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Importance: Clinical trials have suggested that prehospital management in a mobile stroke unit (MSU) improves functional outcomes in patients with acute ischemic stroke who are potentially eligible for intravenous thrombolysis, but there is a paucity of real-world evidence from routine clinical practice on this topic., Objective: To determine the association between prehospital management in an MSU vs standard emergency medical services (EMS) management and the level of global disability at hospital discharge., Design, Setting, and Participants: This was a retrospective, observational, cohort study that included consecutive patients with a final diagnosis of ischemic stroke who received either prehospital management in an MSU or standard EMS management between August 1, 2018, and January 31, 2023. Follow-up ended at hospital discharge. The primary analytic cohort included those who were potentially eligible for IV thrombolysis. A separate, overlapping cohort including all patients regardless of diagnosis was also analyzed. Patient data were obtained from the American Heart Association's Get With The Guidelines-Stroke (GWTG-Stroke) Program, a nationwide, multicenter quality assurance registry. This analysis was completed in May 2024., Exposure: Prehospital management in an MSU (vs standard EMS management)., Main Outcomes and Measures: The primary efficacy end point was the utility-weighted modified Rankin Scale (UW-mRS) score. The secondary efficacy end point was independent ambulation status. The coprimary safety end points were symptomatic intracranial hemorrhage (sICH) and in-hospital mortality., Results: Of 19 433 patients (median [IQR] age, 73 [62-83] years; 9867 female [50.8%]) treated at 106 hospitals, 1237 (6.4%) received prehospital management in an MSU. Prehospital management in an MSU was associated with a better score on the UW-mRS at discharge (adjusted mean difference, 0.03; 95% CI, 0.01-0.05) and a higher likelihood of independent ambulation at discharge (53.3% [468 of 878 patients] vs 48.3% [5868 of 12 148 patients]; adjusted risk ratio [aRR], 1.08; 95% CI, 1.03-1.13). There was no statistically significant difference in sICH (5.2% [57 of 1094] vs 4.2% [545 of 13 014]; aRR, 1.30; 95% CI, 0.94-1.75]) or in-hospital mortality (5.7% [70 of 1237] vs 6.2% [1121 of 18 196]; aRR, 1.03; 95% CI, 0.78-1.27) between the 2 groups., Conclusions and Relevance: Among patients with acute ischemic stroke potentially eligible for intravenous thrombolysis, prehospital management in an MSU compared with standard EMS management was associated with a significantly lower level of global disability at hospital discharge. These findings support policy efforts to expand access to prehospital MSU management.

The current economic burden of cardiovascular-related hospitalizations grouped by diagnoses and procedures in the U.S. has not been well characterized. The objective was to identify current trends in cardiovascular-related hospitalizations, procedural utilization, and health care costs, using the most recent 6 years of hospitalization data. A retrospective analysis of discharge data from the National Inpatient Sample (NIS) database was conducted to determine trends in cardiovascular-related hospitalizations, costs, and procedures for each year from 2016 to the most recent available dataset, 2021. Total cardiovascular-related costs were adjusted to and reported in 2023 dollars. In 2021, there were 4,687,370 cardiovascular-related hospitalizations at a cost of $108 billion. Heart failure hospitalizations accounted for the highest costs at $18.5 billion, followed by Non-ST-Elevation Myocardial Infarction at $11.2 billion, and stroke at $10.9 billion. Significant upward trends in costs from 2016 to 2021 were observed for heart failure, stroke, atrial fibrillation, ST-elevation myocardial infarction, chest pain, hypertensive emergency, ventricular tachycardia, aortic dissection, sudden cardiac death, pericarditis, supraventricular tachycardia, and pulmonary heart disease. Over the 6 observational years, total costs increased by over $10 billion, representing a 10 percent increase. However, the increases were not linear, as there was a significant increase of 6.5% from 2018 to 2019, then a dip of over 7% from 2019 to 2020, followed by a rise of about 6% from 2020 to 2021. By 2030, total CV-related costs are projected to reach $131.3 billion. For all years, coronary procedures were the most performed, followed by ECMO, non-bypass peripheral vascular surgery, pacemaker placement, and CABG. Both TAVR and MitraClip procedures demonstrated significant upward trends from 2016 to 2021. Overall, from the years 2016 to 2021, cardiovascular-related hospitalizations, costs, and procedures demonstrated upward trends. In conclusion, cardiovascular disease remains a high burden in the hospital setting with tremendous health care costs., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Rushi Parikh reports a relationship with Abbott Vascular Inc that includes: consulting or advisory. Rushi Parikh reports a relationship with Bayer Corporation that includes: funding grants. Gregg Fonarow reports a relationship with Abbott Laboratories that includes: consulting or advisory. Gregg Fonarow reports a relationship with Amgen Inc that includes: consulting or advisory. Gregg Fonarow reports a relationship with AstraZeneca Pharmaceuticals LP that includes: consulting or advisory. Gregg Fonarow reports a relationship with Bayer Corporation that includes: consulting or advisory. Gregg Fonarow reports a relationship with Eli Lilly and Company that includes: consulting or advisory. Gregg Fonarow reports a relationship with Johnson & Johnson Services Inc that includes: consulting or advisory. Gregg Fonarow reports a relationship with Medtronic Inc that includes: consulting or advisory. Gregg Fonarow reports a relationship with Merck & Co Inc that includes: consulting or advisory. Gregg Fonarow reports a relationship with Novartis Pharmaceuticals Corporation that includes: consulting or advisory. Gregg Fonarow reports a relationship with Pfizer Inc that includes: consulting or advisory. Peyman Benharash reports a relationship with AtriCure Inc that includes: consulting or advisory. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

Background: Natural language processing (NLP) can facilitate research utilizing data from electronic health records (EHRs). Large language models can potentially improve NLP applications leveraging EHR notes. The objective of this study was to assess the performance of zero-shot learning using Chat Generative Pre-trained Transformer 4 (ChatGPT-4) for extraction of symptoms and signs, and compare its performance to baseline machine learning and rule-based methods developed using annotated data., Methods and Results: From unstructured clinical notes of the national EHR data on the Veterans healthcare system, we extracted 1999 text snippets containing relevant keywords for heart failure symptoms and signs, which were then annotated by two clinicians. We also created 102 synthetic snippets that were semantically similar to snippets randomly selected from the original 1999 snippets. The authors applied zero-shot learning, using two different forms of prompt engineering in a symptom and sign extraction task with ChatGPT-4, utilizing the synthetic snippets. For comparison, baseline models using machine learning and rule-based methods were trained using the original 1999 annotated text snippets, and then used to classify the 102 synthetic snippets. The best zero-shot learning application achieved 90.6 % precision, 100 % recall, and 95 % F1 score, outperforming the best baseline method, which achieved 54.9 % precision, 82.4 % recall, and 65.5 % F1 score. Prompt style and temperature settings influenced zero-shot learning performance., Conclusions: Zero-shot learning utilizing ChatGPT-4 significantly outperformed traditional machine learning and rule-based NLP. Prompt type and temperature settings affected zero-shot learning performance. These findings suggest a more efficient means of symptoms and signs extraction than traditional machine learning and rule-based methods., Competing Interests: Declaration of competing interest None., (Copyright © 2024. Published by Elsevier Inc.)

Background: Optimal systolic blood pressure (SBP) targets for the treatment of hospitalized acute decompensated heart failure (ADHF) patients are not known., Objectives: To investigate the association between SBP <130 mmHg at discharge or within 30 days and all-cause mortality or years of life lost (YLL) after ADHF hospitalization., Methods: We analyzed medical records of 14,611 adults who survived ADHF hospitalization at 17 hospitals (2010-2022) with follow-up until May 2023. Sensitivity analysis included 10,515 patients with post-discharge SBP measured within 30 days., Results: Mortality rates at 30 days, 180 days, 1 year, and 3 years were higher in patients with discharge SBP <130 mmHg (6.9 %, 21.1 %, 29.1 %, and 45.1 %) vs. SBP ≥130 mmHg (4.8 %, 16.0 %, 23.6 %, and 40.3 %). Hazard ratios (HR) for mortality were consistently higher in patients with discharge SBP <130 at 1.30 (95 % CI, 1.11-1.52), 1.45 (95 % CI, 1.33-1.58), 1.40 (95 % CI, 1.30-1.51), 1.31 (95 % CI, 1.23-1.38) at these intervals. The average YLL per deceased individual was 1-2 years greater in the discharge SBP <130 group (incidence rate ratios, 1.004 to 1.230). Restricted cubic spline analysis showed that HR for mortality shifted toward better outcomes at discharge SBP ≥130 Sensitivity analysis supported these findings., Conclusion: In hospitalized ADHF patients, SBP <130 mmHg at discharge or within 30 days post-discharge was linked to higher mortality and YLL, while SBP ≥130 mmHg or improvement to ≥130 mmHg post-discharge led to better short and long-term outcomes. Further research is needed to understand the mechanisms and benefits of SBP optimization., Competing Interests: Declaration of competing interest Dr. Fonarow reports consulted for Abott, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Cytokinetics, Elli Lilly, Johnson & Johnson, Medtronic, Merck, and Pfizer. The other authors have no conflict of interest to report. Dr. Barkoudah reports research support payments from the National Institutes of Health/National Heart, Lung, and Blood Institute, and contracts all made to Brigham and Women's Hospital; payments made to Brigham and Women's Hospital for performing clinical endpoints sponsored by various entities including serving on trials committee; payments from Medscape and WebMD (editor-in-chief of JCOM), and Advisory Board fees from Bayer, Gilead and Novartis. There were non-compensated efforts in consulting through OSG, CaptiOX, and volunteer board positions. All outside the submitted work. The other authors have no disclosures to report., (Copyright © 2024 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.)

Background: National heart failure guidelines recommend quadruple therapy with renin-angiotensin system inhibitors, beta-blockers, mineralocorticoid receptor antagonists, and sodium-glucose cotransporter 2 inhibitors for patients with heart failure with reduced ejection fraction (HFrEF), most of whom also receive loop diuretics. However, the guidelines are less clear about the safe approaches to discontinuing older drugs whose decreasing or residual benefit is less well understood. The objective of this study was to examine whether digoxin can be safely discontinued in patients with HFrEF receiving beta-blockers., Methods: In OPTIMIZE-HF, of 2,477 patients with HFrEF (EF ≤45%) receiving beta-blockers and digoxin, digoxin was discontinued in 450 patients. We assembled a propensity score-matched cohort of 433 pairs of patients in which digoxin continuation vs. discontinuation groups were balanced on 51 baseline characteristics. Using the same approach, from 992 patients not on beta-blockers, we assembled a matched cohort of 198 pairs of patients also balanced on 51 baseline characteristics. Hazard ratios (HRs) and 95% CIs for one-year outcomes were estimated., Results: Among patients receiving beta-blockers, digoxin discontinuation had no association with the combined endpoint of heart failure readmission or death (HR, 1.01; 95% CI, 0.85-1.19), heart failure readmission (HR, 1.03; 95% CI, 0.85-1.25) or death (HR, 0.91; 95% CI, 0.72-1.14). Respective HRs (95% CIs) among patients not receiving beta-blockers were 1.60 (1.25-2.04), 1.62 (1.18-2.22) and 1.43 (1.08-1.89)., Conclusions: Digoxin can be discontinued without increasing the risk of adverse outcomes in patients with HFrEF receiving beta-blockers. Future studies need to examine the residual benefit of older heart failure drugs to ensure their safe discontinuation in patients with HFrEF receiving newer guideline-directed medical therapy., (Copyright © 2024. Published by Elsevier Inc.)

Background: While there are several completed clinical trials that address treatment strategies in patients with symptomatic and recurrent atrial fibrillation (AF), there are no randomized clinical trials that address first-line rhythm control of new-onset AF. Recent data suggest that early initiation of rhythm control within 1 year can improve outcomes., Methods: In this open-label pragmatic clinical trial nested within the Get With The Guidelines Atrial Fibrillation registry, approximately 3,000 patients with first-detected AF will be enrolled at approximately 200 sites. Participants will be randomized (1:1) to treatment with dronedarone in addition to usual care versus usual care alone. The primary endpoint will be time to first cardiovascular (CV) hospitalization or death from any cause through 12 months from randomization. Secondary endpoints will include a WIN ratio (all-cause death, ischemic stroke or systemic embolism, heart failure hospitalization, acute coronary hospitalization), CV hospitalization, and all-cause mortality. Patient reported outcomes will be analyzed based on change in Atrial Fibrillation Effect on Quality of Life (AFEQT) and change in Mayo AF-Specific Symptom Inventory (MAFSI) from baseline to 12 months., Conclusion: CHANGE AFIB will determine if treatment with dronedarone in addition to usual care is superior to usual care alone for the prevention of CV hospitalization or death from any cause in patients with first-detected AF. The trial will also determine whether initiation of rhythm control at the time of first-detected AF affects CV events or improves patient reported outcomes., Clinicaltrials: GOV #: - NCT05130268., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Sodium-glucose cotransporter-2 (SGLT2) inhibitors provide cardiovascular and kidney benefits to patients with heart failure (HF) and/or chronic kidney disease (CKD), regardless of diabetes status and left ventricular ejection fraction (LVEF). Despite robust data demonstrating the efficacy of SGLT-2 inhibitors in both ambulatory and hospital settings, real-world evidence suggests slow and varied adoption of SGLT2 inhibitors among patients hospitalized for HF. Barriers to implementation of SGLT2i may include clinicians' concerns regarding potential adverse events such as diabetic ketoacidosis (DKA), volume depletion, and symptomatic hypoglycemia; or concerns regarding physiologically expected reductions in eGFR. Guidelines lack specific, practical safety data and definitive recommendations regarding in-hospital initiation and continuation of SGLT2i in patients hospitalized with HF. In this review, we discuss the safety of in-hospital SGLT2 inhibitor initiation based on recent trials and highlight the clinical implications of their early use in patients hospitalized for HF., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Although clinical evidence supports rapid institution of guideline-directed medical therapy (GDMT) for heart failure (HF), in actual practice, there remain large gaps in adherence to guideline recommendations. Recent data support safety and efficacy of rapid GDMT implementation; however, rapid GDMT deployment within a general cardiology environment remains unexplored., Objectives: The purpose of this study was to evaluate the efficacy and safety of a GDMT clinic within a general cardiology practice relative to usual care, the impact on prescription of GDMT, HF symptoms, N-terminal pro-B-type natriuretic peptide concentrations and echocardiographic parameters of remodeling., Methods: Individuals with HF with an abnormal ejection fraction (<50%) referred to the GDMT clinic underwent rapid GDMT titration with close monitoring of clinical data. Rates of GDMT prescription were compared with a matched reference group. Patients underwent echocardiography at baseline and after GDMT clinic completion., Results: A total of 114 persons were treated in GDMT clinic. The mean age was 67.6 ± 14.6 years, and 32 (28%) were women. Among those referred, 100 (87.7%) had no contraindications for 4-drug GDMT. From baseline to clinic completion (median 15.8 weeks [Q1-Q3: 10.7-23.0 weeks]), patients without medication contraindications experienced significant increases in 4-drug GDMT use (from 21% to 88%; P < 0.001); of 4-drug GDMT recipients, 92% received angiotensin receptor neprilysin inhibitor. GDMT clinic participants achieved higher medication doses than those in usual care, with greater achievement of ≥50% target dose of angiotensin receptor neprilysin inhibitor (52% vs 8%), beta-blocker (78% vs 6.2%), mineralocorticoid receptor antagonist (98% vs 15.6%), and sodium-glucose cotransporter 2 inhibitors (92% vs 6.2%). Target doses of all 4 drugs were reached in nearly 1 in 4 participants. HF symptoms improved (94% to 75% NYHA functional class II/III; P < 0.001) and N-terminal pro-B-type natriuretic peptide concentration decreased (median 587 to 534 ng/L; P = 0.03) despite loop diuretic reduction. Additionally, we observed an absolute 6% LVEF increase (from 37% [Q1-Q3: 31%-41%] to 43% [Q1-Q3: 38%-53%]; P < 0.001) and substantial decrease in moderate or severe mitral regurgitation. GDMT titration was well-tolerated., Conclusions: Rapid GDMT implementation via an outpatient GDMT clinic was effective, safe, and associated with improvement in key clinical parameters. The more widespread role of GDMT clinics to improve HF care warrants further study., Competing Interests: Funding Support and Author Disclosures Data analysis supported by an unrestricted grant from Novartis Pharmaceuticals Corporation. Dr Cohen has a board position with Kento Health Inc. Dr Khairnar is an employee of Novartis Pharmaceuticals Corporation. Dr Williamson was an employee of Novartis Pharmaceuticals Corporation at the time that this study was conducted and the analyses were completed. Dr Scott has received research support from the REBIRTH study and HOPE registries; and has received consulting income from Mediflix. Dr Greene has received research support from the Duke University Department of Medicine Chair’s Research Award, American Heart Association, Amgen, AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Cytokinetics, Merck, Novartis, Pfizer, and Sanofi; has served on advisory boards or as consultant for Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Corcept Therapeutics, Corteria Pharmaceuticals, CSL Vifor, Cytokinetics, Eli Lilly, Lexicon, Merck, Novo Nordisk, Otsuka, Roche Diagnostics, Sanofi, scPharmaceuticals, Tricog Health, and Urovant Pharmaceuticals; and has received speaker fees from AstraZeneca, Bayer, Boehringer Ingelheim, Cytokinetics, Lexicon, and Roche Diagnostics. Dr Fonarow has consulted for Abbott Laboratories, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Cytokinetics, Eli Lilly, Johnson and Johnson, Medtronic, Merck, Novartis, and Pfizer. Dr Januzzi has a board position with Imbria Pharmaceuticals; has received grant support from Abbott, Applied Therapeutics, AstraZeneca, Bristol Myers Squibb, and Novartis Pharmaceuticals, has received consulting income from Abbott Diagnostics, Beckman-Coulter, Jana Care, Janssen, Novartis, Prevencio, Quidel, and Roche Diagnostics; and serves on clinical endpoint committees/data safety monitoring boards for Abbott, AbbVie, Amgen, CVRx, Medtronic, Pfizer, and Roche Diagnostics. 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.)

Importance: Guideline-directed medical therapy (GDMT) remains underutilized on a global level, with significant disparities in access to treatment worldwide. The potential global benefits of quadruple therapy on patients with heart failure with reduced ejection fraction (HFrEF) have not yet been estimated., Objective: To assess the projected population-level benefit of optimal GDMT use globally among patients with HFrEF., Design, Setting, and Participants: Estimates for HFrEF prevalence, contraindications to GDMT, treatment rates, and the number needed to treat for all-cause mortality at 12 months were derived from previously published sources. Potential lives saved from optimal implementation of quadruple therapy among patients with HFrEF was calculated globally and a sensitivity analysis was conducted to account for uncertainty in the existing data., Main Outcomes and Measures: All-cause mortality., Results: Of an estimated 28.89 million people with HFrEF worldwide, there were 8 235 063 (95% CI, 6 296 020-10 762 972) potentially eligible for but not receiving β-blockers, 20 387 000 (95% CI, 15 867 004-26 184 996) eligible for but not receiving angiotensin receptor-neprilysin inhibitors, 12 223 700 (95% CI, 9 376 895-15 924 973) eligible for but not receiving mineralocorticoid receptor antagonists, and 21 229 170 (95% CI, 16 537 400-27 242 688) eligible for but not receiving sodium glucose cotransporter-2 inhibitors. Optimal implementation of quadruple GDMT could potentially prevent 1 188 277 (95% CI, 767 933-1 914 561) deaths over 12 months. A large proportion of deaths averted were projected in Southeast Asia, Eastern Mediterranean and Africa, and the Western Pacific regions., Conclusions and Relevance: Improvement in use of GDMT could result in substantial mortality benefits on a global scale. Significant heterogeneity also exists across regions, which warrants additional study with interventions tailored to country-level differences for optimization of GDMT worldwide.

Background: Home-time is an emerging, patient-centered outcome that represents the amount of time a patient spends alive and outside of health care facility settings, comprising of hospitals, skilled nursing facilities, and acute rehabilitation centers. Studies evaluating home-time in the context of heart failure are limited, and the impact of quality improvement interventions on home-time has not been studied., Methods: Medicare beneficiaries aged 65 years or older who were hospitalized for heart failure in the Get With the Guidelines-Heart Failure registry between 2019 and 2021 were included. Postdischarge home-time, mortality, and readmission rates at 30 days and 1 year were calculated with the goal of establishing baseline metrics before the initiation of IMPLEMENT-HF, a multicenter quality improvement program aimed at improving heart failure management., Results: Overall, 66 019 patients were included across 437 sites. Median 30-day and 1-year home-time were 30 (18-30) and 333 (139-362) days, respectively. Only 22.1% of patients experienced 100% home-time in the year after discharge. Older patients spent significantly less time at home, with a median 1-year home-time of 302 (86-359) compared with 345 (211-365) days in patients over 85 and those between 65 and 74 years old, respectively ( P <0.001). Black patients also experienced the least amount of home-time with only 328 (151-360) days at 1-year follow-up. Rates of heart failure readmission and all-cause mortality 1-year post-discharge were high at 29.8% and 37.0%, respectively., Conclusions: In this contemporary multicenter cohort, patients hospitalized with heart failure spent a median of 91.2% of their time in the year after discharge alive and at home, largely driven by high mortality rates. These findings serve as a preimplementation baseline for IMPLEMENT-HF, which will evaluate the impact of targeted heart failure initiatives on home-time and other clinical outcomes., Competing Interests: Dr Greene has received research support from the Duke University Department of Medicine Chair’s Research Award, the American Heart Association, Amgen, AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Cytokinetics, Merck, Novartis, Pfizer, and Sanofi; has served on advisory boards or as a consultant for Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Corcept, Corteria Pharmaceuticals, CSL Vifor, Cytokinetics, Lilly, Lexicon, Merck, Novo Nordisk, Otsuka, Roche Diagnostics, Sanofi, scPharmaceuticals, Tricog Health, and Urovant Pharmaceuticals; and has received speaker fees from Bayer, Boehringer Ingelheim, Cytokinetics, Lexicon, and Roche Diagnostics. Dr Butler has consulted for Abbott, American Regent, Amgen, Applied Therapeutics, AskBio, Astellas, AstraZeneca, Bayer, Boehringer Ingelheim, Boston Scientific, Bristol Myers Squibb, Cardiac Dimension, Cardiocell, Cardior, CSL Behring, CVRx, Cytokinetics, Daxor, Edwards, Element Science, Faraday, Foundry, G3P, Innolife, Impulse Dynamics, Imbria, Inventiva, Ionis, Lexicon, Lilly, LivaNova, Janssen, Medtronic, Merck, Occlutech, Owkin, Novartis, Novo Nordisk, Pharmacosmos, Pharmain, Pfizer, Prolaio, Regeneron, Renibus, Roche, Salamandra, Sanofi, SC Pharma, Secretome, Sequana, SQ Innovation, Tenex, Tricog, Ultromics, Vifor, and Zoll. Dr Lewis has received grants from the American Heart Association and Merck and has consulted for AstraZeneca, Intellia, and Merck. Dr Fonarow has consulted for Abbott, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Cytokinetics, Eli Lilly, Johnson & Johnson, Medtronic, Merck, Novartis, and Pfizer.

Background: Oral anticoagulants (OACs) are routinely used for the management of atrial fibrillation (AF) while antiplatelet agents are used in coronary artery disease (CAD). However, data regarding the comparative clinical outcomes of OAC monotherapy versus dual antithrombotic therapy (anticoagulant plus antiplatelet agent) in patients with AF and stable CAD are limited., Methods: A comprehensive search of major databases including PubMed/MEDLINE, Cochrane Library, and Embase was performed from inception to September 1, 2024 to identify randomized control trials (RCTs) that compared OAC monotherapy with dual antithrombotic therapy in patients with AF and stable CAD. The risk ratios (RRs) were estimated with corresponding 95% confidence intervals (CIs) for all outcomes., Results: A total of three RCTs reported data for 3945 patients with AF and stable CAD. The mean age of patients was 73.8 (±11.85) years and the mean follow-up was 22 months. OAC monotherapy was associated with a significantly reduced relative risk of major bleeding (RR: 0.55, 95% CI: 0.32-0.95) compared to dual therapy. The risk of all-cause death (RR: 0.85, 95% CI: 0.49-1.48), cardiovascular death (RR: 0.84, 95% CI: 0.50-1.41), any stroke event (RR: 0.74, 95% CI: 0.46-1.18), and myocardial infarction (RR: 1.57, 95% CI: 0.79-3.12) remained comparable across the two groups., Conclusion: OAC monotherapy led to a significant relative risk reduction for major bleeding with similar rates of ischemic events and mortality compared to dual antithrombotic therapy in patients with AF and stable CAD., (© 2024 The Author(s). Clinical Cardiology published by Wiley Periodicals LLC.)

Background: Disparities in guideline-based quality measures likely contribute to differences in heart failure (HF) outcomes. We evaluated between- and within-hospital differences in the quality of care across sex, race, ethnicity, and insurance for patients hospitalized for HF., Methods: This retrospective analysis included patients hospitalized for HF across 596 hospitals in the Get With the Guidelines-HF registry between 2016 and 2021. We evaluated performance across 7 measures stratified by patient sex, race, ethnicity, and insurance. We evaluated differences in performance with and without adjustment for the treating hospital. We also measured variation in hospital-specific disparities., Results: Among 685 227 patients, the median patient age was 72 (interquartile range, 61-82) and 47.2% were women. Measure performance was significantly lower (worse) for women compared with men for all 7 measures before adjustment. For 4 of 7 measures, there were no significant sex-related differences after patient-level adjustment. For 20 of 25 other comparisons, racial and ethnic minorities and Medicaid/uninsured patients had similar or higher (better) adjusted measure performance compared with White and Medicare/privately insured patients, respectively. Angiotensin receptor neprilysin inhibitor measure performance was significantly lower for Asian, Hispanic, and Medicaid/uninsured patients, and cardiac resynchronization therapy implant/prescription was lower among women and Black patients after hospital adjustment, indicating within-hospital differences. There was hospital-level variation in these differences. For cardiac resynchronization therapy implantation/prescription, 278 hospitals (46.6%) had ≥2% lower implant/prescription for Black versus White patients compared with 109 hospitals (18.3%) with the same or higher cardiac resynchronization therapy implantation/prescription for Black patients., Conclusions: HF quality measure performance was equitable for most measures. There were within-hospital differences in angiotensin receptor neprilysin inhibitor and cardiac resynchronization therapy implant/prescription for historically marginalized groups. The magnitude of hospital-specific disparities varied across hospitals., Competing Interests: Dr Sandhu has received research support from the National Heart, Lung, and Blood Institute (grant 1K23HL151672), the American Heart Association, the Gordon & Betty Moore Foundation, and Sanofi. Dr Sandhu serves as a consultant for Lexicon Pharmaceuticals and Reprieve Cardiovascular. Dr Greene has received research support from the Duke University Department of Medicine Chair’s Research Award, the American Heart Association (929502), the National Heart, Lung, and Blood Institute, Amgen, AstraZeneca, Bristol Myers Squibb, Cytokinetics, Merck, Novartis, Pfizer, and Sanofi; has served on advisory boards for Amgen, AstraZeneca, Boehringer Ingelheim/Lilly, Bristol Myers Squibb, Cytokinetics, Roche Diagnostics, scPharmaceuticals, and Sanofi; serves as a consultant for Amgen, Bayer, Boehringer Ingelheim/Lilly, Bristol Myers Squibb, Corteria Pharmaceuticals, CSL Vifor, Merck, PharmaIN, Roche Diagnostics, Sanofi, Tricog Health, and Urovant Pharmaceuticals; and has received speaker fees from Boehringer Ingelheim, Cytokinetics, and Roche Diagnostics. Dr Fonarow reports consulting for Abbott, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Cytokinetics, Eli Lilly, Johnson & Johnson, Medtronic, Merck, Novartis, and Pfizer. The other authors report no conflicts.

Background: Patients with acute coronary syndrome without standard modifiable cardiovascular risk factors (SMuRFs; hypertension, smoking, dyslipidemia, diabetes) have not been well studied, with little known about their characteristics, quality of care, or outcomes. We sought to systematically analyze patients with ACS without SMuRFs, especially to evaluate the effectiveness of guideline-directed medical therapy for these patients., Methods and Results: In the CCC-ACS (Improving Care for Cardiovascular Disease in China-Acute Coronary Syndrome) project (2014-2019), we examined the presence and absence of SMuRFs and features among 89 462 patients with initial acute coronary syndrome. The main outcome was in-hospital all-cause mortality. Among eligible patients, 11.0% had none of the SMuRFs (SMuRF-less). SMuRF-less patients had higher in-hospital mortality (unadjusted hazard ratio [HR], 1.49 [95% CI, 1.19-1.87]). After adjustment for clinical characteristics and treatments, the associations between SMuRF status and in-hospital mortality persisted (adjusted HR, 1.35 [95% CI, 1.07-1.70]). Guideline-directed optimal medical therapy (receiving angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, β-blockers, and statins) was not associated with lower mortality (adjusted HR, 0.98 [95% CI, 0.58-1.67]) in SMuRF-less patients, unlike the association in patients with SMuRFs (adjusted HR, 0.80 [95% CI, 0.66-0.98]). Sensitivity analyses were consistent with these results., Conclusions: SMuRF-less patients were associated with an increased risk of in-hospital mortality. Guideline-directed medical therapy was less effective in SMuRF-less patients than in patients with SMuRFs. Dedicated studies are needed to confirm the optimal therapy for SMuRF-less patients., Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02306616.

Background: Existing data suggested a rural-urban disparity in thrombolytic utilization for ischemic stroke. Here, we examined the use of guideline-recommended stroke care and outcomes in rural hospitals to identify targets for improvement., Methods: This retrospective cohort study included patients (aged ≥18 years) treated for acute ischemic stroke at Get With The Guidelines-Stroke hospitals from 2017 to 2019. Multivariable mixed-effect logistic regression was used to compare thrombolysis rates, speed of treatment, secondary stroke prevention metrics, and outcomes after adjusting for patient- and hospital-level characteristics and stroke severity., Results: Among the 1 127 607 patients admitted to Get With The Guidelines-Stroke hospitals in 2017 to 2019, 692 839 patients met the inclusion criteria. Patients who presented within 4.5 hours were less likely to receive thrombolysis in rural stroke centers compared with urban stroke centers (31.7% versus 43.5%; adjusted odds ratio [aOR], 0.72 [95% CI, 0.68-0.76]) but exceeded rural nonstroke centers (22.1%; aOR, 1.26 [95% CI, 1.15-1.37]). Rural stroke centers were less likely than urban stroke centers to achieve door-to-needle times of ≤45 minutes (33% versus 44.7%; aOR, 0.86 [95% CI, 0.76-0.96]) but more likely than rural nonstroke centers (aOR, 1.24 [95% CI, 1.04-1.49]). For secondary stroke prevention metrics, rural stroke centers were comparable to urban stroke centers but exceeded rural nonstroke centers (aOR of 1.66, 1.94, 2.44, 1.5, and 1.72, for antithrombotics within 48 hours of admission, antithrombotics at discharge, anticoagulation for atrial fibrillation/flutter, statin treatment, and smoking cessation, respectively). In-hospital mortality was similar between rural and urban stroke centers (aOR, 1.11 [95% CI, 0.99-1.24]) or nonstroke centers (aOR, 1.00 [95% CI, 0.84-1.18])., Conclusions: Rural hospitals had lower thrombolysis utilization and slower treatment times than urban hospitals. Rural stroke centers provided comparable secondary stroke prevention treatment to urban stroke centers and exceeded rural nonstroke centers. These results reveal important opportunities and specific targets for rural health equity interventions., Competing Interests: Dr Uchino served on data safety monitoring board for clinical trials sponsored by Genentech Inc and Evaheart Inc and as consultant for Abbott Laboratories Inc. Dr Dalton received research support from the National Institute on Aging. Dr Fonarow received research support from the Patient Centered Outcome Research Institute and National Institutes of Health and served as consultant for Abbott Pharmaceuticals, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Cytokinetics, Eli Lilly and Company, Jassen Pharmaceuticals, Medtronic, Merck, Novartis, and Pfizer. The other authors report no conflicts.

Existing risk prediction models for hospitalized heart failure patients are limited. We identified patients hospitalized with a diagnosis of heart failure between 7 May 2013 and 26 April 2022 from a large academic, quaternary care medical centre (training cohort). Demographics, medical comorbidities, vitals, and labs were collected and were used to construct random forest machine learning models to predict in-hospital mortality. Models were compared with logistic regression, and to commonly used heart failure risk scores. The models were subsequently validated in patients hospitalized with a diagnosis of heart failure from a second academic, community medical centre (validation cohort). The entire cohort comprised 21 802 patients, of which 14 539 were in the training cohort and 7263 were in the validation cohort. The median age (25th-75th percentile) was 70 (58-82) for the entire cohort, 43.2% were female, and 6.7% experienced inpatient mortality. In the overall cohort, 7621 (35.0%) patients had heart failure with reduced ejection fraction (EF ≤ 40%), 1271 (5.8%) had heart failure with mildly reduced EF (EF 41-49%), and 12 910 (59.2%) had heart failure with preserved EF (EF ≥ 50%). Random forest models in the validation cohort demonstrated a c-statistic (95% confidence interval) of 0.96 (0.95-0.97), sensitivity (SN) of 87.3%, and specificity (SP) of 90.6% for the prediction of in-hospital mortality. Models for those with HFrEF demonstrated a c-statistic of 0.96 (0.94-0.98), SN 88.2%, and SP 91.0%, and those for patients with HFpEF showed a c-statistic of 0.95 (0.93-0.97), SN 87.4%, and SP 89.5% for predicting in-hospital mortality. The random forest model significantly outperformed logistic regression (c-statistic 0.87, SN 75.9%, and SP 86.9%), and current existing risk scores including the Acute Decompensated Heart Failure National Registry risk score (c-statistic of 0.70, SN 69%, and SP 62%), and the Get With the Guidelines-Heart Failure risk score (c-statistic 0.69, SN 67%, and SP 63%); P < 0.001 for comparison. Machine learning models built from commonly recorded patient information can accurately predict in-hospital mortality among patients hospitalized with a diagnosis of heart failure., (© 2024 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Aims: Heart failure (HF) is a clinical syndrome with no definitive diagnostic tests. HF registries are often based on manual reviews of medical records of hospitalized HF patients identified using International Classification of Diseases (ICD) codes. However, most HF patients are not hospitalized, and manual review of big electronic health record (EHR) data is not practical. The US Department of Veterans Affairs (VA) has the largest integrated healthcare system in the nation, and an estimated 1.5 million patients have ICD codes for HF (HF ICD-code universe) in their VA EHR. The objective of our study was to develop artificial intelligence (AI) models to phenotype HF in these patients., Methods and Results: The model development cohort (n = 20 000: training, 16 000; validation 2000; testing, 2000) included 10 000 patients with HF and 10 000 without HF who were matched by age, sex, race, inpatient/outpatient status, hospital, and encounter date (within 60 days). HF status was ascertained by manual chart reviews in VA's External Peer Review Program for HF (EPRP-HF) and non-HF status was ascertained by the absence of ICD codes for HF in VA EHR. Two clinicians annotated 1000 random snippets with HF-related keywords and labelled 436 as HF, which was then used to train and test a natural language processing (NLP) model to classify HF (positive predictive value or PPV, 0.81; sensitivity, 0.77). A machine learning (ML) model using linear support vector machine architecture was trained and tested to classify HF using EPRP-HF as cases (PPV, 0.86; sensitivity, 0.86). From the 'HF ICD-code universe', we randomly selected 200 patients (gold standard cohort) and two clinicians manually adjudicated HF (gold standard HF) in 145 of those patients by chart reviews. We calculated NLP, ML, and NLP + ML scores and used weighted F scores to derive their optimal threshold values for HF classification, which resulted in PPVs of 0.83, 0.77, and 0.85 and sensitivities of 0.86, 0.88, and 0.83, respectively. HF patients classified by the NLP + ML model were characteristically and prognostically similar to those with gold standard HF. All three models performed better than ICD code approaches: one principal hospital discharge diagnosis code for HF (PPV, 0.97; sensitivity, 0.21) or two primary outpatient encounter diagnosis codes for HF (PPV, 0.88; sensitivity, 0.54)., Conclusions: These findings suggest that NLP and ML models are efficient AI tools to phenotype HF in big EHR data to create contemporary HF registries for clinical studies of effectiveness, quality improvement, and hypothesis generation., (© 2024 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.)

The health costs for heart failure (HF) in patients with and without diabetes can help us understand the conjoint burden of diabetes and HF. Using the 2008 to 2019 US national Medical Expenditure Panel Survey data including 2,019 adults with HF and a 2-part adjusted model, we estimated the mean and adjusted incremental direct medical expenditures related to diabetes. The total direct expenditures for patients with HF increased by 27 %: $24,725 (95 % confidence interval [CI] $20,457 to $28,993) in 2008 to 2009 to $31,426 (95 % CI $25,705 to $37,147) in 2018 to 2019. The expenditures increased by 34 % in those with diabetes. Inpatient costs represented the highest fraction of costs ∼43.3 % and were 8 % higher in those with diabetes versus those without diabetes. The drug costs accounted for 24 % of all costs, increased by 44 %, and were 86 % higher in patients with HF with diabetes versus those without diabetes. The adjusted excess costs in patients with HF and diabetes versus HF without diabetes was $6,818 (95 % CI 2,241 to 11,395); the corresponding excess costs for drugs and medical costs other than drugs were $3,297 (95 % CI 2,168 to 4,426) and $3,554 (95 % CI -777 to 7,886). In US adults with HF, the estimated adjusted total direct excess costs were $5.2 billion per year higher in patients with diabetes versus those without diabetes. In conclusion, diabetes is associated with substantially increased health care costs in patients with HF, suggesting the need for an integrated management of diabetes and HF., Competing Interests: Declaration of competing interest Dr. Fonarow reports consulting for Abbott, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Cytokinetics, Eli Lilly Janssen, Medtronic, Merck, Novartis, and Pfizer. The remaining authors have no competing interests to declare., (Copyright © 2024 Elsevier Inc. All rights reserved.)

The spectrum of cardiorenal and metabolic diseases comprises many disorders, including obesity, type 2 diabetes (T2D), chronic kidney disease (CKD), atherosclerotic cardiovascular disease (ASCVD), heart failure (HF), dyslipidemias, hypertension, and associated comorbidities such as pulmonary diseases and metabolism dysfunction-associated steatotic liver disease and metabolism dysfunction-associated steatohepatitis (MASLD and MASH, respectively, formerly known as nonalcoholic fatty liver disease and nonalcoholic steatohepatitis [NAFLD and NASH]). Because cardiorenal and metabolic diseases share pathophysiologic pathways, two or more are often present in the same individual. Findings from recent outcome trials have demonstrated benefits of various treatments across a range of conditions, suggesting a need for practice recommendations that will guide clinicians to better manage complex conditions involving diabetes, cardiorenal, and/or metabolic (DCRM) diseases. To meet this need, we formed an international volunteer task force comprising leading cardiologists, nephrologists, endocrinologists, and primary care physicians to develop the DCRM 2.0 Practice Recommendations, an updated and expanded revision of a previously published multispecialty consensus on the comprehensive management of persons living with DCRM. The recommendations are presented as 22 separate graphics covering the essentials of management to improve general health, control cardiorenal risk factors, and manage cardiorenal and metabolic comorbidities, leading to improved patient outcomes., Competing Interests: Declaration of competing interest None of the Task Force members received monetary renumeration for their contributions to the creation or writing of this consensus document. See the Supplementary Appendix for full declarations of competing interests for each author., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Importance: A composite score for guideline-directed medical therapy (GDMT) for patients with heart failure (HF) is associated with increased survival. Whether hospital performance according to a GDMT score is associated with a broader array of clinical outcomes at lower costs is unknown., Objectives: To evaluate hospital variability in GDMT score at discharge, 90-day risk-standardized clinical outcomes and costs, and associations between hospital GDMT score and clinical outcomes and costs., Design, Setting, and Participants: This was a retrospective cohort study conducted from January 2015 to September 2019. Included for analysis were patients hospitalized for HF with reduced ejection fraction (HFrEF) in the Get With the Guidelines-Heart Failure Registry, a national hospital-based quality improvement registry. Study data were analyzed from July 2022 to April 2023., Exposures: GDMT score at discharge., Main Outcomes and Measures: Hospital variability in GDMT score, a weighted index from 0 to 1 of GDMT prescribed divided by the number of medications eligible, at discharge was evaluated using a generalized linear mixed model using the hospital as a random effect and quantified with the adjusted median odds ratio (AMOR). Parallel analyses centering on 90-day mortality, HF rehospitalization, mortality or HF rehospitalization, home time, and costs were performed. Costs were assessed from the perspective of the Centers of Medicare & Medicaid Services. Associations between hospital GDMT score and clinical outcomes and costs were evaluated using Spearman coefficients., Results: Among 41 161 patients (median [IQR] age, 78 [71-85] years; 25 546 male [62.1%]) across 360 hospitals, there was significant hospital variability in GDMT score at discharge (AMOR, 1.23; 95% CI, 1.21-1.26), clinical outcomes (mortality AMOR, 1.17; 95% CI, 1.14-1.24; HF rehospitalization AMOR, 1.22; 95% CI, 1.18-1.27; mortality or HF rehospitalization AMOR, 1.21; 95% CI, 1.18-1.26; home time AMOR, 1.07; 95% CI, 1.06-1.10) and costs (AMOR, 1.23; 95% CI, 1.21-1.26). Higher hospital GDMT score was associated with lower hospital mortality (Spearman ρ, -0.22; 95% CI, -0.32 to -0.12; P < .001), lower mortality or HF rehospitalization (Spearman ρ, -0.17; 95% CI, -0.26 to -0.06; P = .002), more home time (Spearman ρ, 0.14; 95% CI, 0.03-0.24; P = .01), and lower cost (Spearman ρ, -0.11; 95% CI, -0.21 to 0; P = .047) but not with HF rehospitalization (Spearman ρ, -0.10; 95% CI, -0.20 to 0; P = .06)., Conclusions and Relevance: Results of this cohort study reveal that hospital variability in GDMT score, clinical outcomes, and costs was significant. Higher GDMT score at discharge was associated with lower mortality, lower mortality or hospitalization, more home time, and lower cost. Efforts to increase health care value should include GDMT optimization.

Background: Since January 2020, COVID-19 has affected more than 100 million people in the U.S. Previous studies on racial and ethnic disparities related to characteristics and outcomes of COVID-19 patients have been insightful. However, appropriate epidemiologic age-standardization of the disease burden and disparities for hospitalization data are lacking., Objective: To identify and describe racial and ethnic disparities for primary COVID-19 hospitalizations in the U.S. in 2020., Methods: In this nationally representative observational study, we use the National Inpatient Sample to quantify racial and ethnic disparities in COVID-19 hospitalizations. Descriptive statistics for patient characteristics, common comorbidities, age-standardized hospitalization rates, inpatient complications, and mortality among COVID-19 hospitalizations were contrasted by race and ethnicity., Results: There were 1,058,815 primary COVID-19 hospitalizations in 2020. Of those, 47.2% were female, with median age of 66 (IQR, 54, 77). Overall inpatient mortality rate was 11.1%. When compared to White patients, Black, Hispanic, and Native American patients had higher age-standardized hospitalization rate ratios of 2.42 (95% CI 2.40-2.43), 2.26 (2.25-2.28), and 2.51 (2.46-2.56), respectively. Non-White patients had increased age-adjusted rates for procedures and complications. Factors associated with inpatient mortality include age, male sex, Hispanic or Native American race or ethnicity, lower income, Medicaid, heart failure, arrhythmias, coagulopathy, and chronic liver disease., Conclusions: Marginalized populations in the U.S. had over twice the COVID-19 hospitalization rate relative to White patients. Age-adjusted mortality rates were highest for Black, Hispanic, and Native American patients. Careful consideration for vulnerable populations is encouraged during highly communicable respiratory pandemics., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Background: Immigrants experience changes in cardiovascular risk factors and racial disparities in both cardiovascular health prevention and outcomes upon immigration. We aimed to examine cardiovascular risk factors and outcomes among Chinese American immigrants enrolled in the MESA (Multi-Ethnic Study of Atherosclerosis) cohort., Methods and Results: We analyzed data from 746 Chinese American immigrants in the MESA study with a median follow-up period of 17.8 years. The mean age of the cohort was 62.3 years, with 52.7% being women. Kaplan-Meier curves and Cox proportional hazards models were used to assess the association of immigration history, geographic location, biomarkers, and cardiac imaging parameters with cardiovascular risk factors and cardiovascular outcomes. The Cox hazards models were adjusted for known family history of heart disease, education level, sex, diabetes, hypertension, age, and body mass index. Although immigration history categorized as earlier (<20 years) versus later (≥20 years) showed no association with cardiovascular outcomes, the duration of residence in the United States emerged as a strong predictor for an increased risk of cardiovascular disease death (hazard ratio 1.39 [95% CI, 1.07-1.8]; P =0.012). All-cause mortality differed significantly between the Chinese immigrants from Los Angeles and those from Chicago, with higher survival probability in Chicago (log-rank test, P =0.018). Furthermore, elevated levels of N-terminal pro-brain natriuretic peptide levels, left ventricular mass, and coronary artery calcium scores were associated with the risk of cardiovascular disease among Chinese immigrants., Conclusions: Within the MESA cohort, the duration of residence and geographic location were associated with the risk of cardiovascular disease outcomes among Chinese immigrants.

Heart failure (HF) is a major cause of mortality and morbidity in the United States that carries substantial healthcare costs. Multiple risk prediction models and strategies have been developed over the past 30 years with the aim of identifying those at high risk of developing HF and of implementing preventive therapies effectively. This review highlights recent developments in HF risk prediction tools including emerging risk factors, innovative risk prediction models, and novel screening strategies from artificial intelligence to biomarkers. These developments allow more accurate prediction, but their impact on clinical outcomes remains to be investigated. Implementation of these risk models in clinical practice is a considerable challenge, but HF risk prediction tools offer a promising opportunity to improve outcomes while maintaining value., Competing Interests: Declaration of competing interest Dr. Fonarow reports consulting for Abbott, Amgen, AstraZeneca, Bayer, Cytokinetics, Eli Lilly, Janssen, Medtronic, Merck, Novartis, and Pfizer. Dr. Gulati reports consulting for Esperion, Medtronic, and Novartis. The remaining authors have no competing interest to declare., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: The foundation for managing heart failure with reduced ejection fraction (HFrEF) is adherence to guideline-directed medical therapy. Finding an association between medication adherence and patients' health status (their symptoms, function, and quality of life) can be used to underscore its importance to patients., Methods: The association of self-reported medication adherence in US outpatients with HFrEF enrolled in the Change the Management of Patients with Heart Failure registry from 2015 to 2017 was compared with their health status at baseline and 12 months later. A secondary analysis of changes in adherence between baseline and 6 months with 6-month health status was also performed. Medication adherence was assessed with the self-reported 4-item Morisky-Green-Levine Medication Adherence Scale, with scores ≥1 classified as nonadherent. The primary health status outcome was the disease-specific 12-item Kansas City Cardiomyopathy Questionnaire Overall Summary Score (KCCQ-OS; range, 0-100; higher is better). Robust linear regression models adjusted for confounders were used., Results: After excluding those who died (n=316) or did not provide 12-month KCCQ (n=1285), 3495 outpatients with HFrEF were included, of whom 1108 (31.7%) reported being nonadherent. Nonadherent participants were younger, had significantly worse baseline health status (-5.83-point difference; P <0.001), and showed less improvement at 12 months (-1.7-point difference in mean change; P =0.017) than adherent participants. Among nonadherent patients at baseline, those whose adherence improved trended toward greater 6-month health status improvements than those remaining nonadherent (fully adjusted difference of 2.52 points; P =0.054)., Conclusions: In HFrEF, medication nonadherence was associated with worse health status and less improvement over the following year. Improvements in adherence were associated with better health status than remaining nonadherent, underscoring the importance of supporting adherence with guideline-directed medical therapy in patients with HFrEF., Competing Interests: Dr El-Zein is currently supported by the National Heart, Lung, and Blood Institute (NHLBI) under award number T32H110837. The content is solely the responsibility of the author(s) and does not necessarily represent the official views of the National Institutes of Health. Dr DeVore reports research funding through his institution from the American Heart Association, Amgen, AstraZeneca, Bayer, Intra-Cellular Therapies, American Regent Inc, the NHLBI, Novartis, and Patient-Centered Outcomes Research Institute. He also provides consulting services for Amgen, AstraZeneca, Bayer, CareDx, InnaMed, LivaNova, Mardil Medical, Novartis, Procyrion, scPharmaceuticals, Story Health, and Zoll. He has also received nonfinancial support from Abbott for educational activities. Dr Thomas reports research funding Novartis. Dr Albert reports serving as a consultant to Novartis, Amgen, AstraZeneca, and Boston Scientific. Dr Butler has received research support from the National Institutes of Health, PCORI and the European Union; and serves as a consultant for Amgen, Array, Astra Zeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squib, CVRx, G3 Pharmaceutical, Innolife, Janssen, Luitpold, Medtronic, Merck, Novartis, Relypsa, StealthPeptide, SC Pharma, Vifor, and ZS Pharma. Dr Hernandez has received research support from the American Heart Association, AstraZeneca, Merck, NHLBI, Luitpold, and Novartis, and honorarium from Bayer, Boston Scientific, and Novartis. Dr Patterson reports research funding from Amgen, Bristol Myers Squibb, Merck, and Novartis, and serves as a consultant to Amgen and Novartis. Dr Spertus reports research funding from NIH, Janssen, and Bristol Meyers Sqiubb. He served as a consultant to Bayer, Bristol Meyers Squibb, Merck, Janssen, Kinksia, Imbria, Cytokinetics, Alnylam, Sanofi Aventis, and United Healthcare. He owns the copyright to the Seattle Angina Questionnaire, Kansas City Cardiomyopathy Questionnaire and Peripheral Artery Questionnaire and serves on the Board of Directors for Blue Cross Blue Shield of Kansas City. Dr Fonarow reports research funding from the National Institutes of Health and consulting for Abbott, Amgen, AstraZeneca, Bayer, Cytokinetics, Janssen, Merck, Novartis, and Medtronic. The other authors report no conflicts.

Background: Guideline-directed medical therapy (GDMT) for heart failure with reduced ejection fraction (HFrEF) remains underused. Acute heart failure (HF) hospitalization represents a critical opportunity for rapid initiation of evidence-based medications. However, data on GDMT use at discharge are mostly derived from national quality improvement registries., Objectives: This study aimed to describe contemporary GDMT use patterns across HF hospitalizations at community-based health systems., Methods: The authors identified HF hospitalizations from 2016 to 2022 in a U.S. database aggregating deidentified electronic health record data from more than 30 health systems. In-hospital and discharge rates of GDMT use were reported for eligible HFrEF patients. Factors associated with inpatient GDMT use and predischarge discontinuation were evaluated with the use of multivariable models., Results: A total of 20,387 HF hospitalizations among 13,729 HFrEF patients were identified. Renin-angiotensin system inhibitors, beta-blockers, and mineralocorticoid receptor antagonists were administered during 70%, 86%, and 37% of eligible hospitalizations, respectively. Angiotensin receptor-neprilysin inhibitors and sodium-glucose cotransporter 2 inhibitors were used in 17% and 8% of eligible hospitalizations, respectively. Discharge GDMT rates were low. Triple/quadruple therapy was administered in 26% of hospitalizations, falling to 14% on discharge. Predischarge GDMT discontinuations were associated with inpatient hypotension, hyperkalemia, and worsening renal function, but 43%-57% had no medical contraindications. In adjusted analyses, use of 3 or more GDMT classes was associated with fewer 90-day all-cause deaths and HF readmissions compared with less comprehensive GDMT., Conclusions: Inpatient GDMT use in a national analysis of HF hospitalizations was lower than reported in quality improvement registries. High discontinuation rates emphasize an unmet need for inpatient and postdischarge strategies to optimize GDMT use., Competing Interests: Funding Support and Author Disclosures Dr Zheng has consulted for Reprieve Cardiovascular. Dr Sandhu has received relevant research support from the National Heart Lung, Blood Institute (1K23HL151672) and the American Heart Association and has consulted for Reprieve Cardiovascular, Lexicon Pharmaceuticals, and Cleerly. Dr Bhatt has received relevant research support through grants to his institution from the National Heart, Lung, and Blood Institute, National Institute on Aging, Centers for Disease Control (CDC), and American College of Cardiology Foundation and has received consulting fees from Sanofi Pasteur and Novo Nordisk. Dr Collins receives research support from the National Institutes of Health, Patient-Centered Outcomes Research Institute, Department of Defense, and Beckman Coulter and consulting fees from Abbott, Redesign Health, and Reprieve Cardiovascular. Dr Flint receives relevant grant funding from Abbott and has consulted for Abbott, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Cytokinetics, Eli Lilly, Johnson and Johnson, Medtronic, Merck, Novartis, and Pfizer. Dr Fudim receives research support from Reprieve and consults for Lexicon. Dr Greene has received research support from the Duke University Department of Medicine Chair’s Research Award, American Heart Association (number 929502), Amgen, AstraZeneca, Boehinger Ingelheim, Bristol Myers Squibb, Cytokinetics, Merck, Novartis, Pfizer, and Sanofi; has served on advisory boards or as consultant for Amgen, AstraZeneca, Bayer, Boehringer Ingelheim/Lilly, Bristol Myers Squibb, Corteria, CSL Vifor, Cytokinetics, Lexicon, Merck, Roche Diagnostics, Sanofi, scPharmaceuticals, Tricog Health, and Urovant Pharmaceuticals; and has received speaker fees from Boehringer Ingelheim, Cytokinetics, Lexicon, and Roche Diagnostics. Dr Varshney has received consulting fees from Broadview Ventures. Dr Ambrosy has received relevant research support through grants to his institution from the National Heart, Lung, and Blood Institute (K23HL150159), American Heart Association (2nd Century Early Faculty Independence Award), Permanente Medical Group, Northern California Community Benefits Programs, Garfield Memorial Fund, Abbott Laboratories, Amarin Pharma, Edwards Lifesciences, Esperion Therapeutics, and Novartis. 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.)

Objectives: Mobile health (mHealth) regimens can improve health through the continuous monitoring of biometric parameters paired with appropriate interventions. However, adherence to monitoring tends to decay over time. Our randomized controlled trial sought to determine: (1) if a mobile app with gamification and financial incentives significantly increases adherence to mHealth monitoring in a population of heart failure patients; and (2) if activity data correlate with disease-specific symptoms., Materials and Methods: We recruited individuals with heart failure into a prospective 180-day monitoring study with 3 arms. All 3 arms included monitoring with a connected weight scale and an activity tracker. The second arm included an additional mobile app with gamification, and the third arm included the mobile app and a financial incentive awarded based on adherence to mobile monitoring., Results: We recruited 111 heart failure patients into the study. We found that the arm including the financial incentive led to significantly higher adherence to activity tracker (95% vs 72.2%, P = .01) and weight (87.5% vs 69.4%, P = .002) monitoring compared to the arm that included the monitoring devices alone. Furthermore, we found a significant correlation between daily steps and daily symptom severity., Discussion and Conclusion: Our findings indicate that mobile apps with added engagement features can be useful tools for improving adherence over time and may thus increase the impact of mHealth-driven interventions. Additionally, activity tracker data can provide passive monitoring of disease burden that may be used to predict future events., (© The Author(s) 2024. Published by Oxford University Press on behalf of the American Medical Informatics Association.)

Competing Interests: Dr Greene has received research support from the Duke University Department of Medicine Chair’s Research Award, American Heart Association, Amgen, AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Cytokinetics, Merck, Novartis, Pfizer, and Sanofi; has served on advisory boards or as consultant for Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Corcept, Corteria Pharmaceuticals, CSL Vifor, Cytokinetics, Eli Lilly, Lexicon, Merck, Novo Nordisk, Otsuka, Roche Diagnostics, Sanofi, scPharmaceuticals, Tricog Health, and Urovant Pharmaceuticals; and has received speaker fees from AstraZeneca, Bayer, Boehringer Ingelheim, Cytokinetics, Lexicon, and Roche Diagnostics. Dr Butler has been a consultant to Abbott, American Regent, Amgen, Applied Therapeutic, AskBio, Astellas, AstraZeneca, Bayer, Boehringer Ingelheim, Boston Scientific, Bristol Myers Squibb, Cardiac Dimension, Cardiocell, Cardior, CSL Bearing, CVRx, Cytokinetics, Daxor, Edwards, Element Science, Faraday, Foundry, G3P, Innolife, Impulse Dynamics, Imbria, Inventiva, Ionis, Lexicon, Lilly, LivaNova, Janssen, Medtronics, Merck, Occlutech, Owkin, Novartis, Novo Nordisk, Pfizer, Pharmacosmos, Pharmain, Prolaio, Regeneron, Renibus, Roche, Salamandra, Sanofi, SC Pharma, Secretome, Sequana, SQ Innovation, Tenex, Tricog, Ultromics, Vifor, and Zoll. Dr Fonarow reports consulting for Abbott, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Cytokinetics, Eli Lilly, Johnson & Johnson, Medtronic, Merck, Novartis, and Pfizer.

Study Objective: The association of prior to admission guideline-directed medical therapy (GDMT) use in patients hospitalized with Heart Failure with Reduced Ejection Fraction (HFrEF, ejection fraction ≤40 %) and Coronavirus Disease 2019 (COVID-19) with in-hospital outcomes has not been well studied., Design/setting/participants/interventions/outcome Measures: Using the American Heart Association's Get With The Guidelines Heart Failure Registry, we identified HFrEF patients presenting with acute decompensated heart failure (ADHF) and compared rates of GDMT prescription between those presenting prior to and during the pandemic. In a subgroup of patients with a concomitant COVID-19 diagnosis, we evaluated the association of prior to admission GDMT use with in-hospital mortality and severe COVID-19., Results: 23,899 patients were admitted with HFrEF during the pandemic (2/16/20-3/24/21) and 26,459 patients were admitted in the year prior (2/16/19-2/15/20). In this overall cohort, prior to admission ACEI/ARB/ARNI (45.6 % vs 48.1 %, p < 0.0001) and BB (56.9 % vs 62.4 %, p < 0.0001) use was lower among admitted HFrEF patients during the pandemic when compared to the year prior. Rates of ACEI/ARB/ARNI, MRA, and triple therapy (ACE/ARB/ARNI + BB + MRA) prescription at discharge were higher during the pandemic compared to the year prior. Among a subgroup of those with HFrEF and COVID-19 (n = 333), prior to admission GDMT use was not associated with in-hospital mortality or severe COVID-19., Conclusion: We found no association between prior to admission GDMT use and in-hospital mortality or severe COVID-19 among HFrEF patients admitted with ADHF and COVID-19. GDMT prescription at discharge for HFrEF patients overall has remained either similar or improved during the pandemic., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: GCF reports consulting for Abbott, Amgen, AstraZeneca, Bayer, Cytokinetics, Edwards, Eli Lilly, Johnson&Johnson, Medtronic, Merck, Novartis, and Pfizer. EHY reports research grants/funding from CSL Behring, Boehringer Ingelheim, Eli Lilly, and Bristol Meyers Squibb, and consulting fees from Pfizer. LBD reports consulting for Abbott, Quidel, and Roche; research funding from Vifor; and serves on a clinical endpoint adjudication committee for Applied Therapeutics. RVP receives unrelated research support from Infraredx, Abbott Vascular, and Bayer, and consulting fees from Abbott Vascular., (© 2024 The Authors.)

Background:  Heart failure is a complex clinical syndrome noted on approximately one in eight death certificates in the United States. Vital to reducing complications of heart failure and preventing hospital readmissions is adherence to heart failure self-care routines. Mobile health offers promising opportunities for enhancing self-care behaviors by facilitating tracking and timely reminders., Objectives:  We sought to investigate three characteristics of heart failure patients with respect to their heart failure self-care behaviors: (1) internet use to search for heart failure information; (2) familiarity with mobile health apps and devices; and (3) perceptions of using activity trackers or smartwatches to aid in their heart failure self-care., Methods:  Forty-nine heart failure patients were asked about their internet and mobile health usage. The structured interview included questions adapted from the Health Information National Trends Survey., Results:  Over 50% of the patients had utilized the internet to search for heart failure information in the past 12 months, experience using health-related apps, and thoughts that an activity tracker or smartwatch could help them manage heart failure. Qualitative analysis of the interviews revealed six themes: trust in their physicians, alternatives to mobile health apps, lack of need for mobile health devices, financial barriers to activity tracker and smartwatch ownership, benefits of tracking and reminders, and uncertainty of their potential due to lack of knowledge., Conclusion:  Trust in their physicians was a major factor for heart failure patients who reported not searching for health information on the internet. While those who used mobile health technologies found them useful, patients who did not use them were generally unaware of or unknowledgeable about them. Considering patients' preferences for recommendations from their physicians and tendency to search for heart failure information including treatment and management options, patient-provider discussions about mobile health may improve patient knowledge and impact their usage., Competing Interests: G.C.F. reports consulting for Abbott, Amgen, Bayer, Janssen, Medtronic, and Novartis., (Thieme. All rights reserved.)

Background: Heart failure (HF) is a leading cause of hospitalization in the United States. Decongestion remains a central goal of inpatient management, but contemporary decongestion practices and associated weight loss have not been well characterized nationally., Objectives: This study aimed to describe contemporary inpatient diuretic practices and clinical predictors of weight loss in patients hospitalized for HF., Methods: The authors identified HF hospitalizations from 2015 to 2022 in a U.S. national database aggregating deidentified patient-level electronic health record data across 31 geographically diverse community-based health systems. The authors report patient characteristics and inpatient weight change as a primary indicator of decongestion. Predictors of weight loss were evaluated using multivariable models. Temporal trends in inpatient diuretic practices, including augmented diuresis strategies such as adjunctive thiazides and continuous diuretic infusions, were assessed., Results: The study cohort included 262,673 HF admissions across 165,482 unique patients. The median inpatient weight loss was 5.3 pounds (Q1-Q3: 0.0-12.8 pounds) or 2.4 kg (Q1-Q3: 0.0-5.8 kg). Discharge weight was higher than admission weight in 20% of encounters. An increase of ≥0.3 mg/dL in serum creatinine from admission to inpatient peak occurred in >30% of hospitalizations and was associated with less weight loss. Adjunctive diuretic agents were utilized in <20% of encounters but were associated with greater weight loss., Conclusions: In a large-scale U.S. community-based cohort study of HF hospitalizations, estimated weight loss from inpatient decongestion remains highly variable, with weight gain observed across many admissions. Augmented diuresis strategies were infrequently used. Comparative effectiveness trials are needed to establish optimal strategies for inpatient decongestion for acute HF., Competing Interests: Funding Support and Author Disclosures Dr Zheng has served as a consultant for Reprieve Cardiovascular. Dr Ambrosy has received relevant research support through grants to his institution from the National Heart, Lung, and Blood Institute (number K23HL150159), the American Heart Association (Second Century Early Faculty Independence Award), The Permanente Medical Group, Northern California Community Benefits Programs, Garfield Memorial Fund, Abbott Laboratories, Amarin Pharma, Edwards Lifesciences LLC, Esperion Therapeutics, and Novartis. Dr Bhatt has received relevant research support through grants to his institution from the National Heart, Lung, and Blood Institute, National Institute on Aging, the Centers for Disease Control and Prevention, and the American College of Cardiology Foundation; and previously received consulting fees from Sanofi Pasteur. Dr Collins has received research support from the National Institutes of Health, Patient-Centered Outcomes Research Institute, Department of Defense, and Beckman Coulter; and consulting fees from Abbott, Redesign Health, and Reprieve Cardiovascular, Inc. Dr Flint has received relevant grant funding from Abbott. Dr Fonarow has served as a consultant for Abbott, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Cytokinetics, Eli Lilly, Johnson and Johnson, Medtronic, Merck, Novartis, and Pfizer. Dr Greene has received research support from the Duke University Department of Medicine Chair’s Research Award, American Heart Association (number 929502), Amgen, AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Cytokinetics, Merck, Novartis, Pfizer, and Sanofi; served on the advisory board or as a consultant for Amgen, AstraZeneca, Bayer, Boehringer Ingelheim/Lilly, Bristol Myers Squibb, Corteria, CSL Vifor, Cytokinetics, Lexicon, Merck, Roche Diagnostics, Sanofi, scPharmaceuticals, Tricog Health, and Urovant Pharmaceuticals; and received speaker fees from Boehringer Ingelheim, Cytokinetics, Lexicon, and Roche Diagnostics. Dr Varshney has received consulting fees from Broadview Ventures. Dr Sandhu has received relevant research support from the National Heart, Lung, Blood Institute (number 1K23HL151672) and the American Heart Association; and served as a consultant for Reprieve Cardiovascular, Lexicon Pharmaceuticals, and Cleerly. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Published by Elsevier Inc.)

Background: U.S. nationwide estimates of the proportion of patients newly diagnosed with heart failure with reduced ejection fraction (HFrEF) eligible for quadruple medical therapy, and the associated benefits of rapid implementation, are not well characterized., Objectives: This study sought to characterize the degree to which patients newly diagnosed with HFrEF are eligible for quadruple medical therapy, and the projected benefits of in-hospital initiation., Methods: Among patients hospitalized for newly diagnosed HFrEF in the Get With The Guidelines-Heart Failure registry from 2016 to 2023, eligibility criteria based on regulatory labeling, guidelines, and expert consensus documents were applied for angiotensin receptor-neprilysin inhibitor, beta-blocker, mineralocorticoid receptor antagonist, and sodium-glucose cotransporter 2 inhibitor therapies. Of those eligible, the projected effect of quadruple therapy on 12-month mortality was modeled using treatment effects from pivotal clinical trials utilized by the AHA/ACC/HFSA Guideline for the Management of Heart Failure, and compared with observed outcomes among patients treated with angiotensin-converting enzyme inhibitor/angiotensin receptor blocker and beta-blockers., Results: Of 33,036 patients newly diagnosed with HFrEF, 27,158 (82%) were eligible for quadruple therapy, and 30,613 (93%) were eligible for ≥3 components. From 2021 to 2023, of patients eligible for quadruple therapy, 15.3% were prescribed quadruple therapy and 41.5% were prescribed triple therapy. Among Medicare beneficiaries eligible for quadruple therapy, 12-month incidence of mortality was 24.7% and HF hospitalization was 22.2%. Applying the relative risk reductions in clinical trials, complete implementation of quadruple therapy by time of discharge was projected to yield absolute risk reductions in 12-month mortality of 10.4% (number needed to treat = 10) compared with angiotensin-converting enzyme inhibitor/angiotensin receptor blocker and beta-blocker, and 24.8% (number needed to treat = 4) compared with no GDMT., Conclusions: In this nationwide U.S. cohort of patients hospitalized for newly diagnosed HFrEF, >4 of 5 patients were projected as eligible for quadruple therapy at discharge; yet, <1 in 6 were prescribed it. If clinical trial benefits can be fully realized, in-hospital initiation of quadruple medical therapy for newly diagnosed HFrEF would yield large absolute reductions in mortality., Competing Interests: Funding Support and Author Disclosures The Get With The Guidelines–Heart Failure (GWTG-HF) program is provided by the American Heart Association and sponsored, in part, by Novartis, Boehringer Ingelheim, and Eli Lilly Diabetes Alliance, Novo Nordisk, Sanofi, AstraZeneca, and Bayer. Dr Greene has received research support from the Duke University Department of Medicine Chair’s Research Award, American Heart Association, Amgen, AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Cytokinetics, Merck, Novartis, Pfizer, and Sanofi; has served on advisory boards or as consultant for Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Corteria Pharmaceuticals, CSL Vifor, Cytokinetics, Eli Lilly, Lexicon, Merck, Roche Diagnostics, Sanofi, scPharmaceuticals, Tricog Health, and Urovant Pharmaceuticals; and has received speaker fees from Bayer, Boehringer Ingelheim, Cytokinetics, Lexicon, and Roche Diagnostics. Dr Fonarow has consulted for Abbott, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Cytokinetics, Eli Lilly, Johnson and Johnson, Medtronic, Merck, Novartis, and Pfizer. 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.)

Background: Little is known regarding differences in cause-specific costs between heart failure (HF) with ejection fraction (EF) ≤40% vs >40%, and potential cost implications of sodium glucose co-transporter 2 inhibitor (SGLT2i) therapy., Objectives: This study sought to compare cause-specific health care costs following hospitalization for HF with EF ≤40% vs >40% and estimate the cost offset with implementation of SGLT2i therapy., Methods: This study examined Medicare beneficiaries hospitalized for HF in the Get With The Guidelines-Heart Failure registry from 2016 to 2020. Mean per-patient total (excluding drug costs) and cause-specific costs from discharge through 1-year follow-up were calculated and compared between EF ≤40% vs >40%. Next, risk reductions on total all-cause and HF hospitalizations were estimated in a trial-level meta-analysis of 5 pivotal trials of SGLT2is in HF. Finally, these relative treatment effects were applied to Medicare beneficiaries eligible for SGLT2i therapy to estimate the projected cost offset with implementation of SGLT2i, excluding drug costs., Results: Among 146,003 patients, 50,598 (34.7%) had EF ≤40% and 95,405 (65.3%) had EF >40%. Mean total cost through 1 year was $40,557. Total costs were similar between EF groups overall but were higher for EF ≤40% among patients surviving the 1-year follow-up period. Patients with EF >40% had higher costs caused by non-HF and noncardiovascular hospitalizations, and skilled nursing facilities (all P < 0.001). Trial-level meta-analysis of the 5 SGLT2i clinical trials estimated 11% (rate ratio: 0.89; 95% CI: 0.84-0.93; P < 0.001) and 29% (rate ratio: 0.71; 95% CI: 0.66-0.76; P < 0.001) relative reductions in rates of total all-cause and HF hospitalizations, respectively, regardless of EF. Reductions in all-cause and HF hospitalizations were projected to reduce annual costs of readmission by $2,451 to $2,668 per patient with EF ≤40% and $1,439 to $2,410 per patient with EF >40%., Conclusions: In this large cohort of older U.S. adults hospitalized for HF, cause-specific costs of care differed among patients with EF ≤40% vs >40%. SGLT2i significantly reduced the rate of HF and all-cause hospitalizations irrespective of EF in clinical trials, and implementation of SGLT2i therapy in clinical practice is projected to reduce costs by $1,439 to $2,668 per patient over the 1 year post-discharge, excluding drug costs., Competing Interests: Funding Support and Author Disclosures This analysis, as a part of the TRANSLATE-HF research series, was supported by AstraZeneca. The Get With The Guidelines–Heart Failure (GWTG-HF) program is provided by the American Heart Association. GWTG-HF is sponsored, in part, by Novartis, Boehringer Ingelheim, Novo Nordisk, Bayer, and Bristol Myers Squibb. Dr Vaduganathan has received research grant support, served on advisory boards, or had speaker engagements with American Regent, Amgen, AstraZeneca, Bayer AG, Baxter Healthcare, BMS, Boehringer Ingelheim, Chiesi, Cytokinetics, Lexicon Pharmaceuticals, Merck, Novartis, Novo Nordisk, Pharmacosmos, Relypsa, Roche Diagnostics, Sanofi, and Tricog Health; and participated on clinical trial committees for studies sponsored by AstraZeneca, Galmed, Novartis, Bayer AG, Occlutech, and Impulse Dynamics. Dr Butler has served as a consultant for Abbott, Adrenomed, Amgen, Array, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, CVRx, G3 Pharmaceutical, Impulse Dynamics, Innolife, Janssen, LivaNova, Luitpold, Medtronic, Merck, Novartis, Novo Nordisk, Relypsa, Roche, V-Wave Limited, and Vifor. Drs Huang, Linganathan, and McDermott are employees of AstraZeneca and may own stock options with the company. Dr Vardeny has served as a consultant for Bayer, AstraZeneca, Moderna, and Cardior; and has received institutional research support from Bayer and Cardurion. Dr Fonarow has served as a consultant for Abbott, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Cytokinetics, Eli Lilly, Janssen, Medtronic, Merck, Novartis, and Pfizer. Dr Greene has received research support from the Duke University Department of Medicine Chair’s Research Award, American Heart Association, Amgen, AstraZeneca, Boehinger Ingelheim, Bristol Myers Squibb, Cytokinetics, Merck, Novartis, Pfizer, and Sanofi; served on advisory boards or as a consultant for Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Corteria Pharmaceuticals, CSL Vifor, Cytokinetics, Eli Lilly, Lexicon, Merck, Novo Nordisk, Roche Diagnostics, Sanofi, scPharmaceuticals, Tricog Health, and Urovant Pharmaceuticals; and has received speaker fees from Bayer, Boehringer Ingelheim, Cytokinetics, Lexicon, and Roche Diagnostics. 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.)

Background: Almost half of the US adult population has obesity, which predisposes to atherosclerosis and can lead to poor prognosis in coronary artery disease (CAD). We aim to identify CAD and obesity-related mortality trends among adults in the United States stratified by age, sex, race and geographical location., Methods: The CDC-WONDER database was used to extract death certificate data for adults aged ≥ 25 years. Crude mortality rates (CMR) and age-adjusted mortality rates (AAMRs) per 100,000 persons were calculated, and temporal trends were described by calculating annual percent change (APC) and the average APC (AAPC) in the rates using Joinpoint regression analysis., Results: From 1999 to 2022, a total of 273,761 CAD and obesity-related deaths were recorded in the United States. The AAMR increased consistently from 1999 to 2018 (APC: 4.3, 95% confidence interval (CI): 3.4-4.9) and surged thereafter till 2022 (APC: 11.4; 95% CI: 7.7-19.1). During the COVID-19 pandemic (2020-2022), AAMR almost doubled that of the rest of the study period. Additionally, the AAMR for males was nearly twice that of females. Non-Hispanic (NH) Blacks or African Americans displayed the highest AAMR, followed by NH Whites, Hispanic or Latino, and other NH populations. AAMRs showed minimal variation by census regions. Rural areas exhibited a higher AAMR (AAMR: 5.9, 95% CI: 5.8-5.9) than urban areas (AAMR: 4.4, 95% CI: 4.4-4.5)., Conclusions: We observed increasing trends in CAD and obesity-related deaths throughout the study period reaching a peak during the COVID-19 pandemic., (© 2024 The Author(s). Endocrinology, Diabetes & Metabolism published by John Wiley & Sons Ltd.)

Background: The Get With The Guidelines-Stroke program is a quality improvement initiative designed to enhance adherence to evidence-based stroke care. Since its inception in 2003, over 2800 hospitals in the United States have participated in the program., Methods: We examined patient characteristics, adherence to performance measures, and in-hospital outcomes in patients hospitalized for acute ischemic stroke, subarachnoid hemorrhage, intracerebral hemorrhage, and transient ischemic attack in The Get With The Guidelines-Stroke hospitals from 2003 through 2022. We quantified temporal changes in performance measure adherence and clinical outcomes over time. Performance measure denominators consisted of patients who were eligible, excluding those with contraindications., Results: Over the 20 years of the program, a total of 7837 849 stroke cases (median age 71 years, 51.0% female; 69.2% ischemic strokes, 3.9% SAHs, 11.5% ICHs, and 15.3% TIAs) were entered into the registry. Except for antithrombotics at discharge, in which the baseline performance was >92%, there was sustained improvement in all performance metrics regardless of type of cerebrovascular event ( P <0.01 for all). In patients with acute ischemic stroke, large improvements were observed for anticoagulation for atrial fibrillation (55.7% in 2003 to 97.2% in 2022), smoking cessation counseling (44.7%-97.8%), dysphagia screening (53.8%-83.5%), thrombolytic treatment for patients arriving by 3.5 hours, treat by 4.5 hours (15.2%-92.9%), door-to-needle time within 60 minutes (19.0%-75.3%), and endovascular door-to-puncture time within 90 minutes (54.7%-62.8%). Similar improvements were also observed for measures relevant to patients with subarachnoid hemorrhage, intracerebral hemorrhage, and transient ischemic attack. Multivariable analysis showed that there was a sustained increase in odds of receiving each performance measure over time, independent of patient and hospital characteristics for each type of cerebrovascular event. After risk adjustment, there were temporal trends that patients were less likely to be discharged to a skilled nursing facility, and, for ischemic stroke only, more likely to be discharged directly home., Conclusions: During the first 20 years, Get With The Guidelines-Stroke participation was associated with sustained improvement in evidence-based care and outcomes for patients with stroke and transient ischemic attack in the United States., Competing Interests: Dr Xian reports research funding from the American Heart Association and the National Institute on Aging (R01AG062770 and R01AG066672);grants from Daiichi Sankyo Company; grants from Genentech; travel support from Boehringer Ingelheim; and grants from Janssen Pharmaceuticals Inc. Dr Smith reports service as an editor for the Stroke journal. Dr Saver reports consulting fees for advising on rigorous and safe clinical trial design and conduct from Abbott, Acticor, Aeromics, Amgen, Argenica, Astrocyte, Bayer, Biogen, Boehringer Ingelheim, BrainsGate, BrainQ, CSL Behring, Filterlex, Genentech, Johnson&Johnson, MindRhythm, Medtronic, NeuroMerit, Neuronics, Novo Nordisk, Occlutech, Phenox, Phillips, QuantalX, Rapid Medical, Roche, and Stream Biomedical; compensation from MIVI Neuroscience for data and safety monitoring services; and stock options in Rapid Medical, Neuronics Medical, and MindRhythm. Dr Sheth reports grant support from National Institutes of Health, American Heart Association, and Hyperfine; consulting from Astrocyte, Rhaeos, Cerevasc, Bexorg, Sense and Philips Data and Safety Monitoring Board; and patent with Alva; and compensation from Certus for consultant services; stock options in BrainQ. Dr Messé reports personal compensation from Novo Nordisk for work on the Clinical Event Committee for ONWARDS and Zeus Trials; Terumo for work on the Subject Selection Committee for the RelayBranch Trial; WL Gore for work on the Data Safety Monitoring Committee for the GORE CARDIOFORM Septal Occluder Post Marketing Trial; and Conformal Medical for work on the Clinical Event Committee for work on the Conformal left atrial appendage closure trial. He also reports equity in Neuralert Technologies. Dr Schwamm reports consulting for Genentech (member of TIMELESS steering committee NCT03785678), LifeImage, Penumbra (DSMB MIND NCT03342664), Medtronic (co-PI Stroke AF NCT02700945, advise on stroke prevention), grant funding from NINDS (PI, U24NS107243; Co-I, R01NS111952) and PCORI (R-1609-35995), and serves as member board of directors for the American Heart Association. Dr Fonarow reports consulting for Abbott, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Cytokinetics, Eli Lilly, Johnson & Johnson, Medtronic, Merck, Novartis, and Pfizer. The other authors report no conflicts.

Heart failure continues to pose a significant burden in terms of morbidity, mortality, and healthcare costs worldwide despite the implementation of guideline-directed medical therapy. Addressing this challenge and improving clinical outcomes for this patient population remains an urgent priority. Recognizing the limitations in current medical approaches and exploring strategies to overcome these limitations are crucial steps toward improving future outcomes. Various device-based interventions, such as Cardiac Resynchronization Therapy devices and Left Ventricular Assist Devices, have demonstrated notable benefits for individuals with heart failure. Our review is aimed at summarizing the ongoing research into new device therapies for heart failure, emphasizing their potential to overcome the current challenges in treatment. By utilizing Clinicaltrials.gov, an online repository, we conducted a comprehensive search for trials investigating emerging device therapies for patients dealing with heart failure., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Sodium-glucose cotransporter 2 inhibitors (SGLT2i) have been shown to reduce the risk of hospitalizations from heart failure and cardiovascular mortality. However, SGLT2i therapy's potential effects on the risks of dementia and Parkinson's disease are not well established, with conflicting results based on observational studies. Hence, we sought to evaluate the association between SGLT2i and the risk of dementia and Parkinson's disease in patients with type 2 diabetes mellitus, heart failure, or chronic kidney disease., Methods: We performed a systematic literature search on PubMed, and Clinicaltrial.gov for relevant randomized controlled trials from inception until March 2024 without any language restrictions. Odds ratios (OR) and 95% confidence intervals (CI) were pooled using a random-effect model., Results: A total of 12 randomized controlled trials with 74,442 patients (40,784 in the SGLT2i group and 33,658 in the control group) were included in the analysis. The mean age of patients in SGLT2i and control was 65.3 and 65.2 years, respectively. Pooled analysis showed that there is no significant association between SGLT2i use and the risk of dementia (OR 1.37; 95% CI, 0.70-2.69; P = .36), dementia Alzheimer's type (OR 1.99; 95% CI, 0.59-6.71; P = .27), vascular dementia (OR 0.40; 95% CI, 0.09-1.85; P = .24), and Parkinson's disease (OR 0.63; 95% CI, 0.25-1.61; P = .33) when compared with the control groups., Conclusion: Our study suggests that there is no significant association between SGLT2i use and the risk of dementia, its subtypes, and Parkinson's disease when compared with the control groups., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Optimal medical therapy (OMT) scoring may stratify clinical risk in real-world chronic heart failure with reduced ejection fraction (HFrEF) by integrating use and dosing of guideline-directed medical therapy (GDMT) for HFrEF., Objectives: The purpose of this study was to characterize patients and associated long-term clinical outcomes by OMT score-derived treatment groups., Methods: CHAMP-HF (Change the Management of Patients with Heart Failure) included U.S. outpatients with chronic HFrEF receiving ≥1 GDMT. OMT subgroups were defined as suboptimal (score <3), acceptable (score = 3), and optimal (score ≥4) by baseline use and dose of GDMT, as proposed by the HF Collaboratory consortium. Cox proportional hazard analyses were used to assess for all-cause and cardiovascular death across subgroups, after adjusting for demographic and clinical covariates., Results: The authors studied 4,582 participants enrolled in CHAMP-HF with available 2-year follow-up. Median age was 68 years, 1,327 (29%) were women, and 2,842 (62%) were White, non-Hispanic. Median OMT score across the population was 4 (Q1-Q3: 2-5), and 1,628 (35%) had suboptimal, 665 (14%) had acceptable, and 2,289 (50%) had optimal therapy. Participants with optimal treatment were younger, had higher annual household income, and were enrolled from practices with dedicated HF clinics (all P < 0.001) than participants with acceptable or suboptimal treatment. Participants with optimal treatment had lower all-cause death (adjusted HR: 0.77; 95% CI: 0.64-0.92) and cardiovascular death (adjusted HR: 0.79; 95% CI: 0.65-0.96) than those with suboptimal treatment., Conclusions: Across a large cohort of chronic ambulatory HFrEF, OMT scores stratified risk of all-cause and cardiovascular death., Competing Interests: Funding Support and Author Disclosures CHAMP-HF was supported by Novartis Pharmaceuticals. The funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication. Dr Rao has received salary support by a National Institutes of Health training grant (5T32HL069749-18). Dr Spertus has provided consultative services on patient-reported outcomes and evidence evaluation to Abbott, Alnylam, AstraZeneca, Bayer, Janssen, Bristol Meyers Squibb, Edwards, Terumo, Cytokinetics, and Imbria. He holds research grants from the National Institutes of Health, the Patient-Centered Outcomes Research Institute, the American College of Cardiology Foundation, Bristol Meyers Squibb, Cytokinetics, Imbria, and Janssen. He owns the copyright to the Seattle Angina Questionnaire, Kansas City Cardiomyopathy Questionnaire, and Peripheral Artery Questionnaire and serves on the Board of Directors for Blue Cross Blue Shield of Kansas City. Dr Butler is a consultant to Abbott, American Regent, Amgen, Applied Therapeutic, AskBio, Astellas, AstraZeneca, Bayer, Boehringer Ingelheim, Boston Scientific, Bristol Myers Squibb, Cardiac Dimension, Cardiocell, Cardior, CSL Bearing, CVRx, Cytokinetics, Daxor, Edwards, Element Science, Faraday, Foundry, G3P, Innolife, Impulse Dynamics, Imbria, Inventiva, Ionis, Levator, Lexicon, Lilly, LivaNova, Janssen, Medtronics, Merck, Occlutech, Owkin, Novartis, Novo Nordisk, Pfizer, Pharmacosmos, Pharmain, Prolaio, Pulnovo, Regeneron, Renibus, Roche, Salamandra, Salubris, Sanofi, SC Pharma, Secretome, Sequana, SQ Innovation, Tenex, Tricog, Ultromics, Vifor, and Zoll. Dr DeVore has received research funding through his institution from the American Heart Association, Amgen, AstraZeneca, Bayer, Intra-Cellular Therapies, American Regent, Inc, the National Heart, Lung, and Blood Institute, Novartis, and PCORI; he provides consulting services for Amgen, AstraZeneca, Bayer, CareDx, InnaMed, LivaNova, Mardil Medical, Novartis, Procyrion, scPharmaceuticals, Story Health, and Zoll; and has received nonfinancial support from Abbott for educational activities. 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.)

Objective: Population-based national data on the trends in expenditures related to coexisting atherosclerotic cardiovascular diseases (ASCVD) and diabetes is scarce. We assessed the trends in direct health care expenditures for ASCVD among individuals with and without diabetes, which can help to better define the burden of the co-occurrence of diabetes and ASCVD., Methods: We used 12-year data (2008-2019) from the US national Medical Expenditure Panel Survey including 28,144 U.S individuals aged ≥ 18 years. Using a two-part model (adjusting for demographics, comorbidities and time), we estimated mean and adjusted incremental medical expenditures by diabetes status among individuals with ASCVD. The costs were direct total health care expenditures (out-of-pocket payments and payments by private insurance, Medicaid, Medicare, and other sources) from various sources (office-based visits, hospital outpatient, emergency room, inpatient hospital, pharmacy, home health care, and other medical expenditures)., Results: The total direct expenditures for individuals with ASCVD increased continuously by 30% from $14,713 (95% confidence interval (CI): $13,808-$15,619) in 2008-2009 to $19,145 (95% CI: $17,988-$20,301) in 2008-2019. Individuals with diabetes had a 1.5-fold higher mean expenditure that those without diabetes. A key driver of the observed increase in direct costs was prescription drug costs, which increased by 37% among all individuals with ASCVD. The increase in prescription drug costs was more pronounced among individuals with ASCVD and diabetes, in whom a 45% increase in costs was observed, from $5184 (95% CI: $4721-$5646) in 2008-2009 to $7501 (95% CI: $6678-$8325) in 2018-2019. Individuals with ASCVD and diabetes had $5563 (95% CI: $4643-$6483) higher direct incremental expenditures compared with those without diabetes, after adjusting for demographics and comorbidities. Among US adults with ASCVD, the estimated adjusted total direct excess medical expenditures were $42 billion per year among those with diabetes vs. those without diabetes., Conclusions: In the setting of ASCVD, diabetes is associated with significantly increased health care costs, an increase that was driven by marked increase in medication costs., (© 2024. The Author(s).)

Background: How housing insecurity might affect patients with heart failure (HF) is not well characterized. Housing insecurity increases risks related to both communicable and noncommunicable diseases. For patients with HF, housing insecurity is likely to increase the risk for worse outcomes and rehospitalizations., Methods and Results: We analyzed hospitalizations due to HF in the United States by using the 2020 National Inpatient Sample and Nationwide Readmissions Database to evaluate the impacts of housing insecurity on HF outcomes and hospital use. Individuals were identified as having housing insecurity by using diagnostic International Classification of Disease (ICD)-10 codes. Demographics and comorbidities were compared between patients with HF with and without housing insecurity. An adjusted logistic regression was performed to evaluate the relationships between housing insecurity and socioeconomic status on in-hospital mortality. Using a Cox proportional hazards model, patients with HF and without housing insecurity were evaluated for the risk of all-cause and HF-specific readmissions over time. Of the 1,003,270 hospitalizations for HF in the U.S. in 2020, 16,150 were identified as having housing insecurity (1.6%), and 987,120 were identified as having no housing insecurity (98.4%). The median age of patients with housing insecurity who were hospitalized for HF was 57, as compared to 73 in the population with no housing insecurity. A higher proportion of patients in the housing-insecurity group were Black (35% vs 20.1%) or Hispanic (11.1% vs 7.3%). Patients with housing insecurity were more likely to carry a diagnosis of alcohol-use disorder (15.2% vs 3.3%) or substance-use disorder (70.2% vs 17.8%) but were less likely to use tobacco (18.3% vs 28.7%). Patients with housing insecurity were over 4.5 times more likely to have Medicaid (52.4% vs 11.3%). Median length of stay did not differ between patients with housing insecurity vs those without it. Patients with housing insecurity were more likely to discharge against medical advice (11.4% vs 2.03%). After adjusting for patients' characteristics, housing insecurity was associated with lower in-hospital mortality rates (OR 0.60, 95% CI 0.39-0.92). Housing insecurity was associated with a higher risk of all-cause readmissions at 180 days (HR 1.13, 95% CI 1.12-1.14). However, there was no significant difference in the risk of HF-specific readmissions at 180 days (HR 1.07, 95% CI 0.998-1.14) CONCLUSIONS: Patients with HF and housing insecurity have distinct demographic characteristics. They are also more likely to be readmitted after their initial hospitalization when compared to those without housing insecurity. Identifying and addressing specific comorbid conditions for patients with housing insecurity who are hospitalized for HF may allow clinicians to provide more focused care, with the goal of preventing morbidity, mortality and unnecessary readmissions., Competing Interests: Disclosures GCF reports consulting for Abbott, Amgen, AstraZeneca, Bayer, Boehinger Ingelheim, Cytokinetics, Eli Lilly, Johnson & Johnson, Medtronic, Merck, Novartis, and Pfizer. All other authors have no conflicts of interest to disclose., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Heart failure (HF) patients frequently exhibit iron deficiency, which is associated with a poor prognosis. Although various trials have been conducted, it is uncertain if intravenous (IV) iron replenishment improves clinical outcomes in HF patients with iron deficiency. A comprehensive literature search was conducted using PubMed/MEDLINE, Embase, and the Cochrane Library from inception till 15 September 2023 to retrieve randomized controlled trials (RCTs) that compared IV iron therapy with placebo or standard of care in patients with HF and iron deficiency. Clinical outcomes were assessed by generating forest plots using the random-effects model and pooling odds ratios (ORs) or weighted mean differences (WMDs). Fourteen RCTs with 6651 patients were included. IV iron therapy showed a significantly reduced incidence of the composite of first heart failure hospitalization (HHF) or cardiovascular (CV) mortality as compared with the control group (OR = 0.73, 95% CI: 0.58 to 0.92). The IV iron therapy resulted in a trend towards lower CV mortality (OR = 0.88, 95% CI: 0.76 to 1.01), 1-year all-cause mortality (OR = 0.85, 95% CI: 0.71 to 1.02), and first HHF (OR = 0.73, 95% CI: 0.51 to 1.05), and an improved left ventricular ejection fraction (LVEF) (MD = 4.54, 95% CI: -0.13 to 9.21). Meta-regression showed a significant inverse moderating effect of baseline LVEF on the first HHF or CV death. In patients with HF and iron deficiency, IV iron therapy reduced the incidence of composite of first HHF or CV mortality. There was a trend of lower overall CV and 1-year all-cause mortality, first HHF, and improved LVEF with IV iron therapy., (© 2024 The Author(s). ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Background: Three medications are now guideline-recommended treatments for heart failure with mildly reduced or preserved ejection fraction (HFmrEF/HFpEF), however, the cost-effectiveness of these agents in combination has yet to be established., Objectives: The purpose of this study was to determine the cost-effectiveness of mineralocorticoid receptor antagonists (MRA), angiotensin receptor-neprilysin inhibitors (ARNIs), and sodium glucose co-transporter 2 inhibitors (SGLT2is) in individuals with HFmrEF/HFpEF., Methods: Using a 3-state Markov model, we performed a cost-effectiveness study using simulated cohorts of 1,000 patients with HFmrEF and HFpEF. Treatment with 1-, 2-, and 3-drug combinations was modeled. Based on a United States health care sector perspective, outcome data was used to calculate incremental cost-effectiveness ratios (ICERs) in 2023 United States dollars based on a 30-year time horizon., Results: Treatment with MRA, MRA+SGLT2i, and MRA+SGLT2i+ARNI therapy resulted in an increase in life years of 1.04, 1.58, and 1.80 in the HFmrEF subgroup, respectively, and 0.99, 1.54, and 1.77 in the HFpEF subgroup, respectively, compared with placebo. At a yearly cost of $18, MRA therapy resulted in ICERs of $10,000 per quality-adjusted life year (QALY) in both subgroups. The ICER for the addition of SGLT2i therapy ($4,962 per year) was $113,000 per QALY in the HFmrEF subgroup and $141,000 in the HFpEF subgroup. The addition of ARNI therapy ($5,504 per year) resulted in ICERs >$250,000 per QALY in both subgroups. If SGLT2i and ARNI were available at generic pricing the ICERs become <$10,000 per QALY in both EF subgroups. Outcomes were highly sensitive to assumed benefit in cardiovascular death., Conclusions: For patients with heart failure, MRA was of high value, SGLT2i was of intermediate value, and ARNI was of low value in both HFmrEF and HFpEF subgroups. For patients with HFmrEF/HFpEF increased use of MRA and SGLT2i therapies should be encouraged and be accompanied with efforts to lower the cost of SGLT2i and ARNI therapies., Competing Interests: Funding Support and Author Disclosures Dr Fonarow has consulted for Abbott, Amgen, AstraZeneca, Bayer, Cytokinetics, Eli Lilly, Janssen, Medtronic, Merck, Novartis, and Pfizer. Dr Vaduganathan has received research grant support, served on advisory boards, or has had speaker engagements with 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; and participates on clinical trial committees for studies sponsored by AstraZeneca, Galmed, Novartis, Bayer AG, Occlutech, and Impulse Dynamics. 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.)

Increasing knowledge of the processes leading to heart failure (HF) has allowed significant developments in therapies for HF over the past few decades. Despite the evolution of HF treatment, it still places a large burden on patients and health care systems across the world.We used clinicaltrials.gov to gather information about clinical trials as of August 2023 studying pharmacotherapy for HF. We included interventional trials that were "active, not recruiting", "recruiting", or looking for participants but "not yet recruiting". In total, 119 studies met our criteria of ongoing clinical trials studying novel as well as currently approved HF pharmacotherapies. The major interventions were novel medications/already approved medications for other diseases 29 % (34 trials), sodium-glucose co-transporter inhibitors 21 % (25 trials), angiotensin receptor blocker-neprilysin inhibitors 10 % (12 trials), diuretics 14 % (17 trials) and mineralocorticoid receptor antagonists 5 % (6 trials). Ongoing research will aid in reducing the impact of HF and we summarize clinical trials leading the way to better HF treatment in this review., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Importance: Kidney health has received increasing focus as part of comprehensive heart failure (HF) treatment efforts. However, the occurrence of clinically relevant kidney outcomes in contemporary populations with HF has not been well studied., Objective: To examine rates of incident dialysis and acute kidney injury (AKI) among Medicare beneficiaries after HF hospitalization., Design, Setting, and Participants: This retrospective cohort study evaluated adults aged 65 years or older who were hospitalized for HF across 372 sites in the Get With The Guidelines-Heart Failure registry in the US between January 1, 2014, and December 31, 2018. Patients younger than 65 years or requiring dialysis either during or prior to hospitalization were excluded. Data were analyzed from May 4, 2021, to March 8, 2024., Main Outcomes and Measures: The primary outcome was inpatient dialysis initiation in the year after HF hospitalization and was ascertained via linkage with Medicare claims data. Other all-cause and cause-specific hospitalizations were also evaluated. The covariate-adjusted association between discharge estimated glomerular filtration rate (eGFR) and 1-year postdischarge outcomes was examined using Cox proportional hazards regression models., Results: Overall, among 85 298 patients included in the analysis (mean [SD] age, 80 [9] years; 53% women) mean (SD) left ventricular ejection fraction was 47% (16%) and mean (SD) eGFR was 53 (29) mL/min per 1.73 m2; 54 010 (63%) had an eGFR less than 60 mL/min per 1.73 m2. By 1 year after HF hospitalization, 6% had progressed to dialysis, 7% had progressed to dialysis or end-stage kidney disease, and 7% had been readmitted for AKI. Incident dialysis increased steeply with lower discharge eGFR category: compared with patients with an eGFR of 60 mL/min per 1.73 m2 or more, individuals with an eGFR of 45 to less than 60 and of less than 30 mL/min per 1.73 m2 had higher rates of dialysis readmission (45 to <60: adjusted hazard ratio [AHR], 2.16 [95% CI, 1.86-2.51]; <30: AHR, 28.46 [95% CI, 25.25-32.08]). Lower discharge eGFR (per 10 mL/min per 1.73 m2 decrease) was independently associated with a higher rate of readmission for dialysis (AHR, 2.23; 95% CI, 2.14-2.32), dialysis or end-stage kidney disease (AHR, 2.34; 95% CI, 2.24-2.44), and AKI (AHR, 1.25; 95% CI, 1.23-1.27), with similar findings for all-cause mortality, all-cause readmission, and HF readmission. Baseline left ventricular ejection fraction did not modify the covariate-adjusted association between lower discharge eGFR and kidney outcomes., Conclusions and Relevance: In this study, older adults with HF had substantial risk of kidney complications, with an estimated 6% progressing to dialysis in the year after HF hospitalization. These findings emphasize the need for health care approaches prioritizing kidney health in this high-risk population.