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Cardiac Dysfunction, Congestion and Loop Diuretics: their Relationship to Prognosis in Heart Failure

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Abstract

Background

Diuretics are the mainstay of treatment for congestion but concerns exist that they adversely affect prognosis. We explored whether the relationship between loop diuretic use and outcome is explained by the underlying severity of congestion amongst patients referred with suspected heart failure.

Method and Results

Of 1190 patients, 712 had a left ventricular ejection fraction (LVEF) ≤50 %, 267 had LVEF >50 % with raised plasma NTproBNP (>400 ng/L) and 211 had LVEF >50 % with NTproBNP ≤400 ng/L; respectively, 72 %, 68 % and 37 % of these groups were treated with loop diuretics including 28 %, 29 % and 10 % in doses ≥80 mg furosemide equivalent/day. Compared to patients with cardiac dysfunction (either LVEF ≤50 % or NT-proBNP >400 ng/L) but not taking a loop diuretic, those taking a loop diuretic were older and had more clinical evidence of congestion, renal dysfunction, anaemia and hyponatraemia. During a median follow-up of 934 (IQR: 513–1425) days, 450 patients were hospitalized for HF or died. Patients prescribed loop diuretics had a worse outcome. However, in multi-variable models, clinical, echocardiographic (inferior vena cava diameter), and biochemical (NTproBNP) measures of congestion were strongly associated with an adverse outcome but not the use, or dose, of loop diuretics.

Conclusions

Prescription of loop diuretics identifies patients with more advanced features of heart failure and congestion, which may account for their worse prognosis. Further research is needed to clarify the relationship between loop diuretic agents and outcome; imaging and biochemical measures of congestion might be better guides to diuretic dose than symptoms or clinical signs.

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Authors and Affiliations

  1. Department of Cardiology, Hull and East Yorkshire Medical Research and Teaching Centre, Castle Hill Hospital, Hull York Medical School, Cottingham, Kingston upon Hull, HU16 5JQ, UK

    Pierpaolo Pellicori, John G. F. Cleland, Jufen Zhang, Anna Kallvikbacka-Bennett, Alessia Urbinati, Parin Shah, Syed Kazmi & Andrew L Clark

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  1. Pierpaolo Pellicori
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  2. John G. F. Cleland
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Correspondence to Pierpaolo Pellicori.

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Funding

The author P. Pellicori was receiving a research grant from Societa’ Italiana di Cardiologia (Borsa di studio SIC e MSD Italia-Merck Sharp & Dohme Corporation) whilst involved in this research paper.

Conflict of Interest

Dr. Cleland reports grants and personal fees from Amgen, grants and personal fees from Novartis, grants from Roche, grants and personal fees from Servier, grants and personal fees from Stealth Biopharmaceuticals, personal fees from Trevena, outside the submitted work. Dr. Clark reports personal fees from Novartis, grants and personal fees from Servier, outside the submitted work.

Ethical Approval

All procedures performed were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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Informed consent was obtained from all individual participants included in the study.

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Pellicori, P., Cleland, J.G.F., Zhang, J. et al. Cardiac Dysfunction, Congestion and Loop Diuretics: their Relationship to Prognosis in Heart Failure. Cardiovasc Drugs Ther 30, 599–609 (2016). https://doi.org/10.1007/s10557-016-6697-7

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