Time-Varying Spatial Ventricular Gradient Orientation Is Associated With Anthracycline Heart Failure

BACKGROUND: Anthracycline use is limited by cardiotoxicity resulting in heart failure (HF). The spatial ventricular gradient (SVG) is a vectorcardiographic measurement of myocardial electrical heterogeneity associated with sudden death and incident HF. It is unclear if serial measurement of SVG after anthracycline initiation can help predict subsequent HF. OBJECTIVES: The objective of the study was to determine if time-varying SVG measurements are associated with anthracycline HF. METHODS: Retrospective, single-center study of adult patients with cancer treated with anthracyclines between 1992 to 2019. Standard 12-lead electrocardiograms obtained within 6 months before and up to 5 years after anthracycline initiation were analyzed. Patients with prior HF or ≤1 electrocardiogram within 5 years were excluded. Median vectorcardiograms were constructed, and the SVG vector was obtained by integrating under the X, Y, and Z QRST complexes. Multivariable competing-risks regression was performed with SVG parameters included as time-varying covariates, incident HF as the main outcome, and death as a competing outcome. RESULTS: Among 594 patients (median age 61 years, 48% male), 83 (14%) developed HF within 5 years. In multivariable competing-risks regression, time-varying SVG azimuth (circular angle in the transverse plane) was independently associated with HF (P = 0.0024), demonstrating a 9.4-fold gradient in risk across values. Leftward/anterior azimuth values were the lowest risk areas, whereas posterior/rightward orientations were the highest risk. CONCLUSIONS: Time-varying SVG azimuth was independently associated with HF risk in patients treated with anthracyclines. Assessing dynamic changes in SVG azimuth during anthracycline treatment may enhance early identification of patients at risk for HF and inform the use of cardioprotective strategies during cancer therapy.