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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: It remains unclear whether procedural myocardial infarction (pMI) and spontaneous myocardial infarction (spMI) have a similar impact on prognosis., Objectives: The aim of this study was to assess mortality after pMI and spMI., Methods: Patients with chronic coronary syndrome (CCS) and baseline troponin ≤1× the upper reference level (URL) or with acute spMI who underwent percutaneous coronary intervention (PCI) were included. PMI was defined as post-PCI troponin increase >1× URL in patients with CCS. SpMI comprised any acute coronary syndrome with elevated troponin. The 1-year risk of all-cause death was assessed after pMI and spMI across 3 strata of troponin elevation (>1-5×, >5-35×, and >35× URL), with CCS patients having post-PCI troponin ≤1× URL as a reference group. Conventional troponin I was measured using the Architect methodology (Abbott)., Results: Among 10,707 patients undergoing PCI from 2012 to 2020, 8,515 patients presented with CCS and 2,192 with spMI. Among CCS patients, 913 (10.7%) had pMI. Troponin peaks >1-5×, >5-35×, and >35× URL were observed in 53%, 41%, and 6% of patients with pMI, and in 24%, 38%, and 37% of patients with spMI, respectively. Mortality at 1 year was higher after pMI (7.7%; adjusted HR: 4.40; 95% CI: 1.59-12.2), and spMI (8.5%; adjusted HR: 7.57; 95% CI: 5.44-10.5) with troponin peak >35× URL compared with no-MI (1.4%). Mortality was also increased after spMI with troponin peak >1-5× or >5-35× URL., Conclusions: Mortality at 1 year was significantly increased after pMI and spMI with troponin peak >35× URL, whereas for troponin levels ≤35× only spMI had a relevant impact on mortality., Competing Interests: Funding Support and Author Disclosures Dr Spirito has received a research grant from the Swiss National Science Foundation. Dr Baber has received honoraria from AstraZeneca and Boston Scientific. Dr Khera has received consulting or speaker fees from Medtronic, Edwards Lifesciences, Abbott Structural Heart, Eastend Medical, Terumo, Zoll Medical, and W.L.Gore & Associates; has served as a proctor for Medtronic and Abbott Structural Heart; and is also global principal investigator of a study funded by Teleflex (no compensation). Dr Windecker has received research, travel, or educational grants to the institution without personal remuneration from Abbott, Abiomed, Amgen, AstraZeneca, Bayer, Braun, Biotronik, Boehringer Ingelheim, Boston Scientific, Bristol Myers Squibb, Cardinal Health, CardioValve, Cordis Medical, Corflow Therapeutics, CSL Behring, Daiichi-Sankyo, Edwards Lifesciences, Farapulse Inc, Fumedica, Guerbet, Idorsia, Inari Medical, InfraRedx, Janssen-Cilag, Johnson & Johnson, Medalliance, Medicure, Medtronic, Merck Sharp & Dohm, Miracor Medical, Novartis, Novo Nordisk, Organon, OrPha Suisse, Pharming Tech, Pfizer, Polares, Regeneron, Sanofi-Aventis, Servier, Sinomed, Terumo, Vifor, and V-Wave; has served as advisory board member and/or member of the steering/executive group of trials funded by Abbott, Abiomed, Amgen, AstraZeneca, Bayer, Boston Scientific, Biotronik, Bristol Myers Squibb, Edwards Lifesciences, MedAlliance, Medtronic, Novartis, Polares, Recardio, Sinomed, Terumo, and V-Wave, with payments to the institution but no personal payments; and is also a member of the steering/executive committee group of several investigator-initiated trials that receive funding by industry without impact on his personal remuneration. Dr Dangas has received consulting fees and advisory board fees from AstraZeneca; has received consulting fees from Biosensors; and previously held stock in Medtronic. Dr Mehran has received institutional research grants from Abbott, Affluent Medical, Alleviant Medical, Amgen, AstraZeneca, 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, Sanofi, and Zoll; has received consulting 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, NovoNordisk, PeerView Institute for Medical Education, TERUMO Europe N.V., and Radcliffe; has equity <1% in Elixir Medical, STEL, and CONTROLRAD (spouse); has received honorarium for serving om the Scientific Advisory Board for AMA, JAMA Cardiology (Associate Editor), and the American College of Cardiology; and is a Committe Member for SCAI, Faculty member of the Cardiovascular Research Foundation, and founder of Women as One (no fee). All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024. Published by Elsevier Inc.)

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: U.S. policy efforts have focused on reducing rural-urban health inequities. However, it is unclear whether gaps in care and outcomes remain among older adults with acute cardiovascular conditions., Objectives: This study aims to evaluate rural-urban differences in procedural care and mortality for acute myocardial infarction (AMI), heart failure (HF), and ischemic stroke., Methods: This is a retrospective cross-sectional study of Medicare fee-for-service beneficiaries aged ≥65 years with acute cardiovascular conditions from 2016 to 2018. Cox proportional hazards models with random hospital intercepts were fit to examine the association of presenting to a rural (vs urban) hospital and 30- and 90-day patient-level mortality., Results: There were 2,182,903 Medicare patients hospitalized with AMI, HF, or ischemic stroke from 2016 to 2018. Patients with AMI were less likely to undergo cardiac catherization (49.7% vs 63.6%, P < 0.001), percutaneous coronary intervention (42.1% vs 45.7%, P < 0.001) or coronary artery bypass graft (9.0% vs 10.2%, P < 0.001) within 30 days at rural versus urban hospitals. Thrombolysis rates (3.1% vs 10.1%, P < 0.001) and endovascular therapy (1.8% vs 3.6%, P < 0.001) for ischemic stroke were lower at rural hospitals. After adjustment for demographics and clinical comorbidities, the 30-day mortality HR was significantly higher among patients presenting to rural hospitals for AMI (HR: 1.10, 95% CI: 1.08 to 1.12), HF (HR: 1.15; 95% CI: 1.13 to 1.16), and ischemic stroke (HR: 1.20; 95% CI: 1.18 to 1.22), with similar patterns at 90 days. These differences were most pronounced for the subset of critical access hospitals that serve remote, rural areas., Conclusions: Clinical, public health, and policy efforts are needed to improve rural-urban gaps in care and outcomes for acute cardiovascular conditions., Competing Interests: Funding Support and Author Disclosures This study has received support from the National Heart, Lung, and Blood Institute (K23HL148525) at the National Institutes of Health. Dr Loccoh receives research support from the Sarnoff Cardiovascular Research Fellowship. Dr Joynt Maddox has received research support from the National Heart, Lung, and Blood Institute (R01HL143421) and National Institute on Aging (R01AG060935). Dr Yeh receives research support from the National Heart, Lung, and Blood Institute (R01HL136708 and R01HL157530) and the Richard A. and Susan F. Smith Center for Outcomes Research in Cardiology; and has received grants and personal fees from Abbott Vascular, AstraZeneca, Boston Scientific, and Medtronic, outside the submitted work. Dr Wadhera has received research support from the National Heart, Lung, and Blood Institute (K23HL148525) at the National Institutes of Health; and has been a consultant for Abbott, outside the submitted work. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: International Classification of Disease (ICD)-10 coding of type 1 myocardial infarction (MI) is used for reimbursement, value-based programs, and clinical research., Objectives: This study sought to determine whether the introduction of ICD-10 codes for type 2 and types 3-5 MI was associated with changes in hospitalizations for ICD-10 codes now attributed to type 1 MI., Methods: Using the Nationwide Readmissions Database, we identified patients with ICD-10 codes now attributed to type 1 MI between January 2016 and December 2018. Patients were stratified according to the timing of their event in relation to the introduction of the type 2 and types 3-5 MI codes on October 1, 2017., Results: There were 2,680,323 hospitalizations for ICD-10 codes now attributed to type 1 MI; after adjustment for seasonality, there was a 13.7% decline in hospitalizations after the introduction of the new subtype codes. Patients with ICD-10 codes now attributed to type 1 MI after the coding change were less likely to be female, had lower prevalence of several cardiovascular and noncardiovascular comorbidities, and had higher rates of coronary angiography and revascularization. After introduction of the new codes, there was a positive deflection in the slope of risk-adjusted in-hospital mortality (0.007%; P <0.001) and a negative deflection in risk-adjusted 30-day readmission (-0.002%; P = 0.05) for patients with ICD-10 codes now attributed to type 1 MI., Conclusions: The introduction of ICD-10 codes for type 2 and types 3-5 MI was associated with a decrease in hospitalizations for ICD-10 codes now attributed to type 1 MI and changes in the observed characteristics and treatment patterns of these patients., Competing Interests: Funding Support and Author Disclosures Dr Wasfy has received a grant from the American Heart Association (18 CDA 34110215). Dr Januzzi is supported in part by the Hutter Family Professorship. Dr Vaduganathan serves on advisory boards and/or has received research grant support from American Regent, Amgen, AstraZeneca, Baxter Healthcare, Bayer AG, Boehringer Ingelheim, Cytokinetics, Lexicon Pharmaceuticals, and Relypsa; and participates on clinical endpoint committees for studies sponsored by Galmed and Novartis. Dr Januzzi is a Trustee of the American College of Cardiology; has received grant support from Novartis Pharmaceuticals, Innolife, Applied Therapeutics, and Abbott Diagnostics; has received consulting income from Abbott, Janssen, Novartis, Pfizer, Merck, and Roche Diagnostics; and participates in clinical endpoint committees/data safety monitoring boards for Abbott, AbbVie, Amgen, Bayer, CVRx, and Takeda. Dr Wasfy has received consulting fees from Pfizer, Biotronik, and the Institute for Clinical and Economic Review; serves as chair of New England CEPAC; and has received reimbursements for travel from non-profit professional and academic organizations. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Short-term exposure to ambient air pollution has been linked to occurrence of myocardial infarction (MI); however, only a limited number of studies investigated its association with death from MI, and the results remain inconsistent., Objectives: This study sought to investigate the association of short-term exposure to air pollution across a wide range of concentrations with MI mortality., Methods: A time-stratified case-crossover study was conducted to investigate 151,608 MI death cases in Hubei province (China) from 2013 to 2018. Based on each case's home address, exposure to particulate matter with an aerodynamic diameter ≤2.5 μm (PM 2.5 ), particulate matter with an aerodynamic diameter ≤10 μm (PM 10 ), sulfur dioxide, nitrogen dioxide (NO 2 ), carbon monoxide, and ozone on each of the case and control days was assessed as the inverse distance-weighted average concentration at neighboring air quality monitoring stations. Conditional logistic regression models were implemented to quantify exposure-response associations., Results: Exposure to PM 2.5 , PM 10 , and NO 2 (mean exposure on the same day of death and 1 day prior) was significantly associated with increased odds of MI mortality. The odds associated with PM 2.5 and PM 10 exposures increased steeply before a breakpoint (PM 2.5 , 33.3 μg/m 3 ; PM 10 , 57.3 μg/m 3 ) and flattened out at higher exposure levels, while the association for NO 2 exposure was almost linear. Each 10-μg/m 3 increase in exposure to PM 2.5 (<33.3 μg/m 3 ), PM 10 (<57.3 μg/m 3 ), and NO 2 was significantly associated with a 4.14% (95% confidence interval [CI]: 1.25% to 7.12%), 2.67% (95% CI: 0.80% to 4.57%), and 1.46% (95% CI: 0.76% to 2.17%) increase in odds of MI mortality, respectively. The association between NO 2 exposure and MI mortality was significantly stronger in older adults., Conclusions: Short-term exposure to PM 2.5 , PM 10 , and NO 2 was associated with increased risk of MI mortality., Competing Interests: Author Disclosures This work was supported by the Hubei Provincial Health Commission in China (WJ2019Z016, WJ2018H238, and WJ2015MA027), the Fundamental Research Funds for the Central Universities (19ykpy89), the National Natural Science Foundation of China (91743205), and the Jiangsu Social Development Project (BE2018745). The authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Inhibition of the interleukin (IL)-1β innate immunity pathway is associated with anti-inflammatory effects and a reduced risk of recurrent cardiovascular events in stable patients with previous myocardial infarction (MI) and elevated high-sensitivity C-reactive protein (hs-CRP)., Objectives: This study assessed the association between IL-1β level with all-cause mortality in patients with acute ST-segment elevation MI who underwent primary percutaneous coronary intervention and the interplay between IL-1β and hs-CRP concentrations on the risk of premature death., Methods: IL-1β concentration was measured in 1,398 patients with ST-segment elevation MI who enrolled in a prospective cohort. Crude and hazard ratios for all-cause and cardiovascular mortality were analyzed at 90 days and 1 year using multivariate Cox proportional regression analysis. Major adverse cardiovascular events (MACEs) were analyzed., Results: IL-1β concentration measured at admission was associated with all-cause mortality at 90 days (adjusted hazard ratio [adjHR]: 1.47 per 1 SD increase; 95% confidence interval [CI]: 1.16 to 1.87; p < 0.002). The relation was nonlinear, and the highest tertile of IL-1β was associated with higher mortality rates at 90 days (adjHR: 2.78; 95% CI: 1.61 to 4.79; p = 0.0002) and at 1 year (adjHR: 1.93; 95% CI: 1.21 to 3.06; p = 0.005), regardless of the hs-CRP concentration. Significant relationships were equally observed when considering cardiovascular mortality and MACEs at 90 days (adjHR: 2.42; 95% CI: 1.36 to 4.28; p = 0.002, and adjHR: 2.29; 95% CI: 1.31 to 4.01; p = 0.004, respectively) and at 1 year (adjHR: 2.32; 95% CI: 1.36 to 3.97; p = 0.002, and adjHR: 2.35; 95% CI: 1.39 to 3.96; p = 0.001, respectively)., Conclusions: IL-1β measured at admission in patients with acute MI was independently associated with the risk of mortality and recurrent MACEs., (Copyright © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Numerous definitions for peri-procedural myocardial infarction (PMI) following percutaneous coronary intervention (PCI) and coronary bypass grafting (CABG) surgery exist., Objectives: The purpose of this study was to investigate the PMI rates according to various definitions, their clinically relevant association with all-cause mortality at 10 years, and their impact on composite endpoints at 5 years in the SYNTAXES (Synergy between PCI with Taxus and Cardiac Surgery Extended Survival) trial., Methods: PMI was classified as a myocardial infarction occurring within 48 h of the procedure according to definitions of the SYNTAX (TAXUS Drug-Eluting Stent Versus Coronary Artery Bypass Surgery for the Treatment of Narrowed Arteries), ISCHEMIA (International Study Of Comparative Health Effectiveness With Medical And Invasive Approaches), and EXCEL (Evaluation of XIENCE versus Coronary Artery Bypass Surgery for Effectiveness of Left Main Revascularization) trials; the Fourth Universal Definition of MI; and the Society for Cardiovascular Angiography and Interventions (SCAI). Of the 1,800 patients enrolled, 1,652 with creatine kinase and/or creatine kinase-myocardial band (CK-MB) post-procedure were included. The association between PMI and mortality was analyzed by Cox regression., Results: PMI rates according to the SYNTAX and Fourth Universal Definition of MI, both of which required CK-MB elevation and electrocardiographic evidence of permanent myocardial damage, were 2.7% and 3.0%, respectively, in the PCI arm versus 2.4% and 2.1%, respectively, in the CABG arm. PMI rates according to the SCAI or EXCEL definition were higher in the PCI (5.7%) and CABG (16.5%) arms. PMIs according to the SYNTAX and Fourth Universal Definition of MI were more strongly associated with mortality than EXCEL and SCAI PMIs defined by isolated enzyme elevation when CK-MB was more than 10 times ULN. The impact of these "enzyme-driven events" on time-to-event curves and the composite endpoints was greater in the surgical cohort. PMIs after PCI were associated with 10-year mortality regardless of definition, whereas their impact on mortality after CABG was limited to 1 year., Conclusions: The rates of PMI are highly dependent on their definition, which affects time-to-event curves, composite endpoints, and their lethal prognostic relevance. (Synergy Between PCI With TAXUS and Cardiac Surgery: SYNTAX Extended Survival [SYNTAXES]; NCT03417050; SYNTAX Study: TAXUS Drug-Eluting Stent Versus Coronary Artery Bypass Surgery for the Treatment of Narrowed Arteries [SYNTAX]; NCT00114972)., (Copyright © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Varying definitions of procedural myocardial infarction (PMI) are in widespread use., Objectives: This study sought to determine the rates and clinical relevance of PMI using different definitions in patients with left main coronary artery disease randomized to percutaneous coronary intervention (PCI) versus coronary artery bypass grafting (CABG) surgery in the EXCEL (Evaluation of XIENCE versus Coronary Artery Bypass Surgery for Effectiveness of Left Main Revascularization) trial., Methods: The pre-specified protocol definition of PMI (PMI Prot ) required a large elevation of creatine kinase-MB (CK-MB), with identical threshold for both procedures. The Third Universal Definition of MI (types 4a and 5) (PMI UD ) required lesser biomarker elevations but with supporting evidence of myocardial ischemia, different after PCI and CABG. For the PMI UD , troponins were used preferentially (available in 49.5% of patients), CK-MB otherwise. The multivariable relationship between each PMI type and 5-year mortality was determined., Results: PMI Prot occurred in 34 of 935 (3.6%) patients after PCI and 56 of 923 (6.1%) patients after CABG (difference -2.4%; 95% confidence interval [CI]: -4.4% to -0.5%; p = 0.015). The corresponding rates of PMI UD were 37 (4.0%) and 20 (2.2%), respectively (difference 1.8%; 95% CI: 0.2% to 3.4%; p = 0.025). Both PMI Prot and PMI UD were associated with 5-year cardiovascular mortality (adjusted hazard ratio [HR]: 2.18 [95% CI: 1.13 to 4.23] and 2.87 [95% CI: 1.44 to 5.73], respectively). PMI Prot was associated with a consistent hazard of cardiovascular mortality after both PCI and CABG (p interaction  = 0.86). Conversely, PMI UD was strongly associated with cardiovascular mortality after CABG (adjusted HR: 11.94; 95% CI: 4.84 to 29.47) but not after PCI (adjusted HR: 1.14; 95% CI: 0.35 to 3.67) (p interaction  = 0.004). Results were similar for all-cause mortality and with varying PMI UD biomarker definitions. Only large biomarker elevations (CK-MB ≥10× upper reference limit and troponin ≥70× upper reference limit) were associated with mortality., Conclusions: The rates of PMI after PCI and CABG vary greatly with different definitions. In the EXCEL trial, the pre-specified PMI Prot was associated with similar hazard after PCI and CABG, whereas PMI UD was strongly associated with mortality after CABG but not after PCI. (EXCEL Clinical Trial [EXCEL]; NCT01205776)., (Copyright © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Stress cardiac magnetic resonance (CMR) provides accurate assessment of both myocardial infarction (MI) and ischemia., Objectives: This study aimed to evaluate the incremental prognostic value of unrecognized myocardial infarction (UMI), detected during assessment of coronary artery disease (CAD) by stress CMR, beyond cardiac function and ischemia., Methods: In the multicenter SPINS (Stress CMR Perfusion Imaging in the United States) study, 2,349 consecutive patients (63 ± 11 years of age, 53% were male) with suspected CAD were assessed by stress CMR and followed over a median of 5.4 years. UMI was defined as the presence of late gadolinium enhancement consistent with MI in the absence of medical history of MI. This study investigated the association of UMI with all-cause mortality and nonfatal MI (death and/or MI), and major adverse cardiac events (MACE)., Results: UMI was detected in 347 patients (14.8%) and clinically recognized myocardial infarction (RMI) in 358 patients (15.2%). Compared with patients with RMI, patients with UMI had a similar burden of cardiovascular risk factors, but significantly lower left ventricular ejection fraction (p < 0.001) and lower rates of guideline-directed medical therapies, including aspirin (p < 0.001), statin (p < 0.001), and beta-blockers (p = 0.002). During follow-up, 328 deaths and/or MIs and 528 MACE occurred. In univariate analysis, UMI and RMI were strongly associated with death and/or MI (UMI: hazard ratio [HR]: 2.15; 95% confidence interval [CI]: 1.63 to 2.83; p < 0.001; RMI: HR: 2.45; 95% CI: 1.89 to 3.18) and MACE. Compared with patients with RMI, patients with UMI presented an increased risk for heart failure hospitalization (UMI vs. RMI: HR: 2.60; 95% CI: 1.48 to 4.58; p < 0.001). In a multivariate model including ischemia and left ventricular ejection fraction, UMI and RMI maintained robust prognostic association with death and/or MI (UMI: HR: 1.82; 95% CI: 1.37 to 2.42; p < 0.001; RMI: HR: 1.54; 95% CI: 1.14 to 2.09) and MACE., Conclusions: In a multicenter cohort of patients with suspected CAD, presence of UMI or RMI portended an equally significant risk for death and/or MI, independently of the presence of ischemia. Compared with RMI patients, those with UMI were less likely to receive guideline-directed medical therapies and presented an increased risk for heart failure hospitalization that warrants further study. (Stress CMR Perfusion Imaging in the United States [SPINS]; NCT03192891)., (Copyright © 2020 American College of Cardiology Foundation. All rights reserved.)

Background: Recent emphasis on reduced duration and/or intensity of antiplatelet therapy following percutaneous coronary intervention (PCI) irrespective of indication for PCI may fail to account for the substantial risk of subsequent nontarget lesion events in acute coronary syndrome (ACS) patients., Objectives: The authors sought to examine the effect of more potent antiplatelet therapy on the basis of the timing and etiology of recurrent myocardial infarction (MI) or cardiovascular death following PCI for ACS., Methods: In the TRITON-TIMI 38 study (Trial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet Inhibition With Prasugrel-Thrombolysis In Myocardial Infarction 38), which randomized patients to prasugrel or clopidogrel, 12,844 patients with ACS received at least 1 stent. MI and cardiovascular death were categorized as: 1) procedural (related to revascularization); 2) definite or probable stent thrombosis (ST); or 3) spontaneous (non-ST or non-procedure-related). Median follow-up was 14.5 months., Results: Among the first events occurring within 30 days, 584 (69.0%) were procedural, 126 (14.9%) ST-related, and 136 (16.1%) spontaneous. After 30 days, 22 (4.7%) were procedural, 63 (13.5%) were ST-related, and 383 (81.8%) spontaneous. Prasugrel significantly reduced the incidence of MI or cardiovascular death for ST-related (1.0% vs. 2.1%; p < 0.001) and spontaneous events (3.9% vs. 4.8%; p = 0.012), with a directionally consistent numerical reduction for procedural events (4.4% vs. 5.1%; p = 0.078). Prasugrel increased spontaneous, but not procedural, major bleeding., Conclusions: Long-term potent antithrombotic therapy reduces de novo (spontaneous) atherothrombotic events in addition to preventing complications associated with stenting of the culprit lesion following ACS. In patients undergoing PCI for ACS, spontaneous events predominate after 30 days, with the later-phase cardiovascular benefit of potent dual antiplatelet therapy driven largely by reducing de novo atherothrombotic ischemic events. (Comparison of Prasugrel [CS-747] and Clopidogrel in Acute Coronary Syndrome Subjects Who Are to Undergo Percutaneous Coronary Intervention; NCT00097591)., (Copyright © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Type 2 myocardial infarction (MI) and myocardial injury are associated with increased short-term mortality. However, data regarding long-term mortality are lacking., Objectives: This study compared long-term mortality among young adults with type 1 MI, type 2 MI, or myocardial injury., Methods: Adults age 50 years or younger who presented with troponin >99th percentile or the International Classification of Diseases code for MI over a 17-year period were identified. All cases were adjudicated as type 1 MI, type 2 MI, or myocardial injury based on the Fourth Universal Definition of MI. Cox proportional hazards models were constructed for survival free from all-cause and cardiovascular death., Results: The cohort consisted of 3,829 patients (median age 44 years; 30% women); 55% had type 1 MI, 32% had type 2 MI, and 13% had myocardial injury. Over a median follow-up of 10.2 years, mortality was highest for myocardial injury (45.6%), followed by type 2 MI (34.2%) and type 1 MI (12%) (p < 0.001). In an adjusted model, type 2 MI was associated with higher all-cause (hazard ratio: 1.8; 95% confidence interval: 1.2 to 2.7; p = 0.004) and cardiovascular mortality (hazard ratio: 2.7; 95% confidence interval: 1.4 to 5.1; p = 0.003) compared with type 1 MI. Those with type 2 MI or myocardial injury were younger and had fewer cardiovascular risk factors but had more noncardiovascular comorbidities. They were significantly less likely to be prescribed cardiovascular medications at discharge., Conclusions: Young patients who experience a type 2 MI have higher long-term all-cause and cardiovascular mortality than those who experience type 1 MI, with nearly one-half of patients with myocardial injury and more than one-third of patients with type 2 MI dying within 10 years. These findings emphasize the need to provide more aggressive secondary prevention for patients who experience type 2 MI and myocardial injury., (Copyright © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Readmission rates after acute myocardial infarction (AMI) and heart failure (HF) hospitalizations have decreased in the United States since the implementation of the Hospital Readmissions Reduction Program., Objectives: This study was designed to examine the temporal trends of readmission and mortality after AMI and HF in Ontario, Canada, where reducing hospital readmissions has not had a policy incentive., Methods: The cohort was comprised of AMI or HF patients 65 years of age or older who had been hospitalized from 2006 to 2017. Primary outcomes were 30-day readmission and post-discharge mortality. Secondary outcomes included in-hospital mortality, 30-day mortality from admission, and in-hospital mortality or 30-day mortality post-discharge. Adjusted monthly trends for each outcome were examined over the study period., Results: Our cohorts included 152,808 AMI and 223,283 HF patients. Age- and sex-standardized AMI hospitalization rates in Ontario declined 32% from 2006 to 2017 while HF hospitalization rates declined slightly (9.1%). For AMI, risk-adjusted 30-day readmission rates declined from 17.4% in 2006 to 14.7% in 2017. All AMI risk-adjusted mortality rates also declined from 2006 to 2017 with 30-day post-discharge mortality from 5.1% to 4.4%. For HF, overall risk-adjusted 30-day readmission was largely unchanged from 2006 to 2014 at 21.9%, followed by a decline to 20.8% in 2017. Risk-adjusted 30-day post-discharge mortality declined from 7.1% in 2006 to 6.6% in 2017., Conclusions: The patterns of outcomes in Ontario are consistent with the United States for AMI, but diverge for HF. For AMI and HF, admissions, readmissions, and mortality rates declined over this period. The reasons for the country-specific patterns for HF need further exploration., (Copyright © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Within the SCOT-HEART (Scottish COmputed Tomography of the HEART Trial) trial of patients with stable chest pain, the use of coronary computed tomography angiography (CTA) reduced the rate of death from coronary heart disease or nonfatal myocardial infarction (primary endpoint)., Objectives: This study sought to assess the consistency and mechanisms of the 5-year reduction in this endpoint., Methods: In this open-label trial, 4,146 participants were randomized to standard care alone or standard care plus coronary CTA. This study explored the primary endpoint by symptoms, diagnosis, coronary revascularizations, and preventative therapies., Results: Event reductions were consistent across symptom and risk categories (p = NS for interactions). In patients who were not diagnosed with angina due to coronary heart disease, coronary CTA was associated with a lower primary endpoint incidence rate (0.23; 95% confidence interval [CI]: 0.13 to 0.35 vs. 0.59; 95% CI: 0.42 to 0.80 per 100 patient-years; p < 0.001). In those who had undergone coronary CTA, rates of coronary revascularization were higher in the first year (hazard ratio [HR]: 1.21; 95% CI: 1.01 to 1.46; p = 0.042) but lower beyond 1 year (HR: 0.59; 95% CI: 0.38 to 0.90; p = 0.015). Patients assigned to coronary CTA had higher rates of preventative therapies throughout follow-up (p < 0.001 for all), with rates highest in those with CT-defined coronary artery disease. Modeling studies demonstrated the plausibility of the observed effect size., Conclusions: The beneficial effect of coronary CTA on outcomes is consistent across subgroups with plausible underlying mechanisms. Coronary CTA improves coronary heart disease outcomes by enabling better targeting of preventative treatments to those with coronary artery disease. (Scottish COmputed Tomography of the HEART Trial [SCOT-HEART]; NCT01149590)., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: In patients with diabetes and multivessel coronary artery disease (CAD), the FREEDOM (Future Revascularization Evaluation in Patients with Diabetes Mellitus: Optimal Management of Multivessel Disease) trial demonstrated that, on average, coronary artery bypass grafting (CABG) was superior to percutaneous coronary intervention (PCI) for major acute cardiovascular events (MACE) and angina reduction. Nonetheless, multivessel PCI remains a common revascularization strategy in the real world., Objectives: To translate the results of FREEDOM to individual patients in clinical practice, risk models of the heterogeneity of treatment benefit were built., Methods: Using patient-level data from 1,900 FREEDOM patients, the authors developed models to predict 5-year MACE (all-cause mortality, nonfatal myocardial infarction, and nonfatal stroke) and 1-year angina after CABG and PCI using baseline covariates and treatment interactions. Parsimonious models were created to support clinical use. The models were internally validated using bootstrap resampling, and the MACE model was externally validated in a large real-world registry., Results: The 5-year MACE occurred in 346 (18.2%) patients, and 310 (16.3%) had angina at 1 year. The MACE model included 8 variables and treatment interactions with smoking status (c = 0.67). External validation in stable CAD (c = 0.65) and ACS (c = 0.68) demonstrated comparable performance. The 6-variable angina model included a treatment interaction with SYNTAX score (c = 0.67). PCI was never superior to CABG, and CABG was superior to PCI for MACE in 54.5% of patients and in 100% of patients with history of smoking., Conclusions: To help disseminate the results of FREEDOM, the authors created a personalized risk prediction tool for patients with diabetes and multivessel CAD that could be used in shared decision-making for CABG versus PCI by estimating each patient's personal outcomes with both treatments., (Copyright © 2019 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Data on optimal antiplatelet treatment regimens in patients who undergo multivessel percutaneous coronary intervention (PCI) are sparse., Objectives: This post hoc study investigated the impact of an experimental strategy (1-month dual antiplatelet therapy [DAPT] followed by 23-month ticagrelor monotherapy) versus a reference regimen (12-month DAPT followed by 12-month aspirin monotherapy) according to multivessel PCI., Methods: The GLOBAL LEADERS trial is a prospective, multicenter, open-label, randomized controlled trial, allocating all-comer patients in a 1:1 ratio to either the experimental strategy or the reference regimen. The primary endpoint was the composite of all-cause death or new Q-wave myocardial infarction at 2 years. The secondary safety endpoint was Bleeding Academic Research Consortium type 3 or 5 bleeding., Results: Among the overall study population (n=15,845), 3,576 patients (22.4%) having multivessel PCI experienced a significantly higher risk of ischemic and bleeding events at 2 years, compared to those having single-vessel PCI. There was an interaction between the experimental strategy and multivessel PCI on the primary endpoint (hazard ratio: 0.62; 95% confidence interval: 0.44 to 0.88; p interaction  = 0.031). This difference was largely driven by a lower risk of all-cause mortality. In contrast, the risk of Bleeding Academic Research Consortium type 3 or 5 bleeding was statistically similar between the 2 regimens (hazard ratio: 0.92; 95% confidence interval: 0.61 to 1.39; p interaction  = 0.754)., Conclusions: Long-term ticagrelor monotherapy following 1-month DAPT can favorably balance ischemic and bleeding risks in patients with multivessel PCI. These findings should be interpreted as hypothesis-generating and need to be replicated in future dedicated randomized trials. (GLOBAL LEADERS: A Clinical Study Comparing Two Forms of Anti-platelet Therapy After Stent Implantation; NCT01813435)., (Copyright © 2019 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: The long-term evolution of premature coronary artery disease (CAD) is unknown., Objectives: The objective of this study was to describe the evolution of coronary atherosclerosis in young patients and identify the risk factors of poor outcomes., Methods: Participants age ≤45 years with acute or stable obstructive CAD were prospectively enrolled and followed. The primary endpoint was all-cause death, myocardial infarction (MI), refractory angina requiring coronary revascularization, and ischemic stroke., Results: Eight hundred-eighty patients with premature CAD were included. They were age 40.1 ± 5.7 years, mainly men, smokers, with a family history of CAD or hypercholesterolemia. At baseline presentation, 91.2% underwent coronary revascularization, predominantly for acute MI (78.8%). Over a follow-up of 20 years, one-third (n = 264) of patients presented with a total of 399 ischemic events, and 36% had at least a second recurrent event. MI was the most frequent first recurrent event (n = 131 of 264), mostly related to new coronary lesions (17.3% vs. 7.8%; p = 0.01; hazard ratio [HR]:1.45; 95% confidence interval [CI]: 1.09 to 1.93 for new vs. initial culprit lesion). All-cause death (n = 55; 6.3%) occurred at 8.4 years (median time). Ethnic origin (sub-Saharan African vs. Caucasian, adjusted hazard ratio [adjHR]: 1.95; 95% CI: 1.13 to 3.35; p = 0.02), inflammatory disease (adjHR: 1.58; 95% CI: 1.05 to 2.36; p = 0.03), and persistent smoking (adjHR: 2.32; 95% CI: 1.63 to 3.28; p < 0.01) were the strongest correlates of a first recurrent event. When considering all recurrent events, the same factors and Asian ethnicity predicted poor outcome, but persistent smoking had the greatest impact on prognosis., Conclusions: Premature CAD is an aggressive disease despite the currently recommended prevention measures, with high rates of recurrent events and mortality. Ethnicity and concomitant inflammatory disease are associated with poor prognoses, along with insufficient control of risk factors., (Copyright © 2019 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: The Hospital Readmissions Reduction Program (HRRP) has been associated with reduced 30-day readmissions for acute myocardial infarction (AMI) and heart failure (HF)., Objectives: The purpose of this study was to test whether this 30-day readmission reduction is a manifestation of practices that defer or avoid hospitalizations beyond the 30-day period., Methods: At all U.S. hospitals under HRRP, the authors calculated daily readmission rates for elderly Medicare fee-for-service beneficiaries through day-60 post-discharge following a hospitalization for AMI and HF-the 2 target cardiovascular conditions-as well as pneumonia in July 2008 to June 2016. The authors applied a robust bias-corrected nonparametric regression approach to evaluate for discontinuities in rates around day 30., Results: The authors identified 3,256 eligible hospitals, with median readmission rates in the days 1 to 30 and 31 to 60 post-discharge of 19.6% (interquartile range [IQR]: 16.7% to 22.9%) and 7.8% (IQR: 6.5% to 9.4%) for AMI, 23.0% (IQR: 20.6% to 25.3%) and 11.4% (IQR: 10.2% to 12.6%) for HF, and 17.5% (IQR: 15.4% to 19.8%) and 8.3% (IQR: 7.3% to 9.3%) for pneumonia, respectively. Daily readmission rates decreased across most of the 60 post-discharge days, with no discontinuities in the local polynomial regression for readmission at the 30-day mark, with a >95% power to detect 0.1% difference for each outcome across post-discharge day 30. Similarly, there was no discontinuity in mortality at 30 days post-discharge, or for either outcome at hospitals that incurred readmission penalties., Conclusions: There was no evidence that clinicians adopted strategies that specifically deferred admissions or affected mortality in the 30-day period after discharge. The findings are consistent with the institution of strategies that generally affected readmission risk after discharge., (Copyright © 2019 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Galectin-3 (Gal-3) is implicated in cardiac fibrosis, but its association with adverse outcomes after myocardial infarction (MI) is unknown., Objectives: The purpose of this study was to examine the prognostic value of Gal-3 in a community cohort of incident MI., Methods: A population-based incidence MI cohort was prospectively assembled in Olmsted County, Minnesota, between 2002 and 2012. Gal-3 levels were measured at the time of MI. Patients were followed for heart failure (HF) and death., Results: A total of 1,342 patients were enrolled (mean age 67.1 years; 61.3% male; 78.8% non-ST-segment elevation MI). Patients with elevated Gal-3 were older and had more comorbidities. Over a mean follow-up of 5.4 years, 484 patients (36.1%) died and 368 (27.4%) developed HF. After adjustment for age, sex, comorbidities, and troponin, patients with Gal-3 values in tertiles 2 and 3 had a 1.3-fold (95% confidence interval [CI]: 0.9-fold to 1.7-fold) and a 2.4-fold (95% CI: 1.8-fold to 3.2-fold) increased risk of death, respectively (p trend  < 0.001) compared with patients with Gal-3 values in tertile 1. Patients with Gal-3 values in tertiles 2 and 3 had a higher risk of HF with hazard ratios of 1.4 (95% CI: 1.0 to 2.0) and 2.3 (95% CI: 1.6 to 3.2), respectively (p trend  < 0.001). With further adjustment for soluble suppression of tumorigenicity-2, elevated Gal-3 remained associated with increased risk of death and HF. The increased risk of HF did not differ by HF type and was independent of the occurrence of recurrent MI., Conclusions: Gal-3 is an independent predictor of mortality and HF post-MI. These findings suggest a role for measuring Gal-3 levels for risk stratification post-MI., (Copyright © 2019 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: The value of fractional flow reserve (FFR) evaluation of coronary artery stenosis in coronary artery bypass grafting (CABG) is uncertain, and stenosis assessments usually rely on visual estimates of lesion severity., Objectives: This randomized clinical trial evaluated graft patency and clinical outcome after FFR-guided CABG versus angiography-guided CABG., Methods: A total of 100 patients referred for CABG were randomly assigned to FFR-guided or angiography-guided CABG. Based on the coronary angiogram, a heart team made a graft plan for all patients, and FFR evaluations were performed. In FFR-guided CABG, coronary lesions with FFR >0.80 were deferred, and a new graft plan was designed accordingly, whereas the surgeon was blinded to the FFR values in patients who underwent angiography-guided CABG. The primary endpoint was graft failure in the percentage of all grafts after 6 months., Results: Angiographic follow-up at 6 months was available for 72 patients (39 vs. 33 in the FFR-guided and angiography-guided groups, respectively). Graft failures of all grafts were similar in both groups (16% vs. 12%; p = 0.97). Rates of death, myocardial infarction, and stroke were also similar in the study groups, and no difference was seen in revascularization before angiographic follow-up. After 6 months, deferred lesions (n = 24) showed a significant reduction in mean FFR from index to follow-up (0.89 ± 0.05 vs. 0.81 ± 0.11; p = 0.002). Index FFR did not influence graft patency., Conclusions: FFR-guided CABG had similar graft failure rates and clinical outcomes as angiography-guided CABG. However, FFR was reduced significantly after 6 months in deferred lesions. (Fractional Flow Reserve Versus Angiography Randomization for Graft Optimization [FARGO]; NCT02477371)., (Copyright © 2018 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: It remains unknown how the introduction of high-sensitivity cardiac troponin T (hs-cTnT) has affected the incidence, prognosis, and use of coronary angiographies and revascularizations in patients with myocardial infarction (MI)., Objectives: The aim of this study was to investigate how the incidence of MI and prognosis after a first MI was affected by the introduction of hs-cTnT., Methods: In a cohort study, the authors included all patients with a first MI from the Swedish National Patient Registry from 2009 to 2013. Cox regression was used to calculate hazard ratios (HRs) with 95% confidence intervals (CIs) for risk of all-cause mortality, reinfarction, coronary angiographies, and revascularizations in patients with MI diagnosed using hs-cTnT compared with those diagnosed using conventional troponins (cTn)., Results: During the study period, 47,133 MIs were diagnosed using cTn and 40,746 using hs-cTnT. The rate of MI increased by 5% (95% CI: 0% to 10%) after the introduction of hs-cTnT. During 3.9 ± 2.8 years of follow-up, there were 33,492 deaths, with no difference in the risk of all-cause mortality (adjusted HR: 1.00; 95% CI: 0.97 to 1.02). There were, in total, 15,766 reinfarctions during 3.1 ± 2.3 years of follow-up, with the risk of reinfarction reduced by 11% in patients diagnosed using hs-cTnT (adjusted HR: 0.89; 95% CI: 0.86 to 0.91). The use of coronary angiographies (adjusted HR: 1.16; 95% CI: 1.14 to 1.18) and revascularizations (adjusted HR: 1.13; 95% CI: 1.11 to 1.15) increased in the hs-cTnT group., Conclusions: In a nationwide cohort study including 87,879 patients with a first MI, the introduction of hs-cTnT was associated with an increased incidence of MI, although with no impact on survival. We also found a reduced risk of reinfarction alongside increased use of coronary angiographies and revascularizations., (Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Substance abuse is increasingly prevalent among young adults, but data on cardiovascular outcomes remain limited., Objectives: The objectives of this study were to assess the prevalence of cocaine and marijuana use in adults with their first myocardial infarction (MI) at ≤50 years and to determine its association with long-term outcomes., Methods: The study retrospectively analyzed records of patients presenting with a type 1 MI at ≤50 years at 2 academic hospitals from 2000 to 2016. Substance abuse was determined by review of records for either patient-reported substance abuse during the week before MI or substance detection on toxicology screen. Vital status was identified by the Social Security Administration's Death Master File. Cause of death was adjudicated using electronic health records and death certificates. Cox modeling was performed for survival free from all-cause and cardiovascular death., Results: A total of 2,097 patients had type 1 MI (mean age 44.0 ± 5.1 years, 19.3% female, 73% white), with median follow-up of 11.2 years (interquartile range: 7.3 to 14.2 years). Use of cocaine and/or marijuana was present in 224 (10.7%) patients; cocaine in 99 (4.7%) patients, and marijuana in 125 (6.0%). Individuals with substance use had significantly lower rates of diabetes (14.7% vs. 20.4%; p = 0.05) and hyperlipidemia (45.7% vs. 60.8%; p < 0.001), but they were significantly more likely to use tobacco (70.3% vs. 49.1%; p < 0.001). The use of cocaine and/or marijuana was associated with significantly higher cardiovascular mortality (hazard ratio: 2.22; 95% confidence interval: 1.27 to 3.70; p = 0.005) and all-cause mortality (hazard ratio: 1.99; 95% confidence interval: 1.35 to 2.97; p = 0.001) after adjusting for baseline covariates., Conclusions: Cocaine and/or marijuana use is present in 10% of patients with an MI at age ≤50 years and is associated with worse all-cause and cardiovascular mortality. These findings reinforce current recommendations for substance use screening among young adults with an MI, and they highlight the need for counseling to prevent future adverse events., (Copyright © 2018 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Early outcomes of patients in the PRAGUE-18 (Comparison of Prasugrel and Ticagrelor in the Treatment of Acute Myocardial Infarction) study did not find any significant differences between 2 potent P2Y 12 inhibitors., Objectives: The 1-year follow-up of the PRAGUE-18 study focused on: 1) a comparison of efficacy and safety between prasugrel and ticagrelor; and 2) the risk of major ischemic events related to an economically motivated post-discharge switch to clopidogrel., Methods: A total of 1,230 patients with acute myocardial infarction (MI) treated with primary percutaneous coronary intervention were randomized to prasugrel or ticagrelor with an intended treatment duration of 12 months. The combined endpoint was cardiovascular death, MI, or stroke at 1 year. Because patients had to cover the costs of study medication after hospital discharge, some patients decided to switch to clopidogrel., Results: The endpoint occurred in 6.6% of prasugrel patients and in 5.7% of ticagrelor patients (hazard ratio: 1.167; 95% confidence interval: 0.742 to 1.835; p = 0.503). No significant differences were found in: cardiovascular death (3.3% vs. 3.0%; p = 0.769), MI (3.0% vs. 2.5%; p = 0.611), stroke (1.1% vs. 0.7%; p = 0.423), all-cause death (4.7% vs. 4.2%; p = 0.654), definite stent thrombosis (1.1% vs. 1.5%; p = 0.535), all bleeding (10.9% vs. 11.1%; p = 0.999), and TIMI (Thrombolysis In Myocardial Infarction) major bleeding (0.9% vs. 0.7%; p = 0.754). The percentage of patients who switched to clopidogrel for economic reasons was 34.1% (n = 216) for prasugrel and 44.4% (n = 265) for ticagrelor (p = 0.003). Patients who were economically motivated to switch to clopidogrel had (compared with patients who continued the study medications) a lower risk of major cardiovascular events; however, they also had lower ischemic risk., Conclusions: Prasugrel and ticagrelor are similarly effective during the first year after MI. Economically motivated early post-discharge switches to clopidogrel were not associated with an increased risk of ischemic events. (Comparison of Prasugrel and Ticagrelor in the Treatment of Acute Myocardial Infarction [PRAGUE-18]; NCT02808767)., (Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Angiotensin-converting enzyme (ACE) inhibitors/angiotensin II receptor blockers (ARB), beta-blockers and statins are recommended after acute myocardial infarction (AMI). Patients may adhere to some, but not all, therapies., Objectives: The authors investigated the effect of tradeoffs in adherence to ACE inhibitors/ARBs, beta-blockers, and statins on survival among older people after AMI., Methods: The authors identified 90,869 Medicare beneficiaries ≥65 years of age who had prescriptions for ACE inhibitors/ARBs, beta-blockers, and statins, and survived ≥180 days after AMI hospitalization in 2008 to 2010. Adherence was measured by proportion of days covered (PDC) during 180 days following hospital discharge. Mortality follow-up extended up to 18 months after this period. The authors used Cox proportional hazards models to estimate hazard ratios of mortality for groups adherent to 2, 1, or none of the therapies versus group adherent to all 3 therapies., Results: Only 49% of the patients adhered (PDC ≥80%) to all 3 therapies. Compared with being adherent to all 3 therapies, multivariable-adjusted hazard ratios (95% confidence intervals [CIs]) for mortality were 1.12 (95% CI: 1.04 to 1.21) for being adherent to ACE inhibitors/ARBs and beta-blockers only, 0.98 (95% CI: 0.91 to 1.07) for ACEI/ARBs and statins only, 1.17 (95% CI: 1.10 to 1.25) beta-blockers and statins only, 1.19 (95% CI: 1.07 to 1.32) for ACE inhibitors/ARBs only, 1.32 (95% CI: 1.21 to 1.44) for beta-blockers only, 1.26 (95% CI: 1.15 to 1.38) statins only, and 1.65 (95% CI: 1.54 to 1.76) for being nonadherent (PDC <80%) to all 3 therapies., Conclusions: Patients adherent to ACE inhibitors/ARBs and statins only had similar mortality rates as those adherent to all 3 therapies, suggesting limited additional benefit for beta-blockers in patients who were adherent to statins and ACE inhibitors/ARBs. Nonadherence to ACE inhibitors/ARBs and/or statins was associated with higher mortality., (Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Ticagrelor reduces ischemic risk in patients with prior myocardial infarction (MI). It remains unclear whether ischemic risk and the benefits of prolonged P2Y 12 inhibition in this population remain consistent over time., Objectives: The study sought to investigate the pattern of ischemic risk over time and whether the efficacy and safety of ticagrelor were similar early and late after randomization., Methods: The PEGASUS-TIMI (Prevention of Cardiovascular Events in Patients with Prior Heart Attack Using Ticagrelor Compared to Placebo on a Background of Aspirin-Thrombolysis In Myocardial Infarction) 54 trial randomized patients with prior MI (median 1.7 years prior) to ticagrelor 90 mg, ticagrelor 60 mg, or placebo on a background of aspirin. The rates of cardiovascular (CV) death, MI, and stroke as well as TIMI major bleeding were analyzed at yearly landmarks (years 1, 2, and 3)., Results: A total of 21,162 patients were randomized and followed for 33 months (median), with 28% of patients ≥5 years from MI at trial conclusion. The risk of CV death, MI, or stroke in the placebo arm remained roughly constant over the trial at an ∼3% annualized rate. The benefit of ticagrelor 60 mg was consistent at each subsequent landmark (year 1 hazard ratio [HR]: 0.82; 95% confidence interval [CI]: 0.67 to 0.99; year 2 HR: 0.90; 95% CI: 0.74 to 1.11; and year 3 HR: 0.79; 95% CI: 0.62 to 1.00). TIMI major bleeding was increased with ticagrelor 60 mg at each landmark, but with the greatest hazard in the first year (year 1 HR: 3.22; year 2 HR: 2.07; year 3 HR: 1.65)., Conclusions: Patients with a history of MI remain at persistent high risk for CVD, MI, and stroke as late as 5 years after MI. The efficacy of low-dose ticagrelor is consistent over time with a trend toward less excess bleeding. (Prevention of Cardiovascular Events in Patients with Prior Heart Attack Using Ticagrelor Compared to Placebo on a Background of Aspirin [PEGASUS]; NCT01225562)., (Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Professional guidelines have reduced the recommended minimum number to an average of 50 percutaneous coronary intervention (PCI) procedures performed annually by each operator. Operator volume patterns and associated outcomes since this change are unknown., Objectives: The authors describe herein PCI operator procedure volumes; characteristics of low-, intermediate-, and high-volume operators; and the relationship between operator volume and clinical outcomes in a large, contemporary, nationwide sample., Methods: Using data from the National Cardiovascular Data Registry collected between July 1, 2009, and March 31, 2015, we examined operator annual PCI volume. We divided operators into low- (<50 PCIs per year), intermediate- (50 to 100 PCIs per year), and high- (>100 PCIs per year) volume groups, and determined the adjusted association between annual PCI volume and in-hospital outcomes, including mortality., Results: The median annual number of procedures performed per operator was 59; 44% of operators performed <50 PCI procedures per year. Low-volume operators more frequently performed emergency and primary PCI procedures and practiced at hospitals with lower annual PCI volumes. Unadjusted in-hospital mortality was 1.86% for low-volume operators, 1.73% for intermediate-volume operators, and 1.48% for high-volume operators. The adjusted risk of in-hospital mortality was higher for PCI procedures performed by low- and intermediate-volume operators compared with those performed by high-volume operators (adjusted odds ratio: 1.16 for low versus high; adjusted odds ratio: 1.05 for intermediate vs. high volume) as was the risk for new dialysis post PCI. No volume relationship was observed for post-PCI bleeding., Conclusions: Many PCI operators in the United States are performing fewer than the recommended number of PCI procedures annually. Although absolute risk differences are small and may be partially explained by unmeasured differences in case mix between operators, there remains an inverse relationship between PCI operator volume and in-hospital mortality that persisted in risk-adjusted analyses., (Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: For acute myocardial infarction (AMI) without heart failure (HF), it is unclear if β-blockers are associated with reduced mortality., Objectives: The goal of this study was to determine the association between β-blocker use and mortality in patients with AMI without HF or left ventricular systolic dysfunction (LVSD)., Methods: This cohort study used national English and Welsh registry data from the Myocardial Ischaemia National Audit Project. A total of 179,810 survivors of hospitalization with AMI without HF or LVSD, between January 1, 2007, and June 30, 2013 (final follow-up: December 31, 2013), were assessed. Survival-time inverse probability weighting propensity scores and instrumental variable analyses were used to investigate the association between the use of β-blockers and 1-year mortality., Results: Of 91,895 patients with ST-segment elevation myocardial infarction and 87,915 patients with non-ST-segment elevation myocardial infarction, 88,542 (96.4%) and 81,933 (93.2%) received β-blockers, respectively. For the entire cohort, with >163,772 person-years of observation, there were 9,373 deaths (5.2%). Unadjusted 1-year mortality was lower for patients who received β-blockers compared with those who did not (4.9% vs. 11.2%; p < 0.001). However, after weighting and adjustment, there was no significant difference in mortality between those with and without β-blocker use (average treatment effect [ATE] coefficient: 0.07; 95% confidence interval [CI]: -0.60 to 0.75; p = 0.827). Findings were similar for ST-segment elevation myocardial infarction (ATE coefficient: 0.30; 95% CI: -0.98 to 1.58; p = 0.637) and non-ST-segment elevation myocardial infarction (ATE coefficient: -0.07; 95% CI: -0.68 to 0.54; p = 0.819)., Conclusions: Among survivors of hospitalization with AMI who did not have HF or LVSD as recorded in the hospital, the use of β-blockers was not associated with a lower risk of death at any time point up to 1 year. (β-Blocker Use and Mortality in Hospital Survivors of Acute Myocardial Infarction Without Heart Failure; NCT02786654)., (Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Many patients report adverse reactions to, and may not tolerate, statin therapy. These patients may be at increased risk for coronary heart disease (CHD) events and mortality., Objectives: This study evaluated the risk for recurrent myocardial infarction (MI), CHD events, and all-cause mortality in Medicare beneficiaries with statin intolerance and in those with high adherence to statin therapy., Methods: We studied 105,329 Medicare beneficiaries who began a moderate- or high-intensity statin dosage after hospitalization for MI between 2007 and 2013. Statin intolerance was defined as down-titrating statins and initiating ezetimibe therapy, switching from statins to ezetimibe monotherapy, having International Classification of Diseases, 9th revision, diagnostic codes for rhabdomyolysis or an antihyperlipidemic adverse event, followed by statin down-titration or discontinuation, or switching between ≥3 types of statins within 1 year after initiation. High statin adherence over the year following hospital discharge was defined as proportion of days covered ≥80%. Recurrent MI, CHD events (recurrent MI or a coronary revascularization procedure), and mortality were identified from 1 year after hospital discharge through December 2014., Results: Overall, 1,741 patients (1.65%) had statin intolerance, and 55,567 patients (52.8%) had high statin adherence. Over a median of 1.9 to 2.3 years of follow-up, there were 4,450 recurrent MIs, 6,250 CHD events, and 14,311 deaths. Compared to beneficiaries with high statin adherence, statin intolerance was associated with a 36% higher rate of recurrent MI (41.1 vs. 30.1 per 1,000 person-years, respectively), a 43% higher rate of CHD events (62.5 vs. 43.8 per 1,000 person-years, respectively), and a 15% lower rate of all-cause mortality (79.9 vs. 94.2 per 1,000 person-years, respectively). The multivariate-adjusted hazard ratios (HR) comparing beneficiaries with statin intolerance versus those with high statin adherence were 1.50 (95% confidence interval [CI]: 1.30 to 1.73) for recurrent MI, 1.51 (95% CI: 1.34 to 1.70) for CHD events, and 0.96 (95% CI: 0.87 to 1.06) for all-cause mortality., Conclusions: Statin intolerance was associated with an increased risk for recurrent MI and CHD events but not all-cause mortality., (Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: A 1-year follow-up, polymer-free metallic stent coated with biolimus-A9 followed by 1-month dual antiplatelet therapy is safer and more effective than a bare-metal stent (BMS) for patients with high risk of bleeding., Objectives: This study analyzed 2-year outcomes to determine whether these benefits are maintained., Methods: In a prospective, multicenter, double-blind trial, we randomized 2,466 high bleeding risk patients to receive a drug-coated stent (DCS) or a BMS followed by 1-month dual antiplatelet therapy. The primary safety endpoint was a composite of cardiac death, myocardial infarction, or stent thrombosis. The primary efficacy endpoint was clinically driven target lesion revascularization., Results: At 2 years, the primary safety endpoint had occurred in 147 DCS and 180 BMS patients (15.3%) (hazard ratio: 0.80; 95% confidence interval: 0.64 to 0.99; p = 0.039). Clinically driven target lesion revascularization occurred for 77 DCS and 136 BMS patients (12.0%) (hazard ratio: 0.54; 95% confidence interval: 0.41 to 0.72; p < 0.0001). Major bleeding occurred in 8.9% of DCS and 9.2% of BMS patients (p = 0.95), and a coronary thrombotic event (myocardial infarction and/or stent thrombosis) occurred in 8.2% of DCS and 10.6% of BMS patients (p = 0.045). One-year mortality was 27.1% for a major bleed and 26.3% for a thrombotic event. At 2 years, multivariate correlates of major bleeding were age >75 years, anemia, raised plasma creatinine, and planned long-term anticoagulation. Correlates of the primary safety endpoint were age, anemia, congestive heart failure, multivessel disease, number of stents implanted, and use of a BMS rather than a DCS., Conclusions: Safety and efficacy benefits of DCS over BMS were maintained for 2 years in high bleeding risk patients. Rates of major bleeding and coronary thrombotic events were no different and were associated with a substantial and comparable mortality risk. (A Prospective Randomized Comparison of the BioFreedom Biolimus A9 Drug Coated Stent Versus the Gazelle Bare Metal Stent in Patients With High Risk of Bleeding [LEADERS FREE]; NCT01623180)., (Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Clinical practice guidelines recommend post-operative dual antiplatelet therapy (DAPT) in patients who undergo coronary artery bypass grafting (CABG) following acute coronary syndromes (ACS)., Objectives: The authors have evaluated DAPT utilization rates and associated outcomes among post-CABG patients with diabetes., Methods: In a post hoc, nonrandomized analysis from the FREEDOM (Future REvascularization Evaluation in patients with Diabetes mellitus: Optimal management of Multivessel disease) trial, we compared patients receiving DAPT (aspirin plus thienopyridine) and aspirin monotherapy at 30 days post-operatively. The primary outcome was the risk adjusted 5-year FREEDOM composite of all-cause mortality, nonfatal myocardial infarction, or stroke. Safety outcomes included major bleeding, blood transfusion, and hospitalization for bleeding., Results: At 30 days post-CABG, 544 (68.4%) patients received DAPT and 251 (31.6%) patients received aspirin alone. The median (25th, 75th percentile) duration of clopidogrel therapy was 0.98 (0.23 to 1.91) years. There was no significant difference in the 5-year primary composite outcome between DAPT- and aspirin-treated patients (12.6% vs. 16.0%; adjusted hazard ratio [HR]: 0.83; 95% confidence interval [CI]: 0.54 to 1.27; p = 0.39). The 5-year primary composite outcomes were similar for patients receiving DAPT versus aspirin monotherapy respectively, in subgroups with pre-CABG ACSs (15.2% vs. 16.5%; HR: 1.06; 95% CI: 0.53 to 2.10; p = 0.88) and those with stable angina (11.6% vs. 15.8%; HR: 0.82; 95% CI: 0.50 to 1.343; p = 0.42). The composite outcomes of both treatment groups were also similar by SYNTAX score, duration of DAPT therapy, completeness of revascularization, and in off-pump CABG. No treatment-related differences in major bleeding (5.6% vs. 5.7%; HR: 1.00; 95% CI: 0.50 to 1.99; p = 0.99), blood transfusions (4.8% vs. 4.5%; HR: 1.09; 95% CI: 0.51 to 2.34; p = 0.82), or hospitalization for bleeding (2.6% vs. 3.3%; HR: 0.85; 95% CI: 0.34 to 2.17; p = 0.74) were observed between aspirin- and DAPT-treated patients, respectively., Conclusions: The use of DAPT in patients with diabetes post-CABG in our cohort was high. Compared with aspirin monotherapy, no associated differences were observed in cardiovascular or bleeding outcomes, suggesting that routine use of DAPT may not be clinically warranted. (Future REvascularization Evaluation in patients with Diabetes mellitus: Optimal management of Multivessel disease [FREEDOM]; NCT00086450)., (Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: As a foundation for quality improvement, assessing clinical outcomes across hospitals requires appropriate risk adjustment to account for differences in patient case mix, including presentation after cardiac arrest., Objectives: The aim of this study was to develop and validate a parsimonious patient-level clinical risk model of in-hospital mortality for contemporary patients with acute myocardial infarction., Methods: Patient characteristics at the time of presentation in the ACTION (Acute Coronary Treatment and Intervention Outcomes Network) Registry-GWTG (Get With the Guidelines) database from January 2012 through December 2013 were used to develop a multivariate hierarchical logistic regression model predicting in-hospital mortality. The population (243,440 patients from 655 hospitals) was divided into a 60% sample for model derivation, with the remaining 40% used for model validation. A simplified risk score was created to enable prospective risk stratification in clinical care., Results: The in-hospital mortality rate was 4.6%. Age, heart rate, systolic blood pressure, presentation after cardiac arrest, presentation in cardiogenic shock, presentation in heart failure, presentation with ST-segment elevation myocardial infarction, creatinine clearance, and troponin ratio were all independently associated with in-hospital mortality. The C statistic was 0.88, with good calibration. The model performed well in subgroups based on age; sex; race; transfer status; and the presence of diabetes mellitus, renal dysfunction, cardiac arrest, cardiogenic shock, and ST-segment elevation myocardial infarction. Observed mortality rates varied substantially across risk groups, ranging from 0.4% in the lowest risk group (score <30) to 49.5% in the highest risk group (score >59)., Conclusions: This parsimonious risk model for in-hospital mortality is a valid instrument for risk adjustment and risk stratification in contemporary patients with acute myocardial infarction., (Copyright © 2016 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Few studies have explored percutaneous coronary intervention (PCI) in perioperative myocardial infarction (PMI), even though PMI is a major cause of mortality in patients undergoing urgent/emergent noncardiac surgery., Objectives: This study sought to describe the angiographic characteristics and outcomes in patients presenting to the cardiac catheterization laboratory for myocardial infarction sustained after undergoing noncardiac surgery, with a detailed analysis of those undergoing PCI., Methods: We included all patients presenting to the catheterization laboratory at our institution after PMI from 2003 to 2012, who had noncardiac surgery within the previous 7 days. Data from patients who underwent PCI were analyzed using both standard regression and time-to-event survival analysis., Results: From 2003 to 2012, 1,093 patients with 3,832 person-years of follow-up underwent diagnostic coronary angiography, of whom 281 (40 ST-segment elevation myocardial infarction [STEMI] and 241 non-ST-segment elevation myocardial infarction [NSTEMI] cases) underwent PCI. Using Kaplan-Meier survival analysis, we found 30-day mortality was 5.2% and 1-year mortality was 15% in the overall population. In the PCI subpopulation, we estimated 30-day mortality to be 11.3%. The 30-day death rate in the STEMI cohort was 31.2% and 8.5% in the NSTEMI cohort of the PCI subpopulation. Stepwise logistic regression revealed the following factors as strong predictors of 30-day mortality after PCI: bleeding event after PCI (odds ratio [OR]: 4.33; 95% confidence limits (CL): 1.52 to 12.30), peak troponin T level (OR: 1.20; 95% CL: 1.08 to 1.34), and underlying peripheral vascular disease (OR: 4.86; 95% CL: 1.66 to 14.22). Cox proportional hazard analysis of survival data showed that increasing age (hazard ratio [HR]: 1.03; 95% CL: 1.01 to 1.04), bleeding after PCI (HR: 2.31; 95% CL: 1.61 to 3.32), renal insufficiency (HR: 2.26; 95% CL: 1.51 to 3.39]), and vascular surgery (HR: 1.48; 95% CL: 1.02 to 2.15]) were all significant predictors of long-term mortality after PCI., Conclusions: Perioperative MI has a markedly high mortality rate, despite PCI. Bleeding event, peak troponin T level, and peripheral vascular disease predict mortality within 30 days of PCI in this patient population. Similarly, older age, vascular surgery, bleeding event, and renal dysfunction strongly predict long-term mortality after PCI in the setting of PMI., (Copyright © 2016 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Guideline-based admission therapies for acute myocardial infarction (AMI) significantly improve 30-day survival, but little is known about their association with long-term outcomes., Objectives: This study evaluated the association of 5 AMI admission therapies (aspirin, beta-blockers, acute reperfusion therapy, door-to-balloon [D2B] time ≤90 min, and time to fibrinolysis ≤30 min) with life expectancy and years of life saved after AMI., Methods: We analyzed data from the Cooperative Cardiovascular Project, a study of Medicare beneficiaries hospitalized for AMI, with 17 years of follow-up. Life expectancy and years of life saved after AMI were calculated using Cox proportional hazards regression with extrapolation using exponential models., Results: Survival for recipients and non-recipients of the 5 guideline-based therapies diverged early after admission and continued to diverge during 17-year follow-up. Receipt of aspirin, beta-blockers, and acute reperfusion therapy on admission was associated with longer life expectancy of 0.78 (standard error [SE]: 0.05), 0.55 (SE: 0.06), and 1.03 (SE: 0.12) years, respectively. Patients receiving primary percutaneous coronary intervention (PCI) within 90 min lived 1.08 (SE: 0.49) years longer than patients with D2B times >90 min, and door-to-needle (D2N) times ≤30 min were associated with 0.55 (SE: 0.12) more years of life. A dose-response relationship was observed between longer D2B and D2N times and shorter life expectancy after AMI., Conclusions: Guideline-based therapy for AMI admission is associated with both early and late survival benefits, and results in meaningful gains in life expectancy and large numbers of years of life saved in elderly patients., (Copyright © 2016 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: A direct comparison of outcomes between moderate mixed aortic valve disease (MAVD) and isolated aortic stenosis (AS) or aortic regurgitation (AR) has not been performed, making evidence-based recommendations difficult in patients with MAVD., Objectives: This study sought to determine adverse event (AE) occurrence (the primary endpoint), defined as New York Heart Association functional class III/IV symptoms, aortic valve replacement, or cardiac death, and to compare AE rates between MAVD and isolated AS or AR., Methods: Asymptomatic patients were identified with moderate MAVD and an ejection fraction ≥50% and were followed at Mayo Clinic from 1994 to 2013. Moderate MAVD was defined as a combination of moderate AS and moderate AR. Age- and sex-matched control groups were selected with isolated moderate AR (n = 117), moderate AS (n = 117), or severe AS (n = 117)., Results: At 9.1 ± 4.2 years of follow-up, patients with moderate MAVD (n = 251) had a mean age of 63 ± 11 years, 73% were male, and 38% had bicuspid valve. AE occurred in 193 (77%) patients in this group, including symptom development (69%), aortic valve replacement (67%), and cardiac death (4%). Predictors of AE were older age (hazard ratio [HR]: 1.71 per decade; 95% confidence interval [CI]: 1.38 to 1.97 per decade; p = 0.001), and relative wall thickness >0.42 (HR: 2.01; 95% CI: 1.86 to 2.33; p = 0.002). AE rates were similar in the MAVD and severe AS group (71% vs. 68% at 5 years; p = 0.49), but were significantly higher compared with the moderate AS and AR groups., Conclusions: MAVD patients had outcomes comparable to those with severe AS, and preserved ejection fraction and should be monitored closely for symptoms., (Copyright © 2016 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Respiratory sinus arrhythmia (RSA), a measure of cardiac vagal modulation, provides cardiac risk stratification information. RSA can be quantified from Holter recordings as the high-frequency component of heart rate variability or as the variability of RR intervals in individual respiratory cycles. However, as a risk predictor, RSA is neither exceptionally sensitive nor specific., Objectives: This study aimed to improve RSA determination by quantifying the amount of sinus arrhythmia related to expiration (expiration-triggered sinus arrhythmia [ETA]) from short-term recordings of electrocardiogram and respiratory chest excursions, and investigated the predictive power of ETA in survivors of acute myocardial infarction., Methods: Survivors of acute myocardial infarction (N = 941) underwent 30-min recordings of electrocardiogram and respiratory chest excursions. ETA was quantified as the RR interval change associated with expiration by phase-rectified signal averaging. Primary outcome was 5-year all-cause mortality. Univariable and multivariable Cox regression was used to investigate the association of ETA with mortality., Results: ETA was a strong predictor of mortality, both in univariable and multivariable analysis. In a multivariable model including respiratory rate, left ventricular ejection fraction, diabetes mellitus, and GRACE score, ETA ≤0.19 ms was associated with a hazard ratio of 3.41 (95% confidence interval: 1.10 to 5.89, p < 0.0001). In patient subgroups defined by abnormal left ventricular ejection fraction, increased respiratory rate, high GRACE score, or presence of diabetes mellitus, patients were classified as high or low risk on the basis of ETA., Conclusions: Expiration-triggered sinus arrhythmia (ETA) is a potent and independent post-infarction risk marker., (Copyright © 2016 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Recent studies in animal models and humans have shown that corin is critically involved in the regulation of salt-water balance, blood pressure, and cardiac function., Objectives: The goal of this study was to investigate the prognostic value of plasma soluble corin in patients with acute myocardial infarction (AMI)., Methods: We enrolled 1,382 consecutive AMI patients in a prospective cohort study and explored the association of plasma corin with AMI outcomes using multivariable Cox proportional hazards analysis., Results: Patients with low corin levels were more likely to be female and to have histories of hypertension and heart failure (HF). Kaplan-Meier survival curves indicated that patients with corin levels above the median had a lower incidence of major adverse cardiac events (MACE) and all-cause mortality compared with those whose corin levels were below the median. Multivariate Cox regression analysis suggested that log corin was an independent predictor of MACE (hazard ratio [HR]: 0.61; 95% confidence interval [CI]: 0.42 to 0.96; p = 0.029), together with age, previous histories of AMI, HF, and diabetes, Killip class, percutaneous coronary intervention, coronary artery bypass graft, beta-blocker use, and log N-terminal pro-B-type natriuretic peptide. The C-statistic and integrated discrimination improvement for MACE were improved significantly by the addition of corin to the reference model. Moreover, log corin was also found to be a significant predictor of death (HR: 0.65; 95% CI: 0.41 to 0.97; p = 0.036) and HF hospitalization (HR: 0.48; 95% CI: 0.23 to 0.90; p = 0.009) after adjustment for clinical variables and established biomarkers of adverse prognosis., Conclusions: Our study demonstrates that corin is a valuable prognostic marker of MACE in patients with AMI, independent of established conventional risk factors., (Copyright © 2016 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Out-of-hospital cardiac arrest (OHCA) associated with acute myocardial infarction (MI) confers high in-hospital mortality; however, among those patients who survive, little is known regarding their post-discharge mortality and health care use rates., Objectives: The purpose of this study was to determine 1-year survival and readmission rates after hospital discharge of older MI survivors with and without OHCA., Methods: Using linked Acute Coronary Treatment and Intervention Outcomes Network Registry-Get With the Guidelines and Medicare data, this study analyzed 54,860 patients with MI who were older than 65 years of age and who had been discharged alive from 545 U.S. hospitals between April 2011 and December 2012. Multivariable models examined the associations between MI-associated OHCA and 1-year post-discharge mortality or all-cause readmission rates. Patients discharged to hospice were excluded, given their known poor prognosis., Results: Following hospital discharge, compared with older MI survivors without OHCA (n = 54,219), those with OHCA (n = 641, 1.2%) were more likely to be younger, male, and smokers, but less likely to have diabetes, heart failure, or prior revascularization. OHCA patients presented more often with ST-segment elevation myocardial infarction (63.2% vs. 29.6%) and cardiogenic shock (29.0% vs. 2.2%); however, among in-hospital MI survivors, OHCA was not associated with 1-year post-discharge mortality (unadjusted 13.8% vs. 15.8%, p = 0.17, adjusted hazard ratio [HR]: 0.89; 95% confidence interval [CI]: 0.68 to 1.15). In contrast, MI survivors with OHCA actually had lower unadjusted and adjusted risk of the composite outcome of 1-year mortality or all-cause readmission than patients without OHCA (44.0% vs. 50.0%, p = 0.03, adjusted HR: 0.84; 95% CI: 0.72 to 0.97)., Conclusions: Among older patients with MI who survived to hospital discharge and were not discharged to hospice, those presenting with OHCA did not have higher 1-year mortality or health care use rates compared with those MI survivors without OHCA. These findings show that the early risk of adverse events in patients with OHCA does not persist after hospital discharge, and they support efforts to improve initial survival rates of older patients with MI and OHCA., (Copyright © 2016 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Mineralocorticoid receptor antagonists (MRA) improve outcome in the setting of post-myocardial infarction (MI) heart failure (HF)., Objectives: The study sought to assess the benefit of an early MRA regimen in acute MI irrespective of the presence of HF or left ventricular (LV) dysfunction., Methods: We randomized 1,603 patients to receive an MRA regimen with a single intravenous bolus of potassium canrenoate (200 mg) followed by oral spironolactone (25 mg once daily) for 6 months in addition to standard therapy or standard therapy alone. The primary outcome of the study was the composite of death, resuscitated cardiac arrest, significant ventricular arrhythmia, indication for implantable defibrillator, or new or worsening HF at 6-month follow-up. Key secondary/safety outcomes included death and other individual components of the primary outcome and rates of hyperkalemia at 6 months., Results: The primary outcome occurred in 95 (11.8%) and 98 (12.2%) patients in the treatment and control groups, respectively (hazard ratio [HR]: 0.97; 95% confidence interval [CI]: 0.73 to 1.28). Death occurred in 11 (1.4%) and 17 (2.1%) patients in the treatment and control groups, respectively (HR: 0.65; 95% CI: 0.30 to 1.38). In a non-pre-specified exploratory analysis, the odds of death were reduced in the treatment group (3 [0.5%] vs. 15 [2.4%]; HR: 0.20; 95% CI: 0.06 to 0.70) in the subgroup of ST-segment elevation MI (n = 1,229), but not in non-ST-segment elevation MI (p for interaction = 0.01). Hyperkalemia >5.5 mmol/l(-1) occurred in 3% and 0.2% of patients in the treatment and standard therapy groups, respectively (p < 0.0001)., Conclusions: The study failed to show the benefit of early MRA use in addition to standard therapy in patients admitted for MI. (Aldosterone Lethal effects Blockade in Acute myocardial infarction Treated with or without Reperfusion to improve Outcome and Survival at Six months follow-up; NCT01059136)., (Copyright © 2016 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)