The Spatial Ventricular Gradient Is an Independent Predictor of Anthracycline-Associated Cardiotoxicity

Anthracyclines are effective chemotherapies that are limited by cardiotoxicity. The spatial ventricular gradient (SVG) is a marker of electrical heterogeneity linked to adverse cardiovascular outcomes, including sudden cardiac death and heart failure (HF). The purpose of this study was to assess if SVG values before chemotherapy are associated with the risk of anthracycline-associated HF or cardiomyopathy (CM). We analyzed 12-lead electrocardiograms obtained within 6 months before initiation of anthracyclines in a retrospective cohort treated for cancer between 1992 and 2019 at a single academic medical center. Incident HF and CM were defined by ICD-9/10 codes and confirmed by chart review. Vectorcardiograms were constructed from baseline electrocardiograms, and the SVG was calculated. The cumulative incidence of anthracycline-associated HF or CM was regressed on SVG vector orientation and magnitude with death as a competing risk. In 889 patients (47% male; mean age 58 ± 16 years; 71% hematologic malignancies), larger SVG magnitude prechemotherapy was associated with decreased risk of HF or CM after multivariable adjustment, with a subhazard ratio of 0.76 per 1 SD increase (95% CI: 0.59-0.96; P = 0.024). SVG vector orientation, specifically a more leftward oriented VGx, was associated with decreased risk of HF or CM with a subhazard ratio of 0.77 per 1 SD increase (95% CI: 0.61-0.96; P = 0.023). Larger SVG magnitude and more leftward SVG orientation were associated with a decreased risk of anthracycline cardiotoxicity in a large retrospective cohort. Improved cardiac risk stratification algorithms incorporating the SVG could personalize both cancer and cardioprotective therapy.