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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). [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

With the growing adult congenital heart disease (ACHD) population, the number of catheter ablation procedures is expected to dramatically increase. Data reporting experience and evolution of catheter ablation in ACHD patients, over a significant period of time, remain scarce. We aimed to describe temporal trends in volume and outcomes of catheter ablation in ACHD patients. Retrospective observational study including all consecutive ACHD patients undergoing attempted catheter ablation in a large tertiary referral center over a 15-year period. Acute procedural success rate and freedom from recurrence at 12 months were analyzed. From November 2004 to November 2019, 302 catheter ablations in 221 ACHD patients (43.6 ± 15.0 years, 58.9% males) were performed. The annual number of catheter ablation increased progressively from 4 to 60 cases per year (P < 0.001). Intra-atrial reentrant tachycardia/focal atrial tachycardia was the most common arrhythmia (n = 217, 71.9%). Over the study period, acute procedural success rate increased from 45.0% to 93.4% (P < 0.001). Use of irrigated catheters (OR = 4.03, 95% CI: 1.86–8.55), 3D-mapping system (OR = 3.70, 95% CI: 1.72–7.74), contact force catheters (OR = 3.60, 95% CI: 1.81–7.38), and high-density mapping (OR = 3.69, 95% CI: 1.82–8.14) were associated with acute procedural success. The rate of freedom from any recurrence at 12 months increased from 29.4% to 66.2% (P = 0.001). Seven (2.3%) non-fatal complications occurred (Fig. 1). The number of catheter ablation procedures in ACHD patients has considerably increased over the last 15 years. Growing experience and advances in ablative technologies appear to be associated with a significant improvement in acute and midterm outcomes. [ABSTRACT FROM AUTHOR]

Heart transplant recipients are at high-risk of sudden cardiac death (SCD). However, risk factors of SCD in heart recipients remained poorly described. To assess the predictors of SCD beyond the first-year post-transplant. We enrolled consecutive patients transplanted between 2004 and 2017 in two French referral centres. We excluded patients deceased during the first year. Patients underwent an evaluation at the day of transplantation and during the first year, comprising clinical, biological, histological, immunological (circulating anti-HLA DSA) and interventional (cardiac allograft vasculopathy assessment) parameters. According to the last consensus, SCD was defined as an unexpected out-of-hospital cardiac arrest without obvious non-cardiac cause, in the first hour after initiation of symptoms. A total of 913 patients were included. The median follow-up post-HT was 5.9 years (IQR = 2.9–8.5). Among the 60 parameters tested in univariate analysis, we identified 4 independent factors independently associated with sudden death after 1 year post-HT: donor age (HR = 1.55; 95% CI: 1.14–2.11; P = 0.005), recipient age (HR = 0.74; 95% CI: 0.59–0.93; P = 0.011), ventricular ejection fraction (LVEF) < 55% any time after transplantation (HR: 3.95; 95% CI: 1.95–8.02; P < 0.001), the presence of circulating anti-HLA DSA at the time of transplantation (HR: 2.18; 95% CI: 1.15–4.11; P = 0.017). The incidence rate of SCD was 2.17 per 100 person-year (95% CI: 1.42–4.60) and 1.21 per 100 person-year (95% CI: 0.80–2.58) in patients with FEVG < 55% (n = 73) and in patients with pre-formed DSA (n = 260), respectively (Table 1). In a large multicentric and highly phenotyped cohort of heart transplant recipients, we identified four independent factors associated with SCD beyond the first year. This study provides fresh evidence of SCD assessment for improving risk stratification of HT recipients. [ABSTRACT FROM AUTHOR]

Dilated cardiomyopathy (DCM) is a major cause of systolic heart failure and therefore a major public health issue. Our objective was to better understand the genetic bases of dilated cardiomyopathy. We conducted a 1000G based genome-wide association study for 9,152,885 SNPs on 2,719 sporadic DCM cases and 4,440 controls of European origin followed by a replication step. We then sought for the most likely culprit genes at the new replicated loci through a dedicated strategy including in silico data mining (including tissue specific gene expressions, expression and methylation quantitative trait loci) as well as functional 4C-sequencing analysis on iPSC-derived cardiomyocytes (Fig. 1). We identified two new DCM loci, on chromosome 3p25.1 (lead SNP rs62232870, p = 8.7 × 10−11 and 7.7 × 10−4 in the discovery and replication steps, respectively) and chromosome 22q11.23 (lead SNP rs7284877, P = 3.3 × 10−8 and 1.4 × 10−3, respectively), while confirming two previously identified ones, BAG3 and HSPB7. A Genetic Risk Score was built from the number of risk allele at these four loci and revealed a 27% increased risk of DCM for individuals with 8 risk alleles compared to individuals with 5 risk alleles (median of the referral population). At chr3p25, our selection strategy pinpointed SLC6A6 as the most likely culprit gene. SLC6A6 encodes a taurine transporter whose involvement in myocardial dysfunction and DCM is supported by numerous observations in humans and animals. At the 22q11.23 locus, the same strategy strongly suggested SMARCB1 as the best candidate gene. This study provides new insights in the genetic architecture of DCM and sheds light on novel biological pathways underlying heart failure, with the potential for a therapeutic perspective especially through taurine modulation. [ABSTRACT FROM AUTHOR]

In contrast to acute cellular rejection, non-invasive assessment of antibody-mediated rejection (AMR) remains challenging. The routine surveillance endomyocardial biopsies (EMB) approach to monitor AMR suffers from multiple limitations. The development of an individual AMR risk score may allow for individualization of the EMB protocol. We analyzed a prospective and deeply phenotyped cohort of patients transplanted between 2012 and 2017 at our center (n = 700). Patients were randomly distributed in a training (2/3) and in a test set (1/3). We applied a mixed effect logistic regression with a random intercept to identify predictive variables associated with AMR ≥ pAMR1 at the level of each EMB. An AMR risk score was derived by applying the β-coefficients attributed to each predictive variable. A total of 6403 EMB were analyzed among which 412 (6.4%) were diagnosed as AMR ≥ pAMR 1. In the training set, five predictive variables were independently associated with AMR: time post-transplant (P < 0.001), pre-transplant sensitizing event (P = 0.003), circulating donor-specific antibody at the time of EMB (P = 0.010), left ventricular dysfunction (P = 0.018) and prior history of pAMR2 (P < 0.001). In the test set, the calibration and the discrimination of the model were good (area under the ROC curve = 0.801, Fig. 1A). We observed a stepwise increase in the risk of AMR with increasing AMR risk score, ranging from 1.6% (1.1–2.5%) for score ≤ 1 point to 36.8% of EMB (22.8–53.6%) for scores between 4 and 5 (Fig. 1B). We identified 5 independent predictive variables associated with AMR and derived an AMR risk score that may help clinicians in individualizing the EMB protocol. [ABSTRACT FROM AUTHOR]

A significant increase in the prevalence of sudden cardiac arrest (SCA) with non-shockable rhythm (NSR) has been reported. Factors associated with NSR and the mode to the return of spontaneous circulation (ROSC) may help for a better understanding. We aimed to describe the frequency, characteristics and outcome of NSR related SCA in the community. In this prospective ongoing multicentre population-based registry (6.7 million inhabitants), data from all SCA were analyzed. Medical records for each SCA were reviewed by two cardiologists to identify aetiology and associated conditions. Among the 3,028 SCAs admitted alive out of a total of 18,622 out-of-hospital cardiac arrests from May 2011 to May 2016, 2,904 patients had available information regarding initial rhythm. Among them, 1,314 patients (45.3%) presented with NSR: 1,109 (38.2%) cases with asystole, 197 (6.8%) with pulseless electrical activity and 8 (0.3%) with high degree atrioventricular block. NSR cases were older (60.6 vs. 57.4 years, P < 0.001), with greater proportion of females (34.9 vs. 19.2%, P < 0.001) and less proportion of family history of CAD or SCA. Proportion of symptoms prior to the SCA was higher among patients with NSR (74.3 vs. 64.9%, P < 0.001) but chest pain was lower (24.0 vs. 43.3%, P < 0.001). Survival rate was much lower in NSR cases (7.2 vs. 42.3%, P < 0.001). Among the 1,314 NSR cases, 1,022 (77.8%) did not require external defibrillation although a majority (91.7%) received adrenaline during resuscitation. In this subgroup, main identified cardiac cause was acute coronary syndrome (45.3%), followed by chronic CAD (27.1%), structural non-ischemic heart disease (22.4%), and non-structural heart disease (5.2%). Initial NSR is encountered in almost half of SCA cases admitted alive; mostly occurs in older patients with higher proportion of females. Over three quarters of these cases did not require external defibrillation prior to ROSC. [ABSTRACT FROM AUTHOR]

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Aims Idiopathic atrial fibrillation describes atrial fibrillation of unknown origin occurring without heart disease. Mortality is considered unaffected by idiopathic atrial fibrillation. We used the long follow-up period (23 years on average) of the Paris Prospective Study I to assess the mortality of idiopathic atrial fibrillation subjects in middle-aged men.Methods 7746 working Frenchmen, aged 43–52 in 1967–72, underwent a physical examination plus ECG, answered questionnaires, and provided blood samples. Strict exclusion criteria were used to select idiopathic atrial fibrillation only, and men with known cardiac disease were further excluded from analysis. At 1 January 1994, vital status was unknown for 4·6% of the subjects. The analysis was conducted on the 6722 remaining subjects.Results Twenty-five subjects had idiopathic atrial fibrillation at inclusion. The relative risk (and 95% confidence interval) associated with idiopathic atrial fibrillation was 4·22 [2·10–8·47] for cardiovascular mortality (P=0·0001) and 1·97 [1·14–3·40] for total mortality (P=0·01). When age, systolic blood pressure, cholesterol, body mass index and tobacco consumption were entered into a Cox model, idiopathic atrial fibrillation remained an independent risk factor for cardiovascular (P=0·0008) and total death (P=0·04).Conclusion With a long follow-up period, idiopathic atrial fibrillation was associated with higher mortality in middle aged Frenchmen. [ABSTRACT FROM PUBLISHER]

While outcomes of intra-atrial re-entrant tachycardia (IART) catheter ablation have considerably improved in adult congenital heart disease (ACHD), recurrences remain common with different circuits frequently encountered. We aimed to assess the value of programmed atrial stimulation after successful clinical IART catheter ablation in ACHD patients. Retrospective study including all ACHD patients undergoing IART catheter ablation in a large tertiary centre. After successful catheter ablation of the clinical arrhythmia, survival free from arrhythmia recurrence was analysed according to whether all inducible IART were targeted. From 2004 to 2020, 238 IART catheter ablations were performed (mean age 44.1 ± 15.0 years, 61.3% males). Acute procedural success of clinical arrhythmia was achieved in 208 (87.4%) procedures. Among 122 (58.7%) patients with programmed atrial stimulation, at least one other IART was induced in 61 (50%) patients. All inducible IART were ablated in 54 (88.5%) patients whereas 7 (11.5%) patients had at least one non-targeted inducible IART. Patients with non-targeted inducible IART had a higher risk of atrial arrhythmia recurrence compared to inducible patients with ablation of all IART (HR = 5.7, 95% CI: 1.7–18.4), with 12-month survival rates of 22.9% and 77.7%, respectively. Inducible patients with successful ablation of all IART had a similar risk of atrial arrhythmia recurrence compared to non-inducible patients (HR = 0.6, 95% CI: 0.3–1.3) (Fig. 1). Our findings suggest that final programmed atrial stimulation is associated with improved outcomes in ACHD patients referred for IART ablation when all inducible IART are targeted and successfully ablated. [ABSTRACT FROM AUTHOR]

Sudden cardiac death (SCD) is a major contributor to the rate of mortality after heart transplantation. However, little is known about the incidence of SCD in heart recipients. To assess the incidence of SCD after heart transplantation. We enrolled consecutive patients transplanted between 2004 and 2017 in two French referral centers. We defined 7 main groups of causes of deaths: SCD, cardiovascular (including Cardiac allograft vasculopathy), infection, primary graft dysfunction, graft failure (including late graft dysfunction, rejection), malignancy and others. Causes of deaths were independently adjudicated by two senior cardiologists based on the analysis of death certificates and medical records. Discrepancies were resolved by discussion until a consensus was made. SCD was defined as an unexpected out-of-hospital cardiac arrest without obvious non-cardiac cause, in the first hour after initiation of symptoms. A total of 1,363 patients were included. The median follow-up post-transplant was 3.99 years (IQR = 0.49–7.49). A total of 450 patients (33%) deceased during the first year. The leading cumulative causes of death in the first year after transplantation were infection, primary graft failure, multiple organ failure during the period in intensive car unit. Beyond the post-operative high-risk period of the first year, the leading cumulative cause of death was SCD: among the 213 deaths that occurred beyond the first year, 44 patients (21%) died from SCD. In this period, the incidence rate of SCD reached 0,82 per 100 person-year (95% CI: 0.51–2.05) (Fig. 1). In a large multicentric and highly phenotyped cohort of heart transplant recipients, the leading cumulative cause of death beyond the first-year post transplant was sudden cardiac death. Our results open discussion on management of heart recipient, such as the implementation of cardioverter-defibrillators. [ABSTRACT FROM AUTHOR]

The diagnosis of cardiac allograft rejection is based on the histological analysis of a myocardial tissue sample obtained by endomyocardial biopsy (EMB), an invasive procedure at risk of complications. Our aim is to enable the shift from a protocol biopsy approach, to a precision medicine approach, in which the need for EMB is tailored to each patient's individual risk. To analyze the incidence and the risk factors for biopsy-proven rejections following heart transplantation in a large cohort of highly phenotyped heart-transplant recipients. We performed a multicenter, retrospective, observational study (Pitié-Salpêtrière, HEGP, 2004–2016). We included all patients with ≥ 1 EMB during the first year (n = 1050 patients, 13677 EMB). All EMB performed before 2012 were retrospectively reviewed and graded according to ISHLT guidelines. Rejections were defined as acute cellular rejection (ACR) ≥ 1R1B and/or antibody-mediated rejections (AMR) ≥ pAMR1. Pre-formed DSA were evaluated using Luminex Single Antigen Assay (MFI ≥ 500). Risk factors for rejection were identified using Cox proportional hazard model. Biopsy-proven rejections were diagnosed in 489 patients (46.4%) representing 1009 EMB (7.3%, mostly low-grade rejections: ACR 1R1B or 1R2: n = 724, see Fig. 1). Risk factors for rejection included recipient's age (HR = 0.988 per 1-year increment, P = 0.002), type of transplantation (combined heart-kidney and heart-liver compared to isolated heart: HR = 0.336 and 0.204 respectively, P < 0.001), pre-formed DSA (HR = 1.422, P < 0.001), HLA A-B-DR mismatches (HR = 1.129 per 1-mismatch increment, P = 0.02) and the type of induction (basiliximab compared to anti-thymocyte globulins: HR = 1.725, P = 0.008). We identified five independent risk factors for biopsy-proven rejection during the first-year post-heart transplantation. Our findings might help clinicians to customize post-transplant endomyocardial biopsies monitoring. [ABSTRACT FROM AUTHOR]

Since a large proportion of patients resuscitated from out-of-hospital sudden cardiac arrest (SCA) die in the intensive care unit (ICU), early systematic investigation towards identifying etiology may be crucial to ensure appropriate future prevention among relatives, especially when the index case is young. We hypothesized that etiologic investigations were not initiated in a timely manner in a significant proportion of young SCA patients prior to death. In this prospective ongoing multicenter, population-based registry (6.7 million inhabitants), data from all SCA over a 5-year period were analyzed with a specific focus on young patients (< 45 year-old) alive at hospital admission and who eventually died in ICU. Investigations and diagnoses arrived at were analyzed from the medical records by two cardiologists for each case. Of the 18,622 out-of-hospital cardiac arrests from May 2011 to May 2016, 3,028 were admitted alive to ICU. Among them, 2,190 (72.3%) died in ICU, including 367 (16.8%) young cases (< 45 y.o.). Among the young patients, while 163 cases (44.4%) had a specific diagnosis established, 204 (55.6%) remained unexplained. Coronary angiograms (18.3%), CT scan (brain and chest) (24.5%), and transthoracic echocardiography (29.1%) were all underutilized. Main SCA causes were acute coronary syndrome (44.5%), followed by structural non-ischemic heart disease (25.5%), pulmonary embolism (13.6%), chronic CAD (10%), non-structural heart disease (1.8%) and miscellaneous (4.6%). The proportion of autopsy (10.9%), as well as blood sample collection for further genetic testing (1.4%) was low. Information on family screening was rarely provided in the ICU. More than half of young SCA cases who died in ICU remained unexplained. Efforts to promote early systematic investigation through better collaboration between intensivist and cardiologist may improve future targeted preventive strategies for family members. [ABSTRACT FROM AUTHOR]