Background - A novel concept providing prenatally tissue engineered human autologous heart valves based on routinely obtained fetal amniotic fluid progenitors as single cell source is introduced. Methods and Results - Fetal human amniotic progenitors were isolated from routinely sampled amniotic fluid and sorted using CD133 magnetic beads. After expansion and differentiation, cell phenotypes of CD133- and CD133+ cells were analyzed by immunohistochemistry and flowcytometry. After characterization, CD133- derived cells were seeded onto heart valve leaflet scaffolds (n = 18) fabricated from rapidly biodegradable polymers, conditioned in a pulse duplicator system, and subsequently coated with CD133+ derived cells. After in vitro maturation, opening and closing behavior of leaflets was investigated. Neo-tissues were analyzed by histology, immunohistochemistry, and scanning electron microscopy (SEM). Extracellular matrix (ECM) elements and cell numbers were quantified biochemically. Mechanical properties were assessed by tensile testing. CD133- derived cells demonstrated characteristics of mesenchymal progenitors expressing CD44 and CD105. Differentiated CD133+ cells showed features of functional endothelial cells by eNOS and CD141 expression. Engineered heart valve leaflets demonstrated endothelialized tissue formation with production of ECM elements (GAG 80%, HYP 5%, cell number 100% of native values). SEM showed intact endothelial surfaces. Opening and closing behavior was sufficient under half of systemic conditions. Conclusions - The use of amniotic fluid as single cell source is a promising low-risk approach enabling the prenatal fabrication of heart valves ready to use at birth. These living replacements with the potential of growth, remodeling, and regeneration may realize the early repair of congenital malformations.

Background - Optimal cell sources and scaffold-cell interactions remain unanswered questions for tissue engineering of heart valves. We assessed the effect of different protein precoatings on a single scaffold type (elastomeric poly (glycerol sebacate)) with a single cell source (endothelial progenitor cells). Methods and Results - Elastomeric poly (glycerol sebacate) scaffolds were precoated with laminin, fibronectin, fibrin, collagen types I/III, or elastin. Characterized ovine peripheral blood endothelial progenitor cells were seeded onto scaffolds for 3 days followed by 14 days incubation. Endothelial progenitor cells were CD31(+), vWF(+), and alpha-SMA(-) before seeding confirmed by immunohistochemistry and immunoblotting. Both precoated and uncoated scaffolds demonstrated surface expression of CD31(+) and vWF(+), alpha-SMA(+) cells and were found in the interstitium of the scaffold. Protein precoating of elastomeric poly (glycerol sebacate) scaffolds revealed significantly increased cellularity and altered the phenotypes of endothelial progenitor cells, which resulted in changes in cellular behavior and extracellular matrix production. Moreover, mechanical flexure testing demonstrated decreased effective stiffness of the seeded scaffolds compared with unseeded controls. Conclusions - Scaffold precoating with extracellular matrix proteins can allow more precise engineering of cellular behavior in the development of tissue engineering of heart valves constructs by altering extracellular matrix production and cell phenotype.

Background - Symptomatic prolonged sinus pauses on termination of atrial fibrillation (AF) are an indication for pacemaker implantation. We evaluated sinus node function and clinical outcome in patients with prolonged sinus pauses on termination of arrhythmia who underwent ablation of paroxysmal AF. Methods and Results - Twenty patients with paroxysmal AF and prolonged sinus pauses (greater than or equal to3 seconds) on termination of AF underwent ablation between May 1995 and November 2002. Patients with sinus pauses independent of episodes of AF were excluded from the analysis. The procedure included pulmonary vein and linear atrial ablation. After ablation, sinus node function was assessed during the first week and at 1, 3, and 6 months, by 24-hour ambulatory monitoring to determine the mean heart rate and heart rate range, and by exercise testing to determine the maximal heart rate. Corrected sinus node recovery time was determined at the completion of ablation and at 24.0 +/- 11.3 months at 600 and 400 ms. After AF ablation, there was a significant improvement of sinus node function, with an increase in the mean heart rate ( P = 0.001), maximal heart rate ( P < 0.0001), and heart rate range ( P < 0.0001). The corrected sinus node recovery time decreased in all patients evaluated at 600 ms ( P = 0.016) and 400 ms ( P = 0.019). At 26.0 +/- 17.6 months, 18 patients (85%) had no recurrence of AF ( in the absence of medication), with no symptoms attributable to bradycardia or sinus pauses on ambulatory monitoring. Two patients had infrequent episodes of AF, 1 requiring pacemaker implantation. Conclusion - Prolonged sinus pauses after paroxysms of AF may result from depression of sinus node function that can be eliminated by curative ablation of AF. This is accompanied by improvement in parameters of sinus node function, suggesting reverse remodeling of the sinus node.

Background-Single-center reports have identified retrograde ascending aortic dissection (rAAD) as a potentially lethal complication of thoracic endovascular aortic repair (TEVAR). Methods and Results-Between 1995 and 2008, 28 centers participating in the European Registry on Endovascular Aortic Repair Complications reported a total of 63 rAAD cases (incidence, 1.33%; 95% CI, 0.75 to 2.40). Eighty-one percent of patients underwent TEVAR for acute (n=26, 54%) or chronic type B dissection (n=13, 27%). Stent grafts with proximal bare springs were used in majority of patients (83%). Only 7 (15%) patients had intraoperative rAAD, with the remaining occurring during the index hospitalization (n=10, 21%) and during follow-up (n=31, 64%). Presenting symptoms included acute chest pain (n=16, 33%), syncope (n=12, 25%), and sudden death (n=9, 19%) whereas one fourth of patients were asymptomatic (n=12, 25%). Most patients underwent emergency (n=25) or elective (n=5) surgical repair. Outcome was fatal in 20 of 48 patients (42%). Causes of rAAD included the stent graft itself (60%), manipulation of guide wires/sheaths (15%), and progression of underlying aortic disease (15%). Conclusions-The incidence of rAAD was low (1.33%) in the present analysis with high mortality (42%). Patients undergoing TEVAR for type B dissection appeared to be most prone for the occurrence of rAAD. This complication occurred not only during the index hospitalization but after discharge up to 1050 days after TEVAR. Importantly, the majority of rAAD cases were associated with the use of proximal bare spring stent grafts with direct evidence of stent graft-induced injury at surgery or necropsy in half of the patients. (Circulation. 2009; 120[suppl 1]: S276-S281.)

Background-We investigated the association between trainees performing supervised operations and late outcomes of patients undergoing cardiac surgery. Methods and Results-Data were prospectively collected on patients who underwent coronary artery bypass graft surgery, aortic valve replacement, or a combination of these between 1998 and 2005 at the Maritime Heart Center, Halifax, Canada. In-hospital mortality and a composite outcome of in-hospital mortality, stroke, bleeding, intra-aortic balloon pump insertion, renal failure, and sternal infection was compared between teaching (n=1054) and nonteaching cases (n=5877). Late survival and cardiovascular hospital readmissions were also examined. To adjust for baseline risk disparities, we used logistic regression for dichotomous in-hospital outcomes and Cox proportional hazards regression for survival data. Resident cases were significantly more likely to have high-risk features such as depressed ventricular function, redo operation, and urgent or emergent procedure. Resident as primary operator was not independently associated with in-hospital mortality (OR, 1.09; 95% CI, 0.75 to 1.58; P=0.66) or with the composite outcome (OR, 1.01; 95%, CI 0.82 to 1.26; P=0.90). The Kaplan-Meier event-free survival of the 2 groups was equivalent at 1, 3, and 5 years (log-rank P=0.06). By Cox regression, resident cases were not associated with late death or cardiovascular rehospitalization (hazard ratio, 1.05; 95% CI, 0.94 to 1.17; P=0.42). Conclusions-Cases performed by senior-level cardiac surgery residents were more likely to have greater acuity and complexity than staff surgeon-performed cases. However, clinical outcomes were similar in the short- and long-term. Allowing residents to perform cardiac surgery is not associated with adverse patient outcomes.