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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]

Implantable Cardioverter Defibrillator (ICD) in sudden cardiac arrest (SCA) is indicated in non-reversible cardiac causes. A systematic description of SCA survivors discharged without an ICD has not been undertaken thus far. We aimed to describe the frequency, characteristics and etiologies of SCA survivors discharged without an ICD. In this prospective ongoing multicentre community-based study (6.7 million inhabitants), data from all SCA cases alive at hospital discharge, over a 5-year period, were analyzed with a specific focus on survivors. All medical records were reviewed by two cardiologists to identify underlying mechanisms and ascertain etiologies. Among the 18,622 out-of-hospital cardiac arrests from May 2011 to May 2016, 717 survivors at hospital discharge fulfilled definition for cardiac SCA. Among them, 247 patients (34.5%) received an ICD and 468 (65.4%) did not. Compared to the ICD group, the group without ICD were older (58.9 vs. 52.6 years, P < 0.001). Main etiologies were acute coronary syndrome (ACS) (397, 84.8%), chronic CAD (28, 6.0%), structural non-ischemic heart disease (31, 6.6%) and non-structural heart disease (12, 2.6%). Among survivors with ACS, 93.6% (397 out of 424) were discharged without an ICD and 18 of those were due to coronary spasm (representing 75% of coronary spasm related-SCAs survivors), including three refractory spasms despite pharmacological therapy. Factors independently associated with ICD non-implantation in ACS were the absence of personal CAD history (OR 2.86, CI95% 0.19–6.67, P = 0.014) and immediate angioplasty at admission (OR 2.77, CI95% 1.02–6.78, P = 0.033). Almost two third of SCA survivors were discharged without an ICD; while this was largely related to ACS and coronary stenting, some cases of chronic CAD as well as drug refractory coronary spasm in this population may represent lost opportunity, warranting further studies addressing this specific issue. [ABSTRACT FROM AUTHOR]

Background Existing studies on sports-related sudden cardiac arrest (SCA) have focused principally on young competitive athletes. There is limited information on sports-related SCA in the general population. Purpose We sought to determine the burden, characteristics and etiology of SCA during sports activity in adults. Cases occurring during sports activity were compared to those unrelated to sports regarding characteristics and previous medical history. Methods All cases of SCA occurring in the area (6.6 million inhabitants) were prospectively ascertained over a five-year period in this ongoing multicentre study. Data from all SCA during sports activity in either a competitive or recreational setting were analyzed. Results From May 2011 to May 2016, 3028 patients fulfilling criteria for SCA were admitted alive to hospital. Out of these, 138 (4.6%) SCA occurred during sports. The 3 most common sport activities during the SCA event were running (34.5%), cycling (14.4%) and soccer (8.6%). Sports-related SCA cases were younger (mean age: 52.7 ± 15.6 vs. 59.6 ± 15.6 years old, P < 0.001), more likely to be male (90.6 vs. 71.9%, P < 0.001), had lower cardiovascular risk factors (≥ 1 CVRF, 72.1 vs. 81.4%, P = 0.012), higher rate of bystander cardiopulmonary resuscitation (84.1 vs. 62.9%, P < 0.001) and higher proportion of ventricular fibrillation at EMS arrival (73.9 vs. 51.1%, P < 0.001) compared to other SCA. Among cases admitted alive to hospital with identified cause of SCA (71%), coronary artery disease (72.4%) was the main cardiovascular abnormality identified, mostly acute coronary syndrome (62.2%). Prior to SCA event, 22 cases (15.9%) were known to have heart disease, including CAD (5.8%) and 77 (66.4%) others presented with ≥ 1 CVRF. Conclusion SCA during sports mostly concerns middle-aged men, with CAD being the frequent underlying cause (up to 75%). These results provide information to enhance sport preparticipation screening. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background Considerable apprehension often surrounds the issue of sudden cardiac arrest (SCA) during physical activity, and especially SCA related to sexual activity, which has not been well studied in the community. Purpose We sought to assess the burden, characteristics and outcomes of SCA related to sexual activity compared to other physical activities. Methods In this multicentre prospective ongoing study in the general population, every case of SCA was exhaustively collected. Data from all SCA during physical activity, alive at hospital admission, were analyzed with a specific focus on cases occurring during sexual intercourse. Results Among the 3028 SCAs admitted alive out of a total of 18,622 out-of-hospital cardiac arrests from May 2011 to May 2016, 246 (8.1%) SCA (219 men, 89.0%) occurred during physical activity: 138 (56%) during sports, 91 (37%) during moderate-intensity activity and 17 (7%) during (hetero-) sexual intercourse. SCA during sexual activity were more likely to be male (100.0 vs. 88%, P = 0.22), with higher no flow (8.4 vs. 3.1 min, P < 0.001) and lower frequency of shockable rhythm (41.2 vs. 72.5%, P = 0.01) compared to others. There was no difference for age (53.0 vs. 56.1 years old, P = 0.43), cardiovascular risk (CVR) profile (≥ 1 CVR factor, 81.2 vs. 75.6%, P = 0.65), frequency of warning symptoms (37.5 vs. 53.6%, P = 0.23) and family history of coronary artery disease (CAD) (6.3 vs. 11.5%, P = 0.59). However, bystander CPR (47.1 vs. 80.3%, P = 0.004) and survival rate (11.8 vs. 50.2%, P = 0.002) were lower. Acute CAD (52.3%), and subarachnoid hemorrhage (29.4%), were the main identified causes followed by chronic CAD (17.6%) and structural non-ischemic heart disease (5.6%). Conclusion SCA during sexual intercourse is a relatively rare cause of SCA and is associated with a particularly poor outcome. The low rate of CPR in this setting may be related to the uniquely private circumstances of the arrest and could contribute to low survival rate. [ABSTRACT FROM AUTHOR]

Aims Dilated cardiomyopathy (DCM) is an important cause of heart failure with a strong familial component. We performed an exome-wide array-based association study (EWAS) to assess the contribution of missense variants to sporadic DCM. Methods and results Overall, 116,855 single nucleotide variants (SNVs) were analyzed in 2796 DCM patients and 6877 control subjects from 6 populations of European ancestry. We confirmed two previously identified associations with SNVs in BAG3 and ZBTB17 and discovered six novel DCM-associated loci (Q-value < 0.01). The lead-SNVs at novel loci are common and located in TTN, SLC39A8, MLIP, FLNC, ALPK3 and FHOD3 . In silico fine mapping and protein interaction experiment with BAG3 identified HSPB7 as the most likely candidate at the ZBTB17 locus. Rare variant analysis (MAF < 0.01) demonstrated significant association for TTN variants only ( P = 0.0085). All candidate genes at associated loci but one ( SLC39A8 ) exhibit preferential expression in striated muscle tissues and mutations in TTN, BAG3, FLNC and FHOD3 are known to cause familial cardiomyopathy. These candidate genes also share structural and functional roles suggesting sarcomeric maintenance as an important feature protecting against DCM. Conclusion We identified eight loci independently associated with sporadic DCM. Overlap between susceptibility gene and familial DCM causing gene suggests a continuum of effect size, or penetrance, in DCM associated molecular variants. The functions of the best candidate genes at these loci also suggest that proteostasis regulation might play a role in DCM pathophysiology. [ABSTRACT FROM AUTHOR]

Background Considering that most patients resuscitated from out-of-hospital sudden cardiac arrests (SCA) die in the intensive care unit (ICU), early systematic etiologic investigation may represent an important strategy towards targeted therapy and appropriate prevention to first-degree relatives at risk. Purpose We aimed to determine the extent to which SCA cases who died in the ICU were investigated. Methods In this prospective ongoing multicentre population-based registry, data from all SCA patients who died in ICU were analyzed. The extent of investigations was defined as complete either in case a combination of coronary angiography (CA), brain, chest CT scan, and trans-thoracic echocardiography (TTE) was performed, or diagnosis found after one of those. SCAs dying in the first 24 hours were excluded because of their poor hemodynamic condition for investigation. Results Of the 18,622 out-of-hospital cardiac arrests from May 2011 to May 2016, 3028 SCA (16%) were admitted alive to ICU, and 2190 (72.3%) died in ICU. After first day exclusion, 947/1417 (66.8%) fulfilled criteria for complete investigations and 470/1417 (33.2%) in the other group. In the group with incomplete investigations, CA was performed in 162 patients (34.6%), TTE in 207 (44.2%), and brain and/or chest CT in 186 (39.6%). A final diagnosis was made for 895 patients (94.5%) in the group with complete investigations: 403 (45.0%) acute CAD, 149 (16.7%) chronic CAD, 115 (12.9%) neurological causes, 80 (8.9%) structural non-ischemic heart disease, 48 (5.4%) pulmonary embolism. Overall, among all unexplained SCA who died in ICU, 434 (89.3%) had incomplete investigation. Conclusions Over a third of SCA who died in ICU did not undergo complete etiologic investigations, preventing from potential adequate familial screening. Improvement in systematic medical assessment is crucial to provide appropriate therapy and prevention to family members. [ABSTRACT FROM AUTHOR]

Background Sudden cardiac arrest (SCA) is a major cause of deaths in Europe, but population-based data on specific etiologies, such as structural non ischemic heart disease (SNIHD) are lacking. Purpose We sought to determine the frequency, characteristics and outcomes of SCA associated with SNIHD in the general population. Methods In this prospective ongoing multicentre population-based registry, data from all SCA were analyzed. SNIHD included different non ischemic cardiomyopathies, as well as valvular, hypertensive and congenital heart diseases. Medical records were reviewed by cardiologists to identify clinical conditions underlying SCA. Results Of the 18,622 out-of-hospital cardiac arrests from May 2011 to May 2016, 3028 SCAs (16.2%) were admitted alive to hospital. Two hundred and twenty four (7.4%) SNIHD were diagnosed during hospitalization, including dilated cardiomyopathy (DCM) (44.2%), valvular heart disease (19.2%), hypertrophic cardiomyopathy (13.4%), myocarditis (6.7%), congenital heart disease (3.1%) and arrhythmogenic right ventricular dysplasia (2.7%). As compared to other causes of SCA, SNIHD patients were significantly younger (55.2 vs. 59.6 years, P < 0.001), more likely to be women (35.7% vs. 26.4%, P = 0.003) had fewer cardiovascular risk factors (≥ 1 CVRF, 72.7% vs. 81.8%, P = 0.002), but known heart disease was more likely to be identified (67.4% vs. 30.2%, P < 0.001) in SNIHD. Among patients with previously known DCM, only 46% of cases presented with a left ventricular ejection fraction < 35%. Among survivors, only 87 (74.3%) were implanted with ICD. Conclusion In our registry, SCA associated with SNIHD presented distinctive features compared to non-SNIHD, and overall accounted for only 7% of the overall SCA burden. Main causes were DCM and valvular heart disease. Better characterization of this population, especially the sizeable subgroup with left ventricular ejection fraction > 35% can improve sudden death risk stratification in this group. [ABSTRACT FROM AUTHOR]

An abstract of the study "Differential Survival Benefit of Bisoprolol on Sudden Death and Other Cardiovascular Death. A Post Hoc Analysis of CIBIS and CIBIS II Trials," by J. P. Empana and colleagues is presented.

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. 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). 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. this binational study failed to find any association between a large panel of microRNAs and OSA patients with and without incident CVD. • Obstructive sleep apnea (OSA) is related to cardiovascular diseases (CVD). • microRNAs are a promising tool for a better understanding of the underlying pathways linking OSA and CVD. • 218 matched adult participants with and without OSA, with and without CVD events, were tested for 168 microRNAs. • No association was found between microRNAs expression and OSA or incident CVD events. [ABSTRACT FROM AUTHOR]