Abstract Body (Do not enter title and authors here): BioVAT-HF is an open label, non-randomized, multicenter Phase I/II clinical trial (NCT04396899) evaluating the safety and efficacy of remuscularizing the failing heart by epicardial implantation of Engineered Human Myocardium (EHM) as Biological Ventricular Assist Tissue (BioVAT). EHM represent a first-in-class advanced therapy medicinal product–tissue engineered product (ATMP-TEP) derived from induced pluripotent stem cells (iPSCs) under current Good Manufacturing Practice for first-in-patient investigations in a target patient population with chronic advanced heart failure despite optimal medical therapy. Phase I dose finding identified 20 g EHM produced from 800 million iPSC-derived cardiomyocytes and stromal cells as per study protocol safe maximal dose (SMD); in addition, histological proof of remuscularization was obtained. As of June 2025, 25 patients have been recruited and 19 treated in the dose finding and proof-of-concept cohorts (refer to Table with patient characteristics). Fifteen (1/14 female/male, 12/3 ischemic/dilated cardiomyopathy, all in NYHA III, left ventricular ejection fraction: 24±6%) of the 19 patients were treated with the SMD (10±2 million iPSC-derived cells/kg body weight), marking the number to be treated for the study interim analysis. We made the following key observations in the SMD treated patients: (1) no EHM related adverse events over a cumulative follow-up of 15 years, (2) sustained target heart wall thickening by ~4 mm identified by echocardiography, cardiac CT, or cardiac MRI, (3) enhanced left ventricular ejection fraction (24±6 to 34±6%; p<0.0001), and (4) improved KCCQ-23 Overall Summary Score (54±18 to 67±15; p<0.01). Within the study period of 12 months, four (27%) and two (13%) of 15 treated patients died on study (non-cardiac cause) or were implanted with a left ventricular assists device (LVAD), respectively. Within 12 months of enrollment, two (33%) of the six recruited but not treated patients died due to heart failure decompensation, one patient (17%) was implanted with a LVAD. End of August 2025 marks the timepoint for interim analysis as per study protocol. Detailed efficacy data from the interim analysis will be presented. For the first time an initial assessment of efficacy in patients with advanced heart failure treated with EHM is possible.

Data presented as mean±SD, count, and percent of the respective patient cohort
Statistical testing of pre-post comparison by paired, two-tailed Student’s t-test