Abstract Body (Do not enter title and authors here): Background
Anthracycline use is limited by cardiotoxicity resulting in heart failure (HF). The spatial ventricular gradient (SVG) is a vectorcardiographic (VCG) measurement of myocardial electrical heterogeneity that is associated with adverse outcomes including sudden death and incident HF.
Objective
Determine if serial assessment of SVG direction is associated with anthracycline-associated HF.
Methods
Retrospective analysis of adult cancer patients treated with anthracyclines in 1992-2019 at a single institution. Patients with prior HF were excluded. Standard 12-lead ECGs obtained within 6 months before and up to 5 years after anthracycline initiation were analyzed. VCGs were constructed, and SVG vector coordinates were obtained by integrating under the X, Y, and Z QRST complexes. Multivariable competing-risks regression was performed with SVG azimuth (the angle of the SVG in the transverse plane) included as a time-varying covariate with sine/cosine transformation to account for the circular nature of SVG azimuth, incident HF as the main outcome, and death as a competing outcome.
Results
Among 889 patients (51% male, mean age at drug initiation 58±15 yrs), 70% had hematologic malignancies, 12% breast cancer, and 18% other malignancies. Incident HF developed in 97 patients (11%), and 305 patients (34%) died within 5 yrs of treatment. In unadjusted analyses, time-updated SVG azimuth was associated with incident HF (joint p=0.003). After adjustment for known risk factors for anthracycline-associated HF, including age, sex, hypertension, CAD, diabetes, cumulative doxorubicin equivalent dose, heart rate and QRS duration, SVG azimuth remained significantly associated with incident HF (joint p=0.045) with adjusted sub-distribution hazard ratios (SHRs) ranging from 0.47 to 2.13 across the circular spectrum (4.5-fold SHR variation). The Figure shows how SHRs for incident HF varied significantly by SVG azimuth. Notably, the anterior/leftward orientation, (see Figure green area) was associated with a reduced risk of HF with SHRs ~0.5-0.6, while the posterior/rightward orientation, (see Figure red area) was associated with a ~2-fold increased risk for incident HF.
Conclusion
SVG azimuth is independently associated with increased risk of anthracycline-associated HF. Measuring how SVG azimuth changes during anthracycline treatment may enhance early identification of patients at risk for HF and inform preventive cardioprotective strategies during cancer therapy.