Breaking news for patients with heart disease

Jens Kastrup, Tina Friis, Mandana Haack-Sørensen, Rasmus Ripa, Ulrik S. Kristoffersen, Lene Bindslev, Anders B Mathiasen, Birger Hesse, Andreas Kjær, Ebbe Dickmeiss, Erik Jørgensen,
Cardiovascular Laboratory 2014, The Heart Centre, University Hospital Rigshospitalet, Copenhagen Ø, Denmark
Department of Clinical Physiology, Nuclear Medicine and PET & Cluster for Molecular Imaging

Background:
Mesenchymal stromal cells (MSCs) from adult bone marrow (BM) have been used, in the animal model, to create neovascularization in ischemic hearts. We aimed to evaluate the feasibility, safety and efficacy of ex-vivo expanded bone marrow derived mesenchymal-derived endothelial progenitor cells for autologous cell transplantation to the heart, to improve vascularization in patients with severe myocardial ischemia.

Methods:
A total of 31 patients with stable chronic coronary artery disease (Age: 66+7 years [mean±SD], 26 men and 5 females) were included in an open investigators-initiated clinical trial. The patients had angina CCS 2-3 and reversible myocardial ischemia in an adenosine stress single photon emission computerized tomography (SPECT) and no further revascularization options. Bone marrow was aspirated by needle from the iliac crest. Mesenchymal stem cells were isolated and expanded in culture for 6-8 weeks. The last week cells were stimulated by rhVEGF-A165 to promote differentiation into endothelial progenitor cells. A total of 10 - 40 x10⁶ cells were injected directly into a myocardial area of reversible ischemia using the NOGA-XP® system. As a control group we used 16 patients previously treated with NOGA-XP®-guided intramyocardial injection of placebo plasmid (Age: 62+9 years, 14 men and 2 females). Primary endpoint is feasibility and safety of the treatment. Secondary endpoint is effect on angina and perfusion.

Results:
The 6 months follow-up demonstrated a significant increase in maximal bicycle exercise performance from 6.29 min to 7.15 min (p=0.003), a reduction in angina pectoris attacks from 13.8 to 3.8 attacks/week (p<0.001) and a reduced consumption in nitroglycerin from 10.8 to 4.1 nitroglycerin tablets/week (p=0.002). The CCS classification was reduced from 3.0 to 1.2 (p<0.001). Seattle angina questionnaire scores demonstrated improvement in angina frequency, angina stability, physical limitations and quality of life (p<0.001 for all). It was not possible to detect any improvement in myocardial perfusion measured by SPECT. The treatment was safe without any major adverse events during treatment and in the follow-up period.

Conclusion:
The study demonstrates that direct intramyocardial injections with autologous transplantation of ex-vivo expanded mesenchymal derived VEGF-stimulated endothelial progenitor cells is safe and improve exercise capacity, reduce CCS class, angina attacks and nitroglycerin consumption, and improve quality of life in patients with severe chronic occlusive coronary artery disease.

The study was supported by Lundbeck Foundation, Aase og Ejnar Danielsens Foundation, The Research Council at Rigshospitalet and the Danish Heart Foundation.