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Transcatheter tricuspid valve replacement (TTVR) has emerged as a promising intervention for the treatment of severe tricuspid regurgitation with complex valve morphology. This consensus document provides a comprehensive overview of the current state of orthotopic TTVR, focusing on patient selection, procedural details, and follow-up care. Clinical outcomes from initial studies and compassionate use cases are discussed, highlighting the effectiveness of TTVR in reducing tricuspid regurgitation, inducing reverse right ventricular remodeling, and enhancing patients' quality of life. This review paper also addresses potential complications and challenges associated with TTVR, such as new-onset conduction disturbances, bleeding complications, and afterload mismatch, and provides expert recommendations for the periprocedural management, anticoagulation strategies, and long-term follow-up. With the commercial approval of the first TTVR system in the United States and Europe, it intends to serve as a reference for clinicians and researchers involved in the evolving field of transcatheter tricuspid valve interventions., Competing Interests: Funding Support and Author Disclosures Dr Hausleiter has received research support and speaker honoraria from Edwards Lifesciences. Dr Stolz has received speaker honoraria from Edwards Lifesciences. Dr Lurz has received institutional fees and research grants from Abbott Cardiovascular, Edwards Lifesciences, and Medtronic. Dr Rudolph has received research support and speaker honoraria from Abbott Vascular, Boston Scientific, and Edwards Lifesciences. Dr Hahn has received speaker fees from Abbott Structural, Baylis Medical, Edwards Lifesciences, and Philips Healthcare; has institutional consulting contracts for which she receives no direct compensation with Abbott Structural, Boston Scientific, Edwards Lifesciences, Medtronic, and Novartis; and is Chief Scientific Officer for the Echocardiography Core Laboratory at the Cardiovascular Research Foundation for multiple industry-sponsored trials, for which she receives no direct industry compensation. Dr Estevez-Loureiro is a consultant for and has received fees form Abbott Vascular, Edwards Lifesciences, Boston Scientific, Venus Medtech, and Jenscare. Dr Davidson has received institutional research grant support from Edwards Lifesciences and Abbott Vascular; and is an uncompensated advisor to Edwards Lifesciences. Dr Zahr has received grant support/research support from Edwards Lifesciences and Medtronic; and has received consultant fees/honoraria from Edwards Lifesciences and Medtronic. Dr Kodali has received institutional research grants from Edwards Lifesciences, Medtronic, and Abbott; has received consulting fees from Abbott, Admedus, and Meril Lifesciences; and has equity options from Biotrace Medical and Thubrikar Aortic Valve Inc. Dr Makkar has received research grants from Edwards Lifesciences, Abbott, Medtronic, and Boston Scientific; has served as national principal investigator for Portico (Abbott) and Acurate (Boston Scientific) US investigation device exemption trials; has received personal proctoring fees from Edwards Lifesciences; and has received travel support from Edwards Lifesciences, Abbott, and Boston Scientific. Dr Cheung is a member of the eligibility Committee of the TRINITY CE Trial; and is a consultant for Abbott, Medtronic, Boston Scientific, and Jenscare. Dr Lopes has received research support from Bristol Myers Squibb, GlaxoSmithKline, Medtronic, and Pfizer; and has received consulting fees from Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Daiichi-Sankyo, GlaxoSmithKline, Medtronic, Merck, Pfizer, and Portola. Dr Maisano has received grant or research institutional support from Abbott, Biotronik, Boston Scientific, Edwards Lifesciences, Medtronic, NVT, Terumo, and Venus; has received consulting fees and honoraria (both personal and institutional) from Abbott, Cardiovalve, Edwards Lifesciences, Medtronic, Mtex, Occlufit, Simulands, Squadra, Valgen, Venus, and Xeltis; has received royalty income from Edwards Lifesciences; and is shareholder (including share options) of 4Tech, Magenta, and Transseptal Solutions. Dr Fam is a consultant to Edwards, Abbott, Medtronic, and Venus Medtech. Dr Latib has served on the advisory board for Medtronic, Abbott Vascular, Boston Scientific, Edwards Lifesciences, Shifamed dyne, Philips, and NeoChord Inc. Dr Windecker has received research, travel, or educational grants to the institution without personal remuneration from Abbott, Abiomed, Amgen, AstraZeneca, Bayer, Braun, Biotronik, Boehringer Ingelheim, Boston Scientific, Bristol Myers Squibb, Cardinal Health, CardioValve, Cordis Medical, CorFlow Therapeutics, CSL Behring, Daiichi-Sankyo, Edwards Lifesciences, Farapulse, Fumedica, Guerbet, Idorsia, Inari Medical, Infraredx, Janssen-Cilag, Johnson and Johnson, MedAlliance, Medicure, Medtronic, Merck Sharp and Dohme, Miracor Medical, MonarQ, Novartis, Novo Nordisk, Organon, OrPha Suisse, Pharming Tech, Pfizer, Polares, Regeneron, Sanofi, Servier, Sinomed, Terumo, Vifor, and V-Wave; has served as an advisory board member and/or a member of the steering or executive groups of trials funded by Abbott, Abiomed, Amgen, AstraZeneca, Bayer, Boston Scientific, Biotronik, Bristol Myers Squibb, Edwards Lifesciences, MedAlliance, Medtronic, Novartis, Polares, Recardio, Sinomed, Terumo, and V-Wave, with payments to the institution but no personal payments; and is a member of the steering or executive committee groups of several investigator-initiated trials that receive funding from industry without impact on his personal remuneration. Dr Praz has received a research grant to the institution from Abbott Vascular; and has been compensated for travel expenses by Abbott Vascular, Edwards Lifesciences, Medira, Siemens Healthineers, and InQB8 Medical Technologies. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2025 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Atrial fibrillation (AF) often remains undiagnosed, and it independently raises the risk of ischemic stroke, which is largely reversible by oral anticoagulation. Although randomized trials using longer term screening approaches increase identification of AF, no studies have established that AF screening lowers stroke rates., Objectives: To address this knowledge gap, the GUARD-AF (Reducing Stroke by Screening for Undiagnosed Atrial Fibrillation in Elderly Individuals) trial screened participants in primary care practices using a 14-day continuous electrocardiographic monitor to determine whether screening for AF coupled with physician/patient decision-making to use oral anticoagulation reduces stroke and provides a net clinical benefit compared with usual care., Methods: GUARD-AF was a prospective, parallel-group, randomized controlled trial designed to test whether screening for AF in people aged ≥70 years using a 14-day single-lead continuous electrocardiographic patch monitor could identify patients with undiagnosed AF and reduce stroke. Participants were randomized 1:1 to screening or usual care. The primary efficacy and safety outcomes were hospitalization due to all-cause stroke and bleeding, respectively. Analyses used the intention-to-treat population., Results: Enrollment began on December 17, 2019, and involved 149 primary care sites across the United States. The COVID-19 pandemic led to premature termination of enrollment, with 11,905 participants in the intention-to-treat population. Median follow-up was 15.3 months (Q1-Q3: 13.8-17.6 months). Median age was 75 years (Q1-Q3: 72-79 years), and 56.6% were female. The risk of stroke in the screening group was 0.7% vs 0.6% in the usual care group (HR: 1.10; 95% CI: 0.69-1.75). The risk of bleeding was 1.0% in the screening group vs 1.1% in the usual care group (HR: 0.87; 95% CI: 0.60-1.26). Diagnosis of AF was 5% in the screening group and 3.3% in the usual care group, and initiation of oral anticoagulation after randomization was 4.2% and 2.8%, respectively., Conclusions: In this trial, there was no evidence that screening for AF using a 14-day continuous electrocardiographic monitor in people ≥70 years of age seen in primary care practice reduces stroke hospitalizations. Event rates were low, however, and the trial did not enroll the planned sample size.(Reducing Stroke by Screening for Undiagnosed Atrial Fibrillation in Elderly Individuals [GUARD-AF]; NCT04126486)., Competing Interests: Funding Support and Author Disclosures The Bristol Myers Squibb/Pfizer Alliance funded the GUARD-AF trial but was not involved in data collection, analysis, or interpretation; manuscript preparation; or decision to publish. Dr Lopes has received research grants or contracts from Amgen, Bristol Myers Squibb, GlaxoSmithKline, Medtronic, Pfizer, and Sanofi; has received funding for educational activities or lectures from Pfizer, Daiichi-Sankyo, and Novo Nordisk; and has received funding for consulting or other services from Bayer, Boehringer Ingelheim, Bristol Myers Squibb, and Novo Nordisk. Dr Atlas has received sponsored research support from Bristol Myers Squibb/Pfizer and the American Heart Association (18SFRN34250007); and has consulted for Boehringer Ingelheim, Bristol Myers Squibb, Fitbit, Pfizer, and Premier. Dr Go has received a research grant from Bristol Myers Squibb/Pfizer Alliance. Dr Lubitz is an employee of Novartis. Dr McManus has received grants or research support from Apple, Fitbit, Boehringer Ingelheim, Pfizer, Bristol Myers Squibb, and Flexcon; and has received consulting fees from Fitbit, NAMSA, Avania, and Heart Rhythm Society. Dr Rothberg is a consultant for Blue Cross Blue Shield Association. Prof Crosson is a former employee of iRhythm Technologies,. Dr Aronson and Mr Patlakh are employees of Bristol Myers Squibb. Ms. Mills is a former employee of Bristol Myers Squibb, Inc. Dr O’Brien has received institutional research funding from Pfizer. Dr Singer has received research support from Bristol Myers Squibb; and has consulted for the Bristol Myers Squibb, Pfizer, Medtronic, and Fitbit (Google). 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: Although high rates of P2Y 12 inhibitor pretreatment (defined as the administration before coronary angiography) for non-ST-segment elevation acute coronary syndrome (NSTE-ACS) have been reported, contemporary U.S. practice patterns are not well studied., Objectives: The goal of this study was to investigate the temporal U.S. trends, variability, and clinical outcomes of P2Y 12 inhibitor pretreatment in NSTE-ACS., Methods: Consecutive patients who underwent early invasive strategy for NSTE-ACS (coronary angiography ≤24 hours of arrival) in the National Cardiovascular Data Registry Chest Pain-Myocardial Infarction (MI) Registry were analyzed. A time-trend analysis was conducted on a complete cohort between January 1, 2013, and March 31, 2023. Subsequently, a more recent cohort (January 1, 2019, to March 31, 2023) with a complete set of variables was used to construct hierarchical regression models to quantify the variability in the use of pretreatment among operators and institutions. For this contemporary cohort, instrumental variable analysis, with operator preference as the instrument, was performed to compare the in-hospital outcomes between patients who received pretreatment and those who did not., Results: Use of P2Y 12 inhibitor pretreatment decreased from 24.8% in 2013Q1 to 12.4% in 2023Q1. Among the contemporary cohort of 110,148 patients (2019-2023; mean age 63.9 ± 12.5 years; 33.0% female), 17,509 (15.9%) received pretreatment. Significant variability in P2Y 12 inhibitor pretreatment was observed (range: 0%-100%): hierarchical regression model demonstrated that 2 similar patients would have a >3-fold difference in the odds of pretreatment from 1 random operator or institution as compared with another (median OR: 3.74 [95% CI: 3.57-3.91] and 3.63 [95% CI: 3.51-3.74], respectively). Instrumental variable analysis demonstrated no significant differences in in-hospital all-cause death (1.5% vs 1.7%; P = 0.07), recurrent MI (0.6% vs 0.6%; P = 0.98), or major bleeding (2.7% vs 2.8%; P = 0.98) with pretreatment. However, in patients who underwent coronary artery bypass surgery, pretreatment was associated with a longer length of stay (11.2 ± 5.1 days vs 9.8 ± 5.0 days; P < 0.01)., Conclusions: In a national U.S. registry, we observed significant variability in the use of P2Y 12 inhibitor pretreatment among NSTE-ACS patients. Given the lack of clear advantages and the potential for prolonged hospital stays, our findings highlight the importance of efforts to improve standardization., Competing Interests: Funding Support and Author Disclosures This analysis was funded by the National Cardiovascular Data Registry. Dr Rymer has received research funding from the National Heart, Lung, and Blood Institute, Novo Nordisk, Chiesi, Abiomed, and Pfizer. Dr Sandhu has received prior consulting fees from Lexicon Pharmaceuticals; and has received research funding from the American Heart Association, National Institutes of Health, Novartis Pharmaceuticals, and Reprieve Cardiovascular outside of the submitted work. Dr Masoudi serves on a steering committee for a registry sponsored by Bristol Myers Squibb. Dr Spertus owns the copyright to the Seattle Angina Questionnaire; has received consulting income from Janssen, Bayer, AstraZeneca, Novartis, and Merck; serves on the cardiovascular scientific advisory board of United Healthcare; is on the board of directors for Blue Cross Blue Shield of Kansas City; and holds equity interest in Health Outcomes Sciences. Dr Kohsaka has received research funding from the Japan Society for the Promotion of Science and Pfizer; and has received consulting fees from Novartis and Bristol Myers Squibb, outside of the submitted work. 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: The optimal antithrombotic regimen for patients with atrial fibrillation (AF) who had an acute coronary syndrome (ACS) or have undergone percutaneous coronary intervention (PCI) is not known., Objectives: The authors sought to determine which antithrombotic regimen best balances safety and efficacy., Methods: AUGUSTUS, a multicenter 2 × 2 factorial design randomized trial compared apixaban with vitamin K antagonist (VKA) and aspirin with placebo in patients with AF with recent ACS and/or PCI treated with a P2Y 12 inhibitor. We conducted a 4-way analysis comparing safety and efficacy outcomes in the 4 randomized groups. The primary outcome was a composite of all-cause death, major or clinically relevant nonmajor bleeding, or hospitalization for cardiovascular causes over 6-month follow-up. Secondary outcomes included individual components of the primary endpoint., Results: A total of 4,614 patients were enrolled. All patients were treated with a P2Y 12 inhibitor. The primary endpoint occurred in 21.9% of patients randomized to apixaban plus placebo, 27.3% randomized to apixaban plus aspirin, 28.0% randomized to VKA plus placebo, and 33.3% randomized to VKA plus aspirin. Rates of major or clinically relevant nonmajor bleeding and hospitalization for cardiovascular causes were lower with apixaban and placebo compared with the other 3 antithrombotic strategies. There was no difference between the 4 randomized groups with respect to all-cause death., Conclusions: In patients with AF and a recent ACS and/or PCI, an antithrombotic regimen that included a P2Y 12 inhibitor and apixaban without aspirin resulted in a lower incidence of the composite of death, bleeding, or cardiovascular hospitalization than regimens including VKA, aspirin, or both. (An Open-label, 2 x 2 Factorial, Randomized Controlled, Clinical Trial to Evaluate the Safety of Apixaban vs. Vitamin K Antagonist and Aspirin vs. Aspirin Placebo in Patients with Atrial Fibrillation and Acute Coronary Syndrome or Percutaneous Coronary Intervention; NCT02415400)., Competing Interests: Funding Support and Author Disclosures The AUGUSTUS study and this analysis were funded by Bristol Myers Squibb and Pfizer. Dr Berwanger has received research grants from AstraZeneca, Pfizer, Bayer, Amgen, Novartis, Servier, and Boehringer Ingelheim. Dr Fanaroff has received research grants from the American Heart Association and National Institutes of Health; and has received consulting fees from Abbott Laboratories. Dr Granger has received research grants from Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Daiichi-Sankyo, Janssen, Pfizer, Armetheon, AstraZeneca, U.S. Food and Drug Administration, GlaxoSmithKline, The Medicines Company, Medtronic Foundation, Medtronic Inc, and Novartis; and has received consulting fees from Bayer, Boehringer Ingelheim, Boston Scientific, Bristol Myers Squibb, Daiichi-Sankyo, Janssen, Pfizer, Abbvie, Armetheon, AstraZeneca, Eli Lilly, Gilead, GlaxoSmithKline, Hoffmann-La Roche, The Medicines Company, National Institutes of Health, Novartis, Sirtex, Verseon, Apple, Medscape, LLC, Merck, Novo Nordisk, Roche Diagnostics, and Rho Pharmaceuticals. Dr Mehran has received institutional research grants from AstraZeneca, Bayer, Beth Israel Deaconess, Bristol Myers Squibb/Sanofi, CSL Behring, Eli Lilly/Daiichi-Sankyo, Medtronic, Novartis, and OrbusNeich; has received consulting fees from Boston Scientific, Abbott Vascular, Medscape, Siemens Medical Solutions, Roivant Sciences Inc, and Sanofi; has consulted (no fees) for Regeneron Pharmaceuticals Inc; has received institutional consulting fees from Abbott Vascular, Spectranetics/Phillips/Volcano Corporation, Bristol Myers Squibb, Novartis, and Watermark Research; is an executive committee member for Janssen Pharmaceuticals and Bristol Myers Squibb; and has <1% equity in Claret Medical and Elixir Medical. Dr Aronson is an employee of Bristol Myers Squibb. Dr Windecker has received institutional research and educational grants from Abbott, Amgen, Bayer, Bristol Myers Squibb, CSL Behring, Boston Scientific, Biotronik, Edwards Lifesciences, Medtronic, Polares, and Sinomed. Dr Goodman has received research grant support and/or speaker/consulting honoraria from Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, CSL Behring, Daiichi-Sankyo, Eli Lilly, Esperion, Fenix Group International, Ferring Pharmaceuticals, GlaxoSmithKline, HLS Therapeutics, Janssen/Johnson and Johnson, Luitpold Pharmaceuticals, Matrizyme, Merck, Novartis, Novo Nordisk A/C, Pfizer, Regeneron, Sanofi, Servier, Tenax Therapeutics, Heart and Stroke Foundation of Ontario/University of Toronto, Canadian Heart Research Centre and MD Primer, Canadian VIGOUR Centre, Duke Clinical Research Institute, and PERFUSE. Dr Alexander has received research grants from Bristol Myers Squibb, Boehringer Ingelheim, AstraZeneca, CryoLife, CSL Behring, U.S. Food and Drug Administration, National Institutes of Health, Sanofi, and VoluMetrix; and has received consulting fees from Pfizer, Bristol Myers Squibb, AbbVie Pharmaceuticals, CSL Behring, Novo Nordisk, Portola Pharmaceuticals, Quantum Genomics, Teikoku Pharmaceuticals, VA Cooperative Studies, and Zafgen. Dr Lopes has received research grants or contracts from Amgen, Bristol Myers Squibb, GlaxoSmithKline, Medtronic, Pfizer, and Sanofi; has received funding for educational activities or lectures from Pfizer, Daiichi-Sankyo, and Novo Nordisk; and has received funding for consulting or other services from Bayer, Boehringer Ingelheim, Bristol Myers Squibb, and Novo Nordisk. 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: Emerging data suggest that glucagon-like peptide-1 receptor agonists (GLP-1 RAs) improve kidney outcomes for people with type 2 diabetes (T2D). Direct comparisons of the kidney and cardiovascular effectiveness of GLP-1 RA with sodium-glucose cotransporter 2 inhibitors (SGLT2i), a first-line therapy for this population, are needed., Objectives: The authors compared kidney and cardiovascular outcomes for new users of SGLT2i and GLP-1 RAs with T2D., Methods: Using propensity score overlap weighting, we analyzed electronic health record data from 20 U.S. health systems contributing to PCORnet between 2015 and 2020. The primary kidney outcome was a composite of sustained 40% estimated glomerular filtration rate (eGFR) decline, incident end-stage kidney disease, or all-cause mortality over 2 years or until censoring. In addition, we examined cardiovascular and safety outcomes., Results: The weighted study cohort included 35,004 SGLT2i and 47,268 GLP-1 RA initiators. Over a median of 1.2 years, the primary outcome did not differ between treatments (HR: 0.91; 95% CI: 0.81-1.02), although SGLT2i were associated with a lower risk of 40% eGFR decline (HR: 0.77; 95% CI: 0.65-0.91). Risks of mortality (HR: 1.08; 95% CI: 0.92-1.27), a composite of stroke, myocardial infarction, or death (HR: 1.03; 95% CI: 0.93-1.14), and heart failure hospitalization (HR: 0.95; 95% CI: 0.80-1.13) did not differ. Genital mycotic infections were more common for SGLT2i initiators, but other safety outcomes did not differ. The results were similar regardless of chronic kidney disease status., Conclusions: SGLT2i and GLP-1 RAs led to similar kidney and cardiovascular outcomes in people with T2D, though SGLT2i initiation was associated with a lower risk of 40% eGFR decline. (Evaluating Comparative Effectiveness of Empagliflozin in Type 2 Diabetes Population With and Without Chronic Kidney Disease; NCT05465317)., Competing Interests: Funding Support and Author Disclosures This study was funded by the Boehringer Ingelheim & Lilly Diabetes Alliance. The authors meet criteria for authorship as recommended by the International Committee of Medical Journal Editors (ICMJE). Boehringer Ingelheim was given the opportunity to review the manuscript for medical and scientific accuracy as well as intellectual property considerations. Dr Butler has received consultant honoraria from Abbott, American Regent, Amgen, Applied Therapeutic, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Cardiac Dimension, Cardior, CVRx, Cytokinetics, Edwards, Element Science, Innolife, Impulse Dynamics, Imbria, Inventiva, Lexicon, Lilly, LivaNova, Janssen, Medtronics, Merck, Occlutech, Novartis, Novo Nordisk, Pfizer, Pharmacosmos, Pharmain, Roche, Sequana, SQ Innovation, and Vifor. Dr Pagidipati has received research support from Alnylam, Amgen, Boehringer Ingelheim, Eggland’s Best, Eli Lilly, Novartis, Novo Nordisk, and Verily Life Sciences; has served on consultation/advisory panels for Bayer, Boehringer Ingelheim, CRISPR Therapeutics, Eli Lilly, Esperion, AstraZeneca, Merck, Novartis, and Novo Nordisk; has served as an executive committee member for trials sponsored by Novo Nordisk and Amgen; has served on the Data Safety Monitoring Boards for trials sponsored by Johnson and Johnson and Novartis; and has served on the medical advisory board for Miga Health. Dr Fonseca has received research support (to Tulane) from Fractyl and Jaguar Gene Therapy; has received consultant honoraria from Asahi, Bayer, Abbott, Boehringer Ingelheim, and Corcept; has stock or stock options in Mellitus Health, BRAVO4Health, Amgen, and Abbott; and has patents pending for BRAVO risk engine for predicting diabetes complications and PAX4 gene therapy for type 1 diabetes. 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: ARTESiA (Apixaban for the Reduction of Thrombo-Embolism in Patients With Device-Detected Sub-Clinical Atrial Fibrillation) demonstrated that apixaban, compared with aspirin, significantly reduced stroke and systemic embolism (SE) but increased major bleeding in patients with subclinical atrial fibrillation., Objectives: To help inform decision making, the authors evaluated the efficacy and safety of apixaban according to baseline CHA 2 DS 2 -VASc score., Methods: We performed a subgroup analysis according to baseline CHA 2 DS 2 -VASc score and assessed both the relative and absolute differences in stroke/SE and major bleeding., Results: Baseline CHA 2 DS 2 -VASc scores were <4 in 1,578 (39.4%) patients, 4 in 1,349 (33.6%), and >4 in 1,085 (27.0%). For patients with CHA 2 DS 2 -VASc >4, the rate of stroke was 0.98%/year with apixaban and 2.25%/year with aspirin; compared with aspirin, apixaban prevented 1.28 (95% CI: 0.43-2.12) strokes/SE per 100 patient-years and caused 0.68 (95% CI: -0.23 to 1.57) major bleeds. For CHA 2 DS 2 -VASc <4, the stroke/SE rate was 0.85%/year with apixaban and 0.97%/year with aspirin. Apixaban prevented 0.12 (95% CI: -0.38 to 0.62) strokes/SE per 100 patient-years and caused 0.33 (95% CI: -0.27 to 0.92) major bleeds. For patients with CHA 2 DS 2 -VASc =4, apixaban prevented 0.32 (95% CI: -0.16 to 0.79) strokes/SE per 100 patient-years and caused 0.28 (95% CI: -0.30 to 0.86) major bleeds., Conclusions: One in 4 patients in ARTESiA with subclinical atrial fibrillation had a CHA 2 DS 2 -VASc score >4 and a stroke/SE risk of 2.2% per year. For these patients, the benefits of treatment with apixaban in preventing stroke/SE are greater than the risks. The opposite is true for patients with CHA 2 DS 2 -VASc score <4. A substantial intermediate group (CHA 2 DS 2 -VASc =4) exists in which patient preferences will inform treatment decisions. (Apixaban for the Reduction of Thrombo-Embolism in Patients With Device-Detected Sub-Clinical Atrial Fibrillation; NCT01938248)., Competing Interests: Funding Support and Author Disclosures The ARTESiA study was funded by grants from the Canadian Institutes of Health Research (201610PTJ-378238), the Bristol Myers Squibb–Pfizer Alliance, the Heart and Stroke Foundation of Canada, the Canadian Stroke Prevention Intervention Network, Hamilton Health Sciences, the Accelerating Clinical Trials Network, the Population Health Research Institute, and Medtronic. The sponsors had no role in data analysis, interpretation, or publication. Dr Lopes has received research grants from Amgen, Boehringer Ingelheim, Bristol Myers Squibb, GlaxoSmithKline, Medtronic, Novo Nordisk, Pfizer, and Sanofi US Services Inc; and has served as a consultant to Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Daiichi-Sankyo Company, GlaxoSmithKline, Medtronic, Merck, Novo Nordisk, Pfizer, Portola Pharmaceuticals, and Sanofi US Services Inc. Dr Granger has received research grants from Bayer and Boehringer Ingelheim; and has served as a consultant to Anthos, AstraZeneca, Bayer, Boehringer Ingelheim, Boston Scientific Corporation, Bristol Myers Squibb, Cadrenal, Daiichi-Sankyo Company, Janssen Global Services, LLC, Merck, Pfizer Inc, and Tenac.io. Dr McIntyre has served as a consultant to Servier Pharmaceuticals LLC. Dr Rivard has received research grants from Bayer Inc, Heart and Stroke Foundation, Canadian Institutes of Health Research (CIHR), and FRQS (Fonds de Recherche Quebec-Sante). Dr Atar has received speaker fees from Amgen, Amarin, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Merck Sharp & Dohme, Novartis, Novo Nordisk, Pfizer, Pharmacosmos, Philips, Roche Diagnostics, Sanofi, Takeda, and Vifor; and has received institutional grant support from Bristol Myers Squibb/Pfizer, Medtronic, Bayer, and Roche Diagnostics. Dr Boriani has received speaker fees from Bayer, Boston Scientific, Boehringer Ingelheim, Daiichi-Sankyo, Janssen, and Sanofi. Dr Duray has served as a consultant to Medtronic and Biotronik. Dr Gold has received institutional research support from Abbott, Boston Scientific, and Medtronic; and has received consulting fees from Boston Scientific and Medtronic. Dr Hohnloser has served as a consultant to Pfizer, Bristol Myers Squibb, Boehringer Ingelheim, and Sanofi. Dr Kutyifa has received research grants from Boston Scientific, ZOLL, National Institutes of Health, and Spire Inc; has received speaker fees from Medtronic, Abbott, and Biotronik; and has received consultant fees from Biotronik. Dr Sticherling has served as a consultant to Medtronic, Boston Scientific, and Biotronik. Dr Benz has received lecture fees from Bristol Myers Squibb and AstraZeneca; and has participated in an educational program supported by Boston Scientific (“Fellowship Herzrhythmus”). Dr Linde has received research support from the Swedish Heart Lung Foundation, Swedish Royal Society of Science, and Stockholm County Council; has received consulting fees from AstraZeneca and Roche Diagnostics; has received speaker honoraria from Novartis, AstraZeneca, Bayer, Vifor Pharma, Medtronic, and Impulse Dynamics; and has served on advisory boards for Astra Zeneca. Dr Kautzner has served as a consultant for Abbott Vascular, Biotronik, Boston Scientific Corporation, GE Healthcare, and Medtronic, Inc. Dr Mairesse has received consultant or speaker fees from Abbott, Biotronik, Microport, Bristol Myers Squibb/Pfizer, and Daiichi-Sankyo. Dr Connolly has received research grants from Pfizer Inc; and has served as a consultant for Bayer, Bristol Myers Squibb, Daiichi-Sankyo Company, and Javelin Ventures. Dr Healey has received research grants from Boston Scientific Corporation, Bristol Myers Squibb, Medtronic, and Pfizer; has served as a consultant for Bayer, Boston Scientific Corporation, Medtronic, Novartis, and Servier Affaires Medicales; and has served as an expert witness for Bayer., (Copyright © 2024 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Women have worse outcomes after coronary artery bypass surgery (CABG) than men., Objectives: This study aimed to determine the incidence of CABG graft failure in women, its association with cardiac events, and whether it contributes to sex-related differences in outcomes., Methods: A pooled analysis of individual patient data from randomized clinical trials with systematic imaging follow-up was performed. Multivariable logistic regression models were used to assess the association of graft failure with myocardial infarction and repeat revascularization between CABG and imaging (primary outcome) and death after imaging (secondary outcome). Mediation analysis was performed to evaluate the effect of graft failure on the association between female sex and risk of death., Results: Seven randomized clinical trials (N = 4,413, 777 women) were included. At a median imaging follow-up of 1.03 years, graft failure was significantly more frequent among women than men (37.3% vs 32.9% at the patient-level and 20.5% vs 15.8% at the graft level; P = 0.02 and P < 0.001, respectively). In women, graft failure was associated with an increased risk of myocardial infarction and repeat revascularization (OR: 3.94; 95% CI: 1.79-8.67) and death (OR: 3.18; 95% CI: 1.73-5.85). Female sex was independently associated with the risk of death (direct effect, HR: 1.84; 95% CI: 1.35-2.50) but the association was not mediated by graft failure (indirect effect, HR: 1.04; 95% CI: 0.86-1.26)., Conclusions: Graft failure is more frequent in women and is associated with adverse cardiac events. The excess mortality risk associated with female sex among CABG patients is not mediated by graft failure., Competing Interests: Funding Support and Author Disclosures Dr Di Franco has consulted for Novo Nordisk and Servier; and has served as an Advisory Board Member for Novo Nordisk and Scharper. Dr Fremes has received institutional support from Medtronic, Boston, and Amgen for clinical trial participation. Dr Hare has received research grants, educational grants, honoraria, or consultation fees from Abbott Pharmaceuticals, Abbott Structural Heart, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, CSL-Seqiris, Kaneka (Japan), Lundbeck (Denmark), Menarini (Italy), Merk KA (Germany), Merck, Novartis, Pfizer, Sanofi, Servier, and Vifor; and has received fellowship and research funding from the National Health and Medical Research Council of Australia, the Heart Foundation of Australia, the Austin Medical Research Foundation, and Diabetes Australia. Dr ten Berg has received institutional funding of the POPular CABG trial by AstraZeneca. Dr Bhatt has served on the Advisory Board of Angiowave, Bayer, Boehringer Ingelheim, CellProthera, Cereno Scientific, Elsevier Practice Update Cardiology, High Enroll, Janssen, Level Ex, McKinsey, Medscape Cardiology, Merck, MyoKardia, NirvaMed, Novo Nordisk, PhaseBio, PLx Pharma, and Stasys; has served on the Board of Directors of American Heart Association New York City, Angiowave (stock options), Bristol Myers Squibb (stock), DRS.LINQ (stock options), and High Enroll (stock); has served as a consultant for Broadview Ventures, Hims, SFJ, and Youngene; has served on Data Monitoring Committees for Acesion Pharma, Assistance Publique-Hôpitaux de Paris, Baim Institute for Clinical Research (formerly Harvard Clinical Research Institute, for the PORTICO trial, funded by St. Jude Medical, now Abbott), Boston Scientific (Chair, PEITHO trial), Cleveland Clinic, Contego Medical (Chair, PERFORMANCE 2), Duke Clinical Research Institute, Mayo Clinic, Mount Sinai School of Medicine (for the ENVISAGE trial, funded by Daiichi Sankyo; for the ABILITY-DM trial, funded by Concept Medical; for ALLAY-HF, funded by Alleviant Medical), Novartis, Population Health Research Institute, and Rutgers University (for the National Institutes of Health-funded MINT Trial); has received honoraria from American College of Cardiology (Senior Associate Editor, Clinical Trials and News, ACC.org; Chair, ACC Accreditation Oversight Committee), Arnold and Porter law firm (work related to Sanofi/Bristol Myers Squibb clopidogrel litigation), Baim Institute for Clinical Research (formerly Harvard Clinical Research Institute; RE-DUAL PCI clinical trial steering committee funded by Boehringer Ingelheim; AEGIS-II executive committee funded by CSL Behring), Belvoir Publications (Editor-in-Chief, Harvard Heart Letter), Canadian Medical and Surgical Knowledge Translation Research Group (clinical trial steering committees), CSL Behring (AHA lecture), Cowen and Company, Duke Clinical Research Institute (clinical trial steering committees, including for the PRONOUNCE trial, funded by Ferring Pharmaceuticals), HMP Global (Editor-in-Chief, Journal of Invasive Cardiology), Journal of the American College of Cardiology (Guest Editor; Associate Editor), K2P (Co-Chair, interdisciplinary curriculum), Level Ex, Medtelligence/ReachMD (CME steering committees), MJH Life Sciences, Oakstone CME (Course Director, Comprehensive Review of Interventional Cardiology), Piper Sandler, Population Health Research Institute (for the COMPASS operations committee, publications committee, steering committee, and USA national co-leader, funded by Bayer), WebMD (CME steering committees), and Wiley (steering committee); served as Deputy Editor for Clinical Cardiology; is named on a patent for sotagliflozin assigned to Brigham and Women's Hospital who assigned to Lexicon (neither he nor Brigham and Women's Hospital receive any income from this patent); has received research funding from Abbott, Acesion Pharma, Afimmune, Aker Biomarine, Alnylam, Amarin, Amgen, AstraZeneca, Bayer, Beren, Boehringer Ingelheim, Boston Scientific, Bristol Myers Squibb, Cardax, CellProthera, Cereno Scientific, Chiesi, CinCor, Cleerly, CSL Behring, Eisai, Ethicon, Faraday Pharmaceuticals, Ferring Pharmaceuticals, Forest Laboratories, Fractyl, Garmin, HLS Therapeutics, Idorsia, Ironwood, Ischemix, Janssen, Javelin, Lexicon, Lilly, Medtronic, Merck, Moderna, MyoKardia, NirvaMed, Novartis, Novo Nordisk, Otsuka, Owkin, Pfizer, PhaseBio, PLx Pharma, Recardio, Regeneron, Reid Hoffman Foundation, Roche, Sanofi, Stasys, Synaptic, The Medicines Company, Youngene, and 89Bio; receives royalties from Elsevier (Editor, Braunwald’s Heart Disease); has served as Site Co-Investigator for Abbott, Biotronik, Boston Scientific, CSI, Endotronix, St. Jude Medical (now Abbott), Philips, SpectraWAVE, Svelte, and Vascular Solutions; is a Trustee of the American College of Cardiology; and has performed unfunded research for FlowCo. Dr Alexander has research support through Duke University from Artivion, Bayer, Bristol Myers Squibb, CSL Behring, Ferring, the U.S. Food and Drug Administration, Humacyte, the U.S. National Institutes of Health, and XaTek; and has received consulting payments or honoraria from AbbVie, Akros, Artivion, AtriCure, Bayer, Bristol Myers Squibb, Ferring, GlaxoSmithKline, Janssen, Novostia, Pfizer, Portola, Quantum Genomics, Teikoku, Theravance, and Veralox. 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: The AEGIS-II trial hypothesized that CSL112, an intravenous formulation of human apoA-I, would lower the risk of plaque disruption, decreasing the risk of recurrent events such as myocardial infarction (MI) among high-risk patients with MI., Objectives: This exploratory analysis evaluates the effect of CSL112 therapy on the incidence of cardiovascular (CV) death and recurrent MI., Methods: The AEGIS-II trial was an international, multicenter, randomized, double-blind, placebo-controlled trial that randomized 18,219 high-risk acute MI patients to 4 weekly infusions of apoA-I (6 g CSL112) or placebo., Results: The incidence of the composite of CV death and type 1 MI was 11% to 16% lower in the CSL112 group over the study period (HR: 0.84; 95% CI: 0.7-1.0; P = 0.056 at day 90; HR: 0.86; 95% CI: 0.74-0.99; P = 0.048 at day 180; and HR: 0.89; 95% CI: 0.79-1.01; P = 0.07 at day 365). Similarly, the incidence of CV death or any MI was numerically lower in CSL112-treated patients throughout the follow-up period (HR: 0.92; 95% CI: 0.80-1.05 at day 90, HR: 0.89; 95% CI: 0.79-0.996 at day 180, HR: 0.91; 95% CI: 0.83-1.01 at day 365). The effect of CSL112 treatment on MI was predominantly observed for type 1 MI and type 4b (MI due to stent thrombosis)., Conclusions: Although CSL112 did not significantly reduce the occurrence of the primary study endpoints, patients treated with CSL112 infusions had numerically lower rates of CV death and MI, type-1 MI, and stent thrombosis-related MI compared with placebo. These findings could suggest a role of apoA-I in reducing subsequent plaque disruption events via enhanced cholesterol efflux. Further prospective data would be needed to confirm these observations., Competing Interests: Funding Support and Author Disclosures This study was funded by CSL Behring. Dr Povsic has received research funding paid to his institution from CSL Behring; has received research funding from Xylocor Inc, Ionis, Bayer, Roche, and the National Institutes of Health (NIH); and has received consulting income from Novo Nordisk, Corvia, and Boehringer Ingelheim. Dr Korjian has received research grant support paid to the Beth Israel Deaconess Medical Center, Harvard Medical School from CSL Behring. Dr Bahit has received modest honorarium from MSD, Pfizer, Bristol Myers Squibb, CSL Behring, Janssen, Boehringer Ingelheim, and Anthos Therapeutics. Dr Chi has received research grant support paid to the Beth Israel Deaconess Medical Center, Harvard Medical School from Bayer, Janssen Scientific Affairs, and CSL Behring. Dr Duffy is an employee of CSL Behring. Dr Alexander has received research grants from Artivion/CryoLife, Bayer, Bristol Myers Squibb, CSL Behring, Ferring, the U.S. Food and Drug Administration, Humacyte, and the NIH; and has received advisory board/consulting payments from AbbVie, Artivion/CryoLife, AtriCure, Bayer, Bristol Myers Squibb, Eli Lilly, Ferring, GlaxoSmithKline, Janssen, Novostia, Pfizer, Portola, Theravance, and Veralox. Dr Vinereanu has received research grants from CSL Behring, Bayer, Novartis, Amgen, and Boehringer Ingelheim; and has received consultancy fees from Bayer, Novartis, Amgen, and Boehringer Ingelheim. Dr Tricoci, Ms Mears, and Dr Deckelbaum are employees of CSL Behring. Dr Bonaca is the Executive Director of CPC, a nonprofit academic research organization affiliated with the University of Colorado, that receives or has received research grant/consulting funding between August 2021 and the present from Abbott Laboratories, Agios Pharmaceuticals, Inc, Alexion Pharma, Alnylam Pharmaceuticals, Inc, Amgen Inc, Angionetics, Inc, Anthos Therapeutics, ARCA Biopharma, Inc, Array BioPharma, Inc, AstraZeneca and Affiliates, Atentiv LLC, Audentes Therapeutics, Inc, Bayer and Affiliates, Beth Israel Deaconess Medical Center, Better Therapeutics, Inc, Boston Clinical Research Institute, Bristol Myers Squibb Company, Cambrian Biopharma, Inc, Cardiol Therapeutics Inc, CellResearch Corp, Cleerly Inc, Cook Regentec LLC, CSL Behring LLC, Eidos Therapeutics, Inc, EP Trading Co Ltd, EPG Communication Holdings Ltd, Epizon Pharma, Inc, Esperion Therapeutics, Inc, Everly Well, Inc, Exicon Consulting Pvt Ltd, Faraday Pharmaceuticals, Inc, Foresee Pharmaceuticals Co Ltd, Fortress Biotech, Inc, HDL Therapeutics Inc, HeartFlow Inc, Hummingbird Bioscience, Insmed Inc, Ionis Pharmaceuticals, IQVIA Inc, Janssen and Affiliates, Kowa Research Institute, Inc, Kyushu University, Lexicon Pharmaceuticals, Inc, Medimmune Ltd, Medpace, Merck & Affiliates, Nectero Medical Inc, Novartis Pharmaceuticals Corp, Novo Nordisk, Inc, Osiris Therapeutics Inc, Pfizer Inc, PhaseBio Pharmaceuticals, Inc, PPD Development, LP, Prairie Education and Research Cooperative, Prothena Biosciences Limited, Regeneron Pharmaceuticals, Inc, Regio Biosciences, Inc, Saint Luke’s Hospital of Kansas City, Sanifit Therapeutics S.A., Sanofi-Aventis Groupe, Silence Therapeutics PLC, Smith & Nephew plc, Stanford Center for Clinical Research, Stealth BioTherapeutics Inc, State of Colorado CCPD Grant, The Brigham & Women's Hospital, Inc, The Feinstein Institutes for Medical Research, Thrombosis Research Institute, University of Colorado, University of Pittsburgh, VarmX, Virta Health Corporation, Worldwide Clinical Trials Inc, WraSer, LLC, and Yale Cardiovascular Research Group. Dr Ridker has received institutional research grant support from Kowa, Novartis, Amarin, Pfizer, Esperion, Novo Nordisk, and the National Heart, Lung, and Blood Institute (NHLBI); during the past 5 years has served as a consultant to Novartis, Flame, Agepha, Ardelyx, Arrowhead, AstraZeneca, CSL Behring, Janssen, Civi Biopharm, GlaxoSmithKline, SOCAR, Novo Nordisk, Health Outlook, Montai Health, Eli Lilly, New Amsterdam, Boehringer Ingelheim, RTI, Zomagen, Cytokinetics, Horizon Therapeutics, and Cardio Therapeutics; has minority shareholder equity positions in Uppton, Bitteroot Bio, and Angiowave; and has received compensation for service on the Peter Munk Advisory Board (University of Toronto), the Leducq Foundation, Paris FR, and the Baim Institute (Boston, Massachusetts). Dr Goodman has received research grant support (eg, steering committee or data and safety monitoring committee) and/or speaker/consulting honoraria (eg, advisory boards) from Amgen, Anthos Therapeutics, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, CSL Behring, CYTE Ltd, Daiichi-Sankyo/American Regent, Eli Lilly, Esperion, Ferring Pharmaceuticals, HLS Therapeutics, Idorsia, JAMP Pharma, Merck, Novartis, Novo Nordisk A/C, Pendopharm/Pharmascience, Pfizer, Regeneron, Sanofi, Servier, Tolmar Pharmaceuticals, and Valeo Pharma; and has received salary support/honoraria from the Canadian Heart Failure Society, Canadian Heart Research Centre and MD Primer, Canadian VIGOUR Centre, Cleveland Clinic Coordinating Centre for Clinical Research, Duke Clinical Research Institute, Jewish General Hospital, New York University Clinical Coordinating Centre, PERFUSE Research Institute, Peter Munk Cardiac Centre Clinical Trials and Translation Unit, and TIMI Study Group (Brigham Health). Dr Cornel has served on advisory boards for Amgen and AstraZeneca. Dr Lewis has received consulting fees from Janssen R&D and Idorsia. Prof Parkhomenko has received research grants from CSL Behring, Amgen, Novo Nordisk, and Boehringer Ingelheim; and has received consulting or speaking fees from Novo Nordisk, AstraZeneca, Pfizer, Sanofi, and Boehringer Ingelheim. Dr Lopes has received research grants or contracts from Amgen, Bristol Myers Squibb, GlaxoSmithKline, Medtronic, Pfizer, and Sanofi-Aventis; has received funding for educational activities or lectures from Pfizer, Daiichi-Sankyo, and Novo Nordisk; and has received funding for consulting or other services from Bayer, Boehringer Ingelheim, Bristol Myers Squibb, and Novo Nordisk. Dr Aylward has received research support from CSL and Janssen Advisory Board; and has received honoraria and speaker fees from Novartis, Boehringer Ingelheim, Amgen, and AstraZeneca. Dr Lincoff has received honoraria for consulting activities from Novo Nordisk, Eli Lilly, Akebia, Ardelyx, Becton Dickson, Endologix, Fibrogen, GlaxoSmithKline, Medtronic, Neovasc, Provention Bio, ReCor, Brainstorm Cell, Alnylam, and Intarcia; and has received research funding to his institution from AbbVie, Esperion, AstraZeneca, CSL Behring, Novartis, and Eli Lilly. Dr Heise is an employee of CSL Behring. Dr Sacks has received support from CSL Behring. Dr Nicolau is recipient of a scholarship from National Council of Scientific and Technological Development (Conselho Nacional de Desenvolvimento Científico e Tecnológico – CNPq) # 303448/2021-0; has received research grants from Amgen, AstraZeneca, Bayer, CSL Behring, Daiichi-Sankyo, Dalcor, Esperion, Ionis, Janssen, Novartis, Novo Nordisk, Sanofi, and Vifor; and has received consulting fees from Libbs. Prof Merkely has received direct personal payment (speaker fees, studies) from Abbott, AstraZeneca, Biotronik, Boehringer Ingelheim, CSL Behring, Daiichi-Sankyo, DUKE Clinical Institute, Medtronic, and Novartis; and has received institutional grants (for the Heart and Vascular Center of Semmelweis University) from Abbott, AstraZeneca, Biotronik, Boehringer Ingelheim, Boston Scientific, Bristol Myers Squibb, CSL Behring, Daiichi-Sankyo, DUKE Clinical Institute, Eli Lilly, Medtronic, Novartis, Terumo, and Vifor Pharma. Dr Trebacz has received research support from CSL Behring. Dr Libby is an unpaid consultant to, or involved in clinical trials for Amgen, AstraZeneca, Baim Institute, Beren Therapeutics, Esperion Therapeutics, Genentech, Kancera, Kowa Pharmaceuticals, Medimmune, Merck, Moderna, Novo Nordisk, Novartis, Pfizer, and Sanofi-Regeneron; and is a member of the scientific advisory board for Amgen, Caristo Diagnostics, Cartesian Therapeutics, CSL Behring, DalCor Pharmaceuticals, Eulicid Bioimaging, Kancera, Kowa Pharmaceuticals, Olatec Therapeutics, Medimmune, Novartis, PlaqueTec, TenSixteen Bio, Soley Therapeutics, and XBiotech, Inc; has received research funding to his laboratory in the past 2 years from Novartis, Novo Nordisk, and Genentech; is on the Board of Directors of XBiotech, Inc; has a financial interest in XBiotech, a company developing therapeutic human antibodies, in TenSixteen Bio, a company targeting somatic mosaicism and clonal hematopoiesis of indeterminate potential to discover and develop novel therapeutics to treat age-related diseases, and in Soley Therapeutics, a biotechnology company that is combining artificial intelligence with molecular and cellular response detection for discovering and developing new drugs, currently focusing on cancer therapeutics; and has received funding support from the NHLBI (1R01HL134892 and 1R01HL163099-01), the RRM Charitable Fund, and the Simard Fund. Dr Nicholls has received research support from AstraZeneca, Amgen, Anthera, CSL Behring, Cerenis, Cyclarity, Eli Lilly, Esperion, Resverlogix, New Amsterdam Pharma, Novartis, InfraReDx, and Sanofi-Regeneron; and has served as a consultant for Amgen, Akcea, AstraZeneca, Boehringer Ingelheim, CSL Behring, Eli Lilly, Esperion, Kowa, Merck, Takeda, Pfizer, Sanofi-Regeneron, Vaxxinity, CSL Sequiris, and Novo Nordisk. Dr Pocock has served as a consultant for CSL Behring as a member of executive and publications committees. Dr Bhatt discloses the following relationships: Advisory Board: Angiowave, Bayer, Boehringer Ingelheim, CellProthera, Cereno Scientific, Elsevier Practice Update Cardiology, High Enroll, Janssen, Level Ex, McKinsey, Medscape Cardiology, Merck, MyoKardia, NirvaMed, Novo Nordisk, PhaseBio, PLx Pharma, Stasys; Board of Directors: American Heart Association New York City, Angiowave (stock options), Bristol Myers Squibb (stock), DRS.LINQ (stock options), High Enroll (stock); Consultant: Broadview Ventures, GlaxoSmithKline, Hims, SFJ, Youngene; Data Monitoring Committees: Acesion Pharma, Assistance Publique-Hôpitaux de Paris, Baim Institute for Clinical Research (formerly Harvard Clinical Research Institute, for the PORTICO trial, funded by St. Jude Medical, now Abbott), Boston Scientific (Chair, PEITHO trial), Cleveland Clinic, Contego Medical (Chair, PERFORMANCE 2), Duke Clinical Research Institute, Mayo Clinic, Mount Sinai School of Medicine (for the ENVISAGE trial), funded by Daiichi-Sankyo; for the ABILITY-DM trial, funded by Concept Medical; for ALLAY-HF, funded by Alleviant Medical, Novartis, Population Health Research Institute; Rutgers University (for the NIH-funded MINT Trial); Honoraria: American College of Cardiology (Senior Associate Editor, Clinical Trials and News, ACC.org; Chair, ACC Accreditation Oversight Committee), Arnold and Porter law firm (work related to Sanofi/Bristol Myers Squibb clopidogrel litigation), Baim Institute for Clinical Research (formerly Harvard Clinical Research Institute; RE-DUAL PCI clinical trial steering committee funded by Boehringer Ingelheim; AEGIS-II executive committee funded by CSL Behring), Belvoir Publications (Editor in Chief, Harvard Heart Letter), Canadian Medical and Surgical Knowledge Translation Research Group (clinical trial steering committees), CSL Behring (AHA lecture), Cowen and Company, Duke Clinical Research Institute (clinical trial steering committees, including for the PRONOUNCE trial, funded by Ferring Pharmaceuticals), HMP Global (Editor in Chief, Journal of Invasive Cardiology), Journal of the American College of Cardiology (Guest Editor; Associate Editor), K2P (Co-Chair, interdisciplinary curriculum), Level Ex, Medtelligence/ReachMD (CME steering committees), MJH Life Sciences, Oakstone CME (Course Director, Comprehensive Review of Interventional Cardiology), Piper Sandler, Population Health Research Institute (for the COMPASS operations committee, publications committee, steering committee, and USA national co-leader, funded by Bayer), WebMD (CME steering committees), Wiley (steering committee); Other: Clinical Cardiology (Deputy Editor); Patent: Sotagliflozin (named on a patent for sotagliflozin assigned to Brigham & Women's Hospital who assigned to Lexicon; neither I nor Brigham & Women's Hospital receive any income from this patent); research funding: Abbott, Acesion Pharma, Afimmune, Aker Biomarine, Alnylam, Amarin, Amgen, AstraZeneca, Bayer, Beren, Boehringer Ingelheim, Boston Scientific, Bristol Myers Squibb, Cardax, CellProthera, Cereno Scientific, Chiesi, CinCor, Cleerly, CSL Behring, Eisai, Ethicon, Faraday Pharmaceuticals, Ferring Pharmaceuticals, Forest Laboratories, Fractyl, Garmin, HLS Therapeutics, Idorsia, Ironwood, Ischemix, Janssen, Javelin, Lexicon, Lilly, Medtronic, Merck, Moderna, MyoKardia, NirvaMed, Novartis, Novo Nordisk, Otsuka, Owkin, Pfizer, PhaseBio, PLx Pharma, Recardio, Regeneron, Reid Hoffman Foundation, Roche, Sanofi, Stasys, Synaptic, The Medicines Company, Youngene, 89Bio; royalties: Elsevier (Editor, Braunwald’s Heart Disease); site co-investigator: Abbott, Biotronik, Boston Scientific, CSI, Endotronix, St Jude Medical (now Abbott), Philips, SpectraWAVE, Svelte, Vascular Solutions; trustee: American College of Cardiology; unfunded research: FlowCo. Dr Kastelein has served on a clinical trials steering committee for Novartis, NewAmsterdam Pharma, and CSL Behring; has served as a consultant or speaker for Scribe, CiVi Biotech, Draupnir, 89Bio, and Esperion Therapeutics; and is Chief Science Officer at NewAmsterdam Pharma. Dr Bode has received research support from CSL Behring. Dr Mahaffey has received research funding from the American Heart Association, Apple, Inc, Bayer, California Institute of Regenerative medicine, CLS Behring, Eidos, Ferring, Gilead, Google (Verily), Idorsia, Johnson & Johnson, Luitpold, Novartis, PAC-12, Predordior, and Sanifit; has served as a consultant for Applied Therapeutics, Bayer, BMS, BridgeBio, CSL Behring, Elsevier, Fosun Pharma, Human, Johnson & Johnson, Moderna, Myokardia, Novartis, Novo Nordisk, Otsuka, Phasebio, Portola, Quidel, and Theravance; and has equity in Human, Medeloop, Precordior, and Regencor. Dr Steg has received research grants from Amarin and Sanofi; has served on clinical trials (steering committee, clinical events committee, data and safety monitoring board [DSMB]) for Amarin, Amgen, AstraZeneca, Bayer, Bristol Myers Squibb, CSL Behring, Idorsia, Janssen, Novartis, Novo Nordisk, Pfizer, and Sanofi; has served as a consultant or speaker for Amarin, Amgen, BMS, and Novo Nordisk; and is Senior Associate Editor at Circulation. Dr Tendera has received consultation fees from the PERFUSE Group for participation in the executive committee, sponsored by CSL Behring for meetings of the study; has received consultation fees from Bayer, Janssen-Cilag, Kowa, and Servier for activities unrelated to the study; and has received a lecture honorarium from Bayer. Dr Bainey has received research support from CSL Behring. Dr Harrington has research relationships with Baim Institute (DSMB), CSL (Randomized Controlled Trial [RCT] Executive Committee), Janssen (RCT Chair), NHLBI (RCT Executive Committee; DSMB Chair), PCORI (RCT Co-Chair), and DCRI; has served as a consultant for Atropos Health, Bitterroot Bio, BMS, BridgeBio, Element Science, Edwards Lifesciences, Foresite Labs, and Medscape/WebMD; and has served on the board of directors for American Heart Association, College of the Holy Cross, and Cytokinetics. Dr Mehran has received institutional research payments from Abbott, Abiomed, Affluent Medical, Alleviant Medical, Amgen, AM-Pharma, Arena, AstraZeneca, AtriCure Inc, Biosensors, Biotronik, Boston Scientific, Bristol Myers Squibb, CardiaWave, CeloNova, CERC, Chiesi, Cleerly Health Inc, Concept Medical, Cytosorbents, Daiichi-Sankyo, Duke, Element Science, Essential Medical, Faraday, Idorsia Pharmaceuticals, Janssen, MedAlliance, Mediasphere, Medtelligence, Medtronic, MJH Healthcare, Novartis, OrbusNeich, Penumbra, PhaseBio, Philips, Pi-Cardia, PLx Pharma, Population Health Research Institute, Protembis, RecCor Medical Inc, RenalPro, RM Global, Sanofi, Shockwave, Vivasure, and Zoll; has received personal fees from Affluent Medical, Boehringer Ingelheim, Cardiovascular Research Foundation (CRF), Cordis, Daiichi-Sankyo Brasil, E.R. Squibb & Sons, Esperion Science/Innovative Biopharma, Europa Group/Boston Scientific, Gaffney Events, Educational Trust, Henry Ford Health Cardiology, Ionis Pharmaceuticals, Lilly and Company, MedCon International, Novartis, Novo Nordisk, PeerView Institute for Medical Education, TERUMO Europe N.V., Vectura, VoxMedia, WebMD, IQVIA, Radcliffe, and TARSUS Cardiology; has served on the Scientific Advisory Board fpr AMA; has served as a Women in Innovations Committee Member for SCAI; has received faculty CRF honorarium from JAMA Cardiology (Associate Editor), ACC (BOT Member, SC Member CTR Program); and has equity <1% in Applied Therapeutics, Elixir Medical, Stel, CntrolRad (spouse). Dr Duerschmied has received speaker honoraria from Daiichi-Sankyo, Bayer Healthcare, Boston Scientific, Pfizer, and AOP Health; and has received consulting fees from Boston Scientific, CSL Behring, and Johnson & Johnson. Dr Kingwell is an employee and shareholder of CSL Ltd. Dr Gibson has received research funding from CSL Behring, Janssen Pharmaceuticals, Johnson & Johnson Corporation, and SCAD Alliance; has received consulting from Angel/Avertix Medical Corporation, AstraZeneca, Bayer Corporation, Beren Therapeutics, Boehringer Ingelheim, Boston Clinical Research Institute, Boston Scientific, Bristol Myers Squibb, Cardiovascular Research Foundation, CeleCor Therapeutics, CSL Behring, DCRI, Esperion, EXCITE International ($0 received), Fortress Biotech, Gilead Sciences, Inc, Janssen, Pharmaceuticals, Johnson & Johnson Corporation, MashUp MD, MD Magazine, Microport, MJHealth, Novartis, NovoNordisk, Pfizer, PHRI, PLxPharma, SCAI, Solstic Health/New Amsterdam Pharma, Somahlution/Marizyme, Vectura, Web MD, and Women as One; has equity in nference, Dyad Medical, Absolutys, Fortress Biotech; and has received royalties as contributor to UpToDate., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Little is known about the procedural characteristics, case volumes, and mortality rates for early- vs non-early-career interventional cardiologists in the United States., Objectives: This study examined operator-level data for patients who underwent percutaneous coronary intervention (PCI) between April 2018 and June 2022., Methods: Data were collected from the National Cardiovascular Data Registry CathPCI Registry, American Board of Internal Medicine certification database, and National Plan and Provider Enumeration System database. Early-career operators were within 5 years of the end of training. Annual case volume, expected mortality and bleeding risk, and observed/predicted mortality and bleeding outcomes were evaluated., Results: A total of 1,451 operators were early career; 1,011 changed their career status during the study; and 6,251 were non-early career. Overall, 514,540 patients were treated by early-career and 2,296,576 patients by non-early-career operators. The median annual case volume per operator was 59 (Q1-Q3: 31-97) for early-career and 57 (Q1-Q3: 28-100) for non-early-career operators. Early-career operators were more likely to treat patients presenting with ST-segment elevation myocardial infarction and urgent indications for PCI (both P < 0.001). The median predicted mortality risk was 2.0% (Q1-Q3: 1.5%-2.7%) for early-career and 1.8% (Q1-Q3: 1.2%-2.4%) for non-early-career operators. The median predicted bleeding risk was 4.9% (Q1-Q3: 4.2%-5.7%) for early-career and 4.4% (Q1-Q3: 3.7%-5.3%) for non-early-career operators. After adjustment, an increased risk of mortality (OR: 1.08; 95% CI: 1.05-1.17; P < 0.0001) and bleeding (OR: 1.08; 95% CI: 1.05-1.12; P < 0.0001) were associated with early-career status., Conclusions: Early-career operators are caring for patients with more acute presentations and higher predicted risk of mortality and bleeding compared with more experienced colleagues, with modestly worse outcomes. These data should inform institutional practices to support the development of early-career proceduralists., Competing Interests: Funding Support and Author Disclosures Funding was provided by the American College of Cardiology National Cardiovascular Data Registry. Dr Rymer has received research funding from the National Heart, Lung, and Blood Institute, Novo Nordisk, Chiesi, Abiomed, and Pfizer. Dr Damluji has received research funding from the Pepper Scholars Program of the Johns Hopkins University Claude D. Pepper Older Americans Independence Center funded by the National Institute on Aging P30-AG021334; and has received a mentored patient-oriented research career development award from the National Heart, Lung, and Blood Institute K23-HL153771-01. Dr Shah has received grant funding from the VA Office of Research and Development and National Institutes of Health/National Heart, Lung, and Blood Institute; and has served on the advisory board for Philips Volcano. Dr Nanna has received research support from the American College of Cardiology Foundation supported by the George F. and Ann Harris Bellows Foundation, the Patient-Centered Outcomes Research Institute (PCORI), the Yale Claude D. Pepper Older Americans Independence Center (P30AG021342), and the National Institute on Aging/National Institutes of Health from R03AG074067 (GEMSSTAR award); and has served as a consultant for Heartflow, Inc and Merck. Dr Kearney has performed consulting for and received honoraria from Abbott, Abiomed, Boston Scientific, Medtronic, Teleflex, and Philip. 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: The efficacy and safety of sacubitril/valsartan in patients hospitalized with heart failure (HF) across the spectrum of left ventricular ejection fraction (EF) has not been described., Objectives: Data from randomized trials of sacubitril/valsartan in HF patients with EF ≤40% (PIONEER-HF [Comparison of Sacubitril/Valsartan Versus Enalapril on Effect of NT-proBNP in Patients Stabilized From an Acute Heart Failure Episode] trial) and >40% (PARAGLIDE-HF [Prospective comparison of ARNI with ARB Given following stabiLization In DEcompensated HFpEF] trial) following recent worsening heart failure (WHF) were pooled to examine treatment effect across the EF spectrum., Methods: The PIONEER-HF and PARAGLIDE-HF trials were double-blind, randomized trials of sacubitril/valsartan vs control therapy (enalapril or valsartan, respectively). All participants in the PIONEER-HF trial and 69.5% in the PARAGLIDE-HF trial were enrolled during hospitalization for HF after stabilization. The remainder in the PARAGLIDE-HF trial were enrolled ≤30 days after a WHF event. The primary endpoint of both trials was time-averaged proportional change in N-terminal pro-B-type natriuretic peptide (NT-proBNP) from baseline through weeks 4 and 8. Adjudicated clinical endpoints were analyzed through the end of follow-up, adjusting for trial., Results: The pooled analysis included 1,347 patients (881 from PIONEER-HF, 466 from PARAGLIDE-HF). Baseline characteristics included median age 66 years, 36% women, 31% Black, 34% de novo HF, and median EF 30%. The reduction in NT-proBNP was 24% greater with sacubitril/valsartan vs control therapy (n = 1,130; ratio of change = 0.76; 95% CI: 0.69-0.83; P < 0.0001). Cardiovascular death or hospitalization for HF was reduced by 30% with sacubitril/valsartan vs control therapy (HR: 0.70; 95% CI: 0.54-0.91; P = 0.0077). This effect was consistent across the spectrum of EF ≤60%. Sacubitril/valsartan increased symptomatic hypotension (risk ratio: 1.35; 95% CI: 1.05-1.72)., Conclusions: In patients stabilized after WHF, sacubitril/valsartan led to a greater reduction in plasma NT-proBNP and improved clinical outcome compared with control therapy, in particular across the spectrum of EF ≤60%. (Comparison of Sacubitril/Valsartan Versus Enalapril on Effect of NT-proBNP in Patients Stabilized From an Acute Heart Failure Episode [PIONEER-HF]; NCT02554890; Changes in NT-proBNP, Safety, and Tolerability in HFpEF Patients With a WHF Event [HFpEF Decompensation] Who Have Been Stabilized and Initiated at the Time of or Within 30 Days Post-decompensation [PARAGLIDE-HF]; NCT03988634)., Competing Interests: Funding Support and Author Disclosures The PIONEER-HF and PARAGLIDE-HF trials were supported by Novartis Pharmaceuticals Corp. Drs Morrow and Park are members of the TIMI Study Group, which has received institutional research grant support through Brigham and Women’s Hospital from Abbott, Abiomed, Amgen, Anthos Therapeutics, ARCA Biopharma, AstraZeneca, Bayer HealthCare Pharmaceuticals, Daiichi-Sankyo, Eisai, Intarcia, Ionis Pharmaceuticals, Janssen Research and Development, Merck, Novartis, Pfizer, Quark Pharmaceuticals, Regeneron Pharmaceuticals, Roche, Siemens Healthcare Diagnostics, Softcell Medical Limited, and Zora Biosciences. Dr Morrow has received consulting fees from Abbott Laboratories, ARCA Biopharma, Inflammatix, Merck and Co, Novartis, Regeneron, and Roche Diagnostics. Dr Velazquez has received institutional research grant support and/or honoraria for serving on advisory boards from Novartis, Abiomed, Rednvia, and the National Heart, Lung, and Blood Institute/National Institutes of Health. Dr Desai has received research grants (to Brigham and Women’s Hospital) from Abbott, Alnylam, AstraZeneca, Bayer, and Novartis; and has received personal consulting fees from Abbott, Alnylam, AstraZeneca, Avidity Biopharma, Axon Therapeutics, Bayer, Biofourmis, Cytokinetics, GlaxoSmithKline, Medpace, Merck, New Amsterdam, Novartis, Parexel, Regeneron, River2Renal, Roche, Verily, and Veristat. Dr DeVore has received research funding through his institution from Biofourmis, Bodyport, Cytokinetics, American Regent, Inc, the National Institutes of Health and National Heart, Lung, and Blood Institute, Novartis, and Story Health; and has served as a consultant for and/or received honoraria from Abiomed, Cardionomic, LivaNova, Natera, Novo Nordisk, Story Health, and Zoll. Dr Sharma has served on the advisory board and/or as a consultant for Alleviant, AstraZeneca, Bayer, Boehringer Ingelheim, Edwards Lifesciences, Imbria, Novartis, Novo Nordisk, RIVUS, and ViCardia. Dr Solomon has received research grants from Alnylam, AstraZeneca, Bellerophon, Bayer, Bristol Myers Squibb, Cytokinetics, Eidos, GlaxoSmithKline, Ionis, Lilly, MyoKardia, National Institutes of Health/National Heart, Lung, and Blood Institute, Novartis, Novo Nordisk, Respicardia, Sanofi Pasteur, Theracos, Actelion, Amgen, Bellerophon, Celladon, Gilead, Mesoblast, Neurotronik, and US2; and has served as a consultant for Abbott, Action, Akros, Alnylam, Amgen, Arena, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Cardior, Cardurion, Corvia, Cytokinetics, Daiichi-Sankyo, GlaxoSmithKline, Lilly, Merck, MyoKardia, Novartis, Roche, Theracos, Quantum Genomics, Cardurion, Janssen, Cardiac Dimensions, Tenaya, Sanofi Pasteur, Dinaqor, Tremeau, CellProThera, Moderna, American Regent, Sarepta, Lexicon, Anacardio, Akros, and Valo. Dr Starling has served on the steering committee for the PARAGLIDE trial sponsored by Novartis and for the RESPONDER HF trial sponsored by Corvia Medical. Drs Ward and Williamson are employees of Novartis. Dr Zieroth has received research grant support from, served on advisory boards for, or served as a speaker for Abbott, Akcea AstraZeneca, Amgen, Alnylam, Bayer, Bristol Myers Squibb, Boehringer Ingelheim, Eli Lilly, GlaxoSmithKline, Janssen, Merck, Novartis, Novo Nordisk, Otsuka, Pfizer, Roche, Servier, and Vifor Pharma; and has served on a clinical trial committee or as a national lead for studies sponsored by AstraZeneca, Bayer, Boehringer Ingelheim, Merck, Novartis, and Pfizer. Dr Hernandez has received research grants from American Regent, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Cytokinetics, Merck, Novartis, Novo Nordisk, Somologic, and Verily; and has served as a consultant for Amgen, AstraZeneca, Bayer, Bristol Myers Squibb, Boehringer Ingelheim, Boston Scientific, Cytokinetics, Intellia, Merck, Novartis, and Novo Nordisk. Dr Mentz has received research support and/or honoraria from Novartis, Abbott, American Regent, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Boston Scientific, Cytokinetics, Fast BioMedical, Gilead, Innolife, Eli Lilly, Medtronic, Medable, Merck, Novo Nordisk, Pharmacosmos, Relypsa, Respicardia, Roche, Sanofi, Vifor, Windtree Therapeutics, and Zoll. Dr Braunwald has received grant support to his institution from Novartis for the conduct of the PIONEER-HF trial, for serving on the Executive Committee of the PARADISE-MI trial and the Steering Committee of the PARAGLIDE-HF trial, and for participation in an advisory board meeting; and has served as a consultant for Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Cardurion, Edgewise, and Verve. Dr Lepage has reported that he has 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: In the ISCHEMIA (International Study of Comparative Health Effectiveness with Medical and Invasive Approaches) trial, the risk of ischemic events was similar in patients with stable coronary artery disease treated with an invasive (INV) strategy of angiography and percutaneous coronary intervention (PCI) or surgical (coronary artery bypass grafting [CABG]) coronary revascularization and a conservative (CON) strategy of initial medical therapy., Objectives: The authors analyzed separately the outcomes of INV patients treated with PCI or CABG., Methods: Patients without preceding primary outcome events were categorized as INV-PCI or INV-CABG from the time of revascularization. The ISCHEMIA primary outcome (composite of cardiovascular death, protocol-defined myocardial infarction or hospitalization for unstable angina, heart failure, or resuscitated cardiac arrest) was used., Results: Among INV-CABG patients, primary outcome events occurred in 84 of 512 (16.4%) at a median follow-up of 2.85 years; 48 events (57.1%) occurred within 30 days after CABG, including 40 procedural MIs. Among INV-PCI patients, primary outcome events occurred in 147 of 1,500 (9.8%) at median follow-up of 2.94 years; 31 of which (21.1%) occurred within 30 days after PCI, including 24 procedural MIs. In comparison, 352 of 2,591 CON patients (13.6%) had primary outcome events at a median follow-up of 3.2 years, 22 of which (6.3%) occurred within 30 days of randomization. The adjusted primary outcome risks were higher after both CABG and PCI within 30 days (HR: 16.25 [95% CI: 11.44-23.07] and HR: 2.99 [95% CI: 1.97-4.53]) and lower thereafter (0.63 [95% CI: 0.44-0.89] and 0.66 [95% CI: 0.53-0.82])., Conclusions: In ISCHEMIA, early revascularization by PCI and CABG was associated with higher early risks and lower long-term risks of cardiovascular events compared with CON. The early risk was greatest after CABG, owing to protocol-defined procedural MIs., Competing Interests: Funding Support and Author Disclosures Dr Redfors has received grant support from the European Research Council, the Swedish Scientific Council, Swedish Heart and Lung Foundation, and the Swedish Society for Medical Research; and receives consulting payments from Pfizer and Boehringer Ingelheim. Dr Stone has received speaker honoraria from Medtronic, Pulnovo, Infraredx, Abiomed, Amgen, and Boehringer Ingelheim; has served as a consultant to Abbott, Daiichi-Sankyo, Ablative Solutions, CorFlow, Cardiomech, Robocath, Miracor, Vectorious, Apollo Therapeutics, Valfix, TherOx, HeartFlow, Neovasc, Ancora, Elucid Bio, Occlutech, Impulse Dynamics, Adona Medical, Millennia Biopharma, Oxitope, Cardiac Success, and HighLife; has equity/options from Ancora, Cagent, Applied Therapeutics, Biostar family of funds, SpectraWave, Orchestra Biomed, Aria, Cardiac Success, Valfix, and Xenter; and his employer, Mount Sinai Hospital, receives research grants from Abbott, Abiomed, Bioventrix, Cardiovascular Systems Inc, Phillips, Biosense Webster, Shockwave, Vascular Dynamics, Pulnovo, and V-wave. Dr Alexander receives research grant funding through Duke University from Artivion/CryoLife, Bayer, Bristol Myers Squibb, CSL Behring, Ferring, U.S. FDA, Humacyte, U.S. NIH, and XaTek; and has received consulting or advisory board payments from AbbVie, Akros, Artivion/CryoLife, AtriCure, Bayer, Bristol Myers Squibb, Ferring, GlaxoSmithKline, Janssen, Novostia, Pfizer, Portola, Quantum Genomics, Theravance, and Veralox. Dr Bates has served on the Advisory Board for Angiowave, Bayer, Boehringer Ingelheim, CellProthera, Cereno Scientific, Elsevier Practice Update Cardiology, High Enroll, Janssen, Level Ex, McKinsey, Medscape Cardiology, Merck, MyoKardia, NirvaMed, Novo Nordisk, PhaseBio, PLx Pharma, and Stasys; has served on the Board of Directors for the American Heart Association New York City, Angiowave, Bristol Myers Squibb, DRS.LINQ, and High Enroll; has stock in Angiowave, Bristol Myers Squibb, DRS.LINQ, and High Enroll; has been a consultant for Broadview Ventures, Hims, SFJ, and Youngene; has served on the Data Monitoring Committees for Acesion Pharma, Assistance Publique-Hôpitaux de Paris, Baim Institute for Clinical Research (formerly Harvard Clinical Research Institute, for the PORTICO trial, funded by St. Jude Medical (now Abbott), Boston Scientific (Chair, PEITHO trial), Cleveland Clinic, Contego Medical (Chair, PERFORMANCE 2), Duke Clinical Research Institute, Mayo Clinic, Mount Sinai School of Medicine (for the ENVISAGE trial, funded by Daiichi-Sankyo, for the ABILITY-DM trial, funded by Concept Medical; and for ALLAY-HF, funded by Alleviant Medical), Novartis, Population Health Research Institute; Rutgers University (for the NIH-funded MINT Trial); has received honoraria from the American College of Cardiology (Senior Associate Editor, Clinical Trials and News, ACC.org; Chair, ACC Accreditation Oversight Committee), Arnold and Porter law firm (work related to Sanofi/Bristol Myers Squibb clopidogrel litigation), Baim Institute for Clinical Research (formerly Harvard Clinical Research Institute; RE-DUAL PCI clinical trial steering committee funded by Boehringer Ingelheim; AEGIS-II executive committee funded by CSL Behring), Belvoir Publications (Editor-in-Chief, Harvard Heart Letter), Canadian Medical and Surgical Knowledge Translation Research Group (clinical trial steering committees), CSL Behring (AHA lecture), Cowen and Company, Duke Clinical Research Institute (clinical trial steering committees, including for the PRONOUNCE trial, funded by Ferring Pharmaceuticals), HMP Global (Editor-in-Chief, Journal of Invasive Cardiology), Journal of the American College of Cardiology (Guest Editor; Associate Editor), K2P (Co-Chair, interdisciplinary curriculum), Level Ex, Medtelligence/ReachMD (CME steering committees), MJH Life Sciences, Oakstone CME (Course Director, Comprehensive Review of Interventional Cardiology), Piper Sandler, Population Health Research Institute (for the COMPASS operations committee, publications committee, steering committee, and USA national co-leader, funded by Bayer), WebMD (CME steering committees), Wiley (steering committee), Clinical Cardiology (Deputy Editor); has a patent: sotagliflozin (named on a patent for sotagliflozin assigned to Brigham and Women's Hospital who assigned to Lexicon, neither I nor Brigham and Women's Hospital receive any income from this patent); has received research funding from Abbott, Acesion Pharma, Afimmune, Aker Biomarine, Alnylam, Amarin, Amgen, AstraZeneca, Bayer, Beren, Boehringer Ingelheim, Boston Scientific, Bristol Myers Squibb, Cardax, CellProthera, Cereno Scientific, Chiesi, CinCor, Cleerly, CSL Behring, Eisai, Ethicon, Faraday Pharmaceuticals, Ferring Pharmaceuticals, Forest Laboratories, Fractyl, Garmin, HLS Therapeutics, Idorsia, Ironwood, Ischemix, Janssen, Javelin, Lexicon, Lilly, Medtronic, Merck, Moderna, MyoKardia, NirvaMed, Novartis, Novo Nordisk, Otsuka, Owkin, Pfizer, PhaseBio, PLx Pharma, Recardio, Regeneron, Reid Hoffman Foundation, Roche, Sanofi, Stasys, Synaptic, The Medicines Company, Youngene, and 89Bio; has received royalties from Elsevier (Editor, Braunwald’s Heart Disease); served as a site co-investigator for Abbott, Biotronik, Boston Scientific, CSI, Endotronix, St. Jude Medical (now Abbott), Philips, SpectraWAVE, Svelte, and Vascular Solutions; has served as a trustee for the American College of Cardiology; and has received unfunded research from FlowCo. Dr Biondi-Zoccai has consulted for Amarin, Balmed, Cardionovum, Crannmedical, Endocore Lab, Eukon, Guidotti, Innovheart, Meditrial, Microport, Opsens Medical, Terumo, and Translumina. Dr Caldonazo is supported by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) Clinician Scientist Program OrganAge funding number 413668513, by the Deutsche Herzstiftung (DHS, German Heart Foundation) funding number S/03/23 and by the Interdisciplinary Center of Clinical Research of the Medical Faculty Jena. Dr Gaudino receives grant support from the National Institute of Health, the Canadian Institutes of Health and Research, and the Starr Foundation. 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.)

For most patients, direct oral anticoagulants (DOACs) are preferred over vitamin K antagonists for stroke prevention in atrial fibrillation and for venous thromboembolism treatment. However, randomized controlled trials suggest that DOACs may not be as efficacious or as safe as the current standard of care in conditions such as mechanical heart valves, thrombotic antiphospholipid syndrome, and atrial fibrillation associated with rheumatic heart disease. DOACs do not provide a net benefit in conditions such as embolic stroke of undetermined source. Their efficacy is uncertain for conditions such as left ventricular thrombus, catheter-associated deep vein thrombosis, cerebral venous sinus thrombosis, and for patients with atrial fibrillation or venous thrombosis who have end-stage renal disease. This paper provides an evidence-based review of randomized controlled trials on DOACs, detailing when they have demonstrated efficacy and safety, when DOACs should not be the standard of care, where their safety and efficacy are uncertain, and areas requiring further research., Competing Interests: Funding Support and Author Disclosures Dr Piazza has received research support paid to his institution from Bristol Myers Squibb/Pfizer Alliance, Bayer, Janssen, Alexion, Amgen, and Boston Scientific Corporation; and has received consulting fees from Pfizer, Boston Scientific Corporation, Janssen, and Amgen. Dr Fanikos has served as a consultant to AstraZeneca, Mallinckrodt, and Pfizer. Dr Connors has received research funding to her institution from CSL Behring; has received consulting fees from Abbott; has received honoraria for lectures from Bristol Myers Squibb, Roche, and Sanofi; and has participated on the advisory board of Abbott, Alnylam, Anthos, Bristol Myers Squibb, Sanofi, and Takeda, outside of the submitted work. Dr Siegal is supported by a Tier 2 Canada Research Chair in Anticoagulant Management of Cardiovascular Disease; declares that she has received honoraria paid indirectly to her research institute from AstraZeneca, Bristol Myers Squibb-Pfizer, Roche, and Servier. Dr Barnes has served as a consultant for Pfizer, Bristol Myers Squibb, Janssen, Bayer, AstraZeneca, Sanofi, Anthos, Boston Scientific, and Abbott Vascular; and has received grant funding from Boston Scientific. Dr Martin is supported by National Institutes of Health K23HL157758; and has received research support paid to her institution from Janssen Scientific Affairs. Dr Angiolillo has received consulting fees or honoraria from Abbott, Amgen, AstraZeneca, Bayer, Biosensors, Boehringer Ingelheim, Bristol Myers Squibb, Chiesi, CSL Behring, Daiichi-Sankyo, Eli Lilly, Haemonetics, Janssen, Merck, Novartis, PhaseBio, PLx Pharma, Pfizer, Sanofi, and Vectura; and his institution has received research grants from Amgen, AstraZeneca, Bayer, Biosensors, CeloNova, CSL Behring, Daiichi-Sankyo, Eisai, Eli Lilly, Gilead, Idorsia, Janssen, Matsutani Chemical Industry Co, Merck, Novartis, and the Scott R. MacKenzie Foundation. Dr Kleindorfer has received other support from the University of Michigan College of Medicine. Dr Monreal has received unrestricted grants for research from Sanofi, Leo and Rovi; and has participated in advisory meetings sponsored by Sanofi. Dr Jimenez has served as an advisor or consultant for Pfizer and Sanofi; and has served as a speaker or a member of a Speakers Bureau for Bristol Myers Squibb, Pfizer and Sanofi. Dr Middeldorp has received grants and personal fees from Daiichi-Sankyo, Bayer, Pfizer, and Boehringer Ingelheim; and has received personal fees from Portola/Alexion, Abbvie, Pfizer/Bristol Myers Squibb, Norgine, Viatris, and Sanofi, all paid to her institution and outside of the submitted work. Dr Elkind has received study drug in kind from the Bristol Myers Squibb-Pfizer Alliance; has received ancillary research funding from Roche for a National Institutes of Health-funded trial of stroke prevention; and has received royalties from UpToDate for chapters on stroke. Dr Elkind has received study drug in kind from the Bristol Myers Squibb-Pfizer Alliance and ancillary research funding from Roche for a National Institutes of Health-funded trial of stroke prevention, and royalties from UpToDate for chapters on stroke. Dr Ruff is a member of the TIMI Study Group, which has received institutional research grant support through Brigham and Women’s Hospital from Abbott, Amgen, Anthos Therapeutics, ARCA Biopharma, Inc, AstraZeneca, Bayer HealthCare Pharmaceuticals, Inc, Daiichi-Sankyo, Eisai, Intarcia, Ionis Pharmaceuticals, Inc, Janssen Research and Development, LLC, MedImmune, Merck, Novartis, Pfizer, Quark Pharmaceuticals, Regeneron Pharmaceuticals, Inc, Roche, Siemens Healthcare Diagnostics, Inc, Softcell Medical Limited, The Medicines Company, and Zora Biosciences. Dr Goldhaber has received research support from Bayer, Bristol Myers Squibb, Boston Scientific BTG EKOS, Janssen, National Heart, Lung, and Blood Institute, and Pfizer; and has received consulting fees from Agile, Bayer, and Pfizer, outside of the submitted work. In the past 3 years, Dr Krumholz has received expenses and/or personal fees from UnitedHealth, Element Science, Eyedentifeye, and F-Prime; is a co-founder of Refactor Health and HugoHealth; and is associated with contracts, through Yale New Haven Hospital, from the Centers for Medicare and Medicaid Services and through Yale University from Janssen, Google, and Pfizer. Dr Mehran has received institutional research payments from Abbott, Abiomed, Alleviant Medical, Amgen, AM-Pharma, Arena, AstraZeneca, AtriCure Inc, Biosensors, Biotronik, Boston Scientific, Bristol Myers Squibb, CardiaWave, CeloNova, Chiesi, Concept Medical, Cytosorbents, Daiichi-Sankyo, Element Science, Faraday, Humacyte, Idorsia Pharmaceuticals, Janssen, Magenta, MedAlliance, Mediasphere, Medtelligence, Medtronic, MJH Healthcare, Novartis, OrbusNeich, Penumbra, PhaseBio, Philips, Pi-Cardia, PLx Pharma, Protembis, RenalPro, RM Global, Shockwave, Vivasure, Zoll; has received personal fees from Ionis Pharmaceuticals, J-CalC, Novartis, NovoNordisk, Vectura, VoxMedia, WebMD, IQVIA, McVeigh Global, Overcome, Primer Healthcare of New Jersey, Radcliffe, SL Solutions, TARSUS Cardiology, and Esperion Science/Innovative Biopharma; has received honoraria from JAMA Cardiology (Associate Editor) and the ACC (BOT Member, SC Member CTR Program); and has equity <1% in Applied Therapeutics, Elixir Medical, Stel, ControlRad (spouse). Dr Eikelboom has received fees, honoraria and/or research support from Anthos, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, DSI, Janssen, Pfizer, Servier, and Takeda. Dr Lip is a consultant and speaker for Bristol Myers Squibb/Pfizer, Boehringer Ingelheim, Daiichi-Sankyo, and Anthos, no fees are received personally; and is coprincipal investigator of the AFFIRMO project on multimorbidity in AF, which has received funding from the European Union’s Horizon 2020 research and innovation program under grant agreement #899871. Dr Weitz has served as a consultant and has received honoraria from Alnylam, Anthos, Bayer, Bristol Myers Squibb, Ionis, Janssen, Merck, Pfizer, Regeneron, and Servier. Dr Lopes reports research grants or contracts from Amgen, Bristol Myers Squibb, GlaxoSmithKline, Medtronic, Pfizer, Sanofi; funding for educational activities or lectures from Pfizer, Bristol Myers Squibb, Novo Nordisk, and AstraZeneca; and has received funding for consulting from Bayer, Boehringer Ingelheim, Bristol Myers Squibb, NovoNordisk, and AstraZeneca. Dr Bikdeli is supported by a Career Development Award from the American Heart Association and VIVA Physicians (#938814); was supported by the Scott Schoen and Nancy Adams IGNITE Award; is supported by the Mary Ann Tynan Research Scientist award from the Mary Horrigan Connors Center for Women’s Health and Gender Biology at Brigham and Women’s Hospital, and the Heart and Vascular Center Junior Faculty Award from Brigham and Women’s Hospital; is a consulting expert, on behalf of the plaintiff, for litigation related to 2 specific brand models of IVC filters; has not been involved in the litigation in 2022 or 2023 nor has he received any compensation in 2022 or 2023; is a member of the Medical Advisory Board for the North American Thrombosis Forum; and serves in the Data Safety and Monitory Board of the NAIL-IT trial funded by the National Heart, Lung, and Blood Institute, and Translational Sciences. All other authors have reported that they have no relationships related to the contents of this paper to disclose., (Copyright © 2024 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Atrial fibrillation is the most common atrial arrhythmia and accounts for a significant burden of cardiovascular disease globally. With advances in implanted and wearable cardiac monitoring technology, it is now possible to readily and accurately quantify an individual's time spent in atrial fibrillation. This review summarizes the relationship between atrial fibrillation burden and adverse cardiovascular and cerebrovascular outcomes and discusses the role of catheter ablation to mitigate the morbidity and mortality associated with greater burden of atrial fibrillation., Competing Interests: Funding Support and Author Disclosures Dr Andrade has received grants and personal fees from Medtronic; has received grants from Baylis; and has received personal fees from Biosense-Webster. Dr Wood has received honoraria for speaking/consulting from Milestone Pharmaceuticals. Dr Piccini is supported by R01AG074185 from the National Institutes of Aging; has received grants for clinical research from Abbott, the American Heart Association, the Association for the Advancement of Medical Instrumentation, Bayer, Boston Scientific, iRhythm, and Philips; and has served as a consultant to Abbott, AbbVie, ARCA Biopharma, Bayer, Boston Scientific, Bristol Myers Squibb (Myokardia), Element Science, Itamar Medical, LivaNova, Medtronic, Milestone, ElectroPhysiology Frontiers, ReCor, Sanofi, Philips, and Up-to-Date. Dr Schwennesen has reported that she has no relationships relevant to the contents of this paper to disclose., (Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Sodium-glucose cotransporter-2 (SGLT2) inhibitors and GLP-1 receptor agonists (GLP-1 RAs) reduce adverse cardiovascular outcomes in type 2 diabetes (T2D). However, the efficacy of combination therapy is unclear., Objectives: The aim of this study was to evaluate the effects of GLP-1 RAs on cardiovascular outcomes in patients with T2D treated with or without SGLT2 inhibitors., Methods: Post hoc analysis of Harmony Outcomes (Albiglutide and Cardiovascular Outcomes in Patients With Type 2 Diabetes and Cardiovascular Disease) evaluating the effect of albiglutide in T2D with cardiovascular disease by background SGLT2 inhibitor use. Additionally, a trial-level meta-analysis of Harmony Outcomes and AMPLITUDE-O (Effect of Efpeglenatide on Cardiovascular Outcomes), which evaluated T2D with cardiovascular or renal disease, was performed, combining the treatment effect estimates according to SGLT2 inhibitor use., Results: Of the 9,462 participants in Harmony Outcomes, 575 (6.1%) were treated with SGLT2 inhibitors at baseline. The effect of albiglutide on reducing the composite of cardiovascular death, myocardial infarction, or stroke (major adverse cardiovascular events) was consistent with or without SGLT2 inhibitors (P interaction = 0.70). The effect of albiglutide on secondary outcomes and adverse events was not modified by SGLT2 inhibitors. A meta-analysis of Harmony Outcomes and AMPLITUDE-O included 13,538 patients, of whom 1,193 (8.8%) used SGLT2 inhibitors. Compared to placebo, GLP1-RAs reduced major adverse cardiovascular events without effect modification by SGLT2 inhibitor use (HR: 0.77; 95% CI: 0.68-0.87 without SGLT2 inhibitors; and HR: 0.78; 95% CI: 0.49-1.24 with SGLT2 inhibitors) (P for interaction = 0.95) and reduced heart failure hospitalization (HR: 0.72; 95% CI: 0.55-0.92 vs HR: 0.34; 95% CI: 0.12-0.96) (P for interaction = 0.18)., Conclusions: In patients with T2D and cardiovascular disease, GLP-1 RAs reduced cardiovascular events independently of SGLT2 inhibitor use. These findings suggest that the combination of GLP-1 RAs with SGLT2 inhibitors may further reduce cardiovascular risk. Clinical trials with combination therapy are needed., Competing Interests: Funding Support and Author Disclosures This study was supported by national funds through Fundação para a Ciência e a Tecnologia, I.P., under the scope of the Cardiovascular R&D Center-Cardiovascular R&D Unit (UIDB/00051/2020 and UIDP/00051/2020). Dr Neves has received consulting or speaker fees from AstraZeneca, BIAL, Boehringer Ingelheim, Lilly, Merck, and Novo Nordisk. Dr Borges Canha has received speaker fees from AstraZeneca and Medinfar. Dr Green has received institutional grant funding from Boehringer Ingelheim–Lilly, Merck, Roche, and Sanofi and Lexicon; and has received consultancy fees from Boehringer Ingelheim–Lilly, Bayer, AstraZeneca, Sanofi and Lexicon, Hawthorne Effect and Omada, Pfizer, Valo, Anji, Vertex, and Novo Nordisk. Dr Leiter has received research funding from, has provided continuing medical education on behalf of, and/or has acted as an advisor to AstraZeneca, Boehringer Ingelheim, Eli Lilly, GSK, Lexicon, Merck, Novo Nordisk, Pfizer, Sanofi, and Servier. Dr Granger has received research grants from AKROS, Apple, AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Daiichi-Sankyo, Duke Clinical Research Institute, the U.S. Food and Drug Administration, GlaxoSmithKline, Janssen Pharmaceutical Products, LP, Medtronic Foundation, Novartis Pharmaceuticals, and Pfizer; and has received consulting fees from AbbVie, Abiomed, Anthos Therapeutic, LLC, Bayer Corporation, Boehringer Ingelheim, Boston Scientific Corporation, Bristol Myers Squibb, CeleCor Therapeutics, Correvio, Espero BioPharma, Janssen Pharmaceutica Products, LP, Medscape, LLC, Medtronic Inc, Merck, Novo Nordisk, Novartis Pharmaceutical Company, Pfizer, Phillips, Rhoshan Pharmaceuticals, and Roche Diagnostics. Dr Carvalho has received consulting or speaker fees from AstraZeneca, BIAL, Boehringer Ingelheim, Eli Lilly, GlaxoSmithKline, Merck, Merck Co, Medinfar, Novo Nordisk, and Sanofi. Dr Hernandez has received grants from Amgen, Bayer, Boehringer Ingelheim, Merck Sharp & Dohme, Novartis, Pfizer and Verily; and has received consulting fees from AstraZeneca, Boehringer Ingelheim, Merck Sharp & Dohme, Novartis Pharmaceuticals, and Novo Nordisk. Dr Del Prato has received grants from AstraZeneca and Boehringer Ingelheim; has received consulting fees from Applied Therapeutics, AstraZeneca, Boehringer Ingelheim, Eli Lilly and Company, Hengrui Pharmaceuticals Co, Menarini International, Merck Sharp & Dohme, Novartis Pharmaceuticals, Novo Nordisk, and Sanofi; and has received honoraria for lectures from AstraZeneca, Boehringer Ingelheim, Eli Lilly and Company, Merck Sharp & Dohme, Novartis Pharmaceuticals, Novo Nordisk, and Sanofi. Dr McMurray has received institutional grant funding from AstraZeneca; has received consultancy fees from Abbott, Alkem Metabolics, Eris Lifesciences, Hikma, Lupin, Sun Pharmaceuticals, Heart.Org (Medscape Cardiology), ProAdWise Communications, Radcliffe Cardiology, Servier, and The Corpus; and has received fees paid to his institution for other advisory roles by Cytokinetics, Amgen, AstraZeneca, Theracos, Ionis Pharmaceuticals, DalCor, Cardurion, Novartis, GlaxoSmithKline, Bayer, KBP Biosciences, Boehringer Ingelheim, and Bristol Myers Squibb. Dr Ferreira is a consultant for Boehringer Ingelheim; and has received research support from AstraZeneca and Novartis. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Infection remains a serious complication associated with the cardiac implantable electronic devices (CIEDs), leading to substantial clinical and economic burden globally. This review assesses the burden of cardiac implantable electronic device infection (CIED-I), evidence for treatment recommendations, barriers to early diagnosis and appropriate therapy, and potential solutions. Multiple clinical practice guidelines recommended complete system and lead removal for CIED-I when appropriate. CIED extraction for infection has been consistently reported with high success, low complication, and very low mortality rates. Complete and early extraction was associated with significantly better clinical and economic outcome compared with no or late extraction. However, significant gaps in knowledge and poor recommendation compliance have been reported. Barriers to optimal management may include diagnostic delay, knowledge gaps, and limited access to expertise. A multipronged approach, including education of all stakeholders, a CIED-I alert system, and improving access to experts, could help bring paradigm shift in the treatment of this serious condition., Competing Interests: Funding Support and Author Disclosures This work was supported by Philips Image Guided Therapy Corporation. Dr Lakkireddy is a consultant for Philips and Abbott; and has received honoraria from Abbott, Medtronic, Boston Scientific, and Biosense Webster. Dr Sood is an employee of Philips Image Guided Therapy Corporation. Dr Wu is an employee of EVERSANA which has received funding from Philips Image Guided Therapy Corporation. Dr Rao has received honoraria from Medtronic, Boston Scientific, and Philips for educational activity and consultancy. Dr Sohail is a consultant for Medtronic Inc, Philips, and Aziyo Biologics, Inc. Dr Pokorney receives modest consultant/advisory board support from Boston Scientific, Medtronic, Philips, Bristol Myers Squibb, Pfizer, Sanofi, and Zoll; and has received modest research support from the Food and Drug Administration, Bristol Myers Squibb, Pfizer, Janssen, Gilead, Philips, Sanofi, and Boston Scientific. Dr Blomström-Lundqvist is a consultant for Boston Scientific, Medtronic, Philips, Bristol Myers Squibb, and Cathprint. Dr Piccini is a consultant for Abbott, Biotronik, Boston Scientific, Medtronic, and Philips; has received grants for clinical research from Abbott, American Heart Association, Boston Scientific, and Philips; and is supported by R01AG074185 from the National Institutes of Aging. Dr Granger has clinical research contracts from Boehringer Ingelheim, CeleCor, Bayer, Bristol Myers Squibb, the U.S. Food and Drug Administration, National Institutes of Health, Pfizer, Janssen, and Phillips; has received consulting/honoraria from AbbVie, Bayer, Bristol Myers Squibb, Boston Scientific, Boehringer Ingelheim, Hengrui, Janssen, Pfizer, Lilly, Medtronic, Merck, Novartis, NovoNordisk, and Reata; and has equity from tenac.io. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Few data exist regarding the implementation of high-sensitivity cardiac troponin (hs-cTn) assays in the United States since their approval., Objectives: This study sought to explore trends in hs-cTn assay implementation over time and assess the association of their use with in-hospital cardiac testing and outcomes., Methods: The study examined trends in implementation of hs-cTn assays among participating hospitals in the National Cardiovascular Data Registry Chest Pain-MI [Myocardial Infarction] Registry from January 1, 2019 through September 30, 2021. Associations among hs-cTn use, use of in-hospital diagnostic imaging, and patient outcomes were assessed using generalized estimating equation models with logistic or gamma distributions., Results: Among 550 participating hospitals (N = 251,000), implementation of hs-cTn assays increased from 3.3% in the first quarter of 2019 to 32.6% in the third quarter of 2021 (P trend  < 0.001). Use of hs-cTn was associated with more echocardiography among persons with non-ST-segment elevation acute coronary syndrome (NSTE-ACS; 82.4% vs 75.0%; adjusted odds ratio: 1.43; 95% CI: 1.19-1.73) but not among low-risk chest pain individuals. Use of hs-cTn was associated with less invasive coronary angiography among low-risk patients (3.7% vs 4.5%; adjusted odds ratio: 0.73; 95% CI: 0.58-0.92) but similar use for patients with NSTE-ACS. There was no association between hs-cTn use and noninvasive stress testing or coronary computed tomography angiography testing. Among individuals with NSTE-ACS, hs-cTn use was not associated with revascularization or in-hospital mortality. Use of hs-cTn was associated with a shorter length of stay (median 47.6 hours vs 48.0 hours; ratio: 0.94; 95% CI: 0.90-0.98)., Conclusions: Implementation of hs-cTn among U.S. hospitals is increasing, but most U.S. hospitals continue to use less sensitive assays. The use of hs-cTn was associated with modestly shorter length of stay, greater use of echocardiography for NSTE-ACS, and less use of invasive angiography among low-risk patients., Competing Interests: Funding Support and Author Disclosures This research was supported by the American College of Cardiology’s National Cardiovascular Data Registry (NCDR). The views expressed in this manuscript represent those of the author(s) and do not necessarily represent the official views of the NCDR or its associated professional societies identified at CVQuality.ACC.org/NCDR. Dr McCarthy has received support from the National Heart, Lung, and Blood Institute (NHLBI) T32 postdoctoral training grant (5T32HL094301-12); and has received consulting income from Abbott Laboratories. Dr Wang has received research grants to the Duke Clinical Research Institute from Abbott, AstraZeneca, Bristol Myers Squibb, Boston Scientific, Cryolife, Chiesi, Merck, Portola, and Regeneron; and has received consulting honoraria from AstraZeneca, Bristol Myers Squibb, Cryolife, and Novartis. Dr Sandoval has served on advisory boards for Roche Diagnostics and Abbott Diagnostics without personal financial compensation; and has also been a speaker without personal financial compensation for Abbott Diagnostics. Dr Smilowitz has received partial support from a Career Development Award from NHLBI (K23HL150315); and has received consulting honoraria from Abbott Vascular. Dr Wasfy has received support from the American Heart Association (18 CDA 34110215). Dr de Lemos has received grant support from Abbott Diagnostics and Roche Diagnostics; and has received consulting income from Ortho Clinical Diagnostics, Quidel, Beckman Coulter, and Siemens’s Health Care Diagnostics. Dr Kontos has served as chair of the Chest Pain-MI Steering committee. Dr Apple has served as an Associate Editor of Clinical Chemistry; has participated in the advisory boards of Werfen, Siemens Healthineers, and Qorvo Biotechnology; has received consulting income from AWE Medical and Hytest; and has received cardiac biomarker grant support (nonsalaried) through his institutional research institute from Abbott Diagnostics, Abbott POC, Siemens Healthcare, Ortho-Clinical Diagnostics, Roche Diagnostics, Beckman Coulter, BD, and Quidel. Dr Daniels has received consulting income from Quidel, Roche, and Siemens; and has participated in clinical endpoint committees or data safety monitoring boards for Abbott, Applied Therapeutics, and Quidel. Dr Newby has received research grant support from Roche Diagnostics and BioKier; and has received consulting honoraria from Beckman-Coulter, CSL, and Medtronic. Dr Jaffe has served as a consultant for Abbott, Beckman-Coulter, Siemens, Roche, Ortho Diagnostics, Radiometer, ET Healthcare, Sphingotec, Astellas, RCE Technologies, Amgen, and Novartis. Dr Januzzi has served as a Trustee of the American College of Cardiology; has received grant support from Abbott, Applied Therapeutics, HeartFlow Inc, Innolife, and Roche Diagnostics; has received consulting income from Abbott, Janssen, Novartis, Merck, and Roche Diagnostics; and has participated in clinical endpoint committees or data safety monitoring boards for Abbott, AbbVie, Bayer, CVRx, Pfizer, and Takeda. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: The MITRAL (Mitral Implantation of Transcatheter Valves) trial is the first prospective study for valve-in-mitral annular calcification (ViMAC), mitral valve-in-ring (MViR), and mitral valve-in-valve (MViV) using balloon-expandable aortic transcatheter heart valves. Procedural outcomes beyond 1 year are not well described., Objectives: This study evaluated 2-year outcomes in ViMAC, MViR, and MViV in the MITRAL trial., Methods: This multicenter prospective study enrolled patients with severe MAC, prior failed mitral annuloplasty ring repair, or prior failed bioprosthetic MV replacement who were at high surgical risk at 13 U.S. sites., Results: Between February 1, 2015, and December 31, 2017, 91 patients were enrolled (31 with ViMAC, 30 with MViR, and 30 with MViV). In the ViMAC group, 2-year all-cause mortality was 39.3%, 66.7% were New York Heart Association (NYHA) functional class I-II, and mean MV gradient was 5.6 ± 2.0 mm Hg. In the MViR group, 2-year all-cause mortality was 50%, 65% were NYHA functional class I-II, and mean MV gradient was 6.5 ± 2.7 mm Hg. In the MViV group, 2-year all-cause mortality was 6.7%, 85% were NYHA functional class I-II, and mean MV gradient was 6.9 ± 2.4 mm Hg. At 2 years, all patients had ≤mild mitral regurgitation and survivors in all 3 arms showed sustained improvement in Kansas City Cardiomyopathy Questionnaire scores compared to baseline., Conclusions: Use of balloon-expandable aortic transcatheter heart valves in selected patients with severe MAC, failed annuloplasty ring, and bioprosthetic MV dysfunction is associated with improvements in symptoms, quality of life, and stable prosthesis function at 2-year follow-up. Between 1 and 2 years, the MViR group experienced higher mortality rates than the MViV and ViMAC groups., Competing Interests: Funding Support and Author Disclosures This study was supported by an unrestricted research grant from Edwards Lifesciences. Dr Wang has served as a consultant for Abbott, Boston Scientific, Edwards Lifesciences, Materialise, and NeoChord; and has received research grant support from Boston Scientific assigned to her employer Henry Ford Hospital. Dr Tang has served as a physician proctor and consultant for Medtronic; has served as a consultant and physician advisory board member for Abbott Structural Heart; and has served as a consultant for NeoChord. Dr McCabe has received honoraria from Boston Scientific, CSI, Edwards, and Medtronic. Dr Whisenant has received consulting and speaker fees from Edwards Lifesciences. Dr Hahn has received speaker fees from Abbott Structural, Baylis Medical, Edwards Lifesciences, and Philips Healthcare; has institutional consulting contracts for which she receives no direct compensation with Abbott Structural, Boston Scientific, Edwards Lifesciences, Medtronic, and Novartis; has stock options with Navigate; and has served as Chief Scientific Officer for the Echocardiography Core Laboratory at the Cardiovascular Research Foundation for multiple industry-sponsored trials, for which she has received no direct industry compensation. Dr Guerrero has received institutional research grant support from Edwards Lifesciences; and has served as a consultant for Abbott Structural Heart and Medtronic. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: In patients with suspected obstructive coronary artery disease (CAD), the risk factor-weighted clinical likelihood (RF-CL) model and the coronary artery calcium score-weighted clinical likelihood (CACS-CL) model improves the identification of obstructive CAD compared with basic pretest probability (PTP) models., Objectives: The aim of this study was to assess the prognostic value of the new models., Methods: The incidences of myocardial infarction and death were stratified according to categories by the RF-CL and CACS-CL and compared with categories by the PTP model. We used cohorts from a Danish register (n = 41,177) and a North American randomized study (n = 3,952). All patients were symptomatic and were referred for diagnostic testing because of clinical indications., Results: Despite substantial down-reclassification of patients to a likelihood ≤5% of CAD with either the RF-CL (45%) or CACS-CL (60%) models compared with the PTP (18%), the annualized event rates of myocardial infarction and death were low using all 3 models; RF-CL 0.51% (95% CI: 0.46-0.56), CACS-CL 0.48% (95% CI: 0.44-0.56), and PTP 0.37% (95% CI: 0.31-0.44), respectively. Overall, comparison of the predictive power of the 3 models using Harrell's C-statistics demonstrated superiority of the RF-CL (0.64 [95% CI: 0.63-0.65]) and CACS-CL (0.69 [95% CI: 0.67-0.70]) compared with the PTP model (0.61 [95% CI: 0.60-0.62])., Conclusions: The simple clinical likelihood models that include classical risk factors or risk factors combined with CACS provide improved risk stratification for myocardial infarction and death compared with the standard PTP model. Hence, the optimized RF-CL and CACS-CL models identify 2.5 and 3.3 times more patients, respectively, who may not benefit from further diagnostic testing., Competing Interests: Funding Support and Author Disclosures The PROMISE study was supported by grants from the National Heart, Lung, and Blood Institute (R01HL098237, R01HL098236, R01HL098305, and R01HL098235). Dr Winther has received support from the Novo Nordisk Foundation Clinical Emerging Investigator grant (NNF21OC0066981). Drs Schmidt and Bøttcher have received support from Acarix in the form of an institutional research grant. Dr Schmidt is a part-time consultant for Acarix. Dr Schmidt is a minor shareholder in Acarix. Dr Foldyna has received unrelated research support from National Institutes of Health/National Heart, Lung, and Blood Institute (1R01HL146145-01A1), AstraZeneca, Medtrace Pharma A/C, and Eli Lilly. Dr Hoffmann has received research grants on behalf of Massachusetts General Hospital outside of the submitted work from KOWA Inc, Medimmune LLC, AstraZeneca, and HeartFlow Inc; and has received consultant fees from DCRI and Recor outside of the scope of the submitted work. Dr Knuuti has received speaker fees from GE Healthcare, Merck, Lundbeck, Boehringer Ingelheim, Bayer, and Pfizer; and has received study protocol consultant fees from GE Healthcare and AstraZeneca outside of the submitted work. Dr Bøttcher has participated on Advisory Boards for Novo Nordisk, AstraZeneca, Bayer, Sanofi, and Acarix outside of the submitted work. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: In patients with acute coronary syndrome (ACS), there is residual and variable risk of recurrent ischemic events., Objectives: This study aimed to develop biomarker-based prediction models for 1-year risk of cardiovascular (CV) death and myocardial infarction (MI) in patients with ACS undergoing percutaneous coronary intervention., Methods: We included 10,713 patients from the PLATO (A Comparison of Ticagrelor [AZD6140] and Clopidogrel in Patients With Acute Coronary Syndrome) trial in the development cohort and externally validated in 3,508 patients from the TRACER (Thrombin Receptor Antagonist for Clinical Event Reduction in Acute Coronary Syndrome) trial. Variables contributing to risk of CV death/MI were assessed using Cox regression models, and a score was derived using subsets of variables approximating the full model., Results: There were 632 and 190 episodes of CV death/MI in the development and validation cohorts. The most important predictors of CV death/MI were the biomarkers, growth differentiation factor 15, and N-terminal pro-B-type natriuretic peptide, which had greater prognostic value than all candidate variables. The final model included 8 items: age (A), biomarkers (B) (growth differentiation factor 15 and N-terminal pro-B-type natriuretic peptide), and clinical variables (C) (extent of coronary artery disease, previous vascular disease, Killip class, ACS type, P2Y 12 inhibitor). The model, named ABC-ACS ischemia, was well calibrated and showed good discriminatory ability for 1-year risk of CV death/MI with C-indices of 0.71 and 0.72 in the development and validation cohorts, respectively. For CV death, the score performed better, with C-indices of 0.80 and 0.84 in the development and validation cohorts, respectively., Conclusions: An 8-item score for the prediction of CV death/MI was developed and validated for patients with ACS undergoing percutaneous coronary intervention. The ABC-ACS ischemia score showed good calibration and discrimination and might be useful for risk prediction and decision support in patients with ACS. (A Comparison of Ticagrelor [AZD6140] and Clopidogrel in Patients With Acute Coronary Syndrome [PLATO]; NCT00391872; Trial to Assess the Effects of Vorapaxar [SCH 530348; MK-5348] in Preventing Heart Attack and Stroke in Participants With Acute Coronary Syndrome [TRACER]; NCT00527943)., Competing Interests: Funding Support and Author Disclosures Grants from The Swedish Foundation for Strategic Research (grant number RB13-0197) supported this project. The PLATO trial was funded by AstraZeneca, Cambridge, United Kingdom. The TRACER trial was funded by Merck, Kenilworth, New Jersey, USA. Roche Diagnostics, Rotkreuz, Switzerland, provided GDF-15 assays free of charge. The funding sources had no influence on the work but were given the opportunity to review the final version of the report. Dr Batra has received institutional research grants from Pfizer; has received expert committee and consulting fees to his institution from Bayer; and has received honoraria for lectures and scientific advice from AstraZeneca, Boehringer Ingelheim, Novo Nordisk, Pfizer, and Sanofi. Dr Lindbäck has received institutional research grants from GlaxoSmithKline. Dr Becker has participated on a Data Safety Monitoring Board (DSMB) for Ionis and Novartis; serves on the scientific advisory board for Basking; and has received payment for expert testimony from Plunkett and Cooney. Dr Harrington has received institutional research grants from AstraZeneca during the conduct of the study; has received research grants from Janssen; and has received consulting fees from Bristol Myers Squibb. Dr Held has received institutional research grants from GlaxoSmithKline; has received honoraria and research grants from Pfizer; and has received consultant and Advisory Board fees from AstraZeneca, Bayer, Boehringer Ingelheim, and Coala Life. Dr James has received an institutional research grant, honoraria, and consultant/advisory board fee from AstraZeneca; has received an institutional research grant and consultant/advisory board fee from Medtronic; has received institutional research grants and honoraria from The Medicines Company; and has received consultant/advisory board fees from Janssen, Bayer, Novartis, Amgen, and PhaseBio. Dr Kempf has patents related to GDF-15 that have been licensed to Roche Diagnostics. Dr Lopes has received institutional research grants and consulting fees from Bayer, Bristol Myers Squibb, GlaxoSmithKline, Medtronic, Pfizer, and Sanofi; and has received consulting fees from Boehringer Ingelheim, Daiichi-Sankyo, Merck, and Portola. Dr Mahaffey has received grants and consulting fees from and participation on a DSMB for AstraZeneca and Johnson & Johnson; has received grants and consulting fees from Amgen, Bayer, Novartis, and Sanofi; has received consulting fees and speaker honoraria from Inova, Intermountain Health, Medscape, and Mount Sinai; has received grants and participation on a DSMB for Ferring, Luitpold, and Sanifit; has received consulting fees and participation on a DSMB for Myokardia and Theravance; has received grants from Afferent, American Heart Association, Apple Inc, Cardiva Medical Inc, Eidos, Gilead, Google (Verily), Medtronic, Merck, and St. Jude; has received consulting fees from Anthos Applied Therapeutics, CSL Behring, Elsevier, Mundi Pharma, Novo Nordisk, Otsuka, Portola, and SmartMedics; and participates on a DSMB for National Health and Medical Research Council and The George Institute for Global Health, Australia. Dr Steg has received grants and speaker/consultancy fees from Amarin, Bayer, Sanofi, and Servier; and has received speaker/consultancy fees from AstraZeneca, Amgen, Amarin, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Idorsia, Janssen, Novartis, Pfizer, and Regeneron. Dr Storey has received institutional research grants and speaker/consultancy fees from AstraZeneca, Cytosorbents, GlyCardial Diagnostics, and Thromboserin; and has received speaker/consultancy fees from Alnylam, Bayer, Bristol Myers Squibb/Pfizer, Chiesi, CSL-Behring, Hengrui, Idorsia, Intas Pharmaceuticals, Medscape, Novartis, PhaseBio, Portola, and Sanofi. Dr Wollert has received patents related to GDF-15 that have been licensed to Roche Diagnostics. Dr Siegbahn has received institutional research grants from AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb/Pfizer, GlaxoSmithKline, and Roche Diagnostics; and has received consulting fees from OLINK Proteomics. Dr Wallentin has received institutional research grants from AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb/Pfizer, GlaxoSmithKline, Merck & Co, and Roche Diagnostics; has received consulting fees from Abbott; and has patents related to GDF-15 that have been licensed to Roche Diagnostics. Dr Swahn has reported that she has no relationships relevant to the contents of this paper to disclose., (Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

In addition to the diaphragm's role as the primary respiratory muscle, it also plays an under-recognized role in cardiac function. It serves as a pump facilitating venous and lymph return, modulating left ventricular afterload hemodynamics and pericardial pressures, as well as regulating autonomic tone. Heart failure (HF) is associated with diaphragmatic changes (ie, muscle fiber atrophy and weakness, increased ratio of type I to type II muscle fibers, and altered muscle metaboreflex) that lead to diaphragmatic dysfunction with subsequent symptomatic manifestations of HF. Herein, it is proposed that targeting the diaphragm in patients with HF via inspiratory muscle training or device-based stimulation can provide a novel treatment pathway for HF. Reviewed are several potential mechanisms through which therapies targeting the diaphragm can be beneficial in HF (ie, improving preload reserve, atrial and ventricular synchrony, and metaboreflex activity; reducing pericardial restraint; and restoring diaphragm strength)., Competing Interests: Funding Support and Author Disclosures Dr Goldberg has served as a consultant to Viscardia. Dr Tedford has consulting relationships with Medtronic, Abbott, Aria CV Inc, Acceleron, CareDx, Itamar, Edwards LifeSciences, Eidos Therapeutics, Lexicon Pharmaceuticals, Gradient, and United Therapeutics; has served on a steering committee for Acceleron and Abbott; has served on a research advisory board for Abiomed; and has performed hemodynamic core lab work for Actelion and Merck. Dr Mirro is the chief medical officer of Viscardia. Dr Fudim has received support from the National Heart, Lung, and Blood Institute (K23HL151744), the American Heart Association (20IPA35310955), Mario Family Award, Duke Chair’s Award, Translating Duke Health Award, Bayer, Bodyport, and BTG Specialty Pharmaceuticals; and has received consulting fees from Abbott, AxonTherapies, Bodyguide, Bodyport, Boston Scientific, CVRx, Daxor, Edwards LifeSciences, Feldschuh Foundation, Fire1, Gradient, Inovise Medical, Intershunt, NXT Biomedical, Pharmacosmos, PreHealth, Splendo, Vironix, Viscardia, and Zoll. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Nonadherence to antiplatelet therapy after percutaneous coronary intervention (PCI) is common, even in clinical trials., Objectives: The purpose of this study was to investigate the impact of nonadherence to study protocol regimens in the MASTER DAPT (Management of High Bleeding Risk Patients Post Bioresorbable Polymer Coated Stent Implantation With an Abbreviated Versus Prolonged DAPT Regimen) trial., Methods: At 1-month after PCI, 4,579 high bleeding risk patients were randomized to single antiplatelet therapy (SAPT) for 11 months (or 5 months in patients on oral anticoagulation [OAC]) or dual antiplatelet therapy (DAPT) for ≥2 months followed by SAPT. Coprimary outcomes included net adverse clinical events (NACE), major adverse cardiac and cerebral events (MACE), and major or clinically relevant nonmajor bleeding (MCB) at 335 days. Inverse probability-of-censoring weights were used to correct for nonadherence Academic Research Consortium type 2 or 3., Results: In total, 464 (20.2%) patients in the abbreviated-treatment and 214 (9.4%) in the standard-treatment groups incurred nonadherence Academic Research Consortium type 2 or 3. At inverse probability-of-censoring weights analyses, NACE (HR: 1.01; 95% CI: 0.88-1.27) or MACE (HR: 1.07; 95% CI: 0.83-1.40) did not differ, and MCB was lower with abbreviated compared with standard treatment (HR: 0.51; 95% CI: 0.60-0.73) consistently across OAC subgroups; among OAC patients, SAPT discontinuation 6 months after PCI was associated with similar MACE and lower MCB (HR: 0.47; 95% CI: 0.22-0.99) compared with SAPT continuation., Conclusions: In the MASTER DAPT adherent population, 1-month compared with ≥3-month DAPT was associated with similar NACE or MACE and lower MCB. Among OAC patients, SAPT discontinuation after 6 months was associated with similar MACE and lower MCB than SAPT continuation (Management of High Bleeding Risk Patients Post Bioresorbable Polymer Coated Stent Implantation With an Abbreviated Versus Prolonged DAPT Regimen [MASTER DAPT]; NCT03023020)., Competing Interests: Funding Support and Author Disclosures The MASTER DAPT trial is conducted with support from Terumo. The study sponsor, European Cardiovascular Research Institute (ECRI), Rotterdam, the Netherlands, a nonprofit organization, received grant support from Terumo for the conduct of the MASTER DAPT trial. ECRI outsourced to Clinical trial Unit, Bern, Switzerland all statistical analyses of the present paper under a research contract agreement between the 2 institutions. None of the authors received personal or institutional payment for the present paper. Dr Valgimigli has received grants and personal fees from Terumo; and has received personal fees from AstraZeneca, Alvimedica/CID, Abbott Vascular, Daiichi-Sankyo, Bayer, CoreFLOW, Idorsia Pharmaceuticals Ltd, Universität Basel, Department Klinische Forschung, Vifor, Bristol Myers Squibb SA, Biotronik, Boston Scientific, Medtronic, Vesalio, Novartis, Chiesi, and PhaseBio. Dr Heg’s institution, CTU Bern, University of Bern, has a staff policy of not accepting honoraria or consultancy fees; however, CTU Bern is involved in design, conduct, or analysis of clinical studies funded by not-for-profit and for-profit organizations, and in particular, pharmaceutical and medical device companies provide direct funding to some of these studies. Dr Vranckx has received personal fees from Daiichi-Sankyo, Bayer AG, BLS Bering, and AstraZeneca. Dr Ozaki has received grants from Takeda Pharmaceutical Company Ltd, Daiichi-Sankyo Company Ltd, Otsuka Pharmaceutical Company Ltd, and Sanofi. Dr Morice is a shareholder and CEO of CERC and a minor shareholder of Electroducer (a start-up not involved in the MASTER DAPT trial). Dr Chevalier has received personal fees from Terumo and CERC; and holds stock options in Colibri. Dr Windecker has received grants from Abbott, Amgen, AstraZeneca, Bristol Myers Squibb, Bayer, Biotronik, Boston Scientific, Cardinal Health, CadioValve, CSL Behring, Daiichi-Sankyo, Edwards Lifesciences, Guerbet, InfraRedx, Johnson and Johnson, Medicure, Medtronic, Novartis, Polares, OrPha Suisse, Pfizer, Regeneron Pharmaceuticals, Sanofi, Sinomed, Terumo, and V-Wave; serves as unpaid advisory board member and/or unpaid member of the steering/executive group of trials funded by Abbott, Abiomed, Amgen, AstraZeneca, Bristol Myers Squibb, Boston Scientific, Biotronik, Cardiovalve, Edwards Lifesciences, MedAlliance, Medtronic, Novartis, Polares, Sinomed, V-Wave, and Xeltis, but has not received personal payments by pharmaceutical companies or device manufacturers; is a member of the steering/executive committee group of several investigator-initiated trials that receive funding by industry without impact on his personal remuneration; is an unpaid member of the Pfizer Research Award selection committee in Switzerland and of the Women as One Awards Committee; is a member of the Clinical Study Group of the Deutsches Zentrum für Herz Kreislauf-Forschung and of the Advisory Board of the Australian Victorian Heart Institute; and is chairperson of the ESC Congress Program Committee, former chairperson of the ESC Clinical Practice Guidelines Committee, and Deputy Editor of JACC: Cardiovascular Interventions. Dr Kala has served as a consultant for Boston Scientific; has received research support from Novartis; and has received honoraria from Bayer, Servier, AstraZeneca, Chiesi, and Boehringer Ingelheim. Dr Schultz has received grants and personal fees from Abbott Vascular. Dr Lopes has received institutional research grants and consulting fees from Bristol Myers Squibb, Pfizer, GlaxoSmithKline, Medtronic PLC, and Sanofi; and has received consulting fees from Amgen, Bayer, and Boehringer Ingelheim. Dr Podolec has received grants and personal fees from Amgen, Terumo, The Medicines Company, AstraZeneca, and Meril. Dr Smits has received personal fees from Terumo and Opsense; has received grants and personal fees from Abbott Vascular, Microport, and Daiichi-Sankyo; and has received grants from SMT and Microport. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: The ISCHEMIA (International Study of Comparative Health Effectiveness With Medical and Invasive Approaches) trial randomized participants with chronic coronary disease (CCD) to guideline-directed medical therapy with or without angiography and revascularization. The study examined the association of nonadherence with health status outcomes., Objectives: The study sought to compare 12-month health status outcomes of adherent and nonadherent participants with CCD with an a priori hypothesis that nonadherent patients would have better health status if randomized to invasive management., Methods: Self-reported medication-taking behavior was assessed at randomization with a modified 4-item Morisky-Green-Levine Adherence Scale, and participants were classified as adherent or nonadherent. Twelve-month health status was assessed with the 7-item Seattle Angina Questionnaire (SAQ-7) summary score (SS), which ranges from 0 to 100 (higher score = better). The association of adherence with outcomes was evaluated using Bayesian proportional odds models, including an interaction by study arm (conservative vs invasive)., Results: Among 4,480 randomized participants, 1,245 (27.8%) were nonadherent at baseline. Nonadherent participants had worse baseline SAQ-7 SS in both conservative (72.9 ± 19.3 vs 75.6 ± 18.4) and invasive (71.0 ± 19.8 vs 74.2 ± 18.7) arms. In adjusted analyses, adherence was associated with higher 12-month SAQ-7 SS in both treatment groups (mean difference in SAQ-7 SS with conservative treatment = 1.6 [95% credible interval: 0.3-2.9] vs with invasive management = 1.9 [95% credible interval: 0.8-3.1]), with no interaction by treatment., Conclusions: More than 1 in 4 participants reported medication nonadherence, which was associated with worse health status in both conservative and invasive treatment strategies at baseline and 12 months. Strategies to improve medication adherence are needed to improve health status outcomes in CCD, regardless of treatment strategy. (International Study of Comparative Health Effectiveness With Medical and Invasive Approaches [ISCHEMIA]; NCT01471522)., Competing Interests: Funding Support and Author Disclosures Dr Garcia is supported by the National Heart, Lung, and Blood Institute of the National Institutes of Health under Award Number 5T32H110837. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Dr Spertus owns the copyright to the Kansas City Cardiomyopathy Questionnaire and Seattle Angina Questionnaire; unrelated to this work, he has served as a consultant on patient-reported outcomes for Janssen, Pfizer, Bristol Myers Squibb, Bayer, Merck, Novartis, Corvia, Terumo, and Abbott; has received research grants from the American College of Cardiology Foundation, Janssen, MyoKardia, and Abbott Vascular; has served on the scientific advisory board for United Healthcare; and has served on the Board of Directors of Blue Cross Blue Shield of Kansas City. Dr Newman has received funding from the National Heart, Lung, and Blood Institute. Dr Bangalore has served as a consultant to Abbott Vascular, Biotronik, Pfizer, and Amgen; and has received research grants from the National Heart, Lung, and Blood Institute and Abbott Vascular. Dr Stone has received speaker honoraria from Cook and Infraredx; has served as a consultant to Valfix, TherOx, Robocath, HeartFlow, Ablative Solutions, Vectorious, Miracor, Neovasc, Abiomed, Ancora, Elucid Bio, Occlutech, CorFlow, Apollo Therapeutics, Impulse Dynamics, Reva, Vascular Dynamics, Shockwave, V-Wave, Cardiomech, and Gore; and owns equity or options in Ancora, Cagent, Applied Therapeutics, Biostar family of funds, SpectraWave, Orchestra Biomed, Aria, Cardiac Success, Valfix, and MedFocus family of funds. Dr. Reynolds has received funding from the National Heart, Lung, and Blood Institute; and has received in-kind donations for unrelated research from Abbott Vascular, Siemens, and BioTelemetry. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2022 American College of Cardiology Foundation. All rights reserved.)

Sodium glucose cotransporter-2 (SGLT2) inhibitors improve cardiorenal outcomes in patients with type 2 diabetes mellitus, chronic kidney disease, and chronic heart failure. SGLT2 inhibitors also reduce the risk of cardiovascular mortality and hospitalization for heart failure among patients with type 2 diabetes mellitus and a remote history of myocardial infarction (MI). As a result of the growing body of evidence in diverse disease states, and the hypothesized mechanisms of action, it is reasonable to consider the potential of SGLT2 inhibition to improve outcomes in patients with acute MI as well if initiated early after presentation. Whether these therapies are efficacious and safe to use early in the course of acute coronary heart disease remains relatively unexplored. Here, we describe the contemporary data and continuing evidence gap for considering the use of SGLT2 inhibitors early following an acute MI to reduce cardiovascular morbidity and mortality., Competing Interests: Funding Support and Author Disclosures The authors are Executive Committee Members of the EMPACT-MI trial sponsored by Boehringer Ingelheim. Dr Udell is supported by an Ontario Ministry of Colleges and Universities Early Researcher Award (ER15-11-037), University of Toronto Department of Medicine Merit Award, Women’s College Research Institute and Department of Medicine, Women’s College Hospital, and the Peter Munk Cardiac Centre, Toronto General Hospital; has received speaker/consulting honoraria from Amgen, Boehringer Ingelheim, Janssen, Merck, Novartis, and Sanofi; and has received grant support to his institutions from AstraZeneca, Bayer, Boehringer Ingelheim, Janssen, Novartis, and Sanofi. Dr Jones has received research grants from the Agency for Healthcare Research and Quality, Boehringer Ingelheim, Doris Duke Charitable Foundation, National Institute of Health, and Patient-Centered Outcomes Research Institute; and has received honoraria/other support from Bayer, Bristol Myers Squibb, and Janssen Pharmaceuticals. Dr Petrie is supported by the British Heart Foundation (BHF) Centre of Research Excellence Award (RE/13/5/30177 and RE/18/6/34217+); has received research funding from AstraZeneca, Boehringer Ingelheim, Boston Scientific, Medtronic, Novartis, Novo Nordisk, Pharmacosmos, Roche, and SQ Innovations; and has served as a consultant and on Clinical Trials Committees for Abbvie, AstraZeneca, Bayer, Boehringer Ingelheim, Cardiorentis, Medtronic, Novartis, Novo Nordisk, Pharmacosmos, Siemens, and Takeda. Dr Harrington has received salary support from T32 training grant T32HL069749. Dr Anker has received fees from Abbott, Bayer, Boehringer Ingelheim, Cardiac Dimension, Impulse Dynamics, Novartis, Occlutech, Servier, and Vifor Pharma; and has received grant support from Abbott and Vifor Pharma. Dr Bhatt has served on the Advisory Board of Bayer, Boehringer Ingelheim, Cardax, CellProthera, Cereno Scientific, Elsevier Practice Update Cardiology, Janssen, Level Ex, Medscape Cardiology, Merck, MyoKardia, NirvaMed, Novo Nordisk, PhaseBio, PLx Pharma, Regado Biosciences, and Stasys; has served on the Board of Directors of Boston VA Research Institute, DRS.LINQ (stock options), Society of Cardiovascular Patient Care, and TobeSoft; has served as Inaugural Chair of the American Heart Association Quality Oversight Committee; has served on Data Monitoring Committees for Acesion Pharma, Assistance Publique-Hôpitaux de Paris, Baim Institute for Clinical Research (formerly Harvard Clinical Research Institute, for the PORTICO trial, funded by St. Jude Medical, now Abbott), Boston Scientific (Chair, PEITHO trial), Cleveland Clinic (including for the ExCEED trial, funded by Edwards), Contego Medical (Chair, PERFORMANCE 2), Duke Clinical Research Institute, Mayo Clinic, Mount Sinai School of Medicine (for the ENVISAGE trial, funded by Daiichi-Sankyo; for the ABILITY-DM trial, funded by Concept Medical), Novartis, Population Health Research Institute, and Rutgers University (for the National Institutes of Health-funded MINT Trial); has received honoraria from American College of Cardiology (Senior Associate Editor, Clinical Trials and News, ACC.org; Chair, ACC Accreditation Oversight Committee), Arnold and Porter law firm (work related to Sanofi/Bristol Myers Squibb clopidogrel litigation), Baim Institute for Clinical Research (formerly Harvard Clinical Research Institute; RE-DUAL PCI clinical trial steering committee funded by Boehringer Ingelheim; AEGIS-II executive committee funded by CSL Behring), Belvoir Publications (Editor-in-Chief, Harvard Heart Letter), Canadian Medical and Surgical Knowledge Translation Research Group (clinical trial steering committees), Cowen and Company, Duke Clinical Research Institute (clinical trial steering committees, including for the PRONOUNCE trial, funded by Ferring Pharmaceuticals), HMP Global (Editor-in-Chief, Journal of Invasive Cardiology), Journal of the American College of Cardiology (Guest Editor; Associate Editor), K2P (Cochair, interdisciplinary curriculum), Level Ex, Medtelligence/ReachMD (CME steering committees), MJH Life Sciences, Piper Sandler, Population Health Research Institute (for the COMPASS operations committee, publications committee, steering committee, and USA national co-leader, funded by Bayer), Slack Publications (Chief Medical Editor, Cardiology Today’s Intervention), Society of Cardiovascular Patient Care (Secretary/Treasurer), WebMD (CME steering committees), and Wiley (steering committee); has served as Deputy Editor of Clinical Cardiology; has served as chair of the NCDR-ACTION Registry Steering Committee and VA CART Research and Publications Committee (Chair); has received research funding from Abbott, Afimmune, Aker Biomarine, Amarin, Amgen, AstraZeneca, Bayer, Beren, Boehringer Ingelheim, Bristol Myers Squibb, Cardax, CellProthera, Cereno Scientific, Chiesi, CSL Behring, Eisai, Ethicon, Faraday Pharmaceuticals, Ferring Pharmaceuticals, Forest Laboratories, Fractyl, Garmin, HLS Therapeutics, Idorsia, Ironwood, Ischemix, Janssen, Javelin, Lexicon, Lilly, Medtronic, Merck, Moderna, MyoKardia, NirvaMed, Novartis, Novo Nordisk, Owkin, Pfizer, PhaseBio, PLx Pharma, Recardio, Regeneron, Reid Hoffman Foundation, Roche, Sanofi, Stasys, Synaptic, The Medicines Company, and 89Bio; has received royalties from Elsevier (Editor, Braunwald’s Heart Disease); has served as Site Co-Investigator for Abbott, Biotronik, Boston Scientific, CSI, St. Jude Medical (now Abbott), Philips, and Svelte; has served as Trustee of the American College of Cardiology; and has performed unfunded research for FlowCo and Takeda. Dr Hernandez has received research funding from American Regent, AstraZeneca, Boehringer Ingelheim, Merck, Novartis, and Verily; and has received speaker/consulting honoraria from Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Boston Scientific, Bristol Myers Squibb, Cytokinetics, Merck, Myokardia, Novartis, and Relypsa. Dr Butler has served as a consultant to Abbott, Adrenomed, Amgen, Array, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, CVRx, G3 Pharmaceutical, Impulse Dynamics, Innolife, Janssen, LivaNova, Luitpold, Medtronic, Merck, Novartis, NovoNordisk, Relypsa, Roche, V-Wave Limited, and Vifor., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Numerous sex-based differences are observed across the spectrum of valvular heart disease, starting with pathophysiology and progression of disease, moving on to compensation and comorbidities (both cardiovascular such as coronary artery disease and noncardiovascular such as frailty), assessment of severity and hemodynamics including timing of intervention, and procedural risks/benefits and outcomes. The aortic valve is perhaps best understood with sex differences in both pathologic changes and response to volume and pressure overload, yet large gaps in our understanding still exist. Studies of other valve diseases have focused on differences in prevalence, presentation, and outcomes for surgical or transcatheter therapies. Defining sex-specific responses to valvular heart disease may improve disease recognition, define treatment strategies, and improve outcomes., Competing Interests: Funding Support and Author Disclosures Dr Hahn has received speaker fees from Abbott Structural, Edwards Lifesciences, and Philips Healthcare; has received consulting fees from Abbott Structural, Boston Scientific, Edwards Lifesciences, and Gore & Associates; has equity with Navigate; and is Chief Scientific Officer for the Echocardiography Core Laboratory at the Cardiovascular Research Foundation for multiple industry-sponsored trials, for which she receives no direct industry compensation. Dr Clavel has received core lab contracts with Edwards Lifesciences; and has received research grants from Medtronic. Dr Mascherbauer has received speaker fees from Abbott Vascular, Boston Scientific, and Edwards Lifesciences; has received proctoring fees from Abbott Vascular and Edwards Lifescience; and is on advisory boards for Boston Scientific and Shockwave. Dr Mick has received consulting fees from Medtronic, Johnson & Johnson, and Cryolife. Dr Asgar has received consulting fees from Medtronic, Edwards Lifesciences, and Abbott; and has received research funding from Abbott Vascular. Dr Douglas has reported that she has no relationships relevant to the contents of this paper to disclose., (Copyright © 2022. Published by Elsevier Inc.)

Background: The use of apixaban instead of vitamin K antagonists (VKA) as well as dropping aspirin results in less bleeding and comparable ischemic events in patients with atrial fibrillation and acute coronary syndrome and/or percutaneous coronary intervention treated with a P2Y 12 inhibitor., Objectives: The authors assessed the safety and efficacy of antithrombotic regimens according to HAS-BLED and CHA 2 DS 2 -VASc scores in AUGUSTUS (The Open-Label, 2 × 2 Factorial, Randomized, Controlled Clinical Trial to Evaluate the Safety of Apixaban vs. Vitamin K Antagonist and Aspirin vs. Placebo in Patients with Atrial Fibrillation and Acute Coronary Syndrome and/or Percutaneous Coronary Intervention)., Methods: In AUGUSTUS, 4,614 patients were randomized in a 2-by-2 factorial design to open-label apixaban or VKA and blinded aspirin or placebo. The primary endpoint was major or clinically relevant nonmajor bleeding over 6 months of follow-up. Cox proportional hazards models were used to assess treatment effects by baseline HAS-BLED (≤2 vs ≥3) and CHA 2 DS 2 -VASc (≤2 vs ≥3) scores., Results: Of 4,386 (95.1%) patients with calculable scores, 66.8% had HAS-BLED ≥3 and 81.7% had CHA 2 DS 2 -VASc ≥3. Bleeding rates were lower with apixaban than VKA irrespective of baseline risk (HR: 0.57; 95% CI: 0.41-0.78 [HAS-BLED ≤2]; HR: 0.72; 95% CI: 0.59-0.88 [HAS-BLED ≥3]; interaction P = 0.23). Aspirin increased bleeding irrespective of baseline risk (HR: 1.86; 95% CI: 1.36-2.56 [HAS-BLED ≤2]; HR: 1.81; 95% CI: 1.47-2.23 [HAS-BLED ≥3]; interaction P = 0.88). Apixaban resulted in a lower risk of death or hospitalization than VKA without a significant interaction with baseline stroke risk (HR: 0.92; 95% CI: 0.67-1.25 [CHA 2 DS 2 -VASc ≤2]; HR: 0.82; 95% CI: 0.73-0.94 [CHA 2 DS 2 -VASc ≥3]; interaction P = 0.53)., Conclusions: Our findings support the use of apixaban and a P2Y 12 inhibitor without aspirin for most patients with atrial fibrillation and acute coronary syndrome and/or percutaneous coronary intervention, irrespective of a patient's baseline bleeding and stroke risk (NCT02415400)., Competing Interests: Funding Support and Author Disclosures The AUGUSTUS trial and this analysis were supported by Bristol Myers Squibb and Pfizer. Dr Fanaroff has received research grants and consulting fees from the American Heart Association; and has received research grants from Boston Scientific. Dr Lopes has received institutional research grants and consulting fees from Bristol Myers Squibb, Pfizer, GlaxoSmithKline, Medtronic PLC, and Sanofi; and has received consulting fees from Amgen, Bayer, and Boehringer Ingelheim. Dr Goodman has received research grant support (eg, steering committee or data and safety monitoring committee) and/or speaker/consulting honoraria (eg, advisory boards) from Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, CSL Behring, Daiichi-Sankyo/American Regent, Eli Lilly, Esperion, Ferring Pharmaceuticals, GlaxoSmithKline, HLS Therapeutics, JAMP Pharma, Janssen/Johnson and Johnson, Merck, Novartis, Novo Nordisk A/C, Pendopharm, Pfizer, Regeneron, Sanofi, Servier, and Valeo Pharma; and has received salary support/honoraria from the Heart and Stroke Foundation of Ontario/University of Toronto (Polo) (Chair), Canadian Heart Research Centre and MD Primer, Canadian VIGOUR Centre, Cleveland Clinic Coordinating Centre for Clinical Research, Duke Clinical Research Institute, New York University Clinical Coordinating Centre, and PERFUSE Research Institute. Dr Thomas has received institutional research grants from Akili Interactive Labs Inc, Amgen Inc, Gilead, and Novartis. Dr Aronson is an employee of Bristol Myers Squibb. Dr Windecker has received Institutional research and educational grants from Abbott, Amgen, Bayer, Bristol Myers Squibb, CSL Behring, Boston Scientific, Biotronik, Edwards Lifesciences, Medtronic, Polares, and Sinomed. Dr Mehran has received institutional research grants from AstraZeneca, Bayer, Beth Israel Deaconess, Bristol Myers Squibb/Sanofi, CSL Behring, Eli Lilly/Daiichi-Sankyo, Medtronic, Novartis, and OrbusNeich; has received consulting fees from Boston Scientific, Abbott Vascular, Medscape, Siemens Medical Solutions, Roivant Sciences Inc, and Sanofi; has performed consulting (no fees) for Regeneron Pharmaceuticals; has received institutional consulting fees from Abbott Vascular, Spectranetics/Phillips/Volcano Corporation, Bristol Myers Squibb, Novartis, and Watermark Research; has served as an executive committee member for Janssen Pharmaceuticals and Bristol Myers Squibb; and has <1% equity in Claret Medical and Elixir Medical. Dr Granger has received research grants from Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Daiichi-Sankyo, Janssen, Pfizer, Armetheon, AstraZeneca, the U.S. Food and Drug Administration, GlaxoSmithKline, The Medicines Company, Medtronic Foundation, Medtronic Inc, and Novartis; and has received consulting fees from Bayer, Boehringer Ingelheim, Boston Scientific, Bristol Myers Squibb, Daiichi-Sankyo, Janssen, Pfizer, Abbvie, Armetheon, AstraZeneca, Eli Lilly, Gilead, GlaxoSmithKline, Hoffmann-La Roche, The Medicines Company, National Institutes of Health, Novartis, Sirtex, Verseon, Apple, Medscape, LLC, Merck, Novo Nordisk, Roche Diagnostics, and Rho Pharmaceuticals. Dr Alexander has received institutional research grants and consulting fees/honoraria from Bristol Myers Squibb and CSL Behring; has received institutional research grants from AstraZeneca, CryoLife, the U.S. Food and Drug Administration, National Institutes of Health, Sanofi, VoluMetrix, and Boehringer Ingelheim; and has received consulting fees/honoraria from Pfizer, AbbVie Pharmaceuticals, NovoNordisk, Portola Pharmaceuticals, Quantum Genetics, Teikoku Pharmaceuticals, VA Cooperative Studies Program, and Zafgen. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: The 2018 U.S. cholesterol management guideline recommends additional lipid-lowering therapy with ezetimibe for secondary prevention in very high-risk patients with low-density lipoprotein cholesterol (LDL-C) ≥70 mg/dL despite maximally tolerated statin., Objectives: The purpose of this study was to evaluate the relationship between baseline LDL-C above and below 70 mg/dL and the benefit of adding ezetimibe to statin in patients post-acute coronary syndrome (ACS)., Methods: IMPROVE-IT (Improved Reduction of Outcomes: Vytorin Efficacy International Trial) was a double-blind, placebo-controlled, randomized trial of ezetimibe/simvastatin vs placebo/simvastatin in post-ACS patients followed for 6 years (median). A total of 17,999 patients were stratified by LDL-C at qualifying event into 3 groups (50-<70, 70-<100, and 100-125 mg/dL). The primary endpoint was a composite of cardiovascular death, major coronary events, or stroke., Results: Absolute differences in median LDL-C achieved at 4 months between treatment arms were similar (17-20 mg/dL). The effect of ezetimibe/simvastatin vs placebo/simvastatin on primary endpoint was consistent regardless of baseline LDL-C of 50-<70 mg/dL (HR: 0.92 [95% CI: 0.80-1.05]), 70-<100 mg/dL (HR: 0.93 [95% CI: 0.87-1.01]), or 100-125 mg/dL (HR: 0.94 [95% CI: 0.86-1.03]; P interaction = 0.95). Normalized relative risk reductions per 1-mmol/L difference in achieved LDL-C at 4 months between treatment arms were 21% in patients with baseline LDL-C of 50-<70 mg/dL, 16% in those with 70-<100 mg/dL, and 13% in those with 100-125 mg/dL (P interaction = 0.91). No significant treatment interactions by baseline LDL-C were present for safety endpoints., Conclusions: Adding ezetimibe to statin consistently reduced the risk for cardiovascular events in post-ACS patients irrespective of baseline LDL-C values, supporting the use of intensive lipid-lowering therapy with ezetimibe even in patients with baseline LDL-C <70 mg/dL. (IMPROVE-IT: Examining Outcomes in Subjects With Acute Coronary Syndrome: Vytorin [Ezetimibe/Simvastatin] vs Simvastatin [P04103]; NCT00202878)., Competing Interests: Funding Support and Author Disclosures The IMPROVE-IT trial was supported by Merck and Co. Dr Oyama has received a grant from JSPS Overseas Research Fellowships. Dr Giugliano has received grants from Amgen and Anthos Therapeutics; has received honoraria from Amgen, Centrix, Daiichi-Sankyo, Dr Reddy's Laboratories, Medical Education Resources, Medscape, Menarini, Pfizer, SAJA Pharmaceuticals, Servier, and Voxmedia; and has received consultant fees from Amarin, Amgen, Bayer, CryoLife, Daiichi-Sankyo, Esperion, Gilead, Hengrui, Inari, Pfizer, PhaseBio Pharmaceuticals, St Lukes, and Sanofi. Dr Blazing has received research support from Merck; has received consulting fees from Espirion (<$10,000); and has received indirect support from Sanofi through Duke Clinical Research Institute. Dr Park has received institutional research grant support through Brigham and Women’s Hospital from Abbott, Amgen, Anthos Therapeutics, AstraZeneca, Daiichi-Sankyo, Eisai, Intarcia, MedImmune, Merck, Novartis, Pfizer, Regeneron Pharmaceuticals, Inc, Roche, The Medicines Company, and Zora Biosciences. Dr Tershakovec is a former employee of Merck Sharp and Dohme Corp, a subsidiary of Merck and Co, Inc, and may own stock in the company. Dr Sabatine has received research grant support through Brigham and Women’s Hospital from Amgen, Anthos Therapeutics, AstraZeneca, Bayer, Daiichi-Sankyo, Eisai, Intarcia, IONIS, The Medicines Company, MedImmune, Merck, Novartis, Pfizer, and Quark Pharmaceuticals; and has received consulting fees from Althera, Amgen, Anthos Therapeutics, AstraZeneca, Bristol Myers Squibb, CVS Caremark, DalCor, Dr Reddy's Laboratories, Fibrogen, IFM Therapeutics, Intarcia, MedImmune, Merck, Moderna, and Novo Nordisk. Dr Cannon has received grant support and consulting fees from Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Janssen, Pfizer, and Merck; has received grant support from Daiichi-Sankyo; and has received consulting fees from Aegerion, Alnylam, Amarin, Applied Clinical Therapeutics, Ascendia, Corvidia, HLS Therapeutics, Innovent, Kowa, Eli Lilly, and Rhoshan. Dr Braunwald has received research grants through the Brigham and Women’s Hospital from AstraZeneca, Daiichi-Sankyo, Merck, and Novartis; has served as a consultant for Amgen, Cardurion, MyoKardia, NovoNordisk, Boehringer Ingelheim/Lilly, IMMEDIATE, and Verve; and has performed uncompensated consultancies and lectures for The Medicines Company., (Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Although statins reduce cardiovascular morbidity and mortality, only about one-half of eligible patients receive treatment. Safe and appropriate consumer access to statins could have a significant positive public health impact., Objectives: This study compares the concordance between a participant and clinician assessment of eligibility for statin therapy using a technology-assisted approach., Methods: A total of 500 participants, 83 with limited literacy, completed an at-home Web-based application to assess appropriateness for treatment with rosuvastatin 5 mg. The Web application is designed to assess eligibility for a moderate-intensity statin based on current guidelines and deny access to individuals with contraindications to rosuvastatin. Subsequently, participants visited a research site where clinicians, blinded to the information the participant entered, performed an independent Web application assessment. The Web application is programmed for 1 of 3 rosuvastatin treatment outcomes: "OK to use," "not right for you," or "ask a doctor." The primary endpoint was the percent of participants whose self-selected eligibility for nonprescription rosuvastatin was concordant with clinician assessment., Results: For the primary endpoint, participant selection for statin therapy was concordant with clinician selection in 481 (96.2%) of 500 participants (95% confidence interval: 94.1%-97.7%), of whom 23 (4.6%) were deemed appropriate and 458 (91.6%) were deemed inappropriate for treatment. Discordance was due to incorrect self-selection ("OK to use") in 3 cases, incorrect rejection ("not right for you") in 14 cases and an incorrect "ask a doctor" outcome in 2 cases., Conclusions: The use of a technology-assisted approach to consumer self-selection for statin therapy resulted in participant self-selection that showed substantial agreement with clinician selection., Competing Interests: Funding Support and Author Disclosures This work was funded by AstraZeneca Pharmaceuticals. The sponsor was centrally involved in the study design and reviewed the manuscript, but the final decisions on content were made by the lead author after consultation with the other academic coauthors (Dr Nissen). Dr Nissen reports that the Cleveland Clinic Center for Clinical Research has received funding to perform clinical trials from AbbVie, AstraZeneca, Amgen, Eli Lilly, Esperion, Medtronic, MyoKardia, Novartis, Pfizer, and Silence Therapeutics—he is involved in these clinical trials, but receives no personal remuneration for his participation; and has served as a consultant for many pharmaceutical companies but requires them to donate all honoraria or consulting fees directly to charity so that he receives neither income nor a tax deduction. Dr Hutchinson and Ms Morris are employees of AstraZeneca. Dr Wang has received research grants to the Duke Clinical Research Institute from Abbott, AstraZeneca, Bristol Myers Squibb, Boston Scientific, CryoLife, Chiesi, Merck, Portola, and Regeneron; and has received consulting honoraria from AstraZeneca, Bristol Myers Squibb, CryoLife, and Novartis. Dr Ballantyne has received grants to his institution from Akcea, Amgen, Esperion, Ionis, Novartis, Regeneron, and the American Heart Association; and has served as a consultant for Althera, Amarin, Amgen, Arrowhead, AstraZeneca, Corvidia, Esperion, Genentech, Gilead, Matinas BioPharma Inc., New Amsterdam, Novartis, Novo Nordisk, Pfizer, Regeneron, and Sanofi-Synthelabo. Ms Travis, Dr Miller, and Ms Hynson are employees of Concentrics Research. Dr Ridker has reported that during the course of this project he received unrelated investigator-initiated research grant support from Novartis, Kowa, Amarin, Pfizer, and the National Heart, Lung, and Blood Institute; and has served as a consultant to Corvidia, Novartis, Flame, Agepha, Inflazome, AstraZeneca, Janssen, Civi Biopharm, SOCAR, Novo Nordisk, Uptton, Omeicos, and Boehringer Ingelheim. Ms Wolski has reported that she has no relationships relevant to the contents of this paper to disclose., (Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Consensus as to best practices for the selection, reporting, and interpretation of primary and secondary outcomes of randomized controlled trials is lacking. We reviewed the strategies adopted in publications of randomized controlled trials (RCTs) for the analysis, presentation, and interpretation of efficacy outcomes from a survey of all cardiovascular RCTs published in the New England Journal of Medicine, Lancet, and the Journal of the American Medical Association during 2019. We focus on the choice of primary outcomes, the variety of approaches to selecting secondary outcomes, the options sometimes used to control type I error, and the common practice to not correct for multiple testing in reporting secondary outcomes. We comment on current practice across journals in the reporting of P values and also how conclusions in trial reports frequently adhere to an undue reliance on P < 0.05 as a basis for positive claims of treatment efficacy. We conclude with recommendations for how future RCT reports could best select, report, and interpret their findings on primary and secondary outcomes., Competing Interests: Funding Support and Author Disclosures Dr Pocock has served as a consultant for AstraZeneca, Boehringer Ingelheim, Boston Scientific, Edwards, Medtronic, and Vifor. Dr Stone has received speaker honoraria from Cook and Terumo; has served as a consultant for Valfix, TherOx, Vascular Dynamics, Robocath, HeartFlow, Gore, Ablative Solutions, Miracor, Neovasc, V-Wave, Abiomed, Ancora, MAIA Pharmaceuticals, Vectorious, Reva, and Matrizyme; and owns equity/options in Ancora, Qool Therapeutics, Cagent, Applied Therapeutics, the Biostar family of funds, SpectraWave, Orchestra Biomed, Aria, Cardiac Success, the MedFocus family of funds, and Valfix. Dr Rockhold has received personal fees from Novartis, Eli Lilly, Amgen, Sanofi, NovoNordisk, Merck Research Labs, UCB, Tolerion, Rhythm, KLSMC Stem Cell, Merck KGaA, Janssen, Phathom, Clover Biopharma, Sarepta, Eidos, and Icosavax outside of the submitted work; has received grants and personal fees from AstraZeneca outside of the submitted work; and has equity interest in GlaxoSmithKline, Athira, DataVant, and Spencer Healthcare. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Rhythm control strategies for atrial fibrillation (AF), including catheter ablation, are substantially underused in racial/ethnic minorities in North America., Objectives: This study sought to describe outcomes in the CABANA trial as a function of race/ethnicity., Methods: CABANA randomized 2,204 symptomatic participants with AF to ablation or drug therapy including rate and/or rhythm control drugs. Only participants in North America were included in the present analysis, and participants were subgrouped as racial/ethnic minority or nonminority with the use of National Institutes of Health definitions. The primary endpoint was a composite of death, disabling stroke, serious bleeding, or cardiac arrest., Results: Of 1,280 participants enrolled in CABANA in North America, 127 (9.9%) were racial and ethnic minorities. Compared with nonminorities, racial and ethnic minorities were younger with median age 65.6 versus 68.5 years, respectively, and had more symptomatic heart failure (37.0% vs 22.0%), hypertension (92.1% vs 76.8%, respectively), and ejection fraction <40% (20.8% vs 7.1%). Racial/ethnic minorities treated with ablation had a 68% relative reduction in the primary endpoint (adjusted hazard ratio [aHR]: 0.32; 95% confidence interval [CI]: 0.13-0.78) and a 72% relative reduction in all-cause mortality (aHR: 0.28; 95% CI: 0.10-0.79). Primary event rates in racial/ethnic minority and nonminority participants were similar in the ablation arm (4-year Kaplan-Meier event rates 12.3% vs 9.9%); however, racial and ethnic minorities randomized to drug therapy had a much higher event rate than nonminority participants (27.4% vs. 9.4%)., Conclusion: Among racial or ethnic minorities enrolled in the North American CABANA cohort, catheter ablation significantly improved major clinical outcomes compared with drug therapy. These benefits, which were not seen in nonminority participants, appear to be due to worse outcomes with drug therapy. (Catheter Ablation vs Anti-arrhythmic Drug Therapy for Atrial Fibrillation Trial [CABANA]; NCT00911508)., Competing Interests: Funding Support and Author Disclosures This work was supported by the National Institutes of Health (U01HL89709, U01HL089786, U01HL089907, and U01HL089645), St. Jude Medical Foundation and Corporation, Biosense Webster, Medtronic, and Boston Scientific Corporation. The content of this paper does not necessarily represent the views of the National Heart, Lung, and Blood Institute or the Department of Health and Human Services. Dr. Thomas has received grants from the National Heart, Lung, and Blood Institute (National Institutes of Health), Patient-Centered Outcomes Research Institute, and American Heart Association; and has received consulting fees from Sanofi, Boehringer Ingelheim, Janssen, Bristol Myers Squibb, and Medtronic during the conduct of the study. Dr. Al-Khalidi has received grants from the National Heart, Lung, and Blood Institute (National Institutes of Health) and the Mayo Clinic during the conduct of the study. Dr. Monahan has received grants from the National Heart, Lung, and Blood Institute (National Institutes of Health), St. Jude Foundation and Corporation, Biosense Webster, Medtronic, and Boston Scientific during the conduct of the study; has consulted without compensation from Biosense Webster; and has received personal fees from Thermedical outside the submitted work. Dr. Bahnson has received grants from the National Heart, Lung, and Blood Institute (National Institutes of Health) and the Mayo Clinic for conduct of the study; has received grants from Boston Scientific, St. Jude Medical Corporation, Biosense Webster, and Medtronic; and has received compensation for consulting from Cardiofocus and Ventrix during the conduct of the study but outside of the submitted work. Dr. Poole has received grants from ATriCure outside the submitted work. Dr. Mark has received grants from the National Heart, Lung, and Blood Institute (National Institutes of Health), the Mayo Clinic during the conduct of the study; and has received grants from Merck and HeartFlow outside the submitted work. Dr. Packer in the past 12 months has provided consulting services for Biosense Webster, Inc., Boston Scientific, CyberHeart, Medtronic, Inc., nContact, Sanofi, St. Jude Medical, and Toray Industries but has received no personal compensation for these consulting activities; has received grants from Abbott, Biosense Webster, Boston Scientific, CardioFocus, Medtronic, St. Jude Medical, CardioInsight, National Institutes of Health, Siemens, Thermedical, Endosense, Robertson Foundation, and Hansen Medical; has served on the advisory board without compensation for Abbott, Biosense Webster, Boston Scientific, CardioFocus, Medtronic, St. Jude Medical, Spectrum Dynamics, Siemens, Thermedical, Johnson & Johnson, and SigNum Preemptive Healthcare; has received speaking fees and honoraria from Biotronik and MediaSphere Medical; has received royalties from Wiley & Sons, Oxford, and St. Jude Medical; has joint equity with the Mayo Clinic in a privately held company, External Beam Ablation Medical Devices, outside the submitted work; and has received research funding from the NIH, Medtronic, Inc., Cryo Cath, Siemens AG, EP Limited, Minnesota Partnership for Biotechnology and Medical Genomics/University of Minnesota, Biosense Webster, Inc., and Boston Scientific. Mayo Clinic and Drs. Packer and Robb have a financial interest in mapping technology that may have been used at some of the 10 centers participating in this pilot research; in accordance with the Bayh-Dole Act, this technology has been licensed to St. Jude Medical, and Mayo Clinic and Drs. Packer and Robb received annual royalties >$10,000, the federal threshold for significant financial interest. Dr. Silverstein has reported that he has no relationships relevant to the contents of this paper to disclose., (Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Discrimination and emotional and sexual harassment create a hostile work environment (HWE). The global prevalence of HWE in cardiology is unknown, as is its impact., Objectives: This study sought to evaluate emotional harassment, discrimination, and sexual harassment experienced by cardiologists and its impact on professional satisfaction and patient interactions worldwide., Methods: The American College of Cardiology surveyed cardiologists from Africa, Asia, the Caribbean, Eastern Europe, the European Union, the Middle East, Oceana, and North, Central, and South America. Demographics, practice information, and HWE were tabulated and compared, and their impact was assessed. The p values were calculated using the chi-square, Fisher exact, and Mann-Whitney U tests. Univariate and multivariate logistic regression analysis determined the association of characteristics with HWE and its subtypes., Results: Of 5,931 cardiologists (77% men; 23% women), 44% reported HWE. Higher rates were found among women (68% vs. 37%; odds ratio [OR]: 3.58 vs. men), Blacks (53% vs. 43%; OR: 1.46 vs. Whites), and North Americans (54% vs. 38%; OR: 1.90 vs. South Americans). Components of HWE included emotional harassment (29%; n = 1,743), discrimination (30%; n = 1,750), and sexual harassment (4%; n = 221), and they were more prevalent among women: emotional harassment (43% vs. 26%), discrimination (56% vs. 22%), and sexual harassment (12% vs. 1%). Gender was the most frequent cause of discrimination (44%), followed by age (37%), race (24%), religion (15%), and sexual orientation (5%). HWE adversely affected professional activities with colleagues (75%) and patients (53%). Multivariate analysis showed that women (OR: 3.39; 95% confidence interval: 2.97 to 3.86; p < 0.001) and cardiologists early in their career (OR: 1.27; 95% confidence interval: 1.14 to 1.43; p < 0.001) had the highest odds of experiencing HWE., Conclusions: There is a high global prevalence of HWE in cardiology, including discrimination, emotional harassment, and sexual harassment. HWE has an adverse effect on professional and patient interactions, thus confirming concerns about well-being and optimizing patient care. Institutions and practices should prioritize combating HWE., Competing Interests: Funding Support and Author Disclosures The study was funded by the American College of Cardiology Women in Cardiology Section and Diversity and Inclusion Task Force. Dr. Sharma is supported by the Blumenthal Scholarship in Preventive Cardiology at the Ciccarone Center for the Prevention of Cardiovascular Disease. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Coronary artery disease (CAD) is highly prevalent in patients with heart failure (HF) and accounts for nearly two-thirds of cases. The use of percutaneous coronary intervention (PCI) in HF patients with CAD has markedly increased and has been suggested to be associated with improved outcomes in numerous observational studies. Randomized data comparing the impact of PCI with that of coronary artery bypass graft (CABG) or contemporary guideline-directed medical therapy alone on clinical outcomes and myocardial recovery in patients with HF are lacking. The purpose of this review is to describe the available evidence regarding the impact of PCI in acute HF (in the presence and absence of an acute coronary syndrome), chronic HF with reduced ejection fraction, and HF with preserved ejection fraction. Adequately-powered randomized clinical trials examining the outcomes with PCI in these distinct HF populations are warranted., Competing Interests: Funding Support and Author Disclosures Dr. Parikh has served on the advisory board for AstraZeneca Pharmaceuticals; and has served as a consultant for Medtronic. Dr. Anker has received personal fees from Bayer, Boehringer Ingelheim, Cardiac Dimension, Impulse Dynamics, Novartis, Servier, St. Jude Medical, and Vifor Pharma; and has received grant support from Abbott Vascular and Vifor Pharma. Dr. Bhatt has served on the advisory boards of Cardax, Cereno Scientific, Elsevier Practice Update Cardiology, Medscape Cardiology, PhaseBio, and Regado Biosciences; has served on the Boards of Directors of Boston Veterans Affairs Research Institute, Society of Cardiovascular Patient Care, and TobeSoft; has served as the Chair of American Heart Association Quality Oversight Committee; has served on the Data Monitoring Committees of Baim Institute for Clinical Research (formerly Harvard Clinical Research Institute, for the PORTICO trial, funded by St. Jude Medical, now Abbott), Cleveland Clinic (including for the ExCEED trial, funded by Edwards Lifesciences), Duke Clinical Research Institute, Mayo Clinic, Mount Sinai School of Medicine (for the ENVISAGE trial, funded by Daiichi-Sankyo), and Population Health Research Institute; has received honoraria from American College of Cardiology (Senior Associate Editor, Clinical Trials and News, ACC.org; Vice-Chair, ACC Accreditation Committee), Baim Institute for Clinical Research (formerly Harvard Clinical Research Institute; REDUAL PCI Clinical Trial Steering Committee funded by Boehringer Ingelheim; AEGIS-II Executive Committee funded by CSL Behring, Belvoir Publications (Editor-in-Chief, Harvard Heart Letter), Duke Clinical Research Institute (Clinical Trial Steering Committees, including for the PRONOUNCE trial, funded by Ferring Pharmaceuticals), HMP Global (Editor-in-Chief, Journal of Invasive Cardiology), Journal of the American College of Cardiology (Guest Editor; Associate Editor), Medtelligence/ReachMD (Continuing Medical Education Steering Committees), Population Health Research Institute (for the COMPASS Operations Committee, Publications Committee, Steering Committee, and USA national coleader, funded by Bayer), Slack Publications (Chief Medical Editor, -Cardiology Today’s Intervention), Society of Cardiovascular Patient Care (Secretary/Treasurer), WebMD (Continuing Medical Education Steering Committees), Clinical Cardiology (Deputy Editor), NCDR-ACTION Registry Steering Committee (Chair), and VA CART (U.S. Department of Veterans Affairs Clinical Assessment, Reporting, and Tracking) Research and Publications Committee (Chair); has received research funding from Abbott, Afimmune, Amarin, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Cardax, Chiesi, CSL Behring, Eisai, Ethicon, Ferring Pharmaceuticals, Forest Laboratories, Fractyl, Idorsia, Ironwood, Ischemix, Lexicon, Lilly, Medtronic, Pfizer, PhaseBio, PLx Pharma, Regeneron, Roche, Sanofi, Synaptic, and The Medicines Company; has received royalties from Elsevier (Editor, Cardiovascular Intervention: A Companion to Braunwald’s Heart Disease); has served as a site coinvestigator for Biotronik, Boston Scientific, CSI, St. Jude Medical (now Abbott), and Svelte; has served as a trustee of American College of Cardiology; and has performed unfunded research for FlowCo, Merck, Novo Nordisk, and Takeda. Dr. Fonarow has received research funding from Patient-Centered Outcomes Research Institute and the National Institutes of Health; and has served as a consultant for Abbott, Amgen, AstraZeneca, Bayer, CHF Solutions, Janssen, Medtronic, Merck, and Novartis. Dr. Hernandez has received research funding from American Regent, AstraZeneca, Bristol Myers Squibb, GlaxoSmithKline, Merck, Novartis, and Verily; and has been a consultant for AstraZeneca, Bayer, Boehringer Ingelheim, Boston Scientific, Merck, and Novartis. Dr. Mehran has received institutional research grants from Abbott Laboratories, Abiomed, Applied Therapeutics, AstraZeneca, Bayer, Beth Israel Deaconess, Bristol Myers Squibb, CERC, Chiesi, Concept Medical, CSL Behring, DSI, Medtronic, Novartis Pharmaceuticals, and OrbusNeich; has received consultant fees from Abbott Laboratories, Boston Scientific, CardiaWave, Chiesi, Janssen Scientific Affairs, Medscape/WebMD, Medtelligence (Janssen Scientific Affairs), Roivant Sciences, Sanofi, and Siemens Medical Solutions; has received consultant fees paid to the institution from Abbott Laboratories and Bristol Myers Squibb; has served on the advisory board, funding paid to the institution, for Spectranetics/Philips/Volcano Corp; has served as a consultant (spouse) for Abiomed, The Medicines Company, and Merck; has equity <1% in Claret Medical and Elixir Medical; has served on the Data and Safety Monitoring Board, membership fees paid to the institution, of Watermark Research Partners; has performed consulting (no fee) for Idorsia Pharmaceuticals Ltd. and Regeneron Pharmaceuticals; and has served as Associate Editor for the American College of Cardiology and American Medical Association. Dr. Petrie has received speakers fees, research grants, or consulting honoraria from Takeda, Novartis, AstraZeneca, Maquet, Boehringer Ingelheim, Pfizer, Daiichi-Sankyo, Servier, Eli Lilly, and Novo Nordisk; has served on clinical events committees for Roche, Bayer, Stealth Biotherapeutics, AstraZeneca, GlaxoSmithKline, Astellas, Cardiorentis, Reservlogix, and Boehringer Ingelheim; and is supported by the British Heart Foundation (BHF) Centre of Research Excellence Award (RE/13/5/30177 and RE/18/6/34217+). Dr. Butler has received research support from the National Institutes of Health, Patient-Centered Outcomes Research Institute, and the European Union; and is a consultant for Abbott, Adrenomed, Amgen, Array, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, CVRx, G3 Pharmaceutical, Impulse Dynamics, Janssen, LivaNova, Luitpold, Medtronic, Merck, Novartis, Novo Nordisk, Relypsa, Roche, V-Wave Limited, and Vifor. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Adding to the foundation of statins, ezetimibe and proprotein convertase subtilisin-kexin type 9 inhibitors (PCSK9i), novel, emerging low-density lipoprotein cholesterol (LDL-C)-lowering therapies are under development for the prevention of cardiovascular disease. Inclisiran, a small interfering RNA molecule that inhibits PCSK9, only needs to be dosed twice a year and has the potential to help overcome current barriers to persistence and adherence to lipid-lowering therapies. Bempedoic acid, which lowers LDL-C upstream from statins, provides a novel alternative for patients with statin intolerance. Angiopoetin-like 3 protein (ANGPTL3) inhibitors have been shown to provide potent LDL-C lowering in patients with homozygous familial hypercholesterolemia without major adverse effects as seen with lomitapide and mipomersen, and may reduce the need for apheresis. Finally, CETP inhibitors may yet be effective with the development of obicetrapib. These novel agents provide the clinician the tools to effectively lower LDL-C across the entire range of LDL-C-induced elevation of cardiovascular risk, from primary prevention and secondary prevention to null-null homozygous familial hypercholesterolemia patients., Competing Interests: Funding Support and Author Disclosures Dr. Nurmohamed is cofounder of Lipid Tools. Dr. Navar has received funding for research to her institution from Amgen, Janssen, Amarin, Sanofi, and Regeneron; and has received honoraria and consulting fees from Amarin, Amgen, Astra Zeneca, BI, Esperion, Janssen, Lilly, Sanofi, Regeneron, NovoNordisk, Novartis, The Medicines Company, New Amsterdam, DalCor, 89Bio, and Pfizer. Prof. Kastelein has received personal fees from AstraZeneca, CIVI Biotechnology, CSL Behring, Draupnir, Esperion, Gemphire, Madrigal Pharmaceuticals, Matinas Biopharma, North Sea Therapeutics, Novo Nordisk, Novartis, Regeneron, RegenXBio, Staten Biotech, 89 Bio, Omeicos, and Serometrix; and is a part-time employee of NewAmsterdam Pharma., (Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

The growing population of older adults (age ≥65 years) is expected to lead to higher rates of cardiovascular disease. The expansion of digital health (encompassing telehealth, telemedicine, mobile health, and remote patient monitoring), Internet access, and cellular technologies provides an opportunity to enhance patient care and improve health outcomes-opportunities that are particularly relevant during the current coronavirus disease-2019 pandemic. Insufficient dexterity, visual impairment, and cognitive dysfunction, found commonly in older adults should be taken into consideration in the development and utilization of existing technologies. If not implemented strategically and appropriately, these can lead to inequities propagating digital divides among older adults, across disease severities and socioeconomic distributions. A systematic approach, therefore, is needed to study and implement digital health strategies in older adults. This review will focus on current knowledge of the benefits, barriers, and use of digital health in older adults for cardiovascular disease management., Competing Interests: Author Disclosures Dr. Dorsch is supported by R18 HS026874 and R21 HS026322 from the Agency for Health Research and Quality, R01 AG062582 from the National Institutes of Health (NIH)/National Institute of Aging, and the American Health Association Health IT Research Network; has received honoraria from Janssen; and has received research funding from Bristol Myers Squibb/Pfizer and Amgen in the past 2 years. Dr. Dodson is supported by K23 AG052463 from the NIH/National Institute of Aging, and R01 AG062520 from the NIH/National Institute of Aging. Dr. Masterson Creber is supported by NIH/National Institute of Nursing Research R00NR016275, and NIH/National Heart, Lung, and Blood Institute R01HL152021. Dr. Kitsiou is supported by the NIH/National Institute of Nursing Research R01NR017635 and R21NR018281, NIH/National Heart, Lung, and Blood Institute R61HL139454, and NIH/National Institute on Aging P30AG022849. Dr. Goyal is supported by the National Institute on Aging (NIA) grant R03AG056446 and American Heart Association grant 18IPA34170185. Dr. Maurer has received grant support from National Institutes of Health R01HL139671-01, R21AG058348, and K24AG036778; has received consulting income from Pfizer, GlaxoSmithKline, EIdos, Prothena, Akcea, and Alnylam; and his institution has received clinical trial funding from Pfizer, Prothena, Eidos, and Alnylam. Dr. Batsis is supported in part by the National Institute on Aging of the National Institutes of Health under Award Number K23AG051681 and R01-AG067416; and has part ownership in a patent developed for the Instrumented Resistance Exercise Device (Dartmouth Patent application # 62/672,827). Dr. Turakhia has received grants unrelated to this work from Apple, Janssen, Bayer, AstraZeneca, Boehringer Ingelheim, the American Heart Association, and Bristol Myers Squibb; has been a consultant to Medtronic, Biotronik, Pfizer, Bayer, Novartis, Sanofi, Johnson & Johnson, Myokardia, and Milestone Pharmaceuticals unrelated to this work; and is an editor for JAMA Cardiology. Dr. Forman is supported by the NIH National Institute on Aging R01AG060499-01, R01AG058883, and P30AG024827, and the NIH Common Fund U01AR071130. Dr. Bernacki is supported by T32HL125195-04 from the NIH/National Heart, Lung, and Blood Institute. Dr. Peterson has received research funding from AstraZeneca, Janssen, Amgen, and Sanofi unrelated to this work. Dr. Freeman does nonpromotional speaking for Boehringer Ingelheim; has served on Advisory Boards for The Medicines Company and Regeneron; and has served as a consultant for Actelion, none of which are related to the work submitted. Dr. Bhavnani has served as a scientific advisor to Analytics 4 Life and Blumio; has served as a consultant to Bristol Myers Squibb and Pfizer; and has received research support from Scripps Clinic, Alliance Healthcare Foundation, and the Qualcomm Foundation outside of the present work. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. The views expressed in this paper are by members of the American College of Cardiology’s Innovation Council, Cardiovascular Team Council and the Geriatric Cardiology Section Leadership Council and do not necessarily reflect the views of the Journal of the American College of Cardiology or the American College of Cardiology., (Copyright © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: The prevalence of obstructive coronary artery disease (CAD) in symptomatic patients referred for diagnostic testing has declined, warranting optimization of individualized diagnostic strategies., Objectives: This study sought to present a simple, clinically applicable tool enabling estimation of the likelihood of obstructive CAD by combining a pre-test probability (PTP) model (Diamond-Forrester approach using sex, age, and symptoms) with clinical risk factors and coronary artery calcium score (CACS)., Methods: The new tool was developed in a cohort of symptomatic patients (n = 41,177) referred for diagnostic testing. The risk factor-weighted clinical likelihood (RF-CL) was calculated through PTP and risk factors, while the CACS-weighted clinical likelihood (CACS-CL) added CACS. The 2 calculation models were validated in European and North American cohorts (n = 15,411) and compared with a recently updated PTP table., Results: The RF-CL and CACS-CL models predicted the prevalence of obstructive CAD more accurately in the validation cohorts than the PTP model, and markedly increased the area under the receiver-operating characteristic curves of obstructive CAD: for the PTP model, 72 (95% confidence intervals [CI]: 71 to 74); for the RF-CL model, 75 (95% CI: 74 to 76); and for the CACS-CL model, 85 (95% CI: 84 to 86). In total, 38% of the patients in the RF-CL group and 54% in the CACS-CL group were categorized as having a low clinical likelihood of CAD, as compared with 11% with the PTP model., Conclusions: A simple risk factor and CACS-CL tool enables improved prediction and discrimination of patients with suspected obstructive CAD. The tool empowers reclassification of patients to low likelihood of CAD, who need no further testing., Competing Interests: Author Relationship With Industry This work was supported by the Steno Partner Collaboration Unit, Gødstrup Hospital, Herning, Denmark. Drs. Winther, Schmidt, and Bøttcher have received institutional research grant support from Acarix. Dr. Schmidt is a part-time consultant for Acarix. Dr. Schmidt is a minor shareholder of Acarix. Dr. Hoffmann has received institutional research grants on behalf of Massachusetts General Hospital, outside of the submitted work, from KOWA, MedImmune, AstraZeneca, and HeartFlow; and has received consultant fees from DCRI and Recor, outside of the scope of the submitted work. Dr. Wijns has received research grants and honoraria from MicroPort. Dr. Christiansen has served on the Advisory Board for Novo Nordisk. Dr. Saraste has received speaker fees from AstraZeneca, Amgen, Bayer, Novartis, and Abbott; and has served on the Advisory Board for AstraZeneca and Amgen, outside of the submitted work. Dr. Bøttcher has served on the Advisory Board for Novo Nordisk, AstraZeneca, Bayer, Sanofi, and Acarix, outside of submitted work. Dr. Knuuti has received speaker fees from GE Healthcare, Merck, Lundbeck, and Bayer; and has received study protocol consultant fees from GE Healthcare and AstraZeneca, outside of the submitted work. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Adoption of the results of large-scale randomized controlled trials in percutaneous coronary intervention (PCI) may differ internationally, yet few studies have described the potential variations in PCI practice patterns., Objectives: Using representative national registries, we compared temporal trends in procedural volume, patient characteristics, pre-procedural testing, procedural characteristics, and quality metrics in the United States and Japan., Methods: The National Cardiovascular Data Registry CathPCI was used to describe care in the United States, and the J-PCI was used to assess practice patterns in Japan (numbers of participating hospitals: 1,752 in the United States and 1,108 in Japan). Both registries were summarized between 2013 and 2017., Results: PCI volume increased by 15.8% in the United States from 550,872 in 2013 to 637,650 in 2017, primarily because of an increase in nonelective PCIs (p for trend <0.001). In Japan, the volume of PCIs increased by 36%, from 181,750 in 2013 to 247,274 in 2017, primarily because of an increase in elective PCIs (p for trend <0.001). The proportion of PCI cases for elective conditions was >2-fold greater in Japan (72.7%) than in the United States (33.8%; p < 0.001). Overall, the ratio of nonelective PCI (vs. elective PCI; 27.3% vs. 66.2%; p < 0.001) and the performance of noninvasive stress testing in patients with stable disease (15.2% vs. 55.3%; p < 0.001) was lower in Japan than in the United States. Computed tomography angiography was more commonly used in Japan (22.3% vs. 2.0%; p < 0.001)., Conclusions: Elective PCI is more than twice as common in Japan as in the United States in contemporary practice. Computed tomography angiography is much more frequently used pre-procedurally in Japan than in the United States., (Copyright © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: The PIONEER-HF (comParIson Of sacubitril/valsartaN versus Enalapril on Effect on nt-pRo-bnp in patients stabilized from an acute Heart Failure episode) trial demonstrated the efficacy and safety of sacubitril/valsartan (S/V) in stabilized patients with acute decompensated heart failure (HF) and reduced ejection fraction., Objectives: The study sought to determine whether and how prior HF history and treatment with an angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) affected the results., Methods: The PIONEER-HF trial was a prospective, multicenter, double-blind, randomized clinical trial enrolling 881 patients with an ejection fraction ≤40%. Patients were randomly assigned 1:1 to in-hospital initiation of S/V (n = 440) versus enalapril (n = 441). Pre-specified subgroup analyses were performed based on prior HF history (i.e., de novo HF vs. worsening chronic HF) and treatment with an ACE inhibitor or ARB (i.e., ACE inhibitor or ARB-yes vs. ACE inhibitor or ARB-no) at admission., Results: At enrollment, 303 (34%) patients presented with de novo HF and 576 (66%) patients with worsening chronic HF. A total of 421 (48%) patients had been treated with an ACE inhibitor or ARB, while 458 (52%) had not been treated with an ACE inhibitor or ARB. N-terminal pro-B-type natriuretic peptide declined significantly in all 4 subgroups (p < 0.001), with greater decreases in the S/V versus the enalapril arm (p < 0.001). There was no interaction between prior HF history (p = 0.350) or ACE inhibitor or ARB treatment (p = 0.880) and the effect of S/V versus enalapril on cardiovascular death or rehospitalization for HF. The incidences of adverse events were comparable between S/V and enalapril across all 4 subgroups., Conclusions: Among patients admitted for acute decompensated HF, S/V was safe and well tolerated, led to a significantly greater reduction in N-terminal pro-B-type natriuretic peptide, and improved clinical outcomes compared with enalapril irrespective of previous HF history or ACE inhibitor or ARB treatment. (Comparison of Sacubitril/Valsartan Versus Enalapril on Effect of NT-proBNP in Patients Stabilized From an Acute Heart Failure Episode [PIONEER-HF]; NCT02554890)., (Copyright © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: The 2018 cholesterol guidelines of the American Heart Association and the American College of Cardiology (AHA/ACC) changed 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase inhibitor (statin) eligibility criteria for primary prevention to include multiple risk enhancers and novel intensive lipid-lowering therapies for secondary prevention., Objectives: This study sought to determine how guideline changes affected identification for preventive therapy in young adults with premature myocardial infarction (MI)., Methods: The study identified adults presenting with first MI at Duke University Medical Center in Durham, North Carolina. Statin therapy eligibility was determined using the 2013 ACC/AHA and 2018 AHA/ACC guidelines criteria. The study also determined potential eligibility for intensive lipid-lowering therapies (very high risk) under the 2018 AHA/ACC guidelines, by assessing the composite of all-cause death, recurrent MI, or stroke rates in adults considered "very high risk" versus not., Results: Among 6,639 patients with MI, 41% were <55 years of age ("younger"), 35% were 55 to 65 years of age ("middle-aged"), and 24% were 66 to 75 years of age ("older"). Younger adults were more frequently smokers (52% vs. 38% vs. 22%, respectively) and obese (42% vs. 34% vs. 31%, respectively), with metabolic syndrome (21% vs. 19% vs. 17%, respectively) and higher low-density lipoprotein cholesterol (117 vs. 107 vs. 103 mg/dl, respectively) (p trend <0.01 for all). Pre-MI, fewer younger adults met guideline indications for 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase inhibitor (statin) therapy than middle-aged and older adults. The 2018 guideline identified fewer younger adults eligible for statin therapy at the time of their MI than the 2013 guideline (46.4% vs. 56.7%; p < 0.01). Younger patients less frequently met very high-risk criteria for intensive secondary prevention lipid-lowering therapy (28.3% vs. 40.0% vs. 81.4%, respectively; p < 0.01). Over a median 8 years of follow-up, very high-risk criteria were associated with increased risk of major adverse cardiovascular events in individuals <55 years of age (hazard ratio: 2.09; 95% confidence interval: 1.82 to 2.41; p < 0.001), as was the case in older age groups (p interaction = 0.54)., Conclusions: Most younger patients with premature MI are not identified as statin candidates before their event on the basis of the 2018 guidelines, and most patients with premature MI are not recommended for intensive post-MI lipid management., (Copyright © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Concerns about the external validity of traditional randomized clinical trials (RCTs), together with the widespread availability of real-world data and advanced data analytic tools, have led to claims that common sense and clinical observation, rather than RCTs, should be the preferred method to generate evidence to support clinical decision-making. However, over the past 4 decades, results from well-done RCTs have repeatedly contradicted practices supported by common sense and clinical observation. Common sense and clinical observation fail for several reasons: incomplete understanding of pathophysiology, biases and unmeasured confounding in observational research, and failure to understand risks and benefits of treatments within complex systems. Concerns about traditional RCT models are legitimate, but randomization remains a critical tool to understand the causal relationship between treatments and outcomes. Instead, development and promulgation of tools to apply randomization to real-world data are needed to build the best evidence base in cardiovascular medicine., (Copyright © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Emerging data science techniques of predictive analytics expand the quality and quantity of complex data relevant to human health and provide opportunities for understanding and control of conditions such as heart, lung, blood, and sleep disorders. To realize these opportunities, the information sources, the data science tools that use the information, and the application of resulting analytics to health and health care issues will require implementation research methods to define benefits, harms, reach, and sustainability; and to understand related resource utilization implications to inform policymakers. This JACC State-of-the-Art Review is based on a workshop convened by the National Heart, Lung, and Blood Institute to explore predictive analytics in the context of implementation science. It highlights precision medicine and precision public health as complementary and compelling applications of predictive analytics, and addresses future research and training endeavors that might further foster the application of predictive analytics in clinical medicine and public health., (Copyright © 2020 American College of Cardiology Foundation. All rights reserved.)

Background: The CABANA (Catheter Ablation Versus Antiarrhythmic Drug Therapy for Atrial Fibrillation) trial randomized 2,204 patients with atrial fibrillation (AF) to catheter ablation or drug therapy. Analysis by intention-to-treat showed a nonsignificant 14% relative reduction in the primary outcome of death, disabling stroke, serious bleeding, or cardiac arrest., Objectives: The purpose of this study was to assess recurrence of AF in the CABANA trial., Methods: The authors prospectively studied CABANA patients using a proprietary electrocardiogram recording monitor for symptom-activated and 24-h AF auto detection. The AF recurrence endpoint was any post-90-day blanking atrial tachyarrhythmias lasting 30 s or longer. Biannual 96-h Holter monitoring was used to assess AF burden. Patients who used the CABANA monitors and provided 90-day post-blanking recordings qualified for this analysis (n = 1,240; 56% of CABANA population). Treatment comparisons were performed using a modified intention-to-treat approach., Results: Median age of the 1,240 patients was 68 years, 34.4% were women, and AF was paroxysmal in 43.0%. Over 60 months of follow-up, first recurrence of any symptomatic or asymptomatic AF (hazard ratio: 0.52; 95% confidence interval: 0.45 to 0.60; p < 0.001) or first symptomatic-only AF (hazard ratio: 0.49; 95% confidence interval: 0.39 to 0.61; p < 0.001) were both significantly reduced in the catheter ablation group. Baseline Holter AF burden in both treatment groups was 48%. At 12 months, AF burden in ablation patients averaged 6.3%, and in drug-therapy patients, 14.4%. AF burden was significantly less in catheter ablation compared with drug-therapy patients across the 5-year follow-up (p < 0.001). These findings were not sensitive to the baseline pattern of AF., Conclusions: Catheter ablation was effective in reducing recurrence of any AF by 48% and symptomatic AF by 51% compared with drug therapy over 5 years of follow-up. Furthermore, AF burden was also significantly reduced in catheter ablation patients, regardless of their baseline AF type. (Catheter Ablation vs Anti-arrhythmic Drug Therapy for Atrial Fibrillation Trial [CABANA]; NCT00911508)., (Copyright © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)