Cause-specific death in heart failure across the ejection fraction spectrum

Abstract

Abstract Background Heart failure (HF) is associated with increased cardiovascular (CV) and non-CV mortality, but little data is available on underlying causes of death in HF phenotypes based on ejection fraction (EF). Knowledge about causes of mortality may have implications for healthcare decisions, treatment priorities and clinical trial design. Purpose To examine cause-specific mortality in patients with HF with reduced EF (HFrEF), HF with mildly reduced EF (HFmrEF), and HF with preserved EF (HFpEF). Methods Patients enrolled in the Swedish Heart Failure Registry between 2000-2021 were included. The causes and incidence rates of death across the EF categories were studied. In addition, to examine the association between EF categories and cardiovascular (CV) and non-CV mortality, sub-distributional hazards models were performed accounting for competing risk of death from other causes and adjusted for age and sex. Results Among 100,584 patients (23% HFpEF, 23% HFmrEF, 53% HFrEF), median age (IQR) was 75.0 (66.0-82.0) and 36.5% were females. Of those who died within 5 years, most deaths were ascribed to CV deaths across all EF categories (65% in HFrEF, 59% in HFmrEF and 58% in HFpEF, respectively). Within 5 years, patients with HFpEF had higher risk of non-CV mortality (adjusted HR 1.38, 95% CI 1.33-1.43, p< 0.001) and lower risk of CV mortality (adjusted HR 0.80, 95% CI, 0.78-0.83, p< 0.001) compared to patients with HFrEF. Ischemic heart disease (IHD) was the most common cause of CV-death while cancer was the most common cause of non-CV death across all EF categories. The incidence rate of CV death due to IHD was higher in HFrEF while the incidence rates of CV death due to pulmonary vascular disease, stroke, valvular heart disease and atrial fibrillation were higher in HFpEF compared to HFrEF and HFmrEF (Figure 1). Patients with HFpEF had higher incidence rate of non-CV deaths due to cancer, respiratory disease, accidents and infections including covid -19 compared with HFrEF and HFmrEF patients (figure 2). Conclusion In this large and contemporary cohort of patients with HF, CV death was more common than non-CV death across all EF categories although the risk of non-CV mortality within 5-years was higher with increasing EF. IHD and cancer were the most common causes of CV and non-CV deaths, respectively, regardless of EF category. Patients with HFpEF had a higher burden of non-CV causes of death than patients with HFrEF and HFmrEF.Incidence rate CV deathIncidence rate non-CV death