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

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.

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 waveform 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%.

Baseline ECG variables are predictive of subsequent CTRCD and provide incremental value to established clinical risk factors for CTRCD risk classification.