Background:

Periodic repolarization dynamics (PRD) is an electrocardiographic biomarker that quantifies sympathetic-activity associated instabilities of cardiac repolarization. PRD is a strong predictor of mortality and sudden cardiac death in patients with ischaemic (ICM) and non-ischaemic cardiomyopathy (NICM) and has been proposed as a marker for identification of patients who might benefit from prophylactic ICD implantation. 

Purpose: 

To conduct a systematic review and meta-analysis concerning the prognostic value of PRD for predicting all-cause mortality in relation to prophylactic ICD-implantation.

Methods: 

The reporting of this meta-analysis follows the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. A total of 24 full-text articles were screened. 7 randomized and non-randomized controlled trials were identified and after exclusion of 2 trials, a total of 5 could be included in the final analysis (Fig.1). Included patients were stratified into patients with or without prophylactic ICD-implantation (Fig. 2). The prognostic value of PRD for predicting all-cause mortality was extracted from published data as hazard ratio (HR) per 1deg² increase in PRD.  We used inverse-variance-weighted average meta-analysis to calculate fixed-effect and random-effect models. We finally estimated the overall predictive value of PRD in patients with and without prophylactic ICD-implantation. The interaction between PRD and prophylactic ICD-implantation for predicting all-cause mortality was calculated using meta-regression analysis. All-analyses were performed using CRAN R v.4.1.2 and the meta-package v5.2.0.

Results: 

We included 4,338 patients in this meta-analysis, out of whom 3,167 (73%) suffered from ICM and 1,171 (27%) from NICM. 1,906 (44%) patients were treated with an ICD. During an estimated mean follow-up time of 3.2 years, 604 (14%) patients died. The left side of Figure 2 shows patients without ICD treatment (N = 2,432, 56%). In these patients, a 1deg² increase in PRD was significantly associated with an overall 8% increase in all-cause mortality, using both fixed-effect (HR 1.08; 95% CI 1.06-1.10; p< 0.001) and random-effect models (HR 1.08; 95% CI 1.06-1.11; p < 0.001). The right side of Figure 2 displays patients with ICD treatment (N=1,906) and summarizes the prognostic value of PRD in patients undergoing prophylactic ICD-implantation (N = 1,906). In these patients, a 1deg² increase in PRD was significantly associated with an overall 3% increase in all-cause mortality using both fixed-effect (HR 1.03; 95% CI 1.01-1.05; p< 0.001) and random-effect models (HR 1.03; 95% CI 1.00-1.06; p < 0.001). In patients from the EU-CERT-ICD and the DANISH trial treated with an ICD an increase in PRD was not significantly associated with an increase in all-cause mortality. While PRD was a significant predictor of mortality in both groups, there was a significant interaction between PRD and prophylactic ICD-implantation for predicting all-cause mortality (p = 0.008).

Conclusion: 

In patients with ICM and NICM, PRD is a strong predictor of all-cause mortality in patients with and without prophylactic ICD. There is a significant interaction between PRD and prophylactic ICD-implantation, which most probably implies that the increased risk identified by PRD can be partially reversed by a prophylactic ICD-implantation. Consequently, PRD could prove a useful tool for identifying patients that might benefit from prophylactic ICD-implantation.