Abstract
Background: The prolongation or shortening of heart rate-corrected QT (QTc) predisposes patients to fatal ventricular arrhythmias and sudden cardiac death (SCD), but the association of dynamic change of QTc interval with mortality in the general population remains unclear.Methods: A total of 11,798 middle-aged subjects from the prospective, population-based cohort were included in this analysis. The QTc interval corrected for heart rate was measured on two occasions around 3 years apart in the Atherosclerosis Risk in Communities (ARIC) study. The ΔQTc interval was calculated by evaluating a change in QTc interval from visit 1 to visit 2.Results: After a median follow-up of 19.5 years, the association between the dynamic change of QTc interval and endpoints of death was U-shaped. The multivariate-adjusted hazard ratios (HRs) comparing subjects above the 95th percentile of Framingham–corrected ΔQTc (ΔQTcF) (≥32 ms) with subjects in the middle quintile (0–8 ms) were 2.69 (95% CI, 1.68–4.30) for SCD, 2.51 (1.68–3.74) for coronary heart disease death, 2.10 (1.50–2.94) for cardiovascular death, and 1.30 (1.11–1.55) for death from any cause. The corresponding HRs comparing subjects with a ΔQTcF below the fifth percentile (<-23 ms) with those in the middle quintile were 1.82 (1.09–3.05) for SCD, 1.83 (1.19–2.81) for coronary heart disease death, 2.14 (1.51–2.96) for cardiovascular death, and 1.31 (1.11–1.56) for death from any cause. Less extreme deviations of ΔQTcF were also associated with an increased risk of death. Similar, albeit weaker associations also were observed with ΔQTc corrected with Bazett's formula.Conclusions: A dynamic change of QTc interval is associated with increased mortality risk in the general population, indicating that repeated measurements of the QTc interval may be available to provide additional prognostic information.
Highlights
The QT interval on the electrocardiogram (ECG) mainly reflects cardiac ventricular repolarization as abnormal prolongation and shortening of the heart rate-corrected QT (QTc) interval are wellestablished risk markers for fatal ventricular arrhythmias, sudden cardiac death (SCD), and all-cause mortality in high-risk patients and within the general population [1,2,3,4]
As a considerable overlap of QTc intervals exists between patients with long QT syndrome (LQTS) and short QT syndrome (SQTS) and truly healthy individuals, it is difficult to use a single QTc value to distinguish all cases of pathogenic “long” or “short” from innocuous variants [8]
The incidence rates of adverse outcomes in patients with high QTcF (≥95th) in the prolonged-prolonged group seemed to be higher than those in the normal-prolonged or prolonged-normal group. In this large prospective cohort study, we observed that both QT interval prolongation and shortening were associated with higher risks of SCD, coronary heart disease (CHD) death, cardiovascular disease (CVD) death, and all-cause death compared with a relatively stable QTc interval, with no clear threshold for risk change
Summary
The QT interval on the electrocardiogram (ECG) mainly reflects cardiac ventricular repolarization as abnormal prolongation and shortening of the heart rate-corrected QT (QTc) interval are wellestablished risk markers for fatal ventricular arrhythmias, sudden cardiac death (SCD), and all-cause mortality in high-risk patients and within the general population [1,2,3,4]. Selecting rigorous cutoff values to define the normal QTc interval range in population-based studies would be inevitable at the expense of missing some actual patients or overdiagnosing healthy controls as abnormal patients. The prolongation or shortening of heart rate-corrected QT (QTc) predisposes patients to fatal ventricular arrhythmias and sudden cardiac death (SCD), but the association of dynamic change of QTc interval with mortality in the general population remains unclear
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