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Background: Percutaneous coronary intervention (PCI)-related myonecrosis is frequent and can affect the long-term prognosis of patients. To our knowledge, ticagrelor has not been evaluated in elective PCI and could reduce periprocedural ischaemic complications compared with clopidogrel, the currently recommended treatment. The aim of the ALPHEUS study was to examine if ticagrelor was superior to clopidogrel in reducing periprocedural myocardial necrosis in stable coronary patients undergoing high-risk elective PCI., Methods: The ALPHEUS study, a phase 3b, randomised, open-label trial, was done at 49 hospitals in France and Czech Republic. Patients with stable coronary artery disease were eligible for the study if they had an indication for PCI and at least one high-risk characteristic. Eligible patients were randomly assigned (1:1) to either ticagrelor (180 mg loading dose, 90 mg twice daily thereafter for 30 days) or clopidogrel (300-600 mg loading dose, 75 mg daily thereafter for 30 days) by use of an interactive web response system, and stratified by centre. The primary outcome was a composite of PCI-related type 4 (a or b) myocardial infarction or major myocardial injury and the primary safety outcome was major bleeding, both of which were evaluated within 48 h of PCI (or at hospital discharge if earlier). The primary analysis was based on all events that occurred in the intention-to-treat population. The trial was registered with ClinicalTrials.gov, NCT02617290., Findings: Between Jan 9, 2017, and May 28, 2020, 1910 patients were randomly assigned at 49 sites, 956 to the ticagrelor group and 954 to the clopidogrel group. 15 patients were excluded from the ticagrelor group and 12 from the clopidogrel group. At 48 h, the primary outcome was observed in 334 (35%) of 941 patients in the ticagrelor group and 341 (36%) of 942 patients in the clopidogrel group (odds ratio [OR] 0·97, 95% CI 0·80-1·17; p=0·75). The primary safety outcome did not differ between the two groups, but minor bleeding events were more frequently observed with ticagrelor than clopidogrel at 30 days (105 [11%] of 941 patients in the ticagrelor group vs 71 [8%] of 942 patients in the clopidogrel group; OR 1·54, 95% CI 1·12-2·11; p=0·0070)., Interpretation: Ticagrelor was not superior to clopidogrel in reducing periprocedural myocardial necrosis after elective PCI and did not cause an increase in major bleeding, but did increase the rate of minor bleeding at 30 days. These results support the use of clopidogrel as the standard of care for elective PCI., Funding: ACTION Study Group and AstraZeneca., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

An increasing number of studies of left ventricular myocardial deformation have been published. Layer-specific strain using speckle tracking echocardiography to evaluate left ventricular function is not recommended in clinical practice. However, evaluation of myocardial mechanics using longitudinal and circumferential layer-specific strain enables the detection of subclinical impairment of myocardial deformation in various diseases. Unfortunately, normal values for longitudinal and circumferential strain have not been clearly defined. In normal subjects, layer-specific strain decreases from the endocardial to the epicardial layer, and from the apex to the base of the left ventricle. Although various studies have tried to define normal values for each layer in healthy subjects, studies with more subjects are needed. This tool has good reproducibility in terms of intraobserver and interobserver variability, but, as with monolayer strain, it has poor intervendor variability. Efforts that aim for standardization between vendors will be required before widespread use of this technique can be advocated., (Copyright © 2020 Elsevier Masson SAS. All rights reserved.)

Background: The COVID-19 pandemic has had a profound effect on general health care. We aimed to evaluate the effect of a nationwide lockdown in France on admissions to hospital for acute myocardial infarction, by patient characteristics and regional prevalence of the pandemic., Methods: In this registry study, we collected data from 21 centres participating in the ongoing French Cohort of Myocardial Infarction Evaluation (FRENCHIE) registry, which collects data from all patients admitted for ST segment elevation myocardial infarction (STEMI) or non-ST segment elevation myocardial infarction (NSTEMI) within 48 h of symptom onset. We analysed weekly hospital admissions over 8 weeks: the 4 weeks preceding the institution of the lockdown and the 4 weeks following lockdown. The primary outcome was the change in the number of hospital admissions for all types of acute myocardial infarction, NSTEMI, and STEMI between the 4 weeks before lockdown and the 4 weeks after lockdown. Comparisons between categorical variables were made using χ 2 tests or Fisher's exact tests. Comparisons of continuous variables were made using Student's t tests or Mann-Whitney tests. Poisson regression was used to determine the significance of change in hospital admissions over the two periods, after verifying the absence of overdispersion. Age category, region, and type of acute myocardial infarction (STEMI or NSTEMI) were used as covariables. The FRENCHIE cohort is registered with ClinicalTrials.gov, NCT04050956., Findings: Between Feb 17 and April 12, 2020, 1167 patients were consecutively admitted within 48 h of acute myocardial infarction (583 with STEMI, 584 with NSTEMI) and were included in the study. Admissions for acute myocardial infarction decreased between the periods before and after lockdown was instituted, from 686 before to 481 after lockdown (30% decrease; incidence rate ratio 0·69 [95% CI 0·51-0·70]). Admissions for STEMI decreased from 331 to 252 (24%; 0·72 [0·62-0·85]), and admissions for NSTEMI decreased from 355 to 229 (35%; 0·64 [0·55-0·76]) following institution of the lockdown, with similar trends according to sex, risk factors, and regional prevalence of hospital admissions for COVID-19., Interpretation: A marked decrease in hospital admissions was observed following the lockdown, irrespective of patient characteristics and regional prevalence of COVID-19. Health authorities should be aware of these findings, in order to adapt their message if the COVID-19 pandemic persists or recurs, or in case of future major epidemics., Funding: Recherche Hospitalo-Universitaire en Santé iVasc., (Copyright © 2020 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Background It is unclear whether HIV infection affects the long-term prognosis after an acute coronary syndrome (ACS). The objective of the current study was to compare rates of major adverse cardiac and cerebrovascular events after a first ACS between people living with HIV (PLHIV) and HIV-uninfected (HIV-) patients, and to identify determinants of cardiovascular prognosis. Methods and Results Consecutive PLHIV and matched HIV- patients with a first episode of ACS were enrolled in 23 coronary intensive care units in France. Patients were matched for age, sex, and ACS type. The primary end point was major adverse cardiac and cerebrovascular events (cardiac death, recurrent ACS, recurrent coronary revascularization, and stroke) at 36-month follow-up. A total of 103 PLHIV and 195 HIV- patients (mean age, 49 years [SD, 9 years]; 94.0% men) were included. After a mean of 36.6 months (SD, 6.1 months) of follow-up, the risk of major adverse cardiac and cerebrovascular events was not statistically significant between PLHIV and HIV- patients (17.8% and 15.1%, P =0.22; multivariable hazard ratio [HR], 1.60; 95% CI, 0.67-3.82 [ P =0.29]). Recurrence of ACS was more frequent among PLHIV (multivariable HR, 6.31; 95% CI, 1.32-30.21 [ P =0.02]). Stratified multivariable Cox models showed that HIV infection was the only independent predictor for ACS recurrence. PLHIV were less likely to stop smoking (47% versus 75%; P =0.01) and had smaller total cholesterol decreases (-22.3 versus -35.0 mg/dL; P =0.04). Conclusions Although the overall risk of major adverse cardiac and cerebrovascular events was not statistically significant between PLHIV and HIV- individuals, PLHIV had a higher rate of recurrent ACS. Registration URL: https://www.clini​caltr​ials.gov; Unique identifier: NCT00139958.

Background and Aims: Patients with heterozygous familial hypercholesterolemia (HeFH) present elevated cardiovascular (CV) risk. Current CV risk stratification algorithms developed for the general population are not adapted for heFH patients. It is therefore of singular importance to develop and validate CV prediction tools, which are dedicated to the HeFH population., Methods: Our first objective was to validate the Spanish SAFEHEART-risk equation (RE) in the French HeFH cohort (REFERCHOL), and the second to compare SAFEHEART-RE with the low-density-lipoprotein-cholesterol (LDL-C)-year-score for the prediction of CV events in the HeFH French population., Results: We included HeFH (n = 1473) patients with a genetic or clinical diagnosis (DLCN score ≥8). Among them, 512 patients with a 5-year follow-up were included to validate the 5 year-CV-RE. A total of 152 events (10.3%) occurred in the entire population of 1473 patients during a mean follow-up of 3.9 years. Over the five-year follow-up, non-fatal CV events occurred in 103 patients (20.2%). Almost all the parameters used in the SAFEHEART-RE were confirmed as strong predictors of CV events in the REFERCHOL cohort. The C-statistic revealed a satisfactory performance of both the SAFEHEART-RE and LDL-C-year-scores in predicting CV events for all the patients (primary and secondary prevention) (C-index 0.77 and 0.70, respectively) as well as for those in primary prevention at inclusion (C-index 0.78 and 0.77, respectively)., Conclusions: This analysis represents the first external validation of the SAFEHEART-RE and demonstrated that both SAFEHEART-RE and the LDL-C-year-score are good predictors of CV events in primary prevention HeFH patients., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: Transthoracic echocardiography (TTE) and transoesophageal echocardiography (TOE) can be used to detect the presence of left atrial thrombus and left atrial spontaneous echocardiographic contrast (LASEC)., Aim: To evaluate the prognostic value of TTE and TOE in predicting stroke and all-cause death at 5-year follow-up in patients with non-valvular atrial fibrillation (NVAF)., Methods: This study included patients hospitalised with electrocardiography-diagnosed NVAF in Saint-Antoine University Hospital, Paris, between July 1998 and December 2011, who underwent TTE and TOE evaluation within 24hours of admission. Cox proportional-hazards models were used to identify predictors of the composite outcome (stroke or all-cause death)., Results: During 5 years of follow-up, stroke/death occurred in 185/903 patients (20.5%). By multivariable analysis, independent predictors of stroke/death were CHA 2 DS 2 -VASc score (hazard ratio [HR] 1.35, 95% confidence interval [CI] 1.25-1.47; P<0.001), left atrial area>20 cm 2 (HR 1.59, 95% CI 1.08-2.35; P=0.018), moderate LASEC (HR 1.72, 95% CI 1.13-2.62; P=0.012) and severe LASEC (HR 2.04, 95% CI 1.16-3.58; P=0.013). Independent protective predictors were dyslipidaemia (HR 0.60, 95% CI 0.43-0.83; P=0.002) and discharge prescription of anti-arrhythmics (HR 0.59, 95% CI 0.40-0.87; P=0.008). Adding LASEC to the CHA 2 DS 2 -VASc score modestly improved predictive accuracy and risk classification, with a C index of 0.71 vs. 0.69 (P=0.004)., Conclusions: In this retrospective monocentric study, the presence of moderate/severe LASEC was an independent predictor of stroke/death at 5-year follow-up in patients with NVAF. The inclusion of LASEC in stroke risk scores could modestly improve risk stratification., (Copyright © 2020. Published by Elsevier Masson SAS.)

Background: Clopidogrel associated with aspirin is the recommended treatment for patients undergoing elective percutaneous coronary intervention (PCI). Although severe PCI-related events are rare, evidence suggests that PCI-related myocardial infarction and myocardial injury are frequent complications that can impact the clinical prognosis of the patients. Antiplatelet therapy with a potent P2Y 12 receptor inhibitor such as ticagrelor may reduce periprocedural ischemic complications while maintaining a similar safety profile as compared with conventional dual antiplatelet therapy by aspirin and clopidogrel in this setting., Methods: Assessment of Loading with the P2Y 12 inhibitor ticagrelor or clopidogrel to Halt ischemic Events in patients Undergoing elective coronary Stenting (ALPHEUS) (NCT02617290) is an international, multicenter, randomized, parallel-group, open-label study in patients with stable coronary artery disease who are planned for an elective PCI. In total, 1,900 patients will be randomized before a planned PCI to a loading dose of ticagrelor 180 mg or a loading dose of clopidogrel (300 or 600 mg) in addition to aspirin. Patients will then receive a dual antiplatelet therapy with aspirin and ticagrelor 90 mg twice daily or clopidogrel 75 mg once daily for 30 days. The primary ischemic end point is PCI-related myocardial infarction (myocardial infarction type 4a or 4b) or major myocardial injury within 48 hours (or at hospital discharge if earlier) after elective PCI/stent. Safety will be evaluated by major bleeding events (Bleeding Academic Research Consortium type 3 or 5) at 48 hours (or discharge if it occurs earlier)., Conclusion: ALPHEUS is the first properly sized trial comparing ticagrelor to clopidogrel in the setting of elective PCI and is especially designed to show a reduction in periprocedural events, a surrogate end point for mortality., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: People living with human immunodeficiency virus (PLHIV) are at increased risk of atherosclerotic cardiovascular disease (ASCVD) and are prone to statin-related adverse events from drug-drug interactions with certain antiretroviral regimens., Objectives: This study sought to evaluate the efficacy and safety of evolocumab in dyslipidemic PLHIV., Methods: BEIJERINCK (EvolocumaB Effect on LDL-C Lowering in SubJEcts with Human Immunodeficiency VirRus and INcreased Cardiovascular RisK) is a randomized, double-blind, multinational trial comparing monthly subcutaneous evolocumab 420 mg with placebo in PLHIV with hypercholesterolemia/mixed dyslipidemia taking maximally-tolerated statin therapy. The primary endpoint was the percent change (baseline to week 24) in low-density lipoprotein cholesterol (LDL-C); secondary endpoints included achievement of LDL-C <70 mg/dl and percent change in other plasma lipid and lipoprotein levels. Treatment-emergent adverse events were also examined., Results: A total of 464 patients were analyzed (mean age of 56.4 years, 82.5% male, mean duration with HIV of 17.4 years). ASCVD was documented in 35.6% of patients, and statin intolerance/contraindications to statin use were present in 20.7% of patients. Evolocumab reduced LDL-C by 56.9% (95% confidence interval: 61.6% to 52.3%) from baseline to week 24 versus placebo. An LDL-C level of <70 mg/dl was achieved in 73.3% of patients in the evolocumab group versus 7.9% in the placebo group. Evolocumab also significantly reduced other atherogenic lipid levels, including non-high-density lipoprotein cholesterol, apolipoprotein B, and lipoprotein(a) (all p < 0.0001). Evolocumab was well tolerated, and treatment-emergent adverse events patient incidence was similar among evolocumab and placebo groups., Conclusions: Evolocumab was safe and significantly reduced lipid levels in dyslipidemic PLHIV on maximally-tolerated statin therapy. Evolocumab is an effective therapy for lowering atherogenic lipoproteins in PLHIV with high cardiovascular risk. (Safety, Tolerability & Efficacy on LDL-C of Evolocumab in Subjects With HIV & Hyperlipidemia/Mixed Dyslipidemia; NCT02833844)., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Variants in LMNA , encoding A-type lamins, are responsible for laminopathies including muscular dystrophies, lipodystrophies, and progeroid syndromes. Cardiovascular laminopathic involvement is classically described as cardiomyopathy in striated muscle laminopathies, and arterial wall dysfunction and/or valvulopathy in lipodystrophic and/or progeroid laminopathies. We report unexpected cardiovascular phenotypes in patients with LMNA -associated lipodystrophies, illustrating the complex multitissular pathophysiology of the disease and the need for specific cardiovascular investigations in affected patients. A 33-year-old woman was diagnosed with generalized lipodystrophy and atypical progeroid syndrome due to the newly identified heterozygous LMNA p.(Asp136Val) variant. Her complex cardiovascular phenotype was associated with atherosclerosis, aortic valvular disease and left ventricular hypertrophy with rhythm and conduction defects. A 29-year-old woman presented with a partial lipodystrophy syndrome and a severe coronary atherosclerosis which required a triple coronary artery bypass grafting. She carried the novel heterozygous p.(Arg60Pro) LMNA variant inherited from her mother, affected with partial lipodystrophy and dilated cardiomyopathy. Different lipodystrophy-associated LMNA pathogenic variants could target cardiac vasculature and/or muscle, leading to complex overlapping phenotypes. Unifying pathophysiological hypotheses should be explored in several cell models including adipocytes, cardiomyocytes and vascular cells. Patients with LMNA -associated lipodystrophy should be systematically investigated with 24-h ECG monitoring, echocardiography and non-invasive coronary function testing.

Background: The Data Collection on Adverse Events of Anti-HIV Drugs (DAD) study has reported an increased risk of cardiovascular diseases in people with human immunodeficiency virus who were exposed to darunavir (DRV) but not to atazanavir (ATV). Our objective was to evaluate associations between ATV or DRV exposures and the risk of myocardial infarction (MI) in a nested case-control study within ANRS-CO4 French Hospital Database on HIV (FHDH)., Methods: Cases were individuals who had a first validated MI between 2006 and 2012. Up to 5 controls were selected at random with replacement among individuals with no history of MI, followed at the time of MI diagnosis, and matched for age and sex. Conditional logistic regression models were used to adjust for potential confounders (MI risk factors and HIV-related parameters) and for cumulative exposure to each antiretroviral drug (ARV)., Results: Overall, 408 MI cases and 1250 controls were included: 109 (27%) cases and 288 (23%) controls had been exposed to ATV, and 41 (10%) cases and 107 (9%) controls had been exposed to DRV. There was no significant association between exposure to ATV (adjusted odds ratio [OR] = 1.54; 95% confidence interval [CI], .87-2.73) or DRV (adjusted OR = 0.51; 95% CI, .11-2.32) and the risk of MI., Conclusions: In FHDH, exposures to ATV or to DRV were not significantly associated with the risk of MI, adjusting for complete ARV history, contrary to the analysis in DAD., (© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Background: People living with human immunodeficiency virus (PLHIV) are at higher risk of atherosclerotic cardiovascular disease (ASCVD) due to traditional and HIV- or antiretroviral treatment (ART)-related risk factors. The use of high-intensity statin therapy is often limited by comorbidities and drug-drug interactions with ART. Herein, we present the design and baseline characteristics of the BEIJERINCK study, which will assess the safety and efficacy of evolocumab in PLHIV and hypercholesterolemia/mixed dyslipidemia., Methods: Randomized, double-blind, placebo-controlled, multinational trial that investigates monthly subcutaneous evolocumab 420 mg versus placebo in PLHIV with hypercholesterolemia/mixed dyslipidemia who are treated with maximally-tolerated statin therapy. The primary outcome is the baseline to week 24 percent change in low density lipoprotein cholesterol (LDL-C). Secondary outcomes include achievement of LDL-C < 70 mg/dL and percent change in other plasma lipid and lipoprotein levels. Safety will also be examined., Results: This study enrolled and dosed 464 patients who had a mean age of 56.4 years and were mostly male (82.5%). Mean duration with HIV was 17.4 years, and, by design, HIV viral load at screening was ≤50 copies/mL. ASCVD was documented in 35.6% of patients. Mean LDL-C of enrolled patients at baseline was 133.3 mg/dL. Statin use was prevalent (79.3% overall) with 74.6% receiving moderate or high-intensity statins. In total, 20.7% of patients did not receive statins due to intolerance/contraindications., Conclusions: The BEIJERINCK study is the first clinical trial to examine the lipid-lowering efficacy and safety of a fully human PCSK9 monoclonal antibody inhibitor in a moderate/high cardiovascular risk population of PLHIV., Competing Interests: Disclosures FB reports research grants from Amgen; lecture fees from Janssen, Gilead, ViiV Healthcare, Amgen, Sanofi, MSD, and Servier outside the submitted work. PK reports grants from Amgen, GSK, Merck, Gilead, and TheraTherapeutics, consulting fees from Amgen, GSK, Merck, Gilead, and TheraTherapeutics, and stock in GSK, Merck, Gilead, Pfizer, and Johnson & Johnson. BC receives research support from Boheringer-Ingelheim, Amgen, consulting fees from Amgen, Bayer, honoraria for non-promotional speaking from Servier, Boehringer-Ingelheim, and from Elsevier's Order Sets. AC reports education grants (to the HIV Unit, Geneva University Hospitals) from Janssen, Gilead, ViiV Healthcare, MSD and Amgen. JAGL, SB, and MC are employees and stockholders of Amgen Inc. RSR receives research support from Akcea, Amgen, Medicines Company, Novartis and Regeneron, consulting fees from Amgen, C5, CVS Caremark, Corvidia, Medicines Company, honoraria for non-promotional speaking from Amgen, Kowa, Pfizer and Regeneron, royalties from UpToDate, Inc., and has stock ownership in MediMergent, LLC., (Copyright © 2019. Published by Elsevier Inc.)

Introduction: Previous studies have reported lower rates of coronary angiography and revascularization, and significantly higher mortality among patients infected with human immunodeficiency virus (HIV) presenting with acute myocardial infarction (AMI). This observational study was designed to evaluate characteristics and inpatient outcomes of patients with seropositive HIV infection presenting with AMI., Methods: Using the National Inpatient Sample (NIS) database, we identified patients (admissions) with a primary diagnosis of myocardial infarction and a co-occurring HIV. We described baseline characteristics and outcomes. Our primary outcomes of interest were prevalence of coronary angiography, revascularization (percutaneous coronary intervention (PCI) or CABG), and mortality., Results: From 2010 to 2014, of about 2,977,387 patients with a primary diagnosis of AMI, 10,907 (0.4%) were HIV seropositive. Patients with HIV were younger and more likely to be African American or Hispanic. Coronary angiography and revascularization were performed more frequently in the HIV population. The higher prevalence of revascularization was driven by a higher incidence of PCI. In a multivariable model, patients with HIV were no more likely to undergo revascularization than the general population. This was also the case for PCI. Unadjusted all-cause mortality was lower among patients with HIV. After controlling for confounders, this finding was not significant (OR 0.97, 95% CI 0.75-1.25, p = 0.79). The length of stay between both groups was comparable., Conclusion: In this current analysis, we did not note any treatment bias or difference in the rate of in-hospital total mortality for HIV-seropositive patients presenting with AMI compared with the general population.

Background: HIV-infected individuals undergoing effective antiretroviral therapy (ART) present an increased risk of atherosclerotic cardiovascular disease. We identified serum metabolites associated with carotid intima-media thickness (c-IMT) and its evolution., Methods: One hundred forty-three hydrophilic serum metabolites were measured by ultraperformance liquid chromatography coupled with high-resolution mass spectrometry in 49 HIV+ ART+, 48 HIV+ ART-naïve and 50 HIV-negative, age-matched, never-smoking male triads. Metabolites differentially altered between groups ("features") were defined as having a Benjamini-Hochberg-adjusted P value <.05 from a t test and >0.25 log 2 absolute mean fold change in metabolite levels. c-IMT was measured across 12 sites at inclusion in all individuals and at the carotid artery (cca) after a median of 5.1 years in 32 HIV+ ART+ individuals. The difference in c-IMT (cross-sectional analysis) and slope of cca-IMT regression/progression per year (longitudinal analysis) for each log 10 (area) increase in metabolite level were estimated with linear regression., Results: Compared with HIV-, metabolite features of HIV+ ART+ were increased N6,N6,N6-trimethyl-L-lysine and decreased ferulate and 5-hydroxy-L-tryptophan, whereas features of HIV+ ART-naïve were increased malate, kynurenine, 2-oxoglutarate, and indole-3-acetate and decreased succinate and 5-hydroxy-L-tryptophan. In HIV+ ART+ individuals, quinolinate and/or indole-3-acetate were positively associated with c-IMT ( P <  .03), cca-IMT ( P <  .03), and cca-IMT progression ( P <  .008). These associations were not observed in HIV+ ART-naïve or HIV-negative individuals. In HIV+ ART+ individuals, the metabolites xanthosine and uridine, from nucleotide metabolism, and g-butyrobetaine, from lysine/dietary choline degradation, were also positively or negatively associated with c-IMT and/or cca-IMT (all P <  .01), but not its evolution., Conclusions: In these highly selected HIV-positive ART-controlled males, 2 novel metabolites derived from tryptophan catabolism, indole-3-acetate and quinolinate, were associated with c-IMT and its progression., (© The Author(s) 2019. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Transthoracic echocardiography remains the first-line cardiac imaging for diagnosis, management and screening of heart failure, whatever its phenotype (heart failure with reduced, mid-range and preserved ejection fraction). It allows anatomic characterization, systolic and diastolic functions of left and right ventricles assessment, intracardiac hemodynamic evaluation and for the assessment of valve disease. Myocardial deformation imaging (strain) is indicated in patients with heart failure for the assessment of systolic ventricles function and the diagnosis of specific heart diseases. Strain is indicated for the screening of preclinical myocardial dysfunction in patients at risk or exposed to cardiotoxic treatment. Altered global longitudinal strain is associated with a poor prognosis in heart failure. Cardiac magnetic resonance is recommended for the assessment of myocardial structure and function in subjects with poor acoustic window and patients with complex congenital heart diseases, in order to distinguish between ischemic and non-ischemic myocardial damage in patients with dilated cardiopathy and to characterize myocardial tissue in case of suspected specific heart disease., (Copyright © 2019. Published by Elsevier Masson SAS.)

Background: Cancer and acute myocardial infarction (AMI) have important prognostic consequences. Treatment of some cancers may affect coronary artery disease, myocardial function and/or AMI management. Whether the early and long-term mortality of patients with AMI differ according to their history of cancer remains questionable., Aims: To determine in-hospital outcomes and 5-year mortality following AMI according to patient history of cancer., Methods: The FAST-MI registry is a nationwide French survey collecting data on characteristics, management and outcomes of 3670 consecutive patients admitted for AMI during October 2005., Results: Overall, 246/3664 patients (6.7%) admitted for an AMI (47.6% with ST-segment elevation myocardial infarction [STEMI]; 52.4% with non-STEMI [NSTEMI]) had a history of cancer. In-hospital mortality was not significantly different for patients with versus without a history of cancer, overall (adjusted odds ratio [OR]: 1.15, 95% confidence interval [CI]: 0.68-1.94; P=0.61) and in patients with STEMI (adjusted OR: 1.37, 95% CI: 0.69-2.71; P=0.37) or NSTEMI (adjusted OR: 0.97, 95% CI: 0.41-2.28; P=0.95). All-cause mortality at 5 years was higher among patients with a history of cancer (adjusted hazard ratio [HR]: 1.36, 95% CI: 1.08-1.69; P=0.008), whereas 5-year cardiovascular mortality did not differ (adjusted HR: 1.17, 95% CI: 0.89-1.53; P=0.25), regardless of whether the patients had STEMI or NSTEMI. Similar results were found in populations matched on a propensity score including baseline characteristics and early management., Conclusion: A history of cancer, per se, does not appear to be a risk factor for increased in-hospital mortality or long-term cardiovascular mortality in patients admitted for AMI., (Copyright © 2019. Published by Elsevier Masson SAS.)

Background: Atrial remodelling has been poorly investigated in atrial fibrillation (AF), and few studies have focused on biatrial remodelling., Aim: To evaluate right atrial (RA) and left atrial (LA) remodelling in AF using global atrial reservoir strain and three-dimensional (3D) atrial volumes, according to rhythm outcome at mid-term follow-up., Methods: Two-dimensional and 3D transthoracic echocardiography (TTE) were performed within 24hours after admission (M0) and at 6-month follow-up (M6) in patients admitted for AF. RA and LA variables were assessed: body surface area-indexed maximum 3D volume (Max 3D RA Vol i , Max 3D LA Vol i ) and minimum 3D volume (Min 3D RA Vol i , Min 3D LA Vol i ); atrial emptying fraction (3D RAEF, 3D LAEF); atrial expansion index (3D RAEI, 3D LAEI); and global RA and LA reservoir strain., Results: Forty-eight consecutive patients were included prospectively. Three groups were identified depending on rhythm at M0 and M6: AF at M0 and sinus rhythm (SR) at M6 (AF-SR) in 25 (52.1%) patients; AF at M0 and AF at M6 (AF-AF) in 13 (27.1%) patients; and SR at M0 (spontaneous cardioversion before first TTE) and SR at M6 (SR-SR) in 10 (20.8%) patients. Between M0 and M6 in the AF-SR group, we found: significant decreases in Max 3D RA Vol i (P=0.020), Min 3D RA Vol i (P=0.0008), Max 3D LA Vol i (P=0.001) and Min 3D LA Vol i (P=0.0021); significant increases in 3D RAEF (P=0.037) and 3D RAEI (P=0.034); no significant differences in 3D LAEF and 3D LAEI; and significant increases in global RA and LA reservoir strain (both P<0.0001). There was no significant difference with regard to these variables in the AF-AF and SR-SR groups., Conclusion: 3D volume and strain analyses were useful in the evaluation of RA and LA reverse remodelling in successfully cardioverted patients with AF., (Copyright © 2019. Published by Elsevier Masson SAS.)

Introduction : Efficient antiretroviral-treatment (ART) generally allows control of HIV infection. However, persons-living-with-HIV (PLWH), when aging, present a high prevalence of metabolic diseases. Area covered : Altered adiposity, dyslipidemias, insulin resistance, diabetes, and their consequences are prevalent in PLWH and could be partly related to ART. Expert opinion : At first, personal and lifestyle factors are involved in the onset of these complications. The persistence of HIV in tissue reservoirs could synergize with some ART and enhance metabolic disorders. Altered fat repartition, diagnosed as lipodystrophy, has been related to first-generation nucleoside-reverse-transcriptase-inhibitors (NRTIs) (stavudine zidovudine) and some protease inhibitors (PIs). Recently, use of some integrase-inhibitors (INSTI) resulted in weight/fat gain, which represents a worrisome unresolved situation. Lipid parameters were affected by some first-generation NRTIs, non-NRTIs (efavirenz) but also PIs boosted by ritonavir, with increased total and LDL-cholesterol and triglycerides. Insulin resistance is common associated with abdominal obesity. Diabetes incidence, high with first-generation-ART (zidovudine, stavudine, didanosine, indinavir) has declined with contemporary ART close to that of the general population. Metabolic syndrome, a dysmetabolic situation with central obesity and insulin resistance, and liver steatosis are common in PLWH and could indirectly result from ART-associated fat gain and insulin resistance. All these dysmetabolic situations increase the atherogenic cardiovascular risk.

Background: An accurate estimation of the risk of life-threatening (LT) ventricular tachyarrhythmia (VTA) in patients with LMNA mutations is crucial to select candidates for implantable cardioverter-defibrillator implantation., Methods: We included 839 adult patients with LMNA mutations, including 660 from a French nationwide registry in the development sample, and 179 from other countries, referred to 5 tertiary centers for cardiomyopathies, in the validation sample. LTVTA was defined as (1) sudden cardiac death or (2) implantable cardioverter defibrillator-treated or hemodynamically unstable VTA. The prognostic model was derived using the Fine-Gray regression model. The net reclassification was compared with current clinical practice guidelines. The results are presented as means (SD) or medians [interquartile range]., Results: We included 444 patients, 40.6 (14.1) years of age, in the derivation sample and 145 patients, 38.2 (15.0) years, in the validation sample, of whom 86 (19.3%) and 34 (23.4%) experienced LTVTA over 3.6 [1.0-7.2] and 5.1 [2.0-9.3] years of follow-up, respectively. Predictors of LTVTA in the derivation sample were: male sex, nonmissense LMNA mutation, first degree and higher atrioventricular block, nonsustained ventricular tachycardia, and left ventricular ejection fraction (https://lmna-risk-vta.fr). In the derivation sample, C-index (95% CI) of the model was 0.776 (0.711-0.842), and the calibration slope 0.827. In the external validation sample, the C-index was 0.800 (0.642-0.959), and the calibration slope was 1.082 (95% CI, 0.643-1.522). A 5-year estimated risk threshold ≥7% predicted 96.2% of LTVTA and net reclassified 28.8% of patients with LTVTA in comparison with the guidelines-based approach., Conclusions: In comparison with the current standard of care, this risk prediction model for LTVTA in laminopathies significantly facilitated the choice of candidates for implantable cardioverter defibrillators., Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT03058185.

We examined trends in the MI incidence and age at MI diagnosis among adults living with HIV-1 between 2000 and 2009, by comparison with the French MI registries, by gender. Age standardized incidence rates and standardized incidence-ratios (SIRs) were estimated for individuals included in the French hospital database on HIV (n = 71 204, MI = 663) during three periods: 2000-2002, 2003-2005 and 2006-2009. Median ages at MI diagnosis were compared using the Brown-Mood test. Over the study periods, the absolute rate difference and relative risks were higher in women than in men in 2000-2002 and 2006-2009, with respective SIRs 1.99 (1.39-2.75) and 1.12 (0.99-1.27) in 2006-2009. The trends were different for men and women with a decreasing trend in SIRs in men and no change in women. In both sexes, among individuals with CD4 ≥500/μL and controlled viral-load on cART, the risk was no longer elevated. Age at MI diagnosis was significantly younger than in the general population, especially among women (-6.2 years, p<0.001; men: -2.1 years, p = 0.02). In HIV-1-positive adults, absolute rate difference and relative risks and trends of MI were different between men and women and there was no additional risk among individuals on effective cART., Competing Interests: Aliou BALDE was supported by the Fogarty International Center of the National Institutes of Health under Award Number D43TW007995 and D43TW010350. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. All authors declare no conflict of interest, although several members of the group have, at some stage in the past, received funding from a variety of pharmaceutical companies for research, travel grants, speaking engagements or consultancy fees. Sylvie Lang has received travel grants from Boehringer-Ingelheim. Laurent Cotte has received study grants from ViiV Healthcare and MSD; personal fees from BMS, Gilead Sciences, Janssen, MSD and ViiV healthcare. Jean Ferrières has received grants and lecture fees from Amgen, Merck, and Sanofi. Elisabeth Aslangul has received travel grants from Sanofi, Pfizer and Bristol-Myers-Squibb. Antoine Chéret has received study grants from Merck and personal fees from Gilead, ViiV Healthcare, and Janssen. Jean-Luc Meynard has received honoraria from Gilead, Abbott, ViiV Healthcare and BMS. Jean-Michel Molina has received study grants from Merck and Gilead Sciences; advisory board member for Merck, Gilead Sciences, Janssen, ViiV Healthcare, BMS, and Teva, and a speakers’ bureau for Gilead. Franck Boccara has received study grant from Amgen, speaker fees from AstraZeneca, Merck; advisory board member for Amgen, Sanofi, Gilead, and ViiV Healthcare. Dominique Costagliola has received travel grants, consultancy fees, honoraria or study grants from Abbott, Boehringer-Ingelheim, Bristol-Myers-Squibb, Gilead Sciences, Glaxo-Smith-Kline, Janssen, Merck and Roche.There are no patents, products in development, or marketed products to declare. This does not alter the authors’ adherence to all PLOS ONE policies on sharing data and materials.

Background: Heart failure and atrial fibrillation share common mechanisms that may contribute to hypercoagulability and thrombotic risk. Elevated von Willebrand factor (vWF) concentration has been associated with increased risk of thromboembolism and cardiovascular events., Aim: To investigate whether increased vWF plasma concentration predicts occurrence of a composite endpoint (all-cause death and stroke) in patients with non-valvular atrial fibrillation (NVAF)., Methods: We prospectively studied 122 patients (mean age 70±14years; 46% men) hospitalized with NVAF, and followed over a median (interquartile range) of 5.4 (2.3-9.0)years. Cox proportional models were used to estimate the association of vWF concentration with time to stroke and death., Results: Forty-three patients (35%) had at least a stroke or died during the 5-year follow-up. Kaplan-Meier curves using vWF plasma concentration tertiles (≤191IU/dL;>191 to≤295IU/dL;>295IU/dL) showed that vWF plasma concentrations discriminated groups of patients with higher cardiovascular event rates (log-rank P=0.01). In the multivariable analysis, higher vWF concentrations (middle tertile hazard ratio [HR] 4.59, 95% confidence interval [CI] 1.55-13.50 [P=0.006]; upper tertile HR 4.10, 95% CI 1.43-11.75 [P=0.009]), age≥75years (HR 5.02, 95% CI 1.53-16.49; P=0.008), heart failure (HR 2.05, 1.01-4.19; P=0.048), C-reactive protein, log 2 per unit increase (HR 1.29, 95% CI 1.04-1.61; P=0.021), no warfarin at discharge (HR 4.96, 95% CI 2.02-12.20; P<0.0001) and no aspirin at discharge (HR 4.41, 95% CI 1.71-11.97; P=0.002) were independently associated with an increased risk of stroke and all-cause death, whereas female sex was a protective factor (HR 0.35, 0.16-0.78; P=0.01)., Conclusions: High vWF plasma concentrations may discriminate patients with NVAF at greater risk of stroke or all-cause death., (Copyright © 2017. Published by Elsevier Masson SAS.)

Objective: The study aims to assess the association between proprotein convertase subtilisin/kexin type 9 (PCSK9), a major regulator of LDL cholesterol (LDL-C) homeostasis, and HIV-related dyslipidaemia in a cohort of HIV-positive (HIV+) patients under protease inhibitors., Methods: Plasma PCSK9 levels were measured in 103 HIV+ patients before and after initiating protease inhibitor-based antiretroviral therapy (ART), and in 90 HIV-negative controls matched for age and sex. PCSK9 was measured by ELISA. HIV+ patients who were not virologically suppressed at follow-up or were on lipid-lowering therapy were excluded., Results: In HIV+ (median age 36 years; 77.7% men), PCSK9 levels did not increase after protease inhibitor exposure (median 14 months) (279.5 ng/ml before, 289.6 ng/ml after; P = 0.49) and were significantly elevated versus controls at all timepoints (adjusted P value before and after: <0.05). After protease inhibitor initiation, total cholesterol, LDL-C and HDL cholesterol levels increased, but LDL-C remained lower versus controls. At baseline, PCSK9 levels were positively associated with immunodeficiency and the severity of HIV disease [HIV-1 viral load (P = 0.01), CD4 T-cell count <200/μl, P = 0.002], stage C HIV disease (P = 0.0002). In protease inhibitor-treated patients, PCSK9 levels were no longer associated with HIV-related factors but with total cholesterol (P = 0.0006), LDL-C (P = 0.01), HDL cholesterol (P = 0.01), triglycerides (P = 0.05) and glycaemia (P = 0.006)., Conclusion: PSCK9 levels are elevated in HIV+ patients. In ART-naive patients, the relationship between PCSK9 levels and infection severity suggests an effect of HIV disease. After initiating protease inhibitor-containing ART in virologically suppressed patients, PCSK9 levels were associated with dyslipidaemia similar to controls.

: This series of review articles outlines the complex cause of HIV-related cardiovascular diseases (CVDs) particularly the interactions of viral factors, complications of antiviral therapy such as metabolic derangement, and chronic systemic inflammation. These factors, directly stemming from chronic HIV infection, are important in the pathogenesis of HIV-related CVD. Addressing each issue has likely underpinned the improved morbidity and increased life expectancy enjoyed by patients in the modern era of HIV management. The global management of HIV-related CVD may, however, be simpler than previously imagined, as the disease likely follows a pathway shared by multiple systemic diseases. Other chronic systemic diseases, including diabetes, rheumatoid arthritis, and autoimmune disease, share numerous pathophysiological mechanisms with HIV and provoke similar cardiac complications. CVD risk management in patients living with HIV (PLHIV) may be optimized by drawing upon existing knowledge of chronic systemic diseases which may open up new concepts in treatment and address the current shortfalls in cardiovascular management of PLHIV.

People living with human immunodeficiency virus (HIV) infection and receiving antiretroviral therapy now have the same life expectancy as the general population. However, they have a higher risk of atherosclerotic cardiovascular events because of a complex and polyfactorial vasculopathy, combining the effects of antiretroviral therapy, the HIV virus itself, immune activation, chronic inflammation and metabolic disturbances. Whether people living with HIV infection experience increased vascular aging compared with the general population remains controversial. To summarize current knowledge of the association between HIV infection and aortic stiffness as a marker of vascular aging. This review included 18 clinical studies in adult populations, published between 2009 and 2016, and identified on PubMed/MEDLINE or other databases. Search terms were aortic stiffness, arterial stiffness, vascular aging, pulse wave velocity and HIV. All 18 studies were observational, and compared groups infected (HIV+) and not infected (HIV-) with HIV. Ten studies (55%) reported no significant differences in aortic stiffness between HIV+ groups and age-matched HIV- control groups. The main reported determinants of aortic stiffness were age, blood pressure, smoking, metabolic syndrome and HIV-related variables, including CD4/CD8 ratio, current T-CD4 count < 200/mm 3 and nadir T-CD4+ count < 200/mm 3 . We found discordant results regarding whether HIV+ patients had increased aortic stiffness compared with HIV- controls. However, HIV-related conditions were associated with vascular health. This association has been confirmed in recent prospective studies. There is emerging evidence that HIV itself and immune activity affect vascular health and the large arteries., (Copyright © 2017 Elsevier Masson SAS. All rights reserved.)

Suboptimal drug adherence represents a major challenge to effective primary and secondary prevention of cardiovascular disease. While adherence is influenced by multiple considerations, polypharmacy and dosing frequency appear to be rate-limiting factors in patient satisfaction and subsequent adherence. The cardiovascular and metabolic therapeutic areas have recently benefited from a number of advances in drug therapy, in particular protease proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors and incretin-based therapies, respectively. These drugs are administered subcutaneously and offer efficacious treatment options with reduced dosing frequency. Whilst patients with diabetes and diabetologists are well initiated to injectable therapies, the cardiovascular therapeutic arena has traditionally been dominated by oral agents. It is therefore important to examine the practical aspects of treating patients with these new lipid-lowering agents, to ensure they are optimally deployed in everyday clinical practice.

: Populations living with HIV who access effective antiretroviral therapies are ageing and thus facing chronic disease-related comorbidities. Cardiovascular disease is now a leading cause of morbidity and mortality in the HIV population as in the general population. The increased incidence of cardiovascular complications experienced by the HIV population is due to physiological aging and consequently the increased risk of hypertension, diabetes, and renal failure. Whether HIV itself is an additive and independent risk factor for cardiovascular disease (CVD) remains a central question. If and how HIV impacts the ageing process is an important and related question. The purpose of the present review is to highlight the risk of CVD in the ageing HIV population, particularly concerning atherosclerotic CVD (ASCVD) and heart failure, and to address effective CVD prevention in an aging HIV population at risk of poly-pharmacy.

Aim: To explore platelet reactivity on dual antiplatelet therapy (DAPT) of acute coronary syndrome (ACS) patients infected with HIV., Methods and Results: Acute coronary syndrome patients infected with HIV (n = 80) were matched to ACS patients without HIV (n = 160) on age, sex, diabetes, and DAPT (aspirin 100%, clopidogrel 68%, prasugrel 31%, ticagrelor 1%). Platelet reactivity was evaluated after ACS (>30 days) by measuring residual platelet aggregation (RPA) to aspirin and to P2Y12 inhibitors with light transmission aggregometry (LTA), VerifyNow aspirin assay (ARU), and P2Y12 assay (PRU) and with the VASP platelet reactivity index (VASP-PRI). Proportion of patients with high residual platelet reactivity (HPR) was evaluated. HIV-infected ACS patients had higher levels of platelet reactivity in response to P2Y12 inhibitors (RPA: 23.8 ± 2.7% vs. 15.3 ± 1.3%; P = 0.001; PRU: 132 ± 10 vs. 107.4 ± 6.6; P = 0.04; and VASP-PRI: 45.2 ± 2.6% vs. 32.0 ± 2.0%; P < 0.001) and to aspirin (RPA: 3.6 ± 1.5% vs. 0.4 ± 0.1%; P = 0.004 and ARU: 442 ± 11 vs. 407 ± 5; P = 0.002) compared with non-HIV. HIV-infection was independently associated with increased platelet reactivity regardless of the test used (RPA: P = 0.005; PRU: P < 0.001 and VASP-PRI: P < 0.001) and a higher proportion of HPR (OR = 7.6; P < 0.001; OR = 2.06; P = 0.06; OR = 2.91; P = 0.004, respectively) in response to P2Y12 inhibitors. Similar results were found with aspirin. Protease inhibitors use was associated with increased platelet reactivity and higher rate of HPR., Conclusions: Acute coronary syndrome patients infected with HIV have increased levels of platelet reactivity and higher prevalence of HPR to P2Y12 inhibitors and aspirin than non-HIV patients. These results could provide potential explanations for the observed increase risk of recurrent ischemic events in the HIV-infected population., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2017. For permissions, please email: journals.permissions@oup.com.)

Knowledge about lipid interventions in secondary prevention in HIV-infected individuals is limited; studies are sparse., Methods: A prospective observational multicenter study enrolled 282 patients on statin 1 month after first acute coronary syndrome (ACS) (95 HIV-infected individuals, 187 HIV-uninfected). Data on fasting lipids (total cholesterol [TC], low-density lipoprotein cholesterol, high-density lipoprotein cholesterol [HDL-C], non-HDL-C, triglycerides, TC/HDL-C ratio) were collected over 3 years. The evolution of lipid concentrations was analyzed using mixed-effects models. Achievement of National Cholesterol Education Program Adult Treatment Panel III lipid goals and prescribed statin intensity was assessed., Results: Mean age of patients was 49.0 years, and 94% were men. Baseline lipids were similar in the 2 groups. Six months after first ACS, less low-density lipoprotein cholesterol reduction was observed in the HIV-infected GROUP (adjusted mean change -10.13; 95% CI -20.63 to 0.37; P=.06) than in the HIV-uninfected group (Adjusted mean change -38.51; 95% CI -46.00 to -31.04; P<.0001) Similar trends were observed for TC and non-HDL-C. After ACS, initial statin prescription for HIV-infected compared with HIV-uninfected individuals was more frequently a moderate-intensity statin (66% vs 45%) and less frequently a high-intensity statin (15% vs 45%). Over 3 years of follow-up, the proportion of HIV-infected patients receiving high-intensity statin remained persistently lower than the proportion observed in the HIV-uninfected group., Conclusions: In this observational study, HIV-infected individuals after first ACS exhibited worse lipid profiles than controls particularly during the first 6 months while receiving less potent statins. Appropriate statin intensity should be prescribed in HIV-infected individuals with awareness of potential drug-drug interactions., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Competing Interests: Les participants déclarent avoir eu des activités ayant conduit à des rémunérations ou des crédits de recherche (conférences, essais cliniques ou subventions de recherche) au cours des années 2012-2016. S. Béliard : Aegerion, Amgen, ISIS, MSD, Novartis, Novo Nordisk, Sanofi. F. Bonnet : AMGEN, AstraZeneca, BMS, Boehringer-Ingelheim, Coca-Cola, ISA, Lilly, MSD, Novo Nordisk, Sanofi, Takeda. B. Bouhanick : AstraZeneca, Lilly, Novo Nordisk, Sanofi. É. Bruckert : Aegerion, AMGEN, Chiesi, Danone, Genfit, Ionis-pharmaceuticals, Isis, MSD, Lilly, Regeneron, Rottapharm-MEDA, Sanofi, Unilever. B. Cariou : Amgen, AstraZeneca, Genfit, Janssen, Eli-Lilly, Novartis, MSD, Novo Nordisk, Pierre Fabre, Regeneron, Sanofi, Takeda. S. Charriere : AstraZeneca, Boehringer-Ingelheim, Lilly, Merck Serono, MSD, Novartis, Novo Nordisk, Sanofi. V. Durlach : AstraZeneca,Amgen, Bioprojet, Sanofi. P. Moulin : Aegerion, Akcea/ionis, Amgen, AMT, AstraZeneca/Bristol Myers Squibb, Chiesi, Jansen, Lilly, MSD, Novartis, Novo Nordisk, Olympus, Pierre Fabre, Regeneron, Unicure, Sanofi, Servier. R. Valéro : Amgen, AstraZeneca, Chiesi, Danone, ISIS, Janssen, Lesieur, Lilly, MSD, Novo Nordisk, Sanofi, Unilever. B. Verges : AstraZeneca/Bristol Myers Squibb, Bayer Pharma, Janssen, MSD, Novartis Pharma, Novo Nordisk, Novartis, Sanofi, Servier, Takeda. Les participants déclarent avoir eu des activités ayant conduit à des rémunérations ou des crédits de recherche (conférences, essais cliniques ou subventions de recherche) au cours des années 2012-2016. F. Boccara : Amgen, BMS, Jansen, MSD, Regeneron, Sanofi, Gilead, ViiV Healthcare. M. Farnier : Abbott/Mylan, Akcea/ionis, Amgen, AstraZeneca, Eli Lilly, Kowa, Merck and Co, Pfizer, Roche, Sanofi/Regeneron, Servier. B. Feve : AstraZeneca, Bristol-Myers Squibb, Sanofi Aventis, GlaxoSmithKline, Novartis, NovoJansen, MSD, Novo Nordisk, Eli Lilly, Boehringer Ingelheim, Janssen, Intarcia, Metacure, Pfizer, MSD, Roche Diagnostic, Medtronic, Menarini Diagnostic, Abbott, Vitalaire, Dinno Santé, Orkyn Sanofi, Viiv Healthcare. P. Gourdy : AstraZeneca, Boehringer-Ingelheim, Bristol-Myers-Squibb, Janssen, Eli Lilly, Glaxo-Smith-Kline, Merck Sharpe et Dohme, Novartis, Novo Nordisk, Pierre Fabre, Sanofi, Servier, Takeda. B. Guerci : Abbott, AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Dinno Santé, Eli lilly, Intarcia, Janssen, GlaxoSmithKline, Medtronic, Menarini Diagnostic, Metacure, MSD, Novartis, Novo Nordisk, Orkyn, Pfizer, Roche Diagnostic, Sanofi Aventis, Vitalaire. M. Krempf : Astra Zeneca, AMGEN Boehringer Ingelheim, Danone, Eli Lilly, Ionis pharmaceuticals, Janssen, Menarini Diagnostic, MSD, Novartis, Novo Nordisk, Sanofi, Unilever.

Anthracyclines and molecular targeted agents have improved prognosis of patients undergoing chemotherapeutics for malignancy. However, the use of these therapies is limited because of risk of cardiac toxicity. The severity of the cardiomyopathy can range from an asymptomatic left ventricular (LV) dysfunction to a severe congestive heart failure. Cardiomyopathy can be reversible or irreversible according to the type of chemotherapy, modality of administration and patient's characteristics. Several studies aimed to early detection and the evaluation of tools to characterize patients at risk to develop cardiac side effects in order to prevent severe LV dysfunction. According to this literature, it is recommended that initial assessment and follow-up of patients undergoing these chemotherapies be performed using troponin dosage, assessment of left ventricle ejection fraction and evaluation of LV myocardial deformation assessing LV global longitudinal strain., (Copyright © 2016. Published by Elsevier Masson SAS.)

Objective: We compared aortic stiffness between HIV-infected and HIV-uninfected individuals and examined the determinants of vascular aging during HIV infection., Methods: Aortic stiffness using carotid-femoral pulse wave velocity (cf-PWV) was evaluated cross-sectionally between HIV-infected individuals and uninfected controls frequency-matched for age and sex, and longitudinally in a subgroup of HIV-infected individuals. Determinants of elevated cf-PWV levels were assessed using logistic regression. Changes in cf-PWV levels during follow-up (mixed-effect linear regression) and risk factors for achieving cf-PWV below (Group 1) or above the median (Group 2) at last follow-up visit were evaluated only in HIV-infected individuals., Results: A total of 133 HIV-infected and 135 HIV-uninfected individuals (mean age: 47.7 ± 8.9 years, 91% men) were enrolled. Median cf-PWV at baseline was similar between HIV-infected individuals and controls [7.5 m/s (interquartile range = 6.7-8.4) vs. 7.5 m/s (interquartile range = 6.6-8.4), respectively; P = 0.64]. In multivariable analysis, only mean arterial pressure showed significant association with elevated cf-PWV in the overall population (P = 0.036). In HIV-infected individuals, elevated cf-PWV was associated with current smoking (P = 0.042), and nadir CD4 T-cell count less than 200 cells/μl (P = 0.048). Ninety-one HIV-infected individuals were followed for a mean 7.6 ± 2.0 years. cf-PWV progression was associated with age (P = 0.018), mean arterial pressure (P = 0.020), and nadir CD4 T-cell count (P = 0.005). Patients from Group 2 had higher baseline waist circumference, pulse pressure, and nadir CD4 T-cell count less than 200 cells/μl., Conclusion: We observed no difference in aortic stiffness between HIV-infected and controls. Moreover, aortic stiffness aging was independently associated with past severe immunodeficiency, along with other traditional risk factors. Our results call for early antiretroviral initiation.

Objective: To identify factors associated with troponin elevation and to measure the effect of elevated troponin on survival in cancer patients participating in phase I trials., Methods: Clinical characteristics, cardiovascular risk factors, and biological data from consecutive patients treated in phase I trials (January 2010-November 2012) were reviewed. Troponin value was measured for each patient before study-drug administration and then weekly. Cardiac troponin I was considered elevated if >0.06ng/mL. Incidence and relative risk of elevated troponin adjusted for potential confounding factors were estimated using multivariable Poisson regression models. A conditional Cox proportional hazards model was used to compare overall survival in patients with elevated troponin matched to patients without troponin elevation recruited in the same trial., Results: Of 463 patients, 42 (9%) experienced ≥1 episode of troponin I elevation after a median of 5weeks (interquartile range: 3-13) from drug initiation. Crude incidence of troponin elevation was 36/1000 person-months (95% confidence interval [CI]: 25-47). Troponin elevation was more frequent in patients exposed to antiangiogenic compounds versus other treatments (relative risk: 1.9, 95% CI: 1.1-3.3). Median overall survival from drug initiation was 9months (95% CI: 8-10), and 8months (95% CI: 2-13) in patients with troponin elevation. In the case-control analysis, risk of death was higher in patients with troponin elevation (hazard ratio: 2.9, 95% CI: 1.2-6.8)., Conclusion: Patients exposed to antiangiogenic compounds had a higher risk of troponin elevation, which was associated with a higher risk of death., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Autosomal dominant hypercholesterolemia (ADH) is a human disorder characterized phenotypically by isolated high-cholesterol levels. Mutations in the low density lipoprotein receptor (LDLR), APOB, and proprotein convertase subtilisin/kexin type 9 (PCSK9) genes are well known to be associated with the disease. To characterize the genetic background associated with ADH in France, the three ADH-associated genes were sequenced in a cohort of 120 children and 109 adult patients. Fifty-one percent of the cohort had a possible deleterious variant in LDLR, 3.1% in APOB, and 1.7% in PCSK9. We identified 18 new variants in LDLR and 2 in PCSK9. Three LDLR variants, including two newly identified, were studied by minigene reporter assay confirming the predicted effects on splicing. Additionally, as recently an in-frame deletion in the APOE gene was found to be linked to ADH, the sequencing of this latter gene was performed in patients without a deleterious variant in the three former genes. An APOE variant was identified in three patients with isolated severe hypercholesterolemia giving a frequency of 1.3% in the cohort. Therefore, even though LDLR mutations are the major cause of ADH with a large mutation spectrum, APOE variants were found to be significantly associated with the disease. Furthermore, using structural analysis and modeling, the identified APOE sequence changes were predicted to impact protein function., (Copyright © 2016 by the American Society for Biochemistry and Molecular Biology, Inc.)

Background: Some LMNA mutations responsible for lipodystrophies, and some HIV-protease inhibitors (PIs) induce accumulation of farnesylated prelamin A and premature senescence in some cell types. Patients with LMNA mutations or under PI-based therapy suffer from early atherosclerosis. The metalloprotease ZMPSTE24 is the key enzyme in prelamin A maturation., Aim: We studied whether altered expression of ZMPSTE24 could contribute to vascular cell dysfunction in response to LMNA mutations or PI treatments., Methods: Protein expression of prelamin A and ZMPSTE24 were evaluated in patients' cells and in human cultured VSMCs. Oxidative stress, inflammation, senescence and transdifferentiation/calcification were evaluated in VSMCs., Results: Fibroblasts from LMNA-mutated lipodystrophic patients (mutations R482W, D47Y or R133L) and peripheral blood mononuclear cells from PI-treated-HIV-infected patients expressed increased prelamin A and decreased ZMPSTE24, which was also observed in VSMCs overexpressing mutant LMNA or treated with PIs. These alterations correlated with oxidative stress, inflammation, senescence and calcification (all p < 0.05). ZMPSTE24 silencing in native VSMCs recapitulated the mutant LMNA- and PI-induced accumulation of farnesylated prelamin A, oxidative stress, inflammation, senescence and calcification. A negative regulator of ZMPSTE24, miRNA-141-3p, was enhanced in LMNA-mutated or PI-treated VSMCs. The farnesylation inhibitors pravastatin and FTI-277, or the antioxidant N-acetyl cysteine, partly restored ZMPSTE24 expression, and concomitantly decreased oxidative stress, inflammation, senescence, and calcification of PI-treated VSCMs., Conclusions: ZMPSTE24 downregulation is a major contributor in VSMC dysfunctions resulting from LMNA mutations or PI treatments that could translate in early atherosclerosis at the clinical level. These novel pathophysiological mechanisms could open new therapeutic perspectives for cardiovascular aging., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Aim: This open-label, randomized, and multicentre trial tested the hypothesis that, on a background of aspirin, continuing clopidogrel would be superior to stopping clopidogrel at 12 months following drug-eluting stent (DES) implantation., Methods and Results: Patients (N = 1799) who had undergone placement of ≥1 DES for stable coronary artery disease or acute coronary syndrome were included in 58 French sites (January 2009-January 2013). Patients (N = 1385) free of major cardiovascular/cerebrovascular events or major bleeding and on aspirin and clopidogrel 12 months after stenting were eligible for randomization (1:1) between continuing clopidogrel 75 mg daily (extended-dual antiplatelet therapy, DAPT, group) or discontinuing clopidogrel (aspirin group). The primary outcome was net adverse clinical events defined as the composite of death, myocardial infarction, stroke, or major bleeding. Follow-up was planned from a minimum of 6 to a maximum of 36 months after randomization. Owing to slow recruitment, the study was stopped after enrolment of 1385 of a planned 1966 patients. Median follow-up after stenting was 33.4 months. The primary outcome occurred in 40 patients (5.8%) in the extended-DAPT group and 52 in the aspirin group (7.5%; hazard ratio 0.75, 95% confidence interval 0.50-1.28; P = 0.17). Rates of death were 2.3% in the extended-DAPT group and 3.5% in the aspirin group (HR 0.65, 95% CI 0.34-1.22; P = 0.18). Rates of major bleeding were identical (2.0%, P = 0.95)., Conclusions: Extended DAPT did not achieve superiority in reducing net adverse clinical events compared to 12 months of DAPT after DES placement. The power of the OPTIDUAL trial was however low and reduced by premature termination of enrolment., Clinicaltrialsgov Number: NCT00822536., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.)

Background: The association between obstructive sleep apnoea syndrome (OSAS), left ventricular (LV) diastolic dysfunction and LV geometry remains controversial because of coexisting disorders., Aims: To evaluate LV diastolic dysfunction and its independent predictors in a real-life cohort of OSAS patients, by a standardized approach., Methods: We consecutively included 188 OSAS patients after an overnight polysomnography to undergo clinical evaluation, ambulatory blood pressure measurement and complete echocardiography, combining M-mode, two-dimensional Doppler and tissue Doppler imaging modes. Correlations between OSAS severity and clinical and echocardiographical variables were assessed, and logistic regression models were used to identify possible determining factors of LV diastolic dysfunction., Results: Most patients were hypertensive (n=148, 78.7%) and already receiving treatment by continuous positive airway pressure (n=158, 84.5%). The prevalence of LV hypertrophy, defined by LV mass index (LVMi) normalized by height (2.7), was 12.4%, with a significant correlation with hypertension (P=0.004). The apnoea-hypopnoea index was correlated with body mass index (P<0.0001), 24-hour systolic blood pressure (P=0.01) and LVMi normalized by height (2.7) (P=0.03). Diastolic function assessed by a global approach was impaired for 70 patients (37.2%) and none of the OSAS severity variables was a determining factor after multivariable analysis with adjustment for age and sex., Conclusion: Diastolic dysfunction assessed by a standardized approach is common in OSAS and should be routinely evaluated; it is independently predicted by none of the respiratory severity variables., (Copyright © 2015 Elsevier Masson SAS. All rights reserved.)

Background: The effect of statins on all-cause mortality in the general population has been estimated as 0.86 (95%CI 0.79-0.94) for primary prevention. Reported values in HIV-infected individuals have been discordant. We assessed the impact of statin-based primary prevention on all-cause mortality among HIV-infected individuals., Methods: Patients were selected among controls from a multicentre nested case-control study on the risk of myocardial infarction. Patients with prior cardiovascular or cerebrovascular disorders were not eligible. Potential confounders, including variables that were associated either with statin use and/or death occurrence and statin use were evaluated within the last 3 months prior to inclusion in the case-control study. Using an intention to continue approach, multiple imputation of missing data, Cox's proportional hazard models or propensity based weighting, the impact of statins on the 7-year all-cause mortality was evaluated., Results: Among 1,776 HIV-infected individuals, 138 (8%) were statins users. During a median follow-up of 53 months, 76 deaths occurred, including 6 in statin users. Statin users had more cardiovascular risk factors and a lower CD4 T cell nadir than statin non-users. In univariable analysis, the death rate was higher in statins users (11% vs 7%, HR 1.22, 95%CI 0.53-2.82). The confounders accounted for were age, HIV transmission group, current CD4 T cell count, haemoglobin level, body mass index, smoking status, anti-HCV antibodies positivity, HBs antigen positivity, diabetes and hypertension. In the Cox multivariable model the estimated hazard ratio of statin on all-cause mortality was estimated as 0.86 (95%CI 0.34-2.19) and it was 0.83 (95%CI 0.51-1.35) using inverse probability treatment weights., Conclusion: The impact of statin for primary prevention appears similar in HIV-infected individuals and in the general population.

The widespread use of combination antiretroviral therapy (cART) among people living with HIV in developed countries has lead to significantly improved life expectancy. However, extensive use of the effective cART coincides with increasing reports of coronary heart disease (CHD) among people living with HIV, and CHD has become a major cause of death. CHD results from a complex and multifactorial atherosclerotic process involving the over-representation of traditional cardiovascular risk factors, particularly smoking, uncontrolled viral replication, chronic inflammation, immune activation, and exposure to antiretroviral drugs. Consequently careful selection of antiretroviral drugs, cardiovascular risk reduction, and lifestyle modifications are needed. In individuals living with HIV, cardiovascular risk assessment is becoming an important element of care., (Copyright © 2015 Elsevier Masson SAS. All rights reserved.)

Objective: Some intestinal microbiota-generated metabolites of phosphatidylcholine are recognized to be proatherogenic. As the HIV population is vulnerable to cardiovascular disease and can develop intestinal dysbiosis associated with systemic inflammation, we investigated the novel relationship between microbiota-derived metabolites of phosphatidylcholine and coronary atherosclerosis in HIV., Design/methods: One hundred and fifty-five HIV-infected and 67 non-HIV-infected individuals without known history of cardiovascular disease were previously recruited to assess coronary plaque by computed tomography angiography. In the current study, we evaluate whether serum choline, trimethylamine (TMA), or trimethylamine-N-oxide (TMAO) levels are associated with plaque features., Results: Young, asymptomatic HIV-infected patients (age 47 ± 7 years) demonstrated significantly higher prevalence of plaque (53 vs. 35%, P = 0.01) and number of total plaque segments (1.8 ± 2.5 vs. 1.2 ± 2.2, P = 0.03) when compared with well matched noninfected individuals with similar comorbidities. TMA was significantly associated with calcium score (r = 0.22, P = 0.006), number of total (r = 0.20, P = 0.02) and calcified (r = 0.18, P = 0.03) plaque segments, and calcium plaque volume (r = 0.19, P = 0.02) and mass (r = 0.22, P = 0.009) in the HIV cohort only. In multivariate modeling among HIV-infected patients, TMA remained significantly associated with calcium score (P = 0.008), number of total (P = 0.005) and calcified (P = 0.02) plaque segments, and calcium plaque volume (P = 0.01) and mass (P = 0.007), independent of Framingham risk score. In contrast, there was no association of TMAO to coronary plaque features in either cohort., Conclusion: A link between TMA and atherosclerosis has not previously been established. The current study suggests that TMA may be a nontraditional risk factor related to the number of plaque segments and severity of calcified plaque burden in HIV.

Objectives: Increased risk of cardiovascular disease in patients infected with HIV has been attributed to immune activation, inflammation, and immunosenescence, all of which are linked to chronic immune activation by viral infections, particularly cytomegalovirus (CMV). Our aim is to evaluate the impact of these atherogenic markers in HIV-infected patients who never smoked., Design: Exposure-matched, cross-sectional study., Methods: In 59 HIV-infected individuals [n = 30 undergoing ≥4 years of antiretroviral therapy (ART); n = 29 never treated with ART] and 30 age-matched HIV-negative controls, we measured the level of activation and senescence, as well as the frequency of CMV-specific T cells, on peripheral blood mononuclear cells, while examining their association with carotid intima-media thickness. Partial correlations were adjusted for age, systolic blood pressure, and nadir CD4 cell count., Results: The previously described roles of T-cell activation, CMV, and immunosenescence in the atherosclerotic risk of HIV-infected patients, as assessed by carotid intima-media thickness, were not apparent in our cohort of particularly 'healthy' HIV-infected never-smokers., Conclusion: In HIV-infected individuals at low cardiovascular disease risk, our data show that the increased risk of carotid atherosclerosis is not associated with immunological markers described to be associated with HIV disease progression.

Background: While residual plasma viremia is commonly observed in HIV-infected patients undergoing antiretroviral treatment (ART), little is known about its subclinical consequences., Methods: This cross-sectional study included 47 male, never-smoking, non-diabetic patients with ≥4 years of ART and controlled HIV-replication (HIV-viral load, VL <20 copies/mL for ≥1 year). Residual HIV-VL was measured using an ultrasensitive assay (quantification limit: 1 copy/ml). Patients were categorized as having detectable (D; 1-20 copies/mL, n = 14) or undetectable (UD; <1 copies/mL, n = 33) HIV-VL. Linear regression was used to model the difference in total carotid intima-media thickness [c-IMT, measures averaged across common carotid artery (cca), bifurcation, and internal carotid artery] and cca-IMT alone across detection groups. Multivariable models were constructed for each endpoint in a forward-stepwise approach., Results: No significant differences were observed between viremia groups with respect to median ART-duration (9.6 years, IQR = 6.8-10.9), nadir CD4+T-cell (208/mm3, IQR = 143-378), and CD4+T-cell count (555/mm3, IQR = 458-707). Median adjusted inflammatory markers tended to be higher in patients with D- than UD-viremia, with differences in IL-10 being significant (p = 0.03). After adjustment on age, systolic blood pressure, and insulin resistance, mean cca-IMT was significantly lower in patients with undetectable (0.668 mm±0.010) versus detectable viremia (0.727 mm±0.015, p = 0.002). Cca-IMT was also independently associated with age and insulin resistance. Mean adjusted total c-IMT was no different between viremia groups (p = 0.2), however there was large variability in bifurcation c-IMT measurements., Conclusions: Higher cca-IMT was observed in patients with detectable, compared to undetectable, HIV-VL in never-smoking ART-controlled patients, suggesting that residual HIV viremia may be linked to atherosclerosis.

We examined whether impaired kidney function is an independent risk factor for myocardial infarction in HIV-infected individuals without pre-existing coronary artery disease. The odds ratio for impaired kidney function fell from 1.22 (95% confidence interval 0.90-1.66) to 0.99 (95% confidence interval 0.69-1.41) after adjustment for cardiovascular risk factors and HIV-related parameters, with hypertension, high-density lipoprotein cholesterol, smoking and the CD4 T-cell nadir as most influential confounders. In this setting, no association was found between impaired kidney function and the risk of myocardial infarction.

The management of patients suffering from bronchial and lung tumors depends on conventional chemotherapy and/or targeted molecular therapies. The prescription of these chemotherapies may be accompanied by cardiovascular complications, principally congestive heart failure, arterial hypertension and arterial or venous thrombo-embolism, the frequency of which varies with the molecule administered. The management of these complications is currently poorly standardized and should take account of the patient's oncological prognosis., (Copyright © 2014. Published by Elsevier Masson SAS.)

Objectives: To determine whether the reported increased atherosclerotic risk among HIV-infected individuals is related to antiretroviral therapy (ART) or HIV infection, whether this risk persists in never-smokers, and whether inflammatory profiles are associated with higher risk., Design: Matched cross-sectional study., Methods: A total of 100 HIV-infected patients (50 ART-treated >4 years, 50 ART-naive but HIV-infected >2 years) and 50 HIV-negative controls were recruited in age-matched never-smoking male triads (mean age 40.2 years). Carotid intima-media maximal thickness (c-IMT) was measured across 12 sites. Pro-inflammatory [highly sensitive C-reactive protein (hs-CRP), resistin, interleukin-6, interleukin-18, insulin, serum amyloid A, D-dimer) and anti-inflammatory (total and high molecular weight adiponectin, interleukin-27, interleukin-10) markers were dichotomized into high/low scores (based on median values). c-IMT was compared across HIV/treatment groups or inflammatory profiles using linear regression models adjusted for age, diabetes, hypertension, and, for HIV-infected patients, nadir CD4 cell counts., Results: Although adjusted c-IMT initially tended to be thicker in ART-exposed patients (P=0.2), in post-hoc analyses stratifying by median HIV duration we observed significantly higher adjusted c-IMT in patients with longer (>7.9 years: 0.760±0.008 mm) versus shorter prevalent duration of known HIV infection (<7.9 years: 0.731±0.008 mm, P=0.02), which remained significant after additionally adjusting for ART (P=0.04). Individuals with low anti-inflammatory profile (median score) had thicker c-IMT (0.754±0.006mm versus 0.722±0.006 mm, P<0.001), with anti-inflammatory markers declining as prevalent duration of HIV infection increased (P for linear trend <0.001)., Conclusion: Known HIV duration is related to thicker c-IMT, irrespective of ART, in these carefully selected age-matched never-smoking HIV-treated and ART-naive male individuals. Higher levels of anti-inflammatory markers appeared protective for atherosclerosis.