Preclinical Testing of Living Tissue-Engineered Heart Valves for Pediatric Patients, Challenges and Opportunities.

Introduction: Pediatric patients with cardiac congenital diseases require heart valve implants that can grow with their natural somatic increase in size. Current artificial valves perform poorly in children and cannot grow; thus, living-tissue-engineered valves capable of sustaining matrix homeostasis could overcome the current drawbacks of artificial prostheses and minimize the need for repeat surgeries. Materials and Methods: To prepare living-tissue-engineered valves, we produced completely acellular ovine pulmonary valves by perfusion. We then collected autologous adipose tissue, isolated stem cells, and differentiated them into fibroblasts and separately into endothelial cells. We seeded the fibroblasts in the cusp interstitium and onto the root adventitia and the endothelial cells inside the lumen, conditioned the living valves in dedicated pulmonary heart valve bioreactors, and pursued orthotopic implantation of autologous cell-seeded valves with 6 months follow-up. Unseeded valves served as controls. Results: Perfusion decellularization yielded acellular pulmonary valves that were stable, no degradable in vivo, cell friendly and biocompatible, had excellent hemodynamics, were not immunogenic or inflammatory, non thrombogenic, did not calcify in juvenile sheep, and served as substrates for cell repopulation. Autologous adipose-derived stem cells were easy to isolate and differentiate into fibroblasts and endothelial-like cells. Cell-seeded valves exhibited preserved viability after progressive bioreactor conditioning and functioned well in vivo for 6 months. At explantation, the implants and anastomoses were intact, and the valve root was well integrated into host tissues; valve leaflets were unchanged in size, non fibrotic, supple, and functional. Numerous cells positive for a-smooth muscle cell actin were found mostly in the sinus, base, and the fibrosa of the leaflets, and most surfaces were covered by endothelial cells, indicating a strong potential for repopulation of the scaffold. Conclusions: Tissue-engineered living valves can be generated in vitro using the approach described here. The technology is not trivial and can provide numerous challenges and opportunities, which are discussed in detail in this paper. Overall, we concluded that cell seeding did not negatively affect tissue-engineered heart valve (TEHV) performance as they exhibited as good hemodynamic performance as acellular valves in this model. Further understanding of cell fate after implantation and the timeline of repopulation of acellular scaffolds will help us evaluate the translational potential of this technology.

Challenges in Perioperative Animal Care for Orthotopic Implantation of Tissue-Engineered Pulmonary Valves in the Ovine Model.

BACKGROUND: Development of valvular substitutes meeting the performance criteria for surgical correction of congenital heart malformations is a major research challenge. The sheep is probably the most widely used animal model in heart valves regenerative medicine. Although the standard cardiopulmonary bypass (CPB) technique and various anesthetic and surgical protocols are reported to be feasible and safe, they are associated with significant morbidity and mortality rates. The premise of this paper is that the surgical technique itself, especially the perioperative animal care and management protocol, is essential for successful outcomes and survival. METHODS: Ten juvenile and adult female sheep aged 7.8-37.5 months and weighing 32.0-58.0 kg underwent orthotopic implantation of tissue-engineered pulmonary valve conduits on beating heart under normothermic CPB. The animals were followed-up for 6 months before scheduled euthanasia. RESULTS: Based on our observations, we established a guide for perioperative care, follow-up, and treatment containing information regarding the appropriate clinical, biological, and ultrasound examinations and recommendations for feasible and safe anesthetic, surgical, and euthanasia protocols. Specific recommendations were also included for perioperative care of juvenile versus adult sheep. CONCLUSION: The described surgical technique was feasible, with a low mortality rate and minimal surgical complications. The proposed anesthetic protocol was safe and effective, ensuring both adequate sedation and analgesia as well as rapid recovery from anesthesia without significant complications. The established guide for postoperative care, follow-up and treatment in sheep after open-heart surgery may help other research teams working in the field of heart valves tissue regeneration.

Exploring Current Evidence on the Past, the Present, and the Future of the Heart Team: A Narrative Review.

INTRODUCTION: Including healthcare professionals dealing with cardiovascular diseases, Heart Team is a concept/structure designed for selecting diagnostic strategies, facilitating therapeutic decisions, and improving cardiovascular outcomes in patients with complex heart pathologies, requiring input from different subspecialties and the necessity of a multidisciplinary approach. The aim of this narrative review is to search for and to summarize current evidence regarding Heart Team and to underline the future directions for the development of this concept. METHODS: We searched the electronic database of PubMed, SCOPUS, and Cochrane CENTRAL for studies including Heart Team. Forty-eight studies were included, if reference was made to Heart Team structure and functionality. RESULTS: We depicted the structure and the timeline of Heart Team, along with actual evidence-based recommendations from European Guidelines. We underlined the importance of quality of knowledge-sharing and decision-making inside the Team, analyzing bad decisions which did not reflect members' true beliefs due to "uniformity pressure, closed mindedness, and illusion of invulnerability." The observation that Guidelines' indications regarding Heart Team carry a level C indication underlines the very future of this Team: randomized controlled trials proving solid benefits in an evidence-based world. CONCLUSIONS: Envisioned as a tool for optimizing the management of various complex cardiovascular pathologies, Heart Team should simplify and facilitate the activity in the cardiovascular ward. Finally, these facts should be translated into better cardiovascular outcomes and a lower psychological distress among Team participants. Despite all future changes, there must always be a constant part: the patient should remain at the very center of the Team.

[Surgical ventricular reconstruction for ischemic left ventricular aneurysm. Early and medium-term outcomes for two surgical techniques]. / Az ischaemiás eredetu balkamra-aneurysma sebészi rekonstrukciója. Két sebészi technika korai és középtávú eredményei.

INTRODUCTION: Left ventricular aneurysm is a severe complication of acute myocardial infarction, which contributes significantly to mortality and morbidity associated with this pathology. Despite the progress of correction techniques, there are still controversies about the optimal approach addressing this pathology. AIM: The aim of this study was to analyse short and medium term outcomes of left ventricular reconstruction for ischemic left ventricular aneurysm using two surgical techniques (endoventricular patch plasty and liniar suture) in order to determine if one of these techniques has supperior results. METHOD: 117 patients were included in the study, 48 patients (41%) underwent left ventricular reconstruction with endoventricular patch (Group 1), 69 patients (59%; Group 2) had linear reconstruction. 113 patients (96.5%) required associated procedures: 108 surgical myocardial revascularization, 18 mitral valvuloplasty and 8 ventricular septal defect closure. Short and medium term morbidity, mortality, alteration of ejection fraction and NYHA class were analysed. RESULTS: Perioperative mortality was 11.11%, 4.2% in the endoventricular patch group, and 15.9% in the linear suture group (p = 0.03). The overall 5-year survival was 78.5% (88.7% in Group 1 and 71.2% in Group 2). The left ventricular ejection fraction and NYHA functional class improved in both groups, with greater improvement in the endoventricular patch group. CONCLUSIONS: Surgical ventricular reconstruction is a procedure performed for the correction of ischemic left ventricular aneurysm with good early and medium-term results, but with better results with the endoventricular patch technique regarding early and medium-term mortality, ejection fraction and NYHA functional class improvement. Orv Hetil. 2018; 159(51): 2167-2174.

Functional Heart Valve Scaffolds Obtained by Complete Decellularization of Porcine Aortic Roots in a Novel Differential Pressure Gradient Perfusion System.

There is a great need for living valve replacements for patients of all ages. Such constructs could be built by tissue engineering, with perspective of the unique structure and biology of the aortic root. The aortic valve root is composed of several different tissues, and careful structural and functional consideration has to be given to each segment and component. Previous work has shown that immersion techniques are inadequate for whole-root decellularization, with the aortic wall segment being particularly resistant to decellularization. The aim of this study was to develop a differential pressure gradient perfusion system capable of being rigorous enough to decellularize the aortic root wall while gentle enough to preserve the integrity of the cusps. Fresh porcine aortic roots have been subjected to various regimens of perfusion decellularization using detergents and enzymes and results compared to immersion decellularized roots. Success criteria for evaluation of each root segment (cusp, muscle, sinus, wall) for decellularization completeness, tissue integrity, and valve functionality were defined using complementary methods of cell analysis (histology with nuclear and matrix stains and DNA analysis), biomechanics (biaxial and bending tests), and physiologic heart valve bioreactor testing (with advanced image analysis of open-close cycles and geometric orifice area measurement). Fully acellular porcine roots treated with the optimized method exhibited preserved macroscopic structures and microscopic matrix components, which translated into conserved anisotropic mechanical properties, including bending and excellent valve functionality when tested in aortic flow and pressure conditions. This study highlighted the importance of (1) adapting decellularization methods to specific target tissues, (2) combining several methods of cell analysis compared to relying solely on histology, (3) developing relevant valve-specific mechanical tests, and (4) in vitro testing of valve functionality.

The diagnosis, morphological particularities, and surgical technique in a case of intravascular leiomyoma extended to the right heart chambers.

Intravenous leiomyoma is a benign smooth muscle cell tumor of uterine origin that may grow into the pelvic veins and the inferior vena cava. It usually affects premenopausal women and the majority (90%) are parous. Because cardiac involvement is present in up to 10% of cases, it may be misdiagnosed as a primary cardiac tumor or a venous thrombus-in-transit. We describe a case of intravascular leiomyomatosis with cardiac extension and the morphological particularities of the removed tumor.