Periodic repolarization dynamics for prediction of mortality: a systematic review and meta-analysis

Abstract

Abstract Background Prediction of death is the philosopher's stone of arrhythmology. The electrophysiology has proven to be an important tool to predict the risk of death. Periodic repolarization dynamics (PRD) is a novel electrocardiographic marker that indicates the sympathetic effect on repolarization. PRD qualifies the low-frequency oscillations of cardiac repolarization instability using high-resolution 12 channel 24-h Holter recording. Several studies showed that PRD was an independent predictor of all-cause mortality and cardiac mortality. However, the prediction value of PRD has not been established. Purpose To evaluate the prediction value of PRD as an approach of risk stratification that selects patients at a higher risk of death. Methods We conducted electronic searches of MEDLINE (PubMed), Embase, Cochrane Register of Controlled Trials (CENTRAL), Science Citation Index Expanded, WHO International Clinical Trials Registry platform (ICTRP) and ClinicalTrials.gov from inception to January 9th, 2020. We also screened for relevant abstracts from conferences including ACC Annual Scientific Sessions, ESC Congress and Annual Congress of the EHRA for the last five years (2014–2019). The primary outcome was all-cause mortality and secondary outcome was cardiac mortality. We included study with large sample size while more than one study were found based on the same originated population. We extracted data from included studies and reported pooled outcomes as hazard ratios (HRs) with 95% confidential intervals (CI) for time-to-event outcomes using DerSimonian-Laird random-effects model. We did statistical analyses using Stata version 12.0 and R version 3.6.1. Results 5 studies including 6758 patients met all selection criteria for our meta-analysis. Follow-up period ranged from 20.4 to 75.1 months. Among 5 studies, 3 studies considered PRD as dichotomous variable and the cut-off value was 5.75 deg2, while 2 studies considered PRD as continuous variable and coefficient was expressed in standardized units (increase per standard deviation). We did subgroup analysis according to the type of variable because of heterogeneity. There was a significant higher risk of all-cause mortality in PRD ≥5.75 deg2 patients compared with PRD <5.75 deg2 patients (HR 2.37, 95% CI 1.77–3.17). As for continuous variable, increased PRD was a predictor for all-cause death (HR 1.28, 95% CI 1.14–1.42) (Figure). The cardiac mortality was significantly increased in patients with PRD ≥5.75 deg2 vs PRD <5.75 deg2 (HR 3.06, 95% CI 1.66–5.65). Increased PRD was associated with cardiac mortality in continuous variable subgroup (HR 1.34, 95% CI 1.21–1.48) (Figure). Conclusion Our findings suggest PRD is a significant predictor of all-cause mortality and cardiac mortality. PRD provides new additional electrophysiological indicator for risk stratification until further investigations are available. Funding Acknowledgement Type of funding source: None