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Background Acute heart failure (AHF) is a common serious condition that contributes to about 5% of all emergency hospital admissions in Europe. Hypothesis To assess the type and chronology of the first AHF symptoms before hospitalization and to examine the French healthcare system pathways before, during and after hospitalization. Material and Methods A retrospective observational study including patients hospitalized for AHF Results 793 patients were included, 59.0% were men, 45.6% identified heart failure (HF) as the main cause of hospitalization; 36.0% were unaware of their HF. Mean age was 72.9 ± 14.5 years. The symptoms occurring the most before hospitalization were dyspnea (64.7%) and lower limb edema (27.7%). Prior to hospitalization, 47% had already experienced symptoms for 15 days; 32% of them for 2 months. Referral to hospital was made by the emergency medical assistance service (SAMU, 41.6%), a general practitioner (GP, 22.3%), a cardiologist (19.5%), or the patient (16.6%). The modality of referral depended more on symptom acuteness than on type of symptoms. A sudden onset of AHF symptoms led to making an emergency call or to spontaneously attending an emergency room (ER), whereas cardiologists were consulted when symptoms had already been present for over 15 days. Cardiologists referred more patients to cardiology departments and fewer patients to the ER than general practitioners or the SAMU. Conclusion This study described the French healthcare system pathways before, during and after hospitalization AHF. AHF clinic network should be developed to provide adequate care for all HF patients and create awareness regarding AHF symptoms.

OBJECTIVES We sought to investigate the safety and potential benefit of administrating glycoprotein IIb-IIIa inhibitors (GPIs) on top of more potent P2Y12 inhibitors. BACKGROUND A number of clinical trials, performed at a time when pretreatment and potent platelet inhibition was not part of routine clinical practice, have documented clinical benefits of GPI in ST-segment elevation myocardial infarction (STEMI) patients at the cost of a higher risk of bleeding. METHODS We used the data of a prospective, ongoing registry of patients admitted for STEMI in our center. For the purpose of this study only patients presenting for primary percutaneous coronary intervention and pretreated with new P2Y12 inhibitors (prasugrel or ticagrelor) were included. We compared patients who received GPI with those who did not. RESULTS Eight hundred twenty-four STEMI patients were included in our registry; GPIs were used in 338 patients (41%). GPI patients presented more often with cardiogenic shock and Thrombolysis in myocardial infarction (TIMI) flow grade

Background An accurate estimation of the duration of atrial fibrillation is critical for its safe management. Recent studies suggested that copeptin, carbohydrate antigen-125, galectin-3 and growth differentiation factor-15 are increased in atrial fibrillation. We examined the ability of these markers to identify patients presenting with atrial fibrillation of ≤48 versus >48 h duration. Methods Retrospective analysis of a prospective study that included patients with atrial fibrillation of known duration. Results A total of 98 patients were analysed, 47 with atrial fibrillation ≤48 h and 51 with >48 h. In patients presenting with atrial fibrillation of ≤48 versus >48 h duration, the mean carbohydrate antigen-125 concentration was 16.9 ± 12.5 versus 30.9 ± 36.3 U/mL ( P = 0.01), and growth differentiation factor-15 concentration was 1320 ± 889 versus 2608 ±2163 pg/mL ( P Conclusion The plasma concentrations of carbohydrate antigen-125, growth differentiation factor-15 and copeptin, but not galectin-3, are higher in patients presenting with atrial fibrillation of >48 h duration than in those with atrial fibrillation ≤48 h. The ability to discriminate recent atrial fibrillation offered by carbohydrate antigen-125 and growth differentiation factor-15 seems high.

AimsNo data exist concerning the clinical performances of the subcutaneous implantable cardioverter-defibrillator (S-ICD) atrial fibrillation (AF) detection algorithm. We aimed to study the performances and implications of the latter in a ‘real-world’ setting.Methods and resultsBetween July 2017 and August 2019, 155 consecutive S-ICD recipients were included. Endpoint of the study was the incidence of de novo or recurrent AF using a combined on-site and remote-monitoring follow-up approach. After a mean follow-up of 13 ± 8 months, 2531 AF alerts were generated for 55 patients. A blinded analysis of the 1950 subcutaneous electrocardiograms available was performed. Among them 47% were true AF, 23% were premature atrial contractions or non-sustained AF, 29% were premature ventricular contractions or non-sustained ventricular tachycardia, and 1% were misdetection. Fourteen percent (21/155) patients had at least one correct diagnosis of AF by the S-ICD algorithm. One patient presented symptomatic paroxysmal AF not diagnosed by the S-ICD algorithm (false negative patient). Patient-based sensitivity, specificity, positive, and negative predictive values were respectively 95%, 74%, 38%, and 99%. Among patients with at least one correct diagnosis of AF, 38% (8/21) had subsequent clinical implications (anticoagulation initiation or rhythm control therapies).ConclusionThe S-ICD AF detection algorithm yields a high sensitivity for AF diagnosis. Low specificity and positive predictive value contribute to a high remote monitoring-notification workload and underline the necessity of a manual analysis. Atrial fibrillation diagnosis by the S-ICD AF detection algorithm might lead to significant therapeutic adjustments.

An increase in left ventricular volumes between baseline and follow-up imaging is the main criteria for the quantification of left ventricular remodelling (LVR) after ST-elevation myocardial infarction (STEMI), but without consensual definition. We aimed to review the criteria used for the definition of LVR based on cardiac magnetic resonance imaging (CMR) in STEMI patients. A systematic literature search was conducted using MEDLINE and the Cochrane Library from January 2010 to August 2019. Thirty-seven studies involving 4209 patients were included. Among these studies, 30 (81%) used a cut-off value for defining LVR, with a pooled LVR prevalence estimate of 22.8%, 95% CI [19.4-26.7%] and a major between-study heterogeneity (I2 = 82%). The seven remaining studies (19%) defined LVR as a continuous variable. The definition of LVR using CMR following STEMI is highly variable, among studies including highly selected patients. A 20% increase or a 15% increase in left ventricular volumes between a baseline and a follow-up CMR imaging were the two most common criterion (13 [35%] and 9 [24%] studies, respectively). The most frequent LVR criterion was a 20% increase in end-diastolic volumes or a 15% increase in end-systolic volumes. A composite cut-off value of a 12 to 15% increase in end-systolic volume and a 12 to 20% increase in end-diastolic volume using a follow-up CMR imaging 3 months after STEMI might be proposed as a consensual cut-off for defining adverse LVR for future large-sized, prospective studies with serial CMR imaging and long-term follow-up in unselected patients.

Aims The risk and incidence of cardiovascular (CV) immune-related adverse events (irAEs) associated with immune checkpoint inhibitors (ICIs) in cancer patients remain unknown. Methods and results We systematically reviewed all randomized clinical trials (RCTs) including at least one ICI-containing arm and available CV adverse event (CVAE) data in cancer patients in the ClinicalTrials.gov registry, Medline, and the Cochrane CENTRAL Register of Controlled Trials, up to 31 August 2020 (CRD42020165672). The primary outcome was the summary risk of 16 different CVAEs associated with ICI exposure vs. controls (placebo and non-placebo) in RCTs. CVAEs with an increased risk associated with ICI exposure were considered as CV irAEs. Summary incidences of CV irAEs identified in our primary outcome analyses were computed using all RCTs including at least one ICI-containing arm. We used a random-effects meta-analysis to obtain Peto odds ratios (ORs) with 95% confidence intervals (CIs) and logit transformation and inverse variance weighting to compute summary incidences. Sixty-three unique RCTs with at least one ICI-containing arm (32 518 patients) were retrieved, among which 48 (29 592 patients) had a control arm. Among the 16 CVAEs studied, ICI use was associated with an increased risk of 6 CV irAEs including myocarditis, pericardial diseases, heart failure, dyslipidemia, myocardial infarction, and cerebral arterial ischaemia with higher risks for myocarditis (Peto OR: 4.42, 95% CI: 1.56–12.50, P Conclusion In RCTs, ICI use was associated with six CV irAEs, not confined to myocarditis and pericarditis.

Background Left ventricular remodelling that frequently occurs after acute myocardial infarction is associated with an increased risk of heart failure and cardiovascular death. Although several risk factors have been identified, there is still no marker in clinical use to predict left ventricular remodelling. Plasma concentration of coenzyme Q10, which plays a key role in mitochondrial energy production and as an antioxidant, seems to be negatively correlated with left ventricular function after acute myocardial infarction. Objective The goal of our study was to determine whether the plasma coenzyme Q10 baseline concentrations at time of the ST-elevation myocardial infarction (STEMI) could predict left ventricular remodelling at six months’ follow-up. Methods Sixty-eight patients who were admitted to hospital for STEMI and successfully revascularized with primary percutaneous coronary intervention were recruited. All patients underwent a 3D-echocardiography examination within the first four days after percutaneous coronary intervention and six months later then divided into two groups based on the presence or not of left ventricular remodelling. Plasma coenzyme Q10 concentration at the time of percutaneous coronary intervention was determined using high-performance liquid chromatography-tandem mass spectrometry. Results While we found similar plasma coenzyme Q10 concentrations compared with other studies, no association was evidenced between coenzyme Q10 concentrations and left ventricular remodelling ( P = 0.89). Conclusion We found no evidence for using plasma coenzyme Q10 concentration as an early prediction marker of left ventricular remodelling after STEMI.

Background/Introduction Left ventricular remodeling (LVR) remains common and is associated with outcomes in patients with ST-elevation myocardial infarction (STEMI). Left atrial (LA) volume has been described as a predictor of outcomes in the latter population. Purpose To investigate the association between LA mechanical function using speckle tracking imaging and LVR at follow-up in STEMI patients. Methods Baseline 3D transthoracic echocardiograms were performed in 121 STEMI patients. LA global longitudinal strain was reported separately for the reservoir (LASr), conduit (LAScd), and contraction (LASct) phases. Follow-up echocardiograms were performed at 6 months. Results Mean age was 58.3±12.5 years and 98 (81%) were men. Baseline left ventricular ejection fraction (LVEF) was 46.8% [41.0, 52.9] and significantly improved to 52.1% [45.8, 57.0] at follow-up, (p Conclusion(s) The three components of baseline LA strain were associated with LVEF at follow-up in patients with STEMI. Some of these components were also significantly associated with lower LVEF at baseline or predictive of a significant increase in left ventricular volumes during follow-up, indicating LVR. Funding Acknowledgement Type of funding source: None

Background/Introduction An increase in left ventricular volumes between baseline and follow-up imaging is the main criteria for the quantification of left ventricular remodeling after ST-elevation myocardial infarction, but without consensual definition. Purpose We aimed to review the criterion used for the definition of left ventricular remodeling based on cardiac magnetic resonance imaging in studies including patients with ST-elevation myocardial infarction. Methods A systematic literature search was conducted using MEDLINE and the Cochrane Library from January 2010 to August 2019. Thirty-seven studies involving a total of 4209 patients were included. Results The median age of the patients was 59 years, 82% were male, and 93% underwent primary percutaneous coronary intervention. The median follow-up duration was 6 months (range, 3–12), and the second cardiac magnetic resonance session was performed at 6 months in 14 (38%) studies. Among these studies, 30 (81%) used a cut-off value for defining left ventricular remodeling, with a pooled left ventricular remodeling prevalence estimate of 22.8%, 95%-CI[19.4%-26.7%], and a major between-study heterogeneity (I2=82%). The seven remaining studies (19%) defined left ventricular remodeling as a continuous variable. A 20% increase in end-diastolic volumes or a 15% increase in end-systolic volumes between a baseline and a follow-up cardiac magnetic resonance imaging were the two most common criterion (13 [35%] and 9 [24%] studies, respectively). Seven studies used both end-diastolic and end-systolic vleft ventricular volumes. Conclusion(s) The definition of left ventricular remodeling using cardiac magnetic resonance following ST-elevation myocardial infarction is highly variable, among studies including highly selected patients. The most frequent left ventricular remodeling criterion were a 20% increase in end-diastolic volumes or a 15% increase in end-systolic volumes. A composite cut-off value of a 12% to 15% increase in end-systolic volume and a 12% to 20% increase in end-diastolic volume using a follow-up cardiac magnetic resonance imaging 1 to 3 months after myocardial infarction might be proposed as a consensual cut-off for defining adverse left ventricular remodeling for future large-sized, prospective studies with serial cardiac magnetic resonance imaging and long-term follow-up in unselected patients. Funding Acknowledgement Type of funding source: None

International audience; Importance Limited information is available on the safety of a rechallenge with an immune checkpoint inhibitor (ICI) after an immune-related adverse event (irAE). Objective To identify the recurrence rate of the same irAE that prompted discontinuation of ICI therapy after an ICI rechallenge in patients with cancer and to identify the clinical features associated with such recurrences. Design, Setting, and Participants This observational, cross-sectional, pharmacovigilance cohort study examined individual case safety reports from the World Health Organization database VigiBase, which contains case reports from more than 130 countries. Case reports were extracted from database inception (1967) to September 1, 2019. All consecutive ICI cases with at least 1 associated irAE were included. Main Outcomes and Measures The primary outcome was the rate of recurrence of the initial irAE after an ICI rechallenge. Secondary outcomes included the factors associated with the recurrence after a rechallenge among informative rechallenges, the recurrence rate according to the ICI regimen (anti-programmed cell death 1 or anti-programmed cell death ligand 1 monotherapy, anti-cytotoxic T-lymphocyte antigen-4 monotherapy, or combination therapy), and the rate of occurrence of a different irAE after a rechallenge. Results A total of 24 079 irAE cases associated with at least 1 ICI were identified. Among the irAEs, 452 of 6123 irAEs associated with ICI rechallenges (7.4%) were informative rechallenges. One hundred thirty recurrences (28.8%; 95% CI, 24.8-33.1) of the initial irAE were observed. In a rechallenge, colitis (reporting odds ratio [OR], 1.77; 95% CI, 1.14-2.75; P = .01), hepatitis (reporting OR, 3.38; 95% CI, 1.31-8.74; P = .01), and pneumonitis (reporting OR, 2.26; 95% CI, 1.18-4.32; P = .01) were associated with a higher recurrence rate, whereas adrenal events were associated with a lower recurrence rate (reporting OR, 0.33; 95% CI, 0.13-0.86; P = .03) compared with other irAEs. Conclusions and Relevance This cohort study found a 28.8% recurrence rate of the same irAE associated with the discontinuation of ICI therapy after a rechallenge with the same ICI. Resuming ICI therapy could be considered for select patients, with appropriate monitoring and use of standard treatment algorithms to identify and treat toxic effects.

Background/Introduction Left ventricular remodeling following ST-elevation myocardial infarction (STEMI) is associated with poor outcome. Neprilysin inhibition leads to improved outcome in patients with altered left ventricular ejection fraction (LVEF). Purpose We aimed to assess the association between serum levels of neprilysin and left ventricular (LV) volumes, function and remodeling in STEMI patients with successful myocardial reperfusion. Methods Sixty-eight patients were admitted for STEMI and had both plasma neprilysin measurement at baseline and 3D transthoracic echocardiogram at baseline and at follow-up (7 months). We compared 3 groups: a group with a low-level of plasma neprilysin ( Results Median age was 58.5±12.8 years and 56 (82.4%) were men. Median LVEF was 45.0±8.5%. Baseline characteristics were comparable among groups. At baseline there was a non-significant trend towards lower end-diastolic volume (p=0.07) but significantly lower LVEF in the high neprilysin group (46.4±8.3%, 47.1±8.1% and 39.1±6.9%, p Conclusion(s) Initial high neprilysin levels may identify patients with stunned myocardium early after STEMI, with a recovery of contractility leading to improved LVEF at follow-up. Funding Acknowledgement Type of funding source: None

We aimed to investigate the association between use of anticancer drugs and cardiovascular-related hospitalization (CVRH) among patients with metastatic colorectal cancer (mCRC). A cohort study, the Anticancer Vigilance of Cardiac Events (AVOCETTE) Study, was conducted using data from the digestive tumor registry of a French county, the Département du Calvados. Incident mCRC cases diagnosed between 2008 and 2014 were included. The follow-up end date was December 31, 2016. Data from the county hospital center pharmacy and medical information departments were matched with the registry data. A competing-risks approach was used. Statistical tests were 2-sided. A total of 1,116 mCRC patients were included, and they were administered 12,374 rounds of treatment; fluorouracil, oxaliplatin, irinotecan, and bevacizumab were most common drugs used. A total of 208 CVRH events occurred in 145 patients (13.0%). The International Cancer Survival Standards type 1 standardized incidence was 84.0 CVRH per 1,000 person-years (95% confidence interval: 72.6, 95.5). Anticancer drugs were not associated with a higher incidence of CVRH. Male sex, increasing age, a prior history of CVRH, and a higher Charlson comorbidity index score were associated with a higher incidence of CVRH. CVRH was significantly associated with higher all-cause mortality (multivariable hazard ratio = 1.58, 95% confidence interval: 1.28, 1.95). In this study, anticancer drugs were not associated with a higher incidence of CVRH in mCRC patients.

Summary Background The risk of cardiovascular adverse events from rapidly accelerated fibrosarcoma B-type (BRAF) and mitogen-activated extracellular signal-regulated kinase (MEK) inhibitors is not fully characterized. Aim To evaluate the cardiovascular adverse events risks related to BRAF and/or MEK inhibitors in randomized placebo-controlled clinical trials and in the real-life setting. Methods We used two approaches. First, we conducted a systematic review and meta-analysis of randomized placebo-controlled clinical trials reporting the incidence of cardiovascular adverse events for BRAF and/or MEK inhibitors in cancer patients. Second, we performed a disproportionality analysis, using age- and sex-adjusted reporting odds ratios (arORs) and their 95% confidence intervals (CIs) from the World Health Organization's pharmacovigilance database (VigiBase®) of anticancer drug-associated reports, to investigate real-life data. Results MEK inhibitors increased the risk of ejection fraction decrease (odds ratio [OR] 3.35, 95% CI 1.58–7.07), peripheral oedema (OR 2.87 95% CI 1.93–4.27) and syncope (OR 6.71, 95% CI 3.00–14.99) compared with placebo in randomized placebo-controlled clinical trials. BRAF and MEK inhibitor combination therapy further increased the risk of ejection fraction decrease. In the disproportionality analysis, we found over-reporting of ejection fraction decrease (arOR 8.42, 95% CI 7.03–10.09), peripheral oedema (arOR 1.39, 95% CI 1.17–1.66), syncope (arOR 1.56, 95% CI 1.22–1.99), torsade de pointes/QT prolongation (arOR 6.13, 95% CI 5.04–7.47) and supraventricular arrhythmias (arOR 1.50, 95% CI 1.21–1.85) for BRAF and MEK inhibitors. BRAF and MEK inhibitors were not associated with hypertension in either approach. Conclusions In conclusion, MEK inhibitors increase the risk of ejection fraction decrease, peripheral oedema and syncope in randomized placebo-controlled clinical trials. Real-life data confirm these findings, and suggested additional risks of torsade de pointes/QT prolongation and supraventricular arrhythmias with BRAF/MEK inhibitors.

Background Cardiac resynchronization therapy has been shown to benefit selected patients with heart failure and reduced ejection fraction. Older patients have been underrepresented in randomized trials. This study was conducted to determine whether predictive factors for cardiac resynchronization therapy outcomes differ in patients older and younger than 75 years of age. Methods Consecutive patients who received a cardiac resynchronization device cardiac resynchronization therapy between 2013 and 2016 in our center were retrospectively included in this cohort study. The primary endpoint was cardiac resynchronization therapy effectiveness, which was defined as survival for one year with both no heart failure hospitalization and improvement by one or more NYHA class. The secondary endpoints were mortality, complications, and device therapies. Results Among the 243 patients included, 102 were ≥ 75 years old. Cardiac resynchronization therapy effectiveness was observed in 70 patients (50%) p = 0.69). NYHA class ≥III (OR = 6.02; CI95% [1.33–18.77], p = 0.002) was a predictive factor for cardiac resynchronization therapy effectiveness only in the ≥75-year-old group, while atrial fibrillation was independently negatively associated with the primary endpoint in the p = 0.001). The one-year mortality rate was 14%, with no difference between age groups. Rescue cardiac resynchronization therapy and atrial fibrillation were independent predictive factors for mortality in both age groups. Eighty-two complications occurred in 45 patients (19%), with no difference between groups. Defibrillator use and QRS duration were independent predictive factors for complications in both age groups. There was no difference between groups considering device therapies. Conclusion At one year, cardiac resynchronization therapy response is not compromised by patient age. In older patients, highly symptomatic individuals with NYHA class ≥III have better outcomes after cardiac resynchronization therapy.

Background Despite the emergence of new therapies, Pulmonary Hypertension (PH) still has a high mortality. Several clinical, echocardiographic, biological or hemodynamic prognostic factors have been identified but are of limited predictive value for survival. We aimed to assess whether heart rate (HR) and all ECG abnormalities measured on a 12-lead ECG may help to better identify patients at high risk of death in this population. Methods and results 296 patients followed in a registry were included with all types of PH, except group 2 of the WHO clinical classification. After a median follow-up of 10 years, age, male sex, NYHA III/IV status and, among all ECG parameters, HR and corrected QT interval were associated with mortality. In multivariate analysis, HR, age and male sex remained significant independent predictors of mortality. HR has a higher predictive value in the 238 patients in sinus rhythm. In addition, only HR was significantly correlated with clinical and hemodynamic PH prognostic factors. Conclusion HR measured on a 12-lead ECG at the time of the diagnosis is a strong independent predictor of mortality in PH patients.

International audience; Objectives: We conducted a retrospective study to characterize the cardiac complications in patients with genetically confirmed type 1 facioscapulohumeral dystrophy. Methods: We reviewed baseline cardiac investigations, including electrocardiogram, Holter electrocardiogram and echocardiogram, as well as cardiac complications that occurred during follow-up in 56 adult patients (37 men, mean duration of disease: 20 years). Results: Baseline evaluation revealed minor cardiac anomalies in 23 patients including incomplete right bundle branch block (iRBBB) in 13 patients (23%). Over a mean follow-up period of 7.2 years, there was no cardiac death, no patient developed cardiomyopathy, and 28 patients (50%) experienced cardiac anomalies. Among these patients, 3 had one or more major events (heart failure and/or atrial fibrillation). The remaining 25 patients presented minor cardiac anomalies of which iRBBB was the most frequent (25%). Conclusions: Cardiac anomalies identified during the follow-up of patients with type 1 facioscapulohumeral dystrophy are mainly minor anomalies, dominated by the iRBBB.

Background An accurate estimate of the duration of atrial fibrillation (AF) is critical for its safe and successful management. We examined the ability of midregional pro–atrial natriuretic peptide (MR-proANP) to identify patients presenting with AF of ≤48 vs >48 h in duration. Methods We prospectively studied 106 patients presenting with AF of known duration. We examined the predictive values of MR-proANP and N-terminal pro–brain natriuretic peptide (NT-proBNP) in the detection of recent-onset AF, in addition to other factors identified by multiple variable analyses. Results In patients presenting with AF of ≤48 vs >48 h in duration, the median MR-proANP plasma concentration was 147.7 [95.3–197.4] pmol/L vs 220.4 [154.0–303.1] pmol/L (P Conclusions A score based on a model including heart rate, dyspnea, and plasma MR-proANP concentration was helpful in identifying AF of ≤48 h in duration.

International audience; Background: Screening for Fabry disease is sub-optimal in non-specialised centres.Aim: To assess the diagnostic value of electrocardiographic scores of left ventricular hypertrophy and a combined electrocardiographic and echocardiographic model in Fabry disease.Methods: We retrospectively reviewed the electrocardiograms and echocardiograms of 61 patients (mean age 55.6±11.5 years; 57% men) with Fabry disease and left ventricular hypertrophy, and compared them with those from 59 patients (mean age 44.8±18.3 years; 66% men) with sarcomeric hypertrophic cardiomyopathy. Six electrocardiography criteria for left ventricular hypertrophy were specifically analysed: Sokolow-Lyon voltage index; Cornell voltage index; Gubner index; Romhilt-Estes score; Sokolow-Lyon product (voltage index×QRS duration); and Cornell product (voltage index×QRS duration).Results: Right bundle branch block was more frequent in patients with Fabry disease (54% vs. 22%; P=0.001). QRS duration, Gubner score and Sokolow-Lyon product were significantly higher in patients with Fabry disease. Maximal wall thickness was higher in patients with sarcomeric hypertrophic cardiomyopathy (21.9±5.1 vs. 15.5±2.9mm; P

Background After artery bypass grafting (CABG), the presence of perioperative AF (POAF) is associated with greater short- and long-term cardiovascular morbidity. Underlying POAF mechanisms are complex and include the presence of an arrhythmogenic substrate, cardiac fibrosis and electrical remodeling. Aldosterone is a key component in this process. We hypothesize that perioperative mineralocorticoid receptor (MR) blockade may decrease the POAF incidence in patients with a left ventricular ejection fraction (LVEF) ≥50% who are referred for CABG with or without aortic valve replacement (AVR). Study design The ALDOCURE trial ( NCT03551548 ) will be a multicenter, randomized, double-blind, placebo-controlled trial testing the superiority of a low-cost MR antagonist (MRA, spironolactone) on POAF in 1500 adults referred for on-pump elective CABG surgery with or without AVR, without any history of heart failure or atrial arrhythmia. The primary efficacy end point is the occurrence of POAF from randomization to within 5 days after surgery, assessed in a standardized manner. The main secondary efficacy end points include the following: postoperative AF occurring within 5 days after cardiac surgery, perioperative myocardial injury, major cardiovascular events and death occurring within 30 days of surgery, hospital and intensive care unit length of stay, need for readmission, LVEF at discharge and significant ventricular arrhythmias within 5 days after surgery. Safety end points, including blood pressure, serum potassium levels and renal function, will be monitored regularly throughout the trial duration. Conclusion The ALDOCURE trial will assess the effectiveness of spironolactone in addition to standard therapy for reducing POAF in patients undergoing CABG. Clinical trial registration NCT03551548

Few data exist concerning the right ventricular (RV) physiological adaptation in American-style football (ASF) athletes. We aimed to analyze the RV global and regional responses among ASF-trained athletes. Fifty-nine (20 linemen and 39 non-linemen) ASF athletes were studied before and after inter-seasonal training. During this period, which lasted 7 months, all athletes were exposed to combined dynamic and static exercises. Cardiac longitudinal changes were examined using three-dimensional transthoracic echocardiography. A computational method based on geodesic distances was applied to volumetrically parcellate the RV into apical, outlet, and inlet regions. RV global and regional end-diastolic volumes increased significantly and similarly in linemen and non-linemen after training, with predominant changes in the apex and outlet regions. RV global and regional ejection fractions were preserved. Morphological changes were uniformly distributed among the four cardiac chambers, and it was independent of the field position. Assessment of RV end-diastolic global, inlet and apical volumes showed low intra-observer (3.3%, 4.1%, and 5.3%, respectively) and inter-observer (7%, 12.2%, and 9%, respectively) variability, whereas the outlet regional volumetric assessment was less reproducible. To conclude, ASF inter-seasonal training was associated with a proportionate biventricular enlargement, regardless of the field position. Regional RV analysis allowed us to quantify the amount of exercise-induced remodeling that was larger in the apical and outlet regions. F.T. is supported by a grant from the Fonds de Recherche du Québec—Santé (FRQS). The methodological part of this study was partly supported by the Spanish Ministry of Economy and Competitiveness (Maria de Maeztu Units of Excellence Programme—MDM-2015-0502) and the European Union under the Horizon 2020 Programme for Research, Innovation (grant agreement No. 642676 CardioFunXion).

Background Screening for Fabry disease (FD) remains suboptimal in non-specialized centers. Aims We aimed to evaluate the diagnostic value of electrocardiographic (ECG) scores of left ventricular hypertrophy (LVH) and the diagnostic value of a combined ECG and echocardiographic model for FD. Methods We retrospectively reviewed the ECG and echocardiogram of 61 patients (age: 55.6 ± 11.5 years, 57% men) with FD and LVH, and compared them to 59 patients (age: 44.8 ± 18.3 years, 66% men) with sarcomeric hypertrophic cardiomyopathy (HCM). Six ECG criteria for LVH were specifically analyzed: – Sokolow-Lyon index, – Cornell voltage index 3) Gubner index, – Romhilt-Estes score, – Sokolow-Lyon voltage × QRS duration product, – Cornell voltage × QRS duration product. Results Right Bundle Branch Block (RBBB) was more frequent in FD (54% vs. 22%, P = 0.001). QRS duration, Gubner score, and Sokolov-Lyon product were significantly higher in FD. Maximal thickness wall (MTW) was higher in sarcomeric HCM group (21.9 ± 5.1 mm vs. 15.5 ± 2.9 mm in Fabry, P Conclusion Our model combining easy-to-assess ECG and echocardiographic parameters may be helpful to improve screening and reduce diagnosis delay of FD.

Background Mineralocorticoid receptor antagonists (MRA) improve outcome in the setting of post–myocardial infarction (MI) heart failure (HF). Objectives The study sought to assess the benefit of an early MRA regimen in acute MI irrespective of the presence of HF or left ventricular (LV) dysfunction. Methods We randomized 1,603 patients to receive an MRA regimen with a single intravenous bolus of potassium canrenoate (200 mg) followed by oral spironolactone (25 mg once daily) for 6 months in addition to standard therapy or standard therapy alone. The primary outcome of the study was the composite of death, resuscitated cardiac arrest, significant ventricular arrhythmia, indication for implantable defibrillator, or new or worsening HF at 6-month follow-up. Key secondary/safety outcomes included death and other individual components of the primary outcome and rates of hyperkalemia at 6 months. Results The primary outcome occurred in 95 (11.8%) and 98 (12.2%) patients in the treatment and control groups, respectively (hazard ratio [HR]: 0.97; 95% confidence interval [CI]: 0.73 to 1.28). Death occurred in 11 (1.4%) and 17 (2.1%) patients in the treatment and control groups, respectively (HR: 0.65; 95% CI: 0.30 to 1.38). In a non–pre-specified exploratory analysis, the odds of death were reduced in the treatment group (3 [0.5%] vs. 15 [2.4%]; HR: 0.20; 95% CI: 0.06 to 0.70) in the subgroup of ST-segment elevation MI (n = 1,229), but not in non–ST-segment elevation MI (p for interaction = 0.01). Hyperkalemia >5.5 mmol/l–1 occurred in 3% and 0.2% of patients in the treatment and standard therapy groups, respectively (p Conclusions The study failed to show the benefit of early MRA use in addition to standard therapy in patients admitted for MI. (Aldosterone Lethal effects Blockade in Acute myocardial infarction Treated with or without Reperfusion to improve Outcome and Survival at Six months follow-up; NCT01059136).

Background Patients’ knowledge of their disease is a key point in chronic conditions such as Heart Failure and a prerequisite for treatment adherence. However, data are scarce regarding HF patients’ understanding. Aim To propose an auto-questionnaire for the assessment of patients’ knowledge of HF and to analyze the factors associated with a better understanding. Method During 2 weeks, consecutive patients admitted for HF were included in this prospective study involving 9 French centers. Patients were screened for cognitive disorders using the validated clock-drawing test and only patients who passed this test were submitted to a 16-point knowledge questionnaire. Results Three hundreds and eleven patients were included (mean age 73 ± 13 years, 62% men). Mean LVEF was 45 ± 14%. Regarding level of education, 177 patients (58%) reached primary school, 63 (21%) secondary school and 63 (21%) university or higher. Elderly patients had a mobile phone and internet at home in 71 and 51% of cases. Only 33 patients (11%) benefited from therapeutic education sessions, while 65% of patients had already been hospitalized for HF. Cognitive disorders were found in 81 patients (26%) and 230 patients thus passed the knowledge questionnaire. Mean knowledge score was 6.3 ± 3.4/16 points. It was associated with the level of education (P = 0.01), follow-up by a cardiologist (P 0.001), good adherence to treatment as evaluated by a validated questionnaire (P Conclusion Patients hospitalized for HF have a poor knowledge of their disease and repeated information by all means possible may have a positive impact. The knowledge score was associated with adherence to treatment, which represents a major goal to achieve in chronic HF.

Endothelial dysfunction is common in patients with heart failure and is associated with poor clinical outcome. Cardiac rehabilitation is able to enhance peripheral endothelial function but its impact on coronary vasomotion remains unknown. We aimed to evaluate the effect of cardiac rehabilitation on coronary vasomotion in patients with heart failure.We prospectively enrolled 29 clinically stable heart failure patients from non-ischaemic dilated cardiomyopathy and without coronary risk factors. Myocardial blood flow was quantified using (15)-O water positron emission tomography at rest and during a cold pressor test, before and after 12 weeks of cardiac rehabilitation and optimization of medical therapy.Rest myocardial blood flow was significantly improved after the completion of rehabilitation compared to baseline (1.31 ± 0.38 mL/min/g vs. 1.16 ± 0.41 mL/min/g, p = 0.04). The endothelium-related change in myocardial blood flow from rest to cold pressor test and the percentage of myocardial blood flow increase during the cold pressor test were both significantly improved after cardiac rehabilitation (respectively from -0.03 ± 0.22 mL/min/g to 0.19 ± 0.22 mL/min/g, p 0.001 and from 101.5 ± 16.5% to 118.3 ± 24.4%, p 0.001). Left ventricular ejection fraction, plasma levels of brain natriuretic peptide, maximal oxygen consumption and the Minnesota Living with Heart Failure Questionnaire score were also significantly improved. The improvement was not related to uptitration of medical therapy.Coronary endothelial function is altered in patients with heart failure due to non-ischaemic dilated cardiomyopathy. In these patients, cardiac rehabilitation significantly improves coronary vasomotion.

Background and Purpose: Cardioprotection against ischemia–reperfusion (I/R) damages remains a major concern during prehospital management of acute myocardial infarction. Noble gases have shown beneficial effects in preconditioning studies. Because emergency proceedings in the context of myocardial infarction require postconditioning strategies, we evaluated the effects of argon in such protocols on mammalian cardiac tissue. Experimental Approaches: In rat, cardiac I/R was induced in vivo by transient coronary artery ligature and cardiac functions were evaluated by magnetic resonance imaging. Hypoxia–reoxygenation (H/R)-induced arrhythmias were evaluated in vitro using intracellular microelectrodes on both rat-isolated ventricle and a model of border zone in guinea pig ventricle. Hypoxia–reoxygenation loss of contractile force was assessed in human atrial appendages. In those models, postconditioning was induced by 5 minutes application of argon at the time of reperfusion. Key Results: In the in vivo model, I/R produced left ventricular ejection fraction decrease (24%) and wall motion score increase (36%) which was prevented when argon was applied in postconditioning. In vitro, argon postconditioning abolished H/R-induced arrhythmias such as early after depolarizations, conduction blocks, and reentries. Recovery of contractile force in human atrial appendages after H/R was enhanced in the argon group, increasing from 51% ± 2% in the nonconditioned group to 83% ± 7% in the argon-treated group ( P < .001). This effect of argon was abolished in the presence of wortmannin and PD98059 which inhibit prosurvival phosphatidylinositol-3-kinase (PI3K)/protein kinase B (Akt) and MEK/extracellular receptor kinase 1/2 (ERK 1/2), respectively, or in the presence of the mitochondrial permeability transition pore opener atractyloside, suggesting the involvement of the reperfusion injury salvage kinase pathway. Conclusion and Implications: Argon has strong cardioprotective properties when applied in conditions of postconditioning and thus appears as a potential therapeutic tool in I/R situations.

Postoperative atrial fibrillation (POAF) is associated with poor outcomes after coronary artery bypass graft (CABG) surgery. We aimed to assess the additional value of preoperative plasma aldosterone levels, a biomarker promoting proarrhythmic and profibrotic pathways, for predicting POAF after CABG.We conducted a prospective cohort study involving consecutive patients with left ventricular ejection fraction (LVEF) more than 50% requiring elective CABG in our university hospital. Plasma aldosterone levels, two-dimensional echocardiography including left atrial strain analysis and galectin-3 (Gal-3) examination were assessed before cardiac surgery. The primary endpoint was the occurrence of POAF within 30 days after surgery.POAF occurred in 34 (24.8%) out of the 137 included patients. Compared with controls, patients experiencing POAF were significantly older (73 years old ± 8 vs 65 ± 11, P 0.001) and had higher preoperative plasma aldosterone levels [183 pmol/l (interquartile range 138-300) vs 143 pmol/l (interquartile range 96.5-216.5), P 0.01]. Age [odds ratio (OR), 1.088; 95% confidence interval (CI) (1.038-1.140); P = 0.0004] and plasma aldosterone levels [OR, 1.007; 95% CI (1.003-1.012); P = 0.0013] were independently associated with POAF in multivariate analysis and could therefore be combined to predict the occurrence of POAF ['Aldoscore', OR, 2.7; 95% CI (1.7-4.3); P 0.0001]. Reverse transcriptase PCR analysis performed on right atrial appendage and plasma examination revealed that Gal-3 was activated in POAF patients.We developed the preoperative 'Aldoscore' for POAF risk stratification among patients with preserved LVEF requiring elective CABG. This new tool may be helpful to identify good responders to interventions targeting the proarrhythmic and profibrotic pathways of aldosterone.

Background: The role of tumor necrosis factor-α (TNF-α), Janus kinase/signal transducers and activators of transcription (JAK/STAT) pathway, and mitochondrial Permeability Transition Pore in atorvastatin-induced cardioprotection were examined in human myocardium, in vitro. Methods: Isometric force of contraction of human right atrial trabeculae was recorded during 30-min hypoxia and 60-min reoxygenation (control) and in the presence of atorvastatin (0.1 µm, 1 µm, 10 µm). In early reoxygenation, the TNF-α inhibitor, AG490 (inhibitor of JAK/STAT), or atractyloside (mitochondrial Permeability Transition Pore opener), were administered. Cyclosporine A (inhibitor of mitochondrial Permeability Transition Pore opening) was administered during the first minute of reoxygenation alone or in presence of atorvastatin and TNF-α inhibitor or AG490. The force of contraction (percentage of baseline) at the end of reoxygenation period was compared (mean ± SD; n = 6 in each group). Protein expression of JAK/STAT pathway was measured using Western immunoblotting. Results: Atorvastatin 0.1 µm (70 ± 9%), 1 µm (85 ± 5%), 10 µm (89 ± 5%), and Cyclosporine A (87 ± 10%) improved the recovery of force of contraction at the end of reoxygenation, as compared with control (50 ± 3%). Atorvastatin 1 µm (4.64 ± 2.90ng · ml−1 · g−1 of tissue) decreased the release of troponin Ic after hypoxia-reoxygenation (control: 26.34 ± 19.30ng · ml−1 · g−1; P < 0.001). The enhanced recovery of force of contraction after atorvastatin administration was abolished by TNF-α inhibitor (53 ± 8%), AG490 (56 ± 7%), atractyloside (48 ± 8%). Cyclosporine A restored the atorvastatin-induced cardioprotection abolished by TNF-α inhibitor (87 ± 6%) and AG490 (83 ± 9%). Atorvastatin significantly increased the phosphorylation of JAK-2 and STAT-3, TNF-α inhibitor abolished the enhanced phosphorylation of JAK-2 and STAT-3 by atorvastatin. Conclusions: Atorvastatin-induced cardioprotection involved the inhibition of the mitochondrial Permeability Transition Pore opening via the activation of TNF-α and the JAK/STAT pathway in early reoxygenation.

Sympathetic nervous system (SNS) activation has long been known to be a cardinal feature in the pathophysiology of cardiac remodeling and systolic heart failure (SHF). It was reported to have implications for both disease progression and survival. SNS activation is assumed to be secondary to the decrease of sympathoinhibitory reflexes usually drove by the stimulation of afferent mechanoreceptors and by the increase of efferent sympatho-excitatory mechanisms associated with alteration in autonomic regulation. Activation of cardiac and peripheral sympathetic nervous systems has been linked to the rate of disease progression and sudden death. The main retrospective and prospective studies have shown that cardiac neuronal uptake based on Heart-Mediastinum Ratio (HMR) by I-Metaiodobenzylguanidine (MIBG) imaging was a prognostic indicator of severe heart failure and/or ventricular arrhythmia if HMR was less than 1.6 in patients with a left ventricular ejection fraction less than 35%. These findings have been the rationale for the use of betaadrenergic blocking agents in the management of patients with SHF. Several observations have suggested that ventricular systolic dysfunction per se was not the principal stimulus to sympathetic activation. If the decrease of sympatho-inhibitory reflexes is directly linked to the ventricular systolic dysfunction though the decrease of the cardiac output, mechanisms underlying the autonomic dysregulation seem more generalized. Among the parameters acting on nonbaroreflex-mediated sympathoexcitation, sleep-disordered breathing is one of the main actors.

AIMS:The aim of the study was to assess the early features of diabetic cardiomyopathy using cardiac magnetic resonance within the first week after streptozotocin injection in mice. We focused on the relationship between left ventricular function and hypovolemia markers in diabetic animals compared to a hypovolemic rodent model. METHODS AND RESULTS:Swiss mice were randomized into control (group C), streptozotocin-induced diabetes (group D) and furosemide-induced hypovolemia (group F) groups. Cardiac magnetic resonance, non-invasive blood pressure, urine volume, plasma markers of dehydration and cardiac histology were assessed in all groups. Mean blood glucose was higher in diabetic animals than in groups C and F (30.5±5.8 compared to 10.4±2.1 and 11.1±2.8 mmol/L, respectively; p

In addition to hyperglycaemia, glycaemic variability seems to be associated with poor outcomes after acute myocardial infarction. This study explored the impact of glycaemic variability in diabetic Wistar rats subjected to myocardial ischaemia/reperfusion.Animals with streptozotocin-induced diabetes received insulin either to maintain stable hyperglycaemia (Dh group) or to generate glycaemic variability (Dv). After experimental myocardial ischaemia/reperfusion was surgically induced, 7T cardiac magnetic resonance imaging (CMR) was performed at weeks 1 (w1) and 3 (w3).Twenty-six rats were randomized [sham group (S): n=5; control group (C): n=7; Dh group: n=6; and Dv group: n=8]. The mean amplitude of glucose reflecting glycaemic variability was higher in the Dv than in the Dh group (9.1±2.7mmol/L vs 5.9±1.9mmol/L; P0.05). CMR assessment at w3 revealed ventricular enlargement in both Dh and Dv groups compared with the C and S groups (end-diastolic volume: 1.60±0.22 and 1.36±0.30mL/kg compared with 1.11±0.13 and 0.87±0.11mL/kg, respectively; P0.05). Circumferential strain was altered between w1 and w3 in the remote area only in the Dv group, resulting in a lower value in this group than in the S, C and Dh groups (-0.11±0.01 vs -0.17±0.05, -0.15±0.03 and -0.16±0.03, respectively; P0.05). In addition, at w3, oedema was also higher in the remote area in the Dv than in the C group (18.3±4.9ms vs 14.5±1.7ms, respectively; P0.05).In the context of experimental myocardial ischaemia/reperfusion, our results suggest that glycaemic variability might have a potentially deleterious impact on myocardial outcomes beyond the classical glucose metrics.

Aims Daily practice shows that patients with pre-capillary pulmonary hypertension (PH) may develop a secondary elevation of their pulmonary artery wedge pressure (PAWP) above the 15 mm Hg limit. This phenomenon has not been precisely described yet. We aimed at identifying factors present at initial diagnosis that could predict this secondary elevation of PAWP, its possible causes and impact on survival. Methods and results We included 90 patients followed between 2004 and 2011 in our center. At the end of follow-up (3.0 ± 1.6 years), patients were divided into two groups according to the successive PAWP measurements (always ≤ 15 mm Hg or > 15 mm Hg on at least one right heart catheterization (RHC)). Demographical, biological, echographic and hemodynamical data at first RHC were compared. Possible causes for PAWP > 15 mm Hg were searched. A Kaplan–Meier method was used to assess differences in survival. One third of our cohort developed an elevation of PAWP above 15 mm Hg and patients with idiopathic pulmonary arterial hypertension were at smaller risk (OR 0.20 [0.05–0.82]; p = 0.026). We did not identify any other baseline predictive factors. We highlighted several possible causes and factors that may unmask an underlying left ventricular diastolic dysfunction. Survival was not different between both groups (p = 0.42). Conclusion Secondary elevation of PAWP in pre-capillary PH was frequent but less observed in idiopathic PH. We detailed many possible causes that can be sought, many of which may be related to an underlying left ventricular diastolic dysfunction.

Hypothyroidism is a rare cause of dilated cardiomyopathy. Triiodothyronine was found to target endothelial nitric oxide synthase, which serves to enhance peripheral vascular relaxation by acting on vascular smooth muscle cells. In patients with subclinical hypothyroidism, adenosine-induced coronary flow reserve is significantly reduced. We report the case of a 46-year-old woman with hypothyroid cardiomyopathy manifested as reversible severe left ventricular dysfunction (LVEF = 32%). O-labeled water PET at rest and during cold pressor test showed a severe coronary endothelial dysfunction. In patients with severe hypothyroidism, endothelial function is impaired and may be an important mechanism of heart failure.

Background Primary percutaneous coronary intervention (PPCI) is the preferred reperfusion strategy in patients with ST-elevation myocardial infarction (STEMI), but its benefit over prehospital fibrinolysis (FL) is not clear. Methods We performed a systematic review and meta-analysis of randomized controlled trials in which outcomes of patients with STEMI managed with FL early in the prehospital setting versus PPCI were compared. Results Compared with PPCI, FL was consistently associated with similar rates of short-term (30–90 days) death (relative risk [RR] 0.94, 95 % CI 0.67–1.31) and cardiovascular death (RR 0.95, 95 % CI 0.64–1.4), a decreased risk of cardiogenic shock (RR 0.67, 95 % CI 0.48–0.95), and an increased risk of any stroke (RR 3.57, 95 % CI 1.39–9.17) and hemorrhagic stroke (RR 4.37, 95 % CI 1.25–15.26). FL was also associated with similar rates of 1-year mortality (RR 1.01, 95 % CI 0.75–1.34) and major bleeding (RR 1.31, 95 % CI 0.96–1.78) in comparison with PPCI, but with a notable level (I 2 index 30.5 % and 59.8 %) of heterogeneity among studies. Conclusions Our study suggests that, compared with PPCI, FL performed in the early prehospital setting is associated with similar mortality rates, lower rates of cardiogenic shock, and higher rates of stroke in patients with STEMI. Although the number of studies comparing the two strategies is relatively low, our results support prehospital FL and transfer to hub percutaneous coronary intervention (PCI) centers as a valid alternative to PPCI, allowing potential limitation of resources allocated to developing proximity 24/7 PCI facilities. Electronic supplementary material The online version of this article (doi:10.1186/s13054-016-1530-z) contains supplementary material, which is available to authorized users.

Introduction Atrial fibrillation (AF) is the most common complication after cardiac surgery and is responsible for significant morbidity and mortality. To assess whether preconditioning with renin-angiotensin-aldosterone system agents could limit myocardial tissue injury, we tested the force of contraction of human right atrial trabeculae during hypoxia-reoxygenation when exposed to aldosterone and/or potassium canrenoate. Materials and methods We studied the effect of aldosterone and/or mineralocorticoid receptor (MR) antagonist potassium canrenoate administration prior to hypoxia-reoxygenation and in normoxic condition on force of contraction in 51 human right atrial trabeculae obtained from patients scheduled for coronary artery bypass surgery or aortic valve replacement. We also tested if adosterone exposure results in changes in levels of ERK1/2 phosphorylation. Results The force of contraction of trabeculae was significantly reduced by aldosterone administration under normoxic or hypoxia-reoxygenation conditions. The rapid onset of this effect - 25 minutes - suggests a nongenomic mechanism. When compared with controls, potassium canrenoate by itself was not able to induce cardioprotection. However, coadministration of aldosterone and potassium canrenoate preconditioned isolated human atrial myocardium exposed to hypoxia - reoxygenation. This effect could be MR-dependent or not because both aldosterone and potassium canrenoate have some nongenomic MR-independent actions. Preliminary results showed that aldosterone exposure increased ERK1/2 phosphorylation levels. Conclusion Potassium canrenoate-induced cardioprotection prevents the deleterious effect of aldosterone on human atrial myocardial tissue. Further research required to determine the mechanism involved and the potential beneficial in clinical practice in order to reduce the incidence of postoperative atrial fibrillation. Download : Download full-size image Figure – Experimental conditions