Myocardial Expression of Fas and Recovery of Left Ventricular Function in Patients With Recent-Onset Cardiomyopathy

• Published in: Journal of the American College of Cardiology Vol. 46; no. 6; pp. 1036 - 1042
• Main Authors: Sheppard, Richard, Bedi, Maninder, Kubota, Toru, Semigran, Marc J., Dec, William, Holubkov, Richard, Feldman, Arthur M., Rosenblum, Warren D., McTiernan, Charles F., McNamara, Dennis M.
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 20-09-2005; Elsevier Science; Elsevier Limited
• Subjects: Adult; Apoptosis; Biological and medical sciences; Cardiology; Cardiology. Vascular system; Cardiomyopathies - drug therapy; Cardiomyopathies - metabolism; Cardiomyopathies - physiopathology; Cardiomyopathy; Cytokines; Drug therapy; Enzymes; Fas Ligand Protein; fas Receptor - biosynthesis; Female; Gene expression; Heart; Heart attacks; Heart failure; Humans; Male; Medical sciences; Membrane Glycoproteins - biosynthesis; Middle Aged; Myocarditis. Cardiomyopathies; Pulmonary arteries; Receptors, Tumor Necrosis Factor, Type I - biosynthesis; Recovery of Function; Statistical analysis; Time Factors; Tumor Necrosis Factor-alpha - biosynthesis; Tumor Necrosis Factors - biosynthesis; Ventricular Function, Left; United States > US; California; NYHA; TNFR; IMAC; RNA; FasL; ACEI; LVEF; FLICE; GAPDH; TNF; Human; Cardiomyopathy; Heart disease; Cardiovascular disease; Circulatory system; Cardiology; Gene expression; Left ventricle performance; Myocardial disease; Phlebology; Recovery
• ISSN: 0735-1097; 1558-3597
• DOI: 10.1016/j.jacc.2005.05.067

This study aimed to evaluate the role of gene expression for predicting myocardial recovery in recent-onset cardiomyopathy.
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.
Endomyocardial biopsy samples were obtained in 20 patients with recent-onset (<6 months) idiopathic dilated cardiomyopathy (left ventricular ejection fraction [LVEF] ≤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.
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 (ΔEF = 0.03 ± 0.05) when compared with the intermediate (ΔEF = 0.10 ± 0.13) and lowest tertiles (ΔEF = 0.21 ± 0.11, change in LVEF by tertile, p = 0.006). A similar relationship was seen with TNFR1 expression (highest tertile, ΔEF = 0.06 ± 0.07; lowest tertile, ΔEF = 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.
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.