Neurotrophins are expressed in giant cell arteritis lesions and may contribute to vascular remodeling

International audienceIntroduction: Giant cell arteritis (GCA) is characterized by intimal hyperplasia leading to ischaemic manifestations that involve large vessels. Neurotrophins (NTs) and their receptors (NTRs) are protein factors for growth, differentiation and survival of neurons. They are also involved in the migration of vascular smooth muscle cells (VSMCs). Our aim was to investigate whether NTs and NTRs are involved in vascular remodelling of GCA.Methods: We included consecutive patients who underwent a temporal artery biopsy for suspected GCA. We developed an enzymatic digestion method to obtain VSMCs from smooth muscle cells in GCA patients and controls. Neurotrophin protein and gene expression and functional assays were studied from these VSMCs. Neurotrophin expression was also analysed by immunohistochemistry in GCA patients and controls.Results: Whereas temporal arteries of both GCA patients (n = 22) and controls (n = 21) expressed nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), tropomyosin receptor kinase B (TrkB) and sortilin, immunostaining was more intense in GCA patients, especially in the media and intima, while neurotrophin-3 (NT-3) and P75 receptor (P75NTR) were only detected in TA from GCA patients. Expression of TrkB, a BDNF receptor, was higher in GCA patients with ischaemic complications. Serum NGF was significantly higher in GCA patients (n = 28) vs. controls (n = 48), whereas no significant difference was found for BDNF and NT-3. NGF and BDNF enhanced GCA-derived temporal artery VSMC proliferation and BDNF facilitated migration of temporal artery VSMCs in patients with GCA compared to controls.Conclusions: Our results suggest that NTs and NTRs are involved in vascular remodelling of GCA. In GCA-derived temporal artery VSMC, NGF promoted proliferation and BDNF enhanced migration by binding to TrkB and p75NTR receptors. Further experiments are needed on a larger number of VSMC samples to confirm these results

Transcatheter Aortic Valve Replacement Using Transaortic Access

OBJECTIVES The Registry of the Utilization of the TAo-TAVR approach using the Edwards SAPIEN Valve (ROUTE) was established to assess the effectiveness and safety of the use of transaortic (TAo) access for transcatheter aortic valve replacement (TAVR) procedures (NCT01991431). BACKGROUND TAVR represents an alternative to surgical valve replacement in high-risk patients. Whereas the transfemoral access route is used commonly as the first-line approach, transapical access is an option for patients not suitable for transfemoral treatment mainly due to anatomic conditions. TAo-TAVR has been shown to be a viable alternative surgical access route; however, only limited data on its effectiveness and safety has been published. METHODS ROUTE is a multicenter, international, prospective, observational registry; data were collected from 18 centers across Europe starting in February 2013. Patients having severe calcific aortic stenosis were documented if they were scheduled to undergo TAo-TAVR using an Edwards SAPIEN XT or a SAPIEN 3 valve. The primary endpoint was 30-day mortality. Secondary endpoints were intraprocedural or in hospital and 30-day complication rates. RESULTS A total of 301 patients with a mean age of 81.7 +/- 5.9 years and an Society of Thoracic Surgeons score of 9.0 +/- 7.6% were included. Valve success was documented in 96.7%. The 30-day mortality was 6.1% (18/293) (procedure-related mortality: 3.1%; 9 of 293). The Valve Academic Research Consortium-2 defined complications included myocardial infarction (1.0%), stroke (1.0%), transient ischemic attack (0.3%), major vascular complications (3.4%), life-threatening bleeding (3.4%), and acute kidney injury (9.5%). In 3.3% of patients, paravalvular regurgitation was classified as moderate or severe (10 of 300). Twenty-six patients (8.8%) required permanent pacemaker implantation. CONCLUSIONS TAo access for TAVR seems to be a safe alternative to the transapical procedure. (C) 2016 by the American College of Cardiology Foundation.Peer reviewe

Balloon-expandable transaortic transcatheter aortic valve implantation with or without predilation

Objective: It has been reported that balloon aortic valvuloplasty immediately before transfemoral or transapical transcatheter aortic valve implantation has mostly little to no clinical value. We aimed to provide data on the need for balloon aortic valvuloplasty in patients undergoing transaortic transcatheter aortic valve implantation. Methods: Patients undergoing transaortic transcatheter aortic valve implantation with the Edwards SAPIEN XT (Nyon, Switzerland) or 3 transcatheter heart valve were prospectively included at 18 sites across Europe. In the present analysis, we compare the periprocedural and 30-day outcomes of patients undergoing conventional (thorn balloon aortic valvuloplasty) versus direct (-balloon aortic valvuloplasty) transaortic transcatheter aortic valve implantation. Results: Of the 300 patients enrolled, 222 underwent conventional and 78 underwent direct transaortic transcatheter aortic valve implantation. Peak and mean transvalvular gradients were improved in both groups with no significant difference between groups. Procedural duration, contrast agent volume, and requirement for postdilation were also comparable. A trend toward fewer periprocedural complications was evident in the direct group (3.9% vs 11.3%; P = .053), with significantly lower rates of permanent pacemaker implantation (0% vs 5.0%; P = .034). Balloon aortic valvuloplasty omission had no significant effect on any of the 30-day safety and efficacy outcomes, including Valve Academic Research Consortium-2 composite end points (early safety events: 22.7% vs 17.4%, odds ratio, 1.17, 95% confidence interval, 0.53-2.62; clinical efficacy events: 20.5% vs 18.7%, odds ratio, 1.14, 95% confidence interval, 0.51-2.55). Conclusions: For many patients, balloon aortic valvuloplasty predilation seems to have little clinical value in transaortic transcatheter aortic valve implantation using a balloon expandable transcatheter valve and may result in a higher rate of periprocedural complications, particularly in terms of permanent pacemaker implantation.Peer reviewe

Transaortic transcatheter aortic valve implantation as a first-line choice or as a last resort? An analysis based on the ROUTE registry

OBJECTIVES: Transaortic transcatheter aortic valve implantation (TAo-TAVI) is a recently developed alternative to transapical (TA) or transfemoral (TF) TAVI. We aimed to analyse the effectiveness and safety of TAo-TAVI as a first line approach and to compare it to patients receiving TAo-TAVI as a last resort, which is current practice. METHODS: ROUTE is a prospective, multicentre registry to assess the clinical outcomes of TAo-TAVI. Patients without contraindications for TA-and TF-TAVI (TAo-first) were compared to patients with contraindications for both of these access routes (TAo-last). Outcome analysis was based on VARC II defined clinical end-points. RESULTS: Three hundred and one patients were included, of which 224 patients met TAo-first and 77 TAo-last criteria. The valve was delivered and catheter retrieved successfully in all patients. In the TAo-first group, rates of conversion to open surgery and requirement for a second valve were low and not different compared to TAo-last patients (1% vs. 3%, P = 0.46 and 1% vs. 3%, P = 0.46, respectively). This was also true for the rate of paravalvular regurgitation (>= moderate: 4% vs. 3%). All-cause mortality at 30-days was 6% vs. 5% (P = 0.76), rates of stroke 2% vs. 0% (P = 0.24), pacemaker implantation (11% vs. 4%, P = 0.093), and life-threatening bleeding 4% vs. 3% (P = 0.70). Valve safety (both 85%, P = 0.98) and clinical efficacy (80% vs. 82%; P = 0.73) did not differ between groups. CONCLUSIONS: Although comparative data to TA and TF procedures were not available in the present analysis, findings suggest that TAo may be considered not only as a last resort strategy when classical access routes are deemed unfeasible, but also as a potential first-line option, with only low rates of paravalvular regurgitation and permanent pacemaker implantation.Peer reviewe

Trends in SAVR with biological vs. mechanical valves in middle-aged patients: results from a French large multi-centric survey

Background/introductionCurrently, despite continued issues with durability ( 1), biological prosthetic valves are increasingly chosen over mechanical valves for surgical aortic valve replacement (SAVR) in adult patients of all ages, at least in Western countries. For younger patients, this choice means assuming the risks associated with a redo SAVR or valve-in-valve procedure.PurposeTo assess the use of mechanical vs. biological valve prostheses for SAVR relative to patient's age and implant time in a large population extracted from the French National Database EPICARD.MethodsPatients in EPICARD undergoing SAVR from 2007 to 2022 were included from 22 participating public or private centers chosen to represent a balanced representation of centre sizes and geographical discrepancies. Patients with associated pathology of the aorta (aneurysm or dissection) and requiring a vascular aortic prosthesis were excluded. Comparisons were made amongst centers, valve choice, implant date range, and patient age.ResultsWe considered 101,070 valvular heart disease patients and included 72,375 SAVR (mean age 71.4 ± 12.2 years). We observed a mechanical vs. biological prosthesis ratio (MBPR) of 0.14 for the overall population. Before 50 years old (y-o), MBPR was >1.3 (p < 0.001) while patients above 60 years-old received principally biological SAVR (p < 0.0001). Concerning patients between 50 and 60 years-old patients, MPVR was 1.04 (p = 0.03). Patients 50–60 years-old from the first and second study duration quartile (before August 2015) received preferentially mechanical SAVR (p < 0.001). We observed a shift towards more biological SAVR (p < 0.001) for patients from the third and fourth quartile to reach a MBPR at 0.43 during the last years of the series. Incidentally, simultaneous mitral valve replacement were more common in case of mechanical SAVR (p < 0.0001), while associated CABGs were more frequent in case of biological SAVR (p < 0.0001).ConclusionIn a large contemporary French patient population, real world practice showed a recent shift towards a lower age-threshold for biological SAVR as compared to what would suggest contemporary guidelines

Etude des facteurs influençant la mortalité hospitalière et la survie globale après chirurgie reconstructive de la valvule mitrale pour insuffisance mitrale d'origine dégénérative

AIM OF THE STUDY : We studied the risk factors of operative mortality and the long-term outcome of mitral valve repair for degenerative mitral regurgitation (MR). METHODS : Between 1989 and 2009, 311 patients underwent mitral valve repair for severe degenerative MR by the same surgeon in two centers in Europe. Follow up was complete for 300 patients over a period of 10 years. We studied 7 preoperative parameters : NYHA class, age, left ventricular systolic diameter, ejection fraction, systolic pulmonary arrery pressure (PAP), atrial fibrillation, additive and logistic EuroSCORE. Long-term outcomewas measured by last NYHA class and left ventricular diameters at follow up. RESULTS : The overall repair rate was 97,7 %. Hospital mortality was 2,2 %. Additive and logistic EuroSCORE were good predictors of hospital mortality (p = 0,033 et p = 0,046) and a logistic EuroSCORE > 3 of poor long term outcome (p = 0,027). In multivariate analysis independent predictive risk factors of poor long term outcome were : age over 65 (RR - 2,9, 95 % confidence interval 1,26 - 6,78) and 60 mmHg (RR - 2,8 95 % confidence interval 1,14 - 7,04). Hospital mortality (0 vs 3,3 %) and survival over a period of 10 years (97,7 % vs 89,2 %) between patients in class NYHA I and class NYHA IV were not significant. During follow up NYHA classes III and IV improved (p = 0,018) with significant reduction of LV diameters (p = 0,014 and p = 0,0001 recpectively). Twelve patients had reoperations for recurrent MR (3,8 %). CONCLUSIONS : Surgery for degenerative MR has a very low mortality rate and a repair rate over 97 %. Age at operation and pulmonary hypertension play a major role in long-term survival. The immediate and long-term results are in favor of early surgery for patients with severe degenerative MR.OBJECTIF : Etude des facteurs influençant la mortalité hospitalière et la survie globale après chirurgie reconstructrice de la valve mitrale pour insuffisance mitrale (IM) d'origine dégénérative. METHODES : Entre 1989 et 2009, 311 reconstructions mitrales ont été réalisées par le même chirurgien dans deux centres en Europe chez des patients présentant une IM sévère d'origine dégénérative. Le suivi a été complet pour 300 patients sur une durée de dix ans. Nous avons étudié sept facteurs préopératoires ; la classe NYHA, l'âge, le diamètre télésystolique du ventricule gauche, la fraction d'éjection, la pression artérielle pulmonaire systolique (PAPS), la présence de fibrillation auriculaire, les EuroSCORE additif et logistique. RESULTATS : Le taux de réparation a été de 97,7 %. La mortalité hospitalière a été de 2,2 %. Les EuroSCORE additif et logistique étaient de bons indicateurs du risque opératoire (p = 0,033 et p = 0,046) et un EuroSCORE logistique > 3 d'une moins bonne survie à long terme (p = 0,027). En analyse multivariée, les facteurs prédictifs indépendants d'une moins bonne survie ont été : un âge supérieur à 65 ans (RR = 2,9 : intervalle de confiance à 95 % 1,26 - 6,78) et une PAPS supérieure à 60 mmHg (RR = 2,8 : intervalle de confiance à 95 % 1,14 - 7,04). La différence de mortalité hospitalière (0vs 3,3 %) et de survie à 10 ans (97,7 % vs 09,2 %) entre les patients en classe NYHA IV n'atteignait pas la significativité. Lors du suivi l'amélioration fonctionnelle des patients en classe NYHA III et IV était significative (p = 0,018), et s'associe à une diminution des diamètres télésystolique (p = 0,014) et télédiastolique (p = 0,0001). Douze patients ont été réopérés pour récidive d'IM (3,8 %). CONCLUSIONS : La chirurgie de l'IM d'origine dégénérative est réalisable au prix d'une morbi-mortalité très faible avec un taux de réparation valvulaire > 97 %. L'âge et la présence d'une hypertension artérielle pulmonaire ont un rôle significatif dans la survie à long terme. Les résultats immédiat et à distance sont en faveur d'une chirurgie précoce pour les patients présentant une IM sévère d'origine dégénérative.BORDEAUX2-BU Santé (330632101) / SudocSudocFranceF

Suivi à long terme des dissections aortiques aiguës de type A opérées en clampage simple ou en anastamose ouverte (étude rétrospective portant sur 288 patients)

OBJECTIF : Définir le devenir à long terme des patients opérés de dissection aortique de type A en clampage simple versus en anastomose ouverte. MATERIEL ET METHODES : 288 patients ont été opérés dans notre service de Dissection Aortique de type A entre le 1er Janvier 1995 et le 31 Décembre 2005 : 123 par clampage simple et 165 par anastomose ouverte. Nous avons comparé le devenir à long terme de ces patients en terme de survie, réinterventions et apparition d'anévrysme d'indication chirurgicale au Scanner.RESULTATS : La réalisation d'une anastomose ouverte est liée à une diminution significative de la morbi-mortalité à court terme ainsi qu'à une meilleure survie à 5 ans et une diminution du taux de réinterventions à long terme. CONCLUSION : La réalisation d'une anastomose ouverte est conseillée dans la chirurgie de dissection aortique aigë de type A.BORDEAUX2-BU Santé (330632101) / SudocSudocFranceF

Perioperative management of a patient undergoing a novel mini-invasive percutaneous transcatheter left ventricular reconstruction procedure

International audienceSurvivors of myocardial infarction might have residual damage and higher risks of developing heart failure. This increasing complication encompasses up to 45% of all infarcts. As anesthesiologists we will have to perform anesthesia more frequently in patients with such challenging medical history schedule to undergo mini-invasive surgical procedures. We present the case of a 51-year-old man with severe heart failure post-myocardial infarction with multiple sclerosis undergoing a novel percutaneous transcatheter ventricular reconstruction via a left mini-thoracotomy. To guide the surgeon during the intervention we used a real-time 3D echocardiography, enlightening the fact that guidance is crucial for that kind of procedure. To lower postoperative pain and the inflammatory response we have administered successfully intravenous lidocaine, indicating that it is possible to avoid regional anesthesia in patients with multiple sclerosis scheduled for mini-invasive left ventricular reconstruction requiring a mini-thoracotomy

Preoperative hepatic insufficiency and type III endoleak: a confirmed potential fatal association following endovascular treatment.

International audienceConsumptive coagulopathy is known to occur in patients with aneurysm, especially in the thoracic localization. Compared to open chest surgery, the endovascular treatment leaves in place a large thrombosed aneurysmal sac, which might induce and/or exacerbate the coagulopathy. Although exceptional, some recent reports have raised the potential disastrous issue related to this complication. We report the case of a 74-year-old patient treated for an asymptomatic thoracic aorta aneurysm by endoprosthesis who developed a fatal disseminated intravascular coagulopathy. This complication has been related to a type III endoleak associated with a preoperative hepatic insufficiency