Increased periodic repolarization dynamics (PRD) strongly predicted 5-year total mortality in survivors of acute myocardial infarction (HR 4.75; 95% CI 2.94-7.66; P<0.001).
Cohort (n=3,873)
Does increased periodic repolarization dynamics (PRD) predict mortality in survivors of acute myocardial infarction?
Periodic repolarization dynamics (PRD) is a novel marker of sympathetic activity that strongly predicts 5-year mortality in survivors of acute myocardial infarction.
Effect estimate: HR 4.75 (95% CI 2.94-7.66)
p-value: p=<0.001
BACKGROUND: Enhanced sympathetic activity at the ventricular myocardium can destabilize repolarization, increasing the risk of death. Sympathetic activity is known to cluster in low-frequency bursts; therefore, we hypothesized that sympathetic activity induces periodic low-frequency changes of repolarization. We developed a technique to assess the sympathetic effect on repolarization and identified periodic components in the low-frequency spectral range (≤0.1 Hz), which we termed periodic repolarization dynamics (PRD). METHODS: We investigated the physiological properties of PRD in multiple experimental studies, including a swine model of steady-state ventilation (n=7) and human studies involving fixed atrial pacing (n=10), passive head-up tilt testing (n=11), low-intensity exercise testing (n=11), and beta blockade (n=10). We tested the prognostic power of PRD in 908 survivors of acute myocardial infarction (MI). Finally, we tested the predictive values of PRD and T-wave alternans (TWA) in 2,965 patients undergoing clinically indicated exercise testing. RESULTS: PRD was not related to underlying respiratory activity (P<0.001) or heart-rate variability (P=0.002). Furthermore, PRD was enhanced by activation of the sympathetic nervous system, and pharmacological blockade of sympathetic nervous system activity suppressed PRD (P≤0.005 for both). Increased PRD was the strongest single risk predictor of 5-year total mortality (hazard ratio 4.75, 95% CI 2.94-7.66; P<0.001) after acute MI. In patients undergoing exercise testing, the predictive value of PRD was strong and complementary to that of TWA. CONCLUSION: We have described and identified low-frequency rhythmic modulations of repolarization that are associated with sympathetic activity. Increased PRD can be used as a predictor of mortality in survivors of acute MI and patients undergoing exercise testing. TRIAL REGISTRATION: ClinicalTrials.gov NCT00196274. FUNDING: This study was funded by Angewandte Klinische Forschung, University of Tübingen (252-1-0).
Rizas et al. (2014) conducted a cohort in Acute myocardial infarction survivors and patients undergoing exercise testing (n=3,873). Periodic repolarization dynamics (PRD) was evaluated on 5-year total mortality (HR 4.75, 95% CI 2.94-7.66, p=<0.001). Increased periodic repolarization dynamics (PRD) strongly predicted 5-year total mortality in survivors of acute myocardial infarction (HR 4.75; 95% CI 2.94-7.66; P<0.001).