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We report a case of an active-duty diver who developed severe decompression sickness with concomitant patent foramen ovale that was successfully closed contrary to standard guideline recommendations. This case should prompt evaluation of the role of cardiac screening in occupational divers, including tactical athletes, relative to recreational divers., Competing Interests: Funding Support and Author Disclosures Partial support was received from award HU00011920029 from Defense Health Agency to the Military Cardiovascular Outcomes Research program, Uniformed Services University, Bethesda, Maryland. The authors have reported that they have no relationships relevant to the contents of this paper to disclose. The views expressed in this article are those of the authors and do not reflect the official policy of the Department of Defense (DoD) or the U.S. government. The identification of specific products or scientific instrumentation is considered an integral part of the scientific endeavor and does not constitute endorsement or implied endorsement on the part of the author(s), DoD, or any component agency., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

OBJECTIVES: The aim of this study was to determine if ablation that targets patient-specific atrial fibrillation (AF)-sustaining substrates (rotors or focal sources) is more durable than trigger ablation alone at preventing late AF recurrence. BACKGROUND: Late recurrence substantially limits the efficacy of pulmonary vein isolation for AF and is associated with pulmonary vein reconnection and the emergence of new triggers. METHODS: Three-year follow-up was performed of the CONFIRM (Conventional Ablation for Atrial Fibrillation With or Without Focal Impulse and Rotor Modulation) trial, in which 92 consecutive patients with AF (70.7% persistent) underwent novel computational mapping. Ablation comprised source (focal impulse and rotor modulation [FIRM]) and then conventional ablation in 27 patients (FIRM guided) and conventional ablation alone in 65 patients (FIRM blinded). Patients were followed with implanted electrocardiographic monitors when possible (85.2% of FIRM-guided patients, 23.1% of FIRM-blinded patients). RESULTS: FIRM mapping revealed a median of 2 (interquartile range: 1 to 2) rotors or focal sources in 97.7% of patients during AF. During a median follow-up period of 890 days (interquartile range: 224 to 1,563 days), compared to FIRM-blinded therapy, patients receiving FIRM-guided ablation maintained higher freedom from AF after 1.2 ± 0.4 procedures (median 1; interquartile range: 1 to 1) (77.8% vs. 38.5%, p = 0.001) and a single procedure (p < 0.001) and higher freedom from all atrial arrhythmias (p = 0.003). Freedom from AF was higher when ablation directly or coincidentally passed through sources than when it missed sources (p < 0.001). CONCLUSIONS: FIRM-guided ablation is more durable than conventional trigger-based ablation in preventing 3-year AF recurrence. Future studies should investigate how ablation of patient-specific AF-sustaining rotors and focal sources alters the natural history of arrhythmia recurrence. (The Dynamics of Human Atrial Fibrillation; NCT01008722).

ObjectivesThe aim of this study was to determine the associations between statin use and major adverse cardiovascular and cerebrovascular events (MACCE) and amputation-free survival in critical limb ischemia (CLI) patients.BackgroundCLI is an advanced form of peripheral arterial disease associated with nonhealing arterial ulcers and high rates of MACCE and major amputation. Although statin medications are recommended for secondary prevention in peripheral arterial disease, their effectiveness in CLI is uncertain.MethodsWe reviewed 380 CLI patients who underwent diagnostic angiography or therapeutic endovascular intervention from 2006 through 2012. Propensity scores and inverse probability of treatment weighting were used to adjust for baseline differences between patients taking and not taking statins.ResultsStatins were prescribed for 246 (65%) patients. The mean serum low-density lipoprotein (LDL) level was lower in patients prescribed statins (75 ± 28 mg/dl vs. 96 ± 40 mg/dl, p < 0.001). Patients prescribed statins had more baseline comorbidities including diabetes, coronary artery disease, and hypertension, as well as more extensive lower extremity disease (all p values 130 mg/dl had increased HRs of MACCE and mortality compared with patients with lower levels of LDL.ConclusionsStatins are associated with lower rates of mortality and MACCE and increased amputation-free survival in CLI patients.

ObjectivesThis study was performed to determine predictors of in-stent restenosis from a high volume, single-center practice.BackgroundIntracoronary stents have been shown to reduce the restenosis rate as compared with balloon angioplasty, but in-stent restenosis continues to be an important clinical problem.MethodsBetween April 1993 and March 1997, 1,706 patients with 2,343 lesions were treated with a variety of intracoronary stents. The majority of stents were placed with high pressure balloon inflations and intravascular ultrasound (IVUS) guidance. Angiographic follow-up was obtained in 1,173 patients with 1,633 lesions (70%). Clinical, angiographic and IVUS variables were prospectively recorded and analyzed by univariate and multivariate models for the ability to predict the occurrence of in-stent restenosis defined as a diameter stenosis > or =50%.ResultsIn-stent restenosis was angiographically documented in 282 patients with 409 lesions (25%). The restenosis group had a significantly longer total stent length, smaller reference lumen diameter, smaller final minimal lumen diameter (MLD) by angiography and smaller stent lumen cross-sectional area (CSA) by IVUS. In lesions where IVUS guidance was used, the restenosis rate was 24% as compared with 29% if IVUS was not used (p < 0.05). By multivariate logistic regression analysis, longer total stent length, smaller reference lumen diameter and smaller final MLD were strong predictors of in-stent restenosis. In lesions with IVUS guidance, IVUS stent lumen CSA was a better independent predictor than the angiographic measurements.ConclusionsAchieving an optimal stent lumen CSA by using IVUS guidance during the procedure and minimizing the total stent length may reduce in-stent restenosis.

Stroke is a devastating condition with significant morbidity and mortality worldwide. Antithrombotic therapy plays a crucial role in both primary and secondary prevention of stroke events. Single or dual antiplatelet therapy is generally preferred in cases of large-artery atherosclerosis and small-vessel disease, whereas anticoagulation is recommended in conditions of blood stasis or hypercoagulable states that mostly result in red thrombi. However, the benefit of antithrombotic therapies must be weighed against the increased risk of bleeding, which can pose significant challenges in the pharmacological management of this condition. This review provides a comprehensive summary of the currently available evidence on antithrombotic therapy for ischemic stroke and outlines an updated therapeutic algorithm to support physicians in tailoring the strategy to the individual patient and the underlying mechanism of stroke., Competing Interests: Funding Support and Author Disclosures Prof Capodanno has received speaker honoraria from Daiichi-Sankyo and Sanofi. 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.)

Reducing the incidence and prevalence of standard modifiable cardiovascular risk factors (SMuRFs) is critical to tackling the global burden of coronary artery disease (CAD). However, a substantial number of individuals develop coronary atherosclerosis despite no SMuRFs. SMuRFless patients presenting with myocardial infarction have been observed to have an unexpected higher early mortality compared to their counterparts with at least 1 SMuRF. Evidence for optimal management of these patients is lacking. We assembled an international, multidisciplinary team to develop an evidence-based clinical pathway for SMuRFless CAD patients. A modified Delphi method was applied. The resulting pathway confirms underlying atherosclerosis and true SMuRFless status, ensures evidence-based secondary prevention, and considers additional tests and interventions for less typical contributors. This dedicated pathway for a previously overlooked CAD population, with an accompanying registry, aims to improve outcomes through enhanced adherence to evidence-based secondary prevention and additional diagnosis of modifiable risk factors observed., Competing Interests: Funding Support and Author Disclosures The Centre for Research Excellence is supported by National Health & Medical Research Council of Australia (grant number GNT1196629). Dr Figtree is funded by a National Health & Medical Research Council Practitioner Fellowship (GNT1135920). Dr Ellinor is supported by grants from the National Institutes of Health (1RO1HL092577, 1R01HL157635, 1R01HL157635), by a grant from the American Heart Association Strategically Focused Research Networks (18SFRN34110082), and by a grant from the European Union (MAESTRIA 965286). Dr Psaltis is funded by a National Heart Foundation Level 3 Future Leader Fellowship (106656). Dr Redfern is supported by grants from the National Health & Medical Research Council of Australia (GNT2007946 and GNT1182301). Dr Wilson is supported by grants from the National Health & Medical Research Council of Australia (GNT119600, GNT9100001, GNT1153479). Dr Guzik is funded by the British Heart Foundation and European Research Council (ERC-InflammaTENSION 726318). Dr Arnott has received honoraria from Amgen and AstraZeneca. Dr Brown has received consulting fees from Novartis. Dr Bhatt has received research funding from Abbott, Acesion Pharma, Afimmune, Aker Biomarine, 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 Pharmaceuticals, Fractyl, Garmin, HLS Therapeutics, Idorsia, Ironwood, Ischemix, Janssen, Javelin, Lexicon, Lilly, Medtronic, Merck, Moderna, MyoKardia, NirvaMed, Novartis, Novo Nordisk, Owkin, Pfizer Inc, PhaseBio, PLx Pharma, Recardio, Regeneron, Reid Hoffman Foundation, Roche, Sanofi, Stasys, Synaptic, The Medicines Company, Youngene, and 89bio; has received royalties from Elsevier; has received consulting fees from Broadview Ventures, Hims, and McKinsey; has received payment or honoraria from the American College of Cardiology, Baim Institute for Clinical Research, Belvoir Publications, Boston Scientific, Cleveland Clinic, Duke Clinical Research Institute, Mayo Clinic, Mount Sinai School of Medicine, Novartis, Population Health Research Institute, Rutgers University, Canadian Medical and Surgical Knowledge Translation Research Group, Cowen and Company, HMP Global, Journal of the American College of Cardiology, K2P, Level Ex, Medtelligence/ReachMD, MJH Life Sciences, Oakstone CME, Piper Sandler, Slack Publications, WebMD, Wiley, and Society of Cardiovascular Patient Care; has received payment for expert testimony from Arnold and Porter law firm; has received travel or meeting support from the American College of Cardiology, Society of Cardiovascular Patient Care, and American Heart Association; has been named (no income) on a patent application for sotagliflozin, assigned to Brigham and Women’s Hospital, who assigned to Lexicon; serves on a Data Safety Monitoring Board for Acesion Pharma, Assistance Publique-Hôpitaux de Paris, Baim Institute, Boston Scientific, Cleveland Clinic, Contego Medical, Duke Clinical Research Institute, Mayo Clinic, Mount Sinai School of Medicine, Novartis, and Population Health Research Institute; has served on an Advisory Board for AngioWave, 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 for the American College of Cardiology, AngioWave, Boston VA Research Institute, Bristol Myers Squibb, DRS.LINQ, High Enroll, Society of Cardiovascular Patient Care, and TobeSoft; has stock or stock options with AngioWave, Bristol Myers Squibb, DRS.LINQ, and High Enroll; has financial or other nonfinancial interests in Clinical Cardiology, NCDR-ACTION Registry Steering Committee, Contego Medical, American Heart Association Quality Oversight Committee, VA CART Research and Publications Committee; and is a coinvestigator for Abbott, Biotronik, Boston Scientific, CSI, St Jude Medical, Phillips SpectraWAVE, Svelte, and Vascular Solutions. Dr Brieger has received research grant support from Novartis and has received honoraria from BMS/Pfizer. Dr Chong has received consulting fees from Implicit Bioscience Pty; and has a provisional patent for a cell surface marker signature for arrhythmogenic pluripotent stem cell-derived cardiomyocyte. Dr Cistulli has received research grant support from ResMed and SomnoMed; has received consulting fees from RedMed, SomnoMed, and Signifier Medical Technologies; and has received honoraria from ResMed and SomnoMed. Dr Ellinor has received sponsored research support from Bayer AG and IBM Research; and has served on Advisory Boards or consulted for Bayer AG, MyoKardia, and Novartis. Dr Figtree has received personal fees from Amgen, AstraZeneca, Bayer, CSL, and Janssen; has received grants from Abbott Diagnostic and Sanofi; is a founding director and chief medical officer of Prokardia; has a patent, “Biomarkers and Oxidative Stress,” awarded in the United States in May 2017 (US9638699B2) licensed to Northern Sydney Local Health District; has a patent, “Use of P2X7R Antagonists in Cardiovascular Disease” (PCT/AU2018/050905), licensed to Prokardia; has a patent, “Methods for Treatment and Prevention of Vascular Disease” (PCT/AU2015/000548) licensed to the University of Sydney/Northern Sydney Local Health District; and has a filed provisional patent application, “Methods for Predicting Coronary Artery Disease” (USYD Ref: 2022-009-PRO-0; 2022902660) to the University of Sydney/Northern Sydney Local Health District. Dr Hagström has received research grant support to his institution from Amgen and Pfizer; and has received honoraria from Amgen, AstraZeneca, Bayer, Novo Nordisk, Amarin, and Sanofi. Dr Jenkins has received research grant support from Abbott, Medtronic, and Mylan; and has served on Advisory Boards for Abbott Diabetes Care, Amgen, Insulet, and Medtronic. Dr Keech has received grant support from Abbott, Amgen, and Mylan; has received consulting fees from AstraZeneca, Pfizer, and Sanofi; and has participated as a Data Safety Monitoring Board member for the PROMINENT trial (Kowa Research Institute). Dr Kritharides has received research grant support from Amgen; and has received consulting fees from Seqiris. Dr Meikle has a license agreement with Juvenescence Ltd; and has received consultancy payments (made to Baker Institute) from BCAL Scientific and Juvenescence Ltd. Dr Mehran has received research grant support to her institution from Abbott, Abiomed, Alleviant Medical, AM-Pharma, Amgen, Applied Therapeutics, Arena, AstraZeneca, AtriCure, BAIM, Bayer, Beth Israel Deaconess Biosensors, Biotronik, Boston Scientific, Bristol Myers Squibb, CardiaWave, CellAegis, CeloNova, CERC, Chiesi, Concept Medical, CSL Behring, Cytosorbents, Daiichi-Sankyo, Duke University, Element Science, Faraday, Humacyte, Idorsia, Insel Gruppe AG, Magenta, Medtronic, Novartis, OrbusNeich, PhaseBio, Philips, RenalPro, RM Global, Shockwave, and Vivasure Zoll; has received consulting fees from Cine-Med Research; has served on an Advisory Board with all payments made to institution for Abbott, Janssen, Medtronic, and Novartis; and she and/or her spouse has stock or stock options in Applied Therapeutics, ControlRad, Elixir Medical, and Stel. Dr Natarajan has received research grant support from Apple, Amgen, AstraZeneca, Boston Scientific, and Novartis; has received consulting fees from Apple, AstraZeneca, Blackstone Life Sciences, Foresite Labs, Genetech/Roche, Invitae, Novartis, and TenSixteen Bio; has served on Advisory Boards for Esperion Therapeutics, geneXwell, and TenSixteen Bio; and holds stock or stock options in TenSixteen Bio and geneXwell. Dr Nicholls has received research grant support from AstraZeneca, Amgen, Anthera, Cerenis, Eli Lilly, Esperion, InfraReDx, LipoScience, The Medicines Company, New Amsterdam Pharma, Novartis, Resverlogix, Roche, and Sanofi-Regeneron; and has received consulting fees from Akcea, Amarin, Anthera, AstraZeneca, Boehringer Ingelheim, CSL Behring, Eli Lilly, Esperion, Omthera, Merck, Resverlogix, Sanofi-Regeneron, Takeda, and Vaxxinity. Dr Psaltis has received consulting fees from Amgen, Esperion Therapeutics, and Novartis; has received speaker honoraria from Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Novartis, Pfizer, and Sanofi; has received meeting travel support from Amgen and AstraZeneca; and has submitted a provisional patent for a method and composition for promoting neovascularization. Dr Sundström has stock or stock options with Anagram Kommunikation AB and Symptoms Europe AB. Dr Steg has received research grant support from Amarin, Bayer, Sanofi, and Servier Laboratories; has received consulting fees from Amgen, AstraZeneca, BMS/Myokardia, Merck, Novo Nordisk, and Regeneron; has served on Steering Committees or Critical Event Committees for Amarin, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Idorsia, Novartis, PhaseBio, Pfizer, Sanofi, and Servier; has received honoraria from AstraZeneca, Novartis, and Novo Nordisk; and has served on Data Safety Monitoring Boards for Servier, Sanofi, and PHRI. Dr Guzik has received research funding from the European Commission (ImmuneHyperCog and BrainGutCVD studies); has served as Editor-in-Chief for Cardiovascular Research; and has served as Board Committee member for the European Society of Cardiology. 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.)

Aim: The "2023 AHA/ACC/ACCP/ASPC/NLA/PCNA Guideline for the Management of Patients With Chronic Coronary Disease" provides an update to and consolidates new evidence since the "2012 ACCF/AHA/ACP/AATS/PCNA/SCAI/STS Guideline for the Diagnosis and Management of Patients With Stable Ischemic Heart Disease" and the corresponding "2014 ACC/AHA/AATS/PCNA/SCAI/STS Focused Update of the Guideline for the Diagnosis and Management of Patients With Stable Ischemic Heart Disease.", Methods: A comprehensive literature search was conducted from September 2021 to May 2022. Clinical studies, systematic reviews and meta-analyses, and other evidence conducted on human participants were identified that were published in English from MEDLINE (through PubMed), EMBASE, the Cochrane Library, Agency for Healthcare Research and Quality, and other selected databases relevant to this guideline., Structure: This guideline provides an evidenced-based and patient-centered approach to management of patients with chronic coronary disease, considering social determinants of health and incorporating the principles of shared decision-making and team-based care. Relevant topics include general approaches to treatment decisions, guideline-directed management and therapy to reduce symptoms and future cardiovascular events, decision-making pertaining to revascularization in patients with chronic coronary disease, recommendations for management in special populations, patient follow-up and monitoring, evidence gaps, and areas in need of future research. Where applicable, and based on availability of cost-effectiveness data, cost-value recommendations are also provided for clinicians. Many recommendations from previously published guidelines have been updated with new evidence, and new recommendations have been created when supported by published data., (Copyright © 2023 American Heart Association, Inc., and the American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Among statin-treated patients, inflammation assessed by means of high-sensitivity C-reactive protein (hsCRP) is a more powerful determinant of cardiovascular death and all-cause mortality than low-density-lipoprotein cholesterol (LDL-C). Several therapies that target residual inflammatory risk significantly reduce vascular event rates. For coronary artery disease patients already taking guideline-directed medical care, including statins, low-dose colchicine (0.5 mg/d orally) has been shown to safely lower major adverse cardiovascular events by 31% among those with stable atherosclerosis and by 23% after recent myocardial infarction. These magnitudes of benefit are larger than those seen in contemporary secondary prevention trials of adjunctive lipid-lowering agents. Low-dose colchicine is contraindicated in patients with significant renal or liver dysfunction and should be temporarily discontinued when taking concomitant agents such as clarithromycin, ketoconazole, and cyclosporine that share metabolism pathways. Lipid lowering and inflammation inhibition are not in conflict but are synergistic. In the future, combined use of aggressive LDL-C-lowering and inflammation-inhibiting therapies may become standard of care for most atherosclerosis patients. In June 2023, the U.S. Food and Drug Administration approved the use of low-dose colchicine to reduce the risk of myocardial infarction, stroke, coronary revascularization, and cardiovascular death in adult patients with established atherosclerotic disease or with multiple risk factors for cardiovascular disease., Competing Interests: Funding Support and Author Disclosures Dr Ridker has received institutional research grant support from Kowa, Novartis, Amarin, Pfizer, Esperion, Novo Nordisk, and the National Heart, Lung, and Blood Institute; has served as a consultant to Novartis, Flame, Agepha, AstraZeneca, Janssen, Civi Biopharm, Glaxo Smith Kline, SOCAR, Novo Nordisk, Omeicos, Health Outlook, Montai Health, New Amsterdam, Boehringer Ingelheim, RTI, Zomagen, Cytokinetics, Horizon Therapeutics, and Cardio Therapeutics; has minority shareholder equity positions in Uppton, Bitteroot Bio, and Angiowave; and receives compensation for service on the Peter Munk Advisory Board (University of Toronto), the Leducq Foundation, Paris FR, and the Baim Institute (Boston). 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: Patients with established cardiovascular disease (CVD) are at high risk of incident heart failure (HF), which may in part reflect the impact of systemic inflammation., Objectives: The goal of this study was to determine the association between C-reactive protein (CRP) and incident HF in patients with established CVD., Methods: Patients from the prospective UCC-SMART (Utrecht Cardiovascular Cohort-Second Manifestations of ARTerial disease) cohort with established CVD, but without prevalent HF were included (n = 8,089). Incident HF was defined as a first hospitalization for HF. The association between baseline CRP and incident HF was assessed using Cox proportional hazards models adjusted for established risk factors (ie, age, sex, myocardial infarction, smoking, diabetes mellitus, body mass index, blood pressure, cholesterol, and kidney function)., Results: During a median follow-up of 9.7 years (IQR 5.4-14.1 years), 810 incident HF cases were observed (incidence rate 1.01/100 person-years). Higher CRP was independently associated with an increased risk of incident HF: HR per 1 mg/L: 1.10 (95% CI: 1.07-1.13), and for last vs first CRP quartile: 2.22 (95% CI: 1.76-2.79). The association was significant for both HF with reduced (HR: 1.09; 95% CI: 1.04-1.14) and preserved ejection fraction (HR: 1.12; 95% CI: 1.07-1.18) (P for difference = 0.137). Additional adjustment for medication use and interim myocardial infarction did not attenuate the association, and the association remained consistent beyond 15 years after the CRP measurement., Conclusions: In patients with established CVD, CRP is an independent risk marker of incident HF. These data support ongoing trial efforts to assess whether anti-inflammatory agents can reduce the burden of HF., Competing Interests: Funding Support and Author Disclosures The UCC-SMART study was financially supported by a grant of the University Medical Center Utrecht. The funder had no role in study design, data collection, data analysis, data interpretation, or writing of the report. The authors did not receive any specific funding for the current study. Dr Ridker has received research grant support from Novo Nordisk, Novartis, Kowa, Amarin, Pfizer, Esperion, and the National Heart, Lung, and Blood Institute; has served as a consultant to Novartis, Flame, Agepha, AstraZeneca, Janssen, Civi Biopharm, GlaxoSmithKline, SOCAR, Novo Nordisk, Uptton, Health Outlook, Montai Health, New Amsterdam, Boehringer Ingelheim, Angiowave, RTI, Horizon Therapeutics, Cardio Therapeutics, SOCAR, and Zomagen; and receives compensation for service on the Peter Munk Advisory Board (University of Toronto), the Leducq Foundation (Paris, France), and the Baim Institute (Boston, Massachusetts). 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: Aspirin is the only antiplatelet agent with a Class I recommendation for long-term prevention of cardiovascular events in patients with coronary artery disease (CAD). There is inconsistent evidence on how it compares with alternative antiplatelet agents., Objectives: This study compared P2Y 12 inhibitor monotherapy vs aspirin in patients with CAD., Methods: We conducted a patient-level meta-analysis of randomized trials comparing P2Y 12 inhibitor monotherapy vs aspirin monotherapy for the prevention of cardiovascular events in patients with established CAD. The primary outcome was the composite of cardiovascular death, myocardial infarction, and stroke. Prespecified key secondary outcomes were major bleeding and net adverse clinical events (the composite of the primary outcome and major bleeding). Data were pooled in a 1-step meta-analysis., Results: Patient-level data were obtained from 7 trials. Overall, 24,325 participants were available for analysis, including 12,178 patients assigned to receive P2Y 12 inhibitor monotherapy (clopidogrel in 7,545 [62.0%], ticagrelor in 4,633 [38.0%]) and 12,147 assigned to receive aspirin. Risk of the primary outcome was lower with P2Y 12 inhibitor monotherapy compared with aspirin over 2 years (HR: 0.88; 95% CI: 0.79-0.97; P = 0.012), mainly owing to less myocardial infarction (HR: 0.77; 95% CI: 0.66-0.90; P < 0.001). Major bleeding was similar (HR: 0.87; 95% CI: 0.70-1.09; P = 0.23) and net adverse clinical events were lower (HR: 0.89; 95% CI: 0.81-0.98; P = 0.020) with P2Y 12 inhibitors. The treatment effect was consistent across prespecified subgroups and types of P2Y 12 inhibitors., Conclusions: Given its superior efficacy and similar overall safety, P2Y 12 inhibitor monotherapy might be preferred over aspirin monotherapy for long-term secondary prevention in patients with established CAD. (P2Y 12 Inhibitor or Aspirin Monotherapy as Secondary Prevention in Patients With Coronary Artery Disease: An Individual Patient Data Meta-Analysis of Randomized Trials [PANTHER collaborative initiative]; CRD42021290774)., Competing Interests: Funding Support and Author Disclosures This study was funded by institutional support of the Cardiocentro Ticino Institute, Ente Ospedaliero Cantonale, and the Department of Cardiology at Bern University Hospital, which had no role in the data analysis, interpretation, or writing of the report. There was no industry involvement in the design, analysis, or funding of this study. Dr Valgimigli has received personal fees from AstraZeneca; has received grants and personal fees from Terumo; and has received personal fees from Alvimedica/CID, Abbott Vascular, Daiichi-Sankyo, Bayer, CoreFLOW, Idorsia Pharmaceuticals Ltd, Departement Klinische Forschung of Universität Basel, Bristol Myers Squibb SA, Medscape, Biotronik, and Novartis, outside the submitted work. Dr Windecker has received research and educational grants to the institution from Abbott, Abiomed, Amgen, AstraZeneca, Bayer, Biotronik, Boehringer Ingelheim, Boston Scientific, Bristol Myers Squibb, Cardinal Health, CardioValve, Corflow Therapeutics, CSL Behring, Daiichi-Sankyo, Edwards Lifesciences, Guerbet, Infraredx, Janssen-Cilag, Johnson & Johnson, Medicure, Medtronic, Merck Sharp & Dohme, Miracor Medical, Novartis, Novo Nordisk, Organon, OrPha Swiss, Pfizer, Polares, Regeneron, Sanofi, Servier, Sinomed, Terumo, Vifor, and V-Wave; serves as an unpaid advisory board member and/or unpaid member of the steering/executive group of trials funded by Abbott, Abiomed, Amgen, AstraZeneca, Bayer, Boston Scientific, Biotronik, Bristol Myers Squibb, Edwards Lifesciences, Janssen, MedAlliance, Medtronic, Novartis, Polares, Recardio, Sinomed, Terumo, 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 and Deputy Editor of JACC: Cardiovascular Interventions. Dr Mehran has served on the scientific advisory boards of the American Medical Association, the American College of Cardiology (Board of Trustees Member), the Society for Cardiovascular Angiography & Interventions (Women in Innovations Committee Member), JAMA Cardiology (Associate Editor), and the Cardiovascular Research Foundation (Faculty) (no fee). Dr Woodward is a consultant for Freeline; and has recently been a consultant to Amgen. Dr Schunkert has received personal fees from Amgen, AstraZeneca, Bayer Vital GmbH, Boehringer Ingelheim, Bristol Myers Squibb, Daiichi-Sankyo, Merck Sharp & Dohme, Novartis, Sanofi, Servier, and SYNLAB. Dr Franzone has received payment or honoraria for lectures, presentations, Speaker Bureaus, manuscript writing, or educational events from Edwards Lifesciences and Boehringer Ingelheim. Dr Bhatt discloses the following relationships—advisory board: AngioWave, Bayer, Boehringer Ingelheim, Cardax, CellProthera, Cereno Scientific, Elsevier Practice Update Cardiology, High Enroll, Janssen, Level Ex, McKinsey, Medscape Cardiology, Merck, MyoKardia, NirvaMed, Novo Nordisk, PhaseBio, PLx Pharma, Regado Biosciences, and Stasys; board of directors: AngioWave (stock options), Boston VA Research Institute, Bristol Myers Squibb (stock), DRS.LINQ (stock options), High Enroll (stock), Society of Cardiovascular Patient Care, and TobeSoft; Chair: Inaugural Chair, American Heart Association Quality Oversight Committee; consultant: Broadview Ventures; 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 (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; Rutgers University (for the National Institutes of Health–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), 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), Slack Publications (Chief Medical Editor, Cardiology Today’s Intervention), Society of Cardiovascular Patient Care (Secretary/Treasurer), WebMD (CME steering committees), Wiley (steering committee); other: Clinical Cardiology (Deputy Editor), NCDR-ACTION Registry Steering Committee (Chair), and VA CART Research and Publications Committee (Chair); patent: Sotagliflozin (named on a patent for sotagliflozin assigned to Brigham and Women's Hospital who assigned to Lexicon; neither Dr Bhatt nor Brigham and Women’s Hospital receive any income from this patent); research funding: Abbott, Acesion Pharma, Afimmune, Aker Biomarine, Amarin, Amgen, AstraZeneca, Bayer, Beren, Boehringer Ingelheim, Boston Scientific, Bristol Myers Squibb, Cardax, CellProthera, Cereno Scientific, Chiesi, CinCor, 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, Youngene, and 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, and Vascular Solutions; trustee: American College of Cardiology; and unfunded research: FlowCo and Takeda. Dr Steg has received grants, personal fees, and nonfinancial support from Sanofi; has received grants and personal fees from Amarin, Servier, and Bayer; has received personal fees from Amgen, AstraZeneca, BMS, Boehringer Ingelheim, Idorsia, Pfizer, and Novartis; and has a patent on the use of alirocumab to reduce risk after acute coronary syndrome (royalties to Sanofi) pending. Dr Szarek has served as a consultant or on advisory boards (or both) for CiVi, Resverlogix, Baxter, Esperion, Sanofi, and Regeneron Pharmaceuticals, Inc. 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.)

Regular exercise that meets or exceeds the current physical activity guidelines is associated with a reduced risk of cardiovascular disease (CVD) and mortality. Therefore, exercise training plays an important role in primary and secondary prevention of CVD. In this part 1 of a 4-part focus seminar series, we highlight the mechanisms and physiological adaptations responsible for the cardioprotective effects of exercise. This includes an increase in cardiorespiratory fitness secondary to cardiac, vascular, and skeletal muscle adaptations and an improvement in traditional and nontraditional CVD risk factors by exercise training. This extends to the role of exercise and its prescription in patients with CVDs (eg, coronary artery disease, chronic heart failure, peripheral artery disease, or atrial fibrillation) with special focus on the optimal mode, dosage, duration, and intensity of exercise to reduce CVD risk and improve clinical outcomes in these patients., Competing Interests: Funding Support and Author Disclosures Dr Kovacic is the recipient of an Agilent Thought Leader Award (January 2022), which includes funding for research that is unrelated to the current paper; and has received research support from the National Institutes of Health (R01HL148167), New South Wales health grant RG194194, the Bourne Foundation, and Agilent. 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: Documenting trends in risk factors among individuals with cardiovascular disease (CVD) may inform policy and secondary prevention initiatives., Objectives: This study aimed to examine 20-year trends in risk profiles among U.S. adults with CVD and any racial/ethnic disparities., Methods: In this serial cross-sectional analysis of 6,335 adults with self-reported CVD participating in the National Health and Nutrition Examination Survey from 1999 through 2018, we calculated age- and sex-adjusted proportions with ideal risk factor attainment., Results: The proportions with ideal hemoglobin A1c (<7% if diabetes or <5.7% if not) and body mass index (<25 kg/m 2 ) worsened from 58.7% (95% CI: 55.2%-62.1%) to 52.4% (95% CI: 48.2%-56.6%) and 23.9% (95% CI: 21.5%-26.4%) to 18.2% (95% CI: 15.6%-21.2%) from 1999-2002 to 2015-2018, respectively. After initial improvement, the proportion with blood pressure <130/80 mm Hg declined from 52.1% (95% CI: 48.9%-55.4%) in 2007-2010 to 48.6% (95% CI: 44.2%-52.7%) in 2015-2018. The proportion with non-high-density lipoprotein cholesterol levels <100 mg/dL increased from 7.3% (95% CI: 5.6%-9.5%) in 1999-2002 to 30.3% (95% CI: 25.7%-35.5%) in 2015-2018. The proportions with ideal smoking, physical activity, and diet profiles were unchanged over time, and in 2015-2018 were 77.8% (95% CI: 73.6%-81.4%), 22.4% (95% CI: 19.3%-25.9%), and 1.3% (95% CI: 0.7%-2.6%). Worsening trends were observed in Hispanic adults for cholesterol, and in Black adults for smoking (both P < 0.05 for nonlinear and linear trends). Persistently lower ideal risk factor attainment was observed for blood pressure in Black adults and for hemoglobin A1c levels in Asian adults compared with White adults (all P < 0.05 for differences)., Conclusions: Trends in cardiovascular risk factor profiles in U.S. adults with CVD were suboptimal from 1999 through 2018, with persistent racial/ethnic disparities., Competing Interests: Funding Support and Author Disclosures Dr Martin is a founder of and holds equity in Corrie Health; has received material support from Apple and iHealth; has received funding from the Maryland Innovation Initiative, Wallace H. Coulter Translational Research Partnership, Louis B. Thalheimer Fund, the Johns Hopkins Individualized Health Initiative, the American Heart Association (20SFRN35380046, 20SFRN35490003, COVID19-811000, #878924, and #882415), the Patient-Centered Outcomes Research Institute (ME-2019C1-15328), the National Institutes of Health (P01 HL108800 and R01AG071032), the David and June Trone Family Foundation, the Pollin Digital Innovation Fund, the PJ Schafer Cardiovascular Research Fund, Sandra and Larry Small, CASCADE FH, Google, and Amgen; has received personal fees for serving on scientific advisory boards for Amgen, AstraZeneca, Dalcor, Esperion, Kaneka, Novartis, Novo Nordisk, Sanofi, and 89bio; and is a coinventor on a system for low-density lipoprotein cholesterol estimation. 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.)