Author + information
- Received March 4, 2005
- Revision received April 27, 2005
- Accepted May 3, 2005
- Published online September 20, 2005.
- Richard Sheppard, MD⁎,
- Maninder Bedi, MD†,
- Toru Kubota, MD, PhD‡,
- Marc J. Semigran, MD§,
- William Dec, MD§,
- Richard Holubkov, PhD∥,
- Arthur M. Feldman, MD, PhD¶,
- Warren D. Rosenblum, MD#,
- Charles F. McTiernan, PhD†,
- Dennis M. McNamara, MD†,⁎ (, )
- IMAC Investigators
- ↵⁎Reprint requests and correspondence:
Dr. Dennis M. McNamara, Heart Failure/Transplantation Program, Cardiovascular Institute, University of Pittsburgh Medical Center, 566 Scaife Hall, 200 Lothrop Street, Pittsburgh, Pennsylvania 15213
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] ≤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 (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.
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.
The IMAC study was supported by an educational grant from the Bayer Corporation. National Institutes of Health awards R01 HL75038 and K24 HL69912 also supported this work.
- Received March 4, 2005.
- Revision received April 27, 2005.
- Accepted May 3, 2005.
- American College of Cardiology Foundation