Healthy sleep score changes and incident cardiovascular disease in European prospective community-based cohorts.

BACKGROUND AND AIMS: Evidence on the link between sleep patterns and cardiovascular diseases (CVDs) in the community essentially relies on studies that investigated one single sleep pattern at one point in time. This study examined the joint effect of five sleep patterns at two time points with incident CVD events. METHODS: By combining the data from two prospective studies, the Paris Prospective Study III (Paris, France) and the CoLaus|PsyCoLaus study (Lausanne, Switzerland), a healthy sleep score (HSS, range 0-5) combining five sleep patterns (early chronotype, sleep duration of 7-8 h/day, never/rarely insomnia, no sleep apnoea, and no excessive daytime sleepiness) was calculated at baseline and follow-up. RESULTS: The study sample included 11 347 CVD-free participants aged 53-64 years (44.6% women). During a median follow-up of 8.9 years [interquartile range (IQR): 8.0-10.0], 499 first CVD events occurred (339 coronary heart disease (CHD) and 175 stroke). In multivariate Cox analysis, the risk of CVD decreased by 18% [hazard ratio (HR) 0.82, 95% confidence interval (CI) 0.76-0.89] per one-point increment in the HSS. After a median follow-up of 6.0 years (IQR: 4.0-8.0) after the second follow-up, 262 first CVD events occurred including 194 CHD and 72 stroke. After adjusting for baseline HSS and covariates, the risk of CVD decreased by 16% (HR 0.84, 95% CI 0.73-0.97) per unit higher in the follow-up HSS over 2-5 years. CONCLUSIONS: Higher HSS and HSS improvement over time are associated with a lower risk of CHD and stroke in the community.

Association between basic life support and survival in sports-related sudden cardiac arrest: a meta-analysis.

AIMS: To evaluate the association of basic life support with survival after sports-related sudden cardiac arrest (SR-SCA). METHODS AND RESULTS: In this systematic review and meta-analysis, a search of several databases from each database inception to 31 July 2021 without language restrictions was conducted. Studies were considered eligible if they evaluated one of three scenarios in patients with SR-SCA: (i) bystander presence, (ii) bystander cardiopulmonary resuscitation (CPR), or (iii) bystander automated external defibrillator (AED) use and provided information on survival. Risk of bias was evaluated using Risk of Bias in Non-randomized Studies of Interventions. The primary outcome was survival at the longest follow up. The meta-analysis was conducted using the random-effects model. The Grading of Recommendations Assessment, Development, and Evaluations (GRADE) approach was used to rate certainty in the evidence. In total, 28 non-randomized studies were included. The meta-analysis showed significant benefit on survival in all three groups: bystander presence [odds ratio (OR) 2.55, 95% confidence interval (CI) 1.48-4.37; I2 = 25%; 9 studies-988 patients], bystander CPR (OR 3.84, 95% CI 2.36-6.25; I2 = 54%; 23 studies-2523 patients), and bystander AED use (OR 5.25, 95% CI 3.58-7.70; I2 = 16%; 19 studies-1227 patients). The GRADE certainty of evidence was judged to be moderate. CONCLUSION: In patients with SR-SCA, bystander presence, bystander CPR, and bystander AED use were significantly associated with survival. These results highlight the importance of witness intervention and encourage countries to develop their first aid training policy and AED installation in sport settings.

Ultrasensitive Troponin I and Incident Cardiovascular Disease.

BACKGROUND: To examine the association of ultrasensitive cTnI (cardiac troponin I) with incident cardiovascular disease events (CVDs) in the primary prevention setting. METHODS: cTnI was analyzed in the baseline plasma (2008-2012) of CVD-free volunteers from the Paris Prospective Study III using a novel ultrasensitive immunoassay (Simoa Troponin-I 2.0 Kit, Quanterix, Lexington) with a limit of detection of 0.013 pg/mL. Incident CVD hospitalizations (coronary heart disease, stroke, cardiac arrhythmias, deep venous thrombosis or pulmonary embolism, heart failure, or arterial aneurysm) were validated by critical review of the hospital records. Hazard ratios were estimated per log-transformed SD increase of cTnI in Cox models using age as the time scale. RESULTS: The study population includes 9503 participants (40% women) aged 59.6 (6.3) years. cTnI was detected in 99.6% of the participants (median value=0.63 pg/mL, interquartile range, 0.39-1.09). After a median follow-up of 8.34 years (interquartile range, 8.0-10.07), 516 participants suffered 612 events. In fully adjusted analysis, higher cTnI (per 1 SD increase of log cTnI) was significantly associated with CVD events combined (hazard ratio, 1.18 [1.08-1.30]). Among all single risk factors, cTnI had the highest discrimination capacity for incident CVD events (C index=0.6349). Adding log cTnI to the SCORE 2 (Systematic Coronary Risk Evaluation) risk improved moderately discriminatory capacity (C index 0.698 versus 0.685; bootstrapped C index difference: 0.0135 [95% CI, 0.0131-0.0138]), and reclassification of the participants (categorical net reclassification index, 0.0628 [95% CI, 0.023-0.102]). Findings were consistent using the US pooled cohort risk equation. CONCLUSIONS: Ultrasensitive cTnI is an independent marker of CVD events in the primary prevention setting.

Poor Masticatory Capacity and Blood Biomarkers of Elevated Cardiovascular Disease Risk in the Community: The Paris Prospective Study III.

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Long-Term Follow-Up of Patients With Tetralogy of Fallot and Implantable Cardioverter Defibrillator: The DAI-T4F Nationwide Registry.

BACKGROUND: Tetralogy of Fallot (TOF) is the most common cyanotic congenital heart disease, and sudden cardiac death represents an important mode of death in these patients. Data evaluating the implantable cardioverter defibrillator (ICD) in this patient population remain scarce. METHODS: A Nationwide French Registry including all patients with tetralogy of Fallot with an ICD was initiated in 2010 by the French Institute of Health and Medical Research. The primary time to event end point was the time from ICD implantation to first appropriate ICD therapy. Secondary outcomes included ICD-related complications, heart transplantation, and death. Clinical events were centrally adjudicated by a blinded committee. RESULTS: A total of 165 patients (mean age, 42.2±13.3 years, 70.1% males) were included from 40 centers, including 104 (63.0%) in secondary prevention. During a median (interquartile range) follow-up of 6.8 (2.5-11.4) years, 78 (47.3%) patients received at least 1 appropriate ICD therapy. The annual incidence of the primary outcome was 10.5% (7.1% and 12.5% in primary and secondary prevention, respectively; P=0.03). Overall, 71 (43.0%) patients presented with at least 1 ICD complication, including inappropriate shocks in 42 (25.5%) patients and lead dysfunction in 36 (21.8%) patients. Among 61 (37.0%) patients in primary prevention, the annual rate of appropriate ICD therapies was 4.1%, 5.3%, 9.5%, and 13.3% in patients with, respectively, 0, 1, 2, or ≥3 guidelines-recommended risk factors. QRS fragmentation was the only independent predictor of appropriate ICD therapies (hazard ratio, 3.47 [95% CI, 1.19-10.11]), and its integration in a model with current criteria increased the 5-year time-dependent area under the curve from 0.68 to 0.81 (P=0.006). Patients with congestive heart failure or reduced left ventricular ejection fraction had a higher risk of nonarrhythmic death or heart transplantation (hazard ratio, 11.01 [95% CI, 2.96-40.95]). CONCLUSIONS: Patients with tetralogy of Fallot and an ICD experience high rates of appropriate therapies, including those implanted in primary prevention. The considerable long-term burden of ICD-related complications, however, underlines the need for careful candidate selection. A combination of easy-to-use criteria including QRS fragmentation might improve risk stratification. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03837574.

Depression, antidepressants and low hemoglobin level in the Paris Prospective Study III: A cross-sectional analysis.

Anemia is known to be associated with depression both in community and clinical populations. However, it is still unknown if this association depends or not on antidepressant intake. We investigated the respective association of depression and antidepressant intake with low hemoglobin level in a large community-based cohort. In 8640 volunteers aged 50 to 75 recruited between June 2008 and June 2012 in Paris (France), we assessed hemoglobin levels (g/dl), depressive symptoms and antidepressant intake. We examined the association of both depression and antidepressant intake with hemoglobin level, adjusting for numerous socio-demographic and health variables. We also assessed the association with specific antidepressant classes. Depression and antidepressant intake were independently associated with lower hemoglobin level (ß = -0.074; p = .05 and ß = -0.100; p = .02 respectively in the fully-adjusted model). Regarding antidepressant classes, selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs) intake were associated with lower hemoglobin level (ß = -0.11; p = .01). To conclude, both depression and antidepressant intake were associated with lower hemoglobin level. In particular, as SSRI or SNRIs intake was also related to lower hemoglobin level, these classes should be used with caution in depressed individuals at risk for anemia.

Prophylactic implantable cardioverter-defibrillator in the very elderly.

AIMS: Current guidelines do not propose any age cut-off for the primary prevention implantable cardioverter-defibrillator (ICD). However, the risk/benefit balance in the very elderly population has not been well studied. METHODS AND RESULTS: In a multicentre French study assessing patients implanted with an ICD for primary prevention, outcomes among patients aged ≥80 years were compared with <80 years old controls matched for sex and underlying heart disease (ischaemic and dilated cardiomyopathy). A total of 300 ICD recipients were enrolled in this specific analysis, including 150 patients ≥80 years (mean age 81.9 ± 2.0 years; 86.7% males) and 150 controls (mean age 61.8 ± 10.8 years). Among older patients, 92 (75.6%) had no more than one associated comorbidity. Most subjects in the elderly group got an ICD as part of a cardiac resynchronization therapy procedure (74% vs. 46%, P < 0.0001). After a mean follow-up of 3.0 ± 2 years, 53 patients (35%) in the elderly group died, including 38.2% from non cardiovascular causes of death. Similar proportion of patients received ≥1 appropriate therapy (19.4% vs. 21.6%; P = 0.65) in the elderly group and controls, respectively. There was a trend towards more early perioperative events (P = 0.10) in the elderly, with no significant increase in late complications (P = 0.73). CONCLUSION: Primary prevention ICD recipients ≥80 years in the real world had relatively low associated comorbidity. Rates of appropriate therapies and device-related complications were similar, compared with younger subjects. Nevertheless, the inherent limitations in interpreting observational data on this particular competing risk situation call for randomized controlled trials to provide definitive answers. Meanwhile, a careful multidisciplinary evaluation is needed to guide patient selection for ICD implantation in the elderly population.

Impaired baroreflex sensitivity, carotid stiffness, and exaggerated exercise blood pressure: a community-based analysis from the Paris Prospective Study III.

Aims: People with exaggerated exercise blood pressure (BP) have adverse cardiovascular outcomes. Mechanisms are unknown but could be explained through impaired neural baroreflex sensitivity (BRS) and/or large artery stiffness. This study aimed to determine the associations of carotid BRS and carotid stiffness with exaggerated exercise BP. Methods and results: Blood pressure was recorded at rest and following an exercise step-test among 8976 adults aged 50 to 75 years from the Paris Prospective Study III. Resting carotid BRS (low frequency gain, from carotid distension rate, and heart rate) and stiffness were measured by high-precision echotracking. A systolic BP threshold of ≥ 150 mmHg defined exaggerated exercise BP and ≥140/90 mmHg defined resting hypertension (±antihypertensive treatment). Participants with exaggerated exercise BP had significantly lower BRS [median (Q1; Q3) 0.10 (0.06; 0.16) vs. 0.12 (0.08; 0.19) (ms2/mm) 2×108; P < 0.001] but higher stiffness [mean ± standard deviation (SD); 7.34 ± 1.37 vs. 6.76 ± 1.25 m/s; P < 0.001) compared to those with non-exaggerated exercise BP. However, only lower BRS (per 1SD decrement) was associated with exaggerated exercise BP among people without hypertension at rest {specifically among those with optimal BP; odds ratio (OR) 1.16 [95% confidence intervals (95% CI) 1.01; 1.33], P = 0.04 and high-normal BP; OR, 1.19 (95% CI 1.07; 1.32), P = 0.001} after adjustment for age, sex, body mass index, smoking, alcohol, total cholesterol, high-density lipoprotein cholesterol, resting heart rate, and antihypertensive medications. Conclusion: Impaired BRS, but not carotid stiffness, is independently associated with exaggerated exercise BP even among those with well controlled resting BP. This indicates a potential pathway from depressed neural baroreflex function to abnormal exercise BP and clinical outcomes.

Acellular therapeutic approach for heart failure: in vitro production of extracellular vesicles from human cardiovascular progenitors.

Aims: We have shown that extracellular vesicles (EVs) secreted by embryonic stem cell-derived cardiovascular progenitor cells (Pg) recapitulate the therapeutic effects of their parent cells in a mouse model of chronic heart failure (CHF). Our objectives are to investigate whether EV released by more readily available cell sources are therapeutic, whether their effectiveness is influenced by the differentiation state of the secreting cell, and through which mechanisms they act. Methods and results: The total EV secreted by human induced pluripotent stem cell-derived cardiovascular progenitors (iPSC-Pg) and human induced pluripotent stem cell-derived cardiomyocytes (iPSC-CM) were isolated by ultracentrifugation and characterized by Nanoparticle Tracking Analysis, western blot, and cryo-electron microscopy. In vitro bioactivity assays were used to evaluate their cellular effects. Cell and EV microRNA (miRNA) content were assessed by miRNA array. Myocardial infarction was induced in 199 nude mice. Three weeks later, mice with left ventricular ejection fraction (LVEF) ≤ 45% received transcutaneous echo-guided injections of iPSC-CM (1.4 × 106, n = 19), iPSC-Pg (1.4 × 106, n = 17), total EV secreted by 1.4 × 106 iPSC-Pg (n = 19), or phosphate-buffered saline (control, n = 17) into the peri-infarct myocardium. Seven weeks later, hearts were evaluated by echocardiography, histology, and gene expression profiling, blinded to treatment group. In vitro, EV were internalized by target cells, increased cell survival, cell proliferation, and endothelial cell migration in a dose-dependent manner and stimulated tube formation. Extracellular vesicles were rich in miRNAs and most of the 16 highly abundant, evolutionarily conserved miRNAs are associated with tissue-repair pathways. In vivo, EV outperformed cell injections, significantly improving cardiac function through decreased left ventricular volumes (left ventricular end systolic volume: -11%, P < 0.001; left ventricular end diastolic volume: -4%, P = 0.002), and increased LVEF (+14%, P < 0.0001) relative to baseline values. Gene profiling revealed that EV-treated hearts were enriched for tissue reparative pathways. Conclusion: Extracellular vesicles secreted by iPSC-Pg are effective in the treatment of CHF, possibly, in part, through their specific miRNA signature and the associated stimulation of distinct cardioprotective pathways. The processing and regulatory advantages of EV could make them effective substitutes for cell transplantation.

Implantable cardioverter-defibrillator therapy among patients with non-ischaemic vs. ischaemic cardiomyopathy for primary prevention of sudden cardiac death.

Aim: The magnitude of benefit related to implantable cardioverter defibrillator (ICD) therapy for primary prevention of sudden cardiac death (SCD) in non-ischaemic cardiomyopathy (NICM) and ischaemic cardiomyopathy (ICM) has not been evaluated extensively in clinical practice. Methods and results: Of the 5539 consecutive patients enrolled in the multicentre Défibrillateur Automatique Implantable-Prévention Primaire (DAI-PP) study (2002-12), 5485 patients (with information on underlying heart disease) were included in the present analysis: 2181 (39.8%) had NICM and 3304 (60.2%) had ICM. ICM patients were older (63.7 ±10.3 vs. 60.6 ± 12.2 years, P < 0.0001), with a higher ejection fraction [27% (25-30) vs. 25% (20-30), P < 0.0001], narrower QRS (37.3% vs. 21.4% with QRS <120, P < 0.0001), and higher prevalence of sinus rhythm (77.3% vs. 74.0%, P = 0.009). During a mean follow-up of 3.1 ± 2.2 years, 814 patients died, giving a mortality incidence of 48.6 per 1000 person-years [95% confidence interval (CI) 45.2-51.9], higher among ICM patients (52.3, 95% CI 47.8-56.7) than in NICM patients (42.4, 95% CI 37.3-47.6; P = 0.008) (adjusted hazard ratio 1.31, 95% CI 1.06-1.61, P = 0.01). The increase in mortality among ICM patients was mainly due to non-cardiovascular mortality (P = 0.0002), whereas incidences of cardiovascular mortality (including ICD-unresponsive SCD) were similar in the two groups. Incidences of appropriate ICD interventions (anti-tachycardia pacing, shocks) were similar, but inappropriate therapies were more frequent in NICM (7.94 vs. 5.96%; P = 0.005). Conclusion: NICM and ICM patients had a same rate of ICD therapy for primary prevention of SCD in everyday practice. But, ICM patients more often died of a non- cardiovascular cause of death. Clinical Trial Registration: NCT 01992458.

Association of Cardiovascular Health Level in Older Age With Cognitive Decline and Incident Dementia.

Importance: Evidence is limited regarding the relation between cardiovascular health level and dementia risk. Objective: To investigate the association between cardiovascular health level, defined using the 7-item tool from the American Heart Association (AHA), and risk of dementia and cognitive decline in older persons. Design, Setting, and Participants: Population-based cohort study of persons aged 65 years or older from Bordeaux, Dijon, and Montpellier, France, without history of cardiovascular diseases or dementia at baseline who underwent repeated in-person neuropsychological testing (January 1999-July 2016) and systematic detection of incident dementia (date of final follow-up, July 26, 2016). Exposures: The number of the AHA's Life's Simple 7 metrics at recommended optimal level (nonsmoking, body mass index <25, regular physical activity, eating fish twice a week or more and fruits and vegetables at least 3 times a day, cholesterol <200 mg/dL [untreated], fasting glucose <100 mg/dL [untreated], and blood pressure <120/80 mm Hg [untreated]; score range, 0-7) and a global cardiovascular health score (range, 0-14; poor, intermediate, and optimal levels of each metric assigned a value of 0, 1, and 2, respectively). Main Outcomes and Measures: Incident dementia validated by an expert committee and change in a composite score of global cognition (in standard units, with values indicating distance from population means, 0 equal to the mean, and +1 and -1 equal to 1 SD above and below the mean). Results: Among 6626 participants (mean age, 73.7 years; 4200 women [63.4%]), 2412 (36.5%), 3781 (57.1%), and 433 (6.5%) had 0 to 2, 3 to 4, and 5 to 7 health metrics at optimal levels, respectively, at baseline. Over a mean follow-up duration of 8.5 (range, 0.6-16.6) years, 745 participants had incident adjudicated dementia. Compared with the incidence rate of dementia of 1.76 (95% CI, 1.38-2.15) per 100 person-years among those with 0 or 1 health metrics at optimal levels, the absolute differences in incident dementia rates for 2, 3, 4, 5, and 6 to 7 metrics were, respectively, -0.26 (95% CI, -0.48 to -0.04), -0.59 (95% CI, -0.80 to -0.38), -0.43 (95% CI, -0.65 to -0.21), -0.93 (95% CI, -1.18 to -0.68), and -0.96 (95% CI, -1.37 to -0.56) per 100 person-years. In multivariable models, the hazard ratios for dementia were 0.90 (95% CI, 0.84-0.97) per additional optimal metric and 0.92 (95% CI, 0.89-0.96) per additional point on the global score. Furthermore, the gain in global cognition associated with each additional optimal metric at baseline was 0.031 (95% CI, 0.009-0.053) standard units at inclusion, 0.068 (95% CI, 0.045-0.092) units at year 6, and 0.072 (95% CI, 0.042-0.102) units at year 12. Conclusions and Relevance: In this cohort of older adults, increased numbers of optimal cardiovascular health metrics and a higher cardiovascular health score were associated with a lower risk of dementia and lower rates of cognitive decline. These findings may support the promotion of cardiovascular health to prevent risk factors associated with cognitive decline and dementia.

Association of Change in Cardiovascular Risk Factors With Incident Cardiovascular Events.

Importance: There is consistent evidence of the association between ideal cardiovascular health and lower incident cardiovascular disease (CVD); however, most studies used a single measure of cardiovascular health. Objective: To examine how cardiovascular health changes over time and whether these changes are associated with incident CVD. Design, Setting, and Participants: Prospective cohort study in a UK general community (Whitehall II), with examinations of cardiovascular health from 1985/1988 (baseline) and every 5 years thereafter until 2015/2016 and follow-up for incident CVD until March 2017. Exposures: Using the 7 metrics of the American Heart Association (nonsmoking; and ideal levels of body mass index, physical activity, diet, blood pressure, fasting blood glucose, and total cholesterol), participants with 0 to 2, 3 to 4, and 5 to 7 ideal metrics were categorized as having low, moderate, and high cardiovascular health. Change in cardiovascular health over 10 years between 1985/1988 and 1997/1999 was considered. Main Outcome and Measure: Incident CVD (coronary heart disease and stroke). Results: The study population included 9256 participants without prior CVD (mean [SD] age at baseline, 44.8 [6.0] years; 2941 [32%] women), of whom 6326 had data about cardiovascular health change. Over a median follow-up of 18.9 years after 1997/1999, 1114 incident CVD events occurred. In multivariable analysis and compared with individuals with persistently low cardiovascular health (consistently low group, 13.5% of participants; CVD incident rate per 1000 person-years, 9.6 [95% CI, 8.4-10.9]), there was no significant association with CVD risk in the low to moderate group (6.8% of participants; absolute rate difference per 1000 person-years, -1.9 [95% CI, -3.9 to 0.1]; HR, 0.84 [95% CI, 0.66-1.08]), the low to high group, (0.3% of participants; absolute rate difference per 1000 person-years, -7.7 [95% CI, -11.5 to -3.9]; HR, 0.19 [95% CI, 0.03-1.35]), and the moderate to low group (18.0% of participants; absolute rate difference per 1000 person-years, -1.3 [95% CI, -3.0 to 0.3]; HR, 0.96 [95% CI, 0.80-1.15]). A lower CVD risk was observed in the consistently moderate group (38.9% of participants; absolute rate difference per 1000 person-years, -4.2 [95% CI, -5.5 to -2.8]; HR, 0.62 [95% CI, 0.53-0.74]), the moderate to high group (5.8% of participants; absolute rate difference per 1000 person-years, -6.4 [95% CI, -8.0 to -4.7]; HR, 0.39 [95% CI, 0.27-0.56]), the high to low group (1.9% of participants; absolute rate difference per 1000 person-years, -5.3 [95% CI, -7.8 to -2.8]; HR, 0.49 [95% CI, 0.29-0.83]), the high to moderate group (9.3% of participants; absolute rate difference per 1000 person-years, -4.5 [95% CI, -6.2 to -2.9]; HR, 0.66 [95% CI, 0.51-0.85]), and the consistently high group (5.5% of participants; absolute rate difference per 1000 person-years, -5.6 [95% CI, -7.4 to -3.9]; HR, 0.57 [95% CI, 0.40-0.80]). Conclusions and Relevance: Among a group of participants without CVD who received follow-up over a median 18.9 years, there was no consistent relationship between direction of change in category of a composite metric of cardiovascular health and risk of CVD.

Temporal Trends Over a Decade of Defibrillator Therapy for Primary Prevention in Community Practice.

BACKGROUND: Technology and clinical practice surrounding the use of the primary prevention implantable cardioverter defibrillator (ICD) are in a state of constant evolution. The purpose of the study was to test the hypothesis of significant temporal trends in characteristics and outcomes over a decade of ICD therapy. METHODS: Between 2002 and 2012, 5,539 consecutive patients (age 62.5 ± 11 years, 84.9% male), with ischemic or nonischemic cardiomyopathy, implanted with a primary prevention ICD from 12 centers in France were included. Information on characteristics and outcomes (including causes of death) were evaluated over a median follow-up of 994 days (466-1,667). RESULTS: In addition to a shift in the type of devices implanted with a significant increase in cardiac resynchronization therapy-defibrillator (CRT-D) over time (43.6 to 60.4%, P = 0.0001), an increase in mean age (from 61.5 ± 11.6 to 63.2 ± 10.9 years, P = 0.0016), proportion of nonischemic cardiomyopathy (31.0 to 44.7%, P <0.0001) and women recipients (11.4 to 15.8%, P = 0.004) was observed. A total of 1,181 patients (22.3%) received ≥1 appropriate therapy, inappropriate therapies occurred in 355 patients (6.7%) and 826 patients (15.2%) died, mainly from cardiovascular causes (49.3%). Annual mortality incidence (5.4% to 4.3%, P = 0.05), as well as incidence of appropriate therapy (10.4% to 7.1%, P = 0.0004), significantly decreased over the decade. By contrast, incidence of ICD-related late (>30 days after implant) complications significantly increased (4.6 to 7.6%, P = 0.003). CONCLUSION: Our findings demonstrate significant changes in patterns of use and outcomes in primary prevention ICD over the last decade with reductions in mortality and appropriate therapies, counterbalanced by an increase in complications.

Ideal Cardiovascular Health and Subclinical Markers of Carotid Structure and Function: The Paris Prospective Study III.

OBJECTIVE: We hypothesized that subclinical markers of vascular structure and function, which are independent predictors of cardiovascular disease, would be less frequent in subjects with ideal than poor cardiovascular health (CVH) as defined by the American Heart Association (AHA). APPROACH AND RESULTS: Carotid parameters were measured using high-precision echotracking device in 9155 nonreferred participants attending a health checkup in a large health center in Paris (France) between 2008 and 2012. According to the AHA, participants with 0 to 2, 3 to 4, and 5 to 7 metrics (smoking, physical activity, body mass index, diet, blood glucose and total cholesterol, blood pressure) at the ideal level were categorized as having poor, intermediate, and ideal CVH. Carotid parameters were dichotomized according to their median value, and multivariable logistic regression analysis was performed. Mean age was 59.5 (SD 6.3) years; 39% were females, and ideal CVH was present in 10.11% of the study participants. After adjustment for age, sex, education, and living alone and compared with a poor CVH, an ideal CVH was associated with lower common carotid artery intima-media thickness (odds ratio=1.64; 95% confidence interval 1.40, 1.93), absence of carotid plaques (odds ratio=2.14; 95% confidence interval 1.60, 2.87), lower Young's elastic modulus (odds ratio=2.43; 95% confidence interval 2.07, 2.84), and higher carotid distensibility coefficient (odds ratio=2.90; 95% confidence interval 2.47, 3.41). CONCLUSIONS: In community subjects aged 50 to 75 years, ideal CVH was associated with substantially less arterial stiffness and thickness. These associations might contribute to the lower risk of cardiovascular diseases in subjects with ideal CVH.

Dual- vs. single-chamber defibrillators for primary prevention of sudden cardiac death: long-term follow-up of the Défibrillateur Automatique Implantable-Prévention Primaire registry.

AIMS: Implantable cardioverter defibrillators (ICDs) are an effective primary prevention of sudden cardiac death. We examined whether dual-chamber (DC) ICDs confer a greater benefit than single-chamber (SC) ICDs, and compared the long-term outcomes of recipients of each type of device implanted for primary prevention. METHODS AND RESULTS: Between 2002 and 2012, the DAI-PP registry consecutively enrolled 1258 SC- and 1280 DC-ICD recipients at 12 French medical centres. The devices were interrogated at 4- to 6-month intervals during outpatient visits, with a focus on the therapies delivered. The study endpoints were incidence of appropriate therapies, ICD-related morbidity, and deaths from all and from specific causes. The mean age of the SC- and DC-ICD recipients was 59 ± 12 and 62 ± 11 years, respectively (P< 0.0001). The distribution of genders, New York Heart Association functional classes and glomerular filtration rates, and the rates of ischaemic vs. dilated cardiomyopathies and of defibrillation tests at implant, were similar in both study groups. The rates of periprocedural complications were 12.1% in the DC- vs. 8.8% in the SC-ICD groups (P= 0.008). Over a mean follow-up of 3.1 ± 2.2 years, pulse generators were replaced in 21.9% of the DC- vs. 13.6% of the SC-ICD group (P< 0.0001). The proportions of patients treated with ≥1 appropriate therapies (24.7 vs. 23.8%) and ≥1 inappropriate shocks (8.4 vs. 7.8%), and all-cause mortality (12.4 vs. 13.2%) were similar in both groups. CONCLUSION: In this large registry of ICD implanted for primary prevention, DC-ICDs were associated with higher rates of peri-implant complications and generator replacements, whereas the survival and rates of inappropriate shocks were similar in both groups. CLINICAL TRIAL NUMBER: NCT#01992458.

The CAHP (Cardiac Arrest Hospital Prognosis) score: a tool for risk stratification after out-of-hospital cardiac arrest.

AIMS: Survival after out-of-hospital cardiac arrest (OHCA) remains disappointingly low. Among patients admitted alive, early prognostication remains challenging. This study aims to establish a stratification score for patients admitted in intensive care unit (ICU) after OHCA, according to their neurological outcome. METHODS AND RESULTS: The CAHP (Cardiac Arrest Hospital Prognosis) score was developed from the Sudden Death Expertise Center registry (Paris, France). The primary outcome was poor neurological outcome defined as Cerebral Performance Category 3, 4, or 5 at hospital discharge. Independent prognostic factors were identified using logistic regression analysis and thresholds defined to stratify low-, moderate-, and high-risk groups. The CAHP score was validated in both a prospective and an external data set (Parisian Cardiac Arrest Registry). The developmental data set included 819 patients admitted from May 2011 to December 2012. After multivariate analysis, seven variables were independently associated with poor neurological outcome and subsequently included in the CAHP score (age, non-shockable rhythm, time from collapse to basic life support, time from basic life support to return of spontaneous circulation, location of cardiac arrest, epinephrine dose, and arterial pH). Three risks groups were identified: low risk (score ≤150, 39% of unfavourable outcome), medium risk (score 150-200, 81% of unfavourable outcome) and high-risk group (score ≥200, 100% of unfavourable outcome). The AUC of the CAHP score were 0.93, and the discrimination value in the validation data sets was consistent (respectively, AUC 0.91 and 0.85). CONCLUSION: The CAHP score represents a simple tool for early stratification of patients admitted in ICU after OHCA. A high-risk category of patients with very poor prognosis can be easily identified.

Longitudinal association of carotid plaque presence and intima-media thickness with depressive symptoms in the elderly: the three-city study.

OBJECTIVE: To investigate prospectively whether subclinical vascular disease is associated with future depressive symptoms in the elderly. APPROACH AND RESULTS: A multicenter cohort of community-dwelling individuals aged 65 to 85 years was examined for carotid plaque presence and common carotid artery intima-media thickness at baseline and followed up after 2, 4, 7, and 10 years. At baseline and follow-up examinations, depressive symptoms were assessed using the Center for Epidemiologic Studies Depression Scale (CES-D). High level of depressive symptoms was defined as a CES-D score >16 in men and >22 in women. Among 4125 participants (58% women) at baseline, men more frequently showed carotid plaque presence and had higher mean common carotid artery intima-media thickness than women. After adjustment for major cardiovascular risk factors, carotid plaque presence was associated with a higher CES-D score at the 10-year follow-up in men (+1.46; 95% confidence interval, 0.71-2.20; P<0.001), but not in women. When restricting analyses to individuals without cardiovascular disease at baseline, carotid plaque presence increased the likelihood of high level of depressive symptoms at follow-up examinations in men (odds ratio, 1.47; 95% confidence interval, 1.06-2.05; P=0.022), but not in women. One SD increase in log-transformed common carotid artery intima-media thickness was associated with a higher CES-D score at the 10-year follow-up in women (+0.55; 95% confidence interval, 0.16-0.95; P=0.006) and men (+0.40; 95% confidence interval, 0.02-0.78; P=0.037). Common carotid artery intima-media thickness did not increase the likelihood of high level of depressive symptoms at follow-up in both sexes. CONCLUSIONS: Subclinical vascular disease is associated with the progression of depressive symptoms in elderly men and women and the occurrence of high level of depressive symptoms in elderly men.

Towards a clinical use of human embryonic stem cell-derived cardiac progenitors: a translational experience.

AIM: There is now compelling evidence that cells committed to a cardiac lineage are most effective for improving the function of infarcted hearts. This has been confirmed by our pre-clinical studies entailing transplantation of human embryonic stem cell (hESC)-derived cardiac progenitors in rat and non-human primate models of myocardial infarction. These data have paved the way for a translational programme aimed at a phase I clinical trial. METHODS AND RESULTS: The main steps of this programme have included (i) the expansion of a clone of pluripotent hESC to generate a master cell bank under good manufacturing practice conditions (GMP); (ii) a growth factor-induced cardiac specification; (iii) the purification of committed cells by immunomagnetic sorting to yield a stage-specific embryonic antigen (SSEA)-1-positive cell population strongly expressing the early cardiac transcription factor Isl-1; (iv) the incorporation of these cells into a fibrin scaffold; (v) a safety assessment focused on the loss of teratoma-forming cells by in vitro (transcriptomics) and in vivo (cell injections in immunodeficient mice) measurements; (vi) an extensive cytogenetic and viral testing; and (vii) the characterization of the final cell product and its release criteria. The data collected throughout this process have led to approval by the French regulatory authorities for a first-in-man clinical trial of transplantation of these SSEA-1(+) progenitors in patients with severely impaired cardiac function. CONCLUSION: Although several facets of this manufacturing process still need to be improved, these data may yet provide a useful platform for the production of hESC-derived cardiac progenitor cells under safe and cost-effective GMP conditions.

Causes-of-death analysis of patients with cardiac resynchronization therapy: an analysis of the CeRtiTuDe cohort study.

AIMS: The choice of resynchronization therapy between with (CRT-D) and without (CRT-P) a defibrillator remains a contentious issue. Cause-of-death analysis among CRT-P, compared with CRT-D, patients could help evaluate the extent to which CRT-P patients would have additionally benefited from a defibrillator in a daily clinical practice. METHODS AND RESULTS: A total of 1705 consecutive patients implanted with a CRT (CRT-P: 535 and CRT-D: 1170) between 2008 and 2010 were enrolled in CeRtiTuDe, a multicentric prospective follow-up cohort study, with specific adjudication for causes of death at 2 years. Patients with CRT-P compared with CRT-D were older (P < 0.0001), less often male (P < 0.0001), more symptomatic (P = 0.0005), with less coronary artery disease (P = 0.003), wider QRS (P = 0.002), more atrial fibrillation (P < 0.0001), and more co-morbidities (P = 0.04). At 2-year follow-up, the annual overall mortality rate was 83.80 [95% confidence interval (CI) 73.41-94.19] per 1000 person-years. The crude mortality rate among CRT-P patients was double compared with CRT-D (relative risk 2.01, 95% CI 1.56-2.58). In a Cox proportional hazards regression analysis, CRT-P remained associated with increased mortality (hazard ratio 1.54, 95% CI 1.07-2.21, P = 0.0209), although other potential confounders may persist. By cause-of-death analysis, 95% of the excess mortality among CRT-P subjects was related to an increase in non-sudden death. CONCLUSION: When compared with CRT-D patients, excess mortality in CRT-P recipients was mainly due to non-sudden death. Our findings suggest that CRT-P patients, as currently selected in routine clinical practice, would not potentially benefit with the addition of a defibrillator.

Survival from sports-related sudden cardiac arrest: In sports facilities versus outside of sports facilities.

BACKGROUND: We sought to evaluate frequency, characteristics, and outcomes of sudden cardiac arrest (SCA) during sports activities according to the location of occurrence (in sports facilities vs those occurring outside of sports facilities). METHODS AND RESULTS: This is an observational 5-year prospective national French survey of subjects 10 to 75 years old presenting with SCA during sports (2005-2010), in 60 French administrative regions (covering a population of 35 million people). Of the 820 SCA during sports, 426 SCAs (52%) occurred in sports facilities. Overall, a substantially higher survival rate at hospital discharge was observed among SCA in sports facilities (22.8%, 95% CI 18.8-26.8) compared to those occurring outside (8.0%, 95% CI 5.3-10.7) (P < .0001). Patients with SCA in sports facilities were younger (42.1 vs 51.3 years, P < .0001) and less frequently had known cardiovascular diseases (P < .0001). The events were more often witnessed (99.8% vs 84.9%, 0.0001), and bystander cardiopulmonary resuscitation was more frequently initiated (35.4% vs 25.9%, P = .003). Delays of intervention were significantly shorter when SCA occurred in sports facilities (9.3 vs 13.6, P=0.03), and the proportion of initially shockable rhythm was higher (58.8% vs 33.1%, P < .0001). Better survival in sports facilities was mainly explained by concomitant circumstances of occurrence (adjusted odds ratio 1.48, 95% CI 0.88-2.49, P = .134). CONCLUSIONS: Sports-related SCA is not a homogeneous entity. The 3-fold higher survival rate reported among sports-related SCA is mainly due to cases that occur in sports facilities, whereas SCA during sports occurring outside of sports facilities has the usual very low rate of survival.