Background: The changing demographic of heart failure (HF) increases the exposure to non-cardiovascular (non-CV) events. We investigated the distribution of non-CV mortality/morbidity and the characteristics associated with higher risk of non-CV events in patients with advanced HF. Methods: Patients from the HELP-HF registry were stratified according to the number of 2018 HFA-ESC criteria for advanced HF. Endpoints were non-CV mortality and non-CV hospitalization. Competing risk analyses were performed assessing the association between HFA-ESC criteria and study outcomes and the additional predictors of non-CV endpoints. Results: 1149 patients were included (median age 77 years -IQR 69-83). At 6, 12, 18 and 22 months, cumulative incidence of CV vs non-CV mortality was 13% vs 5%, 17% vs 8%, 20% vs 12%, 23% vs 12%, and of CV vs non-CV hospitalization was 26% vs 11%, 38% vs 17%, 45% vs 20%, 50% vs 21%. HFA-ESC criteria were associated with increasing adjusted risk of CV death, whereas no association was observed for CV hospitalization, non-CV death and non-CV hospitalization. Predictors of non-CV death were age, chronic obstructive pulmonary disease, dementia, preserved ejection fraction, >1 HF hospitalization and hemoglobin. Conclusions: Patients with advanced HF are exposed to high, even though not predominant, burden of non-CV outcomes. HFA-ESC criteria aid to stratify the risk of CV death, but are not associated with lower competing risk of non-CV outcomes. Alternative factors can be useful to define the patients with advanced HF at risk of non-CV events in order to better select patients for treatments specifically reducing CV risk.
