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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.

Objective: The safety of surgical closure of patent ductus arteriosus (PDA) in very low birth weight premature neonates has been questioned because of associated morbidities. However, these studies are vulnerable to significant bias as surgical ligation has historically been utilized as “rescue” therapy. The objective of this study was to review our institutions’ outcomes of surgical PDA ligation. Methods: All neonates with operative weight of ≤1.00 kg undergoing surgical PDA ligation from 2003 to 2015 were analyzed. Records were queried to identify surgical complications, perioperative morbidity, and mortality. Outcomes included pre- and postoperative ventilator requirements, pre- and postoperative inotropic support, acute kidney injury, surgical complications, and 30-day mortality. Results: One hundred sixty-six preterm neonates underwent surgical ligation. One hundred twenty-one (70.3%) had failed indomethacin closure. One hundred sixty-four (98.8%) patients required mechanical ventilation prior to surgery. At 17 postoperative days, freedom from the ventilator reached 50%. Of 109 (66.4%) patients requiring prolonged preoperative inotropic support, 59 (54.1%) were liberated from inotropes by postoperative day 1. Surgical morbidity was encountered in four neonates (2.4%): two (1.2%) patients had a postoperative pneumothorax requiring tube thoracostomy, one (0.6%) patient had a recurrent laryngeal nerve injury, and one (0.6%) patient had significant intraoperative bleeding. The 30-day all-cause mortality was 1.8% (n = 3); no deaths occurred intraoperatively. Conclusion: In this retrospective investigation, surgical PDA closure was associated with low 30-day mortality and minimal morbidity and resulted in rapid discontinuation of inotropic support and weaning from mechanical ventilation. Given the safety of this intervention, surgical PDA ligation merits consideration in the management strategy of the preterm neonate with a PDA.