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Background <p>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 (&gt; 20 years) have not been reported.</p> Aims <p>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.</p> Methods <p>The REMADHE trial (NCT00505050, 2007-07-20) was a prospective, single-center, randomized trial (<i>n</i> = 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.</p> Results <p>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 &gt; 52 years (<i>P</i> = 0.015), Chagas etiology (<i>P</i> = 0.010), LVEF &lt; 45% (<i>P</i> = 0.008), digoxin use (<i>P</i> = 0.002), NYHA IV (<i>P</i> = 0.01), blood urea nitrogen (BUN) (<i>P</i> = 0.03), and lymphopenia (<i>P</i> = 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; <i>P</i> &lt; 0.02).</p> Conclusions <p>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.</p> Graphical abstract <p></p>

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

  • 期刊论文

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  • 发表日期：

    2026年5月26日

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  • Edimar Alcides Bocchi,
  • Guilherme Veiga Guimaraes,
  • Cristhian Espinoza Romero,
  • Silvia Moreira Ayub Ferreira,
  • Bruno Biselli,
  • Paulo Roberto Chizzola,
  • Robinson Tadeu Munhoz,
  • Julia Tizue Fukushima,
  • André Rodrigues Durães,
  • Leonardo Roever,
  • Fátima das Dores Cruz

摘要

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.

Graphical abstract