Aims Although some scores based on traditional statistical methods are available for risk stratification in patients hospitalized in cardiac intensive care units (CICUs), the interest of machine learning (ML) methods for risk stratification in this field is not well established. We aimed to build an ML model to predict in-hospital major adverse events (MAE) in patients hospitalized in CICU. Methods and results In April 2021, a French national prospective multicentre study involving 39 centres included all consecutive patients admitted to CICU. The primary outcome was in-hospital MAE, including death, resuscitated cardiac arrest, or cardiogenic shock. Using 31 randomly assigned centres as an index cohort (divided into training and testing sets), several ML models were evaluated to predict in-hospital MAE. The eight remaining centres were used as an external validation cohort. Among 1499 consecutive patients included (aged 64 +/- 15 years, 70% male), 67 had in-hospital MAE (4.3%). Out of 28 clinical, biological, ECG, and echocardiographic variables, seven were selected to predict MAE in the training set (n = 844). Boosted cost-sensitive C5.0 technique showed the best performance compared with other ML methods [receiver operating characteristic area under the curve (AUROC) = 0.90, precision-recall AUC = 0.57, F1 score = 0.5]. Our ML score showed a better performance than existing scores (AUROC: ML score = 0.90 vs. Thrombolysis In Myocardial Infarction (TIMI) score: 0.56, Global Registry of Acute Coronary Events (GRACE) score: 0.52, Acute Heart Failure (ACUTE-HF) score: 0.65; all P < 0.05). Machine learning score also showed excellent performance in the external cohort (AUROC = 0.88). Conclusion This new ML score is the first to demonstrate improved performance in predicting in-hospital outcomes over existing scores in patients admitted to the intensive care unit based on seven simple and rapid clinical and echocardiographic variables. Trial Registration ClinicalTrials.gov Identifier: NCT05063097.

Abstract Background Anemia is a frequent comorbidity in heart failure (HF) in elderly patients. Few data are available concerning the correlation between anemia and echocardiographic morphologic, functional and hemodynamic markers in acute HF. Purpose The aim of the study was to evaluate 4 cavities myocardial strain in elderly patients hospitalized with acute HF and to evaluate the influence of the presence of concomitant anemia. Methods One hundred and seven patients aged 70 years or older, hospitalized for acute HF were prospectively analyzed. Left ventricle longitudinal strain (LVGLS), left atrial (LA) reservoir, right atrial (RA) reservoir and right ventricle (RV) free wall strain were measured using speckle tracking transthoracic echocardiography (TTE) at admission. The population was divided into 2 groups, with (N = 47) or without (N = 60) of anemia. Results Mean age was 81.2 ± 6.6 years; 67 (62.6%) patients were men. Anemia was documented in 60 (56.1%) patients. Patients with anemia, compared to those without anemia, had more frequently history of hypertension, diabetes, renal insufficiency, and iron deficiency (Table 1). Patients with anemia, compared to those without anemia, had higher indexed cardiac output, LV ejection fraction and tricuspid annular plane systolic excursion, TAPSE (Table 1). Myocardial strain analysis found that patients with anemia, compared to those without anemia, had significantly higher LVGLS, LA and RA reservoir strain (Figure 1). Conclusion Anemia is common in elderly patients with decompensated HF. Patients suffering from both anemia and acute HF exhibited significantly higher myocardial strain (except free wall RV strain), suggesting a possible compensatory mechanism. Further investigations are necessary to understand the pathophysiologic links between HF, anemia and myocardial strain as well as their implications for prognosis.

While recreational drug use is a risk factor for cardiovascular events, its exact prevalence and prognostic impact in patients admitted for these events are not established. We aimed to evaluate the prognostic impact of recreational drug use at 1-year follow-up to predict major adverse cardiovascular and cerebrovascular events (MACCE) in all consecutive patients admitted to in intensive cardiac care units (ICCUs). In the Addiction in Intensive Cardiac Care Units (ADDICT-ICCU) study, systematic screening for recreational drugs was performed by prospective urinary testing all patients admitted to ICCU in 39 French centres from 7 to 22 April 2021. The primary composite outcome was the occurrence of MACCE defined as cardiovascular death, nonfatal myocardial infarction (MI) of stroke. Cox regressions were used to determine the prognostic impact of recreational drugs. We also used a 1:1 propensity-score matched population as sensitivity analysis. Of 1,392 consecutive patients (age 63 ± 15 years, 67% male), 157 (11%) had a positive test for recreational drugs (cannabis: 9.1%, opioids: 2.1%, cocaine: 1.7%, amphetamines: 0.7%, MDMA: 0.6%). Only 57% of these declared recreational drug use. Recreational drugs were associated with a higher rate of MACCE after adjustment for all traditional risk factors (adjusted HR: 2.99; 95%CI: 1.73–5.16, P < 0.001 – Figure 1). Using a 1:1 propensity-score matched population (157 with versus 157 without recreational drugs detected), the use of recreational drugs was associated with a higher incidence of MACCEs (HR: 6.11; 95% CI: 2.77–13.5, P < 0.001). Multiple drug detection was frequent (28% of positive patients) and associated with an even higher incidence of MACCEs (HR: 11.0; 95%CI: 3.80–22.1, P < 0.001). The prevalence of recreational drug use in patients hospitalised in ICCU was 11%. Recreational drug detection was independently associated with a three-fold increase in the risk of MACCE.

Abstract Background In pulmonary embolism (PE), the usual evaluation of early risk of death includes clinical, biological and two-dimensional right ventricular (RV) echocardiographic (TTE) parameters. Purpose We hypothesized that myocardial strain analysis could contribute to risk of death prediction at long term follow up. Methods We retrospectively analyzed 477 patients hospitalized for acute EP. Usual parameters used to define RV dysfunction were evaluated using TTE (RV dilatation, systolic pulmonary arterial pressure, TAPSE, S’, Fractionnal Area Change (FAC), end diastolic RV diameter and right atrial, RA, area). In addition, we evaluated, left ventricle (LV) longitudinal, left atrial (LA), RA and RV free wall strains. Patients without history of cancer (n=419) were analyzed on the primary outcome of death at long term follow up. Results Mean of age was 63.7 ± 17.2 years and 227 (47.6) patients were male. The main clinical and echocardiographic characteristics are displayed in the Table 1. During a mean follow-up was 45.0 ± 16.6 months, the primary outcome occurred in 56 patients. In multivariable analysis, systolic pulmonary arterial pressure, indexed right atrial and left atrial volumes, right ventricle free wall strain, right ventricle global longitudinal strain were the only predictors of death (Table 2). Conclusion Atrial volumes and RV strain appeared as strong predictors of death in PE at long term follow up. Right ventricle myocardial strain analysis should be evaluated in each patient hospitalized for PE.

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

Abstract Background Tricuspid annular plane systolic excursion over systolic pulmonary artery pressure (TAPSE/sPAP) assessed by echocardiography is a good non-invasive approach for right ventricular to pulmonary artery (RV-PA) coupling assessment. Although the prognostic value of this ratio is well known in many cardiovascular diseases, its prognostic value in acute coronary syndrome (ACS) is not established. Purpose To assess one-year prognostic value of TAPSE/sPAP among patients hospitalised for ACS. Methods In the prospective multicentric ADDICT-ICCU study, all consecutive patients hospitalized for ACS (either Non ST-Elevation Myocardial Infarction or ST-Elevation Myocardial Infarction) over two weeks in April 2021 at 39 centres across France were included. The TAPSE/sPAP ratio was measured using the first echocardiography performed within the first 24 hours of hospitalisation. The primary composite outcome was one-year major adverse cardiovascular event (MACE) including: all-cause death or urgent hospitalisation for acute cardiovascular reason (acute heart failure, urgent myocardial revascularisation). C-tree analysis was used to find the optimal TAPSE/sPAP cut-off to predict the primary outcome. Results Among the 772 ACS patients (age 64±12 years, 74% males) included, 113 (15%) experienced 1-year MACE. The best cut-off for TAPSE/sPAP to predict 1-year MACE was 0.67 mm/mmHg. Patients with TAPSE/sPAP ≤0.67 mm/mmHg were more likely older (p<0.001), with previous atrial fibrillation (p<0.001), a higher length of hospitalization in ICCU (p<0.001), a higher NTproBNP (p=0.001) and a worse LVEF value (p<0.001). At one-year, all-cause death occurred in 27 (14%) patients with TAPSE/sPAP ≤0.67, compared to 7 (2.5%) with TAPSE/sPAP>0.67 (p<0.001), and 32 (16%) patients with TAPSE/sPAP ≤0.67 were hospitalised for acute cardiovascular reason against 20 (7%) with TAPSE/sPAP >0.67 (p=0.006). After adjustment for all traditional prognosticators, TAPSE/sPAP <0.67 mm/mmHg remained independently associated with the primary outcome (Table1): model 1 (comorbidities): HR 2.82, 95%CI[2.92-4.38], p<0.001, model 2 (echocardiography): HR=2.38, 95%CI [1,40-4,03], p<0.001). Patients with TAPSE/sPAP ≤0.67 mm/mmHg had worse event-free survival for the primary outcome: HR=2.92, 95%CI[1.98-4.29], p<0.001). Conclusion TAPSE/sPAP, a noninvasive approach for RV-PA coupling, was independently associated with 1-year MACE in patients hospitalised for ACS, even after adjustment with traditional prognosticators, including LVEF.Fig2.Multivariable Cox analysis

High exhaled carbon monoxide (CO) is associated with recent smoking (≤24 hours) and seems to be associated with prognosis after acute coronary syndromes (ACS). Invasive coronary angiography (ICA) features associated with high expired CO remain unknown. To investigate ICA features (evaluated by an angiogiographic core laboratory) associated with high expired CO in patients presenting ACS. From 7 to 21 April 2021, the Addiction in Intensive Cardiac Care Unit (ADDICT-ICCU) study recruited prospectively, all consecutive patients admitted to ICCUs across 39 French hospitals. This prespecified study included patients presenting ACS. Expired CO level was measured in each patient within 2 hours following admission using a standardized exhaled CO measurement device. CO threshold value for recent smoking was set to 10 ppm in accordance with published studies comparing active and non-smokers. An independent angiographic core laboratory analyzed ICAs performed during the study period. ICA features between patients with expired CO > 10 ppm and ≤ 10 ppm were compared. This study included 268 patients (mean age 62 ± 13 years; 77% men) with ACS and available ICA and CO data. At admission, 44 (16%) had expired carbon monoxide level > 10 ppm. Compared to patients with CO ≤ 10 ppm, these patients were younger (57 vs. 63 years; p = 0.01), had lower systolic blood pressure (125 vs. 136 mmHg; p = 0.02) and a trend to higher rate of ST-elevation myocardial infarction (61% vs. 45%; p = 0.06). Concerning ICA features, the mean SYNTAX score did not differ according to CO level (9.6 vs. 10.5 for CO > 10 ppm and CO ≤ 10 ppm respectively; p = 0.48; Figure 1). Although rate of multivessel disease was similar between patients with CO > 10 ppm and CO≤10 ppm (56% vs 56%; p = 1.00), there was a trend to fewer triple-vessel disease in patients with CO > 10 ppm (14 vs. 24%; p = 0.20). The culprit vessel was more likely right coronary artery in the CO > 10 ppm group (47% vs. 32%) and the left anterior descending in the CO ≤ 10 ppm group (36% vs 42%), but these results were not statistically significant (p = 0.50). Patients with higher CO had a trend to a higher thrombus burden score (4.7 vs. 4.0; p = 0.09) resulting in more frequent thrombo-aspiration during PCI (19% vs. 9%; p = 0.10). Invasive coronary angiography features associated with high exhaled CO in ACS suggested similar SYNTAX score and multiple vessel disease rate with higher thrombus burden.

Combustion of cigarettes produces carbon monoxide (CO), which reduces oxygen-carrying capacity of the blood. The impact of CO level on the prognosis of patients with acute cardiac events is unknown. We hypothesized that elevated CO level is associated with impaired prognosis in patients hospitalized for acute cardiac events. From 7 to 22 April 2021, CO level was systematically measured in a prospective study including all consecutive patients admitted to intensive cardiac care unit in 39 centres throughout France. CO measurement was performed within 2 hours following admission using a standardized exhaled CO measurement device. The primary clinical outcome was in-hospital Major Adverse cardiac Events (MAE) defined by death, resuscitated cardiac arrest or cardiogenic shock. Among 1,387 consecutive patients screened (63.6 ± 14.8 years, 69.8% male), 33% were non smokers, 40% were former smokers and 27% were active smokers. CO level was similar in non smokers and former smokers (Mean ± SD 3.6 ± 3.6–3.3 ± 2.8, p = 0.12) and significantly increased in active smokers: 9.9 ± 6.4 ppm, p < 0.001). During hospitalisation, there were 58 (4.2%) in-hospital MAE. CO level was significantly associated with MAE in active smokers (OR [95%CI]: 1.14 [1.08–1.20] per unit ppm). The best threshold was >13 ppm defined by ROC curve analysis. CO level >13 ppm was significantly associated with MAE according to 3 models (model 1: age, sex, comorbidities, the main admission diagnosis: OR [95%CI]: 23.0 [8.1–78.3]– model 2: age, sex, the main admission diagnosis, systolic blood pressure, Killip class, and heart rate): 19.7 [6.9–65.1]– model 3: age, sex, the main admission diagnosis, BMI, previous COPD or asthma, oxygen flow rate – oxygen saturation – hemoglobin level at admission, and IV diuretic treatment): 37.8 [11.4–167]. Similar results were found using propensity score matching 2:1. In smokers with CO level ≤ 13 ppm, MAE rate was similar to non or former smokers (p = 0.65) (Fig. 1). In this prospective multicentre cohort of patients hospitalized for acute cardiac events, in hospital MAE are significantly and independently associated with CO level >13 ppm in smokers.

In heart failure (HF), most of the data available on myocardial strain focused on left heart cavities. Our study aimed to assess four chambers strain profiles in patients with HF. We prospectively evaluated 95 patients hospitalized for HF. Patients were divided into preserved LVEF (LVEF ≥ 50%, HFpEF n = 24), mildly reduced LVEF ((LVEF 41–49%, HFmrEF n = 17), and reduced left ventricular ejection fraction (LVEF) (LVEF ≤ 40%, HFrEF n = 54). In addition to the usual two-dimensional echocardiographic parameters, LV global longitudinal strain, left and right atrial strain (reservoir, conduit, contractile strain) and right ventricular free wall strain were measured using speckle tracking transthoracic echocardiography at admission. Patients with HFrEF were younger in comparison with patients with HFmrEF and HFpEF, (respectively 66.3 ± 14.2, 78.3.0 ± 8.7, 75.6 ± 10.2 years P < 0.001). They were no differences in the prevalence of cardiovascular risk factors and in the history of AF between the 3 groups. Patients with HFrEF had higher LV end-diastolic volume in comparison with patients with HFmrEF and HFpEF (respectively 89.7 (63.9–109.5), 68.6 (49.7–76.0), 41.9 (34.2–48.1) mL/m2, P < 0.001). They were no differences between the 3 groups regarding diastolic function parameters (E/A, E/e’, left atrial indexed volume), the right atrial indexed volume and the tricuspid lateral annular peak systolic velocity (S’). Tricuspid regurgitation (TR) peak velocity was significantly lower in HFmrEF group (P = 0.008). Myocardial strain analyses demonstrated that patients with HFrEF had significant lower LV global and right ventricular strain, lower left atrial reservoir strain, lower left and right atrial conduit strain (Fig. 1). Beyond the alteration of LV function, HFrEF involves alteration of RV, LA and RA functions. Strain analysis is an interesting tool in addition to conventional echocardiographic parameters to assess heart function in heart failure. The prognostic impact of these finding remains to be studied.

In silico trials applying a computational model (CM) of atherosclerotic cardiovascular disease (ASCVD) to virtual patients receiving alternative treatments provide an attractive option to complement randomised clinical trials (RCTs) by adding comparative effectiveness data and facilitating the demonstration of drug benefit. In silico modelling allows comparison between treatments with each virtual patient being his own control, and is not limited by the number of patients, comparative arms or trial duration. This study aims at building a knowledge-based mechanistic model of ASCVD. Once validated, the model will be used to run in silico clinical trials to compare the benefit of inclisiran, an siRNA targeting PCSK9 mRNA, vs other lipid-lowering therapies (LLT) on cardiovascular (CV) events in patients with ASCVD. An extensive literature review was performed to identify pathophysiological mechanisms involved in ASCVD and therapeutic mechanisms of action (MOAs). Every piece of knowledge extracted from the literature is awarded a strength of evidence grading to allow tracking of uncertainty in the model. A panel of multidisciplinary experts reviewed knowledge models and subsequent modelling hypotheses to validate their relevance. Knowledge was translated into mathematical equations. Each functional relationship between entities is represented by a biochemical/biophysical reaction with its reaction rate. A system of ordinary differential equations provides dynamics of modelled biological entities. A strategy of model calibration/validation was defined with the expert panel, by selecting relevant RCT and registry data, that the model should be able to reproduce. A virtual population was generated to account for inter-patient variability. A mechanistic CM of ASCVD (including 72 biological entities, 750 parameters) was built from knowledge, describing lipoproteins metabolism and cholesterol homeostasis, dynamics of atherosclerotic plaque growth with lipoproteins infiltration in the intima and evolution of lipidic, necrotic and fibrotic tissues as well as plaque rupture leading to myocardial infarction, ischemic stroke, lower extremity arterial disease or CV death. It also includes the impact of several risk factors (age, sex medical history, diabetes, hypertension, smoking, systemic inflammation, chronic kidney disease) and available LLT (atorvastatin, rosuvastatin, ezetimibe, evolocumab and inclisiran). After calibration, the model and virtual population reproduce pharmacokinetics of LLT, lipoproteins decrease under combinations of LLT and associated reduction in clinical events. ASCVD is ideally suited for in silico modelling: extensive literature is available regarding the pathophysiology, therapeutic MOAs are known and easily integrated in the model, clinically relevant outcomes are adequate model outputs, RCT and registry data exist to calibrate/validate the model. The next step is validation of the model before using it to run in silico trials.Plaque growth and rupture modelMulti-scale in silico model

Le score calcique coronarien (CAC) est validé, en population générale, pour prédire le risque d'événements cardiovasculaires. Une cohorte Suisse a montré que, pour des CAC médians équivalents, les patients vivants avec le VIH (PVVIH) étaient plus jeunes et avaient moins de plaques coronaires calcifiées que la population générale. L'objectif de notre étude était de comparer les CAC des PPVIH, non pas à la population générale mais à un groupe contrôle HIV négatif (HIV-) à risque cardiovasculaire intermédiaire. Il s'agit d'une étude prospective, bi centrique, réalisée entre 2013 et 2019, en France. A partir de l'inclusion consécutive de tout patient éligible, adressé pour une évaluation du risque cardiovasculaire en consultation spécialisée, nous avons constitué un groupe « PVVIH » et un groupe « contrôle » de patients HIV-. Les patients étaient éligibles s'ils étaient à risque cardiovasculaire intermédiaire (2 facteurs de risque parmi âge, HTA, tabac, hérédité, HDLc, diabète), âgés de plus de 18 ans, n'avaient jamais présenté d'événement cardiovasculaire et avaient bénéficié d'un CAC dans le cadre des soins courants. L'étude a inclus 689 patients (257 PVVIH, 432 HIV -), majoritairement des hommes (374/689, 54%). L'âge médian était de 59.3 ans ± 10.7. Les PVVIH, comparativement au groupe contrôle, étaient plus jeunes (55.8 ± 9.1 vs 61.3 ± 11.3, p< 0.004), moins souvent diabétiques (45/257 soit 18% vs 113/431 soit 26%, p= 0.009) et présentaient des taux de cholestérol plus bas en cholestérol total, LDLc et HDLc (2.0 mmol/l vs 2.2 mmol/l; 1.2 mmol/L vs 1.3 mmol/L; and 1.2 mmol/L vs 1.4 mol/L respectivement, tous p< 0.001). Par contre, les PVVIH avaient un taux de triglycérides plus élevé (1.4 mmol/L vs 1.2 mmol/L, p= 0.01), étaient plus souvent tabagiques (72/257 soit 28% vs 59/418 soit 14%, p< 0.001). Le score ASCVD était identique entre les PVVIH et le groupe contrôle (10.7% vs 9.9%, p=0.15) alors que les PVVIH avaient un score HEART médian plus élevé (3 vs 2, p <0.001). Il n'y avait pas de différence entre les deux groupes concernant la prévalence de CAC égal à 0 (PVVIH 106/257 soit 41.2% vs VIH- 189/432 soit 43.8%, p=0.52), de CAC > 0 (PVVIH 151/257 soit 58.8% vs VIH- 243/432 soit 56.3%, p=0.42), et de valeur médiane de CAC (7.7 vs 8.2, p=0.81). Les facteurs de risque cardiovasculaires traditionnels étaient associés à un CAC > 0 dans les deux groupes tandis que la durée de traitement antirétroviral était associée à un CAC > 0 chez PVVIH. Dans cette cohorte de patients avec un risque cardiovasculaire intermédiaire, nous confirmons les données de la cohorte Suisse (population générale) avec pour des CAC médians équivalents, des PVVIH plus jeunes. Cette étude vient confirmer l'intérêt du CAC chez les PVVIH et suggère l'intérêt d'un dépistage plus précoce de la maladie athéromateuse. Aucun lien d'intérêt

Abstract Background Left atrial (LA) volume is considered an echocardiographic marker of thrombosis risk and prognosis in atrial fibrillation (AF). Limited data is available on the prognostic value of left atrial appendage (LAA) volume in AF as evaluated with three-dimensional (3D) transoesophageal echocardiography (TEE). Purpose We hypothesized that 3D LAA volume is associated with prognosis in patients hospitalized with AF. Methods We prospectively evaluated 206 patients hospitalized for AF with two-dimensional transthoracic echocardiography (TTE) and 3D TEE of the LAA within 24 hours of admission. 3D parameters were analysed off-line using Tomtec software (4D Cardio-View, Generic Volume, Philips). The primary composite outcome was all-cause death during at 2 years follow up. Results The median age of the study group was 66.3 ± 11.5 years with 129 (62.6%) men. In the global population, at admission, the median 3D LAAV was 9.02 (6.96-12.15) ml. Patients were divided into two groups according to the median 3D LAAV: Group 1: LAAV < 9ml (103 patients) and Group 2: LAAV ≥ 9ml (103 patients). Patients with LAAV ≥ 9ml had more frequently a history of heart failure and chronic obstructive pulmonary disease. There were no significant intergroup differences in CHA2DS2-VASc score. Patients with LAAV ≥ 9ml had higher values of BNP and CRP and lower LVEF, higher LA volumes, higher E/e’, lower LAA emptying flow velocity, and higher 3D ES LAA ostium area. There were no statistical differences in LAA spontaneous echo contrast and LAA morphology between groups (Table 1). Kaplan–Meier curves demonstrated a significant difference in survival according to the 3D ES LAAV: 3 deaths occurred in the group with 3D ES LAA volume < 9mL and 11 in the group with 3D ES LAA Volume≥9mL (p=0.0315) (Figure 1). Conclusion Among LAA parameters, 3D LAA end-systolic volume is significantly associated with a worse outcome in patients with AF. Further investigations are needed to evaluate this unique parameter against usual geometric and functional LA/LAA parameters.

Abstract Background Little data is available on the evaluation of left atrial appendage (LAA) geometry and function using three-Dimensional (3D) transoesophageal echocardiography (TEE). Purpose We hypothesized that 3D LAA geometry evaluated using dedicated TEE software could be integrated in the evaluation of the thromboembolic milieu in patients hospitalized for atrial fibrillation (AF). Methods We prospectively studied 206 hospitalized patients with AF with two-dimensional transthoracic echocardiography (TTE) and 3D TEE of the LAA within 24 hours of admission. 3D parameters were analysed off-line using Tomtec software (4D Cardio-View, Generic Volume, Philips) (Figure 1). Patients were divided into two groups according to the presence (n = 35) or absence (n = 171) of LAA sludge/thrombus on admission. Results Patients with LAA sludge/thrombus had more frequently a history of heart failure together with higher values of BNP, CRP and hemoglobin. These patients received less frequently angiotensin II receptor antagonist treatment on admission. Concerning the echocardiographic characteristics, patients with LAA sludge/thrombus exhibited higher left atrial (LA) volume, lower left ventricular ejection fraction (LVEF) and cardiac output. In the 2D TEE study they had lower LAA emptying and filling flow velocities compared to those without sludge/thrombus. 3D TEE showed overall higher 3D end-systolic (ES) and end-diastolic (ED) LAA measurements (ostium area, length, volume), and more frequently the absence of a chicken wing morphology. There were no intergroup differences regarding the number of LAA lobes (Table 1). Conclusion 3D characterization of LAA geometry and function depicts a degree of appendage remodeling in AF that appears to be associated with the degree of thrombogenicity. Further investigation is needed to determine the impact of this remodeling on outcomes in these patients.

Abstract Background Although illicit drug use may induce acute coronary syndrome (ACS), its impacts on coronary angiographic characteristics and the coronary artery disease (CAD) burden are a matter of debate. Purpose To assess the association between illicit drugs use and coronary angiographic findings in a multicenter patients with ACS. Methods From April 7 to 22, 2021, the Addiction in Intensive Cardiac Care Unit (ADDICT-ICCU) study included prospectively 1,499 patients admitted to ICCUs with a systematic urine multidrug test in 39 ICCUs across France. This prespecified study focuses on patients admitted for ACS with an angiography analysed by an independent Angiographic Core Laboratory. Patients with history of coronary artery bypass graft surgery were excluded. We compared coronary angiographic findings between illicit drugs users and others for the following parameters: the prevalence, location, type, and severity of CAD obstruction (stenosis≥50%), SYNTAX score, residual SYNTAX score, and the characteristics of percutaneous coronary intervention (PCI). Results Among the 283 patients with ACS (62±13 years, 77% men), 38 (13.4%) had a positive test for illicit drugs (cannabis: 12%, cocaine: 1.1%, MDMA: 0.7%). Drug users were younger than other patients (51±12 vs 64±12 years, p<0.001), but there were no significant difference in sex ratio (89.5% vs 75.5%, p=0.088). There was no significant difference in the rate of STEMI (52.6% vs 45.7%, p=0.535) and NTSEMI (47.4% vs 54.3%, p=0.535) between drug users and others. Regarding the CAD burden, drug users had significantly less obstructive coronary lesions (1.6±1.1 vs 2.2±1.4, p=0.012), less multivessel obstructive CAD (31% vs 61%, p=0.001), and a trend for a lower initial SYNTAX score (8.3±7.8 vs 10.8±8.4; p=0.084) compared to others. Concerning culprit lesion, drug users had less bifurcation lesions (p=0.008), a trend for more left anterior descending (LAD) artery lesions (p=0.091), a higher thrombus burden score (p=0.057), and less lesions above 20 mm (p=0.183). Conclusion In patients with ACS, recent illicit drug use is associated with less number of significant lesions and less multivessel CAD. Concerning culprit lesions, illicit drugs use is associated with less bifurcation lesions, with a trend for more LAD lesions and a higher thrombus burden score.ACS analysed with Core LaboratoryAngiographic findings according to drug

Objective: The aim of this study was to compare clinical characteristics and adipose/liver tissue histology analysis in HIV-infected and HIV-uninfected subjects undergoing bariatric surgery. Design: This was a cross-sectional study of HIV-infected subjects undergoing single-port sleeve gastrectomy with prospective enrolment and frequency age (±5 years), sex, and body mass index (BMI, ± 5 kg/m2) matched on HIV-uninfected subjects. Methods: This study was conducted at a single clinical site at Pitié-Salpêtrière hospital-Paris-France comprising 19 HIV-uninfected and 21 HIV-infected subjects with plasma VL < 20 copies/mL, all with a BMI > 40 kg/m2 or >35 kg/m2 with comorbidities. Histology of subcutaneous and visceral abdominal adipose tissue (SCAT/VAT) and liver biopsies was collected during single-port sleeve gastrectomy. Outcomes included anthropometric characteristics, comorbidities, cardiovascular parameters, adipose tissue, and liver histology. Results: The age of HIV-infected participants was (median, interquartile range IQR) 48 y (42–51), with 76.2% females, a BMI of 41.4 kg/m2 (37.3–44.4), an antiretroviral duration of 16 y (8–21), current integrase strand transfer inhibitor (INSTI)-based regimen in 15 participants and non-INSTI regimen in 6 participants, and a CD4 count of 864/mm3 (560–1066). The age of controls was 43 y (37–51), with 78.9% females and a BMI of 39.2 kg/m2 (36.3–42.6). Anthropometric characteristics, comorbidities, and cardiovascular parameters did not differ according to HIV status and INSTI treatment. The number of macrophage crown-like structures in SCAT was lower in INSTI-treated participants than in HIV-uninfected participants (P = 0.02) and non–INSTI-treated HIV-infected subjects (P = 0.07). Hepatic steatosis and liver disease severity global score were lower in INSTI-treated participants than in non–INSTI-treated HIV-infected participants (P = 0.05 and P = 0.04, respectively). Conclusions: HIV-infected and HIV-uninfected subjects undergoing bariatric surgery presented a similar profile regarding anthropometric measures, cardiovascular parameters, and comorbidities. However, INSTI-treated participants presented milder SCAT and liver alterations than non–INSTI-treated participants.

Dunnigan syndrome, or Familial Partial Lipodystrophy type 2 (FPLD2; ORPHA 2348), is a rare autosomal dominant disorder due to pathogenic variants of the LMNA gene. The objective of the French National Diagnosis and Care Protocol (PNDS; Protocole National de Diagnostic et de Soins), is to provide health professionals with a guide to optimal management and care of patients with FPLD2, based on a critical literature review and multidisciplinary expert consensus. The PNDS, written by members of the French National Reference Center for Rare Diseases of Insulin Secretion and Insulin Sensitivity (PRISIS), is available on the French Health Authority website (in French). Dunnigan syndrome is characterized by a partial atrophy of the subcutaneous adipose tissue and by an insulin resistance syndrome, associated with a risk of metabolic, cardiovascular and muscular complications. Its prevalence, assessed at 1/100.000 in Europe, is probably considerably underestimated. Thorough clinical examination is key to diagnosis. Biochemical testing frequently shows hyperinsulinemia, abnormal glucose tolerance and hypertriglyceridemia. Elevated hepatic transaminases (hepatic steatosis) and creatine phosphokinase, and hyperandrogenism in women, are common. Molecular analysis of the LMNA gene confirms diagnosis and allows for family investigations. Regular screening and multidisciplinary monitoring of the associated complications are necessary. Diabetes frequently develops from puberty onwards. Hypertriglyceridemia may lead to acute pancreatitis. Early atherosclerosis and cardiomyopathy should be monitored. In women, polycystic ovary syndrome is common. Overall, the management of patients with Dunnigan syndrome requires the collaboration of several health care providers. The attending physician, in conjunction with the national care network, will ensure that the patient receives optimal care through regular follow-up and screening. The various elements of this PNDS are described to provide such a support.

Background and Aims : Children with heterozygous familial hypercholesterolemia (HeFH) are undertreated despite international guidelines advocating for early statin initiation during childhood; dramatically increasing their risk of premature atherosclerotic cardiovascular disease (ASCVD).The objective of the study was to identify childhood and parental factors associated with statin early initiation in HeFH children to promote early treatment.Methods: Design, Setting and Participants: National register-based (REFERCHOL) multicenter, retrospective and prospective cohort study. We selected HeFH children aged 8-18 years and their FH parents, followed between 2014 and 2020. Demographic and clinical characteristics at last visit to the lipid clinic were collected. Vascular damage in parents was defined as a history of ASCVD, and/or a coronary artery calcium score above 100, and/or at least one carotid stenosis (>50%). Main outcome: Statin initiation in HeFH children.Results: We included 245 child-parent pairs. The children age was 14±3 years, and only 135 (58%) were under statin treatment. In multivariate analysis, the predictive childhood factors associated with being treated by a statin were: genetic diagnosis (OR=2.5, 95%CI [1.3; 4.9], p=0.01), older age (OR=4.4, 95%CI [1.8; 10.6], p=0.01), and longer follow-up duration (OR=1.3, 95%CI [1.1; 1.6], p<0.001); whereas the predictive parental factor associated with child treatment was the presence of vascular damage (OR=2.4, 95%CI [1.0; 5.7], p=0.04).Conclusions: A positive genetic diagnosis during childhood and vascular damage in parents were independently associated with statin treatment in HeFH children. Genetic diagnosis seems an important tool for cardiovascular prevention in these future adults. Background and Aims : Children with heterozygous familial hypercholesterolemia (HeFH) are undertreated despite international guidelines advocating for early statin initiation during childhood; dramatically increasing their risk of premature atherosclerotic cardiovascular disease (ASCVD).The objective of the study was to identify childhood and parental factors associated with statin early initiation in HeFH children to promote early treatment. Methods: Design, Setting and Participants: National register-based (REFERCHOL) multicenter, retrospective and prospective cohort study. We selected HeFH children aged 8-18 years and their FH parents, followed between 2014 and 2020. Demographic and clinical characteristics at last visit to the lipid clinic were collected. Vascular damage in parents was defined as a history of ASCVD, and/or a coronary artery calcium score above 100, and/or at least one carotid stenosis (>50%). Main outcome: Statin initiation in HeFH children. Results: We included 245 child-parent pairs. The children age was 14±3 years, and only 135 (58%) were under statin treatment. In multivariate analysis, the predictive childhood factors associated with being treated by a statin were: genetic diagnosis (OR=2.5, 95%CI [1.3; 4.9], p=0.01), older age (OR=4.4, 95%CI [1.8; 10.6], p=0.01), and longer follow-up duration (OR=1.3, 95%CI [1.1; 1.6], p<0.001); whereas the predictive parental factor associated with child treatment was the presence of vascular damage (OR=2.4, 95%CI [1.0; 5.7], p=0.04). Conclusions: A positive genetic diagnosis during childhood and vascular damage in parents were independently associated with statin treatment in HeFH children. Genetic diagnosis seems an important tool for cardiovascular prevention in these future adults.