Prolongation of the heart rate-corrected QT interval is associated with cardiovascular diseases: Systematic review and meta-analysis

Sabrina J.G.C. Welten, Petra J.M. Elders, Sharon Remmelzwaal, Roos Doekhie, Kok Wai Kee, Giel Nijpels, Amber A. van der Heijden, for the ESCAPE-NET investigators

Background. – Conflicting findings have described the association between prolonged heart rate-corrected QT interval (QTc) and cardiovascular disease.

Aims. – To identify articles investigating the association between QTc and cardiovascular disease morbidity and mortality, and to summarize the available evidence for the general and type 2 diabetes populations.

Methods. –Asystematic search was performed in PubMed and Embase in May 2022 to identify studies that investigated the association between QTc prolongation and cardiovascular disease in both the general and type 2 diabetes populations. Screening, full-text assessment, data extraction and risk of bias assessment were performed independently by two reviewers. Effect estimates were pooled across studies using random-effect models.

Results. – Of the 59 studies included, 36 qualified for meta-analysis. Meta-analysis of the general population studies showed a significant association for: overall cardiovascular disease (fatal and non-fatal) (hazard ratio [HR] 1.68, 95% confidence interval [CI] 1.33–2.12; I² = 69%); coronary heart disease (fatal and non-fatal) in women (HR 1.27, 95% CI 1.08–1.50; I² = 38%; coronary heart disease (fatal and non-fatal)in men (HR 2.07, 95% CI 1.26–3.39; I² = 78%); stroke (HR 1.59, 95% CI 1.29–1.96; I² = 45%); sudden cardiac death (HR 1.60, 95% CI 1.14–2.25; I² = 68%); and atrial fibrillation (HR 1.55, 95% CI 1.31–1.83; I² = 0.0%).
No significant association was found for cardiovascular disease in the type 2 diabetes population.