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Background: The appropriate duration of treatment with beta-blocker drugs after a myocardial infarction is unknown. Data are needed on the safety and efficacy of the interruption of long-term beta-blocker treatment to reduce side effects and improve quality of life in patients with a history of uncomplicated myocardial infarction., Methods: In a multicenter, open label, randomized, noninferiority trial conducted at 49 sites in France, we randomly assigned patients with a history of myocardial infarction, in a 1:1 ratio, to interruption or continuation of beta-blocker treatment. All the patients had a left ventricular ejection fraction of at least 40% while receiving long-term beta-blocker treatment and had no history of a cardiovascular event in the previous 6 months. The primary end point was a composite of death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for cardiovascular reasons at the longest follow-up (minimum, 1 year), according to an analysis of noninferiority (defined as a between-group difference of <3 percentage points for the upper boundary of the two-sided 95% confidence interval). The main secondary end point was the change in quality of life as measured by the European Quality of Life-5 Dimensions questionnaire., Results: A total of 3698 patients underwent randomization: 1846 to the interruption group and 1852 to the continuation group. The median time between the last myocardial infarction and randomization was 2.9 years (interquartile range, 1.2 to 6.4), and the median follow-up was 3.0 years (interquartile range, 2.0 to 4.0). A primary-outcome event occurred in 432 of 1812 patients (23.8%) in the interruption group and in 384 of 1821 patients (21.1%) in the continuation group (risk difference, 2.8 percentage points; 95% confidence interval [CI], <0.1 to 5.5), for a hazard ratio of 1.16 (95% CI, 1.01 to 1.33; P = 0.44 for noninferiority). Beta-blocker interruption did not seem to improve the patients' quality of life., Conclusions: In patients with a history of myocardial infarction, interruption of long-term beta-blocker treatment was not found to be noninferior to a strategy of beta-blocker continuation. (Funded by the French Ministry of Health and ACTION Study Group; ABYSS ClinicalTrials.gov number, NCT03498066; EudraCT number, 2017-003903-23.)., (Copyright © 2024 Massachusetts Medical Society.)

Background: Whether ticagrelor in chronic coronary syndrome patients undergoing complex percutaneous coronary intervention (PCI) can prevent cardiovascular events is unknown., Objectives: The authors sought to evaluate outcomes of complex PCI and the efficacy of ticagrelor vs clopidogrel in stable patients randomized in the ALPHEUS (Assessment of Loading with the P2Y 12 inhibitor ticagrelor or clopidogrel to Halt ischemic Events in patients Undergoing elective coronary Stenting) trial., Methods: All PCI procedures were blindly reviewed and classified as complex if they had at least 1 of the following criteria: stent length >60 mm, 2-stent bifurcation, left main, bypass graft, chronic total occlusion, use of atherectomy or guiding catheter extensions, multiwire technique, multiple stents. The primary endpoint was a composite of type 4a or b myocardial infarction (MI) and major myocardial injury during the 48 hours after PCI. We compared the event rates according to the presence or not of complex PCI criteria and evaluated the interaction with ticagrelor or clopidogrel., Results: Among the 1,866 patients randomized, 910 PCI (48.3%) were classified as complex PCI. The primary endpoint was more frequent in complex PCI (45.6% vs 26.6%; P < 0.001) driven by higher rates of type 4 MI and angiographic complications (12.2% vs 4.8 %; P < 0.001 and 19.3% vs 8.6%; P < 0.05, respectively). The composite of death, MI, and stroke at 48 hours (12.7% vs 5.1 %; P < 0.05) and at 30 days (13.4% vs 5.3%; P < 0.05) was more frequent in complex PCI. No interaction was found between PCI complexity and the randomized treatment for the primary endpoint (P interaction  = 0.47) nor the secondary endpoints., Conclusions: In chronic coronary syndrome, patients undergoing a complex PCI have higher rates of periprocedural and cardiovascular events that are not reduced by ticagrelor as compared with clopidogrel., Competing Interests: Funding Support and Author Disclosures The ALPHEUS trial was led by the ACTION Study Group, an academic research organization based at the Pitié-Salpêtrière Hospital (Paris, France). The study was sponsored by Assistance Publique-Hopitaux de Paris and was funded by an unrestricted grant from AstraZeneca. The present work was supported by a grant of the French Federation of Cardiology. Prof Lattuca has received research grants from Biotronik, Boston Scientific, Daiichi Sankyo, Fédération Française de Cardiologie, and the Institute of CardioMetabolism and Nutrition; consulting fees from Daiichi Sankyo and Eli Lilly; and lecture fees from AstraZeneca, Medtronic, and Novartis. Prof Cayla has received consulting fees from Edwards Lifesciences, Medtronic, and Microport CRM; and lecture fees from Amgen, AstraZeneca, Abbott, Bayer, Biotronik, Bristol Myers Squibb, Edwards Lifesciences, Microport, Medtronic, Pfizer, and Sanofi. Prof Ducrocq has received speaker and consulting fees from Abbott, Amgen, AstraZeneca, Bayer, Bristol Myers Squibb, Novo Nordisk, and Sanofi; has served on steering committees for Amgen, Novo Nordisk, and Janssen; and has been a proctor for Boston Scientific. Dr Laredo has received speaker or consulting fees from Abbott and Biotronik. Dr Kala has received consulting fees from Boston Scientific; and lecture fees from AstraZeneca, Edwards Lifesciences, Novartis, Servier, and Terumo. Prof Varenne has received research grants from Abbott and Boston Scientific; and lecture fees from Abbott, AstraZeneca, Boston Scientific, and Servier. Prof Spaulding has received consulting fees from Edwards Lifesciences, Medtronic, Sonivie, Techwald, and Valcare; has received speaker fees from Amgen and Edwards Lifesciences; and is stock shareholder of Techwald and Valcare. Prof Beygui has received consulting and lecture fees from Medtronic, Novartis, and Pfizer; and research grants from Biosensors and Medtronic. Dr Rangé has received speaker or consulting fees from Abbott and Microport. Prof Vicaut has received consulting or speaker fees from Abbott, Amgen, Bristol Myers Squibb, Celgene, LFB, Pfizer, and Sanofi. Prof Collet has received consulting and lecture fees from AstraZeneca, Boston Scientific, Bristol Myers Squibb, COR2ED, Lead-Up, Medtronic, and WebMD. Prof Montalescot has received research grants and consulting or speaker fees from Abbott, Amgen, AstraZeneca, Ascendia, Bayer, Bristol Myers Squibb, Boehringer Ingelheim, Boston Scientific, Celecor, CSL Behring, Idorsia, Lilly, Novartis, Novo, Opalia, Pfizer, Quantum Genomics, Sanofi, and Terumo. Prof Silvain has received research grants and consulting or speaker fees from AstraZeneca, Bayer HealthCare SAS, Abbott Medical, Biotronik, Boehringer Ingelheim France, CSL Behring SA, Gilead Science, and Sanofi France; and is stock Shareholder of Pharmaseeds, Terumo, and Zoll. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: The use of drug-coated balloon in the management of true bifurcation lesions appears to be an attractive option to reduce the rate of stent thrombosis and restenosis particularly at the level of the side branch ostium. We aim to assess the safety and the efficacy of a hybrid approach combining a drug-eluting stent in the main branch and a drug-coated balloon to treat the side branch ostium in patients with de novo true bifurcation., Methods: From September 2020 to March 2022, 45 patients with a de novo true bifurcation lesion Medina (1.1.1) or Medina (0.1.1) were enrolled. All patients underwent a percutaneous coronary intervention with the hybrid approach. Clinical assessment with functional stress imaging test was scheduled at 6 months. In case of documented ischemia, coronary angiography was performed. The primary endpoint was the composite of target lesion failure at 6 months including cardiac death, target vessel MI or ischemia-driven target lesion revascularization. The secondary endpoints were technical success, defined by performing the percutaneous coronary intervention without an additional drug-eluting stent at the level of the side branch ostium, and clinical success, defined by a technical success associated with the absence of severe complications during in-hospital phase., Results: The immediate results show a technical success of the procedure in the majority of cases (88.9 %) with a low rate of bailout side branch stenting (11.1 %). The clinical success was obtained in 86.7 % and only one patient experienced a severe in-hospital complication. A side branch ostial lesion length > 10 mm was the only independent predictor of clinical failure of the procedure (OR 12.49, 95 % CI 1.17-133.6; p = 0.037). At 6 months, the TLF was low and occurred in 1 patient (2.2 %). No cardiac death was observed. No TVMI was observed. Importantly, at 6 months, no side branch thrombosis was observed., Conclusion: The use of a hybrid approach combining a drug-eluting stent in the main branch and a drug-coated balloon in the side branch to treat true bifurcation lesions appears to be safe and efficient with few immediate complications and with satisfactory results at mid-term follow up., Competing Interests: Declaration of competing interest None., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: The long-term use of β-blocker after myocardial infarction (MI) when global left ventricular ejection fraction (LVEF) is preserved has not been studied in the era of modern myocardial reperfusion and secondary prevention therapies. It is unknown whether β-blockers are useful in stable post-MI patients without reduced LVEF and without heart failure., Methods: The Assessment of β-blocker interruption 1 Year after an uncomplicated myocardial infarction on Safety and Symptomatic cardiac events requiring hospitalization (ABYSS) Trial enrolled in 49 centers in France, 3,700 patients with a prior (>6 months) history of MI and a LVEF >40%, chronically treated with a β-blocker and without any major cardiovascular event (MACE) in the past 6 months. These patients were randomized to interruption or continuation of their β-blocker therapy. The primary objective is to demonstrate the noninferiority of interruption vs continuation of the β-blocker therapy on the primary composite endpoint of all-cause death, stroke, MI, hospitalization for any cardiovascular reason at the end of follow-up (accrual follow-up) with a one-year minimum follow-up for the last randomized patient. Secondary objectives will focus on patient reported outcomes with the evaluation of the quality of life before and after randomization with the EQ5D-5L questionnaire. Enrolment has been completed., Conclusion: The ABYSS trial evaluates the cardiovascular safety of β-blocker interruption in stabilized post-MI patients without heart failure nor reduced LVEF. ABYSS trial is a reappraisal of β-blockers life-long therapy in stable post-MI patients without reduced LVEF., Clinical Trial Registration: NCT03498066 (clinicaltrials.gov)., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objectives: Despite growing evidence that aortic valve repair improves long-term patient outcomes and quality of life, aortic valves are mostly replaced. We evaluate the effect of aortic valve repair versus replacement in patients with dystrophic aortic root aneurysm up to 4 years., Methods: The multicentric CAVIAAR (Conservation Aortique Valvulaire dans les Insuffisances Aortiques et les Anévrismes de la Racine aortique) prospective cohort study enrolled 261 patients: 130 underwent standardized aortic valve repair (REPAIR) consisting of remodelling root repair with expansible aortic ring annuloplasty, and 131 received mechanical composite valve and graft replacement (REPLACE). Primary outcome was a composite criterion of mortality, reoperation, thromboembolic or major bleeding events, endocarditis or operating site infections, pacemaker implantation and heart failure, analysed with propensity score-weighted Cox model analysis. Secondary outcomes included major adverse valve-related events and components of primary outcome., Results: The mean age was 56.1 years, and valve was bicuspid in 115 patients (44.7%). Up to 4 years, REPAIR did not significantly differ from REPLACE in terms of primary outcome [Hazard Ratio (HR) 0.66 (0.39; 1.12)] but showed significantly less valve-related deaths (HR 0.09 [0.02; 0.34]) and major bleeding events (HR 0.37 [0.16; 0.85]) without an increased risk of valve-related reoperation (HR 2.10 [0.64; 6.96]). When accounting for the occurrence of multiple events in a single patient, the REPAIR group had half the occurrence of major adverse valve-related events (HR 0.51 [0.31; 0.86])., Conclusions: Although the primary outcome did not significantly differ between the REPAIR and REPLACE groups, the trend is in favour of REPAIR by a significant reduction of valve-related deaths and major bleeding events. Long-term follow-up beyond 4 years is needed to confirm these findings., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Background: Ventricular arrhythmias can be life-threatening complications of ST-segment elevation myocardial infarction (STEMI)., Aims: To describe the incidence, predictors and in-hospital impact of early ventricular arrhythmia (EVA, occurring

Spontaneous coronary artery disease (SCAD) is a particular form of acute coronary syndrome affecting preferentially female patient with few or without traditional cardiovascular risk factors. Male patient is exceptionally concerned by SCAD. We report a case of a young male patient presenting with anterolateral STEMI in relation with SCAD of Left main and left anterior descending artery (LAD). He was initially managed by fibrinolysis, which is then complicated by cardiogenic choc. Coronary angiogram covered by intra-aortic balloon pump (IABP) showed an acute double occlusion of proximal LAD and the ostium of the left circumflex artery (LCX). After thrombus aspirations, the angiographic pattern recalled a SCAD, which is confirmed by OCT (Optical Coherence Tomography). The latter highlighted the intimal flap with true and false lumen involving both Left main and proximal LAD with huge thrombus burden. PCI was then performed successfully with implantation of 3 DES (Drug Eluting Stent). But given the cardiogenic shock persistence despite Dobutamin infusion and IABP, ECMO (Extracorporeal membrane oxygenation) was indicated. Unfortunately, the patient died of haemorrhage during ECMO implantation., (Copyright © 2020 Elsevier Masson SAS. All rights reserved.)

Objectives: The authors sought to assess the association between admission time with patient's care, procedure characteristics, and clinical outcomes within a contemporary ST-segment elevation myocardial infarction (STEMI) network of patients referred for primary percutaneous coronary intervention (PCI)., Background: The effect of admission time on STEMI patient's outcomes remains controversial when primary PCI is the preferred reperfusion strategy., Methods: Characteristics and clinical outcomes of 2,167 consecutive STEMI patients admitted in a tertiary PCI-capable center were collected. On-hours were defined as admission from Monday through Friday between 8 am and 6 pm and off-hours as admission during night shift, weekend, and nonworking holidays. In-hospital and 1-year all-cause mortality were assessed as well as key time delays., Results: A total of 1,048 patients (48.3%) were admitted during on-hours, and 1,119 patients (51.7%) during off-hours. Characteristics were well-balanced between the 2 groups, including rates of cardiac arrest (7.9% vs. 8.8%; p = 0.55) and cardiogenic shock (12.3% vs. 14.7%; p = 0.16). Median symptom-to-first medical contact time and median first medical contact-to-sheath insertion time did not differ according to on- versus off-hours admission (120 min vs. 126 min; p = 0.25 and 90 min vs. 93 min; p = 0.58, respectively), as well as the rate of radial access for catheterization (85.6% vs. 87.5%; p = 0.27). There was no association between on- versus off-hours groups and in-hospital (8.1% vs. 7.0%; p = 0.49) or 1-year mortality (11.0% vs. 11.1%; p = 0.89), respectively., Conclusions: In a contemporary organized STEMI network, patients admitted in a high-volume tertiary primary PCI center during on-hours or off-hours had similar management and 1-year outcomes., (Copyright © 2019 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: The long-term evolution of premature coronary artery disease (CAD) is unknown., Objectives: The objective of this study was to describe the evolution of coronary atherosclerosis in young patients and identify the risk factors of poor outcomes., Methods: Participants age ≤45 years with acute or stable obstructive CAD were prospectively enrolled and followed. The primary endpoint was all-cause death, myocardial infarction (MI), refractory angina requiring coronary revascularization, and ischemic stroke., Results: Eight hundred-eighty patients with premature CAD were included. They were age 40.1 ± 5.7 years, mainly men, smokers, with a family history of CAD or hypercholesterolemia. At baseline presentation, 91.2% underwent coronary revascularization, predominantly for acute MI (78.8%). Over a follow-up of 20 years, one-third (n = 264) of patients presented with a total of 399 ischemic events, and 36% had at least a second recurrent event. MI was the most frequent first recurrent event (n = 131 of 264), mostly related to new coronary lesions (17.3% vs. 7.8%; p = 0.01; hazard ratio [HR]:1.45; 95% confidence interval [CI]: 1.09 to 1.93 for new vs. initial culprit lesion). All-cause death (n = 55; 6.3%) occurred at 8.4 years (median time). Ethnic origin (sub-Saharan African vs. Caucasian, adjusted hazard ratio [adjHR]: 1.95; 95% CI: 1.13 to 3.35; p = 0.02), inflammatory disease (adjHR: 1.58; 95% CI: 1.05 to 2.36; p = 0.03), and persistent smoking (adjHR: 2.32; 95% CI: 1.63 to 3.28; p < 0.01) were the strongest correlates of a first recurrent event. When considering all recurrent events, the same factors and Asian ethnicity predicted poor outcome, but persistent smoking had the greatest impact on prognosis., Conclusions: Premature CAD is an aggressive disease despite the currently recommended prevention measures, with high rates of recurrent events and mortality. Ethnicity and concomitant inflammatory disease are associated with poor prognoses, along with insufficient control of risk factors., (Copyright © 2019 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Elderly (≥75 years old) patients with ST-segment elevation myocardial infarction (STEMI) have higher ischemic and bleeding risk compared with those <75 years old. We investigated the efficacy and safety of intravenous (IV) enoxaparin versus IV unfractionated heparin (UFH) in elderly patients undergoing primary percutaneous coronary intervention (PCI) for STEMI. A prespecified analysis of the Acute Myocardial Infarction Treated with Primary Angioplasty and Intravenous Enoxaparin or Unfractionated Heparin to Lower Ischemic and Bleeding Events at Short- and Long-term Follow-up (ATOLL) study was performed examining the 30-day outcomes in the elderly patients. Of the 165 elderly patients in the ATOLL study, 85 patients received IV enoxaparin 0.5 mg/kg and 80 patients received IV UFH. Intravenous enoxaparin did not reduce the primary end point, the main secondary efficacy end point, major bleeding, major or minor bleeding, and all-cause mortality compared with IV UFH. The rate of minor bleeding (5.9% vs 22.8%, P adjusted = .01) was significantly lower with IV enoxaparin compared with IV UFH. Intravenous enoxaparin appears to be a safe alternative to IV UFH in primary PCI of the elderly patients with STEMI., (© The Author(s) 2016.)

Our aim was to demonstrate that the sequential use of the Verigene® rapid CYP2C19 test for genetic profiling and the VerifyNowTM bedside test for platelet function measurement in ACS patients may optimise P2Y12 inhibition. "Rapid" (CYP2C19*1/*1 or CYP2C19*17 carriers, n=211) and "slow" metabolisers (CYP2C19*2 carriers, n=58) were first put on clopidogrel and prasugrel for ≥ 2 weeks, respectively. Patients with low platelet reactivity (PRU<30) on prasugrel or high platelet reactivity (>208 PRU) on clopidogrel were then switched to clopidogrel and prasugrel, respectively. Our objectives were (i) to demonstrate that the proportion of "rapid" metabolisers on 75 mg of clopidogrel within 30-208 (PRU) of P2Y12 inhibition is non-inferior to "slow" metabolisers on prasugrel 10 mg and (ii) to evaluate the same end-point after switching drugs. The proportion of "rapid" and "slow" metabolisers within 30-208 PRU of P2Y12 inhibition was 71% and 56.9%, respectively, an absolute difference of +14.1% (95% CI, -0.05% to 28.28%) with a non-inferiority margin greater than the predefined margin of -10%. Among patients out of target, all but one "slow" metabolisers displayed low-on prasugrel platelet reactivity while the majority of "rapid" metabolisers (68%) displayed high-on clopidogrel platelet reactivity. After switching, the proportion of patients within 30-208 PRU of P2Y12 inhibition was 83.6% and 79.3% in "rapid" and "slow" metabolisers, respectively (+4.3%, 95% CI -7.3% to 15.9%). In conclusion, this study demonstrates a loose relationship between genotype and platelet function phenotype approaches but that they are complementary to select prasugrel or clopidogrel MD in stented ACS patients.

Background: Patients with renal failure (RF) have been systematically excluded from clinical trials; consequently their outcomes have not been well studied in the setting of percutaneous coronary intervention (PCI)., Aims: To compare cardiovascular outcomes after contemporary PCI in patients with versus without RF, according to clinical presentation (ST-segment elevation myocardial infarction [STEMI], acute coronary syndrome [ACS] or stable coronary artery disease [sCAD])., Methods: Consecutive patients undergoing PCI with stent were prospectively included from 2007 to 2012. RF was defined as creatinine clearance<60mL/min. The primary endpoint was all-cause mortality; secondary endpoints were major adverse cardiovascular and cerebrovascular events (MACCE: composite of cardiovascular death, myocardial infarction, stroke and target lesion revascularization [TLR]), TLR and Academic Research Consortium definite/probable stent thrombosis (ST) at 1 year., Results: Among 5337 patients, 23% had PCI for STEMI, 34% for ACS and 43% for sCAD, while 27% had RF. RF patients had a higher unadjusted death rate than those with preserved renal function (nRF) in all PCI indication groups (STEMI, 41% vs. 7.5%; ACS, 19% vs. 6%; sCAD, 10% vs. 3%; P<0.0001 for all). The rate of MACCE was also higher in RF patients whatever the PCI indication (STEMI, 45% vs. 15%; ACS, 23% vs. 14%; sCAD, 14% vs. 9%; P<0.05 for all). Rates of TLR (5.5-7.4%) and ST (<2.5%) were similar (P>0.05 for both). sCAD-RF and STEMI-nRF patients had similar rates of mortality (P=0.209) and MACCE (P=0.658). RF was independently associated with mortality, with a doubled relative risk in STEMI versus ACS and sCAD groups (odds ratio 5.3, 95% confidence interval 3.627-7.821 vs. 2.1, 1.465-3.140 and 2.3, 1.507-3.469, respectively; P<0.0001)., Conclusion: RF is a stronger independent predictor of death after PCI in STEMI than in ACS or sCAD patients. sCAD-RF and STEMI-nRF patients had similar prognoses., (Copyright © 2015 Elsevier Masson SAS. All rights reserved.)

Platypnea-orthodeoxia syndrome (POS) is a rare clinical disorder characterized by dyspnea caused by the upright position and relieved at recumbent position. Few cases of POS and stroke were reported in literature, and the association between stroke and POS with evidence of patent foramen ovale (PFO) is rare. Stroke may occur in patients with cardiac shunt who undergo contrast echocardiography. We present a patient with POS who experienced transitory ischemic attack (TIA) most likely caused by injection of agitated saline microbubbles during screen for PFO. No case report of TIA/stroke during contrast echocardiography in patients with POS has previously been published., (© 2015, Wiley Periodicals, Inc.)

Background: Recent studies have suggested that ticagrelor 90mg twice daily provides stronger platelet inhibition than prasugrel 10mg once daily in acute coronary syndrome patients undergoing percutaneous coronary intervention., Objectives: To compare the effects of ticagrelor 90 mg twice daily and prasugrel 10mg once daily on platelet reactivity in patients with ST-segment elevation myocardial infarction (STEMI), using: the VerifyNow(®) P2Y12 (VN-P2Y12) assay, expressed in P2Y12 reaction units (PRU); measurement of the vasodilator-stimulated phosphoprotein platelet reactivity index (VASP-PRI; %); and light transmission aggregometry (LTA), expressed as residual platelet aggregation (RPA; %)., Methods: Platelet reactivity was evaluated prospectively using the three assays 30 days after primary PCI in 118 patients with STEMI on a maintenance dose of prasugrel 10mg once daily (n=60) or ticagrelor 90mg twice daily (n=58)., Results: On-treatment platelet reactivity, assessed by the VN-P2Y12 assay, was lower for ticagrelor compared with prasugrel (20.91 ± 4.59 PRU vs. 43.50±6.98 PRU; P=0.008) but was not significantly different when using the more specific VASP-PRI assay (13.05 ± 1.61% vs. 17.44 ± 1.97%; P=0.09) or RPA assessed by LTA (10.49 ± 1.44% vs. 7.20 ± 1.27%; P=0.09)., Conclusions: The difference in platelet reactivity between ticagrelor and prasugrel varies according to the platelet function test in patients with STEMI. The differences observed may be related more to the tests than to the drugs used., (Copyright © 2015 Elsevier Masson SAS. All rights reserved.)

Background: Whether outcomes differ for women and men after percutaneous coronary intervention (PCI) for ST-segment elevation myocardial infarction (STEMI) remains controversial., Aim: To compare 1-year outcomes after primary PCI in women and men with STEMI, matched for age and diabetes., Methods: Consecutive women with STEMI of<24 hours' duration referred (August 2007 to January 2011) for primary PCI were compared with men matched for age and diabetes. Rates of all-cause mortality, target vessel revascularization (TVR) and major cardiovascular and cerebrovascular events (MACCE) (death/myocardial infarction/stroke) were assessed at 1 year., Results: Among 775 consecutive patients, 182 (23.5%) women were compared with 182 matched men. Mean age was 69±15 years, 18% had diabetes. Patient characteristics were similar, except for lower creatinine clearance (73±41 vs 82±38 μmol/L; P=0.041), more cardiogenic shock (14.8% vs 6.6%; P=0.017) and less radial PCI (81.3% vs 90.1%; P=0.024) in women. Rates of 1-year death (22.7% vs 18.1%), TVR (8.3% vs 6.0%) and MACCE (24.3% vs 20.9%) were not statistically different in women (P>0.05 for all). After exclusion of patients with shock (10.7%) and out-of-hospital cardiac arrest (6.6%), death rates were even more similar (11.3% vs 11.8%; P=0.10). Female sex was not independently associated with death (odds ratio 1.01, 95% confidence interval 0.55-1.87; P=0.97)., Conclusion: In our consecutive unselected patient population, women had similar 1-year outcomes to men matched for age and diabetes, after contemporary primary PCI for STEMI, despite having a higher risk profile at baseline., (Copyright © 2015 Elsevier Masson SAS. All rights reserved.)

Background and Objectives: We aimed to assess the incidence and evolution of left ventricular (LV) thrombi in a high-risk population of patients with LV systolic dysfunction after anterior myocardial infarction (ant-MI). We also compared the accuracy of transthoracic echocardiography (TTE) and cardiac magnetic resonance imaging with contrast-delayed enhancement (CMR-DE) in detecting LV thrombi., Methods: We prospectively included 100 consecutive patients with LV ejection fraction (LVEF) <45% at the first TTE performed <7 days after ant-MI. A second evaluation with TTE and CMR-DE (by blinded examiners) was performed at 30 days. A third TTE and assessment of clinical status were performed between 6 and 12 months after ant-MI., Results: Patients (males 71%; mean age 59.1 ± 12.1 years; mean LVEF 33.5% ± 6.0%) were included at a median of 5.5 days (interquartile range 25th-75th percentile 4.25-6.0 days) after ant-MI. Thrombi were detected among 26 (26%) patients at a median of 12.0 days after ant-MI (7 patients at 1-7 days after MI; 15 at 8-30 days; and 4 after day 30). Sensitivity and specificity for LV thrombi detection were 94.7% and 98.5%, respectively, for TTE as compared with CMR-DE. Most thrombi (n = 24; 92.3%) disappeared after triple antithrombotic therapy (vitamin K antagonist in addition to dual antiplatelet therapy)., Conclusion: Left ventricular thrombus is a frequent complication after ant-MI with systolic dysfunction. When a search for thrombus is prespecified, the accuracy of TTE is high as compared with CMR-DE. The best antithrombotic strategy is not known., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Aim: To determine the incidence, type and possible association with mortality of major bleeding in patients with non-ST segment elevation acute coronary syndrome (NSTE-ACS) treated with an invasive strategy using predominantly the radial approach and triple antiplatelet therapy., Methods: In the multicentre randomised ABOARD Study, 352 patients with NSTE-ACS were randomised to an 'immediate percutaneous coronary intervention (PCI)' strategy or a strategy of PCI on the 'next working day'. Radial access was predominantly used in this study population. The present subanalysis evaluated the occurrence of major bleeding complications and their association with mortality at 1 month., Results: Patients were treated with a triple antiplatelet therapy using high loading and maintenance doses of clopidogrel and abciximab in 99% of patients receiving PCI. The trans-radial approach was used in the vast majority of patients (84%). During the first 30 days, major bleeding complications (STEEPLE definition) occurred in 5.4% of patients (n=19), with no difference between immediate and delayed intervention. The most common bleeding complications were occult bleeding (36.8% of bleeding, n=7/19) and overt gastrointestinal bleeding (21% of bleeding, n=4/19). Patients with major bleeding had a higher peak concentration of creatinine during hospitalisation (mean±SD, 170±169 vs 97±57 μmol/l; p=0.005) and a 1-month mortality of 26.3%, much higher than patients without bleeding (0.6%, p<0.0001). Major bleeding was strongly associated with 30-day mortality (OR 50.3; 95% CI 10.1 to 249.7; p<0.0001)., Conclusion: Despite the predominant use of the radial approach, major bleeding (essentially occult and gastrointestinal) remains a common complication, which is highly associated with mortality in patients with NSTE-ACS treated with optimal antithrombotic therapy.

Context: International guidelines recommend an early invasive strategy for patients with high-risk acute coronary syndromes without ST-segment elevation, but the optimal timing of intervention is uncertain., Objective: To determine whether immediate intervention on admission can result in a reduction of myocardial infarction compared with a delayed intervention., Design, Setting, and Patients: The Angioplasty to Blunt the Rise of Troponin in Acute Coronary Syndromes Randomized for an Immediate or Delayed Intervention (ABOARD) study, a randomized clinical trial that assigned, from August 2006 through September 2008 at 13 centers in France, 352 patients with acute coronary syndromes without ST-segment elevation and a Thrombolysis in Myocardial Infarction (TIMI) score of 3 or more to receive intervention either immediately or on the next working day (between 8 and 60 hours after enrollment)., Main Outcome Measures: The primary end point was the peak troponin value during hospitalization; the key secondary end point was the composite of death, myocardial infarction, or urgent revascularization at 1-month follow-up., Results: Time from randomization to sheath insertion was 70 minutes with immediate intervention vs 21 hours with delayed intervention. The primary end point did not differ between the 2 strategies (median [interquartile range] troponin I value, 2.1 [0.3-7.1] ng/mL vs 1.7 [0.3-7.2] ng/mL in the immediate and delayed intervention groups, respectively; P = .70). The key secondary end point was observed in 13.7% (95% confidence interval, 8.6%-18.8%) of the group assigned to receive immediate intervention and 10.2% (95% confidence interval, 5.7%-14.6%) of the group assigned to receive delayed intervention (P = .31). The other end points, as well as major bleeding, did not differ between the 2 strategies., Conclusion: In patients with acute coronary syndromes without ST-segment elevation, a strategy of immediate intervention compared with a strategy of intervention deferred to the next working day (mean, 21 hours) did not result in a difference in myocardial infarction as defined by peak troponin level., Trial Registration: clinicaltrials.gov Identifier: NCT00442949.

Background: Clopidogrel and low-dose aspirin have become the mainstay oral antiplatelet regimen to prevent recurrent ischaemic events after acute coronary syndromes or stent placement. The frequent genetic functional variant 681 G>A (*2) of cytochrome P450 2C19 (CYP2C19) is an important contributor to the wide variability between individuals of the antiplatelet effect of clopidogrel. We assessed whether the CYP2C19*2 polymorphism affected long-term prognosis of patients who were chronically treated with clopidogrel., Methods: Between April 1, 1996, and April 1, 2008, 259 young patients (aged <45 years) who survived a first myocardial infarction and were exposed to clopidogrel treatment for at least a month, were enrolled in a multicentre registry and underwent CYP2C19*2 determination. The primary endpoint was a composite of death, myocardial infarction, and urgent coronary revascularisation occurring during exposure to clopidogrel. Follow-up was every 6 months. The key secondary endpoint was stent thrombosis proven by angiography., Findings: Median clopidogrel exposure time was 1.07 years (IQR 0.28-3.0). Baseline characteristics were balanced between carriers (heterozygous *1/*2, n=64; homozygous *2/*2, n=9) and non-carriers (n=186) of CYP2C19*2 variant. The primary endpoint occurred more frequently in carriers than in non-carriers (15 vs 11 events; hazard ratio [HR] 3.69 [95% CI 1.69-8.05], p=0.0005), as did stent thrombosis (eight vs four events; HR 6.02 [1.81-20.04], p=0.0009). The detrimental effect of the CYP2C19*2 genetic variant persisted from 6 months after clopidogrel initiation up to the end of follow-up (HR 3.00 [1.27-7.10], p=0.009). After multivariable analysis, the CYP2C19*2 genetic variant was the only independent predictor of cardiovascular events (HR 4.04 [1.81-9.02], p=0.0006)., Interpretation: The CYP2C19*2 genetic variant is a major determinant of prognosis in young patients who are receiving clopidogrel treatment after myocardial infarction.

To assess the feasibility and safety of coronary angiography combined, where necessary, with ad hoc angioplasty in an outpatient setting; a prospective, single-center study. The first 172 patients (154 men, 59 +/- 11 years) considered at low risk for complications were enrolled for outpatient-coronary angiography with or without angioplasty via a radial approach. The inclusion criteria were clinical, not based on angiography. After angiography/angioplasty, creatinine and troponin were assayed (outside the hospital) within 24h and patients were telephoned and asked about their clinical condition. Angioplasty was performed in 69 (40%) patients and 130 patients (75.6%) were discharged on the same day. In the angioplasty group, a history of coronary dilatation was more common in patients discharged on the same day (p = 0.05), whereas bifurcation lesions were more frequent in subjects who were kept in hospital (p < 0.0001). No serious complications occurred during the study. Of the 42/172 prolonged hospitalizations, eight were due to minor procedural complications, five due to failure of the radial route and three for indications for bypass surgery; the others were kept in for reasons unrelated to a complication (e.g., the examination was performed late in the day, a particularly complex procedure, etc.). Four (3%) of the 24-hour telephone calls led to a visit, but not hospital admission. Overall, performing angiography and "ad hoc" angioplasty in the course of a single outpatient visit makes it possible to foreshorten the hospital stay and increase patient throughput with a given hospital capacity and, this, without increasing clinical risk. Exactly how these patients are selected remains to be defined and may certainly be improved compared to this initial experiment. An outpatient-coronary angiography and ad hoc angioplasty strategy is a viable option with a low risk for patients selected on the basis of simple clinical criteria. It combines the advantages of increased convenience for the patient and lower costs.

Objective: Hypofibrinolysis promotes atherosclerosis progression and recurrent ischemic events in premature coronary artery disease. We investigated the role of fibrin physical properties in this particular setting., Methods and Results: Biomarkers of recurrent thrombosis and premature coronary artery disease (CAD) were measured in 33 young post-myocardial infarction patients with angiographic-proven CAD and in 33 healthy volunteers matched for age and sex. Ex vivo plasma fibrin physical properties were assessed by measuring fibrin rigidity and fibrin morphological properties using a torsion pendulum and optical confocal microscopy. The fibrinolysis rate was derived from continuous monitoring of the viscoelastic properties after addition of lytic enzymes. Young CAD patients had a significant increase in plasma concentration of fibrinogen, von Willebrand factor, plasminogen activator inhibitor type 1, and lipoprotein(a) as compared with controls (P<0.05). Fibrin of young CAD patients was stiffer (P=0.002), made of numerous (P=0.002) and shorter fibers (P=0.04), and lysed at a slower rate than that of controls (P=0.03). Fibrin stiffness was an independent predictor for both premature CAD and hypofibrinolysis., Conclusions: This first detailed study of clot properties in such a group of patients demonstrated that abnormal plasma fibrin architecture is an important feature of both premature CAD and fibrinolysis rate. The determinants of this particular phenotype warrant further investigation.

Antithrombotic therapies are the corner stone of acute coronary syndrome management. We have the proof that many of them should be initiated during the prehospital care because their clinical benefit is time-dependent. The hypothesis that anticoagulation therapy is an effective treatment of STEMI, which benefit is time-dependent, is now validated. It is also fair to affirm that GP lIb/IIIa receptor inhibitors are the adjuvant therapy of choice for primary PCI. Indeed, these medications reduce short-term and long-term mortality. This clinical benefit is time dependent. Clopidogrel therapy is probably also a medication of the prehospital phase. It is well established now that the biological efficacy of this pro drug is loading dose dependent. It is also demonstrated that its clinical efficacy depends on the time delay between symptom onset and initiation of the therapy. However, the clinical benefit of prehospital administration remains to be established.

Coronary arteries are the most frequent location of atherosclerosis. Coronary artery disease is the first cause of death related to atherothrombosis. In addition, patients with a prior history of acute coronary syndromes exhibit a 10% annual risk of recurrence. Although there seems to be a close correlation between the extension of CAD and the severity of atherosclerotic lesions in extra coronary arterial beds, the prevalence of these extracoronary asymptomatic lesions depends on their location. Hence, the prevalence of renal artery disease defined as stenosis > or = 50% or of peripheral artery disease defined as an ABI < 0.9 is estimated to be 20% up to 30%, whereas the prevalence of both carotid artery disease defined as stenosis > or = 70% or aortic aneurysm is estimated to be 5%. Conversely, the annual absolute risk of stroke among CAD patients is estimated at 1% while it remains unknown for vascular events related to PAD or aortic lesions. These data suggest that a systematic screening for asymptomatic extracoronary atherosclerotic lesions among CAD patients cannot be justified without a better knowledge of the prevalence of these lesions. In addition, the identification of the predicting factors for the presence and the development of these asymptomatic lesions is warranted. Finally, the potential benefit in terms of therapeutic intervention of such screening needs to be evaluated. These important issues warrant further clinical studies with appropriate design.

Unstable angina is the most frequent acute coronary syndrome. Risk stratification to predict coronary morbidity and mortality and the risk of major hemorrhage is the key element of the medical approach. Combined antithrombotic therapy (including aspirin, clopidogrel, low-molecular-weight heparin and, possibly, glycoprotein IIb/IIIa receptor antagonists) has led to a substantial reduction in major coronary events; tolerance is good because the treatment is brief and aggressive. Combined antithrombotic therapy also increases the benefit of early invasive strategies including coronary angiogram with stent-based percutaneous coronary angioplasty.

Background: Oral antiplatelet agents (OAAs) can prevent further vascular events in cardiovascular disease. How prior use or recent discontinuation of OAA affects clinical presentation of acute coronary syndromes (ACS) and clinical outcomes (death, myocardial infarction [MI]) is unclear., Methods and Results: We studied and followed up for up to 30 days a cohort of 1358 consecutive patients admitted for a suspected ACS; of these, 930 were nonusers, 355 were prior users of OAA, and 73 had recently withdrawn OAA. Nonusers were at lower risk, more frequently presented with ST-elevation MI on admission, and more frequently had Q-wave MI at discharge than prior users (36.6% versus 17.5%, P<0.001; and 47.8% versus 28.2%, P<0.001, respectively). However, there was no difference regarding the incidence of death or MI at 30 days between nonusers and prior users (10.3% versus 12.4%, P=NS). In addition, prior users experienced more major bleeds within 30 days compared with nonusers (3.4% versus 1.4%, respectively; P=0.04). Recent withdrawers were admitted on average 11.9+/-0.8 days after OAA withdrawal. Interruption was primarily a physician decision for scheduled surgery (n=47 of 73). Despite a similar cardiovascular risk profile, recent withdrawers had higher 30-day rates of death or MI (21.9% versus 12.4%, P=0.04) and bleedings (13.7% versus 5.9%, P=0.03) than prior users. After multivariate analysis, OAA withdrawal was found to be an independent predictor of both mortality and bleedings at 30 days., Conclusions: Among ACS patients, prior users represent a higher-risk population and present more frequently with non-ST-elevation ACS than nonusers. Although patients with a recent interruption of OAA resemble those chronically treated by OAA, they display worse clinical outcomes.

Background: Low-molecular-weight heparin (LMWH) is recommended in the treatment of unstable angina (UA)/non-ST-segment-elevation myocardial infarction (NSTEMI), but no relationship has ever been shown between anticoagulation levels obtained with LMWH treatment and clinical outcomes., Methods and Results: In all, 803 consecutive patients with UA/NSTEMI were treated with subcutaneous enoxaparin and were followed up for 30 days. The recommended dose of enoxaparin of 1 mg/kg BID was used throughout the population except when physicians decided on dose reduction because of a history of a recent bleeding event or because of a high bleeding risk. Anti-factor Xa activity was >0.5 IU/mL in 93% of patients; subtherapeutic anti-Xa levels (<0.5 IU/mL) were associated with lower doses of enoxaparin. The 30-day mortality rate was significantly associated with low anti-Xa levels (<0.5 IU/mL), with a >3-fold increase in mortality compared with the patients with anti-Xa levels in the target range of 0.5 to 1.2 IU/mL (P=0.004). Multivariate analysis revealed low anti-Xa activity as an independent predictor of 30-day mortality at least as strong as age, left ventricular function, and renal function. In contrast, anti-Xa activity did not predict major bleeding complications within the range of anti-Xa levels observed in this study., Conclusions: In this large unselected cohort of patients with UA/NSTEMI patients, low anti-Xa activity on enoxaparin treatment is independently associated with 30-day mortality, which highlights the need for achieving at least the minimum prescribed anti-Xa level of 0.5 IU/mL with enoxaparin whenever possible.

Context: Glycoprotein IIb/IIIa (Gp IIb/IIIa) inhibitors improve myocardial reperfusion and clinical outcomes of patients undergoing primary percutaneous coronary intervention (PCI), but optimal timing of administration remains unclear. No systematic reviews have comprehensively examined the effects of early vs delayed administration of these agents., Objective: To perform a meta-analysis of randomized trials of early (prior to transfer to the catheterization laboratory) vs late (at the time of PCI) intravenous administration of Gp IIb/IIIa inhibitors in acute ST-segment elevation myocardial infarction (STEMI)., Data Sources: MEDLINE and the Cochrane Controlled Trials Register search of the literature over the past 10 years; papers presented at major cardiac conferences; consultation with national and international colleagues as well as Gp IIb/IIIa inhibitor drug manufacturers; and text and journal article bibliographies., Study Selection and Data Extraction: We examined trials of randomized comparisons between early administration at the point of initial contact (emergency department or ambulance) and late administration (catheterization laboratory) of Gp IIb/IIIa inhibitors in STEMI. Outcome data had to be available on both culprit artery patency evaluated by Thrombolysis in Myocardial Infarction (TIMI) flow grades on admission and mortality. Two authors independently reviewed abstracts or complete articles. Six studies met inclusion criteria. Independent data extraction was performed by 2 reviewers and confirmed by consensus., Data Synthesis: The 6 trials enrolled 931 STEMI patients treated with abciximab (3 trials) or tirofiban (3 trials) in combination with primary PCI. TIMI grade 2 or 3 flow (41.7% [194/465 vs 29.8% [139/466]) as well as TIMI grade 3 flow (20.3% [84/413] vs 12.2% [51/418]) were significantly more frequent in the early group compared with the late group (odds ratio [OR], 1.69; 95% confidence interval [CI], 1.28-2.22; P<.001; and OR, 1.85; 95% CI, 1.26-2.71; P<.001, respectively). The early administration of Gp IIb/IIIa inhibitors was associated with a 28% reduction of mortality from 4.7% to 3.4%, which was not significant but consistent with similar trends for reinfarction and the composite ischemic end point., Conclusions: In a meta-analysis of 6 randomized trials, early administration of Gp IIb/IIIa inhibitors in STEMI appeared to improve coronary patency with favorable trends for clinical outcomes. These findings are supportive of a strategy of facilitated PCI. Further evaluations in adequately powered large trials are awaited to confirm the clinical benefit of this strategy.

Aims: Revised guidelines for diagnosis of rheumatic fever indicate that rheumatic myocarditis may 'contribute' to the genesis of congestive heart failure. Our objective was to assess non-invasively the presence of non-clinical markers of myocardial involvement in acute rheumatic fever., Methods: Echocardiography and assessment of cardiac troponin I (cTnI) blood levels were systematically performed in 95 consecutive patients with acute rheumatic fever, who were divided into three groups. Group 1: patients without carditis (n=22); group 2: patients with carditis and without congestive heart failure (n=59); group 3: patients with carditis and congestive heart failure (n=14)., Results: Left ventricular ejection fraction was normal in all patients and did not differ between groups (group 1: 0.72+/-0.08, group 2: 0.69+/-0.06, and group 3: 0.66+/-0.07, p=0.09). Left ventricular diameters tend to be larger in group 3, but all patients had severe mitral and/or aortic regurgitation. Mean cTnI was 0.077+/-0.017 ng/ml (normal <0.1 ng/ml), did not differ between groups (p=0.45), and only 13 patients (seven with pericardial effusion) had detectable levels (0.2-0.4 ng/ml)., Conclusions: Our study neither detected cTnI elevations nor echocardiographic abnormalities suggesting significant myocardial involvement during rheumatic fever. Congestive heart failure was always associated to severe valve regurgitation.