Study design and rationale for ELPIS: A phase I/IIb randomized pilot study of allogeneic human mesenchymal stem cell injection in patients with hypoplastic left heart syndrome.

Despite advances in surgical technique and postoperative care, long-term survival of children born with hypoplastic left heart syndrome (HLHS) remains limited, with cardiac transplantation as the only alternative for patients with failing single ventricle circulations. Maintenance of systemic right ventricular function is crucial for long-term survival, and interventions that improve ventricular function and avoid or defer transplantation in patients with HLHS are urgently needed. We hypothesize that the young myocardium of the HLHS patient is responsive to the biological cues delivered by bone marrow-derived mesenchymal stem cells (MSCs) to improve and preserve right ventricle function. The ELPIS trial (Allogeneic Human MEsenchymal Stem Cell Injection in Patients with Hypoplastic Left Heart Syndrome: An Open Label Pilot Study) is a phase I/IIb trial designed to test whether MSC injection will be both safe and feasible by monitoring the first 10 HLHS patients for new major adverse cardiac events. If our toxicity stopping rule is not activated, we will proceed to the phase IIb component of our study where we will test our efficacy hypothesis that MSC injection improves cardiac function compared with surgery alone. Twenty patients will be enrolled in a randomized phase II trial with a uniform allocation to MSC injection versus standard surgical care (no injection). The 2 trial arms will be compared with respect to improvement of right ventricular function, tricuspid valve annulus size, and regurgitation determined by cardiac magnetic resonance and reduced mortality, morbidity, and need for transplantation. This study will establish the safety and feasibility of allogeneic mesenchymal stem cell injection in HLHS patients and provide important insights in the emerging field of stem cell-based therapy for congenital heart disease patients.

Simplified mitral valve repair in pediatric patients with connective tissue disorders.

BACKGROUND: In pediatric patients with connective tissue disorders (CTDs), early cardiac presentation often involves severe mitral regurgitation (MR) associated with severe bileaflet prolapse and, less frequently, aortic root enlargement. We adopted a simplified repair to address MR and prevent systolic anterior motion (SAM) in this unique group of patients. MATERIALS AND METHODS: Retrospective review of clinical and echocardiographic data of all pediatric patients (age < 18 years) with CTD and MR undergoing simplified repair at 3 institutions (2000-2014). RESULTS: Eighteen children who underwent surgery for severe MR and bileaflet prolapse were identified. All were treated with ring annuloplasty and Alfieri edge-to-edge repair. Median age and weight were 8.2 years (range, 0.4-17.2 years) and 24.9 kg (5.6-63.3 kg), respectively. Median left ventricular end diastolic dimension median z score was 4.9 (2.1-11.9). One patient died (5.6%), and there were no other major complications. Among survivors, 94.4% had mild regurgitation or less, with no stenosis or SAM at median clinical follow-up of 2.4 years (range, 0-13.9 years). Median left ventricular end-diastolic dimension z score regressed to 1.3 (-0.5 to 4.3). CONCLUSIONS: In pediatric patients with CTD and severe MR, a simplified approach is associated with intermediate-term competence, absence of SAM or significant stenosis, and regression of left ventricular enlargement.