LB4. Prospective, Single Center Randomized Control Trial to Evaluate the Safety and Feasibility of a Novel Allogenic Mesenchymal Precursor Cell Therapy in Patients with Hypoplastic Left Heart Syndrome
Stanford University School of Medicine
Stanford, CA
United States - Contact Me
Michael Ma, MD is Associate Professor of Cardiothoracic Surgery at Stanford University’s School of Medicine. He serves as Chief for the Division of Pediatric Cardiac Surgery, and Surgical Director for the Complex Biventricular Reconstruction and Pediatric Advanced Cardiac Therapies programs. His clinical practice encompasses all aspects of congenital heart disease, with an emphasis on complex reconstructive procedures for achieving biventricular circulation, rehabilitating pulmonary artery pathologies, and device therapy for end-stage heart failure.
Dr. Ma’s translational research utilizes biomechanical engineering principles to optimize existing treatments and develop new procedures and therapies, through collaborations between the Schools of Medicine and Engineering. His lab focuses on understanding the atrioventricular valve in single and complex biventricular circulations; de novo surgical repair strategies and devices are evaluated in computational, ex vivo, and large animal models.
Harvard Medical School
United States - Contact Me
Rachel Wittenberg is an MD/MPH candidate at Harvard Medical School and the Harvard T.H. Chan School of Public Health. She completed her undergraduate degree in Biological Sciences from the University of Chicago in 2017 and researched tuberculosis vaccine development for two years at the University of Oxford prior to medical school. She is interested in congenital heart surgery and biventricular repair strategies for patients with hypoplastic left heart syndrome as well as medical education and improving global disparities in cardiac surgery and cardiovascular care.
Description
Methods: Children <5 years with prior single ventricle palliation undergoing bidirectional Glenn and LV recruitment surgery (mitral valve repair, restriction) were randomized to ~20 million MPCs in ~11 injections in the LV endocardium/papillary muscles (MPC group) or standard-of-care (controls). Primary endpoint of safety was assessed at 12 months with pre-specified follow-up through 24 months for primary serious adverse events (SAEs), other adverse events (AEs), and anti-HLA panel reactive antibodies (PRA). Secondary endpoints included assessments of LV function by echocardiogram, cardiac MRI, and catheterization. Probability of BiV/1.5V conversion was estimated using Kaplan-Meier curves.
Results: 19 subjects were enrolled (15 HLHS, 4 unbalanced atrioventricular canal). Median age at LV recruitment surgery was 1.0 years (range 0.3, 3.4). 9 subjects were randomized to the MPC and 10 to the control group. 1 was lost to follow-up. There were 2 SAEs: 1 bradycardic arrest (day 8) and 1 mortality (21 months), both deemed unrelated to the trial. No cardiac tumors, intracardial hematomas or perioperative ventricular arrhythmias were detected. Median AEs per year was 1.6 for MPCs and 1.1 for controls (p=0.44). At baseline, 11/18 (61%) of patients had PRA>10% and 9/18 (50%) had PRA>90% with no difference in PRA% between groups at 12 months (Fig. 1A). In the full cohort, probability of BiV/1.5V conversion was 0.16 (95% CI: 0.05, 0.41) at 12 months and 0.54 (0.31, 0.79) at 24 months (Fig. 1B). At 12 months, LV mass, LVEDV, and LVEF on MRI were similar between the groups.
Conclusions: In a highly sensitized patient cohort undergoing LV recruitment, adjunct treatment with MPCs was safe and feasible. Over 50% underwent BiV/1.5V conversion within 2 years. Larger trials powered to detect efficacy are needed to further investigate the promising therapeutic potential of MPCs in this population. These may include dose escalation or assessment of the impact of baseline allosensitization on MPC effectiveness.