Capomolla S, Febo O, Gnemmi M, Riccardi G, Opasich C, Caporotondi A, Mortara A, Pinna G D, Cobelli F
"Salvatore Maugeri" Foundation, Institute of Medical Care and Research, Pavia, Italy.
Am Heart J. 2000 Apr;139(4):596-608. doi: 10.1016/s0002-8703(00)90036-x.
In patients with chronic heart failure, the use of carvedilol therapy induces clinical and hemodynamic improvement. However, although the benefits of this beta-blocker have been established in patients with chronic heart failure, the mechanisms underlying them and the changes in left ventricular systolic function, diastolic function, and mitral regurgitation during long-term therapy remain unclear.
To identify the clinical and functional effects of carvedilol, focusing on diastolic function and mitral regurgitation variations.
Forty-five consecutive patients with chronic heart failure (ejection fraction 24% +/- 7%), 17 with dilated ischemic and 28 with nonischemic cardiomyopathy, were treated with carvedilol (mean dose 44 +/- 30 mg) and matched for clinical (New York Heart Association functional class and heart failure duration) and hemodynamic (cardiac index and pulmonary wedge pressure) characteristics to a control group. Clinical and echocardiographic variables were measured in the 2 groups at baseline and after 6 months and the results compared.
After 6 months of treatment with carvedilol, left ventricular ejection 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 vs 93 +/- 37 mL/m(2); P <. 0001). Deceleration time of early diastolic filling increased (134 +/- 74 vs 196 +/- 63 ms; P <.0001). Seventeen of the 27 patients with demonstrated improvement of left ventricular diastolic filling moved from having a restrictive filling pattern to having a normal or pseudonormal left ventricular filling pattern. In the control group, no significant changes in deceleration time of early diastolic filling were found (139 +/- 74 vs 132 +/- 45 ms; P = not significant). The effective regurgitant orifice area decreased significantly in the carvedilol group but not in the control group. These changes were associated with a significant reduction of the mitral regurgitant stroke volume in the carvedilol group (50 +/- 25 vs 16 +/- 13 mL; P <.0001) but not in the control group (57 +/- 29 vs 47 +/- 24 mL; P = not significant). These changes of mitral regurgitation were closely associated with significant improvement of forward aortic stroke volume (r = -.57, P <.0001). These findings were not observed in patients in the control group.
The results of this study show that long-term carvedilol therapy in patients with chronic heart failure was able to prevent or partially reverse progressive left ventricular dilatation. The effects on left ventricular remodeling were associated with a concomitant recovery of diastolic reserve and a decrease of mitral regurgitation, which have been demonstrated to be powerful prognostic predictors in such patients. Overall these findings provide important insights into the pathophysiologic mechanisms by which carvedilol improves the clinical course of patients with chronic heart failure.
在慢性心力衰竭患者中，使用卡维地洛治疗可带来临床和血流动力学改善。然而，尽管这种β受体阻滞剂在慢性心力衰竭患者中的益处已得到证实，但其潜在机制以及长期治疗期间左心室收缩功能、舒张功能和二尖瓣反流的变化仍不清楚。
确定卡维地洛的临床和功能作用，重点关注舒张功能和二尖瓣反流的变化。
连续纳入45例慢性心力衰竭患者（射血分数24%±7%），其中17例为扩张型缺血性心肌病，28例为非缺血性心肌病，接受卡维地洛治疗（平均剂量44±30mg），并根据临床（纽约心脏协会功能分级和心力衰竭病程）和血流动力学（心脏指数和肺楔压）特征与对照组进行匹配。在基线和6个月后测量两组的临床和超声心动图变量，并比较结果。
卡维地洛治疗6个月后，左心室射血分数从24%±7%增加到29%±9%（P<.0001）；这种变化是由于收缩末期容积指数降低（106±41 vs 93±37 mL/m²；P<.0001）。舒张早期充盈减速时间增加（134±74 vs 196±63 ms；P<.0001）。27例左心室舒张充盈改善的患者中有17例从限制性充盈模式转变为正常或假性正常左心室充盈模式。在对照组中，舒张早期充盈减速时间无显著变化（139±74 vs 132±45 ms；P=无显著性差异）。卡维地洛组有效反流口面积显著减小，而对照组未减小。这些变化与卡维地洛组二尖瓣反流卒中容积显著降低相关（50±25 vs 16±13 mL；P<.0001），而对照组未降低（57±29 vs 47±24 mL；P=无显著性差异）。二尖瓣反流的这些变化与主动脉前向卒中容积的显著改善密切相关（r = -.57，P<.0001）。对照组患者未观察到这些结果。
本研究结果表明，慢性心力衰竭患者长期使用卡维地洛治疗能够预防或部分逆转进行性左心室扩张。对左心室重构的影响与舒张储备的恢复和二尖瓣反流的减少同时发生，这已被证明是此类患者强有力的预后预测指标。总体而言，这些发现为卡维地洛改善慢性心力衰竭患者临床病程的病理生理机制提供了重要见解。
