Effects of Transendocardial Delivery of Bone Marrow–Derived CD133+ Cells on Left Ventricle Perfusion and Function in Patients With Refractory AnginaNovelty and Significance: Final Results of Randomized, Double-Blinded, Placebo-Controlled REGENT-VSEL Trial

Rationale: New therapies for refractory angina are needed. Objective: Assessment of transendocardial delivery of bone marrow CD133 + cells in patients with refractory angina. Methods and Results: Randomized, double-blinded, placebo-controlled trial enrolled 31 patients with recurrent Canadian Cardiovascular Society II–IV angina, despite optimal medical therapy, ≥1 myocardial segment with inducible ischemia in Tc-99m SPECT who underwent bone marrow biopsy and were allocated to cells (n=16) or placebo (n=15). Primary end point was absolute change in myocardial ischemia by SPECT. Secondary end points were left ventricular function and volumes by magnetic resonance imaging and angina severity. After 4 months, there were no significant differences in extent of inducible ischemia between groups (summed difference score mean [±SD]: 2.60 [2.6] versus 3.63 [3.6], P =0.52; total perfusion deficit: 3.60 [3.6] versus 5.01 [4.3], P =0.32; absolute changes of summed difference score: −1.38 [5.2] versus −0.73 [1.9], P =0.65; and total perfusion deficit: −1.33 [3.3] versus −2.19 [6.6], P =0.65). There was a significant reduction of left ventricular volumes (end-systolic volume: −4.3 [11.3] versus 7.4 [11.8], P =0.02; end-diastolic volume: −9.1 [14.9] versus 7.4 [15.8], P =0.02) and no significant change of left ventricular ejection fraction in the cell group. There was no difference in number of patients showing improvement of ≥1 Canadian Cardiovascular Society class after 1 (41.7% versus 58.3%; P =0.68), 4 (50% versus 33.3%; P =0.63), 6 (70% versus 50.0%; P =0.42), and 12 months (55.6% versus 81.8%; P =0.33) and use of nitrates after 12 months. Conclusion: Transendocardial CD133 + cell therapy was safe. Study was underpowered to conclusively validate the efficacy, but it did not show a significant reduction of myocardial ischemia and angina versus placebo. Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01660581.