T-wave Alternans As a Prognostic Marker in Patients Referred for Exercise Testing: Quantitative Analysis & Combined Assessment With Exercise Capacity ... Recovery (Acta Universitatis Tamperensis)

T-wave alternans (TWA) is an electrocardiogram (ECG) phenomenon illustrating inhomogeneities in cardiac electrical repolarization. It can be measured from the surface ECG as microvolt-level beat-to-beat alternation in the shape, timing, or amplitude of the ST segment or T wave. TWA has been experimentally and clinically linked to ventricular tachyarrhythmias as well as to the related pathogenesis. Moreover, positive TWA testing has been shown to predict all-cause and cardiovascular mortality as well as sudden cardiac death (SCD) in diverse patient populations. The present study was designed to solve the methodological issues related to the prognostic power of TWA analysis, with quantitative TWA analysis in particular. Furthermore, the prognostic power of TWA in combination with exercise capacity and heart rate recovery (HRR), a marker of autonomic nervous system imbalance, were studied.

This study is part of the Finnish Cardiovascular Study (FINCAVAS), which enrolled 4,178 (2,537 men) consecutive patients attending an exercise stress test at Tampere University Hospital between October 2001 and the end of 2008 (Study IV). A sub-population of 2,212 (1,400 men) were recruited by the end of 2004 (Studies I, II, and III). A continuous digital ECG signal (500 Hz) was recorded during the entire exercise test from the pre-exercise to the post-exercise phase. The Modified Moving Average (MMA) analysis, which allows TWA analysis during a normal symptom-limited exercise test, was employed. Exercise capacity was assessed in the form of metabolic equivalents (METs) in a standard manner, and HRR was determined as the maximum heart rate minus the heart rate at 1 minute after the cessation of exercise. Hazard ratios for all-cause and cardiovascular mortality as well as SCD were estimated with Cox regression analysis.

During the median follow-up of 48 months (37 59 interquartile range [IQ]), there were 126 deaths, 62 cardiovascular deaths, and 33 SCDs in the sub-population (Studies I, II, and III). The overall follow-up time for the 3,609 patients investigated in Study IV was 57 months (35 78 IQ), during which 233 patients died 96 of these deaths were further categorized as cardiovascular deaths. Elevated TWA levels measured during the exercise phase were found to be independently associated with an increased risk of all-cause and cardiovascular mortality and SCD when grouped in increments of 10µV. All-cause and cardiovascular mortality, but not SCD, were also predicted when TWA was measured during the pre- or post-exercise phase (Study I). When analyzed as a continuous variable, increased TWA voltage was a significant predictor of all-cause (Study I) and cardiovascular mortality (Studies I and IV).