Study Protocol of Intramyocardial Injection of Autologous Bone Marrow Stem Cells for Refractory Angina (ReACT)

This was a phase II, non-controlled (single arm) and open label clinical trial. The study was approved by the Institutional Review Board (IRB) and all patients gave informed consent prior to participation.

Refractory angina patients were defined as those with functional class IV (angina at rest) according to the Canadian Cardiovascular Society Angina Classification (CCSAC) despite maximum medical therapy, not suitable for conventional myocardial revascularization and viable myocardium confirmed by nuclear imaging.

Patients were evaluated according to different parameters, for a total period of 12 months, and the primary objectives were:

1. Improvement in functional class and angina symptoms (CCSAC) of the patients with refractory angina pectoris after the infusion of autologous bone marrow mononuclear cells after the intervention; 2. Improvement in myocardial perfusion before and after cell delivery; 3. Evaluate the safety of the delivery of autologous bone marrow mononuclear cells route in individuals with refractory angina.

In the screening evaluation, individuals with the presumptive diagnosis of class IV refractory angina and who met all study criteria were approached about the possibility of participating in the study by the principal investigator. Then, the patients were submitted to a baseline evaluation with a serious of blood and image tests.

The interventions were the Bone Marrow Aspiration - For each patient, a total of 100 cc of bone marrow was aspirated from the iliac crest at the time of anesthesia for their cardiac surgery - and the Infusion - After processing the cells, the surgeon delivered it by a series of epicardial injections into the left ventricular myocardium.

The processing of bone marrow autologous cells aimed to enrich the content of the bone marrow aspirate, separating the mononuclear fraction from the cells which were already differentiated.

The postoperative stage was conducted in an identical way to that of patients who undergo to a myocardial revascularization surgery. It is important to mention that both the ICU and the ward time varied according to the patient's individual evolution.

Finally, the first follow up visit took place at 1 month after the surgery. The subsequent visits were held at 3, 6 and 12 months after the procedure.