Heart-rate turbulence after ventricular premature beats as a predictor of mortality after acute myocardial infarction

Summary

Background

Identification of high-risk patients after acute myocardial infarction is essential for successful prophylactic therapy. The predictive accuracy of currently used risk predictors is modest even when several factors are combined. Thus, establishment of a new powerful method for risk prediction independent of the available stratifiers is of considerable practical value.

Methods

The study investigated fluctuations of sinus-rhythm cycle length after a single ventricular premature beat recorded in Holter electrocardiograms, and characterised the fluctuations (termed heart-rate turbulence) by two numerical parameters, termed turbulence onset and slope. The method was developed on a population of 100 patients with coronary heart disease and blindly applied to the population of the Multicentre Post-Infarction Program (MPIP; 577 survivors of acute infarction, 75 deaths during a median follow-up of 22 months) and to the placebo population of the European Myocardial Amiodarone Trial (EMIAT; 614 survivors of acute myocardial infarction, 87 deaths during median follow-up of 21 months). Multivariate risk stratification was done with the new parameters and conventional risk factors.

Findings

One of the new parameters (turbulence slope) was the most powerful stratifier of follow-up mortality in EMIAT and the second most powerful stratifier in MPIP:MPIP risk ratio 3·5 (95% Cl 2·2–5·5, p< 0·0001), EMIAT risk ratio 2·7 (1·8–4·2, p< 0·0001), In the multivariate analysis, low left-ventricular ejection fraction and turbulence slope were the only independent variables for mortality prediction in MPIP (p< 0·001), whereas in EMIAT, five variables were independent mortality predictors: abnormal turbulence onset, abnormal turbulence slope, history of previous infarction, low left-ventricular ejection fraction, and high mean heart rate (p< 0·001). In both MPIP and EMIAT, the combination of abnormal onset and slope was the most powerful multivariate risk stratifier: MPIP risk ratio 3·2 (1·7–6·0, p< 0·0001), EMIAT risk ratio 3·2 (1·8–5·6, p< 0·0001).

Interpretation

The absence of the heart rate turbulence after ventricular premature beats is a very potent postinfarction risk stratifier that is independent of other known risk factors and which is stronger than other presently available risk predictors.

Introduction

Clinical trials1, 2 suggest that in high-risk patients with ischaemic heart disease, mortality can be effectively reduced by implantation of a cardioverter-defibrillator. Since the selection of high-risk patients is a crucial part of prophylaxis, risk stratification strategies are important. In patients surviving acute myocardial infarction, the predictive value of currently used risk factors, such as left-ventricular dysfunction, 3, 4, 5 frequent ventricular ectopic beats (VPB), ⁶ non-sustained ventricular tachycardia, ⁵ positive late potentials,⁷ heart-rate variability, ⁸ and mean heart rate ⁹ is modest ¹⁰ even when several predictors are combined and methodological issues of such a combination solved.¹¹ Establishment of a new risk predictor independent of the presently available stratifiers is therefore of considerable practical value.

We describe a new method for risk stratification based on a simple expression of ventriculophasic sinus arrhythmia, 12, 13, 14 namely fluctuations of sinus-rhythm cycle length after a single VPB. We term such fluctuations heart-rate turbulence. In low-risk patients, we observed that after a VPB, sinus shythm shows a characteristic pattern of early acceleration and subsequent deceleration. Such a characteristic pattern does not occur in high-risk patients. We propose to characterise this phenomenon by two descriptors, both of which contain independent information on the risk of subsequent mortality.

The new risk predictors were developed in an open study with a training sample of 100 patients accumulated at the medical department of the Technical University in Munich and validated blind, in both univariate and multivariate analyses, in two large independent populations of myocardial-infarction survivors, namely the population of the Multicentre Post-Infarction Program (MPIP) study ⁴ and in the placebo group of the European Myocardial Infarction Amiodarone Trial (EMIAT).¹⁵