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Background: Intra-hospital falls have become an important public health problem globally. The use of movement sensors with alarms has been studied as elements with predictive capacity for falls at hospital level. However, in spite of their use in some hospitals throughout the world, evidence is lacking about their effectiveness in reducing intra-hospital falls. Therefore, this study aims to develop a systematic review and meta-analysis of existing scientific literature exploring the impact of using sensors for fall prevention in hospitalized adults and the elderly population., Methods: We explored literature based on clinical trials in Spanish, English, and Portuguese, assessing the impact of devices used for hospital fall prevention in adult and elderly populations. The search included databases such as IEEE Xplore, the Cochrane Library, Scopus, PubMed, MEDLINE, and Science Direct databases. The critical appraisal was performed independently by two researchers. Methodological quality was assessed based on the ratings of individual biases. We performed the sum of the results, generating an estimation of the grouped effect (Relative Risk, 95% CI) for the outcome first fall for each patient. We assessed heterogeneity and publication bias. The study followed PRISMA guidelines., Results: Results were assessed in three randomized controlled clinical trials, including 29,691 patients. A total of 351 (3%) patients fell among 11,769 patients assigned to the intervention group, compared with 426 (2.4%) patients who fell among 17,922 patients assigned to the control group (general estimation RR 1.20, 95% CI 1.04, 1.37, P = .02, I2 = 0%; Moderate GRADE)., Conclusion: Our results show an increase of 19% in falls among elderly patients who are users of sensors located in their bed, bed-chair, or chair among their hospitalizations. Other types of sensors such as wearable sensors can be explored as coadjutants for fall prevention care in hospitals., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Novel approaches to obesity prevention among youth are needed. Accordingly, the Office of Women's Health, Department of Health and Human Services, sponsored a challenge to create an interactive video game for obesity prevention. Our team took a theory-based, evidence-informed approach to increasing physical activity in girls. Our approach-digitally mediated physical play-allowed us to include computing-based strategies that promote activity without keeping players in front of a screen. Our prize-winning prototype app, Frolic, helps girls choose the perfect game to play in any context, engaging parents for support. The app is used to highlight some opportunities and challenges for interdisciplinary collaboration. However, much work remains to be done to deploy innovative digital obesity interventions and fully capture the contributions of these tools. In order to accelerate advances, funding is needed for projects that combine engineering design principles with traditional obesity research paradigms., (© 2021 The Obesity Society.)

Background: Conventional risk factors for sudden cardiac death (SCD) justify primary prevention through implantable cardioverter-defibrillator (ICD) implantation in hypertrophic cardiomyopathy (HCM) patients. However, the positive predictive values for these conventional SCD risk factors are low. Left ventricular outflow tract obstruction (LVOTO) and midventricular obstruction (MVO) are potential risk modifiers for SCD. The aims of this study were to evaluate whether an elevated intraventricular pressure gradient (IVPG), including LVOTO or MVO, is a potential risk modifier for SCD and ventricular arrhythmias requiring ICD interventions in addition to the conventional risk factors among HCM patients receiving ICDs for primary prevention., Methods: We retrospectively studied 60 HCM patients who received ICDs for primary prevention. An elevated IVPG was defined as a peak instantaneous gradient ≥ 30 mmHg at rest, as detected by continuous-wave Doppler echocardiography. The main outcome was a composite of SCD and appropriate ICD interventions, which were defined as an antitachycardia pacing or shock therapy for ventricular tachycardia or fibrillation. The Cox proportional hazards model was used to assess the relationships between risk factors and the occurrence of SCD and appropriate ICD interventions., Results: Thirty patients met the criteria of elevated IVPG (50%). During the median follow-up period of 66 months, 2 patients experienced SCD, and 10 patients received appropriate ICD interventions. Kaplan-Meier curves showed that the incidence of the main outcome was higher in patients with an IVPG ≥ 30 mmHg than in those without an IVPG ≥ 30 mmHg (log-rank P = 0.03). There were no differences in the main outcome between patients with LVOTO and patients with MVO. The combination of nonsustained ventricular tachycardia (NSVT) and IVPG ≥ 30 mmHg was found to significantly increase the risk of the main outcome (HR 6.31, 95% CI 1.36-29.25, P = 0.02). Five patients experienced ICD implant-related complications., Conclusions: Our findings showed that a baseline IVPG ≥ 30 mmHg was associated with an increased risk of experiencing SCD or appropriate ICD interventions among HCM patients who received ICDs for primary prevention. Combined with NSVT, which is a conventional risk factor, a baseline IVPG ≥ 30 mmHg may be a potential modifier of SCD risk in HCM patients.

Background: Advancing health literacy is a fundamental step toward achieving population health. To that end, the National Institutes of Health (NIH) funded research to increase scientific understanding of how health literacy can reduce disparities and enhance the health of the United States., Objective: This study identified and evaluated NIH-funded health literacy research focusing on disease prevention., Methods: New R01, R03, and R21 research project grants awarded from fiscal year (FY) 2004 to FY 2017 studying health literacy and disease prevention were identified. Study characteristics, including the role of health literacy, how health literacy was measured, populations studied, and study design, were coded for each grant. Administrative grant data were obtained from the NIH's internal database. Research impact was assessed using the relative citation ratio (RCR)., Key Results: There were 192 grants studying health literacy and disease prevention awarded by 18 NIH institutes and centers from FY 2004 to FY 2017, covering a wide variety of health conditions including cancer (26.0%), infectious diseases (13.5%), nutrition (8.3%), drug/alcohol use (7.8%), and cardiovascular disease (6.3%). Most grants studied the health literacy skills of patients (88%), with a few studies assessing the health literacy practices of health care providers (2.1%) or systems (1%). There was good representation of populations with traditionally low levels of health literacy, including Black/African American participants (30.2%), Hispanic/Latinx participants (28.6%), older adults (37%), and people with low income (20.8%). The scientific articles generated by these grants were more than twice (RCR = 2.18) as influential on the field as similar articles., Conclusions: The NIH provided support for a wide array of prevention-focused health literacy research. The value of this research is highlighted by the number of funding institutes and centers, the diversity of populations and health conditions studied, and the effect these grants had on the field. Future research should move beyond patient-level health literacy to health literacy practices of health care systems and providers. [HLRP: Health Literacy Research and Practice. 2020, 4(4):e212-e223.] PLAIN LANGUAGE SUMMARY: This study describes health literacy research funded by the National Institutes of Health that focused on disease prevention. These grants sought to prevent a variety of health conditions, but health literacy research over the past 14 years continued to concentrate on the capacity of patients despite increased attention on the health literacy practices of health care providers and systems., (©2020 Villani, Trivedi.)

Purpose: Implantable cardioverter defibrillators (ICD) are the standard of care for primary prevention (PP) in patients with ischemic cardiomyopathy (ICM). However, PP ICD implantation is underused in Asian countries. This study investigated ICD implantation rates and factors associated with appropriate PP ICD implants for ICM., Materials and Methods: In this prospective multicenter observational registry (ADVANCE-ICM registry), ICM patients who were eligible for PP ICD were screened and enrolled. Factors associated with appropriate ICD implantation, including hospital and clinical factors, were investigated., Results: Of the 1453 ICM patients eligible for PP ICD [1111 male; median age, 71.0 (61.0-78.0) years], only 76 (5.2%) patients underwent ICD implantation. Among hospital factors, a non-monetary incentive for referral (72.4% vs. 52.9%, p =0.001) and total hospital system score (6.0 vs. 5.0, p =0.013) were higher in the ICD than in the no-ICD group. In multivariate analysis, total hospital system score [odds ratio (OR), 1.28; 95% confidence interval (CI), 1.10-1.50] was an independent factor for predicting ICD implantation, along with clinical factors, including high New York Heart Association class (≥III: OR, 7.29; 95% CI, 2.97-17.87) and younger age (<70 years: OR, 2.14; 95% CI, 1.30-3.53)., Conclusion: PP ICD implantation for ICM patients is underused in Korea. Hospital factors were important for improving PP ICD implantation rate, suggesting that new screening and referral systems for ICM patients would improve the PP ICD implantation rate (Clinical trial registration No. NCT03590925)., Competing Interests: Dr. Boyoung Joung has served as a speaker for Bayer, BMS/Pfizer, Medtronic, and Daiichi-Sankyo and has received research funds from Medtronic and Abbott. None of the other authors have any disclosures to make. No fees were directly received personally., (© Copyright: Yonsei University College of Medicine 2020.)

Background: The implantable cardioverter-defibrillator (ICD) is effective for preventing sudden death in patients with hypertrophic cardiomyopathy. However, data on performance and complications of implanted ICDs over particularly long time periods to inform clinical practice is presently incomplete., Methods: The study cohort comprises 217 consecutive hypertrophic cardiomyopathy patients with primary prevention ICDs implanted before 2008 and followed for ≥10 years (mean 12±4; range to 31)., Results: Patients were 38±17 years at implant and 45 (21%) experienced appropriate interventions terminating ventricular tachycardia/ventricular fibrillation. The majority of ICD discharges occurred ≥5 years after implant (29 patients; 64%), including ≥10 years in 16 patients (36%). Initial device therapy increased in frequency from 2.3% of patients at <1 year to 8.5% of patients at ≥10-years after implant ( P =0.005). Inappropriate ICD shocks in 39 patients occurred most commonly <5 years after implant (54%) and decreased in frequency with increasing time from implant (from 9.7% of patients at <5 years to 3.8% at ≥10 years, P =0.02). Other major device complications including infection and lead fractures and dislodgement occurred in 27 patients (12%) but did not increase in frequency over follow-up after implant ( P =0.47). There were no arrhythmic sudden death events among the 217 patients with ICD., Conclusions: In hypertrophic cardiomyopathy, after a primary prevention implant, ICD therapy often followed prolonged periods of device dormancy and increased progressively in frequency over time, including one-third of patients with initial therapy after 5 to 9 years, and an additional one-third of patients at ≥10 years. Frequency of inappropriate shocks decreased over follow-up, likely reflecting standard changes in device programming, while occurrence of device complications, such as lead fractures/infection, did not increase during follow-up.

The COVID-19 pandemic triggered a surge in demand for facemasks to protect against disease transmission. In response to shortages, many public health authorities have recommended homemade masks as acceptable alternatives to surgical masks and N95 respirators. Although mask wearing is intended, in part, to protect others from exhaled, virus-containing particles, few studies have examined particle emission by mask-wearers into the surrounding air. Here, we measured outward emissions of micron-scale aerosol particles by healthy humans performing various expiratory activities while wearing different types of medical-grade or homemade masks. Both surgical masks and unvented KN95 respirators, even without fit-testing, reduce the outward particle emission rates by 90% and 74% on average during speaking and coughing, respectively, compared to wearing no mask, corroborating their effectiveness at reducing outward emission. These masks similarly decreased the outward particle emission of a coughing superemitter, who for unclear reasons emitted up to two orders of magnitude more expiratory particles via coughing than average. In contrast, shedding of non-expiratory micron-scale particulates from friable cellulosic fibers in homemade cotton-fabric masks confounded explicit determination of their efficacy at reducing expiratory particle emission. Audio analysis of the speech and coughing intensity confirmed that people speak more loudly, but do not cough more loudly, when wearing a mask. Further work is needed to establish the efficacy of cloth masks at blocking expiratory particles for speech and coughing at varied intensity and to assess whether virus-contaminated fabrics can generate aerosolized fomites, but the results strongly corroborate the efficacy of medical-grade masks and highlight the importance of regular washing of homemade masks.

Introduction: The coronavirus disease 19 (COVID-19) pandemic, caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), progresses globally, and means to reduce the transmission are needed. In the community, the use of face masks is increasing world-wide, but documentation for the efficacy of this remedy is lacking. This trial investigates whether the use of face masks in the community will reduce wearers' risk of SARS-CoV-2 infection., Methods: This study will be a two-arm, unblinded, randomised controlled trial. We will include adults (>18 years of age) without prior confirmed COVID-19 or symptoms suggestive of COVID-19, who spend more than three hours per day outside the home with exposure to other people. A total of 6,000 participants are randomly assigned 1:1 to use face masks or not for a 30-day period during the pandemic. Participants will perform self-testing; quick test for SARS-CoV-2 antibodies (immunoglobulin M (IgM) and immunoglobulin G (IgG)) (the Livzon lateral flow test) and oropharyngeal/nasal swabs for viral detection using polymerase chain reaction (PCR). The primary endpoint following the 30-day study period is the difference in the number of SARS-CoV-2-infected individuals between the two study groups as assessed by a positive nasopharyngeal swap, a positive antibody test or a hospital-based diagnosis of SARS-CoV-2 infection., Conclusions: We will study whether a face mask protects the wearer of the mask against SARS-CoV-2 infection. The findings are expected to apply to the present pandemic and to future viral outbreaks and to provide evidence for authority recommendations across the world., Funding: This study was funded by Salling Fondene., Trial Registration: ClinicalTrials.gov Identifier: NCT04337541., (Articles published in the DMJ are “open access”. This means that the articles are distributed under the terms of the Creative Commons Attribution Non-commercial License, which permits any non-commercial use, distribution, and reproduction in any medium, provided the original author(s) and source are credited.)

Background: The left ventricular ejection fraction (LVEF) is the key selection criterion for an implanted cardioverter defibrillator (ICD) in primary prevention of sudden cardiac death. LVEF is usually assessed by two-dimensional echocardiography, but cardiovascular magnetic resonance (CMR) imaging is increasingly used. The aim of our study was to evaluate whether LVEF assessment using CMR imaging (CMR-LVEF) or two-dimensional echocardiography (2D echo-LVEF) may predict differently the occurrence of clinical outcomes., Methods: In this retrospective study, we reviewed patients referred for primary prevention ICD implantation to Caen University Hospital from 2005 to 2014. We included 173 patients with either ischemic (n = 120) or dilated cardiomyopathy (n = 53) and who had undergone pre-ICD CMR imaging. The primary composite end point was the time to death from any cause or first appropriate device therapy., Results: The mean CMR-LVEF was significantly lower than the mean 2D echo-LVEF (24% ± 6 vs 28% ± 6, respectively; p < 0.001). CMR-LVEF was a better independent predictive factor for the occurrence of the primary composite endpoint with a cut-off value of 22% (Hazard Ratio [HR] = 2.22; 95% CI [1.34-3.69]; p = 0.002) than 2D echo-LVEF with a cut-off value of 26% (HR = 1.61; 95% CI [0.99-2.61]; p = 0.056). Combination of the presence of scar with CMR-LVEF< 22% improved the predictive value for the occurrence of the primary outcome (HR = 2.58; 95% CI [1.54-4.30]; p < 0.001). The overall survival was higher among patients with CMR-LVEF≥22% than among patients with CMR-LVEF< 22% (p = 0.026), whereas 2D echo-LVEF was not associated with death., Conclusions: CMR-LVEF is better associated with clinical outcomes than 2D echo-LVEF in primary prevention using an ICD. Scar identification further improved the outcome prediction. The combination of CMR imaging and echocardiography should be encouraged in addition to other risk markers to better select patients.

Background There are conflicting data regarding the benefit of primary prevention implantable cardioverter-defibrillators (ICDs) in patients with diabetes mellitus and heart failure (HF) with reduced ejection fraction. We aimed to assess the comparative effectiveness of ICD placement in patients with diabetes mellitus and HF with reduced ejection fraction. Methods and Results Data were obtained from the Get With the Guidelines-Health Failure registry, linked with claims from the Centers for Medicare & Medicaid Services. We used a Cox proportional hazards model censored at 5 years with propensity score matching. Of the 17 186 patients with HF with reduced ejection fraction from the Centers for Medicare & Medicaid Services claims database (6540 with diabetes mellitus; 38%), 1677 (646 with diabetes mellitus; 39%) received an ICD during their index HF hospitalization or were prescribed an ICD at discharge. Patients with diabetes mellitus and an ICD (n=646), as compared with those without an ICD (n=1031), were more likely to be younger (74 versus 78 years of age) and have coronary artery disease (68% versus 60%). After propensity matching, ICD use among patients with diabetes mellitus, as compared with those without an ICD, was associated with a reduced risk of all-cause mortality at 5 years after HF discharge (54% versus 59%; multivariable hazard ratio, 0.73; 95% CI, 0.64-0.82; P <0.0001). Ischemic heart disease did not modify the association between ICD use and all-cause mortality ( P =0.95 for interaction). Similar results were seen in patients without diabetes mellitus. Conclusions Primary prevention ICD use among older patients with HF with reduced ejection fraction and diabetes mellitus was associated with a reduced risk of all-cause mortality. Our analysis supports current guideline recommendations for implantation of primary prevention ICDs among older patients with diabetes mellitus and HF with reduced ejection fraction.

Most implantable cardioverter defibrillators (ICDs) are implanted for the purpose of primary prevention of sudden cardiac death among older patients with heart failure with reduced ejection fraction. Shared decision-making prior to device implantation is guideline-recommended and payer-mandated. This article summarizes patient and provider attitudes toward device placement, device efficacy and effectiveness, potential periprocedural complications, long-term events such as shocks, quality of life, costs, and shared decision-making principles and recommendations. Most patients eligible for an ICD anticipate more than 10 years of survival. Physicians are less likely to offer an ICD to patients ≥80 years of age given a perceived lack of benefit. There is a dearth of data from randomized clinical trials addressing device efficacy among older patients; there is a need for more research in this area. However, currently available data support the use of ICDs irrespective of age provided life expectancy exceeds 1 year. Advanced age is independently associated with complications at the time of device placement but not the risk of device infection. The risk of inappropriate shock may be comparable or lower than that of younger patients. While quality of life is generally not adversely impacted by an ICD, a subset of patients experience post-traumatic stress disorder. ICDs are cost-effective from societal and health care sector perspectives; however, out-of-pocket costs vary according to insurance type and level. Shared decision-making encounters may be incremental and iterative in nature. Providers are encouraged to partner with their patients, providing them counsel tailored to their values, preferences, and clinical presentation inclusive of age., (© 2019 The Authors. Clinical Cardiology published by Wiley Periodicals, Inc.)

Background: Absence of beta-blocker use independently predicts appropriate therapy. Following cardiac resynchronisation therapy (CRT) implant, reverse remodelling and protection against bradycardia allows for beta-blocker dose uptitration. The differential dosing effects on the occurrence of a first episode of appropriate therapy in primary prevention CRT-defibrillator (CRT-D) patients remains unstudied. Methods and Results: Changes in beta-blocker dose following CRT-D in consecutive primary prevention patients implanted between 2008 and 2015 were retrospectively studied. Beta-blocker dose was expressed as percent of target dose. Uptitration of beta-blocker dose following implant was calculated as the change in percent of target dose between implant and 6-months follow-up. Results from a prospectively maintained database of all device analysis were used to determine the occurrence of appropriate therapy. A total of 162 patients (68 ± 8 years) were studied. One hundred and ten (68%) patients underwent uptitration (mean 47 ± 19% in target dose) and 52 (32%) remained on a stable beta-blocker dose. During 37 ± 22 months follow-up, the cumulative percent of appropriate therapy was 31% in patient receiving no-uptitration versus 10% in the uptitrated patients (p < 0.001). After correction for known predictors of appropriate therapy, uptitration was independently associated with an OR = 0.263 (CI = 0.103-0.675; p  = 0.001) for the occurrence of appropriate therapy. Every 1%-increase in target dose for beta-blocker associated with a significant lower risk for appropriate therapy, OR = 0.982 (CI = 0.965-0.999; p  = 0.042). Conclusion: Following implantation of a primary prevention CRT-D, uptitration of beta-blockers associated with a reduced occurrence of a first episode of appropriate therapy for ventricular arrhythmias. An inverse dose-response effect was seen between beta-blocker dose and appropriate therapy.

Objective: Diabetes increases the risk of all-cause mortality and sudden cardiac death (SCD). The exact mechanisms leading to sudden death in diabetes are not well known. We compared the incidence of appropriate shocks and mortality in patients with versus without diabetes with a prophylactic implantable cardioverter defibrillator (ICD) included in the retrospective EU-CERT-ICD registry., Research Design and Methods and Results: A total of 3,535 patients from 12 European EU-CERT-ICD centers with a mean age of 63.7 ± 11.2 years (82% males) at the time of ICD implantation were included in the analysis. A total of 995 patients (28%) had a history of diabetes. All patients had an ICD implanted for primary SCD prevention. End points were appropriate shock and all-cause mortality. Mean follow-up time was 3.2 ± 2.3 years. Diabetes was associated with a lower risk of appropriate shocks (adjusted hazard ratio [HR] 0.77 [95% CI 0.62-0.96], P = 0.02). However, patients with diabetes had significantly higher mortality (adjusted HR 1.30 [95% CI 1.11-1.53], P = 0.001)., Conclusions: All-cause mortality is higher in patients with diabetes than in patients without diabetes with primary prophylactic ICDs. Subsequently, patients with diabetes have a lower incidence of appropriate ICD shocks, indicating that the excess mortality might not be caused primarily by ventricular tachyarrhythmias. These findings suggest a limitation of the potential of prophylactic ICD therapy to improve survival in patients with diabetes with impaired left ventricular function., (© 2019 by the American Diabetes Association.)

The use of conventional implantable cardioverter-defibrillators (ICDs) in children presents important technical challenges. We present the surgical technique necessary to adapt the subcutaneous ICD (S-ICD) implantation designed for adults, to children, including patients weighing less than 20 kg. The implant procedure implies a two-incision technique and interfascial serratus anterior-latissimus dorsi dissection to accommodate the device. S-ICD implantation was successfully performed in three patients of 19, 28, and 24 kg, respectively, two of them suffered cardiorespiratory arrest. Intermuscular thoracic implantation of S-ICD might represent an effective strategy for primary or secondary prevention of sudden cardiac death in pediatric patients., Competing Interests: The authors declare no conflicts of interests related to the publication of this study., (Georg Thieme Verlag KG Stuttgart · New York.)

Introduction: Between 7% and 15% of patients with an indication for an implantable cardioverter-defibrillator (ICD) are not eligible for implantation of a subcutaneous implantable cardioverter-defibrillator (S-ICD) on the basis of the result of the conventional left parasternal electrocardiographic screening (LPES). Our objective was to determine the impact of systematically performing right parasternal electrocardiographic screening (RPES) in addition to conventional LPES, in terms of increasing both the total percentage of potentially eligible patients for S-ICD implantation and the number of suitable vectors per patient., Methods and Results: Consecutive patients from the outpatient device clinic who already had an implanted ICD, and no requirement for pacing were enrolled. Conventional left parasternal electrode position and right parasternal electrode positions were used. The automatic screening tool was used to analyze the recordings. Screenings were performed in the supine and standing positions. Overall, 209 patients were included. The mean age was 63.4 ± 13 years, 59.8% had ischemic heart disease, mean QRS duration was 100 ± 31 ms, and 69.9% had a primary prevention ICD indication. Based on conventional isolated LPES, 12.9% of patients were not eligible for S-ICD compared with 11.5% based on RPES alone (P = .664). Considering LPES and RPES together, only 7.2% of patients were not eligible for S-ICD (P < .001). Moreover, the number of patients with more than one suitable vector increased from 66.5% with isolated LPES to 82.3% (23.7% absolute increase [P < .001])., Conclusion: Adding an automated RPES to the conventional automated LPES increased patient eligibility for the S-ICD significantly. Moreover, combined screening increased the number of suitable vectors per eligible patient., (© 2019 Wiley Periodicals, Inc.)

Sudden cardiac death represents a major public health issue, with up to 50% of the cardiovascular mortality. Coronary artery disease and dilated cardiomyopathy both represent almost 90% of sudden cardiac death burden. Primary prevention using implantable cardioverter defibrillator relies, in this population, on the left ventricle ejection fraction simple measurement. In this paper, we aim to discuss in which extent a better understanding of competing risk situation may help for a better patient selection and eventually for optimizing primary prevention using implantable cardioverter defibrillator., (Copyright © 2019 Elsevier Masson SAS. All rights reserved.)

Background: Hypertrophic cardiomyopathy (HCM) is considered a leading cause of sudden cardiac death (SCD) in younger people. The incidence of HCM-related SCD and its relationship to exercise have not been well studied in large comprehensive studies outside of tertiary care settings. This study sought to estimate the incidence of HCM-related SCD and its association with exercise in a large unselected population., Methods: Using the Office of the Chief Coroner of Ontario database encompassing all deaths attended by the coroner, we identified all HCM-related SCDs in individuals 10 to 45 years of age between 2005 and 2016 (70 million person-years). Confirmation of HCM was based on typical macroscopic and microscopic features (definite HCM-related SCD). Sudden deaths with a prior clinical diagnosis of HCM but no autopsy were considered probable HCM-related SCDs. Cases with typical features but no myofiber disarray were considered possible HCM. The completeness of data was verified in a subset of patients in the Toronto area with the use of a registry of all emergency medical services-attended cardiac arrests, with an autopsy rate of 94%. To estimate the number of HCM-related aborted cardiac arrests and lives potentially saved by implantable cardioverter-defibrillators, all de novo implantations for secondary prevention and all implantations and appropriate shocks for primary prevention in patients with HCM 10 to 45 years of age, respectively, were identified with the use of a registry containing data on implantable cardioverter-defibrillator implantations from all implanting sites throughout Ontario., Results: Forty-four, 3, and 6 cases of definite, probable, and possible HCM-related SCDs, respectively, were identified, corresponding to estimated annual incidence rates of 0.31 per 1000 HCM person-years (95% CI, 0.24-0.44) for definite HCM-related SCD, 0.33 per 1000 HCM person-years (95% CI, 0.34-0.62) for definite or probable HCM-related SCD, and 0.39 per 1000 HCM person-years (95% CI, 0.28-0.49) for definite, probable, or possible HCM-related SCD (estimated 140 740 HCM person-years of observation). The estimated annual incidence rate for HCM-related SCD plus aborted cardiac arrest and HCM-related life-threatening arrhythmia (SCD, aborted cardiac arrest, and appropriate implantable cardioverter-defibrillator shocks) was 0.84 per 1000 HCM person-years (95% CI, 0.70-1.0). The majority (70%) of SCDs occurred in previously undiagnosed individuals. Most SCDs occurred during rest (64.8%) or light activity (18.5%)., Conclusions: The incidence of HCM-related SCD in the general population 10 to 45 years of age is substantially lower than previously reported, with most cases occurring in previously undiagnosed individuals. SCDs are infrequently related to exercise.

Background: Because of previous ventricular arrhythmia (VA) episodes, patients with implantable cardioverter-defibrillator (ICD) for secondary prevention (SP) are generally considered to have a higher burden of VAs than primary prevention (PP) patients. However, when PP patients experienced VA, the difference in the prognosis of these two patient groups was unknown., Methods: The clinical characteristics and follow-up data of 835 ICD patients (364 SP patients and 471 PP patients) with home monitoring feature were retrospectively analysed. The incidence rate and risk of subsequent VA and all-cause mortality were compared between PP patients after the first appropriate ICD therapy and SP patients., Results: During a mean follow-up of 44.72 ± 20.87 months, 210 (44.59%) PP patients underwent appropriate ICD therapy. In the Kaplan-Meier survival analysis, the PP patients after appropriate ICD therapy were more prone to VA recurrence and all-cause mortality than SP patients (P<0.001 for both endpoints). The rate of appropriate ICD therapy and all-cause mortality in PP patients after the first appropriate ICD therapy was significantly higher than that in SP patients (for device therapy, 59.46 vs 20.64 patients per 100 patient-years; incidence rate ratio [IRR] 2.880, 95% confidence interval [CI]: 2.305-3.599; P<0.001; for all-cause mortality, 14.08 vs 5.40 deaths per 100 patient-years; IRR 2.607, 95% CI: 1.884-3.606; P<0.001). After propensity score matching for baseline characteristics, the risk of VA recurrence in PP patients with appropriate ICD therapy was still higher than that in SP patients (41.80 vs 19.10 patients per 100 patient-years; IRR 2.491, 95% CI: 1.889-3.287; P<0.001), but all-cause mortality rates were similar between the two groups (12.61 vs 9.33 deaths per 100 patient-years; IRR 1.352, 95% CI: 0.927-1.972; P = 0.117)., Conclusions: Once PP patients undergo appropriate ICD therapy, they will be more prone to VA recurrence and death than SP patients.

(1) Background: Studies indicate that lesbian, gay, bisexual, transgender and intersex (LGBTI) people constantly face challenges and disadvantages in the health care system that prevent them from getting the best possible patient-centered care. However, the present study is the first to focus on LGBTI-related health in a major German metropolis. It aimed to investigate health care structures, prevention measures and diagnostic as well as treatment procedures that LGBTI individuals need in order to receive appropriate patient-centered health care and health promotion. (2) Methods: Following a participatory approach, five expert interviews with LGBTI people with multiplier function, i.e., people who have a key role in a certain social milieu which makes them able to acquire and spread information in and about this milieu, and three focus groups with LGBTI people and/or health professionals were conducted. Qualitative data were analyzed according to the principles of content analysis. (3) Results: The specific needs of LGBTI individuals must be recognized as a matter of course in terms of depathologization, sensitization, inclusion, and awareness. Such an attitude requires both basic knowledge about LGBTI-related health issues, and specific expertise about sufficient health care services for each of the minorities in the context of sex, sexual orientation and gender identity. (4) Conclusions: For an appropriate approach to LGBTI-centered health care and health promotion, health professionals will need to adopt a better understanding of specific soft and hard skills.

Introduction: Clinical trials did not provide conclusive evidence concerning the benefit of prophylactic implantable cardioverter-defibrillators (ICDs) in patients with severe nonischemic cardiomyopathy (NICM). We aimed to compare incidence of appropriate sustained ventricular arrhythmia (SVA) and device therapy in ischemic cardiomyopathy (ICM) vs NICM ICD and/or cardiac resynchronization therapy (CRT-D) patients., Methods and Results: We analyzed remote-monitoring data from devices of the Home Monitoring Expert Alliance network. SVA recordings were adjudicated by three independent electrophysiologists. Our cohort included 1,946 patients who received either an ICD (55%) or a CRT-D (45%) for primary prevention of sudden cardiac death. Median (interquartile range) age was 70 (62-77) years, 81% were male, and 52% were in the ICM group. Patients were remotely monitored for a maximum follow-up of 5 years. The 5-year product-limit estimate of SVA incidence in patients with an ICD was 47.3% (95% confidence interval [CI], 41.0%-53.9%) in the ICM group and 44.7% (36.9%-53.3%) in the NICM group. In patients with a CRT-D, SVA incidence was 45.7% (37.3%-55.0%) in ICM patients and 49.2% (40.4%-58.7%) in NICM patients. The adjusted hazard ratio for SVA in the ICM vs NICM group was 0.96 (95% CI: 0.70-1.30, P = .77) in ICD patients and 0.85 (95% CI: 0.61-1.18, P = .34) in CRT-D patients. SVAs triggered appropriate device therapies with similar incidence in all groups., Conclusion: In a large cohort of remotely monitored ICD and CRT-D recipients, SVA incidence did not significantly differ in ICM and NICM patients., (© 2019 Wiley Periodicals, Inc.)

Background: Patients with high stroke risk and atrial fibrillation who are unsuitable to oral anticoagulants (OACs) require other stroke prevention strategies. A novel permanent coil filter directly placed into both common carotid arteries (CCAs) was designed to capture emboli >1.4 mm in diameter., Objectives: The multicenter, nonrandomized, first-in-human clinical CAPTURE (Carotid Artery Implant for Trapping Upstream Emboli for Preventing Stroke in Atrial Fibrillation Patients) trial sought to determine the feasibility and safety of bilateral CCA filter placement., Methods: Eligible patients had atrial fibrillation, CHA 2 DS 2 -VASc (Congestive heart failure, Hypertension, Age 75 years, Diabetes, Stroke/transient ischemic attack, Vascular disease, Age 65 to 74 years, Sex category) ≥2, OAC unsuitability, CCA size 4.8 to 9.8 mm, and no carotid stenosis >30%. Under ultrasound guidance, after direct transcutaneous carotid puncture with a 24-gauge needle, a motorized unit expels the filter to unfurl in the artery. Patients received aspirin/clopidogrel for 3 months, and aspirin thereafter. Primary endpoints were: 1) procedural success-bilateral, properly positioned CCA filters; and 2) 30-day incidence of major adverse events-death, stroke, major bleeding, filter migration, CCA thrombus, or stenosis. Carotid ultrasounds were conducted post-procedure, pre-discharge, at 1 week, and at 1, 3, 6, and 12 months., Results: At 3 centers, 25 patients were enrolled: age 71 ± 9 years, CHA 2 DS 2 -VASc = 4.4 ± 1.0, prior embolism in 48%. Procedure success was 92% (23 of 25 patients); 1 patient had unilateral deployment. There were no device/procedure-related major adverse events; minor puncture site hematomas/edema occurred in 5 of 25 (20%). After 6-month mean follow-up, asymptomatic thrombi were detected in 4 patients (1 bilateral, 4 unilateral), adjudicated as captured (n = 3), unclassified (n = 2), or in situ (n = 0). In all patients, the thrombi dissolved with subcutaneous heparin. In 1 patient, 2 device/procedure-unrelated minor strokes occurred., Conclusions: Permanent carotid filter placement for stroke prophylaxis is technically feasible and safe. (Carotid Artery Implant for Trapping Upstream Emboli for Preventing Stroke in Atrial Fibrillation Patients [CAPTURE]; NCT03571789)., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

Aims: The safety of omitting implantable cardioverter-defibrillator (ICD) generator replacement in patients with no prior appropriate therapy, comorbid conditions, and advanced age is unclear. The aim was to investigate incidence of appropriate ICD therapy after generator replacement., Methods and Results: We identified patients implanted with a primary prevention ICD (n = 4630) from 2007 to 2016, who subsequently underwent an elective ICD generator replacement (n = 670) from the Danish Pacemaker and ICD Register. The data were linked to other databases and evaluated the outcomes of appropriate therapy and death. Predictors of ICD therapy were identified using multivariate Cox regression analyses. A total of 670 patients underwent elective ICD generator replacement. Of these, 197 (29.4%) patients had experienced appropriate therapy in their 1st generator period. During follow-up of 2.0 ± 1.6 years, 95 (14.2%) patients experienced appropriate therapy. Predictors of appropriate therapy in 2nd generator period was low initial left ventricular ejection fraction (≤25%) [hazard ratio (HR) 1.87, confidence interval (CI) 1.13-1.95] and appropriate therapy in 1st generator period (HR 3.95, CI 2.57-6.06). For patients with appropriate therapy in 1st generator period, 4-year incidence of appropriate therapy was 50.6% vs. 16.4% in those without (P < 0.001). Among patients >80 years with no prior appropriate therapy 8.8% of patients experienced appropriate therapy after replacement. Comorbidity burden and advanced age were associated with reduced device utilization after replacement and a high competing risk of death without preceding appropriate therapy., Conclusion: A significant residual risk of appropriate therapy in the 2nd generator was present even among patients with advanced age and with a full prior generator period without any appropriate ICD events., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2019. For permissions, please email: journals.permissions@oup.com.)

Objectives: The aim of this study was to assess the utility of left ventricular (LV) entropy, a novel measure of myocardial heterogeneity, for predicting cardiovascular events in patients with dilated cardiomyopathy (DCM)., Background: Current risk stratification for ventricular arrhythmia in patients with DCM is imprecise. LV entropy is a measure of myocardial heterogeneity derived from cardiac magnetic resonance imaging that assesses the probability distribution of pixel signal intensities in the LV myocardium., Methods: A registry-based cohort of primary prevention implantable cardioverter-defibrillator patients with DCM had their LV entropy, late gadolinium enhancement (LGE) presence, and LGE mass measured on cardiac magnetic resonance imaging. Patients were followed from implantable cardioverter-defibrillator placement for arrhythmic events (appropriate implantable cardioverter-defibrillator therapy, ventricular arrhythmia, or sudden cardiac death), end-stage heart failure events (cardiac death, transplantation, or ventricular assist device placement), and all-cause mortality., Results: One hundred thirty patients (mean age 55 years, 83% men, LV ejection fraction 29%, mean LV entropy 5.58 ± 0.72, LGE present in 57%) were followed for a median of 3.2 years. Eighteen (14.0%) experienced arrhythmic events, 17 (13.1%) experienced end-stage heart failure events, and 7 (5.4%) died. LV entropy provided substantial improvement of predictive ability when added to a model containing clinical variables and LGE mass (hazard ratio: 3.5; 95% confidence interval: 1.42 to 8.82; p = 0.007; net reclassification index = 0.345, p = 0.04). For end-stage heart failure events, LV entropy did not improve the model containing clinical variables and LGE mass (hazard ratio: 2.03; 95% confidence interval: 0.78 to 5.28; p = 0.14). Automated LV entropy measurement has excellent intraobserver (mean difference 0.04) and interobserver (mean difference 0.03) agreement., Conclusions: Automated LV entropy measurement is a novel marker for risk stratification toward ventricular arrhythmia in patients with DCM., (Copyright © 2019. Published by Elsevier Inc.)

Introduction: Dual-coil leads (DC-leads) were the standard of choice since the first nonthoracotomy implantable cardioverter/defibrillator (ICD). We used contemporary data to determine if DC-leads offer any advantage over single-coil leads (SC-leads), in terms of defibrillation efficacy, safety, clinical outcome, and complication rates., Methods and Results: In the Shockless IMPLant Evaluation study, 2500 patients received a first implanted ICD and were randomized to implantation with or without defibrillation testing. Two thousand and four hundred seventy-five patients received SC-coil or DC-coil leads (SC-leads in 1025/2475 patients; 41.4%). In patients who underwent defibrillation testing (n = 1204), patients with both lead types were equally likely to achieve an adequate defibrillation safety margin (88.8% vs 91.2%; P = 0.16). There was no overall effect of lead type on the primary study endpoint of "failed appropriate shock or arrhythmic death" (adjusted HR 1.18; 95% CI, 0.86-1.62; P = 0.300), and on all-cause mortality (SC-leads: 5.34%/year; DC-leads: 5.48%/year; adjusted HR 1.16; 95% CI, 0.94-1.43; P = 0.168). However, among patients without prior heart failure (HF), and SC-leads had a significantly higher risk of failed appropriate shock or arrhythmic death (adjusted HR 7.02; 95% CI, 2.41-20.5). There were no differences in complication rates., Conclusion: In this nonrandomized evaluation, there was no overall difference in defibrillation efficacy, safety, outcome, and complication rates between SC-leads and DC-leads. However, DC-leads were associated with a reduction in the composite of failed appropriate shock or arrhythmic death in the subgroup of non-HF patients. Considering riskier future lead extraction with DC-leads, SC-leads appears to be preferable in the majority of patients., (© 2019 Wiley Periodicals, Inc.)

Background: A long-detection interval (LDI) programming has been proved to reduce shock therapy in patients who underwent de novo implantable cardioverter defibrillator (ICD) implantation. We aimed to evaluate effectiveness and safety of this new strategy in old ICD recipients. Methods: We included 147 primary prevention patients with ischaemic and non-ischaemic aetiology. Conventional setting parameters (18 of 24 intervals to detect ventricular arrhythmias (VA's)) were reprogrammed with LDI strategy (30 of 40 intervals to detect VA's). One monitoring zone (between 360 and 330 ms) and two therapy zones were programmed, treating all rhythms of cycle length <330 ms that met the duration criterion of 30/40 intervals and were discriminated as ventricular tachycardia/ventricular fibrillation (VT/VF). The supraventricular tachycardia (SVT) discriminators were used in all patients. Results: At a median follow-up of 24 months, 12.9% ( n  = 19) of patients received shock therapies (± antitachycardia pacing (ATP)). Appropriate and inappropriate shocks occurred in 7.5 and 5.4% of patients during follow-up, respectively. Only one patient experienced an arrhythmic syncope during the follow-up period. There was no death related to LDI programming. The LDI programming helped to stop unnecessary in 10 patients (6.8%), who otherwise would have been treated in the conventional programming. Conclusions: LDI programming was found safe and effective. Hence, old ICD recipients will benefit from this strategy.

Background: Impaired left ventricular (LV) contraction and relaxation may further promote adverse remodeling and may increase the risk of ventricular arrhythmia (VA) in ischemic cardiomyopathy. We aimed to examine the association of cardiovascular magnetic resonance (CMR)-derived circumferential strain parameters for LV regional systolic function, LV diastolic function and mechanical dispersion with the risk of VA in patients with prior myocardial infarction and primary prevention implantable cardioverter defibrillator (ICD)., Methods: Patients with an ischemic cardiomyopathy who underwent CMR prior to primary prevention ICD implantation, were retrospectively identified. LV segmental circumferential strain curves were extracted from short-axis cine CMR. For LV regional strain analysis, the extent of moderately and severely impaired strain (percentage of LV segments with strain between - 10% and - 5% and > - 5%, respectively) were calculated. LV diastolic function was quantified by the early and late diastolic strain rate. Mechanical dispersion was defined as the standard deviation in delay time between each strain curve and the patient-specific reference curve. Cox proportional hazard ratios (HR) (95%CI) were calculated to assess the association between LV strain parameters and appropriate ICD therapy., Results: A total of 121 patients (63 ± 11 years, 84% men, LV ejection fraction (LVEF) 27 ± 9%) were included. During a median (interquartile range) follow-up of 47 (27;69) months, 30 (25%) patients received appropriate ICD therapy. The late diastolic strain rate (HR 1.1 (1.0;1.2) per - 0.25 1/s, P = 0.043) and the extent of moderately impaired strain (HR 1.5 (1.0;2.2) per + 10%, P = 0.048) but not the extent of severely impaired strain (HR 0.9 (0.6;1.4) per + 10%, P = 0.685) were associated with appropriate ICD therapy, independent of LVEF, late gadolinium enhancement (LGE) scar border size and acute revascularization. Mechanical dispersion was not related to appropriate ICD therapy (HR 1.1 (0.8;1.6) per + 25 ms, P = 0.464)., Conclusions: In an ischemic cardiomyopathy population referred for primary prevention ICD implantation, the extent of moderately impaired strain and late diastolic strain rate were associated with the risk of appropriate ICD therapy, independent of LVEF, scar border size and acute revascularization. These findings suggest that disturbed LV contraction and relaxation may contribute to an increased risk of VA after myocardial infarction.

Background: Left ventricular ejection fraction lacks accuracy in predicting sudden cardiac death, resulting in unnecessary implantation of cardioverter defibrillators for the primary prevention of sudden cardiac death. Baroreflex sensitivity could help to stratify patients at risk of ventricular arrhythmia., Aim: To assess the association between cardiac baroreflex sensitivity and ventricular arrhythmias in patients implanted with an implantable cardioverter defibrillator for the primary prevention of sudden cardiac death after myocardial infarction., Methods: This case-control single-centre study took place between 2015 and 2016. Cases (n=10) had experienced ventricular arrhythmias treated by the implantable cardioverter defibrillator in the previous 3 years; controls (n=22) had no arrhythmia during the same period. Baroreflex sensitivity was assessed using the temporal sequence method (mean slope) and cross-spectral analysis (low-frequency gain and high-frequency gain)., Results: The mean age was 65 years; 94% of the patients were men. 24-hour Holter electrocardiogram autonomous nervous system variables, left ventricular ejection fraction and N-terminal prohormone of B-type natriuretic peptide (NT-proBNP) concentration did not differ between cases and controls. The mean slope was lower in cases than in controls (8 vs. 15ms/mmHg [P=0.009] in the supine position; 7 vs. 12ms/mmHg [P=0.038] in the standing position). The mean slope in the supine position was still significantly different between groups after adjustment for age, left ventricular ejection fraction and NT-proBNP (P=0.03). By comparison, low-frequency gain and high-frequency gain did not differ between groups in either the supine or the standing position., Conclusion: Patients with ventricular arrhythmias had a lower mean slope compared with those who were free of arrhythmia. A prospective study is needed to confirm this association., (Copyright © 2019 Elsevier Masson SAS. All rights reserved.)

Aims: Patients with cancer are insufficiently represented in randomized clinical trials investigating efficacy of implantable cardioverter-defibrillators (ICDs). We aimed to describe outcomes in patients with a pre-existing diagnosis of cancer at time of ICD implantation., Methods and Results: We utilized Danish nationwide registries to identify primary and secondary prevention ICD implantations from 2007 to 2012. Multivariable Cox models were used to assess the risk of appropriate ICD therapy and mortality in patients with and without cancer at time of implantation. During a median follow-up of 2.1 years, 2935 primary prevention ICD and 2730 secondary prevention ICD implantations were identified. Out of these [289 (5.1%)] had pre-existing cancer [primary 140 (4.8%), secondary 149 (5.5%)]. No differential risk for appropriate ICD therapy was found between patients with or without cancer, [primary cancer: 19/140, no cancer: 380/2795, hazard ratio (HR) = 1.07 (0.67-1.69)] and [secondary cancer: 42/149, no cancer: 699/2581, HR = 1.28 (0.93-1.75)]. In primary patients, cancer was not associated with higher risk of 1-year [cancer: 10/140, no cancer: 133/2795, HR = 1.20 (0.84-2.28)] or all-time mortality [cancer: 22/140, no cancer: 339/2795, HR = 1.13 (0.74-1.75)]. In secondary patients, cancer was associated with a higher 1-year [cancer: 19/149, no cancer: 108/2581, HR = 2.62 (1.60-4.29)] and all-time mortality [cancer: 44/149, no cancer: 315/2581, HR = 2.36 (1.71-3.24)]., Conclusion: Implantable cardioverter-defibrillators were implanted in a minority of cancer patients. No difference in risk of appropriate therapy was observed between cancer and non-cancer patients, regardless of implant indication. Cancer was associated with increased mortality in secondary prevention ICD patients, but not in primary prevention ICD patients. In secondary prevention ICD patients, the majority of deaths were attributable to cancer., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2018. For permissions, please email: journals.permissions@oup.com.)

Aims: Prospective data regarding the role of implantable cardioverter-defibrillator (ICD) for the primary prevention of sudden cardiac death in patients with long QT syndrome (LQTS) is scarce. Herein, we explore the prospective Rochester LQTS ICD registry to assess the risk for appropriate shock in primary prevention in a real-world setting., Methods and Results: We studied 212 LQTS patients that had ICD implantation for primary prevention. Best-subsets proportional-hazards regression analysis was used to identify clinical variables that were associated with the first appropriate shock. Conditional models of Prentice, Williams, and Peterson were utilized for the analysis of recurrent appropriate shocks. During a median follow-up of 9.2 ± 4.9 years, there were 42 patients who experienced at least one appropriate shock and the cumulative probability of appropriate shock at 8 years was 22%. QTc ≥ 550 ms [hazard ratio (HR) 3.94, confidence interval (CI) 2.08-7.46; P < 0.001) and prior syncope on β-blockers (HR 1.92, CI 1.01-3.65; P = 0.047) were associated with increased risk of appropriate shock. History of syncope while on β-blocker treatment (HR 1.87, CI 1.28-2.72; P = 0.001), QTc 500-549 ms (HR 1.68, CI 1.10-2.81; P = 0.048), and QTc ≥ 550 ms (HR 3.66, CI 2.34-5.72; P < 0.001) were associated with increased risk for recurrent appropriate shocks, while β-blockers were not protective (HR 1.03, CI 0.63-1.68, P = 0.917). LQT2 (HR 2.10, CI 1.22-3.61; P = 0.008) and multiple mutations (HR 2.87, CI 1.49-5.53; P = 0.002) were associated with higher risk for recurrent shocks as compared with LQT1., Conclusion: In this prospective ICD registry, we identified clinical and genetic variables that were associated appropriate shock risk. These data can be used for risk stratification in high-risk patients evaluated for primary prevention with ICD.

Background: The frequency, characteristics and outcomes of primary prevention implantable cardioverter defibrillator (ICD) recipients who eventually undergo heart transplantation (HT) during follow-up have not been well described., Aims: In a cohort of patients with heart failure implanted with an ICD for primary prevention of sudden cardiac death, to identify those at high risk of subsequent HT and evaluate ICD usefulness., Methods: Between 2002 and 2012, 5539 patients received a primary prevention ICD across 12 centers, and were enrolled in the DAI-PP programme, including 5427 with full HT information available., Results: During a median follow-up of 1024 days (interquartile range 484-1702 days), 176 (3.2%) patients underwent HT. Median duration between ICD implantation and HT was 484 days (IQR 169-1117 days). Among those aged≤65 years (theoretical age limit for HT registration in France), the overall incidence per 1000 person-years was 18.03 (95% confidence interval [CI]: 15.32-20.74). Left ventricular ejection fraction<25% (hazard ratio [HR]: 3.43, 95% CI: 2.34-5.04; P<0.0001), younger age (HR: 0.95, 95% CI: 0.93-0.96; P<0.0001), New York Heart Association (NYHA) class III-IV (HR: 2.67, 95% CI: 1.79-4.00; P<0.0001) and no cardiac resynchronization therapy (HR: 2.09, 95% CI: 1.39-3.14; P=0.0004) were independently associated with HT. Patients with these three characteristics (excluding age) had a 1-year HT rate of 15.2%. Incidence of appropriate ICD therapies was 92.7 per 1000 person-years for patients who underwent HT versus 76.1 for those who did not (P=0.64)., Conclusions: The overall incidence of HT in this primary prevention population was relatively high, especially among young patients with a very low ejection fraction, an advanced NYHA class and were unsuitable for cardiac resynchronization therapy (up to 15% annually). Patients awaiting HT experienced a significant rate of appropriate ICD therapies, reinforcing the importance of specific cardiac rhythm management in these patients., (Copyright © 2018. Published by Elsevier Masson SAS.)

Objectives: This study describes the development of a decision support tool to identify the combination of suicide prevention activities and service priorities likely to deliver the greatest reductions in suicidal behaviour in Western Sydney (Australia) over the period 2018-2028., Methods: A dynamic simulation model for the WentWest - Western Sydney Primary Health Network population-catchment was developed in partnership with primary health network stakeholders based on defined pathways to mental health care and suicidal behaviour, and which represented the current incidence of suicide and attempted suicide in Western Sydney. A series of scenarios relating to potential suicide prevention activities and service priorities identified by primary health network stakeholders were investigated to identify the combination of interventions associated with the largest reductions in the forecast number of attempted suicide and suicide cases for a 10-year follow-up period., Results: The largest number of cases averted for both suicide and attempted suicide was associated with (1) post-suicide attempt assertive aftercare (6.1% for both attempted suicide and suicide), (2) improved community support and reductions in psychological distress in the community (5.1% for attempted suicide and 14.8% for suicide), and (3) reductions in the proportion of those lost to services following a mental health service contact (10.5% for both attempted suicide and suicide). In combination, these interventions were forecast to avert approximately 29.7% of attempted suicides and 37.1% of suicides in the primary health network catchment over the 10-year period., Conclusion: This study demonstrates the utility of dynamic simulation models, co-designed with multi-disciplinary stakeholder groups, to capture and analyse complex mental health and suicide prevention regional planning problems. The model can be used by WentWest - Western Sydney Primary Health Network as a decision support tool to guide the commissioning of future service activity, and more efficiently frame the monitoring and evaluation of interventions as they are implemented in Western Sydney.

Aims: There is a paucity of studies investigating a dose-dependent association between beta-blocker therapy and risk of outcome. In a nationwide cohort of primary prevention implantable cardioverter-defibrillator (ICD) patients, we aimed to investigate the dose-dependent association between beta-blocker therapy and risk of ventricular tachyarrhythmias (VT/VF), heart failure (HF) hospitalizations, and death., Methods and Results: Information on ICD implantation, endpoints, comorbidities, beta-blocker usage, type, and dose were obtained through Danish nationwide registers. The two major beta-blockers carvedilol and metoprolol were examined in three dose levels; low (metoprolol ≤ 25 mg; carvedilol ≤ 12.5 mg), intermediate (metoprolol 26-199 mg; carvedilol 12.6-49.9 mg), and high (metoprolol ≥ 200 mg; carvedilol ≥ 50 mg). Time to events was investigated utilizing multivariate Cox models with beta-blocker as a time-dependent variable. From 2007 to 2012, 2935 first-time ICD devices were implanted. During follow-up, 399 patients experienced VT/VF, 728 HF hospitalizations and 361 died. As compared with patients not on beta-blockers, low, intermediate, and high dose had significantly reduced risk of HF hospitalizations {hazard ratio (HR) = 0.68 [0.54-0.87], P = 0.002; HR = 0.53 [0.42-0.66], P < 0.001; HR = 0.43 [0.34-0.54], P < 0.001} and death (HR = 0.47 [0.35-0.64], P < 0.001; HR = 0.29 [0.22-0.39], P = 0.001; HR = 0.24 [0.18-0.33], P < 0.001). For the endpoint of VT/VF, only intermediate and high dose beta-blocker was associated with significantly reduced risk (HR = 0.58 [0.43-0.79], P < 0.001; HR = 0.53 [0.39-0.72], P < 0.001). No significant difference was found between comparable doses of carvedilol and metoprolol on any endpoint (P = 0.06-0.94)., Conclusion: In primary prevention ICD patients, beta-blocker therapy was associated with significantly reduced risk of all endpoints, as compared with patients not on beta-blocker, with the suggestion of a dose-dependent effect. No detectable difference was found between comparable doses of carvedilol and metoprolol.

Aim: Primary prophylactic implantable cardioverter defibrillators (ICDs) have demonstrated a clear all-cause mortality benefit in patients with ischaemic cardiomyopathy, with less compelling evidence supporting its use in patients with non-ischaemic cardiomyopathy (NICM). We performed a meta-analysis of randomized controlled trials (RCTs) evaluating the role of ICD for reduction in total mortality in NICM patients., Methods and Results: An electronic search on PubMed, the Cochrane Library, and EMBASE databases was performed to identify the RCTs evaluating the role of prophylactic ICD placement in NICM patients. Mantel-Haenszel risk ratio (RR) fixed-effects model was used to summarize data across treatment arms. Random-effects model was used if heterogeneity (I2) ≥ 25. Patients with cardiac resynchronization therapy pacemaker (CRT-P) were included in the control group. Six RCTs, with a total of 3128 patients and a mean follow-up period of 48 ± 22 months comparing ICD with medical therapy in NICM were included in this analysis. There was a significant reduction in all-cause mortality in the ICD group compared with the medical therapy group [RR 0.79, 95% confidence interval (95% CI) 0.68-0.92; P = 0.002]. No publication bias was noted., Conclusion: Currently available evidence demonstrates that the use of ICD provides a clear and significant reduction in all-cause mortality among patients with NICM.

Background Implantable cardioverter defibrillators (ICDs) are an important part of therapy for many patients, yet there is little data on population characteristics, complications, or system survival in pediatric patients. Methods A retrospective review of ICD recipients in the National Cardiovascular Data Registry ICD Registry was performed from 2010 to 2016. Patient characteristics and complications between pediatric (≤21 years) and adult populations (>21 years) were compared. Variables associated with complications and early device interventions within the pediatric cohort were evaluated using multivariate modeling. Results There were 562 209 total ICD implants, of which 3461 occurred in the pediatric cohort. Among the pediatric patients, 60% of implants were for primary prevention, and nonischemic cardiomyopathy was the most common underlying disease (60%). Over time, there was an increasing trend of both primary and secondary prevention ICD implantations ( P<0.05). Compared with adults, pediatric patients were more likely to have structural heart disease, hypertrophic cardiomyopathy, and channelopathy, and to receive a single-chamber device (all P<0.001). There was no difference in inhospital complications between the adult and pediatric cohorts (2.4% versus 2.6%, P=0.3). However, among the pediatric patients, lower weight, Ebstein anomaly, worse New York Heart Association class, dual chamber, and cardiac resynchronization therapy-defibrillator were associated with greater risk of complications. Although reintervention for generator replacement or upgrade was more common in adults, the time to reintervention was shorter in the pediatric cohort. Conclusions We observed an increasing trend in ICD device implantation among pediatric patients. The pediatric cohort had similar inhospital complication rates compared with adults but had a shorter time to reintervention.

Prevention of sudden cardiac death (SCD) remains a partly unsolved task in cardiology. The European Society of Cardiology (ESC) guidelines on management of patients with ventricular arrhythmias and prevention of SCD published in 2015 considered the new insights of the natural history of diseases predisposing to SCD. The guidelines improved strategies for management of patients at risk of SCD and included both drug and device therapies. The intention of this survey was to evaluate the extent of the disparities between daily clinical practice and the 2015 SCD ESC guidelines among electrophysiology centres in Europe. The results suggest that the adherence to guidelines is reasonably high and strategies for the management of ischaemic disease are well-established. Implantable cardioverter-defibrillator indications for primary prevention are a difficult topic, particularly in non-ischaemic dilated cardiomyopathy. Disparities in the use of genetic testing are probably due to differences in local availability.

Background: Newer implantable cardioverter defibrillators can monitor intracardiac ECGs , but their ability to detect ischemia is unclear. This study investigated the usefulness of implantable cardioverter defibrillators with an ST-monitoring function in coronary artery disease patients., Methods and Results: We conducted a prospective study of implantable cardioverter defibrillator patients with the ST-monitoring function. One hundred seventy-three patients who received implantable cardioverter defibrillators for primary or secondary prevention of sudden cardiac death. All patients underwent medical examinations at least every 6 months, with standard 12-lead ECGs and device checks that included analysis of the ST-monitoring function. Myocardial perfusion imaging or coronary angiography was performed during the follow-up. The mean follow-up duration was 23.3±7.7 months. Significant ST changes occurred in 15 patients (8.7%), of whom 14 were asymptomatic. The incidence of angina pectoris was significantly higher in the ST change (+) group than that in the ST change (-) group (28.6% versus 7.2%, P =0.03). In the patients who underwent myocardial perfusion imaging, the sensitivity, specificity, and negative predictive value of the ST-monitoring feature to detect ischemia were 75.0%, 72.5%, and 93.5%, respectively. The sensitivity, specificity, and negative predictive value of the ST-monitoring feature to predict residual stenosis evaluated using coronary angiography were 76.9%, 83.5%, and 97.5%, respectively. The percentage of patients with a septal right ventricular lead was significantly lower in the ST change (+) group than in the ST change (-) group (13.5% versus 33.5%, P =0.01)., Conclusions: If intracardiac ECGs ST changes are detected, it is necessary to use additional modalities even in asymptomatic patients., Clinical Trial Registration: URL: upload.umin.ac.jp. Unique identifier: UMIN000011824., (© 2018 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.)

Background: Prior studies have shown a close link between exercise and development of arrhythmogenic right ventricular cardiomyopathy. How much exercise restriction reduces ventricular arrhythmia (VA), how genotype modifies its benefit, and whether it reduces risk sufficiently to defer implantable cardioverter-defibrillator (ICD) placement in arrhythmogenic right ventricular cardiomyopathy are unknown., Methods and Results: We interviewed 129 arrhythmogenic right ventricular cardiomyopathy patients (age: 34.0±14.8 years; male: 60%) with ICDs (36% primary prevention) about exercise participation. Exercise change was defined as annual exercise duration and dose in the 3 years before clinical presentation minus that after presentation. The primary outcome was appropriate ICD therapy for VA. During the 5.1 years (interquartile range: 2.7-10.8 years) after presentation, 74% (95/129) patients reduced exercise dose and 85 (66%) patients experienced the primary outcome. In multivariate analyses, top tertile reduction in exercise duration and dose were both associated with less VA (duration: hazard ratio: 0.23 [95% confidence interval, 0.07-0.81]; dose: hazard ratio: 0.14 [95% confidence interval, 0.04-0.44]). Greater reduction in exercise dose conferred greater reduction in VA ( P =0.01 for trend). Patients without desmosomal mutations and those with primary-prevention ICDs benefited more from exercise reduction ( P =0.16 and P =0.06 for interaction); however, 58% (18/31) of athletes who reduced exercise dose by >80% still experienced VA., Conclusions: Exercise restriction should be recommended to all arrhythmogenic right ventricular cardiomyopathy patients with ICDs. Patients who are "gene-elusive" and those with primary-prevention devices may particularly benefit. Exercise reduction is unlikely to reduce arrhythmia sufficiently in high-risk patients to alter decision-making regarding ICD implantation., (© 2018 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.)

Background: Previous studies report conflicting results about a higher incidence of ventricular arrhythmias in patients with a chronic total coronary occlusion (CTO). We aimed to investigate this association in a large cohort of implantable cardioverter defibrillator patients with long-term follow-up., Methods and Results: All consecutive patients from 1992 onwards who underwent implantable cardioverter defibrillator implantation for ischemic cardiomyopathy at the Leiden University Medical Center were evaluated. Coronary angiograms were reviewed for the presence of a CTO. The occurrence of ventricular arrhythmias and survival status at follow-up were compared between patients with and patients without a CTO. A total of 722 patients constitute the study cohort (age 66±11 years; 84% males; 74% primary prevention, median left ventricular ejection fraction 30% [first-third quartile: 25-37], 44% received a cardiac resynchronization therapy defibrillator). At baseline, 240 patients (33%) had a CTO, and the CTOs were present for at least 44 (2-127) months. The median follow-up duration was 4 (2-6) years. On long-term follow-up, CTO patients had a higher crude appropriate device therapy rate (37% versus 27%, P =0.010) and a lower crude survival rate (51% versus 67%, P <0.001) compared with patients without a CTO. Corrected for baseline characteristics including left ventricular ejection fraction, the presence of a CTO was an independent predictor for appropriate device therapy., Conclusions: The presence of a CTO in implantable cardioverter defibrillator patients was associated with more appropriate device therapy and worse prognosis at long-term follow-up. Further investigation is warranted regarding a potential beneficial effect of CTO revascularization on the incidence of ventricular arrhythmias., (© 2018 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.)

Aims: Several published investigations demonstrated that a longer T-peak to T-end interval (Tpe) implies increased risk for ventricular tachyarrhythmia (VT/VF) and mortality. Tpe has been measured using diverse methods. We aimed to determine the optimal Tpe measurement method for screening purposes., Methods and Results: We evaluated 305 patients with LVEF ≤ 35% and an implantable cardioverter-defibrillator implanted for primary prevention. Tpe was measured using seven different methods described in the literature, including six manual methods and the automated algorithm '12SL', and was corrected for heart rate. Endpoints were VT/VF and death. To account for differences in the magnitude of Tpe measurements, results are expressed in standard deviation (SD) increments. We evaluated the clinical utility of each measurement method based on predictive ability, fraction of immeasurable tracings, and intra- and interobserver correlation. >Over 31 ± 23 months, 82 (27%) patients had VT/VF, and over 49 ± 21 months, 91 (30%) died. Several rate-corrected Tpe measurement methods predicted VT/VF (HR per SD 1.20-1.34; all P < 0.05), and nearly all methods (both corrected and uncorrected) predicted death (HR per SD 1.19-1.35; all P < 0.05). Optimal predictive ability, readability, and correlation were found in the automated 12SL method and the manual tangent method in lead V2., Conclusion: For the prediction of VT/VF, the utility of Tpe depends upon the measurement method, but for the prediction of mortality, most published Tpe measurement methods are similarly predictive. Heart rate correction improves predictive ability. The automated 12SL method performs as well as any manual measurement, and among manual methods, lead V2 is most useful.

Background: Primary prevention implantable cardioverter-defibrillators (ICDs) reduce mortality in selected patients with left ventricular systolic dysfunction by delivering therapies (antitachycardia pacing or shocks) to terminate potentially lethal arrhythmias; inappropriate therapies also occur. We assessed device therapies among adults receiving primary prevention ICDs in 7 healthcare systems., Methods and Results: We linked medical record data, adjudicated device therapies, and the National Cardiovascular Data Registry ICD Registry. Survival analysis evaluated therapy probability and predictors after ICD implant from 2006 to 2009, with attention to Centers for Medicare and Medicaid Services Coverage With Evidence Development subgroups: left ventricular ejection fraction, 31% to 35%; nonischemic cardiomyopathy <9 months' duration; and New York Heart Association class IV heart failure with cardiac resynchronization therapy defibrillator. Among 2540 patients, 35% were <65 years old, 26% were women, and 59% were white. During 27 (median) months, 738 (29%) received ≥1 therapy. Three-year therapy risk was 36% (appropriate, 24%; inappropriate, 12%). Appropriate therapy was more common in men (adjusted hazard ratio [HR], 1.84; 95% confidence interval [CI], 1.43-2.35). Inappropriate therapy was more common in patients with atrial fibrillation (adjusted HR, 2.20; 95% CI, 1.68-2.87), but less common among patients ≥65 years old versus younger (adjusted HR, 0.72; 95% CI, 0.54-0.95) and in recent implants (eg, in 2009 versus 2006; adjusted HR, 0.66; 95% CI, 0.46-0.95). In Centers for Medicare and Medicaid Services Coverage With Evidence Development analysis, inappropriate therapy was less common with cardiac resynchronization therapy defibrillator versus single chamber (adjusted HR, 0.55; 95% CI, 0.36-0.84); therapy risk did not otherwise differ for Centers for Medicare and Medicaid Services Coverage With Evidence Development subgroups., Conclusions: In this community cohort of primary prevention patients receiving ICD, therapy delivery varied across demographic and clinical characteristics, but did not differ meaningfully for Centers for Medicare and Medicaid Services Coverage With Evidence Development subgroups., (© 2018 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.)

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., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2017. For permissions, please email: journals.permissions@oup.com.)

Sudden death is a major health problem all over the world. The most common causes of sudden death are cardiac but there are also other causes such as neurological conditions (stroke, epileptic attacks and brain trauma), drugs, catecholamine toxicity, etc. A common feature of all these diverse pathologies underlying sudden death is the imbalance of the autonomic nervous system control of the cardiovascular system. This paper reviews different pathologies underlying sudden death with emphasis on the autonomic nervous system contribution, possibilities of early diagnosis and prognosis of sudden death using various clinical markers including autonomic markers (heart rate variability and baroreflex sensitivity), present possibilities of management and promising prevention by electrical neuromodulation.

Objective: To determine the incremental value of implantable cardioverter defibrillators (ICD) in contemporary optimally treated patients with heart failure (HF) undergoing cardiac resynchronisation therapy (CRT)., Methods: Consecutive patients with HF undergoing CRT-pacemaker (CRT-P) or CRT-defibrillator (CRT-D) implantation in a single tertiary care centre between October 2008 and August 2015 were retrospectively evaluated. For patients with a primary prevention indication of the CRT-D, no benefit of the ICD was defined as absence of appropriate therapy (device analysis) or lethal ventricular tachyarrhythmias (mode of death analysis) during follow-up., Results: 687 patients (CRT-P/CRT-D; n=361/326) were followed for 38±22 months. CRT-P recipients were older (75.7±9.1 vs 71.8±9.3 years; p<0.001) and had a higher comorbidity burden. Five patients with CRT-P (1%) experienced episodes of sustained ventricular-tachycardia vs 64 (20%) patients with CRT-D (p<0.001). Remote tele-monitoring detected the episodes of sustained ventricular tachycardia in four patients with CRT-P, allowing for elective upgrade to CRT-D. All-cause mortality was higher in patients with CRT-P versus CRT-D (21% vs 12%, p=0.003), even after adjusting for baseline characteristics (HR 2.5; 95% CI 1.36 to 4.60; p=0.003). However, mode of death analysis revealed a predominant non-cardiac mode of death in CRT-P recipients (n=47 (71%) vs n=13 (38%) in CRT-D, p=0.002). Multivariate analysis revealed that age >80 years, New York Heart Association class IV, intolerance to beta-blockers and underlying non-ischaemic cardiomyopathy were independently associated with little incremental value of a primary prevention ICD on top of CRT., Conclusions: The majority of patients with contemporary HF as currently selected for CRT-P exhibit mainly non-cardiac-driven mortality. Weighing risk of ventricular-tachyarrhythmic death versus risk of all-cause mortality helps to address the incremental value of an ICD to CRT-P., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Background: Influenza is an acute respiratory infectious disease with a high incidence rate in the Chinese army, which directly disturbs military training and affects soldiers' health. Influenza surveillance systems are widely used around the world and play an important role in influenza epidemic prevention and control., Methods: As a theater centers for disease prevention and control, we established an influenza monitoring platform (IMP) in 2014 to strengthen the monitoring of influenza-like illness and influenza virus infection. In this study, we introduced the constitution, influenza virus detection, and quality control for an IMP. The monitoring effect was also evaluated by comparing the monitoring data with data from national influenza surveillance systems. The experiences and problems associated with the platform also were summarized., Results: A theater IMP was established based on 3 levels of medical units, including monitoring sites, testing laboratories and a checking laboratory. A series of measures were taken to guarantee the quality of monitoring, such as technical training, a unified process, sufficient supervision and timely communication. The platform has run smoothly for 3 monitoring years to date. In the 2014-2015 and 2016-2017 monitoring years, sample amount coincided with that obtained from the National Influenza Surveillance program. In the 2015-2016 monitoring year, due to the strict prevention and control measures, an influenza epidemic peak was avoided in monitoring units, and the monitoring data did not coincide with that of the National Influenza Surveillance program. Several problems, including insufficient attention, unreasonable administrative intervention or subordination relationships, and the necessity of detection in monitoring sites were still observed., Conclusions: A theater IMP was established rationally and played a deserved role in the prevention and control of influenza. However, several problems remain to be solved.

Background: The DANISH study (Danish Study to Assess the Efficacy of ICDs [Implantable Cardioverter Defibrillators] in Patients With Non-Ischemic Systolic Heart Failure on Mortality) did not demonstrate an overall effect on all-cause mortality with ICD implantation. However, the prespecified subgroup analysis suggested a possible age-dependent association between ICD implantation and mortality with survival benefit seen only in the youngest patients. The nature of this relationship between age and outcome of a primary prevention ICD in patients with nonischemic systolic heart failure warrants further investigation., Methods: All 1116 patients from the DANISH study were included in this prespecified subgroup analysis. We assessed the relationship between ICD implantation and mortality by age, and an optimal age cutoff was estimated nonparametrically with selection impact curves. Modes of death were divided into sudden cardiac death and nonsudden death and compared between patients younger and older than this age cutoff with the use of χ 2 analysis., Results: Median age of the study population was 63 years (range, 21-84 years). There was a linearly decreasing relationship between ICD and mortality with age (hazard ratio [HR], 1.03; 95% confidence interval [CI], 1.003-1.06; P =0.03). An optimal age cutoff for ICD implantation was present at ≤70 years. There was an association between reduced all-cause mortality and ICD in patients ≤70 years of age (HR, 0.70; 95% CI, 0.51-0.96; P =0.03) but not in patients >70 years of age (HR, 1.05; 95% CI, 0.68-1.62; P =0.84). For patients ≤70 years old, the sudden cardiac death rate was 1.8 (95% CI, 1.3-2.5) and nonsudden death rate was 2.7 (95% CI, 2.1-3.5) events per 100 patient-years, whereas for patients >70 years old, the sudden cardiac death rate was 1.6 (95% CI, 0.8-3.2) and nonsudden death rate was 5.4 (95% CI, 3.7-7.8) events per 100 patient-years. This difference in modes of death between the 2 age groups was statistically significant ( P =0.01)., Conclusions: In patients with systolic heart failure not caused by ischemic heart disease, the association between the ICD and survival decreased linearly with increasing age. In this study population, an age cutoff for ICD implantation at ≤70 years yielded the highest survival for the population as a whole., Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT00542945., (© 2017 American Heart Association, Inc.)