Safety and Efficacy of Induced Pluripotent Stem Cell-derived Engineered Human Myocardium as Biological Ventricular Assist Tissue in Terminal Heart Failure (BioVAT-DZHK20): Trial Design and Experience at UKSH Lübeck

Background: The BioVAT-HF trial is testing the hypothesis if cardiomyocyte implantation via Engineered Human Myocardium (EHM) as “Biological Ventricular Assist Tissue” (BioVAT) results in sustained remuscularization and biological enhancement of myocardial performance in patients with advanced HF. Here we report the experience with enrollment of patients at the University Heart Center Luebeck (UKSH).

Methods: BioVAT-HF is a first-in patient, combined, open-label, two-stage, phase I/II safety and efficacy study investigating induced pluripotent stem cell-derived EHM as biological ventricular assist tissue (BioVAT) in patients with terminal HF. Symptomatic, HF patients with functional NYHA class ≥III despite optimal guideline-directed treatment qualify for inclusion if they present with left ventricle ejection fraction (EF) ≤35% and at least one hypo- or dyskinetic segment to demark the implant target area.

Results: EHM were constructed from iPSC-derived cardiomyocytes and stromal cells (800x106cells/EHM) suspended in a bovine collagen type I hydrogel. EHM were produced individually under GMP-conditions at the University Medical Center Göttingen (UMG). All patients (n = 5) were treated in a consecutive pattern to receive induced pluripotent stem cell (iPSC)-derived EHM in an elective left-lateral mini-thoracotomy. Patients received immune suppression (tacrolimus, methylprednisolone) to prevent allograft rejection. Surveillance of graft retention was by echocardiography and MRI or CT. Median age (Q1, Q3) was 63 (60, 66) years, all patients were male (100%). Baseline parameters were: NYHA class 3 (3, 3), INTERMACS level 6 (5.5, 7), left ventricle (LV) ejection fraction 20 (16, 20)%, LV end-diastolic-diameter 61 (54, 77) mm, TAPSE 22 (14, 23) mm, NT-proBNP 941 (643, 8618) ng/L, 6-minute walking distance 331 (302, 350) m, glomerular filtration rate 52 (35, 71) mL/min, Hemoglobin 14.2 (11, 16.7) g/dl, Ferritin 171 (86, 284) ng/mL. Implantation of EHM was feasible and safe in all patients. n = 4 patients are in clinical follow-up. n = 1 patient died of progressive cardio-renal failure 4 days after the procedure.

Conclusion: The BIOVAT trial is a first-in human study on the epicardial implantation of EHM to support the failing heart by remuscularization in patients with advanced HF. Administration of EHM is clinically feasible and apparently safe.

Publication History

Article published online:
13 February 2024