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Biomedical subjects

J G F Cleland

Publications and source records attributed to J G F Cleland.

At least 19 recordsLinked to original sources

Excessive breathlessness in patients with diastolic heart failure.

OBJECTIVES: To establish the prevalence of preserved left ventricular (LV) systolic function (PSF) in 435 consecutive symptomatic patients referred to a heart failure clinic and to examine their ventilatory response to exercise when compared with 134 control volunteers. METHODS: 216 (50%) patients had systolic heart failure (SHF) (ejection fraction < 45%). 51 (11%) had an immediately apparent alternative causes of breathlessness and 168 (39%), with no obvious other cause of breathlessness, were divided into those with PSF and diastolic dysfunction (DD) (PSF(DD); n = 113 or 26% of referrals) and those without DD (PSF(N); n = 55 or 13% of referrals). The controls were divided into those with (C(DD); n = 32) and those without (C(N); n = 102) echocardiographic evidence of DD. RESULTS: Patients with SHF had lower peak oxygen consumption (pVo(2)), steeper slope of minute ventilation (Ve) to carbon dioxide production, lower exercise time and shorter 6 min walk test than PSF patients and controls. PSF(DD) patients had lower pVo(2), exercise time and 6 min walk test than C(DD), although their echocardiograms were not different. Exercise capacity did not differ between PSF(DD) and PSF(N) patients. The slope relating Ve to symptoms (Borg/Ve slope) was less steep in those with SHF than in PSF(DD) (0.17 (0.04) v 0.20 (0.08), p < 0.05) and in PSF(N) (0.19 (0.10), p < 0.05), implying greater symptoms of breathlessness for a given level of Ve. Both PSF groups had a steeper slope than C(DD) (0.14 (0.09), p < 0.05 for both comparisons). CONCLUSIONS: Patients with PSF have exercise tolerance intermediate between that of patients with SHF and controls. Exercise tolerance is similar in PSF(DD) and PSF(N). Both groups have worse exercise tolerance than C(DD). PSF(DD) and PSF(N) patients seem to experience a greater awareness of Ve than C(DD) and patients with SHF.

Aged↗

Cardiac resynchronisation for patients with heart failure due to left ventricular systolic dysfunction -- a systematic review and meta-analysis.

BACKGROUND: Randomised controlled trials generally suggest that cardiac resynchronisation improves outcomes in patients with heart failure due to left ventricular systolic dysfunction and cardiac dyssynchrony. Our objective was to provide a valid synthesis of the effects of CRT on mortality, major morbidity, quality of life and implantation success rates. METHODS: Systematic overview and meta-analysis of randomised trials, both blinded and open, comparing cardiac resynchronisation with control. The primary outcome was all-cause mortality, and secondary outcomes included hospitalisation for worsening heart failure, quality of life and implantation success rates. RESULTS: We identified 8 randomised trials which included 3380 patients and observed a total of 524 deaths. Follow-up ranged from 1 month to a mean of 29.4 months. Most trials were of high quality, with centrally administered randomisation and few patients lost to follow-up. CRT reduced mortality in these trials (odds ratio 0.72, 95% CI 0.59 to 0.88). In addition CRT reduced hospitalisation for worsening heart failure (odds ratio 0.55, 95% CI 0.44 to 0.68) and improved quality of life as measured by the Minnesota Living with Heart Failure Questionnaire (weighted mean difference -7.1, 95% CI -2.9 to -11.4). Implantation success rates in the trials were 87% or greater. CONCLUSION: Cardiac resynchronisation in patients with heart failure characterised by dyssynchrony substantially reduces all-cause mortality, major morbidity and improves quality of life.

Cardiac Output, Low↗

The immediate and long-term outcome of enhanced external counterpulsation in treatment of chronic stable refractory angina.

BACKGROUND: Treatment of angina recalcitrant to conventional pharmacological therapy and revascularization remains problematic. Safe, effective and affordable treatments with high patient acceptability are desirable. Enhanced external counterpulsation (EECP) may fulfil these criteria better than many other proposed interventions. OBJECTIVE: To examine the immediate and long-term effect of EECP in treatment of chronic stable refractory angina. DESIGN: Prospective observational study of consecutive patients treated with EECP and follow-up for 1 year. SETTING: Teaching hospital. MAIN OUTCOME MEASURES: Canadian Cardiovascular Society (CCS) angina grading, weekly angina frequency and glyceryl trinitrate (GTN) use. RESULTS: Sixty-one patients were treated with EECP and 58 completed a course of treatment. Further analysis is confined to those who completed EECP. About 52% of patients suffered from CCS III and IV angina prior to EECP. Immediately post-EECP, angina improved by at least one CCS class in 86% and by two classes in 59%. At 1-year follow-up, sustained improvement in CCS was observed in 78% of the patients. The median weekly angina frequency and GTN use were significantly reduced immediately after EECP [7 (4-14) vs. 1 (0-4) episodes per week and 7 (2-16) vs. 0 (0-2) times per week respectively, P < 0.0001; data in median (interquartile range)]. The reduction was sustained at 1-year follow-up. In 48 patients, their mean exercise time improved significantly after EECP [301 +/- 130 s vs. 379 +/- 147 s, P < 0.0001]. Major adverse treatment-related events were rare. CONCLUSION: This study shows that for patients who fail to respond to conventional measures, a high proportion gain symptomatic benefit from EECP.

Aged↗

Comparison of the dual receptor endothelin antagonist enrasentan with enalapril in asymptomatic left ventricular systolic dysfunction: a cardiovascular magnetic resonance study.

OBJECTIVE: To compare the effect of the dual endothelin A/B receptor antagonist enrasentan with enalapril on left ventricular (LV) remodelling. METHODS: Multicentre, randomised, double blind, parallel group study of 72 asymptomatic patients with LV dysfunction. Patients received enrasentan (60-90 mg/day) or enalapril (10-20 mg/day). The primary end point was the change in LV end diastolic volume index (EDVI) after six months' treatment. RESULTS: LV EDVI increased with enrasentan but decreased with enalapril (3.9 (1.8) v -3.4 (1.4) ml/m2, p = 0.001). Enrasentan increased resting cardiac index compared with enalapril (0.11 (0.07) v -0.10 (0.07) l/m2, p = 0.04), as well as LV mass index (0.67 (1.6) v -3.6 (1.6) g/m2, p = 0.04). Other variables were comparable between groups. Enalapril lowered brain natriuretic peptide more than enrasentan (-19.3 (9.4) v -5.8 (6.9) pg/ml, p = 0.005). Noradrenaline (norepinephrine) (p = 0.02) increased more with enrasentan than with enalapril. Enrasentan was associated with more serious adverse events compared with enalapril (six (16.7%) patients v one (2.8%), p = 0.02); the rate of progression of heart failure did not differ. CONCLUSION: In asymptomatic patients with LV dysfunction, LV EDVI increased over six months with enrasentan compared with enalapril treatment, with adverse neurohormonal effects. This suggests that enrasentan at a dose of 60-90 mg/day over six months causes adverse ventricular remodelling despite an increase in the resting cardiac index.

Adult↗

Clinical determinants of poor six-minute walk test performance in patients with left ventricular systolic dysfunction and no major structural heart disease.

BACKGROUND: The clinical determinants of six-minute walk test (6-MWT) performance in patients with left ventricular systolic dysfunction (LVSD) have rarely been investigated, and it is not clear whether they differ from patients referred for the assessment of symptoms of heart failure who do not have major structural heart disease (MSHD). METHODS AND RESULTS: 571 patients with LVSD enrolled in a chronic disease management programme (79% male; mean age 71+/-10 years; BMI 28+/-5) completed a 6-MWT with a mean distance 337+/-103 m. 688 patients referred with suspected heart failure but in whom MSHD was excluded (49% male; mean age 70+/-11 years; BMI 28+/-6) had a mean 6-MWT distance of 391+/-106 m (P<0.001 compared to patients with LVSD). Relationships with walking distance were determined by calculating odds ratios (ORs) with 95% confidence intervals (CIs) for walking 300 m. In patients with LVSD, predictors of poor walking distance ( or=75 years (OR=4.0, 95% CI=2.4-6.4); low BMI (<20) (OR=3.4, 95% CI=1.6-7.3); anaemia (OR=2.8, 95% CI=1.8-4.2); resting heart rate>80 beats x min(-1) (OR=2.2, 95% CI=1.3-3.5); and being female (OR=2.0, 95% CI=1.3-3.0). Serum creatinine and NT-proBNP showed dose-response effects, as did self-perceived feelings of depression and anxiety. Determinants of 6-MWT in patients without MSHD were similar including age>or=75 years (OR=6.0, 95% CI=3.4-10.4), anaemia (OR=2.8, 95% CI=1.6-4.9), resting HR>80 beats x min(-1) (OR=2.5, 95% CI=1.4-4.4) and being female (OR=1.6, 95% CI=1.9-2.4). NT-proBNP and self-perceived feelings of depression and anxiety also showed dose-response effects. CONCLUSION: The determinants of poor 6-MWT performance depend on physical-cardiovascular and non-cardiovascular, and psychological factors. Clinical predictors for poor walking performance are similar for patients with LVSD and without MSHD.

Aged↗

Prognostic value of systolic mitral annular velocity measured with Doppler tissue imaging in patients with chronic heart failure caused by left ventricular systolic dysfunction.

OBJECTIVE: To assess the prognostic value of various conventional and novel echocardiographic indices in patients with chronic heart failure (CHF) caused by left ventricular (LV) systolic dysfunction. METHODS: 185 patients with a mean (SD) age of 67 (11) years with CHF and LV ejection fraction < 45% despite optimal pharmacological treatment were prospectively enrolled. The patients underwent two dimensional echocardiography with tissue harmonic imaging to assess global LV systolic function and obtain volumetric data. Transmitral flow was assessed with conventional pulse wave Doppler. Systolic (Sm), early, and late diastolic mitral annular velocities were measured with the use of colour coded Doppler tissue imaging. RESULTS: During a median follow up of 32 months (range 24-38 months in survivors), 34 patients died and one underwent heart transplantation. Sm velocity (hazard ratio (HR) 0.648, 95% confidence interval (CI) 0.463 to 0.907, p = 0.011), diastolic arterial pressure (HR 0.965, 95% CI 0.938 to 0.993, p = 0.015), serum creatinine (HR 1.006, 95% CI 1.001 to 1.011, p = 0.023), LV ejection fraction (HR 0.945, 95% CI 0.899 to 0.992, p = 0.024), age (HR 1.035, 95% CI 1.000 to 1.071, p = 0.052), LV end systolic volume index (HR 1.009, 95% CI 0.999 to 1.019, p = 0.067), and restrictive pattern of transmitral flow (HR 0.543, 95% CI 0.278 to 1.061, p = 0.074) predicted the outcome of death or transplantation on univariate analysis. On multivariate analysis, only Sm velocity (HR 0.648, 95% CI 0.460 to 0.912, p = 0.013) and diastolic arterial pressure (HR 0.966, 95% CI 0.938 to 0.994, p = 0.016) emerged as independent predictors of outcome. CONCLUSIONS: In patients with CHF and LV systolic dysfunction despite optimal pharmacological treatment, the strongest independent echocardiographic predictor of prognosis was Sm velocity measured with quantitative colour coded Doppler tissue imaging.

Adult↗

Predicting peak oxygen uptake from 6-min walk test performance in male patients with left ventricular systolic dysfunction.

BACKGROUND: In patients with left ventricular systolic dysfunction (LVSD), peak oxygen uptake (pVO2) has strong predictive power for mortality, and can be used to guide management. However, many patients cannot tolerate standard test protocols. The 6-min walk test (6-MWT) is often used to estimate functional capacity due to its simplicity, cost effectiveness and familiarity to patients with LVSD. The relationship between 6-MWT performance and pVO2 is not certain, but if closely related could allow substitution of an expensive and cumbersome test for a cheaper and more familiar one. METHODS AND RESULTS: 120 male patients with LVSD (LVEF <40%; (mean+/-S.D.) age 68+/-13 years; BMI 28+/-5) performed, in random order, a maximal incremental treadmill exercise test with metabolic gas exchange measurements to derive peak oxygen consumption (pVO2 = 19.8+/-5.8 mL.kg(-1).min(-1)), and a standardised 6-MWT (308+/-142 m; r = 0.44; P = 0.00001). In multivariate models including demographic data, resting blood pressure and heart rate, spirometry, routine blood samples, and walk distance, five variables were independently predictive of peak oxygen consumption. pVO2 = 11.92 + (1.48 x FEV1 (L)) + (1.12 x haemoglobin (g dl(-1))) + (0.016 x distance walked (m)) - (0.33 x BMI) - (0.11 x age (years)). This equation accounted for 48% of the variation in pVO2. CONCLUSIONS: Using these five simple variables, peak oxygen consumption can be estimated with moderate accuracy. In clinical practice, however, when an estimate of peak oxygen consumption is required, incremental exercise testing with metabolic gas exchange measurements cannot be avoided in male patients with LVSD. Further work is needed to assess the relation between estimated pVO2 and outcome.

Adult↗

Chronic heart failure, chronotropic incompetence, and the effects of beta blockade.

OBJECTIVE: To establish the prevalence of chronotropic incompetence in a cohort of patients with chronic heart failure (CHF) taking modern medications for heart failure, and whether this affected exercise capacity and predicted prognosis. METHODS: Heart rate response to exercise was examined in 237 patients with CHF in sinus rhythm, who were compared with 118 control volunteers. The percentage of maximum age predicted peak heart rate (%Max-PPHR) and percentage heart rate reserve (%HRR) were calculated, with a cut off of < 80% as the definition of chronotropic incompetence for both. Patients were followed up for an average (SD) of 2.8 (9) years. Mortality was related to peak oxygen consumption (pVo2), and the presence or absence of chronotropic incompetence. RESULTS: %Max-PPHR < 80% identified 103 (43%) and %HRR < 80% identified 170 patients (72%) as having chronotropic incompetence. Chronotropic incompetence was more common in patients taking beta blockers than in those not taking beta blockers as assessed by both methods (80 (49%) v 23 (32%) by %Max-PPHR and 123 (75%) v 47 (64%) by %HRR, respectively). Patients with chronotropic incompetence by either method had a lower pVo2 than those without. These differences remained significant for both patients taking and not taking a beta blocker. %HRR, Max-PPHR%, and HRR were related to New York Heart Association class and correlated with pVo2. There was no difference in the slopes relating heart rate to pVo2 between patients with and those without chronotropic incompetence (6.1 (1.7) v 5.1 (1.8), p = 0.34). During an average 2.8 year follow up 40 patients (17%) died. In Cox proportional hazard models, pVo2 was the most powerful predictor of survival and neither measure of chronotropic incompetence independently predicted outcome. CONCLUSIONS: pVo2 is a powerful marker of prognosis for patients with CHF whether they are taking beta blockers or not. A low heart rate response to exercise in patients with CHF correlates with worse exercise tolerance but is unlikely to contribute to exercise impairment.

Adrenergic beta-Antagonists↗

Effect of a community heart failure clinic on uptake of beta blockers by patients with obstructive airways disease and heart failure.

OBJECTIVE: To determine the pattern of beta blocker prescribing over one year in a heart failure clinic with a structured approach towards initiation and dose titration and to give a real life perspective on beta blocker use, compliance, and target dose achievement. METHODS: Data were retrospectively analysed on 513 consecutive patients regularly attending a community heart failure clinic over a year. Systolic dysfunction was determined from two dimensional echocardiography (left ventricular ejection fraction < or = 40%) and lung function was assessed by spirometry. All patients were considered for beta blocker initiation and dose up titration. RESULTS: Within one year 157 patients died. 143 patients started beta blockers resulting in 315 (88%) patients taking beta blockers at one year; 38% were taking the target dose. 124 had evidence of airways obstruction at baseline, 100 (81%) of whom were taking beta blockers at one year. Forced expiratory volume in one second (1.1 v 1.5 l, p < 0.01) and forced vital capacity (2.3 v 2.5 l/min, p = 0.2) were not reduced in patients with airways obstruction who received beta blockers. Daily doses of beta blockers at one year did not differ statistically between patients with obstructive and patients with non-obstructive spirometry results. 12 patients discontinued beta blockers and 14 required dose reduction due to side effects. CONCLUSION: The majority of patients with heart failure and obstructive airways disease can safely tolerate low dose initiation and gradual up titration of beta blockers.

Adrenergic beta-Antagonists↗

Baseline characteristics of patients recruited into the CARE-HF study.

BACKGROUND: Cardiac resynchronization therapy (CRT) is a promising new treatment for patients with heart failure and cardiac dyssynchrony. The CARE-HF study is a morbidity/mortality trial designed to provide conclusive evidence of the effects of CRT in patients with moderate to severe heart failure. METHODS: A description of the baseline characteristics of patients randomised in the CARE-HF trial. RESULTS: 813 Patients with predominantly NYHA class III (94%) heart failure were randomised in 82 centres. Their mean age was 65 (interquartile range [IQR] 59 to 72) years, 34% were aged >70 years and 27% were women. Thirty-eight percent of the patients had ischaemic heart disease. Mean heart rate was adequately controlled at 70 (IQR 60 to 78) bpm consistent with the use of beta-blockers. Supine systolic blood pressure was low at 117 (IQR 105 to 130) mm Hg. Eighty-eight percent of patients had a QRS > or =150 ms. Mean LV ejection fraction was 26% (IQR 22 to 29) and end-diastolic dimension was 7.2 (IQR 6.4 to 7.8) cm. Ninety-four percent of patients were receiving loop diuretics, 95% an ACE inhibitor or angiotensin receptor blocker (ARB), 72% a beta-blocker and 56% were taking spironolactone. CONCLUSIONS: The patients enrolled in CARE-HF had moderately severe heart failure and cardiac dysfunction with evidence of cardiac dyssynchrony. The population appears at high risk of events despite pharmacological therapy and therefore appropriate for a trial of CRT.

Aged↗

Prevalence and predictors of anxiety and depression in a sample of chronic heart failure patients with left ventricular systolic dysfunction.

OBJECTIVE: To determine the prevalence and predictors of anxiety and depression in patients with heart failure due to Left Ventricular Systolic Dysfunction (LVSD). BACKGROUND: Psychological adjustment to Chronic Heart Failure (CHF) can be poor, with the prevalence of depression in out-patients ranging from 13% to 48%. The prevalence of anxiety disorders in this population is unknown and the factors that predict anxiety and depression are not well understood. METHODS: 100 out-patients from a community heart failure programme completed a clinical diagnostic interview--the Structured Clinical Interview (SCID-I), to evaluate anxiety and depression. Mean age was 67+/-11 years, 17% were women and 91% were NYHA Class II or III. Other standardised measures were of cognition, biomedical status, social support and previous physical and mental health history. RESULTS: The prevalence rates of anxiety and depression (all subtypes) were 18.4% and 28.6%, respectively. Predictors of depression included a reported history of mental ill-health and NYHA class. Predictors of anxiety included a reported history of mental ill-health, co-morbid physical illness (diabetes and angina) and NYHA class. Severity of LVSD did not predict either anxiety or depression. CONCLUSIONS: Both anxiety and depression are common in CHF patients. The data on the predictors of poor psychological adjustment might assist in targeting bio-psychosocial intervention for patients who are at most at risk of anxiety and depression, within community CHF disease management programmes.

Adaptation, Psychological↗

Epidemiology and management of heart failure and left ventricular systolic dysfunction in the aftermath of a myocardial infarction.

Robust epidemiological data on the incidence of myocardial infarction (MI) are hard to find, but synthesis of data from a number of sources indicates that the average hospital in the UK should admit about two patients with a first MI and one recurrent MI per 1000 population per year. Possibly the most relevant data on the incidence, prevalence, and persistence of post-MI heart failure can be derived from the TRACE study. Most patients will develop heart failure or major left ventricular systolic dysfunction (LVSD) at some time after an MI, most commonly during the index admission. In up to 20% of cases this will be transient, but such patients still have a poor prognosis. There is likely to be around one patient discharged per thousand population per year with heart failure or major LVSD after an acute MI. It is important to organise care structures to ensure that patients with post-MI heart failure and LVSD are identified and managed appropriately.

Adult↗

The Warfarin/Aspirin Study in Heart failure (WASH): a randomized trial comparing antithrombotic strategies for patients with heart failure.

BACKGROUND: Heart failure is commonly associated with vascular disease and a high rate of athero-thrombotic events, but the risks and benefits of antithrombotic therapy are unknown. METHODS: The current study was an open-label, randomized, controlled trial comparing no antithrombotic therapy, aspirin (300 mg/day), and warfarin (target international normalized ratio 2.5) in patients with heart failure and left ventricular systolic dysfunction requiring diuretic therapy. The primary objective was to demonstrate the feasibility and inform the design of a larger outcome study. The primary clinical outcome was death, nonfatal myocardial infarction, or nonfatal stroke. RESULTS: Two hundred seventy-nine patients were randomized and 627 patient-years exposure were accumulated over a mean follow-up time of 27 +/- 1 months. Twenty-six (26%), 29 (32%), and 23 (26%) patients randomized to no antithrombotic treatment, aspirin, and warfarin, respectively, reached the primary outcome (ns). There were trends to a worse outcome among those randomized to aspirin for a number of secondary outcomes. Significantly (P =.044) more patients randomized to aspirin were hospitalized for cardiovascular reasons, especially worsening heart failure. CONCLUSIONS: The Warfarin/Aspirin Study in Heart failure (WASH) provides no evidence that aspirin is effective or safe in patients with heart failure. The benefits of warfarin for patients with heart failure in sinus rhythm have not been established. Antithrombotic therapy in patients with heart failure is not evidence based but commonly contributes to polypharmacy.

Aged↗

Cardiovascular prophylaxis with aspirin: costs of supply and management of upper gastrointestinal and renal toxicity.

AIMS: To determine the cost to the NHS of prescribed low-dose aspirin. METHODS: This was a population based observational cohort study. Patients from Tayside Scotland (17 244 new users of dispensed aspirin each with 10 matched comparators) were included. A pragmatic analysis totalled costs from the start to end of the study and compared these with a matched cohort of aspirin nonusers to estimate excess costs. Fastidious analyses were done of subjects with no prior history of upper gastrointestinal (UGI) or renal disease where the cost that occurred during aspirin exposure, the 30 days following aspirin exposure and subsequent nonexposure was calculated adjusting for risk factors in each period. RESULTS: Subjects took aspirin for only 1.18 of the 2.53 years follow-up (47% compliance). Aspirin use cost an additional 49.86 UK pounds per year (pragmatic analysis) made up of 1.96 UK pounds for aspirin tablets (4%), 5.49 UK pounds for dispensing costs (11%), 24.60 UK pounds for UGI complications (49%) and 17.81 UK pounds for renal complications (36%). The costs for managing complications were substantially lower in the fastidious analysis (2.66 UK pounds for UGI complications and 2.92 UK pounds for renal complications). Assuming that the antiplatelet trial meta-analysis is an accurate assessment of the benefits of aspirin, the costs of preventing one vascular event lay between 62 500 UK pounds (primary prevention, pragmatic analysis) and 867 UK pounds (secondary prevention, fastidious analysis). These costs may be underestimates due to the low compliance observed. CONCLUSIONS: Compliance with aspirin was poor. Serious adverse events were uncommon but despite this aspirin cost the NHS between 6 and 25 times the cost of aspirin tablets due to dispensing costs and the cost of managing adverse effects.

Acute Kidney Injury↗

Effects of carvedilol on left ventricular remodelling in chronic stable heart failure: a cardiovascular magnetic resonance study.

BACKGROUND: The ability of beta blockers to improve left ventricular function has been demonstrated, but data on the effects on cardiac remodelling are limited. OBJECTIVE: To investigate, using cardiovascular magnetic resonance (CMR), the effects of carvedilol on left ventricular remodelling in patients with chronic stable heart failure and left ventricular systolic dysfunction caused by coronary artery disease. DESIGN: Randomised, double blind, placebo controlled study. SETTING: Chronic stable heart failure. PATIENTS AND INTERVENTION: 34 patients with chronic stable heart failure and left ventricular systolic function taking part in the CHRISTMAS trial (double blind carvedilol v placebo) underwent CMR before randomisation and after six months of treatment. MAIN OUTCOME MEASURE: Left ventricular remodelling at six months. RESULTS: The carvedilol and placebo groups were well balanced at baseline, with no significant intergroup differences. Over the study period, there was a significant reduction in end systolic volume index (ESV(I)) and end diastolic volume index (EDV(I)) between the carvedilol and the placebo group (carvedilol -9 v placebo +3 ml/m2, p = 0.0004; carvedilol -8 v placebo 0 ml/m2, p = 0.05). The ejection fraction increased significantly between the groups (carvedilol +3% v placebo -2%, p = 0.003). CONCLUSIONS: Treatment of chronic stable heart failure with carvedilol results in significant improvement in left ventricular volumes and function. These effects might contribute to the benefits of carvedilol on mortality and morbidity in patients with chronic heart failure.

Adrenergic beta-Antagonists↗