Minute Myocardial Injury as Measured by High-Sensitive Troponin T Serum Levels Predicts the Response to Intracoronary Infusion of Bone Marrow-Derived Mononuclear Cells in Patients With Stable Chronic Post-Infarction Heart Failure: Insights From the TOPCARE-CHD Registry


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Abstract

Rationale:Cell-based therapies are a promising option in patients with chronic postinfarction heart failure (ischemic cardiomyopathy [ICM]). However, the responses after intracoronary infusion of autologous bone marrow–derived mononuclear cells (BMCs) are heterogeneous, which may be related to impaired cell retention in patients with ICM. Ischemic injury is associated with upregulation of prototypical chemoattractant cytokines mediating retention and homing of circulating cells. The development of ultrasensitive tests to measure high-sensitive troponin T (hs-TnT) serum levels revealed the presence of ongoing minute myocardial injury even in patients with stable ICM.Objective:To test the hypothesis that serum levels of hs-TnT correlate with cell retention and determine the response to intracoronary BMC application in patients with ICM.Methods and Results:About 157 patients with stable ICM and no substantial impairment of kidney function received intracoronary BMC administration. Immediately prior to cell application, hs-TnT levels to measure myocardial injury and NT-proBNP levels as marker of left ventricular wall stress were determined. Patients with elevated hs-TnT were older and had more severe heart failure. Importantly, only patients with elevated baseline hs-TnT≥15.19 pg/mL (upper tertile) demonstrated a significant (P=0.04) reduction in NT-proBNP serum levels (−250 [−1465; 33] pg/mL; relative reduction −24%) 4 months after BMC administration, whereas NT-proBNP levels remained unchanged in patients in the 2 lower hs-TnT tertiles. The absolute decrease in NT-proBNP at 4 months was inversely correlated with baseline hs-TnT (r=−0.27, P=0.001). Finally, retention of intracoronarily infused, 111Indium-labeled cells within the heart was closely associated with hs-TnT levels in patients with chronic ischemic heart failure (P=0.0008, n=10, triple measurements).Conclusions:The extent of ongoing myocardial injury as measured by serum levels of hs-TnT predicts the reduction of NT-proBNP serum levels at 4 months after intracoronary BMC administration in patients with ICM, suggesting that the beneficial effects of BMC application on LV remodeling and wall stress are confined to patients with ongoing minute myocardial injury.Clinical Trial Registration:URL: www.clinicaltrials.gov. Unique identifier: NCT00962364.

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