In an analysis from the Women’s Health Initiative reported in JACC: CardioOncology, Kerryn W. Reding, PhD, MPH, RN, and colleagues identified the incidence of hospitalization for heart failure among postmenopausal breast cancer survivors, finding that both incidence of hospitalization and risk of mortality were higher for heart failure with preserved left-ventricular ejection fraction (HFpEF) than for heart failure with reduced ejection fraction (HFrEF).

As stated by the investigators, “Breast cancer survivors experience an increased burden of long-term comorbidities, including heart failure. However, there is limited understanding of the risk for the development of heart failure subtypes, such as heart failure with preserved [ejection fraction] in breast cancer survivors…. To date, cardio-oncology research has focused predominantly on heart failure with reduced ejection fraction due to well-recognized associations between cancer treatment and [left-ventricular ejection fraction] declines.”

Kerryn W. Reding, PhD, MPH, RN

Study Details

The study included 2,272 breast cancer survivors (28.6% Black and 64.9% White) followed to determine the incidence of hospitalized heart failure, with adjudication procedures used to determine left-ventricular ejection fraction. Subtypes of heart failure were classified as HFrEF for left-ventricular ejection fraction < 50% and HFpEF for left-ventricular ejection fraction ≥ 50%.

Multivariate analysis for risk of hospitalization for heart failure included factors significant on univariate analysis: age, smoking, waist circumference, history of hypertension, history of diabetes, and history of myocardial infarction. Multivariate analysis for mortality risk was adjusted for race/ethnicity, age at breast cancer diagnosis, cancer stage, hormone receptor status, and history of myocardial infarction.  

Hospitalization for Heart Failure

Over a median follow-up of 7.2 years (interquartile range = 3.6–12.3 years) from breast cancer diagnosis, 138 patients were hospitalized for heart failure; of these, 70 (50.7%) had HFpEF and 42 (30.4%) had HFrEF, with the remaining 26 heart failure events being unclassified. The cumulative incidence of hospitalization was 6.68% for HFpEF and 3.96% for HFrEF, with annualized incidence rates of 0.73% and 0.37%.

Hospitalized Heart Failure Risk Factors

On multivariate analysis, significant risk factors for HFpEF consisted of prior myocardial infarction (hazard ratio [HR] = 2.84, 95% confidence interval [CI] = 1.28–6.29), greater waist circumference (≥ vs < 88 cm; HR = 1.99, 95% CI = 1.14–3.49), history of smoking (HR = 1.72, 95% CI = 1.06–2.77), and each 5-year increase in age since breast cancer diagnosis (HR = 1.55, 95% CI = 1.31–1.82). For HFrEF, hazard ratios were similar for these factors, except for waist circumference (1.18), but were not statistically significant. History of hypertension and history of treated diabetes were not significant risk factors in either analysis.

Mortality Risks

Compared to survivors without heart failure, hazard ratios for overall mortality were 5.65 (95% CI = 4.11–7.76) for hospitalized patients with HFpEF and 3.77 (95% CI = 2.51–5.66) for those hospitalized with HFrEF. Hazard ratios for cardiovascular-specific mortality (including heart failure) were 12.56 (95% CI = 7.68–20.56) and 10.42 (95% CI = 5.96–18.22), respectively. Hazard ratios for breast cancer–specific mortality were 1.98 (95% CI = 0.69–5.73) and 2.18 (95% CI = 0.80–5.98), respectively.

Subgroup Analysis by Breast Cancer Treatment

In a cohort of 1,149 patients with breast cancer treatment data available, age-adjusted analysis showed a significant difference in risk between hospitalized patients with HFrEF and HFpEF associated with anthracycline treatment (P = .046) but no difference for left-sided radiation (P = .16). In multivariate analysis, anthracycline treatment was associated with a trend toward risk for hospitalized HFrEF (HR = 2.47, 95% CI = 0.94-6.46), with no trend observed for hospitalized HFpEF.

The investigators concluded, “In this population of older, racially diverse breast cancer survivors, the incidence of HFpEF, as defined by heart failure hospitalizations, was higher than HFrEF. Heart failure was also associated with an increased mortality risk. Risk factors for heart failure were largely similar to the general population with the exception of prior myocardial infarction for HFpEF. Notably, both waist circumference and smoking represent potentially modifiable factors.”

Dr. Reding, of the University of Washington, Seattle, is the corresponding author for the JACC: CardioOncology article.

Disclosure: The Women’s Health Initiative program is funded by National Heart, Lung, and Blood Institute, National Institutes of Health. For full disclosures of the study authors, visit jacc.org.