Very Long-term Longitudinal Follow-up of Heart Failure on the REMADHE Trial

Background: Heart failure (HF) is associated with frequent hospitalization and worse prognosis. Prognosis factors and survival in very long-term follow-up have not been reported in HF. HF disease management programs(DMP) results are contradictory. DMP efficacy in very long-term follow-up is unknown. We studied the very long-term follow-up of up to 23.6 years and prognostic factors of HF in 412 patients under GDMT included in the REMADHE trial. Methods: The REMADHE trial was a prospective, single-center, randomized trial comparing DMP versus usual care(C). The first patient was randomized on October 5, 1999. The primary outcome of this extended REMADHE was all-cause mortality. Results: The all-cause mortality rate was 88.3%. HF was the first cause of death followed by death at home. 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), use of digoxin (P=0.002), functional class IV (P=0.01), increase in urea (P=0.03), and reduction of lymphocytes (P=0.005). In very long-term follow-up, DMP did not affect mortality in patients under GDMT. HF as a cause of death was more frequent in the C group. Chagas disease, LVEF <45%, and renal function were associated with different modes of death. Conclusion: DMP was not effective in reducing very-long term mortality; however, the causes of death had changed. Our findings that age, LVEF, Chagas disease, functional class, renal function, lymphocytes, and digoxin use were associated with poor prognosis could influence future strategies to improve HF management. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement no apply ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The study was approved by the Research Ethics Board of the Heart Institute and the Human Subject Protection Committee at the Clinics Hospital of the University of São Paulo Medical School (SDC 3972/13/097), and adhered to the Declaration of Helsinki. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes We declare that all data referred to in the manuscript are available upon request to the author.