Abstract and Introduction
Abstract
Aims: As a part of the Finnish Cardiovascular Study, we tested the hypothesis that T-wave alternans (TWA) predicts mortality in a general population of patients referred for a clinical exercise test.
Methods and results: A total of 1037 consecutive patients (mean age ± SD of 58 ± 13 years, 673 men and 364 women) with a clinically indicated exercise test and with technically successful electrocardiographic (ECG) data during a bicycle ergometer test were included in the study. Digital ECGs were recorded and TWA was analysed continuously with the time-domain modified moving average method. The maximum TWA value at heart rate (HR) <125 b.p.m. was derived and its capacity to stratify risk for all-cause death, cardiovascular death, and sudden cardiac death (SCD) was tested. During a follow-up of 44 ± 7 months (mean ± SD), 59 patients died; 34 were due to cardiovascular causes and 20 were due to SCD. In multivariate analysis after adjustment for age, sex, use of ß-blockers, functional class, maximal HR during exercise, previous myocardial infarction, and other common coronary risk factors, the relative risk of TWA ≥65 µV for SCD was 7.4 (95% CI, 2.8-19.4; P < 0.001), for cardiovascular mortality 6.0 (95% CI, 2.8-12.8; P < 0.001), and for all-cause mortality 3.3 (95% CI, 1.8-6.3; P = 0.001).
Conclusion: Time-domain TWA analysis powerfully predicts mortality in a general population undergoing a clinical exercise test.
Introduction
The merits of a clinical exercise test as a prognostic means are well recognized. Exercise capacity, levels and changes of blood pressure, as well as heart rate (HR) profile and certain electrocardiographic (ECG) parameters have been shown to predict all-cause and cardiac mortality. T-wave alternans (TWA) is a relatively novel ECG index representing beat-to-beat alternation in the shape, amplitude, or timing of the ST-segment and the T-wave. The main contemporary use of TWA is based on the spectral analysis of microvolt-level T-wave amplitude during exercise. TWA is considered to represent spatial or temporal variations in ventricular repolarization, and it has been linked to both inducible and spontaneous ventricular tachyarrhythmias as well as to the mechanisms leading to their initiation.
The accuracy and usefulness of exercise-induced TWA in predicting arrhythmic events and death have been investigated in several studies with, however, relatively small numbers of participants, with exception of two larger studies. These studies have mostly included patients with a high risk of life-threatening arrhythmias, such as those with a documented near-fatal arrhythmic event, impaired left ventricular function, congestive heart failure, ischaemic cardiomyopathy, or lower risk patients with prior MI. Surprisingly, despite a decade of research, there have been no studies of the prognostic significance of TWA in more general populations undergoing routine exercise testing. This gap in our knowledge may be attributable to the inherent restrictions of the spectral approach, which, because of data stationarity, dictates the use of a non-standard exercise test to elevate and fix HR for a sustained period and requires specialized electrodes. To circumvent these difficulties, we employed the time-domain modified moving average (MMA) analysis of TWA. The method has undergone extensive testing in the laboratory and has been shown in smaller studies with post-MI, implantable cardioverter defibrillator patients, and in those at increased risk for impending ventricular tachyarrhythmias to be capable of detecting increased cardiac electrical instability and risk for arrhythmia. The present study was designed to test the hypothesis that TWA has prognostic power in a more general population undergoing a clinically indicated exercise test as a part of the Finnish Cardiovascular Study (FINCAVAS).