Background Contemporary outcomes data in Down Syndrome (DS) patients undergoing congenital heart surgery are limited. We describe patient characteristics and post-operative morbidity and mortality in a large multi-center cohort. Patients and Methods This retrospective cohort study utilized The Society of Thoracic Surgeons Congenital Heart Surgery Database to compare patient characteristics and postoperative outcomes in DS and non-DS patients (0–18y) undergoing surgery from 2000–2008. Primary analysis focused on the most common surgeries performed in DS patients. Results A total of 45,579 patients (n=4,350 DS, 41,229 non-DS) were included: median age 7m [interquartile range (IQR) 47d–4yr]; 56% male. DS patients were younger at surgery, with the exception of those undergoing tetralogy of Fallot (TOF) and atrioventricular septal defect (AVSD) repair. Mortality did not differ significantly in DS vs. non-DS patients. Length of stay was prolonged in DS patients undergoing atrial septal defect [4d (IQR 3–5d) vs. 3d (IQR 2–4d), p<0.0001] and ventricular septal defect (VSD) closure [5d (IQR 4–8d) vs. 4d (IQR 3–6d), p<0.0001], and TOF repair [7d (IQR 5–10d) vs. 6d (IQR 5–9d), p<0.001], and was associated with post-operative respiratory and infectious complications. DS patients undergoing VSD closure also had a higher rate of heart block requiring pacemaker placement (2.9% vs. 0.8%, p<0.0001). Conclusion In this large contemporary cohort undergoing congenital heart surgery, DS does not confer a significant mortality risk for the most common operations performed in this population; however post-operative morbidity remains common.

Background Re-coarctation after the Norwood procedure increases risk for mortality. The Single Ventricle Reconstruction (SVR) trial randomized subjects with a single right ventricle undergoing a Norwood procedure to a modified Blalock-Taussig shunt (MBTS) or right ventricle-pulmonary artery shunt (RVPAS). We sought to determine incidence of re-coarctation, risk factors and outcomes in the SVR trial. Methods and Results Re-coarctation was defined by intervention, either catheter-based or surgical. Univariate analysis and multivariable Cox proportional hazard models were performed adjusting for center. Of the 549 SVR subjects, 97 (18%) underwent 131 interventions (92 balloon aortoplasty; 39 surgical) for re-coarctation at median age 4.9 months (range: 1.1–10.5). Intervention typically occurred at pre-stage II catheterization (n=71, 54%) or at stage II surgery (n=38, 29%). In multivariable analysis, re-coarctation was associated with the shunt type in place at the end of the Norwood procedure (HR 2.0 for RVPAS vs. MBTS, p=0.02), and Norwood discharge peak echo-Doppler arch gradient (HR 1.07 per 1 mmHg, p<0.01). Subjects with re-coarctation demonstrated comorbidities at pre-stage II evaluation including higher pulmonary arterial pressures (15.4±3.0 vs. 14.5±3.5 mm Hg; p=0.05), higher pulmonary vascular resistance (2.6±1.6 vs. 2.0±1.0 WU × m2; p=0.04) and increased echocardiographic volumes (end-diastolic volume: 126±39 vs. 112±33 ml/BSA1.3; p=0.02). There was no difference in 12-month post-randomization transplant-free survival between those with and without re-coarctation (p=0.14). Conclusions Re-coarctation is common after Norwood and contributes to pre-stage II comorbidities. Although with intervention there is no associated increase in 1-year transplant/mortality, further evaluation is warranted to evaluate effects of associated morbidities.

ObjectiveTo assess the feasibility, safety, and efficacy of intracoronary allogeneic cardiosphere-derived cells (CAP-1002) in patients with Duchenne muscular dystrophy (DMD).MethodsThe Halt Cardiomyopathy Progression (HOPE)-Duchenne trial is a phase I/II, randomized, controlled, open-label trial (NCT02485938). Patients with DMD >12 years old, with substantial myocardial fibrosis, were randomized (1:1) to usual care (control) or global intracoronary infusion of CAP-1002 (75 million cells). Participants were enrolled at 3 US medical centers between January and August 2016 and followed for 12 months. An independent Data and Safety Monitoring Board provided safety oversight. Cardiac function and structure were assessed by MRI, and analyzed by a blinded core laboratory. Skeletal muscle function was assessed by performance of the upper limb (PUL).ResultsTwenty-five eligible patients (mean age 17.8 years; 68% wheelchair-dependent) were randomized to CAP-1002 (n = 13) or control (n = 12). Incidence of treatment-emergent adverse events was similar between groups. Compared to baseline, MRI at 12 months revealed significant scar size reduction and improvement in inferior wall systolic thickening in CAP-1002 but not control patients. Mid-distal PUL improved at 12 months in 8 of 9 lower functioning CAP-1002 patients, and no controls (p = 0.007).ConclusionsIntracoronary CAP-1002 in DMD appears safe and demonstrates signals of efficacy on both cardiac and upper limb function for up to 12 months. Thus, future clinical research on CAP-1002 treatment of DMD cardiac and skeletal myopathies is warranted.Classification of evidenceThis phase I/II study provides Class II evidence that for patients with DMD, intracoronary CAP-1002 is feasible and appears safe and potentially effective.