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European Journal of Heart Failure 2004 6(6):735-743; doi:10.1016/j.ejheart.2003.11.013
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© 2004 European Society of Cardiology

Restrictive filling pattern is associated with increased humoral activation and impaired exercise capacity in dilated cardiomyopathy

Alexander P. Patrianakos, Frangiskos I. Parthenakis, Evangelos A. Papadimitriou, George F. Diakakis, Panagiotis G. Tzerakis, Dragana Nikitovic and Panos E. Vardas*

Cardiology Department, University Hospital of Heraklion P.O. Box 1352 Stavrakia, Heraklion Crete, Greece

* Corresponding author. Tel.: +30-2810-392632; fax: +30-2810-542055. E-mail address: cardio{at}med.uoc.gr


  Abstract

Objectives: Although heart failure (HF) is characterized by increased proinflammatory cytokines, natriuretic peptide levels and impaired exercise capacity, the effect of concomitant diastolic dysfunction on those parameters has not been adequately studied.

Methods: We analyzed circulating levels of IL-1, IL-6, TNF-{alpha} and its soluble receptors, sTNFRI and sTNFRII, Nt-ANP and Nt-BNP natriuretic peptides in 81 patients, aged 56±12 years, with non-ischemic dilated cardiomyopathy (NIDC), LVEF 29.7±7.75% and functional NYHA class II-III. An echocardiographic study and cardiopulmonary exercise test (CPE) were performed in all patients.

Results: Patients were divided into restrictive (24 patients, group I) and non-restrictive (57 patients, group II) groups, according to their transmitral-filling pattern. No differences in LV dimensions or LVEF were found between the two groups. Group I showed increased levels of IL-6 (P=0.006), TNF-{alpha} (P=0.05), sTNFRII (P=0.02), Nt-ANP (P<0.001) and Nt-BNP (P<0.001) and decreased exercise duration (P<0.001) and PVO2 (P<0.001) compared to group II. The strongest independent predictors for restrictive filling pattern were Nt-ANP and IL-6 levels, while Nt-BNP levels were the strongest PVO2 predictor.

Conclusions: Restrictive filling pattern implying greater diastolic dysfunction may contribute to increased cytokine production in the heart failure syndrome, as well as greater increases in natriuretic peptides and decreased exercise tolerance.

Key Words: Abbreviations • NIDC, non-ischemic dilated cardiomyopathy • HF, heart failure • LV, left ventricle • EF, ejection fraction • RFP, restrictive filling pattern • IL-1, interleukin-1beta • IL-6, interleukin-6 • TNF-{alpha}, tumor necrosis factor-alpha • Nt-ANP, N-terminal pro-atrial natriuretic peptide • Nt-BNP, N-terminal pro-brain natriuretic peptide • CPE, cardiopulmonary exercise test • PVO2, maximal oxygen consumption at peak exercise

Received March 26, 2003; Revised October 23, 2003; Accepted November 30, 2003


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