Abstract Body (Do not enter title and authors here): Introduction: Several ECG parameters accessible via ambulatory Holter recordings may help risk-stratify coronary heart disease (CHD) risk, but their clinical use is mostly limited to arrhythmia detection. Candidate ECG-based measures for CHD include autonomic markers like heart rate variability (HRV) and cardiac repolarization measures involving the T wave and QT interval. We explored several potential ECG digital biomarkers for CHD classification in a cohort of veteran twins to help inform future research on real-time CHD risk assessment with ambulatory ECG monitoring.
Methods: We collected ambulatory Holter data (1,000 Hz, 3 channels) for one week from veteran twins recruited from the Vietnam Era Twins Registry. We assessed CHD if they described either previous MI, CABG, cardiac arrest/ICD shock, or PCI during a clinical history conducted by a trained clinician. We used the Physionet Cardiovascular Signal Toolbox to derive several ECG features from sliding 5-minute windows (table 1). For each ECG feature, we calculated several different statistical summary measures. This resulted in 164 total features. We performed logistic regression with forward selection and corrected for multiple comparisons with Bonferroni correction. We also tested the performance of the newly discovered ECG markers within twin CHD discordant pairs to control for family-level confounding. Lastly, we controlled for traditional CHD risk factors using multivariable models.
Results: We studied 514 men with mean (SD) age 73.4 (2.9) years; 7% were Black, and 23% had a history of CHD (table 2). The mean QT interval and T amplitude in lead I were the most strongly associated with CHD (p<0.0001 for both), and none of the other markers met criteria for statistical significance. The ECG-CHD relationships were similar within 33 twin pairs discordant for CHD (AUC 0.69). Adjustment for traditional risk factors did not reduce the observed ECG-CHD associations. The QT interval (427 ms) was longest in the cardiac arrest/ICD shock subgroup, while the T-amplitude (0.054 mV) was lowest in the subgroup with CABG history (table 3).
Discussion: In this cross-sectional study of older veteran twins, mean QT interval and T amplitude (lead I) were the only two significant Holter parameters associated with CHD after correction for multiple testing. These results can help to inform future studies of CHD risk with Holter monitors and ecological momentary assessments of stress and behavioral exposures.