Abstract P107: Association of Longitudinal Change and Fluctuation in QT Interval with Cardiovascular Outcomes: A Cohort Study in a Managed Care Setting

Abstract

Purpose. Both long and short QT intervals are associated with life-threatening cardiac arrhythmias and adverse cardiovascular (CV) events, but prior studies have typically relied on a single baseline measure of the QT interval. We examined the prospective association of within-person change and fluctuation in QT length over time with subsequent CV outcomes and all-cause mortality in a managed care setting. Methods. We assembled a cohort of 187,901 Northern California Kaiser Permanente Medical Care Program (KPMCP) members who underwent three or more standard 12-lead ECGs as part of regular care between 1995 and 2008. Cohort-specific log-linear models stratified by gender, age and race/ethnicity were used to correct raw QT measurements for heart rate (QTc). Non-fatal and fatal CV outcomes and all-cause mortality were identified between the last ECG and right censoring event (CV event, death, termination of health plan membership or 12/31/2009; the median [SD] follow-up time was 4.1 [3.7] years). Cox regression models adjusting for age, gender, race/ethnicity, hypertension, diabetes, hyperlipidemia, smoking status and average QTc were used to simultaneously generate hazard ratios and 95% CI for tertiles 1 and 3 (versus tertile 2) of the linear slope of QTc (change in ms per year) and for tertiles 2 and 3 (versus tertile 1) of the root mean square error of QTc (RMSE, variability about the linear slope in ms). Results. The mean QTc slope and RMSE were +2.2 ms/year and 15.3 ms in men and +1.4 ms/year and 14.3 ms in women, respectively. In fully-adjusted models, the sex-specific tertile 3 of the QTc slope was associated with increased hazard of acute coronary syndrome (Number of events; Hazard Ratio; 95% Confidence Interval) (17,920; 1.34; 1.30-1.39), ischemic stroke (11,716; 1.30; 1.25-1.36), heart failure (42,909; 1.47; 1.44-1.51), cardiac arrest (4,700; 1.67; 1.55-1.79) and all-cause mortality (72,392; 1.43;1.40-1.45). In turn, the sex-specific tertile 3 of the RMSE was associated with increased hazard of heart failure (1.34;1.31-1.37), cardiac arrest (1.19;1,11-1.28) and all-cause mortality (1.06;1.04-1.08). Conclusions. In an insured population that underwent multiple ECGs, both linear increase and fluctuation of QTc over time were significantly and independently associated with adverse CV outcomes. Whether these associations are causal or represent confounding effects of medications warrant further research.