Abstract 19102: Cell Injection Site Influences the Human Mesenchymal Stem Cell Therapy Effectiveness for Left Ventricular Dysfunction in Ischemic Cardiomyopathy
Introduction: Clinical trials have shown that trans-endocardial stem cell injection (TESI) of mesenchymal stem cells (MSC) both reduced myocardial infarct scars and normalizes cardiac sphericity, 2 important features of reverse remodeling. Because, the anatomic location of MI scar location could affect this response, we tested the hypothesis that the site of TESI could contribute to the reverse remodeling response to cell therapy.
Methods: Patients from the TAC-HFT, POSEIDON and PROMETHEUS trials (n=56), were divided into 3 groups based on the location territory of MSC injection: left coronary artery (LAD; n=7), right coronary artery and/or circumflex artery (RCA/Cx, n=19), or both (n=32) territories. Parameters measured at baseline and 12-13 months after MSC injection included scar size (SS), sphericity index (SI), ejection fraction (EF) and end diastolic (EDV) and systolic (ESV) volume as measured by angio-CT and ECG, and functional parameters such as MLHFQ score and 6-min walk distance (6MWD).
Results: The overall change in SI for all the patients that received MSCs was –0.037±0.009 (95%CI –0.056 to –0.019; P<0.001). Whereas, scar reduction was independent of injection site, the reduction in SI occurred preferentially -0.0425 ± 0.0591 (95%CI -0.065 to -0.019) (p<0.001) when MSCs were injected into both territories. Overall, there was a significant decrease in absolute SS–7.07 ± 0.95 g (95%CI –8.987 to –5.165; P<0.0001), and SS as a % of LV mass (P<0.0001) in all patients from baseline to 12-13 months after injection. The location of TESI didn’t affect scar mass (P=0.42) or % change of SS (P=0.6) LAD: –36.956%±21.20, RCA/Cx: –39.14% ±15.31, both: –32.5248%±23.94. The change in MLHFQ score improved significantly post injection in the LAD compared to the other groups (p<0.009): LAD vs. RCA/Cx= –17.04±6.47 (95%CI –29.86 to 4.23; P=0.009), and LAD vs. Both 15.14±5.67 (95%CI –26.36-3.91; P=0.008), There were no significant differences between groups in EF, EDV, ESV, or 6MWD.
Conclusion: Scar reduction is equivalent regardless of the site of MI and cell therapy; however, only TESI into both territories reduced SI compared to baseline. Therefore, location of the injection in the dysfunctional ischemic area influences the effectiveness of MSC therapy.
Author Disclosures: A.M. Castellanos: None. W. Balkan: None. D.L. DiFede: None. J.M. Hare: Other; Significant; Dr. Hare reported having a patent for cardiac cell-based therapy., Dr. Hare holds equity in Vestion and maintains a professional relationship with Vestion as a consultant and member of the Board of Directors and Scientific Advisory Board. Vestion Inc..
- © 2016 by American Heart Association, Inc.