Abstract 2915: Circulating Fas in Subjects with Acute Cardiomyopathy and Myocarditis: Results from IMAC 1
Introduction In acute cardiomyopathy (ACM), lower myocardial Fas expression is predictive of greater LV recovery during follow up. Whether circulating Fas reflects myocardial activity and predicts recovery is unknown. We examined the predictive value of serum Fas, and its correlation with myocardial expression in subjects in the multicenter IMAC 1 (Intervention in Myocarditis and Acute Cardiomyopathy) trial.
Methods Sixty-two subjects with recent onset dilated CM were enrolled in the IMAC 1 trial between 1996 and 1999. Plasma TNF, soluble TNF receptors 1 and 2, and serum Fas were measured (via ELISA) at entry in 56 subjects. In 20 subjects, myocardial expression of Fas was assessed by RNAse protection assay (RPA). Improvement in LVEF was assessed by radionuclide angiography at 6 and 12 months, and subjects were followed prospectively for up to 3 years. The correlation of serum Fas to circulating TNF and TNFR, and to myocardial Fas was assessed. The predictive value of serum Fas was assessed by comparison of Fas tertiles.
Results The cohort (37M/25F, entry LVEF 0.25 ± 0.08, age 43 ± 12) had a mean serum Fas of 2.6 ± 1.4 ng/ml. Higher NYHA class was associated with higher Fas level (ng/ml): I/II/III/IV=2.4 ± 1.0/2.4 ± 1.1/2.7 ± 1.0/4.1 ± 2.9, p=0.035). Serum Fas demonstrated no correlation with myocardial Fas expression (r=0.169, p=0.50), but was tightly correlated with plasma TNF (r=0.75, p=0.001), TNFRI (r=0.73, p=0.001) and TNFRII (r=0.75, p=0.001). Examination of serum Fas tertiles demonstrate that low Fas was associated with higher RVEF at entry (0.39 ± 0.12 versus 0.31 ± 0.10, p=0.04), but not baseline LVEF (0.25 ± 0.08 versus 0.25 ± 0.09, p=0.97). Low Fas was associated with a trend toward higher improvement in LVEF at 12 months (change LVEF=0.19 ± 0.11, versus 0.12 ± 0.14, p=0.10) which failed to reach significance. Event free survival was similar in the low serum Fas and higher Fas tertiles (p=0.78).
Conclusion Serum Fas was strongly correlated with plasma cytokines (TNF, TNFRI and TNFRII), NYHA class and RVEF. Serum Fas was not correlated with myocardial Fas, and Fas tertiles did not predict subsequent improved LVEF or event free survival. In ACM, serum Fas may reflect systemic peripheral inflammation rather than myocardial processes.