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BACKGROUND: In patients with advanced heart failure (HF), elevated jugular venous pressure (JVP) is the most reliable sign of elevated left-sided filling pressures. However, discordance between right- and left-sided filling pressures (R-L mismatch) could lead to inadequate or excessive therapy guided by JVP. We determined the prevalence of R-L mismatch in the current era and investigated whether mismatch might be identified from clinical information. METHODS AND RESULTS: Right-sided heart catheterization was performed in 537 consecutive patients hospitalized with advanced HF during complete transplantation evaluation. Patients with high filling pressures were categorized as matched (right atrial pressure (RAP) >=10 mm Hg and pulmonary wedge pressure (PCWP) >=22 mm Hg), high-R mismatch (RAP >=10 but PCWP <22 mm Hg) or high-L mismatch (PCWP >=22 but RAP <10 mm Hg). Among all of the patients, 195 (36%) were matched low and 194 (36%) were matched high, and 148 (28%) had R-L mismatch. Among patients with high filling pressures, 194 (57%) were matched high and 82 (24%) had high-L and 66 (19%) high-R mismatch. Mismatches were not associated with differences in demographic or clinical data, including pulmonary and hepatic function, or severity of valvular regurgitation and right ventricular function by echo. However, among all patients with RAP >=10 mm Hg, pulmonary artery systolic pressure (PASP) was higher in those patients with matched high left- and right-sided pressures (59 ± 12 mm Hg) versus high-R mismatch (41 ± 13 mm Hg; P < .0001). Similarly among all patients with low RAP, PASP was lower in patients with matched low right- and left-side pressures (33 ± 11 mm Hg) versus high-L mismatch (53 ± 13 mm Hg; P < .0001). CONCLUSIONS: R-L mismatch was present in >1 in 4 total patients, and >1 in 3 with elevated filling pressures. Regardless of clinical history, when empiric therapy to optimize volume status to JVP is not effective, additional measurement should be considered to establish the R-L relationship. [ABSTRACT FROM AUTHOR]

Background: Impedance cardiography (ICG) is a noninvasive modality that uses changes in impedance across the thorax to assess hemodynamic parameters, including cardiac output (CO). The utility of ICG in patients hospitalized with heart failure is uncertain.Methods: The BioImpedance CardioGraphy in Advanced Heart Failure study was a prospective substudy of the Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness. A total of 170 subjects underwent blinded ICG measurements using BioZ (CardioDynamics, San Diego, CA); of these, 82 underwent right heart catheterization. We compared ICG with invasively measured hemodynamics by simple correlation and compared overall ICG hemodynamic profiles ("wet" [thoracic fluid content > or =47/kOhm in men and > or =37/kOhm in women] and "cold" [cardiac index < or =2.2 L min(-1)m(-2)) versus those determined by invasive measurements (wet [pulmonary capillary wedge pressure > or =22 mm Hg] and cold [cardiac index < or =2.2 L min(-1)m(-2)). We also determined whether ICG measurements were associated with subsequent death or hospitalization within 6 months.Results: There was modest correlation between ICG and invasively measured CO (r = 0.4 to 0.6 on serial measurement). Thoracic fluid content measured by ICG was not a reliable measure of pulmonary capillary wedge pressure. There was poor agreement between ICG and invasively measured hemodynamic profiles (kappa < or =0.1). No ICG variable alone or in combination was associated with outcome.Conclusions: In hospitalized patients with advanced heart failure, ICG provides some information about CO but not left-sided filling pressures. Impedance cardiography did not have prognostic utility in this patient population. [ABSTRACT FROM AUTHOR]

Markers of social health, including kinlessness, social isolation and loneliness, have important implications for quality of life and health for older adults. As the population ages, there is a growing cohort of kinless older adults without living partners or children, particularly among disadvantaged groups. Kinlessness has been associated with worse mental and physical health, significant unmet care needs, increased risk of dementia, higher rates of long-term placement, and higher mortality rates than those for patients with kin. Although other markers of social health have been studied in patients with heart failure, little is known about kinlessness in this population of patients. This review outlines the data on kinlessness and its impact on patients' outcomes, and it proposes novel interventions to mitigate its effects., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Sodium-glucose cotransporter 2 inhibitors (SGLT2is) improve clinical outcomes in persons with heart failure (HF). This class of agents has been consistently associated with an increased risk of mycotic genital infections (MGIs), and in some, but not all trials, urinary tract infections (UTIs). Other medications widely used for cardiac conditions do not cause MGIs and UTIs, so cardiologists and their supporting teams will be encountering clinical questions that they previously did not have to address. This review provides clinicians with practical recommendations about SGLT2i use in individuals with HF as related to the associated MGI and possible UTI risks. Overall, given the benefit of SGLT2is in clinical outcomes, the threshold for not initiating or discontinuing SGLT2is due to concerns for MGIs or UTIs should be high for persons with HF. Likewise, when SGLT2is are discontinued for such concerns, the threshold for reinitiation should be low., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Aims: Heart failure (HF) is a highly prevalent and progressive condition associated with significant morbidity and mortality rates. Acute decompensated HF precipitates millions of hospitalizations each year. Despite therapeutic advances, the overall prognosis of HF is poor. The varying clinical courses and outcomes of patients with this disease may be due to region-specific gaps and since most HF studies are conducted in developed countries, the participation of Latin American and Caribbean countries is low. Considering this, the American Registry of Ambulatory and Acute Decompensated Heart Failure (AMERICCAASS) aims to characterize the population with ambulatory and acute decompensated HF in the American continent and to determine rehospitalization and survival outcomes during the 12 months of follow-up., Methods and Results: AMERICCAASS Registry is an observational, prospective, and hospital-based registry recruiting patients with ambulatory or acute decompensated HF. The registry plans to include between two and four institutions per country from at least 20 countries in the Americas, and at least 60 patients recruited from each participant institution regardless of their ambulatory or acutely decompensated condition. Ambulatory patients with confirmed HF diagnosis or inpatients presenting with acute decompensated HF will be included. Follow-up will be performed at 12 months in ambulatory patients or 1, 6, and 12 months after hospital discharge in acutely decompensated HF patients. This ongoing study began on 1 April 2022, with recruitment scheduled to end on 30 November 2023, and follow-up on 31 January 2025. Ethics approval was obtained from the Biomedical Research Ethics Committee of Fundación Valle del Lili. Data collected in the AMERICCAASS registry is being stored on the electronic platform REDCap (Research Electronic Data Capture), which allows different forms for patient groups to enable unbiased analyses. For quantitative variables comparison, we will use the Student's t-test or non-parametric tests accordingly. Categorical variables will be presented as proportions, and groups will be compared with Fisher's exact test. The significance level will be <0.05 for comparisons. Readmissions and post-discharge mortality will be calculated as proportions at 1, 6, and 12 months, with a survival analysis by conditional probability and the Kaplan-Meier method., Conclusions: AMERICCAASS Registry is intended to be the most important registry of the continent for obtaining important information about demographics, aetiology, co-morbidities, and treatment received, either ambulatory or hospitalized. This registry may contribute to the optimization of national and regional evidence and public policies for the diagnosis and treatment of HF disease., (© 2024 The Author(s). ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Cardiogenic shock after acute myocardial infarction (AMI-CS) carries significant mortality despite advances in revascularization and mechanical circulatory support. We sought to identify the process-based and structural characteristics of centers with lower mortality in AMI-CS. We analyzed 16,337 AMI-CS cases across 440 centers enrolled in the National Cardiovascular Data Registry's Chest Pain-MI Registry, a retrospective cohort database, between January 1, 2015, and December 31, 2018. Centers were stratified across tertiles of risk-adjusted in-hospital mortality rate (RAMR) for comparison. Risk-adjusted multivariable logistic regression was also performed to identify hospital-level characteristics associated with decreased mortality. The median participant age was 66 (interquartile range 57 to 75) years, and 33.0% (n = 5,390) were women. The median RAMR was 33.4% (interquartile range 26.0% to 40.0%) and ranged from 26.9% to 50.2% across tertiles. Even after risk adjustment, lower-RAMR centers saw patients with fewer co-morbidities. Lower-RAMR centers performed more revascularization (92.8% vs 90.6% vs 85.9%, p <0.001) and demonstrated better adherence to associated process measures. Left ventricular assist device capability (odds ratio [OR] 0.78 [0.67 to 0.92], p = 0.002), more frequent revascularization (OR 0.93 [0.88 to 0.98], p = 0.006), and higher AMI-CS volume (OR 0.95 [0.91 to 0.99], p = 0.009) were associated with lower in-hospital mortality. However, several such characteristics were not more frequently observed at low-RAMR centers, despite potentially reflecting greater institutional experience or resources. This may reflect the heterogeneity of AMI-CS even after risk adjustment. In conclusion, low-RAMR centers do not necessarily exhibit factors associated with decreased mortality in AMI-CS, which may reflect the challenges in performing outcomes research in this complex population., Competing Interests: Declaration of competing interest Dr. Bhatt discloses the following relationships - Advisory Board: Angiowave, Bayer, Boehringer Ingelheim, CellProthera, Cereno Scientific, Elsevier Practice Update Cardiology, High Enroll, Janssen, Level Ex, McKinsey, Medscape Cardiology, Merck, MyoKardia, NirvaMed, Novo Nordisk, PhaseBio, PLx Pharma, Stasys; Board of Directors: American Heart Association New York City, Angiowave (stock options), Bristol-Meyers Squibb (stock), DRS.LINQ (stock options), High Enroll (stock); Consultant: Broadview Ventures, GlaxoSmithKline, Hims, SFJ, Youngene; Data Monitoring Committees: Acesion Pharma, Assistance Publique-Hôpitaux de Paris, Baim Institute for Clinical Research (formerly Harvard Clinical Research Institute, for the PORTICO trial, funded by St. Jude Medical, now Abbott), Boston Scientific (Chair, PEITHO trial), Cleveland Clinic, Contego Medical (Chair, PERFORMANCE 2), Duke Clinical Research Institute, Mayo Clinic, Mount Sinai School of Medicine (for the ENVISAGE trial, funded by Daiichi Sankyo; for the ABILITY-DM trial, funded by Concept Medical; for ALLAY-HF, funded by Alleviant Medical), Novartis, Population Health Research Institute; Rutgers University (for the NIH-funded MINT trial); Honoraria: American College of Cardiology (Senior Associate Editor, Clinical Trials and News, ACC.org; Chair, ACC Accrediation Oversight Committee), Arnold and Porter law firm (work related to Sanofi/Bristol-Meyers Squibb clopidogrel litigation), Baim Institute for Clinical Research (formerly Harvard Clinical Research Institute; RE-DUAL PCI clinical trial steering committee funded by Boehringer Ingelheim; AEGIS-II executive committee funded by CSL Behring), Belvoir Publications (Editor in Chief, Harvard Heart Letter), Canadian Medical and Surgical Knowledge Translation Research Group (clinical trial steering committees), CSL Behring (AHA lecture), Cowen and Company, Duke Clinical Research Institute (clinical trial steering committees, including for the PRONOUNCE trial, funded by Ferring Pharmaceuticals), HMP Global (Editor in Chief, Journal of Invasive Cardiology), Journal of the American College of Cardiology (Guest Editor; Associate Editor), K2P (Co-Chair, interdisciplinary curriculum), Level Ex, Medtelligence/ReachMD (CME steering committees), MJH Life Sciences, Oakstone CME (Course Director, Comprehensive Review of Interventional Cardiology), Piper Sandler, Population Health Research Institute (for the COMPASS operations committee, publications committee, steering committee, and USA national co-leader, funded by Bayer), WebMD (CME steering committees), Wiley (steering committee); Other: Clinical Cardiology (Deputy Editor); Patent: Sotagliflozin (named on a patent for sotagliflozin assigned to Brigham and Women's Hospital who assigned to Lexicon; neither I nor Brigham and Women's Hospital receive any income from this patent); Research Funding: Abbott, Acesion Pharma, Afimmune, Aker Biomarine, Alnylam, Amarin, Amgen, AstraZeneca, Bayer, Beren, Boehringer Ingelheim, Boston Scientific, Bristol-Meyers Squibb, Cardax, CellProthera, Cereno Scientific, Chiesi, CinCor, Cleerly, CSL Behring, Eisai, Ethicon, Faraday Pharmaceuticals, Ferring Pharmaceuticals, Forest Laboratories, Fractyl, Garmin, HLS Therapeutics, Idorsia, Ironwood, Ischemix, Janssen, Javelin, Lexicon, Lilly, Medtronic, Merck, Moderna, MyoKardia, NirvaMed, Novartis, Novo Nordisk, Otsuka, Owkin, Pfizer, PhaseBio, PLx Pharma, Recardio, Regeneron, Reid Hoffman Foundation, Roche, Sanofi, Stasys, Synaptic, The Medicines Company, Youngene, 89Bio; Royalties: Elsevier (Editor, Braunwald's Heart Disease); Site Co-Investigator: Abbott, Biotronik, Boston Scientific, CSI, Endotronix, St. Jude Medical (now Abbott), Philips, SpectraWAVE, Svelte, Vascular Solutions; Trustee: American College of Cardiology; Unfunded Research: FlowCo. oooo Dr. Fonarow reports consulting for Abbott, Amgen, AstraZeneca, Bayer, Cytokinetics, Edwards, Janssen, Medtronic, Merck, and Novartis. Dr. Grodin reports consulting for Alnylam, Eidos, Sarepta, and Pfizer. Dr. Khera is a coinventor of US Pending Patent Applications. 63/177,117 and 63/346,610, unrelated to the present study; also a founder of Evidence2Health and Ensight-AI; received support from the National Heart, Lung, and Blood Institute of the National Institutes of Health (R01HL167858 and K23HL153775) and the Doris Duke Charitable Foundation (2,022,060); and receives research support from Bristol-Myers Squibb, Novo Nordisk, and BridgeBio, through Yale. The remaining authors have no competing interests to declare., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Hereditary transthyretin cardiac amyloidosis (ATTRv-CA) has a long latency phase before clinical onset, creating a need to identify subclinical disease. We hypothesized circulating transthyretin (TTR) and retinol binding protein 4 (RBP4) levels would be associated with TTR carrier status and correlated with possible evidence of subclinical ATTRv-CA., Methods: TTR and RBP4 were measured in blood samples from V122I TTR carriers and age-, sex- and race-matched non-carrier controls (1:2 matching) among Dallas Heart Study participants (phases 1 (DHS-1) and 2 (DHS-2)). Multivariable linear regression models determined factors associated with TTR and RBP4., Results: There were 40 V122I TTR carriers in DHS-1 and 54 V122I TTR carriers in DHS-2. In DHS-1 and DHS-2, TTR was lower in V122I TTR carriers ( p  < .001 for both), and RBP4 in DHS-2 was lower in V122I TTR carriers than non-carriers ( p  = .002). Among V122I TTR carriers, TTR was negatively correlated with markers of kidney function, and limb lead voltage ( p  < .05 for both) and TTR and RBP4 were correlated with atrial volume in DHS-2 ( p  < .05)., Conclusions: V122I TTR carrier status is independently associated with lower TTR and RBP4 in comparison with non-carriers. These findings support the hypothesis that TTR and RBP4 may correlate with evidence of subclinical ATTRv-CA.

Competing Interests: Disclosures None.

Background: Individuals with acute decompensated heart failure (ADHF) have a varying response to diuretic therapy. Strategies for the early identification of low diuretic efficiency to inform decongestion therapies are lacking., Objectives: The authors sought to develop and externally validate a machine learning-based phenomapping approach and integer-based diuresis score to identify patients with low diuretic efficiency., Methods: Participants with ADHF from ROSE-AHF, CARRESS-HF, and ATHENA-HF were pooled in the derivation cohort (n = 794). Multivariable finite-mixture model-based phenomapping was performed to identify phenogroups based on diuretic efficiency (urine output over the first 72 hours per total intravenous furosemide equivalent loop diuretic dose). Phenogroups were externally validated in other pooled ADHF trials (DOSE/ESCAPE). An integer-based diuresis score (BAN-ADHF score: blood urea nitrogen, creatinine, natriuretic peptide levels, atrial fibrillation, diastolic blood pressure, hypertension and home diuretic, and heart failure hospitalization) was developed and validated based on predictors of the diuretic efficiency phenogroups to estimate the probability of low diuretic efficiency using the pooled ADHF trials described earlier. The associations of the BAN-ADHF score with markers and symptoms of congestion, length of stay, in-hospital mortality, and global well-being were assessed using adjusted regression models., Results: Clustering identified 3 phenogroups based on diuretic efficiency: phenogroup 1 (n = 370; 47%) had lower diuretic efficiency (median: 13.1 mL/mg; Q1-Q3: 7.7-19.4 mL/mg) than phenogroups 2 (n = 290; 37%) and 3 (n = 134; 17%) (median: 17.8 mL/mg; Q1-Q3: 10.8-26.1 mL/mg and median: 35.3 mL/mg; Q1-Q3: 17.5-49.0 mL/mg, respectively) (P < 0.001). The median urine output difference in response to 80 mg intravenous twice-daily furosemide between the lowest and highest diuretic efficiency group (phenogroup 1 vs 3) was 3,520 mL/d. The BAN-ADHF score demonstrated good model performance for predicting the lowest diuretic efficiency phenogroup membership (C-index: 0.92 in DOSE/ESCAPE validation cohort) that was superior to measures of kidney function (creatinine or blood urea nitrogen), natriuretic peptide levels, or home diuretic dose (DeLong P < 0.001 for all). Net urine output in response to 80 mg intravenous twice-daily furosemide among patients with a low vs high (5 vs 20) BAN-ADHF score was 2,650 vs 660 mL per 24 hours, respectively. Participants with higher BAN-ADHF scores had significantly lower global well-being, higher natriuretic peptide levels on discharge, a longer in-hospital stay, and a higher risk of in-hospital mortality in both derivation and validation cohorts., Conclusions: The authors developed and validated a phenomapping strategy and diuresis score for individuals with ADHF and differential response to diuretic therapy, which was associated with length of stay and mortality., Competing Interests: Funding Support and Author Disclosures Dr Pandey has received research support from the National Institute of Health (5R01MD017529, R21HL169708) and grant funding from Applied Therapeutics and Gilead Sciences; has received honoraria outside of the present study as an advisor/consultant for Tricog Health Inc, Lilly USA, Rivus, Cytokinetics, Roche Diagnostics, Axon Therapies, Medtronic, Edward Lifesciences, Science37, Novo Nordisk, Bayer, Merck, Sarfez Pharmaceuticals, and Emmi Solutions; has received nonfinancial support from Pfizer and Merck; and is also a consultant for Palomarin Inc with stock compensation. Dr Segar has received honoraria from Merck. Dr Patel has served as a consultant to Novo Nordisk. Dr Fonarow has done consulting for Abbott, Amgen, AstraZeneca, Bayer, Cytokinetics, Janssen, Medtronic, Merck, and Novartis. Dr Mentz has received research support and honoraria from Abbott, American Regent, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim/Eli Lilly, Boston Scientific, Cytokinetics, Fast BioMedical, Gilead, Innolife, Medtronic, Merck, Novartis, Relypsa, Respicardia, Roche, Sanofi, Vifor, Windtree Therapeutics, and Zoll. Dr Allen reports grant funding from American Heart Association, National Institutes of Health, and PCORI; and consulting fees from Amgen, Boston Scientific, Cytokinetics, Novartis, and WCG ACI Clinical. Dr Pandey has received grant funding from Applied Therapeutics and Gilead Sciences; has received honoraria outside of the present study as an advisor/consultant for Tricog Health Inc, Lilly USA, Rivus, Cytokinetics, Bayer, Edwards Lifesciences, Medtronic, Sarfez Pharmacuticals, Novo Nordisk, and Roche Diagnostics; has received support from Pfizer and Merck; and is a consultant for Palomarin Inc with stock compensation. Dr Khan serves as an advisory board member for Bayer. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

There is waning interest among cardiology trainees in pursuing an Advanced Heart Failure/Transplant Cardiology (AHFTC) fellowship as evidenced by fewer applicants in the National Resident Matching Program match to this specialty. This trend has generated considerable attention across the heart failure community. In response, the Heart Failure Society of America convened the AHFTC Fellowship Task Force with a charge to develop strategies to increase the value proposition of an AHFTC fellowship. Subsequently, the HFSA sponsored the AHFTC Fellowship Consensus Conference April 26-27, 2023. Before the conference, interviews of 44 expert stakeholders diverse across geography, site of practice (traditional academic medical center or other centers), specialty/area of expertise, sex, and stage of career were conducted virtually. Based on these interviews, potential solutions to address the declining interest in AHFTC fellowship were categorized into five themes: (1) alternative training pathways, (2) regulatory and compensation, (3) educational improvements, (4) exposure and marketing for pipeline development, and (5) quality of life and mental health. These themes provided structure to the deliberations of the AHFTC Fellowship Consensus Conference. The recommendations from the Consensus Conference were subsequently presented to the HFSA Board of Directors to inform strategic plans and interventions. The HFSA Board of Directors later reviewed and approved submission of this document. The purpose of this communication is to provide the HF community with an update summarizing the processes used and concepts that emerged from the work of the HFSA AHFTC Fellowship Task Force and Consensus Conference., Competing Interests: Disclosures The authors have no conflicts of interest to declare., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Previous studies have linked cardiovascular risk factors during midlife to cognitive function in later life. However, few studies have looked at the association between cardiac function, brain structure, and cognitive function and even less have included diverse middle-aged populations., Objectives: The objective of this study was to determine associations between cardiac and brain structure and function in a multiethnic cohort of middle-aged adults., Methods: A cross-sectional study was conducted in participants of the Dallas Heart Study phase 2 (N = 1,919; 46% Black participants). Left ventricular (LV) mass, LV ejection fraction, LV concentricity, and peak systolic strain (LV E cc ) were assessed by cardiac magnetic resonance imaging. White matter hyperintensities (WMH) volume was measured by fluid attenuated inversion recovery magnetic resonance imaging. The Montreal Cognitive Assessment was used to measure cognitive functioning. Associations between cardiac and brain measures were determined using multivariable linear regression after adjusting for cardiovascular risk factors, education level, and physical activity., Results: LV ejection fraction was associated with total Montreal Cognitive Assessment score (β = 0.06 [95% CI: 0.003-0.12], P  = 0.042) and LV E cc was associated with WMH volume (β = 0.08 [95% CI: 0.01-0.14], P  = 0.025) in the overall cohort without significant interaction by race/ethnicity. Higher LV mass and concentricity were associated with larger WMH volume in the overall cohort (β = 0.13 [95% CI: 0.03-0.23], P  = 0.008 and 0.10 [95% CI: 0.03-0.17], P  = 0.005). These associations were more predominant in Black than White participants (β = 0.17 [95% CI: 0.04-0.30] vs β = -0.009 [95% CI: -0.16 to 0.14], P  = 0.036 and β = 0.22 [95% CI: 0.13-0.32] vs β = -0.11 [95% CI: -0.21 to -0.01], P  < 0.0001, for LV mass and concentricity, respectively)., Conclusions: Subclinical cardiac dysfunction indicated by LVEF was associated with lower cognitive function. Moreover, LV mass and concentric remodeling were associated with higher WMH burden, particularly among Black individuals., Competing Interests: The Dallas Heart Study was funded by the Donald W. Reynolds Foundation and was partially supported by the National Center for Advancing Translational Sciences of the National Institutes of Health under award Number UL1TR001105. Dr Vongpatanasin is supported by the 10.13039/100007914UT Southwestern O’Brien Kidney Center, the Charles and Jane Pak Center for Mineral Metabolism and Clinical Research: R01 AG057571. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.PERSPECTIVESCOMPETENCY IN MEDICAL KNOWLEDGE: Subclinical cardiac dysfunction was associated with lower cognitive function. Additionally, subclinical cardiac remodeling was associated with subclinical brain injury. These findings highlight the importance of maintaining optimal cardiovascular health to aid in maintaining brain health. TRANSLATIONAL OUTLOOK: Further studies are needed to determine if strategies to maintain normal cardiac structure and function during midlife offers protection against cognitive decline in late life., (© 2024 The Authors.)

Competing Interests: Declaration of Competing Interest Dr. Grodin receives consultancy fees from Alnylam, AstraZeneca, Pfizer (New York, New York), Eidos/BridgeBio, and Sarepta. Dr. de Lemos has received grant support from Roche Diagnostics and Abbott Diagnostics and consulting fees from Siemen's Health Care Diagnostics, Beckman Coulter, and Quidel. Dr. Cutrell was an unpaid co-investigator on COVID-19 clinical trials sponsored by the NIH, Gilead and Regeneron. Dr. Zaha was supported by a research grant from the Hammon Center for Regenerative Medicine, UT Southwestern Medical Center. Dr. Hendren has received research grant support from Tricog Health. The remaining authors have no competing interests to declare.

The prognostic utility of the oxygen uptake efficiency slope (OUES) in heart failure with reduced ejection fraction is uncertain. In this post hoc analysis of the HF-ACTION (Heart Failure: A Controlled Trial Investigating Outcomes of Exercise Training) trial (n = 2,074), we tested for associations of OUES and peak oxygen uptake (VO 2 ) with heart failure hospitalization or cardiovascular death in multivariable Cox regression models, adjusting for minute ventilation/carbon dioxide production (VE/VCO 2 ) slope and other important confounders. Harrell's C-statistics assessed the discriminatory performance of OUES and peak VO 2 . Lower OUES was associated with increased risk of the outcome (quartile 1 vs 4: hazard ratio 2.1 [1.5 to 2.9, p <0.001]). Peak VO 2 had greater discrimination than OUES in comparable models (e.g., C-statistic = 0.73 vs 0.70, p <0.001, respectively). In the subgroup with respiratory exchange ratio <1 (n = 358), peak VO 2 was associated with the outcome (p <0.001) but OUES was not (p = 0.96). In conclusion, whereas OUES was associated with clinical outcomes independently of VE/VCO 2 slope, its prognostic utility was inferior to that of peak VO 2 , even when measured at submaximal effort., Competing Interests: Declaration of Competing Interest The authors have no conflicts of interest to declare., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Competing Interests: Disclosures JT served on the task force for the 2020 ACC/AHA Clinical Performance and Quality Measures for Adults with Heart Failure. The other authors have no competing interests to report.

Natriuretic peptides, brain (B-type) natriuretic peptide (BNP) and N-terminal prohormone of brain natriuretic peptide (NT-proBNP) are globally and most often used for the diagnosis of heart failure (HF). In addition, they can have an important complementary role in the risk stratification of its prognosis. Since the development of angiotensin receptor neprilysin inhibitors (ARNIs), the use of natriuretic peptides as therapeutic agents has grown in importance. The present document is the result of the Trilateral Cooperation Project among the Heart Failure Association of the European Society of Cardiology, the Heart Failure Society of America and the Japanese Heart Failure Society. It represents an expert consensus that aims to provide a comprehensive, up-to-date perspective on natriuretic peptides in the diagnosis and management of HF, with a focus on the following main issues: (1) history and basic research: discovery, production and cardiovascular protection; (2) diagnostic and prognostic biomarkers: acute HF, chronic HF, inclusion/endpoint in clinical trials, and natriuretic peptides-guided therapy; (3) therapeutic use: nesiritide (BNP), carperitide (ANP) and ARNIs; and (4) gaps in knowledge and future directions., Competing Interests: Disclosures HT receives consultancy fees from Boehringer Ingelheim, Bayer Yakuhin, Novartis Pharma, Ono Pharmaceutical, Astra-Zeneca; remuneration from MSD, Astellas Pharma, Pfizer Japan, Bristol-Myers Squibb Company, Otsuka Pharmaceutical, Daiichi Sankyo, Mitsubishi Tanabe Pharma, Boehringer Ingelheim, Takeda Pharmaceutical, Bayer Yakuhin, Novartis Pharma, Kowa Pharmaceutical, Teijin Pharma; manuscript fees from Medical View, Nippon Rinsho; research funding from Actelion Pharmaceuticals Japan, Japan Tobacco, Mitsubishi Tanabe Pharma Nippon Boehringer Ingelheim, Daiichi Sankyo, IQVIA Services Japan, Omron Healthcare; scholarship funds from Astellas Pharma, Novartis Pharma, Daiichi Sankyo, Takeda Pharmaceutical, Mitsubishi Tanabe Pharma, Teijin Pharma, MSD. AJSC declares having received honoraria and/or lecture fees from Astra Zeneca, Bayer, Boehringer Ingelheim, Menarini, Novartis, Servier, Vifor, Abbott, Actimed, Arena, Cardiac Dimensions, Corvia, CVRx, Enopace, ESN Cleer, Faraday, Impulse Dynamics, Respicardia, and Viatris. SDA has received grants from Abbott Vascular and Vifor International and received personal fees from Amgen, Astra Zeneca, Bayer, Boehringer Ingelheim, Bioventrix, Brahms, Cardiac Dimensions, Cardior, Cordio, CVRx, Edwards, Impulse Dynamics, Janssen, Novartis, Occlutech, Respicardia, Servier, Vectorious and V-Wave, all outside the submitted work; and was named coinventor of 2 patent applications regarding MR-proANP (DE 102007010834, DE 102007022367) but did not benefit personally from the related issued patents. AB-G has received honoraria for lecturing from Abbott, AstraZeneca, Boehringer-Ingelheim, Novartis, Roche Diagnostics, and Vifor. JB was a consultant to Abbott, Adrenomed, American Regent, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, CVRx, Edwards Lifesciences, Faraday, G3 Pharmaceuticals, Impulse Dynamics, Innolife, Janssen, LivaNova, Medtronic, Merck, Novartis, Novo Nordisk, Pfizer, Sequanna, Roche, and Vifor. OC was a consultant for Boehringer Ingelheim. CRD was a consultant for Abbott Diagnostics, FujiRebio, Ortho/Quidel, Roche Diagnostics, and Siemens Healthineers. GMF has received research grants from NHLBI, American Heart Association, Amgen, Bayer, BMS, Merck, Cytokinetics, and CSL-Behring; has acted as a consultant to Novartis, Amgen, BMS, Cytokinetics, Medtronic, Cardionomic, Boehringer-Ingelheim, American Regent, Abbott, Astra-Zeneca, Reprieve, Myovant, Sequana, Windtree Therapeutics, and Whiteswell and has served on clinical endpoint committees/data-safety monitoring boards for Amgen, Merck, Medtronic, EBR Systems, V-Wave, LivaNova, Siemens, and Rocket Pharma. GF reports lecture fees and/or committee membership in trials sponsored by Bayer, Vifor, Medtronic, Novartis, Servier, Boehringer Ingelheim, and research support from the European Union. TI has received research funds from SBI Pharma and Pfizer. JLJ is a trustee of the American College of Cardiology, and a board member of Imbria Pharmaceuticals and has received research support from Abbott, Applied Therapeutics, Innolife, Novartis Pharmaceuticals, and Roche Diagnostics, has received consulting income from Abbott, Beckman, Bristol Myers, Boehringer-Ingelheim, Janssen, Novartis, Pfizer, Merck, Roche Diagnostics and Siemens, and participates in clinical endpoint committees/data-safety monitoring boards for Abbott, AbbVie, Bayer, CVRx, Intercept, Janssen, and Takeda. KK declares no conflicts of interest relevant to the present manuscript and has received grants and personal lecture fees from Astra Zeneca, grants and personal lecture fees from Otsuka Pharmaceutical, Ono Pharmaceutical, Eli Lilly Japan, and Daiichi-Sankyo, Mitsubishi Tanabe Pharma, Boehringer Ingelheim, Bayer Yakuhin, Novartis Pharma, Pfizer Japan, EP-CRSU, Takeda Pharmaceutical, Medtronic Japan, Fukuda Denshi, and Taisho Pharmaceutical, all outside the submitted work. Matsue received an honorarium from Otsuka Pharmaceutical, Novartis Pharma, Bayer, and AstraZeneca, and collaborative research grant from Pfizer Japan, Otsuka Pharmaceutical, EN Otsuka Pharmaceutical, and Nippon Boehringer Ingelheim. YM has received research support and honoraria from Abbott, American Regent, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Boston Scientific, Cytokinetics, Fast BioMedical, Gilead, Innolife, Eli Lilly, Medtronic, Merck, Novartis, Pharmacosmos, Relypsa, Respicardia, Roche, Sanofi, Vifor, Windtree Therapeutics, and Zoll. MM has received fees from Actelion, Amgen, Livanova, Servier, and Vifor Pharma as member of Executive or Data Monitoring Committees of sponsored clinical trials; from Astra-Zeneca, Abbott Vascular, Bayer, Boheringer Ingelhelm, and Edwards Therapeutics for participation in advisory boards and/or speeches at sponsored meetings. AP has received research support from the National Institute on Aging GEMSSTAR Grant (1R03AG067960-01) and the National Institute on Minority Health and Disparities (R01MD017529), grant funding from Applied Therapeutics and Gilead Sciences, honoraria outside of the present study as an advisor/consultant for Tricog Health, Lilly USA, Rivus, Cytokinetics, and Roche Diagnostics, and nonfinancial support from Pfizer and Merck and is also a consultant for Palomarin with stocks as compensation. Saito received research funds from Novartis Pharma, and Roche Diagnostics, and speaker's honoraria from Novartis Pharma, Daiichi Sankyo, and Otsuka Pharmaceutical. YS has received research funds from Roche Diagnostics and speaker's honoraria from Novartis Pharma, Daiichi Sankyo, and Otsuka Pharmaceutical. NS has received speaker's honoraria or consultation fees from Otsuka, Novartis Pharma, Daiichi Sankyo, Bayer, Boehringer-Ingelheim, Ono, AstraZeneca, Kowa, Taisho, and Terumo. KY has received research funds from Otsuka Pharmaceutical and speaker's honoraria from Otsuka Pharmaceutical, Novartis Pharma and Daiichi Sankyo. MY has received research funds from Teijin Pharma, Shionogi, Otsuka Pharmaceutical, and Mochida Pharmaceutical, and speaker's honoraria from Daiichi Sankyo, Mitsubishi Tanabe Pharma Corporation, Pfizer Japan, AstraZeneca, Otsuka Pharmaceutical, Astellas Pharma, Bayer Yakuhin, and Mochida Pharmaceutical. All other authors have nothing to declare that is related to the submitted work., (Copyright © 2023 Elsevier Inc., European Society of Cardiology. Published by Elsevier Inc. All rights reserved.)

Competing Interests: Disclosures No disclosures.

Decreased exercise capacity portends a poor prognosis in heart failure with preserved ejection fraction (HFpEF). The hemodynamic gain index (HGI) is an integrated marker of hemodynamic reserve measured during exercise stress testing and is associated with survival. The goal of this study was to establish the association of HGI with exercise capacity, serum biomarkers, and echocardiography features in subjects with HFpEF. In 209 subjects with HFpEF enrolled in the RELAX (Phosphodiesterase-5 Inhibition to Improve Clinical Status and Exercise Capacity in Diastolic Heart Failure) trial who underwent cardiopulmonary exercise testing, we calculated the HGI ([peak heart rate [HR] × peak systolic blood pressure [SBP]-[HR at rest × SBP at rest])/(HR at rest × SBP at rest) and tested associations with outcomes of interest. The median (interquartile range) HGI was 0.94 (0.5 to 1.3) beats per min/mm Hg. In multivariable-adjusted linear regression, higher HGI was associated with greater peak oxygen consumption (VO 2 ), VO 2 at anaerobic threshold, peak minute ventilation, and 6-minute walk distance (all p <0.001). Higher HGI was associated with lower serum high-sensitivity troponin I, pro-collagen III, N-terminal pro-B-type natriuretic peptide, and creatinine (all p <0.05) and with longer deceleration time, lower E/A ratio, and lower left atrial volume index by echocardiography (all p <0.05). In conclusion, higher HGI in stable HFpEF was associated with greater exercise capacity, a biomarker profile indicating less myocardial injury and fibrosis and less kidney dysfunction, and with less severe diastolic dysfunction. These results suggest that HGI, an easily calculated metric from routine exercise testing, is a marker of functional capacity and disease severity in HFpEF and may serve as a surrogate for VO 2 parameters for use in treadmill testing without gas exchange capability., Competing Interests: Disclosures Dr. Grodin reports personal fees from Pfizer, Alnylam, Eidos, and Sarepta. Dr. Tang reports personal fees from Sequana Medical AG, Cardiol Therapeutics Inc, Genomics plc, Springer Nature, and the American Board of Internal Medicine for exam writing committee participation - all unrelated to the subject and contents of this study. The remaining authors have no conflicts of interest to declare., (Copyright © 2022 Elsevier Inc. All rights reserved.)

The syndrome of heart failure (HF) has historically been dichotomized based on clinical trial inclusion criteria into patients with a reduced or preserved left ventricular ejection fraction (LVEF) using a cut-off of above or below 40%. The majority of trial evidence for the benefits of disease-modifying pharmacological therapy has been in patients with HF with reduced ejection fraction (HFrEF), i.e. those with an LVEF ≤40%. Recently, the sodium-glucose co-transporter 2 inhibitors empagliflozin and dapagliflozin have been shown to be the first drugs to improve outcomes in HF across the full spectrum of LVEF. There is, however, growing evidence that the benefits of many of the neurohumoral modulators shown to be beneficial in patients with HFrEF may extend to those with a higher LVEF above 40% but still below the normal range, i.e. HF with mildly reduced ejection fraction (HFmrEF). Whether the benefits of some of these medications also extend to patients with HF and preserved ejection fraction (HFpEF) is an area of ongoing debate. This article will review the evidence for HF treatments across the full spectrum of LVEF, provide an overview of recently updated clinical practice guidelines, and address the question whether it may now be time to treat HF with some therapies regardless of ejection fraction., Competing Interests: Conflict of interest: K.F.D. declares that his employer, the University of Glasgow, has been remunerated by AstraZeneca for his time spent working on the DAPA-HF trial and he has received lecture fees from AstraZeneca. He has received research funding from AstraZeneca and Boehringer-Ingelheim and serves on an Advisory Board for Us2.ai. A.B.-G. has lectured or participated in advisory boards for Abbott, AstraZeneca, Boehringer-Ingelheim, Novartis, Roche Diagnostics, Vifor. J.B. is a consultant to Abbott, Amgen, American Regent, AstraZeneca, Bayer, Boehringer-Ingelheim, Bristol Myers Squibb, CVRx, G3 Pharmaceutical, Impulse Dynamics, Innolife, Janssen, LivaNova, Medtronic, Merck, Novartis, Novo Nordisk, Pfizer, Roche, and Vifor. A.J.S.C. declares having received honoraria and/or lecture fees from: Astra Zeneca, Boehringer-Ingelheim, Menarini, Novartis, Servier, Vifor, Abbott, Actimed, Arena, Cardiac Dimensions, Corvia, CVRx, Enopace, ESN Cleer, Faraday, Impulse Dynamics, Respicardia, Viatris. C.S.L. is supported by a Clinician Scientist Award from the National Medical Research Council of Singapore; has received research support from Bayer and Roche Diagnostics; has served as a consultant or on the Advisory Board/Steering Committee/Executive Committee for Abbott, Actelion, Alleviant Medical, Allysta Pharma, Amgen, AnaCardio AB, Applied Therapeutics, AstraZeneca, Bayer, Boehringer-Ingelheim, Boston Scientific, Cytokinetics, Darma Inc., EchoNous Inc, Impulse Dynamics, Ionis Pharmaceutical, Janssen Research & Development LLC, Medscape/WebMD Global LLC, Merck, Novartis, Novo Nordisk, Prosciento Inc, Radcliffe Group Ltd., Roche Diagnostics, Sanofi, Siemens Healthcare Diagnostics and Us2.ai; and serves as a co-founder and non-executive director of Us2.ai., (© The Author(s) 2022. Published by Oxford University Press on behalf of European Society of Cardiology.)

Introduction: There are varied opinions in the United States regarding many aspects of care related to COVID-19. The purpose of this study was to examine the opinions of health care personnel and the policies of heart transplant centers concerning practices for the prevention and treatment of COVID-19 in donors and recipients of heart transplants., Methods: Two anonymous, electronic web-based surveys were developed: 1 was administered to health care personnel through a mailing list maintained by the Heart Failure Society of America (HFSA); another was administered to U.S. medical adult and pediatric heart transplant (HT) program directors. Individual and group e-mails were sent with an embedded link to the respective surveys in February 2022., Results: A total of 176 individuals (8.6%) responded to the survey administered through the HFSA. Of medical directors of transplant programs, 78 (54% response rate) completed a separate survey on their centers' policies. Although 95% (n = 167) of individuals indicated vaccination against COVID-19 should be required prior to HT, only 67% (n = 52) of centers mandated that practice. Similarly, 61% of individuals thought vaccination should be required prior to HT for caregivers, but only 13% of transplant centers mandated caregiver vaccination. Of the centers, 63% reported considering donors despite histories of recent COVID-19 infection (within 3 months), and 47% considered donors with current positive polymerase chain reaction tests. Regarding post-transplant care, only 22% of programs routinely measured antibodies to COVID-19, and 71% used tixagevimab/cilgavimab (Evusheld) for pre-exposure prophylaxis., Conclusions: There were significant differences between individual preferences and centers' practices with respect to COVID-19 management of candidates for and recipients of HT. Additionally, there was wide variation in policies among centers, reflecting the need for further study to inform consistent guidance and recommendations across centers to optimize equitable care for this high-risk patient population., (Copyright © 2022 Elsevier Inc. All rights reserved.)