N Engl J Med. 2026 May 28;394(20):1991-2001. doi: 10.1056/NEJMoa2513525.
ABSTRACT
BACKGROUND: Biologic ventricular assist tissue (BioVAT) is formulated from engineered heart muscle composed of cardiomyocytes and stromal cells derived from allogeneic induced pluripotent stem cells for cardiac remuscularization in patients with heart failure and a reduced left ventricular ejection fraction.
METHODS: We conducted an open-label, phase 1-2 study of tissue-engineered heart repair by means of BioVAT transplantation. Patients with heart failure and a left ventricular ejection fraction of 35% or less and at least one hypokinetic or dyskinetic left ventricular segment were treated with BioVAT allografts, which consisted of 5, 10, or 20 engineered-heart-muscle units. All the patients received immunosuppression. Safety was assessed as adverse events related to the procedure. The primary efficacy end points were the change from baseline in the target heart-wall thickness, the left ventricular ejection fraction, and the Kansas City Cardiomyopathy Questionnaire-Overall Summary Score (KCCQ-OSS).
RESULTS: A total of 20 patients were treated in the study. Three patients died during the study (1 each from vasoplegia, coronavirus disease 2019, and aortic dissection). One patient underwent heart transplantation. Immunosuppression was discontinued in 4 patients because of implantation of a left ventricular assist device (in 2 patients), renal failure (in 1 patient), and urothelial carcinoma (in 1 patient). Of the 16 patients who were treated with the safe maximal dose (20 engineered-heart-muscle units), 12 patients completed the prespecified 3-month interim follow-up. The least-squares mean increase in the target-wall thickness was 4.5 mm (90% confidence interval [CI], 3.7 to 5.4; P<0.001), the increase in the left ventricular ejection fraction was 3.9 percentage points (90% CI, 0.9 to 6.8; P = 0.04), and the increase in the KCCQ-OSS was 6.7 points (90% CI, 1.0 to 12.5; P = 0.06). All the patients had at least one adverse event.
CONCLUSIONS: In this interim analysis, cardiac remuscularization with BioVAT was associated with an increase in the target heart-wall thickness, left ventricular ejection fraction, and KCCQ-OSS at 3 months; all the patients had at least one adverse event. Longer-term follow-up and further clinical investigation are warranted. (Funded by the German Center for Cardiovascular Research and Repairon; BioVAT-HF ClinicalTrials.gov number, NCT04396899.).
PMID:42202318 | DOI:10.1056/NEJMoa2513525