Myocardial T1 Is Correlated to Circulating ProCollagen Type I Carboxyterminal Peptide in Dilated Cardiomyopathy and Predictive of Reduction of LVESV after Spironolactone

Determine if myocardial T1 (by cardiac MR), is a useful predictive determinant of clinical response to spironolactone in a heart failure (HF) medical regimen in nonischemic dilated cardiomyopathy (DCM). Pathologic collagen remodeling is a feature of DCM and HF; and circulating collagen markers are elevated and correlated with depressed heart function. Spironolactone improves systolic function in DCM and decreases circulating collagen markers. Myocardial T1 is emerging as an important measure of myocardial tissue characteristics in HF. CMR and T1, therefore, may provide important structural, functional, and tissue characteristic data, potentially predictive of patient response to spironolactone in HF. Twelve patients with nonischemic DCM and NYHA functional class III/IV HF symptoms were enrolled in a pilot study evaluating cardiac metabolism and function in patients undergoing addition of spironolactone therapy to a stable beta blocker and ACE inhibitor/ARB medication regimen. Each patient underwent perfusion and functional gadolinium (Gd) contrasted cardiac MRI at enrollment and after spironolactone treatment. Changes in myocardial structure and function were analyzed, and 10 minute post Gd myocardial T1 values were determined by analyzing Look Locker T1 optimization sequences using MRMap software. Levels of procollagen type I carboxyterminal peptide (PICP), procollagen I N-terminal peptide (PINP), and procollagen type III aminoterminal peptide (PIIINP) were determined by ELISA for 11 patients. At enrollment (before spironolactone therapy), mean PICP was 57,557 pg/mL (SD 29,269), mean PINP 2936 pg/mL (SD 1046), and mean PIIINP 6751 pg/mL (SD 1979). Myocardial T1 on the enrollment MRI was linearly correlated with circulating PICP levels (P=0.02). All patients had improvement in left ventricular (LV) ejection fraction and reduction in LV end systolic volumes (normalized to body surface area, LVESV/m2). The percent reduction in LVESV/m2 that occurred after spironolactone therapy was linearly correlated with the enrollment MR-T1 (P=0.02). Spironolactone therapy added to a standard DCM medication regimen improved cardiac function, consistent with other clinical studies. This pilot cardiac MRI/collagen biomarker study indicated that MR-T1 obtained before spironolactone initiation is correlated to baseline circulating PICP, and may be a useful determinant of potential spironolactone mediated improvement in LVESV in DCM.