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European Heart Journal Advance Access originally published online on November 16, 2005
European Heart Journal 2006 27(2):201-206; doi:10.1093/eurheartj/ehi579
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© The European Society of Cardiology 2005. All rights reserved. For Permissions, please e-mail: journals.permissions@oxfordjournals.org

Effects of biventricular pacing on interstitial remodelling, tumor necrosis factor-{alpha} expression, and apoptotic death in failing human myocardium

Cristoforo D'Ascia{dagger}, Antonio Cittadini{dagger}, Maria Gaia Monti, Giuseppe Riccio and Luigi Saccà*

Department of Internal Medicine and Cardiovascular Sciences, University Federico II, Via Sergio Pansini 5, 80131 Naples, Italy

Received 3 November 2004; revised 29 July 2005; accepted 15 September 2005; online publish-ahead-of-print 16 November 2005.

* Corresponding author. Tel: +39 081 7463519; fax: +39 081 7463199. E-mail address: sacca{at}unina.it

Aims Recent data from the COMPANION trial have documented that cardiac resynchronization therapy (CRT) with biventricular (BiV) pacing reduces mortality and hospitalization in patients with advanced CHF, but little is known regarding the cellular and molecular mechanisms of CRT. Our aim is to evaluate interstitial remodelling, tumor necrosis factor-{alpha} (TNF-{alpha}) expression, and apoptosis in patients with advanced CHF treated with CRT.

Methods and results We performed endomyocardial biopsies in 10 patients, aged 62, with dilated cardiomyopathy before and 6 months after the implantation of a BiV pacing device. Clinical status and left ventricular (LV) architecture and function were assessed as well as myocardial histology, TNF-{alpha} expression, and apoptotic index. CRT improved clinical status, as shown by a significant reduction of the Minnesota living with heart failure questionnaire (MLHFQ) score (from 53 to 40) and 6-min walked distance (from 290 to 330 m) (all P<0.05 vs. baseline). This was associated with reverse LV remodelling substantiated by significant reductions of LV volumes and end-systolic circumferential wall stress. Examination of myocardial tissue revealed a significant decrease of collagen volume fraction (CVF) (from 25.16 to 18.0%), TNF-{alpha} expression (from 9.5 to 3.6 pixelx103), and apoptotic index (from 2030 to 1408 apoptotic nuclei/106), with increased capillary density (from 1801 to 2011 capillary/mm2) after 6 months of CRT (all P<0.05 vs. baseline). Moreover, changes in TNF-{alpha} expression were positively correlated with both CVF and end-systolic circumferential wall stress (r=0.80 and 0.70, respectively).

Conclusion We provide the first evidence that CRT reduces interstitial remodelling, TNF-{alpha} expression, and apoptosis. The data may explain the beneficial effects of CRT on CHF progression and survival.

Key Words: Heart failure • Pacing • Collagen Apoptosis • Resynchronization therapy


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