Prognostic factors related to all-cause mortality in very long-term follow-up of patients with heart failure: the REMADHE trial extended analysis

Background Disease management programs (DMP) have reduced hospitalizations and improved quality of life in heart failure (HF). However, prognostic factors and survival in very long-term follow-up (> 20 years) have not been reported. Aims To evaluate the long-term effects of a disease management program (DMP) on heart failure outcomes and to identify prognostic predictors of all-cause mortality in patients with HF followed for up to 23.6 years. Methods The REMADHE trial (NCT00505050, 2007-07-20) was a prospective, single-center, randomized trial ( n = 412) comparing DMP versus usual care (C) with initial follow-up of 2.47 years. This extended analysis followed patients for 23.6 years to identify prognostic predictors of all-cause mortality. Results The all-cause mortality rate was 88.3%. HF was the first cause of death followed by sudden death. Mortality was higher in the first 6-year follow-up. The predictive variables in multivariate analysis associated with mortality were age > 52 years ( P = 0.015), Chagas etiology ( P = 0.010), LVEF < 45% ( P = 0.008), digoxin use ( P = 0.002), NYHA IV ( P = 0.01), blood urea nitrogen (BUN) ( P = 0.03), and lymphopenia ( P = 0.005). In very long-term follow-up, DMP did not affect mortality in patients under guideline-directed medical therapy (GDMT). HF as a cause of death was more frequent in the C group (41.0% vs. 33.3% in the DMP group; P < 0.02). Conclusions DMP was not effective in reducing very long-term mortality; however, causes of death differed between groups, with more HF-related deaths in controls. Our findings that age, LVEF, Chagas’ disease, NYHA, renal function, lymphocytes, and digoxin use were associated with poor prognosis could influence future strategies to improve HF management.