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Andrew L Clark

Publications and source records attributed to Andrew L Clark.

At least 55 records · Page 3Linked to original sources

Poor relationship between exercise capacity and spirometric measurements in patients with more symptomatic heart failure.

BACKGROUND: The origin of exercise limitation in patients with chronic heart failure (CHF) is multifactorial, and the relative contributions of different abnormalities may vary with severity of heart failure symptoms. The aim of the current study was to determine the extent to which spirometric indices predict peak exercise capacity in patients with differing severity of symptoms. METHODS AND RESULTS: A total of 340 patients with left ventricular systolic dysfunction underwent spirometry, and a ramped, maximal exercise treadmill test with metabolic gas exchange measurements. For comparative purposes, a group of 174 aged-matched controls with no major structural heart disease (MSHD) was also included. In a stepwise linear regression model, forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC) were independent predictors of peak oxygen uptake (pVO2) in controls (r2= 18-25%; P = .001) and New York Heart Association (NYHA) I-II patients (r2= 16-18%; P = .001). No association between spirometric indices (FEV1/FVC) and pVO2 (r2= 1-2%; P > .05) was found in NYHA III-IV patients. CONCLUSION: In aged-matched controls with no MSHD, spirometric variables (FEV1/FVC) explain 18% to 25% of the variance in pVO2, and 16% to 18% of the variance in patients with NYHA class I-II symptoms. As symptoms worsen, the influence of spirometric variables on peak exercise capacity diminishes, and there is no such relation in the NYHA class III-IV patients.

Aged↗

The effects of long-term beta-blockade on the ventilatory responses to exercise in chronic heart failure.

AIMS: Chronic heart failure (CHF) patients complain of breathlessness and fatigue. Beta-blockers improve symptoms, echocardiograpahic variables and prognosis in CHF, but their effect on exercise capacity remains unclear. The aim of this study was to describe the effects of long-term beta-blocker therapy on metabolic gas exchange variables and ventilation during exercise in CHF patients. METHODS: 42 patients with symptomatic heart failure due to left ventricular systolic dysfunction (ejection fraction 33.2 (8.2)) on loop diuretics and angiotensin-converting enzyme inhibitors or angiotensin II antagonists, underwent exercise testing with metabolic gas exchange. They were then initiated onto and uptitrated to the maximum tolerated dose of beta-blockers. After 1 year of follow-up, patients were invited back for repeat testing. RESULTS: 35 patients attended for repeat exercise testing. Four patients had died, and three had not tolerated beta-blockade. After 1 year, exercise time was increased (487 (221) vs. 500 (217), p<0.05), and peak oxygen consumption and V(E)/V(CO(2)) slope were unchanged (20.9 (5.0) vs. 20.0 (5.4), p=0.15 and 36.7 (8.3) vs. 37.3 (7.8), p=0.70). Peak ventilation, (61.5 (12.9) vs. 57.1 (13.4), p<0.05), peak carbon dioxide production (1629 (404) vs. 1496 (375), p<0.02) and hence respiratory exchange ratio (1.02 (0.08) vs. 0.98 (0.06) p<0.02) and p<0.05) were reduced. Submaximal oxygen consumption and carbon dioxide production were lower at matched workloads. The slope relating symptoms to ventilation (Borg/V(E) slope) was less steep following beta-blockade (0.18 (0.09) vs. 0.15 (0.06), p<0.05). CONCLUSION: Long term beta-blocker therapy increases exercise time but not peak oxygen consumption, and reduces peak carbon dioxide production. CHF patients are less symptomatic for a given ventilation during exercise following beta-blocker treatment.

Adrenergic beta-Antagonists↗

Clinical trials update from the American Heart Association meeting: ACORN-CSD, primary care trial of chronic disease management, PEACE, CREATE, SHIELD, A-HeFT, GEMINI, vitamin E meta-analysis, ESCAPE, CARP, and SCD-HeFT cost-effectiveness study.

This article provides information and a commentary on landmark trials presented at the American Heart Association meeting held in November 2004, relevant to the pathophysiology, prevention, and treatment of heart failure. An open trial of the ACORN Cardiac Support Device (CSD) showed encouraging preliminary results in patients with severe heart failure. The PEACE (Prevention of Events with Angiotensin-Converting Enzyme inhibition) study supports data from previous studies showing that ACE inhibitors reduce vascular events in patients at increased risk. The CREATE (clinical trial of metabolic modulation in acute MI treatment evaluation) study of patients with acute myocardial infarction (MI) showed no mortality benefit of a glucose/insulin/potassium regimen, but treatment with reviparin reduced the incidence of death, MI, or stroke. Azimilide was not associated with a significant reduction in shocks, but reduced the shocks or episodes of markedly symptomatic ventricular tachycardia terminated by pacing in the SHIELD (Shock Inhibition Evaluation with Azimilide) study. The addition of isosorbide dinitrate plus hydralazine to standard therapy improved survival in black heart failure patients in the A-HeFT (African-American Heart Failure Trial) study. In an investigation of hypertensive patients with diabetes, carvedilol had fewer adverse effects on diabetic control than metoprolol. A meta-analysis of high-dose vitamin E supplementation suggested an association with increased mortality. The ESCAPE (Evaluation Study of CHF and Pulmonary Artery Catheterisation Effectiveness) study showed no benefit of pulmonary artery catheterisation over clinical management in patients with severe heart failure. Routine prophylactic coronary revascularisation for stable coronary disease prior to major vascular surgery showed no benefit in the CARP (Coronary Artery Revascularization Prophylaxis) study. Analysis of data from SCD-HeFT supports the cost-effectiveness of ICDs in heart failure, although overall cost implications may be prohibitive.

Angiotensin-Converting Enzyme Inhibitors↗

Clinical trials update from the American College of Cardiology meeting: CARE-HF and the remission of heart failure, Women's Health Study, TNT, COMPASS-HF, VERITAS, CANPAP, PEECH and PREMIER.

This article provides information and a commentary on landmark trials presented at the American College of Cardiology meeting held in March 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. CARE-HF showed that Cardiac Re-synchronisation Therapy, administered in addition to expert pharmacological management, reduced all cause mortality and CV hospitalisation in patients with moderate or severe heart failure and cardiac dyssynchrony. The Women's Health Study showed no benefit of vitamin E supplementation or aspirin in the primary prevention of CV disease. The TNT study showed that reducing LDL cholesterol to levels lower than currently recommended, produced a 22% reduction in the incidence of major cardiovascular events. In COMPASS, an implantable device that continuously monitors intra-cardiac pressures was shown to be safe and to improve care in patients with chronic heart failure. Tezosentan failed to show benefit in patients with acute heart failure in the VERITAS study. The CANPAP study failed to show a benefit of continuous positive airway pressure on mortality and heart transplantation in heart failure patients with central sleep apnoea. EECP therapy improved exercise capacity but had no effect on peak VO2 in heart failure patients in the PEECH study. In the PREMIER study the matrix metalloproteinase inhibitor PG-116800 failed to prevent LV remodelling following myocardial infarction.

Cardiac Pacing, Artificial↗

Clinical trials update from the European Society of Cardiology Heart Failure meeting and the American College of Cardiology: darbepoetin alfa study, ECHOS, and ASCOT-BPLA.

This article provides information and a commentary on landmark trials presented at the European Society of Cardiology Heart Failure meeting held in June 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. The erythropoiesis stimulating protein, darbepoetin alfa, increased haemoglobin levels, improved quality of life and showed a trend for improved exercise duration in anaemic patients with symptomatic chronic heart failure. In the ECHOS study, the selective dopamine agonist nolomirole (CHF1035) showed no benefit in heart failure patients. Preliminary results of the ASCOT-BPLA study, which were reported at the American College of Cardiology meeting in March 2005, showed that in hypertensive patients, treatment with a calcium antagonist plus an ACE inhibitor was more effective at reducing cardiovascular outcomes than atenolol plus a diuretic.

Clinical Trials as Topic↗

Clinical trials update from the European Society of Cardiology meeting 2005: CARE-HF extension study, ESSENTIAL, CIBIS-III, S-ICD, ISSUE-2, STRIDE-2, SOFA, IMAGINE, PREAMI, SIRIUS-II and ACTIVE.

This article provides information and a commentary on trials presented at the European Society of Cardiology meeting held in September 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 the CARE-HF extension study, the benefits of cardiac resynchronisation therapy (CRT) observed in the original study were maintained over an increased follow-up period. A study of oral enoximone (25-50 mg t.i.d.) in advanced heart failure (ESSENTIAL) showed limited benefit compared to placebo. The CIBIS-III study showed that heart failure therapy could be safely initiated with bisoprolol followed by the addition of enalapril. A subcutaneous ICD system (S-ICD) showed potential as an alternative to a transvenous ICD. In the ISSUE-2 study, an implantable loop recorder was used to guide therapy in patients with recurrent syncope. The selective endothelin antagonist sitaxsentan improved 6-MWT and functional class in patients with pulmonary arterial hypertension in the STRIDE-2 study. In SOFA, fish oil had no beneficial effect on the incidence of life-threatening arrhythmias in patients with an ICD. In IMAGINE, quinapril showed no benefit when administered to patients following CABG. Perindopril reduced cardiac remodelling in post-MI patients with normal LV function in PREAMI. SIRIUS-II showed encouraging results for the use of intravenous ularitide in symptomatic decompensated chronic heart failure. The ACTIVE W study of warfarin versus aspirin plus clopidogrel in atrial fibrillation has been stopped due to superiority of warfarin.

Cardiac Pacing, Artificial↗

Chronic heart failure and multiple micronutrient supplementation: realistic hope or idealistic conjecture?

Recent studies have demonstrated the inefficacy of nutritional supplements containing various combinations of vitamins and minerals for otherwise healthy elderly people and patients with ischemic heart disease. However, patients with chronic heart failure (CHF) have, up until recently, been excluded from such studies. CHF has a high mortality and morbidity and patients are often elderly with poor general nutrition and high levels of micronutrient deficiency. It is in this population that nutritional supplementation has the most potential benefit. Evidence is accumulating that a strategy of long-term highdose multiple micronutrient supplementation might improve symptoms and cardiac function in elderly patients with CHF. In this article, we review the effects of individual micronutrients and how they might impact on CHF, and present recent data that dietary supplementation might offer an addition to standard therapy for CHF.

Dietary Supplements↗

Are hematinic deficiencies the cause of anemia in chronic heart failure?

BACKGROUND: Anemia in chronic heart failure (CHF) is common, varying in prevalence between 14.4% and 55%, and is more frequent in patients with more severe heart failure. Patients with CHF who have anemia have a poorer quality of life, higher hospital admission rates, and reduced exercise tolerance. We explored the relation between hematinic levels and hemoglobin (Hb) levels and exercise tolerance in a group of patients with CHF. METHODS: We analyzed data from 173 patients with left ventricular systolic dysfunction (LVSD), 123 patients with symptoms of heart failure, but preserved left ventricular (LV) systolic function ("diastolic dysfunction"), and 58 control subjects of similar age. Each underwent echocardiography, a 6-minute walk test, and blood tests for renal function and Hb and hematinic levels (vitamin B12, iron, and folate). We classified patients as having no anemia (Hb level >12.5 g/dL), mild anemia (Hb level from 11.5-12.5 g/dL), or moderate anemia (Hb level <11.5 g/dL). RESULTS: Of patients with LVSD, 16% had moderate anemia and 19% had mild anemia. Of patients with preserved LV function, 16% had moderate anemia and 17% had mild anemia. Four control subjects had a Hb level <12.5 g/dL. Of all patients, 6% were vitamin B12 deficient, 13% were iron deficient, and 8% were folate deficient. There was no difference between patients with LVSD and the diastolic dysfunction group. In patients with LVSDS, the average Hb level was lower in New York Heart Association class III than classes II and I. The distance walked in 6 minutes correlated with Hb level in both groups of patients with CHF (r = 0.29; P <.0001). Patients with anemia achieved a lower pVO2 (15.0 [2.3] vs 19.5 [4.4], P <.05). Peak oxygen consumption correlated with Hb level (r = 0.21, P <.05) in the patients, but not in the control subjects. In patients with anemia, the mean creatinine level was higher than in patients with a Hb level >12.5 g/dL, but there was no clear relationship with simple regression. Hematocrit level and mean corpuscular volume were not different in the patients with diastolic dysfunction, patients with LV dysfunction, or the control subjects. Hematocrit levels were not influenced by diuretic dose. Patients with anemia were not more likely to be hematinic deficient than patients without anemia. CONCLUSIONS: Patients with symptoms and signs of CHF have a high prevalence of anemia (34%) whether they have LV dysfunction or diastolic dysfunction, but few patients have hematinic deficiency. Hemoglobin levels correlate with subjective and objective measures of severity and renal function.

Aged↗

The reversibility of increased airways resistance in chronic heart failure measured by impulse oscillometry.

BACKGROUND: Patients with chronic heart failure complain of breathlessness and fatigue on exercise. Airways resistance is increased and lung compliance is reduced in chronic heart failure patients. The aim of this study was to determine whether the pulmonary abnormalities are reversible and whether any improvements lead to changes to exercise capacity or symptoms. METHODS: Twelve patients with stable chronic heart failure and 10 matched controls underwent repeated assessment of airways resistance using impulse oscillometry and peak exercise testing with metabolic gas exchange after receiving nebulized saline as placebo or combined salbutamol and ipratropium bromide in a double-blind crossover randomized fashion. RESULTS: Patients had lower peak oxygen consumption and a steeper slope relating ventilation to carbon dioxide production than controls. Bronchodilators reduced peripheral airways resistance in patients (0.53 versus 0.38, P<.02) and controls (0.21 versus 0.19, P<.005) and increased measures of compliance in both groups. There was no effect on the peak oxygen consumption, exercise time, ventilation to carbon dioxide slope, or anaerobic threshold. There was an increase in peak tidal volume (VT) in both groups but this did not lead to an increase in peak ventilation. The slope relating symptoms to ventilation (ie, Borg/VE) was significantly reduced in the patients after bronchodilators (17%+/-8%, P<.05). The relationship between the improvement in VT and reduction in gradient of the Borg/VE slope was significant (r=.40, P<.05). CONCLUSIONS: Nebulized bronchodilators improve airways resistance, lung reactance, and peak tidal volume during exercise in chronic heart failure but do not increase peak exercise capacity. They do, however, reduce the symptom of breathlessness.

Aged↗

The effect of aspirin on the ventilatory response to exercise in chronic heart failure.

INTRODUCTION: Patients with chronic heart failure (CHF) experience breathlessness and fatigue on exercise. One of the abnormalities seen on maximal exercise testing is an increased ventilatory response to exercise (VE/VCO(2) slope). The cause of this is unknown, but is likely to be due to a combination of interacting peripheral and central factors. Recent data have demonstrated a relation between VE/VCO(2) slope and prostaglandin levels in contracting muscles. The present study examined the influence of the presence of a potent non-selective prostaglandin inhibitor, aspirin, on the ventilatory response to exercise in a group of patients with CHF. METHODS: We investigated the ventilatory response to exercise of 120 consecutive patients in sinus rhythm attending a specialist heart failure clinic. We excluded those taking clopidogrel (six patients) and those on both warfarin and aspirin or taking other non-steroidal anti-inflammatory agents (five patients). The other 109 patients were grouped according to whether they were taking aspirin (n=52 (48%)) or not (n=57 (52%)). Each patient underwent echocardiography to assess left ventricular function, and exercise testing with metabolic gas exchange to derive peak oxygen consumption (pVO(2)) and the VE/VCO(2) slope. RESULTS: The groups were similar in terms of age, (67 (13) vs. 66 (12) years; P=0.34) drug use, heart failure aetiology, left ventricular function (ejection fraction; 33.3 (9.4) vs. 31.8 (9.9)%; P=0.05)) and exercise tolerance (pVO(2); 20.4 (5.3) vs. 19.9 (6.0); P=0.68, and VE/VCO(2) slope; 35.4 (6.2) vs. 35.7 (9.3); P=0.73). There was no difference in the ventilatory response to exercise or the symptoms of breathlessness between the two groups. CONCLUSIONS: Aspirin does not appear to affect exercise performance in CHF.

Aged↗

Clinical trials update from the American Heart Association meeting: Omega-3 fatty acids and arrhythmia risk in patients with an implantable defibrillator, ACTIV in CHF, VALIANT, the Hanover autologous bone marrow transplantation study, SPORTIF V, ORBIT and PAD and DEFINITE.

The American Heart Association meeting reported the results of several clinical trials of particular interest to those who care for patients with heart failure. Omega-3 fatty acids were associated with a trend to increased recurrence of ventricular arrhythmias but not mortality in patients with an implantable debrillator. The ACTIV in CHF study provides more evidence of a therapeutic role for arginine vasopressin antagonists in the treatment of heart failure. The VALIANT study provides further evidence to suggest that a combination of angiotensin receptor antagonist and ACE inhibitor does not reduce mortality but may reduce morbidity in post-MI patients with heart failure or major LV systolic dysfunction. A study of autologous bone marrow cell transplantation into myocardial scar give gave encouraging results. SPORTIF V showed ximelagation to be as effective as warfarin but with improved safety. ORBIT and PAD showed public access defibrillators saved lives but questioned their cost effectiveness. DEFINITE supported a role for ICDs in patients with non-ischemic cardiomyopathy, although cost-effectiveness remains in doubt.

Antidiuretic Hormone Receptor Antagonists↗

Diastolic heart failure. Paroxysmal or chronic?

Heart failure with preserved systolic function is considered by some to be synonymous with diastolic heart failure (DHF). Although recent epidemiological studies have suggested that DHF constitutes 30-50% of all patients with heart failure, many cardiologists dealing with ambulant heart failure patients on a daily basis find that the vast majority of heart failure patients have systolic dysfunction. What could be the reasons for this? Referral bias and varying diagnostic thresholds and interpretation of results could be one important reason. Heart failure with preserved systolic function comprises a heterogeneous group of conditions: whilst some patients may truly have DHF, others may have heart failure due to subtle systolic dysfunction (noted on tissue Doppler imaging of the left ventricular long axis). Other patients actually have pulmonary disease, obesity or ischaemic heart disease, and have their symptoms attributed to 'diastolic heart failure' on the basis of 'abnormal' mitral diastolic flow indices that may, in fact, simply reflect aging. True DHF may be much less prevalent than suggested. A further possibility is that heart failure in patients with diastolic dysfunction might be paroxysmal rather than chronic. This group of patients may present predominantly to acute units like accident and emergency, coronary care units and intensive care units and are, therefore unlikely to figure prominently in the usual outpatient population of chronic systolic left ventricular dysfunction.

Acute Disease↗

Clinical trials update and cumulative meta-analyses from the American College of Cardiology: WATCH, SCD-HeFT, DINAMIT, CASINO, INSPIRE, STRATUS-US, RIO-Lipids and cardiac resynchronisation therapy in heart failure.

This article continues a series of reports on recent research developments in the field of heart failure. Key presentations made at the American College of Cardiology meeting, held in New Orleans, Louisiana, USA in March 2004 are reported. These new data have been added to existing data in cumulative meta-analyses. The WATCH study randomised 1587 patients with heart failure and left ventricular systolic dysfunction to warfarin, aspirin or clopidogrel. The study showed no difference between the effects of these agents on mortality or myocardial infarction, but hospitalisations for heart failure were higher on aspirin (22.2%) compared to warfarin (16.1%). The SCD-HeFT study showed that ICD therapy reduced all-cause mortality at 5 years by 23% in patients with predominantly NYHA class II heart failure and left ventricular systolic dysfunction, but amiodarone was ineffective. The DINAMIT study showed that ICD therapy was not beneficial in patients with left ventricular dysfunction after a recent MI, even in those with risk factors for arrhythmic death. In CASINO, levosimendan improved survival compared with dobutamine or placebo in patients with decompensated heart failure. INSPIRE showed that SPECT imaging can be used to assess risk early after acute MI safely and accurately. Rimonabant was shown to be safe and effective in treating the combined cardiovascular risk factors of smoking and obesity. An overview of new developments in cardiac resynchronisation therapy (CRT) in heart failure is also reported.

Anticoagulants↗

Clinical trials update from the European Society of Cardiology Heart Failure meeting: SHAPE, BRING-UP 2 VAS, COLA II, FOSIDIAL, BETACAR, CASINO and meta-analysis of cardiac resynchronisation therapy.

This article continues a series of reports on recent research developments in the field of heart failure. Key presentations made at the European Society of Cardiology Heart Failure Update meeting, held in Wroclaw, Poland, in June 2004 are reported. The SHAPE study identified a need to educate general practitioners (GPs) in order to optimise treatment of heart failure in primary care. BRING-UP 2 VAS showed that cognitive impairment is very common in elderly heart failure patients and that these patients require specialist care. Carvedilol was shown to be well tolerated and effective in elderly heart failure patients in the observational COLA II study. In the FOSIDIAL study of patients with end-stage renal disease, fosinopril showed no benefit over placebo in reducing the incidence of cardiovascular events in these high-risk patients. The BETACAR study showed that carvedilol and metoprolol produced a similar effect on left ventricular ejection fraction (+13.1% and +12.0%, respectively). Revised mortality data for the CASINO study and a meta-analysis of the effects of cardiac resynchronisation therapy on mortality in the light of the recently published COMPANION study are reported.

Adrenergic beta-Antagonists↗

Clinical trials update from the European Society of Cardiology: SENIORS, ACES, PROVE-IT, ACTION, and the HF-ACTION trial.

This article provides information and a commentary on landmark trials presented at the European Society of Cardiology Congress in August 2004, relevant to the pathophysiology, prevention or treatment of heart failure. The SENIORS trial suggests that nebivolol is well tolerated and effective in older patients with heart failure, even if left ventricular systolic function is not markedly depressed. However, patients aged >75 years appeared to gain less benefit. Further data on the effects of nebivolol on symptoms and quality of life are awaited. Two new trials of long-term antibiotic prophylaxis after myocardial infarction (ACES and PROVE-IT) showed no benefit. The ACTION trial showed no reduction in serious cardiovascular events with nifedipine GITS in patients with chronic stable angina, despite a substantial reduction in blood pressure. The HF-ACTION trial announced that the first 700 patients of a projected 3000 had been randomised to either an exercise program or encouragement to exercise but without a formal program. The primary outcome measure is death or hospitalisation for any reason.

Adrenergic beta-Antagonists↗

Clinical trials update from the Heart Failure Society of America: EMOTE, HERB-CHF, BEST genetic sub-study and RHYTHM-ICD.

This article summarises key presentations relevant to the pathophysiology, prevention or treatment of heart failure, from the Heart Failure Society of America annual meeting held in Toronto, Canada. Data from the EnoxiMone in intravenous inOTropE-dependent subjects (EMOTE) study suggest that the oral PDE-3 inhibitor enoximone may be effective for weaning severe heart failure patients from intravenous inotropic therapy. Hawthorn Extract Randomised Blinded Trial in CHF (HERB-CHF) failed to show a benefit of hawthorn extract added to conventional heart failure therapy. A genetic sub-group analysis of the Blocker Evaluation of Survival Trial (BEST) study showed that bucindolol reduced mortality and hospitalisations in patients who were homozygous for the Arg389 variant of the beta(1) adrenoceptor. In the Resynchronisation Hemodynamic Treatment for Heart Failure Management (RHYTHM-ICD) study, patients randomised to cardiac resynchronisation therapy (CRT) showed an improvement in symptoms and functional capacity compared to the control group.

3',5'-Cyclic-AMP Phosphodiesterases↗

Fish oils--adjuvant therapy in chronic heart failure?

Despite advances in medical management and device therapy, chronic heart failure (CHF) remains a condition of high mortality and poor quality of life. Patients with CHF endure frequent admissions to hospital, with exacerbations of breathlessness or recurrent acute myocardial infarction and have a high incidence of sudden death. A high intake of marine polyunsaturated fatty acids (PUFAs) is associated with lower cardiovascular mortality in the general population, and diabetics, and can reduce cardiovascular deaths post-infarction. Many of the effects of PUFAs could be of benefit in CHF patients. They can improve endothelial function, reduce vascular tone, reduce platelet aggregability, improve myocardial relaxation, stabilize myocardial cells by prolonging the refractory period, and lead to increased appetite and weight gain. They also have potentially important immune-modulating effects, reducing cytokine production and release and altering prostaglandin metabolism. In this review article we discuss the potential benefits of PUFA supplementation in CHF patients using data from clinical trials and in vitro experiments.

Animals↗