Can electronic cigarettes affect ECG repolarization indices? A systematic review and meta-analysis

The rapid global adoption of electronic cigarettes (e-cigarettes) has sparked concerns about their cardiovascular safety, particularly their impact on ventricular repolarization - a critical electrophysiological process linked to arrhythmia risk. Despite growing usage, evidence on how e-cigarettes affect ECG-derived repolarization parameters remains fragmented and insufficiently explored, highlighting a pressing need for synthesis.

This systematic review and meta-analysis focused exclusively on e-cigarette users, evaluating four ventricular repolarization markers: Tpe/QT ratio, Tp-e/QTc ratio, QT interval (ms), and Tp-e interval (ms). Databases (PubMed, Embase, Cochrane, Scopus, Web of Science) were systematically searched for human studies comparing e-cigarette users to non-smokers. Inclusion criteria mandated clear reporting of at least one repolarization parameter and distinct groups (e-cigarette users vs. non-smokers). Studies from various regions worldwide were included, ensuring broad geographic diversity and a comprehensive analysis of different healthcare systems and populations. Studies with mixed populations (e.g., combined tobacco/e-cigarette users) or marijuana consumers were excluded. No biases were detected after thorough evaluation.

254 patients were included (114 e-cigarette users, 140 controls) from 3 studies. Pooled analyses using random-effects models demonstrated significant adverse effects of e-cigarette use across all parameters. Tp-e/QTc ratio exhibited the strongest association, with a standardized mean difference (SMD) of 1.04 [95 % CI: 0.78-1.31; p < 0.00001], indicating pronounced prolongation in e-cigarette users. Notably, this finding showed remarkable consistency (I² = 0 %), suggesting minimal heterogeneity between studies. For the Tpe/QT ratio, the SMD was 0.81 [0.17-1.46; p = 0.01], though high heterogeneity (I² = 83 %) urged caution in interpretation. The QT interval was prolonged by 8.36 ms [2.44-14.29; p = 0.006], while the Tp-e interval increased by 4.34 ms [1.56-7.12; p < 0.00001], both statistically robust outcomes. Sensitivity analyses and subgroup tests confirmed reliability, with Wald-type confidence intervals and restricted maximum-likelihood (Tau²) methods addressing variability.

E-cigarette use is associated with significant alterations in ventricular repolarization parameters, suggesting potential arrhythmogenic risks. While the results are statistically robust, the meta-analysis included few high-quality studies, reflecting a critical gap in the current evidence base. To confirm these findings and elucidate long-term cardiovascular effects, rigorously designed, large-scale studies are urgently needed. Future research must prioritize standardized methodologies and longitudinal assessments to ensure clinical relevance and reliability.