Safety and outcomes analysis: transcatheter implantation of autologous angiogenic cell precursors for the treatment of cardiomyopathy
Authors: Schubart Jane R. , Zare Amirhossein , Fernandez-de-Castro Roberto M. , Figueroa Hector Rosario , Sarel Ina , Tuchman Kelly , Esposito Kaitlyn , Henderson Fraser C. , von Schwarz Ernst 
Published: October 2023

Abstract
Background
Stem cell transplantation is an emerging therapy for severe cardiomyopathy, proffering stem cell recruitment, anti-apoptosis, and proangiogenic capabilities. Angiogenic cell precursors (ACP-01) are autologous, lineage-specific, cells derived from a multipotent progenitor cell population, with strong potential to effectively engraft, form blood vessels, and support tissue survival and regeneration.

Methods
This IRB approved outcome analysis reports upon 74 consecutive patients who failed medical management for severe cardiomyopathy, and were selected to undergo transcatheter intramyocardial or intracoronary implantation of ACP-01. Serious adverse events (SAEs) were reported. Cell analysis was conducted for each treatment. The left ventricular ejection fraction (LVEF) was measured by multi-gated acquisition scan (MUGA) or echocardiogram at 4 months ± 1.9 months and 12 months ± 5.5 months. Patients reported quality of life statements at 6 months (± 5.6 months).

Results
Fifty-four of 74 patients met requirements for inclusion (48 males and five females; age 68.1 ± 11.3 years). The mean treatment cell number of 57 × 106 ACP-01 included 7.7 × 106 CD34 + and 21 × 106 CD31 + cells with 97.6% viability. SAEs included one death (previously unrecognized silent MI), ventricular tachycardia (n = 2) requiring cardioversion, and respiratory infection (n = 2). LVEF in the ischemic subgroup (n = 41) improved by 4.7% ± 9.7 from pre-procedure to the first follow-up (4 months ± 1.9 months) (p < 0.004) and by 7.2% ± 10.9 at final follow-up (n = 25) at average 12 months (p < 0.004). The non-ischemic dilated cardiomyopathy subgroup (n = 8) improved by 7.5% ± 6.0 at the first follow-up (p < 0.017) and by 12.2% ± 6.4 at final follow-up (p < 0.003, n = 6). Overall improvement in LVEF from pre-procedure to post-procedure was significant (Fisher’s exact test p < 0.004). LVEF improvement was most marked in the patients with the most severe cardiomyopathy (LVEF < 20%) improving from a mean 14.6% ± 3.4% pre-procedurally to 28.4% ± 8% at final follow-up. Quality of life statements reflected improvement in 33/50 (66%), no change in 14/50 (28%), and worse in 3/50 (6%).

Conclusion
Transcatheter implantation of ACP-01 for cardiomyopathy is safe and improves LVEF in the setting of ischemic and non-ischemic cardiomyopathy. The results warrant further investigation in a prospective, blinded, and controlled clinical study.
Trial Registration: IRB from Genetic Alliance #APC01-001, approval date July 25, 2022.

Condensed Abstract
Cardiomyopathy is common and associated with high mortality. Stem cell transplantation is an emerging therapy. Angiogenic cell precursors (ACP-01) are lineage-specific endothelial progenitors, with strong potential for migration, engraftment, angiogenesis, and support of tissue survival and regeneration. A retrospective outcomes analysis of 53 patients with ischemic and non-ischemic dilated cardiomyopathy undergoing transcatheter implantation of ACP-01 demonstrated improvements in the left ventricular ejection fraction of 7.2% ± 10.9 (p < 0.004) and 12.2% ± 6.4, respectively, at 12 months (± 5) follow-up. Quality of life statements reflected improvement in 33/50 (66%) patients.