Langendorff mode and subjected to 20 min of zero-flow global ischemia and 45 min of reperfusion. A preconditioning protocol (PC) was also applied prior to ischemia. HYPO hearts had significantly improved post-ischemic recovery of left ventricular developed pressure, end-diastolic pressure and reduced lactate dehydrogenase release. Furthermore, phospho-JNK and p38 MAPK levels after ischemia and reperfusion were 4.0 and 3.0 fold lower in HYPO as compared to normal hearts (P<0.05). A different response to PC was observed in normal than in HYPO hearts. PC improved the post-ischemic recovery of function and reduced the extent of injury in normal hearts but had no additional effect on the hypothyroid hearts. This response, in the preconditioned normal hearts, resulted in 2.5 and 1.8 fold smaller expression of the phospho-JNK and phospho-p38 MAPK levels at the end of reperfusion, as compared to non-PC hearts (P<0.05), while in HYPO hearts, no additional reduction in the phosphorylation of these kinases was observed after PC. Hypothyroid hearts appear to be tolerant to ischemia-reperfusion injury. This response may be, at least in part, due to the down-regulation of ischemia-reperfusion induced activation of JNKs and p38 MAPK kinases. PC is not associated with further reduction in the activation of these kinases in the hypothyroid hearts and fails to confer added protection in those hearts.

Idiosyncratic heart rate response in men during sexual arousal.

PubMed

Rowland, David L; Crawford, Sara B

2011-05-01

Heart rate, sensitive to sympathetic activation, is known to change during sexual arousal and therefore may be a useful tool for investigating psychosomatic differences between sexually functional and dysfunctional men. However, heart rate during arousal also tends to be highly variable across individual men, making its predictability based on group patterns relatively poor. We wanted to determine whether individual men show idiosyncratic heart rate patterns during sexual arousal, that is, whether they exhibit consistent patterns across similar (though not identical) stimulus situations. Agreement between heart rates under the two conditions, visual sexual stimulation (VSS) and VSS + vibrotactile (VIB), was assessed using the concordance correlation coefficient (CCC).   Thirty-eight men, 25 of whom were diagnosed with premature ejaculation (PE), were monitored for penile response and heart rate under two similar (though not identical) conditions: a 9-minute erotic video (VSS), then a 9-minute erotic video combined with vibrotactile penile stimulation (VSS + VIB). CCC for men with PE was 0.65; for the sexually functional comparison group, CCC was 0.82. For both groups combined, CCC was 0.71. For all groupings, the CCC was relatively high, indicating agreement in heart rate from one session to the next within individual men. Despite high intersubject variation in heart rate patterns, individual men show signature heart rates across similar sexual stimulus sessions. Such stereotypy helps explain previous inconsistent findings and may also serve as a marker for the effectiveness of treatments designed to improve ejaculatory control in men with PE. © 2011 International Society for Sexual Medicine.

The sympathetic/parasympathetic imbalance in heart failure with reduced ejection fraction

PubMed Central

Floras, John S.; Ponikowski, Piotr

2015-01-01

Cardiovascular autonomic imbalance, a cardinal phenotype of human heart failure, has adverse implications for symptoms during wakefulness and sleep; for cardiac, renal, and immune function; for exercise capacity; and for lifespan and mode of death. The objectives of this Clinical Review are to summarize current knowledge concerning mechanisms for disturbed parasympathetic and sympathetic circulatory control in heart failure with reduced ejection fraction and its clinical and prognostic implications; to demonstrate the patient-specific nature of abnormalities underlying this common phenotype; and to illustrate how such variation provides opportunities to improve or restore normal sympathetic/parasympathetic balance through personalized drug or device therapy. PMID:25975657

Beneficial effects of exercise training in heart failure are lost in male diabetic rats.

PubMed

Boudia, Dalila; Domergue, Valérie; Mateo, Philippe; Fazal, Loubina; Prud'homme, Mathilde; Prigent, Héloïse; Delcayre, Claude; Cohen-Solal, Alain; Garnier, Anne; Ventura-Clapier, Renée; Samuel, Jane-Lise

2017-12-01

Exercise training has been demonstrated to have beneficial effects in patients with heart failure (HF) or diabetes. However, it is unknown whether diabetic patients with HF will benefit from exercise training. Male Wistar rats were fed either a standard (Sham, n = 53) or high-fat, high-sucrose diet ( n = 66) for 6 mo. After 2 mo of diet, the rats were already diabetic. Rats were then randomly subjected to either myocardial infarction by coronary artery ligation (MI) or sham operation. Two months later, heart failure was documented by echocardiography and animals were randomly subjected to exercise training with treadmill for an additional 8 wk or remained sedentary. At the end, rats were euthanized and tissues were assayed by RT-PCR, immunoblotting, spectrophotometry, and immunohistology. MI induced a similar decrease in ejection fraction in diabetic and lean animals but a higher premature mortality in the diabetic group. Exercise for 8 wk resulted in a higher working power developed by MI animals with diabetes and improved glycaemia but not ejection fraction or pathological phenotype. In contrast, exercise improved the ejection fraction and increased adaptive hypertrophy after MI in the lean group. Trained diabetic rats with MI were nevertheless able to develop cardiomyocyte hypertrophy but without angiogenic responses. Exercise improved stress markers and cardiac energy metabolism in lean but not diabetic-MI rats. Hence, following HF, the benefits of exercise training on cardiac function are blunted in diabetic animals. In conclusion, exercise training only improved the myocardial profile of infarcted lean rats fed the standard diet. NEW & NOTEWORTHY Exercise training is beneficial in patients with heart failure (HF) or diabetes. However, less is known of the possible benefit of exercise training for HF patients with diabetes. Using a rat model where both diabetes and MI had been induced, we showed that 2 mo after MI, 8 wk of exercise training failed to improve cardiac function and metabolism in diabetic animals in contrast to lean animals.

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.

Parallel effects of β-adrenoceptor blockade on cardiac function and fatty acid oxidation in the diabetic heart: Confronting the maze

PubMed Central

Sharma, Vijay; McNeill, John H

2011-01-01

Diabetic cardiomyopathy is a disease process in which diabetes produces a direct and continuous myocardial insult even in the absence of ischemic, hypertensive or valvular disease. The β-blocking agents bisoprolol, carvedilol and metoprolol have been shown in large-scale randomized controlled trials to reduce heart failure mortality. In this review, we summarize the results of our studies investigating the effects of β-blocking agents on cardiac function and metabolism in diabetic heart failure, and the complex inter-related mechanisms involved. Metoprolol inhibits fatty acid oxidation at the mitochondrial level but does not prevent lipotoxicity; its beneficial effects are more likely to be due to pro-survival effects of chronic treatment. These studies have expanded our understanding of the range of effects produced by β-adrenergic blockade and show how interconnected the signaling pathways of function and metabolism are in the heart. Although our initial hypothesis that inhibition of fatty acid oxidation would be a key mechanism of action was disproved, unexpected results led us to some intriguing regulatory mechanisms of cardiac metabolism. The first was upstream stimulatory factor-2-mediated repression of transcriptional master regulator PGC-1α, most likely occurring as a consequence of the improved function; it is unclear whether this effect is unique to β-blockers, although repression of carnitine palmitoyltransferase (CPT)-1 has not been reported with other drugs which improve function. The second was the identification of a range of covalent modifications which can regulate CPT-1 directly, mediated by a signalome at the level of the mitochondria. We also identified an important interaction between β-adrenergic signaling and caveolins, which may be a key mechanism of action of β-adrenergic blockade. Our experience with this labyrinthine signaling web illustrates that initial hypotheses and anticipated directions do not have to be right in order to open up meaningful directions or reveal new information. PMID:21949571

Parallel effects of β-adrenoceptor blockade on cardiac function and fatty acid oxidation in the diabetic heart: Confronting the maze.

PubMed

Sharma, Vijay; McNeill, John H

2011-09-26

Diabetic cardiomyopathy is a disease process in which diabetes produces a direct and continuous myocardial insult even in the absence of ischemic, hypertensive or valvular disease. The β-blocking agents bisoprolol, carvedilol and metoprolol have been shown in large-scale randomized controlled trials to reduce heart failure mortality. In this review, we summarize the results of our studies investigating the effects of β-blocking agents on cardiac function and metabolism in diabetic heart failure, and the complex inter-related mechanisms involved. Metoprolol inhibits fatty acid oxidation at the mitochondrial level but does not prevent lipotoxicity; its beneficial effects are more likely to be due to pro-survival effects of chronic treatment. These studies have expanded our understanding of the range of effects produced by β-adrenergic blockade and show how interconnected the signaling pathways of function and metabolism are in the heart. Although our initial hypothesis that inhibition of fatty acid oxidation would be a key mechanism of action was disproved, unexpected results led us to some intriguing regulatory mechanisms of cardiac metabolism. The first was upstream stimulatory factor-2-mediated repression of transcriptional master regulator PGC-1α, most likely occurring as a consequence of the improved function; it is unclear whether this effect is unique to β-blockers, although repression of carnitine palmitoyltransferase (CPT)-1 has not been reported with other drugs which improve function. The second was the identification of a range of covalent modifications which can regulate CPT-1 directly, mediated by a signalome at the level of the mitochondria. We also identified an important interaction between β-adrenergic signaling and caveolins, which may be a key mechanism of action of β-adrenergic blockade. Our experience with this labyrinthine signaling web illustrates that initial hypotheses and anticipated directions do not have to be right in order to open up meaningful directions or reveal new information.

Combination of RNA interference and virus receptor trap exerts additive antiviral activity in coxsackievirus B3-induced myocarditis in mice.

PubMed

Stein, Elisabeth A; Pinkert, Sandra; Becher, Peter Moritz; Geisler, Anja; Zeichhardt, Heinz; Klopfleisch, Robert; Poller, Wolfgang; Tschöpe, Carsten; Lassner, Dirk; Fechner, Henry; Kurreck, Jens

2015-02-15

Coxsackievirus B3 (CVB3) is a major heart pathogen against which no therapy exists to date. The potential of a combination treatment consisting of a proteinaceous virus receptor trap and an RNA interference-based component to prevent CVB3-induced myocarditis was investigated. A soluble variant of the extracellular domain of the coxsackievirus-adenovirus receptor (sCAR-Fc) was expressed from an adenoviral vector and 2 short hairpin RNAs (shRdRp2.4) directed against CVB3 were delivered by an adeno-associated virus (AAV) vector. Cell culture experiments revealed additive antiviral activity of the combined application. In a CVB3-induced mouse myocarditis model, both components applied individually significantly reduced inflammation and viral load in the heart. The combination exerted an additive antiviral effect and reduced heart pathology. Hemodynamic measurement revealed that infection with CVB3 resulted in impaired heart function, as illustrated by a drastically reduced cardiac output and impaired contractility and relaxation. Treatment with either sCAR-Fc or shRdRp2.4 significantly improved these parameters. Importantly, the combination of both components led to a further significant improvement of heart function. Combination of sCAR-Fc and shRdRp2.4 exerted additive effects and was significantly more effective than either of the single treatments in inhibiting CVB3-induced myocarditis and preventing cardiac dysfunction. © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Magnetic Targeting Enhances Engraftment and Functional Benefit of Iron-Labeled Cardiosphere-Derived Cells in Myocardial Infarction

PubMed Central

Cheng, Ke; Li, Tao-Sheng; Malliaras, Konstantinos; Davis, Darryl; Zhang, Yiqiang; Marbán, Eduardo

2010-01-01

Rationale The success of cardiac stem cell therapies is limited by low cell retention, due at least in part to washout via coronary veins. Objective We sought to counter the efflux of transplanted cells by rendering them magnetically-responsive and imposing an external magnetic field on the heart during and immediately after injection. Methods and Results Cardiosphere-derived cells (CDCs) were labeled with superparamagnetic microspheres (SPMs). In vitro studies revealed that cell viability and function were minimally affected by SPM labeling. SPM-labeled rat CDCs were injected intramyocardially, with and without a superimposed magnet. With magnetic targeting, cells were visibly attracted towards the magnet and accumulated around the ischemic zone. In contrast, the majority of non-targeted cells washed out immediately after injection. Fluorescence imaging revealed more retention of transplanted cells in the heart, and less migration into other organs, in the magnetically-targeted group. Quantitative PCR confirmed that magnetic targeting enhanced cell retention (at 24 hours) and engraftment (at 3 weeks) in the recipient hearts by ∼3-fold compared to non-targeted cells. Morphometric analysis revealed maximal attenuation of LV remodeling, and echocardiography showed the greatest functional improvement, in the magnetic targeting group. Histologically, more engrafted cells were evident with magnetic targeting, but there was no incremental inflammation. Conclusion Magnetic targeting enhances cell retention, engraftment and functional benefit. This novel method to improve cell therapy outcomes offers the potential for rapid translation into clinical applications. PMID:20378859

Unexpected and rapid recovery of left ventricular function in patients with peripartum cardiomyopathy: impact of cardiac resynchronization therapy.

PubMed

Mouquet, Frederic; Mostefa Kara, Meriem; Lamblin, Nicolas; Coulon, Capucine; Langlois, Stephane; Marquie, Christelle; de Groote, Pascal

2012-05-01

Aim Peripartum cardiomyopathy (PPCM) is a rare cause of dilated cardiomyopathy responsible for heart failure toward the end of pregnancy, which can lead to chronic heart failure in 50% of cases. In this short report, we assessed the benefit of cardiac resynchronization in patients with PPCM and chronic systolic dysfunction despite optimal medical treatment. For the last 10 years, we managed eight patients diagnosed with PPCM. Two of them presented severe systolic dysfunction, and medical treatment resulted in limited improvement from 10% to 25% and from 25% to 28% despite optimal treatment for 9 and 6 years, respectively. These two patients were porposed to receive an implantatable cardioverter defibrillator (ICD) and cardiac resynchronization therapy (CRT). Six months after ICD-CRT treatment, we observed a significant improvement in systolic function from 25% to 45% and 28% to 50%, respectively, and positive remodelling with reduction of left ventricular end-diastolic volume from 216 to 144 mL and from 354 to 105 mL, which represent a 34% and a 70% reduction, respectively. Physicians in charge of patients with PPCM should offer the opportunity of CRT for patients whose cardiac function has not significantly improved under standard medical treatment.

Pyridostigmine ameliorates cardiac remodeling induced by myocardial infarction via inhibition of the transforming growth factor-β1/TGF-β1-activated kinase pathway.

PubMed

Lu, Yi; Liu, Jin-Jun; Bi, Xue-Yuan; Yu, Xiao-Jiang; Kong, Shan-Shan; Qin, Fang-Fang; Zhou, Jun; Zang, Wei-Jin

2014-05-01

Autonomic imbalance characterized by sympathetic predominance coinciding with diminished vagal activity is an independent risk factor in cardiovascular diseases. Several studies show that vagus nerve stimulation exerted beneficial effects on cardiac function and survival. In this study, we investigated the vagomimetic effect of pyridostigmine on left ventricular (LV) remodeling in rats after myocardial infarction. After myocardial infarction, surviving rats were treated with or without pyridostigmine (31 mg·kg⁻¹·d⁻¹) for 2 weeks, and hemodynamic parameters were measured. LV tissue was used to assess infarct size and interstitial fibrosis by Masson's trichrome and 0.1% picrosirius red staining. Protein expression of heart tissues was used to assess the efficacy of the treatment. Pyridostigmine markedly reduced myocardial infarct size and improved cardiac diastolic function. These improvements were accompanied with a significant decrease in matrix metalloproteinase-2 expression and collagen deposition. Additionally, pyridostigmine inhibited both transforming growth factor-β1 (TGF-β1) and TGF-β1-activated kinase expression in hearts postmyocardial infarction. Thus, pyridostigmine reduces collagen deposition, attenuates cardiac fibrosis, and improves LV diastolic function after myocardial infarction via TGF-β1/TGF-β1-activated kinase pathway inhibition.

Human engineered heart tissue as a model system for drug testing.

PubMed

Eder, Alexandra; Vollert, Ingra; Hansen, Arne; Eschenhagen, Thomas

2016-01-15

Drug development is time- and cost-intensive and, despite extensive efforts, still hampered by the limited value of current preclinical test systems to predict side effects, including proarrhythmic and cardiotoxic effects in clinical practice. Part of the problem may be related to species-dependent differences in cardiomyocyte biology. Therefore, the event of readily available human induced pluripotent stem cell (hiPSC)-derived cardiomyocytes (CM) has raised hopes that this human test bed could improve preclinical safety pharmacology as well as drug discovery approaches. However, hiPSC-CM are immature and exhibit peculiarities in terms of ion channel function, gene expression, structural organization and functional responses to drugs that limit their present usefulness. Current efforts are thus directed towards improving hiPSC-CM maturity and high-content readouts. Culturing hiPSC-CM as 3-dimensional engineered heart tissue (EHT) improves CM maturity and anisotropy and, in a 24-well format using silicone racks, enables automated, multiplexed high content readout of contractile function. This review summarizes the principal technology and focuses on advantages and disadvantages of this technology and its potential for preclinical drug screening. Copyright © 2015 Elsevier B.V. All rights reserved.

Chronic Trypanosoma cruzi-elicited cardiomyopathy: from the discovery to the proposal of rational therapeutic interventions targeting cell adhesion molecules and chemokine receptors--how to make a dream come true.

PubMed

Lannes-Vieira, Joseli; Silverio, Jaline Coutinho; Pereira, Isabela Resende; Vinagre, Nathália Ferreira; Carvalho, Cristiano Marcelo Espinola; Paiva, Cláudia Neto; Silva da, Andréa Alice

2009-07-01

One hundred years ago, Carlos Chagas discovered a new disease, the American trypanosomiasis. Chagas and co-workers later characterised the disease's common manifestation, chronic cardiomyopathy, and suggested that parasitic persistence coupled with inflammation was the key underlying pathogenic mechanism. Better comprehension of the molecular mechanisms leading to clinical heart afflictions is a prerequisite to developing new therapies that ameliorate inflammation and improve heart function without hampering parasite control. Here, we review recent data showing that distinct cell adhesion molecules, chemokines and chemokine receptors participate in anti-parasite immunity and/or detrimental leukocyte trafficking to the heart. Moreover, we offer evidence that CC-chemokine receptors may be attractive therapeutic targets aiming to regain homeostatic balance in parasite/host interaction thereby improving prognosis, supporting that it is becoming a non-phantasious proposal.

Coenzyme Q10 for the treatment of heart failure: a review of the literature

PubMed Central

DiNicolantonio, James J; Bhutani, Jaikrit; McCarty, Mark F; O'Keefe, James H

2015-01-01

Coenzyme Q10 (CoQ10) is an endogenously synthesised and diet-supplied lipid-soluble cofactor that functions in the mitochondrial inner membrane to transfer electrons from complexes I and II to complex III. In addition, its redox activity enables CoQ10 to act as a membrane antioxidant. In patients with congestive heart failure, myocardial CoQ10 content tends to decline as the degree of heart failure worsens. A number of controlled pilot trials with supplemental CoQ10 in heart failure found improvements in functional parameters such as ejection fraction, stroke volume and cardiac output, without side effects. Subsequent meta-analyses have confirmed these findings, although the magnitude of benefit tends to be less notable in patients with severe heart failure, or within the context of ACE inhibitor therapy. The multicentre randomised placebo-controlled Q-SYMBIO trial has assessed the impact of supplemental CoQ10 on hard endpoints in heart failure. A total of 420 patients received either CoQ10 (100 mg three times daily) or placebo and were followed for 2 years. Although short-term functional endpoints were not statistically different in the two groups, CoQ10 significantly reduced the primary long-term endpoint—a major adverse cardiovascular event—which was observed in 15% of the treated participants compared to 26% of those receiving placebo (HR=0.50, CI 0.32 to 0.80, p=0.003). Particularly in light of the excellent tolerance and affordability of this natural physiological compound, supplemental CoQ10 has emerged as an attractive option in the management of heart failure, and merits evaluation in additional large studies. PMID:26512330

Mitochondria selective S-nitrosation by mitochondria-targeted S-nitrosothiol protects against post-infarct heart failure in mouse hearts.

PubMed

Methner, Carmen; Chouchani, Edward T; Buonincontri, Guido; Pell, Victoria R; Sawiak, Stephen J; Murphy, Michael P; Krieg, Thomas

2014-07-01

Recently it has been shown that the mitochondria-targeted S-nitrosothiol MitoSNO protects against acute ischaemia/reperfusion (IR) injury by inhibiting the reactivation of mitochondrial complex I in the first minutes of reperfusion of ischaemic tissue, thereby preventing free radical formation that underlies IR injury. However, it remains unclear how this transient inhibition of mitochondrial complex I-mediated free radicals at reperfusion affects the long-term recovery of the heart following IR injury. Here we determined whether the acute protection by MitoSNO at reperfusion prevented the subsequent development of post-myocardial infarction heart failure. Mice were subjected to 30 min left coronary artery occlusion followed by reperfusion and recovery over 28 days. MitoSNO (100 ng/kg) was applied 5 min before the onset of reperfusion followed by 20 min infusion (1 ng/kg/min). Infarct size and cardiac function were measured by magnetic resonance imaging (MRI) 24 h after infarction. MitoSNO-treated mice exhibited reduced infarct size and preserved function. In addition, MitoSNO at reperfusion improved outcome measures 28 days post-IR, including preserved systolic function (63.7 ±1.8% LVEF vs. 53.7 ± 2.1% in controls, P = 0.01) and tissue fibrosis. MitoSNO action acutely at reperfusion reduces infarct size and protects from post-myocardial infarction heart failure. Therefore, targeted inhibition of mitochondrial complex I in the first minutes of reperfusion by MitoSNO is a rational therapeutic strategy for preventing subsequent heart failure in patients undergoing IR injury. © 2014 The Authors. European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.

Effect of anthracycline combined with aerobic exercise on the treatment of breast cancer.

PubMed

Ma, Zhijun

2018-05-01

Anthracycline is a standard drug for the treatment of breast cancer. However, anthracycline has great cardiotoxicity. Some patients stop chemotherapy during severe chemotherapy and even undergo serious heart failure. At the same time, there is lack of clinical study on whether aerobic exercise can reduce the cardiotoxicity of chemotherapy drugs. The purpose of this study is to investigate the effects of aerobic exercise on the cardiac function of patients with breast cancer after anthracycline therapy. The results showed that the control group LVEF decreased significantly. In addition, the E/A value decreased and the DT interval prolonged in the control group, show that anthracycline on myocardial damage, and the observation group LVEF increased significantly (P<0.05), the results show that aerobic exercise can improve heart function, and to a certain extent, it could reverse the damage of chemotherapy drugs on the heart.

Myotonic Dystrophy Initially Presenting as Tachycardiomyopathy Successful Catheter Ablation of Atrial Flutter

PubMed Central

Asbach, S.; Gutleben, K. J.; Dahlem, P.; Brachmann, J.; Nölker, G.

2010-01-01

Myotonic dystrophy is a genetic muscular disease that is frequently associated with cardiac arrhythmias. Bradyarrhythmias, such as sinus bradycardia and atrioventricular block, are more common than tachyarrhythmias. Rarely, previously undiagnosed patients with myotonic dystrophy initially present with a tachyarrhythmia. We describe the case of a 14-year-old boy, who was admitted to the hospital with clinical signs and symptoms of decompensated heart failure and severely reduced left ventricular function. Electrocardiography showed common-type atrial flutter with 2 : 1 conduction resulting in a heart rate of 160 bpm. Initiation of medical therapy for heart failure as well as electrical cardioversion led to a marked clinical improvement. Catheter ablation of atrial flutter was performed to prevent future cardiac decompensations and to prevent development of tachymyopathy. Left ventricular function normalized during followup. Genetic analysis confirmed the clinical suspicion of myotonic dystrophy as known in other family members in this case. PMID:20871860

The influence of a constraint and bimanual training program using a variety of modalities on endurance and on the cardiac autonomic regulation system of children with unilateral cerebral palsy: A self-control clinical trial.

PubMed

Cohen-Holzer, Marilyn; Sorek, Gilad; Schweizer, Maayan; Katz-Leurer, Michal

2017-01-01

An intensive hybrid program, combining constraint with bimanual training, improves upper extremity function as well as walking endurance of children with unilateral cerebral palsy (UCP). Endurance improvement may be associated with the cardiac autonomic regulation system (CARS) adaptation, known to be impaired among these children. To examine the influence of an intensive hybrid program on CARS, walking endurance and the correlation with upper extremity function of children with UCP. Twenty-four children aged 6-10 years with UCP participated in a hybrid program, 10 days, 6 hours per day. Data were collected pre-, post- and 3-months post-intervention. Main outcome measures included the Polar RS800CX for heart rate (HR) and heart rate variability (HRV) data, the 6-Minute Walk Test (6MWT) for endurance, and the Assisting Hand Assessment (AHA) and Jebsen-Taylor Test of Hand Function (JTTHF) for bimanual and unimanual function. A significant reduction in HR and an increase in HRV at post- and 3-month post-intervention was noted (χ22= 8.3, p = 0.016) along with a significant increase in 6MWT with a median increase of 81 meters (χ22= 11.0, p = 0.004) at the same interval. A significant improvement was noted in unimanual and bimanual performance following the intervention. An intensive hybrid program effectively improved CARS function as well as walking endurance and upper extremity function in children with UCP (213).

Exercise restores coronary vascular function independent of myogenic tone or hyperglycemic status in db/db mice.

PubMed

Moien-Afshari, Farzad; Ghosh, Sanjoy; Elmi, Shahrzad; Khazaei, Majid; Rahman, Mohammad M; Sallam, Nada; Laher, Ismail

2008-10-01

Regulation of coronary function in diabetic hearts is an important component in preventing ischemic cardiac events but remains poorly studied. Exercise is recommended in the management of diabetes, but its effects on diabetic coronary function are relatively unknown. We investigated coronary artery myogenic tone and endothelial function, essential elements in maintaining vascular fluid dynamics in the myocardium. We hypothesized that exercise reduces pressure-induced myogenic constriction of coronary arteries while improving endothelial function in db/db mice, a model of type 2 diabetes. We used pressurized mouse coronary arteries isolated from hearts of control and db/db mice that were sedentary or exercised for 1 h/day on a motorized exercise-wheel system (set at 5.2 m/day, 5 days/wk). Exercise caused a approximately 10% weight loss in db/db mice and decreased whole body oxidative stress, as measured by plasma 8-isoprostane levels, but failed to improve hyperglycemia or plasma insulin levels. Exercise did not alter myogenic regulation of arterial diameter stimulated by increased transmural pressure, nor did it alter smooth muscle responses to U-46619 (a thromboxane agonist) or sodium nitroprusside (an endothelium-independent dilator). Moderate levels of exercise restored ACh-simulated, endothelium-dependent coronary artery vasodilation in db/db mice and increased expression of Mn SOD and decreased nitrotyrosine levels in hearts of db/db mice. We conclude that the vascular benefits of moderate levels of exercise were independent of changes in myogenic tone or hyperglycemic status and primarily involved increased nitric oxide bioavailability in the coronary microcirculation.

Pentamidine rescues contractility and rhythmicity in a Drosophila model of myotonic dystrophy heart dysfunction

PubMed Central

Chakraborty, Mouli; Selma-Soriano, Estela; Magny, Emile; Couso, Juan Pablo; Pérez-Alonso, Manuel; Charlet-Berguerand, Nicolas; Artero, Ruben; Llamusi, Beatriz

2015-01-01

ABSTRACT Up to 80% of individuals with myotonic dystrophy type 1 (DM1) will develop cardiac abnormalities at some point during the progression of their disease, the most common of which is heart blockage of varying degrees. Such blockage is characterized by conduction defects and supraventricular and ventricular tachycardia, and carries a high risk of sudden cardiac death. Despite its importance, very few animal model studies have focused on the heart dysfunction in DM1. Here, we describe the characterization of the heart phenotype in a Drosophila model expressing pure expanded CUG repeats under the control of the cardiomyocyte-specific driver GMH5-Gal4. Morphologically, expression of 250 CUG repeats caused abnormalities in the parallel alignment of the spiral myofibrils in dissected fly hearts, as revealed by phalloidin staining. Moreover, combined immunofluorescence and in situ hybridization of Muscleblind and CUG repeats, respectively, confirmed detectable ribonuclear foci and Muscleblind sequestration, characteristic features of DM1, exclusively in flies expressing the expanded CTG repeats. Similarly to what has been reported in humans with DM1, heart-specific expression of toxic RNA resulted in reduced survival, increased arrhythmia, altered diastolic and systolic function, reduced heart tube diameters and reduced contractility in the model flies. As a proof of concept that the fly heart model can be used for in vivo testing of promising therapeutic compounds, we fed flies with pentamidine, a compound previously described to improve DM1 phenotypes. Pentamidine not only released Muscleblind from the CUG RNA repeats and reduced ribonuclear formation in the Drosophila heart, but also rescued heart arrhythmicity and contractility, and improved fly survival in animals expressing 250 CUG repeats. PMID:26515653

Cell Therapy Trials in Congenital Heart Disease.

PubMed

Oh, Hidemasa

2017-04-14

Dramatic evolution in medical and catheter interventions and complex surgeries to treat children with congenital heart disease (CHD) has led to a growing number of patients with a multitude of long-term complications associated with morbidity and mortality. Heart failure in patients with hypoplastic left heart syndrome predicated by functional single ventricle lesions is associated with an increase in CHD prevalence and remains a significant challenge. Pathophysiological mechanisms contributing to the progression of CHD, including single ventricle lesions and dilated cardiomyopathy, and adult heart disease may inevitably differ. Although therapeutic options for advanced cardiac failure are restricted to heart transplantation or mechanical circulatory support, there is a strong impetus to develop novel therapeutic strategies. As lower vertebrates, such as the newt and zebrafish, have a remarkable ability to replace lost cardiac tissue, this intrinsic self-repair machinery at the early postnatal stage in mice was confirmed by partial ventricular resection. Although the underlying mechanistic insights might differ among the species, mammalian heart regeneration occurs even in humans, with the highest degree occurring in early childhood and gradually declining with age in adulthood, suggesting the advantage of stem cell therapy to ameliorate ventricular dysfunction in patients with CHD. Although effective clinical translation by a variety of stem cells in adult heart disease remains inconclusive with respect to the improvement of cardiac function, case reports and clinical trials based on stem cell therapies in patients with CHD may be invaluable for the next stage of therapeutic development. Dissecting the differential mechanisms underlying progressive ventricular dysfunction in children and adults may lead us to identify a novel regenerative therapy. Future regenerative technologies to treat patients with CHD are exciting prospects for heart regeneration in general practice. © 2017 American Heart Association, Inc.

Methamphetamine-Associated Congestive Heart Failure: Increasing Prevalence and Relationship of Clinical Outcomes to Continued Use or Abstinence.

PubMed

Sliman, Sean; Waalen, Jill; Shaw, David

2016-10-01

The purpose of this study was to determine the prevalence of methamphetamine-associated congestive heart failure (MAC) and to evaluate the relationship between methamphetamine abuse and EF and functional status over time. A retrospective review of records from 2009 to 2014 was carried out. Prevalence of methamphetamine abuse among all patients admitted with CHF was calculated for each of the 6 years of the study (n = 141) and was compared with prevalence of cocaine abuse and alcohol abuse. For patients with two or more admissions during the entire time period, the trajectories of NYHA functional class and EF over time were determined (n = 58). MAC has significantly increased from 1.8 to 5.6 % of total CHF patients admitted (n = 3705). Among patients who stopped using methamphetamine, NYHA functional class significantly improved, while among patients who continued methamphetamine use, NYHA was significantly worsened (p < 0.001). Significantly more patients with improved EF stopped using methamphetamine than continued (p = 0.05). There was a significant increase in the prevalence of MAC during the study period for all CHF patients admitted in our hospital system. Continued methamphetamine use is associated with worsening functional status, while cessation of methamphetamine is associated with improvement in functional status.

Treatment of Anemia in Heart Failure: Potential Risks and Benefits of Intravenous Iron Therapy in Cardiovascular Disease

PubMed Central

Jelani, Qurat-ul-ain; Katz, Stuart D.

2010-01-01

Iron-deficiency anemia is common is patients with heart failure (HF), but the optimum diagnostic tests to detect iron deficiency and the treatment options to replete iron have not been fully characterized. Recent studies in patients with HF indicate that intravenous iron can rapidly replenish iron stores in patients having iron-deficiency anemia, with resultant increased hemoglobin levels and improved functional capacity. Preliminary data from a sub-group analysis also suggests that supplemental intravenous iron therapy can improve functional capacity even in those subjects without anemia. The mechanisms responsible for this observation are not fully characterized, but may be related to beneficial effects of iron supplementation on mitochondrial respiration in skeletal muscle. The long-term safety of using intravenous iron supplementation in HF populations is not known. Iron is a known pro-oxidant factor that can inhibit nitric oxide signaling and irreversibly injury cells. Increased iron stores are associated with vascular endothelial dysfunction and increased risk of coronary heart disease events. Additional clinical trials are needed to more fully characterize the therapeutic potential and safety of intravenous iron in HF patients. PMID:20699672

Low Connexin Channel-Dependent Intercellular Communication in Human Adult Hematopoietic Progenitor/Stem Cells: Probing Mechanisms of Autologous Stem Cell Therapy

PubMed Central

Yang, Jian; Darley, Richard L; Hallett, Maurice; Evans, W Howard

2009-01-01

Human bone marrow is a clinical source of autologous progenitor stem cells showing promise for cardiac repair following ischemic insult. Functional improvements following delivery of adult bone marrow CD34+ cells into heart tissue may require metabolic/electrical communication between participating cells. Since connexin43 (Cx43) channels are implicated in cardiogenesis and provide intercellular connectivity in the heart, the authors analyzed the expression of 20 connexins (Cx) in CD34+ cells and in monocytes and granulocytes in bone marrow and spinal cord. Reverse transcriptase-polymerase chain reaction (RT-PCR) detected only low expression of Cx43 and Cx37. Very low level dye coupling was detected by flow cytometry between CD34+ cells and other Cx43 expressing cells, including HL-1 cardiac cells, and was not inhibited by specific gap junction inhibitors. The results indicate that CD34+ cells are unlikely to communicate via gap junctions and the authors conclude that use of CD34+ cells to repair damaged hearts is unlikely to involve gap junctions. The results concur with the hypothesis that bone marrow cells elicit improved cardiac function through release of undefined paracrine mediators. PMID:20298144

Implementation study of an analog spiking neural network for assisting cardiac delay prediction in a cardiac resynchronization therapy device.

PubMed

Sun, Qing; Schwartz, François; Michel, Jacques; Herve, Yannick; Dalmolin, Renzo

2011-06-01

In this paper, we aim at developing an analog spiking neural network (SNN) for reinforcing the performance of conventional cardiac resynchronization therapy (CRT) devices (also called biventricular pacemakers). Targeting an alternative analog solution in 0.13- μm CMOS technology, this paper proposes an approach to improve cardiac delay predictions in every cardiac period in order to assist the CRT device to provide real-time optimal heartbeats. The primary analog SNN architecture is proposed and its implementation is studied to fulfill the requirement of very low energy consumption. By using the Hebbian learning and reinforcement learning algorithms, the intended adaptive CRT device works with different functional modes. The simulations of both learning algorithms have been carried out, and they were shown to demonstrate the global functionalities. To improve the realism of the system, we introduce various heart behavior models (with constant/variable heart rates) that allow pathologic simulations with/without noise on the signals of the input sensors. The simulations of the global system (pacemaker models coupled with heart models) have been investigated and used to validate the analog spiking neural network implementation.

The Effects of Exercise on Cardiovascular Biomarkers: New Insights, Recent Data, and Applications.

PubMed

Che, Lin; Li, Dong

2017-01-01

The benefit of regular exercise or physical activity with appropriate intensity on improving cardiopulmonary function and endurance has long been accepted with less controversy. The challenge remains, however, quantitatively evaluate the effect of exercise on cardiovascular health due in part to the amount and intensity of exercise varies widely plus lack of effective, robust and efficient biomarker evaluation systems. Better evaluating the overall function of biomarker and validate biomarkers utility in cardiovascular health should improve the evidence regarding the benefit or the effect of exercise or physical activity on cardiovascular health, in turn increasing the efficiency of the biomarker on individuals with mild to moderate cardiovascular risk. In this review, beyond traditional cytokines, chemokines and inflammatory factors, we systemic reviewed the latest novel biomarkers in metabolomics, genomics, proteomics, and molecular imaging mainly focus on heart health, as well as cardiovascular diseases such as atherosclerosis and ischemic heart disease. Furthermore, we highlight the state-of-the-art biomarker developing techniques and its application in the field of heart health. Finally, we discuss the clinical relevance of physical activity and exercise on key biomarkers in molecular basis and practical considerations.

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.

Specific inhibition of mitochondrial oxidative stress suppresses inflammation and improves cardiac function in a rat pneumonia-related sepsis model.

PubMed

Zang, Qun S; Sadek, Hesham; Maass, David L; Martinez, Bobbie; Ma, Lisha; Kilgore, Jessica A; Williams, Noelle S; Frantz, Doug E; Wigginton, Jane G; Nwariaku, Fiemu E; Wolf, Steven E; Minei, Joseph P

2012-05-01

Using a mitochondria-targeted vitamin E (Mito-Vit-E) in a rat pneumonia-related sepsis model, we examined the role of mitochondrial reactive oxygen species in sepsis-mediated myocardial inflammation and subsequent cardiac contractile dysfunction. Sepsis was produced in adult male Sprague-Dawley rats via intratracheal injection of S. pneumonia (4 × 10(6) colony formation units per rat). A single dose of Mito-Vit-E, vitamin E, or control vehicle, at 21.5 μmol/kg, was administered 30 min postinoculation. Blood was collected, and heart tissue was harvested at various time points. Mito-Vit-E in vivo distribution was confirmed by mass spectrometry. In cardiac mitochondria, Mito-Vit-E improved total antioxidant capacity and suppressed H(2)O(2) generation, whereas vitamin E offered little effect. In cytosol, both antioxidants decreased H(2)O(2) levels, but only vitamin E strengthened antioxidant capacity. Mito-Vit-E protected mitochondrial structure and function in the heart during sepsis, demonstrated by reduction in lipid and protein oxidation, preservation of mitochondrial membrane integrity, and recovery of respiratory function. While both Mito-Vit-E and vitamin E suppressed sepsis-induced peripheral and myocardial production of proinflammatory cytokines (tumor necrosis factor-α, interleukin-1β, and interleukin-6), Mito-Vit-E exhibited significantly higher efficacy (P < 0.05). Stronger anti-inflammatory action of Mito-Vit-E was further shown by its near-complete inhibition of sepsis-induced myeloperoxidase accumulation in myocardium, suggesting its effect on neutrophil infiltration. Echocardiography analysis indicated that Mito-Vit-E ameliorated cardiac contractility of sepsis animals, shown by improved fractional shortening and ejection fraction. Together, our data suggest that targeted scavenging of mitochondrial reactive oxygen species protects mitochondrial function, attenuates tissue-level inflammation, and improves whole organ activities in the heart during sepsis.

Sustained IGF-1 Secretion by Adipose-Derived Stem Cells Improves Infarcted Heart Function.

PubMed

Bagno, Luiza L; Carvalho, Deivid; Mesquita, Fernanda; Louzada, Ruy A; Andrade, Bruno; Kasai-Brunswick, Taís H; Lago, Vivian M; Suhet, Grazielle; Cipitelli, Debora; Werneck-de-Castro, João Pedro; Campos-de-Carvalho, Antonio C

2016-01-01

The mechanism by which stem cell-based therapy improves heart function is still unknown, but paracrine mechanisms seem to be involved. Adipose-derived stem cells (ADSCs) secrete several factors, including insulin-like growth factor-1 (IGF-1), which may contribute to myocardial regeneration. Our aim was to investigate whether the overexpression of IGF-1 in ADSCs (IGF-1-ADSCs) improves treatment of chronically infarcted rat hearts. ADSCs were transduced with a lentiviral vector to induce IGF-1 overexpression. IGF-1-ADSCs transcribe100- to 200-fold more IGF-1 mRNA levels compared to nontransduced ADSCs. IGF-1 transduction did not alter ADSC immunophenotypic characteristics even under hypoxic conditions. However, IGF-1-ADSCs proliferate at higher rates and release greater amounts of growth factors such as IGF-1, vascular endothelial growth factor (VEGF), and hepatocyte growth factor (HGF) under normoxic and hypoxic conditions. Importantly, IGF-1 secreted by IGF-1-ADSCs is functional given that Akt-1 phosphorylation was remarkably induced in neonatal cardiomyocytes cocultured with IGF-1-ADSCs, and this increase was prevented with phosphatidylinositol 3-kinase (PI3K) inhibitor treatment. Next, we tested IGF-1-ADSCs in a rat myocardial infarction (MI) model. MI was performed by coronary ligation, and 4 weeks after MI, animals received intramyocardial injections of either ADSCs (n = 7), IGF-1-ADSCs (n = 7), or vehicle (n = 7) into the infarcted border zone. Left ventricular function was evaluated by echocardiography before and after 6 weeks of treatment, and left ventricular hemodynamics were assessed 7 weeks after cell injection. Notably, IGF-1-ADSCs improved left ventricular ejection fraction and cardiac contractility index, but did not reduce scar size when compared to the ADSC-treated group. In summary, transplantation of ADSCs transduced with IGF-1 is a superior therapeutic approach to treat MI compared to nontransduced ADSCs, suggesting that gene and cell therapy may bring additional benefits to the treatment of MI.

Improvement of Heart Failure by Human Amniotic Mesenchymal Stromal Cell Transplantation in Rats.

PubMed

Razavi Tousi, Seyed Mohammad Taghi; Faghihi, Mahdieh; Nobakht, Maliheh; Molazem, Mohammad; Kalantari, Elham; Darbandi Azar, Amir; Aboutaleb, Nahid

2016-07-06

Background: Recently, stem cells have been considered for the treatment of heart diseases, but no marked improvement has been recorded. This is the first study to examine the functional and histological effects of the transplantation of human amniotic mesenchymal stromal cells (hAMSCs) in rats with heart failure (HF). Methods: This study was conducted in the years 2014 and 2015. 35 male Wistar rats were randomly assigned into 5 equal experimental groups (7 rats each) as 1- Control 2- Heart Failure (HF) 3- Sham 4- Culture media 5- Stem Cell Transplantation (SCT). Heart failure was induced using 170 mg/kg/d of isoproterenol subcutaneously injection in 4 consecutive days. The failure confirmed by the rat cardiac echocardiography on day 28. In SCT group, 3×10 6 cells in 150 µl of culture media were transplanted to the myocardium. At the end, echocardiographic and hemodynamic parameters together with histological evaluation were done. Results: Echocardiography results showed that cardiac ejection fraction in HF group increased from 58/73 ± 9% to 81/25 ± 6/05% in SCT group (p value < 0.001). Fraction shortening in HF group was increased from 27/53 ± 8/58% into 45/55 ± 6/91% in SCT group (p value < 0.001). Furthermore, hAMSCs therapy significantly improved mean diastolic blood pressure, mean arterial pressure, left ventricular systolic pressure, rate pressure product, and left ventricular end-diastolic pressure compared to those in the HF group, with the values reaching the normal levels in the control group. A marked reduction in fibrosis tissue was also found in the SCT group (p value < 0.001) compared with the animals in the HF group. Conclusion: The transplantation of hAMSCs in rats with heart failure not only decreased the level of fibrosis but also conferred significant improvement in heart performance in terms of echocardiographic and hemodynamic parameters.

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.

LCZ696, an angiotensin receptor-neprilysin inhibitor, improves cardiac function with the attenuation of fibrosis in heart failure with reduced ejection fraction in streptozotocin-induced diabetic mice.

PubMed

Suematsu, Yasunori; Miura, Shin-Ichiro; Goto, Masaki; Matsuo, Yoshino; Arimura, Tadaaki; Kuwano, Takashi; Imaizumi, Satoshi; Iwata, Atsushi; Yahiro, Eiji; Saku, Keijiro

2016-04-01

Angiotensin receptor-neprilysin inhibitors (ARNis) acts an ARB and neprilysin inhibitor. Diabetes mellitus significantly increases the risk of cardiovascular disease and heart failure (HF). Therefore, we evaluated the effects and mechanisms of ARNi in HF with reduced ejection fraction (HFrEF) in streptozotocin-induced diabetic mice. Male C57BL/6J mice were injected with streptozotocin to produce diabetic mice. After myocardial reperfusion injury, diabetic mice were randomized to treatment for 4 weeks with LCZ696 (60 mg/kg), valsartan (30 mg/kg), or no treatment (n = 26-28 in each group). Cardiac function was assessed by a pressure-volume Millar catheter. The ratios of heart weight to body weight in the valsartan (P = 0.02) and LCZ696 (P = 0.005) groups were significantly less than that in the control group. Treatment with LCZ696 improved LVEF (43 ± 3.4%) with a significantly reduction of atrial natriuretic peptide mRNA in the left ventricle compared with that in the control group (29 ± 3.2%) (P = 0.006). The fibrotic area in the LCZ696 group was significantly suppressed compared with those in the control (P = 0.003) and valsartan (P = 0.04) groups. Moreover, the mRNA level of transforming growth factor-β (TGF-β) in the left ventricle was suppressed in the LCZ696 group compared with that in the control (P = 0.002) group. The ARNi LCZ696 improved cardiac function with the reduction of fibrosis in an HF-rEF model in diabetic mice, by suppressing TGF-β. This effect may be due to the specific inhibition of neprilysin, beyond the ARB effect of LCZ696. © 2016 The Authors European Journal of Heart Failure © 2016 European Society of Cardiology.

N-acetylcysteine improves established monocrotaline-induced pulmonary hypertension in rats

PubMed Central

2014-01-01

Background The outcome of patients suffering from pulmonary arterial hypertension (PAH) are predominantly determined by the response of the right ventricle to the increase afterload secondary to high vascular pulmonary resistance. However, little is known about the effects of the current available or experimental PAH treatments on the heart. Recently, inflammation has been implicated in the pathophysiology of PAH. N-acetylcysteine (NAC), a well-known safe anti-oxidant drug, has immuno-modulatory and cardioprotective properties. We therefore hypothesized that NAC could reduce the severity of pulmonary hypertension (PH) in rats exposed to monocrotaline (MCT), lowering inflammation and preserving pulmonary vascular system and right heart function. Methods Saline-treated control, MCT-exposed, MCT-exposed and NAC treated rats (day 14–28) were evaluated at day 28 following MCT for hemodynamic parameters (right ventricular systolic pressure, mean pulmonary arterial pressure and cardiac output), right ventricular hypertrophy, pulmonary vascular morphometry, lung inflammatory cells immunohistochemistry (monocyte/macrophages and dendritic cells), IL-6 expression, cardiomyocyte hypertrophy and cardiac fibrosis. Results The treatment with NAC significantly decreased pulmonary vascular remodeling, lung inflammation, and improved total pulmonary resistance (from 0.71 ± 0.05 for MCT group to 0.50 ± 0.06 for MCT + NAC group, p < 0.05). Right ventricular function was also improved with NAC treatment associated with a significant decrease in cardiomyocyte hypertrophy (625 ± 69 vs. 439 ± 21 μm2 for MCT and MCT + NAC group respectively, p < 0.001) and heart fibrosis (14.1 ± 0.8 vs. 8.8 ± 0.1% for MCT and MCT + NAC group respectively, p < 0.001). Conclusions Through its immuno-modulatory and cardioprotective properties, NAC has beneficial effect on pulmonary vascular and right heart function in experimental PH. PMID:24929652

Online mindfulness as a promising method to improve exercise capacity in heart disease: 12-month follow-up of a randomized controlled trial

PubMed Central

Younge, John O.; Wery, Machteld F.; Utens, Elisabeth M. W. J.; Michels, Michelle; Rizopoulos, Dimitris; van Rossum, Liesbeth F. C.; Roos-Hesselink, Jolien W.; Hunink, Myriam M. G.

2017-01-01

There is increasing evidence that mindfulness can reduce stress, and thereby affect other psychological and physiological outcomes as well. Earlier, we reported the direct 3-month results of an online modified mindfulness-based stress reduction training in patients with heart disease, and now we evaluate the effect at 12-month follow-up. 324 patients (mean age 43.2 years, 53.7% male) were randomized in a 2:1 ratio to additional 3-month online mindfulness training or to usual care alone. The primary outcome was exercise capacity measured with the 6 minute walk test (6MWT). Secondary outcomes were blood pressure, heart rate, respiratory rate, NT-proBNP, cortisol levels (scalp hair sample), mental and physical functioning (SF-36), anxiety and depression (HADS), perceived stress (PSS), and social support (PSSS12). Differences between groups on the repeated outcome measures were analyzed with linear mixed models. At 12-months follow-up, participants showed a trend significant improvement exercise capacity (6MWT: 17.9 meters, p = 0.055) compared to UC. Cohen’s D showed significant but small improvement on exercise capacity (d = 0.22; 95%CI 0.05 to 0.39), systolic blood pressure (d = 0.19; 95%CI 0.03 to 0.36), mental functioning (d = 0.22; 95%CI 0.05 to 0.38) and depressive symptomatology (d = 0.18; 95%CI 0.02 to 0.35). All other outcome measures did not change statistically significantly. In the as-treated analysis, systolic blood pressure decreased significantly with 5.5 mmHg (p = 0.045; d = 0.23 (95%CI 0.05–0.41)). Online mindfulness training shows favorable albeit small long-term effects on exercise capacity, systolic blood pressure, mental functioning, and depressive symptomatology in patients with heart disease and might therefore be a beneficial addition to current clinical care. Trial registration: www.trialregister.nl NTR3453 PMID:28486559

[Experts consensus on the management of the right heart function in critically ill patients].

PubMed

Wang, X T; Liu, D W; Zhang, H M; Long, Y; Guan, X D; Qiu, H B; Yu, K J; Yan, J; Zhao, H; Tang, Y Q; Ding, X; Ma, X C; Du, W; Kang, Y; Tang, B; Ai, Y H; He, H W; Chen, D C; Chen, H; Chai, W Z; Zhou, X; Cui, N; Wang, H; Rui, X; Hu, Z J; Li, J G; Xu, Y; Yang, Y; Ouyan, B; Lin, H Y; Li, Y M; Wan, X Y; Yang, R L; Qin, Y Z; Chao, Y G; Xie, Z Y; Sun, R H; He, Z Y; Wang, D F; Huang, Q Q; Jiang, D P; Cao, X Y; Yu, R G; Wang, X; Chen, X K; Wu, J F; Zhang, L N; Yin, M G; Liu, L X; Li, S W; Chen, Z J; Luo, Z

2017-12-01

To establish the experts consensus on the right heart function management in critically ill patients. The panel of consensus was composed of 30 experts in critical care medicine who are all members of Critical Hemodynamic Therapy Collaboration Group (CHTC Group). Each statement was assessed based on the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) principle. Then the Delphi method was adopted by 52 experts to reassess all the statements. (1) Right heart function is prone to be affected in critically illness, which will result in a auto-exaggerated vicious cycle. (2) Right heart function management is a key step of the hemodynamic therapy in critically ill patients. (3) Fluid resuscitation means the process of fluid therapy through rapid adjustment of intravascular volume aiming to improve tissue perfusion. Reversed fluid resuscitation means reducing volume. (4) The right ventricle afterload should be taken into consideration when using stroke volume variation (SVV) or pulse pressure variation (PPV) to assess fluid responsiveness.(5)Volume overload alone could lead to septal displacement and damage the diastolic function of the left ventricle. (6) The Starling curve of the right ventricle is not the same as the one applied to the left ventricle,the judgement of the different states for the right ventricle is the key of volume management. (7) The alteration of right heart function has its own characteristics, volume assessment and adjustment is an important part of the treatment of right ventricular dysfunction (8) Right ventricular enlargement is the prerequisite for increased cardiac output during reversed fluid resuscitation; Nonetheless, right heart enlargement does not mandate reversed fluid resuscitation.(9)Increased pulmonary vascular resistance induced by a variety of factors could affect right heart function by obstructing the blood flow. (10) When pulmonary hypertension was detected in clinical scenario, the differentiation of critical care-related pulmonary hypertension should be a priority. (11) Attention should be paid to the change of right heart function before and after implementation of mechanical ventilation and adjustment of ventilator parameter. (12) The pulmonary arterial pressure should be monitored timingly when dealing with critical care-related pulmonary hypertension accompanied with circulatory failure.(13) The elevation of pulmonary aterial pressure should be taken into account in critical patients with acute right heart dysfunction. (14) Prone position ventilation is an important measure to reduce pulmonary vascular resistance when treating acute respiratory distress syndrome patients accompanied with acute cor pulmonale. (15) Attention should be paid to right ventricle-pulmonary artery coupling during the management of right heart function. (16) Right ventricular diastolic function is more prone to be affected in critically ill patients, the application of critical ultrasound is more conducive to quantitative assessment of right ventricular diastolic function. (17) As one of the parameters to assess the filling pressure of right heart, central venous pressure can be used to assess right heart diastolic function. (18). The early and prominent manifestation of non-focal cardiac tamponade is right ventricular diastolic involvement, the elevated right atrial pressure should be noticed. (19) The effect of increased intrathoracic pressure on right heart diastolic function should be valued. (20) Ttricuspid annular plane systolic excursion (TAPSE) is an important parameter that reflects right ventricular systolic function, and it is recommended as a general indicator of critically ill patient. (21) Circulation management with right heart protection as the core strategy is the key point of the treatment of acute respiratory distress syndrome. (22) Right heart function involvement after cardiac surgery is very common and should be highly valued. (23) Right ventricular dysfunction should not be considered as a routine excuse for maintaining higher central venous pressure. (24) When left ventricular dilation, attention should be paid to the effect of left ventricle on right ventricular diastolic function. (25) The impact of left ventricular function should be excluded when the contractility of the right ventricle is decreased. (26) When the right heart load increases acutely, the shunt between the left and right heart should be monitored. (27) Attention should be paid to the increase of central venous pressure caused by right ventricular dysfunction and its influence on microcirculation blood flow. (28) When the vasoactive drugs was used to reduce the pressure of pulmonary circulation, different effects on pulmonary and systemic circulation should be evaluated. (29) Right atrial pressure is an important factor affecting venous return. Attention should be paid to the influence of the pressure composition of the right atrium on the venous return. (30) Attention should be paid to the role of the right ventricle in the acute pulmonary edema. (31) Monitoring the difference between the mean systemic filling pressure and the right atrial pressure is helpful to determine whether the infusion increases the venous return. (32) Venous return resistance is often considered to be a insignificant factor that affects venous return, but attention should be paid to the effect of the specific pathophysiological status, such as intrathoracic hypertension, intra-abdominal hypertension and so on. Consensus can promote right heart function management in critically ill patients, optimize hemodynamic therapy, and even affect prognosis.

The National Heart Failure Project: a health care financing administration initiative to improve the care of Medicare beneficiaries with heart failure.

PubMed

Masoudi, F A; Ordin, D L; Delaney, R J; Krumholz, H M; Havranek, E P

2000-01-01

This is the second in a series describing Health Care Financing Administration (HCFA) initiatives to improve care for Medicare beneficiaries with heart failure. The first article outlined the history of HCFA quality-improvement projects and current initiatives to improve care in six priority areas: heart failure, acute myocardial infarction, stroke, pneumonia, diabetes, and breast cancer. This article details the objectives and design of the Medicare National Heart Failure Quality Improvement Project (NHF), which has as its goal the improvement of inpatient heart failure care. (c)2000 by CHF, Inc.

Carvedilol in dogs with dilated cardiomyopathy.

PubMed

Oyama, Mark A; Sisson, D David; Prosek, Robert; Bulmer, Barret J; Luethy, Mike W; Fuentes, Virginia Luis

2007-01-01

Dilated cardiomyopathy (DCM) is characterized by reduced systolic function, heightened sympathetic tone, and high morbidity and mortality. Little is known regarding the safety and efficacy of beta-blocker treatment in dogs with DCM. Carvedilol improves echocardiographic and neurohormonal variables in dogs with DCM over a 4-month treatment period. Prospective, placebo-controlled, double-blinded randomized study. Dogs with DCM underwent echocardiography, ECG, thoracic radiographs, and neurohormonal profiling, followed by titration onto carvedilol (0.3 mg/kg q12h) or placebo over a 4-week period and subsequently received 3 months of therapy. Primary study endpoints included left ventricular volume and function. Sixteen dogs received carvedilol and 7 received placebo. At study end, 13 carvedilol dogs and 5 placebo dogs were alive. There was no difference in the mean percentage change in left ventricular volume at end-diastole (LVVd), left ventricular end-systolic volume (LVVs), and ejection fraction (EF) between treatment groups, suggesting that both groups experienced similar amounts of disease progression. Carvedilol treatment did not result in significant changes in neurohormonal activation, radiographic heart size, heart rate, or owner perceived quality-of-life. Baseline B-type natriuretic peptide (BNP) predicted dogs in the carvedilol-treated group that maintained or improved their EF over the study duration. Carvedilol administration did not improve echocardiographic or neurohormonal indicators of heart function. The lack of effect may be related to severity of disease, carvedilol dose, or brevity of follow-up time. Statistical power of the present study was adversely affected by a high fatality rate in study dogs and small sample size.

A comparison of 16 weeks of continuous vs intermittent exercise training in chronic heart failure patients.

PubMed

Smart, Neil A; Steele, Michael

2012-01-01

The authors compared the effects of continuous (CON) and intermittent (INT) exercise training programs on functional capacity, quality of life (QOL), and cardiac function in 23 congestive heart failure patients. Patients were randomized to CON exercise training (n=13; aged 66±7 years; peak oxygen consumption [VO(2)], 12.4±2.5 mL/kg/min; weight, 83±12 kg; left ventricular ejection fraction [LVEF], 29.5%±7.2%) or INT exercise training (n=10; aged 59±11 years; VO(2), 12.2±6.5 mL/kg/min; weight, 87±24 kg; LVEF 27%±7.9%). These groups completed 16 weeks of stationary cycling at 70% VO(2) thrice weekly for 30 minutes continuously or 60 minutes (60 seconds work:60 seconds rest) intermittently; both groups completed the same absolute volume of work. Three QOL questionnaire responses, VO(2), LVEF, and regional tissue Doppler were quantified. After exercise training, VO(2) increased by 13% in the CON group (P=.12) and significantly by 21% in the INT group (P=.03), although not significantly between the groups (P=.72). In the CON group, Minnesota Living With Heart Failure score improved at 16 weeks (P=.02), while in the INT group, Hare-Davis scores improved (P=.02). Cardiac volumes, resting and peak LVEF, contractile reserve, and tissue velocities were all unchanged from baseline. Intermittent exercise may improve functional capacity to a greater extent than continuous exercise. QOL changes were variable between groups. © 2011 Wiley Periodicals, Inc.

Identification of the heart wall and chamber based on temporal change of ultrasonic scatterer distribution

NASA Astrophysics Data System (ADS)

Takahashi, Kohei; Taki, Hirofumi; Kanai, Hiroshi

2017-07-01

In most current methods for evaluating the cardiac function by ultrasound, the heart wall area is identified manually by an examiner. To eliminate examiner dependence and to improve usability, an automatic heart wall identification method is desirable. Identification based on only echogenicity often fails because of low echogenicity of some areas of the heart wall. In the present study, to determine more essential features, we focused on the relative temporal change of ultrasonic scatterer distribution and proposed three features for identification of the heart wall and the chamber: cross-correlation of RF signals, that of envelopes, and spatial dispersion of movement vectors in small regions. In an in vivo experiment, using echogenicity and the three features, we identified the heart wall and the chamber in the left ventricular long-axis view, resulting in criteria of separability J of 1.69, 1.40, and 3.02 using these features compared with the result of 0.979 using echogenicity.

Clinical trials update from the Heart Failure Society of America: EMOTE, HERB-CHF, BEST genetic sub-study and RHYTHM-ICD.

PubMed

Lalukota, Krishna; Cleland, John G F; Ingle, Lee; Clark, Andrew L; Coletta, Alison P

2004-12-01

This article summarises key presentations relevant to the pathophysiology, prevention or treatment of heart failure, from the Heart Failure Society of America annual meeting held in Toronto, Canada. Data from the EnoxiMone in intravenous inOTropE-dependent subjects (EMOTE) study suggest that the oral PDE-3 inhibitor enoximone may be effective for weaning severe heart failure patients from intravenous inotropic therapy. Hawthorn Extract Randomised Blinded Trial in CHF (HERB-CHF) failed to show a benefit of hawthorn extract added to conventional heart failure therapy. A genetic sub-group analysis of the Blocker Evaluation of Survival Trial (BEST) study showed that bucindolol reduced mortality and hospitalisations in patients who were homozygous for the Arg389 variant of the beta(1) adrenoceptor. In the Resynchronisation Hemodynamic Treatment for Heart Failure Management (RHYTHM-ICD) study, patients randomised to cardiac resynchronisation therapy (CRT) showed an improvement in symptoms and functional capacity compared to the control group.

Effects of combined exercise training and electromyostimulation treatments in chronic heart failure: A prospective multicentre study.

PubMed

Iliou, Marie C; Vergès-Patois, Bénédicte; Pavy, Bruno; Charles-Nelson, Anais; Monpère, Catherine; Richard, Rudy; Verdier, Jean C

2017-08-01

Background Exercise training as part of a comprehensive cardiac rehabilitation is recommended for patients with cardiac heart failure. It is a valuable method for the improvement of exercise tolerance. Some studies reported a similar improvement with quadricipital electrical myostimulation, but the effect of combined exercise training and electrical myostimulation in cardiac heart failure has not been yet evaluated in a large prospective multicentre study. Purpose The aim of this study was to determine whether the addition of low frequency electrical myostimulation to exercise training may improve exercise capacity and/or muscular strength in cardiac heart failure patients. Methods Ninety-one patients were included (mean age: 58 ± 9 years; New York Heart Association II/III: 52/48%, left ventricular ejection fraction: 30 ± 7%) in a prospective French study. The patients were randomised into two groups: 41 patients in exercise training and 50 in exercise training + electrical myostimulation. All patients underwent 20 exercise training sessions. In addition, in the exercise training + electrical myostimulation group, patients underwent 20 low frequency (10 Hz) quadricipital electrical myostimulation sessions. Each patient underwent a cardiopulmonary exercise test, a six-minute walk test, a muscular function evaluation and a quality of life questionnaire, before and at the end of the study. Results A significant improvement of exercise capacity (Δ peak oxygen uptake+15% in exercise training group and +14% in exercise training + electrical myostimulation group) and of quality of life was observed in both groups without statistically significant differences between the two groups. Mean creatine kinase level increased in the exercise training group whereas it remained stable in the combined group. Conclusions This prospective multicentre study shows that electrical myostimulation on top of exercise training does not demonstrate any significant additional improvement in exercise capacity in cardiac heart failure patients.

Managing therapeutic competition in patients with heart failure, lower urinary tract symptoms and incontinence.

PubMed

Tannenbaum, Cara; Johnell, Kristina

2014-02-01

Up to 50% of heart failure patients suffer from lower urinary tract symptoms. Urinary incontinence has been associated with worse functional status in patients with heart failure, occurring three times more frequently in patients with New York Heart Association Class III and IV symptoms compared with those with milder disease. The association between heart failure and urinary symptoms may be directly attributable to worsening heart failure pathophysiology; however, medications used to treat heart failure may also indirectly provoke or exacerbate urinary symptoms. This type of drug-disease interaction, in which the treatment for heart failure precipitates incontinence, and removal of medications to relieve incontinence worsens heart failure, can be termed therapeutic competition. The mechanisms by which heart failure medication such as diuretics, angiotensin-converting enzyme (ACE) inhibitors and β-blockers aggravate lower urinary tract symptoms are discussed. Initiation of a prescribing cascade, whereby antimuscarinic agents or β3-agonists are added to treat symptoms of urinary urgency and incontinence, is best avoided. Recommendations and practical tips are provided that outline more judicious management of heart failure patients with lower urinary tract symptoms. Compelling strategies to improve urinary outcomes include titrating diuretics, switching ACE inhibitors, treating lower urinary tract infections, appropriate fluid management, daily weighing, and uptake of pelvic floor muscle exercises.

Postinfarct intramyocardial injection of mesenchymal stem cells pretreated with TGF-α improves acute myocardial function

PubMed Central

Herrmann, Jeremy L.; Abarbanell, Aaron M.; Weil, Brent R.; Wang, Yue; Poynter, Jeffrey A.; Manukyan, Mariuxi C.

2010-01-01

Stem cell-based therapies offer promising potential for myocardial infarction (MI), but endogenous molecules released in response to injury likely impair posttransplantation stem cell function. Stem cell-mediated cardioprotection occurs in part via paracrine effects, and transforming growth factor-α (TGF-α) has been shown to enhance paracrine function. However, it is unknown whether pretreating stem cells with TGF-α increases stem cell-mediated cardioprotection after acute MI. Mesenchymal stem cells (MSCs) were treated with TGF-α (250 ng/ml) for 24 h. Adult male Sprague-Dawley rat hearts were isolated and perfused using the Langendorff method. MI was induced by ligating the left anterior descending coronary artery. Postligation (30 min), vehicle or 1 × 106 MSCs with or without pretreatment were injected in the infarct border zones, and the hearts were perfused for an additional 60 min. Left ventricular function was continuously measured, and infarct size was assessed with Evans blue dye and 2,3,5-triphenyltetrazolium chloride staining. Myocardial production of interleukin (IL)-1β and IL-6 and caspase 3 activation was also measured. Left ventricular function decreased significantly following coronary artery ligation but improved following injection of untreated MSCs and to a greater extent after injection of pretreated MSCs. In addition, the infarct area, myocardial caspase 3 activation, and IL-6 production were lowest in hearts injected with pretreated cells. Intramyocardial injection of TGF-α-pretreated MSCs after acute MI is associated with increased myocardial function and decreased myocardial injury. This strategy may be useful for optimizing the therapeutic efficacy of stem cells for the treatment of acute MI. PMID:20484699

Impact of Residual Mitral Regurgitation on Right Ventricular Systolic Function After Left Ventricular Assist Device Implantation.

PubMed

Ertugay, Serkan; Kemal, Hatice S; Kahraman, Umit; Engin, Catagay; Nalbantgil, Sanem; Yagdi, Tahir; Ozbaran, Mustafa

2017-07-01

Significant mitral regurgitation (MR) is thought to decrease after left ventricular assist device (LVAD) implantation, and therefore repair of mitral valve is not indicated in current practice. However, residual moderate and severe MR leads to pulmonary artery pressure increase, thereby resulting in right ventricular (RV) dysfunction during follow-up. We examined the impact of residual MR on systolic function of the right ventricle by echocardiography after LVAD implantation. This study included 90 patients (mean age: 51.7 ± 10.9 years, 14.4% female) who underwent LVAD implantation (HeartMate II = 21, HeartWare = 69) in a single center between December 2010 and June 2014. Echocardiograms obtained at 3-6 months and over after implantation were analyzed retrospectively. RV systolic function was graded as normal, mild, moderate, and severely depressed. MR (≥moderate) was observed in 43 and 44% of patients at early and late period, respectively. Systolic function of the RV was severely depressed in 16 and 9% of all patients. Initial analysis (mean duration of support 174.3 ± 42.5 days) showed a statistically significant correlation between less MR and improved systolic function of RV (P = 0.01). Secondary echocardiographic analysis (following a mean duration of support of 435.1 ± 203 days) was also statistically significant for MR degree and RV systolic dysfunction (P = 0.008). Residual MR after LVAD implantation may cause deterioration of RV systolic function and cause right-sided heart failure symptoms. Repair of severe MR, in selected patients such as those with severe pulmonary hypertension and depressed RV, may be considered to improve the patient's clinical course during pump support. © 2016 International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.

Therapeutic Effects of Exercise Training On Selected Cardio-Pulmonary Parameters and Body Composition of Nigerians with Chronic Heart Failure (A Preliminary Study).

PubMed

Ajiboye, O A; Anigbogu, C N; Ajuluchukwu, J N; Jaja, S I

2013-01-01

The use of exercise training in the management of individuals with chronic heart failure has not been widely accepted by health care providers especially in Sub-Saharan Africa because of the possibility that the failing hearts may have a negative response to the increased workload and stress of exercise. The study aimed to evaluate the effects of exercise training (ET) on selected cardio-respiratory and body composition variables of Nigerians with chronic heart failure (CHF). Thirty two Nigerians with CHF (male - 17), aged 30 to 71 years, mean age 54.2 ± 1.9 years and New York Heart Association Functional Class (NYHA) II-III recruited from Cardiology Clinic of Lagos University Teaching Hospital Nigeria participated in the study. They were randomized into exercise (EG) and control groups (CG). Exercise group performed 12-weeks of aerobic and resistance training for 60 minutes, three sessions per week. Selected cardio-respiratory and body composition variables were measured pre and post intervention in both groups. Data was analyzed using SPSS-17 package. Level of significance was set at 0.05. There was no significant difference in the measured variables between the groups at baseline (p > 0.05). Significant improvement was seen in EG in all the measured variables except the systolic (p = 0.29) and diastolic blood pressure (p = 0.45). No adverse effect was observed during the exercise training. No significant improvement was observed in the control group (p > 0.05). Exercise training may improve cardiorespiratory and body composition variables in patients with chronic heart failure.

Exercise training in patients with heart disease: review of beneficial effects and clinical recommendations.

PubMed

Gielen, Stephan; Laughlin, M Harold; O'Conner, Christopher; Duncker, Dirk J

2015-01-01

Over the last decades exercise training has evolved into an established evidence-based therapeutic strategy with prognostic benefits in many cardiovascular diseases (CVDs): In stable coronary artery disease (CAD) exercise training attenuates disease progression by beneficially influencing CVD risk factors (i.e., hyperlipidemia, hypertension) and coronary endothelial function. In heart failure (HF) with reduced ejection fraction (HFrEF) training prevents the progressive loss of exercise capacity by antagonizing peripheral skeletal muscle wasting and by promoting left ventricular reverse remodeling with reduction in cardiomegaly and improvement of ejection fraction. Novel areas for exercise training interventions include HF with preserved ejection fraction (HFpEF), pulmonary hypertension, and valvular heart disease. In HFpEF, randomized studies indicate a lusitropic effect of training on left ventricular diastolic function associated with symptomatic improvement of exercise capacity. In pulmonary hypertension, reductions in pulmonary artery pressure were observed following endurance exercise training. Recently, innovative training methods such as high-intensity interval training, resistance training and others have been introduced. Although their prognostic value still needs to be determined, these approaches may achieve superior improvements in aerobic exercise capacity and gain in muscle mass, respectively. In this review, we give an overview of the prognostic and symptomatic benefits of exercise training in the most common cardiac disease entities. Additionally, key guideline recommendations for the initiation of training programs are summarized. Copyright © 2014 Elsevier Inc. All rights reserved.

Heart rhythm complexity impairment in patients undergoing peritoneal dialysis

NASA Astrophysics Data System (ADS)

Lin, Yen-Hung; Lin, Chen; Ho, Yi-Heng; Wu, Vin-Cent; Lo, Men-Tzung; Hung, Kuan-Yu; Liu, Li-Yu Daisy; Lin, Lian-Yu; Huang, Jenq-Wen; Peng, Chung-Kang

2016-06-01

Cardiovascular disease is one of the leading causes of death in patients with advanced renal disease. The objective of this study was to investigate impairments in heart rhythm complexity in patients with end-stage renal disease. We prospectively analyzed 65 patients undergoing peritoneal dialysis (PD) without prior cardiovascular disease and 72 individuals with normal renal function as the control group. Heart rhythm analysis including complexity analysis by including detrended fractal analysis (DFA) and multiscale entropy (MSE) were performed. In linear analysis, the PD patients had a significantly lower standard deviation of normal RR intervals (SDRR) and percentage of absolute differences in normal RR intervals greater than 20 ms (pNN20). Of the nonlinear analysis indicators, scale 5, area under the MSE curve for scale 1 to 5 (area 1-5) and 6 to 20 (area 6-20) were significantly lower than those in the control group. In DFA anaylsis, both DFA α1 and DFA α2 were comparable in both groups. In receiver operating characteristic curve analysis, scale 5 had the greatest discriminatory power for two groups. In both net reclassification improvement model and integrated discrimination improvement models, MSE parameters significantly improved the discriminatory power of SDRR, pNN20, and pNN50. In conclusion, PD patients had worse cardiac complexity parameters. MSE parameters are useful to discriminate PD patients from patients with normal renal function.

Myocardial Hypertrophy and Its Role in Heart Failure with Preserved Ejection Fraction

PubMed Central

Heinzel, Frank R.; Hohendanner, Felix; Jin, Ge; Sedej, Simon; Edelmann, Frank

2015-01-01

Left ventricular hypertrophy (LVH) is the most common myocardial structural abnormality associated with heart failure with preserved ejection fraction (HFpEF). LVH is driven by neurohumoral activation, increased mechanical load and cytokines associated with arterial hypertension, chronic kidney disease, diabetes and other co-morbidities. Here we discuss the experimental and clinical evidence that links LVH to diastolic dysfunction and qualifies LVH as one diagnostic marker for HFpEF. Mechanisms leading to diastolic dysfunction in LVH are incompletely understood but may include extracellular matrix changes, vascular dysfunction as well as altered cardiomyocyte mechano-elastical properties. Beating cardiomyocytes from HFpEF patients have not yet been studied, but we and others have shown increased Ca2+ turnover and impaired relaxation in cardiomyocytes from hypertrophied hearts. Structural myocardial remodeling can lead to heterogeneity in regional myocardial contractile function, which contributes to diastolic dysfunction in HFpEF. In the clinical setting of patients with compound co-morbidities, diastolic dysfunction may occur independently of LVH. This may be one explanation why current approaches to reduce LVH have not been effective to improve symptoms and prognosis in HFpEF. Exercise training on the other hand, in clinical trials improved exercise tolerance and diastolic function but did not reduce LVH. Thus, current clinical evidence does not support regression of LVH as a surrogate marker for (short-term) improvement of HFpEF. PMID:26183480

Alamandine attenuates hypertension and cardiac hypertrophy in hypertensive rats.

PubMed

Liu, Chi; Yang, Chuan-Xi; Chen, Xi-Ru; Liu, Bo-Xun; Li, Yong; Wang, Xiao-Zhi; Sun, Wei; Li, Peng; Kong, Xiang-Qing

2018-05-12

Oral administration of the peptide alamandine has antihypertensive and anti-fibrotic effects in rats. This work aimed to determine whether subcutaneous alamandine injection would attenuate hypertension and cardiac hypertrophy, and improve the function of a major target of hypertension-related damage, the left ventricle (LV), in spontaneously hypertensive rats (SHRs). This was examined in vivo in SHRs and normotensive rats subjected to 6-week subcutaneous infusion of alamandine or saline control, and in vitro in H9C2-derived and primary neonatal rat cardiomyocytes treated with angiotensin (Ang) II to model cardiac hypertrophy. Tail artery blood pressure measurement and transthoracic echocardiography showed that hypertension and impaired LV function in SHRs were ameliorated upon alamandine infusion. Alamandine administration also decreased the mass gains of heart and lung in SHRs, suppressed cardiomyocyte cross-sectional area expansion, and inhibited the mRNA levels of atrial natriuretic peptide and brain natriuretic peptide. The expression of alamandine receptor Mas-related G protein-coupled receptor, member D was increased in SHR hearts and in cardiomyocytes treated with Ang II. Alamandine inhibited the increases of protein kinase A (PKA) levels in the heart in SHRs and in cardiomyocytes treated with Ang II. In conclusion, the present study showed that alamandine administration attenuates hypertension, alleviates cardiac hypertrophy, and improves LV function. PKA signaling may be involved in the mechanisms underlying these effects.

Neurodevelopmental Abnormalities and Congenital Heart Disease: Insights Into Altered Brain Maturation.

PubMed

Morton, Paul D; Ishibashi, Nobuyuki; Jonas, Richard A

2017-03-17

In the past 2 decades, it has become evident that individuals born with congenital heart disease (CHD) are at risk of developing life-long neurological deficits. Multifactorial risk factors contributing to neurodevelopmental abnormalities associated with CHD have been identified; however, the underlying causes remain largely unknown, and efforts to address this issue have only recently begun. There has been a dramatic shift in focus from newly acquired brain injuries associated with corrective and palliative heart surgery to antenatal and preoperative factors governing altered brain maturation in CHD. In this review, we describe key time windows of development during which the immature brain is vulnerable to injury. Special emphasis is placed on the dynamic nature of cellular events and how CHD may adversely impact the cellular units and networks necessary for proper cognitive and motor function. In addition, we describe current gaps in knowledge and offer perspectives about what can be done to improve our understanding of neurological deficits in CHD. Ultimately, a multidisciplinary approach will be essential to prevent or improve adverse neurodevelopmental outcomes in individuals surviving CHD. © 2017 American Heart Association, Inc.

The pathophysiological basis of the protective effects of metformin in heart failure.

PubMed

Dziubak, Aleksandra; Wójcicka, Grażyna

2017-08-24

Metformin, currently recommended as the drug of first choice in type 2 diabetes mellitus (T2DM), is one of the few antihiperglycemic drugs to reduce cardiovascular risk. Nonetheless, due to the risk of lactic acidosis during metformin therapy, its usage in patients with diabetes and heart failure (HF) is still a matter of debate. The aim of this review is to present data supporting the possibility of using metformin in the treatment of diabetic patients with concomitant heart failure. In the failing heart, metformin through the mechanism related to AMP-activated protein kinase (AMPK) activity, improves free fatty acids (FFA) and glucose metabolism, mitochondrial biogenesis, as well as nitric oxide (NO)-NO synthase pathway. Metformin can also inhibit the generation and accumulation of advanced glycation end products (AGEs) and thereby prevents the development of the adverse structural and functional changes in myocardium.In summary, experimental and clinical data indicate the ability of metformin to prevent the development of the structural and functional changes in myocardium, although further basic research and clinical studies assessing benefits and safety of metformin therapy in patients with HF are required.

NAD+ : A big player in cardiac and skeletal muscle remodeling and aging.

PubMed

Chaturvedi, Pankaj; Tyagi, Suresh C

2018-03-01

In the past decade, NAD+ has gained importance for its beneficial effects as antioxidant and anti-aging molecule. A paper in science by Zhang et al. () has described that NAD+ when replenished, ameliorates muscle dystrophy in mice by improving mitochondrial function. NAD+ was also demonstrated by the authors to improve the life span of mice. Cox et al. () demonstrated the cardiac effects of NAD+ which mitigated chronic heart failure via mitochondrial redox state mechanism. Cox et al. () also demonstrated that NAD+ is provided in the drinking water, it improves cardiac relaxation in volume overload model of heart failure. Although NAD+ has a profound anti-aging and anti-oxidant effects, its effect on humans and use as a dietary supplement needs more exploration. © 2017 Wiley Periodicals, Inc.

Exercise-induced pulmonary artery hypertension in a patient with compensated cardiac disease: hemodynamic and functional response to sildenafil therapy.

PubMed

Nikolaidis, Lazaros; Memon, Nabeel; O'Murchu, Brian

2015-02-01

We describe the case of a 54-year-old man who presented with exertional dyspnea and fatigue that had worsened over the preceding 2 years, despite a normally functioning bioprosthetic aortic valve and stable, mild left ventricular dysfunction (left ventricular ejection fraction, 0.45). His symptoms could not be explained by physical examination, an extensive biochemical profile, or multiple cardiac and pulmonary investigations. However, abnormal cardiopulmonary exercise test results and a right heart catheterization-combined with the use of a symptom-limited, bedside bicycle ergometer-revealed that the patient's exercise-induced pulmonary artery hypertension was out of proportion to his compensated left heart disease. A trial of sildenafil therapy resulted in objective improvements in hemodynamic values and functional class.

Adeno-associated Virus Serotype 9 – Driven Expression of BAG3 Improves Left Ventricular Function in Murine Hearts with Left Ventricular Dysfunction Secondary to a Myocardial Infarction

PubMed Central

Knezevic, Tijana; Myers, Valerie D.; Su, Feifei; Wang, JuFang; Song, Jianliang; Zhang, Xue-Qian; Gao, Erhe; Gao, Guofeng; Muniswamy, Madesh; Gupta, Manish K.; Gordon, Jennifer; Weiner, Kristen N.; Rabinowitz, Joseph; Ramsey, Frederick V.; Tilley, Douglas G.; Khalili, Kamel; Cheung, Joseph Y.; Feldman, Arthur M.

2016-01-01

Objectives The present study was undertaken to test the hypothesis that gene delivery of BCL2-Associated Athanogene 3 (BAG3) to the heart of mice with left ventricular dysfunction secondary to a myocardial infarction could enhance cardiac performance. Background BAG3 is a 575 amino acid protein that has pleotropic functions in the cell including pro-autophagy and anti-apoptosis. Mutations in BAG3 have been associated with both skeletal muscle dysfunction and familial dilated cardiomyopathy and BAG3 levels are diminished in non-familial heart failure. Methods Eight-week-old C57/BL6 mice underwent ligation of the left coronary artery (MI) or sham surgery (Sham). Eight weeks later, mice in both groups were randomly assigned to receive either a retro-orbital injection of rAAV9-BAG3 (MI-BAG3 or Sham-BAG3) or rAAV9-GFP (MI-GFP or Sham GFP). Mice were sacrificed at 3 weeks post-injection and myocytes were isolated from the left ventricle. Results MI-BAG3 mice demonstrated a significantly (p < 0.0001) higher left ventricular ejection fraction (LVEF) 9 days after rAAV9-BAG3 injection with further improvement in LVEF, fractional shortening and stroke volume at 3 weeks post-injection without changes in LV mass or LV volume. Injection of rAAV9-BAG3 had no effect on LVEF in Sham mice. The salutary benefits of rAAV9-BAG3 were also observed in myocytes isolated from MI hearts including improved cell shortening (p<0.05), increased systolic [Ca2+]i, increased [Ca2+]i transient amplitudes and increased maximal ICa amplitude. Implications The results suggest that BAG3 gene therapy may provide a novel therapeutic option for the treatment of heart failure. PMID:28164169

Adeno-associated Virus Serotype 9 - Driven Expression of BAG3 Improves Left Ventricular Function in Murine Hearts with Left Ventricular Dysfunction Secondary to a Myocardial Infarction.

PubMed

Knezevic, Tijana; Myers, Valerie D; Su, Feifei; Wang, JuFang; Song, Jianliang; Zhang, Xue-Qian; Gao, Erhe; Gao, Guofeng; Muniswamy, Madesh; Gupta, Manish K; Gordon, Jennifer; Weiner, Kristen N; Rabinowitz, Joseph; Ramsey, Frederick V; Tilley, Douglas G; Khalili, Kamel; Cheung, Joseph Y; Feldman, Arthur M

2016-12-01

The present study was undertaken to test the hypothesis that gene delivery of BCL2-Associated Athanogene 3 (BAG3) to the heart of mice with left ventricular dysfunction secondary to a myocardial infarction could enhance cardiac performance. BAG3 is a 575 amino acid protein that has pleotropic functions in the cell including pro-autophagy and anti-apoptosis. Mutations in BAG3 have been associated with both skeletal muscle dysfunction and familial dilated cardiomyopathy and BAG3 levels are diminished in non-familial heart failure. Eight-week-old C57/BL6 mice underwent ligation of the left coronary artery (MI) or sham surgery (Sham). Eight weeks later, mice in both groups were randomly assigned to receive either a retro-orbital injection of rAAV9-BAG3 (MI-BAG3 or Sham-BAG3) or rAAV9-GFP (MI-GFP or Sham GFP). Mice were sacrificed at 3 weeks post-injection and myocytes were isolated from the left ventricle. MI-BAG3 mice demonstrated a significantly (p < 0.0001) higher left ventricular ejection fraction (LVEF) 9 days after rAAV9-BAG3 injection with further improvement in LVEF, fractional shortening and stroke volume at 3 weeks post-injection without changes in LV mass or LV volume. Injection of rAAV9-BAG3 had no effect on LVEF in Sham mice. The salutary benefits of rAAV9-BAG3 were also observed in myocytes isolated from MI hearts including improved cell shortening (p<0.05), increased systolic [Ca 2+ ] i , increased [Ca 2+ ] i transient amplitudes and increased maximal I Ca amplitude. The results suggest that BAG3 gene therapy may provide a novel therapeutic option for the treatment of heart failure.

Correlates of Exercise Self-efficacy in a Randomized Trial of Mind-Body Exercise in Patients With Chronic Heart Failure.

PubMed

Yeh, Gloria Y; Mu, Lin; Davis, Roger B; Wayne, Peter M

2016-01-01

Exercise self-efficacy is one of the strongest predictors of physical activity behavior. Prior literature suggests that tai chi, a mind-body exercise, may increase self-efficacy; however, this is not extensively studied. Little is known about the factors associated with development of exercise self-efficacy in a population with heart failure. We utilized data from a randomized controlled trial of 12 weeks of group tai chi classes versus education in patients with chronic heart failure (n = 100). Multivariable linear regression was used to explore possible correlates of change in exercise self-efficacy in the entire sample and in the subgroup who received tai chi (n = 50). Covariates included baseline quality of life, social support, functional parameters, physical activity, serum biomarkers, sociodemographics, and clinical heart failure parameters. Baseline 6-minute walk (β=-0.0003, SE = 0.0001, P = .02) and fatigue score (β= 0.03, SE = 0.01, P = .004) were significantly associated with change in self-efficacy, with those in the lowest tertile for 6-minute walk and higher tertiles for fatigue score experiencing the greatest change. Intervention group assignment was highly significant, with self-efficacy significantly improved in the tai chi group compared to the education control over 12 weeks (β= 0.39, SE = 0.11, P < .001). In the tai chi group alone, lower baseline oxygen uptake (β=-0.05, SE = 0.01, P = .001), decreased mood (β=-0.01, SE = 0.003, P = .004), and higher catecholamine level (epinephrine β= 0.003, SE = 0.001, P = .005) were significantly associated with improvements in self-efficacy. In this exploratory analysis, our initial findings support the concept that interventions like tai chi may be beneficial in improving exercise self-efficacy, especially in patients with heart failure who are deconditioned, with lower functional status and mood.

Dantrolene, a therapeutic agent for malignant hyperthermia, markedly improves the function of failing cardiomyocytes by stabilizing inter-domain interactions within the ryanodine receptor

PubMed Central

Kobayashi, Shigeki; Yano, Masafumi; Suetomi, Takeshi; Ono, Makoto; Tateishi, Hiroki; Mochizuki, Mamoru; Xu, Xiaojuan; Uchinoumi, Hitoshi; Okuda, Shinichi; Yamamoto, Takeshi; Koseki, Noritaka; Kyushiki, Hiroyuki; Ikemoto, Noriaki; Matsuzaki, Masunori

2009-01-01

Objectives To investigate the effect of dantrolene, a drug generally used to treat Malignant Hyperthermia (MH), on the Ca2+ release and cardiomyocyte function in failing hearts. Background The N-terminal (N: 1-600) and Central (C: 2000-2500) domains of the ryanodine receptor (RyR), harbor many mutations associated with MH in skeletal muscle RyR (RyR1) and polymorphic ventricular tachycardia in cardiac RyR (RyR2). There is strong evidence that inter-domain interaction between these regions plays an important role in the mechanism of channel regulation. Methods Sarcoplasmic reticulum (SR) vesicles and cardiomyocytes were isolated from dog LV muscles (normal or rapid ventricular pacing for 4 weeks), for Ca2+ leak, transient, and spark assays. To assess the zipped or unzipped state of the interacting domains, the RyR was fluorescently labeled with methylcoumarin acetate in a site-directed manner. We employed a quartz-crystal microbalance technique to identify the dantrolene binding site within the RyR2. Results Dantrolene specifically bound to domain 601-620 in RyR2. In the SR isolated from pacing-induced dog failing hearts, the defective inter-domain interaction_(domain unzipping) has already occurred, causing spontaneous Ca2+ leak. Dantrolene suppressed both domain unzipping and the Ca2+ leak, showing identical drug concentration-dependence (IC50=0.3 μmol/L). In failing cardiomyocytes, both diastolic Ca2+ sparks and delayed afterdepolarization were frequently observed, but 1 μmol/L dantrolene inhibited both events. Conclusions Dantrolene corrects defective inter-domain interactions within RyR2 in failing hearts, inhibits spontaneous Ca2+ leak, in turn improves cardiomyocyte function in failing hearts. Thus, dantrolene may have a potential to treat heart failure, specifically targeting the RyR2. PMID:19460614

Blood urea nitrogen/creatinine ratio identifies a high-risk but potentially reversible form of renal dysfunction in patients with decompensated heart failure.

PubMed

Brisco, Meredith A; Coca, Steven G; Chen, Jennifer; Owens, Anjali Tiku; McCauley, Brian D; Kimmel, Stephen E; Testani, Jeffrey M

2013-03-01

Identifying reversible renal dysfunction (RD) in the setting of heart failure is challenging. The goal of this study was to evaluate whether elevated admission blood urea nitrogen/creatinine ratio (BUN/Cr) could identify decompensated heart failure patients likely to experience improvement in renal function (IRF) with treatment. Consecutive hospitalizations with a discharge diagnosis of heart failure were reviewed. IRF was defined as ≥20% increase and worsening renal function as ≥20% decrease in estimated glomerular filtration rate. IRF occurred in 31% of the 896 patients meeting eligibility criteria. Higher admission BUN/Cr was associated with in-hospital IRF (odds ratio, 1.5 per 10 increase; 95% confidence interval [CI], 1.3-1.8; P<0.001), an association persisting after adjustment for baseline characteristics (odds ratio, 1.4; 95% CI, 1.1-1.8; P=0.004). However, higher admission BUN/Cr was also associated with post-discharge worsening renal function (odds ratio, 1.4; 95% CI, 1.1-1.8; P=0.011). Notably, in patients with an elevated admission BUN/Cr, the risk of death associated with RD (estimated glomerular filtration rate <45) was substantial (hazard ratio, 2.2; 95% CI, 1.6-3.1; P<0.001). However, in patients with a normal admission BUN/Cr, RD was not associated with increased mortality (hazard ratio, 1.2; 95% CI, 0.67-2.0; P=0.59; p interaction=0.03). An elevated admission BUN/Cr identifies decompensated patients with heart failure likely to experience IRF with treatment, providing proof of concept that reversible RD may be a discernible entity. However, this improvement seems to be largely transient, and RD, in the setting of an elevated BUN/Cr, remains strongly associated with death. Further research is warranted to develop strategies for the optimal detection and treatment of these high-risk patients.

Blood Urea Nitrogen/Creatinine Ratio Identifies a High-Risk but Potentially Reversible Form of Renal Dysfunction in Patients With Decompensated Heart Failure

PubMed Central

Brisco, Meredith A.; Coca, Steven G.; Chen, Jennifer; Owens, Anjali Tiku; McCauley, Brian D.; Kimmel, Stephen E.; Testani, Jeffrey M.

2014-01-01

Background Identifying reversible renal dysfunction (RD) in the setting of heart failure is challenging. The goal of this study was to evaluate whether elevated admission blood urea nitrogen/creatinine ratio (BUN/Cr) could identify decompensated heart failure patients likely to experience improvement in renal function (IRF) with treatment. Methods and Results Consecutive hospitalizations with a discharge diagnosis of heart failure were reviewed. IRF was defined as ≥20% increase and worsening renal function as ≥20% decrease in estimated glomerular filtration rate. IRF occurred in 31% of the 896 patients meeting eligibility criteria. Higher admission BUN/Cr was associated with inhospital IRF (odds ratio, 1.5 per 10 increase; 95% confidence interval [CI], 1.3–1.8; P<0.001), an association persisting after adjustment for baseline characteristics (odds ratio, 1.4; 95% CI, 1.1–1.8; P=0.004). However, higher admission BUN/Cr was also associated with post-discharge worsening renal function (odds ratio, 1.4; 95% CI, 1.1–1.8; P=0.011). Notably, in patients with an elevated admission BUN/Cr, the risk of death associated with RD (estimated glomerular filtration rate <45) was substantial (hazard ratio, 2.2; 95% CI, 1.6–3.1; P<0.001). However, in patients with a normal admission BUN/Cr, RD was not associated with increased mortality (hazard ratio, 1.2; 95% CI, 0.67–2.0; P=0.59; p interaction=0.03). Conclusions An elevated admission BUN/Cr identifies decompensated patients with heart failure likely to experience IRF with treatment, providing proof of concept that reversible RD may be a discernible entity. However, this improvement seems to be largely transient, and RD, in the setting of an elevated BUN/Cr, remains strongly associated with death. Further research is warranted to develop strategies for the optimal detection and treatment of these high-risk patients. PMID:23325460

Megestrol acetate improves cardiac function in a model of cancer cachexia-induced cardiomyopathy by autophagic modulation.

PubMed

Musolino, Vincenzo; Palus, Sandra; Tschirner, Anika; Drescher, Cathleen; Gliozzi, Micaela; Carresi, Cristina; Vitale, Cristiana; Muscoli, Carolina; Doehner, Wolfram; von Haehling, Stephan; Anker, Stefan D; Mollace, Vincenzo; Springer, Jochen

2016-12-01

Cachexia is a complex metabolic syndrome associated with cancer. One of the features of cachexia is the loss of muscle mass, characterized by an imbalance between protein synthesis and protein degradation. Muscle atrophy is caused by the hyperactivation of some of the main cellular catabolic pathways, including autophagy. Cachexia also affects the cardiac muscle. As a consequence of the atrophy of the heart, cardiac function is impaired and mortality is increased. Anti-cachectic therapy in patients with cancer cachexia is so far limited to nutritional support and anabolic steroids. The use of the appetite stimulant megestrol acetate (MA) has been discussed as a treatment for cachexia. In this study the effects of MA were tested in cachectic tumour-bearing rats (Yoshida AH-130 ascites hepatoma). Rats were treated daily with 100 mg/kg of MA or placebo starting one day after tumour inoculation, and for a period of 16 days. Body weight and body composition were assessed at baseline and at the end of the study. Cardiac function was analysed by echocardiography at baseline and at day 11. Locomotor activity and food intake were assessed before tumour inoculation and at day 11. Autophagic markers were assessed in gastrocnemius muscle and heart by western blot analysis. Treatment with 100 mg/kg/day MA significantly attenuated the loss of body weight (-9 ± 12%, P  < 0.05) and the wasting of lean and fat mass (-7.0 ± 6% and -22.4 ± 3 %, P  < 0.001 and P  < 0.05, respectively). Administration of 100 mg/kg/day MA significantly protected the heart from general atrophy (633.8 ± 30 mg vs. placebo 474 ± 13 mg, P  < 0.001). Tumour-bearing rats displayed cardiac dysfunction, as indicated by the significant impairment of the left ventricular ejection fraction, the left ventricular fractional shortening, the stroke volume, the end dyastolic volume, and the end systolic volume. In contrast, MA significantly improved left ventricular ejection fraction, left ventricular fractional shortening, and left ventricular end systolic volume. Western blotting analysis showed an upregulation of the autophagic pathway in the gastrocnemius and hearts of the placebo-treated tumour-bearing rats. Treatment with MA, however, was able to modulate the autophagic markers (e.g. Beclin-1, p62, TRAF6, and LC3) in the gastrocnemius and in the hearts of tumour-bearing rats. Most importantly, 100 mg/kg/day MA reduced mortality [hazard ratio (HR): 0.44; 95%CI: 0.20-1.00; P  = 0.0486]. Megestrol acetate improved survival and reduced wasting through a marked downregulation of autophagy, occurring in both skeletal and heart muscle, the latter effect leading to a significant improvement of cardiac function. Our data suggest that MA might represent a valuable strategy to counteract the development of cancer cachexia-induced cardiomyopathy.

Exercise training preserves vagal preganglionic neurones and restores parasympathetic tonus in heart failure.

PubMed

Ichige, Marcelo H A; Santos, Carla R; Jordão, Camila P; Ceroni, Alexandre; Negrão, Carlos E; Michelini, Lisete C

2016-11-01

Heart Failure (HF) is accompanied by reduced ventricular function, activation of compensatory neurohormonal mechanisms and marked autonomic dysfunction characterized by exaggerated sympathoexcitation and reduced parasympathetic activity. With 6 weeks of exercise training, HF-related loss of choline acetyltransferase (ChAT)-positive vagal preganglionic neurones is avoided, restoring the parasympathetic tonus to the heart, and the immunoreactivity of dopamine β-hydroxylase-positive premotor neurones that drive sympathetic outflow to the heart is reduced. Training-induced correction of autonomic dysfunction occurs even with the persistence of abnormal ventricular function. Strong positive correlation between improved parasympathetic tonus to the heart and increased ChAT immunoreactivity in vagal preganglionic neurones after training indicates this is a crucial mechanism to restore autonomic function in heart failure. Exercise training is an efficient tool to attenuate sympathoexcitation, a hallmark of heart failure (HF). Although sympathetic modulation in HF is widely studied, information regarding parasympathetic control is lacking. We examined the combined effects of sympathetic and vagal tonus to the heart in sedentary (Sed) and exercise trained (ET) HF rats and the contribution of respective premotor and preganglionic neurones. Wistar rats submitted to coronary artery ligation or sham surgery were assigned to training or sedentary protocols for 6 weeks. After haemodynamic, autonomic tonus (atropine and atenolol i.v.) and ventricular function determinations, brains were collected for immunoreactivity assays (choline acetyltransferase, ChATir; dopamine β-hydroxylase, DBHir) and neuronal counting in the dorsal motor nucleus of vagus (DMV), nucleus ambiguus (NA) and rostroventrolateral medulla (RVLM). HF-Sed vs. SHAM-Sed exhibited decreased exercise capacity, reduced ejection fraction, increased left ventricle end diastolic pressure, smaller positive and negative dP/dt, decreased intrinsic heart rate (IHR), lower parasympathetic and higher sympathetic tonus, reduced preganglionic vagal neurones and ChATir in the DMV/NA, and increased RVLM DBHir. Training increased treadmill performance, normalized autonomic tonus and IHR, restored the number of DMV and NA neurones and corrected ChATir without affecting ventricular function. There were strong positive correlations between parasympathetic tonus and ChATir in NA and DMV. RVLM DBHir was also normalized by training, but there was no change in neurone number and no correlation with sympathetic tonus. Training-induced preservation of preganglionic vagal neurones is crucial to normalize parasympathetic activity and restore autonomic balance to the heart even in the persistence of cardiac dysfunction. © 2016 The Authors. The Journal of Physiology © 2016 The Physiological Society.

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

Current Interventional and Surgical Management of Congenital Heart Disease: Specific Focus on Valvular Disease and Cardiac Arrhythmias.

PubMed

Holst, Kimberly A; Said, Sameh M; Nelson, Timothy J; Cannon, Bryan C; Dearani, Joseph A

2017-03-17

Successful outcome in the care of patients with congenital heart disease depends on a comprehensive multidisciplinary team. Surgery is offered for almost every heart defect, despite complexity. Early mortality for cardiac surgery in the neonatal period is ≈10% and beyond infancy is <5%, with 90% to 95% of patients surviving with a good quality of life into the adult years. Advances in imaging have facilitated accurate diagnosis and planning of interventions and surgical procedures. Similarly, advances in the perioperative medical management of patients, particularly with intensive care, has also contributed to improving outcomes. Arrhythmias and heart failure are the most common late complications for the majority of defects, and reoperation for valvar problems is common. Lifelong surveillance for monitoring of recurrent or residual structural heart defects, as well as periodic assessment of cardiac function and arrhythmia monitoring, is essential for all patients. The field of congenital heart surgery is poised to incorporate new innovations such as bioengineered cells and scaffolds that will iteratively move toward bioengineered patches, conduits, valves, and even whole organs. © 2017 American Heart Association, Inc.

High-Intensity Interval Training for Severe Left Ventricular Dysfunction Treated with Left Ventricular Assist Device.

PubMed

Ugata, Yusuke; Wada, Hiroshi; Sakakura, Kenichi; Ibe, Tatsuro; Ito, Miyuki; Ikeda, Nahoko; Fujita, Hideo; Momomura, Shin-Ichi

2018-01-27

Aerobic training based on anaerobic threshold (AT) is well-known to improve cardiac function, exercise capacity, and long-term outcomes of patients with heart failure. Recent reports suggested that high-intensity interval training (HIIT) for patients with cardiovascular disease may improve cardiopulmonary exercise capacity. We present a 61-year-old male patient of severe left ventricular dysfunction with left ventricular assisted device (LVAD). Following HIIT for 8 weeks, exercise capacity and muscle strength have improved without worsening left ventricular function. Our case showed the possibility that HIIT was feasible and effective even in patients with LVAD.

Thioredoxin 1 is Essential for Sodium Sulfide-Mediated Cardioprotection in the Setting of Heart Failure

PubMed Central

Nicholson, Chad K.; Lambert, Jonathan P.; Molkentin, Jeffery D.; Sadoshima, Junichi; Calvert, John W.

2013-01-01

Objective The aim of this study was to determine if thioredoxin-1 (Trx1) mediates the cardioprotective effects of hydrogen sulfide (H2S) in a model of ischemic-induced heart failure. Approach/Results Mice with a cardiac-specific overexpression of a dominant negative mutant of Trx1 (Tg-DN-Trx1) and wild-type littermates were subjected to ischemic-induced heart failure. Treatment with H2S as sodium sulfide (Na2S) not only increased the gene and protein expression of Trx1 in the absence of ischemia, but also augmented the heart failure-induced increase in both. Wild-type mice treated with Na2S experienced less left ventricular (LV) dilatation, improved LV function, and less cardiac hypertrophy after the induction of heart failure. In contrast, Na2S therapy failed to improve any of these parameters in the Tg-DN-Trx1 mice. Studies aimed at evaluating the underlying cardioprotective mechanisms found that Na2S therapy inhibited heart failure-induced apoptosis signaling kinase-1 (ASK1) signaling and nuclear export of histone deacetylase 4 (HDAC4) in a Trx1-dependent manner. Conclusions These findings provide novel information that the upregulation of Trx1 by Na2S therapy in the setting of heart failure sets into motion events, such as the inhibition of ASK1 signaling and HDAC4 nuclear export, which ultimately leads to the attenuation of LV remodeling. PMID:23349187

In vitro and in vivo assessment of heart-homing porous silicon nanoparticles.

PubMed

Ferreira, Mónica P A; Ranjan, Sanjeev; Correia, Alexandra M R; Mäkilä, Ermei M; Kinnunen, Sini M; Zhang, Hongbo; Shahbazi, Mohammad-Ali; Almeida, Patrick V; Salonen, Jarno J; Ruskoaho, Heikki J; Airaksinen, Anu J; Hirvonen, Jouni T; Santos, Hélder A

2016-07-01

Chronic heart failure, predominantly developed after myocardial infarction, is a leading cause of high mortality worldwide. As existing therapies have still limited success, natural and/or synthetic nanomaterials are emerging alternatives for the therapy of heart diseases. Therefore, we aimed to functionalize undecylenic acid thermally hydrocarbonized porous silicon nanoparticles (NPs) with different targeting peptides to improve the NP's accumulation in different cardiac cells (primary cardiomyocytes, non-myocytes, and H9c2 cardiomyoblasts), additionally to investigate the behavior of the heart-targeted NPs in vivo. The toxicity profiles of the NPs evaluated in the three heart-type cells showed low toxicity at concentrations up to 50 μg/mL. Qualitative and quantitative cellular uptake revealed a significant increase in the accumulation of atrial natriuretic peptide (ANP)-modified NPs in primary cardiomyocytes, non-myocytes and H9c2 cells, and in hypoxic primary cardiomyocytes and non-myocytes. Competitive uptake studies in primary cardiomyocytes showed the internalization of ANP-modified NPs takes place via the guanylate cyclase-A receptor. When a myocardial infarction rat model was induced by isoprenaline and the peptide-modified [(111)In]NPs administered intravenously, the targeting peptides, particularly peptide 2, improved the NPs' accumulation in the heart up to 3.0-fold, at 10 min. This study highlights the potential of these peptide-modified nanosystems for future applications in heart diseases. Copyright © 2016 Elsevier Ltd. All rights reserved.

Status of Therapeutic Gene Transfer to Treat Cardiovascular Disease in Dogs and Cats.

PubMed

Sleeper, Meg M

2017-09-01

Gene therapy is a procedure resulting in the transfer of a gene into an individual's cells to treat a disease. One goal of gene transfer is to express a functional gene when the endogenous gene is inactive. However, because heart failure is a complex disease characterized by multiple abnormalities at the cellular level, an alternate gene delivery approach is to alter myocardial protein levels to improve function. This article discusses background information on gene delivery, including packaging, administration, and a brief discussion of some of the candidate transgenes likely to alter the progression of naturally occurring heart disease in dogs and cats. Copyright © 2017 Elsevier Inc. All rights reserved.

Vascularisation to improve translational potential of tissue engineering systems for cardiac repair.

PubMed

Dilley, Rodney J; Morrison, Wayne A

2014-11-01

Cardiac tissue engineering is developing as an alternative approach to heart transplantation for treating heart failure. Shortage of organ donors and complications arising after orthotopic transplant remain major challenges to the modern field of heart transplantation. Engineering functional myocardium de novo requires an abundant source of cardiomyocytes, a biocompatible scaffold material and a functional vasculature to sustain the high metabolism of the construct. Progress has been made on several fronts, with cardiac cell biology, stem cells and biomaterials research particularly promising for cardiac tissue engineering, however currently employed strategies for vascularisation have lagged behind and limit the volume of tissue formed. Over ten years we have developed an in vivo tissue engineering model to construct vascularised tissue from various cell and tissue sources, including cardiac tissue. In this article we review the progress made with this approach and others, together with their potential to support a volume of engineered tissue for cardiac tissue engineering where contractile mass impacts directly on functional outcomes in translation to the clinic. It is clear that a scaled-up cardiac tissue engineering solution required for clinical treatment of heart failure will include a robust vascular supply for successful translation. This article is part of a directed issue entitled: Regenerative Medicine: the challenge of translation. Copyright © 2014 Elsevier Ltd. All rights reserved.

Exercise training in adults with repaired tetralogy of Fallot: A randomized controlled pilot study of continuous versus interval training.

PubMed

Novaković, Marko; Prokšelj, Katja; Rajkovič, Uroš; Vižintin Cuderman, Tjaša; Janša Trontelj, Katja; Fras, Zlatko; Jug, Borut

2018-03-15

Adults with repaired tetralogy of Fallot (ToF) have impaired exercise capacity, vascular and cardiac autonomic function, and quality of life (QoL). Specific effects of high-intensity interval or moderate continuous exercise training on these parameters in adults with repaired ToF remain unknown. Thirty adults with repaired ToF were randomized to either high-intensity interval, moderate intensity continuous training (36 sessions, 2-3 times a week) or usual care (no supervised exercise). Exercise capacity, flow-mediated vasodilation, pulse wave velocity, NT-proBNP and fibrinogen levels, heart rate variability and recovery, and QoL (SF-36 questionnaire) were determined at baseline and after the intervention period. Twenty-seven patients (mean age 39±9years, 63% females, 9 from each group) completed this pilot study. Both training groups improved in at least some parameters of cardiovascular health compared to no exercise. Interval-but not continuous-training improved VO2peak (21.2 to 22.9ml/kg/min, p=0.004), flow-mediated vasodilation (8.4 to 12.9%, p=0.019), pulse wave velocity (5.4 to 4.8m/s, p=0.028), NT-proBNP (202 to 190ng/L, p=0.032) and fibrinogen levels (2.67 to 2.46g/L, p=0.018). Conversely, continuous-but not interval-training improved heart rate variability (low-frequency domain, 0.32 to 0.22, p=0.039), heart rate recovery after 2min post-exercise (40 to 47 beats, p=0.023) and mental domain of SF-36 (87 to 95, p=0.028). Both interval and continuous exercise training modalities were safe. Interval training seems more efficacious in improving exercise capacity, vascular function, NT-proBNP and fibrinogen levels, while continuous training seems more efficacious in improving cardiac autonomic function and QoL. (Clinicaltrials.gov, NCT02643810). Copyright © 2018 Elsevier Ireland Ltd. All rights reserved.

Making better scar: Emerging approaches for modifying mechanical and electrical properties following infarction and ablation.

PubMed

Holmes, Jeffrey W; Laksman, Zachary; Gepstein, Lior

2016-01-01

Following myocardial infarction (MI), damaged myocytes are replaced by collagenous scar tissue, which serves an important mechanical function - maintaining integrity of the heart wall against enormous mechanical forces - but also disrupts electrical function as structural and electrical remodeling in the infarct and borderzone predispose to re-entry and ventricular tachycardia. Novel emerging regenerative approaches aim to replace this scar tissue with viable myocytes. Yet an alternative strategy of therapeutically modifying selected scar properties may also prove important, and in some cases may offer similar benefits with lower risk or regulatory complexity. Here, we review potential goals for such modifications as well as recent proof-of-concept studies employing specific modifications, including gene therapy to locally increase conduction velocity or prolong the refractory period in and around the infarct scar, and modification of scar anisotropy to improve regional mechanics and pump function. Another advantage of scar modification techniques is that they have applications well beyond MI. In particular, ablation treats electrical abnormalities of the heart by intentionally generating scar to block aberrant conduction pathways. Yet in diseases such as atrial fibrillation (AF) where ablation can be extensive, treating the electrical disorder can significantly impair mechanical function. Creating smaller, denser scars that more effectively block conduction, and choosing the location of those lesions by balancing their electrical and mechanical impacts, could significantly improve outcomes for AF patients. We review some recent advances in this area, including the use of computational models to predict the mechanical effects of specific lesion sets and gene therapy for functional ablation. Overall, emerging techniques for modifying scar properties represents a potentially important set of tools for improving patient outcomes across a range of heart diseases, whether used in place of or as an adjunct to regenerative approaches. Copyright © 2015 Elsevier Ltd. All rights reserved.

Total Artificial Heart Implantation as a Bridge to Heart Transplantation in an Active Duty Service Member With Amyloid Cardiomyopathy.

PubMed

Scully, Michael S; Wessman, Dylan E; McKee, James M; Francisco, Gregory M; Nayak, Keshav R; Kobashigawa, Jon A

2017-03-01

Cardiac involvement by light-chain (AL) amyloid occurs in up to 50% of patients with primary AL amyloidosis. The prognosis of amyloid heart disease is poor with 1-year survival rates of 35 to 40%. Historically, heart transplantation was considered controversial for patients with AL amyloid cardiomyopathy (CM) given the systemic nature of the disease and poor survival. We present a case report of an active duty service member diagnosed with advanced cardiac amyloid who underwent total artificial heart transplant as a bridge to heart transplant and eventual autologous stem cell transplant. A 47-year-old active duty male initially evaluated for atypical chest pain was found to have severe concentric left ventricular hypertrophy on echocardiogram but normal voltage on electrocardiogram. Cardiac magnetic resonance imaging, laboratory studies, and bone marrow biopsy established the diagnosis of cardiac amyloidosis. At the time of diagnosis, the patient's prognosis was very poor with a median survival of 5 months on the basis of the Mayo Clinic revised prognostic staging system for amyloidosis. The patient developed rapidly progressive left ventricular dysfunction and heart failure leading to cardiac arrest. The patient received a total artificial heart as a bridge to orthotopic heart and kidney transplantation and eventual stem cell transplant. He continues to be in remission and has a fair functional capacity without restriction in activities of daily living or moderate exercise. Amyloid CM is a rare and devastating disease. The natural course of the disease has made heart transplant in these patients controversial. Modern advancements in chemotherapies and advanced heart failure treatments have improved outcomes for select patients with AL amyloid CM undergoing heart transplantation. There is ongoing research seeking improvement in treatment options and outcomes for patients with this deadly disease. Reprint & Copyright © 2017 Association of Military Surgeons of the U.S.

Heart failure patients utilizing an electric home monitor: What effects does heart failure have on their quality of life?

NASA Astrophysics Data System (ADS)

Simuel, Gloria J.

Heart Failure continues to be a major public health problem associated with high mortality and morbidity. Heart Failure is the leading cause of hospitalization for persons older than 65 years, has a poor prognosis and is associated with poor quality of life. More than 5.3 million American adults are living with heart failure. Despite maximum medical therapy and frequent hospitalizations to stabilize their condition, one in five heart failure patients die within the first year of diagnosis. Several disease-management programs have been proposed and tested to improve the quality of heart failure care. Studies have shown that hospital admissions and emergency room visits decrease with increased nursing interventions in the home and community setting. An alternative strategy for promoting self-management of heart failure is the use of electronic home monitoring. The purpose of this study was to examine what effects heart failure has on patient's quality of life that had been monitoring on an electronic home monitor longer than 2 months. Twenty-one questionnaires were given to patients utilizing an electronic home monitor by their home health agency nurse. Eleven patients completed the questionnaire. The findings showed that there is some deterioration in quality of life with more association with the physical aspects of life than with the emotional aspects of life, which probably was due to the small sample size. There was no significant difference in readmission rates in patients utilizing an electronic home monitor. Further research is needed with a larger population of patients with chronic heart failure and other chronic diseases which may provide more data, and address issues such as patient compliance with self-care, impact of heart failure on patient's quality of life, functional capacity, and heart failure patient's utilization of the emergency rooms and hospital. Telemonitoring holds promise for improving the self-care abilities of persons with HF.

The role of the sca-1+/CD31- cardiac progenitor cell population in postinfarction left ventricular remodeling.

PubMed

Wang, Xiaohong; Hu, Qingsong; Nakamura, Yasuhiro; Lee, Joseph; Zhang, Ge; From, Arthur H L; Zhang, Jianyi

2006-07-01

Cardiac stem cell-like populations exist in adult hearts, and their roles in cardiac repair remain to be defined. Sca-1 is an important surface marker for cardiac and other somatic stem cells. We hypothesized that heart-derived Sca-1(+)/CD31(-) cells may play a role in myocardial infarction-induced cardiac repair/remodeling. Mouse heart-derived Sca-1(+)/CD31(-) cells cultured in vitro could be induced to express both endothelial cell and cardiomyocyte markers. Immunofluorescence staining and fluorescence-activated cell sorting analysis indicated that endogenous Sca-1(+)/CD31(-) cells were significantly increased in the mouse heart 7 days after myocardial infarction (MI). Western blotting confirmed elevated Sca-1 protein expression in myocardium 7 days after MI. Transplantation of Sca-1(+)/CD31(-) cells into the acutely infarcted mouse heart attenuated the functional decline and adverse structural remodeling initiated by MI as evidenced by an increased left ventricular (LV) ejection fraction, a decreased LV end-diastolic dimension, a decreased LV end-systolic dimension, a significant increase of myocardial neovascularization, and modest cardiomyocyte regeneration. Attenuation of LV remodeling was accompanied by remarkably improved myocardial bioenergetic characteristics. The beneficial effects of cell transplantation appear to primarily depend on paracrine effects of the transplanted cells on new vessel formation and native cardiomyocyte function. Sca-1(+)/CD31(-) cells may hold therapeutic possibilities with regard to the treatment of ischemic heart disease.

Patient-specific models of cardiac biomechanics

NASA Astrophysics Data System (ADS)

Krishnamurthy, Adarsh; Villongco, Christopher T.; Chuang, Joyce; Frank, Lawrence R.; Nigam, Vishal; Belezzuoli, Ernest; Stark, Paul; Krummen, David E.; Narayan, Sanjiv; Omens, Jeffrey H.; McCulloch, Andrew D.; Kerckhoffs, Roy C. P.

2013-07-01

Patient-specific models of cardiac function have the potential to improve diagnosis and management of heart disease by integrating medical images with heterogeneous clinical measurements subject to constraints imposed by physical first principles and prior experimental knowledge. We describe new methods for creating three-dimensional patient-specific models of ventricular biomechanics in the failing heart. Three-dimensional bi-ventricular geometry is segmented from cardiac CT images at end-diastole from patients with heart failure. Human myofiber and sheet architecture is modeled using eigenvectors computed from diffusion tensor MR images from an isolated, fixed human organ-donor heart and transformed to the patient-specific geometric model using large deformation diffeomorphic mapping. Semi-automated methods were developed for optimizing the passive material properties while simultaneously computing the unloaded reference geometry of the ventricles for stress analysis. Material properties of active cardiac muscle contraction were optimized to match ventricular pressures measured by cardiac catheterization, and parameters of a lumped-parameter closed-loop model of the circulation were estimated with a circulatory adaptation algorithm making use of information derived from echocardiography. These components were then integrated to create a multi-scale model of the patient-specific heart. These methods were tested in five heart failure patients from the San Diego Veteran's Affairs Medical Center who gave informed consent. The simulation results showed good agreement with measured echocardiographic and global functional parameters such as ejection fraction and peak cavity pressures.

Relationship between cerebral blood flow and blood pressure in long-term heart transplant recipients.

PubMed

Smirl, Jonathan D; Haykowsky, Mark J; Nelson, Michael D; Tzeng, Yu-Chieh; Marsden, Katelyn R; Jones, Helen; Ainslie, Philip N

2014-12-01

Heart transplant recipients are at an increased risk for cerebral hemorrhage and ischemic stroke; yet, the exact mechanism for this derangement remains unclear. We hypothesized that alterations in cerebrovascular regulation is principally involved. To test this hypothesis, we studied cerebral pressure-flow dynamics in 8 clinically stable male heart transplant recipients (62±8 years of age and 9±7 years post transplant, mean±SD), 9 male age-matched controls (63±8 years), and 10 male donor controls (27±5 years). To increase blood pressure variability and improve assessment of the pressure-flow dynamics, subjects performed squat-stand maneuvers at 0.05 and 0.10 Hz. Beat-to-beat blood pressure, middle cerebral artery velocity, and end-tidal carbon dioxide were continuously measured during 5 minutes of seated rest and throughout the squat-stand maneuvers. Cardiac baroreceptor sensitivity gain and cerebral pressure-flow responses were assessed with linear transfer function analysis. Heart transplant recipients had reductions in R-R interval power and baroreceptor sensitivity low frequency gain (P<0.01) compared with both control groups; however, these changes were unrelated to transfer function metrics. Thus, in contrast to our hypothesis, the increased risk of cerebrovascular complication after heart transplantation does not seem to be related to alterations in cerebral pressure-flow dynamics. Future research is, therefore, warranted. © 2014 American Heart Association, Inc.

Impact of CPAP on physical exercise tolerance and sympathetic-vagal balance in patients with chronic heart failure.

PubMed

Reis, Hugo V; Borghi-Silva, Audrey; Catai, Aparecida M; Reis, Michel S

2014-01-01

Chronic heart failure (CHF) leads to exercise intolerance. However, non-invasive ventilation is able to improve functional capacity of patients with CHF. The aim of this study was to evaluate the effectiveness of continuous positive airway pressure (CPAP) on physical exercise tolerance and heart rate variability (HRV) in patients with CHF. Method : Seven men with CHF (62 ± 8 years) and left ventricle ejection fraction of 41 ± 8% were submitted to an incremental symptom-limited exercise test (IT) on the cicloergometer. On separate days, patients were randomized to perform four constant work rate exercise tests to maximal tolerance with and without CPAP (5 cmH2O) in the following conditions: i) at 50% of peak work rate of IT; and ii) at 75% of peak work rate of IT. At rest and during these conditions, instantaneous heart rate (HR) was recorded using a cardiofrequencimeter and HRV was analyzed in time domain (SDNN and RMSSD indexes). For statistical procedures, Wilcoxon test or Kruskall-Wallis test with Dunn's post-hoc were used accordingly. In addition, categorical variables were analysed through Fischer's test (p<0.05). There were significant improvements in exercise tolerance at 75% of peak work rate of IT with CPAP (405 ± 52 vs. 438 ± 58 s). RMSSD indexes were lower during exercise tests compared to CPAP at rest and with 50% of peak work rate of IT. These data suggest that CPAP appears to be a useful strategy to improve functional capacity in patients with CHF. However, the positive impact of CPAP did not generate significant changes in the HRV during physical exercises.

A 4-Week Intervention Involving Mobile-Based Daily 6-Minute Micro-Sessions of Functional High-Intensity Circuit Training Improves Strength and Quality of Life, but Not Cardio-Respiratory Fitness of Young Untrained Adults.

PubMed

Sperlich, Billy; Hahn, Lea-Sofie; Edel, Antonia; Behr, Tino; Helmprobst, Julian; Leppich, Robert; Wallmann-Sperlich, Birgit; Holmberg, Hans-Christer

2018-01-01

The present study was designed to assess the psycho-physiological responses of physically untrained individuals to mobile-based multi-stimulating, circuit-like, multiple-joint conditioning (Circuit HIIT ) performed either once (1xCircuit HIIT ) or twice (2xCircuit HIIT ) daily for 4 weeks. In this single-center, two-arm randomized, controlled study, 24 men and women (age: 25 ± 5 years) first received no training instructions for 4 weeks and then performed 4 weeks of either 1xCircuit HIIT or 2xCircuit HIIT (5 men and 7 women in each group) daily. The 1xCircuit HIIT and 2xCircuit HIIT participants carried out 90.7 and 85.7% of all planned training sessions, respectively, with average heart rates during the 6-min sessions of 74.3 and 70.8% of maximal heart rate. Body, fat and fat-free mass, and metabolic rate at rest did not differ between the groups or between time-points of measurement. Heart rate while running at 6 km⋅h -1 declined after the intervention in both groups. Submaximal and peak oxygen uptake, the respiratory exchange ratio and heart rate recovery were not altered by either intervention. The maximal numbers of push-ups, leg-levers, burpees, 45°-one-legged squats and 30-s skipping, as well as perception of general health improved in both groups. Our 1xCircuit HIIT or 2xCircuit HIIT interventions improved certain parameters of functional strength and certain dimensions of quality of life in young untrained individuals. However, they were not sufficient to enhance cardio-respiratory fitness, in particular peak oxygen uptake.

Transcoronary infusion of cardiac progenitor cells in hypoplastic left heart syndrome: Three-year follow-up of the Transcoronary Infusion of Cardiac Progenitor Cells in Patients With Single-Ventricle Physiology (TICAP) trial.

PubMed

Tarui, Suguru; Ishigami, Shuta; Ousaka, Daiki; Kasahara, Shingo; Ohtsuki, Shinichi; Sano, Shunji; Oh, Hidemasa

2015-11-01

Our aim was to assess midterm safety and clinical outcomes of intracoronary infusion of cardiosphere-derived cells (CDCs) after staged palliation in patients with hypoplastic left heart syndrome (HLHS). In this prospective, controlled study, 14 consecutive patients with HLHS who were undergoing 2- or 3-stage surgical palliations were assigned to receive intracoronary CDC infusion 1 month after cardiac surgery (n = 7), followed by 7 patients allocated to a control group with standard care alone. The primary end point was to assess procedural feasibility and safety; the secondary end point was to evaluate cardiac function and heart failure status through 36-month follow-up. No complications, including tumor formation, were reported within 36 months after CDC infusion. Echocardiography showed significantly greater improvement in right ventricular ejection fraction (RVEF) in infants receiving CDCs than in controls at 36 months (+8.0% ± 4.7% vs +2.2% ± 4.3%; P = .03). These cardiac function improvements resulted in reduced brain natriuretic peptide levels (P = .04), lower incidence of unplanned catheter interventions (P = .04), and higher weight-for-age z score (P = .02) at 36 months relative to controls. As independent predictors of treatment responsiveness, absolute changes in RVEF at 36 months were negatively correlated with age, weight-for-age z score, and RVEF at CDC infusion. Intracoronary CDC infusion after staged procedure in patients with HLHS is safe and improves RVEF, which persists during 36-month follow-up. This therapeutic strategy may enhance somatic growth and reduce incidence of heart failure. Copyright © 2015 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.

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.

[Evalation of Jingzhi Xiaoban Tablet in Improving Heart Function of Coronary Heart Disease Pa- tients by Doppler Tissue Imaging and Speckle Tracking Imaging Technology].

PubMed

Wang, Yue-ai; Yu, Xi-jiao; Cheng, Chou-fu; Yang, Li; Liu, Fang; Zhou, Meng-hong; Tan, Yun

2016-04-01

To evaluate the role of Jiangzhi Xiaoban Tablet (JXT) in improving heartfunction of coronary heart disease (CHD) patients by tissue Doppler imaging (TDI) and speckle trackingimaging (STI) technology. Recruited were 60 inpatients with confirmed CHD by coronary angiography at First Affiliated Hospital, Hunan University of Traditional Chinese Medicine from October 2013to November 2014. They were assigned to the treatment group (group A) and the control group (groupB) according to random digit table, 30 cases in each group. Patients in group A took JXT, 0.45 g/tablet,4 tablets each time, 3 times per day, while those in group B took Simvastatin Tablet, 20 mg/tablet, 1 tablet each time, once per evening. The therapeutic course for all was 8 weeks. The long axis view of theheart of 18 segments STI Peak strain LS and TDI peak systolic Sa parameters were performed in all patients before and after treatment. Before treatment segments of STI strain LS and TDI longitudinal peak systolic peak Sa were not statistically different between the two groups (P > 0.05). Each segment of STI peak longitudinal strain LS and TDI peak systolic Sa in the two groups were higher after treatment than before treatment (P < 0.05). After treatment each segment of STI parameters of LS and eachTDI segment parameters of Sa were significantly lower in group B than in group A (P < 0.01). JXT could improve heart function of CHD patients to different degrees, and its curative effect was betterthan that of routine Western medicine (Simvastatin Tablets) treatment.

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.

Improved biochemical preservation of heart slices during cold storage.

PubMed

Bull, D A; Reid, B B; Connors, R C; Albanil, A; Stringham, J C; Karwande, S V

2000-01-01

Development of myocardial preservation solutions requires the use of whole organ models which are animal and labor intensive. These models rely on physiologic rather than biochemical endpoints, making accurate comparison of the relative efficacy of individual solution components difficult. We hypothesized that myocardial slices could be used to assess preservation of biochemical function during cold storage. Whole rat hearts were precision cut into slices with a thickness of 200 microm and preserved at 4 degrees C in one of the following solutions: Columbia University (CU), University of Wisconsin (UW), D5 0.2% normal saline with 20 meq/l KCL (QNS), normal saline (NS), or a novel cardiac preservation solution (NPS) developed using this model. Myocardial biochemical function was assessed by ATP content (etamoles ATP/mg wet weight) and capacity for protein synthesis (counts per minute (cpm)/mg protein) immediately following slicing (0 hours), and at 6, 12, 18, and 24 hours of cold storage. Six slices were assayed at each time point for each solution. The data were analyzed using analysis of variance and are presented as the mean +/- standard deviation. ATP content was higher in the heart slices stored in the NPS compared to all other solutions at 6, 12, 18 and 24 hours of cold storage (p < 0.05). Capacity for protein synthesis was higher in the heart slices stored in the NPS compared to all other solutions at 6, 12, and 18 hours of cold storage (p < 0.05). CONCLUSIONS This myocardial slice model allows the rapid and efficient screening of cardiac preservation solutions and their components using quantifiable biochemical endpoints. Using this model, we have developed a novel preservation solution which improves the biochemical function of myocardial slices during cold storage.

A correlational study of illness knowledge, self-care behaviors, and quality of life in elderly patients with heart failure.

PubMed

Liu, Min-Hui; Wang, Chao-Hung; Huang, Yu-Yen; Cherng, Wen-Jin; Wang, Kai-Wei Katherine

2014-06-01

Patients with heart failure experience adverse physical symptoms that affect quality of life. The number of patients with heart failure in Taiwan has been growing in recent years. This article examines correlations among illness knowledge, self-care behaviors, and quality of life in elderly patients with heart failure. A cross-sectional research design using three questionnaires was adopted. The study was undertaken in an outpatient department of a teaching hospital in Taiwan from January to June 2008. Potential participants aged 65 years or older were selected by a physician based on several diagnostic findings of heart failure that included an International Classification of Diseases' code 4280 or 4289. Patients who were bedridden or had a prognosis of less than 6 months were excluded from consideration. One hundred forty-one patients with heart failure were recruited. Most participants were men (51.8%), older adults (49.6% older than 71 years old), and either educated to an elementary school level or illiterate (69.5%) and have New York Heart Association class II (61.0%). Participants had an average left ventricular ejection fraction of 41.1%. The illness knowledge of participants was poor (accuracy rate: 29.3%), and most were unaware of the significance of self-care. Illness knowledge correlated with both self-care behaviors (r = -.42, p < .01) and quality of life (r = -.22, p < .01). Illness knowledge and age were identified as significant correlated factors of self-care behaviors (R = .22); and functional class, living independently, and age were identified as significant correlated factors of quality of life (R = .41). Participants in this study with higher self-reported self-care behaviors and quality of life were younger in age and had better illness knowledge. Furthermore, physical function and independence in daily living significantly affected quality of life. Care for patients with heart failure, particularly older adults, should focus on teaching these patients about heart failure illness and symptom management. Assisting elderly patients with heart failure to promote and maintain physical functions to handle activities of daily living independently is critical to improving patient quality of life.

Moxonidine-induced central sympathoinhibition improves prognosis in rats with hypertensive heart failure.

PubMed

Honda, Nobuhiro; Hirooka, Yoshitaka; Ito, Koji; Matsukawa, Ryuichi; Shinohara, Keisuke; Kishi, Takuya; Yasukawa, Keiji; Utsumi, Hideo; Sunagawa, Kenji

2013-11-01

Enhanced central sympathetic outflow is an indicator of the prognosis of heart failure. Although the central sympatholytic drug moxonidine is an established therapeutic strategy for hypertension, its benefits for hypertensive heart failure are poorly understood. In the present study, we investigated the effects of central sympathoinhibition by intracerebral infusion of moxonidine on survival in a rat model of hypertensive heart failure and the possible mechanisms involved. As a model of hypertensive heart failure, we fed Dahl salt-sensitive rats an 8% NaCl diet from 7 weeks of age. Intracerebroventricular (ICV) infusion of moxonidine (moxonidine-ICV-treated group [Mox-ICV]) or vehicle (vehicle-ICV-treated group [Veh-ICV]) was performed at 14-20 weeks of age, during the increased heart failure phase. Survival rates were examined, and sympathetic activity, left ventricular function and remodelling, and brain oxidative stress were measured. Hypertension and left ventricular hypertrophy were established by 13 weeks of age. At around 20 weeks of age, Veh-ICV rats exhibited overt heart failure concomitant with increased urinary norepinephrine (uNE) excretion as an index of sympathetic activity, dilated left ventricle, decreased percentage fractional shortening, and myocardial fibrosis. Survival rates at 21 weeks of age (n = 28) were only 23% in Veh-ICV rats, and 76% (n = 17) in Mox-ICV rats with concomitant decreases in uNE, myocardial fibrosis, collagen type I/III ratio, brain oxidative stress, and suppressed left ventricular dysfunction. Moxonidine-induced central sympathoinhibition attenuated brain oxidative stress, prevented cardiac dysfunction and remodelling, and improved the prognosis in rats with hypertensive heart failure. Central sympathoinhibition can be effective for the treatment of hypertensive heart failure.

Albumin augmentation improves condition of guinea pig hearts after 4 hr of cold ischemia.

PubMed

Jacob, Matthias; Paul, Oliver; Mehringer, Laurenz; Chappell, Daniel; Rehm, Markus; Welsch, Ulrich; Kaczmarek, Ingo; Conzen, Peter; Becker, Bernhard F

2009-04-15

Major causes of death after heart transplantation are right ventricular pump failure and, chronically, cardiac allograft vasculopathy. Traditional preservation techniques focus on immediate cardioplegia, without particularly considering vascular demands. Recently, the endothelial surface layer, composed of the endothelial glycocalyx and plasma proteins, was discovered to play a major role in vascular barrier function, edema formation, and leukocyte-to-endothelial interaction. The impact of augmenting a traditional preservation solution with plasma colloid albumin was therefore investigated. Guinea pig hearts underwent cold ischemic storage for 4 hr using Bretschneider's solution (histidine-tryptophan-ketoglutarate [HTK]) without and with augmentation with 1 g% human albumin. After reperfusion, intracoronary adhesion of polymorphonuclear granulocytes, edema formation, left and right heart performance of pressure-to-volume work, and glycocalyx shedding were assessed. Intracoronary retention of leukocytes was doubled in the traditional group (36.4+/-6.6%), whereas it remained at basal values after albumin preservation (23.5+/-2.4%; P<0.05). Addition of albumin to HTK significantly decreased edema formation (wet to dry weight ratio 6.9+/-0.1 vs. 7.2+/-0.2; P<0.05). Although left heart performance was comparable, right heart cardiac output was doubled in hearts having received HTK containing albumin versus HTK alone (94+/-14 vs. 50+/-11 mL/min/g; P<0.05). Glycocalyx shedding was significantly reduced when the hearts were stored under albumin protection. Augmenting HTK with human albumin improves endothelial integrity and heart performance after 4 hr cold ischemia, because of a marked protection of the endothelial glycocalyx. For the prevention of acute and chronic graft failure, the glycocalyx might represent a new target.

Targeted myocardial delivery of GDF11 gene rejuvenates the aged mouse heart and enhances myocardial regeneration after ischemia-reperfusion injury.

PubMed

Du, Guo-Qing; Shao, Zheng-Bo; Wu, Jie; Yin, Wen-Juan; Li, Shu-Hong; Wu, Jun; Weisel, Richard D; Tian, Jia-Wei; Li, Ren-Ke

2017-01-01

Ischemic cardiac injury is the main contributor to heart failure, and the regenerative capacity of intrinsic stem cells plays an important role in tissue repair after injury. However, stem cells in aged individuals have reduced regenerative potential and aged tissues lack the capacity to renew. Growth differentiation factor 11 (GDF11), from the activin-transforming growth factor β superfamily, has been shown to promote stem cell activity and rejuvenation. We carried out non-invasive targeted delivery of the GDF11 gene to the heart using ultrasound-targeted microbubble destruction (UTMD) and cationic microbubble (CMB) to investigate the ability of GDF11 to rejuvenate the aged heart and improve tissue regeneration after injury. Young (3 months) and old (21 months) mice were used to evaluate the expression of GDF11 mRNA in the myocardium at baseline and after ischemia/reperfusion (I/R) and myocardial infarction. GDF11 expression decreased with age and following myocardial injury. UTMD-mediated delivery of the GDF11 plasmid to the aged heart after I/R injury effectively and selectively increased GDF11 expression in the heart, and improved cardiac function and reduced infarct size. Over-expression of GDF11 decreased senescence markers, p16 and p53, as well as the number of p16 + cells in old mouse hearts. Furthermore, increased proliferation of cardiac stem cell antigen 1 (Sca-1 + ) cells and increased homing of endothelial progenitor cells and angiogenesis in old ischemic hearts occurred after GDF11 over-expression. Repetitive targeted delivery of the GDF11 gene via UTMD can rejuvenate the aged mouse heart and protect it from I/R injury.

Eotaxin/CCL11 levels correlate with myocardial fibrosis and mast cell density in native and transplanted rat hearts.

PubMed

Zweifel, M; Matozan, K; Dahinden, C; Schaffner, T; Mohacsi, P

2010-09-01

Myocardial fibrosis contributes to hemodynamic and cardiac functional alterations commonly observed posttransplantation. Cardiac mast cells (MC) have been linked to fibrosis in posttransplantation hearts. Eotaxin, which has been shown to be involved in fibrogenesis, has been demonstrated to be increased in production in cardiac macrophages. The aim of our study was to correlate myocardial fibrosis during heart transplant rejection in the rat with eotaxin/chemokine [c-c motif] ligand 11 (CCL11) expression, and with various subtypes of infiltrating cardiac MC, namely connective-type MC (CTMC) and mucosa-type MC (MMC). We used tissues from 2 previous studies of ongoing acute rejection in allogeneic Brown-Norway to Lewis rat and an isogeneic Brown-Norway to Brown-Norway heterotopic heart transplantation models under cyclosporin/prednisolone immunosuppression. Collagen fibrils were stained with Masson's trichrome with myocardial fibrosis expressed as percent fibrotic area per total section area. Eotaxin/CCL11 previously measured in heart tissue using enzyme-linked immunosorbent assay (ELISA) was correlated with the extent of myocardial fibrosis. We compared values from native hearts (n = 4) as well as transplants on days 5, 16, and 28 (n = 4 in each group). The area of myocardial fibrosis was significantly increased in the allogeneic compared with the isogeneic group at day 16 (38% vs 21%) and at day 28 (49% vs 22%) after transplantation. Myocardial fibrosis correlated significantly with eotaxin/CCL11 concentrations and the density of MMC, but not with CTMC in heart tissue. Eotaxin-triggered MC infiltration of the heart may contribute to myocardial fibrosis after transplantation. Targeting eotaxin/CCL11 with monoclonal antibodies, such as bertilimumab, could reduce MC infiltration, possibly resulting in decreased myocardial fibrosis and improved contractile function after heart transplantation. 2010 Elsevier Inc. All rights reserved.

Additional use of a phosphodiesterase 5 inhibitor in patients with pulmonary hypertension secondary to chronic systolic heart failure: a meta-analysis.

PubMed

Wu, Xiaojing; Yang, Te; Zhou, Qi; Li, Shuangfei; Huang, Lan

2014-04-01

Increased indiscriminate use of pulmonary artery hypertension-targeted drugs has been observed in patients with pulmonary hypertension (PH) secondary to heart failure. We performed a meta-analysis to evaluate the chronic effects of using phosphodiesterase 5 (PDE5) inhibitors to treat patients with PH secondary to chronic systolic heart failure. PubMed, EMBASE, and the Cochrane Library were searched up to October 2013 for randomized controlled trials (RCTs) assessing PDE5 inhibitor treatments in PH patients secondary to chronic heart failure. Six RCTs involving 206 chronic systolic heart failure patients with PH complications were included. Sildenafil was used in all trials. Sildenafil treatment resulted in fewer hospital admissions compared with the placebo treatment (3.15% vs. 12.20%; risk ratio 0.29; 95% confidence interval 0.11-0.77). Various haemodynamic parameters were improved with additional sildenafil treatment, including reduced mean pulmonary artery pressure [weighted mean difference (WMD) -5.71 mmHg, P<0.05] and pulmonary vascular resistance (WMD -81.5 dynes/cm(-5), P<0.00001), increased LVEF (WMD 3.95%, P<0.01), and unchanged heart rate and blood pressure. The exercise capacity improved (oxygen consumption at peak exercise, WMD 3.20 mL/min(-1)/kg(-1), P<0.00001; ventilation to CO2 production slope, WMD -5.89, P<0.00001), and the clinical symptoms were relieved based on the breathlessness (WMD 7.72, P<0.00001), fatigue (WMD 2.28, P<0.05), and emotional functioning (WMD 5.92, P<0.00001) scores. Additional sildenafil treatment is a potential therapeutic method to improve pulmonary exercise capacity and quality of life by ameliorating PH in patients with chronic systolic heart failure. © 2013 The Authors. European Journal of Heart Failure © 2013 European Society of Cardiology.

Combining computer modelling and cardiac imaging to understand right ventricular pump function.

PubMed

Walmsley, John; van Everdingen, Wouter; Cramer, Maarten J; Prinzen, Frits W; Delhaas, Tammo; Lumens, Joost

2017-10-01

Right ventricular (RV) dysfunction is a strong predictor of outcome in heart failure and is a key determinant of exercise capacity. Despite these crucial findings, the RV remains understudied in the clinical, experimental, and computer modelling literature. This review outlines how recent advances in using computer modelling and cardiac imaging synergistically help to understand RV function in health and disease. We begin by highlighting the complexity of interactions that make modelling the RV both challenging and necessary, and then summarize the multiscale modelling approaches used to date to simulate RV pump function in the context of these interactions. We go on to demonstrate how these modelling approaches in combination with cardiac imaging have improved understanding of RV pump function in pulmonary arterial hypertension, arrhythmogenic right ventricular cardiomyopathy, dyssynchronous heart failure and cardiac resynchronization therapy, hypoplastic left heart syndrome, and repaired tetralogy of Fallot. We conclude with a perspective on key issues to be addressed by computational models of the RV in the near future. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2017. For permissions, please email: journals.permissions@oup.com.

Heart Development, Diseases, and Regeneration　- New Approaches From Innervation, Fibroblasts, and Reprogramming.

PubMed

Ieda, Masaki

2016-09-23

It is well known that cardiac function is tightly controlled by neural activity; however, the molecular mechanism of cardiac innervation during development and the relationship with heart disease remain undetermined. My work has revealed the molecular networks that govern cardiac innervation and its critical roles in heart diseases such as silent myocardial ischemia and arrhythmias. Cardiomyocytes proliferate during embryonic development, but lose their proliferative capacity after birth. Cardiac fibroblasts are a major source of cells during fibrosis and induce cardiac hypertrophy after myocardial injury in the adult heart. Despite the importance of fibroblasts in the adult heart, the role of fibroblasts in embryonic heart development was previously not determined. I demonstrated that cardiac fibroblasts play important roles in myocardial growth and cardiomyocyte proliferation during embryonic development, and I identified key paracrine factors and signaling pathways. In contrast to embryonic cardiomyocytes, adult cardiomyocytes have little regenerative capacity, leading to heart failure and high mortality rates after myocardial infarction. Leveraging the knowledge of developmental biology, I identified cardiac reprogramming factors that can directly convert resident cardiac fibroblasts into cardiomyocytes for heart regeneration. These findings greatly improved our understanding of heart development and diseases, and provide a new strategy for heart regenerative therapy. (Circ J 2016; 80: 2081-2088).

Stem Cell Therapy with Overexpressed VEGF and PDGF Genes Improves Cardiac Function in a Rat Infarct Model

PubMed Central

Das, Hiranmoy; George, Jon C.; Joseph, Matthew; Das, Manjusri; Abdulhameed, Nasreen; Blitz, Anna; Khan, Mahmood; Sakthivel, Ramasamy; Mao, Hai-Quan; Hoit, Brian D.; Kuppusamy, Periannan; Pompili, Vincent J.

2009-01-01

Background Therapeutic potential was evaluated in a rat model of myocardial infarction using nanofiber-expanded human cord blood derived hematopoietic stem cells (CD133+/CD34+) genetically modified with VEGF plus PDGF genes (VIP). Methods and Findings Myocardial function was monitored every two weeks up to six weeks after therapy. Echocardiography revealed time dependent improvement of left ventricular function evaluated by M-mode, fractional shortening, anterior wall tissue velocity, wall motion score index, strain and strain rate in animals treated with VEGF plus PDGF overexpressed stem cells (VIP) compared to nanofiber expanded cells (Exp), freshly isolated cells (FCB) or media control (Media). Improvement observed was as follows: VIP>Exp> FCB>media. Similar trend was noticed in the exercise capacity of rats on a treadmill. These findings correlated with significantly increased neovascularization in ischemic tissue and markedly reduced infarct area in animals in the VIP group. Stem cells in addition to their usual homing sites such as lung, spleen, bone marrow and liver, also migrated to sites of myocardial ischemia. The improvement of cardiac function correlated with expression of heart tissue connexin 43, a gap junctional protein, and heart tissue angiogenesis related protein molecules like VEGF, pNOS3, NOS2 and GSK3. There was no evidence of upregulation in the molecules of oncogenic potential in genetically modified or other stem cell therapy groups. Conclusion Regenerative therapy using nanofiber-expanded hematopoietic stem cells with overexpression of VEGF and PDGF has a favorable impact on the improvement of rat myocardial function accompanied by upregulation of tissue connexin 43 and pro-angiogenic molecules after infarction. PMID:19809493

[The reasonable use of right ventricular protection strategy in right ventricular outflow tract reconstruction].

PubMed

Zhang, Y; Yuan, H Y; Liu, X B; Wen, S S; Xu, G; Cui, H J; Zhuang, J; Chen, J M

2018-06-01

As a result of right ventricular outflow tract reconstruction, which is the important and basic step of complex cardiac surgery, the blood flow of right ventricular outflow tract is unobstructed, while pulmonary valve regurgitation and right heart dysfunction could be happened. These problems are often ignored in early days, more and more cases of right heart dysfunction need clinical intervention, which is quite difficult and less effective. How to protect effectively the right ventricular function is the focus. At present main methods to protect the right ventricular function include trying to avoid or reduce length of right ventricular incision, reserving or rebuilding the function of the pulmonary valve, using growth potential material for surgery. The protection of the right ventricular function is a systemic project, it involves many aspects, single measures is difficult to provide complete protection, only the comprehensive use of various protection strategy, can help to improve the long-term prognosis.

Reduced size liver transplantation from a donor supported by a Berlin Heart.

PubMed

Misra, M V; Smithers, C J; Krawczuk, L E; Jenkins, R L; Linden, B C; Weldon, C B; Kim, H B

2009-11-01

Patients on cardiac assist devices are often considered to be high-risk solid organ donors. We report the first case of a reduced size liver transplant performed using the left lateral segment of a pediatric donor whose cardiac function was supported by a Berlin Heart. The recipient was a 22-day-old boy with neonatal hemochromatosis who developed fulminant liver failure shortly after birth. The transplant was complicated by mild delayed graft function, which required delayed biliary reconstruction and abdominal wall closure, as well as a bile leak. However, the graft function improved quickly over the first week and the patient was discharged home with normal liver function 8 weeks after transplant. The presence of a cardiac assist device should not be considered an absolute contraindication for abdominal organ donation. Normal organ procurement procedures may require alteration due to the unusual technical obstacles that are encountered when the donor has a cardiac assist device.

New concepts: development of a survivorship programme for patients with a functionally univentricular heart.

PubMed

Goldberg, David J; Dodds, Kathryn; Rychik, Jack

2011-12-01

Children with functionally univentricular hearts are now surviving into their third and fourth decades of life. Although survival alone is a remarkable achievement, a lot must still be done to improve the quality and duration of life after the Fontan operation. Challenges that may be faced by these patients include the impact of the Fontan operation on the liver and the density of bone, protein-losing enteropathy, and plastic bronchitis. Paediatric cardiologists are familiar with the haemodynamic issues inherent in Fontan physiology; however, training in cardiology is often not sufficient to give us a complete understanding of the pathophysiology of the complications or of the options for treatment. Collaboration with other subspecialists including gastroenterologists, endocrinologists, and pulmonologists is essential in order to provide the rigorous and nuanced care that our patients need and deserve. A clinic in which a patient can see multiple subspecialists, and in which the subspecialists, as a group, can discuss each patient, can provide a unique and valuable service for patients with a functionally univentricular heart.

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.

A Cycle Ergometer Exercise Program Improves Exercise Capacity and Inspiratory Muscle Function in Hospitalized Patients Awaiting Heart Transplantation: a Pilot Study

PubMed Central

Forestieri, Patrícia; Guizilini, Solange; Peres, Monique; Bublitz, Caroline; Bolzan, Douglas W.; Rocco, Isadora S.; Santos, Vinícius B.; Moreira, Rita Simone L.; Breda, João R.; de Almeida, Dirceu R.; Carvalho, Antonio Carlos de C.; Arena, Ross; Gomes, Walter J.

2016-01-01

Objective The purpose of this study was to evaluate the effect of a cycle ergometer exercise program on exercise capacity and inspiratory muscle function in hospitalized patients with heart failure awaiting heart transplantation with intravenous inotropic support. Methods Patients awaiting heart transplantation were randomized and allocated prospectively into two groups: 1) Control Group (n=11) - conventional protocol; and 2) Intervention Group (n=7) - stationary cycle ergometer exercise training. Functional capacity was measured by the six-minute walk test and inspiratory muscle strength assessed by manovacuometry before and after the exercise protocols. Results Both groups demonstrated an increase in six-minute walk test distance after the experimental procedure compared to baseline; however, only the intervention group had a significant increase (P=0.08 and P=0.001 for the control and intervention groups, respectively). Intergroup comparison revealed a greater increase in the intervention group compared to the control (P<0.001). Regarding the inspiratory muscle strength evaluation, the intragroup analysis demonstrated increased strength after the protocols compared to baseline for both groups; statistical significance was only demonstrated for the intervention group, though (P=0.22 and P<0.01, respectively). Intergroup comparison showed a significant increase in the intervention group compared to the control (P<0.01). Conclusion Stationary cycle ergometer exercise training shows positive results on exercise capacity and inspiratory muscle strength in patients with heart failure awaiting cardiac transplantation while on intravenous inotropic support. PMID:27982348

Role of heat shock transcription factor 1(HSF1)-upregulated macrophage in ameliorating pressure overload-induced heart failure in mice.

PubMed

Du, Peizhao; Chang, Yaowei; Dai, Fangjie; Wei, Chunyan; Zhang, Qi; Li, Jiming

2018-08-15

In order to explore the role of macrophages in HSF1-mediated alleviation of heart failure, mice model of pressure overload-induced heart failure was established using transverse aortic constriction (TAC). Changes in cardiac function and morphology were studied in TAC and SHAM groups using ultrasonic device, tissue staining, electron microscopy, real-time quantitative polymerase chain reaction (RT-QPCR), and Western blotting. We found that mice in the TAC group showed evidence of impaired cardiac function and aggravation of fibrosis on ultrasonic and histopathological examination when compared to those in the SHAM group. The expressions of HSF1, LC3II/LC3I, Becline-1 and HIF-1, as well as autophagosome formation in TAC group were greater than that in SHAM group. On sub-group analyses in the TAC group, improved cardiac function and alleviation of fibrosis was observed in the HSF1 TG subgroup as compared to that in the wild type subgroup. Expressions of LC3II/LC3I, Becline-1 and HIF-1, too showed an obvious increase; and increased autophagosome formation was observed on electron microscopy. Opposite results were observed in the HSF1 KO subgroup. These results collectively suggest that in the pressure overload heart failure model, HSF1 promoted formation of macrophages by inducing upregulation of HIF-1 expression, through which heart failure was ameliorated. Copyright © 2018 Elsevier B.V. All rights reserved.

Hemodynamic Improvement in Cardiac Resynchronization Does Not Require Improvement in Left Ventricular Rotation Mechanics

PubMed Central

Ashikaga, Hiroshi; Leclercq, Christophe; Wang, Jiangxia; Kass, David A.; McVeigh, Elliot R.

2010-01-01

Background Earlier studies have yielded conflicting evidence on whether or not cardiac resynchronization therapy (CRT) improves left ventricular (LV) rotation mechanics. Methods and Results In dogs with left bundle branch block and pacing-induced heart failure (n=7), we studied the effects of CRT on LV rotation mechanics in vivo by 3-dimensional tagged magnetic resonance imaging with a temporal resolution of 14 ms. CRT significantly improved hemodynamic parameters but did not significantly change the LV rotation or rotation rate. LV torsion, defined as LV rotation of each slice with respect to that of the most basal slice, was not significantly changed by CRT. CRT did not significantly change the LV torsion rate. There was no significant circumferential regional heterogeneity (anterior, lateral, inferior, and septal) in LV rotation mechanics in either left bundle branch block with pacing-induced heart failure or CRT, but there was significant apex-to-base regional heterogeneity. Conclusions CRT acutely improves hemodynamic parameters without improving LV rotation mechanics. There is no significant circumferential regional heterogeneity of LV rotation mechanics in the mechanically dyssynchronous heart. These results suggest that LV rotation mechanics is an index of global LV function, which requires coordination of all regions of the left ventricle, and improvement in LV rotation mechanics appears to be a specific but insensitive index of acute hemodynamic response to CRT. PMID:20478988

Large Cardiac Muscle Patches Engineered From Human Induced-Pluripotent Stem Cell-Derived Cardiac Cells Improve Recovery From Myocardial Infarction in Swine.

PubMed

Gao, Ling; Gregorich, Zachery R; Zhu, Wuqiang; Mattapally, Saidulu; Oduk, Yasin; Lou, Xi; Kannappan, Ramaswamy; Borovjagin, Anton V; Walcott, Gregory P; Pollard, Andrew E; Fast, Vladimir G; Hu, Xinyang; Lloyd, Steven G; Ge, Ying; Zhang, Jianyi

2018-04-17

Here, we generated human cardiac muscle patches (hCMPs) of clinically relevant dimensions (4 cm × 2 cm × 1.25 mm) by suspending cardiomyocytes, smooth muscle cells, and endothelial cells that had been differentiated from human induced-pluripotent stem cells in a fibrin scaffold and then culturing the construct on a dynamic (rocking) platform. In vitro assessments of hCMPs suggest maturation in response to dynamic culture stimulation. In vivo assessments were conducted in a porcine model of myocardial infarction (MI). Animal groups included: MI hearts treated with 2 hCMPs (MI+hCMP, n=13), MI hearts treated with 2 cell-free open fibrin patches (n=14), or MI hearts with neither experimental patch (n=15); a fourth group of animals underwent sham surgery (Sham, n=8). Cardiac function and infarct size were evaluated by MRI, arrhythmia incidence by implanted loop recorders, and the engraftment rate by calculation of quantitative polymerase chain reaction measurements of expression of the human Y chromosome. Additional studies examined the myocardial protein expression profile changes and potential mechanisms of action that related to exosomes from the cell patch. The hCMPs began to beat synchronously within 1 day of fabrication, and after 7 days of dynamic culture stimulation, in vitro assessments indicated the mechanisms related to the improvements in electronic mechanical coupling, calcium-handling, and force generation, suggesting a maturation process during the dynamic culture. The engraftment rate was 10.9±1.8% at 4 weeks after the transplantation. The hCMP transplantation was associated with significant improvements in left ventricular function, infarct size, myocardial wall stress, myocardial hypertrophy, and reduced apoptosis in the periscar boarder zone myocardium. hCMP transplantation also reversed some MI-associated changes in sarcomeric regulatory protein phosphorylation. The exosomes released from the hCMP appeared to have cytoprotective properties that improved cardiomyocyte survival. We have fabricated a clinically relevant size of hCMP with trilineage cardiac cells derived from human induced-pluripotent stem cells. The hCMP matures in vitro during 7 days of dynamic culture. Transplantation of this type of hCMP results in significantly reduced infarct size and improvements in cardiac function that are associated with reduction in left ventricular wall stress. The hCMP treatment is not associated with significant changes in arrhythmogenicity. © 2017 American Heart Association, Inc.

Hyperthyroidism causes mechanical insufficiency of myocardium with possibly increased SR Ca2+-ATPase activity.

PubMed

Takeuchi, Koh; Minakawa, M; Otaki, M; Odagiri, S; Itoh, K; Murakami, A; Yaku, H; Kitamura, N

2003-12-01

Hyperthyroidism is known to affect multiple organ functions, and thyroid hormone has been known to improve myocardial function in a failing heart. The purpose of this study is to elucidate the functional and metabolic effects of thyroid hormone on myocardium in a rat model exposed to long-term excess thyroid hormone, particularly focusing on the SR Ca(2+)-ATPase (SERCA2) function. 3,5,3'-Triiodo-L-thyronine (T3), or the vehicle, was subcutaneously given for 4 weeks (T3 and control [C] group). Bolus I.V. Thapsigargin (TG) was used to test the SERCA2 function (C-TG and T3-TG) in Langendorff perfused heart. Myocardial functions such as LV-developed pressure (LVDP; mmHg), +/- dP/dt (mmHg/s), tau (ms), and oxygen consumption (MVO(2); ml/min/g wt) were measured. SERCA2 and GLUT4 protein level were also evaluated by Western immunoblotting. Left ventricle to body weight (LV/BW) ratio was significantly higher in the T3 group. Both negative dP/dt and tau were significantly decreased by TG. It is interesting that the decrement of negative dP/dt and tau attained by TG was significantly larger in the hyperthyroid group (T3-TG) than in a normal heart (C-TG). SERCA2 and GLUT4 protein levels were not significantly different between control and the T3 group. We conclude that prolonged exposure to thyroid hormone causes hypertrophy of the myocardium and an augmentation of the SR Ca(2+) ATPase activity. Care must be taken in hyperthyroid heart during the ischemia-reperfusion process where the SRECA2 function is inhibited.

The acute effects of different spironolactone doses on cardiac function in streptozotocin-induced diabetic rats.

PubMed

Vranic, Aleksandra; Simovic, Stefan; Ristic, Petar; Nikolic, Tamara; Stojic, Isidora; Srejovic, Ivan; Zivkovic, Vladimir; Jakovljevic, Vladimir; Djuric, Dusan

2017-11-01

Currently, cardiovascular diseases are the leading cause of global mortality, while diabetes mellitus remains an important cause of cardiovascular morbidity. A recent study showed that patients with diabetes mellitus treated with mineralocorticoid receptor antagonists have improved coronary microvascular function, leading to improved diastolic dysfunction. In this study, we evaluated the influence of acute administration of spironolactone on myocardial function in rats with streptozotocin-induced diabetes mellitus, with special emphasis on cardiodynamic parameters in diabetic rat hearts. The present study was carried out on 40 adult male Wistar albino rats (8 weeks old). Rats were randomly divided into 4 groups (10 animals per group): healthy rats treated with 0.1 μmol/L of spironolactone, diabetic rats treated with 0.1 μmol/L of spironolactone, healthy rats treated with 3 μmol/L of spironolactone, and diabetic rats treated with 3 μmol/L of spironolactone. Different, dose-dependent, acute responses of spironolactone treatment on isolated, working diabetic and healthy rat heart were observed in our study. In healthy rats, better systolic function was achieved with higher spironolactone dose, while in diabetic rats, similar effects of low and high spironolactone dose were observed.

The hippo pathway in heart development, regeneration, and diseases.

PubMed

Zhou, Qi; Li, Li; Zhao, Bin; Guan, Kun-Liang

2015-04-10

The heart is the first organ formed during mammalian development. A properly sized and functional heart is vital throughout the entire lifespan. Loss of cardiomyocytes because of injury or diseases leads to heart failure, which is a major cause of human morbidity and mortality. Unfortunately, regenerative potential of the adult heart is limited. The Hippo pathway is a recently identified signaling cascade that plays an evolutionarily conserved role in organ size control by inhibiting cell proliferation, promoting apoptosis, regulating fates of stem/progenitor cells, and in some circumstances, limiting cell size. Interestingly, research indicates a key role of this pathway in regulation of cardiomyocyte proliferation and heart size. Inactivation of the Hippo pathway or activation of its downstream effector, the Yes-associated protein transcription coactivator, improves cardiac regeneration. Several known upstream signals of the Hippo pathway such as mechanical stress, G-protein-coupled receptor signaling, and oxidative stress are known to play critical roles in cardiac physiology. In addition, Yes-associated protein has been shown to regulate cardiomyocyte fate through multiple transcriptional mechanisms. In this review, we summarize and discuss current findings on the roles and mechanisms of the Hippo pathway in heart development, injury, and regeneration. © 2015 American Heart Association, Inc.

Absolute and Functional Iron Deficiency Is a Common Finding in Patients With Heart Failure and After Heart Transplantation.

PubMed

Przybylowski, P; Wasilewski, G; Golabek, K; Bachorzewska-Gajewska, H; Dobrzycki, S; Koc-Zorawska, E; Malyszko, J

2016-01-01

Anemia is relatively common in patients with heart failure and heart transplant recipients. Both absolute and functional iron deficiency may contribute to the anemia in these populations. Functional iron deficiency (defined as ferritin greater than 200 ng/mL with TSAT (Transferrin saturation) less than 20%) is characterized by the presence of adequate iron stores as defined by conventional criteria, but with insufficient iron mobilization to adequately support. The aim of this study was to determine prevalence of absolute and functional iron deficiency in patients with heart failure (n = 269) and after heart transplantation (n = 130) and their relation to parameters of iron status and inflammation. Iron status, complete blood count, and creatinine levels were assessed using standard laboratory methods. C-reactive protein, hepcidin and hemojuvelin were measured using commercially available kits. Absolute iron deficiency was present in 15% of patients with heart failure and 30% in heart transplant recipients, whereas functional iron deficiency was present in 18% of patients with heart failure and 17% in heart transplant recipients. Functional iron deficiency was associated with significantly higher C-reactive protein and hepcidin levels in heart failure patients, and higher hepcidin and lower estimate glomerular filtration rates in heart transplant recipients. Prevalence of anemia (according to the World Health Organization) was significantly higher in heart transplant recipients (40% vs 22%, P < .001), they were also younger, but with worse kidney function than patients with heart failure. Both absolute and functional iron deficiency were present in a considerable group of patients. This population should be carefully screened for possible reversible causes of inflammation. Copyright © 2016 Elsevier Inc. All rights reserved.

Bcl-2–associated athanogene 3 protects the heart from ischemia/reperfusion injury

PubMed Central

Su, Feifei; Myers, Valerie D.; Knezevic, Tijana; Wang, JuFang; Gao, Erhe; Madesh, Muniswamy; Tahrir, Farzaneh G.; Gupta, Manish K.; Gordon, Jennifer; Rabinowitz, Joseph; Tilley, Douglas G.; Khalili, Kamel; Cheung, Joseph Y.

2016-01-01

Bcl-2–associated athanogene 3 (BAG3) is an evolutionarily conserved protein expressed at high levels in the heart and the vasculature and in many cancers. While altered BAG3 expression has been associated with cardiac dysfunction, its role in ischemia/reperfusion (I/R) is unknown. To test the hypothesis that BAG3 protects the heart from reperfusion injury, in vivo cardiac function was measured in hearts infected with either recombinant adeno-associated virus serotype 9–expressing (rAAV9-expressing) BAG3 or GFP and subjected to I/R. To elucidate molecular mechanisms by which BAG3 protects against I/R injury, neonatal mouse ventricular cardiomyocytes (NMVCs) in which BAG3 levels were modified by adenovirus expressing (Ad-expressing) BAG3 or siBAG3 were exposed to hypoxia/reoxygenation (H/R). H/R significantly reduced NMVC BAG3 levels, which were associated with enhanced expression of apoptosis markers, decreased expression of autophagy markers, and reduced autophagy flux. The deleterious effects of H/R on apoptosis and autophagy were recapitulated by knockdown of BAG3 with Ad-siBAG3 and were rescued by Ad-BAG3. In vivo, treatment of mice with rAAV9-BAG3 prior to I/R significantly decreased infarct size and improved left ventricular function when compared with mice receiving rAAV9-GFP and improved markers of autophagy and apoptosis. These findings suggest that BAG3 may provide a therapeutic target in patients undergoing reperfusion after myocardial infarction. PMID:27882354

Stimulation of cardiomyocyte regeneration in neonatal mice and in human myocardium with neuregulin reveals a therapeutic window

PubMed Central

Polizzotti, Brian D.; Ganapathy, Balakrishnan; Walsh, Stuart; Choudhury, Sangita; Ammanamanchi, Niyatie; Bennett, David G.; dos Remedios, Cristobal G.; Haubner, Bernhard J.; Penninger, Josef M.; Kuhn, Bernhard

2015-01-01

Background Pediatric patients with heart failure are treated with medical therapies that were developed for adult patients. These therapies have been shown to be ineffective in pediatric trials, leading to the recognition that new pediatric-specific therapies must be developed. We have previously shown that administration of the recombinant growth factor neuregulin-1 (rNRG1) stimulates heart muscle cell (cardiomyocyte) regeneration in adult mice. We hypothesized that rNRG1 administration may be more effective in the neonatal period, which could provide a new therapeutic paradigm for treating heart failure in pediatric patients. Methods We used a cryoinjury model to induce myocardial dysfunction and scar formation for evaluating the effectiveness of rNRG1-administration in neonatal mice. We evaluated the ability of rNRG1 to stimulate cardiomyocyte proliferation in intact cultured myocardium from pediatric patients. Results After cryoinjury in neonatal mice, early administration of rNRG1 from birth for 34 days improved myocardial function and reduced the prevalence of transmural scars. In contrast, late administration of rNRG1 from 4 to 34 days after cryoinjury transiently improved myocardial function. The mechanisms of early administration involved cardiomyocyte protection (38%) and proliferation (62%). rNRG1 induced cardiomyocyte proliferation in myocardium from infants with heart disease less than 6 months of age. Conclusion Our results identify a more effective time period within which to execute future clinical trials of rNRG1 for stimulating cardiomyocyte regeneration. PMID:25834111

Left atrial function in heart failure with impaired and preserved ejection fraction.

PubMed

Fang, Fang; Lee, Alex Pui-Wai; Yu, Cheuk-Man

2014-09-01

Left atrial structural and functional changes in heart failure are relatively ignored parts of cardiac assessment. This review illustrates the pathophysiological and functional changes in left atrium in heart failure as well as their prognostic value. Heart failure can be divided into those with systolic dysfunction and heart failure with preserved ejection fraction (HFPEF). Left atrial enlargement and dysfunction commonly occur in systolic heart failure, in particular, in idiopathic dilated cardiomyopathy. Atrial enlargement and dysfunction also carry important prognostic value in systolic heart failure, independently of known parameters such as left ventricular ejection fraction. In HFPEF, there is evidence of left atrial enlargement, impaired atrial compliance, and reduction of atrial pump function. This occurs not only at rest but also during exercise, indicating significant impairment of atrial contractile reserve. Furthermore, atrial dyssynchrony is common in HFPEF. These factors further contribute to the development of new onset or progression of atrial arrhythmias, in particular, atrial fibrillation. Left atrial function is an integral part of cardiac function and its structural and functional changes in heart failure are common. As changes of left atrial structure and function have different clinical implications in systolic heart failure and HFPEF, routine assessment is warranted.

The CardiAMP Heart Failure trial: A randomized controlled pivotal trial of high-dose autologous bone marrow mononuclear cells using the CardiAMP cell therapy system in patients with post-myocardial infarction heart failure: Trial rationale and study design.

PubMed

Raval, Amish N; Cook, Thomas D; Duckers, Henricus J; Johnston, Peter V; Traverse, Jay H; Abraham, William T; Altman, Peter A; Pepine, Carl J

2018-07-01

Heart failure following myocardial infarction is a common, disabling, and deadly condition. Direct injection of autologous bone marrow mononuclear cells into the myocardium may result in improved functional recovery, relieve symptoms, and improve other cardiovascular outcomes. CardiAMP-HF is a randomized, double-blind, sham-controlled, pivotal trial designed to investigate the safety and efficacy of autologous bone marrow mononuclear cells treatment for patients with medically refractory and symptomatic ischemic cardiomyopathy. The primary end point is change in 6-minute walk distance adjusted for major adverse cardiovascular events at 12 months following treatment. Particularly novel aspects of this trial include a cell potency assay to screen subjects who have bone marrow cell characteristics that suggest a favorable response to treatment, a point-of-care treatment method, a high target dose of 200 million cells, and an efficient transcatheter intramyocardial delivery method that is associated with high cell retention. This novel approach may lead to a new treatment for those with ischemic heart disease suffering from medically refractory heart failure. Copyright © 2018 Elsevier Inc. All rights reserved.

Aging and CaMKII Alter Intracellular Ca2+ Transients and Heart Rhythm in Drosophila melanogaster

PubMed Central

Santalla, Manuela; Valverde, Carlos A.; Harnichar, Ezequiel; Lacunza, Ezequiel; Aguilar-Fuentes, Javier; Mattiazzi, Alicia; Ferrero, Paola

2014-01-01

Aging is associated to disrupted contractility and rhythmicity, among other cardiovascular alterations. Drosophila melanogaster shows a pattern of aging similar to human beings and recapitulates the arrhythmogenic conditions found in the human heart. Moreover, the kinase CaMKII has been characterized as an important regulator of heart function and an arrhythmogenic molecule that participate in Ca2+ handling. Using a genetically engineered expressed Ca2+ indicator, we report changes in cardiac Ca2+ handling at two different ages. Aging prolonged relaxation, reduced spontaneous heart rate (HR) and increased the occurrence of arrhythmias, ectopic beats and asystoles. Alignment between Drosophila melanogaster and human CaMKII showed a high degree of conservation and indicates that relevant phosphorylation sites in humans are also present in the fruit fly. Inhibition of CaMKII by KN-93 (CaMKII-specific inhibitor), reduced HR without significant changes in other parameters. By contrast, overexpression of CaMKII increased HR and reduced arrhythmias. Moreover, it increased fluorescence amplitude, maximal rate of rise of fluorescence and reduced time to peak fluorescence. These results suggest that CaMKII in Drosophila melanogaster acts directly on heart function and that increasing CaMKII expression levels could be beneficial to improve contractility. PMID:25003749

Pharmacological heart rate lowering in patients with a preserved ejection fraction-review of a failing concept.

PubMed

Meyer, Markus; Rambod, Mehdi; LeWinter, Martin

2018-07-01

Epidemiological studies have demonstrated that high resting heart rates are associated with increased mortality. Clinical studies in patients with heart failure and reduced ejection fraction have shown that heart rate lowering with beta-blockers and ivabradine improves survival. It is therefore often assumed that heart rate lowering is beneficial in other patients as well. Here, we critically appraise the effects of pharmacological heart rate lowering in patients with both normal and reduced ejection fraction with an emphasis on the effects of pharmacological heart rate lowering in hypertension and heart failure. Emerging evidence from recent clinical trials and meta-analyses suggest that pharmacological heart rate lowering is not beneficial in patients with a normal or preserved ejection fraction. This has just begun to be reflected in some but not all guideline recommendations. The detrimental effects of pharmacological heart rate lowering are due to an increase in central blood pressures, higher left ventricular systolic and diastolic pressures, and increased ventricular wall stress. Therefore, we propose that heart rate lowering per se reproduces the hemodynamic effects of diastolic dysfunction and imposes an increased arterial load on the left ventricle, which combine to increase the risk of heart failure and atrial fibrillation. Pharmacologic heart rate lowering is clearly beneficial in patients with a dilated cardiomyopathy but not in patients with normal chamber dimensions and normal systolic function. These conflicting effects can be explained based on a model that considers the hemodynamic and ventricular structural effects of heart rate changes.

Functional and pathological improvements of the hearts in diabetes model by the combined therapy of bFGF-loaded nanoparticles with ultrasound-targeted microbubble destruction.

PubMed

Zhao, Ying-Zheng; Tian, Xin-Qiao; Zhang, Ming; Cai, Lu; Ru, Ao; Shen, Xiao-Tong; Jiang, Xi; Jin, Rong-Rong; Zheng, Lei; Hawkins, Kyle; Charkrabarti, Subrata; Li, Xiao-Kun; Lin, Qian; Yu, Wen-Ze; Ge, Shuping; Lu, Cui-Tao; Wong, Ho Lun

2014-07-28

Diabetic cardiomyopathy (DCM) is the leading cause of morbidity and mortality among the diabetic patients and currently there is no effective means to reverse its pathological progress. Basic fibroblast growth factor (bFGF) has shown promise as a molecular therapy for DCM, but its delivery is inefficient and non-specific. In the present study, a therapy combining nanoparticle (NP) carrier and ultrasound-targeted microbubble destruction (UTMD) was reported the first time for bFGF delivery to the heart of diabetic rats. bFGF-loaded NP (bFGF-NP) were prepared with Poloxamer 188-grafted heparin copolymer using water-in-water technique, and the morphology, encapsulation efficiency, and bioactivity of bFGF-NP were studied. The cellular uptake and cytotoxicity of bFGF-NP were evaluated with primary cultures of the left ventricular (LV) cardiomyocytes in vitro. Therapeutic effects of bFGF-NP/UTMD on the heart of DCM rats were studied by measuring LV systolic and diastolic functions, hemodynamic characteristics and indicators of cardiac remodeling including myocardial collagen volume fraction and capillary density. Results demonstrated that bFGF-NP showed good round morphology, efficient bFGF encapsulation and stable bioactivity of bFGF in vitro. bFGF-NP/UTMD combined treatment significantly enhanced the efficiency of bFGF cellular uptake (P<0.05) without obvious cytotoxicity. Significant improvements (P<0.05) in both cardiac functions and tissue morphology in the DCM rats were observed in bFGF-NP/UTMD group. These were not achievable using free bFGF, bFGF-NP or UTMD treatment alone. Our results show that combining a non-viral vector with UTMD technique is an effective strategy to deliver bFGF to the heart, and the resulting growth factor therapy has demonstrated potential to reverse the progress of DCM by restoring the cardiac functions and even the structure of damaged cardiac tissues. Copyright © 2014 Elsevier B.V. All rights reserved.