Author + information
- Su-Hua Wu, MD, PhD⁎ (, )
- Xiao-Xiong Lin, MD,
- Yun-Jiu Cheng, MD,
- Yu-Gang Dong, MD, PhD,
- An-li Tang, MD,
- Jian-Gui He, MD, PhD,
- Jun Liu, MD, PhD and
- Hong Ma, MD
- ↵⁎Department of Cardiology, First Affiliated Hospital, Sun Yat-Sen University, No. 58 Zhongshan Road II, Guangzhou 510080, China
The early repolarization pattern (ERP), which is characterized by an elevation of ≥0.1 mV of the QRS-ST junction (J point) with either QRS slurring or notching in the inferior and/or lateral leads on 12-lead electrocardiography (ECG), has recently been associated with vulnerability to ventricular fibrillation in case-control studies. However, the prognostic significance of ERP in the general population remains controversial. We conducted a meta-analysis to summarize all published prospective studies and case-control studies to date on the risk and incidence of cardiac death, arrhythmia death, and all-cause death in the general population with ERP. The results from our meta-analysis showed that ERP was associated with increased risk of arrhythmia death (risk ratio: 1.70; 95% confidence interval [CI]: 1.19 to 2.42; p = 0.003) but not with cardiac or all-cause death. At the same time, we found that the absolute risk differences of the patients with ERP were 70 cases of arrhythmia death per 100,000 patients per year (1).
Although our meta-analysis included large sample sizes, long durations of follow-up, and well-established prospective studies or case-control studies and our pooled estimates were based on prospective analyses with detailed adjustment for confounding variables, there were some limitations. First, the relatively small number of studies limited our ability to identify which subgroups were at higher risk for reported events. Second, the small number of studies also limited our ability to determine whether heterogeneity in summary estimates was explained by factors related to study quality. Heterogeneity among studies was formally assessed using Q and I2 statistics, and risk ratios and 95% CIs were pooled in random-effects models in our meta-analysis because of big I2 values. Third, we cannot exclude the possibility of patient confounding and publication bias due to misclassification, although there was no evidence of publication bias (p = 0.22) in the patient risk estimates for arrhythmia death. At the same time, sensitivity analysis in our study showed that none of the individual studies substantially influenced the pooled risk ratios for any of the outcomes.
How the ERP increases the risk of arrhythmia death is unclear. Experimental studies have shown that a prominent transient outward current (Ito)–mediated action potential notch in ventricular epicardium, but not endocardium, causes a transmural voltage gradient during early ventricular repolarization that produces J-point elevation on the ECG. An increase in net repolarizing current, due either to a decrease of inward currents or augmentation of outward currents, accentuates the action potential notch and leads to augmentation of the J-point elevation. The prominent Ito responsible for the ERP may facilitate the development of ventricular fibrillation (2–5). The genetic basis for ERP remains unclear.
We consider ERP to have a cardiac electrophysiological unstable and potential intrinsic arrhythmogenic nature that increases the vulnerability to ventricular fibrillation in the presence of some provocative factors. Although primary prevention strategies for patients with ERP are not necessary, it may be important for future researchers to understand the genetic basis and ECG characteristics of the ERP subgroups with a higher risk for arrhythmia death.
- American College of Cardiology Foundation