Depressed heart rate variability identifies postinfarction patients who might benefit from prophylactic treatment with amiodarone: A substudy of EMIAT (the European Myocardial Infarct Amiodarone Trial)

Abstract

OBJECTIVESThis substudy tested a prospective hypothesis that European Myocardial Infarct Amiodarone Trial (EMIAT) patients with depressed heart rate variability (HRV) benefit from amiodarone treatment.BACKGROUNDThe EMIAT randomized 1,486 survivors of acute myocardial infarction (MI) aged ≤75 years with left ventricular ejection fraction (LVEF) ≤40% to amiodarone or placebo. Despite a reduction of arrhythmic mortality on amiodarone, all-cause mortality was not changed.METHODSHeart 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) ≤50 ms and HRV index ≤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 ≤30%, patients with Holter arrhythmia and patients with baseline heart rate ≥75 beats/min.RESULTSCentralized Holter processing produced artificially high SDNN but accurate HRV index values. Heart rate variability index was ≤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 ≥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 ≤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 ≥75 beats/min: 37.9% reduction (p = 0.054).CONCLUSIONMeasurement of HRV in a large set of centrally processed Holter recordings is feasible with robust methods of assessment. Patients with LVEF ≤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.