Left Ventricular Diastolic Function Improvement by Carvedilol Therapy in Advanced Heart Failure

Abstract

Carvedilol treatment in chronic heart failure (CHF) patients has been demonstrated to reduce mortality by improving cardiac systolic function and reducing left ventricular adverse remodeling. However, the effects of the drug on left ventricular (LV) filling are less studied. In this study we evaluated early and long-term diastolic cardiac modifications by an echo-Doppler method during carvedilol therapy in patients with advanced CHF and pseudonormal or restrictive filling pattern. We studied 58 patients with severe but stable CHF (39 in class NYHA III and 19 in IV) having systolic and diastolic dysfunction caused by idiopathic or ischemic cardiomyopathy. Thirty-two patients were randomized to receive previous treatment plus carvedilol (group 1) and 26 continued standard therapy (group 2). In all subjects we evaluated LV volumes, LV mass, LV ejection fraction (EF), and the following transmitral filling parameters: early wave (E), atrial wave (A), E/A ratio, deceleration time (DT), and isovolumetric releasing time (IVRT). After 4 months of therapy, the carvedilol group showed a significant increase of A wave (P < 0.001), DT (P < 0.0001), IVRT (P < 0.0001), and a significant reduction of E/A ratio (P < 0.0005) with respect to group 2. Further improvement was observed at 12 months (A P < 0.0005; DT P < 0.00002; IVRT P < 0.000004; E/A P < 0.0008), although an E wave reduction was observed in group 1 with respect to controls (P < 0.001). Moreover, after 1 year of follow-up a reduction of systolic volume (P < 0.001) and pulmonary pressure (P < 0.0001) and consequent increase of EF (P < 0.001) was observed in the carvedilol group. Carvedilol treatment improved diastolic function in CHF with severe diastolic and systolic impairment at early time, converting a restrictive or pseudonormal filling pattern into an altered pattern. These changes remained significant after 1 year of therapy together with improvement in systolic function.

Comparison of the effects of carvedilol and nebivolol on diastolic functions of the left ventricle in patients with non-ischemic heart failure

“…In our study, mitral E/A ratio was similarly reduced with carvedilol or nebivolol therapy due to reduction of mitral E wave velocity. This finding is in accordance with the results from previous studies [10,[18][19][20]22]. In contrast, Patrianakos et al [9] have reported that mitral E/A ratio was significantly decreased with nebivolol treatment in nonischemic HF patients at 12-month follow-up, but not with carvedilol therapy.…”

“…In HF patients with low EF, carvedilol therapy reduced mitral E velocity, E/A ratio and IVRT while it prolonged DT [18,20,22], as in our study. In contrast, mitral inflow velocities and mitral E/A ratio remained unchanged with carvedilol therapy in HF patients in previous two studies [9,10].…”

“…Carvedilol [7,9,10,18,20,[22][23][24] and nebivolol [8-10, 19, 25, 26] have been reported to have different effects on mitral E wave velocity and E/A ratio in previous studies. In our study, mitral E/A ratio was similarly reduced with carvedilol or nebivolol therapy due to reduction of mitral E wave velocity.…”

Heart Failure with Preserved Ejection Fraction

“…The guidelines recommend their use to control ventricular rate in patients with atrial fibrillation (Class I, LOE: C). However, their use in patients with sinus rhythm and controlled hypertension receives a class IIb recommendation given the scarcity of data in this setting with a limited number of small studies showing symptomatic and/or diastolic function parameters improvement with nebivolol and carvedilol [137][138][139][140]. Contrary to HFrEF where beta-blockers have shown a remarkable survival benefit, they have failed to show any effect on mortality in HFpEF patients to date.…”

Atrial Remodeling And Atrial Fibrillation: Mechanistic Interactions And Clinical Implications

“…Metoprolol and carvedilol can attenuate LV remodeling. [163][164][165] In a double-blind, placebo-controlled study in 394 patients with persistent AF who underwent cardioversion, metoprolol CR/XL was effective in preventing relapse into atrial fibrillation or flutter. 166 …”