Paris Cardiovascular Research Center

Paris, France

Paris Cardiovascular Research Center

Paris, France
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Barra S.,Papworth Hospital NHS Foundation Trust | Boveda S.,Clinique Pasteur | Sadoul N.,University of Lorraine | Duehmke R.,Papworth Hospital NHS Foundation Trust | And 22 more authors.
Journal of the American College of Cardiology | Year: 2017

Background Patients with nonischemic dilated cardiomyopathy (DCM) may be at lower risk for ventricular arrhythmias compared with those with ischemic cardiomyopathy (ICM). In addition, DCM has been identified as a predictor of positive response to cardiac resynchronization therapy (CRT). Objectives The aim of this study was to investigate the impact of an additional implantable cardioverter-defibrillator over CRT, according to underlying heart disease, in a large study group of primary prevention patients with heart failure. Methods This was an observational, multicenter, European cohort study of 5,307 consecutive patients with DCM or ICM, no history of sustained ventricular arrhythmias, who underwent CRT implantation with (n = 4,037) or without (n = 1,270) a defibrillator. Propensity-score and cause-of-death analyses were used to compare outcomes. Results After a mean follow-up period of 41.4 ± 29.0 months, patients with ICM had better survival when receiving CRT with a defibrillator compared with those who received CRT without a defibrillator (hazard ratio for mortality adjusted on propensity score and all mortality predictors: 0.76; 95% confidence interval [CI]: 0.62 to 0.92; p = 0.005), whereas in patients with DCM, no such difference was observed (hazard ratio: 0.92; 95% CI: 0.73 to 1.16; p = 0.49). Compared with recipients of defibrillators, the excess mortality in patients who did not receive defibrillators was related to sudden cardiac death in 8.0% among those with ICM but in only 0.4% of those with DCM. Conclusions Among patients with heart failure with indications for CRT, those with DCM may not benefit from additional primary prevention implantable cardioverter-defibrillator therapy, as opposed to those with ICM. © 2017 American College of Cardiology Foundation

Yu P.,Yale University | Wilhelm K.,Max Planck Institute for Heart and Lung Research | Dubrac A.,Yale University | Tung J.K.,Yale University | And 22 more authors.
Nature | Year: 2017

Blood and lymphatic vasculatures are intimately involved in tissue oxygenation and fluid homeostasis maintenance. Assembly of these vascular networks involves sprouting, migration and proliferation of endothelial cells. Recent studies have suggested that changes in cellular metabolism are important to these processes1. Although much is known about vascular endothelial growth factor (VEGF)-dependent regulation of vascular development and metabolism2,3, little is understood about the role of fibroblast growth factors (FGFs) in this context4. Here we identify FGF receptor (FGFR) signalling as a critical regulator of vascular development. This is achieved by FGF-dependent control of c-MYC (MYC) expression that, in turn, regulates expression of the glycolytic enzyme hexokinase 2 (HK2). A decrease in HK2 levels in the absence of FGF signalling inputs results in decreased glycolysis, leading to impaired endothelial cell proliferation and migration. Pan-endothelial- and lymphatic-specific Hk2 knockouts phenocopy blood and/or lymphatic vascular defects seen in Fgfr1/Fgfr3 double mutant mice, while HK2 overexpression partly rescues the defects caused by suppression of FGF signalling. Thus, FGF-dependent regulation of endothelial glycolysis is a pivotal process in developmental and adult vascular growth and development. © 2017 Macmillan Publishers Limited, part of Springer Nature. All rights reserved.

Marijon E.,Paris Cardiovascular Research Center | Marijon E.,University of Paris Descartes | Le Heuzey J.-Y.,University of Paris Descartes | Connolly S.,Hamilton Health Sciences | And 8 more authors.
Circulation | Year: 2013

BACKGROUND -: Atrial fibrillation is associated with increased mortality, but the specific causes of death and their predictors have not been described among patients on effective anticoagulant therapy. METHODS AND RESULTS -: The Randomized Evaluation of Long-Term Anticoagulant Therapy (RE-LY) trial randomized 18 113 patients (age, 71.5±9 years; male, 64%; CHADS2 score, 2.1±1) to receive dabigatran or warfarin. Median follow-up was 2 years, and complete follow-up was achieved in 99.9% of patients. All deaths were categorized by the investigators using prespecified definitions followed by central adjudication. Overall, 1371 deaths occurred (annual mortality rate, 3.84%; 95% confidence interval [CI], 3.64-4.05). Cardiac deaths (sudden cardiac death and progressive heart failure) accounted for 37.4% of all deaths, whereas stroke-and hemorrhage-related deaths represented 9.8% of the total mortality. An examination of the causes of death according to dabigatran or warfarin showed that dabigatran significantly reduced vascular (embolism and hemorrhage-related) mortality (relative risk, 0.63; 95% CI, 0.45-0.88; P=0.007), whereas other causes of death were similar between treatments, including cardiac mortality (relative risk, 0.96; 95% CI, 0.80-1.15; P=0.638). The two strongest independent predictors of cardiac death in this population were heart failure (hazard ratio, 3.02; 95% CI, 2.45-3.73; P<0.0001), and prior myocardial infarction (hazard ratio, 2.05; 95% CI, 1.61-2.62; P<0.0001). CONCLUSIONS -: The majority of deaths are not related to stroke in a contemporary anticoagulated atrial fibrillation population. These results emphasize the need to identify interventions beyond effective anticoagulation to further reduce mortality in atrial fibrillation. CLINICAL TRIAL REGISTRATION -: URL: http://www. Unique identifier: NCT00262600. © 2013 American Heart Association, Inc.

Providencia R.,University Paul Sabatier | Providencia R.,University of Coimbra | Marijon E.,Paris Cardiovascular Research Center | Albenque J.-P.,University Paul Sabatier | And 6 more authors.
Europace | Year: 2014

Aims The recent availability of the novel oral anticoagulants (NOACs) may have led to a change in the anticoagulation regimens of patients referred to catheter ablation of atrial fibrillation (AF). Preliminary data exist concerning dabigatran, but information regarding the safety and efficacy of rivaroxaban in this setting is currently scarce. Methods and results Of the 556 consecutive eligible patients (age 61.0 ± 9.6; 74.6% men; 61.2% paroxysmal AF) undergoing AF catheter ablation in our centre (October 2012 to September 2013) and enroled in a systematic standardized 30-day follow-up period: 192 patients were under vitamin K antagonists (VKAs), 188 under rivaroxaban, and 176 under dabigatran. Peri-procedural mortality and significant systemic or pulmonary thromboembolism (efficacy outcome), as well as bleeding events (safety outcome) during the 30 days following the ablation were evaluated according to anticoagulation regimen. During a 12-month time interval, the use of the NOACs in this population rose from <10 to 70%. Overall, the rate of events was low with no significant differences regarding: thrombo-embolic events in 1.3% (VKA 2.1%; rivaroxaban 1.1%; dabigatran 0.6%; P = 0.410); major bleeding in 2.3% (VKA 4.2%; rivaroxaban 1.6%; dabigatran 1.1%; P = 0.112), and minor bleeding 1.4% (VKA 2.1%; rivaroxaban 1.6%; dabigatran 0.6%; P = 0.464). No fatal events were observed. Conclusion The use of the NOAC in patients undergoing catheter ablation of AF has rapidly evolved (seven-fold) over 1 year. These preliminary data suggest that rivaroxaban and dabigatran in the setting of catheter ablation of AF are efficient and safe, compared with the traditional VKA. © 2014 Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2014.

PubMed | Louis Pradel Hospital, Clinique Pasteur, University of Strasbourg, Lille University Hospital Center and 18 more.
Type: Comparative Study | Journal: European heart journal | Year: 2016

The choice of resynchronization therapy between with (CRT-D) and without (CRT-P) a defibrillator remains a contentious issue. Cause-of-death analysis among CRT-P, compared with CRT-D, patients could help evaluate the extent to which CRT-P patients would have additionally benefited from a defibrillator in a daily clinical practice.A total of 1705 consecutive patients implanted with a CRT (CRT-P: 535 and CRT-D: 1170) between 2008 and 2010 were enrolled in CeRtiTuDe, a multicentric prospective follow-up cohort study, with specific adjudication for causes of death at 2 years. Patients with CRT-P compared with CRT-D were older (P < 0.0001), less often male (P < 0.0001), more symptomatic (P = 0.0005), with less coronary artery disease (P = 0.003), wider QRS (P = 0.002), more atrial fibrillation (P < 0.0001), and more co-morbidities (P = 0.04). At 2-year follow-up, the annual overall mortality rate was 83.80 [95% confidence interval (CI) 73.41-94.19] per 1000 person-years. The crude mortality rate among CRT-P patients was double compared with CRT-D (relative risk 2.01, 95% CI 1.56-2.58). In a Cox proportional hazards regression analysis, CRT-P remained associated with increased mortality (hazard ratio 1.54, 95% CI 1.07-2.21, P = 0.0209), although other potential confounders may persist. By cause-of-death analysis, 95% of the excess mortality among CRT-P subjects was related to an increase in non-sudden death.When compared with CRT-D patients, excess mortality in CRT-P recipients was mainly due to non-sudden death. Our findings suggest that CRT-P patients, as currently selected in routine clinical practice, would not potentially benefit with the addition of a defibrillator.

Gazit S.L.,Paris Cardiovascular Research Center | Gazit S.L.,University of Paris Pantheon Sorbonne | Gazit S.L.,University Paris - Sud | Gazit S.L.,Monash University
Circulation Research | Year: 2016

RATIONALE:: Sphingosine-1-phosphate (S1P) signaling is essential for vascular development and postnatal vascular homeostasis. The level of redundancy in S1P sources sustaining these processes remains unclear. OBJECTIVE:: To address S1P source redundancy in the regulation of vascular development, integrity and tone. METHODS AND RESULTS:: S1P production was selectively impaired in mouse platelets, erythrocytes, endothelium, and/or smooth muscle cells by targeted deletion of genes encoding sphingosine kinases (Sphks) 1&2. S1P deficiency blunted aggregation and spreading of washed platelets and profoundly impaired their capacity to promote endothelial barrier function ex vivo. However, and in contrast to recent reports, neither platelets nor any other source of S1P was essential for vascular development, vascular integrity, or hemostasis/thrombosis. Yet rapid and profound depletion of plasma S1P during systemic anaphylaxis rendered both platelet- and erythrocyte-derived S1P essential for survival, with a contribution from blood endothelium observed only in the absence of circulating sources. Recovery was sensitive to aspirin in mice with but not without platelet S1P, suggesting that platelet activation and stimulus-response coupling is needed. S1P2 mediated most of the survival benefit of S1P, while endothelial S1P1 was dispensable for survival despite its importance for maintaining vascular integrity. Accordingly, S1P deficiency aggravated vasoplegia, arguing a vital role for S1P in maintaining vascular resistance during recovery from circulatory shock. CONCLUSIONS:: While source redundancy secures essential roles of S1P in vascular development and integrity, profound depletion of plasma S1P during anaphylactic shock renders both erythrocyte and platelet S1P pools necessary for recovery and high basal plasma S1P levels protective. © 2016 American Heart Association, Inc.

Boveda S.,Clinique Pasteur | Providencia R.,Clinique Pasteur | Albenque J.-P.,Clinique Pasteur | Combes N.,Clinique Pasteur | And 7 more authors.
Europace | Year: 2014

Aim: Real-time assessment of pulmonary vein (PV) disconnection is possible using an inner circular mapping catheter during cryoablation of atrial fibrillation (AF). However, it has been recently demonstrated that such continuous monitoring may only be possible in <50 of PVs. We hypothesized that a stepwise mapping approach, including pacing manoeuvres, could optimize monitoring of real-time PV disconnection during ablation. Methods and results: Single-centre, prospective observational study (NCT01843465) including 34 consecutive eligible patients (128 PVs) undergoing a first procedure of cryoballoon ablation of AF using the Artic Front Advance® 28 mm catheter and a 20 mm diameter Achieve® catheter (AC) in all cases. Monitoring of real-time entrance block was possible, when AC was maintained in the standard position (distal to the tip of the Artic Front Advance® catheter) in 47 (36.7) PVs. In an additional 63 cases (49.2), such monitoring was possible after moving AC to a more proximal position and using different torqueing movements. Finally, using supplemental systematic pacing manoeuvres to test exit block, real-time assessment of PV disconnection was possible in 15 (11.7) more PVs. Overall, real-time assessment of PV disconnection was possible in 97.7 of cases, after a mean duration of 48.6 ± 33.0 s. Conclusion: Our results suggest that optimal use of the AC, with a systematic stepwise mapping approach, may dramatically improve the real-time monitoring of PV disconnection during AF cryoablation. All rights reserved. © The Author 2013.

PubMed | Agence Sanitaire et Sociale de Nouvelle Caledonie, University Hospital Amiens, Center Hospitalier Territorial, Paris Cardiovascular Research Center and University of Paris Descartes
Type: | Journal: International journal of cardiology | Year: 2016

The advent of systematic screening for rheumatic heart disease (RHD) by echocardiography in endemic regions has led to a new entity: borderline RHD. The pathogenicity and natural history of borderline RHD needs to be addressed. The aim of this study was to assess the outcomes of children detected by echocardiography as having borderline RHD.Schoolchildren in 4th grade (i.e., aged 9-10years) who were prospectively echo-screened for RHD (2012-2014) in Nouma, New Caledonia, were asked to participate. Children with borderline RHD according to consistent independent review by two cardiologists were included and followed-up in 2015.Among the 8684 schoolchildren screened, 49 were diagnosed with borderline RHD according to the Cardiologist clinically involved in the childs management plan. After independent review by two cardiologists, 25 children were consistently diagnosed with borderline RHD and included in the follow-up study. Overall, inter-observer agreement was moderate with diagnostic kappa values of 0.63 (95% CI 0.45-0.78). After a median follow-up of 23months (IQR (20.5-33.0), 15 children (60.0%) had stability of valvular lesions, 8 (32.0%) had normal findings according to the WHF criteria. Two children (8.0%) had definite RHD on the follow-up echocardiogram, but no clinical events or audible pathological murmur during the study period. No factor could be identified as prognostic of either stability or progression.Borderline RHD diagnosed by systematic screening in high-risk populations remains mostly unchanged at 2years follow-up. Diagnosis of borderline RHD may require two reviewers for consistency.

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