Search

Background There is limited evidence that fractional flow reserve (FFR) is effective in guiding therapeutic strategy in multivessel coronary artery disease (CAD) beyond prespecified percutaneous coronary intervention or coronary graft surgery candidates. Objectives The FUTURE (FUnctional Testing Underlying coronary REvascularization) trial aimed to evaluate whether a treatment strategy based on FFR was superior to a traditional strategy without FFR in the treatment of multivessel CAD. Methods The FUTURE trial is a prospective, randomized, open-label superiority trial. Multivessel CAD candidates were randomly assigned (1:1) to treatment strategy based on FFR in all stenotic (≥50%) coronary arteries or to a traditional strategy without FFR. In the FFR group, revascularization (percutaneous coronary intervention or surgery) was indicated for FFR ≤0.80 lesions. The primary endpoint was a composite of major adverse cardiac or cerebrovascular events at 1 year. Results The trial was stopped prematurely by the data safety and monitoring board after a safety analysis and 927 patients were enrolled. At 1-year follow-up, by intention to treat, there were no significant differences in major adverse cardiac or cerebrovascular events rates between groups (14.6% in the FFR group vs 14.4% in the control group; hazard ratio: 0.97; 95% confidence interval: 0.69-1.36; P = 0.85). The difference in all-cause mortality was nonsignificant, 3.7% in the FFR group versus 1.5% in the control group (hazard ratio: 2.34; 95% confidence interval: 0.97-5.18; P = 0.06), and this was confirmed with a 24 months’ extended follow-up. FFR significantly reduced the proportion of revascularized patients, with more patients referred to exclusively medical treatment (P = 0.02). Conclusions In patients with multivessel CAD, we did not find evidence that an FFR-guided treatment strategy reduced the risk of ischemic cardiovascular events or death at 1-year follow-up. (Functional Testing Underlying Coronary Revascularisation; NCT01881555 )

International audience; For the last two decades, various degradable stents have been proposed to treat coronary artery diseases and replace metallic stents to avoid residual foreign material after healing. To date, the right balance between suitable scaffolding and loss of radial strength soon after endothelium restoration is still an unmet need. The present article reports on the First-in-Man trial of a drug-free bioresorbable stent based on a lactic acid stereocopolymer composed of 98% l-lactyl units selected to release stress shielding earlier than in the case of homopoly(l-lactic acid). Thirty patients with single de novo coronary lesions were included in the trial. The fate of scaffolds was monitored by clinical and imaging follow-ups to assess rate of adverse events, acute recoil, late luminal loss, and late lumen recovery. There was no death, no myocardial infarction, and no stent thrombosis observed over the 36 months trial. Dismantling occurred about 3 months after implantation. Bioresorption was almost completed at 2 years. The late lumen loss observed at the end of the first year was partly compensated one year later by enlarging remodeling. At one year, a neointimal hyperplasia slightly greater than for drug-eluting metallic and bioresorbable stents was shown using optical coherence tomography. The excess of hyperplasia was discussed relative to struts thickness, absence of anti-proliferative drug, and release of degradation by-products.

Many parts of the developing world, especially Sub-Saharan Africa, completely lack access to cardiac pacing. The authors initiated a multinational program to implement cardiac pacing in 14 countries in Sub-Saharan Africa (1996 to 2018), aiming to eventually build self-sustainable capacity in each country. This was based on an "on-site training" approach of performing procedures locally and educating local health care teams to work within resource-limited settings, with prospective evaluation of the program. In 64 missions, a total of 542 permanent pacemakers were implanted. In 11 of these countries, the first pacemaker implant in the country was through the mission. More than one-half of those initially listed as suitable died before the mission(s) arrived. The proportion of implantations that were completely handled by local teams increased from 3% in 1996 to 98% in 2018. These findings demonstrate the feasibility and effectiveness of a proctorship-based approach to the development of local cardiac pacing capabilities in Sub-Saharan African nations.

International audience; Aim: Coronary artery disease (CAD) has recently been emphasized as a major cause of sudden cardiac arrest (SCA) in young adults. We aim to assess the rate of immediate coronary angiography performance in young patients resuscitated from SCA.Methods: From May 2011 to May 2017, all cases of out-of-hospital SCA aged 18-40 years alive at hospital admission were prospectively included in 48 hospitals of the Great Paris area. Cardiovascular causes of SCA were centrally adjudicated, and management including immediate coronary angiography performance was assessed.Results: Out of 3579 SCA admitted alive, 409 (11.4%) patients were under 40 years of age (32.3 ± 6.2 years, 69.7% males), with 244 patients having a definite cause identified. Among those, CAD accounted for 72 (29.5%) cases, of which 64 (88.9%) were acute coronary syndromes. The rate of immediate coronary angiography was only 41.7% compared to 65.1% among those ≥40-years (P < 0.001). During the study period, while the rate of immediate coronary angiography increased from 60.5% to 70.3% (P < 0.001) in patients aged ≥40 years, the rate in patients aged less than 40 years remained stable (43.5% to 45.3%, P = 0.795). Patients younger than 40 years were significantly less likely to undergo immediate coronary angiography (OR = 0.34, 95% CI: 0.25-0.47), although early angiography was associated with survival at hospital discharge (OR = 2.68, 95% CI: 1.21-6.00).Conclusion: CAD is the first cause of SCA in young adults aged less than 40 years. The observed low rates of immediate coronary angiography suggest a missed opportunity for early intervention.

International audience; BACKGROUND:Femoral access is the gold standard for transcatheter aortic valve replacement (TAVR). Guidelines recommend reconsidering surgery when this access is not feasible. However, alternative peripheral accesses exist, although they have not been accurately compared with femoral access.OBJECTIVES:This study compared nonfemoral peripheral (n-FP) TAVR with femoral TAVR.METHODS:Using the data from the national prospective French registry (FRANCE TAVI [French Transcatheter Aortic Valve Implantation]), this study compared the characteristics and outcomes of TAVR procedures according to whether they were performed through a femoral or a n-FP access, using a pre-specified propensity score-based matching between groups. Subanalysis during 2 study periods (2013 to 2015 and 2016 to 2017) and among low/intermediate-low and intermediate-high/high volume centers were performed. RESULTS:Among 21,611 patients, 19,995 (92.5%) underwent femoral TAVR and 1,616 (7.5%) underwent n-FP TAVR (transcarotid, n = 914 or trans-subclavian, n = 702). Patients in the n-FP access group had more severe disease (mean logistic EuroSCORE 19.95 vs. 16.95; p < 0.001), with a higher rate of peripheral vascular disease, known coronary artery disease, chronic pulmonary disease, and renal failure. After matching, there was no difference in the rate of post-procedural death and complications according to access site, except for a 2-fold lower rate of major vascular complications (odds ratio: 0.45; 95% confidence interval: 0.21 to 0.93; p = 0.032) and unplanned vascular repairs (odds ratio: 0.41; 95% confidence interval: 0.29 to 0.59; p < 0.001) in those who underwent n-FP access. The comparison of outcomes provided similar results during the second study period and in intermediate-high/high volume centers.CONCLUSIONS:n-FP TAVR is associated with similar outcomes compared with femoral peripheral TAVR, except for a 2-fold lower rate of major vascular complications and unplanned vascular repairs. n-FP TAVR may be favored over surgery in patients who are deemed ineligible for femoral TAVR and may be a safe alternative when femoral access risk is considered too high.

Many parts of the developing world, especially Sub-Saharan Africa, completely lack access to cardiac pacing. The authors initiated a multinational program to implement cardiac pacing in 14 countries in Sub-Saharan Africa (1996 to 2018), aiming to eventually build self-sustainable capacity in each country. This was based on an "on-site training" approach of performing procedures locally and educating local health care teams to work within resource-limited settings, with prospective evaluation of the program. In 64 missions, a total of 542 permanent pacemakers were implanted. In 11 of these countries, the first pacemaker implant in the country was through the mission. More than one-half of those initially listed as suitable died before the mission(s) arrived. The proportion of implantations that were completely handled by local teams increased from 3% in 1996 to 98% in 2018. These findings demonstrate the feasibility and effectiveness of a proctorship-based approach to the development of local cardiac pacing capabilities in Sub-Saharan African nations.

International audience; Objectives: This study sought to describe the procedural and clinical outcomes of patients undergoing transcarotid (TC) transcatheter aortic valve replacement (TAVR) with the Edwards Sapien 3 device.Background: The TC approach for TAVR holds the potential to become the optimal alternative to the transfemoral gold standard. Limited data exist regarding safety and efficacy of TC-TAVR using the Edwards Sapien 3 device.Methods: The French Transcarotid TAVR prospective multicenter registry included patients between 2014 and 2018. Consecutive patients treated in 1 of the 13 participating centers ineligible for transfemoral TAVR were screened for TC-TAVR. Clinical and echocardiographic data were prospectively collected. Perioperative and 30-day outcomes were reported according to the updated Valve Academic Research Consortium (VARC-2).Results: A total of 314 patients were included with a median (interquartile range) age of 83 (78 to 88) years, 63% were males, Society of Thoracic Surgeons mortality risk score 5.8% (4% to 8.3%). Most patients presented with peripheral artery disease (64%). TC-TAVR was performed under general anesthesia in 91% of cases, mostly using the left carotid artery (73.6%) with a procedural success of 97%. Three annulus ruptures were reported, all resulting in patient death. At 30 days, rates of major bleeding, new permanent pacemaker, and stroke or transient ischemic attack were 4.1%, 16%, and 1.6%, respectively. The 30-day mortality was 3.2%.Conclusions: TC-TAVR using the Edwards Sapien 3 device was safe and effective in this prospective multicenter registry. The TC approach might be considered, in selected patients, as the first-line alternative approach for TAVR whenever the transfemoral access is prohibited. Sapien 3 device was safe and effective in our multicenter cohort.

OBJECTIVES The transcarotid (TC) approach for transcatheter aortic valve implantation (TAVI) is potentially an optimal alternative to the transfemoral (TF) approach. Our goal was to compare the safety and efficacy of TC- and TF-TAVI. METHODS Patients who underwent TF-TAVI or TC-TAVI in the prospectively collected FRANCE TAVI registry between January 2013 and December 2015 were compared. Propensity score inverse probability weighting methods were employed to minimize the impact of bias related to non-random treatment assignment. RESULTS Of the 11 033 patients included in the current study, 10 598 (96%) underwent a TF-TAVI and 435 (4.1%) had a TC-TAVI. Patients in the TC-TAVI access group presented with a higher risk profile but were significantly younger. There were no differences in the perioperative and 2-year mortality rates after adjustment [odds ratio (OR) 1.02, 95% confidence interval (CI) 0.62–1.68; P = 0.99 and hazard ratio 1.03, 95% CI 0.7–1.35; P = 0.83). TC-TAVI was associated with a significant risk of stroke (OR 2.42, 95% CI 2.01–2.92; P CONCLUSIONS TC-TAVI is a safe procedure compared to TF-TAVI, although it holds an increased risk of perioperative complications. It should be considered in case of non-femoral peripheral access as the second access choice, to increase the overall safety of TAVI procedures.

Background The optimal access for patients undergoing transcatheter aortic valve replacement (TAVR) who are not candidates for a transfemoral approach has not been elucidated. The purpose of this study was to compare the safety, feasibility, and early clinical outcomes of transcarotid TAVR compared with thoracic approaches. Methods and Results From a multicenter consecutive cohort of 329 alternative-access TAVR patients (2012–2017), we identified 101 patients who underwent transcarotid TAVR and 228 patients who underwent a transapical or transaortic TAVR. Preprocedural success and 30-day clinical outcomes were compared using multivariable propensity score analysis to account for between-group differences in baseline characteristics. All transcarotid cases were performed under general anesthesia, mainly using the left common carotid artery (97%). Propensity-matched groups had similar rates of 30-day all-cause mortality (2.1% versus 4.6%; P =0.37), stroke (2.1% versus 3.5%; P =0.67; transcarotid versus transapical/transaortic, respectively), new pacemaker implantation, and major vascular complications. Transcarotid TAVR was associated with significantly less new-onset atrial fibrillation (3.2% versus 19.0%; P =0.002), major or life-threatening bleeding (4.3% versus 19.9%; P =0.002), acute kidney injury (none versus 12.1%; P =0.002), and shorter median length of hospital stay (6 versus 8 days; P Conclusions Transcarotid vascular access for TAVR is safe and feasible and is associated with encouraging short-term clinical outcomes. Our data suggest a clinical benefit of transcarotid TAVR with respect to atrial fibrillation, major bleeding, acute kidney injury, and length of stay compared with the more invasive transapical or transaortic strategies. Randomized studies are required to ascertain whether transcarotid TAVR yields equivalent results to other alternative vascular access routes.

BACKGROUND Transcatheter aortic valve replacement (TAVR) has revolutionized management of high-risk patients with severe aortic stenosis. However, survival and the incidence of severe complications have been assessed in relatively small populations and/or with limited follow-up. OBJECTIVES This report details late clinical outcome and its determinants in the FRANCE-2 (FRench Aortic National CoreValve and Edwards) registry. METHODS The FRANCE-2 registry prospectively included all TAVRs performed in France. Follow-up was scheduled at 30 days, at 6 months, and annually from 1 to 5 years. Standardized VARC (Valve Academic Research Consortium) outcome definitions were used. RESULTS A total of 4,201 patients were enrolled between January 2010 and January 2012 in 34 centers. Approaches were transarterial (transfemoral 73%, transapical 18%, subclavian 6%, and transaortic or transcarotid 3%) or, in 18% of patients, transapical. Median follow-up was 3.8 years. Vital status was available for 97.2% of patients at 3 years. The 3-year all-cause mortality was 42.0% and cardiovascular mortality was 17.5%. In a multivariate model, predictors of 3-year all-cause mortality were male sex (p = 2 of 4 (p < 0.001). Severe events according to VARC criteria occurred mainly during the first month and subsequently in < 2% of patients/year. Mean gradient, valve area, and residual aortic regurgitation were stable during follow-up. CONCLUSIONS The FRANCE-2 registry represents the largest database available on late results of TAVR. Late mortality is largely related to noncardiac causes. Incidence rates of severe events are low after the first month. Valve performance remains stable over time. (J Am Coll Cardiol 2016; 68: 1637-47) (C) 2016 by the American College of Cardiology Foundation.

This study sought to describe the procedural and clinical outcomes of patients undergoing transcarotid (TC) transcatheter aortic valve replacement (TAVR) with the Edwards Sapien 3 device.The TC approach for TAVR holds the potential to become the optimal alternative to the transfemoral gold standard. Limited data exist regarding safety and efficacy of TC-TAVR using the Edwards Sapien 3 device.The French Transcarotid TAVR prospective multicenter registry included patients between 2014 and 2018. Consecutive patients treated in 1 of the 13 participating centers ineligible for transfemoral TAVR were screened for TC-TAVR. Clinical and echocardiographic data were prospectively collected. Perioperative and 30-day outcomes were reported according to the updated Valve Academic Research Consortium (VARC-2).A total of 314 patients were included with a median (interquartile range) age of 83 (78 to 88) years, 63% were males, Society of Thoracic Surgeons mortality risk score 5.8% (4% to 8.3%). Most patients presented with peripheral artery disease (64%). TC-TAVR was performed under general anesthesia in 91% of cases, mostly using the left carotid artery (73.6%) with a procedural success of 97%. Three annulus ruptures were reported, all resulting in patient death. At 30 days, rates of major bleeding, new permanent pacemaker, and stroke or transient ischemic attack were 4.1%, 16%, and 1.6%, respectively. The 30-day mortality was 3.2%.TC-TAVR using the Edwards Sapien 3 device was safe and effective in this prospective multicenter registry. The TC approach might be considered, in selected patients, as the first-line alternative approach for TAVR whenever the transfemoral access is prohibited. Sapien 3 device was safe and effective in our multicenter cohort.

Since Tamai were the first to launch the fascinating bioresorbable scaffold in 1999, Abbott took the leadership of the proof of concept in human with Absorb bioresorbable vascular scaffold (BVS; Abbott Vascular, Santa Clara), a 100% poly-l-lactic acid everolimus-eluting bioresorbable scaffold.1,2 Despite encouraging noninferiority randomized trials during the first 2-year follow-up, these studies showed an increase in-scaffold thrombosis compared with the drug-eluting stent (DES; Xience; Abbott). Unfortunately, the 3-year outcome of ABSORB II (A Clinical Evaluation to Compare the Safety, Efficacy and Performance of ABSORB Everolimus Eluting Bioresorbable Vascular Scaffold System Against XIENCE Everolimus Eluting Coronary Stent System in the Treatment of Subjects With Ischemic Heart Disease Caused by de Novo Native Coronary Artery Lesions) confirmed by meta-analyses resulted in the end of Absorb BVS use in Europe and the United States.3,4 In September 2017, Absorb BVS was withdrawn from the market, although higher rates of scaffold thrombosis did not result in increased mortality.5 Moreover, 4 other scaffolds with European Conformity …

Background Arterial Remodeling Technologies bioresorbable scaffold ( ART ‐ BRS ), composed of l ‐ and d ‐lactyl units without drug, has shown its safety in a porcine coronary model at 6 months. However, long‐term performance remains unknown. The aim of this study was to evaluate the ART ‐ BRS compared to a bare metal stent ( BMS ) in a healthy porcine coronary model for up to 3 years. Methods and Results Eighty‐two ART ‐ BRS and 66 BMS were implanted in 64 Yucatan swine, and animals were euthanatized at intervals of 1, 3, 6, 9, 12, 18, 24, and 36 months to determine the vascular response using quantitative coronary angiography, optical coherence tomography, light and scanning electron microscopy, and molecular weight analysis. Lumen enlargement was observed in ART ‐ BRS as early as 3 months, which progressively increased up to 18 months, whereas BMS showed no significant difference over time. Percentage area stenosis by optical coherence tomography was greater in ART ‐ BRS than in BMS at 1 and 3 months, but this relationship reversed beyond 3 months. Inflammation peaked at 6 months and thereafter continued to decrease up to 36 months. Complete re‐endothelialization was observed at 1 month following implantation in both ART ‐ BRS and BMS . Scaffold dismantling started at 3 months, which allowed early vessel enlargement, and bioresorption was complete by 24 months. Conclusions ART ‐ BRS has the unique quality of early programmed dismantling accompanied by vessel lumen enlargement with mild to moderate inflammation. The main distinguishing feature of the ART ‐ BRS from other scaffolds made from poly‐ l ‐lactic acid may result in early and long‐term vascular restoration.

Background - Transcatheter aortic valve replacement (TAVR) is standard therapy for patients with severe aortic stenosis who are at high surgical risk. However, national data regarding procedural characteristics and clinical outcomes over time are limited. Objectives - The aim of this study was to assess nationwide performance trends and clinical outcomes of TAVR during a 6-year period. Methods - TAVRs performed in 48 centers across France between January 2013 and December 2015 were prospectively included in the FRANCE TAVI (French Transcatheter Aortic Valve Implantation) registry. Findings were further compared with those reported from the FRANCE 2 (French Aortic National CoreValve and Edwards 2) registry, which captured all TAVRs performed from January 2010 to January 2012 across 34 centers. Results - A total of 12,804 patients from FRANCE TAVI and 4,165 patients from FRANCE 2 were included in this analysis. The median age of patients was 84.6 years, and 49.7% were men. FRANCE TAVI participants were older but at lower surgical risk (median logistic European System for Cardiac Operative Risk Evaluation [EuroSCORE]: 15.0% vs. 18.4%; p < 0.001). More than 80% of patients in FRANCE TAVI underwent transfemoral TAVR. Transesophageal echocardiography guidance decreased from 60.7% to 32.3% of cases, whereas more recent procedures were increasingly performed in hybrid operating rooms (15.8% vs. 35.7%). Rates of Valve Academic Research Consortium-defined device success increased from 95.3% in FRANCE 2 to 96.8% in FRANCE TAVI (p < 0.001). In-hospital and 30-day mortality rates were 4.4% and 5.4%, respectively, in FRANCE TAVI compared with 8.2% and 10.1%, respectively, in FRANCE 2 (p

Aims Abdominal aortic aneurysm (AAA), frequently diagnosed in old patients, is characterized by chronic inflammation, vascular cell apoptosis and metalloproteinase-mediated extracellular matrix destruction. Despite improvement in the understanding of the pathophysiology of aortic aneurysm, no pharmacological treatment is yet available to limit dilatation and/or rupture. We previously reported that human gingival fibroblasts (GFs) can reduce carotid artery dilatation in a rabbit model of elastase-induced aneurysm. Here, we sought to investigate the mechanisms of GF-mediated vascular protection in two different models of aortic aneurysm growth and rupture in mice. Methods and results In vitro, mouse GFs proliferated and produced large amounts of anti-inflammatory cytokines and tissue inhibitor of metalloproteinase-1 (Timp-1). GFs deposited on the adventitia of abdominal aorta survived, proliferated, and organized as a layer structure. Furthermore, GFs locally produced Il-10, TGF-β, and Timp-1. In a mouse elastase-induced AAA model, GFs prevented both macrophage and lymphocyte accumulations, matrix degradation, and aneurysm growth. In an Angiotensin II/anti-TGF-β model of aneurysm rupture, GF cell-based treatment limited the extent of aortic dissection, prevented abdominal aortic rupture, and increased survival. Specific deletion of Timp-1 in GFs abolished the beneficial effect of cell therapy in both AAA mouse models. Conclusions GF cell-based therapy is a promising approach to inhibit aneurysm progression and rupture through local production of Timp-1.

Purpose The prospective EUROVISION Registry was designed to capture patterns of use and short term outcomes in consecutive patients undergoing PCI with bivalirudin (BIV) in European centres. Methods A total of 2018 consecutive BIV-treated patients were included from 58 sites in 5 countries (Germany, Italy, France, Austria, United Kingdom). In-hospital and 30-day outcomes were prospectively collected and included: death, myocardial infarction (MI), stroke, urgent revascularization (URV), major and minor bleeding, stent thrombosis (ST) and thrombocytopenia (TCP). Results In this all-comer population, indication for PCI included STEMI (34%), NSTEMI (25%), unstable angina (16%) and stable angina (26%). Diabetes was present in 24% of patients and 30% of cases were performed via radial access. Preloading with a P2Y12 inhibitor was frequent (74%) while procedural glycoprotein inhibitor (GPI) use was low at 4.2%. Almost half (45%) of patients had received at least one additional anticoagulant prior to receiving BIV for PCI. The overall 30-day mortality was 1.0%, with low rates of MI (1.1%), URV (0.8%), ST (0.3%) and stroke (0.2%). The rate of ACUITY major bleeding was 1.6% and no TCP was reported. Dosing variations representing possible under- or over-dosing of BIV were frequent at 35%. Conclusion In this prospective registry of consecutive patients intended for PCI, use of BIV was associated with low rates of ischemic complications and excellent safety.

International audience

Friday, Nov 13, 2015. It's 2130 h when the Assistance Publique-Hopitaux de Paris (APHP) is alerted to the explosions that have just occurred at the Stade de France, a stadium in Saint-Denis just outside Paris. Within 20 min, there are shootings at four sites and three bloody explosions in the capital. At 2140 h, a massacre takes place and hundreds of people are held hostage for 3 h in Bataclan concert hall. The emergency medical services (service d'aide medicale d'urgence, SAMU) are immediately mobilised and the crisis cell at the APHP is opened. The APHP crisis unit is able to coordinate 40 hospitals, the biggest entity in Europe with a total of 100 000 health professionals, a capacity of 22 000 beds, and 200 operating rooms. It is very quickly confirmed that the attacks are multiple and that the situation is highly scalable and progressing dangerously. These facts led to a first decision: the activation of the “White Plan” (by the APHP Director General) at 2234 h—mobilising all hospitals, recalling staff, and releasing beds to cope with a large influx of wounded people. The concept of the White Plan was developed 20 years ago, but this is the first time that the plan has been activated. It is a big decision, and timing is key: it would lose its effectiveness if taken too late. On the night of Friday Nov 13 to Saturday Nov 14, the activation of the White Plan had a critical effect. At no time during the emergency was there a shortage of personnel. During these hours, as the number of victims increased, with a sharp increase after the assault was launched inside the Bataclan, we were able to reassure the public and government that our abilities matched the demand. And when we felt that it might be necessary to deal with an influx of severely injured people, two further “reservoir” capacities were prepared: other hospitals in the area were put on alert, together with some university hospitals, more distant from Paris, but with the ability to mobilise ten helicopters to organise the transport of the wounded... Language: en

The gum has an exceptional capacity for healing. To examine the basis for this property and explore the potential of conferring it to organs with inferior healing capacity, we sought the presence of progenitor cells in gingival connective tissue. Colony-forming units of fibroblast-enriched cells from gingival fibroblast cultures were assessed for expression of membrane markers of mesenchymal stem cells; capacity to differentiate into osteoblasts, chondroblasts, and adipocytes; and engraftment efficiency after in vivo transfer. On the basis of their ability to differentiate into several lineages, proliferate from single cells, induce calcium deposits, and secrete collagen in vivo after transfer on hydroxyapatite carriers, we suggest that this population represents gingival multipotent progenitor cells. The discovery of progenitor cells in gingival connective tissue may help improve our understanding of how the wounded gum is capable of almost perfect healing and opens the prospect of cellular therapy for wound healing using readily available cells at limited risk to the patient.

Matrix metalloproteinases (MMP) play a deleterious role in numerous vascular diseases. In contrast, gingival matrix remodelling is adequately regulated by the gingival fibroblast (GF). Here, we aimed to evaluate the GF activity on MMP-7 expression and secretion in coculture with aorta rings. We evaluated MMP-7 transcription and secretion in rabbit aorta rings cultured or not with gingival fibroblasts in collagen gels. GF induced an increase of TIMP-1 transcription and secretion, followed, similarly to other MMPs, by the formation of TIMP-1/MMP-7 complexes. There was also a decrease of MMP-7 mRNA by RT-PCR in aorta rings cocultured with gingival fibroblasts. Interestingly, in contrast with other MMPs (which were not influenced at a transcription level), GF stimulated the release of TGF-beta1, which in turn inhibited the transcription and synthesis of MMP-7, as shown by neutralizing MMP-7 inhibition due to gingival fibroblast by overexpressing decorin (a TGF beta 1 inhibitor) or by silencing TGF beta 1 using siRNA. We showed that healing properties of the GF could be transposed to another organ, i.e., ex vivo aneurism model, implicating a down-regulation of MMP-7.

Objectives This study was designed to study the behavior of a stent deployed inside human stenotic aortic valves. Background Endovascular valved stent (VS) implantation is a promising new therapy for patients with severe calcific aortic stenosis (AS). The precise characteristics of stent deployment in humans have been poorly studied so far. Methods Thirty-five patients with severe AS were included in the study. Sixteen patients (46%) had bicuspid aortic valves. A self-expandable stent specifically designed for VS implantation was deployed intraoperatively inside the aortic valve before surgical aortic valve replacement. Results In tricuspid aortic valves, the shape of stent deployment was circular, triangular, or elliptic in 68%, 21%, or 11%, respectively. Noncircular stent deployment was frequent in bicuspid aortic valves (the elliptic deployment being the rule [79%]), and stent underdeployment was constant. The incidence of gaps between the stent external surface and the aortic valve did not differ between tricuspid and bicuspid valves (58% vs. 43%; p = 0.49). Sharp calcific excrescences protruding inside the stent lumen were present in 3 cases (9%). Ex vivo study of a homemade VS confirmed that the regularity of the coaptation line of the leaflets was critically dependent on the presence or the absence of stent misdeployment. Conclusions Stent misdeployment was constant in bicuspid valves and occurred in one-third of cases of tricuspid valves. Premature failure of implanted VS (secondary to valve distortion or traumatic injury to the leaflets by calcific excrescences) might be an important concern in the future.

Publication Inra prise en compte dans l'analyse bibliométrique des publications scientifiques mondiales sur les Fruits, les Légumes et la Pomme de terre. Période 2000-2012. http://prodinra.inra.fr/record/256699; International audience; Radopholus similis is a worldwide endoparasitic nematode that greatly hampers banana (Musa acuminata, Cavendish subgroup) productivity. Earthworms are known to closely interact with above-ground and under-ground soil biota and particularly with plants and microfaunal communities. This study was aimed at investigating, under greenhouse conditions, the effects of the earthworm Pontoscolex corethrurus on banana growth and nutrient uptake, and assessing the influences of this earthworm on the development of an inoculated population of R. similis. Six-week-old tissue culture banana plants were submitted to four treatments: with P. corethrurus, R. similis, P. corethrurus+R. similis, and a control with no earthworms or nematodes. At the end of the experiment, the P. corethrurus treatments showed significantly higher leaf surface areas, shoot dry root weights, and root fresh weights than those without earthworms. This root growth enhancement probably contributed to the evident but non-significant decrease in the density of nematodes in the roots, even though earthworms did not reduce the total number of nematodes per whole root system. Moreover, the presence of earthworms slightly alleviated the severity of root damage. N bioavailability in the soil, along with N, Ca, and Mg content of banana plants, were also significantly increased in the presence of earthworms. Our results demonstrated that banana plant growth and nutrition were positively influenced by earthworms. Cropping practices that boost the development of earthworm communities in soil should therefore be promoted to enhance sustainability and to naturally alleviate nematode impact.

Although drug-eluting stents (DES) have greatly reduced arterial restenosis, there are persistent concerns about stent thrombosis. DES thrombosis is attributable to retarded vascular re-endothelialization due to both stent-induced flow disturbance and the inhibition by the eluted drug of endothelial cell proliferation and migration. The present computational study aims to determine the effect of DES design on both stent-induced flow disturbance and the concentration of eluted drug at the arterial luminal surface. To this end, we consider three closed-cell stent designs that resemble certain commercial stents as well as three "idealized" stents that provide insight into the impact of specific characteristics of stent design. To objectively compare the different stents, we introduce the Stent Penalty Index (SPI), a dimensionless quantity whose value increases with both the extent of flow disturbance and luminal drug concentration. Our results show that among the three closed-cell designs studied, wide cell designs lead to lower SPI and are thus expected to have a less adverse effect on vascular re-endothelialization. For the idealized stent designs, a spiral stent provides favorable SPI values, whereas an intertwined ring stent leads to an elevated SPI. The present findings shed light onto the effect of stent design on the concentration of the eluted drug at the arterial luminal surface, an important consideration in the assessment of DES performance.

Aortic aneurysms (AAs) consist of slow proteolysis and loss of both collagen and elastin matrix in the aorta wall, leading to wall dilation, weakening and rupture in well-advanced lesions. This can occur in both abdominal aorta (Abdominal Aortic Aneurysm: AAA) and thoracic aorta (Thoracic Aortic Aneurysm: TAA). To date, no non-surgical therapy has been proposed to slow or stop AA progression. Previously published preclinical studies from our team using an aneurysm rabbit model showed a promising concept for treatment of AAs with gingival fibroblast (GFs) which are readily available cells. In this study, we investigated the possible tissue repair of human AAAs and TAAs using ex vivo models co-cultured with GFs. Histological analysis showed that TAA and AAA are two distinct pathologies. Both lesions presented destruction of the aorta wall, highly evidenced in AAA samples. The results have confirmed the presence of the bacterial Porphyromonas gingivalis (Pg) protein in all AAA samples, but not in TAA samples, indicating the possible role of an infectious factor in the developing and progression of AAA lesions compared to TAA. The co-culture of GFs with AA lesions shows increased expression of TIMP-1, the inhibitor of the aneurysm severity marker MMP-9. Our study indicates that GFs might ameliorate aorta wall reestablishment in both AA types by their regenerative and immunomodulatory capacities. It also demonstrates the possible infectious cause of AAA compared with TAA that may explain their different behavior. Electronic supplementary material The online version of this article (doi:10.1186/s40064-015-0976-9) contains supplementary material, which is available to authorized users.

International audience; Mesenchymal stem cell (MSC) therapy has recently been investigated as a potential treatment for cutaneous radiation burns. We tested the hypothesis that injection of local gingival fibroblasts (GFs) would promote healing of radiation burn lesions and compared results with those for MSC transplantation. Human clinical-grade GFs or bone marrow-derived MSCs were intradermally injected into mice 21 days after local leg irradiation. Immunostaining and real-time PCR analysis were used to assess the effects of each treatment on extracellular matrix remodeling and inflammation in skin on days 28 and 50 postirradiation. GFs induced the early development of thick, fully regenerated epidermis, skin appendages, and hair follicles, earlier than MSCs did. The acceleration of wound healing by GFs involved rearrangement of the deposited collagen, modification of the Col/MMP/TIMP balance, and modulation of the expression and localization of tenascin-C and of the expression of growth factors (VEGF, EGF, and FGF7). As MSC treatment did, GF injection decreased the irradiation-induced inflammatory response and switched the differentiation of macrophages toward an M2-like phenotype, characterized by CD163+ macrophage infiltration and strong expression of arginase-1. These findings indicate that GFs are an attractive target for regenerative medicine, for easier to collect, can grow in culture, and promote cutaneous wound healing in irradiation burn lesions. © 2015, Mary Ann Liebert, Inc.

Atherosclerosis results from accumulation of macrophages and extracellular matrix in the arterial wall. Decorin, a small matrix proteoglycan, is able to regulate cell proliferation, migration and growth factors' activity. We investigated the effect of decorin overexpression on atherosclerosis progression in apolipoprotein E-deficient (ApoE(-/-)) mice. Female ApoE(-/-) mice, 10 weeks old (early treatment, n = 20) and 20 weeks old (delayed treatment, n = 20) were administered intravenously with either an adenovirus (2.5 x 10(9) plaque-forming units/mouse) containing human decorin gene (Ad-Dcn) or beta-galactosidase (LacZ), or PBS. Transgenic decorin was mainly expressed in the liver, and was secreted in the plasma up to 4 weeks. Six weeks after treatment, no significant difference in aortic root lesion size was observed between LacZ- and PBS-control groups. In contrast, Ad-Dcn-treated mice showed significantly reduced atherosclerotic lesions as compared to controls in both early and delayed treatment groups (2.9 +/- 1.1% versus 5.5 +/- 0.4%; p = 0.004 and 13.4 +/- 1.3% versus 19.9 +/- 1.41%; p = 0.009, respectively). In parallel, macrophage, gelatinase activity and collagen plaque content were also reduced. Interestingly, plasma triglycerides were reduced and decorin formed complexes with transforming growth factor-beta1 (TGF-beta1) that resulted in reduced circulating free-TGF-beta1. In conclusion, systemic overexpression of decorin reduces inflammation, triglycerides and fibrosis in atherosclerotic plaques of ApoE(-/-) mice resulting in slowing down of disease progression.

Objective— Circulating progenitors and stem cells have been reported to contribute to angiogenesis and arterial repair after injury. In the present study, we investigated whether the arterial wall could host permanently residing progenitor cells under physiological context. Methods and Results— Using the Hoechst-based flow cytometry method, we identified and isolated progenitor cells termed side population (SP) cells at a prevalence of 6.0±0.8% in the tunica media of adult mice aortas. Arterial SP cells expressed the ATP-binding cassette transporter subfamily G member 2, frequently present on SP cell surface, and displayed a Sca-1 + c-kit −/low Lin − CD34 −/low profile. They did not form myeloid or lymphoid hematopoietic colonies after plating in methylcellulose-based medium. Importantly, cultured SP cells were able to acquire the phenotype of endothelial cells (CD31, VE-cadherin, and von Willebrand factor expression) or of smooth muscle cells (α-smooth muscle actin, calponin, and smooth muscle myosin heavy chain expression), in presence of either vascular endothelial growth factor or transforming growth factor (TGF)-β1/PDGF-BB, respectively. Moreover, they generated vascular-like branching structures, composed of both VE-cadherin + cells and α-smooth muscle actin + cells on Matrigel. Conclusions— In this study, we provide the first evidence to our knowledge that in the adult mice, the normal arterial wall harbors SP cells with vascular progenitor properties.

Plasma homocysteine is a modifiable cardiovascular risk factor related to the extent of both coronary and carotid atherosclerosis (1)(2)(3)(4). Plasma homocysteine has been shown to predict the occurrence of cardiac events and mortality in patients with coronary atherosclerosis (5)(6)(7). The predictive value of homocysteine on restenosis after percutaneous coronary intervention (PCI) has been debated (8)(9)(10). Recent evidence, however, indicated that the pre-PCI homocysteine plasma concentration was an independent predictor of death, nonfatal myocardial infarction (MI), and target lesion revascularization (11). Cardiac troponins provide prognostic information in patients with acute coronary syndrome (ACS) (12). Several studies have demonstrated that PCI induces MI as assessed by increases in cardiac troponins, particularly in the case of ACS (13)(14)(15). Furthermore, increased cardiac troponin concentrations after PCI are associated with poor clinical outcome (16)(17)(18)(19). We therefore hypothesized that the pre-PCI plasma homocysteine concentration could be related to the occurrence of MI after PCI, as assessed by changes in plasma cardiac troponin I (cTnI) concentration. Consecutive admissions for nonemergency PCI were studied prospectively. All patients had a stenosis >70% in 1 or more coronary arteries. Two groups were examined: patients with stable angina (SA) pain and those with ACS. The SA pain group had myocardial ischemia during exercise stress testing (n = 29). The ACS group included patients admitted with unstable angina without a subsequent increase in troponin concentrations (n = 28) and those with a definite MI with a documented cTnI increase and electrocardiogram changes that had occurred 7–14 days previously (n = 39). Patients with inflammatory diseases, as well as those being treated with corticosteroids or nonsteroidal antiinflammatory or immunosuppressive drugs, were excluded to minimize potential bias. This study complies …

Aims This study was designed to assess the functional effects of a transvenous coronary sinus technique of skeletal myoblast delivery in infarcted myocardium. Methods and results An anterior myocardial infarction was created percutaneously in 14 sheep. Simultaneously, a muscle biopsy was harvested and expanded. Two weeks later, sheep were instrumented percutaneously with a dedicated catheter incorporating an extendable needle for puncture of the venous wall and, under endovascular ultrasound guidance, a microcatheter was advanced through the needle into the target scar for cell delivery. Following the baseline echocardiographic assessment of left ventricular (LV) function, sheep were randomly allocated to receive four-staged in-scar injections of either autologous cells (n ¼ 7) or culture medium (n ¼ 7). Two months later, LV function was reassessed blindly and hearts were explanted for subsequent histological and immunohistochemical analysis. There were no acute procedural complications. Baseline LV ejection fraction (EF) was significantly lower in transplanted sheep than in controls [38% (35‐48) vs. 51% (38‐55), respectively, P ¼ 0.03; median (range)]. Two months later, LVEF was significantly higher in the transplanted group than in controls [50% (47‐56) vs. 39% (36‐47), respectively, P ¼ 0.002]. Clusters of myoblasts were identified by histology and immunohistochemistry in three of the seven transplanted sheep. Conclusion These data suggest the functional efficacy of the transvenous coronary sinus technique as a less invasive means of cell delivery to infarcted myocardium.

Background: Reactive oxygen species (ROS) production increases after injury and potentially contributes to restenosis after angioplasty. We therefore evaluated the effect of adenovirus-mediated gene transfer (Ad) of superoxide dismutase (SOD) and catalase (CAT) on ROS production and restenosis after balloon angioplasty. Methods: O2– and H2O2 production was quantified in cultured cells after incubation with either LPS or CuSO4. Angioplasty and gene transfer were performed in rabbit atherosclerotic iliac arteries. One artery was injected with AdSOD and AdCAT, while the contralateral artery was injected with an adenovirus carrying no transgene, and served as control. Results: ROS production was significantly decreased after adenovirus-mediated gene transfer of SOD and CAT as compared with control. Treated arteries showed less restenosis (32 ± 27 vs. 63 ± 19%, p = 0.003) and less constrictive remodeling (1.2 ± 0.3 vs. 0.9 ± 0.2, p = 0.02) than control arteries. Arteries injected with AdSOD and AdCAT showed better vasoreactivity to acetylcholine (11 ± 4 vs. –1 ± 6%, p < 0.05), lower collagen density (43 ± 16 vs. 53 ± 23%, p = 0.03), and lower inflammatory cell infiltration (22 ± 6 vs. 36 ± 11%, p = 0.04) than control arteries. Conclusions: Our data suggest that adenovirus-mediated gene transfer of SOD and CAT reduced oxidative stress, restenosis, collagen accumulation, and inflammation and improved endothelial function after angioplasty.

Toxic epidermal necrolysis (TEN) and Stevens-Johnson syndrome (SJS) are considered to be drug-induced diseases, and are characterized by extensive mucocutaneous disorder and epidermal necrosis which result in the detachment of the epidermis. Inactive and active forms of metalloproteinases (MMP2 and MMP9) secreted by skin explants maintained in organ culture for 72 h and in blister fluid from two TEN and three SJS patients were investigated. Interestingly, lesional skin from both the TEN and the SJS patients cultured for 3 days in conditioned medium showed high levels of both 72 kDa progelatinase A and 66 kDa activated gelatinase A, and the 66 kDa activated form was not observed in cultures of skin from control individuals. Furthermore, indirect immunodetection showed the presence of MMP2 and MMP9 in TEN and SJS patients' skin. Increased gelatinase activity in the culture medium of TEN and SJS skin maintained in organ culture and in blister fluid indicates that these gelatinases may be responsible for the detachment of the epidermis in these drug-induced necrolyses.

Background— The mechanisms of thrombosis on plaque erosion are poorly understood. We examined the potential role of endothelial apoptosis in endothelial erosion and vessel thrombosis. Methods and Results— Segments of New Zealand White rabbit femoral arteries were temporarily isolated in vivo. One artery was incubated with staurosporin for 30 minutes, whereas the contralateral artery was incubated with saline and served as control. Three days later, thrombosis was evaluated angiographically and histologically. TUNEL score in the endothelial layer was significantly increased in staurosporin-treated arteries compared with controls (2.43±0.30 versus 0.93±0.44, respectively; P =0.001). Large areas of endothelial denudation were detectable in staurosporin-treated vessels, whereas endothelium integrity was almost preserved in the saline group. Vessel thrombosis occurred in 58% of staurosporin-treated arteries (7 of 12) but in only 8% of saline-treated segments ( P P =0.04). These results were confirmed in balloon-injured atheromatous arteries. Conclusions— In vivo induction of endothelial apoptosis leads to both vessel thrombosis and endothelial denudation. Endothelial apoptosis may be a critical step in the transition from a stable endothelialized plaque to plaque erosion and thrombosis.

Why are bioresorbable scaffolds so exciting? Simply because they fulfil the task of scaffolding the artery wall during the healing period, and thereafter vanish. In other words, their lifetime is adjusted to the healing process, thus avoiding any risk of causing a new disease (eg, late thrombosis, in-stent restenosis, or neoatherosclerosis) as can happen with permanent stents. Permanent stents do a perfect scaffolding job, but remain in place when they are no longer necessary, leading to a foreign body reaction with complications.

Background— Incomplete ST-segment resolution (STR) after successful primary angioplasty for acute myocardial infarction (AMI) is associated with a poor prognosis. We used intracoronary Doppler velocimetry to investigate whether incomplete STR after primary angioplasty is a marker of severe microcirculatory dysfunction. Methods and Results— Fifty patients with ≤12-hour AMI underwent successful primary angioplasty and systematic stenting with a Doppler guidewire. Patients with incomplete (P =0.007) and lower coronary flow velocity reserve (CVR, 1.3 versus 1.6, P P =0.001) and regional (16% versus 20%, P =0.03) left ventricular ejection fractions and 201 Tl rest-redistribution scintigraphy indicated a larger infarct size (34% versus 16% 201 Tl defect, P =0.007) in patients with Conclusions— After successful primary angioplasty with systematic stenting

Decorin is a small leucine-rich proteoglycan that plays a role in control of cell proliferation, cell migration, collagen fibrillogenesis and modulation of the activity of TGF-beta. In the present study, we investigated the effects of decorin on the production of metalloproteinases (MMP-1, -2, -3, -9 and -13), tissue inhibitors of metalloproteinases (TIMP-1, -2) and cytokines (TGF-beta, IL-1beta, IL-4 and TNF-alpha). Decorin was overexpressed in cultured human gingival fibroblasts using adenovirus-mediated gene transfer. Decorin infection resulted in decreased protein levels of MMP-1 and MMP-3 whereas MMP-2 and TIMP-2 secretion was increased. MMP-9, MMP-13 and TIMP-1 were not affected by decorin infection. Cytokine measurements by ELISA showed that decorin overexpression reduced TGF-beta and IL-1beta. In contrast, IL-4 and TNF-alpha levels were markedly increased in decorin-infected cells. These results suggest that decorin could modulate the expression of certain metalloproteinases and their inhibitors, as well as the production of cytokines. Altogether, our data suggest that decorin might play a pivotal role in tissue remodeling by acting on the balance between extracellular matrix synthesis and degradation.

Animal models of stenting probably predict human responses as the stages of healing are remarkably similar. What is characteristically different is the temporal response to healing, which is substantially prolonged in humans. The prevention of restenosis in recent clinical trials of drug eluting stents may represent a near absent or incomplete phase of intimal healing. Continued long term follow up of patients with drug eluting stents for major adverse cardiac events and angiographic restenosis is therefore imperative.