Repeat Cell Therapy for Refractory Angina: Déjà vu All Over Again?

B ecause the mortality for ischemic heart disease has improved, an increasing number of patients exhaust their revascularization options and are left with refractory angina. Previous studies suggested that up to 15% of patients undergoing catheterization are suboptimal candidates for further revas-cularization. 4 This number may be growing because a recent analysis from the Duke Databank for Cardiovascular Disease found that 25% of patients had Canadian Cardiovascular Society (CCS) class II-IV angina and coronary disease not amenable to further revascularization. 5 Contemporary data suggest that mortality in these complex patients is decreasing , despite the significant burden of coronary artery disease , whereas rehospitalization rates and resource utilization remain high, reflecting the poor quality of life and functional status in these patients. Limited treatment options are available for patients with refractory angina beyond pharmacological treatment and revascularization. This unmet clinical need has stimulated the investigation of novel treatment options, including advanced techniques to treat chronic total occlusions, neuromodulation, reduction of the coronary sinus, shockwave therapy, and stem cell therapy. Because the primary problem for these patients is inadequate myocardial perfusion, stem cell therapy using angiogenic progenitors represents a theoretically attractive approach. Initial trials for this specific indication have arguably been the most positive in the field of stem cell therapy. Three recent meta-analysis of patients with refractory angina with or without left ventricular dysfunction reach similar and consistent conclusions that this treatment may result in improvements in angina, quality of life, exercise capacity, left ventricular function , and even mortality. 7–9 Still no definitive Phase 3 trial has been completed, and a large number of questions remain unan-swered, including the ideal cell type and method of delivery. In this issue of Circulation: Cardiovascular Interventions, the group from Leiden builds on their previous work in this area by providing valuable data regarding the benefits of repeat therapy. 10 In 2006, this group first published the results of an open-label trial in 25 patients who were not candidates for revascularization and had CCS III-IV angina, despite optimal medical therapy. 11 The patients were treated with intramyocar-dial injection of autologous bone marrow mononuclear cells (BMMC) using Noga electromechanical mapping for guidance into ischemic regions. At 3 months follow-up, the cell-treated patients had improvement in CCS angina class, left ventricular function and volumes, as well as myocardial perfusion by single photon emission computed tomography, which was greater in the injected segments versus noninjected segments. …