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Adi Finkelstein,1,* Elisheva Leiter,2,* Tanya Reinfeld,2 Ora Levy,2 Sara Hoss,2 Lori Sloman,2 Donna R Zwas2 1Department of Nursing, Faculty of Life and Health Sciences, Jerusalem College of Technology, Jerusalem, Israel; 2Linda Joy Pollin Cardiovascular Wellness Center for Women, Hadassah University Medical Center, Jerusalem, Israel*These authors contributed equally to this workCorrespondence: Elisheva Leiter, Linda Joy Pollin Cardiovascular Wellness Center for Women, Cardiology Department, Hadassah University Medical Center Ein Karem, POB 12000, Jerusalem, 91120, Israel, Tel +1 972 54 332 9044, Email elisheval@hadassah.org.ilPurpose: Cardiovascular disease in women is frequently under-diagnosed and under-treated. Numerous heart centers for women have opened throughout the world to address these disparities; however, there is a paucity of data regarding participants’ perspectives. The current study assesses motivation to participate and perceived benefits in attending a heart center for women (HCW) in Jerusalem, Israel.Methods: This study utilized qualitative methods to assess patients’ motivation and perceived benefits to attending a women’s heart center, particularly as they relate to gender medicine and single-sex staffing. A random sample of 42 clinic patients were asked to participate in interviews. Inclusionary criteria consisted of previous cardiovascular event, active cardiac symptom or three or more cardiovascular disease risk factors. Exclusionary criteria consisted of pregnancy, type 1 diabetes requiring insulin, psychiatric diagnosis that precluded participation, dementia, or other multidisciplinary clinic participation. Interviews were audio recorded and transcribed verbatim. Qualitative data analysis followed Braun and Clarke’s methodology of thematic analysis.Results: The single-sex and gender medicine aspects did not motivate women to attend the HCW, although some participants perceived this as beneficial in retrospect. Women reported that the clinic visit enhanced their knowledge and awareness of issues related to heart disease in women as well as personal health benefits. They reported benefitting from the holistic approach, consideration of their lifestyle, the staff’s expression of concern, personalized attention, common language, and feeling understood.Conclusion: This study describes the patient experience in an all-female HCW, highlighting their motivation for attendance and perceived benefits. While they did not actively seek women-centered care, women reported educational and care provision benefits to their attendance. The care attributes that women identified as beneficial typify the person-centered approach to care. These findings may inform both the design and evaluation of medical care facilities that aim to address the sex and gender disparities in cardiology as well as other medical specialties.Keywords: gender medicine, patient experience, cardiovascular disease, person-centered care

The concept of "type 3 diabetes" has emerged to define alterations in glucose metabolism that predispose individuals to the development of Alzheimer's disease (AD). Novel evidence suggests that changes in the insulin/insulin-like growth factor 1 (IGF-1)/growth hormone (GH) axis, which are characteristic of Diabetes Mellitus, are one of the major factors contributing to excessive amyloid-beta (Aβ) production and neurodegenerative processes in AD. Moreover, molecular findings suggest that insulin resistance and dysregulated IGF-1 signaling promote atherosclerosis via endothelial dysfunction and a pro-inflammatory state. As the pathophysiological role of Aβ1-40 in patients with cardiovascular disease has attracted attention due to its involvement in plaque formation and destabilization, it is of great interest to explore whether a paradigm similar to that in AD exists in the cardiovascular field. Therefore, this review aims to elucidate the intricate interplay between insulin resistance, IGF-1, and Aβ1-40 in the cardiovascular system and assess the applicability of the type 3 diabetes concept. Understanding these relationships may offer novel therapeutic targets and diagnostic strategies to mitigate cardiovascular risk in patients with insulin resistance and dysregulated IGF-1 signaling., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

Introduction: Heart failure with improved ejection fraction (HFimpEF) is a recently defined subtype of HF, characterized by an increase in ejection fraction (EF) after a prior diagnosis of reduced EF. There are limited data on the characteristics and outcome of this patient subset. The study aimed to investigate the clinical profile and prognosis of this patient group., Methods: HFimpEF patients from a large echocardiography database with comprehensive clinical and outcome data were evaluated for clinical characteristics and outcomes including mortality and cardiovascular hospitalizations. HFimpEF was defined as prior HF diagnosis with EF ≤40% followed by an EF increase of ≥10% to >40%., Results: The study included 2,883 patients with an EF ≤40%. 27% (777) fulfilled criteria of HFimpEF. Non-ischemic cardiomyopathy, female sex, and smaller left ventricular dimensions were associated with EF improvement. Median follow-up duration was 1,346 days. Patients with HFimpEF had a significantly improved prognosis compared to those without EF improvement. Patients with a significant improvement in the EF (≥50%) experienced a 30% lower mortality rate (HR: 0.70, 95% CI: 0.57-0.86, p < 0.001) and a decreased risk of cardiovascular hospitalizations., Conclusions: HFimpEF is a distinct clinical entity observed in 27% of patients with initially reduced EF and conveys a better prognosis. However, even with improvement, EF in most patients does not fully recover, and clinical events can still occur., (© 2024 The Author(s). Published by S. Karger AG, Basel.)

Introduction: Anorexia Nervosa (AN) is a psycho-socio-biological disease characterized by severe weight loss as result of dieting and hyperactivity. Effective treatments are scarce, despite its significant prevalence and mortality. AN patients show lower basal insulin levels and increased metabolic clearance, leading to weight loss, cognitive deficits, and hormonal imbalances. Low-dose polymer insulin could potentially reverse these effects by restoring brain function, reducing fear of weight gain, encouraging food intake, and restoring fat depots. This study evaluates an insulin delivery system designed for sustained release and AN treatment., Methods: AN-like model was established through dietary restriction (DR). On days 1-25, mice were on DR, and on days 26-31 they were on ad libitum regimen. An insulin-loaded delivery system was administered subcutaneously (1% w/w insulin). The impact of insulin treatment on gene expression in the hippocampus (cognition, regulation of stress, neurogenesis) and hypothalamus (eating behavior, mood) was assessed. Behavioral assays were conducted to evaluate motor activity and cognitive function., Results: The delivery system demonstrated sustained insulin release, maintaining therapeutic plasma levels. Diet restriction mice treated with the insulin delivery system showed body weight restoration. Gene expression analysis revealed enhanced expression of CB1 and CB2 genes associated with improved eating behavior and cognition, while POMC expression was reduced. Insulin-polymer treatment restored cognitive function and decreased hyperactivity in the AN-like model., Conclusion: The PSA-RA-based insulin delivery system effectively restores metabolic balance, body weight, and cognitive function in the AN model. Its ability to steadily release insulin makes it a promising candidate for AN treatment.", (Copyright © 2024 Elsevier B.V. All rights reserved.)

Heart failure with preserved ejection fraction (HFpEF) is more prevalent in post- compared to pre-menopausal women. The underlying mechanisms are not fully understood. Data in humans is confounded by age and co-morbidities. We investigated the effects of ovariectomy and estrogen replacement on the left ventricular (LV) gene expression of pro-inflammatory and pro-fibrotic factors involved in HFpEF and putative regulating miRNAs. Nine-week-old C57BL/6 female mice were subjected to ovariectomy (OVX) or SHAM operation. OVX and SHAM groups were sacrificed 1-, 6-, and 12-weeks post-surgery (T1/SHAM; T1/OVX; T6/SHAM; T6/OVX, T12/SHAM). 17β-estradiol (E 2 ) or vehicle (VEH) was then administered to the OVX groups for 6 weeks (T12/OVX/E2; T12/OVX/VEH). Another SHAM group was sacrificed 12-weeks post-surgery. RNA and miRNAs were extracted from the LV apex. An early 3-fold increase in the gene expression of IL-1α , IL-6 , Mmp9 , Mmp12 , Col1α1 , and Col3α1 was observed one-week post-surgery in T1/OVX vs. T1/SHAM, but not at later time points. miRNA-26a was lower in T1/OVX vs. T1/SHAM and was inversely correlated with Col1α1 and Col3α1 expression 1-week post-surgery (r = -0.79 p < 0.001; r = -0.6 p = 0.007). miRNAs-26a, 29b, and 133a were significantly higher, while Col1α1 , Col3α1 , IL-1α , IL-6 , Tnfα , Mmp12 , and FasL gene expression was significantly lower in E 2 - compared to vehicle-treated OVX mice. miRNA-26a was inversely correlated with Col3α1 in T12/OVX/ E 2 (r = -0.56 p = 0.02). OVX triggered an early increase in the gene expression of pro-inflammatory and pro-fibrotic factors, highlighting the importance of the early phase post-cessation of ovarian function. E 2 replacement therapy, even if it was not immediately initiated after OVX, reversed these unfavorable changes and upregulated cardiac miRNA-26a, previously unknown to be affected by menopausal status.

Objective: Trimethylamine N-oxide (TMAO) has been associated with atherosclerosis and poor outcome. We evaluated the prognostic impact of intra-hospital TMAO variation on patient outcome., Methods and Results: Blood samples from 149 patients with acute myocardial infarction (AMI) were taken on admission and discharge. Plasma TMAO was determined by HPLC-MS. The endpoint was a composite three-point MACE (major adverse cardiovascular events), including all-cause mortality, re-infarction, or heart failure (HF) development. Median TMAO concentration on admission was significantly higher than on discharge (respectively, 7.81 [3.47-19.98] vs 3.45 [2.3-4.78] μM, p < 0.001). After estimating the 3.45 μM TMAO cut-off with the analysis of the continuous hazard ratio, we divided our cohort into two groups. The first group included 75 (50.3%) patients whose TMAO levels remained below or decreased under cut-off (low-low/high-low; LL/HL), while the second group included 74 (49.7%) patients whose TMAO levels remained high or increased above the cut-off during hospitalisation (high-high/low-high; HH/LH). During the median 30-month follow-up, 21.5% of patients experienced the composite endpoint. At Kaplan-Meier analysis, a trend of increasing MACE risk was observed in patients in the HH/LH group (p = 0.05). At multivariable Cox analysis, patients from the HH/LH group had more than two times higher risk of MACE during the follow-up than the LL/HL group (HR = 2.15 [95% CI, 1.03-4.5], p = 0.04). Other independent predictors of MACE were older age and worse left ventricular systolic function., Conclusion: In patients with AMI, permanently high or increasing TMAO levels during hospitalisation are associated with a higher risk of MACE during long-term follow-up., Competing Interests: Disclosures None., (Copyright © 2024 Hellenic Society of Cardiology. Published by Elsevier Inc. All rights reserved.)

Background and Aims: Vitamin D deficiency is a common cardiovascular risk factor associated with the development of atherosclerosis. We evaluated changes in 25(OH)D concentrations in 1510 patients with acute myocardial infarction (AMI) over a long observation period, including the COVID-19 pandemic., Methods and Results: Patients were separated into four groups according to the year of enrolment, group 1 (2009-2010), group 2 (2014-2016), group 3 (2017-2019), and group 4 (2020-2022). The median 25(OH)D concentration in the overall cohort was 17.15 (10.3-24.7) ng/mL. The median plasma concentrations of 25(OH)D for groups 1, 2, 3, and 4 were 14.45 (7.73-22.58) ng/mL, 17.3 ng/mL (10.33-24.2), 18.95 (11.6-26.73) ng/mL and 19.05 (12.5-27.3) ng/mL, respectively. Although 25(OH)D levels increased over the years, the prevalence of vitamin D deficiency remained high in each group (68.4%, 61.4%, 53.8%, and 52% respectively). Hypovitaminosis D was predicted by the season influence (OR:2.03, p < 0.0001), higher body mass index (OR:1.25; p = 0.001), diabetes mellitus (OR:1.54; p = 0.001), smoking (OR:1.47; p = 0.001), older age (OR:1.07; p = 0.008), higher triglycerides levels (OR:1.02; p = 0.01), and female gender (OR:1.3; p = 0.038). After multivariable adjustment, vitamin D ≤ 20 ng/mL was an independent predictor of mortality., Conclusion: Vitamin D deficiency is highly prevalent and persistent in patients with AMI despite a trend towards increasing 25(OH)D concentrations over the years. The frequent lockdowns did not reduce the levels of 25(OH)D in the fourth group. Low levels of 25(OH)D are an independent predictor of mortality., Competing Interests: Declaration of competing interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.)

Background: Variants in Filamin-C (FLNC) have been associated with various hereditary cardiomyopathies. Recent literature reports a prevalence of sudden cardiac death (SCD) of 13-25% among carriers of truncating-variants, with mean age of 42±15 years for first SCD event. This study reports two familial cases of SCD and the results of cascade screening of their large family., Methods: Molecular-autopsy of the SCD victims revealed a novel truncating-variant in the FLNC gene (chr 7:128496880 [hg19]; NM&#95;001458.5; c.7467&#95;7474del; p.(Ser2490fs)). We screened thirty-two family members following genetic counseling, and variant carriers underwent a comprehensive workup followed by consultation with a cardiologist with expertise in the genetics of cardiac diseases., Results: Seventeen variant carriers were identified: ages between 9 and 85 (mean 47±26). Fifteen underwent clinical evaluation. To date, none of the identified carriers has had major adverse events. In evaluated patients, ECG showed right-axis deviation in 60% (n = 9). Holter recorded frequent premature ventricular contractions (PVCs) (991±2030 per 24 h) in 33% (n = 5) with 4 patients having polymorphic PVC morphology. Three carriers had echocardiographic evidence of mild left-ventricular (LV) systolic dysfunction and another with mild LV dilatation. Cardiac magnetic-resonance (CMR) exhibited late‑gadolinium-enhancement in 10 out of 11 exams, mainly in the mid-myocardium and sub-epicardium, frequently involving the septum and the inferior-lateral wall., Conclusion: This large FLNC truncating variant carrier family exhibits high cardiomyopathy penetrance, best diagnosed by CMR, with variable clinical expressions. These findings present a challenge in SCD prevention management and underscoring the imperative for better risk stratification measures., Competing Interests: Declaration of competing interest The authors have no conflicts to disclose., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Competing Interests: Disclosures None.

Introduction: Smoking is a collective and complex problem in the Palestinian-Arab community in Israel, where women and children are particularly vulnerable to exposure to secondhand smoke (SHS), especially in the home., Aims and Methods: We undertook this study to better understand women's experiences with SHS exposure in the home and to identify pathways for intervention. Using the grounded theory approach, seven focus groups were conducted with 66 women in different localities across Israel. Purposive and snowball sampling techniques were applied to recruit women who have currently or previously been exposed to smoking in the home. Focus groups were audio-recorded and transcribed verbatim, and data were then coded and analyzed using the constant comparison analysis method to identify emergent themes and subthemes., Results: Three core themes emerged from the discussions. These include women's perceptions of smoking among men and exposure to SHS in the home, the implications of smoking on spousal and social relationships, and the women's experiences in coping with this situation and their suggestions for interventions. We identified additional sub-themes, including the consequences to women's and children's health, as well as the complex interaction between smoking in the home and women's social position, agency, and home ownership., Conclusions: Women exposed to SHS in the home experience consequences that affect their health and their spousal and social relationships. They also face several personal and societal challenges in tackling this issue. Culturally tailored interventions targeting both communities and households can raise awareness and impact smoking behaviors in the home., Implications: The findings of this study demonstrate the far-reaching consequences of SHS exposure in the home among women who are exposed. The findings contribute to our understanding of smoking contingencies among men and smoking behaviors in the home. This study lays the groundwork for future community and household-based research and interventions. We suggest several critical junctures that may increase response to smoking cessation interventions and to reduce smoking in the home, such as at the time of marriage when the home policy is set, and the adverse effects of exposure on children and other family members, especially those with illness., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: The delay time from onset of symptoms of a myocardial infarction to seeking medical assistance can have life-threatening consequences. Women delay significantly more often than men do in calling for medical help, once symptoms of a myocardial infarction occur., Objectives: The current qualitative study's main aim was to explore psychosocial factors that contribute to Israeli women's delaying calls for medical assistance and, by contrast, the motivational factors that encourage them to do so., Design: A qualitative study., Method: In total, 12 women were interviewed shortly after experiencing a myocardial infarction. Qualitative data were subjected to thematic analysis., Results: Two major themes emerged describing barriers to seeking help: (1) the use of denial as a defense mechanism and (2) the need for control. The motivational factor which enhanced help-seeking was "fear of death.", Conclusion: These findings may help in designing gender-sensitive interventions with the aim of minimizing the symptom onset to call time and thus preventing irreversible and life-threatening health damage.

Background: Data assessing the long-term safety and efficacy of mavacamten treatment for symptomatic obstructive hypertrophic cardiomyopathy are needed., Objectives: The authors sought to evaluate interim results from the EXPLORER-Long Term Extension (LTE) cohort of MAVA-LTE (A Long-Term Safety Extension Study of Mavacamten in Adults Who Have Completed EXPLORER-HCM; NCT03723655)., Methods: After mavacamten or placebo withdrawal at the end of the parent EXPLORER-HCM (Clinical Study to Evaluate Mavacamten [MYK-461] in Adults With Symptomatic Obstructive Hypertrophic Cardiomyopathy; NCT03470545), patients could enroll in MAVA-LTE. Patients received mavacamten 5 mg once daily; adjustments were made based on site-read echocardiograms., Results: Between April 9, 2019, and March 5, 2021, 231 of 244 eligible patients (94.7%) enrolled in MAVA-LTE (mean age: 60 years; 39% female). At data cutoff (August 31, 2021) 217 (93.9%) remained on treatment (median time in study: 62.3 weeks; range: 0.3-123.9 weeks). At 48 weeks, patients showed improvements in left ventricular outflow tract (LVOT) gradients (mean change ± SD from baseline: resting: -35.6 ± 32.6 mm Hg; Valsalva: -45.3 ± 35.9 mm Hg), N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels (median: -480 ng/L; Q1-Q3: -1,104 to -179 ng/L), and NYHA functional class (67.5% improved by ≥1 class). LVOT gradients and NT-proBNP reductions were sustained through 84 weeks in patients who reached this timepoint. Over 315 patient-years of exposure, 8 patients experienced an adverse event of cardiac failure, and 21 patients had an adverse event of atrial fibrillation, including 11 with no prior history of atrial fibrillation. Twelve patients (5.2%) developed transient reductions in site-read echocardiogram left ventricular ejection fraction of <50%, resulting in temporary treatment interruption; all recovered. Ten patients discontinued treatment due to treatment-emergent adverse events., Conclusions: Mavacamten treatment showed clinically important and durable improvements in LVOT gradients, NT-proBNP levels, and NYHA functional class, consistent with EXPLORER-HCM. Mavacamten treatment was well tolerated over a median 62-week follow-up., Competing Interests: Funding Support and Author Disclosures This study was funded by Bristol Myers Squibb, Princeton, New Jersey, USA. Bristol Myers Squibb’s policy on data sharing is available online at https://www.bms.com/researchers-and-partners/clinical-trials-and-research/disclosure-commitment.html. Dr Rader has received consulting fees from Medtronic, Bristol Myers Squibb, and ReCor Medical. Dr Oręziak has received personal fees from Bristol Myers Squibb. Dr Saberi has received personal fees from Bristol Myers Squibb. Dr Fermin has received consulting fees from Alnylam, Eidos Therapeutics, Bristol Myers Squibb, and Pfizer. Dr Wheeler has received personal fees and research support from Bristol Myers Squibb. Dr Garcia-Pavia has received consulting and speaking fees from Bristol Myers Squibb, Rocket Pharmaceuticals, and Cytokinetics and speaking fees from Bristol Myers Squibb and Cytokinetics. Dr Zwas has received personal fees from Bristol Myers Squibb. Dr Masri has received grants from Akcea, Pfizer, and Ultromics and consulting fees from Alnylam, Cytokinetics, Eidos Therapeutics, Ionis, and Pfizer. Dr Owens has received consulting fees from Bristol Myers Squibb, Cytokinetics, and Pfizer. Dr Hegde serves on the faculty of the Cardiovascular Imaging Core Laboratory at Brigham and Women’s Hospital, and her institution has received payments for her consulting work from Bristol Myers Squibb. Dr Seidler has received consulting fees or honoraria for lectures from Bristol Myers Squibb and Cytokinetics. Dr Balaratnam and Dr Sehnert are employees of Bristol Myers Squibb and own stock of Bristol Myers Squibb. Shawna Fox is an employee of IQVIA, a partner providing statistics services to Bristol Myers Squibb. Dr Olivotto has received grants from Amicus, Boston Scientific, Bristol Myers Squibb, Cytokinetics, Genzyme, and Menarini International and consulting fees from Amicus, Cytokinetics, Genzyme, MS Pharma, Rocket Pharmaceuticals, and Tenaya Therapeutics. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Competing Interests: Declaration of Competing Interest The authors have no conflicts of interest to declare.

Introduction - The obesity pandemic is multifactorial. Nutritional, pharmacologic and surgical interventions are limited in reach and efficacy, raising need for new therapeutics. Aims - Characterization of anorexigenic and cognitive effect and central mechanism of action of novel N-acylethanolamide derivatives. Methods - Sabra mice divided to similar experimental groups, injected IP with: oleyl-L-leucinolamide (1 A), linoleyl-L-leucinolamide (4 A), linoleyl-L-valinolamide (5 A), oleyl-oxycarbonyl-L-valinolamide (1 B), oleyl-oxycarbonyl-D-valinolamide (2 B), oleylamine-carbonyl-L-valinolamide (3 B), oleylamine-carbonyl-D-valinolamide (4 B), and oleyl-L-hydroxyvalineamide (5 B). Control group with vehicle. Body weight and food consumption followed for 39 days. Motor activity and cognitive function by open field test and eight-arm maze. Mice sacrificed and mechanism of action investigated by qPCR. The genes analyzed involved in energy balance and regulation of appetite. Catecholamines and serotonin evaluated. Results - Compounds 1 A, 5 A, 1 B-4 B, caused significant weight loss of 4.2-5.6 % and 5 A, 1 B-4 B, improved cognitive function following 8 i. p. injections of 1 mg/kg during 39 days, by different mechanisms. 5 A, 3 B and 4 B decreased food consumption, whereas 1 A, 5 A and 2 B increased motor activity. 1 A, 4 A, 1 B and 3 B elevated SIRT-1, associated with survival. POMC upregulated by 1 B and 2 B, CART by 1 B, 2 B and 1 A. NPY and CAMKK2 downregulated by 5 A. 4 B enhanced 5-HT levels. 4 A, 5 A, 1 B, 4 B, 5 B decreased FAAH, showing long lasting effect. Conclusions - These new compounds might be developed for the treatment of obesity and for improved cognitive function., (© 2023 Wiley-VHCA AG, Zurich, Switzerland.)

Introduction: A prescribing cascade occurs when a drug is prescribed to manage the often unrecognised side effect of another drug; these cascades are of particular concern for older adults who are at heightened risk for drug-related harm. It is unknown whether, and to what extent, gender bias influences physician decision-making in the context of prescribing cascades. The aim of this transnational study is to explore the potential impact of physician implicit gender biases on prescribing decisions that may lead to the initiation of prescribing cascades in older men and women in two countries, namely: Canada and Italy., Methods and Analysis: Male and female primary care physicians at each site will be randomised 1:1 to a case vignette that features either a male or female older patient who presents with concerns consistent with the side effect of a medication they are taking. During individual interviews, while masked to the true purpose of the study, participants will read the vignette and use the think-aloud method to describe their ongoing thought processes as they consider the patient's concerns and determine a course of action. Interviews will be recorded, transcribed verbatim and thematic analysis will be conducted to highlight differences in decisions in the interviews/transcripts, using a common analytical framework across the sites., Ethics and Dissemination: This study has received ethics approval at each study site. Verbal informed consent will be received from participants prior to data collection and all data will be deidentified and stored on password-protected servers. Results of this study will be disseminated through peer-reviewed journal articles and presented at relevant national and international conferences., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Obesity is a worldwide epidemic which is associated with major cardiovascular (CV) risk factors. Nevertheless, substantial distant data, mostly published more than a decade ago, have demonstrated an obesity paradox, where obese patients generally have a better short- and long-term prognosis than do their leaner counterparts with the same CV profile. Nonetheless, it is not fully elucidated whether the obesity paradox is still relevant in the contemporary cardiology era among patients with acute coronary syndrome (ACS). We aimed to examine temporal trends in the clinical outcomes of ACS patients by their BMI status., Methods: Data from the ACSIS registry including all patients with calculated BMI data between the years 2002-2018. Patients were stratified by BMI groups to underweight, normal, overweight and obese. Clinical endpoints included 30d major cardiovascular events (MACE), and 1-year mortality. Temporal trends were examined in the late (2010-2018) vs. the early period (2002-2008). Multivariable models examined factors associated with clinical outcomes by BMI status., Results: Among the 13,816 patients from the ACSIS registry with available BMI data, 104 were underweight, 3921 were normal weight, 6224 were overweight and 3567 were obese. 1-year mortality was highest among underweight patients (24.8%), as compared to normal weight patients (10.7%) and lowest among overweight and obese patients (7.1% and 7.5% respectively; p for trend <0.001). 30-day MACE rates followed a similar pattern (24.3% for underweight, 13.6% for normal weight, 11.6% for overweight, and 11.7% for obese; p for trend<0.001). Comparing the 2 time-periods, 30-day MACE was significantly lower in the late period in all BMI groups, but unchanged in patients who were underweight. Similarly, 1-year mortality has decreased in normal weight and obese patients but remained similarly high in underweight patients., Conclusions: In ACS patients, during 2-decades, 30-day MACE and 1-year mortality were lower among overweight and obese patients compared to underweight and even normal weight patients. Temporal trends revealed that 30-day MACE and 1-year mortality have decreased among all BMI groups other than the underweight ACS patients, among whom the adverse CV rates were consistently high. Our findings suggest that the obesity paradox is still relevant in ACS patients in the current cardiology era., (Copyright © 2023 Elsevier B.V. All rights reserved.)

A hyperdynamic heart is defined as a left ventricular (LV) with an ejection fraction (EF) above the normal range. Is this favorable? We looked at the diastolic properties of subjects with a hyperdynamic heart and its impact on outcome. Consecutive echocardiography examinations during 5 years were evaluated by EF subgroups, including a hyperdynamic heart (EF >70%). All examinations with significant LV hypertrophy or valve disease were excluded. The study included 16,994 subjects. A total of 720 subjects (4.2%) had a hyperdynamic heart. Subjects with a hyperdynamic heart were older, more likely to be women, and more likely to have hypertension, diabetes, and obesity. A total of 20% of patients had a diagnosis of heart failure. This group had a higher heart rate, smaller ventricular size, and the highest relative wall thickness. All indexes of diastolic dysfunction were significantly more prevalent in the hyperdynamic group. This included a higher LV mass, larger left atrial volume, reduced relaxation (smaller mitral e'), longer deceleration time, and higher LV end-diastolic pressures (high mitral E/e' ratio) and peak tricuspid regurgitation gradient. Diastolic dysfunction, defined by an abnormal functional or structural parameter, was present in 78% of the subjects. Survival was significantly lower in the group with a hyperdynamic heart. The Cox regression analysis after adjustment demonstrated reduced survival during a median 9-year follow-up in the hyperdynamic group compared with those with a normal EF (hazard ratio 1.56, 95% confidence interval 1.38 to 1.76, p <0.001). In conclusion, subjects with a hyperdynamic systolic function have increased prevalence of diastolic dysfunction and reduced survival. A hyperdynamic heart is not a normally functioning heart., Competing Interests: Disclosures The authors have no conflicts of interest to declare., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Introduction: Tricuspid regurgitation (TR) is a common finding which appears to be associated with a worse prognosis. There are conflicting data regarding the prognostic impact of mild TR. We examined the clinical characteristics and echocardiographic properties of subjects with TR and its impact on clinical outcome with particular emphasis on subjects with mild TR., Methods: Consecutive echocardiography examinations during 5 years were evaluated for TR severity and outcome including mortality and cardiovascular hospitalizations., Results: The study included 21,429 subjects; 45% of the subjects had mild TR, 15% had moderate TR, and 6.5% had severe TR. Primary organic TR was evident in 7% of the subjects, a percentage that increased with increasing TR severity. TR severity was incrementally associated with older subjects with an increasing number of comorbidities and echocardiographic abnormalities. 29% of the subjects died at a median follow-up duration of 8.7 years. Increasing severity of TR was independently and incrementally associated with mortality. Subjects with mild TR had a 25% increased mortality rate compared to subjects with minimal TR (HR 1.25, 95% CI: 1.12-1.39, p &lt; 0.001) after adjustment for significant clinical parameters. TR severity was also an independent incrementally graded predictor of cardiovascular hospitalization and mortality (mild TR: HR 1.23, 95% CI: 1.12-1.34, p &lt; 0.001)., Conclusions: TR is associated with older and sicker patients with numerous comorbidities. TR severity is a predictor of a worse clinical outcome. Mild TR was independently associated with decreased survival. TR should be considered a marker of a disease burden with a poor prognosis., (© 2023 S. Karger AG, Basel.)

Background: Implementation of guidelines for evidence-based screening and disease prevention remains a core challenge in health care. The lack of access to accurate and personalized health recommendations may contribute to sub-optimal performance of medical screening, and ultimately increased risk for communicable and non-communicable disease. Many women do not monitor their cardiovascular disease (CVD) risk or receive regular medical screenings. A health recommendation tool (HeaRT) that provides women with profiled, individually tailored information about recommended tests and screening was designed to improve women's engagement in preventive health. This study characterized utilization of the tool in a real world setting., Objective: To describe the development and usage patterns of HeaRT, a novel health web-tool that provides personalized health recommendations for women., Methods: Extracted web-tool data including user input (age, BMI, smoking status and family history of CVD) and time spent in the results screen were analysed. Engagement was assessed by time spent in each results category, number of clicks and whether the user emailed/printed the recommendations. Usage patterns were analysed using multivariate analyses, logistic regression and cluster analyses., Results: HeaRT was used 13,749 times in the years between its launch and data extraction three years later. Web-tool analysis found that 68.6 % of users accessed results and approximately 15 % printed or emailed the list of recommendations. Further analysis found that almost all the users entered the nutrition category (78 %), followed by the risk-factor category (69.5 %) and Physical activity category (61.9 %). Three usage patterns were identified by cluster analysis, including a nutrition/physical activity cluster, a risk-factor cluster and an all-categories cluster. Cluster affiliation analysis found BMI and smoking status were not predictors of cluster affiliation, whereas users over the age of 65 were more likely to solely enter the risk-factor tab ( P  < .001) and users with family history of CVD were more likely to either enter only the risk-factor tab or to enter all tabs ( P  < .01)., Conclusions: HeaRT users looked at health recommendations on a variety of health topics, and 15 % printed or emailed the recommendations. A tailored health recommendation web-tool may empower women to seek preventive-care and health maintenance, and help them interact with health care providers from a position of shared responsibility. This tool and similar programs may enable health care consumers to actively participate in directing their own health maintenance by providing consumers with personalized health recommendations. Additionally, user characteristics may inform future web-tool designers on target population profile and usage patterns., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Authors.)

Background: This study presents an intervention designed to foster the implementation of health promotion programs within District Municipality Community Centers (DMCCs) in Jerusalem, and the creation of a peer network of healthy settings with a shared aspiration of collaborating and implementing health-promoting policies at the community level. We also present the evaluation strategy, based on the EQUIHP and RE-AIM frameworks., Methods: Twenty DMCCs completed our program. This evaluation research involved a comprehensive seminar during the first year for DMCCs coordinators, teaching them the principles of health promotion. An educational kit was distributed during the second year. The evaluation strategy included a process evaluation and annual evaluations based on the EQUIHP and RE-AIM frameworks. The EQUIHP tool was divided into four dimensions of evaluation: 1) Framework of health promotion principles, 2) Project development and implementation, 3) Project management, and 4) Sustainability; while the RE-AIM domains included: 1)Reach, 2)Effectiveness, 3)Adoption, 4)Implementation and 5)Maintenance., Results: The program led to high responsiveness among DMCCs and to the implementation of diverse health promotion initiatives, with a participation of approximately 29,191 residents. The EQUIHP evaluation showed an improvement in program quality in Year 2. The final RE-AIM evaluation presented a total median score of 0.61 for all domains, where 0 was non-performance and 1.0 was full performance. The 'Framework of health promotion principles' and 'Reach' components received the highest median score (0.83, 1.0 and 0.87), while the 'Sustainability and 'Maintenance' components received the lowest (0.5)., Conclusions: This innovative program adapts the Healthy Cities approach (initiated by the World Health Organization in 1986) to the development of community center health-promoting settings within the larger municipal framework, training local community center staff members to assess and address local health concerns and build community capacity. The local focus and efforts may help community actors to create health promotion programs more likely to be adopted, feasible in the 'real-world' and able to produce public health impact in the communities where people live. Moreover, collaboration and cooperation among DMCCs may lead to a broader community health vision, forging coalitions that can advocate more powerfully for health promotion., Trial Registration: NIH trial registration number: NCT04470960. Retrospectively registered on: 14/07/2020., (© 2022. The Author(s).)

Objectives: Women from low socio-economic, culturally insular populations are at increased risk for cardiovascular disease (CVD). The ultra-Orthodox Jewish (UOJ) community in Israel is a rapidly growing low socio-economic, insular, cultural-ethnic minority with numerous obstacles to health. The current cross-sectional study investigates CVD-related health behaviors and risk factors in a sample of UOJ females, comparing sample characteristics with the general population. Design: Self-administered questionnaires completed by a cluster randomized sample of 239 UOJ women included demographics, CVD-related health behaviors (consumption of fruit, vegetables, and sweetened beverages; hours of sleep; secondhand smoke exposure; and physical activity engagement) and risk factors (BMI, reported diagnoses of diabetes, high blood pressure, and heart disease). Results: Compared with the general population, UOJ women were less likely to consume 5 fruits and vegetables a day (12.7% vs. 24.3%, p  < .001); more likely to consume ≥ 5 cups of sweetened beverages a week (18.6% vs. 12.6%, p  = .019), and more likely to sleep <7 hours a night (62.0% vs. 50.6%, p  = .002). UOJ women also reported less secondhand smoke exposure (7.2% vs. 51.4%, p  < .001) and higher rates of physical activity recommendation adherence (60.1% vs. 25.6%, p  < .0001) than the general population. Obesity was higher in UOJ women (24.3% vs. 16.1%, p  < .0001). Increased parity and reduced moderate physical activity were associated with increased BMI. Increased parity was also associated with reduced sleep. Grand multiparous women (a 68% prevalence rate), in particular, were more likely to be overweight or obese than women with less than 5 children. Conclusions: This study suggests that health promotion interventions in this population target healthy weight maintenance, nutrition, and physical activity.

Background: Advanced heart failure (HF) carries a high rate of recurrent HF hospitalizations and a very high mortality rate. Mechanical devices and heart transplantation are limited to a select few. Dialysis may be a good alternative for advanced HF patients with volume overload despite maximal pharmacological therapy., Objectives: To assess the net clinical outcome of peritoneal dialysis or hemodialysis in patients with advanced HF., Methods: We analyzed all advanced HF patients who were referred for dialysis due to volume overload in our institution. Patients were followed for complications, HF hospitalizations, and survival., Results: We assessed 35 patients; 10 (29%) underwent peritoneal dialysis and 25 (71%) underwent hemodialysis; 71% were male; median (interquartile range) age was 74 (67-78) years. Estimated glomerular filtration rate was 20 (13-32) ml/min per 1.73 m2. New York Heart Association functional capacity was III. Median follow-up time was 719 days (interquartile range 658-780). One-year mortality rate was 8/35 (23%) and overall mortality rate was 16/35 (46%). Three patients (9%) died during the first year due to line or peritoneal dialysis related sepsis, and 6 (17%) died during the entire follow-up. The median number of HF hospitalizations was significantly reduced during the year on dialysis compared to the year prior to dialysis (0.0 [0.0-1.0] vs. 2.0 [0.0-3.0], P < 0.001)., Conclusions: Dialysis is reasonably safe and significantly reduced HF hospitalization in advanced HF patients. Dialysis could be a good alternative for advanced HF patients with intractable volume overload.

Introduction: Anorexia nervosa is a psycho-socio-biological disease, characterized by self-starvation and distorted perception of body weight. Patients often over-exercise. Insulin is an anabolic hormone that increases food intake and restores body fat and is present in low levels in anorexia nervosa patients: thus may have therapeutic potential in treating anorexia nervosa., Aims: to explore whether low levels insulin administration may result in recovery of cerebral function and restoration of metabolic disorder providing a treatment option for anorexia nervosa., Methods: Female Sabra mice maintained on DR of 2.0 hours per day for 32 days, in cages with or without wheel attached to an electronic counter (activity wheel). They were then permitted to eat ad libitum for additional 15 days. On the second week, mice were injected ip with 0.5U/kg long acting Insulin(Lantus) or saline and cognitive function was evaluated. Insulin administered three times a week during days 8-32. Mice euthanized on day 48 and cerebral levels of monoamines, 2-AG and expression of genes associated with metabolic status were evaluated., Results: Activity wheel mice decreased body weight, 2-AG, dopamine levels and 5-HT1A and increased Camkk2 and SIRT1 gene expression compared to mice without it. Insulin increased body weight, decreased revolutions, enhanced NPY and normalized Camkk2, SIRT-1, BDNF, elevated 2-AG and improved cognition in the wheel group., Conclusion: low dose insulin administration to animal model of anorexia associated with exercise, led to alterations and normalization in brain metabolic status and improved cognition. Insulin should be further explored as potential novel treatment for anorexia nervosa., (Copyright © 2022 Elsevier Inc. All rights reserved.)

School-based health promotion interventions have been shown to lead to measurable changes in the nutrition and physical activity behaviors. This study examines whether the impact of an intervention program on students’ healthy eating and physical activity was mediated by teacher training and engagement in health promotion. The trial was conducted in three phases: needs assessment of the baseline survey of teachers, mothers’ and children; intervention among seven randomly selected schools that included teacher training in healthy eating and physical activity; and a post-intervention evaluation survey. The SPSS PROCESS for Hayes (Model8) was used to determine moderation and mediation effects. The difference in difference (DID) was calculated for the three main outcomes of the study: eating breakfast daily (DID = 17.5%, p < 0.001); consuming the recommended servings of F&V (DID = 29.4%, p < 0.001); and being physically active for at least 5 days/week (DID = 45.2%, p < 0.001). Schoolchildren’s eating breakfast daily was mediated by their teachers’ training in nutrition (β = 0.424, p = 0.002), teachers’ engagement (β = 0.167, p = 0.036), and mothers preparing breakfast (β = 1.309, p < 0.001). Schoolchildren’s consumption of F&V was mediated by teachers’ engagement (β = 0.427, p = 0.001) and knowing the recommended F&V servings (β = 0.485, p < 0.001). Schoolchildren’s physical activity was mediated by their teachers’ training in physical activity (β = 0.420, p = 0.020) and teachers’ engagement (β = 0.655, p < 0.001). Health behavior changes in the school setting including improvements in eating breakfast, consuming the recommended F&V and physical activity was mediated by teacher training and engagement. Effective teacher training leading to teacher engagement is warranted in the design of health-promotion interventions in the school setting.

Background: Hemoglobin (Hb) is a standard and widely available clinical parameter that predicts clinical outcomes in heart failure (HF) patients. Red cell distribution width (RDW) is also a routinely measured clinical parameter that is predictive of clinical outcomes in HF. The ratio between Hb and RDW has yet to be evaluated in HF., Methods: We evaluated the predictive value of the Hb/RDW ratio on clinical outcomes in patients with HF. All patients diagnosed with chronic HF at a health maintenance organization were evaluated for Hb/RDW ratio and followed for cardiac-related hospitalizations and death., Results: The study cohort included 6888 HF patients. The mean Hb/RDW ratio was 0.85 ± 0.18; median was 0.85 (interquartile range 0.72-0.98). Patients with a lower Hb/RDW ratio were more likely to be women and had more comorbidities. The overall two year-mortality rate was 23.2%. Decreasing quantiles of the Hb/RDW ratio were associated with reduced survival rates and reduced event-free survival from death or cardiovascular-hospitalizations. Multivariable Cox regression analysis after adjustment for significant predictors demonstrated that low Hb/RDW ratio was a significant predictor of mortality, with a graded increased risk as Hb/RDW ratio decreased. Lower Hb/RDW ratio was also a significant independent predictor of the combined endpoint of death or cardiovascular hospitalizations. A sensitivity analysis evaluating Hb/RDW ratio as a continuous parameter using restricted cubic splines demonstrated a continuous increase in the mortality risk with decreasing Hb/RDW ratio, p < 0.0001 for the linear model., Conclusions: Hb/RDW ratio is a significant prognostic tool for predicting HF mortality and cardiovascular hospitalizations.

Bicuspid aortic valve (BAV) is a common congenital heart disease, with a 10-fold higher prevalence in first-degree relatives. BAV has different phenotypes based on the morphology of cusp fusion. These phenotypes are associated with different clinical courses and prognoses. Currently, the determinants of the valve phenotype are unknown. In this study we evaluated the role of genetics using familial cohorts. Patients with BAV and their first-degree relatives were evaluated by echocardiography. The concordance in BAV phenotype between pairs of family members was calculated and compared with the concordance expected by chance. We then performed a systematic literature review to identify additional reports and calculated the overall concordance rate. During the study period, 70 cases from 31 families and 327 sporadic cases were identified. BAV was diagnosed in 14% of the screened relatives. The proportions of the morphologies identified was: 12.3% for type 0, 66.2% for type 1-LR, 15.4% for type 1-RN, 4.6% for type 1-NL, and 1.5% for type 2. For the assessment of morphologic concordance, we included 120 pairs of first-degree relatives with BAV from our original cohort and the literature review. Concordance was found only in 62% of the pairs which was not significantly higher than expected by chance. In conclusion, our finding demonstrates intrafamilial variability in BAV morphology, suggesting that morphology is determined by factors other than Mendelian genetics. As prognosis differs by morphology, our findings may suggest that clinical outcomes may vary even between first-degree relatives., Competing Interests: Disclosures All authors have no conflicts of interest to declare., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Increased weight measured by body mass index is associated with better clinical outcomes in heart failure (HF). The effect of specific components of body mass on outcome is limited. We evaluated the impact of fat-free mass and fat mass on mortality and cardiovascular hospitalization in a large real-world cohort of patients with chronic HF., Methods: Body measurements were assessed in patients with chronic HF. Fat-free mass, fat mass and waist circumference were calculated based on specifically derived formulas., Results: The cohort included 6328 HF patients. Mean follow-up was 744 days. Increased body composition indices including body mass index, fat-free mass index and fat mass index, per cent body fat and waist circumference were associated with better survival. Cox regression analysis after adjustment for other significant parameters demonstrated that these indices were all associated with improved survival. The strongest association was seen with fat-free mass index with a graded increase in survival; lowest death in the highest quartile compared to reference second quartile (hazard ratio 0.79, 95% confidence interval 0.67-0.93, P < .01). There was no interaction with sex or HF type. Analysis of the clinical outcome of death and cardiovascular hospitalization demonstrated that a worse prognosis was in the lowest quartile of all the indices. A sensitivity analysis, analysing these indices as continuous parameters using restricted cubic splines, demonstrated a clear continuous association between these indices and increased survival in both sexes., Conclusions: Body mass including fat-free mass and fat mass was associated with improved survival in patients with HF., (© 2021 Stichting European Society for Clinical Investigation Journal Foundation. Published by John Wiley & Sons Ltd.)

Background: EXPLORER-HCM (Clinical Study to Evaluate Mavacamten [MYK-461] in Adults With Symptomatic Obstructive Hypertrophic Cardiomyopathy) demonstrated that mavacamten, a cardiac myosin inhibitor, improves symptoms, exercise capacity, and left ventricular outflow tract (LVOT) obstruction in patients with obstructive hypertrophic cardiomyopathy (oHCM)., Objectives: The purpose of this study was to evaluate mavacamten's effect on measures of cardiac structure and function and its association with changes in other clinical measures., Methods: Key echocardiographic parameters from serial echocardiograms over 30 weeks from 251 symptomatic oHCM patients (mavacamten [n = 123], placebo [n = 128]) were assessed in a core laboratory., Results: More patients on mavacamten (80.9%; n = 76 of 94) vs placebo (34.0%; n = 33 of 97) showed complete resolution of mitral valve systolic anterior motion after 30 weeks (difference, 46.8%; P < 0.0001). Mavacamten also improved measures of diastolic function vs placebo, including left atrial volume index (LAVI) (mean ± SD baseline: 40 ± 12 mL/m 2 vs 41 ± 14 mL/m 2 ; mean change from baseline of -7.5 mL/m 2 [95% CI: -9.0 to -6.1 mL/m 2 ] vs -0.09 mL/m 2 [95% CI: -1.6 to 1.5 mL/m 2 ]; P < 0.0001) and lateral E/e' (baseline, 15 ± 6 vs 15 ± 8; change of -3.8 [95% CI: -4.7 to -2.8] vs 0.04 [95% CI: -0.9 to 1.0]; P < 0.0001). Among mavacamten-treated patients, improvement in resting, Valsalva, and post-exercise LVOT gradients, LAVI, and lateral E/e' was associated with reduction in N-terminal pro-B-type natriuretic peptide (P ≤ 0.03 for all). Reduction in LAVI was associated with improved peak exercise oxygen consumption (P = 0.04)., Conclusions: Mavacamten significantly improved measures of left ventricular diastolic function and systolic anterior motion. Improvement in LVOT obstruction, LAVI, and E/e' was associated with reduction in a biomarker of myocardial wall stress (N-terminal pro-B-type natriuretic peptide). These findings demonstrate improvement in important markers of the pathophysiology of oHCM with mavacamten. (Clinical Study to Evaluate Mavacamten [MYK-461] in Adults With Symptomatic Obstructive Hypertrophic Cardiomyopathy; NCT03470545)., Competing Interests: Funding Support and Author Disclosures Study funding was provided by MyoKardia, Inc, Brisbane, CA, a wholly owned subsidiary of Bristol Myers Squibb. Dr Hegde serves on the faculty of the Cardiovascular Imaging Core Laboratory at Brigham and Women’s Hospital; and her institution has received payments for her consulting work from MyoKardia. Dr Lester’s institution has received payments for his consulting work for MyoKardia. Dr Solomon is Director of the Cardiovascular Imaging Core Laboratory at Brigham and Women’s Hospital; has received research grants from Actelion, Alnylam, Amgen, AstraZeneca, Bellerophon, Bayer, Bristol Myers Squibb, Celladon, Cytokinetics, Eidos, Gilead, GlaxoSmithKline, Ionis, Lilly, Lone Star Heart, Mesoblast, MyoKardia, National Institutes of Health/National Heart, Lung, and Blood Institute, NeuroTronik, Novartis, Novo Nordisk, Respicardia, Sanofi Pasteur, and Theracos; and has consulted for Abbott, Action Akros, Alnylam, Amgen, Arena, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Cardior, Cardurion, Corvia, Cytokinetics, Daiichi-Sankyo, Gilead, GlaxoSmithKline, Ironwood, Lilly, Merck, MyoKardia, Novartis, Roche, Takeda, Theracos, Quantum Genetics, AOBiome, Janssen, Cardiac Dimensions, Tenaya, Sanofi Pasteur, DiNAQOR, Tremeau, CellProthera, Moderna, and American Regent. Dr Michels has received personal fees and payments as a consultant from MyoKardia. Dr Elliott has received payments as a consultant from MyoKardia, Pfizer, AstraZeneca, and Sanofi Genzyme; and has received speaker fees from Sanofi Genzyme. Dr Zemanek has received speaking honoraria from Abbott and Bayer. Dr Zwas has received personal fees from MyoKardia. Dr Jacoby has received personal fees from MyoKardia. Dr Wang has received grants and payments as a consultant from MyoKardia; and has received personal fees from Cytokinetics. Dr Ho has received payments as a consultant from MyoKardia, Tenaya, Novartis, and Ambry Genetics. Drs Li and Sehnert are employees of and have stocks or stock options in MyoKardia. Dr Olivotto has received grants from MyoKardia, Sanofi Genzyme, Shire, and Bayer; has received personal fees from Sanofi Genzyme, Shire, Amicus, and Bayer; and has received payments as a consultant from MyoKardia and Cytokinetics. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: The COVID-19 pandemic has adversely affected the provision of health care and disease management around the world. COVID-19 carries a high morbidity and mortality rate in elderly and people with comorbidities, including heart failure (HF). The present study addressed the clinical management and outcomes of HF patients during the pandemic., Methods: We evaluated the clinical management and survival rate of HF patients during the COVID-19 pandemic in Israel (March 2020-April 2021)., Results: The cohort included 6748 patients with a diagnosis of HF during the study period. During this period, 843 HF patients (12.5%) were infected with COVID-19, and 194 died from COVID-19, a 23% mortality rate. Patients infected with COVID-19 had a higher percentage of diabetes and obesity. Predictors of mortality included age, male sex, reduced functional capacity, renal dysfunction, and absence of renin-angiotensin system inhibition. During the pandemic, there was a marked decrease in the usage of medical services in the cohort. Cardiovascular hospitalizations, all hospitalization, and emergency room visits were significantly decreased compared to the two years prior to the pandemic, particularly during the lockdowns. There was also an initial decrease in HF clinic visits. Mortality rates were very similar during the pandemic compared to previous years. There was a decline in non-COVID-19 deaths, which were replaced with deaths due to COVID-19. This may result from competing effects and reduced exposure to respiratory infections and other insults due to social distancing., Conclusions: Mortality rates in HF patients infected with COVID-19 were high. The COVID-19 pandemic resulted in the reduced usage of health services but without increased overall mortality.

Background: The workplace provides an ideal setting for health promotion, as adults spend most of their day at work. Middle managers hold a strategic position to lead workplace health promotion. This study evaluates the outcomes of an intensive intervention training middle managers to promote health in the workplace., Methods: A workshop was designed and conducted to train female middle management employees to construct, implement, and evaluate a health promotion program in their workplace. Semi-structured interviews were carried out post-intervention to assess workplace health promotion outcomes according to the RE-AIM framework, and identify variables contributing to success. Additionally, questionnaires were distributed pre and post-program assessing personal health and self-efficacy changes., Results: Eighteen participants from 13 government offices, who serve 19,560 employees, completed the training course. Nine workplaces had workplace health promotion programs in progress 12 months after the course had ended, of which 8 made health promotion changes in organizational policy. Workplace RE-AIM scores showed that 8 workplaces were high or partial performers, and 5 were low or non-performers. Factors that increased the likelihood of successful interventions included management support, steering committee, comprehensive programming, conducting a needs assessment and flexibility in program implementation in the presence of challenges. Post course, participants reported increased health knowledge related to workplace health promotion (p < 0.001), and increased health promotion self-efficacy (p < 0.05)., Conclusions: Training and continued guidance of middle managers resulted in the design and successful implementation of workplace health promotion interventions. A RE-AIM based assessment was found to be an effective method for evaluating multi-content workplace health promotion programs. Registered at ClinicalTrials.gov, https://www.clinicaltrials.gov , registration number: NCT03295136, registration date: 24/09/2017., (© 2021. The Author(s).)

Introduction: Heart failure (HF) and cancer are medical conditions with a rising prevalence resulting in increased co-occurrence. We assessed the impact of cancer on clinical outcome in patients with HF and the prognostic impact of specific types of cancers on different HF subpopulations., Methods: All patients with HF were evaluated for the occurrence of malignant neoplasm at a health maintenance organization and were followed for cardiac-related hospitalizations and death., Results: The study cohort included 7106 HF patients, 1564 of them (22%) had a diagnosis of malignant neoplasm. HF patients with concomitant cancer were older, had more comorbidities and were more likely to have NYHA class III/IV (42% vs. 37%, P < .01), compared with patients with no malignancy. The overall 2-year mortality rate of the entire HF cohort was 23.2%. Survival rate by Kaplan-Meier analysis demonstrated that the presence of a malignancy was directly associated with reduced survival: 67.2 ± 1.2% vs 79.5 ± 0.5%, P < .001. Malignancy was associated with an increase in mortality with a hazard ratio (HR) of 1.36, 95% confidence interval (CI) 1.21-1.54, P < .001. The strongest impact of malignancy on outcomes was related to age; among patients <70 years old, the increase in the risk of mortality was the highest with a HR of 2.07, 95% CI 1.54-2.80, P < .001., Conclusions: Malignancy is common among patients with HF. Patients with concomitant HF and malignancies have poor outcomes, and the impact of cancer on outcome is stronger among young patients., (© 2020 Stichting European Society for Clinical Investigation Journal Foundation. Published by John Wiley & Sons Ltd.)

Palestinian-Arab women are at increased risk of cardiovascular disease due to high prevalence of diabetes and other risk factors. The current study investigates the effectiveness of an intensive group-based intervention on lifestyle habits that can prevent diabetes and cardiovascular disease. To that end, we conducted a group-based intervention based on the diabetes prevention program in two consecutive phases. The first phase consisted of a quasi-experimental study and the second phase included community-wide dissemination, with a 6-month follow-up. Findings from the quasi-experiment indicate increased consumption of fruit, vegetables and whole grains, weight reduction (-2.21 kg, p < 0.01), and a significant increase in the average daily steps in the intervention group (from 4456 to 6404). Findings from the dissemination indicate that average daily vegetables consumption increased from 1.76 to 2.32/day as did physical activity and average daily steps (from 4804 to 5827). There was a significant reduction in blood pressure, total cholesterol and LDL. These gains were sustained over 6 months following the intervention. This community-based, culturally adapted, health-promotion intervention led to improved nutrition and physical activity which were maintained after 6 months. Collaboration with community centers and local community partners created an effective channel for dissemination of the program to pre-clinical individuals.

Background: Few studies have evaluated the effect of pharmacologic treatment of anxiety on outcomes in heart failure (HF) patients. This study examined the impact of treatment with anxiolytics on clinical outcomes in a real-world sample of HF patients with and without depression., Methods: Patients diagnosed with HF were retrieved from a large HMO database. Patients prescribed anxiolytic medication and patients diagnosed with depression and/or prescribed anti-depressant medication were followed for cardiac-related hospitalizations and death., Results: The study cohort included 6293 HF patients. Treatment with anxiolytics was associated with decreased one-year survival compared to untreated individuals, with a greater reduction in survival seen in patients diagnosed with depression and/or treated with anti-depressants. Multi-variable analysis adjusting for age, sex, NYHA class, cardiac risk factors and laboratory parameters found that treatment with anxiolytics remained a predictor of mortality even when adjusting for depression. Depression combined with anxiolytic treatment was predictive of increased mortality, and treatment with anxiolytics alone, depression alone and anxiolytic treatment together with depression were each associated with an increased hazard ratio for a composite outcome of death and hospitalization., Conclusions: In this real-world study of HF patients, both treatment with anxiolytics and depression were associated with increased mortality, and anxiolytic therapy remained a predictor of mortality when adjusting for depression. Treatment of anxiety together with depression was associated with the highest risk of mortality. Safe and effective treatment for anxiety and depression is warranted to alleviate the detrimental impact of these disorders on quality and of life and adverse events.

Aims: Comorbidities are highly prevalent in patients with heart failure (HF) and affect clinical outcome. The CHA 2 DS 2 -VASc score is a validated score to estimate assessment of thromboembolic risk in patients with atrial fibrillation., Methods and Results: We evaluated the predictive value of this score on clinical outcome in patients with HF. All patients with a diagnosis of chronic HF at a health maintenance organization were evaluated for the CHA 2 DS 2 -VASc score. Patients were followed for cardiac related hospitalizations and death. The cohort included 7106 HF patients. Mean follow-up was 744 days; the median CHA 2 DS 2 -VASc score was 5.0 (range 4.0-6.0). The CHA 2 DS 2 -VASc score was a significant predictor of survival and predictive of the combined end point of death and cardiovascular hospitalization. Survival rates were reduced with increasing quintiles of the CHA 2 DS 2 -VASc score: 93.6 ± 0.7% vs. 83.0 ± 1.1% vs. 75.7 ± 1.0% vs. 73.0 ± 1.2% vs. 63.3 ± 1.2%, respectively P < 0.001. After adjustment for other significant predictors, increasing CHA 2 DS 2 -VASc scores were independently predictive of survival and of the combined end point of death and cardiovascular hospitalization by Cox regression analysis. Analysing the CHA 2 DS 2 -VASc score as a continuous parameter by cox regression analysis demonstrated a significant increase with each point increase in the CHA 2 DS 2 -VASc score (hazard ratio 1.21, 95% confidence interval 1.17-1.26, P < 0.0001). Cox regression analysis using restricted cubic splines demonstrated an independent continuous increase in mortality with increasing CHA 2 DS 2 -VASc score (P < 0.0001 adjusted linear model). The predictive value was present in HF with reduced as well as preserved ejection fraction., Conclusions: The CHA 2 DS 2 -VASc score has a significant impact on outcome in HF patients., (© 2020 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of the European Society of Cardiology.)

Psychosocial factors such as depression, anxiety, and stress are associated with increased cardiovascular risk. Health behaviors may play a role in this relationship, as individuals experiencing elevated levels of anxiety, stress, and/or depression may be less likely to engage in risk-reducing behaviors such as diet and exercise. Some evidence suggests that this relationship is particularly relevant for women. This study explored the relationship between levels of anxiety, depression, stress, and specific nutritional behaviors in a sample of 187 women at cardiovascular risk. BMI was explored as a possible moderator of these relationships. Higher levels of depression in patients with high BMI was associated with increased fruit consumption, whereas this was not seen in highly depressed patients with normal BMI. The reverse pattern was seen for consumption of sweet drinks. Anxiety was found to have a complex relationship with consumption of sweetened drinks and white bread, with higher consumption at moderately elevated levels of anxiety and reduced consumption at the highest levels. Possible interpretations of these findings, as well as their implications for lifestyle interventions with this population are discussed. These findings suggest a number of questions for further research., (Copyright © 2020 Eisenberg, Leiter, May, Reinfeld and Zwas.)

Influenza virus infection is associated with significant morbidity and mortality in patients with chronic diseases including heart failure (HF). Annual influenza vaccination is recommended to prevent infection during the winter months. Data regarding its clinical benefit in HF patients are sparse. The purpose of the study was to evaluate the effect of influenza vaccination on clinical outcome in patients with HF. Consecutive patients with HF at a health maintenance organization were evaluated for influenza vaccination status during the winter season of 2017/2018 and its association with cardiac-related hospitalizations and death during 1-year after vaccination. The study cohort included 6,435 HF patients. A total of 4,440 patient were vaccinated during the winter season (69% of the HF cohort). The vast majority (96%) were vaccinated before the winter months (September to November). Patients vaccinated were older patients with more co-morbidities. Cox regression analysis after adjustment for clinically significant predictors demonstrated that vaccination was associated with reduced mortality (hazard ratio [HR] 0.77, 95% confidence interval [CI] 0.65 to 0.91, p <0.01) as well as reduced death and cardiovascular hospitalizations (HR 0.83 95% CI 0.76 to 0.90, p <0.001). Adjustment for drug therapy demonstrated a similar result with improved outcome with influenza vaccine. Propensity score matched control analysis demonstrated that vaccination was associated with improved survival (HR 0.80, 95% CI 0.67 to 0.95, p <0.01) and reduced death and cardiovascular hospitalizations (HR 0.86, 95% CI 0.79 to 0.94, p <0.001). In conclusion, Influenza vaccination in patients with HF was associated with improved clinical outcome including improved survival and reduced death and hospitalizations., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Purpose: To describe the development of the first disease prevention intervention with ultra-Orthodox Jewish (UOJ) women in Israel using mixed methods and community-based participatory research (CBPR)., Design: This collaborative, 7-staged development process used an exploratory sequential mixed methods design integrated into a community-based participatory approach., Setting: The UOJ community in Israel, a high-risk, low socioeconomic, culturally insular minority that practices strict adherence to religious standards, maintains determined seclusion from mainstream culture and preserves traditional practices including extreme modesty and separation between the sexes., Participants: Women from a targeted UOJ community in Israel with distinct geographic, religious, and cultural parameters. These included 5 key informant interviewees, 5 focus groups with 6 to 8 participants in each, a cluster randomized sample of 239 questionnaire respondents (an 87% response rate), and 11 steering committee participants., Method: Qualitative data were analyzed through Interpretative Phenomenological Analysis by 2 researchers. Quantitative data were collected via questionnaire (designed based on qualitative findings) and analyzed utilizing descriptive statistics., Results: Barriers to health behavior engagement and intervention preferences were identified. The final intervention included walking programs, health newsletters, community leader trainings, teacher and student trainings, and health integration into schools., Conclusion: Utilizing mixed methods in CBPR improved cultural tailoring, potentially serving as a model for intervention design in other difficult to access, low socioeconomic, and culturally insular populations.

Background: Urinary albumin to creatinine ratio (UACR) is common in patients with heart failure (HF) and may have an impact on clinical outcome. We evaluated the effect of UACR on clinical outcome in a real-world cohort of patients with HF., Methods: All patients with HF at a health maintenance organization were followed for cardiac-related hospitalizations and death., Results: The study cohort included 4668 patients with HF and was divided into 3 groups based on UACR: normal-range albuminuria (2085 patients; 45%), microalbuminuria (1769 patients; 38%), and macroalbuminuria (814 patients; 17%). Microalbuminuria and macroalbuminuria were both associated with increasing age, diabetes mellitus, hypertension, peripheral vascular disease, atrial fibrillation, and New York Heart Association class III/IV. Microalbuminuria and macroalbuminuria were directly associated with decreased event-free survival from death and death and cardiovascular hospitalizations. Cox regression analysis after adjustment for significant predictors demonstrated that microalbuminuria was associated with increase in mortality (hazard ratio, 1.18; 95% confidence interval, 1.18-1.38; P = 0.03) and macroalbuminuria (hazard ratio, 1.33; 95% confidence interval, 1.10-1.61; P < 0.001). Albuminuria was also an independent predictor of death and cardiovascular hospitalizations. Analysis of albuminuria as a continuous parameter (natural logarithm transformed) showed that UACR was an independent predictor of mortality, and cardiovascular hospitalizations. Subclinical albuminuria (UACR 12-29 μg/mg) was directly associated with reduced survival. Cox regression analysis using restricted cubic splines demonstrated an independent continuous increase in mortality with increasing albuminuria (P < 0.0001 adjusted linear model)., Conclusion: Albuminuria provides important information regarding several detrimental processes in HF and is a significant predictor of a worse outcome., (Copyright © 2019 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

Background: For many women in low socioeconomic status communities, limited health literacy is an obstacle to following medical guidance and engaging in health-promoting behaviours. Low health literacy skills are also associated with an increased risk of cardiovascular disease., Design: A health literacy intervention was designed through focus groups with women in low socioeconomic status communities. The primary health literacy issue identified was communication challenges at doctors' visits. A unique intervention tailored to the participants' preferences was designed consisting of three workshops conducted in community women's groups in low socioeconomic status Jerusalem communities. The intervention aimed to increase patient-physician communication skills through doctor visit preparation and better visit management, improve perceived efficacy in patient-physician interaction and expand cardiovascular disease knowledge., Methods: Questionnaires were completed before and 3 months after the intervention, assessing knowledge of cardiovascular disease risk factors and symptoms, self-report of behaviours in preparations for a doctor's visit, and perceived efficacy in patient-physician interaction., Results: A total of 407 women from low socioeconomic status communities completed questionnaires. Post-intervention, the percentage of women that reported preparing for doctors' visits increased significantly. Women with initially low levels of perceived efficacy in patient-physician interaction showed a significant increase in perceived efficacy, while initially higher perceived efficacy in patient-physician interaction participants showed a decrease. Participants also demonstrated an increase in knowledge of several risk factors for cardiovascular disease and heart attack symptoms., Conclusions: A community-based cardiovascular health literacy intervention improved cardiovascular knowledge and reported doctor visit preparation in low socioeconomic status women as well as increased perceived efficacy in patient-physician interaction among participants with low baseline perceived efficacy in patient-physician interaction. This may lead to improved health care utilisation, preventing chronic illness. Registered at ClinicalTrials.gov, https://www.clinicaltrials.gov , registration number: NCT03203018.

Purpose: Echocardiographic studies have shown an increase in LV mass with advanced age. However, autopsy and MRI studies demonstrate that with aging, LV mass is unchanged or slightly decreased, with a decrease in LV volume and an increase in wall thickness consistent with concentric remodeling. LV structural remodeling with aging may lead to an overestimation of LV mass in older adults when using standard echocardiography measurements and calculations. This study compared CT and echocardiographic LV mass calculation in younger and older patients and parameters associated with age-related LV remodeling., Methods: Same subject modality comparison of echocardiographic and cardiac CT LV measurement with derivation of LV mass was performed retrospectively. Echocardiographic measurements were performed by a single observer in accordance with European Association of Cardiovascular Imaging (EACI)/American Society of Echocardiography (ASE) guidelines. CT measurements were performed in end-diastole on multiplanar reformatted image planes corresponding to those typically used in echocardiography. Calculated CT measurements were based on automatic segmentation of heart chambers via edge-tracing algorithms., Results: 129 patients were identified. In patients age 65 and older, LV mass was significantly higher when calculated using echocardiographic measurements compared to CT. Patients 65 years of age and older were found to have increased average wall thickness measurements with echocardiography but not with CT. The discrepancy between calculated echo and CT LV mass was reduced when using the mid-septal instead of proximal wall width for the EACI convention., Conclusion: In the elderly, increased echo-derived LV mass may reflect remodeling rather than a true increase in LV mass., Competing Interests: The authors have declared that no competing interests exist.

Background: Ghrelin may exert positive effects on cardiac structure and function in heart failure (HF) patients., Methods: We assessed ghrelin levels in 266 dilated cardiomyopathy (DCM) patients and in 200 age, gender and body mass index (BMI) matched controls. Further, we evaluated the expression of ghrelin and growth hormone secretagogue-receptor (GHSR) in the myocardium of 41 DCM patients and in 11 controls., Results: DCM patients had significantly lower levels of total, acylated and unacylated ghrelin when compared to controls ( p < 0.05 for all). In controls, we observed a negative correlation of ghrelin with age, male gender and BMI. These correlations were lost in the DCM group, except for male gender. Total ghrelin was higher in patients with more recent diagnosis when compared to patients with longer duration of the DCM ( p = 0.033). Further, total ghrelin was higher in patients with lower left ventricular systolic function (<40% LVEF, vs. 40% ≤ LVEF < 49% vs. LVEF ≥ 50%: 480.8, vs. 429.7, vs. 329.5 pg/mL, respectively, p = 0.05). Ghrelin prepropeptide was expressed more in DCM patients than in controls (p = 0.0293) while GHSR was expressed less in DCM patients (p < 0.001). Furthermore, ghrelin showed an inverse correlation with its receptor (= -0.406, p = 0.009), and this receptor showed a significant inverse correlation with Interleukin-1 (= -0.422, p = 0.0103)., Conclusion: DCM duration and severity are accompanied by alterations in the ghrelin-GHSR system., Competing Interests: The authors declare no conflict of interest.

Background: Low serum albumin is common in patients with chronic heart failure (HF)., Hypothesis: Albumin may have an impact on clinical outcome in HF. We evaluated the effect of albumin levels on clinical outcome in a real-world cohort of patients with HF., Methods: All patients with HF at a health maintenance organization were followed for cardiac-related hospitalizations and death., Results: A total of 5779 HF patients were included in the study; mean follow-up was 576 days; median serum albumin was 4.0 g/dL (interquartile range 3.7-4.2), and 12% of the patients had hypoalbuminemia (albumin<3.5 g/dL). Low albumin was associated with increasing age, higher urea and C-reactive protein, lower sodium, hemoglobin, iron, less treatment with angiotensin-converting enzyme inhibitor or angiotensin receptor blocker, reduced right ventricular function, and pulmonary hypertension. Cox regression analysis after adjustment for significant predictors demonstrated that decreasing quartiles of albumin was significantly associated with mortality: Lowest quartile compared to highest: hazard ratio (HR) 5.74, 95% confidence interval (CI) 4.08 to 8.07, P < 0.001. Cox regression analysis of albumin as a continuous parameter using restricted cubic splines after adjustment for significant parameters demonstrated that reduced albumin levels were directly associated with increased mortality (P < 0.001 for the adjusted model). Decreasing quartiles of albumin were also a significant predictor of increased cardiac-related hospitalizations. A decrease in albumin on follow-up was an independent predictor of increased mortality by Cox regression analysis: HR 2.58, 95% CI 2.12 to 3.14, P < 0.001., Conclusions: Low albumin provides important information regarding several detrimental processes in HF and is a significant predictor of a worse outcome in these patients., (© 2019 The Authors. Clinical Cardiology Published by Wiley Periodicals, Inc.)

Background: Studies indicate that women with atrial fibrillation (AF) are less likely to receive anticoagulants despite their higher risk of stroke compared with men., Objective: To evaluate whether the efficacy and safety of direct oral anticoagulants (DOACs) differ in women with AF as compared with men. Our secondary aim was to examine gender differences regarding the safety and efficacy of specific DOACs., Data Sources: MEDLINE, EMBASE, Cochrane, and ClinicalTrials.gov were searched through March 2017., Study Selection and Data Extraction: Randomized clinical trials that reported on major bleeding and stroke with DOACs in women and men with AF were included. Meta-analysis and network meta-analysis was performed., Data Synthesis: Five trials met the inclusion criteria. Among 66 389 patients, 37.8% were women. Women treated with DOACs were at higher risk of stroke and systemic embolism compared with men (RR = 1.19; 95% CI = 1.04-1.35; I 2 = 10%) but there was a significantly lower risk of major bleeding in women compared with men (RR = 0.86; 95% CI = 0.78-0.94; I 2 = 0%). Network meta-analyses suggested differences between various DOACs in men and women., Limitations: Patient-level data enabling control for differences in baseline risk and head-to-head comparisons between DOACs were not available. Relevance to Patient Care and Clinical Practice: Undertreatment with DOACs among women cannot be justified., Conclusion: Women treated with DOACs had a lower rate of major bleeding and higher rate of stroke and systemic emboli compared with men. Further investigation of DOACs, including differences between the DOACs in specific populations is warranted.

Blood group systems based on red blood cell antigens are genetically determined and can identify patients at risk. Type non-O of the ABO blood group system has been associated with coronary artery disease, thrombosis, and a worse prognosis. The present study evaluated the distribution of blood group types in patients with heart failure (HF) and the impact on clinical outcome. We evaluated the ABO and Rhesus D antigen (RhD) blood types in a large cohort of chronic HF patients (n = 3,815). ABO blood type distribution in the HF population was not significantly different to that reported in the general national population (A 40%, B 20%, AB 8%, and O 33%). The percentage of Rh-negative per blood type was also similar (A 10%, B 9%, AB 10%, and O 7%). Patients with type O were more likely to be hypertensive compared with non-O type. Mean follow-up was 4.2 years. Overall survival during follow-up was 55%. Cox regression analysis after adjustment for significant predictors demonstrated that RhD-negative was associated with a worse prognosis in patients with ischemic cardiomyopathy (n = 2,881, 76%): hazard ratio 1.26, 95% confidence interval 1.04 to 1.53, p = 0.02. Type non-O was also independently associated with a worse prognosis compared with type O in patients with non-ischemic cardiomyopathy: hazard ratio 1.32, 95% confidence interval 1.04 to 1.67, p = 0.02. In conclusion, blood group type distribution in HF patients are similar to the general population. RhD-negative is associated with a worse prognosis in patients with ischemic cardiomyopathy., (Copyright © 2018. Published by Elsevier Inc.)

Background: Heart failure (HF) is associated with considerable mortality. The electrocardiographic frontal QRS-T angle is a simple parameter to measure, reflects changes in the direction of the repolarization sequence and predicts outcome in patients with HF. Data regarding temporal changes in the frontal QRS-T angle in patients with HF and its impact on outcome is limited., Aim: To evaluate temporal changes in the frontal QRS-T angle and its effect on survival in patients with HF., Methods: Baseline and follow-up QRS-T angle were calculated from the frontal QRS and T axis of the 12-lead surface electrocardiogram. Patients were followed for survival., Results: 2,929 HF patients were evaluated. Median interval between baseline ECG and follow-up ECG was 895 days, median follow-up time was 1526 days. Overall, the QRS-T angle tended to be stable, with minor changes in the angle over time. The median QRS-T angle change was +3° (IQR -19° to +30°). Overall survival during follow-up was 60%. Cox regression analysis after adjustment for significant predictors demonstrated that the QRS-T angle was an incremental predictor of increased mortality. A widening of the QRS-T angle during follow-up was independently associated with an increase in mortality, evident with an increase of the QRS-T angle difference above 0° (P<0.0001 for the adjusted model)., Conclusion: QRS-T angle is relatively stable in patients with HF and is a powerful predictor of outcome. Widening of the QRS-T angle has predictive value and is an ominous sign.