In an analysis from the Women’s Health Initiative reported in JACC: CardioOncology, Kerryn W. Reding, PhD, MPH, RN, of the University of Washington at Seattle, and colleagues, identified the incidence of hospitalization for heart failure among postmenopausal breast cancer survivors. They reported that both incidence of hospitalization and risk of mortality were higher for heart failure with preserved left-ventricular ejection fraction than for heart failure with reduced ejection fraction.1
Kerryn W. Reding, PhD, MPH, RN
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.”
The study included 2,272 breast cancer survivors (28.6% Black, 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 heart failure with reduced ejection fraction for left-ventricular ejection fraction less than 50% and for left-ventricular ejection fraction of at least 50%. Multivariate analysis for risk of hospitalized 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 patients, 70 (50.7%) had heart failure with preserved left-ventricular ejection fraction and 42 (30.4%) had heart failure with reduced ejection fraction, with the remaining 26 heart failure events being unclassified. The cumulative incidence of hospitalization was 6.68% for heart failure with preserved ejection fraction and 3.96% for heart failure with reduced ejection fraction, with annualized incidence rates of 0.73% and 0.37%.
Hospitalized Heart Failure Risk Factors
Factors for heart failure hospitalization not significant on age-adjusted univariate analysis included alcohol intake, body mass index, leisure time physical activity, and nonsteroidal anti-inflammatory drug use.
On multivariate analysis, significant risk factors for heart failure with preserved left-ventricular ejection fraction 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 heart failure with reduced ejection fraction, hazard ratios were similar for prior myocardial infarction (2.34) and history of smoking (1.52) and lower for each 5-year increase in age since breast cancer diagnosis (1.10) and greater waist circumference (1.13), but none were statistically significant. History of hypertension and history of treated diabetes were not significant risk factors in either analysis.
Compared with breast cancer survivors without heart failure, hazard ratios for overall mortality were 5.65 (95% CI = 4.11–7.76) for hospitalized heart failure with preserved left-ventricular ejection fraction and 3.77 (95% CI = 2.51–5.66) for hospitalized heart failure with reduced ejection fraction. Compared to women without heart failure, those with heart failure with preserved left-ventricular ejection fraction had hazard ratios of 12.56 (95% CI = 7.68–20.56) for cardiovascular-specific mortality and 1.98 (95% CI = 0.69–5.73) for breast cancer–specific mortality (P for homogeneity = 0.002). Those with heart failure with reduced ejection fraction had hazard ratios of 10.42 (95% CI = 5.96–18.22) and 2.18 (95% CI = 0.80–5.98), respectively (P for homogeneity = .004).
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 heart failure with reduced ejection fraction and heart failure with preserved left-ventricular ejection fraction associated with anthracycline treatment (P = .046) but no difference for left-sided radiation (P = .16). In a multivariate analysis, anthracycline treatment was associated with a trend toward risk for hospitalized heart failure with reduced ejection fraction (HR = 2.47, 95% CI = 0.94–6.46), with no trend observed for hospitalized heart failure with preserved left-ventricular ejection fraction.
The investigators concluded: “In this population of older, racially diverse [breast cancer] survivors, the incidence of [heart failure with preserved left-ventricular ejection fraction], as defined by [heart failure] hospitalizations, was higher than [heart failure with reduced ejection fraction]. [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 [heart failure with preserved left-ventricular ejection fraction]. Notably, both waist circumference and smoking represent potentially modifiable factors.”
DISCLOSURE: The Women’s Health Initiative program is funded by the National Heart, Lung, and Blood Institute of the National Institutes of Health. Dr. Reding reported no conflicts of interest.
1. Reding KW, Cheng RK, Vasbinder A, et al: Lifestyle and cardiovascular risk factors associated with heart failure subtypes in postmenopausal breast cancer survivors. JACC: CardioOnc 4:53-65, 2022.