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European Journal of Heart Failure 2006 8(2):179-186; doi:10.1016/j.ejheart.2005.07.010
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© 2006 European Society of Cardiology

Independent and incremental prognostic value of endogenous ouabain in idiopathic dilated cardiomyopathy

Maria Vittoria Pitzalisb, John M. Hamlync, Elisabetta Messaggioa, Massimo Iacoviellob, Cinzia Forleob, Roberta Romitob, Elisabetta de Tommasib, Paolo Rizzonb, Giuseppe Bianchia and Paolo Manuntaa,*

a Division of Nephrology, Dialysis and Hypertension, University "Vita-Salute" San Raffaele Hospital Via Olgettina 60, 20132 Milan, Italy
b Institute of Cardiology, University of Bari Bari, Italy
c Department of Physiology, School of Medicine, University of Maryland Baltimore, MD, USA

* Corresponding author. Tel.: +39 0226433891; fax: +39 0226432384. E-mail address: manunta.paolo{at}hsr.it


  Abstract

Increased circulating levels of endogenous ouabain (EO) have been observed in some heart failure patients, but their long term clinical significance is unknown. This study investigated the prognostic value of EO for worsening heart failure among 140 optimally treated patients (age 50±14 years; 104 male; NYHA class 1.9±0.7) with idiopathic dilated cardiomyopathy. Plasma EO was determined by RIA and by liquid chromatography mass spectrometry, values were linearly correlated (r=0.89) in regression analysis. During follow-up (13±5 months), heart failure progression was defined as worsening clinical condition leading to one or more of the following: sustained increase in conventional therapies, hospitalization, cardiac transplant, or death. NYHA functional class, age, LVEF, peak VO2 and plasma levels of EO were predictive for heart failure progression. Heart failure worsened 1.5 fold (HR: 1.005; 95% CI: 1.001—1.007; p<0.01) for each 100 pmol/L increase in plasma EO. Moreover, those patients with higher plasma EO values had an odds ratio of 5.417 (95% CI: 2.044—14.355; p<0.001) for heart failure progression. Following multivariate analysis, LVEF, NYHA class and plasma EO remained significantly linked with clinical events. This study provides the first evidence that circulating EO is a novel, independent and incremental marker that predicts the progression of heart failure.

Key Words: Cardiac failure • Progression • Na pump • Ouabain-like factor

Received November 26, 2004; Revised May 3, 2005; Accepted July 14, 2005


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