Intramyocardial injection of mesenchymal stromal cells in patients with severe stable coronary artery disease and refractory angina - final 3 year follow-up

Abstract

Purpose: Regenerative stem cell therapy is an emerging treatment modality for patients with coronary artery disease (CAD). The study assessed long-term safety and efficacy of percutaneous intramyocardial injection of autologous bone-marrow derived mesenchymal stromal cells (MSC) in patients with severe stable CAD and refractory angina. Methods: Thirty-one patients with severe stable CAD and refractory angina were included. Patients had reversible myocardial ischemia and no further revascularization options. Autologous bone-marrow MSCs were isolated, culture expanded and stimulated with vascular endothelial growth-factor to facilitate endothelial differentiation. MSCs were injected into an ischemic, viable region of the myocardium using a electromechanical guided percutaneous catheter system. Patients were followed for 3 years. Results: We found significant and sustained clinical improvements in exercise time from 6:23±1:43 to 7:00±2:12 minutes (p = 0.0016), angina class (CCS) from 3.0±0.3 to 0.9±1.0 (p < 0.0001)), weekly number of angina attacks from 13.8±13.7 to 4.3±7.3 (p < 0.0001) and weekly uses of nitro-glycerine from 10.7±10.0 to 4.5±6.8 (p = 0.0017). In the Seattle Angina Questionnaire there were significant improvements in physical limitation score, angina stability score, angina frequency score and quality of life score (all p < 0.0001). When comparing all hospital admissions from 3 years before treatment and 3 years after treatment, we observed highly reduced admission rates for stable angina (p < 0.0001), revascularization (p = 0.003) and overall cardiovascular disease (p < 0.0001). No early or late side-effects of the treatment were observed. Conclusions: The final 3-year follow-up data after percutaneous intramyocardial injection of autologous MSCs, in patients with severe CAD and refractory angina, demonstrated sustained and significantly positive clinical effects, reduced hospital admissions for cardiovascular disease and excellent safety. The results indicate that the treatment does not only improve clinical symptoms but also slows down disease progression.