Quantitative kardiale Magnetresonanztomographie zur Analyse künstlichen Herzgewebes für die funktionelle Behandlung von Herzinsuffizienz im Primatenmodell

Background Chronic heart failure affects approximately 4 million individuals in Germany and remains a leading cause of morbidity and mortality despite advances in medical therapy. Following myocardial infarction, approximately 30% of patients develop chronic heart failure. Current therapeutic approaches are limited to symptomatic treatment or organ replacement, while the underlying irreversible loss of cardiomyocytes cannot be addressed due to the heart's limited regenerative capacity. Engineered Heart Muscle (EHM), derived from induced pluripotent stem cells, represents a novel tissue engineering approach for myocardial remuscularization. Prior studies in rat models demonstrated sustained cell retention and improved cardiac function following EHM implantation. Before initiating clinical trials, proof-of-concept in a primate model closely resembling human cardiac physiology was required. Methods Fourteen rhesus macaques were studied in two cohorts receiving either single-dose (n=7, Cohort I) or five-fold dose (n=7, Cohort II) EHM patches implanted epicardially on the left ventricle via minithoracotomy. EHM was generated from three induced pluripotent stem cell lines using established differentiation protocols. Cardiac magnetic resonance imaging was performed at 3 Tesla using FLASH-CINE sequences at baseline (two measurements), followed by assessments at days 28, 56, and 84 post-implantation; Cohort II received an additional measurement at day 168. Primary outcomes included left ventricular mass, wall thickness (basolateral and contralateral), fractional wall thickening, left ventricular ejection fraction, ventricular volumes, longitudinal strain, and T1-mapping for tissue characterization. Statistical analysis employed non-parametric tests (Wilcoxon signed-rank test for paired comparisons, Mann-Whitney U test for group comparisons). Results EHM implantation resulted in sustained, highly significant increases in basolateral end-systolic wall thickness across all follow-up timepoints (baseline: 7.4±1.6 mm vs. day 84: 10.4±3.6 mm; p