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Transthyretin cardiac amyloidosis (ATTR-CA) is an increasingly recognized disease that often results in heart failure and death. Traditionally, biological staging systems are used to stratify disease severity. Reduced aerobic capacity has recently been described as useful in identifying higher risk of cardiovascular events and death. Assessment of lung volume via simple spirometry might also hold prognostic relevance. We aimed to assess the combined prognostic value of spirometry, cardiopulmonary exercise testing (CPET) and biomarker staging in ATTR-CA patients in a multi-parametric approach. We retrospectively reviewed patient records with pulmonary function and CPET testing. Patients were followed until study endpoint (MACE: composite of heart-failure-related hospitalization and all-cause death) or censure (1 April 2022). In total, 82 patients were enrolled. Median follow-up was 9 months with 31 (38%) MACE. Impaired peak VO2 and forced vital capacity (FVC) were independent predictors of MACE-free survival, with peak VO2 < 50% and FVC < 70% defining the highest risk group (HR 26, 95% CI: 5–142, mean survival: 15 months) compared to patients with the lowest risk (peak VO2 ≥ 50% and FVC ≥ 70%). Combined peak VO2, FVC and ATTR biomarker staging significantly improved MACE prediction by 35% compared to ATTR staging alone, with 67% patients reassigned a higher risk category (p < 0.01). In conclusion, combining functional and biological markers might synergistically improve risk stratification in ATTR-CA. Integrating simple, non-invasive and easily applicable CPET and spirometry in the routine management of ATTR-CA patients might prove useful for improved risk prediction, optimized monitoring and timely introduction of newer-generation therapies.

Aim: To analyze the impact of obesity on cardiopulmonary response to exercise in people with chronic post-COVID-19 syndrome. Patients & methods: Consecutive subjects with chronic post-COVID syndrome 6 months after nonsevere acute infection were included. All patients received a complete clinical evaluation, lung function tests and cardiopulmonary exercise testing. A total of 51 consecutive patients diagnosed with chronic post-COVID-19 were enrolled in this study. Results: More than half of patients with chronic post-COVID-19 had a significant alteration in aerobic exercise capacity (VO2peak) 6 months after hospital discharge. Obese long-COVID-19 patients also displayed a marked reduction of oxygen pulse (O2pulse). Conclusion: Obese patients were more prone to have pathological pulmonary limitation and pulmonary gas exchange impairment to exercise compared with nonobese COVID-19 patients.

Background: Animal studies have demonstrated that fetal exposure to high maternal cholesterol levels during pregnancy predisposes to aortic atheroma in the offspring. In humans, little is known about the consequences of this exposure on the development of atherosclerotic cardiovascular disease later in life. We wanted to assess whether maternal/paternal inheritance of familial hypercholesterolemia (FH) gene mutation could be associated with subclinical coronary atherosclerosis. Methods: We retrospectively included 1350 patients, followed in the French registry of FH, with a documented genetic diagnosis. We selected 556 age- and sex-matched pair of patients based on the sex of the parents who transmitted the FH gene mutation, free of coronary cardiovascular event, and with a subclinical coronary atherosclerosis evaluation assessed using coronary artery calcium (CAC) score. We performed univariate and multivariate analysis to assess the individual effect of parental inheritance of the FH gene mutation on the CAC score. Results: In the whole population, patients with maternal inheritance of FH gene mutation (n=639) less frequently had a family history of premature cardiovascular events (27.7% versus 45%, P P =0.02) than those with paternal inheritance (n=711). There was no difference in the prevalence of cardiovascular events between the two groups. In the matched subgroup, maternal inheritance was significantly associated with an increase in CAC score value by 86% (95% CI, 23%–170%; P =0.003), a 1.81-fold risk of having a CAC score ≥100 Agatston units (95% CI, 1.06–3.11; P =0.03), and a 2.72-fold risk of having a CAC score ≥400 Agatston units (95% CI, 1.39–5.51; P =0.004) when compared with paternal inheritance in multivariate analysis. Conclusions: Maternal inheritance of FH gene mutation was associated with more severe subclinical coronary atherosclerosis assessed by CAC score and may be considered as a potential cardiovascular risk factor.

Aims The treatment of heart rhythm disorders has been significantly impacted by direct consequences of the current COVID-19 pandemic, as well as by restrictions aimed towards constraining viral spread. Methods and results Usually, catheter ablations of cardiac arrhythmias are guided by electro-anatomic mapping (EAM) systems. Technical staff with medical training, or medical staff with technical training, are needed to assist the operator. Travel restrictions due to the current COVID-19 pandemic have limited the in-person availability of technical support staff. To overcome these limitations, we explored the feasibility of a trans-atlantic remote technical support for EAM, with an internet-based communication platform, for complex electrophysiological ablation procedures. Conclusion Our first experience, based on nine ablation procedures of different arrhythmias, highlights the feasibility of this approach. Remote support for EAM might therefore facilitate continuous care for patients with arrhythmias during the COVID-19 pandemic, particularly in insular settings. Beyond COVID-19-related challenges, this approach will likely play a greater role in the cardiology field in years to come, due to its significant advantages., Graphical Abstract Graphical Abstract

International audience; ObjectivesThis study aimed at investigating the additional contribution of coronary artery calcium (CAC) score to SAFEHEART (Spanish Familial Hypercholesterolemia Cohort Study) risk equation (SAFEHEART-RE) for cardiovascular risk prediction in heterozygous familial hypercholesterolemia (HeFH).BackgroundCommon cardiovascular risk equations are imprecise for HeFH. Because of the high phenotype variability of HeFH, CAC score could help to better stratify the risk of atherosclerotic cardiovascular disease (ASCVD).MethodsREFERCHOL (French Registry of Familial Hypercholesterolemia) and SAFEHEART are 2 ongoing national registries on HeFH. We analyzed data from primary prevention HeFH patients undergoing CAC quantification. We used probability-weighted Cox proportional hazards models to estimate HRs. Area under the receiver-operating characteristic curve (AUC) and net reclassification improvement (NRI) were used to compare the incremental contribution of CAC score when added to the SAFEHEART-RE for ASCVD prediction. ASCVD was defined as coronary heart disease, stroke or transient ischemic attack, peripheral artery disease, resuscitated sudden death, and cardiovascular death.ResultsWe included 1,624 patients (mean age: 48.5 ± 12.8 years; men: 45.7%) from both registries. After a median follow-up of 2.7 years (interquartile range: 0.4-5.0 years), ASCVD occurred in 81 subjects. The presence of a CAC score of >100 was associated with an HR of 32.05 (95% CI: 10.08-101.94) of developing ASCVD as compared to a CAC score of 0. Receiving-operating curve analysis showed a good performance of CAC score alone in ASCVD prediction (AUC: 0.860 [95% CI: 0.853-0.869]). The addition of log(CAC + 1) to SAFEHEART-RE resulted in a significantly improved prediction of ASCVD (AUC: 0.884 [95% CI: 0.871-0.894] for SAFEHEART-RE + log(CAC + 1) vs AUC: 0.793 [95% CI: 0.779-0.818] for SAFEHEART-RE; P < 0.001). These results were confirmed also when considering only hard cardiovascular endpoints. The addition of CAC score was associated with an estimated overall net reclassification improvement of 45.4%.ConclusionsCAC score proved its use in improving cardiovascular risk stratification and ASCVD prediction in statin-treated HeFH.

© 2020 Elsevier Ltd. All rights reserved., Background: Hereditary transthyretin-mediated amyloidosis is a rare, inherited, progressive disease caused by mutations in the transthyretin (TTR) gene. We assessed the safety and efficacy of long-term treatment with patisiran, an RNA interference therapeutic that inhibits TTR production, in patients with hereditary transthyretin-mediated amyloidosis with polyneuropathy. Methods: This multicentre, open-label extension (OLE) trial enrolled patients at 43 hospitals or clinical centres in 19 countries as of Sept 24, 2018. Patients were eligible if they had completed the phase 3 APOLLO or phase 2 OLE parent studies and tolerated the study drug. Eligible patients from APOLLO (patisiran and placebo groups) and the phase 2 OLE (patisiran group) studies enrolled in this global OLE trial and received patisiran 0·3 mg/kg by intravenous infusion every 3 weeks with plans to continue to do so for up to 5 years. Efficacy assessments included measures of polyneuropathy (modified Neuropathy Impairment Score +7 [mNIS+7]), quality of life, autonomic symptoms, nutritional status, disability, ambulation status, motor function, and cardiac stress, with analysis by study groups (APOLLO-placebo, APOLLO-patisiran, phase 2 OLE patisiran) based on allocation in the parent trial. The global OLE is ongoing with no new enrolment, and current findings are based on the interim analysis of the patients who had completed 12-month efficacy assessments as of the data cutoff. Safety analyses included all patients who received one or more dose of patisiran up to the data cutoff. This study is registered with ClinicalTrials.gov, NCT02510261. Findings: Between July 13, 2015, and Aug 21, 2017, of 212 eligible patients, 211 were enrolled: 137 patients from the APOLLO-patisiran group, 49 from the APOLLO-placebo group, and 25 from the phase 2 OLE patisiran group. At the data cutoff on Sept 24, 2018, 126 (92%) of 137 patients from the APOLLO-patisiran group, 38 (78%) of 49 from the APOLLO-placebo group, and 25 (100%) of 25 from the phase 2 OLE patisiran group had completed 12-month assessments. At 12 months, improvements in mNIS+7 with patisiran were sustained from parent study baseline with treatment in the global OLE (APOLLO-patisiran mean change -4·0, 95 % CI -7·7 to -0·3; phase 2 OLE patisiran -4·7, -11·9 to 2·4). Mean mNIS+7 score improved from global OLE enrolment in the APOLLO-placebo group (mean change from global OLE enrolment -1·4, 95% CI -6·2 to 3·5). Overall, 204 (97%) of 211 patients reported adverse events, 82 (39%) reported serious adverse events, and there were 23 (11%) deaths. Serious adverse events were more frequent in the APOLLO-placebo group (28 [57%] of 49) than in the APOLLO-patisiran (48 [35%] of 137) or phase 2 OLE patisiran (six [24%] of 25) groups. The most common treatment-related adverse event was mild or moderate infusion-related reactions. The frequency of deaths in the global OLE was higher in the APOLLO-placebo group (13 [27%] of 49), who had a higher disease burden than the APOLLO-patisiran (ten [7%] of 137) and phase 2 OLE patisiran (0 of 25) groups. Interpretation: In this interim 12-month analysis of the ongoing global OLE study, patisiran appeared to maintain efficacy with an acceptable safety profile in patients with hereditary transthyretin-mediated amyloidosis with polyneuropathy. Continued long-term follow-up will be important for the overall assessment of safety and efficacy with patisiran.

International audience; Aims: In amyloid patients, cardiac involvement dramatically worsens functional capacity and prognosis. We sought to study how the cardiopulmonary exercise test (CPET) could help in functional assessment and risk stratification of patients with cardiac amyloidosis (CA).Methods and results: We carried out a multicentre study including patients with light chain (AL) or transthyretin (TTR) CA. All patients underwent exhaustive examination including CPET and follow-up. The primary prognostic endpoint was the occurrence of death or heart failure hospitalization. Overall, 150 patients were included (91 AL and 59 TTR CA). Median age, systolic blood pressure, N-terminal pro B-type natriuretic peptide (NT-proBNP) and cardiac troponin T were 70 (64-78) years, 121 [interquartile range (IQR) 109-139] mmHg, 2806 (IQR 1218-4638) ng/L and 64 (IQR 33-120) ng/L, respectively. New York Heart Association classes were I-II in 64%. Median peak oxygen consumption (VO2 ) and circulatory power were low at 13.0 (10.0-16.9) mL/kg/min and 1730 (1318-2614) mmHg/mL/min, respectively. The minute ventilation/carbon dioxide production slope was increased to 37 (IQR 33-45). A total of 77 patients (51%) had chronotropic insufficiency. After a median follow-up of 20 months, there were 37 deaths and 44 heart failure hospitalizations. At multivariate Cox analysis, peak VO2 ≤13 mL/kg/min [hazard ratio (HR) 2.7, 95% confidence interval (CI) 1.6-4.8], circulatory power ≤1730 mmHg/mL/min (HR 2.4, 95% CI 1.2-4.6) and NT-proBNP ≥1800 ng/L (HR 2.2, 95% CI 1.1-4.3) were found to be associated with the primary outcome. No events occurred in patients with both peak VO2 >13 mL/kg/min and NT-proBNP

Obesity-hypoventilation syndrome (OHS) is associated with many comorbidities. The aim of this study was to evaluate the association between previous continuous positive airway pressure (CPAP) and the prevalence of comorbidities in OHS associated with obstructive sleep apnea (OSA). We performed a retrospective, single-center study at the University Hospital of Martinique, the referral hospital for the island of Martinique. A total of 97 patients with OHS associated with severe OSA on non-invasive ventilation (NIV) were included; 54 patients (56%) had previous treatment of OSA with a positive airway pressure (PAP) device before shifting to NIV (PAP group) and 43 (44%) had no previous treatment of OSA with a PAP device before initiating NIV PAP (no PAP group). Sociodemographic characteristics were similar between groups; there were 40 women (74%) in the PAP group versus 34 (79%) in the no PAP group, mean age at OHS diagnosis was 66 ± 15 versus 67 ± 16 years, respectively, and the mean age at inclusion 72 ± 14 versus 71 ± 15 years, respectively. The average number of comorbidities was 4 ± 1 in the PAP group versus 4 ± 2 in the no PAP group; the mean Charlson index was 5 ± 2 in both groups. The mean BMI was 42 ± 8 kg/m2 in both groups. The mean follow-up duration was 5.8 ± 4.4 years in the PAP group versus 4.7 ± 3.5 years in the no PAP group. Chronic heart failure was less common in patients who had a previous PAP 30% versus 53% (p = 0.02). It is also noted that these patients were diagnosed less often in the context of acute respiratory failure in patients with previous PAP: 56% versus 93% (p < 0.0001). In contrast, asthma patients were more frequent in patients with previous treatment of OSA with a PAP device at the time of OHS diagnosis but not significantly: 37% versus 19% (p = 0.07). Early treatment of severe OSA with a PAP device prior to diagnosis of OHS seems to be associated with a reduced prevalence of cardiac diseases, notably chronic heart failure, in patients diagnosed with OHS associated with severe OSA.

International audience; Rationale: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is associated with pulmonary endothelial dysfunction. There are limited data available on the outcomes of coronavirus disease (COVID-19) in patients with pulmonary hypertension (PH), a disease characterized by pulmonary endothelial dysfunction. Objectives: To describe characteristics and outcomes of patients with precapillary PH and COVID-19. Methods: We prospectively collected characteristics, management, and outcomes of adult patients with precapillary PH in the French PH network who had COVID-19 between February 1, 2020, and April 30, 2021. Clinical, functional, and hemodynamic characteristics of PH before COVID-19 were collected from the French PH registry. Measurements and Main Results: A total of 211 patients with PH (including 123 with pulmonary arterial hypertension, 47 with chronic thromboembolic PH, and 41 with other types of PH) experienced COVID-19, and 40.3% of them were outpatients, 32.2% were hospitalized in a conventional ward, and 27.5% were in an ICU. Among hospitalized patients (n = 126), 54.0% received corticosteroids, 37.3% high-flow oxygen, and 11.1% invasive ventilation. Right ventricular and acute renal failure occurred in 30.2% and 19.8% of patients, respectively. Fifty-two patients (all hospitalized) died from COVID-19. Overall mortality was 24.6% (95% CI [confidence interval], 18.8-30.5) and in-hospital mortality 41.3% (95% CI, 32.7-49.9). Nonsurvivors were significantly older, more frequently male and suffering comorbidities (diabetes, chronic respiratory diseases, systemic hypertension, chronic cardiac diseases, and/or chronic renal failure), and had more severe PH at their most recent evaluation preceding COVID-19 diagnosis (in terms of functional class and 6-minute-walk distance; all P < 0.05). Use of pulmonary arterial hypertension therapy was similar between survivors and nonsurvivors. Conclusions: COVID-19 in patients with precapillary PH was associated with a high in-hospital mortality. The typical risk factors for severe COVID-19 and severity of PH were associated with mortality in this population.

Background Transthyretin amyloid cardiomyopathy results from the accumulation of wild-type (ATTRwt) or variant (ATTRv) transthyretin amyloid fibrils in the myocardium. THAOS (Transthyretin Amyloidosis Outcomes Survey) is a global, longitudinal, observational survey of patients with ATTRv and ATTRwt amyloidosis and asymptomatic patients with transthyretin mutations. Objectives This study explored temporal trends in ATTRwt amyloidosis diagnoses using data from THAOS. Methods Using THAOS data from December 2007 to January 2020, the following comparisons were made according to year: ATTRwt amyloidosis diagnoses in the United States versus rest of the world, ATTRwt versus ATTRv amyloidosis with cardiac-associated mutations diagnoses, and ATTRwt amyloidosis diagnoses by tissue biopsy versus bone scintigraphy. Results There were 1,069 patients with ATTRwt amyloidosis and 525 with ATTRv amyloidosis with cardiac mutations enrolled in THAOS. The median time from symptom onset to ATTRwt amyloidosis diagnosis did not change over the past 5 years (>60 months from 2015–2019). ATTRwt amyloidosis diagnoses increased from 2 in 2005 to >100 per year from 2016, with a more pronounced increase in the United States compared with the rest of the world. Diagnoses of ATTRwt amyloidosis by tissue biopsy increased yearly and peaked in 2014 before declining, whereas diagnoses by bone scintigraphy increased markedly since 2011. ATTRv amyloidosis with cardiac mutation diagnoses increased from 3 in 2005 to 37 in 2011, then plateaued. The proportion of patients with ATTRwt amyloidosis diagnosed with New York Heart Association functional class III/IV heart failure decreased from 2012 (46.4%) to 2019 (16.0%). Conclusions In the past decade, ATTRwt amyloidosis diagnoses increased worldwide. Despite the growing utilization of bone scintigraphy, patients are diagnosed several years after symptom onset. (Transthyretin Amyloidosis Outcomes Survey [THAOS]; NCT00628745), Central Illustration

Background: The short and long-term effects of volume overload elimination on left ventricular (LV) volumetric reverse-remodeling and systemic hemodynamic after surgery for chronic primary mitral r...

Sympathetic nervous system activation plays a pivotal role in obese patients with obstructive sleep apnea (OSA), contributing to increased cardiovascular risk. Epicardial adipose tissue (EAT) activates cardiac autonomic nervous system. Our main study objective was to investigate effects of these autonomic dysfunction factors on post-exercise heart rate recovery (HRR). 36 patients, referred for clinical assessment of obesity (BMI > 30 kg/m2), underwent overnight polysomnography, transthoracic echocardiography and cardiopulmonary exercise testing. Compared to non-OSA patients, OSA patients were older and displayed reduced body weight-indexed peak VO2. Cardiac output at peak exercise was similar among groups. Peak exercise arterio-venous oxygen content difference D[a-v]O2 was lower in OSA patients. In univariate linear analysis, age, AHI, EAT thickness, peak VO2 and diabetes were associated with blunted HRR. Multiple linear regression analysis showed that increased EAT thickness, AHI and diabetes were independently associated with lower HRR. For identical AHI value and diabetes status, HRR significantly decreased by 61.7% for every 1 mm increase of EAT volume (p = 0.011). If HRR was treated as a categorical variable, EAT [odds ratio (OR) 1.78 (95% confidence interval [CI] 1.19–2.66); p = 0.005], and type 2 diabetes [OR 8.97 (95% CI 1.16–69.10); p = 0.035] were the only independent predictors of blunted HRR. Aerobic capacity and peak exercise D[a-v]O2 are impaired in obese OSA patients, suggesting abnormal peripheral oxygen extraction. EAT thickness is an independent marker of post-exercise HRR, which is a noninvasive marker of autonomic nerve dysfunction accompanying poor cardiovascular prognosis in obese patients.

Aims This study sought to link cardiac phenotypes in homozygous Sickle Cell Disease (SCD) patients with clinical profiles and outcomes using cluster analysis. Methods We analyzed data of 379 patients included in the French Etendard Cohort. A cluster analyses was performed based on echocardiographic variables, and the association between clusters, clinical profiles and outcomes was assessed. Results Three clusters were identified. Cluster 1 (n=123) patients had the lowest cardiac output, mild left cardiac cavities remodeling, mild diastolic dysfunction, and higher tricuspid regurgitation velocity (TRV). They were predominantly female and displayed the most altered functional limitation. Cluster 2 (n=102) patients had the highest cardiac output and the most remodeled cardiac cavities. Diastolic function and TRV were similar to Cluster 1. These patients had a higher blood pressure and a severe hemolytic anemia. Cluster 3 (n=154) patients had mild left cardiac cavities remodeling, normal diastolic function and lowest TRV values. They were younger with the highest hemoglobin value. Right heart catheterization was performed in 94 patients. Cluster 1 (n=33) included the majority of pre-capillary PH whilst Cluster 2 (n=34) included post-capillary PH. No PH was found in Cluster 3 (n=27). After a follow-up of 11.4±2 years, death occurred in 41 patients (11%). Cluster 2 patients had the worst prognosis with a 19% mortality rate vs. 12% in Cluster 1 and 5% in Cluster 3 (P log-rank=0,003). Conclusion Cluster analysis of echocardiography variables identified 3 hemodynamic and clinical phenotypes amongst SCD patients, each predicting a different prognosis. This article is protected by copyright. All rights reserved.

Background Echocardiography is the main non-invasive screening tool for pulmonary hypertension (PH) in Sickle Cell Disease (SCD), but relies mostly on the tricuspid regurgitation velocity (TRV) assessment, without distinction between pre and postcapillary patterns. Purpose Using Etendard Cohort data, the aim of this study was to refine echocardiographic assessment of PH in SCD patients. Methods The French Etendard Study is a prospective cohort initially designed to assess the prevalence of PH among 398 SCD participants. We analyzed echocardiography data of the 96 Etendard patients who underwent Right Heart Catheterization (RCH), because of a TRV≥2.5m/s, and compared them to invasive haemodynamic measurements. Based on RHC results, patients were classified as follows: Absence of pulmonary hypertension if mean pulmonary arterial pressure (mPAP) was 15mmHg. Results PH was found in 24/96 patients with 11 precapillary and 13 postcapillary. In addition to TRV, multivariate analysis identified indexed left atrial volume (LAVind) and lateral E' wave velocity (E'lat) as independent echocardiographic predictors of PH (OR=1.06 and 0.6 respectively, p48ml/m2 and E'lat Moreover, comparing echocardiography data of pre and post-capillary PH patients, we observed that Pulmonary acceleration time (PAcT) was different in the two groups (104±22ms vs. 160±21ms, p115ms ruled out pre-capillary PH with a NPV of 97%. Conclusion Echocardiography can accurately estimates the probability of PH in SCD patients with an integrated approach using TRV, LAVind and E'lat. In addition, among patients with suspected PH, measuring PAcT as a PVR surrogate allows a good differentiation between pre and post-capillary phenotypes. We propose a new echocardiographic algorithm for the diagnosis of PH in SCD that could be a true assistance in referring patients for RHC. TTE Algorithm for PH in SCD Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): Funded by the French Ministry of Health and Assistance Publique–Hôpitaux de Paris

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

Neurodegenerative diseases (NDs) are very polymorphic and affect people of all ages. They concern both rare diseases and more common diseases. Improving knowledge of NDs in the French Caribbean region requires special attention because of the unique environmental and genetic background of its populations. In Martinique, there is a huge need for scientific research on rare NDs. While epidemiological and clinical research has increased over the past decade in the French West Indies, there is still little or no data on the genetics of NDs in these regions. The advent of Next Generation Sequencing (NGS) on a global scale has the potential to make a difference in this field, provided that technological and analytical knowledge, based on bioinformatics, is available in Martinique. Caribbean Reference Center for rare neuromuscular and neurological disorders (CERCA), is a reference center for diagnosis, health care and treatment of rare NDs. It supports our capacity building project in the clinical characterization of rare NDs with motor impairment, with or without dementia. In collaboration with CERCA, we designed a two-step pilot study, consisting of: 1) the creation of a clinical and biological database to select informative cases, and 2) to screen them by whole exome sequencing. This innovative approach involves: 1) mobilization of medical and clinical knowledge for the characterization of rare ND, with the support of a register of experts, and 2) expertise in molecular biology, molecular pathways and bioinformatics. This preliminary study confirms the need to consider our French West Indian population in these specificities. It reveals the effectiveness of a well-tune database for identifying pathogenic variants in a cohort of French West Indian patients with presumed genetic NDs, associated with motor impairment with or without dementia. It is a proof of concept that the creation of a register of NDs and the mastery of NGS technique, can provide additional expertise in research and patient management in the Caribbean. The continuation of this capacity building project should increase CERCA’s skills and outreach. Such an initiative is clearly innovative for the region and would bring the Caribbean, Latin America and North America communities together, around the subject.

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

RESUME Dans sa strategie nationale de sante pour les maladies hypertensives, la Societe francaise d’HTA ( www.sfhta.eu ) propose des recommandations de prevention globale avec une correction des inegalites sociales et geographiques en integrant les specificites des DOM-ROM (recommandations 5 a 9). Il s’agit d’integrer la prevention de l’HTA dans les actions generales de sante publique a enseigner des la petite enfance, en accord avec les preconisations de la Federation Francaise de Cardiologie ( www.fedecardio.org ) : la lutte contre la sedentarite, la pratique d’une activite physique reguliere, une alimentation equilibree, l’absence de la premiere cigarette, la prevention du stress chronique en particulier au travail et de la depression. Il est recommande de prevoir un plan de lutte specifique contre l’obesite en Outre-Mer et d’amener tous les professionnels de sante a renforcer le depistage du surpoids et de l’obesite a tous âges. Il est necessaire d’informer le patient hypertendu que l’hygiene de vie permet de renforcer l’efficacite du traitement voire de l’alleger. Il convient de favoriser le depistage de l’HTA surtout en presence d’un contexte familial d’HTA ou de mauvaises conditions socio-economiques, notamment en Outre-mer. Le medecin traitant, le pharmacien et l’infirmier y ont leur place ainsi que les centres de sante au travail et les centres d’examens de sante de la Caisse Primaire d’Assurance Maladie.

Sébastien Hulo,1 Jocelyn Inamo,2 Aurélie Dehon,3 Olivier Le Rouzic,4 Jean-Louis Edme,1 Remi Neviere51Université Lille, CHU Lille, EA 4483, IMPact de l’Environnement Chimique sur la Santé humaine, Lille, France; 2Département de Cardiologie – CHU Fort de France, Martinique – Faculté de Médecine – Université des Antilles, France; 3Pôle d’Anesthésie Réanimation ADRU, CHU Nîmes, Nîmes, France; 4Université Lille, CNRS, Inserm, CHU Lille, Institut Pasteur de Lille, Center for Infection and Immunity of Lille, Lille, France; 5Université Lille, Inserm, CHU Lille, Lille Inflammation Research International Center, Lille, FrancePurpose: Metabolic-chronotropic relationship is the only concept that assesses the entire chronotropic function during exercise, as it takes into account individual fitness. To better understand interrelationships between chronotropic incompetence (CI), dynamic hyperinflation (DH) and exercise limitation among Global initiative for chronic Obstructive Lung Disease (GOLD) stages of chronic obstructive pulmonary disease (COPD) disease severity, we evaluated cardiopulmonary responses to symptom-limited cycle exercise in stable patients.Patients and methods: We prospectively studied 47 COPD patients classified by GOLD stage severity. Pulmonary function tests and cardiopulmonary responses to symptom-limited incremental exercise were studied. CI was defined by regression line between percent heart rate (HR) reserve and percent oxygen uptake (V’O2) reserve, ie, chronotropic-metabolic index (CMI). DH was defined from the knot resulting from the nonlinear regressions of inspiratory capacity changes from rest to peak (dynamic inspiratory capacity (ICdyn)) with percentage of maximal HR and CMI.Results: Aerobic capacity (median interquartile ranges) peak V’O2, 24.3 (23.6; 25.2), 18.5 (15.5; 21.8), 17.5 (15.4; 19.1) mL·kg-1·min-1 and CMI worsened according to GOLD severity. The optimal knot of ICdyn was equal to −0.34 L. The multivariate logistic regression showed a strong relationship between CI (outcome) and DH (odds ratio [confidence interval 95]) 25 (3.5; 191.6). Conclusion: COPD patients with DH have a poor cardiovascular response to exercise, which may be attributed to CI.Keywords: COPD, hyperinflation, chronotropic incompetence, exercise

Background Echocardiography is the main non-invasive screening tool for pulmonary hypertension (PH) in sickle cell disease (SCD), but relies mostly on the tricuspid regurgitation velocity (TRV) assessment, without distinction between pre- and post-capillary patterns. Using Etendard Cohort data, the aim of this study was to refine echocardiographic assessment of PH in SCD patients. Methods The French Etendard Study is a prospective cohort initially designed to assess the prevalence of PH among 398 SCD participants. We analysed echocardiography data of the 96 Etendard patients who underwent Right Heart Catheterisation (RCH), because of a TRV ≥ 2.5 m/s, and compared them to invasive haemodynamic measurements. Results PH was found in 24/96 patients with 11 precapillary and 13 post-capillary. In addition to TRV, multivariate analysis identified indexed left atrial volume (LAVind) and lateral E’ wave velocity (E’lat) as independent echocardiographic predictors of PH (OR = 1.06 and 0.6, respectively, P 48 mL/m2 and E’lat Moreover, comparing echocardiography data of pre- and post-capillary PH patients, we observed that pulmonary acceleration time (PAcT) was different in the two groups (104 ± 22 ms vs. 160 ± 21 ms, P Conclusion Echocardiography can accurately estimates the probability of PH in SCD patients with an integrated approach using TRV, LAVind and E’lat. In addition, among patients with suspected PH, measuring PAcT as a surrogate of PVR allows a good differentiation between pre and post-capillary phenotypes.

Introduction Sickle cell disease (SCD) is a common genetic disorder leading to severe hematologic and cardiovascular complications. Increasing lifespan of patients is associated with increased prevalence of cardiovascular diseases, especially high blood pressure (BP). However, the clinical and epidemiological characteristics of high BP in these patients remain poorly defined. Notably, the usefulness of 24h-ambulatory blood pressure monitoring (ABPM) has not been assessed in adults, and specific cut-off for BP values are still debated. Purpose To analyze office blood pressure and 24-h ABPM values in SCD adult patients. Material and methods A prospective pilot study with systematic ABPM readings of SCD adult patients from October 2017 to April 2018, conducted in the SCD reference center of Martinique. Consistent Hypertension was defined as office BP ≥ 140/90 mm Hg and 24-h mean BP ≥ 130/80 mm Hg. Masked hypertension was defined as office BP Results We enrolled twenty-one patients age 50.9 years (± 14.3). Hypertension was diagnosed in 10 patients (47.6%) of which 7 (70% of the hypertensive, 33.3% of the entire group) had consistent hypertension and 3 had masked hypertension (30%, 14.3% respectively). All the patients with masked hypertension had high office BP. One patient (4.8%) was found to have white coat hypertension. In univariate analysis, age, weight and SC genotype were positively associated with presence of hypertension (all P Conclusion This pilot study shows an unexpected high frequency of hypertension, involving nearly one out of two adult patients with Sickle Cell Disease. It underscores the high frequency of masked hypertension, and underlines the need of ABPM in the clinical management of patients with sickle cell disease.

Cardiac involvement is common in sickle cell disease (SCD). Studies are needed to establish haematological determinants of this involvement and prognostic markers. The aim of the study was to identify haematological factors associated with cardiac involvement in SCD and their impact on prognosis.This longitudinal observational study was performed on 1780 SCD patients with SS or S-β(0)-thalassemia referred to our centre. Six hundred fifty-six met our inclusion criteria (availability of a blood-workup and echocardiogram obtained1 year apart, no heart valve surgery and no current pregnancy). Median age was 31 (interquartile range, 25-40) years, and median haemoglobin (Hb) was 87 (80-95)g/L. Left ventricular (LV) dilation, left atrial dilation, cardiac index (CI)4 L/min/m(2), LV ejection fraction55%, and tricuspid regurgitant velocity (TRV) ≥2.5 m/s were found in 35, 78, 23, 8.5, and 17% of patients, respectively. Compared with other patients, those in the fourth quartiles (Q4) of LV end-diastolic dimension index (LVEDDind) and left atrial dimension index (LADind) and those with high CI had significantly lower Hb, % foetal Hb (HbF), and red blood cell (RBC) counts; and significantly higher lactate dehydrogenase, bilirubin, and %dense RBCs. Independent haematologic determinants of Q4 LVEDDind and LADind were low RBC count and %HbF; high %dense RBCs were associated with LADind. Low %HbF and RBC count were associated with high CI. High %dense RBCs or no α-thalassemia gene deletion was associated with greater severity of anaemia and cardiac dilation and with higher CI. During the median follow-up of 48 (32-59) months, 50 (7.6%) patients died. Tricuspid regurgitant velocity ≥ 2.5 m/s was a predictor of mortality. The risk of death increased four-fold when left ventricular ejection fraction55% was present also (P = 0.0001).Cardiac dilation and CI elevation in patients with SCD are associated with haematologic variables reflecting haemolysis, RBC rigidity, and blood viscosity. Tricuspid regurgitant velocity ≥ 2.5 and LV dysfunction (even mild) predict mortality.

The paper by Park et al. [(1)][1] recently published in iJACC offers convincing evidence that patients with concentric left ventricular remodeling and eccentric and concentric left ventricular hypertrophy (LVH) have an increased risk of all-cause mortality after an ischemic stroke, as compared with

International audience; We conducted an observational study to describe the characteristics of infective endocarditis (IE) in French West Indies (FWI) and to identify variables associated with in-hospital case fatality. The records of the patients admitted for IE to the University Hospital of Martinique between 2000 and 2012 were collected using an electronic case report form. Only Duke-Li definite cases were considered for this analysis. Variables associated with in-hospital mortality were tested using univariate logistic regression analysis. The analysis included 201 patients (median age 58 years, sex ratio: two males to one female). There was no previously known heart disease in 45.8%, a prosthetic valve in 21.4%, and previously known native valve disease in 32.8% of the cases. Community-acquired IE represented 59.7% of all cases, health-care-associated IE represented 38.3% and injection-drug-use-acquired IE represented 1.5%. Locations of IE were distributed as follows: 42.3% were mitral valve IE, 34.8% were aortic valve IE, and 7% were right-sided IE. Microorganisms recovered from blood cultures included 30.4% streptococci, 28.9% staphylococci, and 5% enterococci. Blood cultures were negative in 20.9% of the cases. Surgical treatment was performed in 53% of the patients. In-hospital case fatality rate was 19%. Advanced age, Staphylococcus aureus IE, and health-care-associated IE were associated with in-hospital case fatality. The epidemiological and microbiological profile of IE in FWI is in between those observed in developed countries and developing countries: patients were younger, blood cultures were more frequently negative, and IE due to group D streptococci and enterococci were less common than in industrialized countries.

Transthyretin cardiac amyloidosis (CA) is associated with an increased frequency of heart failure but not with increased risk of death among individuals with African ancestry. Unexplained left ventricular (LV) hypertrophy raises the suspicion of CA. Recently, a transversal survey held in Martinique and Guadeloupe found a high frequency of CA among these patients. This preliminary report addresses the risk of death associated with diagnosis of CA in these patients. Methods The TEAM-study prospectively held in 3 hospitals in Guadeloupe and Martinique from January 2013 to June 2014 screened cardiac amyloidosis in patients with left ventricular wall thickness equal or greater than 15 mm, or wall sparkling. Among the 168 participants from Martinique, 51 were eventually diagnosed with cardiac amyloidosis, 44 of them with transthyretin CA. The vital status was determined as of July 2018, mainly by checking the PMSI data, which traces hospitalization and ambulatory visits in all public hospitals in Martinique. Patients whose data were not available were contacted by telephone. Information about the cause of death was collected. Kaplan–Meier curves and Cox analyses were performed. Results In this preliminary report, vital status was checked among 113 participants, 41 with CA, 72 with unexplained LVH (Unexp). There was no significant difference between these 113 and the remaining other patients. Mean follow-up was 46.1 months. Death occurred in 24 (59%) of the CA patients and 17 (23.6%) of the Unexp. The median survival after diagnosis was 2.8 years in the CA patients, and exceeded follow-up in the Unexp. Factors associated with survival in univariate analyses were CA, severe NYHA status, troponine and ProBNP values, cardiac output, and Sokolow indice. In multivariate analysis, CA carried a higher risk of death (HR = 3.21 [1.47; 7.04]). NYHA status was the only other significant factor. Conclusion Diagnosis of CA among patients with LVH implies reduced survival.

Background High blood pressure (HBP) is the most common chronic disease worldwide. In France, its prevalence varies by region. It is high in most Overseas Departments and Regions (DOM-ROM), at 38.2% in Reunion (1), 44% in Mayotte (2), 28% in the French Antilles, 18% in French Guiana, 25% in French Polynesia (3) and 28% in Saint-Martin (4). Purpose To determinate the differences within the same healthcare system between hypertension in Metropolitan France compared to Overseas France Departments and Regions (DOM-ROM) Results Sex-based differences: in contrast to Metropolitan France, in Overseas France the prevalence of HBP is higher in women, although women show better rates of care (screening and rates of patients “normalised” under medical treatment). The main explanation for this is the higher prevalence of obesity in women. Obesity multiplies the risk of developing hypertension by 2.5. Obesity in Guadeloupe affects 14% of men compared to 31% of women. Socio-economic particularities of hypertension in Overseas France: the numerous epidemiological surveys carried out in the French Antilles have demonstrated the major role of socio-economic conditions in the occurrence of hypertension, alongside the usual risk factors such as sedentary lifestyle, salt consumption and obesity (7). In the absence of socio-economic disparity, there is no significant disparity in the prevalence of hypertension specially in men. Conclusions There are differences between France Overseas Regions and Territories (DOM-ROMs) and Metropolitan France in terms of the prevalence, knowledge, treatment and control of hypertension, and these vary according to sex. For men, the prevalence and treatment of hypertension differ very little when considering a population of workers or employees in both regions. On the other hand, for women, the prevalence of hypertension is higher in the French Antilles-Guiana. This difference is not fully explained by the higher prevalence of obesity observed among female employees in the French Antilles-Guiana. For these patients, we also observe better knowledge and better control of hypertension. Care for men in socio-economically disadvantaged situations of precarity must be improved in terms of screening and adherence to treatment.

The objective of this study was to analyze the prevalence, awareness, treatment, and control of diabetes and its risk factors among French Caribbean adults. This cross-sectional study included 18-74-year olds (N = 2252; 56.5 percent women) who underwent a heath examination in Guadeloupe during July-December 2014. Diabetes was defined as using antidiabetic treatment, or fasting glucose ≥7 mmol/l, and glycated hemoglobin (HbA1c) ≥6.5 percent; diabetes control was defined as HbA1c 7 percent. Multilevel logistic regression was used. Diabetes prevalence was 8.2 percent for women and 5 percent for men (age-adjusted odds ratio [aOR] for women = 2.0; 95 percent confidence interval [CI]: 1.4-2.9). The proportion of women with diabetes who were aware of it was 84.5 versus 67.3 percent in men (aOR = 2.7; 95 percent CI: 1.2-6.2). Nearly, all diagnosed participants were being treated. In less than a third of diabetics in both sexes was diabetes control obtained. Most women (55.3 percent) had a waist circumference at or above the National Cholesterol Education Program thresholds versus 14 percent of men (aOR = 9.3; 95 percent CI: 7.5-11.7), which wholly accounted for excess diabetes in women. In women, obesity and diabetes were associated with low education and income. In this French Caribbean sample, abdominal obesity and diabetes affected more women. Diabetes was rarely controlled. A comprehensive women's health policy for the prevention of abdominal obesity and diabetes is needed.

Resume But de l’etude Estimer la relation entre hypertension arterielle (HTA) et precarite percue en population precaire guadeloupeenne. Patients et methodes Prevalence de l’HTA en population precaire guadeloupeenne est une etude transversale portant sur 2420 sujets âges de 18 a 69 ans, reconnus precaires, inclus consecutivement lors de leur passage dans trois centres de sante guadeloupeens. La precarite percue, ou perception de l’insecurite materielle, est definie grâce a une question fermee ; l’HTA est diagnostiquee sur la base de deux visites, soit au total six mesures de la pression arterielle. Resultats La prevalence de l’HTA est estimee a 17,7 % parmi les sujets pensant que leur situation materielle va s’ameliorer dans le futur, a 28,2 % parmi ceux pensant qu’elle va rester identique, et a 43,3 % parmi ceux pensant qu’elle va se degrader. Une analyse multivariee par regression logistique montre que le risque d’HTA est plus que double (OR : 2,35 – p : 0,002) chez les sujets pensant que leur situation materielle va se degrader dans l’avenir, sans grande difference selon le sexe. Plus particulierement vraie chez les sujets de 40 ans et plus (OR : 3,30 – p Conclusion Dans cette population precaire guadeloupeenne, la precarite percue est un facteur psychosocial fortement associe a l’HTA, independamment des comportements a risque. Les sujets âges ou de faible niveau de formation semblent a cet egard les plus vulnerables.

BACKGROUND AND PURPOSE The epidemiological characteristics of hypertension and obesity in French Overseas Territories (FOTs) have never been compared. METHODS This cross-sectional survey included representative population-based samples of 602, 601, 620 and 605 men and women aged more than 15 years, respectively, from four FOTs of Guadeloupe, Martinique, French Guiana, and French Polynesia. Hypertension was defined as blood pressure (BP) at least 140/90 mmHg or the current use of antihypertensive treatment. RESULTS The prevalence of hypertension was 29.2% in Guadeloupe, 17.9% in French Guiana, 27.6% in Martinique and 24.5% in French Polynesia. Considering the Guadeloupe population as the reference group, prevalence of hypertension was significantly lower in French Guiana (P

Resume Objectifs Appreciation du niveau de connaissance, de leur maladie, de patients suivis en medecine generale pour HTA. Evaluation de l’impact de ces connaissances sur l’obtention des objectifs therapeutiques. Methodologie Enquete observationnelle portant sur un echantillon representatif de patients hypertendus traites, suivis par des medecins generalistes (MG) exercant en milieu liberal dans les DOM-TOM. Chaque MG a inclus les cinq premiers patients hypertendus, vus en consultation dont l’HTA a ete diagnostiquee depuis plus de trois mois. La PA etait consideree normalisee si inferieure a 140/90 mmHg. La mesure de la concordance entre l’appreciation du MG et celle du patient concernant les chiffres de PA (PAS et PAD), et sur les facteurs de risque cardiovasculaires associes a ete effectuee. Resultats Cent MG ont recrute 509 patients, 482 patients ont acceptes de repondre. Cinquante-sept pour cent etaient des femmes, 69 % (n = 328) etaient âges de moins de 65 ans, 75 % (n = 341) avaient un niveau d’instruction inferieur au baccalaureat. Seuls, 39 % (n = 185) des patients etaient normalises (PA Conclusion Selon cette enquete, menee en medecine generale dans l’outre-mer, deux tiers des patients suivis pour HTA presentent un risque cardiovasculaire eleve. Environ 40 % des sujets ont une PA equilibree sous traitement (PA

Introduction The prospective ETENDARD study (NCT00434902) evaluated 398 outpatients with sickle cell disease (SCD) enrolled between February 2007 and March 2009 at referral centers in France. All patients were homozygous for hemoglobin S or had Sβ0 thalassemia. This study estimated the prevalence of pulmonary hypertension (PH) related to SCD to be 6%, based on the presence of a tricuspid regurgitation velocity (TRV) ≥2.5 m/s and a mean pulmonary arterial pressure (mPAP) measured by right-sided heart catheterization (RHC) ≥25 mmHg (Parent et al, New Engl J Med 2011). The long-term prognostic value of TRV≥2.5 m/s according to the level of mPAP measured by RHC has not been clearly established. Methods Using updated 10-year follow up data from the ETENDARD cohort study, we analyzed the overall survival of patients according to their TRV/mPAP status, as follows: patients with a TRV Results The 398 enrolled patients were followed-up for a mean time of 106±26 months (median 112 months, interquartile range 106-119). TRV was≥2.5 m/s in 109 patients (27.4%). RHC was performed in 98 of them and confirmed PH diagnosis (mPAP≥25 mmHg) in 24 (6%). Overall survival was significantly decreased in patients with a TRV≥2.5 m/s (groups B/C vs. A; HR=2.5 [CI95 1.3-4.7], p=0.006, Figure 1A). However, after accounting for mPAP level, no statistically significant difference was found between patients with a TRV Conclusion While an isolated VRT≥2.5 m/s on transthoracic echocardiography was found to be a moderate prognostic factor for overall survival, our findings reveal highly contrasted outcomes depending on the mPAP values measured by RHC. Only the combination of a VRT≥2.5 m/s and a mPAP≥25 mmHg is associated with a worse prognosis, confirming that a RHC is mandatory in case of PH suspicion on transthoracic echocardiography in SCD patients. Disclosures Bartolucci: Addmedica: Research Funding; GBT: Membership on an entity's Board of Directors or advisory committees; Fondation Fabre: Research Funding; Novartis US: Membership on an entity's Board of Directors or advisory committees.