Cytokines and LV Recovery in Recent Onset Cardiomyopathy

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DESCRIPTION (provided by applicant): For patients presenting with the recent onset of primary dilated cardiomyopathy, the presence of myocardial inflammation may suggest a potentially self limited and reversible process, and patients with acute "myocarditis" may actually have a better probability of left ventricular recovery than those with more chronic disease. The poor sensitivity of endomyocardial biopsy has limited its clinical utility, and circulating plasma cytokines are potentially more sensitive indicators of a reversible myocardial inflammatory process. This proposal will investigate the hypothesis that the assessment of plasma cytokines in recent onset dilated cardiomyopathy, can help to prospectively delineate patients with greater likelihood of myocardial recovery. Specific Aim 1 will assess the correlation of baseline plasma cytokine levels (TNFa, TNF receptors, and IL-6) with echocardiographic measures of left ventricular systolic and diastolic function. The study will enroll 120 patients with recent onset idiopathic dilated cardiomyopathy or myocarditis with an LVEF less than or equal to 0.40. This will evaluate the hypothesis that plasma cytokines in recent onset cardiomyopathy are markers of cardiac inflammation and will correlate with more profound perturbations of myocardial function. Specific Aim 2 will evaluate the hypothesis that patients with more active myocardial inflammation (higher plasma TNFa) upon presentation, are more likely to have significant recovery of left ventricular systolic function at 12 month follow up. Echocardiographic assessment will be repeated at 6 and 12 months after entry. In addition we will evaluate the hypothesis that patients with higher plasma IL-6 levels will have a poorer event free survival during subsequent follow up. Specific Aim 3 will explore the hypothesis that polymorphisms of cytokine genes, in particular those in the TNFa and IL-6 promoters, will effect levels of their respective mediators, and will subsequently influence clinical outcomes.