beta-blockade therapy in chronic heart failure: Diastolic function and mitral regurgitation improvement by carvedilol

Background In patients with chronic heart failure, the use of carvedilol th erapy induces clinical and hemodynamic improvement. However, although the b enefits of this beta-blocker have been established in patients with chronic heart failure, the mechanisms underlying them and the changes in left vent ricular systolic function, diastolic function, and mitral regurgitation dur ing long-term therapy remain unclear. Objective To identify the clinical and functional effects of carvedilol, fo cusing on diastolic function and mitrat regurgitation variations. Methods Forty-five consecutive patients with chronic heart failure (ejectio n fraction 24% +/- 7%), 17 with dilated ischemic and 28 with nonischemic ca rdiomyopathy, were treated with carvedilol (mean dose 44 +/- 30 mg) and mat ched for clinical (New York Heart Association functional class and heart Fa ilure duration) and hemodynamic (cardiac index and pu lmonary wedge pressur e) characteristics to a control group, Clinical and echocardiographic varia bles were measured in the 2 groups at baseline and after 6 months and the r esults compared. Results After 6 months of treatment with carvedilol, left ventricular elect ion fraction had increased from 24% +/- 7% to 29% +/- 9% (P < .0001); this change was caused by a reduction in end-systolic volume index (106 +/- 41 v s 93 +/- 37 ml/m(2); P < .0001). Deceleration time of early diastolic filli ng increased (134 +/- 74 vs 196 +/- 63 ms; P < .0001). Seventeen of the 27 patients with demonstrated improvement of left ventricular diastolic fillin g moved From having a restrictive filling pattern to having a normal or pse udonormal left ventricular filling pattern. In the control group, no signif icant changes in deceleration time of early diastolic filling were found (1 39 +/- 74 vs 132 +/- 45 ms; P = not significant). The effective regurgitant orifice area decreased significantly in the carvedilol group but not in th e control group. These changes were associated with a significant reduction of the mitral regurgitant stroke volume in the corvedilol group (50 +/- 25 vs 16 +/- 13 mL; P < .0001) but not in the control group (57 +/- 29 vs 47 +/- 24 mt: P = not significant). These changes of mitral regurgitation were closely associated with significant improvement of forward aortic stroke v olume (r = -.57, P < .0001). These findings were not observed in patients i n the control group. Conclusions The results of this study show that long-term corvedilol therap y in patients with chronic heart failure was able to prevent or partially r everse progressive left ventricular dilatation. The effects on left ventric ular remodeling were associated with a concomitant recovery of diastolic re serve and a decrease of mitral regurgitation, which have been demonstrated to be powerful prognostic predictors in such patients. Overall these findin gs provide important insights into the pathophysiologic mech anisms by whic h carvedilol improves the clinical course of patients with chronic heart fa ilure.