Compared with the early-generation devices, TAVR using the new-generation devices was associated with improved procedural outcomes in treating patients with pure native AR. In patients with pure native AR, significant post-procedural AR was independently associated with increased mortality.

Background: Sizing for transcatheter aortic valve implantation in bicuspid aortic valves (BAV) remains controversial. Methods and Results: The aim of the BAVARD (Bicuspid Aortic Valve Anatomy and Relationship With Devices) retrospective registry is to capture the sizing ratios used for transcatheter aortic valve implantation in BAV and analyze the second-generation prostheses geometry postimplantation. About 101 patients with BAV along with available pre- and post-transcatheter aortic valve implantation multidetector computed tomography were compared with 88 tricuspid aortic valves (TAV) patients. Preprocedural multidetector computed tomography diagnosed type 0 and type 1 BAV in, respectively, 12.9% and 86.1 % of BAV. At baseline, the ellipticity index was similar between BAV and TAV patients: 1.2±0.1 versus 1.2±0.1, P =0.09. The mean annular oversizing was, respectively, 1.14±0.04 and 1.04±0.04, P <0.001, in TAV and BAV patients. The mean prosthesis intercommissural distance, ratio was 1.03±0.1. The mean diameter of the prostheses at the annulus matched the mean perimeter-derived diameter of the aortic annulus at baseline with TAV (23.3±2.2 versus 23.6±1.9, P =0.4) and was smaller with BAV (24±2.8 versus 26.8±3.1, P <0.01), confirming 11% underexpansion in BAV. Finally, in situ, prosthesis diameter and ellipticity followed the same pattern, with stable values from the distal edge to 12 mm above, in both groups. Conclusions: Second-generation prostheses similarly reshape the aortic annulus in TAV and BAV. Prostheses keep consistent diameters from distal edge to 12 mm in TAV and BAV. Prosthesis underexpansion is constantly observed in BAV. Annular-based sizing is accurate in BAV with minimal oversizing. The intercommissural distance, 4 mm above the annulus, could be integrated in gray zones. Clinical Trial Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT03495050.

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Background: Large data comparing the performance of new-generation self-expandable versus balloon-expandable transcatheter heart valves in bicuspid aortic stenosis are lacking. We aim to compare the safety and performance of balloon-expandable and self-expandable transcatheter heart valves in the treatment of bicuspid aortic stenosis. Methods: The BEAT (balloon versus self-expandable valve for the treatment of bicuspid aortic valve stenosis) registry included 353 consecutive patients who underwent transcatheter aortic valve implantation using new-generation Evolut R/PRO or Sapien 3 valves in bicuspid aortic valve. Results: A total of 353 patients (n=242 [68.6%] treated with Sapien 3 and n=111 [68.6%] treated with Evolut R (n=70)/PRO [n=41]) were included. Mean age was 77.8±8.3 years and mean Society of Thoracic Surgeons Predicted Risk of Mortality was 4.4±3.3%. Valve Academic Research Consortium-2 device success was similar between Sapien 3 and Evolut R/PRO (85.6% versus 87.2%; P =0.68). In the Sapien 3 group, 4 patients experienced annular rupture whereas this complication did not occur in the Evolut R/PRO group. After propensity score matching, Valve Academic Research Consortium-2 device success was similar between both groups (Sapien 3=85.7% versus Evolut R/Pro=84.4%; P =0.821). Both in the overall and in the matched population, no differences in the rate of permanent pacemaker implant were observed. At 1-year follow-up, the rate of overall death and cardiovascular death were similar between the 2 groups. In the unmatched population, the 1-year echocardiographic follow-up demonstrated similar rate of moderate-to-severe paravalvular aortic regurgitation (Evolut R/PRO 10.5% versus Sapien 3 4.2%, P =0.077); however, after propensity matching, the rate of moderate-to-severe paravalvular leak became significantly higher among patients treated with self-expandable valves (9.3% versus 0%; P =0.043). Conclusions: Our study confirms the feasibility of both Sapien 3 and Evolut R/PRO implantation in bicuspid aortic valve anatomy; a higher rate of moderate-severe paravalvular aortic regurgitation was observed in the Evolut R/PRO group at 1-year follow-up in the matched cohort, although patients treated with balloon-expandable valve had a higher rate of annular rupture.

Rationale: Endothelial progenitor cells (EPCs) are present in the systemic circulation and home to sites of ischemic injury where they promote neoangiogenesis. β 2 -Adrenergic receptor (β 2 AR) plays a critical role in vascular tone regulation and neoangiogenesis. Objective: We aimed to evaluate the role of β 2 AR on EPCs’ function. Methods and Results: We firstly performed in vitro analysis showing the expression of β 2 AR on EPCs. Stimulation of wild-type EPCs with β-agonist isoproterenol induced a significant increase of Flk-1 expression on EPCs as assessed by fluorescence-activated cell sorter. Moreover, β 2 AR 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 β 2 AR KO mice after induction of ischemia, whereas no significant amelioration was observed when β 2 AR 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 β 2 AR KO EPC-treated mice. Conclusions: The present study provides the first evidence that EPCs express a functional β 2 AR. Moreover, β 2 AR 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.

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.

BackgroundBreathlessness is a common and distressing symptom affecting many patients with advanced disease both from malignant and non-malignant origin. A combination of pharmacological and non-pharmacological measures is necessary to treat this symptom successfully. Breathlessness services in various compositions aim to provide comprehensive care for patients and their carers by a multiprofessional team but their effectiveness and cost-effectiveness have not yet been proven. The Breathlessness Support Service (BSS) is a newly created multiprofessional and interdisciplinary outpatient service at a large university hospital in South East London. The aim of this study is to develop and evaluate the effectiveness and cost effectiveness of this multidisciplinary out–patient BSS for the palliation of breathlessness, in advanced malignant and non-malignant disease.MethodsThe BSS was modelled based on the results of qualitative and quantitative studies, and systematic literature reviews. A randomised controlled fast track trial (RCT) comprising two groups: 1) intervention (immediate access to BSS in addition to standard care); 2) control group (standard best practice and access to BSS after a waiting time of six weeks). Patients are included if suffering from breathlessness on exertion or at rest due to advanced disease such as cancer, chronic obstructive pulmonary disease (COPD), chronic heart failure (CHF), interstitial lung disease (ILD) or motor neurone disease (MND) that is refractory to maximal optimised medical management. Both quantitative and qualitative outcomes are assessed in face to-face interviews at baseline, after 6 and 12 weeks. The primary outcome is patients' improvement of mastery of breathlessness after six weeks assessed on the Chronic Respiratory Disease Questionnaire (CRQ). Secondary outcomes for patients include breathlessness severity, symptom burden, palliative care needs, service use, and respiratory measures (spirometry). For analyses, the primary outcome, mastery of breathlessness after six weeks, will be analysed using ANCOVA. Selection of covariates will depend on baseline differences between the groups. Analyses of secondary outcomes will include patients’ symptom burden other than breathlessness, physiological measures (lung function, six minute walk distance), and caregiver burden.DiscussionBreathlessness services aim to meet the needs of patients suffering from this complex and burdensome symptom and their carers. The newly created BSS is different to other current services as it is run in close collaboration of palliative medicine and respiratory medicine to optimise medical care of patients. It also involves professionals from various medical, nursing, physiotherapy, occupational therapy and social work background.Trial registrationClinicalTrials.gov (NCT01165034)