Chiara De Biase

β2-Adrenergic Receptor Stimulation Improves Endothelial Progenitor Cell–Mediated Ischemic Neoangiogenesis

Rationale: Endothelial progenitor cells (EPCs) are present in the systemic circulation and home to sites of ischemic injury where they promote neoangiogenesis. &bgr;2-Adrenergic receptor (&bgr;2AR) plays a critical role in vascular tone regulation and neoangiogenesis. Objective: We aimed to evaluate the role of &bgr;2AR on EPCs’ function. Methods and Results: We firstly performed in vitro analysis showing the expression of &bgr;2AR on EPCs. Stimulation of wild-type EPCs with &bgr;-agonist isoproterenol induced a significant increase of Flk-1 expression on EPCs as assessed by fluorescence-activated cell sorter. Moreover, &bgr;2AR stimulation induced a significant increase of cell proliferation, improved the EPCs migratory activity, and enhanced the EPCs’ ability to promote endothelial cell network formation in vitro. Then, we performed in vivo studies in animals model of hindlimb ischemia. Consistent with our in vitro results, in vivo EPCs’ treatment resulted in an improvement of impaired angiogenic phenotype in &bgr;2AR KO mice after induction of ischemia, whereas no significant amelioration was observed when &bgr;2AR knock out (KO) EPCs were injected. Indeed, wild-type–derived EPCs’ injection resulted in a significantly higher blood flow restoration in ischemic hindlimb and higher capillaries density at histological analysis as compared with not treated or &bgr;2AR KO EPC-treated mice. Conclusions: The present study provides the first evidence that EPCs express a functional &bgr;2AR. Moreover, &bgr;2AR stimulation results in EPCs proliferation, migration, and differentiation, enhancing their angiogenic ability, both in vitro and in vivo, leading to an improved response to ischemic injury in animal models of hindlimb ischemia.

Effects of physical activity on endothelial progenitor cells (EPCs)

Physical activity has a therapeutic role in cardiovascular disease (CVD), through its beneficial effects on endothelial function and cardiovascular system. Circulating endothelial progenitor cells (EPCs) are bone marrow (BM) derived cells that represent a novel therapeutic target in CVD patients, because of their ability to home to sites of ischemic injury and repair the damaged vessels. Several studies show that physical activity results in a significant increase in circulating EPCs, and, in particular, there are some evidence of the beneficial exercise-induced effects on EPCs activity in CVD settings, including coronary artery disease (CAD), heart failure (HF), and peripheral artery disease (PAD). The aim of this paper is to review the current evidence about the beneficial effects of physical exercise on endothelial function and EPCs levels and activity in both healthy subjects and patients with CVD.

T2238C Atrial Natriuretic Peptide Gene Variant and the Response to Antiplatelet Therapy in Stable Ischemic Heart Disease Patients

The T2238C variant of the ANP gene is associated with higher risk of major cardiovascular events. The purpose of this study is to investigate if this polymorphism influences the response to antiplatelet agents and it is responsible of increased platelet reactivity, thus contributing to the adverse outcome. In patients undergoing elective percutaneous coronary intervention (PCI), loaded with antiplatelets, blood samples were withdrawn for genotyping, platelet reactivity assessment and for troponin T measurement to investigate the association between the polymorphism with residual platelet reactivity and with the incidence of PPMI. No significant differences in platelet reactivity nor in PPMI incidence were observed between groups. Nevertheless, higher ARU, PRU, and % PI were detected in diabetic patients, with PRU significantly higher in carriers versus non-carriers. We observed increased residual platelet reactivity exclusively in diabetic carriers of the T2238C variant undergoing elective PCI, suggesting the need of a more effective platelet inhibition in this category of patients.

Genetically Determined Platelet Reactivity and Related Clinical Implications

AbstractMany drugs are nowadays available to inhibit platelet activation and aggregation, especially in patients with acute coronary syndromes and undergoing percutaneous coronary intervention with stent implantation. Primary targets are represented by enzymes or receptors involved in platelet activation. Genetic mutations in these targets contribute to the inter-individual variability in platelet responses therefore weakening the efficacy of antiplatelet agents. High on treatment platelet reactivity is a condition characterized by low levels of platelet inhibition despite the use of antiplatelet drugs. This could be responsible for re-infarction, stent-thrombosis and strokes, affecting short and long-term prognosis after coronary revascularization. So far, to test antiplatelet resistance either the assessment of platelet function or the identification of genetic carriers of poly morphisms have been pursued. Although several methods are now available to test platelet reactivity, it is still debated whether its routine assessment gives real benefits in clinical practice. The present review aims at examining current evidences on genetic polymorphisms affecting optimal platelet inhibition.

Aortic valve anatomy and outcomes after transcatheter aortic valve implantation in bicuspid aortic valves

This original clinical research study id focused on description of baseline anatomy and outcomes after transcatheter aortic valve implantation (TAVI) in patients presenting with severe aortic stenosis (AS) and bicuspid aortic valve (BAV). We compared this BAV population with a population of patients with AS and tricuspid aortic valves after a propensity score matching developed by a multivariate logistic regression according to a non-parsimonious approach. Baseline anatomical characteristics were obtained by transthoracic echocardiography (TTE) and multi-sliced computed tomography (MSCT) and compared by chi-square and t-student tests. Outcomes were evaluated by correct fisher test at in hospital and 30 days follow-up. We found that BAV patients presents more complicated baseline anatomy as compared to patients with tricuspid valves. These anatomical features lead to higher procedural complications as the need for a second device implantation. However this does not translate into increase in mortality rate at 30 days follow-up but rather correlate to a lower device success rate.

Platelet reactivity in patients carrying the e-NOS G894T polymorphism after a loading dose of aspirin plus clopidogrel

Please cite this article as: Teresa Strisciuglio, Giuseppe Di Gioia, Fabio Mangiacapra, Chiara De Biase, Leen Delrue, Mariano Pellicano, Jozef Bartunek, Marc Vanderheyden, Raffaele Izzo, Bruno Trimarco, William Wijns, Emanuele Barbato , Platelet reactivity in patients carrying the e-NOS G894T polymorphism after a loading dose of aspirin plus clopidogrel. The address for the corresponding author was captured as affiliation for all authors. Please check if appropriate. Tr(2017), doi: 10.1016/j.thromres.2017.01.011

Optimizing Transcatheter Aortic Valve Implantation Could Make It Even More Cost-Effective!

This year (2017) we have celebrated the 15th anniversary of transcatheter aortic valve implantation (TAVI); more than 200,000 procedures have been performed worldwide with a dramatic increase inmore recent years. An overwhelming and enthusiastic literature has established TAVI as a real breakthrough. In parallel to continuous technology refinements, we observed a decrease of the risk-profile of patients undergoing TAVI in our institutions. Several steps led to the wide acceptance of TAVI. One of the hurdles to overcome was mortality. Initially quite high and related to the patients’ comorbidities, a regular improvement in 30-day and 1-year survival has been observed, correlated to better transcatheter heart valves (THV) and increased operators’ experience. Apart from the Nordic Aortic stenosis (NOTION) trial, ongoing randomized studies will try to demonstrate the noninferiority of TAVI in comparison to surgical aortic valve replacement (SAVR) for all-comers low risk patients. The economic context in western countries precludes any larger adoption of TAVI, partly because of concerns about its cost-effectiveness. In this issue of Structural Heart, Geisler and colleagues present an interesting Dutch perspective of TAVI cost-effectiveness, based on the CoreValve High risk pivotal trial. Cost-effectiveness has been the focus of few studies, among which a 2012 sub-analysis of the PARTNER IA trial, comparing TAVI with a balloon-expandable valve and SAVR in high-risk patients. In this trial, after stratification of the results by access route, transfemoral TAVI was associated to slightly lower 12-month costs and slightly increased quality-adjusted life years (QALY). At an incremental cost-effectiveness ratio <

Correlation between Angiographic and Physiologic Evaluation of Coronary Artery Narrowings in Patients With Aortic Valve Stenosis

50,000/QALY, transfemoral TAVI was economically attractive in 70.9% of bootstrap replicates, in comparison to only 7.1% of replicates in the transapical cohort. From a United Kingdom perspective, a cost-utility analysis based on the National Institute of Clinical Excellence (NICE) reference case design for technology and TAVI/SAVR effectiveness from the PARTNER IA trial confirmed these findings in 2013. The cost-effectiveness acceptability curve indicated that at a NICE £20,000 willingness to pay threshold per QALY gained, TAVI had a 64.6% likelihood of being cost-effective, compared with 35.4% for SAVR. Most of the analyses were derived from a trial evaluating a balloon-expandable platform. As there are technical and outcome differences between balloon-expandable and selfexpanding devices, dedicated economic study focusing on the latter type of THV are lacking. The work of Geisler and colleagues is the first analysis with a self-expanding device in a European country. The authors confirmed the costeffectiveness of a transcatheter approach: TAVI was projected to add 0.41 (3.69 vs. 3.27) QALY at an increased cost of €9,048, resulting in an incremental cost-effectiveness ratio of €21,946 per QALY gained. The probability of TAVI being cost-effective was 71%. Further cost reduction of approximately €5,400 would be associated to a “lean” scenario and make TAVI the predominant option. One of the main findings from this study is that optimizing TAVI could make it even more cost-effective as compared to SAVR. This simplification results from optimizing the number of operators and nursing staff, decreasing procedural time to reducing hospital stay with early discharge for selected patients. Indeed, in the UK NICE analysis, despite greater procedural costs and THV prices, TAVI was cost-effective compared with SAVR over a 10-year model horizon. The reasons were greater postsurgical costs and hospital stay. This meticulous and coherent analysis from Geisler et al. integrated rehospitalization in their economic model. Indeed, about 17% of TAVI patients are re-admitted within 30 days in the ACC STS/TVT registry. In conclusion, it is now obvious to any heart team across the globe that TAVI is superior to medical therapy in inoperable patients, at least equal to SAVR in high-risk patients and comparable to SAVR at 2 years in intermediate-risk ones, TAVI cost-effectiveness should not be questioned anymore. Simplification and optimization of the TAVI pathway are key for future enhancement of its costeffectiveness. We can be confident and anticipate continuous improvements in THV costs, clinical outcomes and hospital stay. However, before making TAVI the dominant therapy, durability needs to be assessed thoroughly.