Normalization of coronary blood flow in the infarct-related artery after intracoronary progenitor cell therapy: intracoronary Doppler substudy of the TOPCARE-AMI trial

Abstract

Background: Coronary microvascular dysfunction contributes to infarct extension and poor prognosis after an acute myocardial infarction (AMI). Recently, progenitor cell application has been demonstrated to improve neovascularization and myocardial function after experimental myocardial infarction. Therefore, we investigate coronary blood flow regulation in patients after AMI treated with intracoronary progenitor cell therapy.

Methods and results: In the TOPCARE-AMI trial, patients received either bone marrow-derived or circulating progenitor cells into the infarct-related artery 3-7 days after AMI. The present substudy investigates in 40 patients coronary blood flow regulation at the time of progenitor cell therapy and at 4-month follow-up by i.c. Doppler in the infarct artery as well as a reference vessel. At the initial measurement, coronary flow reserve (CFR) was reduced in the infarct artery compared to the reference vessel (median 2.5 vs. 3.4, p<0.001). At 4-month follow-up, intracoronary progenitor cell therapy was associated with a normalization of CFR in the infarct artery (median 3.9 vs. reference vessel 3.8, p=0.15). CFR also improved in the reference vessel, but mechanisms were different: reference vessel increase in CFR was secondary to an increased basal vascular resistance, probably due to reduced need for hypercontractility. In contrast, in the infarct artery, adenosine-induced minimal vascular resistance profoundly decreased, indicating an increased maximal coronary vascular conductance capacity. In addition, in a non-randomized matched control group (n=8), minimal vascular resistance in the infarct artery was significantly elevated compared to progenitor cell treated patients 4 months after AMI (p=0.012).

Conclusions: Intracoronary progenitor cell therapy after AMI is associated with complete restoration of coronary flow reserve due to a substantial improvement of maximal coronary vascular conductance capacity. The clinical importance of improved microcirculation by progenitor cell therapy in patients after AMI has to be established in further randomized trials.