Myocardial viability assessment after acute myocardial infarction: low-dose dobutamine echocardiography versus rest-redistribution thallium-201 SPECT.

PubMed

Castini, D; Bestetti, A; Garbin, M; Di Leo, C; Bigi, R; Sponzilli, C; Concardi, G; Gioventù, M; Tarolo, G L; Lombardi, F; Fiorentini, C

1999-09-01

The presence of tissue viability is of great importance in the prognostic work-up of patients recovering from acute myocardial infarction. However, uncertainty still exists concerning the optimal tool for its assessment. The present study was undertaken in order to compare low-dose dobutamine echocardiography and rest-redistribution thallium SPECT for predicting late improvement of regional left ventricular function after acute myocardial infarction. Fifteen patients undergoing coronary angiography, low-dose dobutamine echocardiography and rest-redistribution thallium SPECT after thrombolyzed anterior acute myocardial infarction were studied. A 3 month follow-up echocardiogram was performed in all patients and 9 underwent coronary revascularization. A significant (> or = 70%) residual stenosis of the infarct-related artery was present in 14 patients, whilst a total occlusion was observed in 1. At 3 month follow-up, 41% of the dyssynergic segments improved. The sensitivity, specificity and accuracy for late wall motion improvement was 61, 89 and 77% for low-dose dobutamine echocardiography and, respectively, 76, 45 and 58% for rest-redistribution thallium SPECT. Tissue viability was detected in 65 and 31% of dyssynergic segments by rest-redistribution thallium SPECT and low-dose dobutamine echocardiography, respectively (p < 0.001). The agreement between the two techniques was 48%. Low-dose dobutamine echocardiography is more accurate than rest-redistribution thallium SPECT for predicting 3 month wall motion improvement in patients with acute anterior myocardial infarction, mainly due to its significantly better specificity.

Late myocardial ischemia with ST-segment elevation after negative dobutamine stress echocardiography in a patient with normal coronary arteries.

PubMed

Cabani, Enrico; Lattanzi, Fabio; Paci, Anna Maria; Pieroni, Andrea; Baria, Luca; Tommasi, Salvatore Mario De

2009-04-01

Late complications after pharmacological stress echocardiography are infrequent but potentially dreadful events. We report the case of a 80-year-old woman admitted to hospital for rest chest pain with trivial troponin increase, normal left ventricular function and no significant ECG changes. A dobutamine stress echocardiography was performed for diagnostic purpose, with a negative result. About 30 min after the end of dobutamine infusion, she developed ST-segment elevation in inferior leads associated with chest pain and left ventricular dyssynergy, promptly resolved by sublingual nitrates. Subsequently, angiography documented the absence of significant coronary stenoses. The following clinical course was uneventful. Transient myocardial ischemia was likely due to dobutamine-induced coronary spasm. The case emphasizes the utility of routine, long-lasting monitoring of patients after stress echocardiography, even if negative, to counteract possible late life-threatening complications.

Strain and Torsion Quantification in Mouse Hearts under Dobutamine Stimulation using 2D Multi-Phase MR DENSE

PubMed Central

Zhong, Jia; Yu, Xin

2010-01-01

In the current study, a 2D multi-phase MR displacement encoding with stimulated echoes (DENSE) imaging and analysis method was developed for direct quantification of Lagrangian strain in the mouse heart. Using the proposed method, less than 10 ms temporal resolution and 0.56 mm in-plane resolution were achieved. A validation study that compared strain calculation by DENSE and by MR tagging showed high correlation between the two methods (R2 > 0.80). Regional ventricular wall strain and twist were characterized in mouse hearts at baseline and under dobutamine stimulation. Dobutamine stimulation induced significant increase in radial and circumferential strains and torsion at peak-systole. A rapid untwisting was also observed during early diastole. This work demonstrates the capability of characterizing cardiac functional response to dobutamine stimulation in the mouse heart using 2D multi-phase MR DENSE. PMID:20740659

Milrinone, dobutamine or epinephrine use in asphyxiated newborn pigs resuscitated with 100% oxygen.

PubMed

Joynt, Chloë; Bigam, David L; Charrois, Gregory; Jewell, Laurence D; Korbutt, Gregory; Cheung, Po-Yin

2010-06-01

After resuscitation, asphyxiated neonates often develop poor cardiac function with hypotension, pulmonary hypertension and multiorgan ischemia. In a swine model of neonatal hypoxia-reoxygenation, effects of epinephrine, dobutamine and milrinone on systemic, pulmonary and regional hemodynamics and oxygen transport were compared. Controlled, block-randomized study. University research laboratory. Mixed breed piglets (1-3 days, 1.5-2.3 kg). In acutely instrumented piglets, normocapnic alveolar hypoxia (10-15% oxygen) was induced for 2 h followed by reoxygenation with 100% oxygen (1 h) then 21% oxygen (3 h). At 2 h of reoxygenation, after volume loading (Ringer's lactate 10 ml/kg), either saline (placebo), epinephrine (0.5 microg/kg/min), dobutamine (20 microg/kg/min) or milrinone (0.75 microg/kg/min) were infused for 2 h in a blinded, block-randomized fashion (n = 6/group). All medications similarly improved cardiac output, stroke volume and systemic oxygen delivery (vs. placebo-controls, p < 0.05). Epinephrine and dobutamine significantly increased, while milrinone maintained, mean arterial pressure over pretreatment values while placebo-treated piglets developed hypotension and shock. The mean arterial to pulmonary arterial pressures ratio was not different among groups. All medications significantly increased carotid and intestinal, but not renal, arterial blood flows and oxygen delivery, whereas milrinone caused lower renal vascular resistance than epinephrine and dobutamine-treated groups. Plasma troponin I, plasma and myocardial lactate levels, and histologic ischemic features were not different among groups. In newborn piglets with hypoxia-reoxygenation, epinephrine, dobutamine and milrinone are effective inotropes to improve cardiac output, carotid and intestinal perfusion, without aggravating pulmonary hypertension. Milrinone may also improve renal perfusion.

Cardiovascular effects of 3,4-methylenedioxymethamphetamine. A double-blind, placebo-controlled trial.

PubMed

Lester, S J; Baggott, M; Welm, S; Schiller, N B; Jones, R T; Foster, E; Mendelson, J

2000-12-19

The psychoactive stimulant 3, 4-methylenedioxymethamphetamine (MDMA), also known as "ecstasy," is widely used in nonmedical settings. Little is known about its cardiovascular effects. To evaluate the acute cardiovascular effects of MDMA by using transthoracic two-dimensional and Doppler echocardiography. Four-session, ascending-dose, double-blind, placebo-controlled trial. Urban hospital. Eight healthy adults who self-reported MDMA use. Echocardiographic effects of dobutamine (5, 20, and 40 microg/kg of body weight per minute) were measured in a preliminary session. Oral MDMA (0.5 and 1.5 mg/kg of body weight) or placebo was administered 1 hour before echocardiographic measurements in three weekly sessions. Heart rate and blood pressure were measured at regular intervals before and after MDMA administration. Echocardiographic measures of stroke volume, ejection fraction, cardiac output, and meridional wall stress were obtained 1 hour after MDMA administration and during dobutamine infusions. At a dose of 1.5 mg/kg, MDMA increased mean heart rate (by 28 beats/min), systolic blood pressure (by 25 mm Hg), diastolic blood pressure (by 7 mm Hg), and cardiac output (by 2 L/min). The effects of MDMA were similar to those of dobutamine, 20 and 40 microg/kg per minute. Inotropism, measured by using meridional wall stress corrected for ejection fraction, decreased after administration of dobutamine, 40 microg/kg per minute, but did not change after either dose of MDMA. Modest oral doses of MDMA increase heart rate, blood pressure, and myocardial oxygen consumption in a magnitude similar to dobutamine, 20 to 40 microg/kg per minute. In contrast to dobutamine, MDMA has no measurable inotropic effects.

Dobutamine stress echocardiography for assessment of systolic function in dogs with experimentally induced mitral regurgitation.

PubMed

Suzuki, R; Matsumoto, H; Teshima, T; Mochizuki, Y; Koyama, H

2014-01-01

Systolic dysfunction is associated with poor outcomes in dogs with myxomatous mitral valve disease. However, assessment of systolic variables by conventional echocardiographic methods is difficult in these dogs because of mitral regurgitation (MR). We hypothesized that assessment of systolic function by dobutamine stress may identify systolic dysfunction in dogs with MR, and that 2-dimensional speckle-tracking echocardiography (2D-STE) could quantitatively evaluate myocardial function. Anesthetized dogs with experimentally induced MR. Dogs were examined for systolic myocardial deformations using 2D-STE during dobutamine infusion before and 3 and 6 months after MR induction. We evaluated peak systolic rotation and rotation rate in each basal and apical view; peak systolic torsion and torsion rate were also calculated. Invasive peak positive first derivatives of left ventricular pressure (dp/dt) were significantly decreased in dogs 6 months after induction of MR compared with pre-MR results. After 3 and 6 months of MR, dogs had diminished peak systolic torsion values and torsion rates in response to dobutamine infusion compared with pre-MR results (3 months, P < .001 and P = .006; 6 months, P = .003 and P = .021). These results were significantly correlated with overall invasive dp/dt (r = 0.644, P < .001; r = 0.696, P < .001). Decreased torsion during dobutamine infusion in dogs with MR may reflect latent systolic dysfunction. Dobutamine infusion, therefore, may be useful for the assessment of systolic function in dogs with MR. Copyright © 2014 by the American College of Veterinary Internal Medicine.

Acute effects of dobutamine on myocardial oxygen consumption and cardiac efficiency measured using carbon-11 acetate kinetics in patients with dilated cardiomyopathy.

PubMed

Beanlands, R S; Bach, D S; Raylman, R; Armstrong, W F; Wilson, V; Montieth, M; Moore, C K; Bates, E; Schwaiger, M

1993-11-01

The aim of this study was to use positron emission tomography (PET)-derived carbon (C)-11 acetate kinetics to determine the effects of dobutamine on oxidative metabolism and its effects on myocardial efficiency in a group of patients with dilated cardiomyopathy. Dobutamine is known to improve myocardial function but may do so at the expense of myocardial oxygen consumption, which could be a potential deleterious effect. Carbon-11 acetate kinetics correlate with myocardial oxygen consumption as shown in animal models. Combining these scintigraphic measurements of oxygen consumption with estimates of cardiac work results in a work-metabolic index, which reflects cardiac efficiency. Eight patients with nonischemic dilated cardiomyopathy underwent dynamic PET imaging, echocardiography and hemodynamic measurements. Seven of these patients were also studied while receiving dobutamine. Direct measurements of myocardial oxygen consumption using coronary sinus catheterization were obtained with eight of the PET studies to validate C-11 acetate in patients with cardiomyopathy. The mean (+/- SD) C-11 clearance rate significantly increased with dobutamine from 0.105 +/- 0.027 to 0.155 +/- 0.023 min-1 (p = 0.001). Directly measured myocardial oxygen consumption had a linear relation to the mean C-11 clearance rate (r = 0.8, p = 0.018). Dobutamine was noted to significantly reduce systemic vascular resistance as well as the severity of mitral regurgitation. The work-metabolic index determined using hemodynamic variables and PET data increased from 2 +/- 0.7 x 10(4) to 2.6 +/- 0.6 x 10(4) (p = 0.04). Efficiency, estimated by employing the oxygen consumption to k2 relation, also increased from 13 +/- 4.5% to 16.9 +/- 6.4% (p = 0.04). Despite an increase in myocardial oxygen consumption, dobutamine led to an increase in work-metabolic index in patients with dilated nonischemic cardiomyopathy. Dobutamine reduced systemic vascular resistance and mitral regurgitation, suggesting that in this group of patients, it had important vasodilatory action in addition to its inotropic effects. The use of the C-11 acetate PET for determining myocardial oxygen consumption and estimating efficiency could potentially complement existing clinical measures of ventricular performance and may allow improved and objective evaluation of therapy in patients with heart failure.

Diesel exhaust worsens cardiac conduction instability in dobutamine-challenged spontaneously hypertensive rats

EPA Science Inventory

This study demonstrated that diesel exhaust worsened arrhythmia and cardiac function during dobutamine (simulated exercise) challenge in normotensive and hypertensive rats. The data presented here are a mathematically-derived indicator of cardiac risk, which can be used for risk ...

[Contrast agent improves diagnostic value of dobutamine stress echocardiography].

PubMed

Uehara, H; Yamamoto, T; Hirano, Y; Ozasa, Y; Yamada, S; Ikawa, H; Ishikawa, K

2001-03-01

Suboptimal endocardial definition reduces the diagnostic value of stress echocardiography for coronary artery disease, but intravenous infusion of a left ventricular contrast agent (Albunex) may enhance endocardial border delineation and improve the diagnostic value of dobutamine stress echocardiography. Fifty-six patients, 38 with myocardial infarction, 16 with angina pectoris and two normal subjects, were enrolled in this study. Dobutamine was infused in scalar doses of 5 to 40 micrograms/kg/min. Intravenous infusion of Albunex (0.15 ml/kg) was administered at rest and during peak dobutamine stress during monitoring of the apical four-chamber view. The left ventricle in the apical four-chamber view was divided into six segments and an endocardial delineation score of 0 to 3 (none to excellent visualization) was given to each segment. Endocardial delineation score was increased after Albunex infusion from 2.0 to 2.3 in the basal-septal, 2.0 to 2.4 in the mid-septal, 1.1 to 1.8 in the apical-septal, 0.7 to 1.2 in the apical-lateral, 0.9 to 1.6 in the mid-lateral, and 1.2 to 1.9 in the basal-lateral segments during peak dobutamine administration. Endocardial border resolution in the lateral wall showed greater improvement than in the septal wall after Albunex infusion. Diagnostic values in the left anterior descending artery territory failed to improve with Albunex infusion (sensitivity 82% to 89%, specificity 94% to 89%, and accuracy 86% to 89%), whereas a higher diagnostic accuracy was noted in the left circumflex artery territory with Albunex compared to without Albunex (sensitivity 63% to 81%, specificity 88% to 98%, and accuracy 80% to 93%, p < 0.05). Contrast agent improves the diagnostic accuracy of dobutamine stress echocardiography in the left circumflex artery territory.

Effect of supplemental oxygen versus dobutamine administration on liver oxygen tension in dPP-guided normovolemic pigs.

PubMed

Pestel, G; Fukui, K; Hager, H; Kurz, A; Hiltebrand, L

2009-01-01

Difference in pulse pressure (dPP) confirms adequate intravascular filling as a prerequisite for tissue perfusion. We hypothesized that both oxygen and dobutamine increase liver tissue oxygen tension (ptO(2)). Eight anesthetized pigs received dPP-guided fluid management. Hepatic pO(2) was measured with Clark-type electrodes placed subcapsularly, and on the liver surface. Pigs received: (1) supplemental oxygen (F(i)O(2) 1.0); (2) dobutamine 2.5 microg/kg/min, and (3) dobutamine 5 microg/kg/min. Data were analyzed using repeated-measures ANOVA followed by a Tukey post-test for multiple comparisons. ptO(2 )measured subcapsularly and at the liver surface were compared using the Bland-Altman plot. Variation in F(i)O(2) changed local hepatic tissue ptO(2) [subcapsular measurement: 39 +/- 12 (F(i)O(2) 0.3), 89 +/- 35 mm Hg (F(i)O(2) 1.0, p = 0.01 vs. F(i)O(2) 0.3), 44 +/- 10 mm Hg (F(i)O(2) 0.3, p = 0.05 vs. F(i)O(2) 1.0); surface measurement: 52 +/- 35 (F(i)O(2) 0.3), 112 +/- 24 mm Hg (F(i)O(2) 1.0, p = 0.001 vs. F(i)O(2) 0.3), 54 +/- 24 mm Hg (F(i)O(2) 0.3, p = 0.001 vs. F(i)O(2) 1.0)]. Surface measurements were widely scattered compared to subcapsular measurements (bias: -15 mm Hg, precision: 76.3 mm Hg). Dobutamine did not affect hepatic oxygenation. Supplemental oxygen increased hepatic tissue pO(2) while dobutamine did not. Although less invasive, the use of surface measurements is discouraged. Copyright 2009 S. Karger AG, Basel.

Effects of dopamine and dobutamine on isoflurane-induced hypotension in Hispaniolan Amazon parrots (Amazona ventralis).

PubMed

Schnellbacher, Rodney W; da Cunha, Anderson F; Beaufrère, Hugues; Queiroz, Patricia; Nevarez, Javier G; Tully, Thomas N

2012-07-01

To assess the effects of dopamine and dobutamine on the blood pressure of isoflurane-anesthetized Hispaniolan Amazon parrots (Amazona ventralis). 8 Hispaniolan Amazon parrots. A randomized crossover study was conducted. Each bird was anesthetized (anesthesia maintained by administration of 2.5% isoflurane in oxygen) and received 3 doses of each drug during a treatment period of 20 min/dose. Treatments were constant rate infusions (CRIs) of dobutamine (5, 10, and 15 μg/kg/min) and dopamine (5, 7, and 10 μg/kg/min). Direct systolic, diastolic, and mean arterial pressure measurements, heart rate, esophageal temperature, and end-tidal partial pressure of CO(2) were recorded throughout the treatment periods. Mean ± SD of the systolic, mean, and diastolic arterial blood pressures at time 0 (initiation of a CRI) were 132.9 ± 22.1 mm Hg, 116.9 ± 20.5 mm Hg, and 101.9 ± 22.0 mm Hg, respectively. Dopamine resulted in significantly higher values than did dobutamine for the measured variables, except for end-tidal partial pressure of CO(2). Post hoc multiple comparisons revealed that the changes in arterial blood pressure were significantly different 4 to 7 minutes after initiation of a CRI. Overall, dopamine at rates of 7 and 10 μg/kg/min and dobutamine at a rate of 15 μg/kg/min caused the greatest increases in arterial blood pressure. Dobutamine CRI at 5, 10, and 15 μg/kg/min and dopamine CRI at 5, 7, and 10 μg/kg/min may be useful in correcting severe hypotension in Hispaniolan Amazon parrots caused by anesthesia maintained with 2.5% isoflurane.

Comparison of exercise, dobutamine-atropine and dipyridamole-atropine stress echocardiography in detecting coronary artery disease

PubMed Central

Nedeljkovic, Ivana; Ostojic, Miodrag; Beleslin, Branko; Djordjevic-Dikic, Ana; Stepanovic, Jelena; Nedeljkovic, Milan; Stojkovic, Sinisa; Stankovic, Goran; Saponjski, Jovica; Petrasinovic, Zorica; Giga, Vojislav; Mitrovic, Predrag

2006-01-01

Background Dipyridamole and dobutamine stress echocardiography testing are most widely utilized, but their sensitivity remained suboptimal in comparison to routine exercise stress echocardiography. The aim of our study is to compare, head-to-head, exercise, dobutamine and dipyridamole stress echocardiography tests, performed with state-of-the-art protocols in a large scale prospective group of patients. Methods Dipyridamole-atropine (Dipatro: 0.84 mg/kg over 10 min i.v. dipyridamole with addition of up to 1 mg of atropine), dobutamine-atropine (Dobatro: up to 40 mcg/kg/min i.v. dobutamine with addition of up to 1 mg of atropine) and exercise (Ex, Bruce) were performed in 166 pts. Of them, 117 pts without resting wall motion abnormalities were enrolled in study (91 male; mean age 54 ± 10 years; previous non-transmural myocardial infarction in 32 pts, angina pectoris in 69 pts and atypical chest pain in 16 pts). Tests were performed in random sequence, in 3 different days, within 5 day period under identical therapy. All patients underwent coronary angiography. Results Significant coronary artery disease (CAD; ≥50% diameter stenosis) was present in 69 pts (57 pts 1-vessel CAD, 12 multivessel CAD) and absent in 48 pts. Sensitivity (Sn) was 96%, 93% and 90%, whereas specificity (Sp) was 92%, 92% and 87% for Dobatro, Dipatro and Ex, respectively (p = ns). Concomitant beta blocker therapy did not influence peak rate-pressure product and Sn of Dobatro and Dipatro (p = ns). Conclusion When state-of-the-art protocols are used, dipyridamole and dobutamine stress echocardiography have comparable and high diagnostic accuracy, similar to maximal post-exercise treadmill stress echocardiography. PMID:16672046

Comparison of exercise, dobutamine-atropine and dipyridamole-atropine stress echocardiography in detecting coronary artery disease.

PubMed

Nedeljkovic, Ivana; Ostojic, Miodrag; Beleslin, Branko; Djordjevic-Dikic, Ana; Stepanovic, Jelena; Nedeljkovic, Milan; Stojkovic, Sinisa; Stankovic, Goran; Saponjski, Jovica; Petrasinovic, Zorica; Giga, Vojislav; Mitrovic, Predrag

2006-05-03

Dipyridamole and dobutamine stress echocardiography testing are most widely utilized, but their sensitivity remained suboptimal in comparison to routine exercise stress echocardiography. The aim of our study is to compare, head-to-head, exercise, dobutamine and dipyridamole stress echocardiography tests, performed with state-of-the-art protocols in a large scale prospective group of patients. Dipyridamole-atropine (Dipatro: 0.84 mg/kg over 10 min i.v. dipyridamole with addition of up to 1 mg of atropine), dobutamine-atropine (Dobatro: up to 40 mcg/kg/min i.v. dobutamine with addition of up to 1 mg of atropine) and exercise (Ex, Bruce) were performed in 166 pts. Of them, 117 pts without resting wall motion abnormalities were enrolled in study (91 male; mean age 54 +/- 10 years; previous non-transmural myocardial infarction in 32 pts, angina pectoris in 69 pts and atypical chest pain in 16 pts). Tests were performed in random sequence, in 3 different days, within 5 day period under identical therapy. All patients underwent coronary angiography. Significant coronary artery disease (CAD; > or =50% diameter stenosis) was present in 69 pts (57 pts 1-vessel CAD, 12 multivessel CAD) and absent in 48 pts. Sensitivity (Sn) was 96%, 93% and 90%, whereas specificity (Sp) was 92%, 92% and 87% for Dobatro, Dipatro and Ex, respectively (p = ns). Concomitant beta blocker therapy did not influence peak rate-pressure product and Sn of Dobatro and Dipatro (p = ns). When state-of-the-art protocols are used, dipyridamole and dobutamine stress echocardiography have comparable and high diagnostic accuracy, similar to maximal post-exercise treadmill stress echocardiography.

Dose-dependent effects of isoflurane and dobutamine on cardiovascular function in dogs with experimental mitral regurgitation.

PubMed

Goya, Seijirow; Wada, Tomoki; Shimada, Kazumi; Hirao, Daiki; Tanaka, Ryou

2018-04-18

To investigate the dose-dependent effects of isoflurane and dobutamine on haemodynamics in dogs with experimentally induced mitral valve insufficiency (MI). Experimental, dose-response study. Six healthy Beagle dogs. Dogs with surgically induced MI were anaesthetized once. First, anaesthesia was maintained at an end-tidal isoflurane concentration (Fe'Iso) 1.0% (ISO1.0) for 20 minutes. Then, dobutamine was infused successively at 2, 4, 8 and 12 μg kg -1 minute -1 (DOB2-12) for 10 minutes at each dose rate. Measurements were recorded at each stage. Dobutamine was discontinued and Fe'Iso was increased to 1.5% (ISO1.5) for 20 minutes. Dobutamine was administered similarly to ISO1.0, and cardiovascular variables were recorded. The same sequence was repeated for Fe'Iso 2.0% (ISO2.0). Aortic pressure (AoP) and left atrial pressure (LAP) were recorded by radiotelemetry. The combination method of the pressure-volume loop analysis and transoesophageal echocardiography was used to measure cardiovascular variables: end-systolic elastance (Ees), effective arterial elastance (Ea), Ea/Ees, forward stroke volume (FSV), heart rate (HR), and cardiac output (CO). High isoflurane concentration resulted in reduced Ees and increased Ea/Ees, which indicated low arterial pressure. High-dose dobutamine administration resulted in increased Ees and FSV at all isoflurane concentrations. In ISO1.5 and ISO2.0, HR was lower at DOB4 than baseline (BL) but increased at DOB12 compared with DOB4. CO increased at ≥ DOB8 compared with BL. In ISO1.5 and ISO2.0, systolic and mean AoP increased at ≥ DOB4 and ≥ DOB8, respectively. LAP did not change under all conditions. The dose-dependent hypotensive effect of isoflurane in MI dogs was mainly derived from the decrease in contractility. Dobutamine increased AoP without increasing LAP by increasing the contractility attenuated by isoflurane. Our findings may improve the cardiovascular management of dogs with MI undergoing general anaesthesia with isoflurane. Copyright © 2018 Association of Veterinary Anaesthetists and American College of Veterinary Anesthesia and Analgesia. Published by Elsevier Ltd. All rights reserved.

Effects of intravenous home dobutamine in palliative end-stage heart failure on quality of life, heart failure hospitalization, and cost expenditure.

PubMed

Martens, Pieter; Vercammen, Jan; Ceyssens, Wendy; Jacobs, Linda; Luwel, Evert; Van Aerde, Herwig; Potargent, Peter; Renaers, Monique; Dupont, Matthias; Mullens, Wilfried

2018-01-17

In patients with palliative end-stage heart failure, interventions that could provide symptomatic relief and prevent hospital admissions are important. Ambulatory continuous intravenous inotropes have been advocated by guidelines for such a purpose. We sought to determine the effect of intravenous dobutamine on symptomatic status, hospital stay, mortality, and cost expenditure. All consecutive end-stage heart failure patients not amenable for advanced therapies and discharged with continuous intravenous home dobutamine from a single tertiary centre between April 2011 and January 2017 were retrospectively analysed. Dobutamine (fixed dose) was infused through a single-lumen central venous catheter with a small pump that was refilled by a nurse on a daily basis. Symptomatic status was longitudinally assessed as the change in New York Heart Association class and patient global assessment scale. Antecedent and incident heart failure hospitalizations were determined in a paired fashion, and cost impact was assessed. A total of 21 patients (age 77 ± 9 years) were followed up for 869 ± 647 days. At first follow-up (6 ± 1 weeks) after the initiation of dobutamine, patients had a significant improvement in New York Heart Association class (-1.29 ± 0.64; P < 0.001), global assessment scale (<0.001), and N-terminal pro-brain natriuretic peptide (6247 vs. 2543 pg/mL; P = 0.033). Incident heart failure hospitalizations assessed at 3, 6, and 12 months were significantly reduced (P < 0.001 for all) in comparison with antecedent heart failure hospitalizations over the same time period. Cost expenditure was significantly lower at 3 (P < 0.001), 6 (P = 0.005), and 12 months (P = 0.001) after initiation of dobutamine. Mortality rate at 1 year was 48% with 9/12 (75%) patients dying at home, most often from progressive pump failure. Continuous intravenous home dobutamine in patients with palliative end-stage heart failure is feasible and associated with improved symptomatic status, heart failure hospitalizations, and health-care-related costs. Nevertheless, results should be interpreted in the context of the small and retrospective design. Larger studies are necessary to evaluate the effect of dobutamine in palliative end-stage heart failure. © 2018 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of the European Society of Cardiology.

Symptoms, adverse effects, and complications associated with dobutamine stress echocardiography. Experience in 1118 patients.

PubMed

Mertes, H; Sawada, S G; Ryan, T; Segar, D S; Kovacs, R; Foltz, J; Feigenbaum, H

1993-07-01

The use of dobutamine stress echocardiography for the evaluation of coronary artery disease is rapidly expanding. New applications of the technique are being investigated in a wide variety of patients including those with advanced coronary artery disease. Despite its widespread use, the safety of dobutamine stress echocardiography has not been sufficiently documented. A consecutive series of 1118 patients undergoing dobutamine stress echocardiography for evaluation of known or suspected coronary artery disease form the basis of this report. Dobutamine stress testing was performed for evaluation of chest pain, risk assessment before noncardiac surgery, after recent myocardial infarction, or as a part of ongoing research protocols. Over the study period, the maximal dose of dobutamine used was increased from 30 to 50 micrograms/kg per minute, and atropine was used in 420 (37%) patients. There were no occurrences of death, myocardial infarction, or episodes of sustained ventricular tachycardia as a result of dobutamine stress testing. The major reasons for test termination were achievement of target heart rate in 583 patients (52.1%), maximum dose in 255 (22.8%), and angina pectoris in 142 (13%). The test was terminated in 36 (3%) patients because of noncardiac side effects including nausea, anxiety, headache, tremor, and urgency. Angina pectoris occurred in 216 (19.3%) patients. Sublingual nitroglycerin, a short-acting beta-blocker, or both types of medication were administered in 80 of these patients for relief of angina pectoris. None required intravenous nitroglycerin. A total of 736 (65%) patients had stable sinus rhythm throughout the test. The most common arrhythmias were frequent premature ventricular complexes (six or more per minute) in 172 patients (15%), and frequent premature atrial complexes in 86 (8%). There were 40 patients with nonsustained ventricular tachycardia. None had symptoms associated with the tachycardia, and only one received specific pharmacological treatment to prevent recurrence of the arrhythmia after the test was terminated. The patients who were evaluated after recent myocardial infarction and those who received atropine did not have a higher frequency of ventricular tachycardia compared with those without recent infarction and those not receiving atropine. Dobutamine stress echocardiography was safely performed using supplemental atropine and an aggressive dosing protocol. Noncardiac side effects were usually minor. Arrhythmias were well tolerated and rarely required treatment. In this study, serious complications from myocardial ischemia did not occur. Symptomatic ischemia was effectively treated with test termination, sublingual nitroglycerin, or short-acting beta-blockers.

Dobutamine cardiac "stress" test reveals increased arrhythmia risk in conscious rats after a single exposure to acrolein

EPA Science Inventory

Mild-to-moderate exercise is often used to stress the cardiovascular (CV) system of patients while monitoring them for electrocardiogram (ECG) abnormalities that may indicate underlying CV disease. We previously demonstrated that dobutamine, which increases heart rate (HR) and co...

A single exposure to diesel exhaust increases the risk of triggered cardiac arrhythmias in conscious rats during dobutamine cardiac "stress" test.

EPA Science Inventory

Mild-to-moderate exercise is often used to stress the cardiovascular (CV) system of patients while monitoring them for electrocardiogram (ECG) abnormalities that may indicate underlying CV disease. We previously used dobutamine, which increases heart rate (HR) and contractility, ...

The effect of N-acetylcysteine on cardiac contractility to dobutamine in rats with streptozotocin-induced diabetes.

PubMed

Cheng, Xing; Xia, Zhengyuan; Leo, Joyce M; Pang, Catherine C Y

2005-09-05

We examined if myocardial depression at the acute phase of diabetes (3 weeks after injection of streptozotocin, 60 mg/kg i.v.) is due to activation of inducible nitric oxide synthase and production of peroxynitrite, and if treatment with N-acetylcysteine (1.2 g/day/kg for 3 weeks, antioxidant) improves cardiac function. Four groups of rats were used: control, N-acetylcysteine-treated control, diabetic and N-acetylcysteine-treated diabetic. Pentobarbital-anaesthetized diabetic rats, relative to the controls, had reduced left ventricular contractility to dobutamine (1-57 microg/min/kg). The diabetic rats also had increased myocardial levels of thiobarbituric acid reactive substances, immunostaining of inducible nitric oxide synthase and nitrotyrosine, and similar baseline 15-F2t-isoprostane. N-acetylcysteine did not affect responses in the control rats; but increased cardiac contractility to dobutamine, reduced myocardial immunostaining of inducible nitric oxide synthase and nitrotyrosine and level of 15-F2t-isoprostane, and increased cardiac contractility to dobutamine in the diabetic rats. Antioxidant supplementation in diabetes reduces oxidative stress and improves cardiac function.

Cardiovascular and adenylate cyclase stimulating effects of colforsin daropate, a water-soluble forskolin derivative, compared with those of isoproterenol, dopamine and dobutamine.

PubMed

Yoneyama, Masahiko; Sugiyama, Atsushi; Satoh, Yoshioki; Takahara, Akira; Nakamura, Yuji; Hashimoto, Keitaro

2002-12-01

Colforsin daropate is a recently developed water-soluble derivative of forskolin that directly stimulates adenylate cyclase, unlike the catecholamines. The chronotropic, inotropic and coronary vasodilator actions of colforsin daropate were compared with those of isoproterenol, dopamine and dobutamine, using canine isolated, blood-perfused heart preparations. The stimulating effect of each drug on adenylate cyclase activity was also assessed. Colforsin daropate, as well as each of the catecholamines, exerted positive chronotropic, inotropic and coronary vasodilator actions. The order of selectivity for the cardiovascular variables of colforsin daropate was coronary vasodilation > positive inotropy > positive chronotropy; whereas that of isoproterenol, dopamine and dobutamine was positive inotropy > coronary vasodilation > positive chronotropy. Thus, a marked characteristic of colforsin daropate is its potent coronary vasodilator action. On the other hand, each drug significantly increased the adenylate cyclase activity in a dose-related manner: colforsin daropate > isoproterenol > dopamine = dobutamine. These results suggest that colforsin daropate may be preferable in the treatment of severe heart failure where the coronary blood flow is reduced and beta-adrenoceptor-dependent signal transduction pathway is down-regulated.

Prognostic value of dobutamine stress echocardiography in patients referred because of suspected coronary artery disease.

PubMed

Kamaran, M; Teague, S M; Finkelhor, R S; Dawson, N; Bahler, R C

1995-11-01

To determine whether dobutamine stress echocardiography (DSE) provides prognostic information beyond that available from routine clinical data, we reviewed the outcome of 210 consecutive patients referred for DSE to evaluate chest pain, perioperative risk, and myocardial viability. Dobutamine was infused in increments of 10 micrograms/kg/min in 5-minute stages to a maximum of 40 micrograms/kg/min. The dobutamine stress echocardiogram was considered abnormal only if dobutamine induced a new wall motion abnormality as determined by review of the digitized echocardiographic images in a quad screen format and on videotape. Thirty percent of tests were abnormal. An abnormal test was more common (p < or = 0.02) in men and patients with angina pectoris, in patients taking nitrate therapy, or those with prior myocardial infarction or abnormal left ventricular wall motion at rest. Twenty-two deaths, 17 of which were cardiac, occurred over a median follow-up of 240 days (range 30 to 760). Sixteen cardiac deaths occurred in the 63 patients with versus 1 cardiac death among the 147 without a new wall motion abnormality (p < or = 0.0001). Other variables associated with cardiac death (p < or = 0.05) were age > 65 years, nitrate therapy, ventricular ectopy during DSE, suspected angina pectoris, and hospitalization at the time of DSE. When cardiac death, myocardial infarction, and revascularization procedures were all considered as adverse outcomes, a new wall motion abnormality continued to be the most powerful predictor of an adverse cardiac event.(ABSTRACT TRUNCATED AT 250 WORDS)

Dobutamine stress magnetic resonance imaging suffices for the demonstration of myocardial ischaemia and viability.

PubMed

Lamers, F P L; van Dijkman, P R M; Kuijpers, Th J A; van Herpen, G

2003-02-01

We report three patients in whom dobutamine stress magnetic imaging (DS-MRI) was essential in assessing myocardial ischaemia. Two patients were referred to the cardiologist because of chest pain. Patient A had typical exertional angina and a normal resting electrocardiogram (ECG). Patient B had typical exercise-induced angina and had recently experienced an attack of severe chest pain at rest for 15 minutes. The ECG showed a complete left bundle branch block (LBBB). Patient C was referred for heart failure of unknown origin. There were no symptoms of chest pain during rest or exercise. Echocardiography in this patient demonstrated global left ventricular (LV) dilatation, systolic dysfunction and a small dyskinetic segment in the inferior wall. In all these patients exercise stress testing had failed to demonstrate myocardial ischaemia. Patients A and C produced normal findings whereas in patient B the abnormal repolarisation due to pre-existent LBBB precluded a diagnosis of ischaemia. Breath-hold DS-MRI was performed to study LV wall motion and wall thickening at rest through increasing doses of dobutamine. A test was considered positive for myocardial ischaemia if wall motion abnormalities developed at high-dose levels of the drug (20 μg/kg/min or more with a maximum of 40 μg/kg/min) in previously normal vascular territories or worsened in a segment that was normal at baseline. Recovery of wall thickening in a previously hypokinetic or akinetic segment at a low dose of dobutamine (5-10 μg/kg/min) was taken as proof of viability. Patients A and B developed hypokinesia progressing into akinesia at high-dose dobutamine in the anteroseptal area of the LV indicative of ischaemia. These findings were corroborated by coronary angiography demonstrating severe coronary artery disease which led to coronary artery bypass grafting (CABG) in patient A and balloon angioplasty in patient B. In patient C global recovery of LV contractions during low-dose dobutamine was followed by hypokinesia in the inferoseptal area during high-dose dobutamine. This biphasic response indicates myocardial viability as well as ischaemia. CABG was carried out because of multiple stenoses in the left coronary artery. Post-operatively LV function normalised. DS-MRI is a valuable method for detecting myocardial ischaemia and viability in patients with suspected coronary artery, and can be applied in every hospital with MRI equipment at its disposal.

Blood magnesium concentration and dopamine or dobutamine infusion demand in patients during CABG (coronary artery bypass grafting) with normovolemic haemodilution.

PubMed

Pasternak, K; Wrońska, J; Dabrowski, W; Sztanke, M

2006-12-01

It is well known that magnesium (Mg) plays an essential role in cardiac protection. Mg has many beneficial effects on the myocardium and cardiac function, e.g. it improves contractility and reduces the number of cardiac arrhythmia episodes. The inotropically positive effects of Mg are interesting and worth stressing. High blood Mg concentration may result in an increase in cardiac contraction strength, which may be important for haemodynamic stabilization, and thus it is likely to decrease the demand for dopamine and dobutamine infusions. However, the exact determination of correlation between blood Mg concentrations and dopamine or dobutamine infusion demand is still unknown. The aim of the study was to assess the demand for dopamine or dobutamine infusion in relation to changes in blood magnesium concentrations in patients undergoing CABG (Coronary artery bypass graft) with extracorporeal circulation and normovolemic haemodilution. The study included 20 male patients, aged 53-70 (61.1 +/- 6.9) who underwent general anaesthesia and coronary artery bypass grafting (CABG) with extracorporeal circulation (ECC) and normovolemic haemodilution (NH) due to stable angina pectoris. The patients were retrospectively divided into three groups: A--patients who did not receive dopamine or dobutamine infusion, B--those receiving only D infusion in the doses dependent on their clinical state and C--those receiving DB infusion in the doses dependent on their clinical state. Mg was measured in 7 stages: 1) just before anaesthesia after the radial artery cannulation, 2) during normovolemic haemodilution and ECC, 3) immediately after surgery, 4) in the evening of the surgery day, 5) in the morning of the lst postoperative day, 6) in the evening of 1st postoperative day, 7) in the morning of the 2nd postoperative day. The spectrophotometric methods were used to determine Mg. The CABG procedure resulted in a decrease in Mg. Its level returned to normal in the evening of surgery day. The NH caused a similar Mg decrease in groups A, B and C, but these significantly low values of Mg were observed only in stage 2. There was no correlation between blood Mg concentrations and dopamine or dobutamine infusion demand. 1) The CABG procedure resulted in decreased blood magnesium concentrations. 2) The Mg changes do not correlate with dopamine or dobutamine infusion demand.

Dobutamine stress magnetic resonance imaging: a valuable method in the noninvasive diagnosis of ischemic heart disease.

PubMed

van Dijkman, Paul R M; Kuijpers, Dirkjan A; Blom, Bernadette M; van Herpen, Gerard

2002-01-01

We assessed the clinical applicability of dobutamine stress magnetic resonance imaging (DS-MRI) for the detection of myocardial ischemia and myocardial viability. One hundred patients with suspected coronary artery disease and inconclusive exercise electrocardiography or significant repolarization abnormalities on the resting ECG underwent breath hold DS-MRI (1 Tesla), 4 days after cessation of anti-ischemic medication. Three left ventricular short axis planes were imaged at increasing doses of dobutamine. Recovery of wall thickening in a previously diminished or non contracting segment at low dose dobutamine was considered proof of viability. Development of hypo-, a- or dyskinesia at higher doses of dobutamine was taken to indicate ischemia. If the DS-MRI test was positive for ischemia, coronary angiography was performed. If indicated, this was followed by revascularization. If DS-MRI did not demonstrate ischemia, neither angiography nor revascularization were carried out. Ninety five DS-MRI investigations were available for diagnosis. Forty two patients had DS-MRI scans positive for ischemia and subsequently coronary angiography assessment of the clinical applicability of DS-MRI for the detection of myocardial ischemia was performed. One patient was false-positive. All 53 patients with non-ischemic DS-MRI scans had follow-up for 11-23 months (mean 17 months). One patient died suddenly 2 weeks after the MRI-test. The other 52 patients did not experience any coronary event nor sudden cardiac death. The predictive value of a positive (for ischemia) DS-MRI test is 98% and the predictive value of a negative DS-MRI test is also 98%.

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.

Dobutamine stress magnetic resonance imaging suffices for the demonstration of myocardial ischaemia and viability

PubMed Central

Lamers, F.P.L.; van Dijkman, P.R.M.; Kuijpers, Th.J.A.; van Herpen, G.

2003-01-01

We report three patients in whom dobutamine stress magnetic imaging (DS-MRI) was essential in assessing myocardial ischaemia. Two patients were referred to the cardiologist because of chest pain. Patient A had typical exertional angina and a normal resting electrocardiogram (ECG). Patient B had typical exercise-induced angina and had recently experienced an attack of severe chest pain at rest for 15 minutes. The ECG showed a complete left bundle branch block (LBBB). Patient C was referred for heart failure of unknown origin. There were no symptoms of chest pain during rest or exercise. Echocardiography in this patient demonstrated global left ventricular (LV) dilatation, systolic dysfunction and a small dyskinetic segment in the inferior wall. In all these patients exercise stress testing had failed to demonstrate myocardial ischaemia. Patients A and C produced normal findings whereas in patient B the abnormal repolarisation due to pre-existent LBBB precluded a diagnosis of ischaemia. Breath-hold DS-MRI was performed to study LV wall motion and wall thickening at rest through increasing doses of dobutamine. A test was considered positive for myocardial ischaemia if wall motion abnormalities developed at high-dose levels of the drug (20 μg/kg/min or more with a maximum of 40 μg/kg/min) in previously normal vascular territories or worsened in a segment that was normal at baseline. Recovery of wall thickening in a previously hypokinetic or akinetic segment at a low dose of dobutamine (5-10 μg/kg/min) was taken as proof of viability. Patients A and B developed hypokinesia progressing into akinesia at high-dose dobutamine in the anteroseptal area of the LV indicative of ischaemia. These findings were corroborated by coronary angiography demonstrating severe coronary artery disease which led to coronary artery bypass grafting (CABG) in patient A and balloon angioplasty in patient B. In patient C global recovery of LV contractions during low-dose dobutamine was followed by hypokinesia in the inferoseptal area during high-dose dobutamine. This biphasic response indicates myocardial viability as well as ischaemia. CABG was carried out because of multiple stenoses in the left coronary artery. Post-operatively LV function normalised. DS-MRI is a valuable method for detecting myocardial ischaemia and viability in patients with suspected coronary artery, and can be applied in every hospital with MRI equipment at its disposal. ImagesFigure 1Figure 2 PMID:25696185

Effect of dobutamine on extravascular lung water index, ventilator function, and perfusion parameters in acute respiratory distress syndrome associated with septic shock.

PubMed

Zhou, Min; Dai, Ji; Du, Min; Wang, Wei; Guo, Changxing; Wang, Yi; Tang, Rui; Xu, Fengling; Rao, Zhuqing; Sun, Gengyun

2016-08-01

The role of dobutamine in the relief of pulmonary edema during septic shock-induced acute respiratory distress syndrome (ARDS) remains undetermined, due to a lack of controllable and quantitative clinical studies. Our objective was to assess the potential effects of dobutamine on extravascular lung water index (ELWI) in septic shock-induced ARDS, reflecting its importance in pulmonary edema. At the same time, ventilator function and perfusion parameters were evaluated. We designed a prospective, non-randomized, non-blinded, controlled study to compare the differences in PiCCO parameters after 6 h of constant dobutamine infusion (15 μg/kg/min), in the baseline parameters in 26 septic shock-related ARDS patients with cardiac index ≥ 2.5I/min/m(2) and hyperlactatemia. These patients (12 survivors/14 non-survivors) were monitored using the PiCCO catheter system within 48 h of onset of septic shock. The dynamic changes in ELWI, which is typically used for quantifying the extent of pulmonary edema, were evaluated, and the corresponding ventilator function and tissue perfusion parameters were also measured. Decreasing ELWI (p = 0.0376) was accompanied by significantly decreased SVRI (p < 0.0001). Despite a significant increase in cardiac output (p < 0.0001), no differences were found in ITBI or GEDI. Moreover, the required dose of norepinephrine was decreased (p = 0.0389), and urine output was increased (p = 0.0358), accompanied by stabilized lactacidemia and MAP. Additionally, airway pressure was moderately improved. During the early stage of septic shock-induced ARDS, dobutamine treatment demonstrated a beneficial effect by relieving pulmonary edema in patients, without a negative elevation in preload or hemodynamics, which might account for the improvements in ventilator function and tissue hypoperfusion.

Inotropes and cardiorenal syndrome in acute heart failure - A retrospective comparative analysis.

PubMed

Madeira, Marta; Caetano, Francisca; Almeida, Inês; Fernandes, Andreia; Reis, Liliana; Costa, Marco; Gonçalves, Lino

2017-09-01

Cardiorenal syndrome (CRS) is common in acute heart failure (AHF), and is associated with dire prognosis. Levosimendan, a positive inotrope that also has diuretic effects, may improve patients' renal profile. Published results are conflicting. We aimed to assess the incidence of CRS in AHF patients according to the inotrope used and to determine its predictors in order to identify patients who could benefit from the most renoprotective inotrope. In a retrospective study, 108 consecutive patients with AHF who required inotropes were divided into two groups according to the inotrope used (levosimendan vs. dobutamine). The primary endpoint was CRS incidence. Follow-up for mortality and readmission for AHF was conducted. Seventy-one percent of the study population were treated with levosimendan and the remainder with dobutamine. No differences were found in heart failure etiology or chronic kidney disease. At admission, the dobutamine group had lower blood pressure; there were no differences in estimated glomerular filtration rate or cystatin C levels. The levosimendan group had lower left ventricular ejection fraction. CRS incidence was higher in the dobutamine group, and they more often had incomplete recovery of renal function at discharge. In multivariate analysis, cystatin C levels predicted CRS. The dobutamine group had higher in-hospital mortality, of which CRS and the inotrope used were predictors. Levosimendan appears to have some renoprotective effect, as it was associated with a lower incidence of CRS and better recovery of renal function at discharge. Identification of patients at increased risk of renal dysfunction by assessing cystatin C may enable more tailored therapy, minimizing the incidence of CRS and its negative impact on outcome in AHF. Copyright © 2017 Sociedade Portuguesa de Cardiologia. Publicado por Elsevier España, S.L.U. All rights reserved.

Intraoperative transit-time flow measurement is not altered in venous bypass grafts covered by the eSVS mesh.

PubMed

Emery, Robert W; Solien, Eric

2013-01-01

The aim of this study was to determine whether the eSVS Mesh interferes with transit-time flow measurement (TTFM) assessing intraoperative coronary vein graft patency. In four swine undergoing off-pump bypass grafting to the anterior descending coronary artery, five TTFMs were sequentially obtained on meshed and bare grafts at baseline and under Dobutamine stress at five separate locations on the graft in each animal. The Medistim VeriQ was used for TTFM. The grafts were examined for patency after the swine were killed. There was no difference in hemodynamics or TTFM either at baseline or under Dobutamine stress between the eSVS Mesh covered and uncovered grafts. Dobutamine, however, significantly increased hemodynamics and graft flow parameters measured from baseline. The eSVS Mesh does not interfere with Doppler flow measurement in covered coronary vein grafts.

Hemodynamic and intravascular ultrasound assessment of myocardial bridging: fractional flow reserve paradox with dobutamine versus adenosine.

PubMed

Hakeem, Abdul; Cilingiroglu, Mehmet; Leesar, Massoud A

2010-02-01

Compared to coronary angiography, both intravascular ultrasound (IVUS) and CT-angiography provide important information with respect to the morphological aspects of myocardial bridging (MB). However, these modalities are limited in defining the hemodynamic and clinical significance of MB. Intracoronary Doppler studies demonstrate a peculiar abnormal Doppler flow profile associated with MB. Fractional flow reserve (FFR) after adenosine infusion has been used to assess the hemodynamic significance of MB, but FFR after adenosine induced hyperemia underestimates the significance of MB. On the other hand, high-dose dobutamine by increasing the contractility of the bridging segment unmasks ischemia induced by MB. This review outlines the role of flow velocity measurement by intracoronary Doppler, FFR, and IVUS for assessment of patients with MB. In addition, we compared FFR measurements after adenosine versus dobutamine infusions for the hemodynamic assessment of MB in two patients.

Oxygen-saving effect of a new cardiotonic agent, MCI-154, in diseased human hearts.

PubMed

Mori, M; Takeuchi, M; Takaoka, H; Hata, K; Hayashi, Y; Yamakawa, H; Yokoyama, M

1997-03-01

The aim of this study was to examine the left ventricular mechanoenergetic effects of a novel Ca2+ sensitizing agent, MCI-154, on diseased human hearts compared with dobutamine. Unlike conventional cardiotonic agents, a Ca2+ sensitizer that could produce a positive inotropic action by altering the responsiveness of myofilament to Ca2+ could generate force with smaller amounts of Ca2+; thus, it may potentially save energy expenditure. The left ventricular pressure-volume relation and myocardial oxygen consumption per beat (Vo2) were measured by a conductance (volume) catheter and a Webster catheter. Left ventricular contractility (Emax), systolic pressure-volume area (PVA [index of left ventricular total mechanical energy]) and Vo2 were assessed before and after infusion of MCI-154 or dobut-amine. The PVA-independent Vo2 (Vo2 mainly for excitation-contraction coupling) was assessed as the Vo2 at zero PVA. Both agents increased Emax comparably (dobutamine: from 3.55 +/- 1.10 [mean +/- SD] to 5.04 +/- 1.16 mm Hg/ml per m2, p < 0.0001; MCI-154: from 3.36 +/- 1.26 to 5.37 +/- 2.14 mm Hg/ml per m2, p < 0.0001); dobutamine increased total Vo2 (from 0.22 +/- 0.08 to 0.27 +/- 0.09 ml O2, p < 0.05) and PVA-independent Vo2 (from 0.019 +/- 0.019 to 0.091 +/- 0.051 ml O2, p < 0.005); but MCI-154 did not change these variables significantly. Consequently, the oxygen cost of contractility (delta PVA-independent Vo2/delta Emax) was less with MCI-154 than with dobutamine (0.14 +/- 0.18 vs. 1.10 +/- 0.80 J/mm Hg per ml per m2, p < 0.05). These results suggest that the cardiotonic action mediated by MCI-154 could provide an energetic advantage over the conventional cardiotonic action with currently used inotropic agents.

[Exercise stress test and dobutamine stress echocardiography for the prognostic stratification after uncomplicated acute myocardial infarction].

PubMed

Vitiello, Nicola; Cirillo, Raffaele; Granato, Luigi; Coppola, Vincenzo; di Palma, Francesco

2007-05-01

Exercise stress test and dobutamine stress echocardiography are usually performed early after an uncomplicated acute myocardial infarction in the prognostic stratification of patients to define the optimal diagnostic and therapeutic procedure. The aim of this study was to evaluate if the association of an imaging test could increase exercise test capability to identify patients with residual ischemia and patients at high risk of events in the follow-up. Four hundred and forty-two consecutive patients underwent exercise stress testing and dobutamine stress echocardiography before discharge and subsequently coronary angiography within 30 days. In case of submaximal negative result at the exercise test, this was repeated 20 days after discharge. The follow-up lasted 26.8 +/- 9 months. The endpoints were death, reinfarction, and unstable angina requiring hospitalization or revascularization intervention. Both tests and their association showed a higher sensitivity in males; in females dobutamine stress echocardiography had a higher specificity. In females, the addition of dobutamine stress echocardiography increased either the negative or the positive prognostic values of exercise stress test by 31% and 5.6%, respectively. In males, the negative prognostic value increased by 15.5%, whereas the positive prognostic value decreased by 12%. A low exercise capability (<6 METs) showed an event predictive value independent of test results and any other variables. The event-free survival curves correlated with exercise capability differed shortly after the first months both in males and females. These results suggest different stratification procedures with regard to gender: in males, the exercise stress test might be sufficient at discharge, to be repeated 20 days later, if submaximal negative. In females, it seems to be useful to associate an imaging test at discharge. In any case, the exercise stress test remains the main step in the stratification procedure also for its capability to identify patients who are at high risk of events in the follow-up.

Successful treatment of inverted Takotsubo cardiomyopathy after severe traumatic brain injury with milrinone after dobutamine failure.

PubMed

Mrozek, Ségolène; Srairi, Mohamed; Marhar, Fouad; Delmas, Clément; Gaussiat, François; Abaziou, Timothée; Larcher, Claire; Atthar, Vincent; Menut, Rémi; Fourcade, Olivier; Geeraerts, Thomas

2016-01-01

Takotsubo cardiomyopathy can occur at the early phase of severe acute brain injuries. In the case of cardiac output decrease or shock, the optimal treatment is still a matter of debate. Due to massive stress hormone release, the infusion of catecholamines may have limited effects and may even aggravate cardiac failure. Other inotropic agents may be an option. Levosimendan has been shown to have potential beneficial effects in this setting, although milrinone has not been studied. We report a case of a young female presenting with inverted Takotsubo cardiomyopathy syndrome after severe traumatic brain injury. Due to hemodynamic instability and increasing levels of infused norepinephrine, dobutamine infusion was begun but rapidly stopped due to tachyarrhythmia. Milrinone infusion stabilized the patient's hemodynamic status and improved cardiac output without deleterious effects. Milrinone could be a good alternative when inotropes are required in Takotsubo cardiomyopathy and when dobutamine infusion is associated with tachyarrhythmia. Copyright © 2016 Elsevier Inc. All rights reserved.

Evoked changes in cardiovascular function in rats by infusion of levosimendan, OR-1896 [(R)-N-(4-(4-methyl-6-oxo-1,4,5,6-tetrahydropyridazin-3-yl)phenyl)acetamide], OR-1855 [(R)-6-(4-aminophenyl)-5-methyl-4,5-dihydropyridazin-3(2H)-one], dobutamine, and milrinone: comparative effects on peripheral resistance, cardiac output, dP/dt, pulse rate, and blood pressure.

PubMed

Segreti, Jason A; Marsh, Kennan C; Polakowski, James S; Fryer, Ryan M

2008-04-01

Levosimendan enhances cardiac contractility primarily via Ca(2+) sensitization, and it induces vasodilation through the activation of ATP-sensitive potassium channels and large conductance Ca(2+)-activated K(+) channels. However, the concentration-dependent hemodynamic effects of levosimendan and its metabolites (R)-N-(4-(4-methyl-6-oxo-1,4,5,6-tetrahydropyridazin-3-yl)phenyl)acetamide (OR-1896) and (R)-6-(4-aminophenyl)-5-methyl-4,5-dihydropyridazin-3(2H)-one (OR-1855) have not been well defined. Thus, levosimendan (0.03, 0.10, 0.30, and 1.0 mumol/kg/30 min; n = 6) was infused as four escalating 30-min i.v. doses targeting therapeutic to supratherapeutic concentrations of levosimendan (C(max), approximately 62.6 ng/ml); metabolites were infused at one-half log-unit lower doses and responses compared to dobutamine (beta(1)-agonist) and milrinone (phosphodiesterase 3 inhibitor). Peak concentrations of levosimendan, OR-1896, and OR-1855 at the end of the high dose were 323 +/- 14, 83 +/- 2, and 6 +/- 2 ng/ml, respectively (OR-1855 rapidly metabolized to OR-1896; peak = 82 +/- 3 ng/ml). Levosimendan and OR-1896 produced dose-dependent reductions in blood pressure and peripheral resistance with a rank potency, based on ED(15) values, of OR-1896 (0.03 mumol/kg) > OR-1855 > levosimendan > milrinone (0.24 mumol/kg); an ED(15) for dobutamine could not be defined. Only dobutamine produced increases in pulse pressure (30 +/- 5%) and rate-pressure product (34 +/- 4%). All of the compounds, with the exception of OR-1855, elicited dose-dependent increases in dP/dt with a rank potency, based on ED(50) values, of dobutamine (0.03 mumol/kg) > levosimendan > OR-1896 > milrinone (0.09 mumol/kg), although only levosimendan produced sustained increases in cardiac output (9 +/- 4%). Thus, levosimendan and OR-1896 are hemodynamically active at sub- to supratherapeutic concentrations (whereas the effects of OR-1855 in the rat are thought to be predominantly mediated by conversion to OR-1896) and produce direct inotropic effects and also direct relaxation of the peripheral vasculature, which clearly differentiates them from dobutamine, which does not elicit K(+) channel activation, suggesting a more balanced effect on the cardiac-contractile state and K(+) channel-mediated changes in vascular resistance.

Strain-encoded cardiac MRI as an adjunct for dobutamine stress testing: incremental value to conventional wall motion analysis.

PubMed

Korosoglou, Grigorios; Lossnitzer, Dirk; Schellberg, Dieter; Lewien, Antje; Wochele, Angela; Schaeufele, Tim; Neizel, Mirja; Steen, Henning; Giannitsis, Evangelos; Katus, Hugo A; Osman, Nael F

2009-03-01

High-dose dobutamine stress MRI is safe and feasible for the diagnosis of coronary artery disease (CAD) in humans. However, the assessment of cine scans relies on the visual interpretation of regional wall motion, which is subjective. Recently, strain-encoded MRI (SENC) has been proposed for the direct color-coded visualization of myocardial strain. The purpose of our study was to compare the diagnostic value of SENC with that provided by conventional wall motion analysis for the detection of inducible ischemia during dobutamine stress MRI. Stress-induced ischemia was assessed by wall motion analysis and by SENC in 101 patients with suspected or known CAD and in 17 healthy volunteers who underwent dobutamine stress MRI in a clinical 1.5-T scanner. Quantitative coronary angiography deemed as the standard reference for the presence or absence of significant CAD (> or =50% diameter stenosis). On a coronary vessel level, SENC detected inducible ischemia in 86 of 101 versus 71 of 101 diseased coronary vessels (P<0.01 versus cine) and showed normal strain response in 189 of 202 versus 194 of 202 vessels with <50% stenosis (P=NS versus cine). On a patient level, SENC detected inducible ischemia in 63 of 64 versus 55 of 64 patients with CAD (P<0.05 versus cine) and showed normal strain response in 32 of 37 versus 34 of 37 patients without CAD (P=NS versus cine). Quantification analysis demonstrated a significant correlation between strain rate reserve and coronary artery stenosis severity (r(2)=0.56, P<0.001), and a cutoff value of strain rate reserve of 1.64 was deemed as a highly accurate marker for the detection of > or =50% stenosis (area under the curve, 0.96; SE, 0.01; 95% CI, 0.94 to 0.98; P<0.001). The direct color-coded visualization of strain on MR images is a useful adjunct for dobutamine stress MRI, which provides incremental value for the detection of CAD compared with conventional wall motion readings on cine images.

Relationship between shortening load, contractility, and myocardial energetics in intact dog.

PubMed

Dell'Italia, L J; Evanochko, W T; Blackwell, G G; Pearce, D J; Pohost, G M

1993-06-01

A canine model was developed to estimate left ventricular wall stress, volumes, contractility, and high-energy phosphate metabolites without the need for major surgery. A percutaneously inserted catheter-tip manometer was used to record high-fidelity left ventricular pressure while gradient echo cinemagnetic resonance (cine-MR) imaging alternated with in vivo 31P-nuclear magnetic resonance (NMR) spectroscopy during pharmacological maneuvers to increase cardiac work. Left ventricular circumferential wall stress, volumes, maximum rate of pressure development (dP/dtmax), and the ratio of phosphocreatine (PCr) to gamma-ATP (PCr/gamma-ATP) were recorded sequentially during control 1, dobutamine infusion, control 2, angiotensin infusion, and control 3 in five anesthetized, closed-chest dogs. PCr/gamma-ATP did not change significantly during controls 1-3, angiotensin, and dobutamine infusion. Left ventricular peak positive dP/dt (+dP/dtmax) increased significantly during dobutamine (3,338 +/- 831 mmHg/s, P < 0.001) but was unchanged during angiotensin (1,818 +/- 317 mmHg/s) and controls 1-3 (1,915 +/- 434 vs. 1,808 +/- 478 vs. 1,859 +/- 414 mmHg/s). However, dobutamine decreased the total systolic stress integral (area under the wall stress-time relationship) and end-diastolic and end-systolic volumes, whereas angiotensin increased these parameters compared with control conditions. The unchanged PCr/gamma-ATP is in accord with the results from other open-chest surface coil 31P-NMR experiments in the normal heart. Our assessment of left ventricular functional parameters provides new information that complements these more invasive studies in which heart rate-pressure product was measured during increases in cardiac work.(ABSTRACT TRUNCATED AT 250 WORDS)

Value of the mitral valve resistance in evaluation of symptomatic patients with mild and moderate mitral stenosis--a dobutamine stress echocardiographic study.

PubMed

Roshdy, Hisham S; Meshrif, Amir M; El-Dosouky, Ibtesam I

2014-03-01

Conventional stenosis indexes poorly reflect the major hemodynamic consequence of mitral stenosis (MS). Valve resistance (VR) is a physiologic expression of stenosis. This study aimed to demonstrate whether the mitral valve resistance (MVR) and its changes, relate to restricted exercise capacity in patients with mild and moderate mitral stenosis. Twenty-four patients with rheumatic mild-to-moderate MS underwent transthoracic echocardiographic study (resting and dobutamine stress echocardiography [DSE]), divided into two groups; group I: symptomatic (12 patients) and group II: asymptomatic (12 patients). Mitral valve area (MVA), mean transmitral diastolic pressure gradient (TMPG), cardiac output (CO), and MVR were measured in all patients at rest and at peak DSE. Changes (∆) in MVA, TMPG, CO, and MVR were calculated. Data underwent statistical analysis. From resting to peak dobutamine infusion, the MVR significantly decreased from 111.4 ± 28.2 to 83.6 ± 27.0 dynes sec/cm(5) in group II (P < 0.001). The increase in MVR in group I (13.8 ± 10.3 dynes sec/cm(5)) compared with its reduction (-27.8 ± 15.6 dynes sec/cm(5)) in group II were highly significant different (P < 0.001). A reduction in MVR by less than 21.5 dynes sec/cm(5) at peak dobutamine infusion reflect a cutoff value considered to detect the hemodynamic significance of mild-to-moderate MS with a sensitivity of 92% and a specificity of 73%. The changes in the MVR can be used as a DSE parameter for expression of stenosis severity and to describe discrepancy in symptom status in patients with mild-to-moderate mitral stenosis. © 2013, Wiley Periodicals, Inc.

Effect of low-dose atropine administration on dobutamine dose requirement in horses anesthetized with detomidine and halothane.

PubMed

Weil, A B; Keegan, R D; Greene, S A

1997-12-01

To determine whether a low dose of atropine is associated with decreased requirement for cardiovascular supportive treatment in horses given detomidine prior to maintenance of general anesthesia with halothane. 3 groups of 10 healthy horses. Detomidine (20 micrograms/kg of body weight, i.m.) was administered to all 30 horses. Then, 10 horses received atropine (0.006 mg/kg, i.v.) 1 hour after detomidine administration, 10 horses received atropine (0.012 mg/kg, i.m.) at the time of detomidine administration, and 10 horses served as a control group. Heart rate was measured prior to detomidine administration and at fixed intervals throughout anesthesia. The dobutamine infusion rate necessary to maintain mean arterial blood pressure between 70 and 80 mm of Hg was recorded. Systemic blood pressures, end-tidal halothane, end-tidal CO2, and arterial blood gas tensions were measured at fixed intervals. Mean heart rate was higher among horses receiving atropine i.v. or i.m., compared with that in control horses. Horses that received atropine i.v. had higher systemic arterial blood pressure and required a lower dobutamine infusion rate than did horses of the other groups. Detomidine-treated, halothane-anesthetized horses given atropine i.v. required less dobutamine, compared with horses receiving or not receiving atropine i.m. Complications, such as colic and dysrhythmias, from use of higher doses of atropine, were not observed at this lower dose of atropine. i.v. administration of a low dose of atropine prior to induction of general anesthesia may result in improved blood pressure in horses that have received detomidine before anesthesia with halothane.

Influence of left ventricular hypertrophy and geometry on diagnostic accuracy of wall motion and perfusion magnetic resonance during dobutamine stress.

PubMed

Gebker, Rolf; Mirelis, Jesus G; Jahnke, Cosima; Hucko, Thomas; Manka, Robert; Hamdan, Ashraf; Schnackenburg, Bernhard; Fleck, Eckart; Paetsch, Ingo

2010-09-01

The purpose of this study was to determine the influence of left ventricular (LV) hypertrophy and geometry on the diagnostic accuracy of wall motion and additional perfusion imaging during high-dose dobutamine/atropine stress magnetic resonance for the detection of coronary artery disease. Combined dobutamine stress magnetic resonance (DSMR)-wall motion and DSMR-perfusion imaging was performed in a single session in 187 patients scheduled for invasive coronary angiography. Patients were classified into 4 categories on the basis of LV mass (normal, ≤ 81 g/m(2) in men and ≤ 62 g/m(2) in women) and relative wall thickness (RWT) (normal, <0.45) as follows: normal geometry (normal mass, normal RWT), concentric remodeling (normal mass, increased RWT), concentric hypertrophy (increased mass, increased RWT), and eccentric hypertrophy (increased mass, normal RWT). Wall motion and perfusion images were interpreted sequentially, with observers blinded to other data. Significant coronary artery disease was defined as ≥ 70% stenosis. In patients with increased LV concentricity (defined by an RWT ≥ 0.45), sensitivity and accuracy of DSMR-wall motion were significantly reduced (63% and 73%, respectively; P<0.05) compared with patients without increased LV concentricity (90% and 88%, respectively; P<0.05). Although accuracy of DSMR-perfusion was higher than that of DSMR-wall motion in patients with concentric hypertrophy (82% versus 71%; P < 0.05), accuracy of DSMR-wall motion was superior to DSMR-perfusion (90% versus 85%; P < 0.05) in patients with eccentric hypertrophy. The accuracy of DSMR-wall motion is influenced by LV geometry. In patients with concentric remodeling and concentric hypertrophy, additional first-pass perfusion imaging during high-dose dobutamine stress improves the diagnostic accuracy for the detection of coronary artery disease.

Cardiovascular response to dobutamine stress predicts outcome in severe sepsis and septic shock.

PubMed

Kumar, Anand; Schupp, Elizabeth; Bunnell, Eugene; Ali, Amjad; Milcarek, Barry; Parrillo, Joseph E

2008-01-01

During septic shock, resistance to the haemodynamic effects of catecholamine vasopressors and inotropes is a well-recognised marker of mortality risk. However, the specific cardiovascular or metabolic response elements that are most closely associated with outcome have not been well defined. The objective of this study was to assess cardiovascular and metabolic responses to dobutamine as correlates of outcome in patients with severe sepsis or septic shock. A prospective, non-randomised, non-blinded interventional study of graded dobutamine challenge (0, 5, 10, and 15 mug/kg/min) in adult patients who had undergone pulmonary artery catheterisation within 48 hours of onset of severe sepsis or septic shock (8 survivors/15 non-survivors) was performed. Radionuclide cineangiography during graded infusion was used to determine biventricular ejection fractions at each increment of dobutamine. In univariate analysis, a variety of cardiovascular or haemodynamic and oxygen transport or metabolic variables (at the point of maximum cardiac index response for a given subject) were associated with survival including: increased stroke volume index (p = 0.0003); right ventricular end-diastolic volume index (p = 0.0047); left ventricular stroke work index (p = 0.0054); oxygen delivery index (p = 0.0084); cardiac index (p = 0.0093); systolic blood pressure/left ventricular end-systolic volume index ratio (p = 0.0188); left ventricular ejection fraction (p = 0.0160); venous oxygen content (p = 0.0208); mixed venous oxygen saturation (p = 0.0234); pulse pressure (p = 0.0403); decreased pulmonary artery diastolic pressure (p = 0.0133); systemic vascular resistance index (p = 0.0154); extraction ratio (p = 0.0160); and pulmonary vascular resistance index (p = 0.0390). Increases of stroke volume index of greater than or less than 8.5 mL/m2 were concordant with survival or death in 21 of 23 cases. Multivariate profile construction showed stroke volume index as the dominant discriminating variable for survival with the systolic blood pressure/left ventricular end-systolic volume index ratio alone among all other variables significantly improving the model. Survivors maintain cardiac responsiveness to catecholamine stimulation during septic shock. Survival from severe sepsis or septic shock is associated with increased cardiac performance and contractility indices during dobutamine infusion. Further studies are required to determine whether these parameters are predictive of outcome in a larger severe sepsis/septic shock population.

Particulate and microbial contamination in in-use admixed intravenous infusions.

PubMed

Yorioka, Katsuhiro; Oie, Shigeharu; Oomaki, Masafumi; Imamura, Akihisa; Kamiya, Akira

2006-11-01

We compared particulate and microbial contamination in residual solutions of peripheral intravenous admixtures after the termination of drip infusion between intravenous fluids admixed with glass ampoule drugs and those admixed with pre-filled syringe drugs. The mean number of particles>or=1.3 microm in diameter per 1 ml of residual solution was 758.4 for fluids (n=60) admixed with potassium chloride in a glass ampoule (20 ml volume), 158.6 for fluids (n=63) admixed with potassium chloride in a pre-filled syringe (20 ml volume), 736.5 for fluids (n=66) admixed with sodium chloride in a glass ampoule (20 ml volume), 179.2 for fluids (n=15) admixed with sodium chloride in a pre-filled syringe (20 ml volume), 1884.5 in fluids (n=30) admixed with dobutamine hydrochloride in 3 glass ampoules (5 ml volume), and 178.9 (n=10) in diluted dobutamine hydrochloride in pre-filled syringes (50 ml volume: For these samples alone, particulate and microbial contamination were evaluated in sealed products.) Thus, for potassium chloride or sodium chloride for injection, the number of particles>or=1.3 microm in diameter in the residual intravenous solution was significantly higher for fluids admixed with glass ampoule drugs than for those admixed with pre-filled syringe drugs (p<0.0001). For dobutamine hydrochloride for injection, the number of particles>or=1.3 microm in diameter in the residual intravenous solution was estimated to be higher for fluids admixed with its glass ampoule drug than for those admixed with its pre-filled syringe drug. Observation of the residual solutions of fluids admixed with potassium chloride, sodium chloride, or dobutamine hydrochloride in glass ampoules using an electron microscope with an X-ray analyzer showed glass fragments in each residual solution. Therefore, for the prevention of glass particle contamination in peripheral intravenous admixtures, the use of pre-filled syringe drugs may a useful method. No microbial contamination was observed in any of the residual solutions of 5 types of admixture.

Myocardial Blood Volume Is Associated with Myocardial Oxygen Consumption: An Experimental Study with CMR in a Canine Model

PubMed Central

McCommis, Kyle S.; Zhang, Haosen; Goldstein, Thomas A.; Misselwitz, Bernd; Abendschein, Dana R.; Gropler, Robert J.; Zheng, Jie

2009-01-01

OBJECTIVES To evaluate the feasibility of cardiovascular MR (CMR) to determine regional myocardial perfusion and O2 metabolism, and assess the role of myocardial blood volume (MBV) on oxygen supply. BACKGROUND Coronary artery disease presents as an imbalance of myocardial oxygen supply and demand. We have developed relevant CMR methods to determine the relationship of myocardial blood flow (MBF) and MBV to oxygen consumption (MVO2) during pharmacologic hyperemia. METHODS Twenty-one mongrel dogs were studied with varying stenosis severities imposed on the proximal left anterior descending (LAD) coronary artery. MBF and MBV were determined by CMR first-pass perfusion, while the oxygen extraction fraction (OEF) and MVO2 were determined by the myocardial Blood-Oxygen-Level-Dependent (BOLD) effect and Fick’s law, respectively. MR imaging was performed at rest, and during either dipyridamole-induced vasodilation or dobutamine-induced hyperemia. Regional differences in myocardial perfusion and oxygenation were then evaluated. RESULTS Dipyridamole and dobutamine both led to 145–200% increases in MBF and 50–80% increases in MBV in normal perfused myocardium. As expected, MVO2 increased more significantly with dobutamine (~175%) than dipyridamole (~40%). Coronary stenosis resulted in an attenuation of MBF, MBV, and MVO2 in both the LAD-subtended stenosis region and the left circumflex subtended remote region. Liner regression analysis showed that MBV reserve appears to be more correlated with MVO2 reserve during dobutamine stress than MBF reserve, particularly in the stenotic regions. Conversely, MBF reserve appears to be more correlated with MVO2 reserve during dipyridamole, although neither of these differences was significant. CONCLUSIONS Noninvasive evaluation of both myocardial perfusion and oxygenation by CMR facilitates direct monitoring of regional myocardial ischemia and provides a valuable tool for better understanding microvascular pathophysiology. These techniques could complement delayed enhancement and wall motion analysis protocols, making MRI a valuable “one-stop shop” for imaging of myocardial ischemia. PMID:19909936

Low STAT3 expression sensitizes to toxic effects of β-adrenergic receptor stimulation in peripartum cardiomyopathy

PubMed Central

Stapel, Britta; Kohlhaas, Michael; Ricke-Hoch, Melanie; Haghikia, Arash; Erschow, Sergej; Knuuti, Juhani; Silvola, Johanna M. U.; Roivainen, Anne; Saraste, Antti; Nickel, Alexander G.; Saar, Jasmin A.; Sieve, Irina; Pietzsch, Stefan; Müller, Mirco; Bogeski, Ivan; Kappl, Reinhard; Jauhiainen, Matti; Thackeray, James T.; Scherr, Michaela; Bengel, Frank M.; Hagl, Christian; Tudorache, Igor; Bauersachs, Johann; Maack, Christoph; Hilfiker-Kleiner, Denise

2017-01-01

Abstract Aims The benefit of the β1-adrenergic receptor (β1-AR) agonist dobutamine for treatment of acute heart failure in peripartum cardiomyopathy (PPCM) is controversial. Cardiac STAT3 expression is reduced in PPCM patients. Mice carrying a cardiomyocyte-restricted deletion of STAT3 (CKO) develop PPCM. We hypothesized that STAT3-dependent signalling networks may influence the response to β-AR agonist treatment in PPCM patients and analysed this hypothesis in CKO mice. Methods and results Follow-up analyses in 27 patients with severe PPCM (left ventricular ejection fraction ≤25%) revealed that 19 of 20 patients not obtaining dobutamine improved cardiac function. All seven patients obtaining dobutamine received heart transplantation (n = 4) or left ventricular assist devices (n = 3). They displayed diminished myocardial triglyceride, pyruvate, and lactate content compared with non-failing controls. The β-AR agonist isoproterenol (Iso) induced heart failure with high mortality in postpartum female, in non-pregnant female and in male CKO, but not in wild-type mice. Iso induced heart failure and high mortality in CKO mice by impairing fatty acid and glucose uptake, thereby generating a metabolic deficit. The latter was governed by disturbed STAT3-dependent signalling networks, microRNA-199a-5p, microRNA-7a-5p, insulin/glucose transporter-4, and neuregulin/ErbB signalling. The resulting cardiac energy depletion and oxidative stress promoted dysfunction and cardiomyocyte loss inducing irreversible heart failure, which could be attenuated by the β1-AR blocker metoprolol or glucose-uptake-promoting drugs perhexiline and etomoxir. Conclusions Iso impairs glucose uptake, induces energy depletion, oxidative stress, dysfunction, and death in STAT3-deficient cardiomyocytes mainly via β1-AR stimulation. These cellular alterations may underlie the dobutamine-induced irreversible heart failure progression in PPCM patients who frequently display reduced cardiac STAT3 expression. PMID:28201733

Right ventricular dysfunction in the R6/2 transgenic mouse model of Huntington's disease is unmasked by dobutamine.

PubMed

Buonincontri, Guido; Wood, Nigel I; Puttick, Simon G; Ward, Alex O; Carpenter, T Adrian; Sawiak, Stephen J; Morton, A Jennifer

2014-01-01

Increasingly, evidence from studies in both animal models and patients suggests that cardiovascular dysfunction is important in HD. Previous studies measuring function of the left ventricle (LV) in the R6/2 model have found a clear cardiac abnormality, albeit with preserved LV systolic function. It was hypothesized that an impairment of RV function might play a role in this condition via mechanisms of ventricular interdependence. To investigate RV function in the R6/2 mouse model of Huntington's disease (HD). Cardiac cine-magnetic resonance imaging (MRI) was used to determine functional parameters in R6/2 mice. In a first experiment, these parameters were derived longitudinally to determine deterioration of cardiac function with disease progression. A second experiment compared the response to a stress test (using dobutamine) of wildtype and early-symptomatic R6/2 mice. There was progressive deterioration of RV systolic function with age in R6/2 mice. Furthermore, beta-adrenergic stimulation with dobutamine revealed RV dysfunction in R6/2 mice before any overt symptoms of the disease were apparent. This work adds to accumulating evidence of cardiovascular dysfunction in R6/2 mice, describing for the first time the involvement of the right ventricle. Cardiovascular dysfunction should be considered, both when treatment strategies are being designed, and when searching for biomarkers for HD.

Doppler ultrasonography and single-fiber laser Doppler flowmetry for measurement of hind limb blood flow in anesthetized horses.

PubMed

Raisis, A L; Young, L E; Taylor, P M; Walsh, K P; Lekeux, P

2000-03-01

To use Doppler ultrasonography and single-fiber laser Doppler flowmetry (LDF) to evaluate blood flow in the dependent and nondependent hind limbs of anesthetized horses and to evaluate changes in femoral arterial blood flow and microvascular skeletal muscle perfusion in response to administration of phenylephrine hydrochloride or dobutamine hydrochloride. 6 healthy adult horses. Horses were anesthetized and positioned in left lateral recumbency. Doppler ultrasonography was used to measure velocity and volumetric flow in the femoral vessels. Single-fiber LDF was used to measure relative microvascular perfusion at a single site in the semimembranosus muscles. Phenylephrine or dobutamine was then administered to decrease or increase femoral arterial blood flow, and changes in blood flow and microvascular perfusion were recorded. Administration of phenylephrine resulted in significant decreases in femoral arterial and venous blood flows and cardiac output and significant increases in mean aortic blood pressure, systemic vascular resistance, and PCV. Administration of dobutamine resulted in significant increases in femoral arterial blood flow, mean aortic blood pressure, and PCV. Significant changes in microvascular perfusion were not detected. Results suggest that Doppler ultrasonography and single-fiber LDF can be used to study blood flows in the hind limbs of anesthetized horses. However, further studies are required to determine why changes in femoral arterial blood flows were not associated with changes in microvascular perfusion.

Roles of myocardial blood volume and flow in coronary artery disease: an experimental MRI study at rest and during hyperemia

PubMed Central

McCommis, Kyle S.; Goldstein, Thomas A.; Abendschein, Dana R.; Misselwitz, Bernd; Pilgram, Thomas; Gropler, Robert J.

2010-01-01

Objective To validate fast perfusion mapping techniques in a setting of coronary artery stenosis, and to further assess the relationship of absolute myocardial blood volume (MBV) and blood flow (MBF) to global myocardial oxygen demand. Methods A group of 27 mongrel dogs were divided into 10 controls and 17 with acute coronary stenosis. On 1.5-T MRI, first-pass perfusion imaging with a bolus injection of a blood-pool contrast agent was performed to determine myocardial perfusion both at rest and during either dipyridamole-induced vasodilation or dobutamine-induced stress. Regional values of MBF and MBV were quantified by using a fast mapping technique. Color microspheres and 99mTc-labeled red blood cells were injected to obtain respective gold standards. Results Microsphere-measured MBF and 99mTc-measured MBV reference values correlated well with the MR results. Given the same changes in MBF, changes in MBV are twofold greater with dobutamine than with dipyridamole. Under dobutamine stress, MBV shows better association with total myocardial oxygen demand than MBF. Coronary stenosis progressively reduced this association in the presence of increased stenosis severity. Conclusions MR first-pass perfusion can rapidly estimate regional MBF and MBV. Absolute quantification of MBV may add additional information on stenosis severity and myocardial viability compared with standard qualitative clinical evaluations of myocardial perfusion. PMID:20182731

[Dobutamine stress magnetic resonance imaging (DS-MRI), a valuable tool for the diagnosis of ischemic heart disease].

PubMed

van Dijkman, P R M; Kuijpers, Th J A; Blom, B M; van Herpen, G

2002-07-13

Assessment of the clinical applicability of DS-MRI for the detection of myocardial ischemia and myocardial viability. Prospective. In the period from 1 November 1999 to 31 October 2000, patients with suspected coronary artery disease who could not be studied by means of conventional bicycle ergometry underwent breath-hold DS-MRI (1 Tesla) 4 days after cessation of anti-ischemic medication. Three left ventricular short-axis planes were examined for the occurrence of disorders in wall movement during infusion of increasing doses of dobutamine (10, 20, 30 and 40 micrograms/kg/min). Temporary recovery of wall thickening in a previously diminished or non-contracting segment under 5 micrograms/kg/min of dobutamine was considered proof of viability. Development of hypo-, a- or dyskinesia at higher doses of dobutamine was taken to indicate ischemia. If the DS-MRI test was positive for ischemia, coronary angiography was performed. If indicated, this was followed by revascularisation. If DS-MRI did not reveal ischemia, the patient was seen at the outpatient department. Of the 100 patients (62 men and 38 women with an average age of 62 years, SD = 12) subjected to DS-MRI, 95 yielded results that were suitable for diagnosis. Of the 42 patients with DS-MRI scans that were considered positive for ischemia and in whom coronary angiography was subsequently performed, 41 had such coronary abnormalities that revascularisation was indicated. One patient was false-positive. All 53 patients with non-ischemic DS-MRI scans were followed-up for 11-23 months (mean 17 months). One patient died suddenly 2 weeks after the MRI-test. The other 52 patients did not experience any coronary events nor sudden cardiac death. The predictive value of a positive DS-MRI scan for ischemia was 98% and the predictive value of a negative DS-MRI scan was also 98%. DS-MRI is a safe diagnostic method for the detection or exclusion of myocardial ischemia and viability in patients with suspected coronary artery disease.

Use of Dobutamine Stress Echocardiography for Periprocedural Evaluation of a Case of Critical Valvular Pulmonary Stenosis with Delayed Presentation.

PubMed

Barik, Ramachandra; Akula, Siva Prasad; Damera, Sheshagiri Rao

2016-01-01

We report a case illustrating a 39-year-old man with delayed presentation of severe pulmonary valve (PV) stenosis, clinical evidence of congestive right heart failure in the form of enlarged liver, raised jugular venous pressure, and anasarca without cyanosis. Echocardiography (echo) was used both for diagnosis and monitoring this patient as main tool. The contractile reserve of the right ventricle (RV) was evaluated by infusion of dobutamine and diuretic for 4 days before pulmonary balloon valvotomy. Both the tricuspid annular peak systolic excursion and diastolic (diastolic anterograde flow through PV) function of RV improved after percutaneous balloon pulmonary valvotomy. These improvements were clinically apparent by complete resolution of anasarca, pericardial effusion, and normalization albumin-globulin ratio. The periprocedural echo findings were quite unique in this illustration.

Use of Dobutamine Stress Echocardiography for Periprocedural Evaluation of a Case of Critical Valvular Pulmonary Stenosis with Delayed Presentation

PubMed Central

Barik, Ramachandra; Akula, Siva Prasad; Damera, Sheshagiri Rao

2016-01-01

We report a case illustrating a 39-year-old man with delayed presentation of severe pulmonary valve (PV) stenosis, clinical evidence of congestive right heart failure in the form of enlarged liver, raised jugular venous pressure, and anasarca without cyanosis. Echocardiography (echo) was used both for diagnosis and monitoring this patient as main tool. The contractile reserve of the right ventricle (RV) was evaluated by infusion of dobutamine and diuretic for 4 days before pulmonary balloon valvotomy. Both the tricuspid annular peak systolic excursion and diastolic (diastolic anterograde flow through PV) function of RV improved after percutaneous balloon pulmonary valvotomy. These improvements were clinically apparent by complete resolution of anasarca, pericardial effusion, and normalization albumin-globulin ratio. The periprocedural echo findings were quite unique in this illustration. PMID:28465962

Immediate flow reserve of Y thoracic artery grafts: an intraoperative flowmetric study.

PubMed

Gaudino, Mario; Di Mauro, Michele; Iacò, Angela Lorena; Canosa, Carlo; Vitolla, Giuseppe; Calafiore, Antonio Maria

2003-10-01

Use of both internal thoracic arteries in a Y graft configuration can raise concerns about the possibility of the single left internal thoracic artery being able to meet the flow requirements of two or three distal territories. We evaluated intraoperatively the flow reserve of a Y thoracic artery graft distally anastomosed to the anterior and lateral territories. In 21 patients who had Y thoracic artery grafts, the flow was measured in the main stem of the left internal thoracic artery, in the left internal thoracic artery branch, and in the right internal thoracic artery. A transit time Doppler flowmeter was used. Measurements were repeated after the injection of a bolus of 20 mug/kg dobutamine. At baseline condition, the mean blood flow was 44.8 +/- 24.2, 23.4 +/- 11.5, and 21.4 +/- 15.3 mL/min in the main stem of the left internal thoracic artery, in the left internal thoracic artery branch, and in the right internal thoracic artery, respectively. After dobutamine injection, these values increased to 93.2 +/- 49.8, 46.1 +/- 22.6, and 42.5 +/- 31.2 mL/min, respectively. Flow reserve was 2.1 +/- 0.6, 2.2 +/- 0.9, and 2.1 +/- 0.9 mL/min, respectively. Intraoperative injection of dobutamine increases the flow in the Y thoracic graft by more than two times, not only in the main stem but also in each branch. This finding attests to the safety of Y thoracic conduits in terms of hemodynamic potential.

A Case of Refractory Heart Failure in Becker Muscular Dystrophy Improved With Corticosteroid Therapy.

PubMed

Nakamura, Makiko; Sunagawa, Osahiko; Hokama, Ryo; Tsuchiya, Hiroyuki; Miyara, Takafumi; Taba, Yoji; Touma, Takashi

2016-09-28

The patient was a 26 year-old man who was referred to our hospital in June 2011 because of severe heart failure. At age 24 years, he was found to have Becker muscular dystrophy. He received enalapril for cardiac dysfunction; however, he had worsening heart failure and was thus referred to our hospital. Echocardiography showed enlargement of the left ventricle, with a diastolic dimension of 77 mm and ejection fraction of 19%. His condition improved temporarily after an infusion of dobutamine and milrinone. He was then administered amiodarone for ventricular tachycardia; however, he subsequently developed hemoptysis. Amiodarone was discontinued and corticosteroid pulse therapy was administered followed by oral prednisolone (PSL). His creatinine phosphokinase (CPK) level and cardiomegaly improved after the corticosteroid therapy. The PSL dose was reduced gradually, bisoprolol was introduced, and the catecholamine infusion was tapered. A cardiac resynchronization device was implanted; however, the patient's condition gradually worsened, which necessitated dobutamine infusion for heart failure. We readministered 30 mg PSL, which decreased the CPK level and improved the cardiomegaly. The dobutamine infusion was discontinued, and the patient was discharged. He was given 7.5 mg PSL as an outpatient, and he returned to normal life without exacerbation of the heart failure. There are similar reports showing that corticosteroids are effective for skeletal muscle improvement in Duchenne muscular dystrophy; however, their effectiveness for heart failure has been rarely reported. We experienced a case of Becker muscular dystrophy in which corticosteroid therapy was effective for refractory heart failure.

The contributions of cardiac myosin binding protein C and troponin I phosphorylation to β‐adrenergic enhancement of in vivo cardiac function

PubMed Central

Gresham, Kenneth S.

2016-01-01

Key points β‐adrenergic stimulation increases cardiac myosin binding protein C (MyBP‐C) and troponin I phosphorylation to accelerate pressure development and relaxation in vivo, although their relative contributions remain unknown.Using a novel mouse model lacking protein kinase A‐phosphorylatable troponin I (TnI) and MyBP‐C, we examined in vivo haemodynamic function before and after infusion of the β‐agonist dobutamine.Mice expressing phospho‐ablated MyBP‐C displayed cardiac hypertrophy and prevented full acceleration of pressure development and relaxation in response to dobutamine, whereas expression of phosphor‐ablated TnI alone had little effect on the acceleration of contractile function in response to dobutamine.Our data demonstrate that MyBP‐C phosphorylation is the principal mediator of the contractile response to increased β‐agonist stimulation in vivo.These results help us understand why MyBP‐C dephosphorylation in the failing heart contributes to contractile dysfunction and decreased adrenergic reserve in response to acute stress. Abstract β‐adrenergic stimulation plays a critical role in accelerating ventricular contraction and speeding relaxation to match cardiac output to changing circulatory demands. Two key myofilaments proteins, troponin I (TnI) and myosin binding protein‐C (MyBP‐C), are phosphorylated following β‐adrenergic stimulation; however, their relative contributions to the enhancement of in vivo cardiac contractility are unknown. To examine the roles of TnI and MyBP‐C phosphorylation in β‐adrenergic‐mediated enhancement of cardiac function, transgenic (TG) mice expressing non‐phosphorylatable TnI protein kinase A (PKA) residues (i.e. serine to alanine substitution at Ser23/24; TnIPKA−) were bred with mice expressing non‐phosphorylatable MyBP‐C PKA residues (i.e. serine to alanine substitution at Ser273, Ser282 and Ser302; MyBPCPKA−) to generate a novel mouse model expressing non‐phosphorylatable PKA residues in TnI and MyBP‐C (DBLPKA−). MyBP‐C dephosphorylation produced cardiac hypertrophy and increased wall thickness in MyBPCPKA− and DBLPKA− mice, and in vivo echocardiography and pressure–volume catheterization studies revealed impaired systolic function and prolonged diastolic relaxation compared to wild‐type and TnIPKA– mice. Infusion of the β‐agonist dobutamine resulted in accelerated rates of pressure development and relaxation in all mice; however, MyBPCPKA− and DBLPKA− mice displayed a blunted contractile response compared to wild‐type and TnIPKA– mice. Furthermore, unanaesthesized MyBPCPKA− and DBLPKA− mice displayed depressed maximum systolic pressure in response to dobutamine as measured using implantable telemetry devices. Taken together, our data show that MyBP‐C phosphorylation is a critical modulator of the in vivo acceleration of pressure development and relaxation as a result of enhanced β‐adrenergic stimulation, and reduced MyBP‐C phosphorylation may underlie depressed adrenergic reserve in heart failure. PMID:26635197

Assessment of myocardial viability: comparison of echocardiography versus cardiac magnetic resonance imaging in the current era.

PubMed

Tomlinson, David R; Becher, Harald; Selvanayagam, Joseph B

2008-06-01

Detecting viable myocardium, whether hibernating or stunned, is of clinical significance in patients with coronary artery disease and left ventricular dysfunction. Echocardiographic assessments of myocardial thickening and endocardial excursion during dobutamine infusion provide a highly specific marker for myocardial viability, but with relatively less sensitivity. The additional modalities of myocardial contrast echocardiography and tissue Doppler have recently been proposed to provide further, quantitative measures of myocardial viability assessment. Cardiac magnetic resonance (CMR) has become popular for the assessment of myocardial viability as it can assess cardiac function, volumes, myocardial scar, and perfusion with high-spatial resolution. Both 'delayed enhancement' CMR and dobutamine stress CMR have important roles in the assessment of patients with ischaemic cardiomyopathy. This article reviews the recent advances in both echocardiography and CMR for the clinical assessment of myocardial viability. It attempts to provide a pragmatic approach toward the patient-specific assessment of this important clinical problem.

Alteration of Left Ventricular Function with Dobutamine Challenge in Patients with Myocardial Bridge

PubMed Central

Jhi, Joon-Hyung; Ha, Jong-kun; Jung, Chan-Woo; kim, Bong-Jae; Park, Seong-Oh; Jo, A-Ra; Kim, Seong-Man; Lee, Hyeon-Gook; Kim, Tae-Ik

2011-01-01

Background/Aims The aim of this study was to identify changes in left ventricular (LV) performance in patients with a myocardial bridge (MB) in the left anterior descending coronary artery during resting and in an inotropic state. Methods Myocardial strain measurement by speckle-tracking echocardiography and conventional LV wall-motion scoring was performed in 18 patients with MB (mean age, 48.1 ± 1.7 years, eight female) during resting and intravenous dobutamine challenge (10 and 20 µg/kg/min). Results Conventional LV wall-motion scoring was normal in all patients during resting and in an inotropic state. Peak regional circumferential strain increased dose dependently upon dobutamine challenge. Longitudinal strains of the anterior and anteroseptal segments were, however, reduced at 20 µg/kg/min and showed a dyssynchronous pattern at 20 µg/kg/min. Although there were no significant differences in radial strain and displacement of all segments at rest compared with under 10 µg/kg/min challenge, radial strain and displacement of anterior segments at 20 µg/kg/min were significantly reduced compared with posterior segments at the papillary muscle level (44.8 ± 14.9% vs. 78.4 ± 20.1% and 5.3 ± 2.3 mm vs. 8.5 ± 1.8 mm, respectively; all p < 0.001), and showed plateau (40%) or biphasic (62%) patterns. Conclusions Reduced LV strain of patients with MB after inotropic stimulation was identified. Speckle-tracking strain echocardiography identified a LV myocardial dyssynchrony that was not demonstrated by conventional echocardiography in patients with MB. PMID:22205841

Near-infrared spectroscopy during stagnant ischemia estimates central venous oxygen saturation and mixed venous oxygen saturation discrepancy in patients with severe left heart failure and additional sepsis/septic shock.

PubMed

Mozina, Hugo; Podbregar, Matej

2010-01-01

Discrepancies of 5-24% between superior vena cava oxygen saturation (ScvO2) and mixed venous oxygen saturation (SvO2) have been reported in patients with severe heart failure. Thenar muscle tissue oxygenation (StO2) measured with near-infrared spectroscopy (NIRS) during arterial occlusion testing decreases slower in sepsis/septic shock patients (lower StO2 deoxygenation rate). The StO2 deoxygenation rate is influenced by dobutamine. The aim of this study was to determine the relationship between the StO2 deoxygenation rate and the ScvO2-SvO2 discrepancy in patients with severe left heart failure and additional sepsis/septic shock treated with or without dobutamine. Fifty-two patients with severe left heart failure due to primary heart disease with additional severe sepsis/septic shock were included. SvO2 and ScvO2 were compared to the thenar muscle StO2 before and during arterial occlusion. SvO2 correlated significantly with ScvO2 (Pearson correlation 0.659, P = 0.001), however, Bland Altman analysis showed a clinically important difference between both variables (ScvO2-SvO2 mean 72 +/- 8%, ScvO2-SvO2 difference 9.4 +/- 7.5%). The ScvO2-SvO2 difference correlated with plasma lactate (Pearson correlation 0.400, P = 0.003) and the StO2 deoxygenation rate (Pearson correlation 0.651, P = 0.001). In the group of patients treated with dobutamine, the ScvO2-SvO2 difference correlated with plasma lactate (Pearson correlation 0.389, P = 0.011) and the StO2 deoxygenation rate (Pearson correlation 0.777, P = 0.0001). In patients with severe heart failure with additional severe sepsis/septic shock the ScvO2-SvO2 discrepancy presents a clinical problem. In these patients the skeletal muscle StO2 deoxygenation rate is inversely proportional to the difference between ScvO2 and SvO2; dobutamine does not influence this relationship. When using ScvO2 as a treatment goal, the NIRS measurement may prove to be a useful non-invasive diagnostic test to uncover patients with a normal ScvO2 but potentially an abnormally low SvO2. NCT00384644 ClinicalTrials.Gov.

Diabetes as an independent predictor of left ventricular longitudinal strain reduction at rest and during dobutamine stress test in patients with significant coronary artery disease.

PubMed

Wierzbowska-Drabik, Karina; Trzos, Ewa; Kurpesa, Malgorzata; Rechcinski, Tomasz; Miskowiec, Dawid; Cieslik-Guerra, Urszula; Uznanska-Loch, Barbara; Sobczak, Maria; Kasprzak, Jaroslaw Damian

2017-12-09

Diabetes (DM) is a strong cardiovascular risk factor modifying also the left ventricular (LV) function that may be objectively assessed with echocardiographic strain analysis. Although the impact of isolated DM on myocardial deformation has been already studied, few data concern diabetics with coronary artery disease (CAD), especially in all stages of dobutamine stress echocardiography (DSE). We compared LV systolic function during DSE in CAD with and without DM using state-of-the art speckle-tracking quantification and assessed the impact of DM on LV systolic strain. DSE was performed in 250 patients with angina who afterwards had coronarography with ≥50% stenosis in the left main artery and ≥70% in other arteries considered as significant. In this analysis, we included 127 patients with confirmed CAD: 42 with DM [DM(+); mean age 64 ± 9 years] and 85 patients without DM [DM(-); mean age 63 ± 9 years]. The severity of CAD and LV ejection fraction (EF) were similar in both groups. Global and regional LV peak systolic longitudinal strain (PSLS) revealed in all DSE phases lower values in DM(+) group: 14.5 ± 3.6% vs. 17.4 ± 4.0% at rest; P = 0.0001, 13.8 ± 3.9% vs. 16.7 ± 4.0% at peak stress; P = 0.0002, and 14.2 ± 3.1% vs. 15.5 ± 3.5% at recovery; P = 0.0432 for global parameters, although dobutamine challenge did not enhance further resting differences. LV EF, body surface area, and diabetes were independent predictors for strain in 16-variable model (R2 = 0, 51, P < 0.001). PSLS although diminished in both groups with CAD was lower in diabetics at all DSE stages, and DM was an independent predictor of this impairment. However, the dobutamine challenge did not deepen the resting differences, suggesting that the direct impact of coronary stenoses effaces the influence of DM during DSE. The comparison with our previous data revealed synergistic, detrimental effect of coexisting CAD and DM on myocardial strain. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2017. For permissions, please email: journals.permissions@oup.com.

76 FR 33310 - Bristol-Myers Squibb Co. et al.; Withdrawal of Approval of 70 New Drug Applications and 97...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-06-08

..., Inc. ANDA 074634 Dobutamine Injection Hospira, Inc. USP, 12.5 mg/mL. ANDA 074643 Minoxidil Topical Bausch & Lomb, Inc. Solution, 2%. ANDA 074743 Minoxidil Topical Sight Solution, 2%. Pharmaceuticals, Inc...

Enhanced pulmonary vasodilator reserve and abnormal right ventricular: pulmonary artery coupling in heart failure with preserved ejection fraction.

PubMed

Andersen, Mads J; Hwang, Seok-Jae; Kane, Garvan C; Melenovsky, Vojtech; Olson, Thomas P; Fetterly, Kenneth; Borlaug, Barry A

2015-05-01

Pulmonary hypertension and right ventricular (RV) dysfunction are common in patients with advanced heart failure with preserved ejection fraction (HFpEF), yet their underlying mechanisms remain poorly understood. We sought to examine RV-pulmonary artery (PA) functional reserve responses and RV-PA coupling at rest and during β-adrenergic stimulation in subjects with earlier stage HFpEF. In a prospective trial, subjects with HFpEF (n=39) and controls (n=18) underwent comprehensive invasive and noninvasive hemodynamic assessment using high fidelity micromanometer catheters, echocardiography, and expired gas analysis at rest and during dobutamine infusion. HFpEF subjects displayed similar RV structure but significantly impaired RV systolic (lower RV dP/dtmax/IP and s') and diastolic function (higher RV τ) coupled with more severe pulmonary vascular disease, manifest by higher PA pressures, higher PA resistance, and lower PA compliance compared with controls. Dobutamine infusion caused greater pulmonary vasodilation in HFpEF compared with controls, with enhanced reductions in PA resistance, greater increase in PA compliance, and a more negative slope in the PA pressure-flow relationship when compared with controls (all P<0.001). RV-PA coupling analysis revealed that dobutamine improved RV ejection in HFpEF subjects through afterload reduction alone, rather than through enhanced contractility, indicating RV systolic reserve dysfunction. Pulmonary hypertension in early stage HFpEF is related to partially reversible pulmonary vasoconstriction coupled with RV systolic and diastolic dysfunction, even in the absence of RV structural remodeling. Pulmonary vascular tone is more favorably responsive to β-adrenergic stimulation in HFpEF than controls, suggesting a potential role for β-agonists in the treatment of patients with HFpEF and pulmonary hypertension. URL: http://www.clinicaltrials.gov. Unique identifier: NCT01418248. © 2015 American Heart Association, Inc.

Does the prognostic value of dobutamine stress echocardiography differ among different age groups?

PubMed

Bernheim, Alain M; Kittipovanonth, Maytinee; Takahashi, Paul Y; Gharacholou, S Michael; Scott, Christopher G; Pellikka, Patricia A

2011-04-01

Age is associated with reduced exercise capacity and greater prevalence of coronary artery disease. Whether the prognostic information obtained from dobutamine stress echocardiography (DSE), a stress test commonly used for patients unable to perform an exercise test, provides differential information based on age is not well known. We studied 6,655 consecutive patients referred for DSE. Patients were divided into 3 age groups: (1) <60 years (n = 1,389), (2) 60 to 74 years (n = 2,978), and (3) ≥75 years (n = 2,288). Mean follow-up was 5.5 ± 2.8 years. End points included all-cause mortality and cardiac events, including myocardial infarction and late (>3 months) coronary revascularization. Peak stress wall motion score index was an independent predictor of cardiac events in all age groups (<60 years: hazard ratio [HR] 1.14, P = .02; 60-74 years: HR 1.70, P < .0001; ≥75 years: HR 1.10, P = .006). In patients ≥75 years, peak wall motion score index (HR 1.10, P < .0001) and abnormal left ventricular end-systolic volume response (HR 1.25, P = .03) were independent predictors of death. In patients aged 60 to 74 years, abnormal left ventricular end-systolic volume response (HR 1.43, P = .0003) was independently related to death, whereas in patients <60 years, the echocardiographic data assessed during stress were not a predictor. Dobutamine stress echocardiography provided independent information predictive of cardiac events among all age groups and death in patients ≥60 years. However, among patients <60 years, stress-induced echocardiographic abnormalities were not independently associated with mortality. Comorbidities, which have precluded exercise testing, may be most relevant in predicting mortality in patients <60 years undergoing DSE. Copyright © 2011 Mosby, Inc. All rights reserved.

Dose-Response Head-to-Head Comparison of Inodilators Dobutamine, Milrinone, and Levosimendan in Chronic Experimental Pulmonary Hypertension.

PubMed

Tavares-Silva, Marta; Alaa, Mohamed; Leite, Sara; Oliveira-Pinto, José; Lopes, Lucas; Leite-Moreira, Adelino F; Lourenço, André P

2017-09-01

The choice of inodilator drug in the acute management of patients with pulmonary hypertension (PH) having right ventricular (RV) failure remains unsettled and challenging. Comprehensive experimental evaluations may provide further insight and fundamental translational research clues to support inodilator selection and clinical trial design. Our aim was to compare acute dose-response hemodynamic effects of inodilators dobutamine (DOB), milrinone (MIL), and levosimendan (LEV) in chronic experimental PH. Seven-week-old male Wistar rats were randomly injected with 60 mg·kg -1 monocrotaline (MCT) or vehicle (Ctrl, n = 7) and underwent systemic and pulmonary artery (PA) pressure and RV pressure-volume (PV) hemodynamic evaluation under halogenate anesthesia 24 to 30 days after injection. The MCT-injected animals (n = 7 each) randomly received dose-response infusions of DOB (1, 3, 6 and 12 μg·kg -1 ·min -1 ), MIL (MIL: 1, 3, 6 and 12 μg·kg -1 ·min -1 ), or LEV (0.3, 0.6, 1.2 and 2.4 μg·kg -1 ·min -1 ). Load-independent indexes were obtained by inferior vena cava occlusion at baseline and after the last dose. All inodilators increased RV ejection fraction, preload recruitable stroke work, and ventricular-vascular coupling without jeopardizing perfusion pressure. Dobutamine raised heart rate and PA pressure. Only LEV increased cardiac index and decreased PA elastance and pulmonary vascular resistance (PVR). Moreover, only LEV downward-shifted the end-diastolic PV relationship, thereby improving RV compliance. Adding sildenafil to LEV further decreased PVR. Levosimendan had beneficial acute systolic and diastolic functional effects in experimental chronic PH and RV afterload compared to DOB and MIL. It should be further tested in clinical trials enrolling patients with PH in the perioperative and critical care settings.

Effects of commonly used inotropes on myocardial function and oxygen consumption under constant ventricular loading conditions

PubMed Central

DeWitt, Elizabeth S.; Black, Katherine J.; Thiagarajan, Ravi R.; DiNardo, James A.; Colan, Steven D.; McGowan, Francis X.

2016-01-01

Inotropic medications are routinely used to increase cardiac output and arterial blood pressure during critical illness. However, few comparative data exist between these medications, particularly independent of their effects on venous capacitance and systemic vascular resistance. We hypothesized that an isolated working heart model that maintained constant left atrial pressure and aortic blood pressure could identify load-independent differences between inotropic medications. In an isolated heart preparation, the aorta and left atrium of Sprague Dawley rats were cannulated and placed in working mode with fixed left atrial and aortic pressure. Hearts were then exposed to common doses of a catecholamine (dopamine, epinephrine, norepinephrine, or dobutamine), milrinone, or triiodothyronine (n = 10 per dose per combination). Cardiac output, contractility (dP/dtmax), diastolic performance (dP/dtmin and tau), stroke work, heart rate, and myocardial oxygen consumption were compared during each 10-min infusion to an immediately preceding baseline. Of the catecholamines, dobutamine increased cardiac output, contractility, and diastolic performance more than clinically equivalent doses of norepinephrine (second most potent), dopamine, or epinephrine (P < 0.001). The use of triiodothyronine and milrinone was not associated with significant changes in cardiac output, contractility or diastolic function, either alone or added to a baseline catecholamine infusion. Myocardial oxygen consumption was closely related to dP/dtmax (r2 = 0.72), dP/dtmin (r2 = 0.70), and stroke work (r2 = 0.53). In uninjured, isolated working rodent hearts under constant ventricular loading conditions, dobutamine increased contractility and cardiac output more than clinically equivalent doses of norepinephrine, dopamine, and epinephrine; milrinone and triiodothyronine did not have significant effects on contractility. PMID:27150829

Dobutamine stress myocardial perfusion imaging: 8-year outcomes in patients with diabetes mellitus.

PubMed

Boiten, Hendrik J; van Domburg, Ron T; Valkema, Roelf; Zijlstra, Felix; Schinkel, Arend F L

2016-08-01

Many studies have examined the prognostic value of myocardial perfusion imaging (MPI) using single-photon emission computed tomography (SPECT) for the prediction of short- to medium-term outcomes. However, the long-term prognostic value of MPI in patients with diabetes mellitus remains unclear. Therefore, this study assessed the long-term prognostic value of MPI in a high-risk cohort of patients with diabetes mellitus. A high-risk cohort of 207 patients with diabetes mellitus who were unable to undergo exercise testing underwent dobutamine stress MPI. Follow-up was successful in 206 patients; 12 patients were excluded due to early revascularization. The current data are based on the remaining 194 patients. Follow-up end points were all-cause mortality, cardiac mortality, and nonfatal myocardial infarction. The Kaplan-Meier survival curves were constructed, and univariable and multivariable analyses were performed to identify predictors of long-term outcome. During a mean follow-up of 8.1 ± 5.9 years, 134 (69%) patients died of which 68 (35%) died due to cardiac causes. Nonfatal myocardial infarction occurred in 24 patients (12%), and late (>60 days) coronary revascularization was performed in 61 (13%) patients. Survival analysis showed that MPI provided optimal risk stratification up to 4 years after testing. After that period, the outcome was comparable in patients with normal and abnormal MPI. Multivariable analyses showed that MPI provided incremental prognostic value up to 4 years after testing. In high-risk patients with diabetes mellitus, dobutamine MPI provides incremental prognostic information in addition to clinical data for a 4-year period after testing. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2016. For permissions please email: journals.permissions@oup.com.

Dobutamine Cardiac “Stress” Test in the Rat: Strain Comparison and Potential Utility in Cardiovascular Toxicity Studies

EPA Science Inventory

The American Heart Association recommends elecardiogram (ECG) exercise testing as the first choice for patients with medium risk of coronary heart disease. The objective is to stress patients with mild to moderate exercise, which increases HR and contractility, and monitor them f...

Dobutamine "stress" test and latent cardiac susceptibility to inhaled diesel exhaust in normal and hypertensive rats**

EPA Science Inventory

Background -Exercise "stress" testing is a screening tool used to determine the amount of stress for which the heart can compensate before developing abnormal rhythm or ischemia, particularly in susceptible people. Although this approach has been used to assess risk in humans exp...

High-dose catecholamine treatment decreases polymorphonuclear leukocyte phagocytic capacity and reactive oxygen production.

PubMed Central

Wenisch, C; Parschalk, B; Weiss, A; Zedwitz-Liebenstein, K; Hahsler, B; Wenisch, H; Georgopoulos, A; Graninger, W

1996-01-01

Flow cytometry was used to study phagocytic function (uptake of fluorescein isothiocyanate-labeled bacteria) and release of reactive oxygen products (dihydrorhodamine 123 converted to rhodamine 123) following phagocytosis by neutrophil granulocytes of heparinized whole blood treated with adrenaline, noradrenaline, dopamine, dobutamine, or orciprenaline. Reduced neutrophil phagocytosis and reactive oxygen production were seen at 12 micrograms of adrenaline per liter (72% each compared with control values); at 120 micrograms of noradrenaline (72% each), dobutamine (83 and 80%, respectively), and orciprenaline (81 and 80%, respectively) per liter; and at 100 micrograms of dopamine per liter (66 and 70%) (P < 0.05 for all). At these dosages, neutrophil chemotaxis was reduced to < 50% of control values for all catecholamines. Treatment with catecholamines at lower dosages had no significant effect on phagocytosis or generation of reactive oxygen products or chemotaxis. The phagocytic capacity of granulocytes was related to the generation of reactive oxygen products (r = 0.789; P < 0.05). The results demonstrate that catecholamines have a suppressive effect on the response of phagocytic cells to bacterial pathogens at high therapeutic levels in blood. PMID:8807207

Effects of a prostagrandin EP4-receptor agonist ONO-AE1-329 on the left ventricular pressure-volume relationship in the halothane-anesthetized dogs.

PubMed

Honda, Atsushi; Nakamura, Yuji; Ohara, Hiroshi; Cao, Xin; Nomura, Hiroaki; Katagi, Jun; Wada, Takeshi; Izumi-Nakaseko, Hiroko; Ando, Kentaro; Sugiyama, Atsushi

2016-03-15

Cardiac effects of a prostagrandin EP4-receptor agonist ONO-AE1-329 were assessed in the halothane-anesthetized dogs under the monitoring of left ventricular pressure-volume relationship, which were compared with those of clinically recommended doses of dopamine, dobutamine and milrinone (n=4-5 for each treatment). ONO-AE1-329 was intravenously administered in doses of 0.3, 1 and 3 ng/kg/min for 10 min with a pause of 20 min. Dopamine in a dose of 3 µg/kg/min for 10 min, dobutamine in a dose of 1 µg/kg/min for 10 min and milrinone in a dose of 5 µg/kg/min for 10 min followed by 0.5 µg/kg/min for 10 min were intravenously administered. Low dose of ONO-AE1-329 increased the stroke volume. Middle dose of ONO-AE1-329 increased the cardiac output, left ventricular end-diastolic volume, ejection fraction, maximum upstroke/downstroke velocities of the left ventricular pressure and external work, but decreased the end-systolic pressure and internal work besides the change by the low dose. High dose of ONO-AE1-329 increased the heart rate and maximum elastance, but decreased the end-systolic volume besides the changes by the middle dose. Dopamine, dobutamine and milrinone exerted essentially similar cardiac effects to ONO-AE1-329, but they did not significantly change the end-diastolic volume, end-systolic volume, stroke volume, ejection fraction, end-systolic pressure, maximum elastance, external work or internal work. Thus, EP4-receptor stimulation by ONO-AE1-329 may have potential to better promote the passive ventricular filling than the conventional cardiotonic drugs, which could become a candidate of novel therapeutic strategy for the treatment of heart failure with preserved ejection fraction. Copyright © 2016 Elsevier B.V. All rights reserved.

SvO(2)-guided resuscitation for experimental septic shock: effects of fluid infusion and dobutamine on hemodynamics, inflammatory response, and cardiovascular oxidative stress.

PubMed

Rosário, André Loureiro; Park, Marcelo; Brunialti, Milena Karina; Mendes, Marialice; Rapozo, Marjorie; Fernandes, Denise; Salomão, Reinaldo; Laurindo, Francisco Rafael; Schettino, Guilherme Paula; Azevedo, Luciano Cesar P

2011-12-01

The pathogenetic mechanisms associated to the beneficial effects of mixed venous oxygen saturation (SvO(2))-guided resuscitation during sepsis are unclear. Our purpose was to evaluate the effects of an algorithm of SvO(2)-driven resuscitation including fluids, norepinephrine and dobutamine on hemodynamics, inflammatory response, and cardiovascular oxidative stress during a clinically resembling experimental model of septic shock. Eighteen anesthetized and catheterized pigs (35-45 kg) were submitted to peritonitis by fecal inoculation (0.75 g/kg). After hypotension, antibiotics were administered, and the animals were randomized to two groups: control (n = 9), with hemodynamic support aiming central venous pressure 8 to 12 mmHg, urinary output 0.5 mL/kg per hour, and mean arterial pressure greater than 65 mmHg; and SvO(2) (n = 9), with the goals above, plus SvO(2) greater than 65%. The interventions lasted 12 h, and lactated Ringer's and norepinephrine (both groups) and dobutamine (SvO(2) group) were administered. Inflammatory response was evaluated by plasma concentration of cytokines, neutrophil CD14 expression, oxidant generation, and apoptosis. Oxidative stress was evaluated by plasma and myocardial nitrate concentrations, myocardial and vascular NADP(H) oxidase activity, myocardial glutathione content, and nitrotyrosine expression. Mixed venous oxygen saturation-driven resuscitation was associated with improved systolic index, oxygen delivery, and diuresis. Sepsis induced in both groups a significant increase on IL-6 concentrations and plasma nitrate concentrations and a persistent decrease in neutrophil CD14 expression. Apoptosis rate and neutrophil oxidant generation were not different between groups. Treatment strategies did not significantly modify oxidative stress parameters. Thus, an approach aiming SvO(2) during sepsis improves hemodynamics, without any significant effect on inflammatory response and oxidative stress. The beneficial effects associated with this strategy may be related to other mechanisms.

Comparison of Hyperemic Impedance Echocardiography with Dobutamine Stress Echocardiography to Detect Inducible Myocardial Ischemia: A Pilot Study.

PubMed

Patel, Jijibhoy J; Gupta, Ankur; Nanda, Navin C

2016-03-01

Stress echocardiography using exercise or pharmacological stressors is either contraindicated or associated with significant side effects in some patients. This pilot study was designed to evaluate a new technique, hyperemic impedance echocardiography (HIE). It is based on reactive coronary hyperemia when transient limb ischemia is induced by tourniquet inflation. We hypothesized that this physiologic coronary hyperemia can identify inducible myocardial ischemia by assessment of regional wall motion abnormalities on echocardiography when compared with dobutamine stress echocardiography (DSE). Twenty consecutive outpatients with suspected stable coronary artery disease (CAD) who underwent clinically indicated DSE were recruited for performance of HIE after informed consent was obtained. Standard graded dobutamine infusion protocol from 5 to 40 μg/kg per min was used for DSE. HIE was performed by inflating tourniquets at a pressure of 10 mmHg below the systolic blood pressure for 1 minute in three of four extremities at a time for total of four cycles. Echocardiography was performed immediately after the last rotating tourniquet deflation. DSE and HIE were classified as abnormal for development of new or worsening wall motion abnormality in at least one myocardial segment. Test characteristics were also determined for a subset of these patients (n = 12) who underwent clinically indicated coronary angiography. Hyperemic impedance echocardiography showed 86% sensitivity, 67% specificity, 86% positive predictive value, and 67% negative predictive value with a test accuracy of 80% to detect inducible myocardial wall motion abnormalities when compared with DSE. HIE also showed 83% sensitivity, 75% negative predictive value with a test accuracy of 66.7% for detection of significant (≥50% diameter stenosis) CAD on coronary angiography. In this pilot study, HIE was a feasible, safe, and promising method for detection of inducible myocardial ischemia by assessment of regional wall motion abnormalities when compared to DSE and coronary angiography. Larger studies are needed to confirm these findings. © 2016, Wiley Periodicals, Inc.

Myocardial and Cardiocirculatory Reserve in Asymptomatic Aortic Stenosis and Preserved Ejection Fraction.

PubMed

Schulz, Olaf; Brala, Debora; Allison, Thomas G; Schimke, Ingolf

2015-07-01

Managing patients with asymptomatic severe aortic stenosis (AS) remains a major challenge. Myocardial as well as cardiocirculatory reserve have been hypothesized to predict outcome in patients with asymptomatic AS. A total of 48 patients (indexed aortic valve area 0.39 +/- 0.12 cm2/m2; ejection fraction (EF) 67 +/- 7%) underwent spiroergometry and dobutamine stress echocardiography. Death or valve surgery served as a combined endpoint for follow up. Thirty-seven patients reached the endpoint after a mean of 756 days (range: 100-2146 days). Age- and gender-corrected univariate Cox proportional analysis revealed the presence of mild obstructive lung disease, stroke work loss (SWL), end-systolic diameter index, and E/Flow propagation velocity as the best predictive clinical, valvular, cardiostructural, and left ventricular filling pressure parameters, respectively. After inclusion of these parameters into a baseline multivariable Cox proportional hazard model, SWL (HR 1.21 per rise of 1 unit, CI 1.08-1.35, p = 0.0005) and female gender (HR 3.37, CI 1.50-7.59, p = 0.0044) were independently predictive. Similarly, the best-performing myocardial parameter, EF after dobutamine, was independently predictive (HR 0.75 per 5 units, CI 0.57-0.99, p = 0.035) after inclusion. The best-performing exercise capacity parameter, Watt(max), was of borderline significance (HR 0.93 per 5 units, CI 0.86-1.00, p = 0.0505). For each parameter, cut-off values were determined by time-dependent receiver-operator characteristics. The Kaplan-Meier curves of the patients above versus below the cut-offs differed significantly for SWL (p = 0.001), Wattm (p = 0.001), and gender (p = 0.013). Besides SWL and female gender, the EF after dobutamine as well as highest exercise stress intensity reached are helpful in determining the prognosis of asymptomatic patients with moderate-severe AS.

Prognostic value of high-dose dobutamine stress magnetic resonance imaging in 1,493 consecutive patients: assessment of myocardial wall motion and perfusion.

PubMed

Korosoglou, Grigorios; Elhmidi, Yacine; Steen, Henning; Schellberg, Dieter; Riedle, Nina; Ahrens, Johannes; Lehrke, Stephanie; Merten, Constanze; Lossnitzer, Dirk; Radeleff, Jannis; Zugck, Christian; Giannitsis, Evangelos; Katus, Hugo A

2010-10-05

This study sought to determine the prognostic value of wall motion and perfusion assessment during high-dose dobutamine stress (DS) cardiac magnetic resonance imaging (MRI) in a large patient cohort. DS-MRI offers the possibility to integrate myocardial perfusion and wall motion analysis in a single examination for the detection of coronary artery disease (CAD). A total of 1,493 consecutive patients with suspected or known CAD underwent DS-MRI, using a standard protocol in a 1.5-T magnetic resonance scanner. Wall motion and perfusion were assessed at baseline and during stress, and outcome data including cardiac death, nonfatal myocardial infarction ("hard events"), and "late" revascularization performed >90 days after the MR scans were collected during a 2 ± 1 year follow-up period. Fifty-three hard events, including 14 cardiac deaths and 39 nonfatal infarctions, occurred during the follow-up period, whereas 85 patients underwent "late" revascularization. Using multivariable regression analysis, an abnormal result for wall motion or perfusion during stress yielded the strongest independent prognostic value for both hard events and late revascularization, clearly surpassing that of clinical and baseline magnetic resonance parameters (for wall motion: adjusted hazard ratio [HR] of 5.9 [95% confidence interval (CI): 2.5 to 13.6] for hard events and of 3.1 [95% CI: 1.7 to 5.6] for late revascularization, and for perfusion: adjusted HR of 5.4 [95% CI: 2.3 to 12.9] for hard events and of 6.2 [95% CI: 3.3 to 11.3] for late revascularization, p < 0.001 for all). DS-MRI can accurately identify patients who are at increased risk for cardiac death and myocardial infarction, separating them from those with normal findings, who have very low risk for future cardiac events. (Prognostic Value of High Dose Dobutamine Stress Magnetic Resonance Imaging; NCT00837005). Copyright © 2010 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Regional and global right ventricular dysfunction in asymptomatic or minimally symptomatic patients with congenitally corrected transposition.

PubMed

Tulevski, Igor I; Zijta, Frank M; Smeijers, Anika S; Dodge-Khatami, Ali; van der Wall, Ernst E; Mulder, Barbara J M

2004-04-01

Patients with congenitally corrected transposition are at risk of right ventricular dysfunction and failure. With this in mind, we examined 13 patients with congenitally corrected transposition, 7 not having undergone surgery, and 6 after physiological repair, comparing them with 6 healthy subjects matched for age and sex, using cardiac magnetic resonance imaging, at rest and during dobutamine stress, in order to determine regional and global right ventricular response to stress. At rest, the patients had significantly decreased overall wall motion compared to their healthy peers (7.2 +/- 0.5, versus 9.8 +/- 0.4 mm). During infusion of dobutamine, overall wall motion increased to 12.8 +/- 0.4 mm in the healthy subjects, versus 8.8 +/- 1.0 mm in patients. At the regional level, significant differences in mural motion were found between patients and controls in the anterior (9.5 +/- 1.1, versus 13.2 +/- 0.6 mm), posterior (10.2 +/- 1.6, versus 13.2 +/- 0.8 mm), and septal segments (5.0 +/- 0.8, versus 11.2 +/- 0.6 mm). At rest, overall mural thickening in patients was similar to that of controls, but significantly less in patients during stress. During dobutamine stress, patients showed significantly less regional wall thickening than controls, particularly in the septal (2.7 +/- 0.6, versus 6.0 +/- 0.4 mm, respectively) and in the anterior segments (4.2 +/- 0.6, versus 7.8 +/- 0.6 mm, respectively). Right ventricular ejection fraction strongly correlated with mural motion and thickening, both at rest and during stress. Abnormal regional function in the systemic morphologically right ventricle may occur in patients with congenitally corrected transposition, which strongly correlates with right ventricular ejection fraction. Our findings support the hypothesis that, in patients with congenitally corrected transposition, ischemia of the right ventricular myocardium contributes to the development of right ventricular dysfunction.

Potential impact of clinical use of noninvasive FFRCT on radiation dose exposure and downstream clinical event rate.

PubMed

Bilbey, Nicolas; Blanke, Philipp; Naoum, Christopher; Arepalli, Chesnel Dey; Norgaard, Bjarne Linde; Leipsic, Jonathon

2016-01-01

This study aims to determine the potential impact of introducing noninvasive fractional flow reserve based on coronary computed tomography angiography (CTA) into clinical practice, with respect to radiation dose exposure and downstream event rate. We modeled a population of 1000 stable, symptomatic patients with suspected coronary artery disease, using the disease prevalence from the CONFIRM registry to estimate the pretest likelihood. Four potential clinical pathways were modeled based on the first noninvasive diagnostic test performed: (1) dobutamine echo; (2) single-photon emission computerized tomography (SPECT); (3) coronary CTA; and (4) CTA+FFRCT and leading to possible invasive coronary angiography. The posttest likelihood of testing positive/negative by each test was based on the presenting disease burden and diagnostic accuracy of each test. The dobutamine echo pathway resulted in the lowest radiation dose of 5.4 mSv, with 4.0 mSv from angiography and 1.4 mSv from percutaneous coronary intervention (PCI). The highest dose was with SPECT, with 26.5 mSv. The coronary computed tomography angiography (cCTA) pathway demonstrated a dose of 14.2 mSv, 3.7 mSv from cCTA, 7.7 mSv from angiography, and 2.8 mSv from PCI. The CTA+FFRCT pathway exhibited a radiation dose of 9.7 mSv, 3.7 mSv for cCTA, 4.2 mSv for angiography, and 1.8 mSv for PCI. Radiation dose exposure for CTA+FFRCT was lower than for SPECT (P<.001). The CTA+FFRCT pathway resulted in the lowest projected death/myocardial infarction rate at 1 year (2.44%) while the dobutamine stress pathway had the highest 1-year event rate (2.84%). Our analysis suggests that integrating FFRCT into the CTA clinical pathway may result in reduced cumulative radiation exposure, while promoting favorable clinical outcomes. Copyright © 2016 Elsevier Inc. All rights reserved.

Prognostic value of cardiac power output to left ventricular mass in patients with left ventricular dysfunction and dobutamine stress echo negative by wall motion criteria.

PubMed

Cortigiani, Lauro; Sorbo, Simone; Miccoli, Mario; Scali, Maria Chiara; Simioniuc, Anca; Morrone, Doralisa; Bovenzi, Francesco; Marzilli, Mario; Dini, Frank Lloyd

2017-02-01

Cardiac power output to left ventricular mass (power/mass) is an index of myocardial efficiency reflecting the rate at which cardiac work is delivered with respect to the potential energy stored in the left ventricular mass. In the present study, we sought to investigate the capability of power/mass assessed at peak of dobutamine stress echocardiography to predict mortality in patients with ischaemic cardiomyopathy and no inducible ischaemia. One-hundred eleven patients (95 males; age 68 ± 10 years) with 35 ± 7% mean left ventricular ejection fraction and a dobutamine stress echocardiography (up to 40 µg/kg/min) negative by wall motion criteria formed the study population. Power/mass at peak stress was obtained as the product of a constant (K = 2.22 × 10 -1 ) with cardiac output and the mean arterial pressure divided by left ventricular mass to convert the units to W/100 g. Patients were followed up for a median of 29 months (inter-quartile range 16-72 months). All-cause mortality was the only accepted clinical end point. Mean peak-stress power/mass was 0.70 ± 0.31 W/100 g. During follow-up, 29 deaths (26%) were registered. With a receiver operating characteristic analysis, a peak-stress power/mass ≤0.50 W/100 g [area under curve 0.72 (95% CI 0.63; 0.80), sensitivity 59%, specificity 80%] was the best value for predicting mortality. Univariate prognostic indicators were age, male sex, peak-stress ejection fraction, peak-stress stroke volume, peak-stress cardiac output, peak-stress cardiac power output ≤1.48 W, and peak-stress power/mass ≤0.50 W/100 g. At multivariate analysis, age (HR 1.08, 95% CI 1.04; 1.14; P = 0.004) and peak-stress power/mass ≤0.50 W/100 g (HR 4.05, 95% CI 1.36; 12.00; P = 0.01) provided independent prognostic information. Three-year mortality was 14% in patients with peak-stress power/mass >0.50 W/100 g and 47% in those with peak-stress power/mass ≤0.50 W/100 g (log-rank 20.4; P < 0.0001). Power/mass assessed at peak of dobutamine stress echocardiography allows effective prognostication in patients with ischaemic cardiomyopathy and test result negative by wall motion criteria. In particular, a peak-stress power/mass ≤50 W/100 g is a strong and multivariable predictor of mortality. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2016. For permissions please email: journals.permissions@oup.com.

Which test for CAD should be used in patients with left bundle branch block?

PubMed

Xu, Bo; Cremer, Paul; Jaber, Wael; Moir, Stuart; Harb, Serge C; Rodriguez, L Leonardo

2018-03-01

Exercise stress electrocardiography is unreliable as a test for obstructive coronary artery disease (CAD) if the patient has left bundle branch block. The authors provide an algorithm for using alternative tests: exercise stress echocardiography, dobutamine echocardiography, computed tomographic (CT) angiography, and nuclear myocardial perfusion imaging. Copyright © 2018 Cleveland Clinic.

Diesel exhaust worsens cardiac conduction instability in dobutamine-challenged Wistar-Kyoto and spontaneously hypertensive rats

EPA Science Inventory

This study shows that a single exposure to diesel exhaust causes conduction instability in rats that is worse in the presence of hypertension. The RoR assessment is shown to be a valuable tool that can be used to reveal the deleterious effects of air pollution, particularly in th...

Pressure-maximal coronary flow relationship in regionally stunned porcine myocardium.

PubMed

Duncker, D J; McFalls, E O; Krams, R; Verdouw, P D

1992-06-01

In view of variable results on maximal coronary blood flow in stunned myocardium, we studied the pressure-maximal coronary flow (PMCF) relationship in stunned myocardium in 12 anesthetized swine by using intracoronary adenosine (20 micrograms/kg). Subendocardial systolic segment shortening (SS) measured with sonomicrometry was 19 +/- 5% (means +/- SD) at baseline and 7 +/- 6% (P less than 0.01) at 30 min of reperfusion after 15 min of low-flow ischemia, at which time postsystolic shortening was present. Myocardial stunning increased the slope of the PMCF regression line (alpha PMCF) from 3.34 +/- 1.03 to 3.89 +/- 1.33 ml.min-1.mmHg-1 (P less than 0.01). Atrial pacing at 40 beats/min above spontaneous heart rate (n = 6) further reduced subendocardial SS to 6 +/- 6% (P less than 0.05). Dobutamine (4 micrograms.kg-1.min-1; n = 6) increased subendocardial SS to 13 +/- 5% (P less than 0.05) and abolished postsystolic shortening. Both interventions left alpha PMCF unchanged. In conclusion, myocardial stunning was associated with an increase in alpha PMCF that most likely resulted from the decreased contractile function. The absence of an effect of dobutamine may be due to its predominant action on diastolic function.

Evaluation of left ventricular function in anesthetized patients using femoral artery dP/dt(max).

PubMed

De Hert, Stefan G; Robert, Dominique; Cromheecke, Stefanie; Michard, Frédéric; Nijs, Jan; Rodrigus, Inez E

2006-06-01

The purpose of this study was to compare dP/dt(max) estimated from a femoral artery pressure tracing to left ventricular (LV) dP/dt(max) during various alterations in myocardial loading and contractile function. Seventy patients scheduled for elective coronary artery bypass surgery. All patients were instrumented with a high-fidelity LV catheter, a pulmonary artery catheter, and a femoral arterial catheter. In 40 patients, hemodynamic measurements were performed before and after passive leg raising and before and after calcium administration (5 mg/kg); and in 30 other patients, hemodynamic measurements were performed before and after dobutamine infusion (5 microg/kg/min over 10 minutes). LV and femoral dP/dt(max) were significantly correlated (r = 0.82, p < 0.001), but femoral dP/dt(max) systematically underestimated LV dP/dt(max) (bias = -361 +/- 96 mmHg/s). Passive leg raising induced significant increases in central venous pressure and LV end-diastolic pressure, but femoral dP/dt(max), stroke volume, and LV dP/dt(max) remained unaltered. Calcium administration induced significant and marked increases in LV dP/dt(max) (23% +/- 9%) and femoral dP/dt(max) (37% +/- 14%) associated with a significant increase in stroke volume (9% +/- 2%). Dobutamine infusion also induced significant and marked increases in LV dP/dt(max) (25% +/- 8%) and femoral dP/dt(max) (35% +/- 12%) associated with a significant increase in stroke volume (14% +/- 3%). Overall, a very close linear relationship (r = 0.93) and a good agreement (bias = -5 +/- 17 mmHg/s) were found between changes in LV dP/dt(max) and changes in femoral dP/dt(max). A very close relationship was also observed between changes in LV dP/dt(max) and changes in femoral dP/dt(max) during each intervention (leg raising, calcium administration, and dobutamine infusion). Femoral dP/dt(max) underestimated LV dP/dt(max), but changes in femoral dP/dt(max) accurately reflected changes in LV dP/dt(max) during various interventions.

Factors Associated with the Incidence and Severity of New-Onset Atrial Fibrillation in Adult Critically Ill Patients

PubMed Central

Leichtweis, Gustavo Elias; Andriolo, Luiza; Delevatti, Yasmim A.; Jorge, Amaury C.; Fumagalli, Andreia C.; Santos, Luiz Claudio; Miura, Cecilia K.; Saito, Sergio K.

2017-01-01

Background Acute Atrial Fibrillation (AF) is common in critically ill patients, with significant morbidity and mortality; however, its incidence and severity in Intensive Care Units (ICUs) from low-income countries are poorly studied. Additionally, impact of vasoactive drugs on its incidence and severity is still not understood. This study aimed to assess epidemiology and risk factors for acute new-onset AF in critically ill adult patients and the role of vasoactive drugs. Method Cohort performed in seven general ICUs (including cardiac surgery) in three cities in Paraná State (southern Brazil) for 45 days. Patients were followed until hospital discharge. Results Among 430 patients evaluated, the incidence of acute new-onset AF was 11.2%. Patients with AF had higher ICU and hospital mortality. Vasoactive drugs use (norepinephrine and dobutamine) was correlated with higher incidence of AF and higher mortality in patients with AF; vasopressin (though used in few patients) had no effect on development of AF. Conclusions In general ICU patients, incidence of new-onset AF was 11.2% with a high impact on morbidity and mortality, particularly associated with the presence of Acute Renal Failure. The use of vasoactive drugs (norepinephrine and dobutamine) could lead to a higher incidence of new-onset AF-associated morbidity and mortality. PMID:28702263

Factors Associated with the Incidence and Severity of New-Onset Atrial Fibrillation in Adult Critically Ill Patients.

PubMed

Duarte, Péricles A D; Leichtweis, Gustavo Elias; Andriolo, Luiza; Delevatti, Yasmim A; Jorge, Amaury C; Fumagalli, Andreia C; Santos, Luiz Claudio; Miura, Cecilia K; Saito, Sergio K

2017-01-01

Acute Atrial Fibrillation (AF) is common in critically ill patients, with significant morbidity and mortality; however, its incidence and severity in Intensive Care Units (ICUs) from low-income countries are poorly studied. Additionally, impact of vasoactive drugs on its incidence and severity is still not understood. This study aimed to assess epidemiology and risk factors for acute new-onset AF in critically ill adult patients and the role of vasoactive drugs. Cohort performed in seven general ICUs (including cardiac surgery) in three cities in Paraná State (southern Brazil) for 45 days. Patients were followed until hospital discharge. Among 430 patients evaluated, the incidence of acute new-onset AF was 11.2%. Patients with AF had higher ICU and hospital mortality. Vasoactive drugs use (norepinephrine and dobutamine) was correlated with higher incidence of AF and higher mortality in patients with AF; vasopressin (though used in few patients) had no effect on development of AF. In general ICU patients, incidence of new-onset AF was 11.2% with a high impact on morbidity and mortality, particularly associated with the presence of Acute Renal Failure. The use of vasoactive drugs (norepinephrine and dobutamine) could lead to a higher incidence of new-onset AF-associated morbidity and mortality.

Cerebral arterial pulsation drives paravascular CSF-interstitial fluid exchange in the murine brain.

PubMed

Iliff, Jeffrey J; Wang, Minghuan; Zeppenfeld, Douglas M; Venkataraman, Arun; Plog, Benjamin A; Liao, Yonghong; Deane, Rashid; Nedergaard, Maiken

2013-11-13

CSF from the subarachnoid space moves rapidly into the brain along paravascular routes surrounding penetrating cerebral arteries, exchanging with brain interstitial fluid (ISF) and facilitating the clearance of interstitial solutes, such as amyloid β, in a pathway that we have termed the "glymphatic" system. Prior reports have suggested that paravascular bulk flow of CSF or ISF may be driven by arterial pulsation. However, cerebral arterial pulsation could not be directly assessed. In the present study, we use in vivo two-photon microscopy in mice to visualize vascular wall pulsatility in penetrating intracortical arteries. We observed that unilateral ligation of the internal carotid artery significantly reduced arterial pulsatility by ~50%, while systemic administration of the adrenergic agonist dobutamine increased pulsatility of penetrating arteries by ~60%. When paravascular CSF-ISF exchange was evaluated in real time using in vivo two-photon and ex vivo fluorescence imaging, we observed that internal carotid artery ligation slowed the rate of paravascular CSF-ISF exchange, while dobutamine increased the rate of paravascular CSF-ISF exchange. These findings demonstrate that cerebral arterial pulsatility is a key driver of paravascular CSF influx into and through the brain parenchyma, and suggest that changes in arterial pulsatility may contribute to accumulation and deposition of toxic solutes, including amyloid β, in the aging brain.

Differential cardiac effects in rats exposed to atmospheric ...

EPA Pesticide Factsheets

The results of this study demonstrate that atmospheric smog generated from both isoprene and toluene cause cardiac effects in rats. In addition, it appears that smog from toluene is more toxic in terms of cardiac arrhythmogenicity. Smog, which is a complex mixture of particulate matter and gaseous irritants (ozone, sulfur dioxide, reactive aldehydes), as well as components which react with sunlight to form secondary pollutants, has recently been linked to increased risk of adverse cardiac responses. The components, and therefore health effects, of atmospheric smog are determined by the fuel used to generate them. In this study we examined the difference between isoprene- and toluene-generated smog in causing cardiac effects in rats and hypothesized that both atmospheres would cause cardiac electrical and functional changes in rats. Male Wistar-Kyoto rats were exposed to either atmospheric smog generated by the USEPA’s mobile reaction chamber using either isoprene or toluene, or filtered air for four hours. One day later, rats were anesthetized and left ventricular functional responses to dobutamine were measured using a Millar probe and arrhythmia sensitivity to aconitine. Baseline left ventricular pressure (LVP) was lower in toluene-exposed animals but not isoprene when compared to air. Increases in LVP with increasing doses of dobutamine were impaired only in toluene-exposed rats. Both isoprene and toluene impaired the rate of ventri

Changes in phasic coronary blood flow velocity profile in relation to changes in hemodynamic parameters during stress in patients with aortic valve stenosis.

PubMed

Petropoulakis, P N; Kyriakidis, M K; Tentolouris, C A; Kourouclis, C V; Toutouzas, P K

1995-09-15

Alterations in phasic coronary flow profile have been demonstrated at rest in patients with aortic valve stenosis (AVS) but have never been studied under conditions of hemodynamic stress. Thirty-four patients with significant pure AVS (21 with exertional symptoms [group 1], 13 asymptomatic [group 2]) and 9 control subjects (group 3), all with normal coronary arteries, were studied successively at rest, during rapid atrial pacing, and after dobutamine infusion (5 to 30 micrograms.kg-1.min-1 i.v.) by proximal left anterior descending (LAD) intracoronary Doppler flow velocimetry concomitant with hemodynamic measurements. Systolic retrograde coronary flow velocity (CFV) was recorded only in patients with AVS, and its resting peak value was positively correlated with peak aortic pressure gradient (APG) (r = .63, P < .001). In group 1, there was lower aortic valve area (0.58 +/- 0.10 versus 0.75 +/- 0.08 cm2, P < .001) and higher resting APG and peak systolic retrograde CFV than in group 2, and also higher resting peak diastolic and mean CFV than in groups 2 and 3. In the two AVS groups, there were no changes from rest in APG and retrograde CFV at peak pacing rate; however, these parameters increased concomitantly and significantly at peak dobutamine stress. The ratio of the resting systolic to diastolic CFV curve area was inversely correlated with mean APG (r = -.54, P < .001); it was significantly lower in group 1 than in groups 2 and 3 (0.19 +/- 0.07 versus 0.29 +/- 0.10 and 0.30 +/- 0.04, respectively, both P < .005) and increased at peak pacing (group 1, to 0.29 +/- 0.14; group 2, to 0.39 +/- 0.12; group 3, to 0.38 +/- 0.07; all P < .001). At peak dobutamine stress, it decreased in patients with AVS (group 1, to 0.05 +/- 0.05; group 2, to 0.08 +/- 0.03; both P < .001) but did not change in group 3 (0.25 +/- 0.05). From rest to peak dobutamine stress, in both AVS groups there was increased retrograde systolic (group 1, 441 +/- 483%; group 2, 681 +/- 356%; both P < .001), decreased total systolic (group 1, -66 +/- 25%, P < .001; group 2, -19 +/- 24%; P = NS), and increased diastolic (group 1, 33.4 +/- 31.7%; group 2, 197.7 +/- 105.1%; both P < .001; group 1 versus group 2, P < .001) CFV curve area. In contrast, group 3 showed comparable increases in both systolic (143.5 +/- 44.4%) and diastolic (197.1 +/- 75.2%) CFV area (both P < .001). The stress-induced increases in the mean CFV and blood flow exceeded or were comparable with the concomitant increases in the estimated myocardial metabolic demand in groups 2 and 3 but were significantly lower in group 1. Stress-induced changes in LAD phasic CFV profile differ significantly between patients with and without AVS. In AVS, these changes are closely related to the concomitant stress-induced changes in hemodynamic parameters.

Current real-life use of vasopressors and inotropes in cardiogenic shock - adrenaline use is associated with excess organ injury and mortality.

PubMed

Tarvasmäki, Tuukka; Lassus, Johan; Varpula, Marjut; Sionis, Alessandro; Sund, Reijo; Køber, Lars; Spinar, Jindrich; Parissis, John; Banaszewski, Marek; Silva Cardoso, Jose; Carubelli, Valentina; Di Somma, Salvatore; Mebazaa, Alexandre; Harjola, Veli-Pekka

2016-07-04

Vasopressors and inotropes remain a cornerstone in stabilization of the severely impaired hemodynamics and cardiac output in cardiogenic shock (CS). The aim of this study was to analyze current real-life use of these medications, and their impact on outcome and on changes in cardiac and renal biomarkers over time in CS. The multinational CardShock study prospectively enrolled 219 patients with CS. The use of vasopressors and inotropes was analyzed in relation to the primary outcome, i.e., 90-day mortality, with propensity score methods in 216 patients with follow-up data available. Changes in cardiac and renal biomarkers over time until 96 hours from baseline were analyzed with linear mixed modeling. Patients were 67 (SD 12) years old, 26 % were women, and 28 % had been resuscitated from cardiac arrest prior to inclusion. On average, systolic blood pressure was 78 (14) and mean arterial pressure 57 (11) mmHg at detection of shock. 90-day mortality was 41 %. Vasopressors and/or inotropes were administered to 94 % of patients and initiated principally within the first 24 hours. Noradrenaline and adrenaline were given to 75 % and 21 % of patients, and 30 % received several vasopressors. In multivariable logistic regression, only adrenaline (21 %) was independently associated with increased 90-day mortality (OR 5.2, 95 % CI 1.88, 14.7, p = 0.002). The result was independent of prior cardiac arrest (39 % of patients treated with adrenaline), and the association remained in propensity-score-adjusted analysis among vasopressor-treated patients (OR 3.0, 95 % CI 1.3, 7.2, p = 0.013); this was further confirmed by propensity-score-matched analysis. Adrenaline was also associated, independent of prior cardiac arrest, with marked worsening of cardiac and renal biomarkers during the first days. Dobutamine and levosimendan were the most commonly used inotropes (49 % and 24 %). There were no differences in mortality, whether noradrenaline was combined with dobutamine or levosimendan. Among vasopressors and inotropes, adrenaline was independently associated with 90-day mortality in CS. Moreover, adrenaline use was associated with marked worsening in cardiac and renal biomarkers. The combined use of noradrenaline with either dobutamine or levosimendan appeared prognostically similar.

The expression of β3-adrenoceptors and their function in the human prostate.

PubMed

Suzuki, Takahisa; Otsuka, Atsushi; Matsumoto, Rikiya; Furuse, Hiroshi; Ozono, Seiichiro

2016-02-01

Little is known about β3-adrenoceptor (AR) expression and function in human prostate. We examined the expression and distribution of β-AR subtypes in normal prostate and benign prostatic hyperplasia (BPH) tissues, and investigated which selective β-AR subtype agonist was most involved in the relaxation of isolated human prostate strips. Messenger RNA (mRNA) expression for β1-, β2-, and β3 -ARs was investigated using reverse transcriptase-polymerase chain reactions (RT-PCR). Quantitative analysis of mRNA expression of β-AR subtypes between normal prostate and BPH tissues was performed using quantitative RT-PCR (qPCR). Distributions were examined by immunohistochemistry (IHC). Strips of human normal prostate or BPH were suspended in organ baths and exposed to isoproterenol, dobutamine, procaterol, and TRK-380 to investigate their relaxant effects on KCl-induced contractions, and their inhibitory effects on electrical field stimulation (EFS)-induced contractions. We confirmed the presence of mRNA for β1-, β2-, and β3-ARs both in normal prostate and in BPH tissues. For β3-AR, mRNA expression in BPH tissues was significantly higher than in normal prostate tissues, but there was no significant difference in β1- and β2-AR expression between normal and BPH tissues. IHC revealed differences in staining intensity between smooth muscle cells and glandular cells, with different proportions for different β-AR subtypes. Staining of β3-AR was particularly intense in smooth muscle cells as opposed to glandular cells. Isoproterenol and TRK-380 significantly decreased the tone of KCl-induced contractions of the normal prostate strips. The rank order of relaxant effects was isoproterenol > TRK-380 > procaterol > dobutamine. All selective β-AR agonists significantly decreased the amplitude of EFS-induced contractions of the normal prostate strips. The rank order of inhibitory effects was isoproterenol > dobutamine >TRK-380 > procaterol. In BPH strips, all selective β-AR agonists showed no significant relaxant or inhibitory effects on KCl- or EFS-induced contractions. β3 -AR is abundant in human prostate smooth muscle, whose relaxation is mediated by β1- and β3-AR stimulation. β3-AR agonists may have clinical use in the treatment of male non-BPH patients or neurogenic bladder patients with voiding dysfunction. © 2015 Wiley Periodicals, Inc.

Myosin Heads Are Displaced from Actin Filaments in the In Situ Beating Rat Heart in Early Diabetes

PubMed Central

Jenkins, Mathew J.; Pearson, James T.; Schwenke, Daryl O.; Edgley, Amanda J.; Sonobe, Takashi; Fujii, Yutaka; Ishibashi-Ueda, Hatsue; Kelly, Darren J.; Yagi, Naoto; Shirai, Mikiyasu

2013-01-01

Diabetes is independently associated with a specific cardiomyopathy, characterized by impaired cardiac muscle relaxation and force development. Using synchrotron radiation small-angle x-ray scattering, this study investigated in the in situ heart and in real-time whether changes in cross-bridge disposition and myosin interfilament spacing underlie the early development of diabetic cardiomyopathy. Experiments were conducted using anesthetized Sprague-Dawley rats 3 weeks after treatment with either vehicle (control) or streptozotocin (diabetic). Diffraction patterns were recorded during baseline and dobutamine infusions simultaneous with ventricular pressure-volumetry. From these diffraction patterns myosin mass transfer to actin filaments was assessed as the change in intensity ratio (I1,0/I1,1). In diabetic hearts cross-bridge disposition was most notably abnormal in the diastolic phase (p < 0.05) and to a lesser extent the systolic phase (p < 0.05). In diabetic rats only, there was a transmural gradient of contractile depression. Elevated diabetic end-diastolic intensity ratios were correlated with the suppression of diastolic function (p < 0.05). Furthermore, the expected increase in myosin head transfer by dobutamine was significantly blunted in diabetic animals (p < 0.05). Interfilament spacing did not differ between groups. We reveal that impaired cross-bridge disposition and radial transfer may thus underlie the early decline in ventricular function observed in diabetic cardiomyopathy. PMID:23473489

End-Systolic Elastance and Ventricular-Arterial Coupling Reserve Predict Cardiac Events in Patients with Negative Stress Echocardiography

PubMed Central

Bombardini, Tonino; Costantino, Marco Fabio; Sicari, Rosa; Ciampi, Quirino; Pratali, Lorenza; Picano, Eugenio

2013-01-01

Background. A maximal negative stress echo identifies a low-risk subset for coronary events. However, the potentially prognostically relevant information on cardiovascular hemodynamics for heart-failure-related events is unsettled. Aim of this study was to assess the prognostic value of stress-induced variation in cardiovascular hemodynamics in patients with negative stress echocardiography. Methods. We enrolled 891 patients (593 males mean age 63 ± 12, ejection fraction 48 ± 17%), with negative (exercise 172, dipyridamole 482, and dobutamine 237) stress echocardiography result. During stress we assessed left ventricular end-systolic elastance index (E LVI), ventricular arterial coupling (VAC) indexed by the ratio of the E LVI to arterial elastance index (E aI), systemic vascular resistance (SVR), and pressure-volume area (PVA). Changes from rest to peak stress (reserve) were tested as predictors of main outcome measures: combined death and heart failure hospitalization. Results. During a median followup of 19 months (interquartile range 8–36), 50 deaths and 84 hospitalization occurred. Receiver-operating-characteristic curves identified as best predictors E LVI reserve for exercise (AUC = 0.871) and dobutamine (AUC = 0.848) and VAC reserve (AUC = 0.696) for dipyridamole. Conclusions. Patients with negative stress echocardiography may experience an adverse outcome, which can be identified by assessment of E LVI reserve and VAC reserve during stress echo. PMID:24024185

Effect of co-medication on the pharmacokinetic parameters of phenobarbital in asphyxiated newborns.

PubMed

Šíma, M; Pokorná, P; Hronová, K; Slanař, O

2015-01-01

Phenobarbital is an anticonvulsive drug widely used in newborns with hypoxic-ischemic encephalopathy. The objective of our study was to describe possible effect of frequently co-administered medications (dopamine, dobutamine, norepinephrine, furosemide, phenytoin, and analgesics) on the phenobarbital pharmacokinetics in full term newborns with hypoxic-ischemic encephalopathy. Phenobarbital pharmacokinetic parameters (standardized intravenous loading dose was 10-20 mg/kg, maintenance dose 2-6 mg/kg/day) were computed using non-compartmental analysis. Co-medication was evaluated throughout the whole treatment period up to 5 days. Volume of distribution, clearance, and half-life median values (95 % CI) for phenobarbital in the whole study population (n=37) were 0.48 (0.41-0.56) l/kg, 0.0034 (0.0028-0.0040) l/h/kg, and 93.7 (88.1-99.2) h, respectively. Phenobarbital pharmacokinetic parameters were not significantly affected by vasoactive drugs (dopamine, dobutamine, and norepinephrine), furosemide, phenytoin, or analgesics. Furthermore, no dose-dependent alteration of phenobarbital pharmacokinetic parameters was noted for vasoactive medication at doses equivalent to cumulative vasoactive-inotropic score (area under the curve in a plot of vasoactive-inotropic score against time) 143.2-8473.6, furosemide at cumulative doses of 0.2-42.9 mg/kg, or phenytoin at cumulative doses of 10.3-46.2 mg/kg. Phenobarbital pharmacokinetics was not affected by investigated co-administered drugs used in newborns with hypoxic-ischemic encephalopathy in real clinical settings.

Improvement of Hyperemic Myocardial Oxygen Extraction Fraction Estimation By A Diffusion Prepared Sequence

PubMed Central

McCommis, Kyle S.; Koktzoglou, Ioannis; Zhang, Haosen; Goldstein, Thomas A.; Northrup, Benjamin E.; Li, Debiao; Gropler, Robert J.; Zheng, Jie

2010-01-01

Myocardial oxygen extraction fraction (OEF) during hyperemia can be estimated using a double-inversion-recovery (DIR) prepared T2-weighted black-blood sequence. Severe irregular ECG-triggering due to elevated heart rate and/or arrhythmias may render it difficult to adequately suppress the flowing left ventricle blood signal and thus potentially cause errors in the estimates of myocardial OEF. Thus, the goal of this study was to evaluate another black-blood technique, a diffusion-weighted (DW)-prepared TSE sequence for its ability to determine regional myocardial OEF during hyperemia. Control dogs and dogs with acute coronary artery stenosis were imaged with both the DIR- and DW-prepared TSE sequences at rest and during either dipyridamole or dobutamine hyperemia. Validation of MRI OEF estimates was performed using blood sampling from the artery and coronary sinus in control dogs. The two methods showed comparable correlations with blood sampling results (R2 = 0.9). Similar OEF estimations for all dogs were observed except for the group of dogs with severe coronary stenosis during dobutamine stress. In these dogs, the DW method provided more physiologically reasonable OEF (hyperemic OEF = 0.75 ± 0.08 vs resting OEF of 0.6) than the DIR method (hyperemic OEF = 0.56 ± 0.10). DW-preparation may be a valuable alternative for more accurate oxygenation measurements during irregular ECG-triggering. PMID:20512871

Enoximon-echocardiography. A new diagnostic approach for the detection of viable myocardium comparison to dobutamin-echocardiography.

PubMed

Baumgart, D; Buck, T; Leischik, R; Oelert, H; Farahati, J; Reiners, C; Erbel, R

1994-08-01

Hypo- or akinetic myocardial regions can be identified as viable myocardium through recruitment of inotropic reserve. Both, dobutamine (D) as well as enoximone (E) mediate their inotropic action via an increase in intracellular c-AMP concentration based on a different action. In 10 patients with documented myocardial infarction either D (5 to 40 micrograms/kg/min, increments of 5 micrograms/kg/min every 3 min) or E (1 to 9 micrograms/kg/min, increments of 1 microgram/kg/min every 2 min) was administered intravenously on two consecutive days. Heart rate (HR), systolic and diastolic blood pressure (BP), as well as a wall motion score in 16 segment (WMS) and ejection fraction (EF) with 2D-echocardiography were determined at rest and during each increment. Viability of myocardial regions was assessed with 201thallium-SPECT (Table 1). *p < 0.05 vs. rest, data: mean +/- SD. While E did not cause any side effects, patients complained about rash (n = 10), headache (n = 8), angina pectoris (n = 5), and anxiety (n = 2) during the administration of D. D and E are both able to recruit a potential inotropic reserve in infarcted myocardium, and thus, identify viable myocardium. In contrast to E, D caused an increase in HR and systolic BP. Enoximone-echocardiography seems to be a new, promising tool for the identification of viable myocardium.

Additive prognostic value of interleukin-6 at peak phase of dobutamine stress echocardiography in patients with coronary artery disease. A 6-year follow-up study.

PubMed

Ikonomidis, Ignatios; Athanassopoulos, George; Stamatelopoulos, Kimon; Lekakis, John; Revela, Ioanna; Venetsanou, Kiriaki; Marinou, Margarita; Monaco, Claudia; Cokkinos, Dennis V; Nihoyannopoulos, Petros

2008-08-01

Interleukin-6 (IL-6) and tissue factor (TF) are elevated after myocardial ischemia during dobutamine stress echo (DSE). We examined the incremental prognostic value of IL-6 or TF measured during DSE over echocardiographic and clinical factors in patients with chronic coronary artery disease (CAD). We studied 106 patients with angiographically documented CAD. IL-6 and TF were measured at rest, peak, and during recovery. A wall motion score index was calculated. Fifty-seven (54%) patients had ischemia at DSE. During follow-up (63.7 +/- 20 months), 36 patients (33%) had an adverse event (12 cardiac deaths, 24 acute coronary events). Patients with events had a higher peak IL-6 (P = .02) but similar rest and recovery IL-6 than those without. Patients with peak IL-6 > or =3.14 pg/mL (upper tertile) had a hazard ratio of 2.7 (95% CI 1.44-5.37) (P < .01 for an adverse event). The addition of peak wall motion score index in a multivariable model including risk factors, ejection fraction, revascularization, and multivessel disease increased the model's c statistic from 0.66 to 0.70 (P = .04). The addition of peak IL-6 further increased the model's c statistic to 0.75 (P = .04). Tissue factor was not related with cardiac events. Interleuikin-6 levels measured during the peak phase of DSE incrementally contribute to risk stratification in patients with chronic CAD.

Baseline mitral regurgitation predicts outcome in patients referred for dobutamine stress echocardiography.

PubMed

O'Driscoll, Jamie M; Gargallo-Fernandez, Paula; Araco, Marco; Perez-Lopez, Manuel; Sharma, Rajan

2017-11-01

A number of parameters recorded during dobutamine stress echocardiography (DSE) are associated with worse outcome. However, the relative importance of baseline mitral regurgitation (MR) is unknown. The aim of this study was to assess the prevalence and associated implications of functional MR with long-term mortality in a large cohort of patients referred for DSE. 6745 patients (mean age 64.9 ± 12.2 years) were studied. Demographic, baseline and peak DSE data were collected. All-cause mortality was retrospectively analyzed. DSE was successfully completed in all patients with no adverse outcomes. MR was present in 1019 (15.1%) patients. During a mean follow up of 5.1 ± 1.8 years, 1642 (24.3%) patients died and MR was significantly associated with increased all-cause mortality (p < 0.001). With Kaplan-Meier analysis, survival was significantly worse for patients with moderate and severe MR (p < 0.001). With multivariate Cox regression analysis, moderate and severe MR (HR 2.78; 95% CI 2.17-3.57 and HR 3.62; 95% CI 2.89-4.53, respectively) were independently associated with all-cause mortality. The addition of MR to C statistic models significantly improved discrimination. MR is associated with all-cause mortality and adds incremental prognostic information among patients referred for DSE. The presence of MR should be taken into account when evaluating the prognostic significance of DSE results.

Cardiac Magnetic Resonance Imaging in Ischemic Heart Disease

PubMed Central

Florian, A.; Jurcut, R.; Ginghina, C.; Bogaert, J.

2011-01-01

Cardiac magnetic resonance imaging (MRI) has emerged as a prime player in the clinical and preclinical detection of ischemic heart disease (IHD) as well in the prognosis assessment by offering a comprehensive approach for all spectrums of coronary artery disease (CAD) patients. The aim of this review is to provide the reader a state–of–the art on how the newest cardiac MRI techniques can be used to study IHD patients. In patients with suspected/stable CAD, functional and perfusion imaging both at rest and during vasodilatatory stress (adenosine, dypiridamole)/dobutamine stress can accurately depict ischemic myocardium secondary to significant coronary artery stenosis. In patients with acute MI, MRI is a robust tool for differentiating and sizing the jeopardized and the infarcted myocardium by using a combination of functional, edema, perfusion and Gd contrast imaging. Moreover, important prognostic factors like myocardial salvage, the presence of microvascular obstruction (MVO), post reperfusion myocardial hemorrhage, RV involvement and infarct related complications can be assessed in the same examination. In patients with chronic ischemic cardiomyopathy, the role of the MRI extends from diagnosis by means of Gadolinium contrast scar imaging to therapy and prognosis by functional assessment and viability testing with rest and dobutamine stress imaging. In all the circumstances mentioned, MRI derived information has been proven valuable in every day clinical decision making and prognosis assessment. Thus, MRI is becoming more and more an accepted alternative to other imaging modalities both in the acute and chronic setting. PMID:22514564

Follow-up of heart transplant recipients with serial echocardiographic coronary flow reserve and dobutamine stress echocardiography to detect cardiac allograft vasculopathy.

PubMed

Sade, Leyla Elif; Eroğlu, Serpil; Yüce, Deniz; Bircan, Aslı; Pirat, Bahar; Sezgin, Atilla; Aydınalp, Alp; Müderrisoğlu, Haldun

2014-05-01

Implementation of reliable noninvasive testing for screening cardiac allograft vasculopathy (CAV) is of critical importance. The most widely used modality, dobutamine stress echocardiography (DSE), has moderate sensitivity and specificity. The aim of this study was to assess the potential role of serial coronary flow reserve (CFR) assessment together with DSE for predicting CAV. A total of 90 studies were performed prospectively over 5 years in 23 consecutive heart transplant recipients who survived >1 year after transplantation. Assessment of CFR with transthoracic Doppler echocardiography, DSE, coronary angiography, and endomyocardial biopsy was performed annually. Results of CFR assessment and DSE were compared with angiographic findings of CAV. Acute cellular rejections were excluded by endomyocardial biopsies. CAV was detected in 17 of 90 angiograms. Mean CFR was similarly lower in both mild (CAV grade 1) and more severe (CAV grades 2 and 3) vasculopathy, but wall motion score index became higher in parallel with increasing grades of vasculopathy. Any CAV by angiography was detected either simultaneously with or later than CFR impairment, yielding 100% sensitivity for CFR. The combination of CFR and DSE increased the specificity of the latter from 64.3% to 87.2% without compromising sensitivity (77.8%). CFR is very sensitive for detecting CAV and increases the diagnostic accuracy of DSE, raising the potential for patient management tailored to risk modification and to avoid unnecessary angiographic procedures. Copyright © 2014 American Society of Echocardiography. Published by Mosby, Inc. All rights reserved.

Usefulness and limitation of dobutamine stress echocardiography to predict acute response to cardiac resynchronization therapy.

PubMed

Sénéchal, Mario; Lancellotti, Patrizio; Garceau, Patrick; Champagne, Jean; Dubois, Michelle; Magne, Julien; Blier, Louis; Molin, Frank; Philippon, François; Dumesnil, Jean G; Pierard, Luc; O'Hara, Gilles

2010-01-01

It has been hypothesized that a long-term response to cardiac resynchronization therapy (CRT) could correlate with myocardial viability in patients with left ventricular (LV) dysfunction. Contractile reserve and viability in the region of the pacing lead have not been investigated in regard to acute response after CRT. Fifty-one consecutive patients with advanced heart failure, LV ejection fraction 120 ms, and intraventricular asynchronism >or= 50 ms were prospectively included. The week before CRT implantation, the presence of viability was evaluated using dobutamine stress echocardiography. Acute responders were defined as a >or=15% increase in LV stroke volume. The average of viable segments was 5.8 +/- 1.9 in responders and 3.9 +/- 3 in nonresponders (P = 0.03). Viability in the region of the pacing lead had an excellent sensitivity (96%), but a low specificity (56%) to predict acute response to CRT. Mitral regurgitation (MR) was reduced in 21 patients (84%) with acute response. The presence of MR was a poor predictor of response (sensibility 93% and specificity 17%). However, combining the presence of MR and viability in the region of the pacing lead yields a sensibility (89%) and a specificity (70%) to predict acute response to CRT. Myocardial viability is an important factor influencing acute hemodynamic response to CRT. In acute responders, significant MR reduction is frequent. The combined presence of MR and viability in the region of the pacing lead predicts acute response to CRT with the best accuracy.

Pharmacological Stress Cardiovascular Magnetic Resonance

PubMed Central

Chotenimitkhun, Runyawan; Hundley, W. Gregory

2013-01-01

Over the past decade, cardiovascular magnetic resonance (CMR) has evolved into a cardiac stress testing modality that can be used to diagnose myocardial ischemia using intravenous dobutamine or vasodilator perfusion agents such as adenosine or dipyridamole. Because CMR produces high-resolution tomographic images of the human heart in multiple imaging planes, it has become a highly attractive noninvasive testing modality for those suspected of having myocardial ischemia. The purpose of this article is to review the clinical, diagnostic, and prognostic utility of stress CMR testing for patients with (or suspected of having) coronary artery disease. PMID:21566427

Anesthetic induction with guaifenesin and propofol in adult horses.

PubMed

Brosnan, Robert J; Steffey, Eugene P; Escobar, André; Palazoglu, Mine; Fiehn, Oliver

2011-12-01

To evaluate whether guaifenesin can prevent adverse anesthetic induction events caused by propofol and whether a guaifenesin-propofol induction combination has brief cardiovascular effects commensurate with rapid drug washout. 8 healthy adult horses. Guaifenesin was administered IV for 3 minutes followed by IV injection of a bolus of propofol (2 mg/kg). Additional propofol was administered if purposeful movement was detected. Anesthesia was maintained for 2 hours with isoflurane or sevoflurane at 1.2 times the minimum alveolar concentration with controlled normocapnic ventilation. Normotension was maintained via a dobutamine infusion. Plasma concentrations of propofol and guaifenesin were measured every 30 minutes. Mean ± SD guaifenesin and propofol doses inducing anesthesia in half of the horses were 73 ± 18 mg/kg and 2.2 ± 0.3 mg/kg, respectively. No adverse anesthetic induction events were observed. By 70 minutes, there was no significant temporal change in the dobutamine infusion rate required to maintain normotension for horses anesthetized with isoflurane or sevoflurane. Mean plasma guaifenesin concentrations were 122 ± 30 μM, 101 ± 33 μM, 93 ± 28 μM, and 80 ± 24 μM at 30, 60, 90, and 120 minutes after anesthetic induction, respectively. All plasma propofol concentrations were below the limit of quantitation. Guaifenesin prevented adverse anesthetic induction events caused by propofol. Guaifenesin (90 mg/kg) followed by propofol (3 mg/kg) should be sufficient to immobilize > 99% of calm healthy adult horses. Anesthetic drug washout was rapid, and there was no change in inotrope requirements after anesthesia for 70 minutes.

Epinephrine increases contextual learning through activation of peripheral β2-adrenoceptors.

PubMed

Alves, Ester; Lukoyanov, Nikolay; Serrão, Paula; Moura, Daniel; Moreira-Rodrigues, Mónica

2016-06-01

Phenylethanolamine-N-methyltransferase knockout (Pnmt-KO) mice are unable to synthesize epinephrine and display reduced contextual fear. However, the precise mechanism responsible for impaired contextual fear learning in these mice is unknown. Our aim was to study the mechanism of epinephrine-dependent contextual learning. Wild-type (WT) or Pnmt-KO (129x1/SvJ) mice were submitted to a fear conditioning test either in the absence or in the presence of epinephrine, isoprenaline (non-selective β-adrenoceptor agonist), fenoterol (selective β2-adrenoceptor agonist), epinephrine plus sotalol (non-selective β-adrenoceptor antagonist), and dobutamine (selective β1-adrenoceptor agonist). Catecholamines were separated by reverse-phase HPLC and quantified by electrochemical detection. Blood glucose was measured by coulometry. Re-exposure to shock context induced higher freezing in WT and Pnmt-KO mice treated with epinephrine and fenoterol than in mice treated with vehicle. In addition, freezing response in Pnmt-KO mice was much lower than in WT mice. Freezing induced by epinephrine was blocked by sotalol in Pnmt-KO mice. Epinephrine and fenoterol treatment restored glycemic response in Pnmt-KO mice. Re-exposure to shock context did not induce a significant difference in freezing in Pnmt-KO mice treated with dobutamine and vehicle. Aversive memories are best retained if moderately high plasma epinephrine concentrations occur at the same moment as the aversive stimulus. In addition, epinephrine increases context fear learning by acting on peripheral β2-adrenoceptors, which may induce high levels of blood glucose. Since glucose crosses the blood-brain barrier, it may enhance hippocampal-dependent contextual learning.

Prophylactic milrinone for the prevention of low cardiac output syndrome and mortality in children undergoing surgery for congenital heart disease.

PubMed

Burkhardt, Barbara E U; Rücker, Gerta; Stiller, Brigitte

2015-03-25

Children with congenital heart disease often undergo heart surgery at a young age. They are at risk for postoperative low cardiac output syndrome (LCOS) or death. Milrinone may be used to provide inotropic and vasodilatory support during the immediate postoperative period. This review examines the effectiveness of prophylactic postoperative use of milrinone to prevent LCOS or death in children having undergone surgery for congenital heart disease. Electronic and manual literature searches were performed to identify randomised controlled trials. We searched CENTRAL, MEDLINE, EMBASE and Web of Science in February 2014 and conducted a top-up search in September 2014 as well as clinical trial registries and reference lists of published studies. We did not apply any language restrictions. Only randomised controlled trials were selected for analysis. We considered studies with newborn infants, infants, toddlers, and children up to 12 years of age. Two review authors independently extracted data according to a pre-defined protocol. We obtained additional information from all study authors. Three of the five included studies compared milrinone versus levosimendan, one study compared milrinone with placebo, and one compared milrinone verus dobutamine, with 101, 242, and 50 participants, respectively. Three trials were at low risk of bias while two were at higher risk of bias. The number and definitions of outcomes were non-uniform as well. In one study comparing two doses of milrinone and placebo, there was some evidence in an overall comparison of milrinone versus placebo that milrinone lowered risk for LCOS (risk ratio (RR) 0.52, 95% confidence interval (CI) 0.28 to 0.96; 227 participants). The results from two small studies do not provide enough information to determine whether milrinone increases the risk of LCOS when compared to levosimendan (RR 1.22, 95% CI 0.32 to 4.65; 59 participants). Mortality rates in the studies were low, and there was insufficient evidence to draw conclusions on the effect of milrinone compared to placebo or levosimendan or dobutamine regarding mortality, the duration of intensive care stay, hospital stay, mechanical ventilation, or maximum inotrope score (where available). Numbers of patients requiring mechanical cardiac support were also low and did not allow a comparison between studies, and none of the participants of any study received a heart transplantation up to the end of the respective follow-up period. Time to death within three months was not reported in any of the included studies. A number of adverse events was examined, but differences between the treatment groups could not be proven for hypotension, intraventricular haemorrhage, hypokalaemia, bronchospasm, elevated serum levels of liver enzymes, or a reduced left ventricular ejection fraction < 50% or reduced left ventricular fraction of shortening < 28%. Our analysis did not prove an increased risk of arrhythmias in patients treated prophylactically with milrinone compared with placebo (RR 3.59, 95% CI 0.83 to 15.42; 238 participants), a decreased risk of pleural effusions (RR 1.78, 95% CI 0.92 to 3.42; 231 participants), or a difference in risk of thrombocytopenia on milrinone compared with placebo (RR 0.86, 95% CI 0.39 to 1.88; 238 participants). Comparisons of milrinone with levosimendan or with dobutamine, respectively, did not clarify the risk of arrhythmia and were not possible for pleural effusions or thrombocytopenia. There is insufficient evidence of the effectiveness of prophylactic milrinone in preventing death or low cardiac output syndrome in children undergoing surgery for congenital heart disease, compared to placebo. So far, no differences have been shown between milrinone and other inodilators, such as levosimendan or dobutamine, in the immediate postoperative period, in reducing the risk of LCOS or death. The existing data on the prophylactic use of milrinone has to be viewed cautiously due to the small number of small trials and their risk of bias.

Positron emission tomography for the assessment of myocardial viability: an evidence-based analysis.

PubMed

2010-01-01

In July 2009, the Medical Advisory Secretariat (MAS) began work on Non-Invasive Cardiac Imaging Technologies for the Assessment of Myocardial Viability, an evidence-based review of the literature surrounding different cardiac imaging modalities to ensure that appropriate technologies are accessed by patients undergoing viability assessment. This project came about when the Health Services Branch at the Ministry of Health and Long-Term Care asked MAS to provide an evidentiary platform on effectiveness and cost-effectiveness of non-invasive cardiac imaging modalities.After an initial review of the strategy and consultation with experts, MAS identified five key non-invasive cardiac imaging technologies that can be used for the assessment of myocardial viability: positron emission tomography, cardiac magnetic resonance imaging, dobutamine echocardiography, and dobutamine echocardiography with contrast, and single photon emission computed tomography.A 2005 review conducted by MAS determined that positron emission tomography was more sensitivity than dobutamine echocardiography and single photon emission tomography and dominated the other imaging modalities from a cost-effective standpoint. However, there was inadequate evidence to compare positron emission tomography and cardiac magnetic resonance imaging. Thus, this report focuses on this comparison only. For both technologies, an economic analysis was also completed.The Non-Invasive Cardiac Imaging Technologies for the Assessment of Myocardial Viability is made up of the following reports, which can be publicly accessed at the MAS website at: www.health.gov.on.ca/mas or at www.health.gov.on.ca/english/providers/program/mas/mas_about.htmlPOSITRON EMISSION TOMOGRAPHY FOR THE ASSESSMENT OF MYOCARDIAL VIABILITY: An Evidence-Based AnalysisMAGNETIC RESONANCE IMAGING FOR THE ASSESSMENT OF MYOCARDIAL VIABILITY: An Evidence-Based Analysis The objective of this analysis is to assess the effectiveness and safety of positron emission tomography (PET) imaging using F-18-fluorodeoxyglucose (FDG) for the assessment of myocardial viability. To evaluate the effectiveness of FDG PET viability imaging, the following outcomes are examined: the diagnostic accuracy of FDG PET for predicting functional recovery;the impact of PET viability imaging on prognosis (mortality and other patient outcomes); andthe contribution of PET viability imaging to treatment decision making and subsequent patient outcomes. CONDITION AND TARGET POPULATION LEFT VENTRICULAR SYSTOLIC DYSFUNCTION AND HEART FAILURE: Heart failure is a complex syndrome characterized by the heart's inability to maintain adequate blood circulation through the body leading to multiorgan abnormalities and, eventually, death. Patients with heart failure experience poor functional capacity, decreased quality of life, and increased risk of morbidity and mortality. In 2005, more than 71,000 Canadians died from cardiovascular disease, of which, 54% were due to ischemic heart disease. Left ventricular (LV) systolic dysfunction due to coronary artery disease (CAD) is the primary cause of heart failure accounting for more than 70% of cases. The prevalence of heart failure was estimated at one percent of the Canadian population in 1989. Since then, the increase in the older population has undoubtedly resulted in a substantial increase in cases. Heart failure is associated with a poor prognosis: one-year mortality rates were 32.9% and 31.1% for men and women, respectively in Ontario between 1996 and 1997. IN GENERAL, THERE ARE THREE OPTIONS FOR THE TREATMENT OF HEART FAILURE: medical treatment, heart transplantation, and revascularization for those with CAD as the underlying cause. Concerning medical treatment, despite recent advances, mortality remains high among treated patients, while, heart transplantation is affected by the limited availability of donor hearts and consequently has long waiting lists. The third option, revascularization, is used to restore the flow of blood to the heart via coronary artery bypass grafting (CABG) or through minimally invasive percutaneous coronary interventions (balloon angioplasty and stenting). Both methods, however, are associated with important perioperative risks including mortality, so it is essential to properly select patients for this procedure. Left ventricular dysfunction may be permanent if a myocardial scar is formed, or it may be reversible after revascularization. Reversible LV dysfunction occurs when the myocardium is viable but dysfunctional (reduced contractility). Since only patients with dysfunctional but viable myocardium benefit from revascularization, the identification and quantification of the extent of myocardial viability is an important part of the work-up of patients with heart failure when determining the most appropriate treatment path. Various non-invasive cardiac imaging modalities can be used to assess patients in whom determination of viability is an important clinical issue, specifically: dobutamine echocardiography (echo),stress echo with contrast,SPECT using either technetium or thallium,cardiac magnetic resonance imaging (cardiac MRI), andpositron emission tomography (PET). Stress echocardiography can be used to detect viable myocardium. During the infusion of low dose dobutamine (5 - 10 μg/kg/min), an improvement of contractility in hypokinetic and akentic segments is indicative of the presence of viable myocardium. Alternatively, a low-high dose dobutamine protocol can be used in which a biphasic response characterized by improved contractile function during the low-dose infusion followed by a deterioration in contractility due to stress induced ischemia during the high dose dobutamine infusion (dobutamine dose up to 40 ug/kg/min) represents viable tissue. Newer techniques including echocardiography using contrast agents, harmonic imaging, and power doppler imaging may help to improve the diagnostic accuracy of echocardiographic assessment of myocardial viability. Intravenous contrast agents, which are high molecular weight inert gas microbubbles that act like red blood cells in the vascular space, can be used during echocardiography to assess myocardial viability. These agents allow for the assessment of myocardial blood flow (perfusion) and contractile function (as described above), as well as the simultaneous assessment of perfusion to make it possible to distinguish between stunned and hibernating myocardium. SPECT: SPECT can be performed using thallium-201 (Tl-201), a potassium analogue, or technetium-99 m labelled tracers. When Tl-201 is injected intravenously into a patient, it is taken up by the myocardial cells through regional perfusion, and Tl-201 is retained in the cell due to sodium/potassium ATPase pumps in the myocyte membrane. The stress-redistribution-reinjection protocol involves three sets of images. The first two image sets (taken immediately after stress and then three to four hours after stress) identify perfusion defects that may represent scar tissue or viable tissue that is severely hypoperfused. The third set of images is taken a few minutes after the re-injection of Tl-201 and after the second set of images is completed. These re-injection images identify viable tissue if the defects exhibit significant fill-in (> 10% increase in tracer uptake) on the re-injection images. The other common Tl-201 viability imaging protocol, rest-redistribution, involves SPECT imaging performed at rest five minutes after Tl-201 is injected and again three to four hours later. Viable tissue is identified if the delayed images exhibit significant fill-in of defects identified in the initial scans (> 10% increase in uptake) or if defects are fixed but the tracer activity is greater than 50%. There are two technetium-99 m tracers: sestamibi (MIBI) and tetrofosmin. The uptake and retention of these tracers is dependent on regional perfusion and the integrity of cellular membranes. Viability is assessed using one set of images at rest and is defined by segments with tracer activity greater than 50%. Cardiac magnetic resonance imaging (cardiac MRI) is a non-invasive, x-ray free technique that uses a powerful magnetic field, radio frequency pulses, and a computer to produce detailed images of the structure and function of the heart. Two types of cardiac MRI are used to assess myocardial viability: dobutamine stress magnetic resonance imaging (DSMR) and delayed contrast-enhanced cardiac MRI (DE-MRI). DE-MRI, the most commonly used technique in Ontario, uses gadolinium-based contrast agents to define the transmural extent of scar, which can be visualized based on the intensity of the image. Hyper-enhanced regions correspond to irreversibly damaged myocardium. As the extent of hyper-enhancement increases, the amount of scar increases, so there is a lower the likelihood of functional recovery. Positron emission tomography (PET) is a nuclear medicine technique used to image tissues based on the distinct ways in which normal and abnormal tissues metabolize positron-emitting radionuclides. Radionuclides are radioactive analogs of common physiological substrates such as sugars, amino acids, and free fatty acids that are used by the body. The only licensed radionuclide used in PET imaging for viability assessment is F-18 fluorodeoxyglucose (FDG). During a PET scan, the radionuclides are injected into the body and as they decay, they emit positively charged particles (positrons) that travel several millimetres into tissue and collide with orbiting electrons. (ABSTRACT TRUNCATED)

Electrophysiology and metabolism of caveolin-3 overexpressing mice

PubMed Central

Schilling, Jan M.; Horikawa, Yousuke T.; Zemljic-Harpf, Alice E.; Vincent, Kevin P.; Tyan, Leonid; Yu, Judith K.; McCulloch, Andrew D.; Balijepalli, Ravi C.; Patel, Hemal H.; Roth, David M.

2017-01-01

Caveolin-3 (Cav-3) plays a critical role in organizing signaling molecules and ion channels involved in cardiac conduction and metabolism. Mutations in Cav-3 are implicated in cardiac conduction abnormalities and myopathies. Additionally, cardiac specific overexpression of Cav-3 (Cav-3 OE) is protective against ischemic and hypertensive injury suggesting a potential role for Cav-3 in basal cardiac electrophysiology and metabolism involved in stress adaptation. We hypothesized that overexpression of Cav-3 may alter baseline cardiac conduction and metabolism. We examined: 1) ECG telemetry recordings at baseline and during pharmacological interventions, 2) ion channels involved in cardiac conduction with immunoblotting and computational modeling, and 3) baseline metabolism in Cav-3 OE and transgene negative littermate control mice. Cav-3 OE mice had decreased heart rates, prolonged PR intervals, and shortened QTc intervals with no difference in activity compared to control mice. Dobutamine or propranolol did not cause significant changes between experimental groups in maximal (dobutamine) or minimal (propranolol) heart rate. Cav-3 OE mice had an overall lower chronotropic response to atropine. Expression of Kv1.4 and Kv4.3 channels, Nav1.5 channels and connexin 43 were increased in Cav-3 OE mice. A computational model integrating the immunoblotting results indicated shortened action potential duration in Cav-3 OE mice linking the change in channel expression to the observed electrophysiology phenotype. Metabolic profiling showed no gross differences in VO2, VCO2, respiratory exchange ratio, and heat generation, feeding or drinking. In conclusion, Cav-3 OE mice have changes in ECG intervals, heart rates, and cardiac ion channel expression. These findings give novel mechanistic insights into previously reported Cav-3 dependent cardioprotection. PMID:27023865

Assessment of strain and strain rate by two-dimensional speckle tracking in mice: comparison with tissue Doppler echocardiography and conductance catheter measurements.

PubMed

Ferferieva, V; Van den Bergh, A; Claus, P; Jasaityte, R; La Gerche, A; Rademakers, F; Herijgers, P; D'hooge, J

2013-08-01

This study was designed in order to compare the strain and strain rate deformation parameters assessed by speckle tracking imaging (STI) with those of tissue Doppler imaging (TDI) and conductance catheter measurements in chronic murine models of left ventricular (LV) dysfunction. Twenty-four male C57BL/6J mice were assigned to wild-type (n = 8), myocardial infarction (n = 8) and transaortic constriction (n = 8) groups. Echocardiographic and conductance measurements were simultaneously performed at rest and during dobutamine infusion (5 µg/kg/min) in all animals 10 weeks post-surgery. The LV circumferential strain (Scirc) and the strain rate (SRcirc) were derived from grey scale and tissue Doppler data at frame rates of 224 and 375 Hz, respectively. Scirc and SRcirc by TDI/STI correlated well with the preload recruitable stroke work (PRSW) (r = -0.64 and -0.71 for TDI; r = -0.46 and -0.50 for STI, P < 0.05). Both modalities showed a good agreement with respect to Scirc and SRcirc (r = 0.60 and r = 0.63, P < 0.05). During stress, however, TDI-estimated Scirc and SRcirc values were predominantly higher than those measured by STI (P < 0.05). The similarity of Scirc and SRcirc measurements with respect to the STI/TDI data was examined by the Bland-Altman analysis. In mice, the STI- and TDI-derived strain and strain rate deformation parameters relate closely to intrinsic myocardial function. At low heart rate-to-frame rate ratios (HR/FR), both STI and TDI are equally acceptable for assessing the LV function non-invasively in these animals. At HR/FR (e.g. dobutamine challenge), however, these methods cannot be used interchangeably as STI underestimates S and SR at high values.

Relation of dyspnea in patients unable to perform exercise stress testing to outcome and myocardial ischemia.

PubMed

Bernheim, Alain M; Kittipovanonth, Maytinee; Scott, Christopher G; McCully, Robert B; Tsang, Teresa S; Pellikka, Patricia A

2009-07-15

Limited information exists regarding the significance of dyspnea in patients who are unable to exercise and the contribution of myocardial ischemia to this symptom. To assess this, we evaluated results of dobutamine stress echocardiography (DSE) and long-term outcome of patients with dyspnea referred for DSE. We studied 6,376 consecutive patients who were unable to perform an exercise test and were referred for DSE. Patients were classified according to presenting symptoms and followed for 5.5 +/- 2.8 years. End points were cardiac ischemic events (myocardial infarction or revascularization), hospitalization for heart failure (HF), and death. Dobutamine stress echocardiogram was positive for ischemia in 19% of patients with dyspnea versus 24% (p = 0.002) of those with typical angina and 17% (p = 0.2) of asymptomatic patients. In multivariate analysis, risk of death was increased in dyspneic patients versus asymptomatic patients (hazard ratio [HR] 1.14, p = 0.02) and patients with chest pain (HR 1.20, p <0.001). Hospitalization for HF occurred more often in patients with dyspnea (HR 1.26, p = 0.05 vs asymptomatic; HR 1.24, p = 0.06 vs chest pain), especially in the subset without previous HF (HR 1.45, p = 0.006 vs chest pain). Risk of cardiac ischemic events in patients with dyspnea was similar versus asymptomatic patients (HR 0.92, p = 0.39) and decreased versus patients with chest pain (HR 0.70, p <0.001). In conclusion, in patients referred for DSE, dyspnea was associated with a poor outcome. This increased hazard seems not to be linked to myocardial ischemia, but instead to HF and death.

Validation of a defibrillation lead ventricular volume measurement compared to three-dimensional echocardiography.

PubMed

Haines, David E; Wong, Wilson; Canby, Robert; Jewell, Coty; Houmsse, Mahmoud; Pederson, David; Sugeng, Lissa; Porterfield, John; Kottam, Anil; Pearce, John; Valvano, Jon; Michalek, Joel; Trevino, Aron; Sagar, Sandeep; Feldman, Marc D

2017-10-01

There is increasing evidence that using frequent invasive measures of pressure in patients with heart failure results in improved outcomes compared to traditional measures. Admittance, a measure of volume derived from preexisting defibrillation leads, is proposed as a new technique to monitor cardiac hemodynamics in patients with an implantable defibrillator. The purpose of this study was to evaluate the accuracy of a new ventricular volume sensor (VVS, CardioVol) compared with 3-dimenssional echocardiography (echo) in patients with an implantable defibrillator. Twenty-two patients referred for generator replacement had their defibrillation lead attached to VVS to determine the level of agreement to a volume measurement standard (echo). Two opposite hemodynamic challenges were sequentially applied to the heart (overdrive pacing and dobutamine administration) to determine whether real changes in hemodynamics could be reliably and repeatedly assessed with VVS. Equivalence of end-diastolic volume (EDV) and stroke volume (SV) determined by both methods was also assessed. EDV and SV were compared using VVS and echo. VVS tracked expected physiologic trends. EDV was modulated -10% by overdrive pacing (14 mL). SV was modulated -13.7% during overdrive pacing (-6 mL) and increased over baseline +14.6% (+8 mL) with dobutamine. VVS and echo mean EDVs were found statistically equivalent, with margin of equivalence 13.8 mL (P <.05). Likewise, mean SVs were found statistically equivalent with margin of equivalence 15.8 mL (P <.05). VVS provides an accurate method for ventricular volume assessment using chronically implanted defibrillator leads and is statistically equivalent to echo determination of mean EDV and SV. Copyright © 2017 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

Low-dose dobutamine gated-SPECT analysis of left ventricular segmental wall thickening in ischemic cardiomyopathy.

PubMed

Candell-Riera, Jaume; Romero-Farina, Guillermo; Milá, Marta; Aguadé-Bruix, Santiago

2008-10-01

The objective of this study was to use low-dose dobutamine (LDD) gated single-photon emission computed tomography (SPECT) to evaluate segmental thickening of the left ventricle (LV) and its relationship with changes in ejection fraction (EF) and ventricular volumes in patients with ischemic cardiomyopathy. This prospective multicenter study involved 89 patients with ischemic cardiomyopathy (i.e., EF < or =40%) who underwent LDD gated-SPECT at rest. The LV was divided into 17 segments and systolic thickening was assessed in a total of 1513 segments during LDD infusion. RESULTS; A significant increase in LVEF (33.2% vs. 30.8%; P< .001) was observed during LDD infusion and occurred at the expense of a reduction in end-systolic volume (130.5 mL vs. 136.4 mL; P=.005). The increase in EF was > or =5% in 33.7% of patients, while the EF decreased by > or =5% in 5.6% of patients. With LDD infusion, both an improvement in > or =3 segments with severely decreased baseline thickening (odds ratio [OR] = 18.3; 95% confidence interval [CI], 5.3-63) and an improvement in > or =10 segments with mild-to-moderate alterations in baseline thickening (OR = 4.53; 95% CI, 1.26-16.16) were associated with a > or =5% increase in LVEF. During the assessment of global left ventricular contractile reserve by LDD gated-SPECT, attention should be paid not only to the behavior of segments with severely decreased baseline thickening, which are generally regarded as indicating viability, but also to segments with mild-to-moderate alterations and to those in which thickening decreases.

And the beat goes on: maintained cardiovascular function during aging in the longest-lived rodent, the naked mole-rat

PubMed Central

Grimes, Kelly M.; Reddy, Anilkumar K.; Lindsey, Merry L.

2014-01-01

The naked mole-rat (NMR) is the longest-lived rodent known, with a maximum lifespan potential (MLSP) of >31 years. Despite such extreme longevity, these animals display attenuation of many age-associated diseases and functional changes until the last quartile of their MLSP. We questioned if such abilities would extend to cardiovascular function and structure in this species. To test this, we assessed cardiac functional reserve, ventricular morphology, and arterial stiffening in NMRs ranging from 2 to 24 years of age. Dobutamine echocardiography (3 μg/g ip) revealed no age-associated changes in left ventricular (LV) function either at baseline or with exercise-like stress. Baseline and dobutamine-induced LV pressure parameters also did not change. Thus the NMR, unlike other mammals, maintains cardiac reserve with age. NMRs showed no cardiac hypertrophy, evidenced by no increase in cardiomyocyte cross-sectional area or LV dimensions with age. Age-associated arterial stiffening does not occur since there are no changes in aortic blood pressures or pulse-wave velocity. Only LV interstitial collagen deposition increased 2.5-fold from young to old NMRs (P < 0.01). However, its effect on LV diastolic function is likely minor since NMRs experience attenuated age-related increases in diastolic dysfunction in comparison with other species. Overall, these findings conform to the negligible senescence phenotype, as NMRs largely stave off cardiovascular changes for at least 75% of their MLSP. This suggests that using a comparative strategy to find factors that change with age in other mammals but not NMRs could provide novel targets to slow or prevent cardiovascular aging in humans. PMID:24906918

Limited Ventricular Preload is the Main Reason for Reduced Stress Reserve After Atrial Baffle Repair.

PubMed

Eicken, Andreas; Michel, Julia; Hager, Alfred; Tanase, Daniel; Kaemmerer, Harald; Cleuziou, Julie; Hess, John; Ewert, Peter

2017-02-01

The atrial baffle repair (ABR) significantly improved the fate of patients with transposition of the great arteries (TGA). However, these patients show impaired exercise tolerance and some present severe decline of systemic ventricular function. Intrinsic myocardial weakness, low heart rate response to exercise and diastolic filling impairment are discussed to be causative. Forty-nine long-term survivors with TGA (median age 23.7 year) after ABR were catheterized with measured oxygen consumption in four conditions (baseline, volume, atrial pacing, dobutamine) and the results were compared to 10 normal controls. Median cardiac output was significantly lower in the ABR group (2.2 vs. 2.6 l/min/m 2 ; p = 0.015), and systemic resistance was significantly elevated (28.9 vs. 22.2 U m 2 ; p = 0.04) in comparison with normals. While stroke volume rose by 27% in the control group, it dropped by 7% in patients after ABR at atrial pacing (80/min). Stroke volume increase after dobutamine was significantly lower after ABR in comparison with normal controls (34 vs. 106%; p = 0.001). Higher NYHA class (p = 0.043), degree of tricuspid regurgitation (p = 0.009) and ventricular function (p = 0.028) were associated with lower stroke volume increase. Limited exercise capability of patients after ABR for TGA is primarily due to limited diastolic filling of the ventricles due to stiff non-compliant atrial pathways. Elevated systemic resistance may lead to severe myocardial hypertrophy with possible ischemia and contribute to the multifactorial decline of ventricular function in some patients.

Pressure-volume Relationship in the Stress-echocardiography Laboratory: Does (Left Ventricular End-diastolic) Size Matter?

PubMed

Bombardini, Tonino; Mulieri, Louis A; Salvadori, Stefano; Costantino, Marco Fabio; Scali, Maria Chiara; Marzilli, Mario; Picano, Eugenio

2017-02-01

The variation between rest and peak stress end-systolic pressure-volume relation is an afterload-independent index of left ventricular contractility. Whether and to what extent it depends on end-diastolic volume remains unclear. The aim of this study was to assess the dependence of the delta rest-stress end-systolic pressure-volume relation on end-diastolic volume in patients with negative stress echo and all ranges of resting left ventricular function. We analyzed interpretable data obtained in 891 patients (593 men, age 63 ± 12 years) with ejection fraction 47% ± 12%: 338 were normal or near-normal or hypertensive; 229 patients had coronary artery disease; and 324 patients had ischemic or nonischemic dilated cardiomyopathy. They were studied with exercise (n = 172), dipyridamole (n = 482) or dobutamine (n = 237) stress echocardiography. The end-systolic pressure-volume relation was evaluated at rest and peak stress from raw measurement of systolic arterial pressure by cuff sphygmomanometer and end-systolic volume by biplane Simpson rule 2-dimensional echocardiography. Absolute values of delta rest-stress end-systolic pressure-volume relation were higher for exercise and dobutamine than for dipyridamole. In the overall population, an inverse relationship between end-systolic pressure-volume relation and end-diastolic volume was present at rest (r 2 = 0.69, P < .001) and peak stress (r 2 = 0.56, P < .001), but was absent if the delta rest-stress end-systolic pressure-volume relation was considered (r 2 = 0.13). Left ventricular end-diastolic volume does not affect the rest-stress changes in end-systolic pressure-volume relation in either normal or abnormal left ventricles during physical or pharmacological stress. Copyright © 2016 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.

The prognostic value of dobutamine stress echocardiography amongst British Indian Asian and Afro-Caribbean patients: a comparison with European white patients.

PubMed

O'Driscoll, Jamie M; Rossato, Claire; Gargallo-Fernandez, Paula; Araco, Marco; Giannoglou, Dimitrios; Sharma, Sanjay; Sharma, Rajan

2015-08-06

The incidence of cardiovascular disease is considerably disparate among different racial and ethnic populations. While dobutamine stress echocardiography (DSE) has been shown to be useful in Caucasian patients, its role among ethnic minority groups remains unclear. This study aimed to investigate the prognostic importance of DSE in three ethnic groups in the UK. DSE was performed on 6231 consecutive patients. After exclusions, 5329 patients formed the study (2676 [50.2%] Indian Asian, 2219 [41.6%] European white and 434 [8.1%] Afro-Caribbean). Study outcome measures were non-fatal cardiac events (NFCE) and all-cause mortality. There were 849 (15.9%) NFCE and 1365 (25.6%) deaths over a median follow-up period of 4.6 years. In total 1174 (22%) patients had inducible myocardial ischaemia during DSE, 859 (16.1%) had fixed wall motion abnormalities and 3645 (68.4%) patients had a normal study. Ethnicity did not predict events. Among the three ethnic groups, ischaemia on DSE was associated with 2 to 2.5 times the risk of non-fatal cardiac events and 1.2 to 1.4 times the risk of all-cause mortality. Peak wall motion score index was the strongest independent predictor of non-fatal cardiac events and all-cause mortality in all groups. The C statistic for the prediction of NFCE and all-cause mortality were significantly higher when DSE parameters were added to the standard risk factors for all ethnic groups. DSE is a strong predictor of NFCE and all-cause mortality and provides predictive information beyond that provided by standard risk factors in three major racial and ethnic groups. No major differences among racial and ethnic groups in the predictive value of DSE was detected.

Comparison of detomidine and romifidine as premedicants before ketamine and halothane anesthesia in horses undergoing elective surgery.

PubMed

Taylor, P M; Bennett, R C; Brearley, J C; Luna, S P; Johnson, C B

2001-03-01

To compare detomidine hydrochloride and romifidine as premedicants in horses undergoing elective surgery. 100 client-owned horses. After administration of acepromazine (0.03 mg/kg, IV), 50 horses received detomidine hydrochloride (0.02 mg/kg of body weight, IV) and 50 received romifidine (0.1 mg/kg, IV) before induction and maintenance of anesthesia with ketamine hydrochloride (2 mg/kg) and halothane, respectively. Arterial blood pressure and blood gases, ECG, and heart and respiratory rates were recorded. Induction and recovery were timed and graded. Mean (+/- SD) duration of anesthesia for all horses was 104 +/- 28 minutes. Significant differences in induction and recovery times or grades were not detected between groups. Mean arterial blood pressure (MABP) decreased in both groups 30 minutes after induction, compared with values at 10 minutes. From 40 to 70 minutes after induction, MABP was significantly higher in detomidine-treated horses, compared with romifidine-treated horses, although more romifidine-treated horses received dobutamine infusions. In all horses, mean respiratory rate ranged from 9 to 11 breaths/min, PaO2 from 200 to 300 mm Hg, PaCO2 from 59 to 67 mm Hg, arterial pH from 7.33 to 7.29, and heart rate from 30 to 33 beats/min, with no significant differences between groups. Detomidine and romifidine were both satisfactory premedicants. Romifidine led to more severe hypotension than detomidine, despite administration of dobutamine to more romifidine-treated horses. Both detomidine and romifidine are acceptable alpha2-adrenoceptor agonists for use as premedicants before general anesthesia in horses; however, detomidine may be preferable when maintenance of blood pressure is particularly important.

Impact of Dobutamine in Patients With Septic Shock: A Meta-Regression Analysis.

PubMed

Nadeem, Rashid; Sockanathan, Shivani; Singh, Mukesh; Hussain, Tamseela; Kent, Patrick; AbuAlreesh, Sarah

2017-05-01

Septic shock frequently requires vasopressor agents. Conflicting evidence exists for use of inotropes in patients with septic shock. Data from English studies on human adult septic shock patients were collected. A total of 83 studies were reviewed, while 11 studies with 21 data sets including 239 patients were pooled for meta-regression analysis. For VO2, pooled difference in means (PDM) was 0.274. For cardiac index (CI), PDM was 0.783. For delivery of oxygen, PDM was -0.890. For heart rate, PDM was -0.714. For left ventricle stroke work index, PDM was 0.375. For mean arterial pressure, PDM was -0.204. For mean pulmonary artery pressure, PDM was 0.085. For O2 extraction, PDM was 0.647. For PaCO2, PDM was -0.053. For PaO2, PDM was 0.282. For pulmonary artery occlusive pressure, PDM was 0.270. For pulmonary capillary wedge pressure, PDM was 0.300. For PVO2, PDM was -0.492. For right atrial pressure, PDM was 0.246. For SaO2, PDM was 0.604. For stroke volume index, PDM was 0.446. For SvO2, PDM was -0.816. For systemic vascular resistance, PDM was -0.600. For systemic vascular resistance index, PDM was 0.319. Meta-regression analysis was performed for VO2, DO2, CI, and O2 extraction. Age was found to be significant confounding factor for CI, DO2, and O2 extraction. APACHE score was not found to be a significant confounding factor for any of the parameters. Dobutamine seems to have a positive effect on cardiovascular parameters in patients with septic shock. Prospective studies with larger samples are required to further validate this observation.

Effect of spinal cord stimulation on myocardial perfusion reserve in patients with refractory angina pectoris.

PubMed

Saraste, Antti; Ukkonen, Heikki; Varis, Antti; Vasankari, Tuija; Tunturi, Satu; Taittonen, Markku; Rautakorpi, Pirkka; Luotolahti, Matti; Airaksinen, K E Juhani; Knuuti, Juhani

2015-04-01

Epidural spinal cord stimulation (SCS) provides symptom relief in refractory angina pectoris, but its mechanism of action remains incompletely understood. We studied effects of short-term SCS therapy on myocardial ischaemia tolerance, myocardial perfusion reserve (MPR), and endothelium-mediated vasodilatation induced by cold pressor test (CPT) in patients with refractory angina pectoris. We prospectively recruited 18 patients with refractory angina pectoris and studied them after implantation of SCS device at baseline before starting the therapy and after 3 weeks of continuous SCS therapy. Myocardial ischaemia was evaluated by dobutamine stress echocardiography. Global and regional myocardial blood flow (MBF) were measured using positron emission tomography and (15)O-water at rest, during adenosine stress, and in response to CPT. Systemic haemodynamics were comparable before and after 3 weeks of SCS at rest, during adenosine stress and during CPT. Appearance of angina pectoris induced by dobutamine stress was delayed after SCS therapy. Global MPR increased (P = 0.02) from 1.7 ± 0.6 at baseline to 2.0 ± 0.6 after 3-week SCS therapy. This was associated with a significant reduction in global MBF at rest and increase in MBF induced by adenosine in the ischaemic regions. Global MBF response to CPT was improved after SCS (0.27 ± 0.20 vs. 0.40 ± 0.15, P = 0.03). Short-term SCS therapy improved myocardial ischaemia tolerance, absolute MPR, and endothelium-mediated vasomotor function in refractory angina pectoris, indicating that this therapy can alleviate myocardial perfusion abnormalities in advanced CAD. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2014. For permissions please email: journals.permissions@oup.com.

Comparison of Quantitative Wall Motion Analysis and Strain For Detection Of Coronary Stenosis With Three-Dimensional Dobutamine Stress Echocardiography

PubMed Central

Parker, Katherine M.; Clark, Alexander P.; Goodman, Norman C.; Glover, David K.; Holmes, Jeffrey W.

2015-01-01

Background Quantitative analysis of wall motion from three-dimensional (3D) dobutamine stress echocardiography (DSE) could provide additional diagnostic information not available from qualitative analysis. In this study we compare the effectiveness of 3D fractional shortening (3DFS), a measure of wall motion computed from 3D echocardiography (3DE), to strain and strain rate measured with sonomicrometry for detecting critical stenoses during DSE. Methods Eleven open-chest dogs underwent DSE both with and without a critical stenosis. 3DFS was measured from 3DE images acquired at peak stress. 3DFS was normalized by subtracting average 3DFS during control peak stress (Δ3DFS). Strains in the perfusion defect (PD) were measured from sonomicrometry, and PD size and location were measured with microspheres. Results A Δ3DFS abnormality indicated the presence of a critical stenosis with high sensitivity and specificity (88% and 100%, respectively), and Δ3DFS abnormality size correlated with PD size (R2=0.54). The sensitivity and specificity for Δ3DFS was similar to that for area strain (88%, 100%) and circumferential strain and strain rate (88%, 92% and 88%, 86%, respectively), while longitudinal strain and strain rate were less specific. Δ3DFS correlated significantly with both coronary flow reserve (R2=0.71) and PD size (R2=0.97), while area strain correlated with PD size only (R2=0.67), and other measures were not significantly correlated with flow reserve or PD size. Conclusion Quantitative wall motion analysis using Δ3DFS is effective for detecting critical stenoses during DSE, performing similarly to 3D strain, and provides potentially useful information on the size and location of a perfusion defect. PMID:24815588

Impact of scar thickness on the assessment of viability using dobutamine echocardiography and thallium single-photon emission computed tomography: a comparison with contrast-enhanced magnetic resonance imaging.

PubMed

Nelson, Charles; McCrohon, Jane; Khafagi, Frederick; Rose, Stephen; Leano, Rodel; Marwick, Thomas H

2004-04-07

We sought to determine whether the transmural extent of scar (TES) explains discordances between dobutamine echocardiography (DbE) and thallium single-photon emission computed tomography (Tl-SPECT) in the detection of viable myocardium (VM). Discrepancies between DbE and Tl-SPECT are often attributed to differences between contractile reserve and membrane integrity, but may also reflect a disproportionate influence of nontransmural scar on thickening at DbE. Sixty patients (age 62 +/- 12 years; 10 women and 50 men) with postinfarction left ventricular dysfunction underwent standard rest-late redistribution Tl-SPECT and DbE. Viable myocardium was identified when dysfunctional segments showed Tl activity >60% on the late-redistribution image or by low-dose augmentation at DbE. Contrast-enhanced magnetic resonance imaging (ceMRI) was used to divide TES into five groups: 0%, <25%, 26% to 50%, 51% to 75%, and >75% of the wall thickness replaced by scar. As TES increased, both the mean Tl uptake and change in wall motion score decreased significantly (both p < 0.001). However, the presence of subendocardial scar was insufficient to prevent thickening; >50% of segments still showed contractile function with TES of 25% to 75%, although residual function was uncommon with TES >75%. The relationship of both tests to increasing TES was similar, but Tl-SPECT identified VM more frequently than DbE in all groups. Among segments without scar or with small amounts of scar (<25% TES), >50% were viable by SPECT. Both contractile reserve and perfusion are sensitive to the extent of scar. However, contractile reserve may be impaired in the face of no or minor scar, and thickening may still occur with extensive scar.

A Novel Feature-Tracking Echocardiographic Method for the Quantitation of Regional Myocardial Function

PubMed Central

Pirat, Bahar; Khoury, Dirar S.; Hartley, Craig J.; Tiller, Les; Rao, Liyun; Schulz, Daryl G.; Nagueh, Sherif F.; Zoghbi, William A.

2012-01-01

Objectives The aim of this study was to validate a novel, angle-independent, feature-tracking method for the echocardiographic quantitation of regional function. Background A new echocardiographic method, Velocity Vector Imaging (VVI) (syngo Velocity Vector Imaging technology, Siemens Medical Solutions, Ultrasound Division, Mountain View, California), has been introduced, based on feature tracking—incorporating speckle and endocardial border tracking, that allows the quantitation of endocardial strain, strain rate (SR), and velocity. Methods Seven dogs were studied during baseline, and various interventions causing alterations in regional function: dobutamine, 5-min coronary occlusion with reperfusion up to 1 h, followed by dobutamine and esmolol infusions. Echocardiographic images were acquired from short- and long-axis views of the left ventricle. Segment-length sonomicrometry crystals were used as the reference method. Results Changes in systolic strain in ischemic segments were tracked well with VVI during the different states of regional function. There was a good correlation between circumferential and longitudinal systolic strain by VVI and sonomicrometry (r = 0.88 and r = 0.83, respectively, p < 0.001). Strain measurements in the nonischemic basal segments also demonstrated a significant correlation between the 2 methods (r = 0.65, p < 0.001). Similarly, a significant relation was observed for circumferential and longitudinal SR between the 2 methods (r = 0.94, p < 0.001 and r = 0.90, p < 0.001, respectively). The endocardial velocity relation to changes in strain by sonomicrometry was weaker owing to significant cardiac translation. Conclusions Velocity Vector Imaging, a new feature-tracking method, can accurately assess regional myocardial function at the endocardial level and is a promising clinical tool for the simultaneous quantification of regional and global myocardial function. PMID:18261685

A novel feature-tracking echocardiographic method for the quantitation of regional myocardial function: validation in an animal model of ischemia-reperfusion.

PubMed

Pirat, Bahar; Khoury, Dirar S; Hartley, Craig J; Tiller, Les; Rao, Liyun; Schulz, Daryl G; Nagueh, Sherif F; Zoghbi, William A

2008-02-12

The aim of this study was to validate a novel, angle-independent, feature-tracking method for the echocardiographic quantitation of regional function. A new echocardiographic method, Velocity Vector Imaging (VVI) (syngo Velocity Vector Imaging technology, Siemens Medical Solutions, Ultrasound Division, Mountain View, California), has been introduced, based on feature tracking-incorporating speckle and endocardial border tracking, that allows the quantitation of endocardial strain, strain rate (SR), and velocity. Seven dogs were studied during baseline, and various interventions causing alterations in regional function: dobutamine, 5-min coronary occlusion with reperfusion up to 1 h, followed by dobutamine and esmolol infusions. Echocardiographic images were acquired from short- and long-axis views of the left ventricle. Segment-length sonomicrometry crystals were used as the reference method. Changes in systolic strain in ischemic segments were tracked well with VVI during the different states of regional function. There was a good correlation between circumferential and longitudinal systolic strain by VVI and sonomicrometry (r = 0.88 and r = 0.83, respectively, p < 0.001). Strain measurements in the nonischemic basal segments also demonstrated a significant correlation between the 2 methods (r = 0.65, p < 0.001). Similarly, a significant relation was observed for circumferential and longitudinal SR between the 2 methods (r = 0.94, p < 0.001 and r = 0.90, p < 0.001, respectively). The endocardial velocity relation to changes in strain by sonomicrometry was weaker owing to significant cardiac translation. Velocity Vector Imaging, a new feature-tracking method, can accurately assess regional myocardial function at the endocardial level and is a promising clinical tool for the simultaneous quantification of regional and global myocardial function.

Effects of Calorie Restriction on Cardioprotection and Cardiovascular Health

PubMed Central

Ahmet, Ismayil; Tae, Hyun-Jin; de Cabo, Rafael; Lakatta, Edward G.; Talan, Mark I.

2011-01-01

Multiple health benefits of calorie restriction (CR) and alternate day fasting (ADF) regimens are widely recognized. Experimental data concerning the effects of calorie restriction on cardiac health are more controversial, ranging from evidence that ADF protects heart from ischemic damage but results in developing of diastolic dysfunction, to reports that CR ameliorates the age-associated diastolic dysfunction. Here we investigated the effects of chronic CR on morphology and function of the cardiovascular system of aged rats and cardioprotective effect of CR against ischemic damage in the experimental rat model of MI. Cardiovascular fitness of 24-mo old Fisher 344 rats maintained through life on ad libitum (AL) or CR diets was extensively evaluated via echocardiography, dobutamine stress test, pressure-volume loop analyses, pulse wave velocity measurements, and histology. Groups of 2-mo old AL and 29-mo old CR rats were studied for comparison. Myocardial infarction (MI) was induced by a permanent ligation of the anterior descending coronary artery in 5-mo old rats maintained for 3 months on CR or AL. MI size was evaluated histologically 24 hrs following coronary ligation. Cardiac remodeling was followed-up via echocardiography. Age-associated changes in 24-mo old rats consisted of 33% increase of fibrosis in the myocardium and more than 2 fold increase of the collagen in the tunica media of the aorta. There was a significant decrease in the density and total number of cardiomyocytes, while their size was increased. These morphological changes were manifested in a decline of systolic and diastolic cardiac function, increase of left ventricular and aortic stiffness, and arterio-ventricular uncoupling. Tachycardic response to dobutamine challenge was absent in the old rats. Compared to AL rats, 24-mo old CR rats had reduced levels of cardiac and aortic fibrosis, increased density of cardiomyocytes that were smaller in size, attenuated diastolic dysfunction, normal systolic function and arterio-ventricular coupling. Tachycardic response to dobutamine was also intact in CR 24-mo old rats and aortic stiffness was reduced. Adjustment for body weight differences through ratiometric or allometric scaling did not affect the overall pattern of differences between AL and CR rats. Attenuation of morphological and functional age-associated changes in 24-mo old CR rats either was not observed at all or was smaller in 29-mo old CR rats. Size of MI induced by a permanent coronary ligation as well as post-MI cardiac remodeling and function were similar in CR and AL rats. CR does not increase tolerance of myocardium to ischemic damage, but attenuates the age-associated changes in the heart and major vessels. The attenuation of age-associated changes by CR cannot be explained by the effect of lower body weight but are attributable to more intimate cellular mechanisms of CR itself. Attenuation of age-associated changes by CR waned with advancing age, and is consistent with the idea that CR postponed senescence. PMID:21586294

New developments for the detection and treatment of cardiac vasculopathy.

PubMed

Clerkin, Kevin J; Ali, Ziad A; Mancini, Donna M

2017-02-15

Cardiac allograft vasculopathy (CAV) is a major limitation to long-term survival after heart transplantation. Innovative new techniques to diagnose CAV have been applied to detect disease. This review will examine the current diagnostic and treatment options available to clinicians for CAV. Diagnostic modalities addressing the pathophysiology underlying CAV (arterial wall thickening and decreased coronary blood flow) improve diagnostic sensitivity when compared to traditional (angiography and dobutamine stress echocardiography) techniques. Limited options are available to prevent and treat CAV; however, progress has been made in making an earlier and more accurate diagnosis. Future research is needed to identify the optimal time to modify immunosuppression and investigate novel treatments for CAV.

Determination of fenoterol in human plasma by HPLC with fluorescence detection after derivatization.

PubMed

Meineke, Ingolf; Steinmetz, Hannelore; Kramer, Skaidrit; Gleiter, Christoph H

2002-06-20

A new method for the determination of fenoterol is described, which uses HPLC separation with fluorescence detection. Dobutamine is employed as an internal standard. The separation was achieved on a short reversed phase column with a mobile phase consisting of water, acetonitrile and methanol. Prior to chromatography both analytes are derivatized with 9-chloroformyl-carbazole. Isolation of the analytes from plasma is carried out by liquid-liquid extraction into 2-butanol after protein precipitation with acetonitrile. The method is capable of estimating fenoterol concentrations in the sub-nanogram per ml range with sufficient accuracy and precision. The determination of fenoterol can now be carried out in the average laboratory without radiolabelled material.

Magnetic resonance imaging (MRI) for the assessment of myocardial viability: an evidence-based analysis.

PubMed

2010-01-01

In July 2009, the Medical Advisory Secretariat (MAS) began work on Non-Invasive Cardiac Imaging Technologies for the Assessment of Myocardial Viability, an evidence-based review of the literature surrounding different cardiac imaging modalities to ensure that appropriate technologies are accessed by patients undergoing viability assessment. This project came about when the Health Services Branch at the Ministry of Health and Long-Term Care asked MAS to provide an evidentiary platform on effectiveness and cost-effectiveness of noninvasive cardiac imaging modalities.After an initial review of the strategy and consultation with experts, MAS identified five key non-invasive cardiac imaging technologies that can be used for the assessment of myocardial viability: positron emission tomography, cardiac magnetic resonance imaging, dobutamine echocardiography, and dobutamine echocardiography with contrast, and single photon emission computed tomography.A 2005 review conducted by MAS determined that positron emission tomography was more sensitivity than dobutamine echocardiography and single photon emission tomography and dominated the other imaging modalities from a cost-effective standpoint. However, there was inadequate evidence to compare positron emission tomography and cardiac magnetic resonance imaging. Thus, this report focuses on this comparison only. For both technologies, an economic analysis was also completed.A summary decision analytic model was then developed to encapsulate the data from each of these reports (available on the OHTAC and MAS website).The Non-Invasive Cardiac Imaging Technologies for the Assessment of Myocardial Viability is made up of the following reports, which can be publicly accessed at the MAS website at: www.health.gov.on.ca/mas or at www.health.gov.on.ca/english/providers/program/mas/mas_about.htmlPOSITRON EMISSION TOMOGRAPHY FOR THE ASSESSMENT OF MYOCARDIAL VIABILITY: An Evidence-Based AnalysisMAGNETIC RESONANCE IMAGING FOR THE ASSESSMENT OF MYOCARDIAL VIABILITY: An Evidence-Based Analysis The objective of this analysis is to assess the effectiveness and cost-effectiveness of cardiovascular magnetic resonance imaging (cardiac MRI) for the assessment of myocardial viability. To evaluate the effectiveness of cardiac MRI viability imaging, the following outcomes were examined: the diagnostic accuracy in predicting functional recovery and the impact of cardiac MRI viability imaging on prognosis (mortality and other patient outcomes). CONDITION AND TARGET POPULATION LEFT VENTRICULAR SYSTOLIC DYSFUNCTION AND HEART FAILURE: Heart failure is a complex syndrome characterized by the heart's inability to maintain adequate blood circulation through the body leading to multiorgan abnormalities and, eventually, death. Patients with heart failure experience poor functional capacity, decreased quality of life, and increased risk of morbidity and mortality. In 2005, more than 71,000 Canadians died from cardiovascular disease, of which, 54% were due to ischemic heart disease. Left ventricular (LV) systolic dysfunction due to coronary artery disease (CAD) () is the primary cause of heart failure accounting for more than 70% of cases. The prevalence of heart failure was estimated at one percent of the Canadian population in 1989. Since then, the increase in the older population has undoubtedly resulted in a substantial increase in cases. Heart failure is associated with a poor prognosis: one-year mortality rates were 32.9% and 31.1% for men and women, respectively in Ontario between 1996 and 1997. IN GENERAL, THERE ARE THREE OPTIONS FOR THE TREATMENT OF HEART FAILURE: medical treatment, heart transplantation, and revascularization for those with CAD as the underlying cause. Concerning medical treatment, despite recent advances, mortality remains high among treated patients, while, heart transplantation is affected by the limited availability of donor hearts and consequently has long waiting lists. The third option, revascularization, is used to restore the flow of blood to the heart via coronary artery bypass grafting (CABG) or, in some cases, through minimally invasive percutaneous coronary interventions (balloon angioplasty and stenting). Both methods, however, are associated with important perioperative risks including mortality, so it is essential to properly select patients for this procedure. Left ventricular dysfunction may be permanent, due to the formation of myocardial scar, or it may be reversible after revascularization. Reversible LV dysfunction occurs when the myocardium is viable but dysfunctional (reduced contractility). Since only patients with dysfunctional but viable myocardium benefit from revascularization, the identification and quantification of the extent of myocardial viability is an important part of the work-up of patients with heart failure when determining the most appropriate treatment path. Various non-invasive cardiac imaging modalities can be used to assess patients in whom determination of viability is an important clinical issue, specifically: dobutamine echocardiography (echo),stress echo with contrast,SPECT using either technetium or thallium,cardiac magnetic resonance imaging (cardiac MRI), andpositron emission tomography (PET). Stress echocardiography can be used to detect viable myocardium. During the infusion of low dose dobutamine (5 - 10 µg/kg/min), an improvement of contractility in hypokinetic and akentic segments is indicative of the presence of viable myocardium. Alternatively, a low-high dose dobutamine protocol can be used in which a biphasic response characterized by improved contractile function during the low-dose infusion followed by a deterioration in contractility due to stress induced ischemia during the high dose dobutamine infusion (dobutamine dose up to 40 ug/kg/min) represents viable tissue. Newer techniques including echocardiography using contrast agents, harmonic imaging, and power doppler imaging may help to improve the diagnostic accuracy of echocardiographic assessment of myocardial viability. Intravenous contrast agents, which are high molecular weight inert gas microbubbles that act like red blood cells in the vascular space, can be used during echocardiography to assess myocardial viability. These agents allow for the assessment of myocardial blood flow (perfusion) and contractile function (as described above), as well as the simultaneous assessment of perfusion to make it possible to distinguish between stunned and hibernating myocardium. SPECT: SPECT can be performed using thallium-201 (Tl-201), a potassium analogue, or technetium-99 m labelled tracers. When Tl-201 is injected intravenously into a patient, it is taken up by the myocardial cells through regional perfusion, and Tl-201 is retained in the cell due to sodium/potassium ATPase pumps in the myocyte membrane. The stress-redistribution-reinjection protocol involves three sets of images. The first two image sets (taken immediately after stress and then three to four hours after stress) identify perfusion defects that may represent scar tissue or viable tissue that is severely hypoperfused. The third set of images is taken a few minutes after the re-injection of Tl-201 and after the second set of images is completed. These re-injection images identify viable tissue if the defects exhibit significant fill-in (> 10% increase in tracer uptake) on the re-injection images. The other common Tl-201 viability imaging protocol, rest-redistribution, involves SPECT imaging performed at rest five minutes after Tl-201 is injected and again three to four hours later. Viable tissue is identified if the delayed images exhibit significant fill-in of defects identified in the initial scans (> 10% increase in uptake) or if defects are fixed but the tracer activity is greater than 50%. There are two technetium-99 m tracers: sestamibi (MIBI) and tetrofosmin. The uptake and retention of these tracers is dependent on regional perfusion and the integrity of cellular membranes. Viability is assessed using one set of images at rest and is defined by segments with tracer activity greater than 50%. Positron emission tomography (PET) is a nuclear medicine technique used to image tissues based on the distinct ways in which normal and abnormal tissues metabolize positron-emitting radionuclides. Radionuclides are radioactive analogs of common physiological substrates such as sugars, amino acids, and free fatty acids that are used by the body. The only licensed radionuclide used in PET imaging for viability assessment is F-18 fluorodeoxyglucose (FDG). During a PET scan, the radionuclides are injected into the body and as they decay, they emit positively charged particles (positrons) that travel several millimetres into tissue and collide with orbiting electrons. This collision results in annihilation where the combined mass of the positron and electron is converted into energy in the form of two 511 keV gamma rays, which are then emitted in opposite directions (180 degrees) and captured by an external array of detector elements in the PET gantry. Computer software is then used to convert the radiation emission into images. The system is set up so that it only detects coincident gamma rays that arrive at the detectors within a predefined temporal window, while single photons arriving without a pair or outside the temporal window do not active the detector. This allows for increased spatial and contrast resolution. Cardiac magnetic resonance imaging (cardiac MRI) is a non-invasive, x-ray free technique that uses a powerful magnetic field, radio frequency pulses, and a computer to produce detailed images of the structure and function of the heart. (ABSTRACT TRUNCATED)

Usefulness for Predicting Cardiac Events After Orthotopic Liver Transplantation of Myocardial Perfusion Imaging and Dobutamine Stress Echocardiography Preoperatively.

PubMed

Snipelisky, David; Ray, Jordan; Vallabhajosyula, Saraschandra; Matcha, Gautam; Squier, Samuel; Lewis, Jacob; Holliday, Rex; Aggarwal, Niti; Askew, J Wells; Shapiro, Brian; Anavekar, Nandan

2017-04-01

Patients undergoing orthotopic liver transplantation have high rates of cardiac morbidity and mortality. Although guidelines recommend noninvasive stress testing as part of the preoperative evaluation, little data have evaluated clinical outcomes following orthotopic liver transplantation. A retrospective study at 2 high-volume liver transplantation centers was performed. All patients undergoing noninvasive stress testing (myocardial perfusion imaging [MPI] or dobutamine stress echocardiography [DSE]) over a 5-year period were included. Descriptive analyses, including clinical outcomes and perioperative and postoperative ischemic events, were performed. Comparisons were made between subsets of patients within each stress modality based on abnormal versus normal results. A total of 506 patients were included, of which 343 underwent DSE and 163 MPI. Few patients had abnormal results, with 19 (5.5%) in the DSE group and 13 (8%) in the MPI group. Perioperative and postoperative cardiac complications were low (n = 20, 5.8% and n = 3, 0.9% in DSE group and n = 15, 9.2% and n = 3, 1.8% in MPI group). Comparisons between abnormal versus normal findings showed a trend toward periprocedural cardiac complications in the abnormal DSE group (n = 3, 15.8% vs n = 17, 5.25%; p = 0.09) with no difference in 6-month postprocedural complications (n = 0 vs n = 3, 0.9%; p = 1.0). In the MPI group, a trend toward periprocedural ischemic complications (n = 3, 23.1% vs n = 12, 8%; p = 0.1) was noted with no difference in 6-month postprocedural complications (n = 0 vs n = 3, 2%; p = 1.0). In conclusion, our study found a significantly lower than reported cardiac event rate. In addition, it demonstrated that ischemic cardiac events are uncommon in patients with normal stress testing. Copyright © 2017 Elsevier Inc. All rights reserved.

Head-to-head comparison of the diagnostic performance of coronary computed tomography angiography and dobutamine-stress echocardiography in the evaluation of acute chest pain with normal ECG findings and negative troponin tests: A prospective multicenter study.

PubMed

Durand, Eric; Bauer, Fabrice; Mansencal, Nicolas; Azarine, Arshid; Diebold, Benoit; Hagege, Albert; Perdrix, Ludivine; Gilard, Martine; Jobic, Yannick; Eltchaninoff, Hélène; Bensalah, Mourad; Dubourg, Benjamin; Caudron, Jérôme; Niarra, Ralph; Chatellier, Gilles; Dacher, Jean-Nicolas; Mousseaux, Elie

2017-08-15

To perform a head-to-head comparison of coronary CT angiography (CCTA) and dobutamine-stress echocardiography (DSE) in patients presenting recent chest pain when troponin and ECG are negative. Two hundred seventeen patients with recent chest pain, normal ECG findings, and negative troponin were prospectively included in this multicenter study and were scheduled for CCTA and DSE. Invasive coronary angiography (ICA), was performed in patients when either DSE or CCTA was considered positive or when both were non-contributive or in case of recurrent chest pain during 6month follow-up. The presence of coronary artery stenosis was defined as a luminal obstruction >50% diameter in any coronary segment at ICA. ICA was performed in 75 (34.6%) patients. Coronary artery stenosis was identified in 37 (17%) patients. For CCTA, the sensitivity was 96.9% (95% CI 83.4-99.9), specificity 48.3% (29.4-67.5), positive likelihood ratio 2.06 (95% CI 1.36-3.11), and negative likelihood ratio 0.07 (95% CI 0.01-0.52). The sensitivity of DSE was 51.6% (95% CI 33.1-69.9), specificity 46.7% (28.3-65.7), positive likelihood ratio 1.03 (95% CI 0.62-1.72), and negative likelihood ratio 1.10 (95% CI 0.63-1.93). The CCTA: DSE ratio of true-positive and false-positive rates was 1.70 (95% CI 1.65-1.75) and 1.00 (95% CI 0.91-1.09), respectively, when non-contributive CCTA and DSE were both considered positive. Only one missed acute coronary syndrome was observed at six months. CCTA has higher diagnostic performance than DSE in the evaluation of patients with recent chest pain, normal ECG findings, and negative troponine to exclude coronary artery disease. Copyright © 2017. Published by Elsevier B.V.

Coronary Flow Velocity Reserve during Dobutamine Stress Echocardiography

PubMed Central

de Abreu, José Sebastião; Lima, José Wellington Oliveira; Diógenes, Tereza Cristina Pinheiro; Siqueira, Jordana Magalhães; Pimentel, Nayara Lima; Gomes, Pedro Sabino; de Abreu, Marília Esther Benevides; Paes, José Nogueira

2014-01-01

Background A coronary flow velocity reserve (CFVR) ≥ 2 is adequate to infer a favorable prognosis or the absence of significant coronary artery disease. Objective To identify parameters which are relevant to obtain CFVR (adequate or inadequate) in the left anterior descending coronary artery (LAD) during dobutamine stress echocardiography (DSE). Methods 100 patients referred for detection of myocardial ischemia by DSE were evaluated; they were instructed to discontinue the use of β-blockers 72 hours prior to the test. CFVR was calculated as a ratio of the diastolic peak velocity (cm/s) (DPV) on DSE (DPV-DSE) to baseline DPV at rest (DPV-Rest). In group I, CFVR was < 2 and, in group II, CFVR was ≥ 2. The Fisher's exact test and Student's t test were used for the statistical analyses. P values < 0.05 were considered statistically significant. Results At rest, the time (in seconds) to obtain Doppler in LAD in groups I and II was not different (53±31 vs. 45±32; p=0.23). During DSE, LAD was recorded in 92 patients. Group I patients were older (65.9±9.3 vs. 61.2±10.8 years; p=0.04), had lower ejection fraction (61±10 vs. 66±6%; p=0.005), higher DPV-Rest (36.81±08 vs. 25.63 ± 06cm/s; p<0.0001) and lower CFVR (1.67 ± 0.24 vs. 2.53 ± 0.57; p<0.0001), but no difference was observed regarding DPVDSE (61.40±16 vs. 64.23±16cm/s; p=0.42). β-blocker discontinuation was associated with a 4-fold higher chance of a CFVR < 2 (OR= 4; 95% CI [1.171-13.63], p=0.027). Conclusion DPV-Rest was the main parameter to determine an adequate CFVR. β-blocker discontinuation was significantly associated with inadequate CFVR. The high feasibility and the time to record the LAD corroborate the use of this methodology. PMID:24676368

Standard and Strain Measurements by Echocardiography Detect Early Overloaded Right Ventricular Dysfunction: Validation against Hemodynamic and Myocyte Contractility Changes in a Large Animal Model.

PubMed

Hodzic, Amir; Bobin, Pierre; Mika, Delphine; Ly, Mohamed; Lefebvre, Florence; Lechêne, Patrick; Le Bret, Emmanuel; Gouadon, Elodie; Coblence, Mathieu; Vandecasteele, Grégoire; Capderou, André; Leroy, Jérôme; Rucker-Martin, Catherine; Lambert, Virginie

2017-11-01

Early detection of right ventricular (RV) failure is required to improve the management of patients with congenital heart diseases. The aim of this study was to validate echocardiography for the early detection of overloaded RV dysfunction, compared with hemodynamic and myocyte contractility assessment. Using a porcine model reproducing repaired tetralogy of Fallot, RV function was evaluated over 4 months using standard echocardiography and speckle-tracking compared with hemodynamic parameters (conductance catheter). Sarcomere shortening and calcium transients were recorded in RV isolated myocytes. Contractile reserve (ΔE max ) was assessed by β-adrenergic stimulation in vivo (dobutamine 5 μg/kg) and ex vivo (isoproterenol 100 nM). Six operated animals were compared with four age- and sex-matched controls. In the operated group, hemodynamic RV efficient ejection fraction was significantly decreased (29.7% [26.2%-34%] vs 42.9% [40.7%-48.6%], P < .01), and inotropic responses to dobutamine were attenuated (ΔE max was 51% vs 193%, P < .05). Echocardiographic measurements of fraction of area change, tricuspid annular plane systolic excursion, tricuspid annular peak systolic velocity (S') and RV free wall longitudinal systolic strain and strain rate were significantly decreased. Strain rate, S', and tricuspid annular plane systolic excursion were correlated with ΔE max (r = 0.75, r = 0.78, and r = 0.65, respectively, P < .05). These alterations were associated in RV isolated myocytes with the decrease of sarcomere shortening in response to isoproterenol and perturbations of calcium homeostasis assessed by the increase of spontaneous calcium waves. In this porcine model, both standard and strain echocardiographic parameters detected early impairments of RV function and cardiac reserve, which were associated with cardiomyocyte excitation-contraction coupling alterations. Copyright © 2017 American Society of Echocardiography. Published by Elsevier Inc. All rights reserved.

The safety and clinical usefulness of dobutamine stress echocardiography among octogenarians.

PubMed

O'Driscoll, Jamie M; Marciniak, Anna; Ray, Kausik K; Schmid, Katharina; Smith, Robert; Sharma, Rajan

2014-07-01

Increasing numbers of octogenarians are being referred for investigation of chest pain. While dobutamine stress echocardiography (DSE) has been shown to be useful in younger patients, its role among octogenarians remains unclear. This investigation aimed to investigate the safety and prognostic benefits of DSE on cardiac events and total mortality in octogenarians. 550 consecutive patients aged ≥80 years underwent DSE for suspected cardiac chest pain. All subjects were followed-up prospectively until March 2011, and the study end-points were a major cardiac event and total mortality. One hundred and eighty-three (33%) patients had a positive DSE result, 271 (49%) had a normal study, and 164 (30%) had fixed-wall motion abnormalities. During a mean follow-up of 2.14±1.13 years, there were 217 (39%) cardiac events and 63 (11%) deaths, of which 46 (73%) were cardiac. The absolute risk of cardiac events increased with burden of ischaemia on DSE, from 13%/year (none), to 26%/year (1-3 ischaemic (LV) segments), and 38%/year (>3 ischaemic LV segments), p<0.001. Any ischaemia was associated with an additional 13 cardiac events per 100 person-years. In multivariate analysis, compared with non-ischaemic patients, the relative hazard of cardiac events for 1-3 and >3 ischaemic LV segments were 1.34 (95% CI 1.13 to 1.29) and 1.86 (95% CI 1.16 to 2.98), respectively. Addition of echocardiographic parameters to basic models improved the C statistic from 0.77 to 0.89 (p<0.001). Among octogenarians referred with suspected cardiac chest pain, DSE is safe and, importantly, identifies a subset at high risk of cardiac events. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Effects of a constant rate infusion of detomidine on cardiovascular function, isoflurane requirements and recovery quality in horses.

PubMed

Schauvliege, Stijn; Marcilla, Miguel Gozalo; Verryken, Kirsten; Duchateau, Luc; Devisscher, Lindsey; Gasthuys, Frank

2011-11-01

To examine the influence of a detomidine constant rate infusion (CRI) on cardiovascular function, isoflurane requirements and recovery quality in horses undergoing elective surgery. Prospective, randomized, blinded, clinical trial. Twenty adult healthy horses. After sedation (detomidine, 10 μg kg(-1) intravenously [IV]) and induction of anaesthesia (midazolam 0.06 mg kg(-1) , ketamine 2.2 mg kg(-1) IV), anaesthesia was maintained with isoflurane in oxygen/air (inspiratory oxygen fraction 55%). When indicated, the lungs were mechanically ventilated. Dobutamine was administered when MAP<70 mmHg. The horses were randomly allocated to one of two groups and throughout anaesthesia, received either a detomidine (5 μg kg(-1)  hour(-1) ) (D) or saline (S) CRI, with the anaesthetist unaware of the treatment. Monitoring included end-tidal isoflurane concentration, arterial pH, PaCO(2) , PaO(2) , dobutamine administration rate, heart rate (HR), arterial pressure, cardiac index (CI), systemic vascular resistance (SVR), stroke index and oxygen delivery index (ḊO(2) I). For recovery from anaesthesia, all horses received 2.5 μg kg(-1) detomidine IV. Recovery quality and duration were recorded in each horse. For statistical analysis, anova, Pearson chi-square and Wilcoxon rank sum tests were used as relevant. Heart rate (p=0.0176) and ḊO(2) I (p= 0.0084) were lower and SVR higher (p=0.0126) in group D, compared to group S. Heart rate (p=0.0011) and pH (p=0.0187) increased over time. Significant differences in isoflurane requirements were not detected. Recovery quality and duration were comparable between treatments. A detomidine CRI produced cardiovascular effects typical for α(2) -agonists, without affecting isoflurane requirements, recovery duration or recovery quality. © 2011 The Authors. Veterinary Anaesthesia and Analgesia. © 2011 Association of Veterinary Anaesthetists and the American College of Veterinary Anesthesiologists.

Magnetic Resonance for Noninvasive Detection of Microcirculatory Disease Associated With Allograft Vasculopathy: Intracoronary Measurement Validation.

PubMed

Mirelis, Jesús G; García-Pavía, Pablo; Cavero, Miguel A; González-López, Esther; Echavarria-Pinto, Mauro; Pastrana, Miguel; Segovia, Javier; Oteo, Juan F; Alonso-Pulpón, Luis; Escaned, Javier

2015-07-01

Cardiac allograft vasculopathy affects both epicardial and microcirculatory coronary compartments. Magnetic resonance perfusion imaging has been proposed as a useful tool to assess microcirculation mostly outside the heart transplantation setting. Instantaneous hyperemic diastolic flow velocity-pressure slope, an intracoronary physiology index, has demonstrated a better correlation with microcirculatory remodelling in cardiac allograft vasculopathy than other indices such as coronary flow velocity reserve. To investigate the potential of magnetic resonance perfusion imaging to detect the presence of microcirculatory remodeling in cardiac allograft vasculopathy, we compared magnetic resonance perfusion data with invasive intracoronary physiological indices to study microcirculation in a population of heart transplantation recipients with macrovascular nonobstructive disease demonstrated with intravascular ultrasound. We studied 8 heart transplantation recipients (mean age, 61 [12] years, 100% male) with epicardial allograft vasculopathy defined by intravascular ultrasound, nonsignificant coronary stenoses and negative visually-assessed wall-motion/perfusion dobutamine stress magnetic resonance. Quantitative stress and rest magnetic resonance perfusion data to build myocardial perfusion reserve index, noninvasively, and 4 invasive intracoronary physiological indices were determined. Postprocessed data showed a mean (standard deviation) myocardial perfusion reserve index of 1.22 (0.27), while fractional flow reserve, coronary flow velocity reserve, hyperemic microvascular resistance and instantaneous hyperemic diastolic flow velocity-pressure slope were 0.98 (0.02), cm/s/mmHg, 2.34 (0.55) cm/s/mmHg, 2.00 (0.69) cm/s/mmHg and 0.91 (0.65) cm/s/mmHg, respectively. The myocardial perfusion reserve index correlated strongly only with the instantaneous hyperemic diastolic flow velocity-pressure slope (r=0.75; P=.033). Myocardial perfusion reserve index derived from a comprehensive dobutamine stress magnetic resonance appears to be a reliable technique for noninvasive detection of microcirculatory coronary disease associated with cardiac allograft vasculopathy. Copyright © 2014 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.

[Impact of screening and treatment of low systemic blood flow in the prevention of severe intraventricular haemorrhage and/or death in pre-term infants].

PubMed

Oulego Erroz, Ignacio; Alonso Quintela, Paula; Jiménez Gonzalez, Aquilina; Terroba Seara, Sandra; Rodríguez Blanco, Silvia; Rosón Varas, María; Castañón López, Leticia

2018-04-02

To assess the effect of a protocolised intervention for low systemic blood flow (SBF) in the occurrence of severe intraventricular haemorrhage (IVH) or death in pre-term infants. A study with a quasi-experimental design with retrospective controls was conducted on pre-term infants of less than 30weeks of gestational age, born between January 2016 and July 2017, who were consecutively included in the intervention period. The control cohort included pre-term infants (born between January 2013 and December 2015) matched by gestational age, birth weight, and gender (two controls for each case). The cases of low SBF diagnosed according to functional echocardiography during the study period received dobutamine (5-10μg/kg/min) for 48hours. The study included 29 cases (intervention period) and 54 controls (pre-intervention period). Ten out of 29 (34.5%) infants received dobutamine for low SBF during the intervention period, with 3/29 (10.3%) cases of severe IVH and/or death compared to 17/54 (31.5%) in the control cohort (p=.032). There was an independent association between the intervention and a decreased occurrence of severe IVH/death after adjusting for confounding factors both in the logistic regression model [OR 0.11 (95%CI: 0.01-0.65), p=.015], as well as in the sensitivity analysis using inverse probability of treatment weighting [OR 0.23 (95%CI: 0.09-0.56); p=.001]. In this study with retrospective controls, a protocolised screening, and treatment for low SBF was associated with a decreased occurrence of severe IVH or death in preterm infants. Large, adequately powered trials, are needed in order to determine whether postnatal interventions directed at low SBF can improve neurological outcomes. Copyright © 2018. Publicado por Elsevier España, S.L.U.

The value of fractional and coronary flow reserve in predicting myocardial recovery in patients with previous myocardial infarction.

PubMed

Beleslin, Branko; Ostojic, Miodrag; Djordjevic-Dikic, Ana; Vukcevic, Vladan; Stojkovic, Sinisa; Nedeljkovic, Milan; Stankovic, Goran; Orlic, Dejan; Milic, Natasa; Stepanovic, Jelena; Giga, Vojislav; Saponjski, Jovica

2008-11-01

The aim of the study was to evaluate the relation between fractional flow reserve (FFR) and simultaneously evaluated coronary flow reserve by thermodilution (CFRthermo), with the improvement of left ventricular (LV) function in patients with previous myocardial infarction (MI) undergoing percutaneous coronary intervention (PCI). Study population consisted of 46 patients (mean age 53 +/- 7 years; 36 male) with previous MI and significant coronary stenosis undergoing PCI of infarct-related coronary artery. In all patients, we evaluated FFR and CFRthermo by single pressure/thermo wire during maximal hyperaemia before and immediately after PCI. We performed echocardiographic assessment of LV ejection fraction before and 6 months after PCI. Dobutamine stress echocardiography test was also performed before PCI. LV functional improvement was observed in 33/46 (72%) of patients. In patients with LV functional recovery in comparison with patients with no recovery, there was a significant difference in FFR before PCI (0.56 +/- 0.14 vs. 0.70 +/- 0.07, P < 0.001), improvement of FFR (0.35 +/- 0.14 vs. 0.21 +/- 0.07, P < 0.001), improvement of CFRthermo (1.3 +/- 0.6 vs. 0.5 +/- 0.3, P < 0.001), and CFRthermo after PCI (2.6 +/- 0.7 vs. 2.0 +/- 0.4, P < 0.001). When only parameters evaluated before PCI were taken into account, FFR before angioplasty (P = 0.001) and dobutamine-assessed viability (P = 0.006) were the most significant multivariate predictors of myocardial recovery. When all significant univariate parameters were evaluated, the most significant independent predictors for improvement in myocardial function were the improvement of CFRthermo during angioplasty (P < 0.001) and FFR before angioplasty (P = 0.002). Simultaneous evaluation of FFR and CFRthermo provide significant complementary data on the improvement in myocardial function in patients with previous MI. However, the evaluation of FFR before angioplasty identifies viable myocardium that may recover following revascularization and may be used as an alternative to non-invasive testing.

[Monitoring and Modern Hemodynamic Concepts in Cardiac Anesthesia].

PubMed

Heringlake, Matthias; Schmidt, Christian; Brandt, Sebastian

2018-05-01

Patients undergoing cardiac surgery are growing older, present with more comorbidities, and are frequently scheduled for more complex and prolonged surgical procedures. Routine application of neurological as well as extended hemodynamic monitoring combined with goal-directed perioperative hemodynamic optimization, targeting optimization of systemic and cerebral oxygen balance, show promise to reduce postoperative complications and to improve mortality in this high risk population. Expert recommendations suggest to avoid synthetic colloids for fluid optimization. Additionally, pathophysiological reasoning and results from recent trials suggest to start inotropic and vasoactive therapy primarily with non-adrenergic drugs like levosimendan and vasopressin and to add classical catecholamines like dobutamine and noradrenalin only if necessary to accomplish hemodynamic goals. Georg Thieme Verlag KG Stuttgart · New York.

Sequential big endothelin plasma levels in heart transplant recipients during bridging therapy and after successful heart transplantation.

PubMed

Strametz-Juranek, Jeanette; Pacher, Richard; Kos, Thomas; Woloszczuk, Wolfgang; Grimm, Michael; Zuckermann, Andreas; Stanek, Brigitte

2003-07-01

The purpose of this study was to investigate the impact of successful heart transplantation in patients with refractory heart failure receiving bridging therapy on sequential plasma levels of big endothelin, norepinephrine, atrial natriuretic peptide and aldosterone. Fourteen patients (2 women, 12 men) accepted for heart transplantation were studied. All had severe chronic heart failure refractory to optimized oral therapy with angiotensin-converting enzyme inhibitors and furosemide, were in New York Heart Association functional Class IV, and had a left ventricular ejection fraction of <15%, Right heart catheterization was performed in all patients (cardiac index 1.9 +/- 0.1 liters/min. m(2), pulmonary capillary wedge pressure 30 +/- 2 mmHg, systemic vascular resistance index 2,827 +/- 253 dyn. s/cm(5). m(2)). As bridging therapy, patients received either prostaglandin E(1), prostaglandin E(1) and dobutamine or dobutamine alone as a continuous infusion. Neurohumoral variables were measured prior to bridging therapy and 3.5 months before and 7 and 10 months after successful heart transplantation. Big endothelin, norepinephrine and atrial natriuretic peptide plasma levels decreased from 7.4 +/- 2.9 fmol/ml, 1112 +/- 686 pg/ml and 366 +/- 312 pg/ml to 6.0 +/- 4.5 fmol/ml, 720 +/- 503 pg/ml and 198 +/- 160 pg/ml, respectively, after bridging therapy, and further to 2.1 +/- 0.9 fmol/ml (p < 0.00001 vs baseline), 527 +/- 31 pg/ml (p < 0.02 vs baseline) and 115 +/- 70 pg/ml (p < 0.03 vs baseline), respectively, after cardiac transplantation. Aldosterone plasma levels decreased from 242 +/- 220 pg/ml to 183 +/- 142 pg/ml during bridging therapy and increased after heart transplantation to 252 +/- 189 pg/ml. Plasma creatinine levels increased from 1.2 +/- 0.4 mg/dl at baseline to 1.4 +/- 0.2 mg/dl after transplantation (NS). The study suggests that excessive overproduction of big endothelin, atrial natriuretic peptide and norepinephrine is predominantly related to pump failure and, after cardiac transplantation, a moderate spillover of big endothelin persists. Its specific origin, however, remains to be elucidated. Furthermore, our data suggest a protective effect of prostaglandin E(1) on kidney function after heart transplantation.

Strain-Encoded Cardiac Magnetic Resonance Imaging as an Adjunct for Dobutamine Stress Testing. Incremental Value to Conventional Wall Motion Analysis

PubMed Central

Korosoglou, Grigorios; Lossnitzer, Dirk; Schellberg, Dieter; Lewien, Antje; Wochele, Angela; Schaeufele, Tim; Neizel, Mirja; Steen, Henning; Giannitsis, Evangelos; Katus, Hugo A.; Osman, Nael F.

2009-01-01

Background High-dose dobutamine stress magnetic resonance imaging (DS-MRI) is safe and feasible for the diagnosis of coronary artery disease (CAD) in humans. However, the assessment of cine scans relies on the visual interpretation of regional wall motion, which is subjective. Recently, Strain-Encoded MRI (SENC) has been proposed for the direct color-coded visualization of myocardial strain. The purpose of our study was to compare the diagnostic value of SENC to that provided by conventional wall motion analysis for the detection of inducible ischemia during DS-MRI. Methods and Results Stress induced ischemia was assessed by wall motion analysis and by SENC in 101 patients with suspected or known CAD and in 17 healthy volunteers who underwent DS-MRI in a clinical 1.5T scanner. Quantitative coronary angiography deemed as the standard reference for the presence or absence of significant CAD (≥50% diameter stenosis). On a coronary vessel level, SENC detected inducible ischemia in 86/101 versus 71/101 diseased coronary vessels (p<0.01 versus cine), and showed normal strain response in 189/202 versus 194/202 vessels with <50% stenosis (p=NS versus cine). On a patient level, SENC detected inducible ischemia in 63/64 versus 55/64 patients with CAD (p<0.05 versus cine), and showed normal strain response in 32/37 versus 34/37 patients without CAD (p=NS versus cine).Quantification analysis demonstrated a significant correlation between strain rate reserve (SRreserve) and coronary artery stenosis severity (r²=0.56, p<0.001), and a cut-off value of SRreserve=1.64 deemed as a highly accurate marker for the detection of stenosis≥50% (AUC=0.96, SE=0.01, 95% CI = 0.94–0.98, p<0.001). Conclusions The direct color-coded visualization of strain on MR-images is a useful adjunct for DS-MRI, which provides incremental value for the detection of CAD compared to conventional wall motion readings on cine images. PMID:19808579

Phase analysis of gated blood pool SPECT for multiple stress testing assessments of ventricular mechanical dyssynchrony in a tachycardia-induced dilated cardiomyopathy canine model.

PubMed

Salimian, Samaneh; Thibault, Bernard; Finnerty, Vincent; Grégoire, Jean; Harel, François

2017-02-01

Stress-induced dyssynchrony has been shown to be independently correlated with clinical outcomes in patients with dilated cardiomyopathy (DCM) and narrow QRS complexes. However, the extent to which stress levels affect inter- and intraventricular dyssynchrony parameters remains unknown. Ten large dogs were submitted to tachycardia-induced DCM by pacing the right ventricular apex for 3-4 weeks to reach a target ejection fraction (EF) of 35% or less. Stress was then induced in DCM dogs by administering intravenous dobutamine up to a maximum of 20 μg·kg -1 ·min -1 . Hemodynamic and ventricular dyssynchrony data were analyzed by left ventricular (LV) pressure measurements and gated blood pool SPECT (GBPS) imaging. In order to assess mechanical dyssynchrony in DCM subjects and compare it with that of 8 normal counterparts, we extracted the following data: count-based indices of LV contraction homogeneity index (CHI), entropy and phase standard deviation, and interventricular dyssynchrony index. A significant LV intraventricular dyssynchrony (CHI: 96.4 ± 1.3% in control vs 78.6% ± 10.9% in DCM subjects) resulted in an intense LV dysfunction in DCM subjects (EF: 49.5% ± 8.4% in control vs 22.6% ± 6.0% in DCM), compared to control subjects. However, interventricular dyssynchrony did not vary significantly between the two groups. Under stress, DCM subjects showed a significant improvement in ventricular functional parameters at each level (EF: 22.6% ± 6.0% at rest vs 48.1% ± 5.8% at maximum stress). All intraventricular dyssynchrony indices showed a significant increase in magnitude of synchrony from baseline to stress levels of greater than or equal to 5 μg·kg -1 ·min -1 dobutamine. There were individual differences in the magnitude and pattern of change in interventricular dyssynchrony during the various levels of stress. Based on GBPS analyses, different levels of functional stress, even in close intervals, can have a significant impact on hemodynamic and intraventricular dyssynchrony parameters in a DCM model with narrow QRS complex.

The Role of CMR in Cardiomyopathies

PubMed Central

Kramer, Christopher M.

2015-01-01

Cardiac magnetic resonance imaging (CMR) has made major inroads in the new millenium in the diagnosis and assessment of prognosis for patients with cardiomyopathies. Imaging of left and right ventricular structure and function and tissue characterization with late gadolinium enhancement (LGE) as well as T1 and T2 mapping enable accurate diagnosis of the underlying etiology. In the setting of coronary artery disease, either transmurality of LGE or contractile reserve in response to dobutamine can assess the likelihood of recovery of function after revascularization. The presence of scar reduces the likelihood of response to medical therapy and to cardiac resynchronization therapy in heart failure. The presence and extent of LGE relate to overall cardiovascular outcome in cardiomyopathies. An emerging major role for CMR in cardiomyopathies is to identify myocardial scar for diagnostic and prognostic purposes. PMID:26033902

Cardiac involvement in facio-scapulo-humeral muscular dystrophy: a family study using Thallium-201 single-photon-emission-computed tomography.

PubMed

Faustmann, P M; Farahati, J; Rupilius, B; Dux, R; Koch, M C; Reiners, C

1996-12-01

Fifteen persons from two consecutive generations of one family affected with facio-scapulo-humeral muscular dystrophy (FSHD) were clinically and neurophysiologically examined. Diagnostic muscle biopsies were obtained from two members. Linkage analysis showed that all four affected members of the family inherit the same 4q35 haplotype giving a lod score of z = +1.44. Six family members were examined by ECG at rest and under stress, by two-dimensional echocardiography, and by cardiac Thallium-201 single-photon-emission computed tomography (Tl-201-SPECT) under dobutamine stress and at rest. Abnormal reduced Tl-201 uptake in cardiac SPECT was only found in the affected members of the family. Therefore we suggest that cardiac Tl-201-SPECT abnormalities in FSHD reflect cardiomyogenic changes in this type of muscular disease.

Magnetic Resonance Imaging (MRI) for the Assessment of Myocardial Viability

PubMed Central

2010-01-01

Executive Summary In July 2009, the Medical Advisory Secretariat (MAS) began work on Non-Invasive Cardiac Imaging Technologies for the Assessment of Myocardial Viability, an evidence-based review of the literature surrounding different cardiac imaging modalities to ensure that appropriate technologies are accessed by patients undergoing viability assessment. This project came about when the Health Services Branch at the Ministry of Health and Long-Term Care asked MAS to provide an evidentiary platform on effectiveness and cost-effectiveness of noninvasive cardiac imaging modalities. After an initial review of the strategy and consultation with experts, MAS identified five key non-invasive cardiac imaging technologies that can be used for the assessment of myocardial viability: positron emission tomography, cardiac magnetic resonance imaging, dobutamine echocardiography, and dobutamine echocardiography with contrast, and single photon emission computed tomography. A 2005 review conducted by MAS determined that positron emission tomography was more sensitivity than dobutamine echocardiography and single photon emission tomography and dominated the other imaging modalities from a cost-effective standpoint. However, there was inadequate evidence to compare positron emission tomography and cardiac magnetic resonance imaging. Thus, this report focuses on this comparison only. For both technologies, an economic analysis was also completed. A summary decision analytic model was then developed to encapsulate the data from each of these reports (available on the OHTAC and MAS website). The Non-Invasive Cardiac Imaging Technologies for the Assessment of Myocardial Viability is made up of the following reports, which can be publicly accessed at the MAS website at: www.health.gov.on.ca/mas or at www.health.gov.on.ca/english/providers/program/mas/mas_about.html Positron Emission Tomography for the Assessment of Myocardial Viability: An Evidence-Based Analysis Magnetic Resonance Imaging for the Assessment of Myocardial Viability: An Evidence-Based Analysis Objective The objective of this analysis is to assess the effectiveness and cost-effectiveness of cardiovascular magnetic resonance imaging (cardiac MRI) for the assessment of myocardial viability. To evaluate the effectiveness of cardiac MRI viability imaging, the following outcomes were examined: the diagnostic accuracy in predicting functional recovery and the impact of cardiac MRI viability imaging on prognosis (mortality and other patient outcomes). Clinical Need: Condition and Target Population Left Ventricular Systolic Dysfunction and Heart Failure Heart failure is a complex syndrome characterized by the heart’s inability to maintain adequate blood circulation through the body leading to multiorgan abnormalities and, eventually, death. Patients with heart failure experience poor functional capacity, decreased quality of life, and increased risk of morbidity and mortality. In 2005, more than 71,000 Canadians died from cardiovascular disease, of which, 54% were due to ischemic heart disease. Left ventricular (LV) systolic dysfunction due to coronary artery disease (CAD) 1 is the primary cause of heart failure accounting for more than 70% of cases. The prevalence of heart failure was estimated at one percent of the Canadian population in 1989. Since then, the increase in the older population has undoubtedly resulted in a substantial increase in cases. Heart failure is associated with a poor prognosis: one-year mortality rates were 32.9% and 31.1% for men and women, respectively in Ontario between 1996 and 1997. Treatment Options In general, there are three options for the treatment of heart failure: medical treatment, heart transplantation, and revascularization for those with CAD as the underlying cause. Concerning medical treatment, despite recent advances, mortality remains high among treated patients, while, heart transplantation is affected by the limited availability of donor hearts and consequently has long waiting lists. The third option, revascularization, is used to restore the flow of blood to the heart via coronary artery bypass grafting (CABG) or, in some cases, through minimally invasive percutaneous coronary interventions (balloon angioplasty and stenting). Both methods, however, are associated with important perioperative risks including mortality, so it is essential to properly select patients for this procedure. Myocardial Viability Left ventricular dysfunction may be permanent, due to the formation of myocardial scar, or it may be reversible after revascularization. Reversible LV dysfunction occurs when the myocardium is viable but dysfunctional (reduced contractility). Since only patients with dysfunctional but viable myocardium benefit from revascularization, the identification and quantification of the extent of myocardial viability is an important part of the work-up of patients with heart failure when determining the most appropriate treatment path. Various non-invasive cardiac imaging modalities can be used to assess patients in whom determination of viability is an important clinical issue, specifically: dobutamine echocardiography (echo), stress echo with contrast, SPECT using either technetium or thallium, cardiac magnetic resonance imaging (cardiac MRI), and positron emission tomography (PET). Dobutamine Echocardiography Stress echocardiography can be used to detect viable myocardium. During the infusion of low dose dobutamine (5 – 10 µg/kg/min), an improvement of contractility in hypokinetic and akentic segments is indicative of the presence of viable myocardium. Alternatively, a low-high dose dobutamine protocol can be used in which a biphasic response characterized by improved contractile function during the low-dose infusion followed by a deterioration in contractility due to stress induced ischemia during the high dose dobutamine infusion (dobutamine dose up to 40 ug/kg/min) represents viable tissue. Newer techniques including echocardiography using contrast agents, harmonic imaging, and power doppler imaging may help to improve the diagnostic accuracy of echocardiographic assessment of myocardial viability. Stress Echocardiography with Contrast Intravenous contrast agents, which are high molecular weight inert gas microbubbles that act like red blood cells in the vascular space, can be used during echocardiography to assess myocardial viability. These agents allow for the assessment of myocardial blood flow (perfusion) and contractile function (as described above), as well as the simultaneous assessment of perfusion to make it possible to distinguish between stunned and hibernating myocardium. SPECT SPECT can be performed using thallium-201 (Tl-201), a potassium analogue, or technetium-99 m labelled tracers. When Tl-201 is injected intravenously into a patient, it is taken up by the myocardial cells through regional perfusion, and Tl-201 is retained in the cell due to sodium/potassium ATPase pumps in the myocyte membrane. The stress-redistribution-reinjection protocol involves three sets of images. The first two image sets (taken immediately after stress and then three to four hours after stress) identify perfusion defects that may represent scar tissue or viable tissue that is severely hypoperfused. The third set of images is taken a few minutes after the re-injection of Tl-201 and after the second set of images is completed. These re-injection images identify viable tissue if the defects exhibit significant fill-in (> 10% increase in tracer uptake) on the re-injection images. The other common Tl-201 viability imaging protocol, rest-redistribution, involves SPECT imaging performed at rest five minutes after Tl-201 is injected and again three to four hours later. Viable tissue is identified if the delayed images exhibit significant fill-in of defects identified in the initial scans (> 10% increase in uptake) or if defects are fixed but the tracer activity is greater than 50%. There are two technetium-99 m tracers: sestamibi (MIBI) and tetrofosmin. The uptake and retention of these tracers is dependent on regional perfusion and the integrity of cellular membranes. Viability is assessed using one set of images at rest and is defined by segments with tracer activity greater than 50%. Cardiac Positron Emission Tomography Positron emission tomography (PET) is a nuclear medicine technique used to image tissues based on the distinct ways in which normal and abnormal tissues metabolize positron-emitting radionuclides. Radionuclides are radioactive analogs of common physiological substrates such as sugars, amino acids, and free fatty acids that are used by the body. The only licensed radionuclide used in PET imaging for viability assessment is F-18 fluorodeoxyglucose (FDG). During a PET scan, the radionuclides are injected into the body and as they decay, they emit positively charged particles (positrons) that travel several millimetres into tissue and collide with orbiting electrons. This collision results in annihilation where the combined mass of the positron and electron is converted into energy in the form of two 511 keV gamma rays, which are then emitted in opposite directions (180 degrees) and captured by an external array of detector elements in the PET gantry. Computer software is then used to convert the radiation emission into images. The system is set up so that it only detects coincident gamma rays that arrive at the detectors within a predefined temporal window, while single photons arriving without a pair or outside the temporal window do not active the detector. This allows for increased spatial and contrast resolution. Cardiac Magnetic Resonance Imaging Cardiac magnetic resonance imaging (cardiac MRI) is a non-invasive, x-ray free technique that uses a powerful magnetic field, radio frequency pulses, and a computer to produce detailed images of the structure and function of the heart. Two types of cardiac MRI are used to assess myocardial viability: dobutamine stress magnetic resonance imaging (DSMR) and delayed contrast-enhanced cardiac MRI (DE-MRI). DE-MRI, the most commonly used technique in Ontario, uses gadolinium-based contrast agents to define the transmural extent of scar, which can be visualized based on the intensity of the image. Hyper-enhanced regions correspond to irreversibly damaged myocardium. As the extent of hyper-enhancement increases, the amount of scar increases, so there is a lower the likelihood of functional recovery. Evidence-Based Analysis Research Questions What is the diagnostic accuracy of cardiac MRI for detecting myocardial viability? What is the impact of cardiac MRI viability imaging on prognosis (mortality and other clinical outcomes)? How does cardiac MRI compare with cardiac PET imaging for the assessment of myocardial viability? What is the contribution of cardiac MRI viability imaging to treatment decision making? Is cardiac MRI cost-effective compared with other cardiac imaging modalities for the assessment of myocardial viability? Literature Search A literature search was performed on October 9, 2009 using OVID MEDLINE, MEDLINE In-Process and Other Non-Indexed Citations, EMBASE, the Cochrane Library, and the International Agency for Health Technology Assessment (INAHTA) for studies published from January 1, 2005 until October 9, 2009. Abstracts were reviewed by a single reviewer and, for those studies meeting the eligibility criteria full-text articles were obtained. In addition, published systematic reviews and health technology assessments were reviewed for relevant studies published before 2005. Reference lists were also examined for any additional relevant studies not identified through the search. The quality of evidence was assessed as high, moderate, low or very low according to GRADE methodology. Inclusion Criteria English language full-reports Published between January 1, 2005 and October 9, 2009 Health technology assessments, systematic reviews, meta-analyses, randomized controlled trials (RCTs), and observational studies Patients with chronic, known coronary artery disease (CAD) Used contrast-enhanced MRI Assessment of functional recovery ≥ 3 months after revascularization Exclusion Criteria < 20 patients < 18 years of age Patients with non-ischemic heart disease Studies conducted exclusively in patients with acute myocardial infarction (MI) Studies where TP, TN, FP, FN cannot be determined Outcomes of Interest Sensitivity Specificity Positive predictive value (PPV) Negative Predictive value (NPV) Positive likelihood ratio Negative likelihood ratio Diagnostic accuracy Mortality rate (for prognostic studies) Adverse events Summary of Findings Based on the available very low quality evidence, MRI is a useful imaging modality for the detection of viable myocardium. The pooled estimates of sensitivity and specificity for the prediction of regional functional recovery as a surrogate for viable myocardium are 84.5% (95% CI: 77.5% – 91.6%) and 71.0% (95% CI: 68.8% – 79.2%), respectively. Subgroup analysis demonstrated a statistically significant difference in the sensitivity of MRI to assess myocardial viability for studies using ≤25% hyperenhancement as a viability threshold versus studies using ≤50% hyperenhancement as their viability threshold [78.7 (95% CI: 69.1% - 88.2%) and 96.2 (95% CI: 91.8 – 100.6); p=0.0044 respectively]. Marked differences in specificity were observed [73.6 (95% CI: 62.6% - 84.6%) and 47.2 (95% CI: 22.2 – 72.3); p=0.2384 respectively]; however, these findings were not statistically significant. There were no statistically significant differences between the sensitivities or specificities for any other subgroups including mean preoperative LVEF, imaging method for function recovery assessment, and length of follow-up. There was no evidence available to determine whether patients with viable myocardium who are revascularized have a lower mortality rate than those who are treated with medical therapy. PMID:23074392

Cardiopulmonary effects and anaesthesia recovery quality in horses anaesthetized with isoflurane and low-dose S-ketamine or medetomidine infusions.

PubMed

Menzies, M Paula Larenza; Ringer, Simone K; Conrot, Aude; Theurillat, Regula; Kluge, Katharina; Kutter, Annette Pn; Jackson, Michelle; Thormann, Wolfgang; Bettschart-Wolfensberger, Regula

2016-11-01

To evaluate cardiopulmonary effects and anaesthesia recovery quality in horses anaesthetized with isoflurane receiving medetomidine or S-ketamine infusions. Randomized, blinded, prospective clinical trial. Fifty horses undergoing elective surgery. After acepromazine and flunixin meglumine premedication, horses received medetomidine (7 μg kg -1 ) intravenously (IV). Anaesthesia was induced with midazolam and racemic ketamine (Med treatment group; 2.2 mg kg -1 ; n = 25) or S-ketamine (S-ket treatment group; 1.1 mg kg -1 ; n = 25) IV and maintained with isoflurane in oxygen/air and medetomidine (Med; 3.5 μg kg -1 hour -1 ) or S-ketamine (S-ket; 0.5 mg kg -1 hour -1 ). All horses were mechanically ventilated. Cardiopulmonary variables were evaluated. Isoflurane end-tidal concentrations (Fe'Iso), dobutamine requirements and thiopental boli were recorded. Plasma samples were collected in six horses to evaluate S-ketamine and S-norketamine concentrations. After surgery, medetomidine 2 μg kg -1 was administered IV. Four independent observers scored recovery using a visual analogue scale and a numerical rating scale. Both groups required similar mean Fe'Iso (1%). However, S-ket horses needed more thiopental boli. Median intraoperative cardiac index values were higher with S-ket (4.5 L minute -1  m -2 ) than Med (3.9 L minute -1  m -2 ). Overall, there were no differences in heart rate, blood pressure or dobutamine requirements; however, horses in S-ket showed higher heart rate values at 30 minutes after anaesthesia induction. Compared with Med horses, S-ket horses showed decreased PaO 2 and increased pulmonary venous admixture values estimated with the Fshunt calculation. Recoveries were shorter and of poorer quality with S-ket. During infusion, S-ketamine and S-norketamine plasma concentrations lay in the ranges of 0.209-0.917 μg mL -1 and 0.250-0.723 μg mL -1 , respectively. Despite the higher intraoperative cardiac index with S-ket, both protocols were considered to provide acceptable cardiovascular function. However, recovery quality was significantly better in the Med group. © 2016 Association of Veterinary Anaesthetists and the American College of Veterinary Anesthesia and Analgesia.

Detomidine and the combination of detomidine and MK-467, a peripheral alpha-2 adrenoceptor antagonist, as premedication in horses anaesthetized with isoflurane.

PubMed

Pakkanen, Soile Ae; Raekallio, Marja R; Mykkänen, Anna K; Salla, Kati M; de Vries, Annemarie; Vuorilehto, Lauri; Scheinin, Mika; Vainio, Outi M

2015-09-01

To investigate MK-467 as part of premedication in horses anaesthetized with isoflurane. Experimental, crossover study with a 14 day wash-out period. Seven healthy horses. The horses received either detomidine (20 μg kg(-1) IV) and butorphanol (20 μg kg(-1) IV) alone (DET) or with MK-467 (200 μg kg(-1) IV; DET + MK) as premedication. Anaesthesia was induced with ketamine (2.2 mg kg(-1) ) and midazolam (0.06 mg kg(-1) ) IV and maintained with isoflurane. Heart rate (HR), mean arterial pressure (MAP), end-tidal isoflurane concentration, end-tidal carbon dioxide tension, central venous pressure, fraction of inspired oxygen (FiO2 ) and cardiac output were recorded. Blood samples were taken for blood gas analysis and to determine plasma drug concentrations. The cardiac index (CI), systemic vascular resistance (SVR), ratio of arterial oxygen tension to inspired oxygen (Pa O2 /FiO2 ) and tissue oxygen delivery (DO2 ) were calculated. Repeated measures anova was applied for HR, CI, MAP, SVR, lactate and blood gas variables. The Student's t-test was used for pairwise comparisons of drug concentrations, induction times and the amount of dobutamine administered. Significance was set at p < 0.05. The induction time was shorter, reduction in MAP was detected, more dobutamine was given and HR and CI were higher after DET+MK, while SVR was higher with DET. Arterial oxygen tension and Pa O2 /FiO2 (40 minutes after induction), DO2 and venous partial pressure of oxygen (40 and 60 minutes after induction) were higher with DET+MK. Plasma detomidine concentrations were reduced in the group receiving MK-467. After DET+MK, the area under the plasma concentration time curve of butorphanol was smaller. MK-467 enhances cardiac function and tissue oxygen delivery in horses sedated with detomidine before isoflurane anaesthesia. This finding could improve patient safety in the perioperative period. The dosage of MK-467 needs to be investigated to minimise the effect of MK-467 on MAP. © 2014 Association of Veterinary Anaesthetists and the American College of Veterinary Anesthesia and Analgesia.

Cardiovascular studies using the chimpanzee (Pan troglodytes)

NASA Technical Reports Server (NTRS)

Hinds, J. E.; Cothran, L. N.; Hawthorne, E. W.

1977-01-01

Despite the phylogenetic similarities between chimpanzees and man, there exists a paucity of reliable data on normal cardiovascular function and the physiological responses of the system to standard interventions. Totally implanted biotelemetry systems or hardwire analog techniques were used to examine the maximum number of cardiovascular variables which could be simultaneously monitored without significantly altering the system's performance. This was performed in order to acquire base-line data not previously obtained in this species, to determine cardiovascular response to specific forcing functions such as ventricular pacing, drug infusions, and lower body negative pressure. A cardiovascular function profile protocol was developed in order to adjust independently the three major factors which modify ventricular performance, namely, left ventricular performance, left ventricular preload, afterload, and contractility. Cardiac pacing at three levels above the ambient rate was used to adjust end diastolic volume (preload). Three concentrations of angiotensin were infused continuously to evaluate afterload in a stepwide fashion. A continuous infusion of dobutamine was administered to raise the manifest contractile state of the heart.

Validation of a new micro-manometer pressure sensor for cardiovascular measurements in mice.

PubMed

Trevino, Rodolfo J; Jones, Douglas L; Escobedo, Daniel; Porterfield, John; Larson, Erik; Chisholm, Gary B; Barton, Amanda; Feldman, Marc D

2010-01-01

Abstract The Scisense (London, ON, Canada) micro-manometer pressure sensor is currently being used by investigators to evaluate cardiovascular physiology in mice, but has not been validated to date. The purpose of the current study is to compare the 1.2 F Scisense pressure sensor to the current gold standard produced by Millar Instruments (Houston, TX) (1.4 F). In vitro comparisons were preformed including temperature drift, frequency response analysis up to 250 Hz, and damping coefficient and natural frequency determined via a pop test. The authors also performed in vivo comparisons including pressure drift, dose-response studies to IV isoproterenol, maximum adrenergic stimulation with IV dobutamine, and simultaneous placement of both micro-manometer pressure sensors in the same intact murine hearts. The authors conclude that both sensors are equivalent, and that the Scisense pressure sensor represents an alternative to the current gold standard, the Millar micro-manometer pressure sensor for in vivo pressure measurements in the mouse.

[The clinical economic analysis of the methods of ischemic heart disease diagnostics].

PubMed

Kalashnikov, V Iu; Mitriagina, S N; Syrkin, A L; Poltavskaia, M G; Sorokina, E G

2007-01-01

The clinical economical analysis was applied to assess the application of different techniques of ischemic heart disease diagnostics - the electro-cardiographic monitoring, the treadmill-testing, the stress-echo cardiographic with dobutamine, the single-photon computerized axial tomography with load, the multi-spiral computerized axial tomography with coronary arteries staining in patients with different initial probability of disease occurrence. In all groups, the best value of "cost-effectiveness" had the treadmill-test. The patients with low risk needed 17.4 rubles to precise the probability of ischemic heart disease occurrence at 1%. In the group with medium and high risk this indicator was 9.4 and 24.7 rubles correspondingly. It is concluded that to precise the probability of ischemic heart disease occurrence after tredmil-test in the patients with high probability it is appropriate to use the single-photon computerized axial tomography with load and in the case of patients with low probability the multi-spiral computerized axial tomography with coronary arteries staining.

[Aortic Valve Replacement after Balloon Valvuloplasty for Aortic Valve Stenosis in a Dialysis Patient with Cardiogenic Shock;Report of a Case].

PubMed

Takamatsu, Masanori; Hirotani, Takashi; Ohtsubo, Satoshi; Saito, Sumikatsu; Takeuchi, Shigeyuki; Hasegawa, Tasuku; Endo, Ayaka; Yamasaki, Yu; Hayashida, Kentaro

2015-06-01

A 67-year-old man on chronic hemodialysis was admitted with worsening congestive heart failure due to critical aortic stenosis. Echocardiography showed severe aortic stenosis with a valve area of 0.67 cm2 and an ejection fraction of 0.31. Cardiac catheterization revealed severe pulmonary hypertension with pulmonary artery pressures of 62/32 mmHg. In the middle of cardiac catheterization, the systolic pressure declined to 60 mmHg due to cardiogenic shock. Dopamine hydrochloride and dobutamine hydrochloride infusions were necessary to maintain a systolic pressure greater than 80 mmHg. Balloon aortic valvuloplasty was urgently performed. The patient's symptoms rapidly resolved except for angina on exertion. One month later, elective aortic valve replacement was performed. The postoperative course was uneventful and the he was discharged on the 60th postoperative day. A follow-up echocardiogram 6 months postoperatively revealed normal prosthetic valve function and an ejection fraction of 0.6.

An indirect component in the evoked compound action potential of the vagal nerve.

PubMed

Ordelman, Simone C M A; Kornet, Lilian; Cornelussen, Richard; Buschman, Hendrik P J; Veltink, Peter H

2010-12-01

The vagal nerve plays a vital role in the regulation of the cardiovascular system. It not only regulates the heart but also sends sensory information from the heart back to the brain. We hypothesize that the evoked vagal nerve compound action potential contains components that are indirect via the brain stem or coming via the neural network on the heart. In an experimental study of 15 pigs, we identified four components in the evoked compound action potentials. The fourth component was found to be an indirect component, which came from the periphery. The latency of the indirect component increased when heart rate and contractility were decreased by burst stimulation (P = 0.01; n = 7). When heart rate and contractility were increased by dobutamine administration, the latency of the indirect component decreased (P = 0.01; n = 9). This showed that the latency of the indirect component of the evoked compound action potentials may relate to the state of the cardiovascular system.

A polymorphism in the glucocorticoid receptor gene is associated with refractory hypotension in premature infants.

PubMed

Ogasawara, Kei; Sato, Maki; Hashimoto, Koichi; Imamura, Takashi; Go, Hayato; Hosoya, Mitsuaki

2018-06-01

Glucocorticoids play an important role in endocrine control. The association of glucocorticoid receptor (GR) gene polymorphisms with altered sensitivity to glucocorticoid therapy has been reported in adults. However, there are few such reports in infants. The present study analyzed the prevalence of four GR polymorphisms in preterm infants born before 30 weeks of gestation and determined the associations between these polymorphisms and clinical outcomes in the infants. Totally, 41 preterm infants born at two hospitals in Fukushima were retrospectively screened for the presence of four GR gene polymorphisms, using a TaqMan single-nucleotide polymorphism genotyping assay. The effect of GR gene polymorphisms on clinical outcomes during hospitalization was evaluated. The following primary clinical outcomes were assessed: refractory hypotension in the acute phase and/or severe bronchopulmonary dysplasia, maximum dopamine and dobutamine doses administered, and total hydrocortisone dose administered in the first 48 h of life. Multivariate analysis with logistic regression was used to assess the association between clinical factors and refractory hypotension. Of the four GR polymorphisms, only the BclI polymorphism was detected. The genotype distribution was as follows: C/C, 33; C/G, 8; and G/G, 0 infants. Significant differences were observed between the C/C and C/G genotypes with respect to the following variables: refractory hypotension (6% vs. 50%), dopamine dose [3.0 (2.0-4.0) vs. 4.8 (4.0-7.5) μg/kg/min], dobutamine dose [2.4 (0.0-3.6) vs. 4.0 (0-10.0) μg/kg/min], and total hydrocortisone dose administered in the first 48 h of life [2.0 (0-10.0) vs. 6.0 (0-12.0) mg/kg]. Multivariate analysis showed that the BclI genotype (C/C) was significantly less associated with refractory hypotension in the acute phase (odds ratio, 0.008; 95% confidence interval, 0.000-0.371; p = 0.013). The incidence of refractory hypotension in infants with the C/C genotype was initially expected to be higher than that in infants with the C/G genotype. However, the results of this study were rather different from what we originally expected. The suppressive effect of antenatal steroid use on the HPA axis of the preterm infants with the BclI variant may be associated with refractory hypotension in the acute phase. Copyright © 2017. Published by Elsevier B.V.

The cardiovascular status of isoflurane-anaesthetized horses with and without dexmedetomidine constant rate infusion evaluated at equivalent depths of anaesthesia.

PubMed

Risberg, Åse I; Ranheim, Birgit; Krontveit, Randi I; Lervik, Andreas; Haga, Henning A

2016-07-01

To compare cardiac index and oxygen extraction at equivalent depths of anaesthesia between isoflurane-anaesthetized horses and horses anesthetized with isoflurane and dexmedetomidine CRI. Sequential, blinded, randomized, balanced, crossover study. Eight horses weighing a mean ± standard deviation of 478 ± 58 kg. Horses were premedicated with 0.03 mg kg(-1) acepromazine intramuscularly (IM) and 8 μg kg(-1) dexmedetomidine intravenously (IV). Anaesthesia was induced with 2.5 mg kg(-1) ketamine and 0.1 mg kg(-1) midazolam IV and maintained with isoflurane in oxygen and air. Horses were mechanically ventilated. Fractional concentration of end-tidal isoflurane (Fe'Iso) was stabilized at 1.7% with a CRI of 0.9% NaCl (IsoNaCl), or at 1.1% with 1.75 μg kg(-1)  hour(-1) dexmedetomidine (IsoDex). Mean arterial blood pressure was maintained above 60 mmHg by dobutamine infusion. Following nociceptive electrical stimulation, Fe'Iso was stabilized at a 0.1% lower concentration and nociceptive stimulation was repeated. This procedure was continued until the horse moved. Fe'Iso values prior to the concentration at which movement occurred were considered to indicate equivalent depths of anaesthesia between treatments. Cardiac index and oxygen extraction were compared at equivalent depths of anaesthesia using a paired Student's t-test. Cardiac index differed between IsoNaCl at 61 ± 12 mL kg(-1)  minute(-1) and IsoDex at 48 ± 10 mL kg(-1)  minute(-1) (p = 0.047). In addition, oxygen extraction differed between IsoNaCl at 3.4 ± 0.8 mL kg(-1)  minute(-1) and IsoDex at 4.5 ± 0.5 mL kg(-1)  minute(-1) (p = 0.0042). Two horses receiving IsoNaCl were administered dobutamine at equivalent depths of anaesthesia (7.0 and 28.8 μg kg(-1)  hour(-1) , respectively). Cardiovascular function in horses receiving isoflurane and 1.75 μg kg(-1)  minute(-1) dexmedetomidine is more compromised than in horses receiving a higher concentration of isoflurane and 0.9% NaCl CRI. © 2015 Association of Veterinary Anaesthetists and the American College of Veterinary Anesthesia and Analgesia.

Bone Blood Flow During Simulated Microgravity: Physiological and Molecular Mechanisms

NASA Technical Reports Server (NTRS)

Bloomfield, Susan A.

1999-01-01

Blood flow to bone has been shown to affect bone mass and presumably bone strength. Preliminary data indicate that blood flow to the rat femur decreases after 14 days of simulated microgravity, using hindlimb suspension (HLS). If adult rats subjected to HLS are given dobutamine, a synthetic catecholamine which can cause peripheral vasodilation and increased blood flow, the loss of cortical bone area usually observed is prevented. Further, mechanisms exist at the molecular level to link changes in bone blood flow to changes in bone cell activity, particularly for vasoactive agents like nitric oxide (NO). The decreases in fluid shear stress created by fluid flow associated with the shifts of plasma volume during microgravity may result in alterations in expression of vasoactive agents such as NO, producing important functional effects on bone cells. The primary aim of this project is to characterize changes in 1) bone blood flow, 2) indices of bone mass, geometry, and strength, and 3) changes in gene expression for modulators of nitric oxide activity (e.g., nitric oxide synthase) and other candidate genes involved in signal transduction of mechanical loading after 3, 7, 14, 21, and 28 days of HLS in the adult rat. Using a rat of at least 5 months of age avoids inadvertently studying effects of simulated microgravity on growing, rather than adult, bone. Utilizing the results of these studies, we will then define how altered blood flow contributes to changes in bone with simulated microgravity by administering a vasodilatory agent (which increases blood flow to tissues) during hindlimb suspension. In all studies, responses in the unloaded hindlimb bones (tibial shaft, femoral neck) will be compared with those in the weightbearing humeral shaft and the non-weightbearing calvarium (skull) from the same animal. Bone volumetric mineral density and geometry will be quantified by peripheral quantitative CT; structural and material properties of the long bones will be determined by 3-point bending (tibia, humerus) or compression (femoral neck) testing to failure. A unique aspect of these studies will be defining the time course of changes in gene expression in bone cell populations with unloading, accomplished with Northern blots, in situ hybridization, and immunohistochemistry. These studies have high relevance for concurrent protocols being proposed by investigators on NSBRI Cardiovascular and Muscle teams, with blood flow data available on a number of tissues other than bone. Further, dobutamine and other Beta-agonists have been tested as countermeasures for altered muscle and cardiovascular function. Results of the intervention tested in our studies have potential relevance for a number of systemic changes seen with prolonged spaceflight.

Using terlipressin in a pediatric patient with septic shock resistant to catecholamines

PubMed Central

Erdogan, Seher; Bosnak, Mehmet

2017-01-01

Sepsis and septic shock are important causes of morbidity and mortality in critically ill children. The goal of treatment is to ensure adequate mean arterial pressure to maintain organ perfusion. The growing number of instances of peripheral vascular hyporeactivity to catecholamines has necessitated the search for alternative vasopressors. A 14-year-old boy had septic shock, with a high cardiac index and low systemic vascular resistance index (SVRI) measurements according to pulse contour analysis, despite treatment with dopamine, dobutamine, adrenaline, and noradrenaline infusions. A terlipressin (TP) 10 μg/kg intravenous bolus was administered, followed by a 1 μg/kg/minute continuous infusion. The response to TP treatment was assessed using pulse contour analysis. The mean arterial pressure and SVRI increased, and the cardiac index and heart rate decreased within 10 minutes after bolus administration of TP. Noradrenaline infusion could be reduced to 0.7 μg/kg/minute within 5 hours. The goal in presenting this case was to evaluate the vasoconstrictor effects of TP, a long-acting vasopressin analogue, in septic shock. PMID:29270582

The Role of Diacylglycerol Acyltransferase (DGAT) 1 and 2 in Cardiac Metabolism and Function.

PubMed

Roe, Nathan D; Handzlik, Michal K; Li, Tao; Tian, Rong

2018-03-21

It is increasingly recognized that synthesis and turnover of cardiac triglyceride (TG) play a pivotal role in the regulation of lipid metabolism and function of the heart. The last step in TG synthesis is catalyzed by diacylglycerol:acyltransferase (DGAT) which esterifies the diacylglycerol with a fatty acid. Mammalian heart has two DGAT isoforms, DGAT1 and DGAT2, yet their roles in cardiac metabolism and function remain poorly defined. Here, we show that inactivation of DGAT1 or DGAT2 in adult mouse heart results in a moderate suppression of TG synthesis and turnover. Partial inhibition of DGAT activity increases cardiac fatty acid oxidation without affecting PPARα signaling, myocardial energetics or contractile function. Moreover, coinhibition of DGAT1/2 in the heart abrogates TG turnover and protects the heart against high fat diet-induced lipid accumulation with no adverse effects on basal or dobutamine-stimulated cardiac function. Thus, the two DGAT isoforms in the heart have partially redundant function, and pharmacological inhibition of one DGAT isoform is well tolerated in adult hearts.

Using terlipressin in a pediatric patient with septic shock resistant to catecholamines.

PubMed

Erdogan, Seher; Bosnak, Mehmet

2017-01-01

Sepsis and septic shock are important causes of morbidity and mortality in critically ill children. The goal of treatment is to ensure adequate mean arterial pressure to maintain organ perfusion. The growing number of instances of peripheral vascular hyporeactivity to catecholamines has necessitated the search for alternative vasopressors. A 14-year-old boy had septic shock, with a high cardiac index and low systemic vascular resistance index (SVRI) measurements according to pulse contour analysis, despite treatment with dopamine, dobutamine, adrenaline, and noradrenaline infusions. A terlipressin (TP) 10 μg/kg intravenous bolus was administered, followed by a 1 μg/kg/minute continuous infusion. The response to TP treatment was assessed using pulse contour analysis. The mean arterial pressure and SVRI increased, and the cardiac index and heart rate decreased within 10 minutes after bolus administration of TP. Noradrenaline infusion could be reduced to 0.7 μg/kg/minute within 5 hours. The goal in presenting this case was to evaluate the vasoconstrictor effects of TP, a long-acting vasopressin analogue, in septic shock.

[Acute brain expansion during emergency neck clipping surgery for cerebral aneurysms in a patient with dilated cardiomyopathy].

PubMed

Nakao, M; Kawaguchi, R; Nakatani, K; Niinai, H; Takezaki, T; Hanaki, C

1996-06-01

A 61-year-old male with coma and undiagnosed dilated cardiomyopathy received emergency cerebral aneurysm surgery. Anesthesia was induced with thiamylal, fentanyl and vecuronium and maintained with 66% N2O and 1.0% isoflurane. Five hundred ml of 20% mannitol was infused in 30 min. At the end of the infusion, hypotension occurred. Immediately after the injection of ephedrine, acute brain swelling was observed. The operation was switched to external decompression. Post-operative echocardiography revealed the presence of dilated cardiomyopathy (DCM). The ejection fraction was 34%. Two weeks later, the second operation was scheduled. The anesthesia was induced with fentanyl, midazolam and vecuronium and maintained with N2O and 0.7% isoflurane. Nitroglycerine, lidocaine, PGE1, dopamine and dobutamine were infused throughout the operation. Five hundred ml of 20% mannitol was infused in 60 min. There were no considerable hemodynamic changes and no episode of brain expansion during operation. We conclude that the rapid infusion of mannitol can trigger acute cardiac failure and brain edema in patients with DCM.

Biventricular assist device for scombroid poisoning with refractory myocardial dysfunction: a bridge to recovery.

PubMed

Grinda, Jean-Michel; Bellenfant, Florence; Brivet, François Gilles; Carel, Yvan; Deloche, Alain

2004-09-01

We report the usefulness of biventricular mechanical circulatory support in a 36-yr-old woman with refractory myocardial dysfunction resulting from scombroid poisoning. Case report. Medical and surgical university care units. A previously healthy 36-yr-old woman with severe myocardial dysfunction unresponsive to epinephrine (1.3 microg/kg/min) and dobutamine (18 microg/kg/min) after the ingestion of cooked fresh tuna. Implantation at day 3 of a biventricular assist device consisting of two paracorporeal pneumatic pumps set at 70 beats/min to reach an output of 5.6 L/min during 8 days. The biventricular mechanical circulatory assist device allowed weaning of the inotropic drugs, maintenance of end-organ function, and support of the patient until myocardial recovery. The patient was successfully explanted 11 days after ingestion. Cardiac function had totally recovered, but a stroke was noted. At 3-yrs follow-up, there was no cardiac or neurologic sequela. This report describes severe myocardial dysfunction secondary to scombroid poisoning and demonstrates the usefulness of a mechanical circulatory assist device as a bridge to recovery.

Abnormal stress echocardiography findings in cardiac amyloidosis.

PubMed

Ong, Kevin C; Askew, J Wells; Dispenzieri, Angela; Maleszewski, Joseph J; Klarich, Kyle W; Anavekar, Nandan S; Mulvagh, Sharon L; Grogan, Martha

2016-06-01

Cardiac involvement in immunoglobulin light chain (amyloid light chain, AL) amyloidosis is characterized by myocardial interstitial deposition but can also cause obstructive deposits in the coronary microvasculature. We retrospectively identified 20 patients who underwent stress echocardiography within 1 year prior to the histologic diagnosis of AL amyloidosis. Only patients with cardiac amyloidosis and no known obstructive coronary disease were included. Stress echocardiograms (13 exercise; 7 dobutamine) were performed for evaluation of dyspnea and/or chest pain. Stress-induced wall motion abnormalities (WMAs) occurred in 11 patients (55%), 4 of whom had normal left ventricular wall thickness. Coronary angiogram was performed in 9 of 11 patients and demonstrated no or mild epicardial coronary artery disease. Seven (54%) patients had an abnormal exercise blood pressure which occurred with similar likelihood between those with and without stress-induced WMAs. Stress-induced WMAs and abnormal exercise blood pressure may occur in patients with cardiac AL amyloidosis despite the absence of significant epicardial coronary artery disease. This finding should raise the possibility of cardiac amyloidosis even in the absence of significant myocardial thickening.

Effect of Pre- and Postoperative Phenylbutazone and Morphine Administration on the Breathing Response to Skin Incision, Recovery Quality, Behavior, and Cardiorespiratory Variables in Horses Undergoing Fetlock Arthroscopy: A Pilot Study

PubMed Central

Conde Ruiz, Clara; Cruz Benedetti, Inga-Catalina; Guillebert, Isabelle; Portier, Karine Genevieve

2015-01-01

This prospective blinded randomized study aimed to determine whether the timing of morphine and phenylbutazone administration affects the breathing response to skin incision, recovery quality, behavior, and cardiorespiratory variables in horses undergoing fetlock arthroscopy. Ten Standardbred horses were premedicated with acepromazine (0.04 mg kg−1 IM) and romifidine (0.04 mg kg−1 IV). Anesthesia was induced with diazepam (0.05 mg kg−1) and ketamine (2.2 mg kg−1) IV at T0. Horses in group PRE (n = 5) received morphine (0.1 mg kg−1) and phenylbutazone (2.2 mg kg−1) IV after induction and an equivalent amount of saline after surgery. Horses in group POST (n = 5) received the inversed treatment. Anesthesia was maintained with isoflurane 2% in 100% oxygen. Hypotension (mean arterial pressure <60 mmHg) was treated with dobutamine. All horses breathed spontaneously. Dobutamine requirements, respiratory rate (fR), heart rate (HR), mean arterial blood pressure, end-tidal CO2, inspired (i) and expired (e) tidal and minute volume (VT and V˙E), inspiratory time (IT), and the inspiratory gas flow (VTi/IT) were measured every 5 min. Data were averaged during four 15 min periods before (P1 and P2) and after the incision (P3 and P4). Serial blood–gas analyses were also performed. Recoveries were unassisted, video recorded, and scored by three anesthetists blinded to the treatment. The postoperative behavior of the horses (25 demeanors), HR, and fR were recorded at three time points before induction (T0–24 h, T0–12 h, and T0–2 h) and six time points after recovery (TR) (TR + 2, 4, 6, 12, 24, 48 h). Data were compared between groups using a Wilcoxon test and within groups using a Friedman test or a Kruskal–Wallis signed-rank test when applicable. Tidal volumes (VTe and VTi) were higher in PRE than in POST during all the considered periods but the difference between groups was only significant during P2 (VTe in mL kg−1 in PRE: 13 [9, 15], in POST: 9 [8, 9], p = 0.01). None of the other variables were significantly different between and within groups. Under our experimental conditions, skin incision did not affect respiratory variables. Administration of pre- versus postoperative phenylbutazone and morphine did not influence recovery quality, HR, fR, or animal behavior. PMID:26664985

Dystrophic heart failure blocked by membrane sealant poloxamer

NASA Astrophysics Data System (ADS)

Yasuda, Soichiro; Townsend, Dewayne; Michele, Daniel E.; Favre, Elizabeth G.; Day, Sharlene M.; Metzger, Joseph M.

2005-08-01

Dystrophin deficiency causes Duchenne muscular dystrophy (DMD) in humans, an inherited and progressive disease of striated muscle deterioration that frequently involves pronounced cardiomyopathy. Heart failure is the second leading cause of fatalities in DMD. Progress towards defining the molecular basis of disease in DMD has mostly come from studies on skeletal muscle, with comparatively little attention directed to cardiac muscle. The pathophysiological mechanisms involved in cardiac myocytes may differ significantly from skeletal myofibres; this is underscored by the presence of significant cardiac disease in patients with truncated or reduced levels of dystrophin but without skeletal muscle disease. Here we show that intact, isolated dystrophin-deficient cardiac myocytes have reduced compliance and increased susceptibility to stretch-mediated calcium overload, leading to cell contracture and death, and that application of the membrane sealant poloxamer 188 corrects these defects in vitro. In vivo administration of poloxamer 188 to dystrophic mice instantly improved ventricular geometry and blocked the development of acute cardiac failure during a dobutamine-mediated stress protocol. Once issues relating to optimal dosing and long-term effects of poloxamer 188 in humans have been resolved, chemical-based membrane sealants could represent a new therapeutic approach for preventing or reversing the progression of cardiomyopathy and heart failure in muscular dystrophy.

Comparative Definitions for Moderate-Severe Ischemia in Stress Nuclear, Echocardiography, and Magnetic Resonance Imaging

PubMed Central

Shaw, Leslee J.; Berman, Daniel S.; Picard, Michael H.; Friedrich, Matthias G.; Kwong, Raymond Y.; Stone, Gregg W.; Senior, Roxy; Min, James K.; Hachamovitch, Rory; Scherrer-Crosbie, Marielle; Mieres, Jennifer H.; Marwick, Thomas H.; Phillips, Lawrence M.; Chaudhry, Farooq A.; Pellikka, Patricia A.; Slomka, Piotr; Arai, Andrew E.; Iskandrian, Ami E.; Bateman, Timothy M.; Heller, Gary V.; Miller, Todd D.; Nagel, Eike; Goyal, Abhinav; Borges-Neto, Salvador; Boden, William E.; Reynolds, Harmony R.; Hochman, Judith S.; Maron, David J.; Douglas, Pamela S.

2014-01-01

The lack of standardized reporting of the magnitude of ischemia on noninvasive imaging contributes to variability in translating the severity of ischemia across stress imaging modalities. We identified the risk of coronary artery disease (CAD) death or myocardial infarction (MI) associated with ≥10% ischemic myocardium on stress nuclear imaging as the risk threshold for stress echocardiography and cardiac magnetic resonance. A narrative review revealed that ≥10% ischemic myocardium on stress nuclear imaging was associated with a median rate of CAD death or MI of 4.9%/year (interquartile range: 3.75% to 5.3%). For stress echocardiography, ≥3 newly dysfunctional segments portend a median rate of CAD death or MI of 4.5%/year (interquartile range: 3.8% to 5.9%). Although imprecisely delineated, moderate-severe ischemia on cardiac magnetic resonance may be indicated by ≥4 of 32 stress perfusion defects or ≥3 dobutamine-induced dysfunctional segments. Risk-based thresholds can define equivalent amounts of ischemia across the stress imaging modalities, which will help to translate a common understanding of patient risk on which to guide subsequent management decisions. PMID:24925328

Vasoactive drugs and the gut: is there anything new?

PubMed

Woolsey, Cheryl A; Coopersmith, Craig M

2006-04-01

Systemic changes in blood pressure and cardiac output induced by pressors and inotropes do not always correlate to improvements in regional perfusion. Since the gut is often referred to as the 'motor' of the systemic inflammatory response syndrome, the impact of vasoactive agents on splanchnic perfusion has theoretical importance. This review will highlight recent studies examining secondary effects of vasoactive agents on intestinal perfusion, metabolism, and barrier function. Norepinephrine has minimal impact on mesenteric blood flow although the combination of norepinephrine and dobutamine increases splanchnic blood flow in sepsis. Dopamine also increases mesenteric blood flow although this may be associated with negative hepatic energy balance at high does. Vasopressin and epinephrine both have negative effects on splanchnic blood flow. Newer inodilators levosimendan and olprinone preferentially improve mesenteric perfusion in animal models. Secondary effects of norepinephrine and dopamine on splanchnic perfusion are minor compared with their systemic effects. While vasopressin usage is increasing in the intensive care unit, caution should be used because of its adverse effects on gut perfusion. Experimental agents for the treatment of heart failure have beneficial gut-specific effects although the clinical significance of this is currently limited by their availability.

Dynamic release and clearance of circulating microparticles during cardiac stress.

PubMed

Augustine, Daniel; Ayers, Lisa V; Lima, Eduardo; Newton, Laura; Lewandowski, Adam J; Davis, Esther F; Ferry, Berne; Leeson, Paul

2014-01-03

Microparticles are cell-derived membrane vesicles, relevant to a range of biological responses and known to be elevated in cardiovascular disease. To investigate microparticle release during cardiac stress and how this response differs in those with vascular disease. We measured a comprehensive panel of circulating cell-derived microparticles by a standardized flow cytometric protocol in 119 patients referred for stress echocardiography. Procoagulant, platelet, erythrocyte, and endothelial but not leukocyte, granulocyte, or monocyte-derived microparticles were elevated immediately after a standardized dobutamine stress echocardiogram and decreased after 1 hour. Twenty-five patients developed stress-induced wall motion abnormalities suggestive of myocardial ischemia. They had similar baseline microparticle levels to those who did not develop ischemia, but, interestingly, their microparticle levels did not change during stress. Furthermore, no stress-induced increase was observed in those without inducible ischemia but with a history of vascular disease. Fourteen patients subsequently underwent coronary angiography. A microparticle rise during stress echocardiography had occurred only in those with normal coronary arteries. Procoagulant, platelet, erythrocyte, and endothelial microparticles are released during cardiac stress and then clear from the circulation during the next hour. This stress-induced rise seems to be a normal physiological response that is diminished in those with vascular disease.

Halloysite clay nanotubes and platinum nanoparticles dispersed in ionic liquid applied in the development of a catecholamine biosensor.

PubMed

Brondani, Daniela; Scheeren, Carla Weber; Dupont, Jairton; Vieira, Iolanda Cruz

2012-08-21

Halloysite clay nanotubes were used as a support for the immobilization of the enzyme peroxidase from clover sprouts (Trifolium), and employed together with platinum nanoparticles in 1-butyl-3-methylimidazolium hexafluorophosphate ionic liquid (Pt-BMI·PF(6)) in the development of a new biosensor for the determination of catecholamines by square-wave voltammetry. Under optimized conditions, the analytical curves showed detection limits of 0.05, 0.06, 0.07, 0.12 μM for dopamine, isoproterenol, dobutamine and epinephrine, respectively. The biosensor demonstrated high sensitivity, good repeatability and reproducibility, and long-term stability (18% decrease in response over 150 days). A recovery study of dopamine in pharmaceutical samples gave values from 97.5 to 101.4%. The proposed biosensor was successfully applied to the determination of dopamine in pharmaceutical samples, with a maximum relative error of ±1.0% in relation to the standard (spectrophotometric) method. The good analytical performance of the proposed method can be attributed to the efficient immobilization of the peroxidase in the nanoclay, and the facilitation of electron transfer between the protein and the electrode surface due to the presence of the Pt nanoparticles and ionic liquid.

[Catecholamine therapy in cardiogenic shock: helpful, useless or dangerous?].

PubMed

Schwertz, H; Müller-Werdan, U; Prondzinsky, R; Werdan, K; Buerke, M

2004-09-10

Cardiogenic shock is characterized by inadequate organ and tissue perfusion, due to cardiac dysfunction, predominantly following acute myocardial infarction. Mortality rates for patients with cardiogenic shock remain high, ranging from 50-70 % despite effective therapy. Rapid diagnostics, aggressive therapeutic approach (invasive or surgical revascularisation) and pharmacological support are currently used to improve the clinical outcome and survival. In the first line commonly sympathomimetics like dopamine, dobutamine, epinephrine and norepinephrine are used for the pharmacological treatment. They have a high affinity for alpha- and beta adrenergic receptors, leading to a positive inotropic cardiac function, an increase in heart rate, oxygen enhanced demand, and an increase in vasoconstriction. However, there are also some disadvantages in the use of sympathomimetics in patients with cardiogenic shock. Clearly, metabolic acidosis due to the increased oxygen demand can be observed. Vasoconstriction induced by sympathomimetics can lead to perfusion mismatch or even deficit within the microcirculation. Additionally, in some studies which give evidence that the use of sympathomimetics can directly lead to enhanced systemic inflammatory response due to an increased IL-6 expression. However, sympathomimetics are still first line therapeutics for treatment of cardiogenic shock -- with respect to dosage and duration of treatment.

Dobutamine Stress Echocardiography for Management of Low-Flow, Low-Gradient Aortic Stenosis.

PubMed

Annabi, Mohamed-Salah; Touboul, Eden; Dahou, Abdellaziz; Burwash, Ian G; Bergler-Klein, Jutta; Enriquez-Sarano, Maurice; Orwat, Stefan; Baumgartner, Helmut; Mascherbauer, Julia; Mundigler, Gerald; Cavalcante, João L; Larose, Éric; Pibarot, Philippe; Clavel, Marie-Annick

2018-02-06

In the American College of Cardiology/American Heart Association guidelines, patients are considered to have true-severe stenosis when the mean gradient (MG) is ≥40 mm Hg with an aortic valve area (AVA) ≤1 cm 2 during dobutamine stress echocardiography (DSE). However, these criteria have not been previously validated. The aim of this study was to assess the value of these criteria to predict the presence of true-severe AS and the occurrence of death in patients with low-flow, low-gradient aortic stenosis (LF-LG AS). One hundred eighty-six patients with low left ventricular ejection fraction (LVEF) LF-LG AS were prospectively recruited and underwent DSE, with measurement of the MG, AVA, and the projected AVA (AVA Proj ), which is an estimate of the AVA at a standardized normal flow rate. Severity of AS was independently corroborated by macroscopic evaluation of the valve at the time of valve replacement in 54 patients, by measurement of the aortic valve calcium by computed tomography in 25 patients, and by both methods in 8 patients. According to these assessments, 50 of 87 (57%) patients in the study cohort had true-severe stenosis. Peak stress MG ≥40 mm Hg, peak stress AVA ≤1 cm 2 , and the combination of peak stress MG ≥40 mm Hg and peak stress AVA ≤1 cm 2 correctly classified AS severity in 48%, 60%, and 47% of patients, respectively, whereas AVA Proj  ≤1 cm 2 was better than all the previous markers (p < 0.007), with 70% correct classification. Among the subset of 88 patients managed conservatively (47% of the cohort), 52 died during a follow-up of 2.8 ± 2.5 years. After adjustment for age, sex, functional capacity, chronic kidney failure, and peak stress LVEF, peak stress MG and AVA were not predictors of mortality in this subset. In contrast, AVA Proj  ≤1 cm 2 was a strong predictor of mortality under medical management (hazard ratio: 3.65; p = 0.0003). In patients with low LVEF LF-LG AS, the DSE criteria of a peak stress MG ≥40 mm Hg, or the composite of a peak stress MG ≥40 mm Hg and a peak stress AVA ≤1 cm 2 proposed in the guidelines to identify true-severe AS and recommend valve replacement, have limited value to predict actual stenosis severity and outcomes. In contrast, AVA Proj better distinguishes true-severe AS from pseudo-severe AS and is strongly associated with mortality in patients under conservative management. (Multicenter Prospective Study of Low-Flow Low-Gradient Aortic Stenosis [TOPAS]; NCT01835028). Copyright © 2018 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Behavior of B-type natriuretic peptide during mechanical ventilation and spontaneous breathing after extubation.

PubMed

Principi, T; Falzetti, G; Elisei, D; Donati, A; Pelaia, P

2009-04-01

The behavior of B-type natriuretic peptide (BNP) is assessed during mechanical ventilation (MV) and spontaneous breathing after extubation in critical patients. Thirty patients admitted in the Intensive Care Unit (ICU) were enrolled. BNP, fluid balance (FB), airway pressure (AP) and dobutamine infusion needing (DP) were registered in three stages: T0, admission to ICU; T1, before extubation; T2, 24 h after extubation. Patients with congestive heart failure (CHF) had BNP values higher than other patients. The value of BNP during MV was greater than normal in all patients. The cut-off to discriminate patients with heart failure during MV was 286 pgxmL(-1)(sensitivity: 86%; specificity: 90%). The increase of BNP during MV directly correlated with FB and inversely correlated with AP and DP. The plasmatic level of BNP remained higher than normal values 24 h after extubation. The underlying disease of an ICU patient seems to play a relevant role for BNP production and is probably linked to different aspects of therapeutic approach required by the patient. Our data suggest a cut-off value of BNP higher than the usual is necessary to discriminate mechanically-ventilated patients without CHF. This study should be repeated with an enlarged population.

Detection and monitoring of cardiotoxicity-what does modern cardiology offer?

PubMed

Jurcut, Ruxandra; Wildiers, Hans; Ganame, Javier; D'hooge, Jan; Paridaens, Robert; Voigt, Jens-Uwe

2008-05-01

With new anticancer therapies, many patients can have a long life expectancy. Treatment-related comorbidities become an issue for cancer survivors. Cardiac toxicity remains an important side effect of anticancer therapies. Myocardial dysfunction can become apparent early or long after end of therapy and may be irreversible. Detection of cardiac injury is crucial since it may facilitate early therapeutic measures. Traditionally, chemotherapy-induced cardiotoxicity has been detected by measuring changes in left ventricular ejection fraction. This parameter is, however, insensitive to subtle changes in myocardial function as they occur in early cardiotoxicity. This review will discuss conventional and modern cardiologic approaches of assessing myocardial function. It will focus on Doppler myocardial imaging, a method which allows to sensitively measure myocardial function parameters like myocardial velocity, deformation (strain), or deformation rate (strain rate) and which has been shown to reliably detect early abnormalities in both regional and global myocardial function in an early stage. Other newer echocardiographic function estimators are based on automated border detection algorithms and ultrasonic integrated backscatter analysis. A further technique to be discussed is dobutamine stress echocardiography. The use of new biomarkers like B-type natriuretic peptide and troponin and less often used imaging techniques like magnetic resonance imaging and computed tomography will also be mentioned.

Resection of subvalvular aortic stenosis. Surgical and perioperative management in seven dogs.

PubMed

Komtebedde, J; Ilkiw, J E; Follette, D M; Breznock, E M; Tobias, A H

1993-01-01

Open heart surgery was performed during cardiopulmonary bypass (CPB) to surgically correct subvalvular aortic stenosis in seven dogs. After initiation of total CPB, cardiac arrest was induced by antegrade and retrograde administration of blood cardioplegia. The subvalvular fibrous stenosis was resected through a transverse aortotomy. Intraoperatively and postoperatively, dobutamine, nitroprusside, lidocaine, blood(-products), and crystalloid solutions were used to manage hypotension and optimize cardiac index. Aortic cross-clamp time varied from 73 to 166 minutes, and duration of CPB varied from 130 to 210 minutes. Iatrogenic incision into the mitral valve in two dogs was the most significant intraoperative complication. Postoperative complications included: hypoproteinemia (n = 7), premature ventricular depolarization (n = 6), increased systemic vascular resistance index (n = 5), increased O2 extraction (n = 3), pulmonary edema (n = 2), and decreased cardiac index (n = 1). All seven dogs were discharged alive and in stable condition. Six dogs are alive and in stable condition after a mean follow up of 15.8 months. This is the first detailed report of CPB in a series of clinical veterinary patients. Using the techniques described in this paper, open heart surgery of considerable duration can be performed successfully in dogs with significant myocardial hypertrophy and endomyocardial fibrosis secondary to subvalvular aortic stenosis.

Cardiac Function in Young and Old Little Mice

PubMed Central

Reddy, Anilkumar K.; Amador-Noguez, Daniel; Darlington, Gretchen J.; Scholz, Beth A.; Michael, Lloyd H.; Hartley, Craig J.; Entman, Mark L.; Taffet, George E.

2009-01-01

We studied cardiac function in young and old, wild-type (WT), and longer-living Little mice using cardiac flow velocities, echocardiographic measurements, and left ventricular (LV) pressure (P) to determine if enhanced reserves were in part responsible for longevity in these mice. Resting/baseline cardiac function, as measured by velocities, LV dimensions, +dP/dtmax, and −dP/dtmax, was significantly lower in young Little mice versus young WT mice. Fractional shortening (FS) increased significantly, and neither +dP/dtmax nor −dP/dtmax declined with age in Little mice. In contrast, old WT mice had no change in FS but had significantly lower +dP/dtmax and −dP/dtmax versus young WT mice. Significant decreases were observed in the velocity indices of old Little mice versus old WT mice, but other parameters were unchanged. The magnitude of dobutamine stress response remained unchanged with age in Little mice, while that in WT mice decreased. These data suggest that while resting cardiac function in Little mice versus WT mice is lower at young age, it is relatively unaltered with aging. Additionally, cardiac function in response to stress was maintained with age in Little mice but not in their WT counterparts. Thus, some mouse models of increased longevity may not be associated with enhanced reserves. PMID:18166681

Spontaneous pulmonary hematoma in a patient with sepsis treated with dual antiplatelet therapy.

PubMed

Vlaović, Janko; Voga, Gorazd

2016-12-01

A 72-year-old patient was admitted to the medical intensive care unit due to a right-sided, hospital-acquired pneumonia and septic shock with respiratory failure and deterioration of chronic renal failure. During hospitalization the patient required hemodynamic support with norepinephrine and dobutamine, mechanical ventilation and hemodialysis. The patient suffered a non-ST segment elevation myocardial infarction (NSTEMI) and received dual antiplatelet therapy. After 14 days an acute intrapulmonary infiltrate of unknown origin developed, accompanied by fever and a significant increase of the C‑reactive protein (CRP) level. Chest radiography and a computed tomography (CT) scan showed a well-defined, round, high-attenuation lesion in the lungs and a suspected infected pulmonary hematoma, which was confirmed by percutaneous aspiration biopsy. There was no evidence of trauma and it is believed that the hematoma occurred spontaneously, probably because of the dual antiplatelet therapy. Double antibiotic treatment was started but no surgery was performed after consultation with a thoracic surgeon. The antiplatelet drugs were temporarily withdrawn until the size of the hematoma showed no further increase and then antiplatelet therapy was continued. After stabilization the patient was discharged from hospital and 6 months later a follow-up chest X‑ray showed almost complete resolution of the hematoma.

Clinical trials update from the American Heart Association: REPAIR-AMI, ASTAMI, JELIS, MEGA, REVIVE-II, SURVIVE, and PROACTIVE.

PubMed

Cleland, John G F; Freemantle, Nick; Coletta, Alison P; Clark, Andrew L

2006-01-01

This article provides information and a commentary on trials presented at the American Heart Association meeting held in November 2005, relevant to the pathophysiology, prevention and treatment of heart failure. All reports should be considered as preliminary data, as analyses may change in the final publication. In REPAIR-AMI an improvement in ejection fraction was observed in post-MI patients following infusion of bone marrow stem cells. However, the ASTAMI study showed no benefit of stem cell implantation in a similar patient cohort. The JELIS study reported a reduction in major coronary events in patients receiving statins plus fish oil compared to statins alone. MEGA showed that low dose statins in a low risk population reduce the incidence of major cardiovascular events. Two studies of levosimendan in acute heart failure gave conflicting results, in the REVIVE-II study levosimendan was reported to have a superior effect on the composite primary outcome compared to placebo, however, in SURVIVE despite a trend to early benefit with levosimendan, there was no difference in effect on long-term outcome versus dobutamine. The PROACTIVE study showed encouraging results for the use of pioglitazone in post-myocardial infarction patients with concomitant type 2 diabetes.

Primary angioplasty for infarction due to isolated right ventricular artery occlusion.

PubMed

Chahal, Anwar A; Kim, Min-Young; Borg, Alexander N; Al-Najjar, Yahya

2014-11-26

We report an unusual case of an isolated right ventricular infarction with haemodynamic compromise caused by spontaneous isolated proximal occlusion of the right ventricular branch of the right coronary artery (RCA), successfully treated by balloon angioplasty. A 58-year-old gentleman presented with epigastric pain radiating into both arms. Electrocardiograph with right ventricular leads confirmed ST elevation in V4R and a diagnosis of isolated right ventricular infarction was made. Urgent primary percutaneous intervention was performed which revealed occlusion of the right ventricular branch of the RCA. During the procedure, the patient's blood pressure dropped to 80/40 mmHg, and echocardiography showed impaired right ventricular systolic function. Despite aggressive fluid resuscitation, the patient remained hypotensive, continued to have chest pain and persistent electrocardiograph changes, and hence balloon angioplasty was performed on the proximal right ventricular branch which restored flow to the vessel and revealed a severe ostial stenosis. This was treated with further balloon angioplasty which restored TIMI 3 flow with resolution of patient's symptoms. Repeat echocardiography showed complete resolution of the ST-elevation in leads V4R and V5R and partial resolution in V1. Subsequent dobutamine-stress echocardiography at 4 wk showed good left and right ventricular contractions. The patient was discharged after a 3-d in-patient stay without any complications.

Iatrogenic Skin Disorders and Related Factors in Newborn Infants.

PubMed

Csoma, Zsanett Renáta; Meszes, Angéla; Ábrahám, Rita; Kemény, Lajos; Tálosi, Gyula; Doró, Péter

2016-09-01

Recent technological advances and diagnostic and therapeutic innovations have resulted in an impressive improvement in the survival of newborn infants requiring intensive care. Consequently, with the use of modern invasive diagnostic and therapeutic procedures, the incidence of iatrogenic events has also increased. The aim of this study was to assess various iatrogenic complications in neonates requiring intensive care and determine possible contributing factors to the injuries. Our prospective cross-sectional cohort survey was conducted in a central regional level III neonatal intensive care unit (NICU). Correlations between intensive therapeutic interventions, complications, factors influencing attendance and prognosis, and the prevalence of iatrogenic skin injuries (ISIs) were investigated over a 2-year study period. Between January 31, 2012, and January 31, 2014, 460 neonates were admitted to the NICU, 83 of whom exhibited some kind of ISI. The major risk factors for ISIs were low birthweight, young gestational age, long NICU stay, use of the intubation-surfactant-extubation (INSURE) technique, surfactant use, mechanical ventilation, insertion of an umbilical arterial catheter, circulatory and cardiac support with dopamine or dobutamine, pulmonary hemorrhage, intracranial hemorrhage, patent ductus arteriosus, bronchopulmonary dysplasia, and positive microbiology culture results. To prevent ISIs, careful consideration of risk factors and the creation of protocols ensuring efficient treatment of injuries are needed. © 2016 Wiley Periodicals, Inc.

Time course of pressure and flow in ascending aorta during ejection.

PubMed

Perlini, S; Soldà, P L; Piepoli, M; Calciati, A; Paro, M; Marchetti, G; Meno, F; Finardi, G; Bernardi, L

1991-02-01

To analyze aortic flow and pressure relationships, 10 closed-chest anaesthetised dogs were instrumented with electromagnetic aortic flow probes and micromanometers in the left ventricle and ascending aorta. Left ventricular ejection time was divided into: time to peak flow (T1) (both pressure and flow rising), peak flow to peak pressure time (T2) (pressure rising, flow decreasing), and peak pressure to dicrotic notch time (T3) (pressure and flow both decreasing). These time intervals were expressed as percent of total ejection time. Load-active interventions rose markedly T2 (from 4.2 +/- 5.5 to 19.4 +/- 3.5 after phenylephrine (p less than 0.02); from 4.2 +/- 6.5 to 21.2 +/- 5.3 after dextran (p less than 0.02)). Conversely, dobutamine reduced T2 from 4.4 +/- 5.9 to -2.5 +/- 6.5 (p less than 0.05). Thus, during load-active interventions aortic pressure increases for a longer T2 time although forward flow is decreasing, as a result of higher aortic elastic recoil during ejection. Conversely, beta 1-adrenergic stimulation significantly shortens T2. Dynamic pressure-flow relationship is thus continuously changing during ejection. T2 seems to be inversely related to the efficiency of left ventricular ejection dynamics.

Positron Emission Tomography for the Assessment of Myocardial Viability

PubMed Central

2010-01-01

Executive Summary In July 2009, the Medical Advisory Secretariat (MAS) began work on Non-Invasive Cardiac Imaging Technologies for the Assessment of Myocardial Viability, an evidence-based review of the literature surrounding different cardiac imaging modalities to ensure that appropriate technologies are accessed by patients undergoing viability assessment. This project came about when the Health Services Branch at the Ministry of Health and Long-Term Care asked MAS to provide an evidentiary platform on effectiveness and cost-effectiveness of non-invasive cardiac imaging modalities. After an initial review of the strategy and consultation with experts, MAS identified five key non-invasive cardiac imaging technologies that can be used for the assessment of myocardial viability: positron emission tomography, cardiac magnetic resonance imaging, dobutamine echocardiography, and dobutamine echocardiography with contrast, and single photon emission computed tomography. A 2005 review conducted by MAS determined that positron emission tomography was more sensitivity than dobutamine echocardiography and single photon emission tomography and dominated the other imaging modalities from a cost-effective standpoint. However, there was inadequate evidence to compare positron emission tomography and cardiac magnetic resonance imaging. Thus, this report focuses on this comparison only. For both technologies, an economic analysis was also completed. The Non-Invasive Cardiac Imaging Technologies for the Assessment of Myocardial Viability is made up of the following reports, which can be publicly accessed at the MAS website at: www.health.gov.on.ca/mas or at www.health.gov.on.ca/english/providers/program/mas/mas_about.html Positron Emission Tomography for the Assessment of Myocardial Viability: An Evidence-Based Analysis Magnetic Resonance Imaging for the Assessment of Myocardial Viability: An Evidence-Based Analysis Objective The objective of this analysis is to assess the effectiveness and safety of positron emission tomography (PET) imaging using F-18-fluorodeoxyglucose (FDG) for the assessment of myocardial viability. To evaluate the effectiveness of FDG PET viability imaging, the following outcomes are examined: the diagnostic accuracy of FDG PET for predicting functional recovery; the impact of PET viability imaging on prognosis (mortality and other patient outcomes); and the contribution of PET viability imaging to treatment decision making and subsequent patient outcomes. Clinical Need: Condition and Target Population Left Ventricular Systolic Dysfunction and Heart Failure Heart failure is a complex syndrome characterized by the heart’s inability to maintain adequate blood circulation through the body leading to multiorgan abnormalities and, eventually, death. Patients with heart failure experience poor functional capacity, decreased quality of life, and increased risk of morbidity and mortality. In 2005, more than 71,000 Canadians died from cardiovascular disease, of which, 54% were due to ischemic heart disease. Left ventricular (LV) systolic dysfunction due to coronary artery disease (CAD)1 is the primary cause of heart failure accounting for more than 70% of cases. The prevalence of heart failure was estimated at one percent of the Canadian population in 1989. Since then, the increase in the older population has undoubtedly resulted in a substantial increase in cases. Heart failure is associated with a poor prognosis: one-year mortality rates were 32.9% and 31.1% for men and women, respectively in Ontario between 1996 and 1997. Treatment Options In general, there are three options for the treatment of heart failure: medical treatment, heart transplantation, and revascularization for those with CAD as the underlying cause. Concerning medical treatment, despite recent advances, mortality remains high among treated patients, while, heart transplantation is affected by the limited availability of donor hearts and consequently has long waiting lists. The third option, revascularization, is used to restore the flow of blood to the heart via coronary artery bypass grafting (CABG) or through minimally invasive percutaneous coronary interventions (balloon angioplasty and stenting). Both methods, however, are associated with important perioperative risks including mortality, so it is essential to properly select patients for this procedure. Myocardial Viability Left ventricular dysfunction may be permanent if a myocardial scar is formed, or it may be reversible after revascularization. Reversible LV dysfunction occurs when the myocardium is viable but dysfunctional (reduced contractility). Since only patients with dysfunctional but viable myocardium benefit from revascularization, the identification and quantification of the extent of myocardial viability is an important part of the work-up of patients with heart failure when determining the most appropriate treatment path. Various non-invasive cardiac imaging modalities can be used to assess patients in whom determination of viability is an important clinical issue, specifically: dobutamine echocardiography (echo), stress echo with contrast, SPECT using either technetium or thallium, cardiac magnetic resonance imaging (cardiac MRI), and positron emission tomography (PET). Dobutamine Echocardiography Stress echocardiography can be used to detect viable myocardium. During the infusion of low dose dobutamine (5 – 10 μg/kg/min), an improvement of contractility in hypokinetic and akentic segments is indicative of the presence of viable myocardium. Alternatively, a low-high dose dobutamine protocol can be used in which a biphasic response characterized by improved contractile function during the low-dose infusion followed by a deterioration in contractility due to stress induced ischemia during the high dose dobutamine infusion (dobutamine dose up to 40 ug/kg/min) represents viable tissue. Newer techniques including echocardiography using contrast agents, harmonic imaging, and power doppler imaging may help to improve the diagnostic accuracy of echocardiographic assessment of myocardial viability. Stress Echocardiography with Contrast Intravenous contrast agents, which are high molecular weight inert gas microbubbles that act like red blood cells in the vascular space, can be used during echocardiography to assess myocardial viability. These agents allow for the assessment of myocardial blood flow (perfusion) and contractile function (as described above), as well as the simultaneous assessment of perfusion to make it possible to distinguish between stunned and hibernating myocardium. SPECT SPECT can be performed using thallium-201 (Tl-201), a potassium analogue, or technetium-99 m labelled tracers. When Tl-201 is injected intravenously into a patient, it is taken up by the myocardial cells through regional perfusion, and Tl-201 is retained in the cell due to sodium/potassium ATPase pumps in the myocyte membrane. The stress-redistribution-reinjection protocol involves three sets of images. The first two image sets (taken immediately after stress and then three to four hours after stress) identify perfusion defects that may represent scar tissue or viable tissue that is severely hypoperfused. The third set of images is taken a few minutes after the re-injection of Tl-201 and after the second set of images is completed. These re-injection images identify viable tissue if the defects exhibit significant fill-in (> 10% increase in tracer uptake) on the re-injection images. The other common Tl-201 viability imaging protocol, rest-redistribution, involves SPECT imaging performed at rest five minutes after Tl-201 is injected and again three to four hours later. Viable tissue is identified if the delayed images exhibit significant fill-in of defects identified in the initial scans (> 10% increase in uptake) or if defects are fixed but the tracer activity is greater than 50%. There are two technetium-99 m tracers: sestamibi (MIBI) and tetrofosmin. The uptake and retention of these tracers is dependent on regional perfusion and the integrity of cellular membranes. Viability is assessed using one set of images at rest and is defined by segments with tracer activity greater than 50%. Cardiac Magnetic Resonance Imaging Cardiac magnetic resonance imaging (cardiac MRI) is a non-invasive, x-ray free technique that uses a powerful magnetic field, radio frequency pulses, and a computer to produce detailed images of the structure and function of the heart. Two types of cardiac MRI are used to assess myocardial viability: dobutamine stress magnetic resonance imaging (DSMR) and delayed contrast-enhanced cardiac MRI (DE-MRI). DE-MRI, the most commonly used technique in Ontario, uses gadolinium-based contrast agents to define the transmural extent of scar, which can be visualized based on the intensity of the image. Hyper-enhanced regions correspond to irreversibly damaged myocardium. As the extent of hyper-enhancement increases, the amount of scar increases, so there is a lower the likelihood of functional recovery. Cardiac Positron Emission Tomography Positron emission tomography (PET) is a nuclear medicine technique used to image tissues based on the distinct ways in which normal and abnormal tissues metabolize positron-emitting radionuclides. Radionuclides are radioactive analogs of common physiological substrates such as sugars, amino acids, and free fatty acids that are used by the body. The only licensed radionuclide used in PET imaging for viability assessment is F-18 fluorodeoxyglucose (FDG). During a PET scan, the radionuclides are injected into the body and as they decay, they emit positively charged particles (positrons) that travel several millimetres into tissue and collide with orbiting electrons. This collision results in annihilation where the combined mass of the positron and electron is converted into energy in the form of two 511 keV gamma rays, which are then emitted in opposite directions (180 degrees) and captured by an external array of detector elements in the PET gantry. Computer software is then used to convert the radiation emission into images. The system is set up so that it only detects coincident gamma rays that arrive at the detectors within a predefined temporal window, while single photons arriving without a pair or outside the temporal window do not active the detector. This allows for increased spatial and contrast resolution. Evidence-Based Analysis Research Questions What is the diagnostic accuracy of PET for detecting myocardial viability? What is the prognostic value of PET viability imaging (mortality and other clinical outcomes)? What is the contribution of PET viability imaging to treatment decision making? What is the safety of PET viability imaging? Literature Search A literature search was performed on July 17, 2009 using OVID MEDLINE, MEDLINE In-Process and Other Non-Indexed Citations, EMBASE, the Cochrane Library, and the International Agency for Health Technology Assessment (INAHTA) for studies published from January 1, 2004 to July 16, 2009. Abstracts were reviewed by a single reviewer and, for those studies meeting the eligibility criteria, full-text articles were obtained. In addition, published systematic reviews and health technology assessments were reviewed for relevant studies published before 2004. Reference lists of included studies were also examined for any additional relevant studies not already identified. The quality of the body of evidence was assessed as high, moderate, low or very low according to GRADE methodology. Inclusion Criteria Criteria applying to diagnostic accuracy studies, prognosis studies, and physician decision-making studies: English language full-reports Health technology assessments, systematic reviews, meta-analyses, randomized controlled trials (RCTs), and observational studies Patients with chronic, known CAD PET imaging using FDG for the purpose of detecting viable myocardium Criteria applying to diagnostic accuracy studies: Assessment of functional recovery ≥3 months after revascularization Raw data available to calculate sensitivity and specificity Gold standard: prediction of global or regional functional recovery Criteria applying to prognosis studies: Mortality studies that compare revascularized patients with non-revascularized patients and patients with viable and non-viable myocardium Exclusion Criteria Criteria applying to diagnostic accuracy studies, prognosis studies, and physician decision-making studies: PET perfusion imaging < 20 patients < 18 years of age Patients with non-ischemic heart disease Animal or phantom studies Studies focusing on the technical aspects of PET Studies conducted exclusively in patients with acute myocardial infarction (MI) Duplicate publications Criteria applying to diagnostic accuracy studies Gold standard other than functional recovery (e.g., PET or cardiac MRI) Assessment of functional recovery occurs before patients are revascularized Outcomes of Interest Diagnostic accuracy studies Sensitivity and specificity Positive and negative predictive values (PPV and NPV) Positive and negative likelihood ratios Diagnostic accuracy Adverse events Prognosis studies Mortality rate Functional status Exercise capacity Quality of Life Influence on PET viability imaging on physician decision making Statistical Methods Pooled estimates of sensitivity and specificity were calculated using a bivariate, binomial generalized linear mixed model. Statistical significance was defined by P values less than 0.05, where “false discovery rate” adjustments were made for multiple hypothesis testing. Using the bivariate model parameters, summary receiver operating characteristic (sROC) curves were produced. The area under the sROC curve was estimated by numerical integration with a cubic spline (default option). Finally, pooled estimates of mortality rates were calculated using weighted means. Quality of Evidence The quality of evidence assigned to individual diagnostic studies was determined using the QUADAS tool, a list of 14 questions that address internal and external validity, bias, and generalizibility of diagnostic accuracy studies. Each question is scored as “yes”, “no”, or “unclear”. The quality of the body of evidence was then assessed as high, moderate, low, or very low according to the GRADE Working Group criteria. The following definitions of quality were used in grading the quality of the evidence: High Further research is very unlikely to change confidence in the estimate of effect. Moderate Further research is likely to have an important impact on confidence in the estimate of effect and may change the estimate. Low Further research is very likely to have an important impact on confidence in the estimate of effect and is likely to change the estimate. Very Low Any estimate of effect is very uncertain Summary of Findings A total of 40 studies met the inclusion criteria and were included in this review: one health technology assessment, two systematic reviews, 22 observational diagnostic accuracy studies, and 16 prognosis studies. The available PET viability imaging literature addresses two questions: 1) what is the diagnostic accuracy of PET imaging for the assessment; and 2) what is the prognostic value of PET viability imaging. The diagnostic accuracy studies use regional or global functional recovery as the reference standard to determine the sensitivity and specificity of the technology. While regional functional recovery was most commonly used in the studies, global functional recovery is more important clinically. Due to differences in reporting and thresholds, however, it was not possible to pool global functional recovery. Functional recovery, however, is a surrogate reference standard for viability and consequently, the diagnostic accuracy results may underestimate the specificity of PET viability imaging. For example, regional functional recovery may take up to a year after revascularization depending on whether it is stunned or hibernating tissue, while many of the studies looked at regional functional recovery 3 to 6 months after revascularization. In addition, viable tissue may not recover function after revascularization due to graft patency or re-stenosis. Both issues may lead to false positives and underestimate specificity. Given these limitations, the prognostic value of PET viability imaging provides the most direct and clinically useful information. This body of literature provides evidence on the comparative effectiveness of revascularization and medical therapy in patients with viable myocardium and patients without viable myocardium. In addition, the literature compares the impact of PET-guided treatment decision making with SPECT-guided or standard care treatment decision making on survival and cardiac events (including cardiac mortality, MI, hospital stays, unintended revascularization, etc). The main findings from the diagnostic accuracy and prognosis evidence are: Based on the available very low quality evidence, PET is a useful imaging modality for the detection of viable myocardium. The pooled estimates of sensitivity and specificity for the prediction of regional functional recovery as a surrogate for viable myocardium are 91.5% (95% CI, 88.2% – 94.9%) and 67.8% (95% CI, 55.8% – 79.7%), respectively. Based the available very low quality of evidence, an indirect comparison of pooled estimates of sensitivity and specificity showed no statistically significant difference in the diagnostic accuracy of PET viability imaging for regional functional recovery using perfusion/metabolism mismatch with FDG PET plus either a PET or SPECT perfusion tracer compared with metabolism imaging with FDG PET alone. FDG PET + PET perfusion metabolism mismatch: sensitivity, 89.9% (83.5% – 96.4%); specificity, 78.3% (66.3% – 90.2%); FDG PET + SPECT perfusion metabolism mismatch: sensitivity, 87.2% (78.0% – 96.4%); specificity, 67.1% (48.3% – 85.9%); FDG PET metabolism: sensitivity, 94.5% (91.0% – 98.0%); specificity, 66.8% (53.2% – 80.3%). Given these findings, further higher quality studies are required to determine the comparative effectiveness and clinical utility of metabolism and perfusion/metabolism mismatch viability imaging with PET. Based on very low quality of evidence, patients with viable myocardium who are revascularized have a lower mortality rate than those who are treated with medical therapy. Given the quality of evidence, however, this estimate of effect is uncertain so further higher quality studies in this area should be undertaken to determine the presence and magnitude of the effect. While revascularization may reduce mortality in patients with viable myocardium, current moderate quality RCT evidence suggests that PET-guided treatment decisions do not result in statistically significant reductions in mortality compared with treatment decisions based on SPECT or standard care protocols. The PARR II trial by Beanlands et al. found a significant reduction in cardiac events (a composite outcome that includes cardiac deaths, MI, or hospital stay for cardiac cause) between the adherence to PET recommendations subgroup and the standard care group (hazard ratio, .62; 95% confidence intervals, 0.42 – 0.93; P = .019); however, this post-hoc sub-group analysis is hypothesis generating and higher quality studies are required to substantiate these findings. The use of FDG PET plus SPECT to determine perfusion/metabolism mismatch to assess myocardial viability increases the radiation exposure compared with FDG PET imaging alone or FDG PET combined with PET perfusion imaging (total-body effective dose: FDG PET, 7 mSv; FDG PET plus PET perfusion tracer, 7.6 – 7.7 mSV; FDG PET plus SPECT perfusion tracer, 16 – 25 mSv). While the precise risk attributed to this increased exposure is unknown, there is increasing concern regarding lifetime multiple exposures to radiation-based imaging modalities, although the incremental lifetime risk for patients who are older or have a poor prognosis may not be as great as for healthy individuals. PMID:23074393

The Effect of Intermittent Noise Stress on Ozone-Induced ...

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Previous studies have established that acute exposure to air pollution increases the risk of cardiovascular dysfunction. Intrinsic factors are likely the most important determinants of how the body responds to an exposure. But data also suggests that non-environmental stressors like noise, which is a common urban public health problem, can modify and indeed worsen the response. Noise can cause obvious psychological disturbances typical of non-specific stress, but also changes that can increase the number of cardiovascular disease related mortalities. Therefore, we hypothesized that short-term exposure to noise would worsen the cardiovascular response to ozone. Male Wistar-Kyoto rats were implanted with radiotelemeters for the measurement of heart rate (HR), blood pressure (BP) and electrocardiogram (ECG) and exposed to intermittent noise (85-90 dB) for one week after which they were exposed to either ozone (0.8 ppm) or filtered air. Left ventricular functional responses to dobutamine were measured using a Millar probe as well as arrhythmic sensitivity to aconitine in a separate set of untelemetered rats 24 hours after exposure. HR and BP decreased in all telemetered animals during ozone exposure; noise caused BP and HR to increase. Baseline left ventricular pressure (LVP) was significantly higher in animals exposed to both noise and ozone when compared to no noise; furthermore those animals had the least amount of change in LVP, dP/dT max and min with increasi

Secondary Increase of Lactate Levels in Asphyxiated Newborns during Hypothermia Treatment: Reflect of Suboptimal Hemodynamics (A Case Series and Review of the Literature)

PubMed Central

Al Balushi, Asim; Guilbault, Marie-Pier; Wintermark, Pia

2015-01-01

Objective To evaluate whether a secondary increase of serum lactate levels in asphyxiated newborns during hypothermia treatment may reflect suboptimal dynamics. Methods–Retrospective case series and review of the literature. We present the clinical course of four asphyxiated newborns treated with hypothermia who presented with hypotension requiring inotropic support, and who displayed a secondary increase of serum lactate levels during hypothermia treatment. Serial serum lactate levels are correlated with blood pressure and inotropic support within the first 96 hours of life. Results Lactate levels initially decreased in the four patients. However, each of them started to present lower blood pressure, and lactate levels started to increase again. Inotropic support was started to raise blood pressure. The introduction of an epinephrine drip consistently worsened the increase of lactate levels in these newborns, whereas dopamine and dobutamine enabled the clearance of lactate in addition to raising the blood pressure. Rewarming was associated with hemodynamics perturbations (a decrease of blood pressure and/or an increase of lactate levels) in the three newborns who survived. Conclusions Lactate levels during the first 4 days of life should be followed as a potential marker for suboptimal hemodynamic status in term asphyxiated newborns treated with hypothermia, for whom the maintenance of homeostasis during hypothermia treatment is of utmost importance to alleviate brain injury. PMID:26929870

Use of atropine in patients with submaximal heart rate during exercise myocardial perfusion SPECT.

PubMed

De Lorenzo, Andrea; Foerster, James; Sciammarella, Maria G; Suey, Cathy; Hayes, Sean W; Friedman, John D; Berman, Daniel S

2003-01-01

Failure to reach 85% of maximal predicted heart rate (MPHR) during exercise may render a myocardial perfusion single photon emission computed tomography (MPS) study nondiagnostic for ischemia detection. Although commonly used to increase heart rate (HR) during dobutamine stress, the administration of atropine for patients failing to achieve 85% of MPHR during exercise performed for MPS is still infrequent. Patients undergoing dual-isotope MPS were considered candidates for the study when, during exercise treadmill testing, they had less than 85% of MPHR and were unable to continue because of fatigue, without an ischemic response. Forty-seven patients (aged 65.3 +/- 12.5 years, 78.7% men) received atropine (0.6-1.2 mg). Maximal HR achieved before and after atropine was 118.0 +/- 14.8 beats/min (76.3% +/- 6.2% of MPHR) and 146.4 +/- 12.6 beats/min (94.4% +/- 8.1% of MPHR), respectively (P < .001). Of patients, 44 (93.6%) reached at least 85% of MPHR after atropine and had diagnostic MPS studies. After atropine, arrhythmias occurred in 14 patients (29.8%) and other minor side effects in 1 (2.1%). Atropine allows patients initially failing to achieve 85% of MPHR during exercise to increase HR and have a diagnostic MPS study, without major complications. It may provide an alternative to pharmacologic stress for patients with a blunted HR response to exercise.

Stroke Volume estimation using aortic pressure measurements and aortic cross sectional area: Proof of concept.

PubMed

Kamoi, S; Pretty, C G; Chiew, Y S; Pironet, A; Davidson, S; Desaive, T; Shaw, G M; Chase, J G

2015-08-01

Accurate Stroke Volume (SV) monitoring is essential for patient with cardiovascular dysfunction patients. However, direct SV measurements are not clinically feasible due to the highly invasive nature of measurement devices. Current devices for indirect monitoring of SV are shown to be inaccurate during sudden hemodynamic changes. This paper presents a novel SV estimation using readily available aortic pressure measurements and aortic cross sectional area, using data from a porcine experiment where medical interventions such as fluid replacement, dobutamine infusions, and recruitment maneuvers induced SV changes in a pig with circulatory shock. Measurement of left ventricular volume, proximal aortic pressure, and descending aortic pressure waveforms were made simultaneously during the experiment. From measured data, proximal aortic pressure was separated into reservoir and excess pressures. Beat-to-beat aortic characteristic impedance values were calculated using both aortic pressure measurements and an estimate of the aortic cross sectional area. SV was estimated using the calculated aortic characteristic impedance and excess component of the proximal aorta. The median difference between directly measured SV and estimated SV was -1.4ml with 95% limit of agreement +/- 6.6ml. This method demonstrates that SV can be accurately captured beat-to-beat during sudden changes in hemodynamic state. This novel SV estimation could enable improved cardiac and circulatory treatment in the critical care environment by titrating treatment to the effect on SV.

Remote Left Ventricular Hemodynamic Monitoring Using a Novel Intracardiac Sensor.

PubMed

Mondritzki, Thomas; Boehme, Philip; White, Jason; Park, Jin Woo; Hoffmann, Jessica; Vogel, Julia; Kolkhof, Peter; Walsh, Stuart; Sandner, Peter; Bischoff, Erwin; Dinh, Wilfried; Hüser, Jörg; Truebel, Hubert

2018-05-01

Heart failure (HF) remains the most common reason for hospital admission in patients aged >65 years. Despite modern drug therapy, mortality and readmission rates for patients hospitalized with HF remain high. This necessitates further research to identify early patients at risk for readmission to limit hospitalization by timely adjustment of medical therapy. Implantable devices can monitor left ventricular (LV) hemodynamics and remotely and continuously detect the early signs of decompensation to trigger interventions and reduce the risk of hospitalization for HF. Here, we report the first preclinical study validating a new batteryless and easy to implant LV-microelectromechanical system to assess LV performance. A miniaturized implantable wireless pressure sensor was adapted for implantation in the LV apex. The LV-microelectromechanical system sensor was tested in a canine model of HF. The wireless pressure sensor measurements were compared with invasive left heart catheter-derived measurements at several time points. During different pharmacological challenge studies with dobutamine or vasopressin, the device was equally sensitive compared with invasive standard procedures. No adverse events or any observable reaction related to the implantation and application of the device for a period of 35 days was observed. Our miniaturized wireless pressure sensor placed in the LV (LV-microelectromechanical system) has the potential to become a new telemetric tool to earlier identify patients at risk for HF decompensation and to guide the treatment of patients with HF. © 2018 American Heart Association, Inc.

Ventricular untwisting: a temporal link between left ventricular relaxation and suction.

PubMed

Notomi, Yuichi; Popovic, Zoran B; Yamada, Hirotsugu; Wallick, Don W; Martin, Maureen G; Oryszak, Stephanie J; Shiota, Takahiro; Greenberg, Neil L; Thomas, James D

2008-01-01

Left ventricular (LV) untwisting starts early during the isovolumic relaxation phase and proceeds throughout the early filling phase, releasing elastic energy stored by the preceding systolic deformation. Data relating untwisting, relaxation, and intraventricular pressure gradients (IVPG), which represent another manifestation of elastic recoil, are sparse. To understand the interaction between LV mechanics and inflow during early diastole, Doppler tissue images (DTI), catheter-derived pressures (apical and basal LV, left atrial, and aortic), and LV volume data were obtained at baseline, during varying pacing modes, and during dobutamine and esmolol infusion in seven closed-chest anesthetized dogs. LV torsion and torsional rate profiles were analyzed from DTI data sets (apical and basal short-axis images) with high temporal resolution (6.5 +/- 0.7 ms). Repeated-measures regression models showed moderately strong correlation of peak LV twisting with peak LV untwisting rate (r = 0.74), as well as correlations of peak LV untwisting rate with the time constant of LV pressure decay (tau, r = -0.66) and IVPG (r = 0.76, P < 0.0001 for all). In a multivariate analysis, peak LV untwisting rate was an independent predictor of tau and IVPG (P < 0.0001, for both). The start of LV untwisting coincided with the beginning of relaxation and preceded suction-aided filling resulting from elastic recoil. Untwisting rate may be a useful marker of diastolic function or even serve as a therapeutic target for improving diastolic function.

Right ventricular contractile reserve in mitral stenosis: implications on hemodynamic burden and clinical outcome.

PubMed

Sade, Leyla Elif; Ozin, Bülent; Ulus, Taner; Açikel, Sadik; Pirat, Bahar; Bilgi, Muhammed; Uluçam, Melek; Müderrisoğlu, Haldun

2009-06-26

We investigated whether isovolumic acceleration (IVA) under inotropic stimulation as a means of right ventricular (RV) contractile reserve, is a surrogate for hemodynamic burden and has prognostic value in patients with mitral stenosis (MS). Thirty-one pure MS patients and 20 controls underwent cardiac catheterization, exercise test, and dobutamine stress echocardiography. RV fractional area change (FAC), +dP/dt/P(max), RV tissue Doppler indices (isovolumic contraction [IVC] and systolic [S] velocity, and IVA) were measured. Patients were followed-up for the occurrence of cardiac adverse events. Inotropic modulation unmasked statistically significant differences regarding magnitude of changes in IVA, IVC, S, and +dP/dt/P(max), but not RV FAC. Inability to increase IVA more than 6.5 m/s(2) was the only independent determinant of pulmonary capillary wedge pressure >or=18 mm Hg (P=.004). Although MS severity did not predict the RV contractile reserve and pulmonary artery pressure (PAP) behavior during inotropic stimulation, the RV contractile reserve was related to the degree of systolic PAP. IVA increases of <3.4 m/s(2) had 86% sensitivity and 75% specificity to predict unfavorable outcomes during long-term follow-up (20+/-8 months). RV contractile reserve provides complementary data to the hemodynamic significance of MS severity, may contribute to clinical decision making, and be of prognostic value in these patients.

Inward rectifier K+ channel and T-type Ca2+ channel contribute to enhancement of GABAergic transmission induced by β1-adrenoceptor in the prefrontal cortex.

PubMed

Luo, Fei; Zheng, Jian; Sun, Xuan; Tang, Hua

2017-02-01

The functions of prefrontal cortex (PFC) are sensitive to norepinephrine (NE). Endogenously released NE influences synaptic transmission through activation of different subtypes of adrenergic receptors in PFC including α 1 , α 2 , β 1 or β 2 -adrenoceptor. Our recent study has revealed that β 1 -adrenoceptor (β 1 -AR) activation modulates glutamatergic transmission in the PFC, whereas the roles of β 1 -AR in GABAergic transmission are elusive. In the current study, we probed the effects of the β 1 -AR agonist dobutamine (Dobu) on GABAergic transmission onto pyramidal neurons in the PFC of juvenile rats. Dobu increased both the frequency and amplitude of miniature IPSCs (mIPSCs). Ca 2+ influx through T-type voltage-gated Ca 2+ channel was required for Dobu-enhanced mIPSC frequency. We also found that Dobu facilitated GABA release probability and the number of releasable vesicles through regulating T-type Ca 2+ channel. Dobu depolarized GABAergic fast-spiking (FS) interneurons with no effects on the firing rate of action potentials (APs) of interneurons. Dobu-induced depolarization of FS interneurons required inward rectifier K + channel (Kir). Our results suggest that Dobu increase GABA release via inhibition of Kir, which further depolarizes FS interneurons resulting in Ca 2+ influx via T-type Ca 2+ channel. Copyright © 2016 Elsevier Inc. All rights reserved.

Prognostic Value of Coronary Flow Reserve Obtained on Dobutamine Stress Echocardiography and its Correlation with Target Heart Rate.

PubMed

Abreu, José Sebastião de; Rocha, Eduardo Arrais; Machado, Isadora Sucupira; Parahyba, Isabelle O; Rocha, Thais Brito; Paes, Fernando José Villar Nogueira; Diogenes, Tereza Cristina Pinheiro; Abreu, Marília Esther Benevides de; Farias, Ana Gardenia Liberato Ponte; Carneiro, Marcia Maria; Paes, José Nogueira

2017-05-01

Normal coronary flow velocity reserve (CFVR) (≥ 2) obtained in the left anterior descending coronary artery (LAD) from transthoracic echocardiography is associated with a good prognosis, but there is no study correlating CFVR with submaximal target heart rate (HR). To evaluate the prognostic value of CFVR obtained in the LAD of patients with preserved (>50%) left ventricular ejection fraction (LVEF) who completed a dobutamine stress echocardiography (DSE), considering target HR. Prospective study of patients with preserved LVEF and CFVR obtained in the LAD who completed DSE. In Group I (GI = 31), normal CFVR was obtained before achieving target HR, and, in Group II (GII = 28), after that. Group III (G III=24) reached target HR, but CFVR was abnormal. Death, acute coronary insufficiency, coronary intervention, coronary angiography without further intervention, and hospitalization were considered events. In 28 ± 4 months, there were 18 (21.6%) events: 6% (2/31) in GI, 18% (5/28) in GII, and 46% (11/24) in GIII. There were 4 (4.8%) deaths, 6 (7.2%) coronary interventions and 8 (9.6%) coronary angiographies without further intervention. In event-free survival by regression analysis, GIII had more events than GI (p < 0.001) and GII (p < 0.045), with no difference between GI and GII (p = 0.160). After adjustment, the only difference was between GIII and GI (p = 0.012). In patients with preserved LVEF and who completed their DSE, normal CFVR obtained before achieving target HR was associated with better prognosis. A reserva de velocidade de fluxo coronariano (RVFC) adequada (≥ 2) obtida na artéria descendente anterior (ADA) através do ecocardiograma transtorácico associa-se a bom prognóstico, mas não há estudo correlacionando-a com a frequência cardíaca (FC) alvo (submáxima). Avaliar o valor prognóstico da RVFC obtida na ADA de pacientes com fração de ejeção do ventrículo esquerdo (FEVE) preservada (>50%) e ecocardiograma sob estresse com dobutamina (EED) concluído, considerando a FC alvo submáxima. studo prospectivo de pacientes com FEVE preservada e RVFC obtida na ADA durante EED concluído. No Grupo I (GI=31), a RVFC adequada foi obtida antes de se atingir a FC alvo, e no Grupo II (G II=28), após. O Grupo III (G III=24) atingiu a FC alvo, mas a RVFC foi inadequada. Foram considerados eventos: óbito, insuficiência coronariana aguda, intervenção coronariana, coronariografia sem intervenção subsequente e internamento hospitalar. Em 28 ± 4 meses, ocorreram 18 (21,6%) eventos, sendo 6% (2/31) no GI, 18% (5/28) no GII e 46% (11/24) no GIII. Foram 4 (4,8%) óbitos, 6 (7,2%) intervenções coronarianas e 8 (9,6%) coronariografias sem intervenção subsequente. Na sobrevida livre de eventos pela análise de regressão, GIII apresentou mais eventos do que GI (p < 0,001) ou GII (p < 0,045), não havendo diferença entre GI e GII (p = 0,160). Após o ajustamento, foi mantida a diferença apenas entre GIII e GI (p = 0,012). Em pacientes com FEVE preservada e EED concluído, a RVFC adequada obtida antes da FC alvo associou-se ao melhor prognóstico.

Dobutamine Stress Echocardiography Safety in Chagas Disease Patients.

PubMed

Rassi, Daniela do Carmo; Vieira, Marcelo Luiz Campos; Furtado, Rogerio Gomes; Turco, Fabio de Paula; Melato, Luciano Henrique; Hotta, Viviane Tiemi; Nunes, Colandy Godoy de Oliveira; Rassi, Luiz; Rassi, Salvador

2017-02-01

A few decades ago, patients with Chagas disease were predominantly rural workers, with a low risk profile for obstructive coronary artery disease (CAD). As urbanization has increased, they became exposed to the same risk factors for CAD of uninfected individuals. Dobutamine stress echocardiography (DSE) has proven to be an important tool in CAD diagnosis. Despite being a potentially arrhythmogenic method, it is safe for coronary patients without Chagas disease. For Chagas disease patients, however, the indication of DSE in clinical practice is uncertain, because of the arrhythmogenic potential of that heart disease. To assess DSE safety in Chagas disease patients with clinical suspicion of CAD, as well as the incidence of arrhythmias and adverse events during the exam. Retrospective analysis of a database of patients referred for DSE from May/2012 to February/2015. This study assessed 205 consecutive patients with Chagas disease suspected of having CAD. All of them had their serology for Chagas disease confirmed. Their mean age was 64±10 years and most patients were females (65.4%). No patient had significant adverse events, such as acute myocardial infarction, ventricular fibrillation, asystole, stroke, cardiac rupture and death. Regarding arrhythmias, ventricular extrasystoles occurred in 48% of patients, and non-sustained ventricular tachycardia in 7.3%. DSE proved to be safe in this population of Chagas disease patients, in which no potentially life-threatening outcome was found. Até poucas décadas atrás, os pacientes chagásicos eram predominantemente trabalhadores rurais, com baixo perfil de risco para doença obstrutiva coronária. Com a crescente urbanização, passaram a ter os mesmos fatores de risco para doença aterosclerótica que indivíduos não infectados. O ecocardiograma sob estresse com dobutamina (EED) é uma importante ferramenta no diagnóstico de coronariopatia. É referido, porém, como um método potencialmente arritmogênico, mas seguro, em pacientes coronarianos não chagásicos. Entretanto, há insegurança na prática clínica de indicá-lo no paciente chagásico, devido ao potencial arritmogênico já intrínseco nesta cardiopatia. Analisar a segurança do EED em uma população de chagásicos com suspeita clínica de coronariopatia. Análise retrospectiva de um banco de dados de pacientes encaminhados para a realização do EED entre maio/2012 e fevereiro/2015. Avaliou-se pacientes consecutivos portadores de doença de Chagas e com suspeita de coronariopatia. Confirmou-se a sorologia para doença de Chagas em todos os pacientes. A média etária dos 205 pacientes analisados foi de 64 ± 10 anos, sendo a maioria do sexo feminino (65,4%). Nenhum paciente apresentou eventos adversos significativos, como infarto agudo do miocárdio, fibrilação ventricular, assistolia, acidente vascular encefálico, ruptura cardíaca ou morte. Quanto às arritmias, extrassístoles ventriculares frequentes ocorreram em 48% dos pacientes, taquicardia ventricular não sustentada em 7,3%, bigeminismo em 4,4%, taquicardia supraventricular e taquicardia ventricular sustentada em 1% e fibrilação atrial em 0,5%. O EED mostrou ser um exame seguro nessa população de pacientes chagásicos, onde nenhum desfecho grave foi encontrado.

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

Nadel, G.L.; Malik, K.U.; Lew, D.B.

The purpose of this study was to examine arachidonic acid (AA) metabolism and to characterize the type of adrenergic receptor (AR) involved in the production of the major metabolite of this fatty acid. ({sup 14}C)AA was incubated with GPT-rings and the radiolabelled products were extracted and separated by TLC method. The medium was also assayed for radiolabelled immunoreactive PG's (iPG's) and leukotrienes (LT) B4 and C4 by RIA or Enzyme immunoassay (EIA) after exposure to various AR agonists. ({sup 14}C)AA was incorporated into GPT-rings and metabolized mainly into iPGE2 and smaller amounts into PGF2{alpha}. Trace amounts of PGD2 and 6-keto-PGF1{alpha}more » but not LTB4 or LTC4 were detected by RIA and/or EIA. Incubation of GPT rings for 15 minutes with isoproterenol and salbutamol resulted in a significant increase of PGE2 synthesis (optimum conc: 10{sup {minus}7}, 10{sup {minus}7}M respectively). In contrast, dobutamine, norepinephrine, phenylnephrine and xylazine (up to 10{sup {minus}6}M) did not significantly increase PGE2 production. Isoproterenol-induced iPGE2 production was inhibited by a selective {beta}2 antagonist, butoxamine (70%: 10{sup {minus}7}M, 91%: 10{sup {minus}6}M) and somewhat reduced by {beta}1 antagonists practolol and metoprolol (30-64%:10{sup {minus}6}M). These data suggest that isoproterenol induced iPGE2 synthesis is primarily mediated via activation of {beta}2 adrenergic receptor.« less

Echocardiographic dimensions and function in adults with primary growth hormone resistance (Laron syndrome).

PubMed

Feinberg, M S; Scheinowitz, M; Laron, Z

2000-01-15

Patients with primary growth hormone (GH) resistance-Laron Syndrome (LS)-have no GH signal transmission, and thus, no generation of circulating insulin-like growth factor-I (IGF-I), and should serve as a unique model to explore the controversies concerning the longterm effect of GH/IGF-I deficiency on cardiac dimension and function. We assessed 8 patients with LS (4 men, 4 women) with a mean (+/- SD) age of 38+/-7 years (range 22 to 45), and 8 aged-matched controls (4 men, 4 women) with a mean age of 38+/-9 years (range 18 to 47) by echocardiography at rest, following exercise, and during dobutamine administration. Left ventricular (LV) septum, posterior wall, and end-diastolic diameter were significantly reduced in untreated patients with LS compared with the control group (p<0.05 for all). Systolic Doppler-derived parameters, including LV stroke volume, stroke index, cardiac output, and cardiac index, were significantly lower (p<0.05 for all) than in the control subjects, whereas LV diastolic Doppler parameters, including mitral valve waves E, A, E/A ratio, and E deceleration time, were similar in both groups. LV ejection fraction at rest as well as the stress-induced increment of the LV ejection fraction were similar in both groups. Our results show that untreated patients with long-term IGF-I deficiency have reduced cardiac dimensions and output but normal LV ejection fraction at rest and LV contractile reserve following stress.

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.

In vitro study on antioxidant potential of various drugs used in the perioperative period.

PubMed

Kang, M Y; Tsuchiya, M; Packer, L; Manabe, M

1998-01-01

Since surgical trauma not only intensifies the oxidative stress by generating reactive oxygen species (ROS), but also weakens the biological defense system against ROS attack, the antioxidant activity of drugs used during the perioperative period, which possibly normalizes the impaired redox state in the patient, is of fundamental importance and great clinical interest. We have applied the phycoerythrin fluorescence-based assay, in which 2,2'-azobis (2-amidinopropane) dihydrochloride (AAPH)-generated peroxyl radical attacks B-phycoerythrin (B-PE) to lead to a sensitive decrease in its fluorescence intensity linearly, to evaluate the antioxidant activity of major drugs in anesthetic practice. By the protective effect on B-PE fluorescence decay, the antioxidant activities of the drugs were classified into three groups: Group I drugs, which only slowed B-PE fluorescence decay (nicardipine, verapamil, diltiazem, ephedrine, aminophylline, vecuronium, lidocaine, mepivacaine, midazolam, thiamylal, droperidol, ketamine, hydroxyzine, butorphanol, prednisolone, hydrocortisone, betamethasone, dexamethasone, methylprednisolone, and furosemide); Group II drugs, which protected B-PE oxidation completely and stopped fluorescence decay in a certain duration (dopamine, epinephrine, norepinephrine, dobutamine, isoproterenol, and buprenorphine); and Group III drugs, which had no protective effect on B-PE oxidation (nitroglycerin, prostaglandin E1, neostigmine, pancuronium, suxamethonium, atropine, bupivacaine, pentazocine, and heparin). These results indicate that Group I and II drugs exert some antioxidant activity in vitro, as measured by their protection of fluorescence decay of B-PE. Careful consideration of these properties might, then, serve to facilitate more efficient drug application.

Transthoracic echocardiography and mortality in sepsis: analysis of the MIMIC-III database.

PubMed

Feng, Mengling; McSparron, Jakob I; Kien, Dang Trung; Stone, David J; Roberts, David H; Schwartzstein, Richard M; Vieillard-Baron, Antoine; Celi, Leo Anthony

2018-06-01

While the use of transthoracic echocardiography (TTE) in the ICU is rapidly expanding, the contribution of TTE to altering patient outcomes among ICU patients with sepsis has not been examined. This study was designed to examine the association of TTE with 28-day mortality specifically in that population. The MIMIC-III database was employed to identify patients with sepsis who had and had not received TTE. The statistical approaches utilized included multivariate regression, propensity score analysis, doubly robust estimation, the gradient boosted model, and an inverse probability-weighting model to ensure the robustness of our findings. Significant benefit in terms of 28-day mortality was observed among the TTE patients compared to the control (no TTE) group (odds ratio = 0.78, 95% CI 0.68-0.90, p < 0.001). The amount of fluid administered (2.5 vs. 2.1 L on day 1, p < 0.001), use of dobutamine (2% vs. 1%, p = 0.007), and the maximum dose of norepinephrine (1.4 vs. 1 mg/min, p = 0.001) were significantly higher for the TTE patients. Importantly, the TTE patients were weaned off vasopressors more quickly than those in the no TTE group (vasopressor-free days on day 28 of 21 vs. 19, p = 0.004). In a general population of critically ill patients with sepsis, use of TTE is associated with an improvement in 28-day mortality.

Hibernating myocardium, morphological studies on intraoperatory myocardial biopsies and on chronic ischemia experimental model.

PubMed

Laky, D; Parascan, Liliana

2007-01-01

Hibernating myocardium represent a prolonged but potentially reversible myocardial contractile dysfunction, an incomplete adaptation caused by chronic myocardial ischemia and persisting at least until blood flow restored. The purpose of this study was to investigate the morphological changes and weather relations exist among function, metabolism and structure in left ventricular hibernating myocardium. Material and methods. Experimental study is making on 12 dogs incomplete coronary obstruction during six weeks for morphologic studies of ischemic zones. On 48 patients with coronary stenosis myocardial biopsies was effectuated during aorto-coronarian bypass graft. On 60 patients with valvular disease associated with segmental coronary atherosclerotic obstructions during surgical interventions on a effectuated repeatedly biopsies from ischemic zones. Dyskinetic ischemic areas was identified by angiography, scintigraphy, low dose dobutamine echography to identify the cells viability. On myocardial biopsies various histological, histoenzymological, immunohistochemical and ultrastructural methods were performed. The morphological cardiomyocytic changes can summarized: loss of myofilaments, accumulation of glycogen, small mitochondria with reversible lesions, decrease of smooth reticulum, absence of T tubules, depression of titin in puncted pattern, loss of cardiotonin, disorganization of cytoskeleton, dispersed nuclear heterochromatin, embryofetal dedifferentiation, and persistence of viability. Extracellular matrix is enlarged with early matrix protein such fibronectin, tenascin, fibroblasts. In experimental material the morphological changes present similarities with the human biopsies, but intermixed with postinfarction scar tissue. Redifferentiation of hibernanting cells end remodeling of extracellular matrix is possible after quigle revascularization through aorto-coronary bypass grafts.

Determinants of diastolic myocardial tissue Doppler velocities: influences of relaxation and preload.

PubMed

Firstenberg, M S; Greenberg, N L; Main, M L; Drinko, J K; Odabashian, J A; Thomas, J D; Garcia, M J

2001-01-01

Myocardial tissue Doppler echocardiography (TDE) has been proposed as a tool for the assessment of diastolic function. Controversy exists regarding whether TDE measurements are influenced by preload. In this study, left ventricular volume and high-fidelity pressures were obtained in eight closed-chest dogs during intermittent caval occlusion. The time constant of isovolumic ventricular relaxation (tau) was altered with varying doses of dobutamine and esmolol. Peak early diastolic myocardial (E(m)) and transmitral (E) velocities were measured before and after preload reduction. The relative effects of changes in preload and relaxation were determined for E(m) and compared with their effects on E. The following results were observed: caval occlusion significantly decreased E (DeltaE = 16.4 +/- 3.3 cm/s, 36.6 +/- 13.7%, P < 0.01) and E(m) (DeltaE(m) = 1. 3 +/- 0.4 cm/s, 32.5 +/- 26.1%, P < 0.01) under baseline conditions. However, preload reduction was similar for E under all lusitropic conditions (P = not significant), but these effects on E(m) decreased with worsening relaxation. At tau < 50 ms, changes in E(m) with preload reduction were significantly greater (DeltaE(m) = 2.8 +/- 0.6 cm/s) than at tau = 50-65 ms (DeltaE(m) = 1.2 +/- 0.2 cm/s) and at tau >65 ms (DeltaE(m) = 0.5 +/- 0.1 cm/s, P < 0.05). We concluded that TDE E(m) is preload dependent. However, this effect decreases with worsening relaxation.

Importance of circulating IGF-1 for normal cardiac morphology, function and post infarction remodeling.

PubMed

Scharin Täng, M; Redfors, B; Lindbom, M; Svensson, J; Ramunddal, T; Ohlsson, C; Shao, Y; Omerovic, E

2012-12-01

IGF-1 plays an important role in cardiovascular homeostasis, and plasma levels of IGF-1 correlate inversely with systolic function in heart failure. It is not known to what extent circulating IGF-1 secreted by the liver and local autocrine/paracrine IGF-1 expressed in the myocardium contribute to these beneficial effects on cardiac function and morphology. In the present study, we used a mouse model of liver-specific inducible deletion of the IGF-1 gene (LI-IGF-1 -/- mouse) in an attempt to evaluate the importance of circulating IGF-I on cardiac morphology and function under normal and pathological conditions, with an emphasis on its regulatory role in myocardial phosphocreatine metabolism. Echocardiography was performed in LI-IGF-1 -/- and control mice at rest and during dobutamine stress, both at baseline and post myocardial infarction (MI). High-energy phosphate metabolites were compared between LI-IGF-1 -/- and control mice at 4 weeks post MI. We found that LI-IGF-1 -/- mice had significantly greater left ventricular dimensions at baseline and showed a greater relative increase in cardiac dimensions, as well as deterioration of cardiac function, post MI. Myocardial creatine content was 17.9% lower in LI-IGF-1 -/- mice, whereas there was no detectable difference in high-energy nucleotides. These findings indicate an important role of circulating IGF-1 in preserving cardiac structure and function both in physiological settings and post MI. Copyright © 2012 Elsevier Ltd. All rights reserved.

Cardiac Imaging for Assessing Low-Gradient Severe Aortic Stenosis.

PubMed

Clavel, Marie-Annick; Burwash, Ian G; Pibarot, Philippe

2017-02-01

Up to 40% of patients with aortic stenosis (AS) harbor discordant Doppler-echocardiographic findings, the most common of which is the presence of a small aortic valve area (≤1.0 cm 2 ) suggesting severe AS, but a low gradient (<40 mm Hg) suggesting nonsevere AS. The purpose of this paper is to present the role of multimodality imaging in the diagnostic and therapeutic management of this challenging entity referred to as low-gradient AS. Doppler-echocardiography is critical to determine the subtype of low-gradient AS: that is, classical low-flow, paradoxical low-flow, or normal-flow. Patients with low-flow, low-gradient AS generally have a worse prognosis compared with patients with high-gradient or with normal-flow, low-gradient AS. Patients with low-gradient AS and evidence of severe AS benefit from aortic valve replacement (AVR). However, confirmation of the presence of severe AS is particularly challenging in these patients and requires a multimodality imaging approach including low-dose dobutamine stress echocardiography and aortic valve calcium scoring by multidetector computed tomography. Transcatheter AVR using a transfemoral approach may be superior to surgical AVR in patients with low-flow, low-gradient AS. Further studies are needed to confirm the best valve replacement procedure and prosthetic valve for each category of low-gradient AS and to identify patients with low-gradient AS in whom AVR is likely to be futile. Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Divergent agonist selectivity in activating β1- and β2-adrenoceptors for G-protein and arrestin coupling.

PubMed

Casella, Ida; Ambrosio, Caterina; Grò, Maria Cristina; Molinari, Paola; Costa, Tommaso

2011-08-15

The functional selectivity of adrenergic ligands for activation of β1- and β2-AR (adrenoceptor) subtypes has been extensively studied in cAMP signalling. Much less is known about ligand selectivity for arrestin-mediated signalling pathways. In the present study we used resonance energy transfer methods to compare the ability of β1- and β2-ARs to form a complex with the G-protein β-subunit or β-arrestin-2 in response to a variety of agonists with various degrees of efficacy. The profiles of β1-/β2-AR selectivity of the ligands for the two receptor-transducer interactions were sharply different. For G-protein coupling, the majority of ligands were more effective in activating the β2-AR, whereas for arrestin coupling the relationship was reversed. These data indicate that the β1-AR interacts more efficiently than β2-AR with arrestin, but less efficiently than β2-AR with G-protein. A group of ligands exhibited β1-AR-selective efficacy in driving the coupling to arrestin. Dobutamine, a member of this group, had 70% of the adrenaline (epinephrine) effect on arrestin via β1-AR, but acted as a competitive antagonist of adrenaline via β2-AR. Thus the structure of such ligands appears to induce an arrestin-interacting form of the receptor only when bound to the β1-AR subtype. © The Authors Journal compilation © 2011 Biochemical Society

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

Cardiac stress test as a risk-stratification tool for posttransplant cardiac outcomes in diabetic kidney transplant recipients.

PubMed

Singh, Neeraj; Parikh, Samir; Bhatt, Udayan; Vonvisger, Jon; Nori, Uday; Hasan, Ayesha; Samavedi, Srinivas; Andreoni, Kenneth; Henry, Mitchell; Pelletier, Ronald; Rajab, Amer; Elkhammas, Elmahdi; Pesavento, Todd

2012-12-27

The utility of cardiac stress testing as a risk-stratification tool before kidney transplantation remains debatable owing to discordance with coronary angiography and outcome yields at different centers. We conducted a retrospective study of 273 diabetic kidney transplant recipients from 2006 to 2010. By protocol, all diabetic patients underwent pharmacological radionucleotide stress test or dobutamine stress echocardiography before transplant. We compared the 1-year cardiac outcomes between those with negative stress test results and those with positive stress test results. Patients with a positive stress test result (n=67) underwent coronary angiogram, and significant coronary artery disease (≥70% coronary stenosis) was found in 35 (52.2%) patients. Of the latter, 32 (91.4%) underwent cardiac revascularization (24 underwent cardiac stenting and 8 underwent coronary artery bypass grafting). The rest (n=35) were treated medically. Within 1 year after transplant, the group with positive stress test results experienced more cardiac events (34.3% vs. 3.9%, P<0.001) including acute myocardial infarction (22.4% vs. 3.4%, P<0.001) and ventricular arrhythmias (8.9% vs. 0.05%, P=0.001), higher all-cause mortality (19.4% vs. 4.8%, P<0.001), and cardiac mortality (17.9% vs. 0.9%, P<0.001) compared with the group with negative stress test results. In this diabetic population, stress testing showed positive and negative predictive values of 34.3% and 96.1%, respectively. Pharmacological cardiac stress testing provided excellent risk stratification in diabetic kidney transplant recipients.

A porcine model of hypertensive cardiomyopathy: implications for heart failure with preserved ejection fraction.

PubMed

Schwarzl, Michael; Hamdani, Nazha; Seiler, Sebastian; Alogna, Alessio; Manninger, Martin; Reilly, Svetlana; Zirngast, Birgit; Kirsch, Alexander; Steendijk, Paul; Verderber, Jochen; Zweiker, David; Eller, Philipp; Höfler, Gerald; Schauer, Silvia; Eller, Kathrin; Maechler, Heinrich; Pieske, Burkert M; Linke, Wolfgang A; Casadei, Barbara; Post, Heiner

2015-11-01

Heart failure with preserved ejection fraction (HFPEF) evolves with the accumulation of risk factors. Relevant animal models to identify potential therapeutic targets and to test novel therapies for HFPEF are missing. We induced hypertension and hyperlipidemia in landrace pigs (n = 8) by deoxycorticosteroneacetate (DOCA, 100 mg/kg, 90-day-release subcutaneous depot) and a Western diet (WD) containing high amounts of salt, fat, cholesterol, and sugar for 12 wk. Compared with weight-matched controls (n = 8), DOCA/WD-treated pigs showed left ventricular (LV) concentric hypertrophy and left atrial dilatation in the absence of significant changes in LV ejection fraction or symptoms of heart failure at rest. The LV end-diastolic pressure-volume relationship was markedly shifted leftward. During simultaneous right atrial pacing and dobutamine infusion, cardiac output reserve and LV peak inflow velocities were lower in DOCA/WD-treated pigs at higher LV end-diastolic pressures. In LV biopsies, we observed myocyte hypertrophy, a shift toward the stiffer titin isoform N2B, and reduced total titin phosphorylation. LV superoxide production was increased, in part attributable to nitric oxide synthase (NOS) uncoupling, whereas AKT and NOS isoform expression and phosphorylation were unchanged. In conclusion, we developed a large-animal model in which loss of LV capacitance was associated with a titin isoform shift and dysfunctional NOS, in the presence of preserved LV ejection fraction. Our findings identify potential targets for the treatment of HFPEF in a relevant large-animal model. Copyright © 2015 the American Physiological Society.

Control of nasal vasculature and airflow resistance in the dog.

PubMed Central

Lung, M A; Phipps, R J; Wang, J C; Widdicombe, J G

1984-01-01

Nasal vascular and airflow resistances have been measured in dogs, simultaneously on both sides separately. Vascular resistance was measured either by constant flow perfusion of the terminal branch of the maxillary artery (which supplies, via the sphenopalatine artery, the nasal septum, most of the turbinates and the nasal sinuses) or by measuring blood flow through this artery, maintained by the dog's own blood pressure. Airflow resistance was assessed by inserting balloon-tipped endotracheal catheters into the back of each nasal cavity via the nasopharynx, and measuring transnasal pressure at constant airflow through each side of the nose simultaneously. Preliminary experiments indicated that there was 5-10% collateral anastomosis between the two sides. Close-arterial injection of drugs showed different patterns of response. Adrenaline, phenylephrine, chlorpheniramine and low doses of prostaglandin F2 alpha increased vascular resistance and lowered airway resistance. Salbutamol, methacholine and histamine lowered vascular resistance and increased airway resistance. Dobutamine decreased airway resistance with a small increase in vascular resistance. Prostaglandins E1, E2 and F2 alpha (high dose) decreased both vascular and airway resistances. Substance P, eledoisin-related peptide and vasoactive intestinal polypeptide lowered vascular resistance with little change in airway resistance. The results are interpreted in terms of possible drug actions on precapillary resistance vessels, sinusoids and venules, and arteriovenous anastomoses. It is concluded that nasal airway resistance cannot be correlated with vascular resistance or blood flow, since the latter has a complex and ill-defined relationship with nasal vascular blood volume. PMID:6204040

Control of nasal vasculature and airflow resistance in the dog.

PubMed

Lung, M A; Phipps, R J; Wang, J C; Widdicombe, J G

1984-04-01

Nasal vascular and airflow resistances have been measured in dogs, simultaneously on both sides separately. Vascular resistance was measured either by constant flow perfusion of the terminal branch of the maxillary artery (which supplies, via the sphenopalatine artery, the nasal septum, most of the turbinates and the nasal sinuses) or by measuring blood flow through this artery, maintained by the dog's own blood pressure. Airflow resistance was assessed by inserting balloon-tipped endotracheal catheters into the back of each nasal cavity via the nasopharynx, and measuring transnasal pressure at constant airflow through each side of the nose simultaneously. Preliminary experiments indicated that there was 5-10% collateral anastomosis between the two sides. Close-arterial injection of drugs showed different patterns of response. Adrenaline, phenylephrine, chlorpheniramine and low doses of prostaglandin F2 alpha increased vascular resistance and lowered airway resistance. Salbutamol, methacholine and histamine lowered vascular resistance and increased airway resistance. Dobutamine decreased airway resistance with a small increase in vascular resistance. Prostaglandins E1, E2 and F2 alpha (high dose) decreased both vascular and airway resistances. Substance P, eledoisin-related peptide and vasoactive intestinal polypeptide lowered vascular resistance with little change in airway resistance. The results are interpreted in terms of possible drug actions on precapillary resistance vessels, sinusoids and venules, and arteriovenous anastomoses. It is concluded that nasal airway resistance cannot be correlated with vascular resistance or blood flow, since the latter has a complex and ill-defined relationship with nasal vascular blood volume.

[Beta-1 adrenoceptor blockade decreases the firing rate to painful stimuli in spinal wide-dynamic range neurons in rats].

PubMed

Lamothe-Molina, Paul J; Lamothe-Molina, Pedro A; López-Ávila, Alberto

2014-01-01

It is known that epinephrine/norepinephrine inhibit acute pain transmission. However, the role of ß-adrenoceptors is not clear. Thus, we analyzed if beta-1 and/or beta-2 adrenoceptors can modulate acute pain transmission by performing in vivo single unit recordings during painful and non-painful peripheral stimulation in rats. Longitudinal study in which we analyzed seven groups of male rats Wistar: control group (n = 11): saline (0.9 %); EPI group (n = 8): epinephrine 100 mcg; beta-1 agonist group (n = 8): dobutamine 125 mcg; beta-1-antagonist group (n = 9): metoprolol 100 mcg; beta-2-agonist group (n = 7): clenbuterol 100 mcg; beta-2-antagonist group (n = 8): butoxamine 100 mcg; beta-1-antagonist + EPI group (n = 10): metoprolol 100 mcg + epinephrine 100 mcg. For the statistical analysis we used ANOVA. Epinephrine significantly reduced the basal firing rate (BFR) in 34.1 % (p < 0.05) and also the evoked response by painful stimulation in 56 % (p < 0.05). No change was observed in the evoked response by non-painful stimulation. ANTß1 was the only beta-adrenoceptor acting drug that significantly reduced the evoked response by painful stimulation in 41 % (p < 0.05). None of the other drugs alone affected either the BFR or the evoked response to non-painful or painful stimulation. It is the first time that a beta-1-adrenoceptor antagonist (metoprolol) probes to be effective in reducing the response to painful stimulation in WDR neurons.

Infusion of guaifenesin, ketamine, and medetomidine in combination with inhalation of sevoflurane versus inhalation of sevoflurane alone for anesthesia of horses.

PubMed

Yamashita, Kazuto; Muir, William W; Tsubakishita, Sae; Abrahamsen, Eric; Lerch, Phillip; Izumisawa, Yasuharu; Kotani, Tadao

2002-10-15

To evaluate effects of infusion of guaifenesin, ketamine, and medetomidine in combination with inhalation of sevoflurane versus inhalation of sevoflurane alone for anesthesia of horses. Randomized clinical trial. 40 horses. Horses were premedicated with xylazine and anesthetized with diazepam and ketamine. Anesthesia was maintained by infusion of guaifenesin, ketamine, and medetomidine and inhalation of sevoflurane (20 horses) or by inhalation of sevoflurane (20 horses). A surgical plane of anesthesia was maintained by controlling the inhaled concentration of sevoflurane. Sodium pentothal was administered as necessary to prevent movement in response to surgical stimulation. Hypotension was treated with dobutamine; hypoxemia and hypercarbia were treated with intermittent positive-pressure ventilation. The quality of anesthetic induction, maintenance, and recovery and the quality of the transition to inhalation anesthesia were scored. The delivered concentration of sevoflurane (ie, the vaporizer dial setting) was significantly lower and the quality of transition to inhalation anesthesia and of anesthetic maintenance were significantly better in horses that received the guaifenesin-ketamine-medetomidine infusion than in horses that did not. Five horses, all of which received sevoflurane alone, required administration of pentothal. Recovery time and quality of recovery were not significantly different between groups, but horses that received the guaifenesin-ketamine-medetomidine infusion required fewer attempts to stand. Results suggest that in horses, the combination of a guaifenesin-ketamine-medetomidine infusion and inhalation of sevoflurane resulted in better transition and maintenance phases while improving cardiovascular function and reducing the number of attempts needed to stand after the completion of anesthesia, compared with inhalation of sevoflurane.

Use of Inotropic Agents in Treatment of Systolic Heart Failure.

PubMed

Tariq, Sohaib; Aronow, Wilbert S

2015-12-04

The most common use of inotropes is among hospitalized patients with acute decompensated heart failure, with reduced left ventricular ejection fraction and with signs of end-organ dysfunction in the setting of a low cardiac output. Inotropes can be used in patients with severe systolic heart failure awaiting heart transplant to maintain hemodynamic stability or as a bridge to decision. In cases where patients are unable to be weaned off inotropes, these agents can be used until a definite or escalated supportive therapy is planned, which can include coronary revascularization or mechanical circulatory support (intra-aortic balloon pump, extracorporeal membrane oxygenation, impella, left ventricular assist device, etc.). Use of inotropic drugs is associated with risks and adverse events. This review will discuss the use of the inotropes digoxin, dopamine, dobutamine, norepinephrine, milrinone, levosimendan, and omecamtiv mecarbil. Long-term inotropic therapy should be offered in selected patients. A detailed conversation with the patient and family shall be held, including a discussion on the risks and benefits of use of inotropes. Chronic heart failure patients awaiting heart transplants are candidates for intravenous inotropic support until the donor heart becomes available. This helps to maintain hemodynamic stability and keep the fluid status and pulmonary pressures optimized prior to the surgery. On the other hand, in patients with severe heart failure who are not candidates for advanced heart failure therapies, such as transplant and mechanical circulatory support, inotropic agents can be used for palliative therapy. Inotropes can help reduce frequency of hospitalizations and improve symptoms in these patients.

Doppler-derived myocardial systolic strain rate is a strong index of left ventricular contractility

NASA Technical Reports Server (NTRS)

Greenberg, Neil L.; Firstenberg, Michael S.; Castro, Peter L.; Main, Michael; Travaglini, Agnese; Odabashian, Jill A.; Drinko, Jeanne K.; Rodriguez, L. Leonardo; Thomas, James D.; Garcia, Mario J.

2002-01-01

BACKGROUND: Myocardial fiber strain is directly related to left ventricular (LV) contractility. Strain rate can be estimated as the spatial derivative of velocities (dV/ds) obtained by tissue Doppler echocardiography (TDE). The purposes of the study were (1) to determine whether TDE-derived strain rate may be used as a noninvasive, quantitative index of contractility and (2) to compare the relative accuracy of systolic strain rate against TDE velocities alone. METHODS AND RESULTS: TDE color M-mode images of the interventricular septum were recorded from the apical 4-chamber view in 7 closed-chest anesthetized mongrel dogs during 5 different inotropic stages. Simultaneous LV volume and pressure were obtained with a combined conductance-high-fidelity pressure catheter. Peak elastance (Emax) was determined as the slope of end-systolic pressure-volume relationships during caval occlusion and was used as the gold standard of LV contractility. Peak systolic TDE myocardial velocities (Sm) and peak (epsilon'(p)) and mean (epsilon'(m)) strain rates obtained at the basal septum were compared against Emax by linear regression. Emax as well as TDE systolic indices increased during inotropic stimulation with dobutamine and decreased with the infusion of esmolol. A stronger association was found between Emax and epsilon'(p) (r=0.94, P<0.01, y=0.29x+0.46) and epsilon'(m) (r=0.88, P<0.01) than for Sm (r=0.75, P<0.01). CONCLUSIONS: TDE-derived epsilon'(p) and epsilon'(m) are strong noninvasive indices of LV contractility. These indices appear to be more reliable than S(m), perhaps by eliminating translational artifact.

Ablation of PGC-1β Results in Defective Mitochondrial Activity, Thermogenesis, Hepatic Function, and Cardiac Performance

PubMed Central

Petrovic, Natasa; Kis, Adrienn; Feldmann, Helena M; Bjursell, Mikael; Parker, Nadeene; Curtis, Keira; Campbell, Mark; Hu, Ping; Zhang, Dongfang; Litwin, Sheldon E; Zaha, Vlad G; Fountain, Kimberly T; Boudina, Sihem; Jimenez-Linan, Mercedes; Blount, Margaret; Lopez, Miguel; Meirhaeghe, Aline; Bohlooly-Y, Mohammad; Storlien, Leonard; Strömstedt, Maria; Snaith, Michael; Orešič, Matej; Abel, E. Dale; Cannon, Barbara; Vidal-Puig, Antonio

2006-01-01

The transcriptional coactivator peroxisome proliferator-activated receptor-gamma coactivator-1β (PGC-1β) has been implicated in important metabolic processes. A mouse lacking PGC-1β (PGC1βKO) was generated and phenotyped using physiological, molecular, and bioinformatic approaches. PGC1βKO mice are generally viable and metabolically healthy. Using systems biology, we identified a general defect in the expression of genes involved in mitochondrial function and, specifically, the electron transport chain. This defect correlated with reduced mitochondrial volume fraction in soleus muscle and heart, but not brown adipose tissue (BAT). Under ambient temperature conditions, PGC-1β ablation was partially compensated by up-regulation of PGC-1α in BAT and white adipose tissue (WAT) that lead to increased thermogenesis, reduced body weight, and reduced fat mass. Despite their decreased fat mass, PGC1βKO mice had hypertrophic adipocytes in WAT. The thermogenic role of PGC-1β was identified in thermoneutral and cold-adapted conditions by inadequate responses to norepinephrine injection. Furthermore, PGC1βKO hearts showed a blunted chronotropic response to dobutamine stimulation, and isolated soleus muscle fibres from PGC1βKO mice have impaired mitochondrial function. Lack of PGC-1β also impaired hepatic lipid metabolism in response to acute high fat dietary loads, resulting in hepatic steatosis and reduced lipoprotein-associated triglyceride and cholesterol content. Altogether, our data suggest that PGC-1β plays a general role in controlling basal mitochondrial function and also participates in tissue-specific adaptive responses during metabolic stress. PMID:17090215

Anomalous Coronary Arteries and Myocardial Bridges: Risk Stratification in Children Using Novel Cardiac Catheterization Techniques.

PubMed

Agrawal, Hitesh; Molossi, Silvana; Alam, Mahboob; Sexson-Tejtel, S Kristen; Mery, Carlos M; McKenzie, E Dean; Fraser, Charles D; Qureshi, Athar M

2017-03-01

The evaluation of the vast majority of children with anomalous aortic origin of a coronary artery (AAOCA) and/or myocardial bridges is performed with non-invasive testing. However, a subset of these patients may benefit from invasive testing for risk stratification. All patients included in the Coronary Anomalies Program (CAP) at Texas Children's Hospital who underwent cardiac catheterization were included. Techniques included selective coronary angiograms (SCA), intravascular ultrasound (IVUS), and fractional flow reserve (FFR) measurements with provocative testing using adenosine and/or dobutamine infusions. Out of the 131 patients followed by the CAP between 12/12-4/16, 8 (6%) patients underwent 9 cath investigations at median age 13.1 (2.6-18.7) years and median weight 49.5 (11.4-142.7) kg. Six patients presented with cardiac signs/symptoms. Four patients had myocardial bridges of the left anterior descending (LAD) coronary artery, 2 patients had isolated AAOCA, and 2 patients had an anomalous left coronary artery (LCA) with an intramyocardial course of the LAD. SCA was performed in all patients. FFR was positive in 4/6 patients: IVUS showed >70% intraluminal narrowing in 3/5 patients. One patient had hemodynamic instability that reversed with catheter removal from the coronary ostium. Based on the catheterization data obtained, findings were reassuring in three patients, surgery was performed in three patients, and two patients are being medically managed/restricted from competitive sports. In our small cohort of patients, we demonstrated that IVUS and FFR can safely be performed in children and may help to risk stratify some patients with AAOCA and myocardial bridges.

[Anesthesia in single and bilateral sequential lung transplantation. Lung Transplantation Group].

PubMed

Della Rocca, G; Coccia, C; Pugliese, F; Pompei, L; Ruberto, F; Costa, M G; Venuta, F; Rendina, E A; De Giacomo, T; Pietropaoli, P; Gasparetto, A

2000-04-01

Anesthesia for lung transplantation: intraoperative complications and long term results. 52 patients were scheduled for 16 single lung transplantations (SLT) (9 fibrosis and 7 emphysema) and 36 bilateral sequential lung transplantations (DLT) (4 bronchiectasis, 6 emphysema, 3 fibrosis, 22 cystic fibrosis and 1 pulmonary hypertension). Anesthesia was induced with propofol or midazolam, and fentanyl or alfentanil. As muscle relaxant vecuronium bromide was used. Anesthesia was maintained with isoflurane, fentanyl in boluses or sufentanil continuous infusion in O2 100%. Prostaglandin E1 (20-300 ng/kg/min), inhaled nitric oxide (10-40 ppm), dobutamine (5-15 mcg/kg/min), norepinephrine (0.05-3 mcg/kg/min) and ephedrine (5-10 mg per bolus) were used for hemodynamic management. In 2 patients inhaled areosolized prostacyclin were administered. Mean pulmonary arterial pressure (mPA) and pulmonary vascular resistance (PVRI) increased after pulmonary artery clamping during first lung (mPA: 3347 nel DLT, 3643 nel SLT; PVRI; 375488 nel DLT, 377420 nel SLT) and second lung implantation (mPA: 3746; PVRI: 263553) and decreased after reperfusion of the first (mPA: 4737 nel DLT, 4329 nel SLT; PVRI: 488263 nel DLT, 420233 nel SLT) and the second lung (mPA: 4629; PVRI: 553260). Only in 9 cases (7 DLT and 2 SLT) C-P bypass was used. With a strong drug support with pulmonary vasodilators, positive inotropic and systemic vasoconstrictor drugs, in most patients we transplanted C-P bypass can be avoided. Intraoperative deaths were not observed. Two years actuarial survival is 65% for DLT and 60% for SLT.

Safety and feasibility of inpatient exercise training in pediatric heart failure: a preliminary report.

PubMed

McBride, Michael G; Binder, Tracy Jo; Paridon, Stephen M

2007-01-01

To determine the safety and feasibility of an inpatient exercise training program for a group of pediatric heart transplantation candidates on multiple inotropic support. Children with end-stage heart disease often require heart transplantation. Currently, no data exist on the safety and feasibility of an inpatient exercise training program in pediatric patients awaiting heart transplantation while on inotropic support. Twenty ambulatory patients (11 male; age, 13.6 +/- 3.2 years) were admitted, listed, and subsequently enrolled into an exercise training program while awaiting heart transplantation. Patient diagnoses consisted of dilated cardiomyopathy (n = 15), restrictive cardiomyopathy (n = 1), and failing single-ventricle physiology (n = 4). Inotropic support consisted of a combination of dobutamine, dopamine, or milrinone. Exercise sessions were scheduled three times a week lasting from 30 to 60 minutes and consisted of aerobic and musculoskeletal conditioning. Over 6.2 +/- 4.2 months, 1,251 of a possible 1,508 exercise training sessions were conducted, with a total of 615 hours (26.3 +/- 2.7 min/session) dedicated to low-intensity aerobic exercise. Reasons for noncompliance included a change in medical status, staffing, or patient cooperation. Two adverse episodes (seizures) occurred, neither of which resulted in termination from the program. No adverse episodes of hypotension or significant complex arrhythmias occurred. No complication of medication administration or loss of intravenous access occurred. Data from this study indicate that pediatric patients on inotropic support as a result of systemic ventricular or biventricular heart failure can safely participate in exercise training programs with relatively moderate to high compliance.

Extracorporeal shockwave myocardial revascularization improves clinical symptoms and left ventricular function in patients with refractory angina.

PubMed

Zuozienė, Gitana; Laucevičius, Aleksandras; Leibowitz, David

2012-01-01

Medical therapy for refractory angina is limited and the prognosis is poor. Experimental data suggest that the use of extracorporeal shockwave myocardial revascularization (ESMR) can contribute to angiogenesis and improve symptoms of angina and left ventricular (LV) function. The objective of this study was to examine the effects of ESMR on clinical symptoms as well as LV function as assessed by cardiac MRI in patients with refractory angina. Patients with Canadian Cardiovascular Society (CCS) class III-IV angina despite medical therapy and ischemia documented on thallium or echo-dobutamine were eligible for the study. ESMR therapy was applied with a commercially available cardiac shockwave generator system under echocardiographic guidance. LV function was assessed before and 6 months after therapy by cardiac MRI. Twenty patients (four women, 16 men; mean age 64 years, range 45-83) were included in the study. The CCS class after treatment improved in all patients (16 patients angina pectoris CCS from III to II and four patients from IV to III). The use of sublingual nitroglycerin was significantly reduced as well. There was a significant improvement in LV ejection fraction as assessed by blinded MRI following therapy in the overall population (51 vs. 59%, P<0.05). This study demonstrates the potential efficacy of ESMR for the treatment of refractory angina pectoris. The patients showed both a significant clinical response as well as improved LV ejection fraction on serial MRI imaging. Larger studies are needed to adequately define the clinical utility of this novel therapy.

Altered in vivo left ventricular torsion and principal strains in hypothyroid rats

PubMed Central

Chen, Yong; Somji, Aleefia; Yu, Xin

2010-01-01

The twisting and untwisting motions of the left ventricle (LV) lead to efficient ejection of blood during systole and filling of the ventricle during diastole. Global LV mechanical performance is dependent on the contractile properties of cardiac myocytes; however, it is not known how changes in contractile protein expression affect the pattern and timing of LV rotation. At the myofilament level, contractile performance is largely dependent on the isoforms of myosin heavy chain (MHC) that are expressed. Therefore, in this study, we used MRI to examine the in vivo mechanical consequences of altered MHC isoform expression by comparing the contractile properties of hypothyroid rats, which expressed only the slow β-MHC isoform, and euthyroid rats, which predominantly expressed the fast α-MHC isoform. Unloaded shortening velocity (Vo) and apparent rate constants of force development (ktr) were measured in the skinned ventricular myocardium isolated from euthyroid and hypothyroid hearts. Increased expression of β-MHC reduced LV torsion and fiber strain and delayed the development of peak torsion and strain during systole. Depressed in vivo mechanical performance in hypothyroid rats was related to slowed cross-bridge performance, as indicated by significantly slower Vo and ktr, compared with euthyroid rats. Dobutamine infusion in hypothyroid hearts produced smaller increases in torsion and strain and aberrant transmural torsion patterns, suggesting that the myocardial response to β-adrenergic stress is compromised. Thus, increased expression of β-MHC alters the pattern and decreases the magnitude of LV rotation, contributing to reduced mechanical performance during systole, especially in conditions of increased workload. PMID:20729398

Increased Efferent Cardiac Sympathetic Nerve Activity and Defective Intrinsic Heart Rate Regulation in Type 2 Diabetes.

PubMed

Thaung, H P Aye; Baldi, J Chris; Wang, Heng-Yu; Hughes, Gillian; Cook, Rosalind F; Bussey, Carol T; Sheard, Phil W; Bahn, Andrew; Jones, Peter P; Schwenke, Daryl O; Lamberts, Regis R

2015-08-01

Elevated sympathetic nerve activity (SNA) coupled with dysregulated β-adrenoceptor (β-AR) signaling is postulated as a major driving force for cardiac dysfunction in patients with type 2 diabetes; however, cardiac SNA has never been assessed directly in diabetes. Our aim was to measure the sympathetic input to and the β-AR responsiveness of the heart in the type 2 diabetic heart. In vivo recording of SNA of the left efferent cardiac sympathetic branch of the stellate ganglion in Zucker diabetic fatty rats revealed an elevated resting cardiac SNA and doubled firing rate compared with nondiabetic rats. Ex vivo, in isolated denervated hearts, the intrinsic heart rate was markedly reduced. Contractile and relaxation responses to β-AR stimulation with dobutamine were compromised in externally paced diabetic hearts, but not in diabetic hearts allowed to regulate their own heart rate. Protein levels of left ventricular β1-AR and Gs (guanine nucleotide binding protein stimulatory) were reduced, whereas left ventricular and right atrial β2-AR and Gi (guanine nucleotide binding protein inhibitory regulatory) levels were increased. The elevated resting cardiac SNA in type 2 diabetes, combined with the reduced cardiac β-AR responsiveness, suggests that the maintenance of normal cardiovascular function requires elevated cardiac sympathetic input to compensate for changes in the intrinsic properties of the diabetic heart. © 2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

Forward and Backward Pressure Waveform Morphology in Hypertension

PubMed Central

Li, Ye; Gu, Haotian; Fok, Henry; Alastruey, Jordi

2017-01-01

We tested the hypothesis that increased pulse wave reflection and altered backward waveform morphology contribute to increased pulse pressure in subjects with higher pulse pressure compared with lower pulse pressure and to actions of vasoactive drugs to increase pulse pressure. We examined the relationship of backward to forward wave morphology in 158 subjects who were evaluated for hypertension (including some normotensive subjects) divided into 3 groups by central pulse pressure: group 1, 33±6.5 mm Hg; group 2, 45±4.1 mm Hg; and group 3, 64±12.9 mm Hg (means±SD) and in healthy normotensive subjects during administration of inotropic and vasomotor drugs. Aortic pressure and flow in the aortic root were estimated by carotid tonometry and Doppler sonography, respectively. Morphology of the backward wave relative to the forward wave was similar in subjects in the lowest and highest tertiles of pulse pressure. Similar results were seen with the inotropic, vasopressor and vasodilator drugs, dobutamine, norepinephrine, and phentolamine, with the backward wave maintaining a constant ratio to the forward wave. However, nitroglycerin, a drug with a specific action to dilate muscular conduit arteries, reduced the amplitude of the backward wave relative to the forward wave from 0.26±0.018 at baseline to 0.19±0.019 during nitroglycerin 30 μg/min IV (P<0.01). These results are best explained by an approximately constant amount of reflection of the forward wave from the peripheral vasculature. The amount of reflection can be modified by dilation of peripheral muscular conduit arteries but contributes little to increased pulse pressure in hypertension. PMID:27920128

Low-dose adenosine stress echocardiography: detection of myocardial viability.

PubMed

Djordjevic-Dikic, Ana; Ostojic, Miodrag; Beleslin, Branko; Nedeljkovic, Ivana; Stepanovic, Jelena; Stojkovic, Sinisa; Petrasinovic, Zorica; Nedeljkovic, Milan; Saponjski, Jovica; Giga, Vojislav

2003-06-03

The aim of this study was to evaluate the diagnostic potential of low-dose adenosine stress echocardiography in detection of myocardial viability. Vasodilation through low dose dipyridamole infusion may recruit contractile reserve by increasing coronary flow or by increasing levels of endogenous adenosine. Forty-three patients with resting dyssynergy, due to previous myocardial infarction, underwent low-dose adenosine (80, 100, 110 mcg/kg/min in 3 minutes intervals) echocardiography test. Gold standard for myocardial viability was improvement in systolic thickening of dyssinergic segments of >or= 1 grade at follow-up. Coronary angiography was done in 41 pts. Twenty-seven patients were revascularized and 16 were medically treated. Echocardiographic follow up data (12 +/- 2 months) were available in 24 revascularized patients. Wall motion score index improved from rest 1.55 +/- 0.30 to 1.33 +/- 0.26 at low-dose adenosine (p < 0.001). Of the 257 segments with baseline dyssynergy, adenosine echocardiography identified 122 segments as positive for viability, and 135 as necrotic since no improvement of systolic thickening was observed. Follow-up wall motion score index was 1.31 +/- 0.30 (p < 0.001 vs. rest). The sensitivity of adenosine echo test for identification of viable segments was 87%, while specificity was 95%, and diagnostic accuracy 90%. Positive and negative predictive values were 97% and 80%, respectively. Low-dose adenosine stress echocardiography test has high diagnostic potential for detection of myocardial viability in the group of patients with left ventricle dysfunction due to previous myocardial infarction. Low dose adenosine stress echocardiography may be adequate alternative to low-dose dobutamine test for evaluation of myocardial viability.

Combined thallium-201 and dynamic iodine-123 iodophenylpentadecanoic acid single-photon emission computed tomography in patients after acute myocardial infarction with effective reperfusion.

PubMed

Richter, W S; Beckmann, S; Cordes, M; Schuppenhauer, T; Schartl, M; Munz, D L

2000-12-01

Considerable derangements of energy metabolism are to be expected during ischemia and reperfusion. In ischemic myocardium, the oxidative degradation of carbohydrates is shifted toward the anaerobic production of lactate and the oxidation of fatty acids is suppressed. The aim of this study was to examine the uptake and metabolism of iodine-123 (123I) iodophenylpentadecanoic acid (IPPA) in stunned myocardium. In 15 patients, SPECT with 201Tl and 123I IPPA as well as echocardiography with low-dose dobutamine stimulation were performed 12 +/- 5 days after myocardial infarction with reperfusion. Follow-up echocardiography was carried out 24 +/- 8 days later for documentation of functional improvement. Uptake of 201Tl and 123I IPPA were obtained in five left ventricular segments, and dynamic SPECT imaging was used for calculation of the fast and the slow components of the biexponential myocardial 123I IPPA clearance. Wall motion improved in 14 of 26 dysfunctional segments (54%). Stunned segments were characterized by a reduced 123I IPPA extraction, a shorter half-life of the fast, and a longer half-life of the slow clearance component. All parameters of the combined 201Tl/123I IPPA study predicted functional recovery with similar accuracies (area under the receiver operator characteristic curves between 0.68 and 0.76; p = NS). Analysis of 201Tl uptake alone could not predict functional recovery in this study. Stunned myocardium is characterized by a disturbance of fatty acid metabolism. For prediction of functional improvement, 123I IPPA imaging added significant diagnostic information.

Positron Emission Tomography for the Assessment of Myocardial Viability

PubMed Central

2005-01-01

Executive Summary Objective The objective was to update the 2001 systematic review conducted by the Institute For Clinical Evaluative Sciences (ICES) on the use of positron emission tomography (PET) in assessing myocardial viability. The update consisted of a review and analysis of the research evidence published since the 2001 ICES review to determine the effectiveness and cost-effectiveness of PET in detecting left ventricular (LV) viability and predicting patient outcomes after revascularization in comparison with other noninvasive techniques. Background Left Ventricular Viability Heart failure is a complex syndrome that impairs the contractile ability of the heart to maintain adequate blood circulation, resulting in poor functional capacity and increased risk of morbidity and mortality. It is the leading cause of hospitalization in elderly Canadians. In more than two-thirds of cases, heart failure is secondary to coronary heart disease. It has been shown that dysfunctional myocardium resulting from coronary heart disease (CAD) may recover contractile function (i.e. considered viable). Dysfunctional but viable myocardium may have been stunned by a brief episode of ischemia, followed by restoration of perfusion, and may regain function spontaneously. It is believed that repetitive stunning results in hibernating myocardium that will only regain contractile function upon revascularization. For people with CAD and severe LV dysfunction (left ventricular ejection fraction [LVEF] <35%) refractory to medical therapy, coronary artery bypass and heart transplantation are the only treatment options. The opportunity for a heart transplant is limited by scarcityof donor hearts. Coronary artery bypass in these patients is associated with high perioperative complications; however, there is evidence that revascularization in the presence of dysfunctional but viable myocardium is associated with survival benefits and lower rates of cardiac events. The assessment of left ventricular (LV) viability is, therefore, critical in deciding whether a patient with coronary artery disease and severe LV dysfunction should undergo revascularization, receive a heart transplant, or remain on medical therapy. Assessment of Left Ventricular Viability Techniques for assessing myocardial viability depend on the measurement of a specific characteristic of viable myocytes such as cell membrane integrity, preserved metabolism, mitochondria integrity, and preserved contractile reserve. In Ontario, single photon emission computed tomography (SPECT) using radioactive 201thallium is the most commonly used technique followed by dobutamine echocardiography. Newer techniques include SPECT using technetium tracers, cardiac magnetic resonance imaging, and PET, the subject of this review. Positron Emission Tomography PET is a nuclear imaging technique based on the metabolism of radioactive analogs of normal substrates such as glucose and water. The radiopharmaceutical used most frequently in myocardial viability assessment is F18 fluorodeoxyglucose (FDG), a glucose analog. The procedure involves the intravenous administration of FDG under controlled glycemic conditions, and imaging with a PET scanner. The images are reconstructed using computer software and analyzed visually or semi-quantitatively, often in conjunction with perfusion images. Dysfunctional but stunned myocardium is characterized by normal perfusion and normal FDG uptake; hibernating myocardium exhibits reduced perfusion and normal/enhanced FDG uptake (perfusion/metabolism mismatch), whereas scar tissue is characterized by reduction in both perfusion and FDG uptake (perfusion/metabolism match). Review Strategy The Medical Advisory Secretariat used a search strategy similar to that used in the 2001 ICES review to identify English language reports of health technology assessments and primary studies in selected databases, published from January 1, 2001 to April 20, 2005. Patients of interest were those with CAD and severe ventricular dysfunction being considered for revascularization that had undergone viability assessment using either PET and/or other noninvasive techniques. The outcomes of interest were diagnostic and predictive accuracy with respect to recovery of regional or global LV function, long-term survival and cardiac events, and quality of life. Other outcomes of interest were impact on treatment decision, adverse events, and cost-effectiveness ratios. Of 456 citations, 8 systematic reviews/meta-analyses and 37 reports on primary studies met the selection criteria. The reports were categorized using the Medical Advisory Secretariat levels of evidence system, and the quality of the reports was assessed using the criteria of the Quality Assessment of Diagnostic Accuracy Studies (QUADAS) developed by the Centre for Dissemination of Research (National Health Service, United Kingdom). Analysis of sensitivity, specificity, predictive values and likelihood ratios were conducted for all data as well as stratified by mean left ventricular ejection fraction (LVEF). There were no randomized controlled trials. The included studies compared PET with one or more other noninvasive viability tests on the same group of patients or examined the long-term outcomes of PET viability assessments. The quality assessment showed that about 50% or more of the studies had selection bias, interpreted tests without blinding, excluded uninterpretable segments in the analysis, or did not have clearly stated selection criteria. Data from the above studies were integrated with data from the 2001 ICES review for analysis and interpretation. Summary of Findings The evidence was derived from populations with moderate to severe ischemic LV dysfunction with an overall quality that ranges from moderate to low. PET appears to be a safe technique for assessing myocardial viability. CAD patients with moderate to severe ischemic LV dysfunction and residual viable myocardium had significantly lower 2-year mortality rate (3.2%) and higher event-free survival rates (92% at 3 years) when treated with revascularization than those who were not revascularized but were treated medically (16% mortality at 2-years and 48% 3-year event-free survival). A large meta-analysis and moderate quality studies of diagnostic accuracy consistently showed that compared to other noninvasive diagnostic tests such as thallium SPECT and echocardiography, FDG PET has: Higher sensitivity (median 90%, range 71%–100%) and better negative likelihood ratio (median 0.16, range 0–0.38; ideal <0.1) for predicting regional myocardial function recovery after revascularization. Specificity (median 73%, range 33%–91%) that is similar to other radionuclide imaging but lower than that of dobutamine echocardiography Less useful positive likelihood ratio (median 3.1, range 1.4 –9.2; ideal>10) for predicting segmental function recovery. Taking positive and negative likelihood ratios together suggests that FDG PET and dobutamine echocardiography may produce small but sometimes important changes in the probability of recovering regional wall motion after revascularization. Given its higher sensitivity, PET is less likely to produce false positive results in myocardial viability. PET, therefore, has the potential to identify some patients who might benefit from revascularization, but who would not have been identified as suitable candidates for revascularization using thallium SPECT or dobutamine echocardiography. PET appears to be superior to other nuclear imaging techniques including SPECT with 201thallium or technetium labelled tracers, although recent studies suggest that FDG SPECT may have comparable diagnostic accuracy as FDG PET for predicting regional and global LV function recovery. No firm conclusion can be reached about the incremental value of PET over other noninvasive techniques for predicting global function improvement or long-term outcomes in the most important target population (patients with severe ischemic LV dysfunction) due to lack of direct comparison. An Ontario-based economic analysis showed that in people with CAD and severe LV dysfunction and who were found to have no viable myocardium or indeterminate results by thallium SPECT, the use of PET as a follow-up assessment would likely result in lower cost and better 5-year survival compared to the use of thallium SPECT alone. The projected annual budget impact of adding PET under the above scenario was estimated to range from $1.5 million to $2.3 million. Conclusion In patients with severe LV dysfunction, that are deemed to have no viable myocardium or indeterminate results in assessments using other noninvasive tests, PET may have a role in further identifying patients who may benefit from revascularization. No firm conclusion can be drawn on the impact of PET viability assessment on long-term clinical outcomes in the most important target population (i.e. patients with severe LV dysfunction). PMID:23074467

Low-gradient aortic stenosis

PubMed Central

Clavel, Marie-Annick; Magne, Julien; Pibarot, Philippe

2016-01-01

Abstract An important proportion of patients with aortic stenosis (AS) have a ‘low-gradient’ AS, i.e. a small aortic valve area (AVA <1.0 cm2) consistent with severe AS but a low mean transvalvular gradient (<40 mmHg) consistent with non-severe AS. The management of this subset of patients is particularly challenging because the AVA-gradient discrepancy raises uncertainty about the actual stenosis severity and thus about the indication for aortic valve replacement (AVR) if the patient has symptoms and/or left ventricular (LV) systolic dysfunction. The most frequent cause of low-gradient (LG) AS is the presence of a low LV outflow state, which may occur with reduced left ventricular ejection fraction (LVEF), i.e. classical low-flow, low-gradient (LF-LG), or preserved LVEF, i.e. paradoxical LF-LG. Furthermore, a substantial proportion of patients with AS may have a normal-flow, low-gradient (NF-LG) AS: i.e. a small AVA—low-gradient combination but with a normal flow. One of the most important clinical challenges in these three categories of patients with LG AS (classical LF-LG, paradoxical LF-LG, and NF-LG) is to differentiate a true-severe AS that generally benefits from AVR vs. a pseudo-severe AS that should be managed conservatively. A low-dose dobutamine stress echocardiography may be used for this purpose in patients with classical LF-LG AS, whereas aortic valve calcium scoring by multi-detector computed tomography is the preferred modality in those with paradoxical LF-LG or NF-LG AS. Although patients with LF-LG severe AS have worse outcomes than those with high-gradient AS following AVR, they nonetheless display an important survival benefit with this intervention. Some studies suggest that transcatheter AVR may be superior to surgical AVR in patients with LF-LG AS. PMID:27190103

Zero-order metoprolol pharmacokinetics after therapeutic doses: severe toxicity and cardiogenic shock.

PubMed

Isbister, Geoffrey K; Ang, Karyn; Gorman, Kieron; Cooper, Joyce; Mostafa, Ahmed; Roberts, Michael S

2016-11-01

Acute beta-blocker overdose can cause severe cardiac dysfunction. Chronic toxicity is rare but potentially severe. We report therapeutic dosing of metoprolol resulting in unusual pharmacokinetics and toxicity, given high-dose insulin therapy for treatment. A 90-year-old female presented with hypotension, tachycardia and severe cardiac dysfunction after commencing a rapidly increasing metoprolol dose of 250 mg split daily. She was admitted to intensive care and given high-dose insulin therapy (10 U/kg/h), noradrenaline, adrenaline and dobutamine for severe cardiac dysfunction (cardiac index, 0.76 L/min/m 2 ). She developed acute renal failure, ischaemic hepatitis and disseminated intravascular coagulopathy. Inotropes and high-dose insulin were weaned over four days with complete recovery. Metoprolol was quantified with liquid chromatography-tandem mass spectrometry and concentration-time data were analysed using MONOLIX ® vs 4.3 ( www.lixoft.com ). Admission metoprolol concentration was 2.39 μg/mL (therapeutic reference range: 0.035-0.5 μg/mL). Data best fitted a one compartmental model with Michaelis-Menten kinetics and zero order elimination at high concentrations. Final parameter estimates were V, 63.4 L, maximum rate [V m ], 9.57 mg h -1 , Michaelis constant [K m ], 1.97 mg L -1 . Predicted elimination half-life decreased from 20 h over time until there was first order elimination with a half-life 9 h. The time course of cardiac dysfunction was longer than acute overdose but consistent with prolonged zero order elimination of metoprolol, suggesting the patient was a poor CYP2D6 metaboliser. High-dose insulin euglycaemia appeared to be effective in combination with vasoconstrictors/inotropes.

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.

Dual implantation of a radio-telemeter and vascular access port allows repeated hemodynamic and pharmacological measures in conscious lean and obese rats.

PubMed

Bussey, C T; Leeuw, A E de; Cook, R F; Ashley, Z; Schofield, J; Lamberts, R R

2014-07-01

Expansion of physiological knowledge increasingly requires examination of processes in the normal, conscious state. The current study describes a novel approach combining surgical implantation of radio-telemeters with vascular access ports (VAPs) to allow repeated hemodynamic and pharmacological measures in conscious rats. Dual implantation was conducted on 16-week-old male lean and obese Zucker rats. Continued viability one month after surgery was observed in 67% of lean and 44% of obese animals, giving an overall 54% completion rate. Over the five-week measurement period, reliable and reproducible basal mean arterial pressure and heart rate measures were observed. VAP patency and receptor-independent vascular reactivity were confirmed by consistent hemodynamic responses to sodium nitroprusside (6.25 µg/kg). Acutely, minimal hemodynamic responses to repeated bolus administration of 0.2 mL saline indicated no significant effect of increased blood volume or administration stress, making repeated acute measures viable. Similarly, repeated administration of the β-adrenoceptor agonist dobutamine (30 µg/kg) at 10 min intervals resulted in reproducible hemodynamic changes in both lean and obese animals. Therefore, our study demonstrates that this new approach is viable for the acute and chronic assessment of hemodynamic and pharmacological responses in both lean and obese conscious rats. This technique reduces the demand for animal numbers and allows hemodynamic measures with minimal disruption to animals' welfare, while providing reliable and reproducible results over several weeks. In conclusion, dual implantation of a radio-telemeter and VAP introduces a valuable technique for undertaking comprehensive studies involving repeated pharmacological tests in conscious animals to address important physiological questions. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

Utility of detailed preoperative cardiac testing and incidence of post-thoracotomy myocardial infarction.

PubMed

Jaroszewski, Dawn E; Huh, Joseph; Chu, Danny; Malaisrie, S Chris; Riffel, Anthony D; Gordon, Howard S; Wang, Xing Li; Bakaeen, Faisal

2008-03-01

Recent literature has questioned the efficacy of routine detailed preoperative cardiac ischemia testing and preoperative cardiac intervention before noncardiac surgical procedures. We performed a retrospective review of patients undergoing thoracotomy (n = 294) between January of 1999 and January of 2005. The median age was 62 years. Detailed preoperative cardiac testing was performed on 184 patients (63%) and went beyond a thorough history, physical examination, and electrocardiogram to include at least one of the following: dobutamine stress echo (n = 116), nuclear stress test (n = 66), treadmill test (n = 8), and coronary angiogram (n = 40). Evidence for coronary disease was detected in 43% of tests (99/230) performed. Revascularization was performed in 10% of all patients (4/40) who underwent coronary angiography. Postoperative myocardial infarction occurred in 7 patients (2.4%) with 4 myocardial infarction-related mortalities. No significant difference was found in the incidence of myocardial infarction in patients with (n = 184) or without (n = 110) detailed preoperative cardiac testing (3.3% vs 0.9%, P = .29). Of the 4 patients (1.4%) who underwent revascularization to treat coronary lesions identified during prethoracotomy workup, 2 had a myocardial infarction, 1 of which was caused by thrombosis of a coronary stent. In the subset of patients who underwent lobectomy (n = 149), detailed cardiac testing was performed on 107 patients (72%). The incidence of myocardial infarction was similar in tested and untested patients (2.8% vs 2.4% respectively, P = 1.0). Selective use of detailed preoperative cardiac testing refines risk stratification and identifies patients for corrective cardiac interventions; however, it did not prove fully protective against myocardial infarction after thoracotomy in our study.

Ischemia reperfusion dysfunction changes model-estimated kinetics of myofilament interaction due to inotropic drugs in isolated hearts

PubMed Central

Rhodes, Samhita S; Camara, Amadou KS; Ropella, Kristina M; Audi, Said H; Riess, Matthias L; Pagel, Paul S; Stowe, David F

2006-01-01

Background The phase-space relationship between simultaneously measured myoplasmic [Ca2+] and isovolumetric left ventricular pressure (LVP) in guinea pig intact hearts is altered by ischemic and inotropic interventions. Our objective was to mathematically model this phase-space relationship between [Ca2+] and LVP with a focus on the changes in cross-bridge kinetics and myofilament Ca2+ sensitivity responsible for alterations in Ca2+-contraction coupling due to inotropic drugs in the presence and absence of ischemia reperfusion (IR) injury. Methods We used a four state computational model to predict LVP using experimentally measured, averaged myoplasmic [Ca2+] transients from unpaced, isolated guinea pig hearts as the model input. Values of model parameters were estimated by minimizing the error between experimentally measured LVP and model-predicted LVP. Results We found that IR injury resulted in reduced myofilament Ca2+ sensitivity, and decreased cross-bridge association and dissociation rates. Dopamine (8 μM) reduced myofilament Ca2+ sensitivity before, but enhanced it after ischemia while improving cross-bridge kinetics before and after IR injury. Dobutamine (4 μM) reduced myofilament Ca2+ sensitivity while improving cross-bridge kinetics before and after ischemia. Digoxin (1 μM) increased myofilament Ca2+ sensitivity and cross-bridge kinetics after but not before ischemia. Levosimendan (1 μM) enhanced myofilament Ca2+ affinity and cross-bridge kinetics only after ischemia. Conclusion Estimated model parameters reveal mechanistic changes in Ca2+-contraction coupling due to IR injury, specifically the inefficient utilization of Ca2+ for contractile function with diastolic contracture (increase in resting diastolic LVP). The model parameters also reveal drug-induced improvements in Ca2+-contraction coupling before and after IR injury. PMID:16512898

Hypotension following patent ductus arteriosus ligation: the role of adrenal hormones.

PubMed

Clyman, Ronald I; Wickremasinghe, Andrea; Merritt, T Allen; Solomon, Tabitha; McNamara, Patrick; Jain, Amish; Singh, Jaideep; Chu, Alison; Noori, Shahab; Sekar, Krishnamurthy; Lavoie, Pascal M; Attridge, Joshua T; Swanson, Jonathan R; Gillam-Krakauer, Maria; Reese, Jeff; DeMauro, Sara; Poindexter, Brenda; Aucott, Sue; Satpute, Monique; Fernandez, Erika; Auchus, Richard J

2014-06-01

To test the hypothesis that an impaired adrenal response to stress might play a role in the hypotension that follows patent ductus arteriosus (PDA) ligation. We performed a multicenter study of infants born at <32 weeks' gestation who were about to undergo PDA ligation. Serum adrenal steroids were measured 3 times: before and after a cosyntropin (1.0 μg/kg) stimulation test (performed before the ligation), and at 10-12 hours after the ligation. A standardized approach for diagnosis and treatment of postoperative hypotension was followed at each site. A modified inotrope score (1 × dopamine [μg/kg/min] + 1 × dobutamine) was used to monitor the catecholamine support an infant received. Infants were considered to have catecholamine-resistant hypotension if their greatest inotrope score was >15. Of 95 infants enrolled, 43 (45%) developed hypotension and 14 (15%) developed catecholamine-resistant hypotension. Low postoperative cortisol levels were not associated with the overall incidence of hypotension after ligation. However, low cortisol levels were associated with the refractoriness of the hypotension to catecholamine treatment. In a multivariate analysis: the OR for developing catecholamine-resistant hypotension was OR 36.6, 95% CI 2.8-476, P = .006. Low cortisol levels (in infants with catecholamine-resistant hypotension) were not attributable to adrenal immaturity or impairment; their cortisol precursor concentrations were either low or unchanged, and their response to cosyntropin was similar to infants without catecholamine-resistant hypotension. Infants with low cortisol concentrations after PDA ligation are likely to develop postoperative catecholamine-resistant hypotension. We speculate that decreased adrenal stimulation, rather than an impaired adrenal response to stimulation, may account for the decreased production. Copyright © 2014 Elsevier Inc. All rights reserved.

Hypotension following patent ductus arteriosus ligation: the role of adrenal hormones

PubMed Central

Clyman, Ronald I.; Wickremasinghe, Andrea; Merritt, T. Allen; Solomon, Tabitha; McNamara, Patrick; Jain, Amish; Singh, Jaideep; Chu, Alison; Noori, Shahab; Sekar, Krishnamurthy; Lavoie, Pascal M.; Attridge, Joshua T.; Swanson, Jonathan R.; Gillam-Krakauer, Maria; Reese, Jeff; DeMauro, Sara; Poindexter, Brenda; Aucott, Sue; Satpute, Monique; Fernandez, Erika; Auchus, Richard J.

2014-01-01

Objective To test the hypothesis that an impaired adrenal response to stress might play a role in the hypotension that follows patent ductus arteriosus (PDA) ligation. Study design We performed a multicenter study of infants born at <32 weeks gestation who were about to undergo PDA ligation. Serum adrenal steroids were measured three times: before and after a cosyntropin (1.0 microgram/kg) stimulation test (performed prior to the ligation), and at 10–12 hours after the ligation. A standardized approach for diagnosis and treatment of postoperative hypotension was followed at each site. A modified Inotrope Score (1 x dopamine (μg/kg/min) + 1 x dobutamine) was used to monitor the catecholamine support an infant received. Infants were considered to have catecholamine-resistant hypotension if their highest Inotrope Score was >15. Results Of 95 infants enrolled, 43 (45%) developed hypotension and 14 (15%) developed catecholamine-resistant hypotension. Low post-operative cortisol levels were not associated with the overall incidence of hypotension following ligation. However, low cortisol levels were associated with the refractoriness of the hypotension to catecholamine treatment. In a multivariate analysis: the odds ratio for developing catecholamine-resistant hypotension was OR=36.6, CI=2.8–476, p=0.006. Low cortisol levels (in infants with catecholamine-resistant hypotension) were not due to adrenal immaturity or impairment; their cortisol precursor concentrations were either low or unchanged and their response to cosyntropin was similar to infants without catecholamine-resistant hypotension. Conclusion Infants with low cortisol concentrations following PDA ligation are likely to develop postoperative catecholamine-resistant hypotension. We speculate that decreased adrenal stimulation, rather than an impaired adrenal response to stimulation, may account for the decreased production. PMID:24636853

[Extracorporeal cardiac shock wave therapy for treatment of coronary artery disease].

PubMed

Wang, Yu; Guo, Tao; Cai, Hong-Yan; Ma, Tie-Kun; Tao, Si-Ming; Chen, Ming-Qing; Gu, Yun; Pan, Jia-Hua; Xiao, Jian-Ming; Zhao, Ling; Yang, Xi-Yun; Yang, Chao

2010-08-01

To evaluate the feasibility and efficiency of extracorporeal cardiac shock wave therapy (CSWT) for treatment of coronary artery disease. Twenty-five patients with 1 - 16 years history of chronic angina pectoris underwent the CSWT. Before and after the treatment, low-dose Dobutamine stress echocardiography and (99)Tc(m)-MIBI myocardial perfusion SPECT were applied to locate the ischemic segments, detect the viable myocardium and evaluate the effect of CSWT. Under the guidance of echocardiography, CSWT was applied in R-wave-triggered manner with low energy (0.09 mJ/mm(2)) at 200 shoots/spot for 9 spots (-1-0-+1 combination). Patients were divided group A and group B. Sixteen patients in group A were applied 9 sessions on 29 segments within 3 month and nine patients in group B were applied 9 sessions on 13 segments within 1 month. Ten chronic angina pectoris patients receiving standard medication served as controls. All patients completed the 9 sessions without procedural complications or adverse effects. CSWT significantly improved symptoms as evaluated by NYHA, Canadian Cardiovascular Society (CCS) class sores, Seattle angina questionnaire (SAQ), 6-min walk and the use of nitroglycerin (P < 0.05). CSWT also improved myocardial perfusion and regional myocardium function as evaluated by rest SPECT and stress peak systolic strain rate (PSSR) (P < 0.01). Myocardial perfusion improvement was more significant in group A compared with group B (1.21 ± 0.86 vs. 0.83 ± 0.80, P < 0.01). All parameters remained unchanged in control group during follow up. These preliminary results indicate that CSWT is safe and effective on ameliorating anginal symptoms for chronic angina pectoris patients.

In Silico Identification and Pharmacological Evaluation of Novel Endocrine Disrupting Chemicals That Act via the Ligand-Binding Domain of the Estrogen Receptor α

PubMed Central

Kufareva, Irina; Abagyan, Ruben

2014-01-01

Endocrine disrupting chemicals (EDCs) pose a significant threat to human health, society, and the environment. Many EDCs elicit their toxic effects through nuclear hormone receptors, like the estrogen receptor α (ERα). In silico models can be used to prioritize chemicals for toxicological evaluation to reduce the amount of costly pharmacological testing and enable early alerts for newly designed compounds. However, many of the current computational models are overly dependent on the chemistry of known modulators and perform poorly for novel chemical scaffolds. Herein we describe the development of computational, three-dimensional multi-conformational pocket-field docking, and chemical-field docking models for the identification of novel EDCs that act via the ligand-binding domain of ERα. These models were highly accurate in the retrospective task of distinguishing known high-affinity ERα modulators from inactive or decoy molecules, with minimal training. To illustrate the utility of the models in prospective in silico compound screening, we screened a database of over 6000 environmental chemicals and evaluated the 24 top-ranked hits in an ERα transcriptional activation assay and a differential scanning fluorimetry-based ERα binding assay. Promisingly, six chemicals displayed ERα agonist activity (32nM–3.98μM) and two chemicals had moderately stabilizing effects on ERα. Two newly identified active compounds were chemically related β-adrenergic receptor (βAR) agonists, dobutamine, and ractopamine (a feed additive that promotes leanness in cattle and poultry), which are the first βAR agonists identified as activators of ERα-mediated gene transcription. This approach can be applied to other receptors implicated in endocrine disruption. PMID:24928891

In silico identification and pharmacological evaluation of novel endocrine disrupting chemicals that act via the ligand-binding domain of the estrogen receptor α.

PubMed

McRobb, Fiona M; Kufareva, Irina; Abagyan, Ruben

2014-09-01

Endocrine disrupting chemicals (EDCs) pose a significant threat to human health, society, and the environment. Many EDCs elicit their toxic effects through nuclear hormone receptors, like the estrogen receptor α (ERα). In silico models can be used to prioritize chemicals for toxicological evaluation to reduce the amount of costly pharmacological testing and enable early alerts for newly designed compounds. However, many of the current computational models are overly dependent on the chemistry of known modulators and perform poorly for novel chemical scaffolds. Herein we describe the development of computational, three-dimensional multi-conformational pocket-field docking, and chemical-field docking models for the identification of novel EDCs that act via the ligand-binding domain of ERα. These models were highly accurate in the retrospective task of distinguishing known high-affinity ERα modulators from inactive or decoy molecules, with minimal training. To illustrate the utility of the models in prospective in silico compound screening, we screened a database of over 6000 environmental chemicals and evaluated the 24 top-ranked hits in an ERα transcriptional activation assay and a differential scanning fluorimetry-based ERα binding assay. Promisingly, six chemicals displayed ERα agonist activity (32nM-3.98μM) and two chemicals had moderately stabilizing effects on ERα. Two newly identified active compounds were chemically related β-adrenergic receptor (βAR) agonists, dobutamine, and ractopamine (a feed additive that promotes leanness in cattle and poultry), which are the first βAR agonists identified as activators of ERα-mediated gene transcription. This approach can be applied to other receptors implicated in endocrine disruption. © The Author 2014. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Long-term prognostic value of a comprehensive assessment of cardiac magnetic resonance indexes after an ST-segment elevation myocardial infarction.

PubMed

Merlos, Pilar; López-Lereu, Maria P; Monmeneu, Jose V; Sanchis, Juan; Núñez, Julio; Bonanad, Clara; Valero, Ernesto; Miñana, Gema; Chaustre, Fabián; Gómez, Cristina; Oltra, Ricardo; Palacios, Lorena; Bosch, Maria J; Navarro, Vicente; Llácer, Angel; Chorro, Francisco J; Bodí, Vicente

2013-08-01

A variety of cardiac magnetic resonance indexes predict mid-term prognosis in ST-segment elevation myocardial infarction patients. The extent of transmural necrosis permits simple and accurate prediction of systolic recovery. However, its long-term prognostic value beyond a comprehensive clinical and cardiac magnetic resonance evaluation is unknown. We hypothesized that a simple semiquantitative assessment of the extent of transmural necrosis is the best resonance index to predict long-term outcome soon after a first ST-segment elevation myocardial infarction. One week after a first ST-segment elevation myocardial infarction we carried out a comprehensive quantification of several resonance parameters in 206 consecutive patients. A semiquantitative assessment (altered number of segments in the 17-segment model) of edema, baseline and post-dobutamine wall motion abnormalities, first pass perfusion, microvascular obstruction, and the extent of transmural necrosis was also performed. During follow-up (median 51 months), 29 patients suffered a major adverse cardiac event (8 cardiac deaths, 11 nonfatal myocardial infarctions, and 10 readmissions for heart failure). Major cardiac events were associated with more severely altered quantitative and semiquantitative resonance indexes. After a comprehensive multivariate adjustment, the extent of transmural necrosis was the only resonance index independently related to the major cardiac event rate (hazard ratio=1.34 [1.19-1.51] per each additional segment displaying>50% transmural necrosis, P<.001). A simple and non-time consuming semiquantitative analysis of the extent of transmural necrosis is the most powerful cardiac magnetic resonance index to predict long-term outcome soon after a first ST-segment elevation myocardial infarction. Copyright © 2013 Sociedad Española de Cardiología. Published by Elsevier Espana. All rights reserved.

Extravasation of Noncytotoxic Drugs: A Review of the Literature.

PubMed

Le, Ann; Patel, Samit

2014-07-01

Extravasation is a potential complication associated with intravenous therapy administration. Inadvertent leakage of medications with vesicant properties can cause severe tissue necrosis, which can lead to devastating long-term consequences. Recognizing potential agents is an essential step in mitigating the risk of extravasation. A literature search was carried out using PubMed with the following key words: extravasation, soft tissue injury, phlebitis, and infiltration, from January 1961 through January 2014. The publications were screened manually and reviewed to identify reports for medications that included synonyms of the International Nonproprietary Name, while excluding antineoplastic agents, radiographic contrast material, investigational or nonmarketed drugs, and animal data, to yield 70 articles. Furthermore, reference citations from publications were also reviewed for relevance and yielded 4 articles. We discovered 232 cases of extravasation involving 37 agents (in order of frequency): phenytoin, parenteral nutrition, calcium gluconate, potassium chloride, calcium chloride, dopamine, dextrose solutions, epinephrine, sodium bicarbonate, nafcillin, propofol, norepinephrine, mannitol, arginine, promethazine, vancomycin, tetracycline, dobutamine, vasopressin, sodium thiopental, acyclovir, amphotericin, ampicillin, cloxacillin, gentamicin, metronidazole, oxacillin, penicillin, amiodarone, albumin, furosemide, lipids, lorazepam, immunoglobulin, morphine, and sodium valproate. Potential properties contributing to extravasation include the following: pH, osmolarity, diluent, vasoactive properties, and inactive ingredients. Antidotes and supportive care agents used in the management of these cases of extravasation include hyaluronidase, phentolamine, terbutaline, topical anesthetics (such as lidocaine and prilocaine cream), topical antimicrobials (such as silver sulfadiazine and chlorhexidine), topical debridement agents (collagenase ointment), topical steroids, and topical vasodilators (nitroglycerin). Data on the management of noncytotoxic extravasations is sparse, consisting primarily of case reports and anecdotal evidence. Fortunately, this adverse outcome is preventable and identification of vesicant agents plays a pivotal role. The intent of this review is to provide a reference identifying noncytotoxic vesicants and the management of extravasations associated with specific agents. © The Author(s) 2014.

Multipoint Pacing versus conventional ICD in Patients with a Narrow QRS complex (MPP Narrow QRS trial): study protocol for a pilot randomized controlled trial.

PubMed

Gasparini, Maurizio; Galimberti, Paola; Bragato, Renato; Ghio, Stefano; Raineri, Claudia; Landolina, Maurizio; Chieffo, Enrico; Lunati, Maurizio; Mulargia, Ederina; Proclemer, Alessandro; Facchin, Domenico; Rordorf, Roberto; Vicentini, Alessandro; Marcantoni, Lina; Zanon, Francesco; Klersy, Catherine

2016-12-03

Despite an intensive search for predictors of the response to cardiac resynchronization therapy (CRT), the QRS duration remains the simplest and most robust predictor of a positive response. QRS duration of ≥ 130 ms is considered to be a prerequisite for CRT; however, some studies have shown that CRT may also be effective in heart failure (HF) patients with a narrow QRS (<130 ms). Since CRT can now be performed by pacing the left ventricle from multiple vectors via a single quadripolar lead, it is possible that multipoint pacing (MPP) might be effective in HF patients with a narrow QRS. This article reports the design of the MPP Narrow QRS trial, a prospective, randomized, multicenter, controlled feasibility study to investigate the efficacy of MPP using two LV pacing vectors in patients with a narrow QRS complex (100-130 ms). Fifty patients with a standard ICD indication will be enrolled and randomized (1:1) to either an MPP group or a Standard ICD group. All patients will undergo a low-dose dobutamine stress echo test and only those with contractile reserve will be included in the study and randomized. The primary endpoint will be the percentage of patients in each group that have reverse remodeling at 12 months, defined as a reduction in left ventricular end-systolic volume (LVESV) of >15% from the baseline. This feasibility study will determine whether MPP improves reverse remodeling, as compared with standard ICD, in HF patients who have a narrow QRS complex (100-130 ms). ClinicalTrials.gov, NCT02402816 . Registered on 25 March 2015.

Milrinone therapy for enterovirus 71-induced pulmonary edema and/or neurogenic shock in children: a randomized controlled trial.

PubMed

Chi, Chia-Yu; Khanh, Truong Huu; Thoa, Le Phan Kim; Tseng, Fan-Chen; Wang, Shih-Min; Thinh, Le Quoc; Lin, Chia-Chun; Wu, Han-Chieh; Wang, Jen-Ren; Hung, Nguyen Thanh; Thuong, Tang Chi; Chang, Chung-Ming; Su, Ih-Jen; Liu, Ching-Chuan

2013-07-01

Enterovirus 71-induced brainstem encephalitis with pulmonary edema and/or neurogenic shock (stage 3B) is associated with rapid mortality in children. In a small pilot study, we found that milrinone reduced early mortality compared with historical controls. This prospective, randomized control trial was designed to provide more definitive evidence of the ability of milrinone to reduce the 1-week mortality of stage 3B enterovirus 71 infections. Prospective, unicenter, open-label, randomized, controlled study. Inpatient ward of a large tertiary teaching hospital in Ho Chi Minh City, Vietnam. Children (≤ 18 yr old) admitted with proven enterovirus 71-induced pulmonary edema and/or neurogenic shock. Patients were randomly assigned to receive intravenous milrinone (0.5 μg/kg/min) (n = 22) or conventional management (n = 19). Both groups received dopamine or dobutamine and intravenous immunoglobulin. The primary endpoint was 1-week mortality. The secondary endpoints included length of ventilator dependence and hospital stay and adverse events. The median age was 2 years with a predominance of boys in both groups. The 1-week mortality was significantly lower, 18.2% (4/22) in the milrinone compared with 57.9% (11/19) in the conventional management group (relative risk = 0.314 [95% CI, 0.12-0.83], p = 0.01). The median duration of ventilator-free days was longer in the milrinone treatment group (p = 0.01). There was no apparent neurologic sequela in the survivors in either group, and no drug-related adverse events were documented. Milrinone significantly reduced the 1-week mortality of enterovirus 71-induced pulmonary edema and/or neurogenic shock without adverse effects. Further studies are needed to determine whether milrinone might be useful to prevent progression of earlier stages of brainstem encephalitis.

Heart function in magnetic resonance imaging and the mesenteric artery reactivity in rats receiving lead-contaminated drinking water.

PubMed

Skoczynska, A; Skórka, T; Wojakowska, A; Nowacki, D; Turczyn, B; Poręba, R; Tyrankiewicz, U; Byk, K; Szuba, A

2014-05-01

The aim of this study was to evaluate the effect of lead (Pb)-contaminated drinking water on magnetic resonance imaging (MRI)-estimated cardiac function, vascular reactivity, and serum lipids in rats. For 3 months, male Wistar rats, aged 4-6 weeks, were given drinking water with the addition of lead acetate at a concentration of 100 ppm Pb (10 rats) or water free from Pb (8 control rats). The cardiac MRI was performed at rest and under β-adrenergic stimulation on a 4.7 T scanner using electrocardiogram-triggered gradient echo (FLASH) cine sequence. After 1-2 weeks of the MRI test, experiments were performed ex vivo. After stabilization of perfusion pressure (PP), norepinephrine at doses from 0.01 to 5.0 μg was dissolved in Krebs solution, injected in a volume of 100 μl, and next infused at a concentration of 0.5 μg/ml into the isolated mesenteric artery. In this manner, preconstricted mesenteric bed was used to determine PP changes induced by acetylcholine, given at doses from 0.05 to 5.0 μg, before and during the infusion of nitric oxide synthase inhibitor (1.0 μg/ml). At the end, dobutamine (5 mg), followed by potassium chloride (10.5 mg), was injected. Lipid levels were determined enzymatically, blood Pb level was measured by the atomic absorption spectrophotometer. This study showed that Pb impairs the left ventricular systolic and diastolic function. Pb-induced changes in response to resistance of vessels to vasoactive agents may be secondary to the reduced left ventricular ejection fraction. The high-density lipoprotein subfraction 2 (HDL2) is involved in the cardiovascular effect of Pb.

Hemodynamic and neurochemical determinates of renal function in chronic heart failure.

PubMed

Gilbert, Cameron; Cherney, David Z I; Parker, Andrea B; Mak, Susanna; Floras, John S; Al-Hesayen, Abdul; Parker, John D

2016-01-15

Abnormal renal function is common in acute and chronic congestive heart failure (CHF) and is related to the severity of congestion. However, treatment of congestion often leads to worsening renal function. Our objective was to explore basal determinants of renal function and their response to hemodynamic interventions. Thirty-seven patients without CHF and 59 patients with chronic CHF (ejection fraction; 23 ± 8%) underwent right heart catheterization, measurements of glomerular filtration rate (GFR; inulin) and renal plasma flow (RPF; para-aminohippurate), and radiotracer estimates of renal sympathetic activity. A subset (26 without, 36 with CHF) underwent acute pharmacological intervention with dobutamine or nitroprusside. We explored the relationship between baseline and drug-induced hemodynamic changes and changes in renal function. In CHF, there was an inverse relationship among right atrial mean pressure (RAM) pressure, RPF, and GFR. By contrast, mean arterial pressure (MAP), cardiac index (CI), and measures of renal sympathetic activity were not significant predictors. In those with CHF there was also an inverse relationship among the drug-induced changes in RAM as well as pulmonary artery mean pressure and the change in GFR. Changes in MAP and CI did not predict the change in GFR in those with CHF. Baseline values and changes in RAM pressure did not correlate with GFR in those without CHF. In the CHF group there was a positive correlation between RAM pressure and renal sympathetic activity. There was also an inverse relationship among RAM pressure, GFR, and RPF in patients with chronic CHF. The observation that acute reductions in RAM pressure is associated with an increase in GFR in patients with CHF has important clinical implications. Copyright © 2016 the American Physiological Society.

Agreement between invasive blood pressures measured in three peripheral arteries in anaesthetized horses under clinical conditions.

PubMed

Wilson, Keely A T; Raisis, Anthea L; Drynan, Eleanor A; Lester, Guy D; Hosgood, Giselle L

2018-05-01

To determine agreement between invasive blood pressures measured in three peripheral arteries in anaesthetized horses undergoing elective surgery. Prospective balanced incomplete block design. A total of 18 client-owned horses. Invasive blood pressure (IBP) was measured simultaneously in one of the following three combinations: 1) transverse facial and facial artery; 2) transverse facial and metatarsal artery; and 3) facial and metatarsal artery. The agreement in blood pressure measured for each combination was performed in six horses. At each sample time, systolic (SAP), mean (MAP) and diastolic (DAP) arterial pressures were measured concurrently in each artery, and the mean of three consecutive measurements was recorded. The position of horse, heart rate and use of dobutamine were also recorded. Bland-Altman analysis was used to assess agreement between sites. A total of 54 paired measurements were obtained, with 18 paired measurements from each combination. All paired measurements showed poor and haphazard (nonsystematic) agreement. The widest limit of agreement was 51 mmHg for SAP measured in the facial artery and metatarsal artery, with a bias of -11 mmHg. The smallest limit of agreement was 16 mmHg for MAP measured in the transverse facial and metatarsal artery, with a bias of 1 mmHg. There was poor and haphazard agreement for SAP, MAP and DAP measured in each pair of peripheral arteries in this study. These results show that blood pressure measured in different peripheral arteries cannot be used interchangeably. This has implications for studies that use IBP as an outcome variable and studies determining agreement between noninvasive blood pressure and IBP measurements in horses under general anaesthesia. Copyright © 2018 Association of Veterinary Anaesthetists and American College of Veterinary Anesthesia and Analgesia. Published by Elsevier Ltd. All rights reserved.

Measurement of aortic valve calcification using multislice computed tomography: correlation with haemodynamic severity of aortic stenosis and clinical implication for patients with low ejection fraction.

PubMed

Cueff, Caroline; Serfaty, Jean-Michel; Cimadevilla, Claire; Laissy, Jean-Pierre; Himbert, Dominique; Tubach, Florence; Duval, Xavier; Iung, Bernard; Enriquez-Sarano, Maurice; Vahanian, Alec; Messika-Zeitoun, David

2011-05-01

Measurement of the degree of aortic valve calcification (AVC) using electron beam computed tomography (EBCT) is an accurate and complementary method to transthoracic echocardiography (TTE) for assessment of the severity of aortic stenosis (AS). Whether threshold values of AVC obtained with EBCT could be extrapolated to multislice computed tomography (MSCT) was unclear and AVC diagnostic value in patients with low ejection fraction (EF) has never been specifically evaluated. Patients with mild to severe AS underwent prospectively within 1 week MSCT and TTE. Severe AS was defined as an aortic valve area (AVA) of less than 1 cm(2). In 179 patients with EF greater than 40% (validation set), the relationship between AVC and AVA was evaluated. The best threshold of AVC for the diagnosis of severe AS was then evaluated in a second subset (testing set) of 49 patients with low EF (≤40%). In this subgroup, AS severity was defined based on mean gradient, natural history or dobutamine stress echocardiography. Correlation between AVC and AVA was good (r=-0.63, p<0.0001). A threshold of 1651 arbitrary units (AU) provided 82% sensitivity, 80% specificity, 88% negative-predictive value and 70% positive-predictive value. In the testing set (patients with low EF), this threshold correctly differentiated patients with severe AS from non-severe AS in all but three cases. These three patients had an AVC score close to the threshold (1206, 1436 and 1797 AU). In this large series of patients with a wide range of AS, AVC was shown to be well correlated to AVA and may be a useful adjunct for the evaluation of AS severity especially in difficult cases such as patients with low EF.

Improving prediction of outcomes in African Americans with normal stress echocardiograms using a risk scoring system.

PubMed

Sutter, David A; Thomaides, Athanasios; Hornsby, Kyle; Mahenthiran, Jothiharan; Feigenbaum, Harvey; Sawada, Stephen G

2013-06-01

Cardiovascular mortality is high in African Americans, and those with normal results on stress echocardiography remain at increased risk. The aim of this study was to develop a risk scoring system to improve the prediction of cardiovascular events in African Americans with normal results on stress echocardiography. Clinical data and rest echocardiographic measurements were obtained in 548 consecutive African Americans with normal results on rest and stress echocardiography and ejection fractions ≥50%. Patients were followed for myocardial infarction and death for 3 years. Predictors of cardiovascular events were determined with Cox regression, and hazard ratios were used to determine the number of points in the risk score attributed to each independent predictor. During follow-up of 3 years, 47 patients (8.6%) had events. Five variables-age (≥45 years in men, ≥55 years in women), history of coronary disease, history of smoking, left ventricular hypertrophy, and exercise intolerance (<7 METs in men, <5 METs in women, or need for dobutamine stress)-were independent predictors of events. A risk score was derived for each patient (ranging from 0 to 8 risk points). The area under the curve for the risk score was 0.82 with the optimum cut-off risk score of 6. Among patients with risk scores ≥6, 30% had events, compared with 3% with risk score <6 (p <0.001). In conclusion, African Americans with normal results on stress echocardiography remain at significant risk for cardiovascular events. A risk score can be derived from clinical and echocardiographic variables, which can accurately distinguish high- and low-risk patients. Copyright © 2013 Elsevier Inc. All rights reserved.

[Intracoronary, human autologous stem cell transplantation for myocardial regeneration following myocardial infarction].

PubMed

Strauer, B E; Brehm, M; Zeus, T; Gattermann, N; Hernandez, A; Sorg, R V; Kögler, G; Wernet, P

2001-08-24

The regenerative potential of human autologous adult stem cells on myocardial regeneration and neovascularisation after myocardial infarction may contribute to healing of the infarction area. But no clinical application has previously been reported. We here describe for the first time the results of this method applied in a patient who had sustained an acute myocardial infarction. 14 hours after the onset of left precordial pain a 46-year-old man was admitted to our hospital for interventional diagnosis and treatment. Coronary angiography demonstrated occlusion of the anterior descending branch of the left coronary artery with transmural infarction. This was treated by percutaneous transluminal catheter angioplasty and stent placement. Mononuclear bone marrow cells of the patient were prepared and 6 days after infaction 1,2 infinity 107 cells were transplanted at low pressure via a percutaneous transluminal catheter placed in the infarct-related artery. Before and 10 weeks after this procedure left ventricular function, infarct size, ventricular geometry and myocardial perfusion were measured by (201)thallium SPECT both at rest and on exercise, together with bull's-eye analysis, dobutamine stress echocardiography, right heart catheterisation and radionuclide ventriculography. At 10 weeks after the stem cell transplantation the transmural infarct area had been reduced from 24.6 % to 15.7 % of left ventricular circumference, while ejection fraction, cardiac index and stroke volume had increased by 20-30 %. On exercise the end diastolic volume had decreased by 30 % and there was a comparable fall in left ventricular filling pressure (mean pulmonary capillary pressure). These results for the first time demonstrate that selective intracoronary transplantation of human autologous adult stem cells is possible under clinical conditions and that it can lead to regeneration of the myocardial scar after transmural infarction. The therapeutic effects may be ascribed to stem cell-associated myocardial regeneration and neovascularisation.

Hypertension Is a Conditional Factor for the Development of Cardiac Hypertrophy in Type 2 Diabetic Mice

PubMed Central

Brouwers, Olaf; Janssen, Ben J. A.; Derks, Wouter J. A.; Brouns, Agnieszka E.; Munts, Chantal; Schalkwijk, Casper G.; van der Vusse, Ger J.; van Nieuwenhoven, Frans A.

2014-01-01

Background Type 2 diabetes is frequently associated with co-morbidities, including hypertension. Here we investigated if hypertension is a critical factor in myocardial remodeling and the development of cardiac dysfunction in type 2 diabetic db/db mice. Methods Thereto, 14-wks-old male db/db mice and non-diabetic db/+ mice received vehicle or angiotensin II (AngII) for 4 wks to induce mild hypertension (n = 9–10 per group). Left ventricular (LV) function was assessed by serial echocardiography and during a dobutamine stress test. LV tissue was subjected to molecular and (immuno)histochemical analysis to assess effects on hypertrophy, fibrosis and inflammation. Results Vehicle-treated diabetic mice neither displayed marked myocardial structural remodeling nor cardiac dysfunction. AngII-treatment did not affect body weight and fasting glucose levels, and induced a comparable increase in blood pressure in diabetic and control mice. Nonetheless, AngII-induced LV hypertrophy was significantly more pronounced in diabetic than in control mice as assessed by LV mass (increase +51% and +34%, respectively, p<0.01) and cardiomyocyte size (+53% and +31%, p<0.001). This was associated with enhanced LV mRNA expression of markers of hypertrophy and fibrosis and reduced activation of AMP-activated protein kinase (AMPK), while accumulation of Advanced Glycation End products (AGEs) and the expression levels of markers of inflammation were not altered. Moreover, AngII-treatment reduced LV fractional shortening and contractility in diabetic mice, but not in control mice. Conclusions Collectively, the present findings indicate that type 2 diabetes in its early stage is not yet associated with adverse cardiac structural changes, but already renders the heart more susceptible to hypertension-induced hypertrophic remodeling. PMID:24416343

Myocardial Perfusion SPECT 2015 in Germany

PubMed Central

Burchert, Wolfgang; Schäfer, Wolfgang; Hacker, Marcus

2016-01-01

Summary Aim The working group Cardiovascular Nuclear Medicine of the German Society of Nuclear Medicine presents the results of the 7th survey of myocardial perfusion SPECT (MPS) of the reporting year 2015. Method 268 questionnaires (173 practices [PR], 67 hospitals [HO], 28 university hospitals [UH]) were evaluated. Results of the last survey from 2012 are set in squared brackets. Results MPS of 121 939 [105 941] patients were reported. 98 % [95 %] of all MPS were performed with Tc-99m radiopharmaceuticals and 2 % [5 %] with Tl-201. 78 % [79 %] of all patients were studied in PR, 14 % [15 %] in HO, and 8 % [6 %] in UH. A pharmacological stress test was performed in 43 % [39 %] (22 % [24 %] adenosine, 20 % [9 %] regadenoson, 1% [6 %] dipyridamole or dobutamine). Attenuation correction was applied in 25 % [2009: 10 %] of MPS. Gated SPECT was performed in 78 % [70 %] of all rest MPS, in 80 % [73 %] of all stress and in 76 % [67 %] of all stress and rest MPS. 53 % [33 %] of all nuclear medicine departments performed MPS scoring by default, whereas 24 % [41 %] did not apply any quantification. 31 % [26 %] of all departments noticed an increase in their counted MPS and 29 % [29 %] no changes. Data from 89 departments which participated in all surveys showed an increase in MPS count of 11.1 % (PR: 12.2 %, HO: 4.8 %, UH: 18.4 %). 70 % [60 %] of the MPS were requested by ambulatory care cardiologists. Conclusion The 2015 MPS survey reveals a high-grade adherence of routine MPS practice to current guidelines. The positive trend in MPS performance and number of MPS already observed in 2012 continues. Educational training remains necessary in the field of SPECT scoring. PMID:27909712

Stress-induced ST-segment deviation in relation to the presence and severity of coronary artery disease in patients with normal myocardial perfusion imaging.

PubMed

Weinsaft, Jonathan W; Manoushagian, Shant J; Patel, Taral; Shakoor, Aqsa; Kim, Robert J; Mirchandani, Sunil; Lin, Fay; Wong, Franklin J; Szulc, Massimiliano; Okin, Peter M; Kligfield, Paul D; Min, James K

2009-01-01

To assess the utility of stress electrocardiography (ECG) for identifying the presence and severity of obstructive coronary artery disease (CAD) defined by coronary computed tomographic angiography (CCTA) among patients with normal nuclear myocardial perfusion imaging (MPI). The study population comprised 119 consecutive patients with normal MPI who also underwent CCTA (interval 3.5+/-3.8 months). Stress ECG was performed at the time of MPI. CCTA and MPI were interpreted using established scoring systems, and CCTA was used to define the presence and extent of CAD, which was quantified by a coronary artery jeopardy score. Within this population, 28 patients (24%) had obstructive CAD identified by CCTA. The most common CAD pattern was single-vessel CAD (61%), although proximal vessel involvement was present in 46% of patients. Patients with CAD were nearly three times more likely to have positive standard test responses (1 mm ST-segment deviation) than patients with patent coronary arteries (36 vs. 13%, P=0.007). In multivariate analysis, a positive ST-segment test response was an independent marker for CAD (odds ratio: 2.02, confidence interval: 1.09-3.78, P=0.03) even after adjustment for a composite of clinical cardiac risk factors (odds ratio: 1.85, confidence interval: 1.05-3.23, P=0.03). Despite uniformly normal MPI, mean coronary jeopardy score was three-fold higher among patients with positive compared to those with negative ST-segment response to exercise or dobutamine stress (1.9+/-2.7 vs. 0.5+/-1.4, P=0.03). Stress-induced ST-segment deviation is an independent marker for obstructive CAD among patients with normal MPI. A positive stress ECG identifies patients with a greater anatomic extent of CAD as quantified by coronary jeopardy score.

Diagnosis of Myocardial Viability by Fluorodeoxyglucose Distribution at the Border Zone of a Low Uptake Region

PubMed Central

Sone, Teruki; Yoshikawa, Kunihiko; Mimura, Hiroaki; Hayashida, Akihiro; Wada, Nozomi; Obase, Kikuko; Imai, Koichiro; Saito, Ken; Maehama, Tomoko; Fukunaga, Masao; Yoshida, Kiyoshi

2010-01-01

Purpose In cardiac 2-[F-18]fluoro-2-deoxy-D-glucose (FDG)-positron emission tomography (PET) examination, interpretation of myocardial viability in the low uptake region (LUR) has been difficult without additional perfusion imaging. We evaluated distribution patterns of FDG at the border zone of the LUR in the cardiac FDG-PET and established a novel parameter for diagnosing myocardial viability and for discriminating the LUR of normal variants. Materials and Methods Cardiac FDG-PET was performed in patients with a myocardial ischemic event (n = 22) and in healthy volunteers (n = 22). Whether the myocardium was not a viable myocardium (not-VM) or an ischemic but viable myocardium (isch-VM) was defined by an echocardiogram under a low dose of dobutamine infusion as the gold standard. FDG images were displayed as gray scaled-bull's eye mappings. FDG-plot profiles for LUR (= true ischemic region in the patients or normal variant region in healthy subjects) were calculated. Maximal values of FDG change at the LUR border zone (a steepness index; Smax scale/pixel) were compared among not-VM, isch-VM, and normal myocardium. Results Smax was significantly higher for n-VM compared to those with isch-VM or normal myocardium (ANOVA). A cut-off value of 0.30 in Smax demonstrated 100% sensitivity and 83% specificity for diagnosing n-VM and isch-VM. Smax less than 0.23 discriminated LUR in normal myocardium from the LUR in patients with both n-VM and isch-VM with a 94% sensitivity and a 93% specificity. Conclusion Smax of the LUR in cardiac FDG-PET is a simple and useful parameter to diagnose n-VM and isch-VM, as well as to discriminate thr LUR of normal variants. PMID:20191007

Ischemia/reperfusion-induced alterations of enzymatic and signaling functions of the rat cardiac Na+/K+-ATPase: protection by ouabain preconditioning.

PubMed

Belliard, Aude; Gulati, Gaurav K; Duan, Qiming; Alves, Rosana; Brewer, Shannon; Madan, Namrata; Sottejeau, Yoann; Wang, Xiaoliang; Kalisz, Jennifer; Pierre, Sandrine V

2016-10-01

Cardiac glycosides (CG) are traditionally known as positive cardiac inotropes that inhibit Na + /K + -ATPase-dependent ion transport. CG also trigger-specific signaling pathways through the cardiac Na + /K + -ATPase, with beneficial effects in ischemia/reperfusion (I/R) injury (e.g., ouabain preconditioning, known as OPC) and hypertrophy. Our current understanding of hypersensitivity to CG and subsequent toxicity in the ischemic heart is mostly based on specific I/R-induced alterations of the Na + /K + -ATPase enzymatic function and has remained incomplete. The primary goal of this study was to investigate and compare the impact of I/R on Na + /K + -ATPase enzymatic and signaling functions. Second, we assessed the impact of OPC on both functions. Langendorff-perfused rat hearts were exposed to 30 min of ischemia and 30 min of reperfusion. At the inotropic concentration of 50 μmol/L, ouabain increased ERK and Akt phosphorylation in control hearts. In I/R hearts, this concentration did not induced positive inotropy and failed to induce Akt or ERK phosphorylation. The inotropic response to dobutamine as well as insulin signaling persisted, suggesting specific alterations of Na + /K + -ATPase. Indeed, Na + /K + -ATPase protein expression was intact, but the enzyme activity was decreased by 60% and the enzymatic function of the isoform with high affinity for ouabain was abolished following I/R. Strikingly, OPC prevented all I/R-induced alterations of the receptor. Further studies are needed to reveal the respective roles of I/R-induced modulations of Na + /K + -ATPase enzymatic and signaling functions in cardiomyocyte death. © 2016 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.

Rationale and design of the Transcatheter Aortic Valve Replacement to UNload the Left ventricle in patients with ADvanced heart failure (TAVR UNLOAD) trial.

PubMed

Spitzer, Ernest; Van Mieghem, Nicolas M; Pibarot, Philippe; Hahn, Rebecca T; Kodali, Susheel; Maurer, Mathew S; Nazif, Tamim M; Rodés-Cabau, Josep; Paradis, Jean-Michel; Kappetein, Arie-Pieter; Ben-Yehuda, Ori; van Es, Gerrit-Anne; Kallel, Faouzi; Anderson, William N; Tijssen, Jan; Leon, Martin B

2016-12-01

Coexistence of moderate aortic stenosis (AS) in patients with heart failure (HF) with reduced ejection fraction is not uncommon. Moderate AS increases afterload, whereas pharmacologic reduction of afterload is a pillar of contemporary HF management. Unloading the left ventricle by reducing the transaortic gradient with transfemoral transcatheter aortic valve replacement (TAVR) may improve clinical outcomes in patients with moderate AS and HF with reduced ejection fraction. The TAVR UNLOAD (NCT02661451) is an international, multicenter, randomized, open-label, clinical trial comparing the efficacy and safety of TAVR with the Edwards SAPIEN 3 Transcatheter Heart Valve in addition to optimal heart failure therapy (OHFT) vs OHFT alone in patients with moderate AS (defined by a mean transaortic gradient ≥20 mm Hg and <40 mm Hg, and an aortic valve area >1.0 cm 2 and ≤1.5 cm 2 at rest or after dobutamine stress echocardiography) and reduced ejection fraction. A total of 600 patients will be randomized in a 1:1 fashion. Clinical follow-up is scheduled at 1, 6, and 12 months, and 2 years after randomization. The primary end point is the hierarchical occurrence of all-cause death, disabling stroke, hospitalizations related to HF, symptomatic aortic valve disease or nondisabling stroke, and the change in the Kansas City Cardiomyopathy Questionnaire at 1 year. Secondary end points capture effects on clinical outcome, biomarkers, echocardiographic parameters, and quality of life. The TAVR UNLOAD trial aims to test the hypothesis that TAVR on top of OHFT improves clinical outcomes in patients with moderate AS and HF with reduced ejection fraction. Copyright © 2016 Elsevier Inc. All rights reserved.

Quantification of Regional Myocardial Oxygenation by Magnetic Resonance Imaging: Validation with Positron Emission Tomography

PubMed Central

McCommis, Kyle S.; Goldstein, Thomas A.; Abendschein, Dana R.; Herrero, Pilar; Misselwitz, Bernd; Gropler, Robert J.; Zheng, Jie

2011-01-01

Background A comprehensive evaluation of myocardial ischemia requires measures of both oxygen supply and demand. Positron emission tomography (PET) is currently the gold standard for such evaluations, but its use is limited due to its ionizing radiation, limited availability, and high cost. A cardiac magnetic resonance imaging (MRI) method was developed for assessing myocardial oxygenation. The purpose of this study was to evaluate and validate this technique compared to PET during pharmacologic stress in a canine model of coronary artery stenosis. Methods and Results Twenty-one beagles and small mongrel dogs without coronary artery stenosis (controls), or with moderate to severe acute coronary artery stenosis underwent MRI and PET imaging at rest and during dipyridamole vasodilation or dobutamine stress to induce a wide range of changes in cardiac perfusion and oxygenation. MRI first-pass perfusion imaging was performed to quantify myocardial blood flow (MBF) and volume (MBV). The MRI blood-oxygen-level-dependent (BOLD) technique was used to determine the myocardial oxygen extraction fraction (OEF) during pharmacologic hyperemia. Myocardial oxygen consumption (MVO2) was determined by Fick’s law. In the same dogs, 15O-water and 11C-acetate were used to measure MBF and MVO2, respectively, by PET. Regional assessments were performed for both MR and PET. MRI data correlated nicely with PET values for MBF (R2 = 0.79, P < 0.001), MVO2 (R2 = 0.74, P < 0.001), and OEF (R2 = 0.66, P < 0.01). Conclusions Cardiac MRI methods may provide an alternative to radionuclide imaging in settings of myocardial ischemia. Our newly developed quantitative MRI oxygenation imaging technique may be a valuable non-invasive tool to directly evaluate myocardial energetics and efficiency. PMID:19933371

Forward and Backward Pressure Waveform Morphology in Hypertension.

PubMed

Li, Ye; Gu, Haotian; Fok, Henry; Alastruey, Jordi; Chowienczyk, Philip

2017-02-01

We tested the hypothesis that increased pulse wave reflection and altered backward waveform morphology contribute to increased pulse pressure in subjects with higher pulse pressure compared with lower pulse pressure and to actions of vasoactive drugs to increase pulse pressure. We examined the relationship of backward to forward wave morphology in 158 subjects who were evaluated for hypertension (including some normotensive subjects) divided into 3 groups by central pulse pressure: group 1, 33±6.5 mm Hg; group 2, 45±4.1 mm Hg; and group 3, 64±12.9 mm Hg (means±SD) and in healthy normotensive subjects during administration of inotropic and vasomotor drugs. Aortic pressure and flow in the aortic root were estimated by carotid tonometry and Doppler sonography, respectively. Morphology of the backward wave relative to the forward wave was similar in subjects in the lowest and highest tertiles of pulse pressure. Similar results were seen with the inotropic, vasopressor and vasodilator drugs, dobutamine, norepinephrine, and phentolamine, with the backward wave maintaining a constant ratio to the forward wave. However, nitroglycerin, a drug with a specific action to dilate muscular conduit arteries, reduced the amplitude of the backward wave relative to the forward wave from 0.26±0.018 at baseline to 0.19±0.019 during nitroglycerin 30 μg/min IV (P<0.01). These results are best explained by an approximately constant amount of reflection of the forward wave from the peripheral vasculature. The amount of reflection can be modified by dilation of peripheral muscular conduit arteries but contributes little to increased pulse pressure in hypertension. © 2016 The Authors.

Aortic Valve Replacement for Moderate Aortic Stenosis with Severe Calcification and Left Ventricualr Dysfunction-A Case Report and Review of the Literature.

PubMed

Narang, Nikhil; Lang, Roberto M; Liarski, Vladimir M; Jeevanandam, Valluvan; Hofmann Bowman, Marion A

2017-01-01

A 55-year-old man with a history of erosive, seropositive rheumatoid arthritis (RA), and interstitial lung disease presented with shortness of breath. Echocardiography showed new-onset severe left ventricular (LV) dysfunction with an ejection fraction (EF) of 15% and moderately increased mean aortic valve gradient of 20 mmHg in a trileaflet aortic valve with severe sclero-calcific degeneration. Coronary angiography revealed no significant obstructive coronary disease. Invasive hemodynamic studies and dobutamine stress echocardiography were consistent with moderate aortic stenosis. Guideline directed medical therapy for heart failure with reduced EF was initiated; however, diuretics and neurohormonal blockade (beta-blocker and angiotensin receptor blocker) provided minimal improvement, and the patient remained functionally limited. Of interest, echocardiography performed 1 year prior to his presentation showed normal LV EF and mild aortic leaflet calcification with moderate stenosis, suggesting a rapid progressing of calcific aortic valve disease. Subsequently, the patient underwent surgical aortic valve replacement and demonstrated excellent postsurgical recovery of LV EF (55%). Calcific aortic valve disease is commonly associated with aging, bicuspid aortic valve, and chronic kidney disease. Pathophysiological mechanism for valvular calcification is incompletely understood but include osteogenic transformation of valvular interstitial cells mediated by local and systemic inflammatory processes. Several rheumatologic diseases including RA are associated with premature atherosclerosis and arterial calcification, and we speculated a similar role of RA accelerating calcific aortic valve disease. We present a case of accelerated aortic valve calcification with (only) moderate stenosis, complicated by a rapid decline in LV systolic performance. Guidelines for AVR in moderate stenosis without concomitant cardiac surgery are not well established, although it should be considered in selected patients.

Australasian trends in intra-aortic balloon counterpulsation weaning: results of a postal survey.

PubMed

Lewis, Peter A; Mullany, Daniel V; Courtney, Mary; Coyer, Fiona

2006-12-01

To generate baseline data describing Australasian intra-aortic balloon counterpulsation (IABP) weaning practice. A five-part questionnaire was mailed in April 2005 to all 192 intensive care units in Australia and New Zealand. 116 ICUs responded (response rate, 60%), and 54 reported using IABP. Most of the 54 were in hospitals which were public government-funded (65%), had between 100 and 500 beds (69%), and treated a minimum of 11 patients annually with IABP (60%). The most common method of withdrawing IABP support was ratio reduction alone (61%). ICUs most likely to undertake ratio weaning were higherend users of IABP (> 20 cases per annum) (P = 0.04). Other weaning practices involved a combination of ratio followed by volume reduction (17%), volume then ratio (11%), and volume only (4%). Approaching statistical significance, ratio reduction weaning less frequently required IABP reinsertion or inotropic increase after balloon removal (P = 0.07). ICUs with documented weaning policies were less likely to require IABP reinsertion or inotropic increase after balloon removal (P = 0.06). Criteria considered important before IABP weaning or removal were: blood pressure (92%); heart rate (76%); pulmonary artery wedge pressure (59%); noradrenaline dose (78%); adrenaline dose (57%); and dobutamine dose (57%). Ninety per cent of ICUs reported increasing inotropes after balloon removal only rarely (1:50 patients) or occasionally (1:10 patients), while 87% of ICUs reported never needing to reinsert the balloon or only rarely. The Australasian approach to IABP weaning is eclectic. While ratio reduction weaning appears the most successful manner of support withdrawal, it may be a consequence of a volume-outcome relationship, with high- end users achieving better results through IABP familiarity.

β1- and β2-adrenergic receptor stimulation differ in their effects on PGC-1α and atrogin-1/MAFbx gene expression in chick skeletal muscle.

PubMed

Shimamoto, Saki; Ijiri, Daichi; Kawaguchi, Mana; Nakashima, Kazuki; Tada, Osamu; Inoue, Hiroki; Ohtsuka, Akira

2017-09-01

Adrenaline changes expression of the genes encoding peroxisome proliferator-activated receptor-gamma coactivator-1 alpha (PGC-1α), which is known as a regulator of muscle size, and atrogin-1/muscle atrophy F-box (MAFbx), which is a muscle-specific ubiquitin ligase. However, the subtype of β-adrenergic receptor (β-AR) involved in regulating these genes in skeletal muscle is not yet well defined. In this study, the effects of intraperitoneal injection of adrenaline and three β 1-3 -AR selective agonists on chick skeletal muscle metabolism were examined, to evaluate the functions of β-AR subtypes. Adrenaline decreased atrogin-1/MAFbx mRNA levels accompanied by an increase in PGC-1α mRNA and protein levels. However, among the three selective agonists, only the β 1 -AR agonist, dobutamine, increased PGC-1α mRNA and protein levels, while the β 2 -AR agonist, clenbuterol, suppressed atrogin-1/MAFbx mRNA levels. In addition, preinjection of the β 1 -AR antagonist, acebutolol, and the β 2 -AR antagonist, butoxamine, inhibited the adrenaline-induced increase in PGC-1α mRNA levels and the decrease in atrogin-1/MAFbx mRNA levels, respectively. Compared with adrenaline administration, the β 3 -AR agonist, BRL37344, decreased PGC-1α mRNA levels and increased atrogin-1/MAFbx mRNA levels. These results suggest that, in chick skeletal muscle, PGC-1α is induced via the β 1 -AR, while atrogin-1/MAFbx is suppressed via the β 2 -AR. Copyright © 2017. Published by Elsevier Inc.

Low-dose adenosine stress echocardiography: Detection of myocardial viability

PubMed Central

Djordjevic-Dikic, Ana; Ostojic, Miodrag; Beleslin, Branko; Nedeljkovic, Ivana; Stepanovic, Jelena; Stojkovic, Sinisa; Petrasinovic, Zorica; Nedeljkovic, Milan; Saponjski, Jovica; Giga, Vojislav

2003-01-01

Objective The aim of this study was to evaluate the diagnostic potential of low-dose adenosine stress echocardiography in detection of myocardial viability. Background Vasodilation through low dose dipyridamole infusion may recruit contractile reserve by increasing coronary flow or by increasing levels of endogenous adenosine. Methods Forty-three patients with resting dyssynergy, due to previous myocardial infarction, underwent low-dose adenosine (80, 100, 110 mcg/kg/min in 3 minutes intervals) echocardiography test. Gold standard for myocardial viability was improvement in systolic thickening of dyssinergic segments of ≥ 1 grade at follow-up. Coronary angiography was done in 41 pts. Twenty-seven patients were revascularized and 16 were medically treated. Echocardiographic follow up data (12 ± 2 months) were available in 24 revascularized patients. Results Wall motion score index improved from rest 1.55 ± 0.30 to 1.33 ± 0.26 at low-dose adenosine (p < 0.001). Of the 257 segments with baseline dyssynergy, adenosine echocardiography identified 122 segments as positive for viability, and 135 as necrotic since no improvement of systolic thickening was observed. Follow-up wall motion score index was 1.31 ± 0.30 (p < 0.001 vs. rest). The sensitivity of adenosine echo test for identification of viable segments was 87%, while specificity was 95%, and diagnostic accuracy 90%. Positive and negative predictive values were 97% and 80%, respectively. Conclusion Low-dose adenosine stress echocardiography test has high diagnostic potential for detection of myocardial viability in the group of patients with left ventricle dysfunction due to previous myocardial infarction. Low dose adenosine stress echocardiography may be adequate alternative to low-dose dobutamine test for evaluation of myocardial viability. PMID:12812523

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

What do Polish interventional cardiologists know about indications and qualification for recanalisation of chronic total coronary artery occlusions?

PubMed

Bryniarski, Krzysztof L; Zabojszcz, Michał; Dębski, Grzegorz; Marchewka, Jakub; Legutko, Jacek; Jankowski, Piotr; Siudak, Zbigniew; Żmudka, Krzysztof; Dudek, Dariusz; Bryniarski, Leszek

2015-01-01

Chronic total occlusions (CTO) are diagnosed in about 20% of patients with significant coronary artery disease. A disproportion between the high prevalence of CTOs and low rate of invasive treatment still exists. Technical difficulties, clinical uncertainties whether patients benefit from recanalisation, and a lack of knowledge of CTO may be responsible for this fact. To assess the knowledge of coronary arteries CTO among Polish interventional cardiologists. A self-designed questionnaire was used during two major Polish invasive cardiology workshops held in 2014. The study included 113 physicians, mostly cardiologists certified as independent operators. Average self-declared efficacy of CTO recanalisation was 63.5%. Most of the respondents agreed that the operator involved in the CTO recanalisation program should perform at least 30-50 procedures per year. Only 67% stated that before CTO revascularisation the evaluation of myocardial viability should be performed with dobutamine stress echocardiography as a preferred test. One third of the physicians agreed that CTO percutaneous coronary intervention (PCI) should not be performed directly after diagnostic angiography, and 51.5% believed that in patients with multi-vessel coronary artery disease PCI of CTO should be performed first. Multi-slice spiral computed tomography during the qualification and planning of the CTO revascularisation, in the opinion of 91% of the responders, should not be used before each procedure but could be useful in selected cases. Polish interventional cardiologists remains in compliance with current opinions about recanalisation of chronic coronary artery occlusions and the consensus of the EuroCTO Club, but there is still an unceasing need for further education and promotion of knowledge about CTOs.

A nonerythropoietic derivative of erythropoietin protects the myocardium from ischemia–reperfusion injury

PubMed Central

Fiordaliso, Fabio; Chimenti, Stefano; Staszewsky, Lidia; Bai, Antonio; Carlo, Eleonora; Cuccovillo, Ivan; Doni, Mirko; Mengozzi, Manuela; Tonelli, Rossella; Ghezzi, Pietro; Coleman, Thomas; Brines, Michael; Cerami, Anthony; Latini, Roberto

2005-01-01

The cytokine erythropoietin (EPO) protects the heart from ischemic injury, in part by preventing apoptosis. However, EPO administration can also raise the hemoglobin concentration, which, by increasing oxygen delivery, confounds assignment of cause and effect. The availability of EPO analogs that do not bind to the dimeric EPO receptor and lack erythropoietic activity, e.g., carbamylated EPO (CEPO), provides an opportunity to determine whether EPO possesses direct cardioprotective activity. In vivo, cardiomyocyte loss after experimental myocardial infarction (MI) of rats (40 min of occlusion with reperfusion) was reduced from ≈57% in MI-control to ≈45% in animals that were administered CEPO daily for 1 week (50 μg/kg of body weight s.c.) with the first dose administered intravenously 5 min before reperfusion. CEPO did not increase the hematocrit, yet it prevented increases in left ventricular (LV) end-diastolic pressure, reduced LV wall stress in systole and diastole, and improved LV response to dobutamine infusion compared with vehicle-treated animals. In agreement with the cardioprotective effect observed in vivo, staurosporine-induced apoptosis of adult rat or mouse cardiomyocytes in vitro was also significantly attenuated (≈35%) by CEPO, which is comparable with the effect of EPO. These data indicate that prevention of cardiomyocyte apoptosis, in the absence of an increase in hemoglobin concentration, explains EPO's cardioprotection. Nonerythropoietic derivatives such as CEPO, devoid of the undesirable effects of EPO, e.g., thrombogenesis, could represent safer and more effective alternatives for treatment of cardiovascular diseases, such as MI and heart failure. Furthermore, these findings expand the activity spectrum of CEPO to tissues outside the nervous system. PMID:15671158

Inorganic Nitrate in Angina Study: A Randomized Double-Blind Placebo-Controlled Trial.

PubMed

Schwarz, Konstantin; Singh, Satnam; Parasuraman, Satish K; Rudd, Amelia; Shepstone, Lee; Feelisch, Martin; Minnion, Magdalena; Ahmad, Shakil; Madhani, Melanie; Horowitz, John; Dawson, Dana K; Frenneaux, Michael P

2017-09-08

In this double-blind randomized placebo-controlled crossover trial, we investigated whether oral sodium nitrate, when added to existing background medication, reduces exertional ischemia in patients with angina. Seventy patients with stable angina, positive electrocardiogram treadmill test, and either angiographic or functional test evidence of significant ischemic heart disease were randomized to receive oral treatment with either placebo or sodium nitrate (600 mg; 7 mmol) for 7 to 10 days, followed by a 2-week washout period before crossing over to the other treatment (n=34 placebo-nitrate, n=36 nitrate-placebo). At baseline and at the end of each treatment, patients underwent modified Bruce electrocardiogram treadmill test, modified Seattle Questionnaire, and subgroups were investigated with dobutamine stress, echocardiogram, and blood tests. The primary outcome was time to 1 mm ST depression on electrocardiogram treadmill test. Compared with placebo, inorganic nitrate treatment tended to increase the primary outcome exercise time to 1 mm ST segment depression (645.6 [603.1, 688.0] seconds versus 661.2 [6183, 704.0] seconds, P =0.10) and significantly increased total exercise time (744.4 [702.4, 786.4] seconds versus 760.9 [719.5, 802.2] seconds, P =0.04; mean [95% confidence interval]). Nitrate treatment robustly increased plasma nitrate (18.3 [15.2, 21.5] versus 297.6 [218.4, 376.8] μmol/L, P <0.0001) and almost doubled circulating nitrite concentrations (346 [285, 405] versus 552 [398, 706] nmol/L, P =0.003; placebo versus nitrate treatment). Other secondary outcomes were not significantly altered by the intervention. Patients on antacid medication appeared to benefit less from nitrate supplementation. Sodium nitrate treatment may confer a modest exercise capacity benefit in patients with chronic angina who are taking other background medication. URL: https://www.clinicaltrials.gov/. Unique identifier: NCT02078921. EudraCT number: 2012-000196-17. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

Mapping of intracellular pH in the in vivo rodent heart using hyperpolarized [1-13C]pyruvate.

PubMed

Lau, Angus Z; Miller, Jack J; Tyler, Damian J

2017-05-01

To demonstrate the feasibility of mapping intracellular pH within the in vivo rodent heart. Alterations in cardiac acid-base balance can lead to acute contractile depression and alterations in Ca 2+ signaling. The transient reduction in adenosine triphosphate (ATP) consumption and cardiac contractility may be initially beneficial; however, sustained pH changes can be maladaptive, leading to myocardial damage and electrical arrhythmias. Spectrally selective radiofrequency (RF) pulses were used to excite the HCO3- and CO 2 resonances individually while preserving signal from the injected hyperpolarized [1- 13 C]pyruvate. The large flip angle pulses were placed within a three-dimensional (3D) imaging acquisition, which exploited CA-mediated label exchange between HCO3- and CO 2 . Images at 4.5 × 4.5 × 5 mm 3 resolution were obtained in the in vivo rodent heart. The technique was evaluated in healthy rodents scanned at baseline and during high cardiac workload induced by dobutamine infusion. The intracellular pH was measured to be 7.15 ± 0.04 at baseline, and decreased to 6.90 ± 0.06 following 15 min of continuous β-adrenergic stimulation. Volumetric maps of intracellular pH can be obtained following an injection of hyperpolarized [1- 13 C]pyruvate. The new method is anticipated to enable assessment of stress-inducible ischemia and potential ventricular arrythmogenic substrates within the ischemic heart. Magn Reson Med 77:1810-1817, 2017. © 2016 The Authors Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. © 2016 The Authors Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine.

Adverse cardiac events after orthotopic liver transplantation: a cross-sectional study in 389 consecutive patients.

PubMed

Nicolau-Raducu, Ramona; Gitman, Marina; Ganier, Donald; Loss, George E; Cohen, Ari J; Patel, Hamang; Girgrah, Nigel; Sekar, Krish; Nossaman, Bobby

2015-01-01

Current American College of Cardiology/American Heart Association guidelines caution that preoperative noninvasive cardiac tests may have poor predictive value for detecting coronary artery disease in liver transplant candidates. The purpose of our study was to evaluate the role of clinical predictor variables for early and late cardiac morbidity and mortality and the predictive values of noninvasive cardiac tests for perioperative cardiac events in a high-risk liver transplant population. In all, 389 adult recipients were retrospectively analyzed for a median follow-up time of 3.4 years (range = 2.3-4.4 years). Overall survival was 83%. During the first year after transplantation, cardiovascular morbidity and mortality rates were 15.2% and 2.8%. In patients who survived the first year, cardiovascular morbidity and mortality rates were 3.9% and 2%, with cardiovascular etiology as the third leading cause of death. Dobutamine stress echocardiography (DSE) and single-photon emission computed tomography had respective sensitivities of 9% and 57%, specificities of 98% and 75%, positive predictive values of 33% and 28%, and negative predictive values of 89% and 91% for predicting early cardiac events. A rate blood pressure product less than 12,000 with DSE was associated with an increased risk for postoperative atrial fibrillation. Correspondence analysis identified a statistical association between nonalcoholic steatohepatitis/cryptogenic cirrhosis and postoperative myocardial ischemia. Logistic regression identified 3 risk factors for postoperative acute coronary syndrome: age, history of coronary artery disease, and pretransplant requirement for vasopressors. Multivariable analysis showed statistical associations of the Model for End-Stage Liver Disease score and the development of acute kidney injury as risk factors for overall cardiac-related mortality. These findings may help in identifying high-risk patients and may lead to the development of better cardiac tests. © 2014 American Association for the Study of Liver Diseases.

Stimulation of spinal dorsal horn β2-adrenergic receptor ameliorates neuropathic mechanical hypersensitivity through a reduction of phosphorylation of microglial p38 MAP kinase and astrocytic c-jun N-terminal kinase.

PubMed

Zhang, Fang Fang; Morioka, Norimitsu; Abe, Hiromi; Fujii, Shiori; Miyauchi, Kazuki; Nakamura, Yoki; Hisaoka-Nakashima, Kazue; Nakata, Yoshihiro

2016-12-01

The noradrenaline-adrenergic system has a crucial role in controlling nociceptive transduction at the spinal level. While α-adrenergic receptors are known to regulate nociceptive neurotransmitter release at the spinal presynaptic level, it is not entirely clear whether β-adrenergic receptors are involved in controlling pain transduction at the spinal level as well. The current study elucidated a role of β-adrenergic receptors in neuropathic pain in mice following a partial sciatic nerve ligation (PSNL). In addition, the cellular and intracellular signaling cascade induced by β-adrenergic receptors in neuropathic mice was elaborated. Intrathecal injection of isoproterenol (1 nmol), a nonselective β-adrenergic receptor agonist, briefly ameliorated hind paw mechanical hypersensitivity of PSNL mice. Isoproterenol's antinociceptive effect was mediated through β2-adrenergic receptors since pretreatment with ICI118551, a selective β2-adrenergic receptor antagonist, but not with CGP20712A, a selective β1-adrenergic receptor antagonist, significantly attenuated isoproterenol's effect. Furthermore, intrathecal treatment with a selective β2-adrenergic receptor agonist, terbutaline, but not a selective β1-adrenergic receptor agonist, dobutamine, also significantly ameliorated neuropathic pain. Fourteen days after PSNL, increased phosphorylation of both p38 Mitogen-activated protein kinase (MAPK) in microglia and c-jun N-terminal kinase (JNK) in astrocytes of ipsilateral spinal dorsal horn were observed. Phosphorylation of both microglial p38 MAPK and astrocytic JNK were downregulated by stimulation of the β2-adrenergic receptor. Together, these results suggest that spinal β2-adrenergic receptor have an inhibitory role in neuropathic nociceptive transduction at the spinal level through a downregulation of glial activity, perhaps through modulation of MAP kinases phosphorylation. Thus, targeting of β2-adrenergic receptors could be an effective therapeutic strategy in treating neuropathic pain. Copyright © 2016 Elsevier Ltd. All rights reserved.

Similar hemodynamic decongestion with vasodilators and inotropes: systematic review, meta-analysis, and meta-regression of 35 studies on acute heart failure.

PubMed

Ishihara, Shiro; Gayat, Etienne; Sato, Naoki; Arrigo, Mattia; Laribi, Said; Legrand, Matthieu; Placido, Rui; Manivet, Philippe; Cohen-Solal, Alain; Abraham, William T; Jessup, Mariell; Mebazaa, Alexandre

2016-12-01

Acute heart failure (AHF) with reduced left-ventricular ejection fraction (LVEF) is often a biventricular congested state. The comparative effect of vasodilators and inotropes on the right- and/or left-sided congestion is unknown. A systematic review, meta-analysis, and meta-regression of AHF studies using pulmonary artery catheter were performed using PubMed, Embase, and Cochrane library. Data from 35 studies, including 3016 patients, were studied. Included patients had a weighted mean age of 60 years, left-ventricular ejection fraction (LVEF) of 24 %, and plasma B-type natriuretic peptide (BNP) of 892 pg/ml. Both the left- and right-ventricular filling pressures were elevated: weighted mean pulmonary artery wedge pressure (PAWP) was 25 mmHg (range 17-31 mmHg) and right atrial pressure (RAP) 12 mmHg (range 7-18 mmHg). Vasodilators and inotropes had similar beneficial effects on PAWP [-6.3 mmHg (95 % CI -7.4 to -5.2 mmHg) and -5.8 mmHg (95 % CI -7.6 to -4.0 mmHg), respectively] and RAP [-2.9 mmHg (95 % CI -3.8 to -2.1 mmHg) and -2.8 mmHg (95 % CI -3.8 to -1.7 mmHg), respectively]. Among inotropes, inodilators, such as levosimendan, have greater beneficial effect on the left-ventricular filling pressure than dobutamine. Drug-induced improvement of PAWP tightly paralleled that of RAP with all studied drugs (r 2  = 0.90, p < 0.001). Vasodilators and inotropes had no short-term effect of renal function. The left- and right-sided filling pressures are similarly improved by vasodilators or inotropes, in AHF with reduced LVEF.

Amitraz poisoning: A case report of an unusual pesticide poisoning in Sri Lanka and literature review.

PubMed

Herath, H M M T B; Pahalagamage, S P; Yogendranathan, Nilukshana; Wijayabandara, M D M S; Kulatunga, Aruna

2017-01-23

Amitraz is a pesticide used worldwide on animals and in agriculture. It contains triazapentadiene, which is a centrally acting alpha-2 adrenergic agonist. Amitraz poisoning is fairly uncommon in humans and occurs via oral, dermal or inhalational routes. Only a limited number of case reports of human intoxication have been published and most of them are of accidental ingestion by children. A twenty-year-old Sri Lankan female presented following self-ingestion of 20 ml of amitraz resulting in 37.8 mg/ kg of amitraz poisoning. She lost consciousness after 20 min of ingestion, developed bradycardia and hypotension, which needed intravenous fluid resuscitation and dobutamine. Gastric lavage was performed. Her bradycardia persisted for 36 h and she was drowsy for 48 h. She did not develop respiratory depression, convulsions or hypothermia and the urine output was normal. Arterial blood gas revealed mild respiratory alkalosis. She recovered fully within 48 h and was discharged on day 3. The clinical manifestations of amitraz (impaired consciousness, drowsiness, vomiting, disorientation, miosis, mydriasis, hypotension, bradycardia, respiratory depression, hypothermia, generalized seizures, hyperglycemia and glycosuria) can be explained by the agonist action of amitraz on α1 and α2 receptors. Management of amitraz poisoning is still considered to be supportive and symptomatic with monitoring of nervous system, cardiovascular and respiratory systems. Activated charcoal may still be considered for treatment and the place for gastric lavage is controversial. Atropine is effective for symptomatic bradycardia and inotropic support is needed for hypotension that does not respond to fluid resuscitation. Diazepam or Lorazepam is used for convulsions and some patients may require intubation and ICU care. Several α2 adrenergic antagonists like yohimbine have been tried on animals, which have successfully reversed the effects of amitraz. Since the majority of amitraz poisoning cases are due to accidental ingestion, manufactures, regulatory authorities and national poisons control centers have a significant role to play in minimizing its occurrence.

Identifying Vasopressor and Inotrope Use for Health Services Research

PubMed Central

Fawzy, Ashraf; Bradford, Mark; Lindenauer, Peter K.

2016-01-01

Rationale: Identifying vasopressor and inotrope (vasopressor) use from administrative claims data may provide an important resource to study the epidemiology of shock. Objectives: Determine accuracy of identifying vasopressor use using International Classification of Disease, Ninth Revision, Clinical Modification (ICD-9-CM) coding. Methods: Using administrative data enriched with pharmacy billing files (Premier, Inc., Charlotte, NC), we identified two cohorts: adult patients admitted with a diagnosis of sepsis from 2010 to 2013 or pulmonary embolism (PE) from 2008 to 2011. Vasopressor administration was obtained using pharmacy billing files (dopamine, dobutamine, epinephrine, milrinone, norepinephrine, phenylephrine, vasopressin) and compared with ICD-9-CM procedure code for vasopressor administration (00.17). We estimated performance characteristics of the ICD-9-CM code and compared patients’ characteristics and mortality rates according to vasopressor identification method. Measurements and Main Results: Using either pharmacy data or the ICD-9-CM procedure code, 29% of 541,144 patients in the sepsis cohort and 5% of 81,588 patients in the PE cohort were identified as receiving a vasopressor. In the sepsis cohort, the ICD-9-CM procedure code had low sensitivity (9.4%; 95% confidence interval, 9.2–9.5), which increased over time. Results were similar in the PE cohort (sensitivity, 5.8%; 95% confidence interval, 5.1–6.6). The ICD-9-CM code exhibited high specificity in the sepsis (99.8%) and PE (100%) cohorts. However, patients identified as receiving vasopressors by ICD-9-CM code had significantly higher unadjusted in-hospital mortality, had more acute organ failures, and were more likely hospitalized in the Northeast and West. Conclusions: The ICD-9-CM procedure code for vasopressor administration has low sensitivity and selects for higher severity of illness in studies of shock. Temporal changes in sensitivity would likely make longitudinal shock surveillance using ICD-9-CM inaccurate. PMID:26653145

Neuromuscular electrical stimulation improves exercise tolerance in patients with advanced heart failure on continuous intravenous inotropic support use-randomized controlled trial.

PubMed

Forestieri, Patrícia; Bolzan, Douglas W; Santos, Vinícius B; Moreira, Rita Simone Lopes; de Almeida, Dirceu Rodrigues; Trimer, Renata; de Souza Brito, Flávio; Borghi-Silva, Audrey; de Camargo Carvalho, Antonio Carlos; Arena, Ross; Gomes, Walter J; Guizilini, Solange

2018-01-01

To evaluate the impact of a short-term neuromuscular electrical stimulation program on exercise tolerance in hospitalized patients with advanced heart failure who have suffered an acute decompensation and are under continuous intravenous inotropic support. A randomized controlled study. Initially, 195 patients hospitalized for decompensated heart failure were recruited, but 70 were randomized. Patients were randomized into two groups: control group subject to the usual care ( n = 35); neuromuscular electrical stimulation group ( n = 35) received daily training sessions to both lower extremities for around two weeks. The baseline 6-minute walk test to determine functional capacity was performed 24 hours after hospital admission, and intravenous inotropic support dose was daily checked in all patients. The outcomes were measured in two weeks or at the discharge if the patients were sent back home earlier than two weeks. After losses of follow-up, a total of 49 patients were included and considered for final analysis (control group, n = 25 and neuromuscular electrical stimulation group, n = 24). The neuromuscular electrical stimulation group presented with a higher 6-minute walk test distance compared to the control group after the study protocol (293 ± 34.78 m vs. 265.8 ± 48.53 m, P < 0.001, respectively). Neuromuscular electrical stimulation group also demonstrated a significantly higher dose reduction of dobutamine compared to control group after the study protocol (2.72 ± 1.72 µg/kg/min vs. 3.86 ± 1.61 µg/kg/min, P = 0.001, respectively). A short-term inpatient neuromuscular electrical stimulation rehabilitation protocol improved exercise tolerance and reduced intravenous inotropic support necessity in patients with advanced heart failure suffering a decompensation episode.

A systematic review of diastolic stress tests in heart failure with preserved ejection fraction, with proposals from the EU-FP7 MEDIA study group.

PubMed

Erdei, Tamás; Smiseth, Otto A; Marino, Paolo; Fraser, Alan G

2014-12-01

Cardiac function should be assessed during stress in patients with suspected heart failure with preserved ejection fraction (HFPEF), but it is unclear how to define impaired diastolic reserve. We conducted a systematic review to identify which pathophysiological changes serve as appropriate targets for diagnostic imaging. We identified 38 studies of 1111 patients with HFPEF (mean age 65 years), 744 control patients without HFPEF, and 458 healthy subjects. Qualifying EF was >45-55%; diastolic dysfunction at rest was a required criterion in 45% of studies. The initial workload during bicycle exercise (25 studies) varied from 12.5 to 30 W (mean 23.1 ± 4.6), with increments of 10-25 W (mean 19.9 ± 6) and stage duration 1-5 min (mean 2.5 ± 1); targets were submaximal (n = 8) or maximal (n = 17). Other protocols used treadmill exercise, handgrip, dobutamine, lower body negative pressure, nitroprusside, fluid challenge, leg raising, or atrial pacing. Reproducibility of echocardiographic variables during stress and validation against independent reference criteria were assessed in few studies. Change in E/e' was the most frequent measurement, but there is insufficient evidence to establish this or other tests for routine use when evaluating patients with HFPEF. To meet the clinical requirements of performing stress testing in elderly subjects, we propose a ramped exercise protocol on a semi-supine bicycle, starting at 15 W, with increments of 5 W/min to a submaximal target (heart rate 100-110 b.p.m., or symptoms). Measurements during submaximal and recovery stages should include changes from baseline in LV long-axis function and indirect echocardiographic indices of LV diastolic pressure. © 2014 The Authors. European Journal of Heart Failure © 2014 European Society of Cardiology.

A prospective follow-up of alcohol septal ablation for symptomatic hypertrophic obstructive cardiomyopathy--the Baylor experience (1996-2002).

PubMed

Fernandes, Valerian L; Nagueh, Sherif F; Wang, Wei; Roberts, Robert; Spencer, William H

2005-03-01

There is a paucity of data on the long-term outcome of alcohol septal ablation (ASA) for symptomatic hypertrophic obstructive cardiomyopathy (HOCM). The study was undertaken to evaluate the longer-term outcome of ASA therapy for symptomatic HOCM. In all, 137 patients were enrolled consecutively (1996-1999) and 130 (95%) (74 men, 56 women, aged 51 +/- 17 years) underwent ASA and had serial prospective follow-up for up to 5 years (mean follow-up 3.6 +/- 1.4 years). Evaluation included angina (Canadian Cardiovascular Society [CCS] score), dyspnea (New York Heart Association [NYHA] class), duration of exercise on treadmill, and echocardiographic indices. Ethanol (3.5 +/- 1.5 cc), injected into 1.5 +/- 0.6 arteries, induced a mean peak plasma creatine kinase (CK) of 1676 +/- 944 units. Complications of procedures included death 1.5% (2/130), heart block requiring permanent pacemaker 13% (17/130), and coronary dissection 4.4% (6/130). Baseline versus last follow-up visit: NYHA class decreased from 3.0 +/- 0.4 to 1.2 +/- 0.6 (p < 0.01); CCS angina score from 2.0 +/- 0.8 to 0.08 +/- 0.4 (p < 0.01); and duration of exercise increased from 322 +/- 207 to 443 +/- 200 s (p < 0.01). Resting left ventricular outflow tract gradient at baseline versus last follow-up visit showed a decrease from 74 +/- 30 to 4 +/- 13 (p < 0.01), and the dobutamine-provoked gradient of 88 +/- 29 decreased to 21 +/- 21 (p < 0.01) mmHg. All-cause mortality over the duration of follow-up was 7.7% (10) giving an annual rate of 2.1%, and cardiac mortality was 2.3% (3) reflecting an annual rate of 0.6%. Alcohol septal ablation decreased symptoms and improved exercise performance, indicating that it is an effective procedure for symptomatic HOCM.

Diagnostic and therapeutic considerations in acute, severe mitral regurgitation: experience in 42 consecutive patients entering the intensive care unit with pulmonary edema.

PubMed

Horstkotte, D; Schulte, H D; Niehues, R; Klein, R M; Piper, C; Strauer, B E

1993-09-01

Forty-two consecutive patients received emergency treatment for acute mitral insufficiency causing pulmonary edema between 1984 and 1992. The underlying diagnoses were acute myocardial infarction (n = 21), acute bacterial endocarditis on the native mitral valve (n = 9), prosthetic endocarditis in the mitral position (n = 4), acute failure of a replacement valve (n = 5), blunt chest trauma (n = 1) and chordal rupture in Marfan's syndrome (n = 2). Dysfunction of the subvalvular apparatus was present in 24 patients, verified by transthoracic echocardiography in 18 (75%) and by transoesophageal echocardiography in all patients in whom this technique was used. There were four cases of outflow strut fracture of a Björk-Shiley mitral prosthesis; a reliable diagnosis was made by fluoroscopy in all patients. Bedside hemodynamic monitoring was found to be unreliable both for differential diagnosis and for the quantitative assessment of the degree of mitral insufficiency. The right ventricular filling pressure was normal in 32/39 patients (82%), and the pulmonary artery and pulmonary capillary pressures elevated in 37/39 (95%). Diagnostically important, high pulmonary capillary v-waves were documented in 13 patients (33%). The left ventricular impedance could be influenced with sodium nitroprussid combined in some cases with dobutamin, and the resultant decrease of the peripheral vascular resistance from 1480 +/- 222 to 702 +/- 86 dyn x sec x cm-5 was followed by a proportionate reduction in the transmitral regurgitant fraction. Three patients died prior to the intended emergency surgical intervention. Emergency surgery was completed in 21 patients with an early mortality of 23.8% (n = 5). Ten patients underwent elective surgery within, and another three later than one year from the onset of the acute symptoms with an early mortality of 7.7% (n = 1). Four patients are alive and clinically well with medical treatment alone.

Hemodynamic variables and progression of acute kidney injury in critically ill patients with severe sepsis: data from the prospective observational FINNAKI study

PubMed Central

2013-01-01

Introduction Knowledge of the association of hemodynamics with progression of septic acute kidney injury (AKI) is limited. However, some recent data suggest that mean arterial pressure (MAP) exceeding current guidelines (60–65 mmHg) may be needed to prevent AKI. We hypothesized that higher MAP during the first 24 hours in the intensive care unit (ICU), would be associated with a lower risk of progression of AKI in patients with severe sepsis. Methods We identified 423 patients with severe sepsis and electronically recorded continuous hemodynamic data in the prospective observational FINNAKI study. The primary endpoint was progression of AKI within the first 5 days of ICU admission defined as new onset or worsening of AKI by the Kidney Disease: Improving Global Outcomes (KDIGO) criteria. We evaluated the association of hemodynamic variables with this endpoint. We included 53724 10-minute medians of MAP in the analysis. We analysed the ability of time-adjusted MAP to predict progression of AKI by receiver operating characteristic (ROC) analysis. Results Of 423 patients, 153 (36.2%) had progression of AKI. Patients with progression of AKI had significantly lower time-adjusted MAP, 74.4 mmHg [68.3-80.8], than those without progression, 78.6 mmHg [72.9-85.4], P < 0.001. A cut-off value of 73 mmHg for time-adjusted MAP best predicted the progression of AKI. Chronic kidney disease, higher lactate, higher dose of furosemide, use of dobutamine and time-adjusted MAP below 73 mmHg were independent predictors of progression of AKI. Conclusions The findings of this large prospective multicenter observational study suggest that hypotensive episodes (MAP under 73 mmHg) are associated with progression of AKI in critically ill patients with severe sepsis. PMID:24330815

Low-gradient aortic stenosis.

PubMed

Clavel, Marie-Annick; Magne, Julien; Pibarot, Philippe

2016-09-07

An important proportion of patients with aortic stenosis (AS) have a 'low-gradient' AS, i.e. a small aortic valve area (AVA <1.0 cm(2)) consistent with severe AS but a low mean transvalvular gradient (<40 mmHg) consistent with non-severe AS. The management of this subset of patients is particularly challenging because the AVA-gradient discrepancy raises uncertainty about the actual stenosis severity and thus about the indication for aortic valve replacement (AVR) if the patient has symptoms and/or left ventricular (LV) systolic dysfunction. The most frequent cause of low-gradient (LG) AS is the presence of a low LV outflow state, which may occur with reduced left ventricular ejection fraction (LVEF), i.e. classical low-flow, low-gradient (LF-LG), or preserved LVEF, i.e. paradoxical LF-LG. Furthermore, a substantial proportion of patients with AS may have a normal-flow, low-gradient (NF-LG) AS: i.e. a small AVA-low-gradient combination but with a normal flow. One of the most important clinical challenges in these three categories of patients with LG AS (classical LF-LG, paradoxical LF-LG, and NF-LG) is to differentiate a true-severe AS that generally benefits from AVR vs. a pseudo-severe AS that should be managed conservatively. A low-dose dobutamine stress echocardiography may be used for this purpose in patients with classical LF-LG AS, whereas aortic valve calcium scoring by multi-detector computed tomography is the preferred modality in those with paradoxical LF-LG or NF-LG AS. Although patients with LF-LG severe AS have worse outcomes than those with high-gradient AS following AVR, they nonetheless display an important survival benefit with this intervention. Some studies suggest that transcatheter AVR may be superior to surgical AVR in patients with LF-LG AS. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2016. For permissions please email: journals.permissions@oup.com.

Inhibition of glycogen synthase kinase 3beta during heart failure is protective.

PubMed

Hirotani, Shinichi; Zhai, Peiyong; Tomita, Hideharu; Galeotti, Jonathan; Marquez, Juan Pablo; Gao, Shumin; Hong, Chull; Yatani, Atsuko; Avila, Jesús; Sadoshima, Junichi

2007-11-26

Glycogen synthase kinase (GSK)-3, a negative regulator of cardiac hypertrophy, is inactivated in failing hearts. To examine the histopathological and functional consequence of the persistent inhibition of GSK-3beta in the heart in vivo, we generated transgenic mice with cardiac-specific overexpression of dominant negative GSK-3beta (Tg-GSK-3beta-DN) and tetracycline-regulatable wild-type GSK-3beta. GSK-3beta-DN significantly reduced the kinase activity of endogenous GSK-3beta, inhibited phosphorylation of eukaryotic translation initiation factor 2B epsilon, and induced accumulation of beta-catenin and myeloid cell leukemia-1, confirming that GSK-3beta-DN acts as a dominant negative in vivo. Tg-GSK-3beta-DN exhibited concentric hypertrophy at baseline, accompanied by upregulation of the alpha-myosin heavy chain gene and increases in cardiac function, as evidenced by a significantly greater Emax after dobutamine infusion and percentage of contraction in isolated cardiac myocytes, indicating that inhibition of GSK-3beta induces well-compensated hypertrophy. Although transverse aortic constriction induced a similar increase in hypertrophy in both Tg-GSK-3beta-DN and nontransgenic mice, Tg-GSK-3beta-DN exhibited better left ventricular function and less fibrosis and apoptosis than nontransgenic mice. Induction of the GSK-3beta transgene in tetracycline-regulatable wild-type GSK-3beta mice induced left ventricular dysfunction and premature death, accompanied by increases in apoptosis and fibrosis. Overexpression of GSK-3beta-DN in cardiac myocytes inhibited tumor necrosis factor-alpha-induced apoptosis, and the antiapoptotic effect of GSK-3beta-DN was abrogated in the absence of myeloid cell leukemia-1. These results suggest that persistent inhibition of GSK-3beta induces compensatory hypertrophy, inhibits apoptosis and fibrosis, and increases cardiac contractility and that the antiapoptotic effect of GSK-3beta inhibition is mediated by myeloid cell leukemia-1. Thus, downregulation of GSK-3beta during heart failure could be compensatory.

A multicenter, prospective study to evaluate the use of contrast stress echocardiography in early menopausal women at risk for coronary artery disease: trial design and baseline findings.

PubMed

Abdelmoneim, Sahar S; Bernier, Mathieu; Hagen, Mary E; Eifert-Rain, Susan; Bott-Kitslaar, Dalene; Wilansky, Susan; Castello, Ramon; Bhat, Gajanan; Pellikka, Patricia A; Best, Patricia J M; Hayes, Sharonne N; Mulvagh, Sharon L

2013-02-01

This multisite prospective trial, Stress Echocardiography in Menopausal Women At Risk for Coronary Artery Disease (SMART), aimed to evaluate the prognostic value of contrast stress echocardiography (CSE), coronary artery calcification (CAC), and cardiac biomarkers for prediction of cardiovascular events after 2 and 5 years in early menopausal women experiencing chest pain symptoms or risk factors. This report describes the study design, population, and initial test results at study entry. From January 2004 through September 2007, 366 early menopausal women (age 54±5 years, Framingham risk score 6.51%±4.4 %, range 1%-27%) referred for stress echocardiography were prospectively enrolled. Image quality was enhanced with an ultrasound contrast agent. Tests for cardiac biomarkers [high-sensitivity C-reactive protein (hsCRP), atrial natriuretic protein (ANP), brain natriuretic protein (BNP), endothelin (ET-1)] and cardiac computed tomography (CT) for CAC were performed. CSE (76% exercise, 24% dobutamine) was abnormal in 42 women (11.5%), and stress electrocardiogram (ECG) was positive in 22 women (6%). Rest BNP correlated weakly with stress wall motion score index (WMSI) (r=0.189, p<0.001). Neither hsCRP, ANP, endothelin, nor CAC correlated with stress WMSI. Predictors of abnormal CSE were body mass index (BMI), diabetes mellitus, family history of premature coronary artery disease (CAD), and positive stress ECG. Twenty-four women underwent clinically indicated coronary angiography (CA); 5 had obstructive (≥50%), 15 had nonobstructive (10%-49%), and 4 had no epicardial CAD. The SMART trial is designed to assess the prognostic value of CSE in early menopausal women. Independent predictors of positive CSE were BMI, diabetes mellitus, family history of premature CAD, and positive stress ECG. CAC scores and biomarkers (with the exception of rest BNP) were not correlated with CSE results. We await the follow-up data.

A Multicenter, Prospective Study to Evaluate the Use of Contrast Stress Echocardiography in Early Menopausal Women at Risk for Coronary Artery Disease: Trial Design and Baseline Findings

PubMed Central

Abdelmoneim, Sahar S.; Bernier, Mathieu; Hagen, Mary E.; Eifert-Rain, Susan; Bott-Kitslaar, Dalene; Wilansky, Susan; Castello, Ramon; Bhat, Gajanan; Pellikka, Patricia A.; Best, Patricia J. M.; Hayes, Sharonne N.

2013-01-01

Abstract Aims This multisite prospective trial, Stress Echocardiography in Menopausal Women At Risk for Coronary Artery Disease (SMART), aimed to evaluate the prognostic value of contrast stress echocardiography (CSE), coronary artery calcification (CAC), and cardiac biomarkers for prediction of cardiovascular events after 2 and 5 years in early menopausal women experiencing chest pain symptoms or risk factors. This report describes the study design, population, and initial test results at study entry. Methods From January 2004 through September 2007, 366 early menopausal women (age 54±5 years, Framingham risk score 6.51%±4.4 %, range 1%–27%) referred for stress echocardiography were prospectively enrolled. Image quality was enhanced with an ultrasound contrast agent. Tests for cardiac biomarkers [high-sensitivity C-reactive protein (hsCRP), atrial natriuretic protein (ANP), brain natriuretic protein (BNP), endothelin (ET-1)] and cardiac computed tomography (CT) for CAC were performed. Results CSE (76% exercise, 24% dobutamine) was abnormal in 42 women (11.5%), and stress electrocardiogram (ECG) was positive in 22 women (6%). Rest BNP correlated weakly with stress wall motion score index (WMSI) (r=0.189, p<0.001). Neither hsCRP, ANP, endothelin, nor CAC correlated with stress WMSI. Predictors of abnormal CSE were body mass index (BMI), diabetes mellitus, family history of premature coronary artery disease (CAD), and positive stress ECG. Twenty-four women underwent clinically indicated coronary angiography (CA); 5 had obstructive (≥50%), 15 had nonobstructive (10%–49%), and 4 had no epicardial CAD. Conclusions The SMART trial is designed to assess the prognostic value of CSE in early menopausal women. Independent predictors of positive CSE were BMI, diabetes mellitus, family history of premature CAD, and positive stress ECG. CAC scores and biomarkers (with the exception of rest BNP) were not correlated with CSE results. We await the follow-up data. PMID:23398128

International online survey to assess current practice in equine anaesthesia.

PubMed

Wohlfender, F D; Doherr, M G; Driessen, B; Hartnack, S; Johnston, G M; Bettschart-Wolfensberger, R

2015-01-01

Multicentre Confidential Enquiries into Perioperative Equine Fatalities (CEPEF) have not been conducted since the initial CEPEF Phases 1-3, 20 years ago. To collect data on current practice in equine anaesthesia and to recruit participants for CEPEF-4. Online questionnaire survey. An online questionnaire was prepared and the link distributed internationally to veterinarians possibly performing equine anaesthesia, using emails, posters, flyers and an editorial. The questionnaire included 52 closed, semiclosed and open questions divided into 8 subgroups: demographic data, anaesthetist, anaesthesia management (preoperative, technical equipment, monitoring, drugs, recovery), areas of improvements and risks and motivation for participation in CEPEF-4. Descriptive statistics and Chi-squared tests for comparison of categorical variables were performed. A total of 199 questionnaires were completed by veterinarians from 14 different countries. Of the respondents, 43% worked in private hospitals, 36% in private practices and 21% in university teaching hospitals. In 40 institutions (23%) there was at least one diplomate of the European or American colleges of veterinary anaesthesia and analgesia on staff. Individual respondents reported routinely employ the following anaesthesia monitoring modalities: electrocardiography (80%), invasive arterial blood pressures (70%), pulse oximetry (60%), capnography (55%), arterial blood gases (47%), composition of inspired and expired gases (45%) and body temperature (35%). Drugs administered frequently or routinely as part of a standard protocol were: acepromazine (44%), xylazine (68%), butorphanol (59%), ketamine (96%), diazepam (83%), isoflurane (76%), dobutamine (46%), and, as a nonsteroidal anti-inflammatory drug, phenylbutazone (73%) or flunixin meglumine (66%). Recovery was routinely assisted by 40%. The main factors perceived by the respondents to affect outcome of equine anaesthesia were the preoperative health status of the animal and training of the anaesthetist. Current practice in equine anaesthesia varies widely, and the study has highlighted important topics relevant for designing a future prospective multicentre cohort study (CEPEF-4). The Summary is available in Chinese - see Supporting information. © 2014 EVJ Ltd.

Exploratory use of cardiovascular magnetic resonance imaging in liver transplantation: a one-stop shop for preoperative cardiohepatic evaluation.

PubMed

Reddy, Sahadev T; Thai, Ngoc L; Fakhri, Asghar A; Oliva, Jose; Tom, Kusum B; Dishart, Michael K; Doyle, Mark; Yamrozik, June A; Williams, Ronald B; Grant, Saundra B; Poydence, Jacqueline; Shah, Moneal; Singh, Anil; Nathan, Swami; Biederman, Robert W W

2013-11-15

Preoperative cardiovascular risk stratification in orthotopic liver transplantation candidates has proven challenging due to limitations of current noninvasive modalities. Additionally, the preoperative workup is logistically cumbersome and expensive given the need for separate cardiac, vascular, and abdominal imaging. We evaluated the feasibility of a "one-stop shop" in a magnetic resonance suite, performing assessment of cardiac structure, function, and viability, along with simultaneous evaluation of thoracoabdominal vasculature and liver anatomy. In this pilot study, patients underwent steady-state free precession sequences and stress cardiac magnetic resonance (CMR), thoracoabdominal magnetic resonance angiography, and abdominal magnetic resonance imaging (MRI) on a standard MRI scanner. Pharmacologic stress was performed using regadenoson, adenosine, or dobutamine. Viability was assessed using late gadolinium enhancement. Over 2 years, 51 of 77 liver transplant candidates (mean age, 56 years; 35% female; mean Model for End-stage Liver Disease score, 10.8; range, 6-40) underwent MRI. All referred patients completed standard dynamic CMR, 98% completed stress CMR, 82% completed late gadolinium enhancement for viability, 94% completed liver MRI, and 88% completed magnetic resonance angiography. The mean duration of the entire study was 72 min, and 45 patients were able to complete the entire examination. Among all 51 patients, 4 required follow-up coronary angiography (3 for evidence of ischemia on perfusion CMR and 1 for postoperative ischemia), and none had flow-limiting coronary disease. Nine proceeded to orthotopic liver transplantation (mean 74 days to transplantation after MRI). There were six ascertained mortalities in the nontransplant group and one death in the transplanted group. Explant pathology confirmed 100% detection/exclusion of hepatocellular carcinoma. No complications during CMR examination were encountered. In this proof-of-concept study, it appears feasible to perform a comprehensive, efficient, and safe preoperative liver transplant imaging in a CMR suite-a one-stop shop, even in seriously ill patients.

Intermittent cardiac overload results in adaptive hypertrophy and provides protection against left ventricular acute pressure overload insult.

PubMed

Moreira-Gonçalves, Daniel; Henriques-Coelho, Tiago; Fonseca, Hélder; Ferreira, Rita; Padrão, Ana Isabel; Santa, Cátia; Vieira, Sara; Silva, Ana Filipa; Amado, Francisco; Leite-Moreira, Adelino; Duarte, José Alberto

2015-09-01

The present study aimed to test whether a chronic intermittent workload could induce an adaptive cardiac phenotype Chronic intermittent workload induced features of adaptive hypertrophy This was paralleled by protection against acute pressure overload insult The heart may adapt favourably to balanced demands, regardless of the nature of the stimuli. The present study aimed to test whether submitting the healthy heart to intermittent and tolerable amounts of workload, independently of its nature, could result in an adaptive cardiac phenotype. Male Wistar rats were subjected to treadmill running (Ex) (n = 20), intermittent cardiac overload with dobutamine (ITO) (2 mg kg(-1) , s.c.; n = 20) or placebo administration (Cont) (n = 20) for 5 days week(-1) for 8 weeks. Animals were then killed for histological and biochemical analysis or subjected to left ventricular haemodynamic evaluation under baseline conditions, in response to isovolumetric contractions and to sustained LV acute pressure overload (35% increase in peak systolic pressure maintained for 2 h). Baseline cardiac function was enhanced only in Ex, whereas the response to isovolumetric heartbeats was improved in both ITO and Ex. By contrast to the Cont group, in which rats developed diastolic dysfunction with sustained acute pressure overload, ITO and Ex showed increased tolerance to this stress test. Both ITO and Ex developed cardiomyocyte hypertrophy without fibrosis, no overexpression of osteopontin-1 or β-myosin heavy chain, and increased expression of sarcoplasmic reticulum Ca(2+) protein. Regarding hypertrophic pathways, ITO and Ex showed activation of the protein kinase B/mammalian target of rapamycin pathway but not calcineurin. Mitochondrial complex IV and V activities were also increased in ITO and Ex. Chronic submission to controlled intermittent cardiac overload, independently of its nature, results in an adaptive cardiac phenotype. Features of the cardiac overload, such as the duration and magnitude of the stimuli, may play a role in the development of an adaptive or maladaptive phenotype. © 2015 The Authors. The Journal of Physiology © 2015 The Physiological Society.

Nonsurgical reduction of the interventricular septum in patients with hypertrophic cardiomyopathy.

PubMed

Shamim, Waqar; Yousufuddin, Mohammed; Wang, Duolao; Henein, Michael; Seggewiss, Hubert; Flather, Marcus; Coats, Andrew J S; Sigwart, Ulrich

2002-10-24

In patients with hypertrophic cardiomyopathy and obstruction of the left ventricular outflow tract, nonsurgical reduction of the septum is a treatment option when medical therapy has failed. We investigated the long-term effects of nonsurgical reduction of the septum on functional capacity and electrocardiographic and echocardiographic characteristics. Sixty-four consecutive patients with hypertrophic cardiomyopathy and a mean (+/-SD) age of 48.5+/-17.2 years underwent nonsurgical reduction of the septum by injection of ethanol into the septal perforator branch of the left anterior descending coronary artery. These patients were assessed by exercise testing, electrocardiography, and resting and dobutamine (stress-induced) echocardiography after a mean period of 3.0+/-1.3 years. At follow-up, patients had significant improvements in New York Heart Association class, peak oxygen consumption (from 18.4+/-5.8 to 30.0+/-4.4 ml per kilogram of body weight per minute, P<0.001), and left ventricular outflow tract gradients (resting gradient, from 64+/-36 to 16+/-15 mm Hg; P<0.001; stress-induced gradient, from 132+/-34 to 45+/-19 mm Hg; P<0.001). Procedure-related complications included right bundle-branch block in all patients, complete heart block in 31 patients (48 percent), and significant increases in QRS and corrected QT intervals. Seventeen patients (27 percent) required permanent pacing. R-wave amplitude was significantly decreased (from 32+/-8 to 17+/-7 mV, P<0.001). The dimensions of the left ventricular cavity increased, and the interventricular septal thickness was reduced. Nonsurgical septal reduction leads to sustained improvements in both subjective and objective measures of exercise capacity in association with a persistent reduction in resting and stress-induced left ventricular outflow tract gradients. It is also associated with a high incidence of procedure-related complete heart block, however, often requiring permanent pacing. Copyright 2002 Massachusetts Medical Society

Long-term echocardiographic and cardioscintigraphic effects of growth hormone treatment in adults with Prader-Willi syndrome.

PubMed

Marzullo, Paolo; Marcassa, Claudio; Minocci, Alessandro; Campini, Riccardo; Eleuteri, Ermanno; Gondoni, Luca Alessandro; Aimaretti, Gianluca; Sartorio, Alessandro; Scacchi, Massimo; Grugni, Graziano

2015-05-01

In Prader-Willi syndrome (PWS), an altered GH secretion has been related to reduced cardiac mass and systolic function compared to controls. The objective was to evaluate the cardiovascular response to a 4-year GH therapy in adult PWS patients. Study participants were nine severely obese PWS adults (three females, six males) and 13 age-, gender-, and body mass index-matched obese controls. In an open-label prospective study, assessment of endocrine parameters and metabolic outcome, whole-body and abdominal fat scans, echocardiography, and radionuclide angiography in unstimulated and dobutamine-stimulated conditions were conducted at baseline and after 1 and 4 years of GH treatment. GH treatment increased IGF-1 (P < .0001), decreased C-reactive protein levels (P < .05), improved visceral fat mass (P < .05), and achieved near-significant changes of fat and fat-free body mass in PWS patients. Left ventricle mass indexed by fat mass increased significantly after 1 and 4 years of GH therapy (P < .05) without evident abnormalities of diastolic function, while a trend toward a reduction of the ejection fraction was documented by echocardiography (P = .054). Radionuclide angiography revealed stable values throughout the study of both the left and right ventricle ejection fractions, although this was accompanied by a statistically nonsignificant reduction of the left ventricle filling rate. A positive association between lean body mass and left ventricle ejection fraction was evident during the study (P < .05). GH therapy increased the cardiac mass of PWS adults without causing overt abnormalities of systolic and diastolic function. Although the association between lean mass and left ventricle ejection fraction during GH therapy corroborates a favorable systemic outcome of long-term GH treatment in adults with PWS, subtle longitudinal modifications of functional parameters advocate appropriate cardiac monitoring in the long-term therapeutic strategy for PWS.

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

Marks, Louise, E-mail: louise.marks@astrazeneca.com; Borland, Samantha; Philp, Karen

Despite rigorous preclinical and clinical safety evaluation, adverse cardiac effects remain a leading cause of drug attrition and post-approval drug withdrawal. A number of cardiovascular screens exist within preclinical development. These screens do not, however, provide a thorough cardiac liability profile and, in many cases, are not preventing the progression of high risk compounds. We evaluated the suitability of the anaesthetised guinea-pig for the assessment of drug-induced changes in cardiovascular parameters. Sodium pentobarbitone anaesthetised male guinea-pigs received three 15 minute intravenous infusions of ascending doses of amoxicillin, atenolol, clonidine, dobutamine, dofetilide, flecainide, isoprenaline, levosimendan, milrinone, moxifloxacin, nifedipine, paracetamol, verapamil ormore » vehicle, followed by a 30 minute washout. Dose levels were targeted to cover clinical exposure and above, with plasma samples obtained to evaluate effect/exposure relationships. Arterial blood pressure, heart rate, contractility function (left ventricular dP/dt{sub max} and QA interval) and lead II electrocardiogram were recorded throughout. In general, the expected reference compound induced effects on haemodynamic, contractility and electrocardiographic parameters were detected confirming that all three endpoints can be measured accurately and simultaneously in one small animal. Plasma exposures obtained were within, or close to the expected clinical range of therapeutic plasma levels. Concentration–effect curves were produced which allowed a more complete understanding of the margins for effects at different plasma exposures. This single in vivo screen provides a significant amount of information pertaining to the cardiovascular risk of drug candidates, ultimately strengthening strategies addressing cardiovascular-mediated compound attrition and drug withdrawal. -- Highlights: ► Evaluation of the anaesthetised guinea-pig to determine cardiac liability. ► Haemodynamic, contractility, ECG parameters and plasma exposure all measurable. ► Single small animal model offering extensive evaluation of a drug's CV risk. ► Potential to strengthen drug discovery cardiovascular strategy. ► Potential to halt progression of drugs with CV liability, reducing drug attrition.« less

Myocardial perfusion SPECT 2015 in Germany. Results of the 7th survey.

PubMed

Lindner, Oliver; Burchert, Wolfgang; Schäfer, Wolfgang; Hacker, Marcus

2017-02-14

The working group Cardiovascular Nuclear Medicine of the German Society of Nuclear Medicine presents the results of the 7th survey of myocardial perfusion SPECT (MPS) of the reporting year 2015. 268 questionnaires (173 practices [PR], 67 hospitals [HO], 28 university hospitals [UH]) were evaluated. Results of the last survey from 2012 are set in squared brackets. MPS of 121 939 [105 941] patients were reported. 98 % [95 %] of all MPS were performed with Tc-99m radiopharmaceuticals and 2 % [5 %] with Tl-201. 78 % [79 %] of all patients were studied in PR, 14 % [15 %] in HO, and 8 % [6 %] in UH. A pharmacological stress test was performed in 43 % [39 %] (22 % [24 %] adenosine, 20 % [9 %] regadenoson, 1 % [6 %] dipyridamole or dobutamine). Attenuation correction was applied in 25 % [2009: 10 %] of MPS. Gated SPECT was performed in 78 % [70 %] of all rest MPS, in 80 % [73 %] of all stress and in 76 % [67 %] of all stress and rest MPS. 53 % [33 %] of all nuclear medicine departments performed MPS scoring by default, whereas 24 % [41 %] did not apply any quantification. 31 % [26 %] of all departments noticed an increase in their counted MPS and 29 % [29 %] no changes. Data from 89 departments which participated in all surveys showed an increase in MPS count of 11.1 % (PR: 12.2 %, HO: 4.8 %, UH: 18.4 %). 70 % [60 %] of the MPS were requested by ambulatory care cardiologists. The 2015 MPS survey reveals a high-grade adherence of routine MPS practice to current guidelines. The positive trend in MPS performance and number of MPS already observed in 2012 continues. Educational training remains necessary in the field of SPECT scoring.

Adenoviral gene transfer of Akt enhances myocardial contractility and intracellular calcium handling

PubMed Central

Cittadini, A; Monti, MG; Iaccarino, G; Di Rella, F; Tsichlis, PN; Di Gianni, A; Strömer, H; Sorriento, D; Peschle, C; Trimarco, B; Saccà, L; Condorelli, G

2010-01-01

The serine-threonine kinase Akt/PKB mediates stimuli from different classes of cardiomyocyte receptors, including the growth hormone/insulin like growth factor and the β-adrenergic receptors. Whereas the growth-promoting and antiapoptotic properties of Akt activation are well established, little is known about the effects of Akt on myocardial contractility, intracellular calcium (Ca2+) handling, oxygen consumption, and β-adrenergic pathway. To this aim, Sprague–Dawley rats were subjected to a wild-type Akt in vivo adenoviral gene transfer using a catheter-based technique combined with aortopulmonary crossclamping. Left ventricular (LV) contractility and intracellular Ca2+ handling were evaluated in an isolated isovolumic buffer-perfused, aequorin-loaded whole heart preparations 10 days after the surgery. The Ca2+–force relationship was obtained under steady-state conditions in tetanized muscles. No significant hypertrophy was detected in adenovirus with wild-type Akt (Ad.Akt) versus controls rats (LV-to-body weight ratio 2.6±0.2 versus 2.7±0.1 mg/g, controls versus Ad.Akt, P, NS). LV contractility, measured as developed pressure, increased by 41% in Ad.Akt. This was accounted for by both more systolic Ca2+ available to the contractile machinery (+19% versus controls) and by enhanced myofilament Ca2+ responsiveness, documented by an increased maximal Ca2+-activated pressure (+19% versus controls) and a shift to the left of the Ca2+–force relationship. Such increased contractility was paralleled by a slight increase of myocardial oxygen consumption (14%), while titrated dose of dobutamine providing similar inotropic effect augmented oxygen consumption by 39% (P<0.01). Phospholamban, calsequestrin, and ryanodine receptor LV mRNA and protein content were not different among the study groups, while sarcoplasmic reticulum Ca2+ ATPase protein levels were significantly increased in Ad.Akt rats. β-Adrenergic receptor density, affinity, kinase-1 levels, and adenylyl cyclase activity were similar in the three animal groups. In conclusion, our results support an important role for Akt/PKB in the regulation of myocardial contractility and mechanoenergetics. PMID:16094411

Temporary epicardial cardiac resynchronisation versus conventional right ventricular pacing after cardiac surgery: study protocol for a randomised control trial.

PubMed

Russell, Stuart J; Tan, Christine; O'Keefe, Peter; Ashraf, Saeed; Zaidi, Afzal; Fraser, Alan G; Yousef, Zaheer R

2012-02-20

Heart failure patients with stable angina, acute coronary syndromes and valvular heart disease may benefit from revascularisation and/or valve surgery. However, the mortality rate is increased- 5-30%. Biventricular pacing using temporary epicardial wires after surgery is a potential mechanism to improve cardiac function and clinical endpoints. A multi-centred, prospective, randomised, single-blinded, intervention-control trial of temporary biventricular pacing versus standard pacing. Patients with ischaemic cardiomyopathy, valvular heart disease or both, an ejection fraction ≤ 35% and a conventional indication for cardiac surgery will be recruited from 2 cardiac centres. Baseline investigations will include: an electrocardiogram to confirm sinus rhythm and measure QRS duration; echocardiogram to evaluate left ventricular function and markers of mechanical dyssynchrony; dobutamine echocardiogram for viability and blood tests for renal function and biomarkers of myocardial injury- troponin T and brain naturetic peptide. Blood tests will be repeated at 18, 48 and 72 hours. The principal exclusions will be subjects with permanent atrial arrhythmias, permanent pacemakers, infective endocarditis or end-stage renal disease.After surgery, temporary pacing wires will be attached to the postero-lateral wall of the left ventricle, the right atrium and right ventricle and connected to a triple chamber temporary pacemaker. Subjects will be randomised to receive either temporary biventricular pacing or standard pacing (atrial inhibited pacing or atrial-synchronous right ventricular pacing) for 48 hours.The primary endpoint will be the duration of level 3 care. In brief, this is the requirement for invasive ventilation, multi-organ support or more than one inotrope/vasoconstrictor. Haemodynamic studies will be performed at baseline, 6, 18 and 24 hours after surgery using a pulmonary arterial catheter. Measurements will be taken in the following pacing modes: atrial inhibited; right ventricular only; atrial synchronous-right ventricular; atrial synchronous-left ventricular and biventricular pacing. Optimisation of the atrioventricular and interventricular delay will be performed in the biventricular pacing group at 18 hours. The effect of biventricular pacing on myocardial injury, post operative arrhythmias and renal function will also be quantified. ClinicalTrials.gov: NCT01027299.

A pilot study on reparixin, a CXCR1/2 antagonist, to assess safety and efficacy in attenuating ischaemia–reperfusion injury and inflammation after on-pump coronary artery bypass graft surgery

PubMed Central

Opfermann, P; Derhaschnig, U; Felli, A; Wenisch, J; Santer, D; Zuckermann, A; Dworschak, M; Jilma, B; Steinlechner, B

2015-01-01

Reparixin, a CXCR 1/2 antagonist, has been shown to mitigate ischaemia–reperfusion injury (IRI) in various organ systems in animals, but data in humans are scarce. The aim of this double-blinded, placebo-controlled pilot study was to evaluate the safety and efficacy of reparixin to suppress IRI and inflammation in patients undergoing on-pump coronary artery bypass grafting (CABG). Patients received either reparixin or placebo (n = 16 in each group) after induction of anaesthesia until 8 h after cardiopulmonary bypass (CPB). We compared markers of systemic and pulmonary inflammation, surrogates of myocardial IRI and clinical outcomes using Mann–Whitney U- and Fisher's exact tests. Thirty- and 90-day mortality was 0% in both groups. No side effects were observed in the treatment group. Surgical revision, pleural and pericardial effusion, infection and atrial fibrillation rates were not different between groups. Reparixin significantly reduced the proportion of neutrophil granulocytes in blood at the beginning [49%, interquartile range (IQR) = 45–57 versus 58%, IQR = 53–66, P = 0·035], end (71%, IQR = 67–76 versus 79%, IQR = 71–83, P = 0·023) and 1 h after CPB (73%, IQR = 71–75 versus 77%, IQR = 72–80, P = 0·035). Reparixin patients required a lesser positive fluid balance during surgery (2575 ml, IQR = 2027–3080 versus 3200 ml, IQR = 2928–3778, P = 0·029) and during ICU stay (2603 ml, IQR = 1023–4288 versus 4200 ml, IQR = 2313–8160, P = 0·021). Numerically, more control patients required noradrenaline ≥ 0·11 μg/kg/min (50 versus 19%, P = 0·063) and dobutamine (50 versus 25%, P = 0·14). Therefore, administration of reparixin in CABG patients appears to be feasible and safe. It concurrently attenuated postoperative granulocytosis in peripheral blood. PMID:25402332

Increasing use of less-invasive hemodynamic monitoring in 3 specialty surgical intensive care units: a 5-year experience at a tertiary medical center.

PubMed

Kirton, Orlando C; Calabrese, Rebecca C; Staff, Ilene

2015-01-01

Less-invasive hemodynamic monitoring (eg, esophageal doppler monitoring [EDM] and arterial pressure contour analysis, FloTrac) is increasingly used as an alternative to pulmonary artery catheters (PACs) in critically ill intensive care unit (ICU). The decrease in use of PACs is not associated with increased mortality. Five-year retrospective review of 1894 hemodynamically monitored patients admitted to 3 surgical ICUs in a university-affiliate, tertiary care urban hospital. Data included the number of admissions, diagnosis-related group discharge case mix, length of stay, insertion of monitoring devices (PAC, EDM, and FloTrac probes), administered intravenous vasoactive agents (β-predominant agonists--dobutamine, epinephrine, and dopamine; vasopressors--norepinephrine and phenylephrine), and mortality. Data from hospital administrative databases were compiled to create patient characteristic and monitoring variables across a 5-year time period, 2005 to 2009 inclusive. Chi-square for independent proportions, 1-way analysis of variance, and Kruskal-Wallis tests were used; tests for trend were conducted. An α level of .05 was considered significant. Statistical Package for the Social Sciences v14 was used for all statistical testing. There was a significant change in the type of hemodynamic monitors inserted in 2 of the 3 surgical ICUs (in the general surgery and neurointensive care but not in the cardiac ICU) from PACs to less-invasive devices (FloTrac or EDM) during the 5-year study period (P < .001). There was no change in mortality rate over the time period (P = .492). There was an overall increase in the proportion of monitored patients who received intravenous vasoactive agents (P < .001) with a progressive shift from β-agonists to vasopressors (P < .002). Multivariate analyses indicated that age, case mix, and use of vasoactive agents were all independent predictors of inhospital mortality (P = .001) but that type of monitoring was not (P = .638). In a 5-year period, the decreased insertions of PACs were replaced by increased utilization of less-invasive hemodynamic monitoring devices. This change in practice did not adversely impact mortality. © The Author(s) 2013.

Estimation of left ventricular blood flow parameters: clinical application of patient-specific CFD simulations from 4D echocardiography

NASA Astrophysics Data System (ADS)

Larsson, David; Spühler, Jeannette H.; Günyeli, Elif; Weinkauf, Tino; Hoffman, Johan; Colarieti-Tosti, Massimiliano; Winter, Reidar; Larsson, Matilda

2017-03-01

Echocardiography is the most commonly used image modality in cardiology, assessing several aspects of cardiac viability. The importance of cardiac hemodynamics and 4D blood flow motion has recently been highlighted, however such assessment is still difficult using routine echo-imaging. Instead, combining imaging with computational fluid dynamics (CFD)-simulations has proven valuable, but only a few models have been applied clinically. In the following, patient-specific CFD-simulations from transthoracic dobutamin stress echocardiography have been used to analyze the left ventricular 4D blood flow in three subjects: two with normal and one with reduced left ventricular function. At each stress level, 4D-images were acquired using a GE Vivid E9 (4VD, 1.7MHz/3.3MHz) and velocity fields simulated using a presented pathway involving endocardial segmentation, valve position identification, and solution of the incompressible Navier-Stokes equation. Flow components defined as direct flow, delayed ejection flow, retained inflow, and residual volume were calculated by particle tracing using 4th-order Runge-Kutta integration. Additionally, systolic and diastolic average velocity fields were generated. Results indicated no major changes in average velocity fields for any of the subjects. For the two subjects with normal left ventricular function, increased direct flow, decreased delayed ejection flow, constant retained inflow, and a considerable drop in residual volume was seen at increasing stress. Contrary, for the subject with reduced left ventricular function, the delayed ejection flow increased whilst the retained inflow decreased at increasing stress levels. This feasibility study represents one of the first clinical applications of an echo-based patient-specific CFD-model at elevated stress levels, and highlights the potential of using echo-based models to capture highly transient flow events, as well as the ability of using simulation tools to study clinically complex phenomena. With larger patient studies planned for the future, and with the possibility of adding more anatomical features into the model framework, the current work demonstrates the potential of patient-specific CFD-models as a tool for quantifying 4D blood flow in the heart.

Effects of systolic anterior motion of the mitral valve on haemodynamics. Evaluation by a direct method.

PubMed

Kaku, T; Sakurai, S; Furuno, Y; Yashiro, A; Nakashima, Y; Kuroiwa, A

1995-08-01

We evaluated the effects of systolic anterior motion systolic anterior motion of the mitral valve on cardiac haemodynamics. Seven adult mongrel dogs in which systolic anterior motion-septal contact was observed after dobutamine administration were used. To exclude the effects of left ventricular function and morphology, a stone removal basket catheter was placed in the left ventricular outflow tract, and haemodynamics were compared with the basket closed and opened. The basket was opened five times in three dogs not showing systolic anterior motion-septal contact, but the basket itself did not effect the haemodynamics. In the seven dogs that showed systolic anterior motion-septal contact without left ventricular hypertrophy, the basket was opened a total of 33 times in the presence of various degrees of systolic anterior motion-septal contact. After opening the basket, systolic anterior motion was reduced echocardiographically, and significant (P<0.01) changes were observed in the left ventricle-aorta pressure gradient (from 68 +/- 22 to 25 +/- 15 mm Hg), the systolic ejection period (from 146 +/- 19 to 135 +/- 16 ms), and the stroke volume (SV; from 9.4 +/- 2.9 to 10.1 +/- 3.3 ml). After basket inflation, aortic pressure and aortic flow waveforms changed but the peak pressure and flow velocity did not. The temporal distribution of left ventricular ejection also definitely changed after the basket was opened. No changes were observed in the peak dp/dt, peak negative dp/dt, time constant, left ventricular end-diastolic pressure, or left atrial pressure. These observations in this animal model of systolic anterior motion without left ventricular hypertrophy suggest that: (1) there is no potential for generation of an intra-cavity gradient in the absence of systolic anterior motion of the mitral valve, so that (2) systolic anterior motion narrowed the left ventricular outflow tract and, consequently, produced the systolic ejection period, and affected the left ventricular ejection dynamics, and that (3) the basket catheter is useful because it allows these assessments in the same heart with a nearly fixed left ventricular contractility, at least in our animal model.

[Reporting echocardiography exams with the G8-Cardio ANMCO software].

PubMed

Badano, L P; Marchesini, A; Pizzuti, A; Mantero, A; Cianflone, D; Neri, E; Caira, P; Tubaro, M

2001-03-01

The availability of a common computerized program for echocardiographic study archiving and reporting at national and/or international level could make it possible to standardize the echo reports of different echocardiographic laboratories, and to use the wealth of data thus obtainable with echocardiography, and to exploit its capillary territorial distribution, with the aim of collecting echocardiographic data in a standard format for epidemiological, scientific and administrative purposes. To develop such a software, an ad hoc joint National Association of Hospital Cardiologists and Italian Society of Echocardiography task force worked in conjunction with the Italian Branch of Agilent Technologies to standardize the phraseology of accepted echocardiographic terms and of the quantitative parameters derived from transthoracic and transesophageal echocardiographic examination at rest as well as during exercise and pharmacological stress, and to develop an ad hoc software. This echocardiographic study archiving and reporting program is part of the whole G8-Cardio ANMCO software developed to computerize the whole cardiological chart. The software has been developed by Agilent Technologies to provide a fast, easy-access and easy to use report generator for the non-computer specialist using DBMS Oracle 7.3 database and Power Builder 5.0 to develop a user-friendly interface. The number of qualitative and quantitative variables contained in the program is 733 for echocardiography at rest, while it depends on the stressor and on the length of the examination for the stress echo (dipyridamole 214-384, dobutamine 236-406, exercise 198-392). The program was tested and refined in our laboratory between November 1999 and May 2000. During this time period, 291 resting and 56 stress echocardiographic studies were reported and recorded in a database. On average, each resting echocardiographic study lasting 10 +/- 4 (range 5-17) min was recorded using 50 +/- 11 (range 33-67) variables and 41,566 bytes of hard-disk memory space. Stress echocardiographic studies, each lasting 7 +/- 5 (range 5-21) min, were recorded using 143 +/- 74 (range 38-194) variables and 38,531 bytes of hard-disk memory space. To our knowledge this software represents the first experience of a common computerized program for echo archiving and reporting carried out at national level.

Excess ω-6 fatty acids influx in aging drives metabolic dysregulation, electrocardiographic alterations, and low-grade chronic inflammation.

PubMed

Kain, Vasundhara; Ingle, Kevin A; Kachman, Maureen; Baum, Heidi; Shanmugam, Gobinath; Rajasekaran, Namakkal S; Young, Martin E; Halade, Ganesh V

2018-02-01

Maintaining a balance of ω-6 and ω-3 fatty acids is essential for cardiac health. Current ω-6 and ω-3 fatty acids in the American diet have shifted from the ideal ratio of 2:1 to almost 20:1; while there is a body of evidence that suggests the negative impact of such a shift in younger organisms, the underlying age-related metabolic signaling in response to the excess influx of ω-6 fatty acids is incompletely understood. In the present study, young (6 mo old) and aging (≥18 mo old) mice were fed for 2 mo with a ω-6-enriched diet. Excess intake of ω-6 enrichment decreased the total lean mass and increased nighttime carbohydrate utilization, with higher levels of cardiac cytokines indicating low-grade chronic inflammation. Dobutamine-induced stress tests displayed an increase in PR interval, a sign of an atrioventricular defect in ω-6-fed aging mice. Excess ω-6 fatty acid intake in aging mice showed decreased 12-lipoxygenase with a concomitant increase in 15-lipoxygenase levels, resulting in the generation of 15( S)-hydroxyeicosatetraenoic acid, whereas cyclooxygenase-1 and -2 generated prostaglandin E 2 , leukotriene B 4, and thromboxane B 2 . Furthermore, excessive ω-6 fatty acids led to dysregulated nuclear erythroid 2-related factor 2/antioxidant-responsive element in aging mice. Moreover, ω-6 fatty acid-mediated changes were profound in aging mice with respect to the eicosanoid profile while minimal changes were observed in the size and shape of cardiomyocytes. These findings provide compelling evidence that surplus consumption of ω-6 fatty acids, coupled with insufficient intake of ω-3 fatty acids, is linked to abnormal changes in ECG. These manifestations contribute to functional deficiencies and expansion of the inflammatory mediator milieu during later stages of aging. NEW & NOTEWORTHY Aging has a profound impact on the metabolism of fatty acids to maintain heart function. The excess influx of ω-6 fatty acids in aging perturbed electrocardiography with marked signs of inflammation and a dysregulated oxidative-redox balance. Thus, the quality and quantity of fatty acids determine the cardiac pathology and energy utilization in aging.

Improved pressure contour analysis for estimating cardiac stroke volume using pulse wave velocity measurement.

PubMed

Kamoi, Shun; Pretty, Christopher; Balmer, Joel; Davidson, Shaun; Pironet, Antoine; Desaive, Thomas; Shaw, Geoffrey M; Chase, J Geoffrey

2017-04-24

Pressure contour analysis is commonly used to estimate cardiac performance for patients suffering from cardiovascular dysfunction in the intensive care unit. However, the existing techniques for continuous estimation of stroke volume (SV) from pressure measurement can be unreliable during hemodynamic instability, which is inevitable for patients requiring significant treatment. For this reason, pressure contour methods must be improved to capture changes in vascular properties and thus provide accurate conversion from pressure to flow. This paper presents a novel pressure contour method utilizing pulse wave velocity (PWV) measurement to capture vascular properties. A three-element Windkessel model combined with the reservoir-wave concept are used to decompose the pressure contour into components related to storage and flow. The model parameters are identified beat-to-beat from the water-hammer equation using measured PWV, wave component of the pressure, and an estimate of subject-specific aortic dimension. SV is then calculated by converting pressure to flow using identified model parameters. The accuracy of this novel method is investigated using data from porcine experiments (N = 4 Pietrain pigs, 20-24.5 kg), where hemodynamic properties were significantly altered using dobutamine, fluid administration, and mechanical ventilation. In the experiment, left ventricular volume was measured using admittance catheter, and aortic pressure waveforms were measured at two locations, the aortic arch and abdominal aorta. Bland-Altman analysis comparing gold-standard SV measured by the admittance catheter and estimated SV from the novel method showed average limits of agreement of ±26% across significant hemodynamic alterations. This result shows the method is capable of estimating clinically acceptable absolute SV values according to Critchely and Critchely. The novel pressure contour method presented can accurately estimate and track SV even when hemodynamic properties are significantly altered. Integrating PWV measurements into pressure contour analysis improves identification of beat-to-beat changes in Windkessel model parameters, and thus, provides accurate estimate of blood flow from measured pressure contour. The method has great potential for overcoming weaknesses associated with current pressure contour methods for estimating SV.

Voluntary exercise does not affect stress-induced tachycardia, but improves resistance to cardiac arrhythmias in rats.

PubMed

Beig, Mirza I; Callister, Robin; Saint, David A; Bondarenko, Eugene; Walker, Frederick R; Day, Trevor A; Nalivaiko, Eugene

2011-01-01

1. It is currently unknown whether long-term voluntary exercise has enduring cardioprotective effects in animal models. 2. The present study was conducted in three groups of rats: (i) sedentary controls (n = 6); (ii) 24 h runners (n = 8; unlimited access to running wheels); and (iii) 2 h runners (n = 8; access to running wheels limited to 2 h daily). After termination of the 6 week exercise protocol, all rats were implanted with the telemetric electrocardiogram transmitters and were studied 1 week later. 3. Resting heart rate (HR) values in the control rats, 24 h runners and 2 h runners were 372 ± 7, 361 ± 9 and 298 ± 5 b.p.m., respectively (P < 0.05 for 2 h runners vs controls). The high-frequency spectral power in the control rats, 24 h runners and 2 h runners was 3.9 ± 0.2, 4.3 ± 0.3 and 5.3 ± 0.3 s², respectively (P < 0.05 for 2 h runners vs controls), whereas intrinsic HR was 383 ± 3, 377 ± 2 and 346 ± 3 b.p.m., respectively (P < 0.001 for 2 h runners vs controls). Restraint stress provoked tachycardia of similar magnitude in all groups. 4. After completion of telemetric studies, haemodynamic indices and susceptibility to cardiac arrhythmias were assessed in anaesthetized animals, there were no major between-group differences in HR, arterial pressure, contractility indices or sensitivity to β-adrenoceptor stimulation (dobutamine) or blockade (atenolol). The effective refractory period in the control rats, 24 h runners and 2 h runners was 49 ± 2, 55 ± 2 and 60 ± 4 ms, respectively (P = 0.054 for 2 h runners vs controls). A significantly higher dose of aconitine was required to provoke ventricular arrhythmias in the 24 h and 2 h running groups compared with controls (489 ± 76, 505 ± 88 and 173 ± 33 μg, respectively; P < 0.05). 5. We conclude that, in rats, long-term voluntary exercise has enduring cardioprotective effects mediated at the level of both the central nervous system and the heart. © 2010 The Authors. Clinical and Experimental Pharmacology and Physiology © 2010 Blackwell Publishing Asia Pty Ltd.

Percutaneous coronary intervention in stable angina (ORBITA): a double-blind, randomised controlled trial.

PubMed

Al-Lamee, Rasha; Thompson, David; Dehbi, Hakim-Moulay; Sen, Sayan; Tang, Kare; Davies, John; Keeble, Thomas; Mielewczik, Michael; Kaprielian, Raffi; Malik, Iqbal S; Nijjer, Sukhjinder S; Petraco, Ricardo; Cook, Christopher; Ahmad, Yousif; Howard, James; Baker, Christopher; Sharp, Andrew; Gerber, Robert; Talwar, Suneel; Assomull, Ravi; Mayet, Jamil; Wensel, Roland; Collier, David; Shun-Shin, Matthew; Thom, Simon A; Davies, Justin E; Francis, Darrel P

2018-01-06

Symptomatic relief is the primary goal of percutaneous coronary intervention (PCI) in stable angina and is commonly observed clinically. However, there is no evidence from blinded, placebo-controlled randomised trials to show its efficacy. ORBITA is a blinded, multicentre randomised trial of PCI versus a placebo procedure for angina relief that was done at five study sites in the UK. We enrolled patients with severe (≥70%) single-vessel stenoses. After enrolment, patients received 6 weeks of medication optimisation. Patients then had pre-randomisation assessments with cardiopulmonary exercise testing, symptom questionnaires, and dobutamine stress echocardiography. Patients were randomised 1:1 to undergo PCI or a placebo procedure by use of an automated online randomisation tool. After 6 weeks of follow-up, the assessments done before randomisation were repeated at the final assessment. The primary endpoint was difference in exercise time increment between groups. All analyses were based on the intention-to-treat principle and the study population contained all participants who underwent randomisation. This study is registered with ClinicalTrials.gov, number NCT02062593. ORBITA enrolled 230 patients with ischaemic symptoms. After the medication optimisation phase and between Jan 6, 2014, and Aug 11, 2017, 200 patients underwent randomisation, with 105 patients assigned PCI and 95 assigned the placebo procedure. Lesions had mean area stenosis of 84·4% (SD 10·2), fractional flow reserve of 0·69 (0·16), and instantaneous wave-free ratio of 0·76 (0·22). There was no significant difference in the primary endpoint of exercise time increment between groups (PCI minus placebo 16·6 s, 95% CI -8·9 to 42·0, p=0·200). There were no deaths. Serious adverse events included four pressure-wire related complications in the placebo group, which required PCI, and five major bleeding events, including two in the PCI group and three in the placebo group. In patients with medically treated angina and severe coronary stenosis, PCI did not increase exercise time by more than the effect of a placebo procedure. The efficacy of invasive procedures can be assessed with a placebo control, as is standard for pharmacotherapy. NIHR Imperial Biomedical Research Centre, Foundation for Circulatory Health, Imperial College Healthcare Charity, Philips Volcano, NIHR Barts Biomedical Research Centre. Copyright © 2018 Elsevier Ltd. All rights reserved.

Pulmonary vascular and right ventricular dysfunction in adult critical care: current and emerging options for management: a systematic literature review.

PubMed

Price, Laura C; Wort, Stephen J; Finney, Simon J; Marino, Philip S; Brett, Stephen J

2010-01-01

Pulmonary vascular dysfunction, pulmonary hypertension (PH), and resulting right ventricular (RV) failure occur in many critical illnesses and may be associated with a worse prognosis. PH and RV failure may be difficult to manage: principles include maintenance of appropriate RV preload, augmentation of RV function, and reduction of RV afterload by lowering pulmonary vascular resistance (PVR). We therefore provide a detailed update on the management of PH and RV failure in adult critical care. A systematic review was performed, based on a search of the literature from 1980 to 2010, by using prespecified search terms. Relevant studies were subjected to analysis based on the GRADE method. Clinical studies of intensive care management of pulmonary vascular dysfunction were identified, describing volume therapy, vasopressors, sympathetic inotropes, inodilators, levosimendan, pulmonary vasodilators, and mechanical devices. The following GRADE recommendations (evidence level) are made in patients with pulmonary vascular dysfunction: 1) A weak recommendation (very-low-quality evidence) is made that close monitoring of the RV is advised as volume loading may worsen RV performance; 2) A weak recommendation (low-quality evidence) is made that low-dose norepinephrine is an effective pressor in these patients; and that 3) low-dose vasopressin may be useful to manage patients with resistant vasodilatory shock. 4) A weak recommendation (low-moderate quality evidence) is made that low-dose dobutamine improves RV function in pulmonary vascular dysfunction. 5) A strong recommendation (moderate-quality evidence) is made that phosphodiesterase type III inhibitors reduce PVR and improve RV function, although hypotension is frequent. 6) A weak recommendation (low-quality evidence) is made that levosimendan may be useful for short-term improvements in RV performance. 7) A strong recommendation (moderate-quality evidence) is made that pulmonary vasodilators reduce PVR and improve RV function, notably in pulmonary vascular dysfunction after cardiac surgery, and that the side-effect profile is reduced by using inhaled rather than systemic agents. 8) A weak recommendation (very-low-quality evidence) is made that mechanical therapies may be useful rescue therapies in some settings of pulmonary vascular dysfunction awaiting definitive therapy. This systematic review highlights that although some recommendations can be made to guide the critical care management of pulmonary vascular and right ventricular dysfunction, within the limitations of this review and the GRADE methodology, the quality of the evidence base is generally low, and further high-quality research is needed.

Downregulation of β1 -adrenergic receptors in rat C6 glioblastoma cells by hyperforin and hyperoside from St John's wort.

PubMed

Jakobs, Daniel; Hage-Hülsmann, Anne; Prenner, Lars; Kolb, Christiane; Weiser, Dieter; Häberlein, Hanns

2013-06-01

While the use of St John's wort extracts as treatment for mild to moderate depression is well established the mode of action is still under investigation. Individual constituents of St John's wort extract were tested for possible effects on the β1 AR density and a subsequent change in downstream signalling in rat C6 glioblastoma cells. The effect of compounds from St John's wort extract on the downregulation of β1 -adrenergic receptor-GFP fusion proteins (β1 AR-green fluorescent protein (GFP)) of transfected rat C6 gliobastoma cells (C6-β1 AR-GFP) was investigated by means of confocal laser scanning microscopy (LSM). The influence on the lateral mobility of β1 AR-GFP in C6-β1 AR-GFP was investigated by fluorescence correlation spectroscopy. The formation of second messenger was determined by c-AMP-assay. Confocal LSM revealed that pretreatment of cells with 1 μm of hyperforin and hyperoside for 6 days, respectively, led to an internalization of β1 AR-GFP under non-stimulating conditions. Observation by fluorescence correlation spectroscopy showed two diffusion time constants for control cells, with τdiff1  = 0.78 ± 0.18 ms and τdiff2  = 122.53 ± 69.41 ms, similarly distributed. Pretreatment with 1 μm hyperforin or 1 μm hyperoside for 3 days did not alter the τdiff values but decreased the fraction of τdiff1 whereas the fraction of τdiff2 increased significantly. An elevated level of β1 AR-GFP with hindered lateral mobility was in line with β1 AR-GFP internalization induced by hyperforin and hyperoside, respectively. A reduced β1 -adrenergic responsiveness was assumed for C6 gliobastoma cells after pretreatment for 6 days with 1 μm of both hyperforin and hyperoside, which was confirmed by decreased cAMP formation of about 10% and 5% under non-stimulating conditions. Decrease in cAMP formation by 23% for hyperforin and 15% for hyperoside was more pronounced after stimulation with 10 μm dobutamine for 30 min. The treatment of C6 gliobastoma cells with hyperforin and hyperoside results in a reduced β1 AR density in the plasma membrane and a subsequent reduced downstream signalling. © 2013 Royal Pharmaceutical Society.

Alkaptonuric aortic stenosis: a case report.

PubMed

Gonzales, M E

1999-04-01

Alkaptonuria is a rare disease of phenylalanine, aromatic amino acids, and tyrosine metabolism. Because of a genetic deficiency of the enzyme homogentisic acid oxidase, an accumulation of homogentisic acid causes ochronotic pigment deposition. The most common clinical manifestations are arthropathy, urinary calculi and discoloration, cutaneous and cartilaginous pigmentation, and cardiac valvular disease. Arthropathy and aortic stenosis are the most debilitating manifestations of the disease. A case of alkaptonuric aortic stenosis is described. A 75-year-old woman with a history of alkaptonuria presented in the emergency department with complaints of progressive dyspnea. Upon examination, the patient was hypertensive, tachypneic, and tachycardic with premature ventricular contractions. She had pitting edema of the lower extremities and complaints of generalized weakness. Chest x-rays revealed congestive heart failure and pulmonary edema. Diuretics were administered, and a continuous nitroglycerin infusion was initiated in the emergency department. The patient was admitted for further evaluation. The patient's respiratory status continued to decline. She was intubated endotracheally 1 day after admission. Subsequent cardiac evaluation revealed an ejection fraction of 35%, severe aortic stenosis, mild coronary artery disease, ischemic cardiomyopathy, and anteroapical akinesis. A dobutamine infusion was instituted for persistent hypotension, and renal dose dopamine was initiated for oliguric renal failure. The patient underwent an emergency operation for an aortic valve replacement with a Dacron patch 10 days after admission. Cardiopulmonary bypass and mild hypothermia were used during the procedure. The patient's hemodynamic status remained tenuous throughout the procedure. Although the first attempt to wean off cardiopulmonary bypass failed, the second attempt was successful with the aid of an intra-aortic balloon pump, inotropic support, and atrioventricular pacing. These measures were maintained during transport to the surgical intensive care unit. In the intensive care unit, the patient did not have an audible blood pressure or a palpable pulse without the support of the intra-aortic balloon pump and atrioventricular pacing. Coarse atrial fibrillation was the underlying electrocardiogram rhythm in the absence of atrioventricular pacing. Sodium bicarbonate was given without improvement. After discussion with the family, all life support measures were discontinued. The patient died 10 minutes after her arrival in the intensive care unit. Alkaptonuria's pathogenesis is manifested as both local and systemic in nature. Collagen vascular diseases share a similar pattern of multisystem involvement. Despite the negative outcome for the patient described, valuable insight can be obtained by studying this case and noting the anesthetic considerations specific to collagen vascular diseases in general.

Transient adrenocortical insufficiency of prematurity and systemic hypotension in very low birthweight infants

PubMed Central

Ng, P; Lee, C; Lam, C; Ma, K; Fok, T; Chan, I; Wong, E

2004-01-01

Objectives: A proportion of preterm, very low birthweight (VLBW, < 1500 g) infants may show inadequate adrenal response to stress in the immediate postnatal period. The human corticotrophin releasing hormone (hCRH) stimulation test was used to: (a) determine the relation between pituitary-adrenal response and systemic blood pressure in these infants; (b) characterise the endocrinological features of transient adrenocortical insufficiency of prematurity (TAP). Study design: A total of 226 hCRH tests were performed on 137 VLBW infants on day 7 and 14 of life in a tertiary neonatal centre. Results: Basal, peak, and incremental rise in serum cortisol (ΔCort0–30) on day 7 were associated significantly with the lowest systolic, mean, and diastolic blood pressures recorded during the first two weeks of life (r > 0.25, p < 0.005). These cortisol concentrations also correlated significantly but negatively with the maximum and total cumulative dose of dopamine (r > -0.22, p < 0.02), dobutamine (r > -0.18, p < 0.04), and adrenaline (r > -0.26, p < 0.004), total volume of crystalloid (r > -0.22, p < 0.02), and duration of inotrope treatment (r > -0.25, p < 0.006). Multivariate regression analysis of significant factors showed that the lowest systolic, mean, and diastolic blood pressures remained independently associated with serum cortisol (basal, peak, and ΔCort0–30) on day 7. Hypotensive infants requiring inotropes (group 2) were significantly less mature and more sick than infants with normal blood pressure (group 1). The areas under the ACTH response curves were significantly greater in group 2 than in group 1, on both day 7 (p = 0.004) and day 14 (p = 0.004). In contrast, the area under the cortisol response curve was significantly greater in group 1 than in group 2 on day 7 (p = 0.001), but there was no significant difference between the two groups on day 14. In addition, serum cortisol at the 50th centile in hypotensive infants had high specificity and positive predictive value (0.80–0.93 and 0.81–0.89 respectively) for predicting early neonatal hypotension. Conclusions: This study characterises the fundamental endocrinological features of TAP: normal or exaggerated pituitary response; adrenocortical insufficiency; good recovery of adrenal function by day 14 of postnatal life. The results also provide the centiles of serum cortisol for hypotensive patients and infants with normal blood pressure, and show a significant relation between serum cortisol and blood pressure in VLBW infants. PMID:14977894

Effect of postoperative goal-directed therapy in cancer patients undergoing high-risk surgery: a randomized clinical trial and meta-analysis.

PubMed

Gerent, Aline Rejane Muller; Almeida, Juliano Pinheiro; Fominskiy, Evgeny; Landoni, Giovanni; de Oliveira, Gisele Queiroz; Rizk, Stephanie Itala; Fukushima, Julia Tizue; Simoes, Claudia Marques; Ribeiro, Ulysses; Park, Clarice Lee; Nakamura, Rosana Ely; Franco, Rafael Alves; Cândido, Patricia Inês; Tavares, Cintia Rosa; Camara, Ligia; Dos Santos Rocha Ferreira, Graziela; de Almeida, Elisangela Pinto Marinho; Filho, Roberto Kalil; Galas, Filomena Regina Barbosa Gomes; Hajjar, Ludhmila Abrahão

2018-05-23

Perioperative goal-directed hemodynamic therapy (GDHT) has been advocated in high-risk patients undergoing noncardiac surgery to reduce postoperative morbidity and mortality. We hypothesized that using cardiac index (CI)-guided GDHT in the postoperative period for patients undergoing high-risk surgery for cancer treatment would reduce 30-day mortality and postoperative complications. A randomized, parallel-group, superiority trial was performed in a tertiary oncology hospital. All adult patients undergoing high-risk cancer surgery who required intensive care unit admission were randomly allocated to a CI-guided GDHT group or to a usual care group. In the GDHT group, postoperative therapy aimed at CI ≥ 2.5 L/min/m 2 using fluids, inotropes and red blood cells during the first 8 postoperative hours. The primary outcome was a composite endpoint of 30-day all-cause mortality and severe postoperative complications during the hospital stay. A meta-analysis was also conducted including all randomized trials of postoperative GDHT published from 1966 to May 2017. A total of 128 patients (64 in each group) were randomized. The primary outcome occurred in 34 patients of the GDHT group and in 28 patients of the usual care group (53.1% vs 43.8%, absolute difference 9.4 (95% CI, - 7.8 to 25.8); p = 0.3). During the 8-h intervention period more patients in the GDHT group received dobutamine when compared to the usual care group (55% vs 16%, p < 0.001). A meta-analysis of nine randomized trials showed no differences in postoperative mortality (risk ratio 0.85, 95% CI 0.59-1.23; p = 0.4; p for heterogeneity = 0.7; I 2  = 0%) and in the overall complications rate (risk ratio 0.88, 95% CI 0.71-1.08; p = 0.2; p for heterogeneity = 0.07; I 2  = 48%), but a reduced hospital length of stay in the GDHT group (mean difference (MD) - 1.6; 95% CI - 2.75 to - 0.46; p = 0.006; p for heterogeneity = 0.002; I 2  = 74%). CI-guided hemodynamic therapy in the first 8 postoperative hours does not reduce 30-day mortality and severe complications during hospital stay when compared to usual care in cancer patients undergoing high-risk surgery. www.clinicaltrials.gov , NCT01946269 . Registered on 16 September 2013.

One-year follow-up of myocardial perfusion and function evaluated by gated SPECT MIBI in patients with earlier myocardial infarction and chronic total occlusion.

PubMed

Pavlovic, Smiljana V; Sobic-Saranovic, Dragana P; Beleslin, Branko D; Ostojic, Miodrag C; Nedeljkovic, Milan A; Giga, Vojislav L; Petrasinovic, Zorica R; Artiko, Vera M; Todorovic-Tirnanic, Mila V; Obradovic, Vladimir B

2009-01-01

Optimal treatment for chronic total occlusion (CTO) in the infarct-related coronary artery is not clear. Our aim was to assess myocardial perfusion, left ventricular ejection fraction (EF), and left ventricular size using gated single-photon emission computed tomography (SPECT) myocardial perfusion imaging with 99mTc-methoxy-isobutyl-isonitrile in patients with CTO before and 1 year after recanalization. Thirty patients with earlier myocardial infarction and at least one CTO underwent percutaneous coronary intervention (PCI) as well as nitrate-enhanced gated SPECT myocardial perfusion and dobutamine stress echocardiography before and 11 +/- 1 months after recanalization. They were divided into three groups based on the outcome of the follow-up angiography: (i) successful recanalization with no evidence of in-stent restenosis (n=13); (ii) successful recanalization with in-stent restenosis (n=7) and (iii) unsuccessful recanalization (n=10). Overall success of recanalization for CTO was 74%. In group 1, myocardial viability was preserved in 11 of 13 (85%) patients at baseline. Gated SPECT at 1 year showed a significant decrease in perfusion abnormalities (29 +/- 12 to 23 +/- 14%, P < 0.05) and left ventricular end-diastolic volume (EDV) (168 +/- 47 to 151 +/- 47 ml, P < 0.05). Improvement in EF (51 +/- 11 to 54 +/- 13%, P > 0.05) and reduction in left ventricular end-systolic volume (ESV) (84 +/- 37 to 77 +/- 40 ml, P > 0.05) did not reach the level of significance. Myocardial viability was preserved in only two of seven patients (28%) in group 2. Neither mean perfusion abnormalities (37 +/- 24 to 35 +/- 22%, P > 0.05) nor global left ventricular parameters (EF 41 +/- 15 vs. 42 +/- 19%, EDV 298 +/- 33 vs. 299 +/- 57 mL, ESV 197 +/- 12 vs. 195 +/- 32 ml; P > 0.05) changed at the follow-up. In group 3, myocardial viability was preserved in seven of 10 patients (70%) at baseline, but no significant changes in perfusion (40 +/- 18 vs. 41 +/- 19%, P > 0.05) and left ventricular function (EF 42 +/- 17 vs. 44 +/- 14%, EDV 228 +/- 101 vs. 227 +/- 81 ml, ESV 143 +/- 87 vs. 146 +/- 8 ml; P > 0.05) were seen at the follow-up. Myocardial perfusion and EDV may significantly improve 1 year after PCI provided recanalization of CTO was successful. Our preliminary findings suggest that successful recanalization of CTO may have favorable outcome on left ventricular perfusion and function, particularly in patients with viable myocardium before PCI. The gated SPECT myocardial perfusion imaging with 99mTc-methoxy-isobutyl-isonitrile may be useful for monitoring long-term functional outcome of PCI in patients with CTO.

Prognostic Utility of Stress Testing and Cardiac Biomarkers in Menopausal Women at Low to Intermediate Risk for Coronary ARTery Disease (SMART Study): 5-Year Outcome.

PubMed

Abdelmoneim, Sahar S; Ball, Caroline A; Mantovani, Francesca; Hagen, Mary E; Eifert-Rain, Susan; Wilansky, Susan; Castello, Ramon; Pellikka, Patricia A; Best, Patricia J M; Mulvagh, Sharon L

2018-05-01

In women with low to intermediate risk of coronary artery disease (CAD), prognostic detection strategies have been controversial. We present the follow-up data of the SMART trial in peri/postmenopausal women at low to intermediate risk of CAD. To determine the value of contrast stress echocardiography (CSE), stress electrocardiogram (sECG), and serum biomarkers for prediction of cardiovascular events (CE) in peri/postmenopausal women at low to intermediate risk of CAD. From January 2004 to August 2007, 400 peri/postmenopausal women were prospectively enrolled. All women had detailed risk factor assessment, and underwent simultaneous CSE (Definity ® , Lantheus Medical Imaging) and sECG. Laboratories included brain natriuretic peptide (BNP), atrial natriuretic peptide, endothelin, and high sensitivity C-reactive protein. Wall motion score index was based on a 16-segment model. Abnormal CSE was defined as new or worsening wall motion abnormality at stress, while abnormal sECG was ≥1 mm horizontal/downsloping ST segment depression/elevation (80 mseconds duration). Self-reported outcome data were collected from a mailed Women's Heart Clinic Questionnaire. CE outcomes included all-cause mortality, nonfatal myocardial infarction (MI), heart failure, chest pain hospitalization or development of typical angina (CP), and revascularization (REVASC). Adjusted Cox proportional hazard ratios (HR; 95% confidence intervals) were reported. A total of 366 women (54.4 ± 5.5 years, Framingham risk 6.5% ± 4.4%) completed simultaneous CSE and sECG. Forty-two (11.5%) had abnormal CSE, while sECG was abnormal in 22 (6%) women. Follow-up (4.4 ± 1.2 years) was available in 315/366 (86%) women (78% exercise-CSE, 22% dobutamine-CSE). In those who completed follow-up, CSE was abnormal in 33 women (10.5%) and sECG was abnormal in 21 (6.7%). In 33 women with abnormal CSE, sECG was abnormal in 7 (21.2%) and normal in 26 (79%), p = 0.0004. CE occurred in 27 (8.6%) women: 8 all-cause mortality, 2 nonfatal MI, 13 CP, and 4 REVASC. CE occurred in 21% versus 7% of women with abnormal versus normal CSE, p = 0.014 and 38% versus 6% of women with abnormal versus normal sECG, p < 0.0001. Rest BNP was higher in women with CE versus those without (p = 0.018). Abnormal sECG and abnormal CSE were associated with CE, while only abnormal sECG was an independent predictor of CE (adjusted HR 10.3 [1.9-61.4], p = 0.007). Of the laboratory results, only BNP was associated with CE (adjusted HR 2.9 [1.1-7.3], p = 0.028). sECG and rest BNP were independent predictors of subsequent CE within 5 years in peri/postmenopausal women at low to intermediate risk of CAD.

Factors Associated with Mortality and Graft Failure in Liver Transplants: A Hierarchical Approach

PubMed Central

Andraus, Wellington; de Martino, Rodrigo Bronze; Ortega, Neli Regina de Siqueira; Abe, Jair Minoro; D’Albuquerque, Luiz Augusto Carneiro

2015-01-01

Background Liver transplantation has received increased attention in the medical field since the 1980s following the introduction of new immunosuppressants and improved surgical techniques. Currently, transplantation is the treatment of choice for patients with end-stage liver disease, and it has been expanded for other indications. Liver transplantation outcomes depend on donor factors, operating conditions, and the disease stage of the recipient. A retrospective cohort was studied to identify mortality and graft failure rates and their associated factors. All adult liver transplants performed in the state of São Paulo, Brazil, between 2006 and 2012 were studied. Methods and Findings A hierarchical Poisson multiple regression model was used to analyze factors related to mortality and graft failure in liver transplants. A total of 2,666 patients, 18 years or older, (1,482 males; 1,184 females) were investigated. Outcome variables included mortality and graft failure rates, which were grouped into a single binary variable called negative outcome rate. Additionally, donor clinical, laboratory, intensive care, and organ characteristics and recipient clinical data were analyzed. The mortality rate was 16.2 per 100 person-years (py) (95% CI: 15.1–17.3), and the graft failure rate was 1.8 per 100 py (95% CI: 1.5–2.2). Thus, the negative outcome rate was 18.0 per 100 py (95% CI: 16.9–19.2). The best risk model demonstrated that recipient creatinine ≥ 2.11 mg/dl [RR = 1.80 (95% CI: 1.56–2.08)], total bilirubin ≥ 2.11 mg/dl [RR = 1.48 (95% CI: 1.27–1.72)], Na+ ≥ 141.01 mg/dl [RR = 1.70 (95% CI: 1.47–1.97)], RNI ≥ 2.71 [RR = 1.64 (95% CI: 1.41–1.90)], body surface ≥ 1.98 [RR = 0.81 (95% CI: 0.68–0.97)] and donor age ≥ 54 years [RR = 1.28 (95% CI: 1.11–1.48)], male gender [RR = 1.19(95% CI: 1.03–1.37)], dobutamine use [RR = 0.54 (95% CI: 0.36–0.82)] and intubation ≥ 6 days [RR = 1.16 (95% CI: 1.10–1.34)] affected the negative outcome rate. Conclusions The current study confirms that both donor and recipient characteristics must be considered in post-transplant outcomes and prognostic scores. Our data demonstrated that recipient characteristics have a greater impact on post-transplant outcomes than donor characteristics. This new concept makes liver transplant teams to rethink about the limits in a MELD allocation system, with many teams competing with each other. The results suggest that although we have some concerns about the donors features, the recipient factors were heaviest predictors for bad outcomes. PMID:26274497

Prognosis of cirrhotic patients admitted to intensive care unit: a meta-analysis.

PubMed

Weil, Delphine; Levesque, Eric; McPhail, Marc; Cavallazzi, Rodrigo; Theocharidou, Eleni; Cholongitas, Evangelos; Galbois, Arnaud; Pan, Heng Chih; Karvellas, Constantine J; Sauneuf, Bertrand; Robert, René; Fichet, Jérome; Piton, Gaël; Thevenot, Thierry; Capellier, Gilles; Di Martino, Vincent

2017-12-01

The best predictors of short- and medium-term mortality of cirrhotic patients receiving intensive care support are unknown. We conducted meta-analyses from 13 studies (2523 cirrhotics) after selection of original articles and response to a standardized questionnaire by the corresponding authors. End-points were in-ICU, in-hospital, and 6-month mortality in ICU survivors. A total of 301 pooled analyses, including 95 analyses restricted to 6-month mortality among ICU survivors, were conducted considering 249 variables (including reason for admission, organ replacement therapy, and composite prognostic scores). In-ICU, in-hospital, and 6-month mortality was 42.7, 54.1, and 75.1%, respectively. Forty-eight patients (3.8%) underwent liver transplantation during follow-up. In-ICU mortality was lower in patients admitted for variceal bleeding (OR 0.46; 95% CI 0.36-0.59; p < 0.001) and higher in patients with SOFA > 19 at baseline (OR 8.54; 95% CI 2.09-34.91; p < 0.001; PPV = 0.93). High SOFA no longer predicted mortality at 6 months in ICU survivors. Twelve variables related to infection were predictors of in-ICU mortality, including SIRS (OR 2.44; 95% CI 1.64-3.65; p < 0.001; PPV = 0.57), pneumonia (OR 2.18; 95% CI 1.47-3.22; p < 0.001; PPV = 0.69), sepsis-associated refractory oliguria (OR 10.61; 95% CI 4.07-27.63; p < 0.001; PPV = 0.76), and fungal infection (OR 4.38; 95% CI 1.11-17.24; p < 0.001; PPV = 0.85). Among therapeutics, only dopamine (OR 5.57; 95% CI 3.02-10.27; p < 0.001; PPV = 0.68), dobutamine (OR 8.92; 95% CI 3.32-23.96; p < 0.001; PPV = 0.86), epinephrine (OR 5.03; 95% CI 2.68-9.42; p < 0.001; PPV = 0.77), and MARS (OR 2.07; 95% CI 1.22-3.53; p = 0.007; PPV = 0.58) were associated with in-ICU mortality without heterogeneity. In ICU survivors, eight markers of liver and renal failure predicted 6-month mortality, including Child-Pugh stage C (OR 2.43; 95% CI 1.44-4.10; p < 0.001; PPV = 0.57), baseline MELD > 26 (OR 3.97; 95% CI 1.92-8.22; p < 0.0001; PPV = 0.75), and hepatorenal syndrome (OR 4.67; 95% CI 1.24-17.64; p = 0.022; PPV = 0.88). Prognosis of cirrhotic patients admitted to ICU is poor since only a minority undergo liver transplant. The prognostic performance of general ICU scores decreases over time, unlike the Child-Pugh and MELD scores, even recorded in the context of organ failure. Infection-related parameters had a short-term impact, whereas liver and renal failure had a sustained impact on mortality.

Inflammatory Markers-Serum Level of C-Reactive Protein, Tumor Necrotic Factor-α, and Interleukin-6 as Predictors of Outcome for Peripartum Cardiomyopathy.

PubMed

Sarojini, A; Sai Ravi Shanker, A; Anitha, M

2013-08-01

Peripartum cardiomyopathy (PPCM) is a disorder of unknown etiology in which symptoms of heart failure occur between the last month of pregnancy and 5 months post-partum. These findings prompted us to carry out a more detailed study aimed at correlating plasma levels of C-reactive protein TNF-α and IL-6 as prognostic value for major clinical in-hospital events and 6-month follow-up in patients with PPCM. After ethical clearance, in the present prospective case-control study, a total of 86 subjects were enrolled [patients (n = 46) and controls (n = 40)]. After checking for the inclusion and exclusion criteria, informed consent was obtained and patients were enrolled. The details of history of pre-eclampsia and mode of delivery were obtained from the patients. The history of onset of symptoms and signs was recorded at the first presentation and at 6 months. Clinical assessment, echocardiography, and blood analysis were done at baseline and after 6 months of standard therapy. All patients received treatment with diuretics and the ACE inhibitor (ramipril), Carvedilol if not contraindicated, and inotropic support inj-Dobutamine. Inflammatory markers (C-reactive protein, TNF-α, and IL-6) were measured at baseline and at 6 months. Data were analyzed using the SAS version 9.1 statistical program. The characteristics of the study population at first presentation to the cardiac clinic are similar (compared with controls): 0.91 % of the study patients were diagnosed as PPCM patients for the first time and 49 % patients presented within one month after delivery. C-reactive protein (22 vs 08 mg/dl, p < 0.05), TNF-α (9.6 vs 3.2 pg/dl, p < 001), and IL-6 (73.19 ± 34.4 vs 31.52 ± 8.83 pg/dl, p < 0.005) were significantly abnormal, and these patients showed significantly higher LV dimensions, LV EDD (61.6 ± 7.1 vs 46 ± 9 mm p < 0.004) LV ESD (53.1 ± 7 vs 32 ± 8, p < 0.005), and significantly lower echocardiographic left ventricular ejection fraction (LVEF) (25.9 ± 8.2 vs 55 ± 12 p < 0.001) and correlate well with NYHA FC and death. LVEF improved from 25.9 ± 8.2 to 42.9 + 13.6 % at 6 months (p < 0.0001). Patients who completed 6 months of standard care showed a significant reduction of heart rate, LV dimensions, and NYHA FC (p < 0.001). However, normalization of LVEF (>50 %) was only observed in 11 (35 %) patients. Seven patients died within 6 months of diagnoses and eight patients were lost to follow-up. Plasma markers of inflammation were significantly elevated in PPCM patients and correlated with increased LV dimensions and lower EF at presentation. Baseline CRP, IL-6, TNF-α, and higher NYHA FC were the only predictors of mortality. These results contribute to inflammation which may contribute to the pathogenesis of PPCM and its complications and predictors of mortality.

Stress Echocardiography for the Diagnosis of Coronary Artery Disease

PubMed Central

2010-01-01

Executive Summary In July 2009, the Medical Advisory Secretariat (MAS) began work on Non-Invasive Cardiac Imaging Technologies for the Diagnosis of Coronary Artery Disease (CAD), an evidence-based review of the literature surrounding different cardiac imaging modalities to ensure that appropriate technologies are accessed by patients suspected of having CAD. This project came about when the Health Services Branch at the Ministry of Health and Long-Term Care asked MAS to provide an evidentiary platform on effectiveness and cost-effectiveness of non-invasive cardiac imaging modalities. After an initial review of the strategy and consultation with experts, MAS identified five key non-invasive cardiac imaging technologies for the diagnosis of CAD. Evidence-based analyses have been prepared for each of these five imaging modalities: cardiac magnetic resonance imaging, single photon emission computed tomography, 64-slice computed tomographic angiography, stress echocardiography, and stress echocardiography with contrast. For each technology, an economic analysis was also completed (where appropriate). A summary decision analytic model was then developed to encapsulate the data from each of these reports (available on the OHTAC and MAS website). The Non-Invasive Cardiac Imaging Technologies for the Diagnosis of Coronary Artery Disease series is made up of the following reports, which can be publicly accessed at the MAS website at: www.health.gov.on.ca/mas"> www.health.gov.on.ca/mas or at www.health.gov.on.ca/english/providers/program/mas/mas_about.html Single Photon Emission Computed Tomography for the Diagnosis of Coronary Artery Disease: An Evidence-Based Analysis Stress Echocardiography for the Diagnosis of Coronary Artery Disease: An Evidence-Based Analysis Stress Echocardiography with Contrast for the Diagnosis of Coronary Artery Disease: An Evidence-Based Analysis 64-Slice Computed Tomographic Angiography for the Diagnosis of Coronary Artery Disease: An Evidence-Based Analysis Cardiac Magnetic Resonance Imaging for the Diagnosis of Coronary Artery Disease: An Evidence-Based Analysis Pease note that two related evidence-based analyses of non-invasive cardiac imaging technologies for the assessment of myocardial viability are also available on the MAS website: Positron Emission Tomography for the Assessment of Myocardial Viability: An Evidence-Based Analysis Magnetic Resonance Imaging for the Assessment of Myocardial Viability: an Evidence-Based Analysis The Toronto Health Economics and Technology Assessment Collaborative has also produced an associated economic report entitled: The Relative Cost-effectiveness of Five Non-invasive Cardiac Imaging Technologies for Diagnosing Coronary Artery Disease in Ontario [Internet]. Available from: http://theta.utoronto.ca/reports/?id=7 Objective The objective of the analysis is to determine the diagnostic accuracy of stress echocardiography (ECHO) in the diagnosis of patients with suspected coronary artery disease (CAD) compared to coronary angiography (CA). Stress Echocardiography Stress ECHO is a non-invasive technology that images the heart using ultrasound. It is one of the most commonly employed imaging techniques for investigating a variety of cardiac abnormalities in both community and hospital settings. A complete ECHO exam includes M-mode, 2-dimensional (2-D) images and Doppler imaging. In order to diagnosis CAD and assess whether myocardial ischemia is present, images obtained at rest are compared to those obtained during or immediately after stress. The most commonly used agents used to induce stress are exercise and pharmacological agents such as dobutamine and dipyridamole. The hallmark of stress-induced myocardial ischemia is worsening of wall motion abnormalities or the development of new wall motion abnormalities. A major challenge for stress ECHO is that the interpretation of wall motion contractility and function is subjective. This leads to inter-observer variability and reduced reproducibility. Further, it is estimated that approximately 30% of patients have sub-optimal stress ECHO exams. To overcome this limitation, contrast agents for LV opacification have been developed. Although stress ECHO is a relatively easy to use technology that poses only a low risk of adverse events compared to other imaging technologies, it may potentially be overused and/or misused in CAD diagnosis. Several recent advances have been made focusing on quantitative methods for assessment, improved image quality and enhanced portability, however, evidence on the effectiveness and clinical utility of these enhancements is limited. Evidence-Based Analysis Research Questions What is the diagnostic accuracy of stress ECHO for the diagnosis of patients with suspected CAD compared to the reference standard of CA? What is the clinical utility1 of stress ECHO? Literature Search A literature search was performed on August 28, 2009 using OVID MEDLINE, MEDLINE In-Process and Other Non-Indexed Citations, EMBASE, the Cumulative Index to Nursing & Allied Health Literature (CINAHL), the Cochrane Library, and the International Agency for Health Technology Assessment (INAHTA) for studies published from January 1, 2004 until August 21, 2009. Abstracts were reviewed by a single reviewer and, for those studies meeting the eligibility criteria, full-text articles were obtained. Reference lists were also examined for any relevant studies not identified through the search. Inclusion Criteria Systematic reviews, meta-analyses, randomized controlled trials, prospective observational studies, retrospective analyses Minimum sample size of 20 enrolled patients Comparison to CA (reference standard) Definition of CAD specified as either ≥50%, ≥70% or ≥75% coronary artery stenosis on CA Reporting accuracy data on individual patients (rather than accuracy data stratified by segments of the heart) English Human Exclusion Criteria Duplicate studies Non-systematic reviews, case reports Grey literature (e.g., conference abstracts) Insufficient data for independent calculation of sensitivity and specificity Use of ECHO for purposes other than diagnosis of CAD (e.g., arrhythmia, valvular disease, mitral stenosis, pre-operative risk of MI) Transesophageal ECHO since its primary use is for non-CAD indications such as endocarditis, intracardiac thrombi, valvular disorders Only resting ECHO performed Outcomes of Interest Accuracy outcomes (sensitivity, specificity, positive predictive value, negative predictive value) Costs Summary of Findings Given the vast amount of published literature on stress ECHO, it was decided to focus on the studies contained in the comprehensive 2007 review by Heijenbrok-Kal et al. (1) as a basis for the MAS evidence-based analysis. In applying our inclusion and exclusion criteria, 105 observational studies containing information on 13,035 patients were included. Six studies examined stress ECHO with adenosine, 26 with dipyridamole and 77 with dobutamine, the latter being the most commonly used pharmacological stress ECHO agent in Ontario. A further 18 studies employed exercise as the stressor.2 The prevalence of CAD ranged from 19% to 94% with a mean estimated prevalence of 70%. Based on the results of these studies the following conclusions were made: Based on the available evidence, stress ECHO is a useful imaging modality for the diagnosis of CAD in patients with suspected disease. The overall pooled sensitivity is 0.80 (95% CI: 0.77 – 0.82) and the pooled specificity is 0.84 (95% CI: 0.82 – 0.87) using CA as the reference standard. The AUC derived from the sROC curve is 0.895 and the DOR is 20.64. For pharmacological stress, the pooled sensitivity is 0.79 (95% CI: 0.71 – 0.87) and the pooled specificity is 0.85 (95% CI: 0.83 – 0.88). When exercise is employed as the stress agent, the pooled sensitivity is 0.81 (95% CI: 0.76– 0.86) and the pooled specificity is 0.79 (95% CI: 0.71 – 0.87). Although pharmacological stress and exercise stress would be indicated for different patient populations based on ability to exercise there were no significant differences in sensitivity and specificity. Based on clinical experts, diagnostic accuracy on stress ECHO depends on the patient population, the expertise of the interpreter and the quality of the image. PMID:23074412

Stress echocardiography for the diagnosis of coronary artery disease: an evidence-based analysis.

PubMed

2010-01-01

In July 2009, the Medical Advisory Secretariat (MAS) began work on Non-Invasive Cardiac Imaging Technologies for the Diagnosis of Coronary Artery Disease (CAD), an evidence-based review of the literature surrounding different cardiac imaging modalities to ensure that appropriate technologies are accessed by patients suspected of having CAD. This project came about when the Health Services Branch at the Ministry of Health and Long-Term Care asked MAS to provide an evidentiary platform on effectiveness and cost-effectiveness of non-invasive cardiac imaging modalities.After an initial review of the strategy and consultation with experts, MAS identified five key non-invasive cardiac imaging technologies for the diagnosis of CAD. Evidence-based analyses have been prepared for each of these five imaging modalities: cardiac magnetic resonance imaging, single photon emission computed tomography, 64-slice computed tomographic angiography, stress echocardiography, and stress echocardiography with contrast. For each technology, an economic analysis was also completed (where appropriate). A summary decision analytic model was then developed to encapsulate the data from each of these reports (available on the OHTAC and MAS website).The Non-Invasive Cardiac Imaging Technologies for the Diagnosis of Coronary Artery Disease series is made up of the following reports, which can be publicly accessed at the MAS website at: www.health.gov.on.ca/mas">www.health.gov.on.ca/mas or at www.health.gov.on.ca/english/providers/program/mas/mas_about.htmlSINGLE PHOTON EMISSION COMPUTED TOMOGRAPHY FOR THE DIAGNOSIS OF CORONARY ARTERY DISEASE: An Evidence-Based AnalysisSTRESS ECHOCARDIOGRAPHY FOR THE DIAGNOSIS OF CORONARY ARTERY DISEASE: An Evidence-Based AnalysisSTRESS ECHOCARDIOGRAPHY WITH CONTRAST FOR THE DIAGNOSIS OF CORONARY ARTERY DISEASE: An Evidence-Based Analysis64-Slice Computed Tomographic Angiography for the Diagnosis of Coronary Artery Disease: An Evidence-Based AnalysisCARDIAC MAGNETIC RESONANCE IMAGING FOR THE DIAGNOSIS OF CORONARY ARTERY DISEASE: An Evidence-Based AnalysisPease note that two related evidence-based analyses of non-invasive cardiac imaging technologies for the assessment of myocardial viability are also available on the MAS website:POSITRON EMISSION TOMOGRAPHY FOR THE ASSESSMENT OF MYOCARDIAL VIABILITY: An Evidence-Based AnalysisMAGNETIC RESONANCE IMAGING FOR THE ASSESSMENT OF MYOCARDIAL VIABILITY: an Evidence-Based AnalysisThe Toronto Health Economics and Technology Assessment Collaborative has also produced an associated economic report entitled:The Relative Cost-effectiveness of Five Non-invasive Cardiac Imaging Technologies for Diagnosing Coronary Artery Disease in Ontario [Internet]. Available from: http://theta.utoronto.ca/reports/?id=7 OBJECTIVE: The objective of the analysis is to determine the diagnostic accuracy of stress echocardiography (ECHO) in the diagnosis of patients with suspected coronary artery disease (CAD) compared to coronary angiography (CA). STRESS ECHOCARDIOGRAPHY: Stress ECHO is a non-invasive technology that images the heart using ultrasound. It is one of the most commonly employed imaging techniques for investigating a variety of cardiac abnormalities in both community and hospital settings. A complete ECHO exam includes M-mode, 2-dimensional (2-D) images and Doppler imaging. In order to diagnosis CAD and assess whether myocardial ischemia is present, images obtained at rest are compared to those obtained during or immediately after stress. The most commonly used agents used to induce stress are exercise and pharmacological agents such as dobutamine and dipyridamole. The hallmark of stress-induced myocardial ischemia is worsening of wall motion abnormalities or the development of new wall motion abnormalities. A major challenge for stress ECHO is that the interpretation of wall motion contractility and function is subjective. This leads to inter-observer variability and reduced reproducibility. Further, it is estimated that approximately 30% of patients have sub-optimal stress ECHO exams. To overcome this limitation, contrast agents for LV opacification have been developed. Although stress ECHO is a relatively easy to use technology that poses only a low risk of adverse events compared to other imaging technologies, it may potentially be overused and/or misused in CAD diagnosis. Several recent advances have been made focusing on quantitative methods for assessment, improved image quality and enhanced portability, however, evidence on the effectiveness and clinical utility of these enhancements is limited. EVIDENCE-BASED ANALYSIS: What is the diagnostic accuracy of stress ECHO for the diagnosis of patients with suspected CAD compared to the reference standard of CA?What is the clinical utility() of stress ECHO? A literature search was performed on August 28, 2009 using OVID MEDLINE, MEDLINE In-Process and Other Non-Indexed Citations, EMBASE, the Cumulative Index to Nursing & Allied Health Literature (CINAHL), the Cochrane Library, and the International Agency for Health Technology Assessment (INAHTA) for studies published from January 1, 2004 until August 21, 2009. Abstracts were reviewed by a single reviewer and, for those studies meeting the eligibility criteria, full-text articles were obtained. Reference lists were also examined for any relevant studies not identified through the search. Systematic reviews, meta-analyses, randomized controlled trials, prospective observational studies, retrospective analysesMinimum sample size of 20 enrolled patientsComparison to CA (reference standard)Definition of CAD specified as either ≥50%, ≥70% or ≥75% coronary artery stenosis on CAReporting accuracy data on individual patients (rather than accuracy data stratified by segments of the heart)EnglishHuman Duplicate studiesNon-systematic reviews, case reportsGrey literature (e.g., conference abstracts)Insufficient data for independent calculation of sensitivity and specificityUse of ECHO for purposes other than diagnosis of CAD (e.g., arrhythmia, valvular disease, mitral stenosis, pre-operative risk of MI)Transesophageal ECHO since its primary use is for non-CAD indications such as endocarditis, intracardiac thrombi, valvular disordersOnly resting ECHO performed Accuracy outcomes (sensitivity, specificity, positive predictive value, negative predictive value)Costs Given the vast amount of published literature on stress ECHO, it was decided to focus on the studies contained in the comprehensive 2007 review by Heijenbrok-Kal et al. (1) as a basis for the MAS evidence-based analysis. In applying our inclusion and exclusion criteria, 105 observational studies containing information on 13,035 patients were included. Six studies examined stress ECHO with adenosine, 26 with dipyridamole and 77 with dobutamine, the latter being the most commonly used pharmacological stress ECHO agent in Ontario. A further 18 studies employed exercise as the stressor.() The prevalence of CAD ranged from 19% to 94% with a mean estimated prevalence of 70%. Based on the results of these studies the following conclusions were made: Based on the available evidence, stress ECHO is a useful imaging modality for the diagnosis of CAD in patients with suspected disease. The overall pooled sensitivity is 0.80 (95% CI: 0.77 - 0.82) and the pooled specificity is 0.84 (95% CI: 0.82 - 0.87) using CA as the reference standard. The AUC derived from the sROC curve is 0.895 and the DOR is 20.64.For pharmacological stress, the pooled sensitivity is 0.79 (95% CI: 0.71 - 0.87) and the pooled specificity is 0.85 (95% CI: 0.83 - 0.88). When exercise is employed as the stress agent, the pooled sensitivity is 0.81 (95% CI: 0.76- 0.86) and the pooled specificity is 0.79 (95% CI: 0.71 - 0.87). Although pharmacological stress and exercise stress would be indicated for different patient populations based on ability to exercise there were no significant differences in sensitivity and specificity.Based on clinical experts, diagnostic accuracy on stress ECHO depends on the patient population, the expertise of the interpreter and the quality of the image.

Surviving Sepsis Campaign: International guidelines for management of severe sepsis and septic shock: 2008

PubMed Central

Levy, Mitchell M.; Carlet, Jean M.; Bion, Julian; Parker, Margaret M.; Jaeschke, Roman; Reinhart, Konrad; Angus, Derek C.; Brun-Buisson, Christian; Beale, Richard; Calandra, Thierry; Dhainaut, Jean-Francois; Gerlach, Herwig; Harvey, Maurene; Marini, John J.; Marshall, John; Ranieri, Marco; Ramsay, Graham; Sevransky, Jonathan; Thompson, B. Taylor; Townsend, Sean; Vender, Jeffrey S.; Zimmerman, Janice L.; Vincent, Jean-Louis

2007-01-01

Objective To provide an update to the original Surviving Sepsis Campaign clinical management guidelines, “Surviving Sepsis Campaign guidelines for management of severe sepsis and septic shock,” published in 2004. Design Modified Delphi method with a consensus conference of 55 international experts, several subsequent meetings of subgroups and key individuals, teleconferences, and electronic-based discussion among subgroups and among the entire committee. This process was conducted independently of any industry funding. Methods We used the GRADE system to guide assessment of quality of evidence from high (A) to very low (D) and to determine the strength of recommendations. A strong recommendation [1] indicates that an intervention's desirable effects clearly outweigh its undesirable effects (risk, burden, cost), or clearly do not. Weak recommendations [2] indicate that the tradeoff between desirable and undesirable effects is less clear. The grade of strong or weak is considered of greater clinical importance than a difference in letter level of quality of evidence. In areas without complete agreement, a formal process of resolution was developed and applied. Recommendations are grouped into those directly targeting severe sepsis, recommendations targeting general care of the critically ill patient that are considered high priority in severe sepsis, and pediatric considerations. Results Key recommendations, listed by category, include: early goal-directed resuscitation of the septic patient during the first 6 hrs after recognition (1C); blood cultures prior to antibiotic therapy (1C); imaging studies performed promptly to confirm potential source of infection (1C); administration of broad-spectrum antibiotic therapy within 1 hr of diagnosis of septic shock (1B) and severe sepsis without septic shock (1D); reassessment of antibiotic therapy with microbiology and clinical data to narrow coverage, when appropriate (1C); a usual 7–10 days of antibiotic therapy guided by clinical response (1D); source control with attention to the balance of risks and benefits of the chosen method (1C); administration of either crystalloid or colloid fluid resuscitation (1B); fluid challenge to restore mean circulating filling pressure (1C); reduction in rate of fluid administration with rising filing pressures and no improvement in tissue perfusion (1D); vasopressor preference for norepinephrine or dopamine to maintain an initial target of mean arterial pressure ≥ 65 mm Hg (1C); dobutamine inotropic therapy when cardiac output remains low despite fluid resuscitation and combined inotropic/vasopressor therapy (1C); stress-dose steroid therapy given only in septic shock after blood pressure is identified to be poorly responsive to fluid and vasopressor therapy (2C); recombinant activated protein C in patients with severe sepsis and clinical assessment of high risk for death (2B except 2C for post-operative patients). In the absence of tissue hypoperfusion, coronary artery disease, or acute hemorrhage, target a hemoglobin of 7–9 g/dL (1B); a low tidal volume (1B) and limitation of inspiratory plateau pressure strategy (1C) for acute lung injury (ALI)/acute respiratory distress syndrome (ARDS); application of at least a minimal amount of positive end-expiratory pressure in acute lung injury (1C); head of bed elevation in mechanically ventilated patients unless contraindicated (1B); avoiding routine use of pulmonary artery catheters in ALI/ARDS (1A); to decrease days of mechanical ventilation and ICU length of stay, a conservative fluid strategy for patients with established ALI/ARDS who are not in shock (1C); protocols for weaning and sedation/analgesia (1B); using either intermittent bolus sedation or continuous infusion sedation with daily interruptions or lightening (1B); avoidance of neuromuscular blockers, if at all possible (1B); institution of glycemic control (1B) targeting a blood glucose < 150 mg/dL after initial stabilization ( 2C ); equivalency of continuous veno-veno hemofiltration or intermittent hemodialysis (2B); prophylaxis for deep vein thrombosis (1A); use of stress ulcer prophylaxis to prevent upper GI bleeding using H2 blockers (1A) or proton pump inhibitors (1B); and consideration of limitation of support where appropriate (1D). Recommendations specific to pediatric severe sepsis include: greater use of physical examination therapeutic end points (2C); dopamine as the first drug of choice for hypotension (2C); steroids only in children with suspected or proven adrenal insufficiency (2C); a recommendation against the use of recombinant activated protein C in children (1B). Conclusion There was strong agreement among a large cohort of international experts regarding many level 1 recommendations for the best current care of patients with severe sepsis. Evidenced-based recommendations regarding the acute management of sepsis and septic shock are the first step toward improved outcomes for this important group of critically ill patients. PMID:18058085

European Association of Cardiovascular Imaging/Cardiovascular Imaging Department of the Brazilian Society of Cardiology recommendations for the use of cardiac imaging to assess and follow patients after heart transplantation.

PubMed

Badano, Luigi P; Miglioranza, Marcelo H; Edvardsen, Thor; Colafranceschi, Alexandre Siciliano; Muraru, Denisa; Bacal, Fernando; Nieman, Koen; Zoppellaro, Giacomo; Marcondes Braga, Fabiana G; Binder, Thomas; Habib, Gilbert; Lancellotti, Patrizio

2015-09-01

The cohort of long-term survivors of heart transplant is expanding, and the assessment of these patients requires specific knowledge of the surgical techniques employed to implant the donor heart, the physiology of the transplanted heart, complications of invasive tests routinely performed to detect graft rejection (GR), and the specific pathologies that may affect the transplanted heart. A joint EACVI/Brazilian cardiovascular imaging writing group committee has prepared these recommendations to provide a practical guide to echocardiographers involved in the follow-up of heart transplant patients and a framework for standardized and efficient use of cardiovascular imaging after heart transplant. Since the transplanted heart is smaller than the recipient's dilated heart, the former is usually located more medially in the mediastinum and tends to be rotated clockwise. Therefore, standard views with conventional two-dimensional (2D) echocardiography are often difficult to obtain generating a large variability from patient to patient. Therefore, in echocardiography laboratories equipped with three-dimensional echocardiography (3DE) scanners and specific expertise with the technique, 3DE may be a suitable alternative to conventional 2D echocardiography to assess the size and the function of cardiac chambers. 3DE measurement of left (LV) and right ventricular (RV) size and function are more accurate and reproducible than conventional 2D calculations. However, clinicians should be aware that cardiac chamber volumes obtained with 3DE cannot be compared with those obtained with 2D echocardiography. To assess cardiac chamber morphology and function during follow-up studies, it is recommended to obtain a comprehensive echocardiographic study at 6 months from the cardiac transplantation as a baseline and make a careful quantitation of cardiac chamber size, RV systolic function, both systolic and diastolic parameters of LV function, and pulmonary artery pressure. Subsequent echocardiographic studies should be interpreted in comparison with the data obtained from the 6-month study. An echocardiographic study, which shows no change from the baseline study, has a high negative predictive value for GR. There is no single systolic or diastolic parameter that can be reliably used to diagnose GR. However, in case several parameters are abnormal, the likelihood of GR increases. When an abnormality is detected, careful revision of images of the present and baseline study (side-by-side) is highly recommended. Global longitudinal strain (GLS) is a suitable parameter to diagnose subclinical allograft dysfunction, regardless of aetiology, by comparing the changes occurring during serial evaluations. Evaluation of GLS could be used in association with endomyocardial biopsy (EMB) to characterize and monitor an acute GR or global dysfunction episode. RV size and function at baseline should be assessed using several parameters, which do not exclusively evaluate longitudinal function. At follow-up echocardiogram, all these parameters should be compared with the baseline values. 3DE may provide a more accurate and comprehensive assessment of RV size and function. Moreover, due to the unpredictable shape of the atria in transplanted patients, atrial volume should be measured using the discs' summation algorithm (biplane algorithm for the left atrium) or 3DE. Tricuspid regurgitation should be looked for and properly assessed in all echocardiographic studies. In case of significant changes in severity of tricuspid regurgitation during follow-up, a 2D/3D and colour Doppler assessment of its severity and mechanisms should be performed. Aortic and mitral valves should be evaluated according to current recommendations. Pericardial effusion should be serially evaluated regarding extent, location, and haemodynamic impact. In case of newly detected pericardial effusion, GR should be considered taking into account the overall echocardiographic assessment and patient evaluation. Dobutamine stress echocardiography might be a suitable alternative to routine coronary angiography to assess cardiac allograft vasculopathy (CAV) at centres with adequate experience with the methodology. Coronary flow reserve and/or contrast infusion to assess myocardial perfusion might be combined with stress echocardiography to improve the accuracy of the test. In addition to its role in monitoring cardiac chamber function and in diagnosis the occurrence of GR and/or CAV, in experienced centres, echocardiography might be an alternative to fluoroscopy to guide EMB, particularly in children and young women, since echocardiography avoids repeated X-ray exposure, permits visualization of soft tissues and safer performance of biopsies of different RV regions. Finally, in addition to the indications about when and how to use echocardiography, the document also addresses the role of the other cardiovascular imaging modalities during follow-up of heart transplant patients. In patients with inadequate acoustic window and contraindication to contrast agents, pharmacological SPECT is an alternative imaging modality to detect CAV in heart transplant patients. However, in centres with adequate expertise, intravascular ultrasound (IVUS) in conjunction with coronary angiography with a baseline study at 4-6 weeks and at 1 year after heart transplant should be performed to exclude donor coronary artery disease, to detect rapidly progressive CAV, and to provide prognostic information. Despite the fact that coronary angiography is the current gold-standard method for the detection of CAV, the use of IVUS should also be considered when there is a discrepancy between non-invasive imaging tests and coronary angiography concerning the presence of CAV. In experienced centres, computerized tomography coronary angiography is a good alternative to coronary angiography to detect CAV. In patients with a persistently high heart rate, scanners that provide high temporal resolution, such as dual-source systems, provide better image quality. Finally, in patients with insufficient acoustic window, cardiac magnetic resonance is an alternative to echocardiography to assess cardiac chamber volumes and function and to exclude acute GR and CAV in a surveillance protocol. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.

Ethical pitfalls in neonatal comparative effectiveness trials.

PubMed

Modi, Neena

2014-01-01

Evidence-based medicine has been embraced wholeheartedly, and rightly so, as the best approach for reducing clinical uncertainty and ensuring that patients receive treatment and care that are efficacious (i.e. they work) and effective (i.e. they work in real life). High-quality evidence comes from high-quality clinical research. It would hence be reasonable to assume that these two would form a closely integrated partnership. Alas, this is not yet the case. So many uncertainties in medical care relate to treatments and practices already widely in use. In neonatal medicine, for example, some of us use protein-carbohydrate fortification of human milk and some of us do not, some of us stop enteral feeds during blood transfusions whereas some of us do not, some of us reach for dopamine when blood pressure falls while some of us use dobutamine. For our patients, these uncertainties represent a lottery, the throw of the dice that determines whether they receive the treatment advocated by Dr. A or Dr. B. They deserve better than this. Randomization is considered the gold standard approach to eliminating the clinician bias that very often dominates the choice of treatments. Randomization reduces the influence on outcomes of confounding by unknown factors, and ensures that every patient has a fair and equal chance of receiving the best possible treatment when this is, in fact, not known. In an ideal world, every medical uncertainty would be addressed in this way. The evaluation of treatments that are in accepted use has been termed 'comparative effectiveness research', i.e. the comparison of existing healthcare interventions to determine which works best, for whom and under which circumstances. Recently a long-standing uncertainty, the optimum saturation target for preterm babies receiving oxygen was put to the test of randomization. The accepted standard-of-care saturation range of 85-95% has been used for a considerable time and its use is intended to avoid both levels of oxygen that are too low or too high. Investigators in the UK, Australia, New Zealand and the USA designed randomized controlled trials to provide more precise guidance, by determining whether targeting the lower end of the accepted range (85-89%) resulted in reduced retinopathy of prematurity when compared with the upper end of the accepted range (91-95%). Between 2004 and 2009, the US SUPPORT trial (Surfactant, Positive Pressure and Oxygenation Randomized Trial) recruited approximately 1,300 infants and showed that babies at the higher end of the recommended oxygen saturation range had a greater incidence of retinopathy of prematurity, but that, unexpectedly, babies at the lower end had a higher risk of death [1]. The data monitoring committees of the BOOST II (Oxygen Saturation and Outcomes in Preterm Infants) trials in the UK, Australia and New Zealand reviewed their interim data, confirmed the higher risk of death in babies randomized to the lower saturation range, and halted further recruitment [2]. Without the trials, the lower saturation target would have continued to be applied to many babies, and many would have died as a result. Though many uncertainties remain, the trials facilitated advances in care. However, in March 2013, the lead investigators for the SUPPORT trial were informed by the US 'Office for Human Research Protections' that they were 'in violation of the regulatory requirements for informed consent, stemming from the failure to describe the reasonably foreseeable risks of blindness, neurological damage and death' [3]. This extraordinary conclusion indicates that the US regulators considered the researchers to be at fault for failing to foresee an unexpected trial result, and for randomizing babies to receive oxygen within the accepted standard-of-care limits. The ruling further implies that the regulators consider that clinicians are acting ethically when they deliver an accepted but non-evidence-based treatment based upon their personal bias, but are acting unethically when they make the selection by randomization. Clearly, there is a gulf between the view of the medical profession and that of the regulators regarding the ethical and scientific validity of randomization as a means to select treatments in comparative effectiveness research aimed at reducing uncertainties in care. What are the ways forward? I suggest that, in order for medicine to advance, a paradigm shift is necessary, involving a deeper public (and regulator) understanding of randomization as the fairest approach to allocating treatments that are in wide and accepted use, but where the evidence base is actually uncertain, so that the chance of receiving the as yet unknown best treatment is unaffected by clinician bias, and where care is delivered along a clearly designed, closely monitored pathway. In practice, peer review, regulatory approval, patient involvement and the delivery of explanation and information would be the same as for research involving experimental treatments. The key difference would be that randomization would be the recommended default and patients would be offered the opportunity to opt out, rather than be invited to opt in. For neonatal medicine, this would reduce the risk of 'injurious misconception', where trial entry is inappropriately rejected by parents because of an exaggerated and disproportionate perception of risk [4] that is brought on or magnified by the burden of making decisions at this difficult and stressful time. Randomization to treatments that fall within accepted practice and are considered standard-of-care involves no research-related risks to participants, and as trial data can increasingly be extracted from electronic clinical records [5], the costs and burden of data collection placed upon clinical teams will be minimized and, ultimately, the resolution of uncertainties about treatment can be hastened. It should also be noted that this approach fulfils the four cardinal principles of research ethics, namely: autonomy, justice, beneficence and nonmaleficence as well as upholding the responsibility of all doctors to strive to reduce uncertainty in the care they provide to their patients [6].

Surviving Sepsis Campaign: international guidelines for management of severe sepsis and septic shock, 2012.

PubMed

Dellinger, R P; Levy, Mitchell M; Rhodes, Andrew; Annane, Djillali; Gerlach, Herwig; Opal, Steven M; Sevransky, Jonathan E; Sprung, Charles L; Douglas, Ivor S; Jaeschke, Roman; Osborn, Tiffany M; Nunnally, Mark E; Townsend, Sean R; Reinhart, Konrad; Kleinpell, Ruth M; Angus, Derek C; Deutschman, Clifford S; Machado, Flavia R; Rubenfeld, Gordon D; Webb, Steven; Beale, Richard J; Vincent, Jean-Louis; Moreno, Rui

2013-02-01

To provide an update to the "Surviving Sepsis Campaign Guidelines for Management of Severe Sepsis and Septic Shock," last published in 2008. A consensus committee of 68 international experts representing 30 international organizations was convened. Nominal groups were assembled at key international meetings (for those committee members attending the conference). A formal conflict of interest policy was developed at the onset of the process and enforced throughout. The entire guidelines process was conducted independent of any industry funding. A stand-alone meeting was held for all subgroup heads, co- and vice-chairs, and selected individuals. Teleconferences and electronic-based discussion among subgroups and among the entire committee served as an integral part of the development. The authors were advised to follow the principles of the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system to guide assessment of quality of evidence from high (A) to very low (D) and to determine the strength of recommendations as strong (1) or weak (2). The potential drawbacks of making strong recommendations in the presence of low-quality evidence were emphasized. Recommendations were classified into three groups: (1) those directly targeting severe sepsis; (2) those targeting general care of the critically ill patient and considered high priority in severe sepsis; and (3) pediatric considerations. Key recommendations and suggestions, listed by category, include: early quantitative resuscitation of the septic patient during the first 6 h after recognition (1C); blood cultures before antibiotic therapy (1C); imaging studies performed promptly to confirm a potential source of infection (UG); administration of broad-spectrum antimicrobials therapy within 1 h of the recognition of septic shock (1B) and severe sepsis without septic shock (1C) as the goal of therapy; reassessment of antimicrobial therapy daily for de-escalation, when appropriate (1B); infection source control with attention to the balance of risks and benefits of the chosen method within 12 h of diagnosis (1C); initial fluid resuscitation with crystalloid (1B) and consideration of the addition of albumin in patients who continue to require substantial amounts of crystalloid to maintain adequate mean arterial pressure (2C) and the avoidance of hetastarch formulations (1B); initial fluid challenge in patients with sepsis-induced tissue hypoperfusion and suspicion of hypovolemia to achieve a minimum of 30 mL/kg of crystalloids (more rapid administration and greater amounts of fluid may be needed in some patients (1C); fluid challenge technique continued as long as hemodynamic improvement is based on either dynamic or static variables (UG); norepinephrine as the first-choice vasopressor to maintain mean arterial pressure ≥65 mmHg (1B); epinephrine when an additional agent is needed to maintain adequate blood pressure (2B); vasopressin (0.03 U/min) can be added to norepinephrine to either raise mean arterial pressure to target or to decrease norepinephrine dose but should not be used as the initial vasopressor (UG); dopamine is not recommended except in highly selected circumstances (2C); dobutamine infusion administered or added to vasopressor in the presence of (a) myocardial dysfunction as suggested by elevated cardiac filling pressures and low cardiac output, or (b) ongoing signs of hypoperfusion despite achieving adequate intravascular volume and adequate mean arterial pressure (1C); avoiding use of intravenous hydrocortisone in adult septic shock patients if adequate fluid resuscitation and vasopressor therapy are able to restore hemodynamic stability (2C); hemoglobin target of 7-9 g/dL in the absence of tissue hypoperfusion, ischemic coronary artery disease, or acute hemorrhage (1B); low tidal volume (1A) and limitation of inspiratory plateau pressure (1B) for acute respiratory distress syndrome (ARDS); application of at least a minimal amount of positive end-expiratory pressure (PEEP) in ARDS (1B); higher rather than lower level of PEEP for patients with sepsis-induced moderate or severe ARDS (2C); recruitment maneuvers in sepsis patients with severe refractory hypoxemia due to ARDS (2C); prone positioning in sepsis-induced ARDS patients with a PaO (2)/FiO (2) ratio of ≤100 mm Hg in facilities that have experience with such practices (2C); head-of-bed elevation in mechanically ventilated patients unless contraindicated (1B); a conservative fluid strategy for patients with established ARDS who do not have evidence of tissue hypoperfusion (1C); protocols for weaning and sedation (1A); minimizing use of either intermittent bolus sedation or continuous infusion sedation targeting specific titration endpoints (1B); avoidance of neuromuscular blockers if possible in the septic patient without ARDS (1C); a short course of neuromuscular blocker (no longer than 48 h) for patients with early ARDS and a PaO (2)/FI O (2) <150 mm Hg (2C); a protocolized approach to blood glucose management commencing insulin dosing when two consecutive blood glucose levels are >180 mg/dL, targeting an upper blood glucose ≤180 mg/dL (1A); equivalency of continuous veno-venous hemofiltration or intermittent hemodialysis (2B); prophylaxis for deep vein thrombosis (1B); use of stress ulcer prophylaxis to prevent upper gastrointestinal bleeding in patients with bleeding risk factors (1B); oral or enteral (if necessary) feedings, as tolerated, rather than either complete fasting or provision of only intravenous glucose within the first 48 h after a diagnosis of severe sepsis/septic shock (2C); and addressing goals of care, including treatment plans and end-of-life planning (as appropriate) (1B), as early as feasible, but within 72 h of intensive care unit admission (2C). Recommendations specific to pediatric severe sepsis include: therapy with face mask oxygen, high flow nasal cannula oxygen, or nasopharyngeal continuous PEEP in the presence of respiratory distress and hypoxemia (2C), use of physical examination therapeutic endpoints such as capillary refill (2C); for septic shock associated with hypovolemia, the use of crystalloids or albumin to deliver a bolus of 20 mL/kg of crystalloids (or albumin equivalent) over 5-10 min (2C); more common use of inotropes and vasodilators for low cardiac output septic shock associated with elevated systemic vascular resistance (2C); and use of hydrocortisone only in children with suspected or proven "absolute"' adrenal insufficiency (2C). Strong agreement existed among a large cohort of international experts regarding many level 1 recommendations for the best care of patients with severe sepsis. Although a significant number of aspects of care have relatively weak support, evidence-based recommendations regarding the acute management of sepsis and septic shock are the foundation of improved outcomes for this important group of critically ill patients.

Surviving sepsis campaign: international guidelines for management of severe sepsis and septic shock: 2012.

PubMed

Dellinger, R Phillip; Levy, Mitchell M; Rhodes, Andrew; Annane, Djillali; Gerlach, Herwig; Opal, Steven M; Sevransky, Jonathan E; Sprung, Charles L; Douglas, Ivor S; Jaeschke, Roman; Osborn, Tiffany M; Nunnally, Mark E; Townsend, Sean R; Reinhart, Konrad; Kleinpell, Ruth M; Angus, Derek C; Deutschman, Clifford S; Machado, Flavia R; Rubenfeld, Gordon D; Webb, Steven A; Beale, Richard J; Vincent, Jean-Louis; Moreno, Rui

2013-02-01

To provide an update to the "Surviving Sepsis Campaign Guidelines for Management of Severe Sepsis and Septic Shock," last published in 2008. A consensus committee of 68 international experts representing 30 international organizations was convened. Nominal groups were assembled at key international meetings (for those committee members attending the conference). A formal conflict of interest policy was developed at the onset of the process and enforced throughout. The entire guidelines process was conducted independent of any industry funding. A stand-alone meeting was held for all subgroup heads, co- and vice-chairs, and selected individuals. Teleconferences and electronic-based discussion among subgroups and among the entire committee served as an integral part of the development. The authors were advised to follow the principles of the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system to guide assessment of quality of evidence from high (A) to very low (D) and to determine the strength of recommendations as strong (1) or weak (2). The potential drawbacks of making strong recommendations in the presence of low-quality evidence were emphasized. Some recommendations were ungraded (UG). Recommendations were classified into three groups: 1) those directly targeting severe sepsis; 2) those targeting general care of the critically ill patient and considered high priority in severe sepsis; and 3) pediatric considerations. Key recommendations and suggestions, listed by category, include: early quantitative resuscitation of the septic patient during the first 6 hrs after recognition (1C); blood cultures before antibiotic therapy (1C); imaging studies performed promptly to confirm a potential source of infection (UG); administration of broad-spectrum antimicrobials therapy within 1 hr of recognition of septic shock (1B) and severe sepsis without septic shock (1C) as the goal of therapy; reassessment of antimicrobial therapy daily for de-escalation, when appropriate (1B); infection source control with attention to the balance of risks and benefits of the chosen method within 12 hrs of diagnosis (1C); initial fluid resuscitation with crystalloid (1B) and consideration of the addition of albumin in patients who continue to require substantial amounts of crystalloid to maintain adequate mean arterial pressure (2C) and the avoidance of hetastarch formulations (1C); initial fluid challenge in patients with sepsis-induced tissue hypoperfusion and suspicion of hypovolemia to achieve a minimum of 30 mL/kg of crystalloids (more rapid administration and greater amounts of fluid may be needed in some patients) (1C); fluid challenge technique continued as long as hemodynamic improvement, as based on either dynamic or static variables (UG); norepinephrine as the first-choice vasopressor to maintain mean arterial pressure ≥ 65 mm Hg (1B); epinephrine when an additional agent is needed to maintain adequate blood pressure (2B); vasopressin (0.03 U/min) can be added to norepinephrine to either raise mean arterial pressure to target or to decrease norepinephrine dose but should not be used as the initial vasopressor (UG); dopamine is not recommended except in highly selected circumstances (2C); dobutamine infusion administered or added to vasopressor in the presence of a) myocardial dysfunction as suggested by elevated cardiac filling pressures and low cardiac output, or b) ongoing signs of hypoperfusion despite achieving adequate intravascular volume and adequate mean arterial pressure (1C); avoiding use of intravenous hydrocortisone in adult septic shock patients if adequate fluid resuscitation and vasopressor therapy are able to restore hemodynamic stability (2C); hemoglobin target of 7-9 g/dL in the absence of tissue hypoperfusion, ischemic coronary artery disease, or acute hemorrhage (1B); low tidal volume (1A) and limitation of inspiratory plateau pressure (1B) for acute respiratory distress syndrome (ARDS); application of at least a minimal amount of positive end-expiratory pressure (PEEP) in ARDS (1B); higher rather than lower level of PEEP for patients with sepsis-induced moderate or severe ARDS (2C); recruitment maneuvers in sepsis patients with severe refractory hypoxemia due to ARDS (2C); prone positioning in sepsis-induced ARDS patients with a PaO2/FIO2 ratio of ≤ 100 mm Hg in facilities that have experience with such practices (2C); head-of-bed elevation in mechanically ventilated patients unless contraindicated (1B); a conservative fluid strategy for patients with established ARDS who do not have evidence of tissue hypoperfusion (1C); protocols for weaning and sedation (1A); minimizing use of either intermittent bolus sedation or continuous infusion sedation targeting specific titration endpoints (1B); avoidance of neuromuscular blockers if possible in the septic patient without ARDS (1C); a short course of neuromuscular blocker (no longer than 48 hrs) for patients with early ARDS and a Pao2/Fio2 < 150 mm Hg (2C); a protocolized approach to blood glucose management commencing insulin dosing when two consecutive blood glucose levels are > 180 mg/dL, targeting an upper blood glucose ≤ 180 mg/dL (1A); equivalency of continuous veno-venous hemofiltration or intermittent hemodialysis (2B); prophylaxis for deep vein thrombosis (1B); use of stress ulcer prophylaxis to prevent upper gastrointestinal bleeding in patients with bleeding risk factors (1B); oral or enteral (if necessary) feedings, as tolerated, rather than either complete fasting or provision of only intravenous glucose within the first 48 hrs after a diagnosis of severe sepsis/septic shock (2C); and addressing goals of care, including treatment plans and end-of-life planning (as appropriate) (1B), as early as feasible, but within 72 hrs of intensive care unit admission (2C). Recommendations specific to pediatric severe sepsis include: therapy with face mask oxygen, high flow nasal cannula oxygen, or nasopharyngeal continuous PEEP in the presence of respiratory distress and hypoxemia (2C), use of physical examination therapeutic endpoints such as capillary refill (2C); for septic shock associated with hypovolemia, the use of crystalloids or albumin to deliver a bolus of 20 mL/kg of crystalloids (or albumin equivalent) over 5 to 10 mins (2C); more common use of inotropes and vasodilators for low cardiac output septic shock associated with elevated systemic vascular resistance (2C); and use of hydrocortisone only in children with suspected or proven "absolute"' adrenal insufficiency (2C). Strong agreement existed among a large cohort of international experts regarding many level 1 recommendations for the best care of patients with severe sepsis. Although a significant number of aspects of care have relatively weak support, evidence-based recommendations regarding the acute management of sepsis and septic shock are the foundation of improved outcomes for this important group of critically ill patients.

Cardiac magnetic resonance imaging for the diagnosis of coronary artery disease: an evidence-based analysis.

PubMed

2010-01-01

In July 2009, the Medical Advisory Secretariat (MAS) began work on Non-Invasive Cardiac Imaging Technologies for the Diagnosis of Coronary Artery Disease (CAD), an evidence-based review of the literature surrounding different cardiac imaging modalities to ensure that appropriate technologies are accessed by patients suspected of having CAD. This project came about when the Health Services Branch at the Ministry of Health and Long-Term Care asked MAS to provide an evidentiary platform on effectiveness and cost-effectiveness of non-invasive cardiac imaging modalities.After an initial review of the strategy and consultation with experts, MAS identified five key non-invasive cardiac imaging technologies for the diagnosis of CAD. Evidence-based analyses have been prepared for each of these five imaging modalities: cardiac magnetic resonance imaging, single photon emission computed tomography, 64-slice computed tomographic angiography, stress echocardiography, and stress echocardiography with contrast. For each technology, an economic analysis was also completed (where appropriate). A summary decision analytic model was then developed to encapsulate the data from each of these reports (available on the OHTAC and MAS website).The Non-Invasive Cardiac Imaging Technologies for the Diagnosis of Coronary Artery Disease series is made up of the following reports, which can be publicly accessed at the MAS website at: www.health.gov.on.ca/mas or at www.health.gov.on.ca/english/providers/program/mas/mas_about.htmlSINGLE PHOTON EMISSION COMPUTED TOMOGRAPHY FOR THE DIAGNOSIS OF CORONARY ARTERY DISEASE: An Evidence-Based AnalysisSTRESS ECHOCARDIOGRAPHY FOR THE DIAGNOSIS OF CORONARY ARTERY DISEASE: An Evidence-Based AnalysisSTRESS ECHOCARDIOGRAPHY WITH CONTRAST FOR THE DIAGNOSIS OF CORONARY ARTERY DISEASE: An Evidence-Based Analysis64-Slice Computed Tomographic Angiography for the Diagnosis of Coronary Artery Disease: An Evidence-Based AnalysisCARDIAC MAGNETIC RESONANCE IMAGING FOR THE DIAGNOSIS OF CORONARY ARTERY DISEASE: An Evidence-Based AnalysisPease note that two related evidence-based analyses of non-invasive cardiac imaging technologies for the assessment of myocardial viability are also available on the MAS website:POSITRON EMISSION TOMOGRAPHY FOR THE ASSESSMENT OF MYOCARDIAL VIABILITY: An Evidence-Based AnalysisMAGNETIC RESONANCE IMAGING FOR THE ASSESSMENT OF MYOCARDIAL VIABILITY: an Evidence-Based AnalysisThe Toronto Health Economics and Technology Assessment Collaborative has also produced an associated economic report entitled:The Relative Cost-effectiveness of Five Non-invasive Cardiac Imaging Technologies for Diagnosing Coronary Artery Disease in Ontario [Internet]. Available from: http://theta.utoronto.ca/reports/?id=7 OBJECTIVE: The objective of this analysis was to determine the diagnostic accuracy of cardiac magnetic resonance imaging (MRI) for the diagnosis of patients with known/suspected coronary artery disease (CAD) compared to coronary angiography. Stress cardiac MRI is a non-invasive, x-ray free imaging technique that takes approximately 30 to 45 minutes to complete and can be performed using to two different methods, a) perfusion imaging following a first pass of an intravenous bolus of gadolinium contrast, or b) wall motion imaging. Stress is induced pharmacologically with either dobutamine, dipyridamole, or adenosine, as physical exercise is difficult to perform within the magnet bore and often induces motion artifacts. Alternatives to stress cardiac perfusion MRI include stress single-photon emission computed tomography (SPECT) and stress echocardiography (ECHO). The advantage of cardiac MRI is that it does not pose the radiation burden associated with SPECT. During the same sitting, cardiac MRI can also assess left and right ventricular dimensions, viability, and cardiac mass. It may also mitigate the need for invasive diagnostic coronary angiography in patients with intermediate risk factors for CAD. EVIDENCE-BASED ANALYSIS: A literature search was performed on October 9, 2009 using OVID MEDLINE, MEDLINE In-Process and Other Non-Indexed Citations, EMBASE, the Cumulative Index to Nursing & Allied Health Literature (CINAHL), the Cochrane Library, and the International Agency for Health Technology Assessment (INAHTA) for studies published from January 1, 2005 to October 9, 2008. Abstracts were reviewed by a single reviewer and, for those studies meeting the eligibility criteria, full-text articles were obtained. Reference lists were also examined for any relevant studies not identified through the search. Articles with unknown eligibility were reviewed with a second clinical epidemiologist and then a group of epidemiologists until consensus was established. The quality of evidence was assessed as high, moderate, low or very low according to GRADE methodology. Given the large amount of clinical heterogeneity of the articles meeting the inclusion criteria, as well as suggestions from an Expert Advisory Panel Meeting held on October 5, 2009, the inclusion criteria were revised to examine the effectiveness of cardiac MRI for the detection of CAD. Inclusion CriteriaExclusion CriteriaHeath technology assessments, systematic reviews, randomized controlled trials, observational studies≥20 adult patients enrolled.Published 2004-2009Licensed by Health CanadaFor diagnosis of CAD:Reference standard is coronary angiographySignificant CAD defined as ≥ 50% coronary stenosisPatients with suspected or known CADReported results by patient, not segmentNon-English studiesGrey literaturePlanar imagingMUGAPatients with recent MI (i.e., within 1 month)Patients with non-ischemic heart diseaseStudies done exclusively in special populations (e.g., women, diabetics) Sensitivity and specificityArea under the curve (AUC)Diagnostic odds ratio (DOR) SUMMARY OF FINDINGS: Stress cardiac MRI using perfusion analysis yielded a pooled sensitivity of 0.91 (95% CI: 0.89 to 0.92) and specificity of 0.79 (95% CI: 0.76 to 0.82) for the detection of CAD.Stress cardiac MRI using wall motion analysis yielded a pooled sensitivity of 0.81 (95% CI: 0.77 to 0.84) and specificity of 0.85 (95% CI: 0.81 to 0.89) for the detection of CAD.Based on DORs, there was no significant difference between pooled stress cardiac MRI using perfusion analysis and pooled stress cardiac MRI using wall motion analysis (P=0.26) for the detection of CAD.Pooled subgroup analysis of stress cardiac MRI using perfusion analysis showed no significant difference in the DORs between 1.5T and 3T MRI (P=0.72) for the detection of CAD.One study (N=60) was identified that examined stress cardiac MRI using wall motion analysis with a 3T MRI. The sensitivity and specificity of 3T MRI were 0.64 (95% CI: 0.44 to 0.81) and 1.00 (95% CI: 0.89 to 1.00), respectively, for the detection of CAD.The effectiveness of stress cardiac MRI for the detection of CAD in unstable patients with acute coronary syndrome was reported in only one study (N=35). Using perfusion analysis, the sensitivity and specificity were 0.72 (95% CI: 0.53 to 0.87) and 1.00 (95% CI: 0.54 to 1.00), respectively, for the detection of CAD. According to an expert consultant, in Ontario: Stress first pass perfusion is currently performed in small numbers in London (London Health Sciences Centre) and Toronto (University Health Network at the Toronto General Hospital site and Sunnybrook Health Sciences Centre).Stress wall motion is only performed as part of research protocols and not very often.Cardiac MRI machines use 1.5T almost exclusively, with 3T used in research for first pass perfusion.On November 25 2009, the Cardiac Imaging Expert Advisory Panel met and made the following comments about stress cardiac MRI for perfusion analysis: Accessibility to cardiac MRI is limited and generally used to assess structural abnormalities. Most MRIs in Ontario are already in 24-hour, constant use and it would thus be difficult to add cardiac MRI for CAD diagnosis as an additional indication.The performance of cardiac MRI for the diagnosis of CAD can be technically challenging. The quality of the body of evidence was assessed according to the GRADE Working Group criteria for diagnostic tests. For perfusion analysis, the overall quality was determined to be low and for wall motion analysis the overall quality was very low.

Cardiac Magnetic Resonance Imaging for the Diagnosis of Coronary Artery Disease

PubMed Central

2010-01-01

Executive Summary In July 2009, the Medical Advisory Secretariat (MAS) began work on Non-Invasive Cardiac Imaging Technologies for the Diagnosis of Coronary Artery Disease (CAD), an evidence-based review of the literature surrounding different cardiac imaging modalities to ensure that appropriate technologies are accessed by patients suspected of having CAD. This project came about when the Health Services Branch at the Ministry of Health and Long-Term Care asked MAS to provide an evidentiary platform on effectiveness and cost-effectiveness of non-invasive cardiac imaging modalities. After an initial review of the strategy and consultation with experts, MAS identified five key non-invasive cardiac imaging technologies for the diagnosis of CAD. Evidence-based analyses have been prepared for each of these five imaging modalities: cardiac magnetic resonance imaging, single photon emission computed tomography, 64-slice computed tomographic angiography, stress echocardiography, and stress echocardiography with contrast. For each technology, an economic analysis was also completed (where appropriate). A summary decision analytic model was then developed to encapsulate the data from each of these reports (available on the OHTAC and MAS website). The Non-Invasive Cardiac Imaging Technologies for the Diagnosis of Coronary Artery Disease series is made up of the following reports, which can be publicly accessed at the MAS website at: www.health.gov.on.ca/mas or at www.health.gov.on.ca/english/providers/program/mas/mas_about.html Single Photon Emission Computed Tomography for the Diagnosis of Coronary Artery Disease: An Evidence-Based Analysis Stress Echocardiography for the Diagnosis of Coronary Artery Disease: An Evidence-Based Analysis Stress Echocardiography with Contrast for the Diagnosis of Coronary Artery Disease: An Evidence-Based Analysis 64-Slice Computed Tomographic Angiography for the Diagnosis of Coronary Artery Disease: An Evidence-Based Analysis Cardiac Magnetic Resonance Imaging for the Diagnosis of Coronary Artery Disease: An Evidence-Based Analysis Pease note that two related evidence-based analyses of non-invasive cardiac imaging technologies for the assessment of myocardial viability are also available on the MAS website: Positron Emission Tomography for the Assessment of Myocardial Viability: An Evidence-Based Analysis Magnetic Resonance Imaging for the Assessment of Myocardial Viability: an Evidence-Based Analysis The Toronto Health Economics and Technology Assessment Collaborative has also produced an associated economic report entitled: The Relative Cost-effectiveness of Five Non-invasive Cardiac Imaging Technologies for Diagnosing Coronary Artery Disease in Ontario [Internet]. Available from: http://theta.utoronto.ca/reports/?id=7 Objective The objective of this analysis was to determine the diagnostic accuracy of cardiac magnetic resonance imaging (MRI) for the diagnosis of patients with known/suspected coronary artery disease (CAD) compared to coronary angiography. Cardiac MRI Stress cardiac MRI is a non-invasive, x-ray free imaging technique that takes approximately 30 to 45 minutes to complete and can be performed using to two different methods, a) perfusion imaging following a first pass of an intravenous bolus of gadolinium contrast, or b) wall motion imaging. Stress is induced pharmacologically with either dobutamine, dipyridamole, or adenosine, as physical exercise is difficult to perform within the magnet bore and often induces motion artifacts. Alternatives to stress cardiac perfusion MRI include stress single-photon emission computed tomography (SPECT) and stress echocardiography (ECHO). The advantage of cardiac MRI is that it does not pose the radiation burden associated with SPECT. During the same sitting, cardiac MRI can also assess left and right ventricular dimensions, viability, and cardiac mass. It may also mitigate the need for invasive diagnostic coronary angiography in patients with intermediate risk factors for CAD. Evidence-Based Analysis Literature Search A literature search was performed on October 9, 2009 using OVID MEDLINE, MEDLINE In-Process and Other Non-Indexed Citations, EMBASE, the Cumulative Index to Nursing & Allied Health Literature (CINAHL), the Cochrane Library, and the International Agency for Health Technology Assessment (INAHTA) for studies published from January 1, 2005 to October 9, 2008. Abstracts were reviewed by a single reviewer and, for those studies meeting the eligibility criteria, full-text articles were obtained. Reference lists were also examined for any relevant studies not identified through the search. Articles with unknown eligibility were reviewed with a second clinical epidemiologist and then a group of epidemiologists until consensus was established. The quality of evidence was assessed as high, moderate, low or very low according to GRADE methodology. Given the large amount of clinical heterogeneity of the articles meeting the inclusion criteria, as well as suggestions from an Expert Advisory Panel Meeting held on October 5, 2009, the inclusion criteria were revised to examine the effectiveness of cardiac MRI for the detection of CAD. Inclusion Criteria Exclusion Criteria Heath technology assessments, systematic reviews, randomized controlled trials, observational studies ≥20 adult patients enrolled. Published 2004-2009 Licensed by Health Canada For diagnosis of CAD: Reference standard is coronary angiography Significant CAD defined as ≥ 50% coronary stenosis Patients with suspected or known CAD Reported results by patient, not segment Non-English studies Grey literature Planar imaging MUGA Patients with recent MI (i.e., within 1 month) Patients with non-ischemic heart disease Studies done exclusively in special populations (e.g., women, diabetics) Outcomes of Interest Sensitivity and specificity Area under the curve (AUC) Diagnostic odds ratio (DOR) Summary of Findings Stress cardiac MRI using perfusion analysis yielded a pooled sensitivity of 0.91 (95% CI: 0.89 to 0.92) and specificity of 0.79 (95% CI: 0.76 to 0.82) for the detection of CAD. Stress cardiac MRI using wall motion analysis yielded a pooled sensitivity of 0.81 (95% CI: 0.77 to 0.84) and specificity of 0.85 (95% CI: 0.81 to 0.89) for the detection of CAD. Based on DORs, there was no significant difference between pooled stress cardiac MRI using perfusion analysis and pooled stress cardiac MRI using wall motion analysis (P=0.26) for the detection of CAD. Pooled subgroup analysis of stress cardiac MRI using perfusion analysis showed no significant difference in the DORs between 1.5T and 3T MRI (P=0.72) for the detection of CAD. One study (N=60) was identified that examined stress cardiac MRI using wall motion analysis with a 3T MRI. The sensitivity and specificity of 3T MRI were 0.64 (95% CI: 0.44 to 0.81) and 1.00 (95% CI: 0.89 to 1.00), respectively, for the detection of CAD. The effectiveness of stress cardiac MRI for the detection of CAD in unstable patients with acute coronary syndrome was reported in only one study (N=35). Using perfusion analysis, the sensitivity and specificity were 0.72 (95% CI: 0.53 to 0.87) and 1.00 (95% CI: 0.54 to 1.00), respectively, for the detection of CAD. Ontario Health System Impact Analysis According to an expert consultant, in Ontario: Stress first pass perfusion is currently performed in small numbers in London (London Health Sciences Centre) and Toronto (University Health Network at the Toronto General Hospital site and Sunnybrook Health Sciences Centre). Stress wall motion is only performed as part of research protocols and not very often. Cardiac MRI machines use 1.5T almost exclusively, with 3T used in research for first pass perfusion. On November 25 2009, the Cardiac Imaging Expert Advisory Panel met and made the following comments about stress cardiac MRI for perfusion analysis: Accessibility to cardiac MRI is limited and generally used to assess structural abnormalities. Most MRIs in Ontario are already in 24–hour, constant use and it would thus be difficult to add cardiac MRI for CAD diagnosis as an additional indication. The performance of cardiac MRI for the diagnosis of CAD can be technically challenging. GRADE Quality of Evidence for Cardiac MRI in the Diagnosis of CAD The quality of the body of evidence was assessed according to the GRADE Working Group criteria for diagnostic tests. For perfusion analysis, the overall quality was determined to be low and for wall motion analysis the overall quality was very low. PMID:23074389