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)-alpha, 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-alpha levels. At baseline, myocardial TNF-alpha levels were increased in all patients. After NSRT, myocyte size, collagen content, and TNF-alpha 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-alpha may play a pathogenetic role in the hypertrophy of pressure overload.
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)-alpha, 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-alpha levels. At baseline, myocardial TNF-alpha levels were increased in all patients. After NSRT, myocyte size, collagen content, and TNF-alpha 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-alpha may play a pathogenetic role in the hypertrophy of pressure overload.
Authors: Nawal M Al-Rasheed; Nouf M Al-Rasheed; Yieldez A Bassiouni; Iman H Hasan; Maha A Al-Amin; Hanaa N Al-Ajmi; Raeesa A Mohamad Journal: J Physiol Biochem Date: 2015-05-01 Impact factor: 4.158
Authors: Danita M Yoerger; Catherine A Best; Brendan M McQuillan; Gregory E Supple; J Luis Guererro; Joanne E Cluette-Brown; Ali Hasaba; Michael H Picard; James R Stone; Michael Laposata Journal: Am J Pathol Date: 2006-05 Impact factor: 4.307
Authors: Dan Frenkel; Alok S Pachori; Lunan Zhang; Adi Dembinsky-Vaknin; Dorit Farfara; Sanja Petrovic-Stojkovic; Victor J Dzau; Howard L Weiner Journal: Int Immunol Date: 2009-06-10 Impact factor: 4.823
Authors: Johanna Kuusisto; Vesa Kärjä; Petri Sipola; Ivana Kholová; Keijo Peuhkurinen; Pertti Jääskeläinen; Anita Naukkarinen; Seppo Ylä-Herttuala; Kari Punnonen; Markku Laakso Journal: Heart Date: 2012-03-24 Impact factor: 5.994