Malik M, Camm A J, Janse M J, Julian D G, Frangin G A, Schwartz P J
Department of Cardiological Sciences, St. George's Hospital Medical School, London, United Kingdom.
J Am Coll Cardiol. 2000 Apr;35(5):1263-75. doi: 10.1016/s0735-1097(00)00571-4.
This substudy tested a prospective hypothesis that European Myocardial Infarct Amiodarone Trial (EMIAT) patients with depressed heart rate variability (HRV) benefit from amiodarone treatment.
The EMIAT randomized 1,486 survivors of acute myocardial infarction (MI) aged < or =75 years with left ventricular ejection fraction (LVEF) < or =40% to amiodarone or placebo. Despite a reduction of arrhythmic mortality on amiodarone, all-cause mortality was not changed.
Heart rate variability was assessed from prerandomization 24-h Holter tapes in 1,216 patients (606 on amiodarone). Two definitions of depressed HRV were used: standard deviation of normal to normal intervals (SDNN) < or =50 ms and HRV index < or =20 units. The survival of patients with depressed HRV was compared in the placebo and amiodarone arms. A retrospective analysis investigated the prospective dichotomy limits. All tests were repeated in five subpopulations: patients with first MI, patients on beta-adrenergic blocking agents, patients with LVEF < or =30%, patients with Holter arrhythmia and patients with baseline heart rate > or =75 beats/min.
Centralized Holter processing produced artificially high SDNN but accurate HRV index values. Heart rate variability index was < or =20 U in 363 (29.9%) patients (183 on amiodarone) with all-cause mortality 22.8% on placebo and 17.5% on amiodarone (23.2% reduction, p = 0.24) and cardiac arrhythmic mortality 12.8% on placebo and 4.4% on amiodarone (66% reduction, p = 0.0054). Among patients with prospectively defined depressed HRV, the largest reduction of all-cause mortality was in patients with first MI (placebo 17.9%, amiodarone 10.3%, 42.5% reduction, p = 0.079) and in patients with heart rate < or =75 beats/min (placebo 29.0%, amiodarone 19.3%, 33.7% reduction, p = 0.075). Among patients with first MI and depressed HRV, amiodarone treatment was an independent predictor of survival in a multivariate Cox analysis. The retrospective analysis found a larger reduction of mortality on amiodarone in 313 (25.7%) patients with HRV index < or =19 U: 23.9% on placebo and 17.1% on amiodarone (28.4% reduction, p = 0.15). This was more expressed in patients with first MI: 49.4% mortality reduction on amiodarone (p = 0.046), on beta-blockers: 69.0% reduction (p = 0.047) and with heart rate > or =75 beats/min: 37.9% reduction (p = 0.054).
Measurement of HRV in a large set of centrally processed Holter recordings is feasible with robust methods of assessment. Patients with LVEF < or =40% and depressed HRV benefit from prophylactic antiarrhythmic treatment with amiodarone. However, this finding needs confirmation in an independent data set before clinical practice is changed.
本亚组研究检验了一个前瞻性假设，即心率变异性（HRV）降低的欧洲心肌梗死胺碘酮试验（EMIAT）患者能从胺碘酮治疗中获益。
EMIAT将1486例年龄≤75岁、左心室射血分数（LVEF）≤40%的急性心肌梗死（MI）幸存者随机分为胺碘酮组或安慰剂组。尽管胺碘酮降低了心律失常死亡率，但全因死亡率未改变。
对1216例患者（606例服用胺碘酮）随机分组前的24小时动态心电图记录进行心率变异性评估。采用了两种HRV降低的定义：正常到正常间期的标准差（SDNN）≤50毫秒和HRV指数≤20单位。比较了安慰剂组和胺碘酮组中HRV降低患者的生存率。一项回顾性分析研究了前瞻性二分法界限。在五个亚组中重复了所有测试：首次发生MI的患者、使用β-肾上腺素能阻滞剂的患者、LVEF≤30%的患者、动态心电图出现心律失常的患者以及基线心率≥75次/分钟的患者。
集中的动态心电图处理产生了人为偏高的SDNN，但HRV指数值准确。363例（29.9%）患者的心率变异性指数≤20 U（183例服用胺碘酮），安慰剂组全因死亡率为22.8%，胺碘酮组为17.5%（降低23.2%，p = 0.24），安慰剂组心律失常性死亡率为12.8%，胺碘酮组为4.4%（降低66%，p = 0.0054）。在预期定义为HRV降低的患者中，全因死亡率降低幅度最大的是首次发生MI的患者（安慰剂组17.9%，胺碘酮组10.3%，降低42.5%，p = 0.079）和心率≤75次/分钟的患者（安慰剂组29.0%，胺碘酮组19.3%，降低33.7%，p = 0.075）。在首次发生MI且HRV降低的患者中，在多变量Cox分析中，胺碘酮治疗是生存的独立预测因素。回顾性分析发现，313例（25.7%）HRV指数≤19 U的患者使用胺碘酮后死亡率降低幅度更大：安慰剂组为23.9%，胺碘酮组为17.1%（降低28.4%，p = 0.15）。这在首次发生MI的患者中表现得更为明显：胺碘酮使死亡率降低49.4%（p = 0.046），在使用β受体阻滞剂的患者中：降低69.0%（p = 0.047），在心率≥75次/分钟的患者中：降低37.9%（p = 0.054）。
采用可靠的评估方法对大量集中处理的动态心电图记录进行HRV测量是可行的。LVEF≤40%且HRV降低的患者可从胺碘酮预防性抗心律失常治疗中获益。然而，在改变临床实践之前，这一发现需要在独立数据集中得到证实。
