Prognostic capacity of a clinically indicated exercise test for cardiovascular mortality is enhanced by combined analysis of exercise capacity, heart rate recovery and T-wave alternans.

BACKGROUND: Exercise capacity, heart rate recovery and T-wave alternans are independent predictors of cardiovascular mortality. We tested whether these parameters contain supplementary prognostic information. METHODS: A total of 3609 consecutive patients (2157 men) referred for a routine, clinically indicated bicycle exercise test were enrolled in the Finnish Cardiovascular Study (FINCAVAS). Exercise capacity was measured in metabolic equivalents, heart rate recovery as the decrease in heart rate from maximum to one minute post-exercise, and T-wave alternans by time-domain Modified Moving Average method. RESULTS: During 57-month median follow-up (interquartile range 35-78 months), 96 patients died of cardiovascular causes (primary endpoint) and 233 from any cause. All three parameters were independent predictors of cardiovascular mortality when analysed as continuous variables. Adding metabolic equivalents (p < 0.001), heart rate recovery (p = 0.002) or T-wave alternans (p = 0.01) to the linear model improved its predictive power for cardiovascular mortality. The combination of low exercise capacity (<6 metabolic equivalents), reduced heart rate recovery (≤12 beats/min) and elevated T-wave alternans (≥60 µV) yielded the highest hazard ratio for cardiovascular mortality of 16.5 (95% confidence interval 4.0-67.7, p < 0.001). Harrell's C index was 0.719 (confidence interval 0.665-0.772) for cardiovascular mortality with previously defined cutpoints (<8 units for metabolic equivalents, ≤18 beats/min for heart rate recovery and ≥60 µV for T-wave alternans). CONCLUSION: The prognostic capacity of the clinical exercise test is enhanced by combined analysis of exercise capacity, heart rate recovery and T-wave alternans.

Importance of regional specificity of T-wave alternans in assessing risk for cardiovascular mortality and sudden cardiac death during routine exercise testing.

BACKGROUND: T-wave alternans (TWA) indicates increased risk for life-threatening arrhythmias. However, the regional distribution and predictivity of TWA among precordial leads remain unknown. OBJECTIVE: We analyzed the magnitude and prognostic power of TWA in precordial leads separately and in combination during routine exercise stress testing in the largest TWA study conducted to date. METHODS: The Finnish Cardiovascular Study (FINCAVAS) enrolled consecutive patients (n = 3,598, 56 ± 13 [mean ± standard deviation] years old, 2,164 men, 1,434 women) with a clinically indicated exercise test with bicycle ergometer. TWA was analyzed with the time-domain modified moving average method. RESULTS: During a follow-up of 55 months (interquartile range of 35-78 months), 231 patients died; 97 deaths were cardiovascular, and 46 were classified as sudden cardiac deaths (SCDs). In Cox analysis after adjustment for common coronary risk factors, each 20-µV increase in TWA in leads V1-V6 multiplied the hazard ratio for cardiovascular mortality by 1.486-fold (95% confidence interval [CI] 1.127-1.952; P = .005). Each 20-µV increase in TWA in lead V5 amplified the hazard ratio for cardiovascular mortality by 1.545 (95% CI 1.150-2.108; P = .004) and for SCD by 1.576 (95% CI 1.041-2.412; P = .033). CONCLUSIONS: Maximum TWA monitored from anterolateral precordial lead V5 is the strongest predictor of cardiovascular mortality and SCD during routine exercise testing in our analysis. Higher TWA values indicate greater cardiovascular mortality and SCD risk, supporting the concept that quantification of TWA should receive more attention.

Atrioventricular conduction and cardiovascular mortality: assessment of recovery PR interval is superior to pre-exercise measurement.

BACKGROUND: A prolonged electrocardiographic PR interval at rest has been considered a benign phenomenon until recently. OBJECTIVE: We hypothesized that measurement of the PR interval during recovery from physical exertion could improve cardiovascular mortality risk stratification because it would track the dynamic influences of homeostatic mechanisms controlling atrioventricular (AV) conduction. METHODS: A total of 1,979 consecutive patients (1,244 men and 735 women) with clinically indicated bicycle ergometer tests enrolled in FINCAVAS (the Finnish Cardiovascular Study) were included in the study. The PR interval was measured at 1 min before and at 2 min after exercise. RESULTS: During the mean follow-up period of 47 months (interquartile range: 37 to 59 months), 50 cardiovascular deaths (end point) were registered. The unadjusted hazard ratios (HR) in Cox regression analyses were significant for both continuous PR interval and first-degree atrioventricular (AV) block for pre- and post-exercise phases. After adjustment for standard markers, the PR interval for 20-ms increments (HR: 1.17, P = .117) and first-degree AV block (HR: 1.85, P = .138) during the pre-exercise phase were not prognostic. However, during recovery from exercise, prolonged AV conduction achieved significance both in continuous (HR: 1.29, P = .006) and dichotomized analyses (HR: 2.41, P = .045). CONCLUSION: The PR interval before exercise is not a robust risk stratifier for cardiovascular death during 4-year follow-up. Post-exercise assessment of AV conduction may offer improved prediction because of functional abnormalities that become manifest only during this physiologic challenge to the heart.

Impaired exercise capacity predicts sudden cardiac death in a low-risk population: enhanced specificity with heightened T-wave alternans.

AIMS: Because sudden cardiac death (SCD) is due to cardiac electrical instability, we postulated that prediction of this mode of death by exercise capacity will be enhanced by combined assessment with T-wave alternans (TWA), an index of repolarization abnormality. MATERIAL AND METHODS: The Finnish Cardiovascular Study enrolled consecutive patients (n=2,044) with a routine clinically indicated exercise test. Exercise capacity was measured in metabolic equivalents (METs) and TWA by time-domain modified moving average method. RESULTS: During 47.2+/-12.8-month follow-up (mean+/-SD) 120 patients died; 58 were cardiovascular deaths, and 29 were SCD. In multivariate analysis after adjustment for sex, age, smoking, use of beta-blockers, as well as other common coronary risk factors, the relative risk of patients whose exercise capacity was depressed (MET < 8) was 8.8 (95% CI 2.0-38.9, P=0.004) for SCD. The combination of low exercise capacity (MET < 8) and elevated TWA (> or =65 microV) yielded relative risks for SCD of 36.1 (6.3-206.0, P<0.001), for cardiovascular mortality of 21.1 (6.7-66.2, P<0.001), and for all-cause mortality of 7.8 (3.5-17.4, P<0.001) over patients with neither factor. CONCLUSIONS: Reduced exercise capacity, particularly in combination with heightened TWA, indicating enhanced cardiac electrical instability, powerfully predicts risk for SCD in patients referred for exercise testing.

Combined assessment of heart rate recovery and T-wave alternans during routine exercise testing improves prediction of total and cardiovascular mortality: the Finnish Cardiovascular Study.

BACKGROUND: Identification of individuals who are at risk for cardiovascular death remains a pressing public health challenge. Derangements in autonomic function acting upon an electrically unstable substrate are thought to be critical elements in triggering cardiovascular events. OBJECTIVE: The purpose of this study was to analyze heart rate recovery (HRR) in combination with T-wave alternans (TWA) to improve risk assessment. METHODS: The Finnish Cardiovascular Study (FINCAVAS) enrolled consecutive patients (N = 1,972 [1,254 men and 718 women], age 57 +/- 13 years [mean +/- SD]) with a clinically indicated exercise test using bicycle ergometer. TWA was analyzed continuously with the time-domain modified moving average method. Maximum TWA at heart rates <125 bpm was derived. RESULTS: During 48 +/- 13 months of follow-up (mean +/- SD), 116 patients died; 55 deaths were cardiovascular. In multivariable Cox analysis after adjustment for common coronary risk factors, high exercise-based TWA (> or =60 microV) and low HRR (< or =18 bpm) yielded relative risks for all-cause mortality of 5.0 (95% confidence 2.1-12.1, P <.01) and for cardiovascular mortality of 12.3 (95% confidence interval 4.3-35.3, P <.01). High recovery-based TWA (> or =60 microV) and low HRR (< or =18 bpm) yielded relative risks for all-cause death of 6.1 (95% confidence interval 2.8-13.2, P <.01) and for cardiovascular mortality of 8.0 (95% confidence interval 2.9-22.0, P <.01). Prediction by HRR and TWA, both singly and in combination, exceeded that of standard cardiovascular risk factors. CONCLUSION: Reduced HRR and heightened TWA powerfully predict risk for cardiovascular and all-cause death in a low-risk population. This novel approach could aid in screening of general populations during routine exercise protocols as well as improve insights into pathophysiology.