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Introduction: Breast cancer (BC) survivors (BCS) are at increased risk for incident heart failure (HF). In this population, the risk for HF with preserved ejection fraction (HFpEF) has been understudied compared to HF with reduced EF (HFrEF). The purpose of this study was to estimate 1) the incidence of HFpEF and HFrEF, and 2) the phenotypic profiles conferring risk for incident HFpEF and HFrEF in BCS. Methods: This Women’s Health Initiative analysis was conducted in women with invasive BC stages I-IV in the Medical Records Cohort (MRC). Those with pre-existing HF were excluded. Exposures of interest were lifestyle factors [e.g. body mass index (BMI)], comorbidities [e.g. hypertension, diabetes, and myocardial infarction (MI)], and BC treatment. Lifestyle factors and comorbidities most proximal and prior to BC diagnosis were assessed. In the MRC, BC and HF as well as left ventricular EF (LVEF) were ascertained through chart review and physician-adjudication. LVEF ≥50% was classified as HFpEF; and Results: In 2,250 BCS, 153 developed HF after BC during a median follow-up of 7.3 years. Of those, 49 had HFrEF and 75 had HFpEF. The cumulative incidences of HFrEF and HFpEF over follow-up were 7.3% and 4.6%, respectively. Diabetes and MI were associated with both HFpEF and HFrEF (Table). Smoking, BMI ≥30, and hypertension were associated with HFpEF. Anthracycline use was associated with HFrEF but not HFpEF (p=0.03). Conclusions: In BCS, lifestyle factors were associated with incident HFpEF, whereas anthracycline use was associated with a higher risk for HFrEF. Understanding risk factors associated with incident HFpEF and HFrEF in BCS is important to guide the implementation of risk profile-specific preventative measures and interventions.

Background: Autonomic dysfunction (AD) as measured by heart rate variability (HRV) is associated with increased risk of cardiovascular disease (CVD) and breast cancer. No study has utilized a large prospective multi-center cohort of diverse women to assess differences in HRV associated with incident breast cancer. Objectives: To identify heart rate variability changes in women with breast cancer compared to controls in the Women’s Health Initiative (WHI). Methods: In a retrospective cohort study, we utilized 5,031 women in the WHI CT cohort who were breast cancer free at baseline and compared 1) those with incident breast cancer v. 2) those who were breast cancer free during the ECG follow-up period as controls. HRV was calculated utilizing 10-second ECG with two measures of two-domain HRV: standard deviation of all normal-to-normal RR intervals (SDNN) and the root mean square of successive differences in normal-to-normal RR intervals (rMSSD). HRV was measured from ECGs collected at baseline, years 3, 6, and 9 in the comparison groups. An adjusted mixed linear model was used to evaluate the differences in SDNN and rMSSD comparing women with incident breast cancer to controls. Cardiovascular risk factors utilized in the adjusted model were determined via questionnaire at baseline. Results: At baseline, women with incident breast cancer diagnosed by years 3, 6, or 9 were significantly older (median age 63 vs. 61, PFigure 1 ). Conclusions: HRV as a measure of AD is significantly lower in women with incident breast cancer compared to women without breast cancer. Reduction in HRV is associated with CVD outcomes in the literature. Our study suggests HRV may predict CVD in breast cancer patients.