Decreased expression of tumor necrosis factor-α and regression of hypertrophy after nonsurgical septal reduction therapy for patients with hypertrophic obstructive cardiomyopathy

Sherif Nagueh, Sonny J. Stetson, Nasser M. Lakkis, Donna Killip, Alex Perez-Verdia, Mark L. Entman, William H. Spencer, Guillermo Torre

Research output: Contribution to journalArticle

58 Scopus citations

Abstract

Background - Nonsurgical septal reduction therapy (NSRT) is a novel therapeutic strategy for patients with hypertrophic obstructive cardiomyopathy (HOCM). Although the clinical benefits of this technique appear to be clear, the structural and functional changes that lead to improvements in cardiac function are not completely defined. In these studies, we sought to define the effect of NSRT on myocardial function as well as various markers of hypertrophy including the expression of tumor necrosis factor (TNF)-α, a cytokine capable of producing fibrosis, left ventricular hypertrophy (LVH), and cardiomyopathy. Methods and Results - We performed endomyocardial biopsies of the RV side of the septum and echocardiograms on 15 HOCM patients at baseline and after successful NSRT. Comparative analysis on paired myocardial samples were performed to determine the effects of NSRT on LVH, end-diastolic volume and chamber stiffness, myocyte size, collagen content, and TNF-α levels. At baseline, myocardial TNF-α levels were increased in all patients. After NSRT, myocyte size, collagen content, and TNF-α were significantly decreased. These changes were accompanied by an increase in left ventricular volumes and a reduction in LVH and chamber stiffness. Conclusions - We suggest that pressure overload in HOCM patients contributes to the development of hypertrophy. These data provide the initial experimental evidence to suggest that TNF-α may play a pathogenetic role in the hypertrophy of pressure overload.

Original languageEnglish (US)
Pages (from-to)1844-1850
Number of pages7
JournalCirculation
Volume103
Issue number14
DOIs
StatePublished - Apr 10 2001

Keywords

  • Cardiomyopathy
  • Hypertrophy
  • Surgery

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

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