Independent and Incremental Value of ECG Markers for Prediction of Cancer Therapy-Related Cardiac Dysfunction

BACKGROUND: Strategies to estimate risk of cancer therapy-related cardiac dysfunction (CTRCD) before initiating cardiotoxic cancer treatment are needed. We hypothesized that baseline ECG markers could identify patients at risk for CTRCD. METHODS AND RESULTS: In this retrospective cohort study, 1278 female patients with stage I–III HER2 (human epidermal growth factor receptor 2)-positive breast cancer meeting the following inclusion criteria were included: baseline ECG with QRS <120 milliseconds, baseline echocardiogram, and ≥1 follow-up echocardiogram. Quantitative measurements of ECG wave-form parameters were performed using MUSE (GE Healthcare). The primary outcome of interest was CTRCD at 1 year, defined by left ventricular ejection fraction decline (≥10% to <53% or ≥16% from baseline), or clinical heart failure (New York Heart Association class III/IV). Mean age was 51.7±11.1 years, 990 (77%) received anthracyclines, and all received HER2-targeted therapy. CTRCD occurred in 160 (13%) patients. In a multivariable Cox proportional hazards model adjusting for our previously published CTRCD risk score (composed of patient and treatment-specific factors), 4 ECG markers remained independently associated with CTRCD risk: QRS axis, R-wave duration (lead II), ST segment deviation (lead II), and Sokolow–Lyon voltage (all P<0.05). Compared with a model using only clinical CTRCD risk variables, addition of ECG parameters provided incremental value for predicting CTRCD risk (P<0.001, likelihood ratio test) with continuous net reclassification improvement of 34.9% and integrated discrimination improvement of 3.4%. CONCLUSIONS: Baseline ECG variables are predictive of subsequent CTRCD and provide incremental value to established clinical risk factors for CTRCD risk classification.