Mechanisms Underlying Improvements in Ejection Fraction With Carvedilol in Heart Failure

Abstract

Background-Reductions in heart rate (HR) with ␤-blocker therapy have been associated with improvements in ejection fraction (EF). However, the relative contributions of HR reduction, positive inotropism, afterload reduction, and reverse remodeling to improvements in EF are unknown. Methods and Results-Twenty-nine patients (63Ϯ12 years old) with New York Heart Association class II-III heart failure underwent serial measurements of left ventricular volumes using 3-dimensional echocardiography and blood pressures by sphygmomanometry at baseline, 2 weeks, 2, 6, and 12 months after initiation of carvedilol. From these parameters, left ventricular contractility (indexed by the end-systolic pressure-volume ratio), total peripheral resistance, and effective arterial elastance (E a ) were derived. Overall, EF increased by 7-percentage points after 6 months of therapy (from 25Ϯ9 to 32Ϯ9, PϽ0.0001). This change was due to an increase in stroke volume (PϽ0.001) with no significant change in end-diastolic volume (Pϭ0.15). The EF change correlated with increased contractility, decreased HR and decreased total peripheral resistance (PϽ0.003 in each case). In those patients whose EF increased at least 5 points, Ϸ60% of the increase was due to HR reduction, Ϸ30% was due to increased contractility, and Ͻ20% was due to the decrease in total peripheral resistance. Conclusions-Decreased

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

“…Such results are comparable to previous studies [18,[26][27][28]. It was reported that HR reduction has most significant contribution to improved LVEF with carvedilol therapy [29]. In the present study, HR decreased during the first month of bisoprolol therapy without any further decrease thereafter; in contrast, LVEF gradually improved over 12 month along with the inhibition of myocardial collagen degradation.…”

Effects of Early, Late, and Long-term Nonselective β-Blockade on Left Ventricular Remodeling, Function, and Survival in Chronic Organic Mitral Regurgitation

“…In this study, carvedilol (a nonselective adrenergic receptor antagonist) was used because it has beneficial effects of reducing heart rate and afterload, as well as improving myocardial contractility and LVEF, in congestive heart failure. 28 Similar to previous findings, 11,12 heart rate and blood pressure decreased in the β-blockade group in the current study. Rats with organic MR tolerated carvedilol well at the early stages of MR.…”

Pressure-Volume Loops in Clinical Research

“…However, with recent technological and conceptual advances that allow noninvasive estimation of these relationships (9)(10)(11), this situation is changing. Originally validated (9-11) and used (12)(13)(14) in studies involving small numbers of patients, reports have started appearing in which these noninvasive approaches are being used in relatively large numbers of patients (15,16).…”