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AIM: The 2023 ACC/AHA/ACCP/HRS Guideline for the Diagnosis and Management of Patients With Atrial Fibrillation provides recommendations to guide clinicians in the treatment of patients with atrial fibrillation. METHODS: A comprehensive literature search was conducted from May 12, 2022, to November 3, 2022, encompassing studies, reviews, and other evidence conducted on human subjects that were published in English from PubMed, EMBASE, the Cochrane Library, the Agency for Healthcare Research and Quality, and other selected databases relevant to this guideline. Additional relevant studies, published through November 2022, during the guideline writing process, were also considered by the writing committee and added to the evidence tables, where appropriate. STRUCTURE: Atrial fibrillation is the most sustained common arrhythmia, and its incidence and prevalence are increasing in the United States and globally. Recommendations from the 2014 AHA/ACC/HRS Guideline for the Management of Patients With Atrial Fibrillation and the 2019 AHA/ACC/HRS Focused Update of the 2014 AHA/ACC/HRS Guideline for the Management of Patients With Atrial Fibrillation have been updated with new evidence to guide clinicians. In addition, new recommendations addressing atrial fibrillation and thromboembolic risk assessment, anticoagulation, left atrial appendage occlusion, atrial fibrillation catheter or surgical ablation, and risk factor modification and atrial fibrillation prevention have been developed.

BackgroundMitochondrial dysfunction results in an imbalance between energy supply and demand in a failing heart. An innovative therapy that targets the intracellular bioenergetics directly through mitochondria transfer may be necessary.ObjectivesThe purpose of this study was to establish a preclinical proof-of-concept that extracellular vesicle (EV)-mediated transfer of autologous mitochondria and their related energy source enhance cardiac function through restoration of myocardial bioenergetics.MethodsHuman-induced pluripotent stem cell-derived cardiomyocytes (iCMs) were employed. iCM-conditioned medium was ultracentrifuged to collect mitochondria-rich EVs (M-EVs). Therapeutic effects of M-EVs were investigated using in vivo murine myocardial infarction (MI) model.ResultsElectron microscopy revealed healthy-shaped mitochondria inside M-EVs. Confocal microscopy showed that M-EV-derived mitochondria were transferred into the recipient iCMs and fused with their endogenous mitochondrial networks. Treatment with 1.0 × 108/ml M-EVs significantly restored the intracellular adenosine triphosphate production and improved contractile profiles of hypoxia-injured iCMs as early as 3 h after treatment. In contrast, isolated mitochondria that contained 300× more mitochondrial proteins than 1.0 × 108/ml M-EVs showed no effect after 24 h. M-EVs contained mitochondrial biogenesis-related messenger ribonucleic acids, including proliferator-activated receptor γ coactivator-1α, which on transfer activated mitochondrial biogenesis in the recipient iCMs at 24 h after treatment. Finally, intramyocardial injection of 1.0 × 108 M-EVs demonstrated significantly improved post-MI cardiac function through restoration of bioenergetics and mitochondrial biogenesis.ConclusionsM-EVs facilitated immediate transfer of their mitochondrial and nonmitochondrial cargos, contributing to improved intracellular energetics in vitro. Intramyocardial injection of M-EVs enhanced post-MI cardiac function in vivo. This therapy can be developed as a novel, precision therapeutic for mitochondria-related diseases including heart failure.

BackgroundReliable methods for predicting myocardial infarction in patients with established coronary artery disease are lacking. Coronary 18F-sodium fluoride (18F-NaF) positron emission tomography (PET) provides an assessment of atherosclerosis activity.ObjectivesThis study assessed whether 18F-NaF PET predicts myocardial infarction and provides additional prognostic information to current methods of risk stratification.MethodsPatients with known coronary artery disease underwent 18F-NaF PET computed tomography and were followed up for fatal or nonfatal myocardial infarction over 42 months (interquartile range: 31 to 49 months). Total coronary 18F-NaF uptake was determined by the coronary microcalcification activity (CMA).ResultsIn a post hoc analysis of data collected for prospective observational studies, the authors studied 293 study participants (age: 65 ± 9 years; 84% men), of whom 203 (69%) showed increased coronary 18F-NaF activity (CMA >0). Fatal or nonfatal myocardial infarction occurred only in patients with increased coronary 18F-NaF activity (20 of 203 with a CMA >0 vs. 0 of 90 with a CMA of 0; p 1.56 had a >7-fold increase in fatal or nonfatal myocardial infarction (hazard ratio: 7.1; 95% confidence interval: 2.2 to 25.1; p = 0.003) independent of age, sex, risk factors, segment involvement and coronary calcium scores, presence of coronary stents, coronary stenosis, REACH and SMART scores, the Duke coronary artery disease index, and recent myocardial infarction.ConclusionsIn patients with established coronary artery disease, 18F-NaF PET provides powerful independent prediction of fatal or nonfatal myocardial infarction.

BACKGROUND: Macrophages and fibroblasts are 2 major cell types involved in healing after myocardial infarction (MI), contributing to myocardial remodeling and fibrosis. Post-MI fibrosis progression is characterized by a decrease in cardiac macrophage content. OBJECTIVES: This study explores the potential of macrophages to express fibroblast genes and the direct role of these cells in post-MI cardiac fibrosis. METHODS: Prolonged in vitro culture of human macrophages was used to evaluate the capacity to express fibroblast markers. Infiltrating cardiac macrophages was tracked in vivo after experimental MI of LysM(Cre/+);ROSA26(EYFP/+) transgenic mice. The expression of Yellow Fluorescent Protein (YFP) in these animals is restricted to myeloid lineage allowing the identification of macrophage-derived fibroblasts. The expression in YFP-positive cells of fibroblast markers was determined in myocardial tissue sections of hearts from these mice after MI. RESULTS: Expression of the fibroblast markers type I collagen, prolyl-4-hydroxylase, fibroblast specific protein-1, and fibroblast activation protein was evidenced in YFP-positive cells in the heart after MI. The presence of fibroblasts after MI was evaluated in the hearts of animals after depletion of macrophages with clodronate liposomes. This macrophage depletion significantly reduced the number of Mac3+Col1A1+ cells in the heart after MI. CONCLUSIONS: The data provide both in vitro and in vivo evidence for the ability of macrophages to transition and adopt a fibroblast-like phenotype. Therapeutic manipulation of this macrophage-fibroblast transition may hold promise for favorably modulating the fibrotic response after MI and after other cardiovascular pathological processes.

Autonomic nervous system control of the heart is a dynamic process in both health and disease. A multilevel neural network is responsible for control of chronotropy, lusitropy, dromotropy, and inotropy. Intrinsic autonomic dysfunction arises from diseases that directly affect the autonomic nerves, such as diabetes mellitus and the syndromes of primary autonomic failure. Extrinsic autonomic dysfunction reflects the changes in autonomic function that are secondarily induced by cardiac or other disease. An array of tests interrogate various aspects of cardiac autonomic control in either resting conditions or with physiological perturbations from resting conditions. The prognostic significance of these assessments have been well established. Clinical usefulness has not been established, and the precise mechanistic link to mortality is less well established. Further efforts are required to develop optimal approaches to delineate cardiac autonomic dysfunction and its adverse effects to develop tools that can be used to guide clinical decision-making.

Background: Following an acute myocardial infarction (AMI), patients remain at risk for subsequent cardiovascular (CV) events. In the AEGIS-II trial, CSL112, a human apolipoprotein A-I derived from plasma that enhances cholesterol efflux, did not significantly reduce the first occurrence of CV death, myocardial infarction (MI), or stroke through 90 days compared with placebo. However, an analysis involving only the first event may not capture the totality of the clinical impact of an intervention because patients may experience multiple events., Objectives: This prespecified exploratory analysis examines the effect of CSL112 on total burden of nonfatal ischemic events (ie, recurrent MI and stroke) and CV death., Methods: A total of 18,219 patients with AMI, multivessel coronary artery disease, and additional CV risk factors were randomized to either 4 weekly infusions of 6 g CSL112 (n = 9,112) or matching placebo (n = 9,107). A negative binomial regression model was applied to estimate the effect of CSL112 compared with placebo on the rate ratio (RR) of ischemic events., Results: For CV death, MI, and stroke, there were numerically fewer total events at 90 days (503 vs 545 events; rate ratio [RR]: 0.88; 95% CI: 0.76-1.03, P = 0.11), and nominally significantly fewer total events at 180 days (745 vs 821 events, RR: 0.87; 95% CI: 0.77-0.99; P = 0.04) and 365 days (1,120 vs 1,211 events; RR: 0.89; 95% CI: 0.80-0.99; P = 0.04). Subsequent events constituted 13% of events at 90 days, 17% at 180 days, and 22% at 1 year. Similar findings were seen with the total occurrence of nonfatal MI and CV death. When type II MIs, unlikely to be modified by enhancing cholesterol efflux, were excluded, there were nominally significant reductions in the total occurrence of nonfatal MI (excluding type 2) and CV death at all time points (90 days: RR: 0.81; 95% CI: 0.68-0.97; P = 0.02; 180 days: RR: 0.82; 95% CI: 0.71-0.95; P < 0.01; 365 days: RR: 0.86; 95% CI: 0.76-0.98; P = 0.02)., Conclusions: In this prespecified exploratory analysis of the AEGIS-II trial, 4 weekly infusions of CSL112 among high-risk patients after AMI significantly reduced the total burden of nonfatal ischemic events and CV death at 180 and 365 days compared with placebo. (AEGIS-II [Study to Investigate CSL112 in Subjects With Acute Coronary Syndrome]; NCT03473223)., Competing Interests: Funding Support and Author Disclosures The study was sponsored by CSL Behring. CSL Behring was involved in the study design, data collection, data analysis, data interpretation, and the preparation, review, and approval of the manuscript. The decision to submit the manuscript for publication was made by the academic leadership of the steering committee. Dr Gibson has received research funding from CSL Behring, Janssen Pharmaceuticals, Johnson and Johnson Corporation, and SCAD Alliance; has been a consultant for 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, Novo Nordisk, 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, and Fortress Biotech; and has received royalties as a contributor to UpToDate. Dr Chi has received research grant support paid to the Beth Israel Deaconess Medical Center, Harvard Medical School from Bayer, CSL Behring, Janssen Scientific Affairs, and SCAD Alliance. Dr Duffy has received salary as an employee of CSL Behring. Dr Bahit has received honoraria from MSD, Pfizer, Bristol Myers Squibb, CSL Behring, Janssen, Boehringer Ingelheim, and Anthos Therapeutics. Dr White has received grant support to institution from Sanofi, Regeneron Pharmaceuticals, Eli Lilly, Omthera Pharmaceuticals, American Regent, Eisai Inc, DalCor Pharma UK Inc., CSL Behring, NHI, Sanofi-Aventis Australia Pty Ltd, Esperion Therapeutics Inc, and National Institutes of Health; has received fees for serving on Steering Committees of the ODYSSEY trial from Sanofi and Regeneron Pharmaceuticals, the ISCHEMIA and the MINT studies from the National Institutes of Health, the STRENGTH trial from Omthera Pharmaceuticals, the HEART-FID study from American Regent, the DAL-GENE study from DalCor Pharma UK Inc., the AEGIS-II study from CSL Behring, the SCORED trial and the SOLOIST-WHF trial from Sanofi Australia Pty Ltd, and the CLEAR OUTCOMES study from Esperion Therapeutics. Dr Korjian has received research grant support paid to the Beth Israel Deaconess Medical Center, Harvard Medical School from CSL Behring. Dr Alexander has received research grants through Duke University from Artivion/CryoLife, Bayer, Bristol Myers Squibb, CSL Behring, Ferring, the U.S. FDA, Humacyte, and the U.S. NIH; has served as advisory board member or received honoraria or consulting payments from AbbVie, Artivion/CryoLife, AtriCure, Bayer, Bristol Myers Squibb, Curis, Eli Lilly, Ferring, GlaxoSmithKline, Janssen, Novostia, Pfizer, Portola, Theravance, and Veralox. Dr Lincoff has received research funding from Esperion, Eli Lilly, Novartis, AstraZeneca, AbbVie; and has been a consultant for Novo Nordisk, Eli Lilly, Glaxo, Akebia, Endologix, Fibrogen, Provention, Becton Dickson, Brainstorm Cell, Intarcia, Medtronic, and Recor. Dr Anschuetz has received a salary as an employee of CSL Behring. Dr Girgis has received a salary as an employee of CSL Behring. Dr Nicolau has received a scholarship from the National Council of Scientific and Technological Development (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. Dr Lopes has received grant support from Amgen, Bristol Myers Squibb, GlaxoSmithKline, Medtronic, Pfizer, and Sanofi; has been a consultant for AstraZeneca, Bayer, Boehringer, Bristol Myers Squibb, and Novo Nordisk; and has participated in educational activities for Daiichi-Sankyo, AstraZeneca, Novo Nordisk, and Pfizer. Dr Bainey has received research support from CSL Behring. Dr Libby has served on a scientific advisory board for Amgen, Kowa Pharmaceuticals, Novo Nordisk, Caristo, CSL Behring, DalCor, Dewpoint, Euclid Bioimaging, Xbiotech, Olatec, Medimmune, PlaqueTec, Polygon Therapeutics, TenSixteen Bio, Soley Therapeutics; and has been a consultant for Amgen, Baim Institute Beren, Esperion, Genentech, Kancera, Kowa Pharmaceuticals, Novo Nordisk, Novartis, and Sanofi-Regeneron. Dr Sacks has received support from CSL Behring. Dr Ridker has received institutional research grant support from Kowa, Novartis, Amarin, Pfizer, Esperion, Novo Nordisk, and the NHLBI; has served as a consultant to numerous companies including 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; holds 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, 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 Alnylam, 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, Roche, Sanofi, Servier, Tolmar Pharmaceuticals, Valeo Pharma; 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∖CIUSSS Centre-Ouest-de-l'Ile-de-Montreal, New York University Clinical Coordinating Centre, PERFUSE Research Institute, Peter Munk Cardiac Centre Clinical Trials and Translation Unit, Ted Rogers Centre for Heart Research, and TIMI Study Group (Brigham Health). Dr Mahaffey has received grants from AHA, Apple Inc, Bayer, California Institute Regenerative Medicine, CSL Behring, Eidos, Ferring, Gilead, Google (Verily), Idorsia, Johnson & Johnson, Luitpold, Novartis, PAC-12, Precordior, Sanifit; has received consulting fees from applied Therapeutics, Bayer, BMS, BridgeBio, CSL Behring, Elsevier, Fosun Pharma, Human, Johnson & Johnson, Moderna, Myokardia, Novartis, Novo Nordisk, Otsuka, Phasebio, Portola, Quidel, Theravance; has received payment or honoraria from CSL Behring; and has stock or stock options in Human, Medeloop, Precordior, and Regencor. Dr Nicholls has received research support from AstraZeneca, Amgen, Anthera, CSL Behring, Cerenis, Eli Lilly, Esperion, Resverlogix, Novartis, InfraReDx, and Sanofi-Regeneron; and has been a consultant for Amgen, Akcea, AstraZeneca, Boehringer Ingelheim, CSL Behring, Daiichi-Sankyo, Eli Lilly, Esperion, Kowa, Merck, Takeda, Pfizer, Sanofi-Regeneron, Novo Nordisk, CSL Sequiris, and Vaxxinity. Dr Pocock has been a consultant to CSL Behring. Dr Mehran has received institutional research payments from Abbott, Affluent Medical, Alleviant Medical, Amgen, AstraZeneca, BAIM, Beth Israel Deaconess Medical Center, Boston Scientific, Bristol Myers Squibb, CardiaWave, CERC, Chiesi, Concept Medical, Daiichi-Sankyo, Duke, Faraday, Idorsia, Janssen, MedAlliance, Medscape, Mediasphere, Medtelligence, Medtronic, Novartis, OrbusNeich, Pi-Cardia, Protembis, RM Global Bioaccess Fund Management, and Sanofi; has received personal fees from Affluent Medical, Boehringer Ingelheim, Chiesi USA, Cordis, Daiichi-Sankyo, Esperion Science/Innovative Biopharma, Gaffney Events, Educational Trust, Global Clinical Trial Partners, Ltd., IQVIA, Medscape/WebMD Global, Novo Nordisk, PeerView Institute for Medical Education, TERUMO Europe N.V., and Radcliffe; has held equity <1% in Elixir Medical, Stel, ControlRad (spouse); has received an honorarium from AMA; is associate editor of JAMA Cardiology; and is a BOT Member, SC Member CTR Program of ACC. Dr Harrington has research relationships with Baim Institute, CSL, Janssen, NHLBI, PCORI, and DCRI; has consulting relationships with Atropos Health, Bitterroot Bio, BMS, BridgeBio, Element Science, Edwards Lifesciences, Foresite Labs, Medscape/WebMD; and serves on boards of directors for the American Heart Association, College of the Holy Cross, and Cytokinetics. Dr Cornel 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: The effectiveness of complete revascularization is well established in patients with ST-segment elevation myocardial infarction (STEMI), but it is less investigated in those with non-ST-segment elevation myocardial infarction (NSTEMI)., Objectives: This study aimed to assess whether complete revascularization, compared with culprit-only revascularization, was associated with consistent outcomes in older patients with STEMI and NSTEMI., Methods: In the FIRE (Functional Assessment in Elderly MI Patients with Multivessel Disease) trial, 1,445 older patients with myocardial infarction (MI) were randomized to culprit-only or physiology-guided complete revascularization, stratified by STEMI (n = 256 culprit-only vs n = 253 complete) and NSTEMI (n = 469 culprit-only vs n = 467 complete). The primary outcome comprised a composite of death, MI, stroke, or revascularization at 1 year. The key secondary outcome included a composite of cardiovascular death or MI at 1 year., Results: In the overall study population, physiology-guided complete revascularization reduced both primary and key secondary outcomes. The primary outcome occurred in 54 (21.1%) STEMI patients randomized to culprit-only vs 41 (16.2%) STEMI patients of the complete group (HR: 0.75; 95% CI: 0.50-1.13) and in 98 (20.9%) NSTEMI patients randomized to culprit-only vs 72 (15.4%) NSTEMI patients of the complete group (HR: 0.71; 95% CI: 0.53-0.97), with negative interaction testing (P for interaction, 0.846). Similarly, no signal of heterogeneity with respect to the initial clinical presentation was observed for the key secondary endpoint (P for interaction, 0.654)., Conclusions: Physiology-guided complete revascularization, compared with culprit-only revascularization, provided consistent benefit across the whole spectrum of patients with MI. (FIRE [Functional Assessment in Elderly MI Patients With Multivessel Disease]; NCT03772743)., Competing Interests: Funding Support and Author Disclosures Sahajanand Medical Technologies Ltd (SMT), Medis Medical Imaging Systems, Eukon S.r.l., Siemens Healthineers, General Electric (GE) Healthcare, and Insight Lifetech provided unrestricted funding to the study sponsor for the conduction of the trial. These companies had no involvement in the trial design, data collection, analysis, interpretation, or writing of the manuscript. Dr Campo has received research grants and personal fees from Abbott Vascular, GADA, Menarini, Amgen, Daichi-Sankyo, and Sanofi, outside the submitted work. Dr Moreno has received speaker/consulting fees from Abbott Vascular, AMGEN, AstraZeneca, Biosensors, Biotronik, Boston Scientific, Daiichi-Sankyo, Edwards, Medtronic, and Philips, outside the submitted work. Dr Biscaglia has received funding from the Italian Health Minister (Ricerca Finalizzata 2021, GR-2021-12372516) for the conduction of the Functional Coronary Angiography Guided Revascularization in STEMI trial; and has received personal fees from Abbott Vascular and Siemens Healthcare, outside 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: Beyond serving as a marker for insufficient physical activity, sedentary behavior may directly affect future cardiovascular (CV) disease risk., Objectives: This study sought to examine associations between accelerometer-measured sedentary behavior with risk of specific CV outcomes, including potential relations with moderate to vigorous physical activity (MVPA)., Methods: Among participants of the UK Biobank prospective cohort study, we fit Cox models adjusted for demographic and lifestyle factors to assess associations between accelerometer-measured daily sedentary time with incident atrial fibrillation (AF), myocardial infarction (MI), heart failure (HF), and CV mortality. We assessed the potential effect of MVPA on associations between sedentary time and CV disease by including MVPA as an adjustment variable, as well as performing subgroup analyses stratified at the guideline-recommended MVPA threshold (ie, ≥150 min/wk). We then performed compositional analyses to estimate the effects of reallocating sedentary time to other activities., Results: Among 89,530 individuals (age 62 ± 8 years, 56.4% women) undergoing 1 week of accelerometry, median sedentary time was 9.4 h/d (Q1-Q3: 8.2-10.6). In multivariable models, using the second quartile (8.2-9.4 h/d) as a referent, sedentary time in the top quartile (>10.6 h/d) was associated with greater risks of HF (HR: 1.45; 95% CI: 1.28-1.65) and CV mortality (HR: 1.62; 95% CI: 1.34-1.96), with an inflection of risk at 10.6 h/d. Higher sedentary time was also associated with greater risks of incident AF (HR: 1.11; 95% CI: 1.01-1.21) and MI (HR: 1.15; 95% CI: 1.00-1.32), with an approximately linear relation. Associations with HF and CV mortality persisted among individuals meeting guideline-recommended MVPA levels. Among individuals with >10.6 h/d of sedentary time, reallocating sedentary behavior to other activities substantially reduced the excess CV risk conferred by sedentary behavior (eg, 30-minute decrease in sedentary time for HF: HR: 0.93; 95% CI: 0.90-0.96), even among individuals meeting guideline-recommended MVPA (HR: 0.93; 95% CI: 0.87-0.99)., Conclusions: Sedentary behavior is broadly associated with future adverse CV outcomes, with particularly prominent effects on HF and CV mortality, where risk inflected at approximately 10.6 h/d. Although guideline-adherent MVPA partially mitigates excess risk, optimizing sedentary behavior appears to be important even among physically active individuals., Competing Interests: Funding Support and Author Disclosures Dr Ajufo is supported by the John S. LaDue Memorial Fellowship in Cardiovascular Medicine or Vascular Biology grant. Dr Kany is supported by the Walter Benjamin Fellowship from the Deutsche Forschungsgemeinschaft (521832260). Dr Rämö is supported by a research fellowship from the Sigrid Jusélius Foundation. Dr Churchill is supported by the National Institutes of Health (K23HL159262-01A1). Dr Guseh is supported by the American Heart Association (19AMFDP34990046) and the President and Fellows of Harvard College (5KL2TR002542-04). Dr Aragam is supported by grants from the National Institutes of Health (1K08HL153937) and the American Heart Association (862032); receives sponsored research support from Sarepta Therapeutics and Bayer AG; and receives a research collaboration with the Novartis Institutes for Biomedical Research. Dr Ellinor is supported by grants from the National Institutes of Health (RO1HL092577, R01HL157635), from the American Heart Association (18SFRN34230127, 961045), and from the European Union (MAESTRIA 965286); receives sponsored research support from Bayer AG, IBM Research, Bristol Myers Squibb, Pfizer and Novo Nordisk; and has served on Advisory Boards and/or consulted for Bayer AG. Dr Khurshid is supported by the NIH (K23HL169839-01) and the American Heart Association (2023CDA1050571)., (Copyright © 2024 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Angiographic evidence of the anatomy of coronary arteries and the type of coronary artery lesions in women with a history of hypertensive disorders of pregnancy (HDP) are poorly documented., Objectives: This study sought to determine the role of a history of HDP as a unique risk factor for early coronary artery disease (CAD) and type of acute coronary syndrome (ACS) (ie, atherosclerotic vs myocardial infarction with nonobstructive coronary arteries [MINOCA]) in women who underwent coronary angiography., Methods: This study used a population-based cohort of parous female patients with incident CAD who underwent coronary angiography and age-matched control subjects. The SYNTAX (Synergy between PCI [percutaneous coronary intervention] with TAXUS [Boston Scientific] and Cardiac Surgery) score was assessed to determine the complexity and degree of CAD; MINOCA was diagnosed in the presence of clinical acute myocardial infarction in the absence of obstructive coronary disease., Results: A total of 506 parous female Olmsted County, Minnesota (USA) residents had incident CAD and angiographic data from November 7, 2002 to December 31, 2016. Women with HDP were younger than normotensive women at the time of the event (median: 64.8 years vs 71.8 years; P = 0.030). There was a strong association between HDP and ACS (unadjusted P = 0.018). Women with HDP compared with women with normotensive pregnancies were more likely to have a higher SYNTAX score (OR: 2.28; 95% CI: 1.02-5.12; P = 0.046), and MINOCA (OR: 2.08; 95% CI: 1.02-4.25; P = 0.044)., Conclusions: A history of HDP is associated with CAD earlier in life and with a future risk for myocardial infarction with both obstructive and nonobstructive coronary arteries. This study underscores the need for timely detection and treatment of nonobstructive disease, in addition to traditional risk factors., Competing Interests: Funding Support and Author Disclosures This study used the resources of the Rochester Epidemiology Project (REP) medical records-linkage system, which is supported by the National Institute on Aging (grant AG 058738), by the Mayo Clinic Research Committee, and by fees paid annually by REP users. The content of this article is solely the responsibility of the authors and does not represent the official views of the National Institutes of Health (NIH) or the Mayo Clinic. Dr Garovic has received support from NIH grant R01HL136348. 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: In the BRIGHT-4 (Bivalirudin With Prolonged Full-Dose Infusion During Primary PCI Versus Heparin Trial-4), anticoagulation with bivalirudin plus a 2- to 4-hour high-dose infusion after percutaneous coronary intervention (PCI) reduced all-cause mortality and bleeding without increasing reinfarction or stent thrombosis compared with heparin alone in patients with ST-segment elevation myocardial infarction (STEMI). These findings require external validation., Objectives: This study sought to determine outcomes of bivalirudin vs heparin anticoagulation during PCI in STEMI., Methods: We performed an individual-patient-data meta-analysis of all large randomized trials of bivalirudin vs heparin in STEMI patients undergoing primary PCI performed before BRIGHT-4. The primary endpoint was all-cause mortality., Results: Six trials randomizing 15,254 patients were included. Pooled across all regimens of bivalirudin and glycoprotein IIb/IIIa inhibitor (GPI) use, bivalirudin reduced 30-day all-cause mortality (2.5% vs 2.9%; adjusted OR: 0.78; 95% CI: 0.62-0.99), cardiac mortality (adjusted OR: 0.69; 95% CI: 0.54-0.88), and major bleeding (adjusted OR: 0.53; 95% CI: 0.44-0.64) but increased reinfarction (adjusted OR: 1.30; 95% CI: 1.02-1.65) and stent thrombosis (adjusted OR: 1.43; 95% CI: 1.05-1.93) compared with heparin. In 4 trials in which 6,244 patients were randomized to bivalirudin plus a high-dose post-PCI infusion vs heparin without planned GPI use (the BRIGHT-4 regimens), 30-day all-cause mortality occurred in 1.8% vs 2.9% of patients, respectively (adjusted OR: 0.74; 95% CI: 0.48-1.12), and bivalirudin reduced cardiac mortality (adjusted OR: 0.62; 95% CI: 0.39-0.97) and major bleeding (adjusted OR: 0.49; 95% CI: 0.35-0.70), with similar rates of reinfarction (adjusted OR: 0.89; 95% CI: 0.58-1.38) and stent thrombosis (adjusted OR: 0.80; 95% CI: 0.41-1.57)., Conclusions: In STEMI patients undergoing primary PCI, bivalirudin with a 2- to 4-hour post-PCI high-dose infusion reduced cardiac mortality and major bleeding without an increase in ischemic events compared with heparin monotherapy with provisional GPI use, confirming the BRIGHT-4 results., Competing Interests: Funding Support and Author Disclosures The present study was supported by a research grant from The Medicines Company to the Cardiovascular Research Foundation. Dr Bikdeli is supported by the Scott Schoen and Nancy Adams IGNITE Award from the Mary Horrigan Connors Center for Women’s Health and Gender Biology at Brigham and Women’s Hospital, and a Career Development Award from the American Heart Association and VIVA Physicians (#938814). Dr Stone has received speaker honoraria from Medtronic, Pulnovo, 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, Cardiomech, Gore, Amgen, Adona Medical, and Millennia Biopharma; and has equity/options from Ancora, Cagent, Applied Therapeutics, Biostar family of funds, SpectraWave, Orchestra Biomed, Aria, Cardiac Success, Valfix, and Xenter. Dr Stone’s employer, Mount Sinai Hospital, receives research support from Abbott, Abiomed, Bioventrix, Cardiovascular Systems Inc, Phillips, Biosense Webster, Shockwave, Vascular Dynamics, Pulnovo, and V-wave. Dr Valgimigli has received grants from Terumo; and has received personal fees from AstraZeneca, Alvimedica/CID, Abbott Vascular, Daiichi-Sankyo, Bayer, CorFlow, Idorsia Pharmaceuticals, Universität Basel Dept Klinische Forschung, Bristol Myers Squibb SA, Medscape, Biotronik, and Novartis, outside the submitted work. Dr Erlinge has received honoraria for advisory boards from AstraZeneca, Bayer, Chiesi, and Sanofi; and has received speaker honoraria from Bayer, AZ, Novartis, and Chiesi. Dr Steg has received research grants from Amarin, AstraZeneca, Bayer, Sanofi, and Servier; and has received honoraria for clinical trials (serving on the steering committee, clinical endpoint committee, data and safety monitoring committee) from Amarin, AstraZeneca, Bayer, Bristol Myers Squibb, Idorsia, Novartis, PhaseBio, Pfizer, Sanofi, Servier, and The Medicines Company; has received fees for consulting or speaking from Amarin, Amgen, BMS, Novo Nordisk, and Regeneron; and is a Senior Associate Editor at Circulation. Dr James’s employer has received research grants from Novartis, Amgen, Janssen, Bayer, AstraZeneca, and Infraredex. Dr Mehran has received institutional research funding from Abbott, Abiomed, Alleviant Medical, AM-Pharma, Amgen, Applied Therapeutics, Arena, AstraZeneca, AtriCure, Bayer, Biosensors, Biotronik, Boston Scientific, Bristol Myers Squibb, CardiaWave, CeloNova, Chiesi, Concept Medical, CSL Behring, Cytosorbents, Daiichi-Sankyo, Element Science, Faraday, Humacyte, Idorsia, Janssen, Magenta, Medtronic, Novartis, OrbusNeich, PhaseBio, Philips, Pi-Cardia, RenalPro, RM Global, Shockwave, Vivasure, and Zoll; has received personal fees from Cine-Med Research and WebMD; holds equity in Applied Therapeutics, Elixir Medical, and Stel; has served on scientific advisory boards for the AMA, ACC (BOT member), and SCAI (Women in Innovations Committee member); has served as an associate editor of JAMA; is an unpaid member of the faculty of CRF; and her spouse has received personal fees from ControlRad. Dr Bikdeli has been a consulting expert, on behalf of the plaintiff, for litigation related to 2 brand models of IVC filters. 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.)

BackgroundAlthough early reperfusion is the most desirable intervention after ischemic myocardial insult, it may add to damage through oxidative stress.ObjectivesThis study investigated the cardioprotective effects of a single intravenous dose of heat shock protein-72 (HSP72) coupled to a single-chain variable fragment (Fv) of monoclonal antibody 3E10 (3E10Fv) in a rabbit ischemia-reperfusion model. The Fv facilitates rapid transport of HSP72 into cells, even with intact membranes.MethodsA left coronary artery occlusion (40 min) reperfusion (3 h) model was used in 31 rabbits. Of these, 12 rabbits received the fusion protein (Fv-HSP72) intravenously. The remaining 19 control rabbits received a molar equivalent of 3E10Fv alone (n = 6), HSP72 alone (n = 6), or phosphate-buffered saline (n = 7). Serial echocardiographic examinations were performed to assess left ventricular function before and after reperfusion. Micro-single-photon emission computed tomography imaging of 99mTc-labeled annexin-V was performed with micro-computed tomography scanning to characterize apoptotic damage in vivo, followed by gamma counting of the excised myocardial specimens to quantify cell death. Histopathological characterization of the myocardial tissue and sequential cardiac troponin I measurements were also undertaken.ResultsMyocardial annexin-V uptake was 43% lower in the area at risk (p = 0.0003) in Fv-HSP72-treated rabbits compared with control animals receiving HSP72 or 3E10Fv alone. During reperfusion, troponin I release was 42% lower and the echocardiographic left ventricular ejection fraction 27% higher in the Fv-HSP72-treated group compared with control animals. Histopathological analyses confirmed penetration of 3E10Fv-containing molecules into cardiomyocytes in vivo, and treatment with Fv-HSP72 showed fewer apoptotic nuclei compared with control rabbits.ConclusionsSingle-dose administration of Fv-HSP72 fusion protein at the time of reperfusion reduced myocardial apoptosis by almost one-half and improved left ventricular functional recovery after myocardial ischemia-reperfusion injury in rabbits. It might have potential to serve as an adjunct to early reperfusion in the management of myocardial infarction.

BackgroundUnderstanding the relationship between alcohol abuse, a common and theoretically modifiable condition, and the most common cause of death in the world, cardiovascular disease, may inform potential prevention strategies.ObjectivesThe study sought to investigate the associations among alcohol abuse and atrial fibrillation (AF), myocardial infarction (MI), and congestive heart failure (CHF).MethodsUsing the Healthcare Cost and Utilization Project database, we performed a longitudinal analysis of California residents ≥21 years of age who received ambulatory surgery, emergency, or inpatient medical care in California between 2005 and 2009. We determined the risk of an alcohol abuse diagnosis on incident AF, MI, and CHF. Patient characteristics modifying the associations and population-attributable risks were determined.ResultsAmong 14,727,591 patients, 268,084 (1.8%) had alcohol abuse. After multivariable adjustment, alcohol abuse was associated with an increased risk of incident AF (hazard ratio [HR]: 2.14; 95% confidence interval [CI]: 2.08 to 2.19; p < 0.0001), MI (HR: 1.45; 95% CI: 1.40 to 1.51; p < 0.0001), and CHF (HR: 2.34; 95% CI: 2.29 to 2.39; p

BackgroundPim1 kinase plays an important role in cell division, survival, and commitment of precursor cells towards a myocardial lineage, and overexpression of Pim1 in ckit+ cardiac stem cells (CSCs) enhances their cardioreparative properties.ObjectivesThe authors sought to validate the effect of Pim1-modified CSCs in a translationally relevant large animal preclinical model of myocardial infarction (MI).MethodsHuman cardiac stem cells (hCSCs, n = 10), hckit+ CSCs overexpressing Pim1 (Pim1+; n = 9), or placebo (n = 10) were delivered by intramyocardial injection to immunosuppressed Yorkshire swine (n = 29) 2 weeks after MI. Cardiac magnetic resonance and pressure volume loops were obtained before and after cell administration.ResultsWhereas both hCSCs reduced MI size compared to placebo, Pim1+ cells produced a ∼3-fold greater decrease in scar mass at 8 weeks post-injection compared to hCSCs (-29.2 ± 2.7% vs. -8.4 ± 0.7%; p < 0.003). Pim1+ hCSCs also produced a 2-fold increase of viable mass compared to hCSCs at 8 weeks (113.7 ± 7.2% vs. 65.6 ± 6.8%; p

Kawasaki disease is an acute, self-limited vasculitis of unknown etiology that occurs predominantly in infants and children. If not treated early with high-dose intravenous immunoglobulin, 1 in 5 children develop coronary artery aneurysms; this risk is reduced 5-fold if intravenous immunoglobulin is administered within 10 days of fever onset. Coronary artery aneurysms evolve dynamically over time, usually reaching a peak dimension by 6 weeks after illness onset. Almost all the morbidity and mortality occur in patients with giant aneurysms. Risk of myocardial infarction from coronary artery thrombosis is greatest in the first 2 years after illness onset. However, stenosis and occlusion progress over years. Indeed, Kawasaki disease is no longer a rare cause of acute coronary syndrome presenting in young adults. Both coronary artery bypass surgery and percutaneous intervention have been used to treat Kawasaki disease patients who develop myocardial ischemia as a consequence of coronary artery aneurysms and stenosis.

BackgroundPersistent severe left ventricular (LV) systolic dysfunction after myocardial infarction (MI) is associated with increased mortality and is a class I indication for implantation of a cardioverter-defibrillator.ObjectivesThis study developed models and assessed independent predictors of LV recovery to >35% and ≥50% after 90-day follow-up in patients presenting with acute MI and severe LV dysfunction.MethodsOur multicenter prospective observational study enrolled participants with ejection fraction (EF) of ≤35% at the time of MI (n = 231). Predictors for EF recovery to >35% and ≥50% were identified after multivariate modeling and validated in a separate cohort (n = 236).ResultsIn the PREDICTS (PREDiction of ICd Treatment Study) study, 43% of patients had persistent EF ≤35%, 31% had an EF of 36% to 49%, and 26% had an EF ≥50%. The model that best predicted recovery of EF to >35% included EF at presentation, length of stay, prior MI, lateral wall motion abnormality at presentation, and peak troponin. The model that best predicted recovery of EF to ≥50% included EF at presentation, peak troponin, prior MI, and presentation with ventricular fibrillation or cardiac arrest. After predictors were transformed into point scores, the lowest point scores predicted a 9% and 4% probability of EF recovery to >35% and ≥50%, respectively, whereas profiles with the highest point scores predicted an 87% and 49% probability of EF recovery to >35% and ≥50%, respectively.ConclusionsIn patients with severe systolic dysfunction following acute MI with an EF ≤35%, 57% had EF recovery to >35%. A model using clinical variables present at the time of MI can help predict EF recovery.

Background: Lower air temperature and cold spells have been associated with an increased risk of various diseases. However, the short-term effect of lower air temperature and cold spells on myocardial infarction (MI) remains incompletely understood., Objectives: The purpose of this study was to investigate the short-term effects of lower air temperature and cold spells on the risk of hospitalization for MI in Sweden., Methods: This population-based nationwide study included 120,380 MI cases admitted to hospitals in Sweden during the cold season (October to March) from 2005 to 2019. Daily mean air temperature (1 km 2 resolution) was estimated using machine learning, and percentiles of daily temperatures experienced by individuals in the same municipality were used as individual exposure indicators to account for potential geographic adaptation. Cold spells were defined as periods of at least 2 consecutive days with a daily mean temperature below the 10th percentile of the temperature distribution for each municipality. A time-stratified case-crossover design incorporating conditional logistic regression models with distributed lag nonlinear models using lag 0 to 1 (immediate) and 2 to 6 days (delayed) was used to evaluate the short-term effects of lower air temperature and cold spells on total MI, non-ST-segment elevation myocardial infarction (NSTEMI) and ST-segment elevation myocardial infarction (STEMI)., Results: A decrease of 1-U in percentile temperature at a lag of 2 to 6 days was significantly associated with increased risks of total MI, NSTEMI, and STEMI, with ORs of 1.099 (95% CI: 1.057-1.142), 1.110 (95% CI: 1.060-1.164), and 1.076 (95% CI: 1.004-1.153), respectively. Additionally, cold spells at a lag of 2 to 6 days were significantly associated with increased risks for total MI, NSTEMI, and STEMI, with ORs of 1.077 (95% CI: 1.037-1.120), 1.069 (95% CI: 1.020-1.119), and 1.095 (95% CI: 1.023-1.172), respectively. Conversely, lower air temperature and cold spells at a lag of 0 to 1 days were associated with decreased risks for MI., Conclusions: This nationwide case-crossover study reveals that short-term exposures to lower air temperature and cold spells are associated with an increased risk of hospitalization for MI at lag 2 to 6 days., Competing Interests: Funding Support and Author Disclosures This study has received funding from the European Union’s Horizon 2020 research and innovation program under grant agreement no. 820655 (EXHAUSTION). This work was supported by a scholarship under the State Scholarship Fund by the China Scholarship Council (File No. 201906010316). The 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: Early invasive revascularization guided by moderate to severe ischemia did not improve outcomes over medical therapy alone, underlying the need to identify high-risk patients for a more effective invasive referral. CMR could determine the myocardial extent and matching locations of ischemia and infarction., Objectives: This study sought to investigate if CMR peri-infarct ischemia is associated with adverse events incremental to known risk markers., Methods: Consecutive patients were included in an expanded cohort of the multicenter SPINS (Stress CMR Perfusion Imaging in the United States) study. Peri-infarct ischemia was defined by the presence of any ischemic segment neighboring an infarcted segment by late gadolinium enhancement imaging. Primary outcome events included acute myocardial infarction and cardiovascular death, whereas secondary events included any primary events, hospitalization for unstable angina, heart failure hospitalization, and late coronary artery bypass surgery., Results: Among 3,915 patients (age: 61.0 ± 12.9 years; 54.7% male), ischemia, infarct, and peri-infarct ischemia were present in 752 (19.2%), 1,123 (28.8%), and 382 (9.8%) patients, respectively. At 5.3 years (Q1-Q3: 3.9-7.2 years) of median follow-up, primary and secondary events occurred in 406 (10.4%) and 745 (19.0%) patients, respectively. Peri-infarct ischemia was the strongest multivariable predictor for primary and secondary events (HR adjusted : 1.72 [95% CI: 1.23-2.41] and 1.71 [95% CI: 1.32-2.20], respectively; both P < 0.001), adjusted for clinical risk factors, left ventricular function, ischemia extent, and infarct size. The presence of peri-infarct ischemia portended to a >6-fold increased annualized primary event rate compared to those with no infarct and ischemia (6.5% vs 0.9%)., Conclusions: Peri-infarct ischemia is a novel and robust prognostic marker of adverse cardiovascular events., Competing Interests: Funding Support and Author Disclosures SPINS was funded in part by the Society for Cardiovascular Magnetic Resonance. The Society for Cardiovascular Magnetic Resonance was supported by a joint research grant from Bayer AG and Siemens Medical Systems. The 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.)

The bioprosthetic or native aortic scallop intentional laceration to prevent iatrogenic coronary artery obstruction (BASILICA) procedure allows patients with severe aortic stenosis and anatomical challenges from aortic leaflet orientation, positioning of coronary ostia, and height of sinuses of Valsalva to undergo TAVR. We present a case of intraprocedural cardiac arrest secondary to iatrogenic left main coronary artery obstruction following a successful BASILICA procedure., Competing Interests: Funding Support and Author Disclosures The authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Complete revascularization with percutaneous coronary intervention improves outcomes compared with culprit revascularization following myocardial infarction (MI) with multivessel coronary artery disease. An all-cause mortality reduction has never been demonstrated. Debate also remains regarding the optimal timing of complete revascularization (immediate or staged), and method of evaluation of nonculprit lesions (physiology or angiography)., Objectives: This study aims to perform an updated systematic review with frequentist and Bayesian network meta-analyses including the totality of randomized data investigating revascularization strategies in patients presenting with MI and multivessel coronary artery disease., Methods: The primary comparison tested complete vs culprit revascularization. Timing and methods of achieving complete revascularization were assessed. The prespecified primary outcome was all-cause mortality. Outcomes were expressed as relative risk (RR) (95% CI)., Results: Twenty-four eligible trials randomized 16,371 patients (weighted mean follow-up: 26.4 months). Compared with culprit revascularization, complete revascularization reduced all-cause mortality in patients with any MI (RR: 0.85; 95% CI: 0.74-0.99; P = 0.04). Cardiovascular mortality, MI, major adverse cardiac events and repeat revascularization were also significantly reduced. In patients presenting with ST-segment elevation myocardial infarction, the point estimate for all-cause mortality with complete revascularization was RR: 0.91 (95% CI: 0.78-1.05; P = 0.18). Rates of stent thrombosis, major bleeding, and acute kidney injury were similar. Immediate complete revascularization ranked higher than staged complete revascularization for all endpoints., Conclusions: Complete revascularization following MI reduces all-cause mortality, cardiovascular mortality, MI, major adverse cardiac events, and repeat revascularization. There may be benefits to immediate complete revascularization, but additional head-to-head trials are needed., Competing Interests: Funding Support and Author Disclosures Dr Howard has received grants from the British Heart Foundation (FS/ICRF/22/26039). Dr Ahmad has received consulting fees from Cardiovascular Systems Inc and Shockwave; and has served on the Medical Advisory Board of Boston Scientific. 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: In the CLEAR (Cholesterol Lowering via Bempedoic Acid, an ACL-Inhibiting Regimen) Outcomes trial, treatment of statin-intolerant patients with bempedoic acid produced a 21% decrease in low-density lipoprotein cholesterol (LDL-C) relative to placebo and a 13% relative reduction in the risk of major adverse cardiovascular events., Objectives: This study sought to determine whether the relationship between LDL-C lowering and cardiovascular benefit achieved with bempedoic acid resembles that observed with statins when standardized per unit change in LDL-C., Methods: To compare the treatment effect of bempedoic acid with statins, the methodology of the Cholesterol Treatment Trialists' Collaboration (CTTC) was applied to outcomes among the 13,970 patients enrolled in the CLEAR Outcomes trial. The CTTC endpoint of "major vascular event" was a composite of coronary heart disease death, nonfatal myocardial infarction, fatal or nonfatal stroke, or coronary revascularization. HRs for CTTC-defined endpoints were normalized to 1 mmol/L differences in LDL-C levels between bempedoic acid and placebo groups., Results: A first major vascular event occurred in 703 (10.1%) patients in the bempedoic acid group and 816 (11.7%) patients in the placebo group (HR: 0.85; 95% CI: 0.77-0.94). When normalized per 1 mmol/L reduction in LDL-C, the HR was 0.75 (95% CI: 0.63-0.90), comparable to the rate ratio of 0.78 reported for statins in the CTTC meta-analysis. Normalized risk reductions were similar for bempedoic acid and statins for the endpoints of major coronary events, nonfatal myocardial infarction, and coronary revascularization., Conclusions: Cardiovascular risk reduction with bempedoic acid is similar to that achieved with statins for a given absolute magnitude of LDL-C lowering. (Evaluation of Major Adverse Cardiovascular Events in Participants With, or at High Risk for, Cardiovascular Disease Who Are Statin Intolerant Treated with Bempedoic Acid [ETC-1002] or Placebo [CLEAR Outcomes]; NCT02993406)., Competing Interests: Funding Support and Author Disclosures This work was funded by Esperion Therapeutics, Inc. The trial was designed by the sponsor, Esperion Therapeutics, in collaboration with the Cleveland Clinic Coordinating Center for Clinical Research (C5Research) and an academic Executive Committee. At the completion of the trial, the database was transferred to C5Research. Statisticians at Esperion conducted data analyses for this paper. Dr Lincoff wrote the first draft and all subsequent drafts of the paper, which was reviewed and approved by all authors. The sponsor reviewed the paper and provided suggested revisions, but the final decision on content was reserved for the academic authors. Dr Lincoff has received research funding for this trial from Esperion; has received grants from Eli Lilly, AbbVie, CSL, AstraZeneca, and Novartis; has received personal fees from Novo Nordisk, Eli Lilly, Akebia, Alnylam, Amgen, Ardelyx, Becton-Dickson, Brainstorm Cell, Cadrenal, Endologix, Fibrogen, GlaxoSmithKline, Intarcia, Medtronic, Neovasc, Provention Bio, and ReCor; and has received travel support for attending steering committee meetings from Novo Nordisk, Esperion, and Eli Lilly. Dr Ray has received unrestricted research grants (in the last 3 years) to Imperial College London from Amgen, Sanofi, Regeneron, Daiichi-Sankyo, and Ultragenix; has received consulting fees for serving as a member of the steering committee and executive committee of clinical trials and roles as principal investigator and national lead investigator from Novartis, Daiichi-Sankyo, Kowa, Esperion, Novo Nordisk, MSD, Lilly, Silence Therapeutics, AstraZeneca, New Amsterdam Pharma, Bayer, Beren Therapeutics, Cleerly, EmendoBio, Scribe, CRISPR, Vaxxinity, Amarin, Regeneron, Ultragenix, Cargene, and Resverlogix; has served on advisory boards, providing advice on data, its interpretation, and future lines of research; has received lecture fees for Continuing Medical Education and non–Continuing Medical Education symposia at international meetings from Novartis, Boehringer Ingelheim, AstraZeneca, Novo Nordisk, Viatris, Amarin, Biologix Pharma, Sanofi, Amgen, Esperion, Daiichi-Sankyo, and Macleod Pharma; owns stock options in New Amsterdam Pharma and PEMI31; and has served as European Atherosclerosis Society President (unpaid). Dr Sasiela was an employee of, has served as a paid consultant for, and owns stock in Esperion Therapeutics, Inc. Dr Nicholls has received research support from AstraZeneca, Amgen, Anthera, CSL Behring, Cerenis, Eli Lilly, Esperion, Resverlogix, 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, Novo Nordisk, CSL Sequiris, and Vaxxinity. Dr Li is an employee of Esperion Therapeutics, Inc. Dr Cho has served on the steering committee for the CLEAR Outcomes trial. Dr Libby has served as an unpaid consultant for Amgen, AstraZeneca, Baim Institute, Beren Therapeutics, Kancera, Kowa Pharmaceuticals, Medimmune, Merck, Novo Nordisk, Novartis, Pfizer, Sanofi-Regeneron, Cartesian, Esperion, Genentech, and Moderna; has served as an unpaid scientific advisory board member for the Baim Institute, Medimmune, Dewpoint, Pfizer, DalCor Pharmaceuticals, Olatec Therapeutics, XBiotech Inc, Caristo, CSL Behring, PlaqueTech, TenSixteen Bio, Soley Therapeutics, and Elucid Bioimaging; has received laboratory funding from Pfizer and CSL Behring; holds patents pending for use of canakinumab and for treatment for brain ischemia-reperfusion injury; has served as an unpaid consultant or been involved in clinical trials for Amgen, AstraZeneca, the Baim Institute, Beren Therapeutics, Esperion Therapeutics, Genentech, Kancera, Kowa Pharmaceuticals, Medimmune, Merck, Moderna, Novo Nordisk, Novartis, Pfizer, and Sanofi-Regeneron; has served on the scientific advisory board for Amgen, Caristo Diagnostics, Cartesian Therapeutics, CSL Behring, DalCor Pharmaceuticals, Dewpoint Therapeutics, 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 last 2 years from Novartis, Novo Nordisk, and Genentech; has served on the board of directors for XBiotech Inc; has held a financial interest in Xbiotech (a company developing therapeutic human antibodies), 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 Soley Therapeutics (a biotechnology company combining artificial intelligence with molecular and cellular response detection for discovering and developing new drugs, currently focusing on cancer therapeutics); and has had his interests reviewed and managed by Brigham and Women’s Hospital and Mass General Brigham in accordance with their conflict-of-interest policies. 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, Valeo Pharma; and has received salary support/honoraria from the Heart and Stroke Foundation of Ontario/University of Toronto (Polo) Chair, 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, New York University Clinical Coordinating Centre, PERFUSE Research Institute, and TIMI Study Group (Brigham Health). Dr Nissen has received grant support from Esperion for the CLEAR Outcomes Trial; and the Cleveland Clinic Center for Clinical Research has received funding to perform clinical trials from AbbVie, AstraZeneca, Arrowhead, Amgen, Bristol Myers Squibb, Eli Lilly, Medtronic, MyoKardia, New Amsterdam Pharmaceuticals, Novartis, and Silence Therapeutics, in which Dr Nissen is involved in these clinical trials but receives no personal remuneration for his participation. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

The lack of consistent definitions and nomenclature across clinical trials of novel devices, drugs, or biologics poses a significant barrier to accrual of knowledge in and across peripheral artery disease therapies and technologies. Recognizing this problem, the Peripheral Academic Research Consortium, together with the U.S. Food and Drug Administration and the Japanese Pharmaceuticals and Medical Devices Agency, has developed a series of pragmatic consensus definitions for patients being treated for peripheral artery disease affecting the lower extremities. These consensus definitions include the clinical presentation, anatomic depiction, interventional outcomes, surrogate imaging and physiological follow-up, and clinical outcomes of patients with lower-extremity peripheral artery disease. Consistent application of these definitions in clinical trials evaluating novel revascularization technologies should result in more efficient regulatory evaluation and best practice guidelines to inform clinical decisions in patients with lower extremity peripheral artery disease.

ObjectivesThis study sought to report full 1-year results, detailed magnetic resonance imaging analysis, and determinants of efficacy in the prospective, randomized, controlled CADUCEUS (CArdiosphere-Derived aUtologous stem CElls to reverse ventricUlar dySfunction) trial.BackgroundCardiosphere-derived cells (CDCs) exerted regenerative effects at 6 months in the CADUCEUS trial. Complete results at the final 1-year endpoint are unknown.MethodsAutologous CDCs (12.5 to 25 × 10(6)) grown from endomyocardial biopsy specimens were infused via the intracoronary route in 17 patients with left ventricular dysfunction 1.5 to 3 months after myocardial infarction (MI) (plus 1 infused off-protocol 14 months post-MI). Eight patients were followed as routine-care control patients.ResultsIn 13.4 months of follow-up, safety endpoints were equivalent between groups. At 1 year, magnetic resonance imaging revealed that CDC-treated patients had smaller scar size compared with control patients. Scar mass decreased and viable mass increased in CDC-treated patients but not in control patients. The single patient infused 14 months post-MI responded similarly. CDC therapy led to improved regional function of infarcted segments compared with control patients. Scar shrinkage correlated with an increase in viability and with improvement in regional function. Scar reduction correlated with baseline scar size but not with a history of temporally remote MI or time from MI to infusion. The changes in left ventricular ejection fraction in CDC-treated subjects were consistent with the natural relationship between scar size and ejection fraction post-MI.ConclusionsIntracoronary administration of autologous CDCs did not raise significant safety concerns. Preliminary indications of bioactivity include decreased scar size, increased viable myocardium, and improved regional function of infarcted myocardium at 1 year post-treatment. These results, which are consistent with therapeutic regeneration, merit further investigation in future trials. (CArdiosphere-Derived aUtologous stem CElls to reverse ventricUlar dySfunction [CADUCEUS]; NCT00893360).

ObjectivesThe purpose of this study was to compare the incidence of new-onset diabetes (NOD) with cardiovascular (CV) event reduction at different levels of NOD risk.BackgroundStatins reduce the number of CV events but increase the incidence of NOD. We previously reported that 4 factors independently predicted NOD: fasting blood glucose >100 mg/dl, fasting triglycerides >150 mg/dl, body mass index >30 kg/m(2), and history of hypertension.MethodsWe compared NOD incidence with CV event reduction among 15,056 patients with coronary disease but without diabetes at baseline in the TNT (Treating to New Targets) (n = 7,595) and IDEAL (Incremental Decrease in Endpoints Through Aggressive Lipid Lowering) (n = 7,461) trials. CV events included coronary heart disease death, myocardial infarction, stroke, and resuscitated cardiac arrest.ResultsAmong 8,825 patients with 0 to 1 of the aforementioned NOD risk factors at baseline, NOD developed in 142 of 4,407 patients in the atorvastatin 80 mg group and in 148 of 4,418 in the atorvastatin 10 mg and simvastatin 20 to 40 mg groups (3.22% vs. 3.35%; hazard ratio [HR]: 0.97; 95% confidence intervals [CI]: 0.77 to 1.22). Among the remaining 6,231 patients with 2 to 4 NOD risk factors, NOD developed in 448 of 3,128 in the atorvastatin 80 mg group and in 368 of 3,103 in the lower-dose groups (14.3% vs. 11.9%; HR: 1.24; 95% CI: 1.08 to 1.42; p = 0.0027). The number of CV events was significantly reduced with atorvastatin 80 mg in both NOD risk groups.ConclusionsCompared with lower-dose statin therapy, atorvastatin 80 mg/day did not increase the incidence of NOD in patients with 0 to 1 NOD risk factors but did, by 24%, among patients with 2 to 4 NOD risk factors. The number of CV events was significantly reduced with atorvastatin 80 mg in both NOD risk groups.

Background: ST-segment elevation myocardial infarction (STEMI) is associated with high early mortality. However, it remains unclear if patients surviving the early phase have long-term excess mortality., Objectives: This study aims to assess excess mortality in STEMI patients treated with primary percutaneous coronary intervention (PCI) compared with an age- and- sex-matched general population at landmark periods 0 to 30 days, 31 to 90 days, and 91 days to 10 years., Methods: Using the Western Denmark Heart Registry, we identified first-time PCI-treated patients who had primary PCI for STEMI from January 2003 to October 2018. Each patient was matched by age and sex to 5 individuals from the general population., Results: We included 18,818 patients with first-time STEMI and 94,090 individuals from the general population. Baseline comorbidity burden was similar in STEMI patients and matched individuals. Compared with the matched individuals, STEMI was associated with a 5.9% excess mortality from 0 to 30 days (6.0% vs 0.2%; HR: 36.44; 95% CI: 30.86-43.04). An excess mortality remained present from 31 to 90 days (0.9% vs 0.4%; HR: 2.43; 95% CI: 2.02-2.93). However, in 90-day STEMI survivors, the absolute excess mortality was only 2.1 percentage points at 10-year follow-up (26.5% vs 24.5%; HR: 1.04; 95% CI: 1.01-1.08). Use of secondary preventive medications such as statins, antiplatelet therapy, and beta-blockers was very high in STEMI patients throughout 10-year follow-up., Conclusions: In primary PCI-treated STEMI patients with high use of guideline-recommended therapy, patients surviving the first 90 days had 10-year mortality that was only 2% higher than that of a matched general population., Competing Interests: Funding Support and Author Disclosures The study was supported by a grant from Aase and Ejnar Danielsen’s Foundation. Dr Olesen has received grants from the Danish Cardiovascular Academy funded by the Danish Heart Association and Novo Nordisk. Dr Mortensen has received lecture fees from Novo Nordisk, Amgen, Sanofi, AstraZeneca, and Amarin. Dr Kristensen is national coordinating investigator in the SOS-AMI (Suspected Acute Myocardial Infarction) trial (Idorsia). Dr Maeng has received grants from the Novo Nordisk Foundation (grant number NNF22OC0074083); has received lecture and/or advisory board fees from AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, and Novo Nordisk; has received a travel grant from Novo Nordisk; has received institutional research grants from Philips, Bayer, and Novo Nordisk; has ongoing research contracts with Janssen, Novo Nordisk, and Philips; and is a minor shareholder in Novo Nordisk, Eli Lilly and Company, and Verve Therapeutics. 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: Telemedicine programs can provide remote diagnostic information to aid clinical decisions that could optimize care and reduce unplanned readmissions post-acute coronary syndrome (ACS)., Objectives: TELE-ACS (Remote Acute Assessment of Patients With High Cardiovascular Risk Post-Acute Coronary Syndrome) is a randomized controlled trial that aims to compare a telemedicine-based approach vs standard care in patients following ACS., Methods: Patients were suitable for inclusion with at least 1 cardiovascular risk factor and presenting with ACS and were randomized (1:1) before discharge. The primary outcome was time to first readmission at 6 months. Secondary outcomes included emergency department (ED) visits, major adverse cardiovascular events, and patient-reported symptoms. The primary analysis was performed according to intention to treat., Results: A total of 337 patients were randomized from January 2022 to April 2023, with a 3.6% drop-out rate. The mean age was 58.1 years. There was a reduced rate of readmission over 6 months (HR: 0.24; 95% CI: 0.13-0.44; P < 0.001) and ED attendance (HR: 0.59; 95% CI: 0.40-0.89) in the telemedicine arm, and fewer unplanned coronary revascularizations (3% in telemedicine arm vs 9% in standard therapy arm). The occurrence of chest pain (9% vs 24%), breathlessness (21% vs 39%), and dizziness (6% vs 18%) at 6 months was lower in the telemedicine group., Conclusions: The TELE-ACS study has shown that a telemedicine-based approach for the management of patients following ACS was associated with a reduction in hospital readmission, ED visits, unplanned coronary revascularization, and patient-reported symptoms. (Telemedicine in High-Risk Cardiovascular Patients Post-ACS [TELE-ACS]; NCT05015634)., Competing Interests: Funding Support and Author Disclosures This work was funded by the British Heart Foundation; King Khalid University, Abha, Saudi Arabia via The Saudi Arabian Cultural Bureau (SACB); Sansour Fund, Imperial Healthcare Charity; and the Safwan Sobhan Fund at Imperial College London. TELE-ACS was an investigator-initiated trial sponsored by Imperial College London. All 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: Total coronary atherosclerotic plaque activity across the entire coronary arterial tree is associated with patient-level clinical outcomes., Objectives: We aimed to investigate whether vessel-level coronary atherosclerotic plaque activity is associated with vessel-level myocardial infarction., Methods: In this secondary analysis of an international multicenter study of patients with recent myocardial infarction and multivessel coronary artery disease, we assessed vessel-level coronary atherosclerotic plaque activity using coronary 18 F-sodium fluoride positron emission tomography to identify vessel-level myocardial infarction., Results: Increased 18 F-sodium fluoride uptake was found in 679 of 2,094 coronary arteries and 414 of 691 patients. Myocardial infarction occurred in 24 (4%) vessels with increased coronary atherosclerotic plaque activity and in 25 (2%) vessels without increased coronary atherosclerotic plaque activity (HR: 2.08; 95% CI: 1.16-3.72; P = 0.013). This association was not demonstrable in those treated with coronary revascularization (HR: 1.02; 95% CI: 0.47-2.25) but was notable in untreated vessels (HR: 3.86; 95% CI: 1.63-9.10; P interaction  = 0.024). Increased coronary atherosclerotic plaque activity in multiple coronary arteries was associated with heightened patient-level risk of cardiac death or myocardial infarction (HR: 2.43; 95% CI: 1.37-4.30; P = 0.002) as well as first (HR: 2.19; 95% CI: 1.18-4.06; P = 0.013) and total (HR: 2.50; 95% CI: 1.42-4.39; P = 0.002) myocardial infarctions., Conclusions: In patients with recent myocardial infarction and multivessel coronary artery disease, coronary atherosclerotic plaque activity prognosticates individual coronary arteries and patients at risk for myocardial infarction., Competing Interests: Funding Support and Author Disclosures The PRE(18)FFIR study was funded by the Wellcome Trust (WT103782AIA). The funder played no roles in the design and conduct of the study, collection, management, analysis, and interpretation of the data, preparation, review, or approval of the manuscript, and any decisions to submit the manuscript for publication. The University of Edinburgh and the National Health Service Lothian Health Board were cosponsors. Dr Rudd is part-supported by the National Institute for Health and Care Research Cambridge Biomedical Research Centre, the British Heart Foundation, the Higher Education Funding Council for England, the Engineering and Physical Sciences Research Council, and the Wellcome Trust. Dr Piotr is supported by the National Heart, Lung, and Blood Institute at the National Institutes of Health (R35HL161195). Dr Mills is supported by the British Heart Foundation (CH/F/21/90010, RE/18/5/34216, and RG/20/10/34966). Dr van Beek is supported by the Scottish Imaging Network. Dr Williams is supported by the British Heart Foundation (FS/ICRF/20/26002). Dr Dweck is supported by the British Heart Foundation (FS/SCRF/21/32010). Dr Newby is supported by the British Heart Foundation (CH/09/002, RE/18/5/34216, and RG/F/22/110093). Dr Moss is a current employee of AstraZeneca. Dr Williams has given talks for Canon Medical Systems, Novartis, and Siemens Healthineers. 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.)

Ventricular septal rupture remains a dreadful complication of acute myocardial infarction. Although less commonly observed than during the prethrombolytic era, the condition remains complex and is often associated with refractory cardiogenic shock and death. Corrective surgery, although superior to medical treatment, has been associated with high perioperative morbidity and mortality. Transcatheter closure techniques are less invasive to surgery and offer a valuable alternative, particularly in patients with cardiogenic shock. In these patients, percutaneous mechanical circulatory support represents a novel opportunity for immediate stabilization and preserved end-organ function. Multimodality imaging can identify favorable septal anatomy for the most appropriate type of repair. The heart team approach will define optimal timing for surgery vs percutaneous repair. Emerging concepts are proposed for a deferred treatment approach, including orthotropic heart transplantation in ideal candidates. Finally, for futile situations, palliative care experts and a medical ethics team will provide the best options for end-of-life clinical decision making., Competing Interests: Funding Support and Author Disclosures Dr Lorusso has been the principal investigator of PERSIST-AVR (Perceval Sutureless Implant vs Standard Aortic Valve Replacement), sponsored by LivaNova; and has performed consulting for Medtronic, LivaNova, Abiomed, and Eurosets with all honoraria paid to the university. 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. All rights reserved.)

Background: Myocardial infarction can be ruled out in patients with a single cardiac troponin measurement. Whether use of a uniform rule-out threshold has resulted in sex differences in care remains unclear., Objectives: The purpose of this study was to evaluate implementation of a uniform rule-out threshold in females and males with possible myocardial infarction, and to derive and validate sex-specific thresholds., Methods: The implementation of a uniform rule-out threshold (<5 ng/L) with a high-sensitivity cardiac troponin I assay was evaluated in consecutive patients presenting with possible myocardial infarction. The proportion of low-risk patients discharged from the emergency department and incidence of myocardial infarction or cardiac death at 30 days were determined. Sex-specific thresholds were derived and validated, and proportion of female and male patients were stratified as low-risk compared with uniform threshold., Results: In 16,792 patients (age 58 ± 17 years; 46% female) care was guided using a uniform threshold. This identified more female than male patients as low risk (73% vs 62%), but a similar proportion of low-risk patients were discharged from the emergency department (81% for both) with fewer than 5 (<0.1%) patients having a subsequent myocardial infarction or cardiac death at 30 days. Compared with a uniform threshold of <5 ng/L, use of sex-specific thresholds would increase the proportion of female (61.8% vs 65.9%) and reduce the proportion of male (54.8% vs 47.8%) patients identified as low risk., Conclusions: Implementation of a uniform rule-out threshold for myocardial infarction was safe and effective in both sexes. Sex-specific rule-out thresholds should be considered, but their impact on effectiveness and safety may be limited., Competing Interests: Funding Support and Author Disclosures This work was supported by DataLoch, which is funded by the Data Driven Innovation program within the Edinburgh and South East Scotland City Region Deal. Abbott Laboratories provided cardiac troponin assay reagents, calibrators, and controls without charge for the conduct of the High-STEACS trial. The HiSTORIC trial was funded by the British Heart Foundation (grant PG/15/51/31596) with support from British Heart Foundation Research Excellence Awards (awards RE/18/5/34216 and RE/18/6134217). The High-STEACS trial was funded by the British Heart Foundation (SP/12/10/29922). Dr Wereski is supported by Clinical Research Training Fellowship (MR/V007017/1) from the Medical Research Council. Drs Lowry and Doudesis are supported by Medical Research Council (MR/W000598/1; MR/N013166/1). Dr McDermott is supported by the British Heart Foundation Clinical Research Training Fellowship (FS/CRTF/23/24491). Dr Chapman is supported by a British Cardiovascular Interventional Society (BCIS) Advanced Coronary Intervention Fellowship. Dr Lee is supported by an ECAT/SCREDS Clinical Lectureship in Cardiology. Dr Anand is supported by a Clinical Lectureship from the Chief Scientist Office (PCL/18/05). Dr Mills is supported by the British Heart Foundation through a Chair Award (CH/F/21/90010), a Programme Grant (RG/20/10/34966), and a Research Excellence Award (RE/18/5/34216) from the British Heart Foundation. Dr Kimenai is supported by a British Heart Foundation Intermediate Basic Science Research Fellowship (FS/IBSRF/23/25161). The funders played no role in the design, conduct, data collection, analysis, or reporting of the trial. Dr Mills has received honoraria from Abbott Diagnostics, Roche Diagnostics, Siemens Healthineers, LumiraDx, and Psyros Diagnostics; and is employed by the University of Edinburgh, who has received research funding from Abbott Diagnostics, Siemens Healthineers, and Roche Diagnostics unrelated to the current work. Dr Chapman is supported by a BCIS Advanced Coronary Intervention Fellowship, which is in part funded by Abbott Cardiovascular and Edwards Lifesciences. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Crown Copyright © 2024. Published by Elsevier Inc. All rights reserved.)

Background: Lipoprotein(a) (Lp[a]) is associated with an increased risk of myocardial infarction (MI). However, the mechanism underlying this association has yet to be fully elucidated., Objectives: This multicenter study aimed to investigate whether association between Lp(a) and MI risk is reinforced by the presence of low-attenuation plaque (LAP) identified by coronary computed tomography angiography (CCTA)., Methods: In a derivation cohort, a total of 5,607 patients with stable chest pain suspected of coronary artery disease who underwent CCTA and Lp(a) measurement were prospectively enrolled. In validation cohort, 1,122 patients were retrospectively collected during the same period. High Lp(a) was defined as Lp(a) ≥50 mg/dL. The primary endpoint was a composite of time to fatal or nonfatal MI. Associations were estimated using multivariable Cox proportional hazard models., Results: During a median follow-up of 8.2 years (Q1-Q3: 7.2-9.3 years), the elevated Lp(a) levels were associated with MI risk (adjusted HR [aHR]: 1.91; 95% CI: 1.46-2.49; P < 0.001). There was a significant interaction between Lp(a) and LAP (P interaction  <0.001) in relation to MI risk. When stratified by the presence or absence of LAP, Lp(a) was associated with MI in patients with LAP (aHR: 3.03; 95% CI: 1.92-4.76; P < 0.001). Mediation analysis revealed that LAP mediated 73.3% (P < 0.001) for the relationship between Lp(a) and MI. The principal findings remained unchanged in the validation cohort., Conclusions: Elevated Lp(a) augmented the risk of MI during 8 years of follow-up, especially in patients with LAP identified by CCTA. The presence of LAP could reinforce the relationship between Lp(a) and future MI occurrence., Competing Interests: Funding Support and Author Disclosures This study is supported by the National Natural Science Foundation of China (Grant Nos. 82102033; 82300375), Shanghai Rising Stars of Medical Talent Youth Development Program [Grant No. SHWRS(2023)-062], Shanghai Sailing Program (Grant No. 20YF1435900), Shanghai Pujiang Program (Grant No. 21PJD012), and Science Foundation of Shanghai Municipal Health Commission (Grant No. 202040349). The 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.)

Severe acute mitral regurgitation after myocardial infarction includes partial and complete papillary muscle rupture or functional mitral regurgitation. Although its incidence is <1%, mitral regurgitation after acute myocardial infarction frequently causes hemodynamic instability, pulmonary edema, and cardiogenic shock. Medical management has the worst prognosis, and mortality has not changed in decades. Surgery represents the gold standard, but it is associated with high rates of morbidity and mortality. Recently, transcatheter interventions have opened a new door for management that may improve survival. Mechanical circulatory support restores vital organ perfusion and offers the opportunity for a steadier surgical repair. This review focuses on the diagnosis and the interventional management, both surgical and transcatheter, with a glance on future perspectives to enhance patient management and eventually decrease mortality., Competing Interests: Funding Support and Author Disclosures Dr Estévez-Loureiro is a consultant for Abbott Vascular, Edwards Lifesciences, Boston Scientific, and Venus Medtech. Dr Taramasso has served as a consultant for Abbott Vascular, Boston Scientific, 4TECH, and CoreMedic; and has received speaker honoraria from Edwards Lifesciences. Dr Lorusso is a consultant for Medtronic, Abiomed, and ChinaBridge Medical; is a member of the Medical Advisory Board of Eurosets and Xenios; and has received a grant for research activity from Medtronic. 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. All rights reserved.)

Right ventricular infarction (RVI) complicates 50% of cases of acute inferior ST-segment elevation myocardial infarction, and is associated with high in-hospital morbidity and mortality. Ischemic right ventricular (RV) systolic dysfunction decreases left ventricular preload delivery, resulting in low-output hypotension with clear lungs, and disproportionate right heart failure. RV systolic performance is generated by left ventricular contractile contributions mediated by the septum. Augmented right atrial contraction optimizes RV performance, whereas very proximal occlusions induce right atrial ischemia exacerbating hemodynamic compromise. RVI is associated with vagal mediated bradyarrhythmias, both during acute occlusion and abruptly with reperfusion. The ischemic dilated RV is also prone to malignant ventricular arrhythmias. Nevertheless, RV is remarkably resistant to infarction. Reperfusion facilitates RV recovery, even after prolonged occlusion and in patients with severe shock. However, in some cases hemodynamic compromise persists, necessitating pharmacological and mechanical circulatory support with dedicated RV assist devices as a "bridge to recovery.", Competing Interests: Funding Support and Author Disclosures The authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 American College of Cardiology Foundation. All rights reserved.)