Nucleotide metabolic mismatches in mammalian hearts: implications for transplantation

INTRODUCTION: Human donor organ shortages have led surgeons and scientists to explore the use of animals as alternative organ sources. Acute thrombovascular rejection (AVR) is the main hurdle in xenotransplantation. Disparities in nucleotide metabolism in the vessels of different species may contribute significantly to the microvascular component of AVR. METHODS: We evaluated the extent of nucleotide metabolism mismatch in selected organs and endothelial cells of different mammals with particular focus on the changes in activity of ecto-5’-nucleotidase (E5’N) elicited by exposure of porcine hearts or endothelial cells to human blood (ex vivo) or human plasma (in vitro). RESULTS: E5’N activity in the rat heart was significantly higher than in other species. We noted a significant difference (p<0.001) in E5’N activity between human and pig endothelial cell lines. Initial pig aortic endothelial E5’N activity decreased in vitro after a three-hour exposure to human and porcine plasma while remaining constant in controls. Ex vivo perfusion with fresh human blood for four hours resulted in a significant decrease of E5’N activity in both wild type and transgenic pig hearts overexpressing human decay accelerating factor (p<0.001). CONCLUSIONS: This study provides evidence that mismatches in basal mammalian metabolic pathways and humoral immunity interact in a xenogeneic environment. Understanding the role of nucleotide metabolism and signalling in xenotransplantation may identify new targets for genetic modifications and may lead to the development of new therapies extending graft survival

Update on hypertrophic cardiomyopathy and a guide to the guidelines

Hypertrophic cardiomyopathy (HCM) is the most common inherited cardiovascular disorder, affecting 1 in 500 individuals worldwide. Existing epidemiological studies might have underestimated the prevalence of HCM, however, owing to limited inclusion of individuals with early, incomplete phenotypic expression. Clinical manifestations of HCM include diastolic dysfunction, left ventricular outflow tract obstruction, ischaemia, atrial fibrillation, abnormal vascular responses and, in 5% of patients, progression to a 'burnt-out' phase characterized by systolic impairment. Disease-related mortality is most often attributable to sudden cardiac death, heart failure, and embolic stroke. The majority of individuals with HCM, however, have normal or near-normal life expectancy, owing in part to contemporary management strategies including family screening, risk stratification, thromboembolic prophylaxis, and implantation of cardioverter-defibrillators. The clinical guidelines for HCM issued by the ACC Foundation/AHA and the ESC facilitate evaluation and management of the disease. In this Review, we aim to assist clinicians in navigating the guidelines by highlighting important updates, current gaps in knowledge, differences in the recommendations, and challenges in implementing them, including aids and pitfalls in clinical and pathological evaluation. We also discuss the advances in genetics, imaging, and molecular research that will underpin future developments in diagnosis and therapy for HCM

Single-center experience using the Freedom SOLO aortic bioprosthesis

Objective: This study reviews a single institution experience with the Freedom SOLO (Sorin Group, Saluggia, Italy) aortic bioprosthesis. Methods: Between October 2006 and February 2010, 128 patients (64 men, 64 women; mean age, 75.8 ± 5.1 years) underwent aortic valve replacement using the Freedom SOLO stentless aortic valve. The follow-up time was 36.7 ± 1.2 months and 100% complete. Results: Concomitant procedures were performed in 77 patients (60%). The mean standard European System for Cardiac Operative Risk Evaluation was 9 ± 2.7. Grade 3 aortic stenosis was present in 73% of patients, mixed aortic stenosis and regurgitation were present in 40% of patients, and mitral regurgitation was present in 46% of patients. The mean crossclamp time was 53 ± 12 minutes for isolated Freedom SOLO aortic valve implantation and 80 ± 28 minutes for concomitant procedures, and the mean cardiopulmonary bypass time was 103 ± 31 minutes. The mean implanted valve size was 22.6 ± 1.4 mm. The mean intensive care unit and hospital stays were 2.4 ± 1.1 days and 8.8 ± 2.6 days, respectively. Three patients underwent reoperation for bleeding. The 15-day, 30-day, and perioperative mortality were all 4.6%. The 36-month survival was 95.4% ± 1.6% for the cohort with a low European System for Cardiac Operative Risk Evaluation (&lt;9) and 88.6% ± 1.7% for the cohort with a high European System for Cardiac Operative Risk Evaluation (&gt;9). Echocardiographic data preoperatively, immediately postoperatively, and at 3, 6, and 12 months postoperatively showed peak transvalvular gradients of 75 ± 23, 17 ± 6, 18 ± 6.5, 16 ± 6, and 16 ± 9 mm Hg, respectively (P &lt;.001), and a mean left ventricular end-diastolic diameter of 51 ± 7, 50 ± 6, 48 ± 8, 47 ± 6, and 46.5 ± 7.5 mm, respectively (P &lt;.05). There were only 3 cases of early mild aortic regurgitation (grade 1), which remained stable at 12 months. Conclusions: The Freedom SOLO stentless aortic valve has excellent early and intermediate-term results. © 2013 by The American Association for Thoracic Surgery

Porcine or human stentless valves for aortic valve replacement? Results of a 10-year comparative study.

BACKGROUND AND AIM OF THE STUDY: Stentless porcine valves in the aortic position exhibit similar excellent hemodynamic performance to homografts, but have the advantage of availability. Their performance was compared over a 10-year period in a single-surgeon and single-institution series. METHODS: Demographic, operative and mortality data were obtained retrospectively. Survivors were interviewed by telephone according to a defined protocol. Definitions and analyses were in accordance with joint STS/AATS guidelines. RESULTS: A total of 408 stentless porcine and homograft aortic valve replacements (AVR) was performed between 1991 and 2001. Five patients were excluded due to incomplete data, in addition to 82 patients who underwent AVR with a free-standing root replacement technique. Hence, 321 patients (217 males, 104 females; mean age 67 +/- 12 years) had a subcoronary implant. The median time to follow up was 4.9 years (range: 2.9-6.6 years). No differences were noted between homograft and stentless porcine valves in one- and five-year freedom from structural valve deterioration (99.1 versus 97.2% and 95.7 versus 93.1%; p = 0.10), reoperation (99.2 versus 99.4% and 97.8 versus 96.7%; p = 0.45) and endocarditis (98.3 versus 99.4% and 97.4 versus 99.4%; p = 0.14). Overall one- and five-year survival comparing homograft to stentless porcine valve was 90.4 versus 92.3% and 80.8 versus 73.7%, respectively; p = 0.23. Independent predictors of mortality on multivariate analysis were: ventricular function (p &lt; 0.0001), increasing age (p &lt; 0.001), increasing serum creatinine (p &lt; 0.001) and concomitant coronary surgery (p = 0.05). Treated hypercholesterolemia was independently protective against mortality, with an odds ratio of 0.26 (CI 0.10 to 0.66; p = 0.005). CONCLUSION: The porcine stentless valve, when implanted in the subcoronary position, is an excellent alternative to the homograft and shows excellent clinical performance and durability at mid term