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OBJECTIVES: To compare the impact of negotiated vs. mainstreamed follow-up with telephone reinforcement (TR) on maintenance of physical activity (PA) after Fit and Strong! ended. METHODS: A multisite comparative effectiveness trial with repeated measures. RESULTS: Single group random effects analyses showed significant improvements at 2, 6, 12, and 18 months on PA maintenance, lower-extremity (LE) pain and stiffness, LE function, sit-stand, 6-minute distance walk, and anxiety/depression. Analyses by follow-up condition showed persons in the negotiated with TR group maintained a 21% increase in caloric expenditures over baseline at 18 months, with lesser benefits seen in the negotiated-only, mainstreamed-with-TR, and mainstreamed-only groups. Significant benefits of telephone dose were also seen on LE joint stiffness, pain, and function as well as anxiety and anxiety/depression. CONCLUSIONS: The negotiated follow-up contract that Fit and Strong! uses, bolstered by TR, is associated with enhanced long-term PA maintenance and health outcomes. [ABSTRACT FROM AUTHOR]

OBJECTIVE: States vary greatly in their support for home- and community-based services (HCBS) that are intended to help disabled seniors live in the community. This article examines how states' generosity in providing HCBS affects the risk of nursing home admission among older Americans and how family availability moderates such effects. METHODS: We conducted discrete time survival analysis of first long-term (90 or more days) nursing home admissions that occurred between 1995 and 2002, using Health and Retirement Study panel data from respondents born in 1923 or earlier. RESULT: State HCBS effects were conditional on child availability among older Americans. Living in a state with higher HCBS expenditures was associated with lower risk of nursing home admission among childless seniors (p <.001). However, the association was not statistically significant among seniors with living children. Doubling state HCBS expenditures per person aged 65 or older would reduce the risk of nursing home admission among childless seniors by 35%. DISCUSSION: Results provided modest but important evidence supportive of increasing state investment in HCBS. Within-state allocation of HCBS resources, however, requires further research and careful consideration about fairness for individual seniors and their families as well as cost effectiveness. [ABSTRACT FROM AUTHOR]

Historically, there has been a large gap between African Americans and Whites in access to health care, but this gap was ostensibly lessened by the advent of Medicare and Medicaid for older adults in the mid 1960s. The extent to which older African Americans continue to receive less access to medical care as a result of economic inequalities, institutionalized forms of discrimination, and life-style factors remains a subject of policy debate. Empirical enquiry has produced inconsistent results. The purpose of this study is to test the same set of models of medical use using identically measured predictor variables in three nationally representative data sets of older Americans: 1984 Study of Aging (SOA); 1984 National Long-Term Care Survey (NLTC); and the 1987 National Medical Care Expenditure Survey (NMES). Multivariate logistic regression of use of physician and hospital services and Poisson regression of amount of service use identified inconsistent results in race differences across data sets, but consistent results in terms of the importance of health status and insurance as predictors of use and amount of use. The findings suggest that health status and financial resources may be more relevant areas for policy interventions than considerations related to race and ethnicity. [ABSTRACT FROM AUTHOR]

Background: With nearly 49,000 authorized retailers nationwide, a policy change that added fruits and vegetables (FV) to the U.S. Department of Agriculture's Special Supplemental Nutrition Program for Women, Infants, and Children (WIC) food packages in 2009 had the potential to expand neighborhood FV availability.Purpose: This study examined changes in availability and selection of commonly consumed and culturally specific FV at authorized retailers (WIC vendors) before and after implementation of the revised WIC food packages.Methods: Quasi-experimental, one-group design with two pre-policy observations and one post-policy observation. Trained observers assessed a list of fresh, frozen, and canned FV at each vendor in seven northern Illinois counties. Eight indices of FV availability and selection were derived. Multiple regression estimated relationships. Data were collected in 2008-2010 and analyzed in 2011.Results: Overall, availability and selection of commonly consumed fresh FV and availability of African-American culturally specific fresh FV improved after implementation of the new policy. Modest improvements in the overall availability of canned low-sodium vegetables and frozen FV were observed. Changes differed by vendor type (large vendor, small vendor, and pharmacy). Changes in availability or selection did not differ by neighborhood characteristics (population density, median household income, racial/ethnic composition).Conclusions: Expansion of WIC foods was associated with small positive externalities on the food environment. Larger subsidies to create more demand and more-substantial stocking requirements for retailers may yield significantly larger improvements and thus warrant further investigation. Approaches targeting rural, low-income, and racial/ethnic minority neighborhoods also may be needed. [ABSTRACT FROM AUTHOR]

Aims: In the absence of randomized trial evidence, we performed a large observational analysis of the association between beta-blocker (BB) use and clinical outcomes in patients with heart failure (HF) and mildly reduced (HFmrEF) and preserved ejection fraction (HFpEF)., Methods and Results: We pooled individual patient data from four large HFmrEF/HFpEF trials (I-Preserve, TOPCAT, PARAGON-HF, and DELIVER). The primary outcome was the composite of cardiovascular death or HF hospitalization. Among the 16 951 patients included, the mean left ventricular ejection fraction (LVEF) was 56.8%, and 13 400 (79.1%) had HFpEF (LVEF ≥50%). Overall, 12 812 patients (75.6%) received a BB. The median bisoprolol-equivalent dose of BB was 5.0 (Q1-Q3: 2.5-5.0) mg with BB continuation rates of 93.1% at 2 years (in survivors). The unadjusted hazard ratio (HR) for the primary outcome did not differ between BB users and non-users (HR 0.98, 95% confidence interval [CI] 0.91-1.05), but the adjusted HR was lower in BB users than non-users (0.81, 95% CI 0.74-0.88), and this association was maintained across LVEF (p interaction  = 0.88). In subgroup analyses, the adjusted risk of the primary outcome was similar in BB users and non-users with or without a history of myocardial infarction, hypertension, or a baseline heart rate <70 bpm. By contrast, a better outcome with BB use was seen in patients with atrial fibrillation compared to those without atrial fibrillation (p intreraction  = 0.02)., Conclusions: In this observational analysis of non-randomized BB treatment, there was no suggestion that BB use was associated with worse HF outcomes in HFmrEF/HFpEF, even after extensive adjustment for other prognostic variables., (© 2024 European Society of Cardiology.)

Aims: Although the prevalence of heart failure (HF) increases markedly with advancing age, surprisingly little is known about HF in the very elderly. The aim of this study was to describe the clinical characteristics and outcomes of octogenarians with HF., Methods and Results: Individual participant meta-analysis of patients with HF and reduced, mildly reduced, and preserved ejection fraction (HFrEF, HFmrEF, and HFpEF, respectively) enrolled in eight large randomized trials. Overall, the proportion of octogenarians was 1518 of 20 168 patients (7.5%) with HFrEF, 610 of 4609 (13.2%) with HFmrEF, and 3130 of 15 354 (20.4%) with HFpEF. Regardless of HF phenotype, octogenarian patients were more often female and had more comorbidities, more symptoms and signs of congestion, and worse health status (but not quality of life), in comparison to patients aged <80 years. The incidence (per 100 person-years) of the composite of cardiovascular death or HF hospitalization was 13.3 (95% confidence interval [CI] 12.7-14.0) in octogenarians versus 9.5 (95% CI 9.3-9.7) in non-octogenarians (adjusted hazard ratio [aHR] 1.40, 95% CI 1.32-1.48). Each component of the composite was more frequent in octogenarians with rates of cardiovascular mortality of 7.0 (95% CI 6.5-7.4) per 100 person-years versus 4.9 (95% CI 4.8-5.1) in non-octogenarians (aHR 1.60, 95% CI 1.48-1.72, p < 0.001). Octogenarians received less evidence-based therapy, especially mineralocorticoid receptor antagonists, than younger patients., Conclusion: Despite worse health status and higher hospitalization and mortality rates, octogenarians were undertreated compared to younger patients., (© 2024 European Society of Cardiology.)

Aims: Patients with a reduced left ventricular ejection fraction (LVEF) following an acute myocardial infarction (MI) are at risk of progressive adverse cardiac remodelling that can lead to the development of heart failure and death. The early addition of a sodium-glucose cotransporter 2 (SGLT2) inhibitor to standard treatment may delay or prevent progressive adverse remodelling in these patients., Methods and Results: EMpagliflozin to PREvent worSening of left ventricular volumes and Systolic function after Myocardial Infarction (EMPRESS-MI) is a randomized, double-blind, placebo-controlled, multi-centre trial designed to assess the effect of empagliflozin on cardiac remodelling evaluated using cardiovascular magnetic resonance (CMR) in 100 patients with left ventricular systolic dysfunction following MI. Eligible patients were those ≥12 h and ≤14 days following acute MI, with an LVEF <45% by CMR. Patients were randomized to empagliflozin 10 mg once a day or matching placebo. The primary outcome will be change in left ventricular end-systolic volume indexed to body surface area over 24 weeks from randomization. Secondary endpoints include measures of left ventricular and atrial volumes, left ventricular mass, LVEF, and circulating cardiac biomarkers., Conclusions: EMPRESS-MI will assess the effect of the SGLT2 inhibitor empagliflozin on cardiac remodelling in patients with left ventricular systolic dysfunction after an acute MI., (© 2024 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Background: Predischarge risk stratification of patients with acute heart failure (AHF) could facilitate tailored treatment and follow-up, however, simple scores to predict short-term risk for HF readmission or death are lacking., Methods: We sought to develop a congestion-focused risk score using data from a prospective, two-center observational study in adults hospitalized for AHF. Laboratory data were collected on admission. Patients underwent physical examination, 4-zone, and in a subset 8-zone, lung ultrasound (LUS), and echocardiography at baseline. A second LUS was performed before discharge in a subset of patients. The primary endpoint was the composite of HF hospitalization or all-cause death., Results: Among 350 patients (median age 75 years, 43% women), 88 participants (25%) were hospitalized or died within 90 days after discharge. A stepwise Cox regression model selected four significant independent predictors of the composite outcome, and each was assigned points proportional to its regression coefficient: NT-proBNP ≥2000 pg/mL (admission) (3 points), systolic blood pressure < 120 mmHg (baseline) (2 points), left atrial volume index ≥60 mL/m 2 (baseline) (1 point) and ≥ 9 B-lines on predischarge 4-zone LUS (3 points). This risk score provided adequate risk discrimination for the composite outcome (HR 1.48 per 1 point increase, 95% confidence interval: 1.32-1.67, p < 0.001, C-statistic: 0.70). In a subset of patients with 8-zone LUS data (n = 176), results were similar (C-statistic: 0.72)., Conclusions: A four-variable risk score integrating clinical, laboratory and ultrasound data may provide a simple approach for risk discrimination for 90-day adverse outcomes in patients with AHF if validated in future investigations., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Conventional time-to-first-event analyses cannot incorporate recurrent hospitalizations and patient well-being in a single outcome., Objectives: To overcome this limitation, we tested an integrated measure that includes days lost from death and hospitalization, and additional days of full health lost through diminished well-being., Methods: The effect of dapagliflozin on this integrated measure was assessed in the DAPA-HF (Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure) trial, which examined the efficacy of dapagliflozin, compared with placebo, in patients with NYHA functional class II to IV heart failure and a left ventricular ejection fraction ≤40%., Results: Over 360 days, patients in the dapagliflozin group (n = 2,127) lost 10.6 ± 1.0 (2.9%) of potential follow-up days through cardiovascular death and heart failure hospitalization, compared with 14.4 ± 1.0 days (4.0%) in the placebo group (n = 2,108), and this component of all measures of days lost accounted for the greatest between-treatment difference (-3.8 days [95% CI: -6.6 to -1.0 days]). Patients receiving dapagliflozin also had fewer days lost to death and hospitalization from all causes vs placebo (15.5 ± 1.1 days [4.3%] vs 20.3 ± 1.1 days [5.6%]). When additional days of full health lost (ie, adjusted for Kansas City Cardiomyopathy Questionnaire-overall summary score) were added, total days lost were 110.6 ± 1.6 days (30.7%) with dapagliflozin vs 116.9 ± 1.6 days (32.5%) with placebo. The difference in all measures between the 2 groups increased over time (ie, days lost by death and hospitalization -0.9 days [-0.7%] at 120 days, -2.3 days [-1.0%] at 240 days, and -4.8 days [-1.3%] at 360 days)., Conclusions: Dapagliflozin reduced the total days of potential full health lost due to death, hospitalizations, and impaired well-being, and this benefit increased over time during the first year. (Study to Evaluate the Effect of Dapagliflozin on the Incidence of Worsening Heart Failure or Cardiovascular Death in Patients With Chronic Heart Failure; NCT03036124)., Competing Interests: Funding Support and Author Disclosures Drs Jhund and McMurray are supported by a British Heart Foundation Centre of Research Excellence Grant RE/18/6/34217 and the Vera Melrose Heart Failure Research Fund. DAPA-HF was funded by AstraZeneca. Dr Kondo has received speaker fees from Abbott, Ono Pharma, Otsuka Pharma, Novartis, AstraZeneca, Bristol Myers Squibb, Boehringer Ingelheim, and Abiomed. Drs Gasparyan, Bengtsson, and Sabatine are employees and shareholders of AstraZeneca. Dr Campbell has received speakers’ honoraria from AstraZeneca; has served on an advisory board for Bayer AG; and has received grant support from AstraZeneca (paid to his institution). Dr Docherty has received honoraria from AstraZeneca; and has received a research grant to his institution from Boehringer Ingelheim. Dr de Boer has received research grants and fees from AstraZeneca, Abbott, Boehringer Ingelheim, Cardio Pharmaceuticals GmbH, Ionis Pharmaceuticals, Novo Nordisk, and Roche (outside the submitted work); and has received speaker fees from Abbott, AstraZeneca, Bayer, Novartis, and Roche (outside the submitted work). Dr Inzucchi has served on clinical trial committees or as a consultant to AstraZeneca, Boehringer Ingelheim, Novo Nordisk, Lexicon, Merck, Pfizer, vTv Therapeutics, Abbott, Esperion, and Bayer; and has given lectures sponsored by AstraZeneca and Boehringer Ingelheim. Dr Køber has received financial support from AstraZeneca; and has received personal fees from Novartis and Bristol Myers Squibb as a speaker. Dr Kosiborod has received research grant support from AstraZeneca, and Boehringer Ingelheim; has served as a consultant or on an advisory board for Amgen, Applied Therapeutics, AstraZeneca, Bayer, Boehringer Ingelheim, Eli Lilly, Esperion Therapeutics, Janssen, Merck (Diabetes and Cardiovascular), Novo Nordisk, Sanofi, and Vifor Pharma; has received other research support from AstraZeneca; and has received honorarium from AstraZeneca, Boehringer Ingelheim, and Novo Nordisk. Dr Martinez has received personal fees from AstraZeneca. Dr Sabatine has received grants and personal fees from AstraZeneca during the conduct of the study; has received grants and personal fees from Amgen, Intarcia, Janssen Research and Development, The Medicines Company, MedImmune, Merck, and Novartis; has received personal fees from Anthos Therapeutics, Bristol Myers Squibb, CVS Caremark, DalCor, Dyrnamix, Esperion, IFM Therapeutics, and Ionis; has received grants from Daiichi-Sankyo, Bayer, Pfizer, Poxel, Eisai, GlaxoSmithKline, Quark Pharmaceuticals, and Takeda outside the submitted work; and is a member of the TIMI Study Group, which has also received institutional research grant support through Brigham and Women’s Hospital from Abbott, Aralez, Roche, and Zora Biosciences. Dr Vaduganathan has received research grant support or served on advisory boards for American Regent, Amgen, AstraZeneca, Bayer AG, Baxter Healthcare, Boehringer Ingelheim, Chiesi, Cytokinetics, Lexicon Pharmaceuticals, Novartis, Novo Nordisk, Pharmacosmos, Relypsa, Roche Diagnostics, Sanofi, and Tricog Health; has had speaker engagements with AstraZeneca, Novartis, and Roche Diagnostics; and has participated on clinical trial committees for studies sponsored by AstraZeneca, Occlutech, Impulse Dynamicx, Galmed, and Novartis. Dr Solomon has received research grants from Actelion, Alnylam, Amgen, AstraZeneca, Bellerophon, Bayer, Bristol Myers Squibb, Celladon, Cytokinetics, Eidos, Gilead, GlaxoSmithKline, Ionis, Lilly, Mesoblast, MyoKardia, National Institutes of Health/NHLBI, Neurotronik, Novartis, NovoNordisk, Respicardia, Sanofi Pasteur, Theracos, and US2.AI; and has consulted for Abbott, Action, Akros, Alnylam, Amgen, Arena, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Cardior, Cardurion, Corvia, Cytokinetics, Daiichi-Sankyo, GlaxoSmithKline, Lilly, Merck, Myokardia, Novartis, Roche, Theracos, Quantum Genomics, Cardurion, Janssen, Cardiac Dimensions, Tenaya, Sanofi-Pasteur, Dinaqor, Tremeau, CellPro- Thera, Moderna, American Regent, and Sarepta. Dr Jhund has received speaker fees from AstraZeneca, Novartis, Alkem Metabolics, ProAdWise Communications, Sun Pharmaceuticals, and Intas Pharmaceuticals; has received advisory board fees from AstraZeneca, Boehringer Ingelheim, and Novartis; has received research funding from AstraZeneca, Boehringer Ingelheim, and Analog Devices Inc; his employer the University of Glasgow has been remunerated for clinical trial work from AstraZeneca, Bayer AG, Novartis, and NovoNordisk; and he is a Director of the Global Clinical Trial Partners (GCTP). Dr McMurray has received payments through Glasgow University from work on clinical trials, consulting, and other activities from Amgen, AstraZeneca, Bayer, Cardurion, Cytokinetics, GlaxoSmithKline, KBP Biosciences, and Novartis; has received personal consultancy fees from Alnylam Pharma., Bayer, Bristol Myers Squibb, George Clinical PTY Ltd, Ionis Pharma, Novartis, Regeneron Pharma, and River 2 Renal Corporation; has received personal lecture fees from Abbott, Alkem Metabolics, AstraZeneca, Blue Ocean Scientific Solutions Ltd, Boehringer Ingelheim, Canadian Medical and Surgical Knowledge, Emcure Pharma. Ltd, Eris Lifesciences, European Academy of CME, Hikma Pharmaceuticals, Imagica health, Intas Pharma, J.B. Chemicals & Pharma. Ltd, Lupin Pharma, Medscape/Heart.Org, ProAdWise Communications, Radcliffe Cardiology, Sun Pharma, The Corpus, Translation Research Group, and Translational Medicine Academy; and is a director of Global Clinical Trial Partners Ltd. 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.)

Importance: Accurate risk prediction of morbidity and mortality in patients with heart failure with preserved ejection fraction (HFpEF) may help clinicians risk stratify and inform care decisions., Objective: To develop and validate a novel prediction model for clinical outcomes in patients with HFpEF using routinely collected variables and to compare it with a biomarker-driven approach., Design, Setting, and Participants: Data were used from the Dapagliflozin Evaluation to Improve the Lives of Patients With Preserved Ejection Fraction Heart Failure (DELIVER) trial to derive the prediction model, and data from the Angiotensin Receptor Neprilysin Inhibition in Heart Failure With Preserved Ejection Fraction (PARAGON-HF) and the Irbesartan in Heart Failure With Preserved Ejection Fraction Study (I-PRESERVE) trials were used to validate it. The outcomes were the composite of HF hospitalization (HFH) or cardiovascular death, cardiovascular death, and all-cause death. A total of 30 baseline candidate variables were selected in a stepwise fashion using multivariable analyses to create the models. Data were analyzed from January 2023 to June 2023., Exposures: Models to estimate the 1-year and 2-year risk of cardiovascular death or hospitalization for heart failure, cardiovascular death, and all-cause death., Results: Data from 6263 individuals in the DELIVER trial were used to derive the prediction model and data from 4796 individuals in the PARAGON-HF trial and 4128 individuals in the I-PRESERVE trial were used to validate it. The final prediction model for the composite outcome included 11 variables: N-terminal pro-brain natriuretic peptide (NT-proBNP) level, HFH within the past 6 months, creatinine level, diabetes, geographic region, HF duration, treatment with a sodium-glucose cotransporter 2 inhibitor, chronic obstructive pulmonary disease, transient ischemic attack/stroke, any previous HFH, and heart rate. This model showed good discrimination (C statistic at 1 year, 0.73; 95% CI, 0.71-0.75) in both validation cohorts (C statistic at 1 year, 0.71; 95% CI, 0.69-0.74 in PARAGON-HF and 0.75; 95% CI, 0.73-0.78 in I-PRESERVE) and calibration. The model showed similar discrimination to a biomarker-driven model including high-sensitivity cardiac troponin T and significantly better discrimination than the Meta-Analysis Global Group in Chronic (MAGGIC) risk score (C statistic at 1 year, 0.60; 95% CI, 0.58-0.63; delta C statistic, 0.13; 95% CI, 0.10-0.15; P < .001) and NT-proBNP level alone (C statistic at 1 year, 0.66; 95% CI, 0.64-0.68; delta C statistic, 0.07; 95% CI, 0.05-0.08; P < .001). Models derived for the prediction of all-cause and cardiovascular death also performed well. An online calculator was created to allow calculation of an individual's risk., Conclusions and Relevance: In this prognostic study, a robust prediction model for clinical outcomes in HFpEF was developed and validated using routinely collected variables. The model performed better than NT-proBNP level alone. The model may help clinicians to identify high-risk patients and guide treatment decisions in HFpEF.

Aims: Subcutaneous (SC) furosemide has potential advantages over intravenous (IV) furosemide by enabling self-administration or administration by a lay caregiver, such as facilitating early discharge, preventing hospitalizations, and in palliative care. A high-concentration, pH-neutral furosemide formulation has been developed for SC administration via a small patch infusor pump. We aimed to compare the bioavailability, pharmacokinetic (PK), and pharmacodynamic (PD) profiles of a new SC furosemide formulation with conventional IV furosemide and describe the first use of a bespoke mini-pump to administer this formulation., Methods and Results: A novel pH-neutral formulation of SC furosemide containing 80 mg furosemide in ∼2.7 mL (infused over 5 h) was investigated. The first study was a PK/PD study of SC furosemide compared with 80 mg IV furosemide administered as a bolus in ambulatory patients with heart failure (HF). The primary outcome was absolute bioavailability of SC compared with IV furosemide. The second study investigated the same SC furosemide preparation delivered by a patch infusor in patients hospitalized with HF. Primary outcome measures were treatment-emergent adverse events, infusion site pain, device performance, and PK measurements.The absolute bioavailability of SC furosemide in comparison to IV furosemide was 112%, resulting in equivalent diuresis and natriuresis. When SC furosemide was administered via the patch pump, there were no treatment-emergent adverse events and 95% of participants reported no/minor discomfort at the infusion site., Conclusion: The novel preparation of SC furosemide had similar bioavailability to IV furosemide. Administration via a patch pump was feasible and well tolerated., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background and Aims: Randomized controlled trials (RCTs) have assessed the effects of renin-angiotensin system (RAS) blockers in adults with coronavirus disease 2019 (COVID-19). This meta-analysis provides estimates of the safety and efficacy of treatment with (vs. without) RAS blockers from these trials., Methods: PubMed, Web of Science, and ClinicalTrials.gov were searched (1 March-12 April 2023). Event/patient numbers were extracted, comparing angiotensin-converting enzyme (ACE) inhibitor/angiotensin-receptor blocker (ARB) treatment with no treatment, for the outcomes: intensive care unit (ICU) admission, mechanical ventilation, vasopressor use, acute kidney injury (AKI), renal replacement therapy (RRT), acute myocardial infarction, stroke/transient ischaemic attack, heart failure, thromboembolic events, and all-cause death. Fixed-effects meta-analysis estimates were pooled., Results: Sixteen RCTs including 3492 patients were analysed. Compared with discontinuation of RAS blockers, continuation was not associated with increased risk of ICU [risk ratio (RR) 0.96, 0.66-1.41], ventilation (RR 0.77, 0.55-1.09), vasopressors (RR 0.92, 0.58-1.44), AKI (RR 1.01, 0.40-2.56), RRT (RR 1.01, 0.46-2.21), or thromboembolic events (RR 1.07, 0.36-3.19). RAS blocker initiation was not associated with increased risk of ICU (RR 0.71, 0.47-1.08), ventilation (RR 1.12, 0.91-1.38), AKI (RR 1.28, 0.89-1.86), RRT (RR 1.66, 0.89-3.12), or thromboembolic events (RR 1.20, 0.06-23.70), although vasopressor use increased (RR 1.27, 1.02-1.57). The RR for all-cause death in the continuation/discontinuation trials was 1.24 (0.80-1.92), and 1.22 (0.96-1.55) in the initiation trials. In patients with severe/critical COVID-19, RAS blocker initiation increased the risk of all-cause death (RR 1.31, 1.01-1.72)., Conclusion: ACE inhibitors and ARBs may be continued in non-severe COVID-19 infection, where indicated. Conversely, initiation of RAS blockers may be harmful in critically ill patients.PROSPERO registration number: CRD42023408926., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Introduction: Cardiovascular diseases are a substantial burden on healthcare systems, contributing significantly to avoidable hospital admissions. We propose a Cardiology Ambulatory Care Pathway., Methods: Conducted a 1 month study redirecting admission streams from primary and emergency care, into a Cardiology Ambulatory Care Hub providing triage in Hot Clinic, and access to a Multi-Modal Testing Platform., Results: 98 patients were referred to the Ambulatory Care Hub, 91 of which avoided admission. 52 patients received care in the cardiology hub, 38 of which required further testing., Conclusion: We successfully streamlined various service streams, reducing admissions, and improving patient outcomes. Outpatient CTCA, ambulatory ECG, and echocardiography proved instrumental. We project a cost saving of £53,379 per month in bed days (£640,556 annual saving).

Aims: Patients with heart failure (HF) and mildly reduced ejection fraction (HFmrEF) and preserved ejection fraction (HFpEF) are often treated with calcium channel blockers (CCBs), although the safety of CCBs in these patients is uncertain. We aimed to investigate the association between CCB use and clinical outcomes in patients with HFmrEF/HFpEF; CCBs were examined overall, as well as by subtype (dihydropyridine and non-dihydropyridine)., Methods and Results: We pooled individual patient data from four large HFpEF/HFmrEF trials. The association between CCB use and outcomes was assessed. Among the 16 954 patients included, the mean left ventricular ejection fraction (LVEF) was 56.8%, and 13 402 (79.0%) had HFpEF (LVEF ≥50%). Altogether, 5874 patients (34.6%) received a CCB (87.6% dihydropyridines). Overall, the risks of death and HF hospitalization were not higher in patients treated with a CCB, particularly dihydropyridines. The risk of pump failure death was significantly lower (hazard ratio [HR] 0.76, 95% confidence interval [CI] 0.60-0.96), while the risk of stroke was higher (HR 1.26, 95% CI 1.06-1.50) in patients treated with a CCB compared to those not. These risks remained different in patients treated and not treated with a CCB after adjustment for other prognostic variables. Although the majority of patients were treated with dihydropyridine CCBs, the pattern of outcomes was broadly similar for both dihydropyridine and non-dihydropyridine CCBs., Conclusion: Although this is an observational analysis of non-randomized treatment, there was no suggestion that CCBs were associated with worse HF outcomes. Indeed, CCB use was associated with a lower incidence of pump failure death., (© 2023 European Society of Cardiology.)

Background: It is unknown how the efficacy and safety of mineralocorticoid receptor antagonists vary according to duration of heart failure with reduced ejection fraction (HFrEF)., Objectives: In this study, we sought to evaluate the safety and efficacy of eplerenone according to duration of HFrEF., Methods: In the EMPHASIS-HF trial, 3 patient groups were created according to HFrEF duration: <1 year, 1 to <5 years, and ≥5 years. The primary outcome was the composite of heart failure (HF) hospitalization or cardiovascular death. Outcomes were adjusted for prespecified prognostic variables and examined with the use of Cox regression models., Results: The numbers of patients in each group were: 975, <1 year; 769, 1 to <5 years; and 988, ≥5 years. Patients with longer-standing HF were older and more frequently had cardiovascular and noncardiovascular comorbidities. The rate of the primary outcome (per 100 person-years) increased with HFrEF duration: 9.8 (95% CI: 8.4-11.4) for <1 year, 13.5 (95% CI: 11.6-15.7) for 1 to <5 years, and 17.6 (95% CI: 15.6-19.8) for ≥5 years. The benefits of eplerenone were consistent across HF duration: HRs for the primary outcome were 0.57 (95% CI: 0.42-0.79) for <1 year, 0.81 (95% CI: 0.60-1.10) for 1 to <5 years, and 0.61 (95% CI: 0.48-0.78) for ≥5 years; P interaction  = 0.24. The absolute benefit was greatest in the longest-duration group: the number needed to treat for the primary outcome was 14 for <1 year, 13 for 1 to <5 years, and 10 for ≥5 years duration., Conclusions: Patients with longer-standing HFrEF had worse clinical status and a higher rate of events, but the benefit of eplerenone was consistent regardless of HFrEF duration. (A Comparison of Outcomes in Patients in NYHA Class II Heart Failure When Treated With Eplerenone or Placebo in Addition to Standard Heart Failure Medicines [EMPHASIS-HF]; NCT00232180)., Competing Interests: Funding Support and Author Disclosures The EMPHASIS-HF trial was sponsored by Pfizer. Drs Jhund and McMurray are supported by a British Heart Foundation Centre of Research Excellence Grant RE/18/6/34217 and the Vera Melrose Heart Failure Research Fund. Dr Matsumoto has received research grants and personal fees from Abott, Bayer Pharma, Boehringer Ingelheim, Daiichi-Sankyo, Medtronic, Novartis, Ono Pharma, Orbus Neich, Otsuka Pharma, and the Uehara Memorial Foundation. Dr Kondo has received speaker fees from Abbott, Ono Pharma, Otsuka Pharma, Novartis, AstraZeneca, Bristol Myers Squibb, Boehringer Ingelheim, and Abiomed. Dr Jhund has received speaker fees from AstraZeneca, Novartis, Alkem Metabolics, ProAdWise Communications, Sun Pharmaceuticals, and Intas Pharmaceuticals; has received advisory board fees from AstraZeneca, Boehringer Ingelheim, and Novartis; has received research funding from AstraZeneca, Boehringer Ingelheim, and Analog Devices; is a director of Global Clinical Trial Partners; and his employer, the University of Glasgow, has been remunerated for clinical trial work from AstraZeneca, Bayer, Novartis, and Novo Nordisk. Dr Campbell has received consultancy honoraria from Bayer and speaking honoraria from AstraZeneca. Dr Swedberg has received honoraria from AstraZeneca, Boehringer Ingelheim, and Novartis. Dr Pocock has received consulting fees and payment or honoraria for lectures, presentations, Speaker Bureau, manuscript writing, and educational events from Boehringer Ingelheim. Dr Pitt has served as a consultant for Bayer, AstraZeneca, Boehringer Ingelheim, Merck, Lexicon, KBP BioSciences (with stock options), Vifor (with stock options), Sarfez (with stock options), scPharmaceuticals (with stock options), SQ Innovation (with stock options), G3 Pharmaceuticals, Proton Intel (with stock options), Cereno Scientific (with stock options), and Brainstorm Medical (with stock options); has U.S. patent 9931422 (site-specific delivery of eplerenone to the myocardium); and has U.S. patent pending 63/045783 (histone acetylation modulating agents for the protection and treatment of organ damage). Dr Zannad has received personal fees from Boehringer Ingelheim during the conduct of the study; has received personal fees from Janssen, Novartis, Boston Scientific, Amgen, CVRx, AstraZeneca, Vifor Fresenius, Cardior, Cereno Pharmaceutical, Applied Therapeutics, Merck, Bayer, and Cellprothera; and is cofounder of CVCT and Cardiorenal, outside the submitted work. Dr McMurray has received payments through Glasgow University for work on clinical trials, consulting, and other activities from Amgen, AstraZeneca, Bayer, Cardurion, Cytokinetics, GSK, KBP Biosciences, and Novartis; has received personal consultancy fees from Alnylam Pharma, Bayer, Bristol Myers Squibb, George Clinical PTY, Ionis Pharma, Novartis, Regeneron Pharma, and River 2 Renal Corporation; and has received personal lecture fees from Abbott, Alkem Metabolics, AstraZeneca, Blue Ocean Scientific Solutions, Boehringer Ingelheim, Canadian Medical and Surgical Knowledge, Emcure Pharma, Eris Lifesciences, European Academy of CME, Hikma Pharmaceuticals, Imagica health, Intas Pharma, J.B. Chemicals & Pharma, Lupin Pharma, Medscape/Heart.Org, ProAdWise Communications, Radcliffe Cardiology, Sun Pharma, The Corpus, Translation Research Group, and Translational Medicine Academy; and is a director of Global Clinical Trial Partners., (Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background and Aims: To examine the decongestive effect of the sodium-glucose cotransporter 2 inhibitor dapagliflozin compared to the thiazide-like diuretic metolazone in patients hospitalized for heart failure and resistant to treatment with intravenous furosemide., Methods and Results: A multi-centre, open-label, randomized, and active-comparator trial. Patients were randomized to dapagliflozin 10 mg once daily or metolazone 5-10 mg once daily for a 3-day treatment period, with follow-up for primary and secondary endpoints until day 5 (96 h). The primary endpoint was a diuretic effect, assessed by change in weight (kg). Secondary endpoints included a change in pulmonary congestion (lung ultrasound), loop diuretic efficiency (weight change per 40 mg of furosemide), and a volume assessment score. 61 patients were randomized. The mean (±standard deviation) cumulative dose of furosemide at 96 h was 977 (±492) mg in the dapagliflozin group and 704 (±428) mg in patients assigned to metolazone. The mean (±standard deviation) decrease in weight at 96 h was 3.0 (2.5) kg with dapagliflozin compared to 3.6 (2.0) kg with metolazone [mean difference 0.65, 95% confidence interval (CI) -0.12,1.41 kg; P = 0.11]. Loop diuretic efficiency was less with dapagliflozin than with metolazone [mean 0.15 (0.12) vs. 0.25 (0.19); difference -0.08, 95% CI -0.17,0.01 kg; P = 0.10]. Changes in pulmonary congestion and volume assessment score were similar between treatments. Decreases in plasma sodium and potassium and increases in urea and creatinine were smaller with dapagliflozin than with metolazone. Serious adverse events were similar between treatments., Conclusion: In patients with heart failure and loop diuretic resistance, dapagliflozin was not more effective at relieving congestion than metolazone. Patients assigned to dapagliflozin received a larger cumulative dose of furosemide but experienced less biochemical upset than those assigned to metolazone., Trial Registration: ClinicalTrials.gov Identifier: NCT04860011., Competing Interests: Conflict of interest: S.E.Y. reports no conflicts of interest. J.O. reports no conflicts of interest. M.C.P. reports research grants from Boehringer Ingelheim, Roche, SQ Innovations, AstraZeneca, Novartis, Novo Nordisk, Medtronic, Boston Scientific, Pharmacosmos. M.C.P. reports consulting fees from Boehringer Ingelheim, Novartis, AstraZeneca, Novo Nordisk, Abbvie, Bayer, Takeda, Corvia, Cardiorentis, Pharmacosmos, Siemens, Vifor. M.C.P. reports honoraria from Boehringer Ingelheim, Novartis, Astra Zeneca, Novo Nordisk, Abbvie, Bayer, Takeda, Corvia, Cardiorentis, Pharmacosmos, Siemens, Vifor. M.C.P. is a director of Global Clinical Trial Partners Ltd. K.J.M.B. reports no conflict of interest. A.L.C. reports speaking honoraria from AstraZeneca, and consultancy honoraria from Vifor. K.F.D. reports that his employer, the University of Glasgow, has been remunerated by AstraZeneca for work related to clinical trials. K.F.D. has received speakers’ honoraria from AstraZeneca and Radcliffe Cardiology, has served on an advisory board for Us2.ai and Bayer AG, served on a clinical endpoint committee for Bayer AG, and has received grant support from Boehringer Ingelheim, Novartis and AstraZeneca (paid to his institution). P.W.X.F. reports research grant funding from Medtronic, honoraria from Pharmacosmos, and consulting fees for Medtronic. K.G. has previously received honoraria from AstraZeneca, Servier Laboratories, Boehringer Ingleheim, Novartis. An unrestricted educational grant from Biotronik limited and travel assistance from Medtronic, Boston Scientific and Abbott. C.A.H. reports no conflicts of interest. P.S.J. reports speakers’ fees from AstraZeneca, Novartis, Alkem Metabolics, ProAdWise Communications, Sun Pharmaceuticals, Intas Pharma; advisory board fees from AstraZeneca, Boehringer Ingelheim, Novartis; research funding from AstraZeneca, Boehringer Ingelheim, Analog Devices Inc, Roche Diagnostics. P.S.J.’s employer the University of Glasgow has been remunerated for clincal trial work from AstraZeneca, Bayer AG, Novartis and NovoNordisk. Director, Global Clinical Trial Partners (GCTP). P.R.K. reports research grants from British Heart Foundation and Pharmacosmos; consulting fees from Ackea, Amgen, Boehringer Ingelheim, Pharmacosmos, Servier, and Vifor Pharma; payment for lectures from AstraZeneca, Bayer, Novartis, Pfizer, Pharmacosmos, and Vifor Pharma; support for attending meetings from Pharmacosmos; is a data safety monitoring board member for the STOP-ACE trial and EMPRESS-MI trial; and has served as Chair of the British Society for Heart Failure. G.M. reports no conflict of interest. N.N.L. reports research grants from AstraZeneca, Boehringer Ingelheim, British Heart Foundation, and Roche Diagnostics; consulting fees from AstraZeneca, Akero Therapeutics and Bristol-Myers Squibb; payment for lectures from Novartis and Roche. M.M.Y.L.'s employer, the University of Glasgow, receives grant support from AstraZeneca and Boehringer Ingelheim. He serves on clinical endpoint committees for Bayer, and steering committees for Cytokinetics. A.M. reports no conflict of interest. J.J.M. reports being an employee of AstraZeneca. E.P.’s employer has received support from Novartis for consulting work, and she has consulted for scPharmaceuticals outside of the submitted work. She has received research support from the NIH and the American Heart Association. P.S. reports being an employee of AstraZeneca. A.S. reports no conflict of interest. B.S. reports no conflict of interest. R.A.P.W. reports no conflict of interest. P.W. reports grant income from Roche Diagnostics, Astrazeneca, Boehringer Ingelheim, and Novartis, and speaker fees from Novo Nordisk and Raisio, outside the submitted work. J.J.V.M. reports payments through Glasgow University from work on clinical trials, consulting and other activities from: Amgen, AstraZeneca, Bayer, Cardurion, Cytokinetics, GSK, KBP Biosciences, and Novartis. Personal consultancy fees from: Alnylam Pharma., Bayer, BMS, George Clinical PTY Ltd., Ionis Pharma, Novartis, Regeneron Pharma., River 2 Renal Corporation. J.J.V.M. has received personal lecture fees from: Abbott, Alkem Metabolics, Astra Zeneca, Blue Ocean Scientific Solutions Ltd., Boehringer Ingelheim, Canadian Medical and Surgical Knowledge, Emcure Pharma Ltd., Eris Lifesciences, European Academy of CME, Hikma Pharmaceuticals, Imagica health, Intas Pharma, J.B. Chemicals & Pharma Ltd., Lupin Pharma, Medscape/Heart.Org, ProAdWise. J.J.V.M. has received honoraria for communications, Radcliffe Cardiology, Sun Pharma, The Corpus, Translation Research Group, Translational Medicine Academy. J.J.V.M. is a director of Global Clinical Trial Partners Ltd. R.T.C. has received consultancy honoraria from Bayer and speaking honoraria from AstraZeneca., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Aim: Mortality from acute myocardial infarction (AMI) has declined, increasing the pool of survivors at risk of later development of heart failure (HF). However, coronary reperfusion limits infarct size and secondary prevention therapies have improved. In light of these competing influences, we examined long-term trends in the risk of HF hospitalization (HFH) following a first AMI occurring in Scotland over 25 years., Methods and Results: All patients in Scotland discharged alive after a first AMI between 1991 and 2015 were followed until a first HFH or death until the end of 2016 (minimum follow-up 1 year, maximum 26 years). A total of 175 672 people with no prior history of HF were discharged alive after a first AMI during the period of study. A total of 21 445 (12.2%) patients had a first HFH during a median follow-up of 6.7 years. Incidence of HFH (per 1000 person-years) at 1 year following discharge from a first AMI decreased from 59.3 (95% confidence interval [CI] 54.2-64.7) in 1991 to 31.3 (95% CI 27.3-35.8) in 2015, with consistent trends seen for HF occurring within 5 and 10 years. Accounting for the competing risk of death, the adjusted risk of HFH at 1 year after discharge decreased by 53% (95% CI 45-60%), with similar decreases at 5 and 10 years., Conclusion: The incidence of HFH following AMI in Scotland has decreased since 1991. These trends suggest that better treatment of AMI and secondary prevention are having an impact on the risk of HF at a population level., (© 2023 The Authors. European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Water and salt retention, in other words congestion, are fundamental to the pathophysiology of heart failure and are important therapeutic targets. Echocardiography is the key tool with which to assess cardiac structure and function in the initial diagnostic workup of patients with suspected heart failure and is essential for guiding treatment and stratifying risk. Ultrasound can also be used to identify and quantify congestion in the great veins, kidneys and lungs. More advanced imaging methods might further clarify the aetiology of heart failure and its consequences for the heart and periphery, thereby improving the efficiency and quality of care tailored with greater precision to individual patient need., Competing Interests: Disclosure: FJG has received financial support from Pharmacosmos for travel to international meetings. RTC has received grants and honoraria from AstraZeneca and has participated in an advisory board for Bayer HealthCare Pharmaceuticals LLC. JGFC has received funding from British Heart Foundation; personal fees from Abbott, Amgen, Novartis, Medtronic, Idorsia, Servier, AstraZeneca, Innolife, Torrent and Respicardia; grants and personal fees from Bayer, Bristol Myers Squibb, Vifor, Johnson & Johnson, Myokardia and Viscardia; personal fees and non-financial support from Boehringer Ingelheim and NI Medical; and grants from Pharma Nord and Pharmacosmos. PP has received consultancy honoraria and/or sponsorship support from Boehringer Ingelheim, Pharmacosmos, Novartis, Vifor, AstraZeneca and Caption Health; and research support from Bristol Myers Squibb. All other authors have no conflicts of interest to declare., (Copyright © 2023, Radcliffe Cardiology.)

Background: Chemotherapy-induced peripheral neuropathy (CIPN) is a painful, debilitating consequence of cancer treatment affecting up to 60% of patients. Pharmacological approaches to CIPN are often ineffective and cause adverse effects. Essential oils are an underutilized non-pharmacological approach to pain reduction., Aims: To ascertain the efficacy of an essential oil intervention to reduce CIPN., Design: A single-blind, pilot randomized controlled trial., Methods: Participants (n = 27) were stratified by baseline pain scores and randomized to intervention (n = 13) and placebo groups (n = 14). Participants topically-applied the essential oil intervention or placebo every eight hours for six weeks. Pain was assessed using the Short-Form-McGill Pain Questionnaire-2 weekly and the Visual Analogue Scale daily. Quality-of-life was assessed using the Quality-of-Life: CIPN-20 and Quality-of-Life Adult Cancer Survivor questionnaires. Data were analyzed in SPSS using generalized estimating equations., Results: No significant difference was observed between groups in pain or quality-of-life scores over seven weeks, but improvement was observed in both groups. Participants using the intervention with pain medications showed a significant reduction in pain compared to placebo (p = .001). Educational level (p = .041) and annual income (p = .005) were significant covariates mirroring these social determinates of pain. Older participants felt less negatively about their CIPN (p = .002). Positive placebo effect and spatiotemporal interactions were observed., Conclusions: This pilot study demonstrated that participants adhered to the intervention for six weeks. Essential oils have potential direct and adjuvant pain-reducing effects and should be studied further., Competing Interests: Conflict of interest None., (Copyright © 2023 American Society for Pain Management Nursing. Published by Elsevier Inc. All rights reserved.)

Background: ET-1 (endothelin-1) is implicated in the pathophysiology of heart failure and renal disease. Its prognostic importance and relationship with kidney function in patients with heart failure with reduced ejection fraction receiving contemporary treatment are uncertain. We investigated these and the efficacy of dapagliflozin according to ET-1 level in the DAPA-HF trial (Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure)., Methods: We investigated the incidence of the primary outcome (cardiovascular death or worsening heart failure), change in kidney function, and the effect of dapagliflozin according to baseline ET-1 concentration, adjusting in Cox models for other recognized prognostic variables in heart failure including NT-proBNP (N-terminal pro-B-type natriuretic peptide). We also examined the effect of dapagliflozin on ET-1 level., Results: Overall, 3048 participants had baseline ET-1 measurements: tertile 1 (T1; ≤3.28 pg/mL; n=1016); T2 (>3.28-4.41 pg/mL; n=1022); and T3 (>4.41 pg/mL; n=1010). Patients with higher ET-1 were more likely male, more likely obese, and had lower left ventricular ejection fraction, lower estimated glomerular filtration rate, worse functional status, and higher NT-proBNP and hs-TnT (high-sensitivity troponin-T). In the adjusted Cox models, higher baseline ET-1 was independently associated with worse outcomes and steeper decline in kidney function (adjusted hazard ratio for primary outcome of 1.95 [95% CI, 1.53-2.50] for T3 and 1.36 [95% CI, 1.06-1.75] for T2; both versus T1; estimated glomerular filtration rate slope: T3, -3.19 [95% CI, -3.66 to -2.72] mL/min per 1.73 m 2 per y, T2, -2.08 [95% CI, -2.52 to -1.63] and T1 -2.35 [95% CI, -2.79 to -1.91]; P =0.002). The benefit of dapagliflozin was consistent regardless of baseline ET-1, and the placebo-corrected decrease in ET-1 with dapagliflozin was 0.13 pg/mL (95% CI, 0.25-0.01; P =0.029)., Conclusions: Higher baseline ET-1 concentration was independently associated with worse clinical outcomes and more rapid decline in kidney function. The benefit of dapagliflozin was consistent across the range of ET-1 concentrations measured, and treatment with dapagliflozin led to a small decrease in serum ET-1 concentration., Registration: URL: https://www., Clinicaltrials: gov; Unique identifier: NCT03036124., Competing Interests: Disclosures K.F.D. reported that his employer, the University of Glasgow, has been remunerated by AstraZeneca for working on the DAPA-HF and DELIVER trials. He has received speaker honoraria from AstraZeneca and Radcliffe Cardiology, has served on an advisory board for Us2.ai and Bayer AG, served on a clinical end point committee for Bayer AG, and has received research grant support from Boehringer Ingelheim, AstraZeneca, and Novartis (paid to his institution). R.T.C reports speaker honoraria from AstraZeneca and has served on an advisory board for Bayer AG. P.S.J reported his employer being paid by AstraZeneca for his time working on the study and receiving personal fees from, and his employer being paid by, Novartis; grants and personal fees from Boehringer Ingelheim; personal fees from Cytokinetics and Vifor Pharma outside the submitted work; and being the director of Global Clinical Trials Partners Ltd. A.H. is an employee of AstraZeneca. H.J.L.H reports grant funding and honoraria for consultancy as a member of the steering committee of the DAPA-CKD trial paid to his institution from AstraZeneca; research grants paid to his employer from AstraZeneca, Boehringer Ingelheim, Janssen, and Novo Nordisk for clinical trials; consulting fees, paid to his employer from Abbvie, Boehringer Ingelheim, Travere Pharmaceuticals, and Novo Nordisk; fees for steering committee membership paid to his employer from Bayer, Chinook, CSL Pharma, Janssen, and Gilead; honoraria for lectures from AstraZeneca and Mitsubishi Tanabe; and has received honoraria for advisory board participation for Merck (paid to his employer), Mitsubishi Tanabe, and Mundipharma. P.J. reports research support from Abbott Laboratories, Amgen, Inc, AstraZeneca, LP, Daiichi-Sankyo, Inc, GlaxoSmithKline, Merck & Co., Inc, Regeneron, Roche Diagnostics Corporation, and Siemens Healthineers. L.K. has received other support from AstraZeneca and personal fees from Novartis and Bristol Myers Squibb as a speaker. M.N.K. reported receiving grants and personal fees from AstraZeneca and Boehringer Ingelheim and personal fees from Sanofi, Amgen, Novo Nordisk, Merck, Eisai, Janssen, Bayer, GlaxoSmithKline, Glytec, Intarcia, Novartis, Applied Therapeutics, Amarin, and Eli Lilly outside the submitted work. F.A.M. reported receiving personal fees from AstraZeneca during the conduct of the study. P.P. reported receiving personal fees and fees to his institution for participation as an investigator in clinical trials from AstraZeneca during the conduct of the study and from Boehringer Ingelheim, Servier, Novartis, Berlin-Chemie, Bayer, Renal Guard Solutions, Pfizer, Respicardia, Cardiorentis, and Cibiem; grants, personal fees, and fees to his institution from Impulse Dynamics; and fees to his institution from Vifor, Corvia, and Revamp Medical outside the submitted work. S.D.S. reported receiving grants from AstraZeneca during the conduct of the study and grants from Alnylam, Amgen, AstraZeneca, Bellerophon, Bayer, Bristol Myers Squibb, Celladon, Cytokinetics, Eidos, Gilead, GlaxoSmithKline, Ionis, Lone Star Heart, Mesoblast, MyoKardia, National Institutes of Health/National Heart, Lung, and Blood Institute, Novartis, Sanofi Pasteur, and Theracos; and personal fees from Akros, Alnylam, Amgen, Arena, AstraZeneca, Bayer, Bristol Myers Squibb, Cardior, Corvia, Cytokinetics, Daiichi-Sankyo, Gilead, GlaxoSmithKline, Ironwood, Merck, Myokardia, Novartis, Roche, Takeda, Theracos, Quantum Genetics, Cardurion, AoBiome, Janssen, Cardiac Dimensions, and Tenaya outside the submitted work. M.S., O.B., and P.J.G. are employees and/or shareholders of AstraZeneca. N.S. reports personal fees from Afimmune, Amgen, Eli Lilly, Hanmi Pharmaceuticals, Merck Sharp & Dohme, Novo Nordisk, Pfizer, and Sanofi; grants and personal fees from AstraZeneca, Boehringer Ingelheim, and Novartis; and a grant from Roche Diagnostics, outside the submitted work. P.W. reports grant income from Roche Diagnostics, AstraZeneca, Boehringer Ingelheim, and Novartis; and personal fees from Novo Nordisk outside the submitted work. M.S.S. reported receiving grants and personal fees from AstraZeneca during the conduct of the study; grants and personal fees from Amgen, Intarcia, Janssen Research and Development, Medicines Company, MedImmune, Merck, and Novartis; personal fees from Anthos Therapeutics, Bristol Myers Squibb, CVS Caremark, DalCor, Dyrnamix, Esperion, IFM Therapeutics, and Ionis; and grants from Daiichi-Sankyo, Bayer, Pfizer, Poxel, Eisai, GlaxoSmithKline, Quark Pharmaceuticals, and Takeda outside the submitted work; and is a member of the TIMI Study Group, which has also received institutional research grant support through Brigham and Women’s Hospital from Abbott, Aralez, Roche, and Zora Biosciences. D.A.M. reports grants to the TIMI Study Group from Abbott Laboratories, Amgen, AnthosTherapeutics, AstraZeneca, BRAHMS, Eisai, GlaxoSmithKline, Medicines Company, Merck, Novartis, Pfizer, Roche Diagnostics, Quark, Siemens, and Takeda, and consultant fees from InCardia, Merck & Co, Novartis, and Roche Diagnostics. J.J.V.M. reports payments through Glasgow University from work on clinical trials, consulting, and other activities from Amgen, AstraZeneca, Bayer, Cardurion, Cytokinetics, GSK, KBP Biosciences, and Novartis; and personal consultancy fees from Alnylam Pharma, Bayer, BMS, George Clinical PTY Ltd, Ionis Pharma, Novartis, Regeneron Pharma, River 2 Renal Corporation; personal lecture fees from Abbott, Alkem Metabolics, Astra Zeneca, Blue Ocean Scientific Solutions Ltd, Boehringer Ingelheim, Canadian Medical and Surgical Knowledge, Emcure Pharma Ltd, Eris Lifesciences, European Academy of CME, Hikma Pharmaceuticals, Imagica Health, Intas Pharma, J.B. Chemicals & Pharma Ltd, Lupin Pharma, Medscape/Heart.Org, ProAdWise Communications, Radcliffe Cardiology, Sun Pharma, the Corpus, Translation Research Group, and Translational Medicine Academy. He is a director of Global Clinical Trial Partners Ltd. The other authors report no conflicts.

Cardiac rhythm monitoring is performed to search for atrial fibrillation (AF) after ischaemic stroke or transient ischaemic attack (TIA). Prolonged cardiac rhythm monitoring increases AF detection but is challenging to implement in many healthcare settings and is not needed for all people after ischaemic stroke/TIA. We aimed to develop and validate a model that includes clinical, electrocardiogram (ECG), blood-based, and genetic biomarkers to identify people with a low probability of AF detection after ischaemic stroke or TIA. We will recruit 675 consenting participants who are aged over 18 years, who were admitted with ischaemic stroke or TIA in the 5 days prior, who are not known to have AF, and who would be suitable for anticoagulation if AF is found. We will collect baseline demographic and clinical data, a 12-lead ECG, and a venous blood sample for blood biomarkers (including midregional pro-atrial natriuretic peptide, MRproANP) and genetic data. We will perform up to 28 days of cardiac rhythm monitoring using an R-test or patch device to search for AF in all participants. The sample size of 675 participants is based on true sensitivity of 92.5%, null hypothesis sensitivity of 80%, 80% power, and 5% significance. The primary outcome is AF detection ≥30 s duration during 28 days of cardiac rhythm monitoring. Secondary outcomes are AF detection at 1-year, recurrent cardiovascular events, and mortality and will be identified by electronic linkage and telephone follow-up. The results will guide the development of a more personalized care pathway to search for AF after ischaemic stroke or TIA. This could help to reduce cardiac rhythm monitoring for people with a low probability of AF detection and allow more intensive cardiac monitoring to be focused on people who are more likely to have AF and benefit. Participants will be consented for their data to be used in future research studies, providing a rich resource for stroke and cardiovascular research communities., (© 2022 The Author(s). Published by S. Karger AG, Basel.)

Aims: The aim of this study was to examine the association between patient-reported symptoms and the extent of pulmonary congestion in acute heart failure (AHF)., Methods and Results: In this prospective, observational study, patient-reported symptoms were assessed at baseline using the Kansas City Cardiomyopathy Questionnaire total symptom score (KCCQ-TSS) (range 0-100; 0 worst) in patients hospitalized for AHF. In a subset, patient-reported dyspnoea at rest and on exertion was examined (range 0-10; 10 worst) at baseline. In addition, 4-zone lung ultrasound (LUS) was performed at baseline at the time of echocardiography. B-lines were quantified offline, blinded to clinical findings, by a core laboratory. Chest X-ray (CXR) and physical examination findings were collected from the medical records. Among 322 patients (mean age 72, 60% men, mean left ventricular ejection fraction 39%) with AHF, the median KCCQ-TSS score was 33 (interquartile range 18-48). Worse KCCQ-TSS was associated with worse New York Heart Association class, dyspnoea at rest and on exertion, and peripheral oedema (p trend <0.001 for all). However, KCCQ-TSS was not associated with the extent of pulmonary congestion, as assessed by the number of B-lines on LUS, or findings on CXR, or physical examination (p trend >0.25 for all). Similarly, KCCQ-TSS was not significantly associated with echocardiographic markers of left ventricular filling pressure, pulmonary pressure or with N-terminal pro-B-type natriuretic peptide level., Conclusions: Among patients hospitalized for AHF, at baseline, KCCQ-TSS was not associated with pulmonary congestion assessed by LUS, CXR, or physical examination. These findings suggest that the profound reduction in KCCQ-TSS in patients with AHF may not be solely explained by pulmonary congestion., (© 2022 European Society of Cardiology.)

Background: Demographic differences in expected NT-proBNP (N-terminal pro-B-type natriuretic peptide) concentration are not well established. We aimed to establish reference ranges for NT-proBNP and explore the determinants of moderately elevated NT-proBNP under the universal definition of heart failure criteria., Methods: This is a cross-sectional study. NT-proBNP was measured in serum from 18 356 individuals without previous cardiovascular disease in the Generation Scotland Scottish Family Health Study. Age- and sex-stratified medians and 97.5th centiles were generated. Sex stratified risk factors for moderately elevated NT-proBNP (≥125 pg/mL) were investigated., Results: In males, median (97.5th centile) NT-proBNP concentration at age <30 years was 21 (104) pg/mL, rising to 38 (195) pg/ml at 50 to 59 years, and 281 (6792) pg/mL at ≥80 years. In females, median NT-proBNP at age <30 years was 51 (196) pg/mL, 66 (299) pg/mL at 50 to 59 years, and 240 (2704) pg/mL at ≥80 years. At age <30 years, 9.8% of females and 1.4% of males had elevated NT-proBNP, rising to 76.5% and 81.0%, respectively, at age ≥80 years. After adjusting for risk factors, an NT-proBNP ≥125 pg/mL was more common in females than males (OR, 9.48 [95% CI, 5.60-16.1]). Older age and smoking were more strongly associated with elevated NT-proBNP in males than in females ( P sex interaction <0.001, 0.07, respectively). Diabetes was inversely associated with odds of elevated NT-proBNP in females only ( P sex interaction =0.007)., Conclusions: An NT-proBNP ≥125 pg/mL is common in females without classical cardiovascular risk factors as well as older people. If NT-proBNP becomes widely used for screening in the general population, interpretation of NT-proBNP levels will require that age and sex-specific thresholds are used to identify patients with potential pathophysiology.

Background: Up to 20% of patients in heart failure with reduced ejection fraction (HFrEF) trials are not taking diuretic agents at baseline, but little is known about them., Objectives: The aim of this study was to examine outcomes in patients with HFrEF not taking diuretic medications and after diuretic medications are started., Methods: Patient characteristics and outcomes were compared between patients taking or not taking diuretic drugs at baseline in the ATMOSPHERE (Aliskiren Trial of Minimizing Outcomes for Patients With Heart Failure) and PARADIGM-HF (Prospective Comparison of ARNI With ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure Trial) trials combined. Patients starting diuretic medications were also compared with those remaining off diuretic drugs during follow-up. Symptoms (Kansas City Cardiomyopathy Questionnaire Clinical Summary Score [KCCQ-CSS]), hospitalization for worsening heart failure (HF), mortality, and kidney function (estimated glomerular filtration rate slope) were examined., Results: At baseline, the 3,079 of 15,415 patients (20%) not taking diuretic medications had a less severe HF profile, less neurohumoral activation, and better kidney function. They were less likely to experience the primary outcome (hospitalization for HF or cardiovascular death) than patients taking diuretic agents (adjusted HR: 0.77; 95% CI: 0.74-0.80; P < 0.001) and death of any cause. Commencement of a diuretic drug was associated with higher subsequent risk for death (adjusted HR: 2.05; 95% CI: 1.99-2.11; P < 0.001) and greater decreases in KCCQ-CSS and estimated glomerular filtration rate. The 5 strongest predictors of initiation of diuretic medications were higher N-terminal pro-B-type natriuretic peptide, higher body mass index, older age, history of diabetes, and worse KCCQ-CSS. In PARADIGM-HF, fewer patients who were treated with sacubitril/valsartan commenced diuretic agents (OR: 0.72; 95% CI: 0.58-0.88; P = 0.002)., Conclusions: Patients with HFrEF not taking diuretic medications and those who remained off them had better outcomes than patients treated with diuretic agents or who commenced them., Competing Interests: Funding Support and Author Disclosures The PARADIGM-HF and ATMOSPHERE trials were funded by Novartis. All authors (except Drs Curtain, Campbell, and Jackson) or their institutions were paid by Novartis for their participation in one or both of these trials. Dr Petrie has received research funding from Boehringer Ingelheim, Roche, SQ Innovations, AstraZeneca, Novartis, Novo Nordisk, Medtronic, Boston Scientific, and Pharmacosmos; and is a consultant and endpoint committee member for Boehringer Ingelheim, Novartis, AstraZeneca, Novo Nordisk, AbbVie, Bayer, Takeda, Cardiorentis, and Pharmacosmos. Dr Abraham has received research support from Abbott Vascular; and is a consultant for Abbott Vascular. Dr Desai has received research grant support from Abbott, Alnylam, AstraZeneca, Bayer, and Novartis; and has received consulting fees from Abbott, Alnylam, Amgen, AstraZeneca, Biofourmis, Boehringer Ingelheim, Boston Scientific, Cytokinetics, Lupin Pharma, Merck, Novartis, Relypsa, Regeneron, and Sun Pharma. Dr Dickstein has served as a member of the executive steering committee for the ATMOSPHERE trial. Dr Kober has received honoraria from Novartis, Boehringer, Novo, and AstraZeneca. Dr Rouleau has received grants and consulting fees from Novartis; and has received consulting fees from AstraZeneca. Dr Swedberg has received consulting for Novartis. Dr Zile has received research funding from Novartis and has been a consultant for Novartis, Abbott, Boston Scientific, CVRx, EBR, Endotronics, Ironwood, Merck, Medtronic, and Myokardia V Wave. Dr Solomon 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, the 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, Cardurion, AoBiome, Janssen, Cardiac Dimensions, Tenaya, Sanofi-Pasteur, Dinaqor, Tremeau, CellProThera, Moderna, and American Regent. Dr Jhund has received consulting, advisory board, and speaker fees from Novartis; has received advisory board fees from Cytogenetics; and a has received grant from Boehringer Ingelheim. Dr McMurray has received support from British Heart Foundation Centre of Research Excellence Grant RE/18/6/34217; has received payments through Glasgow University from work on clinical trials, consulting, and other activities from Alnylam, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Cardurion, Cytokinetics, DalCor, GlaxoSmithKline, KBP Biosciences, Novartis, Pfizer, and Theracos; and has received personal payments from Abbott, Hikma, Ionis, Sun Pharmaceuticals, and Servier. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Home food availability (HFA) checklists can be completed by self-report to assess the home food environment. Checklists developed for Black/African American (B/AA) and Hispanic/Latinx (H/L) households are seldom validated against objective approaches such as exhaustive in-home food inventories. This study validated a self-report HFA checklist developed for B/AA and H/L households (n = 97) against researcher-completed HFA checklists verified by exhaustive in-home food inventories. Mean estimates of sensitivity, specificity, and area of the receiver operating curve (ROC), and interrater agreement (Gwet AC1) were calculated to examine the accuracy and agreement of self-reported checklists against direct observation of individual food items. Mean differences in HFA food group scores were compared (self-report vs observed) to examine group-level relative validity. The predictive validity of this self-reported measure on observed scores and dietary intake were also examined with linear regression. The average values for ROC area (average of sensitivity and specificity) ranged from acceptable (0.76 for sweets) to excellent (0.81 for vegetables, fruits). Average interrater agreement values ranged from moderate (0.41-0.60: sweets) to substantial (0.61-0.79: vegetables, fruit, SSBs, savory foods). Self-reported mean scores, compared to observed scores, were higher for vegetables (mean diff: 1.04) and lower for sweets (mean diff: 0.38, p = 0.01), but regression analyses demonstrated that self-reported scores were good predictors of observed scores with absolute error (based on standard deviation of residuals) ranging from ±1.27 to 1.69 points. Self-reported scores also predicted multiple aspects of dietary intake but more so among H/L households. In conclusion, the HFA checklist obtained via self-report performed well based on multiple indicators of validity suggesting that this self-reported measure can be used to assess home food environments among of B/AA and H/L households., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Aims: Heart failure (HF) is a major public health concern worldwide. The diversity of HF makes it challenging to decipher the underlying complex pathological processes using single biomarkers. We examined the association between urinary peptides and HF with reduced (HFrEF), mid-range (HFmrEF) and preserved (HFpEF) ejection fraction, defined based on the European Society of Cardiology guidelines, and the links between these peptide biomarkers and molecular pathophysiology., Methods and Results: Analysable data from 5608 participants were available in the Human Urinary Proteome database. The urinary peptide profiles from participants diagnosed with HFrEF, HFmrEF, HFpEF and controls matched for sex, age, estimated glomerular filtration rate, systolic and diastolic blood pressure, diabetes and hypertension were compared applying the Mann-Whitney test, followed by correction for multiple testing. Unsupervised learning algorithms were applied to investigate groups of similar urinary profiles. A total of 577 urinary peptides significantly associated with HF were sequenced, 447 of which (77%) were collagen fragments. In silico analysis suggested that urinary biomarker abnormalities in HF principally reflect changes in collagen turnover and immune response, both associated with fibrosis. Unsupervised clustering separated study participants into two clusters, with 83% of non-HF controls allocated to cluster 1, while 65% of patients with HF were allocated to cluster 2 (P < 0.0001). No separation based on HF subtype was detectable., Conclusions: Heart failure, irrespective of ejection fraction subtype, was associated with differences in abundance of urinary peptides reflecting collagen turnover and inflammation. These peptides should be studied as tools in early detection, prognostication, and prediction of therapeutic response., (© 2021 The Authors. European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Importance: Coronary artery disease (CAD) and coronary microvascular dysfunction (CMD) may contribute to the pathophysiologic characteristics of heart failure with preserved ejection fraction (HFpEF). However, the prevalence of CAD and CMD have not been systematically studied., Objective: To examine the prevalence of CAD and CMD in hospitalized patients with HFpEF., Design, Setting, and Participants: A total of 106 consecutive patients hospitalized with HFpEF were evaluated in this prospective, multicenter, cohort study conducted between January 2, 2017, and August 1, 2018; data analysis was performed from March 4 to September 6, 2019. Participants underwent coronary angiography with guidewire-based assessment of coronary flow reserve, index of microvascular resistance, and fractional flow reserve, followed by coronary vasoreactivity testing. Cardiac magnetic resonance imaging was performed with late gadolinium enhancement and assessment of extracellular volume. Myocardial perfusion was assessed qualitatively and semiquantitatively using the myocardial-perfusion reserve index., Main Outcomes and Measures: The prevalence of obstructive epicardial CAD, CMD, and myocardial ischemia, infarction, and fibrosis., Results: Of 106 participants enrolled (53 [50%] women; mean [SD] age, 72 [9] years), 75 had coronary angiography, 62 had assessment of coronary microvascular function, 41 underwent coronary vasoreactivity testing, and 52 received cardiac magnetic resonance imaging. Obstructive epicardial CAD was present in 38 of 75 participants (51%, 95% CI, 39%-62%); 19 of 38 (50%; 95% CI, 34%-66%) had no history of CAD. Endothelium-independent CMD (ie, coronary flow reserve <2.0 and/or index of microvascular resistance ≥25) was identified in 41 of 62 participants (66%; 95% CI, 53%-77%). Endothelium-dependent CMD (ie, abnormal coronary vasoreactivity) was identified in 10 of 41 participants (24%; 95% CI, 13%-40%). Overall, 45 of 53 participants (85%; 95% CI, 72%-92%) had evidence of CMD and 29 of 36 (81%; 95% CI, 64%-91%) of those without obstructive epicardial CAD had CMD. Cardiac magnetic resonance imaging findings included myocardial-perfusion reserve index less than or equal to 1.84 (ie, impaired global myocardial perfusion) in 29 of 41 patients (71%; 95% CI, 54%-83%), visual perfusion defect in 14 of 46 patients (30%; 95% CI, 19%-46%), ischemic late gadolinium enhancement (ie, myocardial infarction) in 14 of 52 patients (27%; 95% CI, 16%-41%), and extracellular volume greater than 30% (ie, diffuse myocardial fibrosis) in 20 of 48 patients (42%; 95% CI, 28%-56%). Patients with obstructive CAD had more adverse events during follow-up (28 [74%]) than those without obstructive CAD (17 [46%])., Conclusions and Relevance: In this cohort study, 91% of patients with HFpEF had evidence of epicardial CAD, CMD, or both. Of those without obstructive CAD, 81% had CMD. Obstructive epicardial CAD and CMD appear to be common and often unrecognized in hospitalized patients with HFpEF and may be therapeutic targets.

The use of electronic cigarettes (ECs) has become widespread despite many unknowns around their long-term health impact. ECs work by vapourising a liquid, known as an e-liquid, typically consisting of propylene glycol, glycerol, flavourings and nicotine. The chemical constituents and resultant impact on cells and tissue are dependent on several factors, including the flavourings used, the vaping topography/use pattern, and the device used. ECAM (Electronic Cigarette Aerosol Machine) is an open source, portable device for creating EC aerosol - for condensate collection and in vitro studies - using a controlled methodology. ECAM was developed as a low cost, automated, and customisable alternative to commercial devices. ECAM consists of a micro diaphragm gas pump to draw air/EC aerosol through the system. The device is automated using an Arduino and solenoid pinch valves are used to alternate between air and EC vapour. Condensate is collected in a vial within a cold-water bath. Each ECAM unit uses a temperature/humidity sensor to measure ambient air conditions and a differential pressure sensor to determine the pressure within the system. ECAM is programmed to adhere to International Standards Organisation 20768:2018. The design files, source code, and build instructions for this device can be found at https://dx.doi.org/10.17605/OSF.IO/3NGU4., 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., (© 2021 The Author(s).)

Background: Patients with left ventricular (LV) systolic dysfunction after myocardial infarction are at a high risk of developing heart failure. The addition of neprilysin inhibition to renin angiotensin system inhibition may result in greater attenuation of adverse LV remodeling as a result of increased levels of substrates for neprilysin with vasodilatory, antihypertrophic, antifibrotic, and sympatholytic effects., Methods: We performed a prospective, multicenter, randomized, double-blind, active-comparator trial comparing sacubitril/valsartan 97/103 mg twice daily with valsartan 160 mg twice daily in patients ≥3 months after myocardial infarction with a LV ejection fraction ≤40% who were taking a renin angiotensin system inhibitor (equivalent dose of ramipril ≥2.5 mg twice daily) and a β-blocker unless contraindicated or intolerant. Patients in New York Heart Association class ≥II or with signs and symptoms of heart failure were excluded. The primary outcome was change from baseline to 52 weeks in LV end-systolic volume index measured using cardiac magnetic resonance imaging. Secondary outcomes included other magnetic resonance imaging measurements of LV remodeling, change in NT-proBNP (N-terminal pro-B-type natriuretic peptide) and high-sensitivity cardiac troponin I, and a patient global assessment of change questionnaire., Results: From July 2018 to June 2019, we randomized 93 patients with the following characteristics: mean age, 60.7±10.4 years; median time from myocardial infarction, 3.6 years (interquartile range, 1.2-7.2); mean LV ejection fraction, 36.8%±7.1%; and median NT-proBNP, 230 pg/mL (interquartile range, 124-404). Sacubitril/valsartan, compared with valsartan, did not significantly reduce LV end-systolic volume index; adjusted between-group difference, -1.9 mL/m 2 (95% CI, -4.9 to 1.0); P =0.19. There were no significant between-group differences in NT-proBNP, high-sensitivity cardiac troponin I, LV end-diastolic volume index, left atrial volume index, LV ejection fraction, LV mass index, or patient global assessment of change., Conclusions: In patients with asymptomatic LV systolic dysfunction late after myocardial infarction, treatment with sacubitril/valsartan did not have a significant reverse remodeling effect compared with valsartan. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03552575.

Aims: We sought to examine sex differences in congestion in patients hospitalized for acute heart failure (AHF). Understanding congestive patterns in women and men with AHF may provide insights into sex differences in the presentation and prognosis of AHF patients., Methods and Results: In a prospective, two-site study in adults hospitalized for AHF, four-zone lung ultrasound (LUS) was performed at the time of echocardiography at baseline (LUS1) and, in a subset, pre-discharge (LUS2). B-lines on LUS and echocardiographic images were analysed offline, blinded to clinical information and outcomes. Among 349 patients with LUS1 data (median age 74, 59% male, and 87% White), women had higher left ventricular ejection fraction (mean 43% vs. 36%, P < 0.001), higher tricuspid annular plane systolic excursion (mean 17 vs. 15 mm, P = 0.021), and higher measures of filling pressures (median E/e' 20 vs. 16, P < 0.001). B-line number on LUS1 (median 6 vs. 6, P = 0.69) and admission N-terminal pro-B-type natriuretic peptide levels (median 3932 vs. 3483 pg/mL, P = 0.77) were similar in women and men. In 121 patients with both LUS1 and LUS2 data, there was a similar and significant decrease in B-lines from baseline to discharge in both women and men. The risk of the composite 90 day outcome increased with higher B-line number on four-zone LUS2: unadjusted hazard ratio for each B-line tertile was 1.86 (95% confidence interval 1.08-3.20, P = 0.025) in women and 1.65 (95% confidence interval 1.03-2.64, P = 0.037) in men (interaction P = 0.72)., Conclusions: Among patients with AHF, echocardiographic markers differed between women and men at baseline, whereas B-line number on LUS did not. The dynamic changes in B-lines during a hospitalization for AHF were similar in women and men., (© 2021 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

A chaplain was conducting a funeral for a long-time patient who had recently died. While he was the only one present with the body, his thoughts turn to the ways we can feel God close to us, even when we otherwise might feel alone.

Background: Sodium-glucose cotransporter 2 inhibitors reduce the risk of heart failure hospitalization and cardiovascular death in patients with heart failure and reduced ejection fraction (HFrEF). However, their effects on cardiac structure and function in HFrEF are uncertain., Methods: We designed a multicenter, randomized, double-blind, placebo-controlled trial (the SUGAR-DM-HF trial [Studies of Empagliflozin and Its Cardiovascular, Renal and Metabolic Effects in Patients With Diabetes Mellitus, or Prediabetes, and Heart Failure]) to investigate the cardiac effects of empagliflozin in patients in New York Heart Association functional class II to IV with a left ventricular (LV) ejection fraction ≤40% and type 2 diabetes or prediabetes. Patients were randomly assigned 1:1 to empagliflozin 10 mg once daily or placebo, stratified by age (<65 and ≥65 years) and glycemic status (diabetes or prediabetes). The coprimary outcomes were change from baseline to 36 weeks in LV end-systolic volume indexed to body surface area and LV global longitudinal strain both measured using cardiovascular magnetic resonance. Secondary efficacy outcomes included other cardiovascular magnetic resonance measures (LV end-diastolic volume index, LV ejection fraction), diuretic intensification, symptoms (Kansas City Cardiomyopathy Questionnaire Total Symptom Score, 6-minute walk distance, B-lines on lung ultrasound, and biomarkers (including N-terminal pro-B-type natriuretic peptide)., Results: From April 2018 to August 2019, 105 patients were randomly assigned: mean age 68.7 (SD, 11.1) years, 77 (73.3%) male, 82 (78.1%) diabetes and 23 (21.9%) prediabetes, mean LV ejection fraction 32.5% (9.8%), and 81 (77.1%) New York Heart Association II and 24 (22.9%) New York Heart Association III. Patients received standard treatment for HFrEF. In comparison with placebo, empagliflozin reduced LV end-systolic volume index by 6.0 (95% CI, -10.8 to -1.2) mL/m 2 ( P =0.015). There was no difference in LV global longitudinal strain. Empagliflozin reduced LV end-diastolic volume index by 8.2 (95% CI, -13.7 to -2.6) mL/m 2 ( P =0.0042) and reduced N-terminal pro-B-type natriuretic peptide by 28% (2%-47%), P =0.038. There were no between-group differences in other cardiovascular magnetic resonance measures, diuretic intensification, Kansas City Cardiomyopathy Questionnaire Total Symptom Score, 6-minute walk distance, or B-lines., Conclusions: The sodium-glucose cotransporter 2 inhibitor empagliflozin reduced LV volumes in patients with HFrEF and type 2 diabetes or prediabetes. Favorable reverse LV remodeling may be a mechanism by which sodium-glucose cotransporter 2 inhibitors reduce heart failure hospitalization and mortality in HFrEF. Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT03485092.

Aims: In patients at high risk of heart failure following myocardial infarction (MI) as a result of residual left ventricular systolic dysfunction (LVSD), the angiotensin receptor neprilysin inhibitor sacubitril/valsartan may result in a greater attenuation of adverse left ventricular (LV) remodelling than renin angiotensin aldosterone system inhibition alone, due to increased levels of substrates for neprilysin with vasodilatory, anti-hypertrophic, anti-fibrotic, and sympatholytic effects., Methods: We designed a randomized, double-blinded, active-comparator trial to examine the effect of sacubitril/valsartan to the current standard of care in reducing adverse LV remodelling in patients with asymptomatic LVSD following MI. Eligible patients were ≥3 months following MI, had an LV ejection fraction ≤40% as measured by echocardiography, were New York Heart Association functional classification I, tolerant of an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker at equivalent dose of ramipril 2.5 mg twice daily or greater, and taking a beta-blocker unless contraindicated or intolerant. Patients were randomized to sacubitril/valsartan (target dose 97/103 mg twice daily) or valsartan (target dose 160 mg twice daily). The primary endpoint will be change in LV end-systolic volume indexed for body surface area measured using cardiac magnetic resonance imaging over 52 weeks from randomization. Secondary endpoints include other magnetic resonance imaging-based metrics of LV remodelling, biomarkers associated with LV remodelling and neurohumoral activation, and change in patient well-being assessed using a patient global assessment questionnaire., Conclusions: This trial will investigate the effect of neprilysin inhibition on LV remodelling and the neurohumoral actions of sacubitril/valsartan in patients with asymptomatic LVSD following MI., (© 2020 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Background: The home food environment can shape the diets of young children. However, little is known about modifiable factors that influence home food availability and dietary intake., Objective: The purpose of this study was to examine the relationship between grocery shopping frequency with home- and individual-level diet quality., Design: This was a secondary, cross-sectional analyses of data from the Study on Children's Home Food Availability Using TechNology. Data were collected in the homes of participants from November 2014 through March 2016., Participants/settings: A purposive sample of 97 low-income African American and Hispanic or Latinx parent-child dyads residing in Chicago, IL, enrolled in the study., Main Outcome Measures: The main outcomes were home- and individual-level diet quality. Healthy Eating Index-2010 (HEI-2010) scores were calculated from home food inventory data collected in participants' homes to assess home-level diet quality. To assess individual-level diet quality, HEI-2010 scores were based on multiple 24-hour diet recalls from parent-child dyads., Statistical Analyses: Grocery shopping frequency was examined in relation to diet quality at the home and individual levels. Grocery shopping frequency was defined as the number of times households shopped on a monthly basis (ie, once a month, twice a month, 3 times a month, or 4 times or more a month). Multivariable linear regression analysis, controlling for covariates, tested the relationships between grocery shopping frequency and HEI-2010 total and component scores at the home and individual levels., Results: Grocery shopping frequency was positively associated with home-level HEI-2010 scores for total diet, whole grains, and empty calories (higher scores reflect better diet quality) and with individual-level HEI-2010 scores for total and whole fruit (parents only), vegetables (children only), and sodium (children only)., Conclusions: Grocery shopping frequency was associated with multiple dimensions of diet quality at the home and individual levels. These results offer a potential strategy to intervene on home food availability and individual dietary intake., (Copyright © 2020 Academy of Nutrition and Dietetics. Published by Elsevier Inc. All rights reserved.)

Background: Early detection of colon cancer is essential to successful treatment and survival, yet most patients are diagnosed only after onset of symptoms. Previous studies suggest differences in colon cancer screening and presentation by gender and race, but reasons for this are not understood. The purpose of this study was to identify barriers and facilitators to early detection of colon cancer and to compare by gender and race. Materials and Methods: In the Colon Cancer Patterns of Care in Chicago study, non-Hispanic Black and White (NHB, NHW) patients aged 30-79 newly diagnosed with colon cancer between 2010 and 2014 ( n  = 249) underwent in-depth semistructured interviews regarding the pathway to colon cancer diagnosis. Mixed qualitative and quantitative methods were used to analyze patient narratives and to compare response patterns by gender and race within prespecified domains: health care access factors, provider-related factors, patient-related factors, and diagnostic workup factors. Results: Women reported more barriers than facilitators to early detection than men (barrier: facilitator ratio of 0.60 vs. 0.48). Thematic differences were seen, with women reporting more barriers related to health care access, scheduling of follow-ups, symptom recognition, and inappropriate or inconclusive diagnostic tests. Fewer women than men reported facilitators related to provider factors such as ease of scheduling follow-ups and receiving referrals for screening or a specialist. NHBs and NHWs reported similar ratios of barriers to facilitators (0.55 vs. 0.53), but more NHBs than NHWs reported barriers related to health care access, scheduling follow-ups, and clinical delays, and fewer NHBs reported facilitators related to health care accessibility (existing relationship with provider, ease of scheduling follow-ups). Conclusions: In this diverse population of patients recently diagnosed with colon cancer, we identified substantive gender- and race-based differences in the types and burden of barriers and facilitators to early detection experienced in the path to diagnosis. These differences should be explored further as they may contribute to disparities in the diagnosis and prognosis of colon cancer.