Left ventricular diastolic function improvement by carvedilol therapy in advanced heart failure

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.