Mitral transcatheter edge-to-edge repair vs. isolated mitral surgery for severe mitral regurgitation: a French nationwide study.

BACKGROUND AND AIMS: Mitral valve surgery and, more recently, mitral transcatheter edge-to-edge repair (TEER) are the two treatments of severe mitral regurgitation in eligible patients. Clinical comparison of both therapies remains limited by the number of patients analysed. The objective of this study was to analyse the outcomes of mitral TEER vs. isolated mitral valve surgery at a nationwide level in France. METHODS: Based on the French administrative hospital discharge database, the study collected information for all consecutive patients treated for mitral regurgitation with isolated TEER or isolated mitral valve surgery between 2012 and 2022. Propensity score matching was used for the analysis of outcomes. RESULTS: A total of 57 030 patients were found in the database. After matching on baseline characteristics, 2160 patients were analysed in each arm. At 3-year follow-up, TEER was associated with significantly lower incidence of cardiovascular death (hazard ratio 0.685, 95% confidence interval 0.563-0.832; P = .0001), pacemaker implantation, and stroke. Non-cardiovascular death (hazard ratio 1.562, 95% confidence interval 1.238-1.971; P = .0002), recurrent pulmonary oedema, and cardiac arrest were more frequent after TEER. No significant differences between the two groups were observed regarding all-cause death (hazard ratio 0.967, 95% confidence interval 0.835-1.118; P = .65), endocarditis, major bleeding, atrial fibrillation, and myocardial infarction. CONCLUSIONS: Our results suggest that TEER for severe mitral regurgitation was associated with lower cardiovascular mortality than mitral surgery at long-term follow-up. Pacemaker implantation and stroke were less frequently observed after TEER.

Net clinical benefit of dual antiplatelet therapy in elderly patients with acute coronary syndrome: A systematic review and meta-analysis.

BACKGROUND: Contemporary dual antiplatelet therapy (DAPT) strategies, such as short-term DAPT or de-escalation of DAPT, have emerged as attractive strategies to treat patients with acute coronary syndrome (ACS). However, it remains uncertain whether they are suitable for elderly patients. METHODS: PubMed, Embase, and Cochrane CENTRAL databases were searched in September 2022. Randomized controlled trials (RCTs) investigating DAPT strategies, including standard (12 months), short-term, uniform de-escalation, and guided-selection strategies for elderly patients with ACS (age ≥ 65 years) were identified, and a network meta-analysis was conducted. The primary endpoint was the net clinical benefit outcome, a composite of major adverse cardiovascular events (MACEs: cardiovascular death, myocardial infarction, or stroke) and clinically relevant bleeding (equivalent to bleeding of at least type 2 according to the Bleeding Academic Research Consortium). The secondary outcomes were MACE and major bleeding. RESULTS: Sixteen RCTs with a combined total of 47,911 patients were included. The uniform de-escalation strategy was associated with an improved net clinical benefit compared with DAPT using potent P2Y12 inhibitors. The short-term DAPT strategy was associated with reduced risks of the primary outcome and major bleeding compared with DAPT using potent P2Y12 inhibitors, however, it was ranked as the least effective strategy for MACE compared with other DAPT strategies. CONCLUSIONS: Uniform de-escalation and short-term DAPT strategies may be advantageous for elderly patients, but need to be tailored based on individual bleeding and ischemic risks. Further RCTs of contemporary DAPT strategies specifically designed for elderly patients are warranted to confirm the findings of the present study.

The everolimus eluting Synergy MegatronTM drug-eluting stent platform: Early outcomes from the European Synergy MegatronTM Implanters' Registry.

BACKGROUND: The Synergy MegatronTM is an everolimus-drug eluting stent that may offer advantages in the treatment of aorto-ostial disease and large proximal vessels. AIMS: To report the short- to medium-term clinical outcomes from the European Synergy MegatronTM Implanters' Registry. METHODS: This registry was an investigator-initiated study conducted at 14 European centers. The primary outcome was target lesion failure (TLF), defined as the composite of cardiovascular death, target vessel myocardial infarction (MI), and target lesion revascularisation. RESULTS: Five hundred seventy-five patients underwent PCI with MegatronTM between 2019 and 2021. Patients were 69 ± 12 years old, 26% had diabetes mellitus, 24% had moderate-severe left ventricular impairment and 59% presented with an acute coronary syndrome. 15% were deemed prohibitively high risk for surgical revascularisation. The target vessel involved the left main stem in 55%, the ostium of the RCA in 13% and was a true bifurcation (Medina 1,1,1) in 50%.  At 1 year, TLF was observed in 40 patients, with 26 (65%) occurring within the first 30 days. The cumulative incidence of TLF was 4.5% at 30 days and 8.6% (95% CI 6.3-11.7) at 1 year. The incidence of stent thrombosis was 0.5% with no late stent thromboses. By multivariate analysis, the strongest independent predictors of TLF were severe left ventricular impairment (HR 3.43, 95% CI: 1.67-6.76, p < 0.001) and a target vessel involving the left main (HR 4.00 95% CI 1.81-10.15 p = 0.001). CONCLUSIONS: Use of the Synergy MegatronTM everolimus eluting stent in a 'real-world' setting shows favorable outcomes at 30 days and 1 year.

Valve-in-valve transcatheter aortic valve replacement or re-surgical aortic valve replacement in degenerated bioprostheses: A systematic review and meta-analysis of short and midterm results.

INTRODUCTION: Despite limited to short and midterm outcomes, valve-in-valve (ViV) transcatheter aortic valve implantation (TAVI) has emerged as a valid alternative to re-surgical aortic valve replacement (re-SAVR) for high- and intermediate-risk patients with degenerated surgical bioprosthesis. METHODS: All studies comparing multivariate adjustment between ViV TAVI and re-SAVR were screened. The primary end-points were all-cause and cardiovascular (CV) mortality at 30 days and at Midterm follow-up. Short-term complications were the secondary endpoints. RESULTS: We obtained data from 11 studies, encompassing 8570 patients, 4224 undergoing ViV TAVI, and 4346 re-SAVR. Four studies included intermediate-risk patients and seven high-risk patients. 30-day all-cause and CV mortality were significantly lower in ViV (odds ratio [OR] 0.43, 95% confidence intervals [CIs] 0.29-0.64 and OR 0.44, 0.26-0.73 respectively), while after a mean follow-up of 717 (180-1825) days, there was no difference between the two groups (OR 1.04, 0.87-1.25 and OR 1.05, 0.78-1.43, respectively). The risk of stroke (OR 1.03, 0.59-1.82), MI (OR 0.70, 0.34-1.44), major vascular complications (OR 0.92, 0.50-1.67), and permanent pacemaker implantation (OR 0.67, 0.36-1.25) at 30 days did not differ, while major bleedings and new-onset atrial fibrillation were significantly lower in ViV patients (OR 0.41, 0.25-0.67 and OR 0.23, 0.12-0.42, respectively, all 95% CIs). CONCLUSIONS: In high- and intermediate-risk patients with degenerated surgical bioprostheses, ViV TAVI is associated with reduced short-term mortality, compared with re-SAVR. Nevertheless, no differences were found in all-cause and CV mortality at midterm follow-up. PROSPERO CRD42021226488.

Impact of Sapien 3 Balloon-Expandable Versus Evolut R Self-Expandable Transcatheter Aortic Valve Implantation in Patients With Aortic Stenosis: Data From a Nationwide Analysis.

BACKGROUND: Two competing transcatheter aortic valve replacement (TAVR) technologies are currently available. Head-to-head comparisons of the relative performances of these 2 devices have been published. However, long-term clinical outcome evaluation remains limited by the number of patients analyzed, in particular, for recent-generation devices. METHODS: Based on the French administrative hospital-discharge database, the study collected information for all consecutive patients treated with a TAVR device commercialized in France between 2014 and 2018. Propensity score matching was used for the analysis of outcomes during follow-up. The objective of this study was to analyze the outcomes of TAVR according to Sapien 3 balloon-expandable (BE) versus Evolut R self-expanding TAVR technology at a nationwide level in France. RESULTS: A total of 31 113 patients treated with either Sapien 3 BE or Evolut R self-expanding TAVR were found in the database. After matching on baseline characteristics, 20 918 patients were analyzed (10 459 in each group with BE or self-expanding valves). During follow-up (mean [SD], 358 [384]; median [interquartile range], 232 [10-599] days), BE TAVR was associated with a lower yearly incidence of all-cause death (relative risk, 0.88; corrected P=0.005), cardiovascular death (relative risk, 0.82; corrected P=0.002), and rehospitalization for heart failure (relative risk, 0.84; corrected P<0.0001). BE TAVR was also associated with lower rates of pacemaker implantation after the procedure (relative risk, 0.72; corrected P<0.0001). CONCLUSIONS: On the basis of the largest cohort available, we observed that Sapien 3 BE valves were associated with lower rates of all-cause death, cardiovascular death, rehospitalization for heart failure, and pacemaker implantation after a TAVR procedure.

Rapid deployment versus trans-catheter aortic valve replacement in intermediate-risk patients: A propensity score analysis.

BACKGROUND: There are insufficient studies comparing rapid deployment aortic valve replacement (RDAVR) and trans-aortic valve replacement (TAVR) in intermediate-risk patients with severe aortic stenosis (AS). AIMS: We compared 2-year outcomes between RDAVR with INTUITY and TAVR with SAPIEN 3 in intermediate-risk patients with AS. METHODS: Inclusion criteria were patients with severe AS at a EuroSCORE II ≥ 4%, who received RDAVR or TAVR implantation and clinical evaluation by the Heart Team. Regression adjustment for the propensity score was used to compare RDAVR and TAVR. Primary outcome was the composite criterion of death, disabling stroke, or rehospitalization. SECONDARY OUTCOMES: major bleeding complications postoperation, paravalvular regurgitation ≥ 2, patient-prosthesis mismatch, and pacemaker implantation. RESULTS: A total of 152 patients were included from 2012 to 2018: 48 in the RDAVR group and 104 in the TAVR group. The mean age was 82.7 ± 6.0,51.3% patients were female, the mean EuroSCORE II was 6.03 ± 1.6%, mean baseline LVEF was 56 ± 13%, mean indexed effective orifice area was 0.41 ± 0.1 cm/m2 , and the mean gradient was 51.7 ± 14.7 mmHg. RDAVR patients were younger (79.5 ± 6 years vs. 82.6 ± 6 years; p = .01), and at higher risk (EuroSCORE II, 6.61 ± 1.8% vs. 5.63 ± 1.5%; p = .005), Twenty-two patients (45.99%) in the RDAVR group and 32 (66.67%) in the TAVR group met the composite criterion. Through the 1:1 propensity score matching analysis, there was a significant difference between the groups, favoring RDAVR (HR = 0.58 [95% CI: 0.34-1.00]; p = .04). No differences were observed in terms of patient-prosthesis mismatch (0.83 [0.35-1.94]; p = .67), major bleeding events (1.33 [0.47-3.93]; p = .59), paravalvular regurgitation ≥ 2 (0.33[0-6.28]; p = .46), or pacemaker implantation (0.84 [0.25-2.84]; p = .77) CONCLUSION: RDAVR was associated with better 2-year outcomes than TAVR in intermediate-risk patients with severe symptomatic AS.

Hyperhomocysteinemia and Cardiovascular Disease: Is the Adenosinergic System the Missing Link?

The influence of hyperhomocysteinemia (HHCy) on cardiovascular disease (CVD) remains unclear. HHCy is associated with inflammation and atherosclerosis, and it is an independent risk factor for CVD, stroke and myocardial infarction. However, homocysteine (HCy)-lowering therapy does not affect the inflammatory state of CVD patients, and it has little influence on cardiovascular risk. The HCy degradation product hydrogen sulfide (H2S) is a cardioprotector. Previous research proposed a positive role of H2S in the cardiovascular system, and we discuss some recent data suggesting that HHCy worsens CVD by increasing the production of H2S, which decreases the expression of adenosine A2A receptors on the surface of immune and cardiovascular cells to cause inflammation and ischemia, respectively.

Adenosine Receptor Reserve and Long-Term Potentiation: Unconventional Adaptive Mechanisms in Cardiovascular Diseases?

While the concept of a receptor reserve (spare receptors) is old, their presence on human cells as an adaptive mechanism in cardiovascular disease is a new suggestion. The presence of spare receptors is suspected when the activation of a weak fraction of receptors leads to maximal biological effects, in other words, when the half-maximal effective concentration (EC50) for a biological effect (cAMP production, for example) is lower than the affinity (KD) of the ligand for a receptor. Adenosine is an ATP derivative that strongly impacts the cardiovascular system via its four membrane receptors, named A1R, A2AR, A2BR, and A3R, with the A1R being more particularly involved in heart rhythm, while the A2AR controls vasodilation. After a general description of the tools necessary to explore the presence of spare receptors, this review focuses on the consequences of the presence of spare adenosine receptors in cardiovascular physiopathology. Finally, the role of the adenosinergic system in the long-term potentiation and its possible consequences on the physiopathology are also mentioned.

Homocysteine concentration and adenosine A2A receptor production by peripheral blood mononuclear cells in coronary artery disease patients.

Hyperhomocysteinemia is associated with coronary artery disease (CAD). The mechanistic aspects of this relationship are unclear. In CAD patients, homocysteine (HCy) concentration correlates with plasma level of adenosine that controls the coronary circulation via the activation of adenosine A2A receptors (A2A R). We addressed in CAD patients the relationship between HCy and A2A R production, and in cellulo the effect of HCy on A2A R function. 46 patients with CAD and 20 control healthy subjects were included. We evaluated A2A R production by peripheral blood mononuclear cells using Western blotting. We studied in cellulo (CEM human T cells) the effect of HCy on A2A R production as well as on basal and stimulated cAMP production following A2A R activation by an agonist-like monoclonal antibody. HCy concentration was higher in CAD patients vs controls (median, range: 16.6 [7-45] vs 8 [5-12] µM, P < 0.001). A2A R production was lower in patients vs controls (1.1[0.62-1.6] vs 1.53[0.7-1.9] arbitrary units, P < 0.001). We observed a negative correlation between HCy concentration and A2A R production (r = -0.43; P < 0.0001), with decreased A2A R production above 25 µM HCy. In cellulo, HCy inhibited A2A R production, as well as basal and stimulated cAMP production. In conclusion, HCy is negatively associated with A2A R production in CAD patients, as well as with A2A R and cAMP production in cellulo. The decrease in A2A R production and function, which is known to hamper coronary blood flow and promote inflammation, may support CAD pathogenesis.

Adenosine and Its Receptors: An Expected Tool for the Diagnosis and Treatment of Coronary Artery and Ischemic Heart Diseases.

Adenosine is an endogenous nucleoside which strongly impacts the cardiovascular system. Adenosine is released mostly by endothelial cells and myocytes during ischemia or hypoxia and greatly regulates the cardiovascular system via four specific G-protein-coupled receptors named A1R, A2AR, A2BR, and A3R. Among them, A2 subtypes are strongly expressed in coronary tissues, and their activation increases coronary blood flow via the production of cAMP in smooth muscle cells. A2A receptor modulators are an opportunity for intense research by the pharmaceutical industry to develop new cardiovascular therapies. Most innovative therapies are mediated by the modulation of adenosine release and/or the activation of the A2A receptor subtypes. This review aims to focus on the specific exploration of the adenosine plasma level and its relationship with the A2A receptor, which seems a promising biomarker for a diagnostic and/or a therapeutic tool for the screening and management of coronary artery disease. Finally, a recent class of selective adenosine receptor ligands has emerged, and A2A receptor agonists/antagonists are useful tools to improve the management of patients suffering from coronary artery disease.

Adenosine plasma level in patients with paroxysmal or persistent atrial fibrillation and normal heart during ablation procedure and/or cardioversion.

The mechanism of atrial fibrillation (AF) in patients with normal heart remains unclear. While exogenous adenosine can trigger AF, nothing is known about the behavior of endogenous adenosine plasma level (APL) at the onset of AF and during ablation procedure. Ninety-one patients (68 with paroxysmal AF: 40 males, 66 ± 16 years; 23 with persistent AF: 14 males, 69 ± 11 years) and 18 controls were included. Among paroxysmal patients: i) medical therapy alone was performed in 45 cases and ablation procedure in 23. AF was spontaneously resolutive in 6 cases; ii) 23 underwent ablation procedure and blood was collected simultaneously in a brachial vein and in the left atrium; 17 were spontaneously in sinus rhythm while 6 were in sinus rhythm after direct current cardioversion. Among persistent patients: i) in 17 patients, blood samples were collected in a brachial vein before and after direct current cardioversion; ii) in 6 patients, blood samples were collected simultaneously in a brachial vein and in left atrium before and after cardioversion during ablation procedure. CV-APL was higher in patients with persistent AF vs patients with paroxysmal AF (median [range]: 0.9[0.6-1.1] vs 0.7[0.4-1.1] µM; p < 0.001). In patients with paroxysmal AF, LA-APL increased during the AF episode (0.95[0.85-1.4] vs 2.7[1.5-7] µM; p = 0.03) and normalized in sinus rhythm after DCCV. In patients with persistent AF, LA-APL was higher than CV-APL (1.2[0.7-1.8] vs 0.9[0.6-1.1] µM; p < 0.001), and both normalized in sinus rhythm (CV-APL: 0.8[0.6-1.1] vs 0.75[0.4-1] µM; p = 0.03), (LA-APL: 1.95[1.3-3] vs 1[0.5-1.15] µM; p = 0.03). The occurrence of AF is associated with a strong increase of APL in the atrium. The cause of this increase needs further investigations.

Timing of Angiography and Outcomes in High-Risk Patients With Non-ST-Segment-Elevation Myocardial Infarction Managed Invasively: Insights From the TAO Trial (Treatment of Acute Coronary Syndrome With Otamixaban).

BACKGROUND: In patients with non-ST-segment-elevation myocardial infarction (NSTEMI) and GRACE (Global Registry of Acute Coronary Events) score >140, coronary angiography (CAG) is recommended by European and American guidelines within 24 hours. We sought to study the association of very early (ie, ≤12 hours), early (12-24 hours), and delayed (>24 hours) CAG in patients with NSTEMI with GRACE score >140 with ischemic outcomes. METHODS: The TAO trial (Treatment of Acute Coronary Syndrome With Otamixaban) randomized patients with NSTEMI and CAG scheduled within 72 hours to heparin plus eptifibatide versus otamixaban. In this post hoc analysis, patients with a GRACE score >140 were categorized into 3 groups according to timing of CAG from admission (<12, ≥12-<24, and ≥24 hours). The primary ischemic outcome was the composite of all-cause death and myocardial infarction within 180 days of randomization. RESULTS: CAG was performed in 4071 patients (<12 hours, n=1648 [40.5%]; 12-24 hours, n=1420 [34.9%]; ≥24 hours, n=1003 [24.6%]). With CAG ≥24 hours as a reference, CAG from 12 to 24 hours was not associated with a lower risk of primary ischemic outcome at 180 days (odds ratio, 0.96; 95% confidence interval, 0.75-1.23), whereas CAG <12 hours was associated with a lower risk of death and myocardial infarction (odds ratio, 0.71; 95% confidence interval, 0.55-0.91). Performing CAG <12 hours was also associated with a lower risk of death and myocardial infarction (odds ratio, 0.76; 95% confidence interval, 0.61-0.94; P=0.01) compared with CAG performed at 12 to 24 hours. No difference was observed in bleeding complications. CONCLUSIONS: In patients with high-risk NSTEMI, undergoing CAG within the initial 12 hours after admission (as opposed to later, either 12-24 or ≥24 hours) was associated with lower risk of ischemic outcomes at 180 days.

Benefit of switching dual antiplatelet therapy after acute coronary syndrome: the TOPIC (timing of platelet inhibition after acute coronary syndrome) randomized study.

AIMS: Newer P2Y12 blockers (prasugrel and ticagrelor) demonstrated significant ischaemic benefit over clopidogrel after acute coronary syndrome (ACS). However, both drugs are associated with an increase in bleeding complications. The objective of the present study was to evaluate the benefit of switching dual antiplatelet therapy (DAPT) from aspirin plus a newer P2Y12 blocker to aspirin plus clopidogrel 1 month after ACS. METHODS AND RESULTS: We performed an open-label, monocentric, and randomized trial. From March 2014 to April 2016, patients admitted with ACS requiring coronary intervention, on aspirin and a newer P2Y12 blocker and without adverse event at 1 month, were assigned to switch to aspirin and clopidogrel (switched DAPT) or continuation of their drug regimen (unchanged DAPT). The primary outcome was a composite of cardiovascular death, urgent revascularization, stroke and bleeding as defined by the Bleeding Academic Research Consortium (BARC) classification ≥2 at 1 year post ACS. Six hundred and forty six patients were randomized and 645 analysed, corresponding to 322 patients in the switched DAPT and 323 in the unchanged DAPT group. The primary endpoint occurred in 43 (13.4%) patients in the switched DAPT group and in 85 (26.3%) patients in the unchanged DAPT (HR 95%CI 0.48 (0.34-0.68), P < 0.01). No significant differences were reported on ischaemic endpoints, while BARC ≥ 2 bleeding occurred in 13 (4.0%) patients in the switched DAPT and in 48 (14.9%) in the unchanged DAPT group (HR 95%CI 0.30 (0.18-0.50), P < 0.01). CONCLUSION: A switched DAPT is superior to an unchanged DAPT strategy to prevent bleeding complications without increase in ischaemic events following ACS.

Primary percutaneous coronary intervention of native chronic total occlusions to treat ST elevation myocardial infarction secondary to acute vein graft occlusion.

Primary percutaneous coronary intervention (PCI) is the treatment modality of choice in patients presenting with ST elevation myocardial infarction (STEMI). Clinical outcomes have dramatically improved with the wide adoption of primary PCI in patients with STEMI because of acute thrombotic native coronary artery occlusion. However, patients with prior coronary artery bypass graft (CABG) surgery who present with STEMI because of acute saphenous vein graft (SVG) occlusion continue to have worse outcomes because of poor acute and long-term results of SVG stenting. Therefore, it may be preferable to treat the native coronary artery supplied by the occluded graft although this can be challenging if the native vessel is a chronic total occlusion (CTO). Recent advances in technology and techniques in CTO PCI have significantly improved the success rate and efficiency of CTO procedures. At our institution we have developed a high volume CTO programme with high success rates. We present three cases of acute inferior STEMI because of SVG occlusion which were treated with successful retrograde PCI of the native vessel CTO, utilising the occluded graft as a retrograde channel in two cases and native septal collaterals in the other. Thrombolysis In Myocardial Infarction (TIMI) 3 flow in the native coronary artery was achieved in all three cases with good acute outcomes. Our case series highlights the benefits of a high volume CTO programme. With recent advances in CTO techniques, acute PCI to native vessel CTO is feasible and may be the treatment of choice in selected cases of acute SVG failure. © 2017 Wiley Periodicals, Inc.

High homocysteine levels prevent via H2 S the CoCl2 -induced alteration of lymphocyte viability.

High homocysteine (HCy) levels are associated with lymphocyte-mediated inflammatory responses that are sometimes in turn related to hypoxia. Because adenosine is a potent lymphocyte suppressor produced in hypoxic conditions and shares metabolic pathways with HCy, we addressed the influence of high HCy levels on the hypoxia-induced, adenosine-mediated, alteration of lymphocyte viability. We treated mitogen-stimulated human lymphocytes isolated from healthy individuals and the human lymphoma T-cell line CEM with cobalt chloride (CoCl2 )to reproduce hypoxia. We found that CoCl2 -altered cell viability was dose-dependently reversed using HCy. In turn, the HCy effect was inhibited using DL-propargylglycine, a specific inhibitor of the hydrogen sulphide (H2 S)-synthesizing enzyme cystathionine-γ-lyase involved in HCy catabolism. We then addressed the intracellular metabolic pathway of adenosine and HCy, and the role of the adenosine A2A receptor (A2 A R). We observed that: (i) hypoxic conditions lowered the intracellular concentration of HCy by increasing adenosine production, which resulted in high A2 A R expression and 3', 5'-cyclic adenosine monophosphate production; (ii) increasing intracellular HCy concentration reversed the hypoxia-induced adenosinergic signalling despite high adenosine concentration by promoting both S-adenosylhomocysteine and H2 S production; (iii) DL-propargylglycine that inhibits H2 S production abolished the HCy effect. Together, these data suggest that high HCy levels prevent, via H2 S production and the resulting down-regulation of A2 A R expression, the hypoxia-induced adenosinergic alteration of lymphocyte viability. We point out the relevance of these mechanisms in the pathophysiology of cardiovascular diseases.

Is platelet inhibition correlated with time from last intake on P2Y12 blockers after an acute coronary syndrome? A pilot study.

Delay from the last intake of drug could be an important and unexplored variable in the biological response to antiplatelet agents after acute coronary syndrome (ACS) discharge. The objective was to define the impact of the delay from P2Y12 blocker intake on the platelet inhibition level. We compared ticagrelor-, prasugrel-, and clopidogrel-treated patients. All consecutive patients, who had been addressed between 2013 and 2014 for ACS, treated with aspirin and a P2Y12 blocker as maintenance dose, were eligible. One month after discharge, blood sample and a questionnaire were proposed to the patient by a nurse blinded to the protocol. On this questionnaire, three questions about name of the drug, regularity of the intakes, and hour of the last intake were collected. The response to antiplatelet therapy was assessed using platelet reactivity index vasodilator-stimulated phosphoprotein (PRI VASP) and % of adenosine-5'-diphosphate-induced aggregation (%ADP).The primary objective of this study was to evaluate the correlation between platelet inhibition and delay from drug intake. We enrolled 474 ACS treated with clopidogrel 75 mg in 182 cases (38% patients), prasugrel in 190 cases (40%), or ticagrelor in 102 patients (22%). We observed a significant correlation between delay from intake and PRI VASP and %ADP for ticagrelor (r = 0.25, p = 0.01; r = 0.21, p = 0.03; respectively). On clopidogrel (r = 0.09, p = 0.24; r = 0.02, p = 0.80; respectively) and prasugrel (r = 0.02, p = 0.82; r = 0.11, p = 0.12 respectively), no correlation exists. In conclusion, ticagrelor, unlike thienopyridines, is associated with a significant correlation between delay from the last intake and platelet inhibition.

Young Women with a Long Past of Resistant Hypertension Cured after Surgery of Severe Bilateral Ostial Renal Artery Stenosis.

Fibromuscular dysplasia (FMD) is an underdiagnosed disease which can affect young people and with poor prognosis such as dissection or aneurysm rupture if unknown. This case illustrates a multi-vessel FMD with symptomatic severe bilateral ostial renal artery stenosis and intracranial aneurysms. One of the original features is a very late delay to diagnosis with 23 years between onset of hypertension and renal stenosis diagnosis, particularly due to lower quality of initial CT scan with milder and uncommon abnormalities. The experiment neuroradiologist had suspected the diagnosis of renal FMD because she developed intracranial aneurysms and he confirmed this diagnosis with an artery renal contrast injection during an intracranial angiogram Because of very tight and short stenosis, surgery was chosen for treatment and permitted the cure of hypertension, with normal home blood pressure after 6 months. Several particularities of FMD were presented in this case: important delay diagnosis due to rare lesion and lower sensitivity of CT in this form, the possibility to perform an angiography in high suspicion of FMD, poor prognosis risk with intracranial aneurisms and premature birth child, and the choice for surgery with cure of hypertension. We thought that hypertension etiologic evaluation must be repeated in case of resistant hypertension in young patients, particularly when they developed intracranial aneurysms.

Exercise-induced acute coronary syndrome in a 24-year-old man with massive cannabis consumption.

Coronary artery disease (CAD) remains a major public health problem in the world. Acute coronary syndromes (ACS) mainly affect patients with cardiovascular risk factors. We report the case of an exercise-induced ACS in a 24-year-old soccer player without any classic cardiovascular risk factor, but with a history of massive cannabis addiction. Coronary angiography showed complete occlusion of the proximal right coronary artery and intravascular ultrasound revealed an atherosclerotic plaque disruption. Thromboaspiration and antithrombotic treatment were successful and coronary stenting was not performed. The respective roles of cannabis toxicity and physical activity as triggers for ACS in young people are discussed.

Short-Term DAPT and DAPT De-Escalation Strategies for Patients With Acute Coronary Syndromes: A Systematic Review and Network Meta-Analysis.

BACKGROUND: Short-term (≤6 months) dual antiplatelet therapy (DAPT) and DAPT de-escalation become attractive for patients with acute coronary syndrome. METHODS: A systemic search identified randomized controlled trials that included patients with acute coronary syndrome treated using (1) standard DAPT (12 months) with clopidogrel, prasugrel (standard/low dose), or ticagrelor; (2) extended DAPT (≥18 months); (3) short-term DAPT (≤6 months) followed by P2Y12 inhibitor or aspirin; (4) 12-month DAPT with unguided de-escalation from potent P2Y12 inhibitors to low-dose potent P2Y12 inhibitor or clopidogrel at 1 month; and (5) guided selection DAPT with genotype or platelet function tests. The primary efficacy outcome (major adverse cardiovascular events) was a composite of cardiovascular death, myocardial infarction, or stroke. The primary safety outcome was major or minor bleeding. RESULTS: This meta-analysis included 32 randomized controlled trials with 103 497 patients. While there were no differences in efficacy between short, unguided de-escalation and guided selection strategies, unguided de-escalation was associated with reduced risk of major adverse cardiovascular events compared with standard DAPT with clopidogrel or ticagrelor (hazard ratio [95% CI], 0.67 [0.49-0.93] and 0.68 [0.50-0.93]). Both short DAPT followed by P2Y12 inhibitor and unguided de-escalation were associated with reduced risks in safety compared with other strategies, including guided selection (hazard ratio [95% CI], 0.66 [0.47-0.93] and 0.48 [0.33-0.71]). Short DAPT followed by a P2Y12 inhibitor was associated with reduced risk of major bleeding and all-cause death compared with standard, extended DAPT (eg, versus DAPT with clopidogrel; hazard ratio [95% CI], 0.64 [0.42-0.97] and 0.60 [0.44-0.82]). By rankogram, unguided de-escalation strategy was the safest and most effective strategy in reducing major adverse cardiovascular events and major or minor bleeding while short DAPT followed by P2Y12 inhibitor was ranked the best for major bleeding and all-cause death. CONCLUSIONS: In patients with acute coronary syndrome, unguided de-escalation was associated with the lowest risk of major adverse cardiovascular events and major or minor bleeding outcomes, while short DAPT followed by P2Y12 inhibitor was associated with the lowest risk of major bleeding and all-cause death.