Novel Predictor of Prognosis From Exercise Stress Testing
Background: Although the prognostic power of heart rate variability (HRV) at rest has been demonstrated, the prognostic potential of exercise-induced HRV has not been investigated. We aimed to evaluate the prognostic power of exercise-induced HRV during and after standard exercise testing.
Methods: Time- and frequency-domain HRV analysis was performed on R-R interval data taken from 1335 subjects (95% male, mean age 58 years) during the first and last 2 minutes of exercise treadmill testing and the first 2 minutes of recovery. Cox survival analysis was performed for the 53 cardiovascular and 133 all-cause mortality end points that accrued during the 5.0-year mean follow-up.
Results: After adjusting for potential confounders, greater root mean square successive difference in R-R interval during peak exercise and recovery, greater high-frequency (HF) power and percentage of HF power, lower percentage of low-frequency power, and lower ratio of low frequency to HF during recovery were significantly associated with increased risks for all-cause and cardiovascular death. Of all time-domain variables considered, the log of the root mean square successive difference during recovery was the strongest predictor of cardiovascular mortality (adjusted hazard ratio 5.0, 95% CI 1.5-17.0 for the top quintile compared with the lowest quintile). Log HF power during recovery was the strongest predictor of cardiovascular mortality in the frequency domain (adjusted hazard ratio 5.9, 95% CI 1.3-25.8 for the top quintile compared with the lowest quintile).
Conclusions: Exercise-induced HRV variables during and after clinical exercise testing strongly predict both cardiovascular and all-cause mortality independent of clinical factors and exercise responses in our study population.
The heart rate response to exercise and heart rate recovery from exercise reflect autonomic control of heart rate and have been shown to predict cardiovascular prognosis. The postulated pathophysiologic basis of these observations is that autonomic imbalance can increase the risk for experiencing cardiovascular events. Heart rate variability (HRV), or differences in beat-to-beat interval (R-R interval) among successive heart rate cycles, is also thought to reflect cardiovascular responses to autonomic activity. Heart rate variability has been related to respirations, baroreflexes, and thermal regulation. These factors are reflected in spectral analysis studies of HRV, which have identified 3 major components of the HRV spectrum: a high-frequency (HF) peak (HF >0.1 Hz) corresponding to respiratory sinus arrhythmia under ordinary circumstances, a low-frequency (LF) peak (LF 0.04-0.09 Hz) that is thought to be related to arterial pressure control, and a very low-frequency (VLF) component (VLF <0.04 Hz) that is thought to be an expression of peripheral vasomotor regulation.
Low time- and frequency-domain HRV have been shown to be associated with increased mortality in the Framingham cohort and in survivors of acute myocardial infarction, increased incidence of new cardiac events, and increased incidence of cardiovascular morbidity and mortality in subjects without coronary disease. The frequency of the prevalent LF oscillation has also been shown to predict outcome in patients with previous myocardial infarctions. All of these studies evaluated HRV at rest. To date, however, no studies have been performed to investigate the prognostic potential of exercise-induced HRV (EI-HRV). We aimed to investigate the prognostic potential of EI-HRV by retrospective analysis of EI-HRV data and outcomes for 1335 patients who underwent a standard clinical exercise test.
Abstract and Introduction
Abstract
Background: Although the prognostic power of heart rate variability (HRV) at rest has been demonstrated, the prognostic potential of exercise-induced HRV has not been investigated. We aimed to evaluate the prognostic power of exercise-induced HRV during and after standard exercise testing.
Methods: Time- and frequency-domain HRV analysis was performed on R-R interval data taken from 1335 subjects (95% male, mean age 58 years) during the first and last 2 minutes of exercise treadmill testing and the first 2 minutes of recovery. Cox survival analysis was performed for the 53 cardiovascular and 133 all-cause mortality end points that accrued during the 5.0-year mean follow-up.
Results: After adjusting for potential confounders, greater root mean square successive difference in R-R interval during peak exercise and recovery, greater high-frequency (HF) power and percentage of HF power, lower percentage of low-frequency power, and lower ratio of low frequency to HF during recovery were significantly associated with increased risks for all-cause and cardiovascular death. Of all time-domain variables considered, the log of the root mean square successive difference during recovery was the strongest predictor of cardiovascular mortality (adjusted hazard ratio 5.0, 95% CI 1.5-17.0 for the top quintile compared with the lowest quintile). Log HF power during recovery was the strongest predictor of cardiovascular mortality in the frequency domain (adjusted hazard ratio 5.9, 95% CI 1.3-25.8 for the top quintile compared with the lowest quintile).
Conclusions: Exercise-induced HRV variables during and after clinical exercise testing strongly predict both cardiovascular and all-cause mortality independent of clinical factors and exercise responses in our study population.
Introduction
The heart rate response to exercise and heart rate recovery from exercise reflect autonomic control of heart rate and have been shown to predict cardiovascular prognosis. The postulated pathophysiologic basis of these observations is that autonomic imbalance can increase the risk for experiencing cardiovascular events. Heart rate variability (HRV), or differences in beat-to-beat interval (R-R interval) among successive heart rate cycles, is also thought to reflect cardiovascular responses to autonomic activity. Heart rate variability has been related to respirations, baroreflexes, and thermal regulation. These factors are reflected in spectral analysis studies of HRV, which have identified 3 major components of the HRV spectrum: a high-frequency (HF) peak (HF >0.1 Hz) corresponding to respiratory sinus arrhythmia under ordinary circumstances, a low-frequency (LF) peak (LF 0.04-0.09 Hz) that is thought to be related to arterial pressure control, and a very low-frequency (VLF) component (VLF <0.04 Hz) that is thought to be an expression of peripheral vasomotor regulation.
Low time- and frequency-domain HRV have been shown to be associated with increased mortality in the Framingham cohort and in survivors of acute myocardial infarction, increased incidence of new cardiac events, and increased incidence of cardiovascular morbidity and mortality in subjects without coronary disease. The frequency of the prevalent LF oscillation has also been shown to predict outcome in patients with previous myocardial infarctions. All of these studies evaluated HRV at rest. To date, however, no studies have been performed to investigate the prognostic potential of exercise-induced HRV (EI-HRV). We aimed to investigate the prognostic potential of EI-HRV by retrospective analysis of EI-HRV data and outcomes for 1335 patients who underwent a standard clinical exercise test.