Institute du Thorax

Nantes, France

Institute du Thorax

Nantes, France
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Derimay F.,French Institute of Health and Medical Research | Guerin P.,Institute du Thorax | Pilet P.,Institute du Thorax | Ohayon J.,CNRS Complex Medical Engineering Laboratory | And 3 more authors.
JACC: Cardiovascular Interventions | Year: 2016

Objectives The aim of this fractal bifurcation bench study was to compare provisional bifurcation stenting with a “re-POT” sequence, comprising a proximal optimizing technique (POT), side branch inflation, and final POT, between a bioresorbable vascular scaffold (BVS) and a metallic stent. Background Re-POT proved significantly better than kissing balloon inflation in maintaining circular geometry without overstretch in metal stents, while significantly reducing side branch ostium strut obstruction and global strut malapposition. This should be useful for BVSs, which are more easily breakable. Methods Twenty left main–like and 20 left anterior descending–like fractal coronary bifurcation bench models used 10 each 2.5 × 24 mm and 3.5 × 24 mm Absorb (Ab) BVSs and 10 each 2.5 × 24 mm and 3.5 × 24 mm XIENCE Xpedition (XX) metal stents, implanted by re-POT, with optical coherence tomographic analysis at each step and micro–computed tomographic analysis of Ab devices to detect strut fracture. Results With Ab devices, re-POT reduced percentage strut malapposition close to XX rates (0.8 ± 0.7% vs. 0.0 ± 0.0%, p < 0.05; 3.5 ± 1.7% vs. 0.3 ± 0.6%, p < 0.05), conserving proximal circularity (elliptical ratio, 1.04 vs. 1.03 and 1.04 vs. 1.04; p = NS). Mean post-re-POT proximal expansion was 0.6 ± 0.1 mm (+21.6 ± 2.1%) for 2.5-mm and 1.0 ± 0.1 mm (+23.6 ± 2.2%) for 3.5-mm Ab devices, with only 1 strut fracture (left anterior descending–like bench). Side branch ostium strut obstruction was greater with Ab scaffolds than XX stents: 41.1 ± 9.4% versus 16.4 ± 8.1% (p < 0.05) and 31.8 ± 3.2% versus 10.0 ± 5.3% (p < 0.05), respectively, for 2.5- and 3.5-mm scaffolds and stents. Ab scaffolds showed 2 ± 1% moderate but significant late recoil as of 1 h, reaching 4 ± 2% by 24 h (p < 0.05). Conclusions Re-POT optimized most Ab provisional bifurcation treatments, without fracture, respecting fractal geometry, and without exceeding 1.0-mm proximal differential diameter. © 2016 American College of Cardiology Foundation

Charpentier G.,Sud Francilien Hospital | Benhamou P.-Y.,University Hospital | Dardari D.,Sud Francilien Hospital | Clergeot A.,University Hospital | And 8 more authors.
Diabetes Care | Year: 2011

OBJECTIVE - To demonstrate that Diabeo software enabling individualized insulin dose adjustments combined with telemedicine support significantly improves HbA1c in poorly controlled type 1 diabetic patients. RESEARCH DESIGN AND METHODS - In a six-month open-label parallel-group, multicenter study, adult patients (n = 180) with type 1 diabetes (>1 year), on a basal-bolus insulin regimen (>6 months), with HbA1c ≥8%, were randomized to usual quarterly follow-up (G1), home use of a smartphone recommending insulin doses with quarterly visits (G2), or use of the smartphone with short teleconsultations every 2 weeks but no visit until point end (G3). RESULTS - Six-month mean HbA1c in G3 (8.41 ± 1.04%) was lower than in G1 (9.10 ± 1.16%; P = 0.0019). G2 displayed intermediate results (8.63 ± 1.07%). The Diabeo system gave a 0.91% (0.60; 1.21) improvement in HbA1c over controls and a 0.67% (0.35; 0.99) reduction when used without teleconsultation. There was no difference in the frequency of hypoglycemic episodes or in medical time spent for hospital or telephone consultations. However, patients in G1 and G2 spent nearly 5 h more than G3 patients attending hospital visits. CONCLUSIONS - The Diabeo system gives a substantial improvement to metabolic control in chronic, poorly controlled type 1 diabetic patients without requiring more medical time and at a lower overall cost for the patient than usual care. © 2011 by the American Diabetes Association.

Kirsch M.,Institute Of Cardiologie | Mazzucotelli J.-P.,Nouvel Hopital Civil | Roussel J.-C.,Institute du Thorax | Bouchot O.,Hopital du Bocage | And 4 more authors.
Journal of Heart and Lung Transplantation | Year: 2012

Background: Biventricular support can be achieved using paracorporeal biventricular assist devices (BiVADs), the total artificial heart (TAH), and implantable VADs. This study evaluated the influence of the device on patient survival. Methods: Data from 383 patients (321 men [84%]) undergoing primary, planned biventricular support using durable devices between 2000 and 2010 were extracted from the French multicentric Groupe de Réflexion sur l'Assistance Mécanique (GRAM) registry. Mean age was 41.6 ± 14.0 years. Patients were classified as group 1, 255 (67%) with paracorporeal BiVADs; group 2, 90 (24%) with TAH; and group 3, 38 (10%) with implantable BiVADs. Results: Mean patient support duration was 82.8 ± 107.4 days and similar among groups (p = 0.53). Bridging to transplantation was successful in 211 patients (55%) and to recovery in 23 (6%). Mortality on device was similar among groups (p = 0.16). TAH patients had a significantly lower stroke rate (p < 0.0001). Actuarial estimates for survival while on support were 75.2% ± 2.3%, 64.4% ± 2.7%, 61.1% ± 2.8%, and 56.8% ± 3.1% at 30, 60, 90, and 180 days, respectively, and were similar among groups. However, TAH patients undergoing prolonged support (<90 days) showed a trend toward improved survival (p = 0.08). Actuarial post-transplant survival estimates were, respectively, 81.7 ± 2.7, 75.3 ± 3.0, 73.0 ± 3.0, and 64.7 ± 3.7 at 1 month and 1, 3, and 5 years and were similar among groups (p = 0.84). Conclusion: Survival while on support and after heart transplantation did not differ significantly in patients supported with paracorporeal BiVADs, implantable BiVADs, or the TAH. Patients undergoing prolonged support (>90 days) tended to have improved survival when supported with TAH compared with BiVADs, which may be related to a lower incidence of neurologic events. © 2012 International Society for Heart and Lung Transplantation. All rights reserved.

PubMed | Societe Francaise de Cardiologie, University of Rennes 1, Institute du Thorax, University Paris - Sud and 8 more.
Type: Journal Article | Journal: European heart journal | Year: 2016

Increased left ventricular wall thickness (LVWT) is a common finding in cardiology. It is not known how often hereditary transthyretin-related familial amyloid cardiomyopathy (mTTR-FAC) is responsible for LVWT. Several therapeutic modalities for mTTR-FAC are currently in clinical trials; thus, it is important to establish the prevalence of TTR mutations (mTTR) and the clinical characteristics of the patients with mTTR-FAC.In a prospective multicentre, cross-sectional study, the TTR gene was sequenced in 298 consecutive patients diagnosed with increased LVWT in primary cardiology clinics in France. Among the included patients, median (25-75th percentiles) age was 62 [50;74]; 74% were men; 23% were of African origin; and 36% were in NYHA Class III-IV. Median LVWT was 18 (16-21) mm. Seventeen (5.7%; 95% confidence interval [CI]: [3.4;9.0]) patients had mTTR of whom 15 (5.0%; 95% CI [2.9;8.2]) had mTTR-FAC. The most frequent mutations were V142I (n = 8), V50M (n = 2), and I127V (n = 2). All mTTR-FAC patients were older than 63 years with a median age of 74 [69;79]. Of the 15 patients with mTTR-FAC, 8 were of African descent while 7 were of European descent. In the African descendants, mTTR-FAC median age was 74 [72;79] vs. 55 [46;65] years in non-mTTR-FAC (P < 0.001). In an adjusted multivariate model, African origin, neuropathy, carpal tunnel syndrome, electrocardiogram (ECG) low voltage, and late gadolinium enhancement (LGE) at cardiac-magnetic resonance imaging were all independently associated with mTTR-FAC.Five per cent of patients diagnosed with hypertrophic cardiomyopathy have mTTR-FAC. Mutated transthyretin genetic screening is warranted in elderly subjects with increased LVWT, particularly, those of African descent with neuropathy, carpal tunnel syndrome, ECG low voltage, or LGE.

Gagnadoux F.,Angers University Hospital Center | Vaillant M.L.,French National Center for Scientific Research | Goupil F.,Center Hospitalier | Pigeanne T.,Pole sante des Olonnes | And 5 more authors.
Chest | Year: 2014

Background: The outcome of depressive symptoms under CPAP therapy for OSA-hypopnea syndrome (OSAHS) has been poorly evaluated. In this multicenter, prospective cohort study, we evaluated the prevalence and correlates of persistent depressive symptoms after long-term CPAP therapy for OSAHS. Methods: This study included 300 patients with OSAHS and depressive symptoms (13-item, selfrated Pichot depression scale [QD2A] ≥ 7) at diagnosis. The primary dependent variable was persistent depressive symptoms after ≥ 1 year of CPAP therapy. Multivariate regression analyses were performed to determine variables independently associated with the persistence of depressive symptoms. Results: After an average of 529 days (range, 365-1,569 days) of CPAP therapy, the mean (SD) QD2A score decreased from 9.2 (2.0) to 5.4 (4.0) ( P < .0001), but 125 patients (41.7%) presented persistent depressive symptoms. The persistence of depressive symptoms was independently associated with persistent excessive daytime sleepiness (EDS) (OR, 2.72; 95% CI, 1.33-5.61), comorbid cardiovascular disease (OR, 1.76; 95% CI, 1.02-3.00), and female sex (OR, 1.53; 95% CI, 1.09-2.13). A positive linear trend was observed for the adjusted OR of persistent depressive symptoms with decreasing CPAP effect on the Epworth sleepiness scale ( P < .0001). Conclusions: CPAP therapy does not resolve depressive symptoms in many patients with OSAHS. Persistent depressive symptoms are strongly associated with EDS. Active monitoring of depressive symptoms is needed in patients with OSAHS who are treated with CPAP. Interventional trials are required to evaluate the impact of antidepressants, cognitive behavioral therapy, or both on comorbid depression in patients with OSAHS. © 2014 American College of Chest Physicians.

Gagnadoux F.,University of Angers | Gagnadoux F.,Angers University Hospital Center | Vaillant M.,French Institute of Health and Medical Research | Goupil F.,Center Hospitalier | And 7 more authors.
PLoS ONE | Year: 2011

Background: Long-term adherence is a major issue in patients receiving home continuous positive airway pressure (CPAP) therapy for obstructive sleep apnea-hypopnea syndrome (OSAHS). In a multicenter prospective cohort (the Institut de Recherche en Santé Respiratoire des Pays de la Loire [IRSR] sleep cohort) of consecutive OSAHS patients in whom CPAP had been prescribed for at least 90 days, we studied the impact on long-term treatment adherence of socioeconomic factors, patients and disease characteristics prior to CPAP initiation. Methods and Principal Findings: Among 1,141 patients in whom CPAP had been prescribed for an average of 504±251 days (range: 91 to 1035), 674 (59%) were adherent with a mean daily use of CPAP≥4 h (mean: 6.42±1.35 h). Stepwise regression analysis identified 4 independent factors of CPAP adherence including apnea-hypopnea index (AHI) (OR: 1.549, 95%CI 1.163 to 2.062 for AHI≥30 vs. AHI<30; p = 0.003), body mass index (BMI) (OR: 1.786, 95%CI 1.131 to 2.822 for BMI≥25 and <30 kg/m 2, p = 0.01; OR: 1.768, 95%CI 1.145-2.731 for BMI≥30 kg/m 2, p = 0.01 vs. BMI<25 kg/m 2), employment status (OR: 1.414, 95%CI 1.097-1.821 for retired vs. employed; p = 0.007) and marital status (OR: 1.482, 95%CI 1.088-2.019 for married or living as a couple vs. living alone; p = 0.01). Age, gender, Epworth sleepiness scale, depressive syndrome, associated cardiovascular morbidities, educational attainment and occupation category did not influence CPAP adherence. Conclusions: Marital status and employment status are independent factors of CPAP adherence in addition to BMI and disease severity. Patients living alone and/or working patients are at greater risk of non-adherence, whereas adherence is higher in married and retired patients. These findings suggest that the social context of daily life should be taken into account in risk screening for CPAP non-adherence. Future interventional studies targeting at-risk patients should be designed to address social motivating factors and work-related barriers to CPAP adherence. © 2011 Gagnadoux et al.

Finet G.,University of Lyon | Derimay F.,University of Lyon | Motreff P.,Estaing University Hospital Center | Guerin P.,Institute du Thorax | And 4 more authors.
JACC: Cardiovascular Interventions | Year: 2015

Objectives This study used a fractal bifurcation bench model to compare 6 optimization sequences for coronary bifurcation provisional stenting, including 1 novel sequence without kissing balloon inflation (KBI), comprising initial proximal optimizing technique (POT) + side-branch inflation (SBI) + final POT, called "re-POT." Background In provisional bifurcation stenting, KBI fails to improve the rate of major adverse cardiac events. Proximal geometric deformation increases the rate of in-stent restenosis and target lesion revascularization. Methods A bifurcation bench model was used to compare KBI alone, KBI after POT, KBI with asymmetric inflation pressure after POT, and 2 sequences without KBI: initial POT plus SBI, and initial POT plus SBI with final POT (called "re-POT"). For each protocol, 5 stents were tested using 2 different drug-eluting stent designs: that is, a total of 60 tests. Results Compared with the classic KBI-only sequence and those associating POT with modified KBI, the re-POT sequence gave significantly (p < 0.05) better geometric results: it reduced SB ostium stent-strut obstruction from 23.2 ± 6.0% to 5.6 ± 8.3%, provided perfect proximal stent apposition with almost perfect circularity (ellipticity index reduced from 1.23 ± 0.02 to 1.04 ± 0.01), reduced proximal area overstretch from 24.2 ± 7.6% to 8.0 ± 0.4%, and reduced global strut malapposition from 40 ± 6.2% to 2.6 ± 1.4%. Conclusions In comparison with 5 other techniques, the re-POT sequence significantly optimized the final result of provisional coronary bifurcation stenting, maintaining circular geometry while significantly reducing SB ostium strut obstruction and global strut malapposition. These experimental findings confirm that provisional stenting may be optimized more effectively without KBI using re-POT. © 2015 American College of Cardiology Foundation.

The Saxagliptin assessment of vascular outcomes recorded in patients with diabetes mellitus-thrombolysis in myocardial infarction (SAVOR-TIMI 53) trial was designed to test the effect of saxagliptin, a DPP-4 inhibitor, on the prevention of the occurrence of cardiovascular events in patients with type 2 diabetes (T2D). It is a 5-year, randomized, double-blind trial, conducted against placebo in 27 countries on 16,496 T2D patients. They received either a placebo or the saxagliptin 5 mg, or 2,5 mg in patients with renal failure (creatinine clearance <50 ml/minute). The treatment was given in addition to the usual treatment but gliptins or GLP-1 analogues were excluded. Patients were in secondary (80%) or primary cardiovascular prevention but with an additional risk factor (20%). The primary endpoint was a combined endpoint of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke. The trial was built to test a hypothesis from a non-inferiority to suggest the cardiovascular safety of the saxagliptin but also an assumption of superiority in cardiovascular prevention with a goal to reduce the relative risk of major cardiovascular events (primary endpoint) by 17%. The number of patients enrolled allowed testing these hypotheses with a good statistical power when 1040 events were observed. Patients were included in 27 countries with a large majority in North America and Western Europe. At inclusion the average age was 65.0 years with predominantly male (67%) patients. The average duration of diabetes was 11.9 years and mean HbA1c at baseline was 8.0+1.4%. Almost 12% of patients had retinopathy, 18% nephropathy and 2.5% amputation. Only 5% had no diabetes treatment and ~41% received insulin ± oral antidiabetics. The vast majority of patients (80%) received treatment with statins, antihypertensive and antiplatelet agents. Patients with cardiovascular history had more microvascular complications and were more often treated with insulin. The overall incidence of the primary endpoint was 2%/year. Investigators were asked to minimize the drop out of the patients less than 2,8%/year. The results of this study are expected in September 2013. © 2013 - Elsevier Masson SAS - Tous droits réservés.

Familial hypercholesterolemia (FH) is a frequent monogenetic disease (1/500 for heterozygous and 1/1,000,000 for homozygous). The FH patients are exposed to a dramatic increase of vascular risk of about 50% for men and 30% for women compared to the general population. The diagnosis can be suspected in case of high plasma concentration of LDL-C over 2.20. mg/dL, first relatives with FH in the family, xantomas and early cardiovascular events. The "Simon Broone criteria" or the Deutch scale are useful tools to ascertain the diagnosis but DNA testing is the gold standard. The mutations are mainly located on the LDL receptor gene and less frequently on Apo B100 or PCSK9 genes. The "cascade" testing of the family from the index patient is a critical step to detect new cases and start early treatment. Long-term treatment with statins has dramatically decreased the vascular risk to the level of the general population. In primary prevention, LDL-C should be less than 130. mg/dL and in secondary prevention less than 100. mg/dL (as a best. <. 70. mg/dL). It is often difficult to reach these goals and combined treatments with ezetimibe or other drugs can be used. When the goals are not reached with the maximum tolerated drug treatment, a decrease of 50% of LDL-C can be acceptable but the patients should be referred to lipid clinics. A yearly vascular survey of the FH patients is recommended, especially in adults or when the treatment goal is not reached. Homozygous FH patients must be referred to a specialized center. © 2013 Elsevier Masson SAS.

PubMed | French Institute of Health and Medical Research and Institute du Thorax
Type: Journal Article | Journal: European journal of immunology | Year: 2016

In the thymus, a T-cell repertoire able to confer protection against infectious and noninfectious agents in a peptide-dependent, self-MHC-restricted manner is selected. Direct detection of Ag-specific thymocytes, and analysis of the impact of the expression of the MHC-restricting allele on their frequency or function has never been studied in humans because of the extremely low precursor frequency. Here, we used a tetramer-based enrichment protocol to analyze the ex vivo frequency and activation-phenotype of human thymocytes specific for self, viral and tumor-antigens presented by HLA-A*0201 (A2) in individuals expressing or not this allele. Ag-specific thymocytes were quantified within both CD4CD8 double or single-positive compartments in every donor. Our data indicate that the maturation efficiency of Ag-specific thymocytes is poorly affected by HLA-A2 expression, in terms of frequencies. Nevertheless, A2-restricted T-cell lines from A2(+) donors reacted to A2(+) cell lines in a highly peptide-specific fashion, whereas their alloreactive counterparts showed off-target activity. This first ex vivo analysis of human antigen-specific thymocytes at different stages of human T-cell development should open new perspectives in the understanding of the human thymic selection process.

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