The Experts below are selected from a list of 270 Experts worldwide ranked by ideXlab platform
Michael R. Bristow - One of the best experts on this subject based on the ideXlab platform.
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Adrenergic receptor polymorphisms and prevention of ventricular arrhythmias with Bucindolol in patients with chronic heart failure.
Circulation. Arrhythmia and electrophysiology, 2012Co-Authors: Ryan G. Aleong, Alastair D. Robertson, William H Sauer, Stephen B Liggett, Michael R. BristowAbstract:Background— β-blockers prevent cardiac arrhythmias in patients with chronic heart failure and reduced left ventricular ejection fraction, including ventricular tachycardia/ventricular fibrillation (VT/VF). We hypothesized that prevention of ventricular arrhythmias by the β-blocker/sympatholytic agent Bucindolol is influenced by genetic variation in adrenergic receptors. Methods and Results— From a substudy of the β-Blocker Evaluation of Survival Trial (n=1040), we identified those with the high functioning 389Arg versus the lower function 389Gly β1 adrenergic receptor variant, and the loss of function α2c322-325 adrenergic receptor deletion versus the 322 to 325 wild-type (Wt)/deletion variant. VT/VF was recorded on case report forms as an adverse event. There were 493 Arg 389 β1 receptor homozygotes (β1389 Arg/Arg) versus 547 Gly389 carriers and 207 α2c322-325 deletion carriers versus 833 homozygous Wts (α2c322-325 Wt/Wt). In all genotypes Bucindolol was associated with a lower incidence of VT/VF (subhazard ratio, 0.42 [0.27–0.64]; P =0.00006). Bucindolol reduced VT/VF in β1389 Arg homozygotes (subhazard ratio, 0.26 [0.14–0.50]; P =0.00005) but not in β1389 Gly carriers (subhazard ratio, 0.60 [0.34–1.07]; P =0.09). For genotype combinations, the α2c322-325 polymorphism altered the VT/VF Bucindolol response in β1389 Gly carriers, with α2c deletion genotypes associated with complete efficacy loss. A test of interaction was statistically significant ( P =0.028) for the treatment group and a β1389/α2c322-325 three genotype construct, effectively identifying patients who exhibited enhanced response, no substantial response modification and loss of response. Conclusions— Bucindolol prevents VT/VF in subjects with heart failure and reduced left ventricular ejection fractions, and this effect is modulated by β1389 Arg/Gly and α2c322-325 Wt/deletion adrenergic receptor polymorphisms.
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Outcomes according to subtype.
2012Co-Authors: David P. Kao, Michael R. Bristow, Brandie D. Wagner, Alastair D. Robertson, Brian D. LowesAbstract:Plac = placebo, Buc = Bucindolol.
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Kaplan-Meier survival curves according to Latent Class Model A subtype, Bucindolol vs. placebo.
2012Co-Authors: David P. Kao, Michael R. Bristow, Brandie D. Wagner, Alastair D. Robertson, Brian D. LowesAbstract:Kaplan-Meier survival curves according to Latent Class Model A subtype, Bucindolol vs. placebo.
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Figure 4a: Key features of Latent Class Model A, mortality trends, and response to Bucindolol.
2012Co-Authors: David P. Kao, Michael R. Bristow, Brandie D. Wagner, Alastair D. Robertson, Brian D. LowesAbstract:Figure 4b: Key features of Latent Class Model B, mortality trends, and response to Bucindolol.
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Kaplan-Meier survival curves for all nonischemic patients and according to Latent Class Model B subtype, Bucindolol vs. placebo.
2012Co-Authors: David P. Kao, Michael R. Bristow, Brandie D. Wagner, Alastair D. Robertson, Brian D. LowesAbstract:Kaplan-Meier survival curves for all nonischemic patients and according to Latent Class Model B subtype, Bucindolol vs. placebo.
Michel White - One of the best experts on this subject based on the ideXlab platform.
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Bucindolol for the maintenance of sinus rhythm in a genotype defined hf population the genetic af trial
Jacc-Heart Failure, 2019Co-Authors: Jonathan P Piccini, Michel White, William T Abraham, Christopher Dufton, Ian A Carroll, Jeff S Healey, Dirk J Van Veldhuisen, William H Sauer, Inder S Anand, Stephen B WiltonAbstract:Abstract Objectives The purpose of this study was to compare the effectiveness of Bucindolol with that of metoprolol succinate for the maintenance of sinus rhythm in a genetically defined heart failure (HF) population with atrial fibrillation (AF). Background Bucindolol is a beta-blocker whose unique pharmacologic properties provide greater benefit in HF patients with reduced ejection fraction (HFrEF) who have the beta1-adrenergic receptor (ADRB1) Arg389Arg genotype. Methods A total of 267 HFrEF patients with a left ventricular ejection fraction (LVEF) Results The hazard ratio (HR) for the primary endpoint was 1.01 (95% confidence interval [CI]: 0.71 to 1.42), but trends for Bucindolol benefit were observed in several subgroups. Precision therapeutic phenotyping revealed that a differential response to Bucindolol was associated with the interval of time from the initial diagnoses of AF and HF to randomization and with the onset of AF relative to that of the initial HF diagnosis. In a cohort whose first AF and HF diagnoses were Conclusions Pharmacogenetically guided Bucindolol therapy did not reduce the recurrence of AF/AFL or ACM compared to that of metoprolol therapy in HFrEF patients, but populations were identified who merited further investigation in future phase 3 trials.
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a genotype directed comparative effectiveness trial of Bucindolol and metoprolol succinate for prevention of symptomatic atrial fibrillation atrial flutter in patients with heart failure rationale and design of the genetic af trial
American Heart Journal, 2017Co-Authors: Jonathan P Piccini, William T Abraham, Jeff S Healey, William H Sauer, Benjamin A. Steinberg, Stuart J Connolly, Hussein R Alkhalidi, Patricia Dignacco, Dirk J Van Veldhuisen, Michel WhiteAbstract:Background Few therapies are available for the safe and effective treatment of atrial fibrillation (AF) in patients with heart failure. Bucindolol is a non-selective beta-blocker with mild vasodilator activity previously found to have accentuated antiarrhythmic effects and increased efficacy for preventing heart failure events in patients homozygous for the major allele of the ADRB1 Arg389Gly polymorphism (ADRB1 Arg389Arg genotype). The safety and efficacy of Bucindolol for the prevention of AF or atrial flutter (AFL) in these patients has not been proven in randomized trials. Methods/design The Genotype-Directed Comparative Effectiveness Trial of Bucindolol and Metoprolol Succinate for Prevention of Symptomatic Atrial Fibrillation/Atrial Flutter in Patients with Heart Failure (GENETIC-AF) trial is a multicenter, randomized, double-blinded “seamless” phase 2B/3 trial of Bucindolol hydrochloride versus metoprolol succinate, for the prevention of symptomatic AF/AFL in patients with reduced ejection fraction heart failure (HFrEF). Patients with pre-existing HFrEF and recent history of symptomatic AF are eligible for enrollment and genotype screening, and if they are ADRB1 Arg389Arg, eligible for randomization. A total of approximately 200 patients will comprise the phase 2B component and if pre-trial assumptions are met, 620 patients will be randomized at approximately 135 sites to form the Phase 3 population. The primary endpoint is the time to recurrence of symptomatic AF/AFL or mortality over a 24-week follow-up period, and the trial will continue until 330 primary endpoints have occurred. Conclusions GENETIC-AF is the first randomized trial of pharmacogenetic guided rhythm control, and will test the safety and efficacy of Bucindolol compared with metoprolol succinate for the prevention of recurrent symptomatic AF/AFL in patients with HFrEF and an ADRB1 Arg389Arg genotype. ( ClinicalTrials.gov NCT01970501 ).
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Time to all-cause mortality or cardiac transplantation for Group 1/2 (A), Group 3 (B), and Group 4 (C), and time to heart failure progression (combination endpoint of heart failure mortality, cardiac transplantation, heart failure hospitalization, or
2013Co-Authors: Christopher M. O'connor, Mona Fiuzat, Inder S Anand, Peter E. Carson, Jonathan F. Plehn, Stephen S. Gottlieb, Marc A. Silver, Joann Lindenfeld, Alan B. Miller, Michel WhiteAbstract:Abbreviations: AC, all-cause; BUC, Bucindolol; Del, deletion; HF, heart failure; PBO, placebo.
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Bucindolol, Systolic Blood Pressure, and Outcomes in Systolic Heart Failure: A Prespecified Post Hoc Analysis of BEST
The Canadian journal of cardiology, 2011Co-Authors: Michel White, Ravi V. Desai, Jason L. Guichard, Marjan Mujib, Inmaculada Aban, Mustafa I. Ahmed, Margaret A. Feller, Simon De Denus, Ali AhmedAbstract:Abstract Background In the Beta-Blocker Evaluation of Survival Trial (BEST), systolic blood pressure (SBP) ≤ 120 mm Hg was an independent predictor of poor prognosis in ambulatory patients with chronic systolic heart failure (HF). Because SBP is an important predictor of response to β-blocker therapy, the BEST protocol prespecified a post hoc analysis to determine whether the effect of Bucindolol varied by baseline SBP. Methods In the BEST, 2706 patients with chronic systolic (left ventricular ejection fraction 120 mm Hg at baseline. Results Among patients with SBP > 120 mm Hg, all-cause mortality occurred in 28% and 22% of patients receiving placebo and Bucindolol, respectively (hazard ratio when Bucindolol was compared with placebo, 0.77; 95% confidence interval [CI], 0.59-0.99; P = 0.039). In contrast, among those with SBP ≤ 120 mm Hg, 36% and 35% of patients in the placebo and Bucindolol groups died, respectively (hazard ratio, 0.95; 95% CI, 0.81-1.12; P = 0.541). Hazard ratios (95% CIs; P values) for HF hospitalization associated with Bucindolol use were 0.70 (0.56-0.89; P = 0.003) and 0.82 (0.71-0.95; P = 0.008) for patients with SBP > 120 and ≤ 120 mm Hg, respectively. Conclusion Bucindolol, a nonselective β-blocker with weak α 2 -blocking properties, significantly reduced HF hospitalization in systolic HF patients regardless of baseline SBP. However, Bucindolol reduced mortality only in those with SBP > 120 mm Hg.
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Abstract 901: Effects of Bucindolol on Cardiovascular Mortality and Morbidity are Determined by the Beta-1 389 Arg/Gly Receptor Polymorphism
Circulation, 2007Co-Authors: Michel White, Christopher M. O'connor, Inder S Anand, Peter E. Carson, Jonathan F. Plehn, Stephen S. Gottlieb, Marc A. Silver, Joann Lindenfeld, Alan B. Miller, Mona FiuzatAbstract:Introduction: Bucindolol is a nonselective beta-adrenergic blocker with potent sympatholytic properties. The Beta-blocker Evaluation of Survival Trial (BEST) reported that the administration of buc...
Brian D. Lowes - One of the best experts on this subject based on the ideXlab platform.
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Outcomes according to subtype.
2012Co-Authors: David P. Kao, Michael R. Bristow, Brandie D. Wagner, Alastair D. Robertson, Brian D. LowesAbstract:Plac = placebo, Buc = Bucindolol.
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Kaplan-Meier survival curves according to Latent Class Model A subtype, Bucindolol vs. placebo.
2012Co-Authors: David P. Kao, Michael R. Bristow, Brandie D. Wagner, Alastair D. Robertson, Brian D. LowesAbstract:Kaplan-Meier survival curves according to Latent Class Model A subtype, Bucindolol vs. placebo.
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Figure 4a: Key features of Latent Class Model A, mortality trends, and response to Bucindolol.
2012Co-Authors: David P. Kao, Michael R. Bristow, Brandie D. Wagner, Alastair D. Robertson, Brian D. LowesAbstract:Figure 4b: Key features of Latent Class Model B, mortality trends, and response to Bucindolol.
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Kaplan-Meier survival curves for all nonischemic patients and according to Latent Class Model B subtype, Bucindolol vs. placebo.
2012Co-Authors: David P. Kao, Michael R. Bristow, Brandie D. Wagner, Alastair D. Robertson, Brian D. LowesAbstract:Kaplan-Meier survival curves for all nonischemic patients and according to Latent Class Model B subtype, Bucindolol vs. placebo.
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Logistic regression odds ratio for mortality and EF response according to Latent Class Models A and B subtype, SHFM Score and Bucindolol treatment.
2012Co-Authors: David P. Kao, Michael R. Bristow, Brandie D. Wagner, Alastair D. Robertson, Brian D. LowesAbstract:Logistic regression odds ratio for mortality and EF response according to Latent Class Models A and B subtype, SHFM Score and Bucindolol treatment.
Jonathan P Piccini - One of the best experts on this subject based on the ideXlab platform.
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Bucindolol for the maintenance of sinus rhythm in a genotype defined hf population the genetic af trial
Jacc-Heart Failure, 2019Co-Authors: Jonathan P Piccini, Michel White, William T Abraham, Christopher Dufton, Ian A Carroll, Jeff S Healey, Dirk J Van Veldhuisen, William H Sauer, Inder S Anand, Stephen B WiltonAbstract:Abstract Objectives The purpose of this study was to compare the effectiveness of Bucindolol with that of metoprolol succinate for the maintenance of sinus rhythm in a genetically defined heart failure (HF) population with atrial fibrillation (AF). Background Bucindolol is a beta-blocker whose unique pharmacologic properties provide greater benefit in HF patients with reduced ejection fraction (HFrEF) who have the beta1-adrenergic receptor (ADRB1) Arg389Arg genotype. Methods A total of 267 HFrEF patients with a left ventricular ejection fraction (LVEF) Results The hazard ratio (HR) for the primary endpoint was 1.01 (95% confidence interval [CI]: 0.71 to 1.42), but trends for Bucindolol benefit were observed in several subgroups. Precision therapeutic phenotyping revealed that a differential response to Bucindolol was associated with the interval of time from the initial diagnoses of AF and HF to randomization and with the onset of AF relative to that of the initial HF diagnosis. In a cohort whose first AF and HF diagnoses were Conclusions Pharmacogenetically guided Bucindolol therapy did not reduce the recurrence of AF/AFL or ACM compared to that of metoprolol therapy in HFrEF patients, but populations were identified who merited further investigation in future phase 3 trials.
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a genotype directed comparative effectiveness trial of Bucindolol and metoprolol succinate for prevention of symptomatic atrial fibrillation atrial flutter in patients with heart failure rationale and design of the genetic af trial
American Heart Journal, 2017Co-Authors: Jonathan P Piccini, William T Abraham, Jeff S Healey, William H Sauer, Benjamin A. Steinberg, Stuart J Connolly, Hussein R Alkhalidi, Patricia Dignacco, Dirk J Van Veldhuisen, Michel WhiteAbstract:Background Few therapies are available for the safe and effective treatment of atrial fibrillation (AF) in patients with heart failure. Bucindolol is a non-selective beta-blocker with mild vasodilator activity previously found to have accentuated antiarrhythmic effects and increased efficacy for preventing heart failure events in patients homozygous for the major allele of the ADRB1 Arg389Gly polymorphism (ADRB1 Arg389Arg genotype). The safety and efficacy of Bucindolol for the prevention of AF or atrial flutter (AFL) in these patients has not been proven in randomized trials. Methods/design The Genotype-Directed Comparative Effectiveness Trial of Bucindolol and Metoprolol Succinate for Prevention of Symptomatic Atrial Fibrillation/Atrial Flutter in Patients with Heart Failure (GENETIC-AF) trial is a multicenter, randomized, double-blinded “seamless” phase 2B/3 trial of Bucindolol hydrochloride versus metoprolol succinate, for the prevention of symptomatic AF/AFL in patients with reduced ejection fraction heart failure (HFrEF). Patients with pre-existing HFrEF and recent history of symptomatic AF are eligible for enrollment and genotype screening, and if they are ADRB1 Arg389Arg, eligible for randomization. A total of approximately 200 patients will comprise the phase 2B component and if pre-trial assumptions are met, 620 patients will be randomized at approximately 135 sites to form the Phase 3 population. The primary endpoint is the time to recurrence of symptomatic AF/AFL or mortality over a 24-week follow-up period, and the trial will continue until 330 primary endpoints have occurred. Conclusions GENETIC-AF is the first randomized trial of pharmacogenetic guided rhythm control, and will test the safety and efficacy of Bucindolol compared with metoprolol succinate for the prevention of recurrent symptomatic AF/AFL in patients with HFrEF and an ADRB1 Arg389Arg genotype. ( ClinicalTrials.gov NCT01970501 ).
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Pharmacogenomics of Bucindolol in Atrial Fibrillation and Heart Failure.
Current heart failure reports, 2017Co-Authors: Kishan S. Parikh, Jonathan P PicciniAbstract:We explore the pharmacogenomics of the beta-blocker Bucindolol by discussing relevant beta-1 adrenergic receptor (ADRB1) polymorphisms and recent beta-blocker studies. Through this, we will understand how Bucindolol may help patients with atrial fibrillation and heart failure with reduced ejection fraction (AF-HFrEF), which carries poor prognosis. Retrospective study of the Heart Failure: A Controlled Trial Investigating Outcomes of Exercise Training trial revealed the interaction between the optimal beta-blocker dose and the ADRB1 Arg389 genotype for HFrEF clinical outcomes. Further, a combinatorial genotype analysis in the Beta-Blocker Evaluation of Survival Trial showed that the Arg389Arg genotype, but not the Gly carrier, was associated with 40% lower mortality risk with Bucindolol. Finally, the AF-HFrEF subgroup with the ADRB1 Arg389Arg genotype had greater heart rate reduction and suggestion for mortality benefit. Therapeutic response to beta-blockers varies by beta-blocker mechanism, ADRB1 Arg389 genotype, and clinical setting (AF, HFrEF, AF-HFrEF). The ongoing trial A Genotype-Directed Comparative Effectiveness Trial of Bucindolol and Toprol-XL for Prevention of Symptomatic Atrial Fibrillation/Atrial Flutter in Patients with Heart Failure prospectively identifies AF-HFrEF patients with favorable genotype for Bucindolol to prevent AF recurrence.
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Bucindolol hydrochloride in atrial fibrillation and concomitant heart failure
Expert review of cardiovascular therapy, 2015Co-Authors: Eric Black-maier, Benjamin A. Steinberg, Jonathan P PicciniAbstract:Atrial fibrillation (AF) is the most prevalent cardiac arrhythmia and it increases the risk of thromboembolic stroke and death. AF is common in patients with heart failure and reduced ejection fraction (HFrEF), affecting between 30 and 40% of patients with HFrEF. AF increases the risk of death and hospitalization in patients with HFrEF. Only two antiarrhythmic drugs (amiodarone and dofetilide) are guideline-recommended in patients with AF and heart failure (HF). Meta-analyses of studies of major trials in HF suggest that patients with AF/HFrEF do not benefit from conventional β-blockers. Bucindolol has shown promise in the treatment of patients with AF/HFrEF. We will explore how the shared pathophysiology of AF/HF is targeted by the unique pharmacology of Bucindolol and review the existing data for Bucindolol in AF/HF. We will explore findings that support a pharmacogenetically modulated effect of Bucindolol in patients with polymorphisms in β1-adrenergic receptor and provide an overview of ongoing studies.
Eric J Eichhorn - One of the best experts on this subject based on the ideXlab platform.
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Myocardial Contractile Reserve by Dobutamine Stress Echocardiography Predicts Improvement in Ejection Fraction With β-Blockade in Patients With Heart Failure The β-Blocker Evaluation of Survival Trial (BEST)
Circulation, 2003Co-Authors: Eric J Eichhorn, Paul A Grayburn, Jonathan F. Plehn, Susan A. Mayer, Martin St. John Sutton, Christopher P. Appleton, Barry H. Greenberg, Anthony N. Demaria, Robert P. FrantzAbstract:Background— β-Blockers improve survival and reduce hospitalization in chronic heart failure (CHF) by biologically improving left ventricular ejection fraction (LVEF). However, a good predictor of improvement with this therapy has not been identified. This substudy of BEST examined whether myocardial contractile reserve, as determined by dobutamine stress echocardiography, predicts improvement in LVEF. Methods and Results— Seventy-nine patients with class III/IV CHF underwent dobutamine stress echocardiography before treatment with Bucindolol (n=41) or placebo (n=38). Regional wall motion score index (WMSI) was calculated as the sum of the scores in each segment divided by the total number of segments visualized. WMSI was compared with change in LVEF after 3 months of therapy as determined by gated radionuclide scan. Change in WMSI correlated inversely with change in LVEF after 3 months of Bucindolol (r=−0.72, P
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A trial of the beta-blocker Bucindolol in patients with advanced chronic heart failure.
The New England journal of medicine, 2001Co-Authors: Eric J Eichhorn, Michael R. Bristow, Heidi Krause-steinrauf, Michael J. Domanski, Philip W. LavoriAbstract:BACKGROUND Although beta-adrenergic-receptor antagonists reduce morbidity and mortality in patients with mild-to-moderate chronic heart failure, their effect on survival in patients with more advanced heart failure is unknown. METHODS A total of 2708 patients with heart failure designated as New York Heart Association (NYHA) functional class III (in 92 percent of the patients) or IV (in 8 percent) and a left ventricular ejection fraction of 35 percent or lower were randomly assigned to double-blind treatment with either Bucindolol (1354 patients) or placebo (1354 patients) and followed for the primary end point of death from any cause. RESULTS The data and safety monitoring board recommended stopping the trial after the seventh interim analysis. At that time, there was no significant difference in mortality between the two groups (unadjusted P=0.16). The results presented here are based on complete follow-up at the time of study termination (average, 2.0 years). There were a total of 449 deaths in the placebo group (33 percent) and 411 deaths in the Bucindolol group (30 percent; adjusted P=0.13). The risk of the secondary end point of death from cardiovascular causes was lower in the Bucindolol group (hazard ratio, 0.86; 95 percent confidence interval, 0.74 to 0.99), as was the risk of heart transplantation or death (hazard ratio, 0.87; 95 percent confidence interval, 0.77 to 0.99). CONCLUSIONS In a demographically diverse group of patients with NYHA class III and IV heart failure, Bucindolol resulted in no significant overall survival benefit.
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Effect of selective versus nonselective beta blockade on QT dispersion in patients with nonischemic dilated cardiomyopathy.
The American journal of cardiology, 1999Co-Authors: Susan I Fesmire, Lucille Marcoux, Debra S Lyyski, Michael K. Sprague, Harold L. Kennedy, Eric J EichhornAbstract:We retrospectively examined the electrocardiograms in all of our patients with nonischemic dilated cardiomyopathy and normal sinus rhythm before and after at least 3 months of metoprolol (n = 12), Bucindolol (n = 8), carvedilol (n = 6), or no beta blocker (n = 9). Both beta1-selective and nonselective beta-adrenergic blockade reduced QTc dispersion equally in patients with dilated cardiomyopathy.
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Hemodynamic and energetic comparison of Bucindolol and metoprolol for the treatment of congestive heart failure
The American journal of cardiology, 1995Co-Authors: Christian M. Heesch, Lucille Marcoux, Barbara Hatfield, Eric J EichhornAbstract:Abstract Although β blockers have demonstrated a salutary effect on ventricular function in patients with heart failure, it is unclear whether a nonselective third-generation β blocker produces different hemodynamic and energetic effects than a second-generation β 1 selective agent. In 30 male patients with heart failure, we retrospectively analyzed hemodynamic data from 2 protocols examining the effects of a nonselective β antagonist Bucindolol [n = 15), and a highly selective β 1 antagonist metoprolol (n = 15). Both studies were conducted in a similar fashion with patients undergoing cardiac catheterization before and after receiving 3 months of β blockade. Both groups were matched at baseline in terms of ventricular function, β blockade resulted in similar reductions in heart rate and similar improvements in ejection fraction, ventricular volumes, stroke and minute work, peak +dP/dt, and isovolumic relaxation in both groups. Only patients faking Bucindolol had a significant within-group decrease in resting left ventricular end-diastolic pressure. The metoprolol group had a greater decrease in coronary sinus blood flow and myocardial oxygen consumption. Bucindolol increased cardiac index more than metoprolol, but did not increase stroke volume index more than metoprolol. The Bucindolol group had an increase in systolic elastance, whereas the metoprolol group had a parallel left shift in this relation, thus, metoprolol reduces coronary blood flow and myocardial oxygen consumption more than Bucindolol, whereas Bucindolol produces slightly more favorable improvements in resting cardiac index and end-diastolic pressure. Otherwise, these 2 agents produced similar hemodynamic changes.
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Effects of Bucindolol in heart failure.
The American journal of cardiology, 1993Co-Authors: Eric J EichhornAbstract:Abstract Bucindolol hydrochloride is a phenoxypropanolamine with potent nonselective β antagonist and mild vasodilatory properties. In humans with congestive heart failure, it is extremely well tolerated and produces improvements in left ventricular systolic (ejection fraction, systolic elastance, cardiac index, and stroke work) and diastolic (isovolumic relaxation) performance while reducin pulmonary artery pressures and heart rate. These improvements occur without an increase in myocardial oxygen extraction or oxygen consumption. In addition, functional class improves with this agent although exercise tolerance and maximal oxygen consumption (VO 2max ) does not change, an effect that is not unexpected with a β-adrenergic antagonist. Bucindolol produces a decrease in plasma renin activity and plasma norepinephrine, effects that may be beneficial for the long-term treatment of congestive heart failure. However, these effects are most marked in patients with idiopathic dilated cardiomyopathy compared with patients with ischemic heart disease. This agent holds great promise for the treatment of heart failure patients.
