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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)

Marek Malik, PhD, MD, FACC^*, A. John Camm, MD, FACC^*, Michiel J. Janse, MD, Desmond G. Julian, MD, FACC, Gerald A. Frangin, MD, Peter J. Schwartz, MD, FACC^|| on behalf of the EMIAT Investigators

^* Department of Cardiological Sciences, St. George’s Hospital Medical School, London, United Kingdom
Department of Clinical and Experimental Cardiology, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands
Netherhall Gardens, London, United Kingdom
Sanofi Recherche, Montpellier, France
^|| Department of Cardiology, University of Pavia and Policlinico S. Matteo IRCCS, Pavia, Italy

View larger version (32K): [in a new window]   Figure 1 Scatter diagram of heart rate variability values obtained from the RR interval datafiles used in the study.

View larger version (24K): [in a new window]   Figure 2 Curves of arrhythmia-free survival in patients selected by a prospectively defined criterion heart rate variability index 20 U. In each case, the p value corresponds to the log-rank statistics of the Kaplan-Meier survival model. Bold line = placebo arm; fine line = amiodarone arm. Arrhythmia = arrhythmia signs on Holter (see the text for details); fast heart rate = baseline short-term heart rate 75 beats/min; low LVEF = left ventricular ejection fraction 30%; MI = myocardial infarction.

View larger version (55K): [in a new window]   Figure 3 Dependence of mortality during EMIAT follow-up on the cut-off values of depressed HRV. For each HRV value, the graphs show the mortality in patients with HRV measure the value on the horizontal axis (that is, when using the value on the horizontal axis as a dichotomy cut-off). Open areas = noncardiac mortality; grey areas = cardiac nonarrhythmic mortality; solid areas = arrhythmic mortality. HRV = heart rate variability.

View larger version (54K): [in a new window]   Figure 4 Top graphs = mortality reduction on amiodarone in patients with depressed HRV. For each patient category and for each dichotomy of HRV, the graphs show the mortality reduction on amiodarone during the follow-up of EMIAT, that is, the value ([mortality on placebo] – [mortality on amiodarone])/[mortality on placebo], in patients with HRV the given dichotomy. Bottom graphs = statistical significance of the difference between survival on placebo and survival on amiodarone in groups of patients selected in the same way (the vertical axes show the l/p values—the higher the more significant; the statistical significance p = 0.05 corresponds to the value of 20 on the vertical axes). Note that the ranges of horizontal axes of graphs for both HRV index and standard deviation of normal to normal intervals correspond approximately to the range of 10% to 40% of the population of the study. arrhythmia = arrhythmia signs on Holter (see the text for details); BB = beta-blockers; fast HR = baseline short-term heart rate 75 beats/min; HRV = heart rate variability; low LVEF = left ventricular ejection fraction 30%; MI = myocardial infarction. Solid line = all patients; open square = first MI; solid square = on beta-blockers; open triangle = low LVEF; open diamond = arrhythmia; Ex = fast heart rate.

View larger version (24K): [in a new window]   Figure 5 Survival curves in patients selected by a retrospectively defined criterion heart rate variability index 19 U. In each case, the p value corresponds to the log-rank statistics of the Kaplan-Meier survival model. Bold line = placebo arm; fine line = amiodarone arm. arrhythmia = arrhythmia signs on Holter (see the text for details); fast heart rate = baseline short-term heart rate 75 beats/min; low LVEF = left ventricular ejection fraction 30%; MI = myocardial infarction.