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.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Midcareer Investigator Award in Patient-Oriented Research (K24)
Project #
Application #
Study Section
Special Emphasis Panel (ZHL1-CSR-F (F1))
Program Officer
Commarato, Michael
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of Pittsburgh
Internal Medicine/Medicine
Schools of Medicine
United States
Zip Code
Nagatomo, Yuji; McNamara, Dennis M; Alexis, Jeffrey D et al. (2017) Myocardial Recovery in Patients With Systolic Heart Failure and Autoantibodies Against ?1-Adrenergic Receptors. J Am Coll Cardiol 69:968-977
Nayak, Aditi; Neill, Colin; Kormos, Robert L et al. (2017) Chemokine receptor patterns and right heart failure in mechanical circulatory support. J Heart Lung Transplant 36:657-665
Sheppard, Richard; Hsich, Eileen; Damp, Julie et al. (2016) GNB3 C825T Polymorphism and Myocardial Recovery in Peripartum Cardiomyopathy: Results of the Multicenter Investigations of Pregnancy-Associated Cardiomyopathy Study. Circ Heart Fail 9:e002683
McNamara, Dennis M; Taylor, Anne L; Tam, S William et al. (2014) G-protein beta-3 subunit genotype predicts enhanced benefit of fixed-dose isosorbide dinitrate and hydralazine: results of A-HeFT. JACC Heart Fail 2:551-7
McTiernan, Charles F; Ramani, Ravi; Burkhead, Benjamin et al. (2012) The methionine 196 arginine polymorphism of the TNF receptor 2 gene (TNFRSF1B) is not associated with worse outcomes in heart failure. Cytokine 60:838-42
Cooper, Leslie T; Mather, Paul J; Alexis, Jeffrey D et al. (2012) Myocardial recovery in peripartum cardiomyopathy: prospective comparison with recent onset cardiomyopathy in men and nonperipartum women. J Card Fail 18:28-33
Sheppard, Richard; Mather, Paul J; Alexis, Jeffrey D et al. (2012) Implantable cardiac defibrillators and sudden death in recent onset nonischemic cardiomyopathy: results from IMAC2. J Card Fail 18:675-81
Refaat, Marwan M; Tanaka, Toshikazu; Kormos, Robert L et al. (2012) Survival benefit of implantable cardioverter-defibrillators in left ventricular assist device-supported heart failure patients. J Card Fail 18:140-5
McNamara, Dennis M; Starling, Randall C; Cooper, Leslie T et al. (2011) Clinical and demographic predictors of outcomes in recent onset dilated cardiomyopathy: results of the IMAC (Intervention in Myocarditis and Acute Cardiomyopathy)-2 study. J Am Coll Cardiol 58:1112-8
Simon, Marc A; Primack, Brian A; Teuteberg, Jeffrey et al. (2010) Left ventricular remodeling and myocardial recovery on mechanical circulatory support. J Card Fail 16:99-105

Showing the most recent 10 out of 25 publications