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  • Title: Myocardial expression of fas and recovery of left ventricular function in patients with recent-onset cardiomyopathy.
    Author: Sheppard R, Bedi M, Kubota T, Semigran MJ, Dec W, Holubkov R, Feldman AM, Rosenblum WD, McTiernan CF, McNamara DM, IMAC Investigators.
    Journal: J Am Coll Cardiol; 2005 Sep 20; 46(6):1036-42. PubMed ID: 16168288.
    Abstract:
    OBJECTIVES: This study aimed to evaluate the role of gene expression for predicting myocardial recovery in recent-onset cardiomyopathy. BACKGROUND: Apoptosis may limit ventricular recovery. We examined the myocardial expression of Fas, Fas ligand (FasL), tumor necrosis factor (TNF)-alpha, and TNF receptor 1 (TNFR1), and myocardial recovery in patients from the multicenter Intervention in Myocarditis and Acute Cardiomyopathy (IMAC) study. METHODS: Endomyocardial biopsy samples were obtained in 20 patients with recent-onset (<6 months) idiopathic dilated cardiomyopathy (left ventricular ejection fraction [LVEF] < or =0.40). The LVEF was assessed at baseline and at 6 and 12 months by nuclear scans. Myocardial expression was assessed by ribonuclease (RNase) protection, normalized to a constitutively active gene (glyceraldehydes 3-phosphate dehydrogenase [GAPDH]) and reported as percent GAPDH expression. The change in LVEF at 6 and 12 months was compared by tertiles of expression. RESULTS: For all patients (14 men, 6 women; age 46.5 +/- 10.7 years), the mean LVEF was 0.28 +/- 0.05 at baseline and 0.40 +/- 0.14 at six months. Patients in the highest tertile of Fas expression had minimal improvement at six months (DeltaEF = 0.03 +/- 0.05) when compared with the intermediate (DeltaEF = 0.10 +/- 0.13) and lowest tertiles (DeltaEF = 0.21 +/- 0.11, change in LVEF by tertile, p = 0.006). A similar relationship was seen with TNFR1 expression (highest tertile, DeltaEF = 0.06 +/- 0.07; lowest tertile, DeltaEF = 0.21 +/- 0.11, p = 0.02). In contrast with Fas and TNFR1, expression of TNF-alpha and FasL did not predict recovery of LV function. CONCLUSIONS: In cardiomyopathy of recent onset, increased expression of Fas and TNFR1 was associated with minimal recovery of LV function. Apoptosis limits myocardial recovery, and represents a potential target for therapeutic intervention.
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