Fractional Flow Reserve to Guide Treatment of Patients With Multivessel Coronary Artery Disease.

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).

First-in-Man trial of a drug-free bioresorbable stent designed to minimize the duration of coronary artery scaffolding.

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.

Out-of-hospital cardiac arrest during the COVID-19 pandemic in Paris, France: a population-based, observational study.

BACKGROUND: Although mortality due to COVID-19 is, for the most part, robustly tracked, its indirect effect at the population level through lockdown, lifestyle changes, and reorganisation of health-care systems has not been evaluated. We aimed to assess the incidence and outcomes of out-of-hospital cardiac arrest (OHCA) in an urban region during the pandemic, compared with non-pandemic periods. METHODS: We did a population-based, observational study using data for non-traumatic OHCA (N=30 768), systematically collected since May 15, 2011, in Paris and its suburbs, France, using the Paris Fire Brigade database, together with in-hospital data. We evaluated OHCA incidence and outcomes over a 6-week period during the pandemic in adult inhabitants of the study area. FINDINGS: Comparing the 521 OHCAs of the pandemic period (March 16 to April 26, 2020) to the mean of the 3052 total of the same weeks in the non-pandemic period (weeks 12-17, 2012-19), the maximum weekly OHCA incidence increased from 13·42 (95% CI 12·77-14·07) to 26·64 (25·72-27·53) per million inhabitants (p<0·0001), before returning to normal in the final weeks of the pandemic period. Although patient demographics did not change substantially during the pandemic compared with the non-pandemic period (mean age 69·7 years [SD 17] vs 68·5 [18], 334 males [64·4%] vs 1826 [59·9%]), there was a higher rate of OHCA at home (460 [90·2%] vs 2336 [76·8%]; p<0·0001), less bystander cardiopulmonary resuscitation (239 [47·8%] vs 1165 [63·9%]; p<0·0001) and shockable rhythm (46 [9·2%] vs 472 [19·1%]; p<0·0001), and longer delays to intervention (median 10·4 min [IQR 8·4-13·8] vs 9·4 min [7·9-12·6]; p<0·0001). The proportion of patients who had an OHCA and were admitted alive decreased from 22·8% to 12·8% (p<0·0001) in the pandemic period. After adjustment for potential confounders, the pandemic period remained significantly associated with lower survival rate at hospital admission (odds ratio 0·36, 95% CI 0·24-0·52; p<0·0001). COVID-19 infection, confirmed or suspected, accounted for approximately a third of the increase in OHCA incidence during the pandemic. INTERPRETATION: A transient two-times increase in OHCA incidence, coupled with a reduction in survival, was observed during the specified time period of the pandemic when compared with the equivalent time period in previous years with no pandemic. Although this result might be partly related to COVID-19 infections, indirect effects associated with lockdown and adjustment of health-care services to the pandemic are probable. Therefore, these factors should be taken into account when considering mortality data and public health strategies. FUNDING: The French National Institute of Health and Medical Research (INSERM).

Low rates of immediate coronary angiography among young adults resuscitated from sudden cardiac arrest.

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.

Cardiac Pacing in Sub-Saharan Africa: JACC International.

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.

Femoral Versus Nonfemoral Peripheral Access for Transcatheter Aortic Valve Replacement.

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.

Carotid versus femoral access for transcatheter aortic valve implantation: a propensity score inverse probability weighting study.

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 < 0.001), ST-elevation myocardial infarction (OR 7.32, 95% CI 3.87-13.87; P < 0.001), infections (OR 2.36, 95% CI 2.04-2.71; P < 0.001), bleeding (OR 2.01, 95% CI 1.76-2.29; P < 0.001), renal failure (OR 2.23, 95% CI 1.90-2.60; P < 0.001) and need for dialysis (OR 2.36, 95% CI 2.01-2.76, P < 0.001). Conversely, TC-TAVI was not confirmed as a risk factor for pacemaker implantation after adjustment (OR 1.05, 95% CI 0.96-1.15; P < 0.28) and was a protective factor for vascular complications (OR 0.37, 95% CI 0.32-0.43; P < 0.001). 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.

Transcarotid Approach for Transcatheter Aortic Valve Replacement With the Sapien 3 Prosthesis: A Multicenter French Registry.

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.

Transcarotid Compared With Other Alternative Access Routes for Transcatheter Aortic Valve Replacement.

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<0.001). 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.

Comparison of a Drug-Free Early Programmed Dismantling PDLLA Bioresorbable Scaffold and a Metallic Stent in a Porcine Coronary Artery Model at 3-Year Follow-Up.

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.

Gingival fibroblasts protect against experimental abdominal aortic aneurysm development and rupture through tissue inhibitor of metalloproteinase-1 production.

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-ß, 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-ß 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.

Drug-Eluting Stent Design is a Determinant of Drug Concentration at the Endothelial Cell Surface.

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.