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A comprehensive, longitudinal description of the in-hospital and post-discharge clinical, laboratory, and neurohormonal course of patients with heart failure who die or are re-hospitalized within 90 days: analysis from the EVEREST trial

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Abstract

Hospitalization for worsening chronic heart failure results in high post-discharge mortality, morbidity, and cost. However, thorough characterization, soon after discharge of patients with early post-discharge events has not been previously performed. The objectives of this study were to describe the baseline, in-hospital, and post-discharge clinical, laboratory, and neurohormonal profiles of patients hospitalized for worsening heart failure with reduced ejection fraction (EF) who die or are re-admitted for cardiovascular (CV) causes within 90 days of initial hospitalization. Retrospective analysis of 4,133 patients hospitalized for worsening heart failure with EF ≤40% in the Efficacy of Vasopressin Antagonism in Heart Failure: Outcome Study with Tolvaptan (EVEREST) trial, which randomized patients to tolvaptan or placebo, both in addition to standard therapy. Clinical and laboratory parameters were obtained within 48 h of admission, during hospitalization, and post-discharge weeks 1, 4, 8, and every 8 weeks thereafter for a median of 9.9 months. Patients with events within 90 days were compared with those with later/no events. All-cause mortality (ACM) and CV re-hospitalization were independently adjudicated. Within 90 days of admission, 395 patients (9.6%) died and 801 patients (19.4%) were re-hospitalized for CV causes. Significant baseline and longitudinal differences were seen between groups with early versus later (>90 days) or no events at 12 months post-randomization. Post-discharge outcomes were similar in the tolvaptan and placebo groups. Patients with early post-discharge events experienced clinically significant worsening in signs and symptoms, laboratory values, and neurohormonal parameters soon after discharge. Identifying these abnormalities may facilitate efforts to reduce post-discharge mortality and re-hospitalization.

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Conflict of interest

Dr. Gheorghiade has been a consultant and/or received honoraria from Bayer, Debiopharm, GlaxoSmithKline, J&J, Medtronic, Merck, Novartis, Otsuka, PeriCor, Solvay Pharmaceuticals, SigmaTau, and Takeda. Dr. Pang has been a consultant for Bayer, J&J, Medtronic, Novartis, Otsuka, SigmaTau, and Trevena and a member of the DSMB for J&J and the Medicines Company. He has received research support from Abbott. Gloria Lan or Dr. Philip Schmidt has no conflicts of interest or financial ties to disclose. Dr. Filippatos reports an affiliation with Medtronic and having served as a consultant and/or on the advisory board for Protein Design Laboratories with research support from Roche diagnostics, Brahms, Otsuka, SigmaTau. Dr. Konstam has been a consultant and/or received research support from Otsuka, J&J, Cardiokine, and Trevena. Dr. Swedberg has been a consultant for Servier and Novartis, research grants from AstraZeneca, Servier, and Amgen and receiving honoraria from AstraZeneca, Otzuka, Amgen, and Servier. Mr. Traver has received salary support through a contract between the University of Wisconsin and Otsuka Pharmaceutical Development & Commercialization, Inc. Dr. Cook has received salary support through a contract between the University of Wisconsin and Otsuka Pharmaceutical Development & Commercialization, Inc. Dr. Maggioni received research support from Novartis, SigmaTau, and Astra Zeneca. He is a member of a DSMB for Bayer and Actelion. He has received honoraria for lectures from Otsuka, Novartis, SigmaTau, and Astra Zeneca. Dr. Burnett has received research grants from the National Institutes of Health, Microbia, and Theravance, a consultant for Abbott, Bayer, Otsuka, Wyeth, and Astellas, and has received honoraria from Scios, Otsuka, and Orqis. Dr. Grinfeld reported research grants and/or honoraria from GlaxoSmithKline, Otsuka, Amgen, Cordis, and Bristol, a consultant for Cordis. Dr. Udelson is or has been a consultant for Otsuka and Medtronic received research grants from Otsuka, Cytori, and Angioblast. Dr. Zannad is or has been a consultant for Servier, Johnson & Johnson, research grants from Bayer, and honoraria from AstraZeneca, Pfizer, Boehring Ingelheim, Abbott, Sanofi-Aventis, and Otsuka.

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Correspondence to Mihai Gheorghiade.

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This work was presented as a Late-Breaking Clinical Trial at the European Society of Cardiology in Munich, Germany, September 2008.

Appendix

Appendix

Fig. 4
figure 4figure 4

Follow up measures by survival status: tolvaptan and placebo. Clinical, laboratory, and neurohormonal parameters of patients with ACM within 90 days (blue line) versus those with events from 3 to 12 months (green line) versus those without events at 1 year (black line) as plots of the mean value with standard deviation. The first panel represents the in-hospital period. The gray bar within the second panel represents the in-hospital period

Fig. 5
figure 5figure 5figure 5

Laboratory measures by survival status: tolvaptan and placebo. Clinical, laboratory, and neurohormonal parameters of patients with ACM within 90 days (blue line) versus those with events from 3 to 12 months (green line) versus those without events at 1 year (black line) as plots of the mean value with standard deviation. The first panel represents the in-hospital period. The gray bar within the second panel represents the in-hospital period

Fig. 6
figure 6figure 6

Follow-up measures by CV hospitalization status: tolvaptan and placebo. Clinical, laboratory, and neurohormonal parameters of patients with CV Re-hospitalization within 90 days (blue line) versus those with events from 3 to 12 months (green line) versus those without events at 1 year (black line) as plots of the mean value with standard deviation. The first panel represents the in-hospital period. The gray bar within the second panel represents the in-hospital period

Fig. 7
figure 7figure 7figure 7

Laboratory measures by CV hospitalization status: tolvaptan and placebo. Clinical, laboratory, and neurohormonal parameters of patients with CV Re-hospitalization within 90 days (blue line) versus those with events from 3 to 12 months (green line) versus those without events at 1 year (black line) as plots of the mean value with standard deviation. The first panel represents the in-hospital period. The gray bar within the second panel represents the in-hospital period

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Gheorghiade, M., Pang, P.S., Ambrosy, A.P. et al. A comprehensive, longitudinal description of the in-hospital and post-discharge clinical, laboratory, and neurohormonal course of patients with heart failure who die or are re-hospitalized within 90 days: analysis from the EVEREST trial. Heart Fail Rev 17, 485–509 (2012). https://doi.org/10.1007/s10741-011-9280-0

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