Long-term follow-up of cardiac arrest survivors: Protocol of the DESAC (Devenir des survivants d'Arrets Cardiaques) study, a French multicentric prospective cohort.

Background: While the short-term prognosis of cardiac arrest patients - nearly 250,000 new cases per year in Europe - has been extensively studied, less is known regarding the mid and long-term outcome of survivors. Objective: The aim of the DESAC study is to describe mid- and long-term survival rate and functional status of cardiac arrest survivors, and to assess the influence of pre and intra hospital therapeutic strategies on these two outcomes. Methods: Between Jul 2015 and Oct 2018, adult patients over 18 years who were discharged alive from any intensive care units (public and private hospitals) in the Ile-de-France area (Paris and suburbs, France) after a non-traumatic cardiac arrest were screened for participation in this multicentric study. Survivors were included after they signed (or the proxies) an informed consent before discharge during initial hospitalisation. We calculated that including 600 patients in total would allow an 80% power to demonstrate a 2 years survival rate difference of 10% between patients who did and those who did not receive therapeutic hypothermia after resuscitation. Pre- and in-hospital data related to the circumstances surrounding the event and to the therapeutic interventions (such as cardio-pulmonary resuscitation, defibrillation, emergent coronary revascularization, neuroprotective therapeutics) were collected. After discharge, patients were interviewed at 3 months, 6 months and every year thereafter for a minimum follow-up of 26 months and a maximum follow-up of 48 months. Information on vital status, occurrence of cardiovascular events, medications and a comprehensive assessment of the functional status (qualitive of life as assessed by the Short-Form General Health Survey (SF36) scale, activities of daily living (ADL) scale, neurological Cerebral Performance Categories (CPC) and Overall Performance Categories (OPC) scales, socio-professional activities) were collected at follow-up interviews. Discussion: The DESAC study should provide important information regarding several dimensions of the mid and long-term prognosis of cardiac arrest survivors and on the benefit (and potentially harm) of early therapeutic strategies.

Obstructive sleep apnea, circulating microRNAs, and risk of cardiovascular disease.

OBJECTIVE: while obstructive sleep apnea is strongly associated with incident cardiovascular diseases (CVD), the underlying mechanisms remain to be elucidated. This study aimed to compare the patterns of microRNAs expression between OSA and control patients with and without incident CVD. METHODS: 218 matched adult participants with and without OSA and with and without incident CVD were selected from two independent community-based prospective cohorts in France and Switzerland, and 168 microRNAs on average were detected per sample. OSA was diagnosed using the validated Berlin questionnaire in one study (Paris Prospective Study 3) and during a full-night polysomnography in the second study (HypnoLaus Study). RESULTS: there were 78 OSA patients (39 with and 39 without CVD) and 140 controls (70 with and 70 without CVD). Participants were male in 54.6% (n = 119) and mean age was 58.7 years (±9.2). Of the 183 miRNAs screened, a mean 168 assays were detected per sample, and 129 in all samples. There was no pattern of blood microRNAs expression that discriminated OSA patients with and without CVD events. CONCLUSIONS: this binational study failed to find any association between a large panel of microRNAs and OSA patients with and without incident CVD.

Organ donation after out-of-hospital cardiac arrest: a population-based study of data from the Paris Sudden Death Expertise Center.

BACKGROUND: Organ shortage is a major public health issue, and patients who die after out-of-hospital cardiac arrest (OHCA) could be a valuable source of organs. Here, our objective was to identify factors associated with organ donation after brain death complicating OHCA, in unselected patients entered into a comprehensive real-life registry covering a well-defined geographic area. METHODS: We prospectively analyzed consecutive adults with OHCA who were successfully resuscitated, but died in intensive care units in the Paris region in 2011-2018. The primary outcome was organ donation after brain death. Independent risk factors were identified using logistic regression analysis. One-year graft survival was assessed using Cox and log-rank tests. RESULTS: Of the 3061 included patients, 136 (4.4%) became organ donors after brain death, i.e., 28% of the patients with brain death. An interaction between admission pH and post-resuscitation shock was identified. By multivariate analysis, in patients with post-resuscitation shock, factors associated with organ donation were neurological cause of OHCA (odds ratio [OR], 14.5 [7.6-27.4], P < 0.001), higher pH (OR/0.1 increase, 1.3 [1.1-1.6], P < 0.001); older age was negatively associated with donation (OR/10-year increase, 0.7 [0.6-0.8], P < 0.001). In patients without post-resuscitation shock, the factor associated with donation was neurological cause of OHCA (OR, 6.9 [3.0-15.9], P < 0.001); higher pH (OR/0.1 increase, 0.8 [0.7-1.0], P = 0.04) and OHCA at home (OR, 0.4 [0.2-0.7], P = 0.006) were negatively associated with organ donation. One-year graft survival did not differ according to Utstein characteristics of the donor. CONCLUSIONS: 4% of patients who died in ICU after OHCA led to organ donation. Patients with OHCA constitute a valuable source of donated organs, and special attention should be paid to young patients with OHCA of neurological cause.

Oral Condition and Incident Coronary Heart Disease: A Clustering Analysis.

Poor oral health has been linked to coronary heart disease (CHD). Clustering clinical oral conditions routinely recorded in adults may identify their CHD risk profile. Participants from the Paris Prospective Study 3 received, between 2008 and 2012, a baseline routine full-mouth clinical examination and an extensive physical examination and were thereafter followed up every 2 y until September 2020. Three axes defined oral health conditions: 1) healthy, missing, filled, and decayed teeth; 2) masticatory capacity denoted by functional masticatory units; and 3) gingival inflammation and dental plaque. Hierarchical cluster analysis was performed with multivariate Cox proportional hazards regression models and adjusted for age, sex, smoking, body mass index, education, deprivation (EPICES score; Evaluation of Deprivation and Inequalities in Health Examination Centres), hypertension, type 2 diabetes, LDL and HDL serum cholesterol (low- and high-density lipoprotein), triglycerides, lipid-lowering medications, NT-proBNP and IL-6 serum level. A sample of 5,294 participants (age, 50 to 75 y; 37.10% women) were included in the study. Cluster analysis identified 3,688 (69.66%) participants with optimal oral health and preserved masticatory capacity (cluster 1), 1,356 (25.61%) with moderate oral health and moderately impaired masticatory capacity (cluster 2), and 250 (4.72%) with poor oral health and severely impaired masticatory capacity (cluster 3). After a median follow-up of 8.32 y (interquartile range, 8.00 to 10.05), 128 nonfatal incident CHD events occurred. As compared with cluster 1, the risk of CHD progressively increased from cluster 2 (hazard ratio, 1.45; 95% CI, 0.98 to 2.15) to cluster 3 (hazard ratio, 2.47; 95% CI, 1.34 to 4.57; P < 0.05 for trend). To conclude, middle-aged individuals with poor oral health and severely impaired masticatory capacity have more than twice the risk of incident CHD than those with optimal oral health and preserved masticatory capacity (ClinicalTrials.gov NCT00741728).

[Fighting against unexplained sudden death]. / Mort subite, en quête d'une explication.

Sudden cardiac death, mostly related to ventricular arrhythmia, is a major public health issue, with still very poor survival at hospital discharge. Although coronary artery disease remains the leading cause, other etiologies should be systematically investigated. Exhaustive and standardized exploration is required to eventually offer specific therapeutics and management to the patient as well as his/her family members in case of inherited cardiac disease. Identification and establishing direct causality of the detected cardiac anomaly may remain challenging, underlying the need for a multidisciplinary and experimented team.

Body Silhouette Trajectories Over the Lifespan and Insomnia Symptoms: The Paris Prospective Study 3.

Insomnia symptoms are highly prevalent and associated with several adverse medical conditions, but only few determinants, including non-modifiable ones, have been highlighted. We investigated associations between body silhouette trajectories over the lifespan and insomnia symptoms in adulthood. From a community-based study, 7 496 men and women aged 50-75 years recalled their body silhouette at age 8, 15, 25, 35 and 45, and rated the frequency of insomnia symptoms on a standardized sleep questionnaire. An Epworth Sleepiness Scale ≥11 defined excessive daytime sleepiness (EDS). Using a group-based trajectory modeling, we identified five body silhouette trajectories: a 'lean-stable' (32.7%), a 'heavy-stable' (8.1%), a 'moderate-stable' (32.5%), a 'lean-increase' (11%) and a 'lean-marked increase' (15.7%) trajectory. In multivariate logistic regression, compared to the 'lean-stable' trajectory, the 'lean-marked increase' and 'heavy-stable' trajectories were associated with a significant increased odd of having ≥1 insomnia symptoms as compared to none and of having a proxy for insomnia disorder (≥1 insomnia symptom and EDS). The association with the 'lean-marked increase' trajectory' was independent from body mass index measured at study recruitment. In conclusion, increasing body silhouette over the lifespan is associated with insomnia symptoms in adulthood, emphasizing the importance of weight gain prevention during the entire lifespan.

[Tropical endomyocardial fibrosis: Perspectives]. / Fibrose endomyocardique tropicale : perspectives.

Tropical endomyocardial fibrosis (FET) is a leading cause of heart failure and the most common restrictive cardiomyopathy worldwide. Extensive fibrosis of the ventricular endocardium causing architectural distortion, impaired filling and valvular insufficiency define the disease. Confined to peculiar and limited geographical areas, the aetiology remains blurred and it carries a grim prognosis. The changing burden reported recently in some endemic areas and the refinement of diagnostic tools have emphasized alternative routes for understanding and treatment of the disease.

Sickle cell retinopathy and other chronic complications of sickle cell anemia: A clinical study of 84 Sub-Saharan African cases (Cameroon).

OBJECTIVE: Sickle retinopathy is a severe complication of sickle cell disease than can lead to blindness. We aim to describe the epidemiology of sickle retinopathy in homozygous sickle cell (SS) African patients and to analyze its association with non-ophthalmologic disease complications of sickle cell anemia. METHODS: We conducted a nested study within the CADRE cohort in Cameroon. Eighty-four consecutive SS outpatients, aged 10 years and older, with no visual symptoms, underwent an ophthalmologic examination. Mean age was 23±10 years. Clinical and biological features were compared between patients with and without sickle retinopathy. We compared the prevalence of the clinical complications and main biological characteristics in patients with and without sickle retinopathy using a univariate logistic regression. The same analysis was used to compare the patients with non-proliferative sickle retinopathy to those with proliferative sickle retinopathy. Statistical analyses were done using the R software (version 3.1.2). RESULTS: Fifty-two patients (62%) displayed sickle retinopathy, among them 23 (27%) had a non-proliferative sickle retinopathy, and 29 (35%) had proliferative sickle retinopathy. Patients with proliferative sickle cell retinopathy had a mean age of 28±11 years. Sickle retinopathy was associated with higher hemoglobin level (P=0.047) and fewer leg ulcers (P=0.018). Proliferative SR was associated with increasing age (P=0.008) and male sex (P=0.025) independently of the hemoglobin level. CONCLUSIONS: Sickle retinopathy is particularly frequent in sub-Saharan sickle cell SS patients, which advocates for early systematic screening.

[Sudden cardiac death: A better understanting for a better prevention]. / Mort subite de l'adulte : une meilleure compréhension pour une meilleure prévention.

Sudden cardiac death is defined as a natural and unexpected death, in a previous apparently healthy individual. It represents a major public health issue, with up to 50% of the cardiovascular mortality. Using data from the Paris Sudden Death Expertise Centre registry, this article summarises the main cardiovascular abnormalities associated with sudden cardiac death, the different preventives approaches, and provides a systematic diagnostic approach.

[Silhouettes at different age of life: Retrospective appreciation of corpulence and his impact on prevalence of hypertension at 60years]. / Silhouettes aux différents âges de la vie : méthode d'appréciation rétrospective de la corpulence et de son impact sur la prévalence de l'hypertension à 60 ans.

PURPOSE OF THE STUDY: In epidemiological studies, recall of weight and height are not readily available at different ages of life. In order to improve the knowledge of the weight history, Sörensen et al. in 1983, developed a tool from silhouettes allowing an individual to evaluate his corpulence at different ages of life. Validity studies showed that measured weight and size were correlated to 80% in the reported silhouette. Studies have also shown that silhouettes are a good way to trace the weight history in an individual's life. Very few epidemiological studies have used this tool. A French study revealed a decrease of the risk of breast cancer in obese girls between the age of 8 and adolescence. Another study showed that a low birth weight or a thin silhouette before adulthood was associated with an increased risk of diabetes. On the basis of these findings, it was interesting to evaluate the relationship between the silhouette at 20years and the risk of hypertension at the age of 60years. RESULTS: It was shown that the prevalence of hypertension at age 60 was higher among obese subjects at 20years than among thin subjects (45.3% vs 36.7% (P<0.05). CONCLUSION: The classification between slimness and obesity is relevant using this tool. The history of corpulence is an important element to consider in the determinants of pathology, especially in hypertension.

Protein S Heerlen mutation heterozygosity is associated with venous thrombosis risk.

Hereditary Protein S (PS) deficiency is a rare coagulation disorder associated with an increased risk of venous thrombosis (VT). The PS Heerlen (PSH) mutation is a rare S501P mutation that was initially considered to be a neutral polymorphism. However, it has been later shown that PSH has a reduced half-life in vivo which may explain the association of PSH heterozygosity with mildly reduced levels of plasma free PS (FPS). Whether the risk of VT is increased in PSH carriers remains unknown. We analyzed the association of PSH (rs121918472 A/G) with VT in 4,173 VT patients and 5,970 healthy individuals from four independent case-control studies. Quantitative determination of FPS levels was performed in a subsample of 1257 VT patients. In the investigated populations, the AG genotype was associated with an increased VT risk of 6.57 [4.06-10.64] (p = 1.73 10-14). In VT patients in whom PS deficiency was excluded, plasma FPS levels were significantly lower in individuals with PSH when compared to those without [72 + 13 vs 91 + 21 UI/dL; p = 1.86 10-6, mean + SD for PSH carriers (n = 21) or controls (n = 1236) respectively]. We provide strong evidence that the rare PSH variant is associated with VT in unselected individuals.

[Sudden cardiac death: Are women different?] / Mort subite : y a-t-il une spécificité féminine ?

Sudden cardiac death is a major public health problem with around 40,000 cases per year in France. Epidemiological, clinical and prognostic differences according to gender have been described in most cardiovascular diseases, including sudden cardiac death. In this article, we will review gender differences in sudden cardiac death incidence, circumstance of occurrence, management, and prognosis.

Cross-sectional analysis of deprivation and ideal cardiovascular health in the Paris Prospective Study 3.

AIMS: We hypothesised that deprivation might represent a barrier to attain an ideal cardiovascular health (CVH) as defined by the American Heart Association (AHA). METHODS AND RESULTS: The baseline data of 8916 participants of the Paris Prospective Study 3, an observational cohort on novel markers for future cardiovascular disease, were used. The AHA 7-item tool includes four health behaviours (smoking, body weight, physical activity and optimal diet) and three biological measures (blood cholesterol, blood glucose and blood pressure). A validated 11-item score of individual material and psychosocial deprivation, the Evaluation de la Précarité et des Inégalités dans les Centres d'Examens de Santé-Evaluation of Deprivation and Inequalities in Health Examination centres (EPICES) score was used. The mean age was 59.5 years (standard deviation 6.2), 61.2% were men and 9.98% had an ideal CVH. In sex-specific multivariable polytomous logistic regression, the odds ratio (OR) for ideal behavioural CVH progressively decreased with quartile of increasing deprivation, from 0.54 (95% CI 0.41 to 0.72) to 0.49 (0.37 to 0.65) in women and from 0.61 (0.50 to 0.76) to 0.57 (0.46 to 0.71) in men. Associations with ideal biological CVH were confined to the most deprived women (OR=0.60; 95% CI 0.37 to 0.99), whereas in men, greater deprivation was related to higher OR of intermediate biological CVH (OR=1.28; 95% CI 1.05 to 1.57 for the third quartile vs the first quartile). CONCLUSIONS: Higher material and psychosocial deprivation may represent a barrier to reach an ideal CVH. TRIAL REGISTRATION NUMBER: NCT00741728.

High level of depressive symptoms as a barrier to reach an ideal cardiovascular health. The Paris Prospective Study III.

We hypothesized that depression might represent a barrier to reach an ideal cardiovascular health (CVH) as estimated by the 7-item tool proposed by the American Heart Association. Between 2008 and 2012, 9,417 subjects 50-75 years of age were examined in a large health center and enrolled in the Paris Prospective Study III (PPS3). Participants with 0-2, 3-4 and 5-7 health metrics at the ideal level were categorized as having poor, intermediate and ideal CVH, respectively. Participants with a score ≥ 7 on the 13-item Questionnaire of Depression 2nd version, Abridged or who were on antidepressants were referred as having high level of depressive symptoms (HLDS). The mean age of the 9417 study participants was 59.57 (SD 6.28) years and 61.16% were males. A total of 9.55% had HLDS. Poor, intermediate and ideal CVH was present in 40.38%, 49.52% and 10.10% of the participants. In multivariate polytomous logistic regression analysis, HLDS was inversely associated with ideal CVH (odds ratio = 0.70; 95% CI: 0.55;0.90). This was driven by an association with the behavioural component of the CVH. Participants with HLDS had a substantial reduced chance of reaching an ideal CVH.

Late Failing Heart Allografts: Pathology of Cardiac Allograft Vasculopathy and Association With Antibody-Mediated Rejection.

In heart transplantation, there is a lack of robust evidence of the specific causes of late allograft failure. We hypothesized that a substantial fraction of failing heart allografts may be associated with antibody-mediated injury and immune-mediated coronary arteriosclerosis. We included all patients undergoing a retransplantation for late terminal heart allograft failure in three referral centers. We performed an integrative strategy of heart allograft phenotyping by assessing the heart vascular tree including histopathology and immunohistochemistry together with circulating donor-specific antibodies. The main analysis included 40 explanted heart allografts patients and 402 endomyocardial biopsies performed before allograft loss. Overall, antibody-mediated rejection was observed in 19 (47.5%) failing heart allografts including 16 patients (40%) in whom unrecognized previous episodes of subclinical antibody-mediated rejection occurred 4.5 ± 3.5 years before allograft loss. Explanted allografts with evidence of antibody-mediated rejection demonstrated higher endothelitis and microvascular inflammation scores (0.89 ± 0.26 and 2.25 ± 0.28, respectively) compared with explanted allografts without antibody-mediated rejection (0.42 ± 0.11 and 0.36 ± 0.09, p = 0.046 and p < 0.0001, respectively). Antibody-mediated injury was observed in 62.1% of failing allografts with pure coronary arteriosclerosis and mixed (arteriosclerosis and atherosclerosis) pattern, while it was not observed in patients with pure coronary atherosclerosis (p = 0.0076). We demonstrate that antibody-mediated rejection is operating in a substantial fraction of failing heart allografts and is associated with severe coronary arteriosclerosis. Unrecognized subclinical antibody-mediated rejection episodes may be observed years before allograft failure.

Screening for transfusion transmissible infections using rapid diagnostic tests in Africa: a potential hazard to blood safety?

Rapid diagnostic tests (RDTs) are routinely used in African blood centres. We analysed data from two cross-sectional studies representing 95 blood centres in 29 African countries. Standardized panels of sera containing varying concentrations of anti-human immunodeficiency virus (HIV) antibodies (Ab), hepatitis B virus antigen (HBsAg) and antihepatitis C virus (HCV) Ab were screened using routine operational testing procedures at the centres. Sensitivity of detection using RDTs was high for HIV Ab-positive samples, but low for intermediately HBsAg (51·5%) and HCV Ab (40·6%)-positive samples. These findings suggest that current RDT use in Africa could pose a hazard to blood safety.

Base excess and lactate as prognostic indicators for patients treated by extra corporeal life support after out hospital cardiac arrest due to acute coronary syndrome.

OBJECTIVE: To examine whether values of arterial base excess or lactate taken 3 h after starting ECLS indicate poor prognosis and if this can be used as a screening tool to follow Extra Corporeal Life Support after Out Hospital Cardiac Arrest due to acute coronary syndrome. DESIGN: Single Centre retrospective observational study. SETTING: University teaching hospital general adult intensive care unit. PATIENTS: 15 consecutive patients admitted to the intensive care unit after refractory Out Hospital Cardiac Arrest due to acute coronary syndrome treated by Extra Corporeal Life Support. INTERVENTIONS: Arterial base excess and lactate concentrations were measured immediately after starting ECLS and every 3 h after. RESULTS: Both base excess and arterial lactate measured 3 h after starting ECLS effectively predict multi-organ failure occurrence and mortality in the following 21 h (area under the curve on receiver operating characteristic analysis of 0.97, 0.95 respectively). The best predictive values were obtained with a base excess level measured 3 h after starting ECLS of less than -10 mmol/l and lactate concentrations greater than 12 mmol/l. The combination of these two markers measured 3 h after starting ECLS predicted multiorgan failure occurrence and mortality in the following 21 h with a sensitivity of 70% and a specificity of 100%. CONCLUSIONS: Combination of base excess and lactate, measured 3 h after starting ECLS, can be used to predict multiorgan failure occurrence and mortality in the following 21 h in patients admitted to an intensive care unit for refractory Out Hospital Cardiac Arrest due to acute coronary syndrome treated by Extra Corporeal Life Support. These parameters can be obtained simply and rapidly and help in the decision process to continue ECLS for refractory CA.

Very late heart transplant rejection is associated with microvascular injury, complement deposition and progression to cardiac allograft vasculopathy.

In heart transplants, the significance of very late rejection (after 7 years post-transplant, VLR) detected by routine endomyocardial biopsies (EMB) remains uncertain. Here, we assessed the prevalence, histopathological and immunological phenotype, and outcome of VLR in clinically stable patients. Between 1985 and 2009, 10 662 protocol EMB were performed at our institution in 398 consecutive heart transplants recipients. Among the 196 patients with >7-year follow-up, 20 (10.2%) presented subclinical ≥3A/2R-ISHLT rejection. The VLR group was compared to a matched control group of patients without rejection. All biopsies were stained for C4d/C3d/CD68 with sera screened for the presence of donor-specific antibodies (DSAs). In addition to cellular infiltrates with myocyte damage, 60% of VLR patients had evidence of intravascular macrophages. C4d and/or C3d-capillary deposition was found in 55% VLR EMB. All cases of VLR associated with microcirculation injury had DSAs (mean DSA(max) -MFI = 1751 ± 583). This entity was absent from the control group (p < 0.0001). Finally, after a similar follow-up postreference EMB of 6.4 ± 1 years, the mean of CAV grade was 0.76 ± 0.18 in the control group compared to 2.06 ± 0.26 in the VLR group respectively, p = 0.001). There was no difference in patient survival between study and control groups. In conclusion, VLR is frequently associated with complement-cascade activation, microvascular injury and DSA, suggesting an antibody-mediated process. VLR is associated with a dramatic progression to severe CAV in long-term follow-up.