Mortara A, La Rovere M T, Pinna G D, Maestri R, Capomolla S, Cobelli F
Department of Cardiology, Centro Medico di Montescano, S. Maugeri Foundation, IRCCS, Pavia, Italy.
J Am Coll Cardiol. 2000 Nov 1;36(5):1612-8. doi: 10.1016/s0735-1097(00)00900-1.
The purpose of this study was to investigate in a case-controlled study whether carvedilol increased baroreflex sensitivity and heart rate variability (HRV).
In chronic heart failure (CHF), beta-adrenergic blockade improves symptoms and ventricular function and may favorably affect prognosis. Although beta-blockade therapy is supposed to decrease myocardial adrenergic activity, data on restoration of autonomic balance to the heart and, particularly, on vagal reflexes are limited.
Nineteen consecutive patients with moderate, stable CHF (age 54 +/- 7 years, New York Heart Association [NYHA] class II to III, left ventricular ejection fraction [LVEF] 24 +/- 6%), treated with optimized conventional medical therapy, received carvedilol treatment. Controls with CHF were selected from our database on the basis of the following matching criteria: age +/- 3 years, same NYHA class, LVEF +/- 3%, pulmonary wedge pressure +/- 3 mm Hg, peak volume of oxygen +/- 3 ml/kg/min, same therapy. All patients underwent analysis of baroreflex sensitivity (phenylephrine method) and of HRV (24-h Holter recording) at baseline and after six months.
Beta-blockade therapy was associated with a significant improvement in symptoms (NYHA class 2.1 +/- 0.4 vs. 1.8 +/- 0.5, p < 0.01), systolic and diastolic function (LVEF 23 +/- 7 vs. 28 +/- 9%, p < 0.01; pulmonary wedge pressure 17 +/- 8 vs. 14 +/- 7 mm Hg, p < 0.05) and mitral regurgitation area (7.0 +/- 5.1 vs. 3.6 +/- 3.0 cm2, p < 0.01). No significant differences were observed in either clinical or hemodynamic indexes in control patients. Phenylephrine method increased significantly after carvedilol (from 3.7 +/- 3.4 to 7.1 +/- 4.9 ms/mm Hg, p < 0.01) as well as RR interval (from 791 +/- 113 to 894 +/- 110 ms, p < 0.001), 24-h standard deviation of normal RR interval and root mean square of successive differences (from 56 +/- 17 to 80 +/- 28 ms and from 12 +/- 7 to 18 +/- 9 ms, all p < 0.05), while all parameters remained unmodified in controls. During a mean follow-up of 19 +/- 8 months a reduced number of cardiac events (death plus heart transplantation, 58% vs. 31%) occurred in those patients receiving beta-blockade.
Besides the well-known effects on ventricular function, treatment with carvedilol in CHF restores both autonomic balance and the ability to increase reflex vagal activity. This protective mechanism may contribute to the beneficial effect of beta-blockade treatment on prognosis in CHF.
本研究旨在通过病例对照研究，探讨卡维地洛是否能提高压力反射敏感性和心率变异性（HRV）。
在慢性心力衰竭（CHF）中，β-肾上腺素能阻滞剂可改善症状和心室功能，并可能对预后产生有利影响。尽管β-阻滞剂疗法被认为可降低心肌肾上腺素能活性，但关于恢复心脏自主神经平衡，特别是迷走反射的数据有限。
19例接受优化常规药物治疗的中度、稳定CHF连续患者（年龄54±7岁，纽约心脏协会[NYHA]II至III级，左心室射血分数[LVEF]24±6%）接受卡维地洛治疗。CHF对照组从我们的数据库中根据以下匹配标准选取：年龄±3岁、相同NYHA分级、LVEF±3%、肺楔压±3 mmHg、氧峰值容量±3 ml/kg/min、相同治疗。所有患者在基线和6个月后均接受压力反射敏感性分析（去氧肾上腺素法）和HRV分析（24小时动态心电图记录）。
β-阻滞剂疗法与症状显著改善相关（NYHA分级2.1±0.4 vs. 1.8±0.5，p<0.01）、收缩和舒张功能改善（LVEF 23±7 vs. 28±9%，p<0.01；肺楔压17±8 vs. 14±7 mmHg，p<0.05）以及二尖瓣反流面积减小（7.0±5.1 vs. 3.6±3.0 cm²，p<0.01）。对照组患者在临床或血流动力学指标上未观察到显著差异。卡维地洛治疗后，去氧肾上腺素法显著增加（从3.7±3.4至7.1±4.9 ms/mmHg，p<0.01），RR间期也增加（从791±113至894±110 ms，p<0.001），24小时正常RR间期标准差和逐次差值均方根增加（从56±17至80±28 ms以及从12±7至18±9 ms，均p<0.05），而对照组所有参数均未改变。在平均随访时间19±8个月期间，接受β-阻滞剂治疗的患者发生的心脏事件（死亡加心脏移植）数量减少（58% vs. 31%）。
除了对心室功能的众所周知的影响外，CHF患者使用卡维地洛治疗可恢复自主神经平衡以及增加反射性迷走神经活动的能力。这种保护机制可能有助于β-阻滞剂治疗对CHF预后产生有益影响。
