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Angina pectoris may arise from obstructive coronary artery disease (CAD) or in the absence of significant CAD (ischemia with nonobstructed coronary arteries [INOCA]). Therapeutic strategies for patients with angina and obstructive CAD focus on reducing cardiovascular events and relieving symptoms, whereas in INOCA the focus shifts toward managing functional alterations of the coronary circulation. In obstructive CAD, coronary revascularization might improve angina status, although a significant percentage of patients present angina persistence or recurrence, suggesting the presence of functional mechanisms along with epicardial CAD. In patients with INOCA, performing a precise endotype diagnosis is crucial to allow a tailored therapy targeted toward the specific pathogenic mechanism. In this expert opinion paper, we review the evidence for the management of angina, highlighting the complementary role of coronary revascularization, optimal medical therapy, and lifestyle interventions and underscoring the importance of a personalized approach that targets the underlying pathobiology., Competing Interests: Funding Support and Author Disclosures The authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Telemedicine programs can provide remote diagnostic information to aid clinical decisions that could optimize care and reduce unplanned readmissions post-acute coronary syndrome (ACS)., Objectives: TELE-ACS (Remote Acute Assessment of Patients With High Cardiovascular Risk Post-Acute Coronary Syndrome) is a randomized controlled trial that aims to compare a telemedicine-based approach vs standard care in patients following ACS., Methods: Patients were suitable for inclusion with at least 1 cardiovascular risk factor and presenting with ACS and were randomized (1:1) before discharge. The primary outcome was time to first readmission at 6 months. Secondary outcomes included emergency department (ED) visits, major adverse cardiovascular events, and patient-reported symptoms. The primary analysis was performed according to intention to treat., Results: A total of 337 patients were randomized from January 2022 to April 2023, with a 3.6% drop-out rate. The mean age was 58.1 years. There was a reduced rate of readmission over 6 months (HR: 0.24; 95% CI: 0.13-0.44; P < 0.001) and ED attendance (HR: 0.59; 95% CI: 0.40-0.89) in the telemedicine arm, and fewer unplanned coronary revascularizations (3% in telemedicine arm vs 9% in standard therapy arm). The occurrence of chest pain (9% vs 24%), breathlessness (21% vs 39%), and dizziness (6% vs 18%) at 6 months was lower in the telemedicine group., Conclusions: The TELE-ACS study has shown that a telemedicine-based approach for the management of patients following ACS was associated with a reduction in hospital readmission, ED visits, unplanned coronary revascularization, and patient-reported symptoms. (Telemedicine in High-Risk Cardiovascular Patients Post-ACS [TELE-ACS]; NCT05015634)., Competing Interests: Funding Support and Author Disclosures This work was funded by the British Heart Foundation; King Khalid University, Abha, Saudi Arabia via The Saudi Arabian Cultural Bureau (SACB); Sansour Fund, Imperial Healthcare Charity; and the Safwan Sobhan Fund at Imperial College London. TELE-ACS was an investigator-initiated trial sponsored by Imperial College London. All authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Management of stable coronary artery disease (CAD) has been based on the assumption that flow-limiting atherosclerotic obstructions are the proximate cause of angina and myocardial ischemia in most patients and represent an important target for revascularization. However, the role of revascularization in reducing long-term cardiac events in these patients has been limited mainly to those with left main disease, 3-vessel disease with diabetes, or decreased ejection fraction. Mounting evidence indicates that nonepicardial coronary causes of angina and ischemia, including coronary microvascular dysfunction, vasospastic disorders, and derangements of myocardial metabolism, are more prevalent than flow-limiting stenoses, raising concerns that many important causes other than epicardial CAD are neither considered nor probed diagnostically. There is a need for a more inclusive management paradigm that uncouples the singular association between epicardial CAD and revascularization and better aligns diagnostic approaches that tailor treatment to the underlying mechanisms and precipitants of angina and ischemia in contemporary clinical practice., Competing Interests: Funding Support and Author Disclosures This publication was supported by an educational grant from Servier, Suresnes Cedex, France. Support in the development of the manuscript was also provided by Liberum IME, London, United Kingdom. Dr Boden receives research grant support from AbbVie, Amarin Pharmaceuticals, Amgen, AstraZeneca, Sanofi, Massachusetts Veterans Epidemiology Research and Information Center, VA New England Healthcare System’s Clinical Trials Network, and the National Heart, Lung, and Blood Institute (NHLBI), where he served as national co-principal investigator for the ISCHEMIA trial; is on the Board of Directors for the Boston VA Research Institute; receives consulting fees from Amarin Pharmaceuticals, Amgen, Janssen Pharmaceuticals, Metuchen Pharmaceuticals, and Servier; is on the VA Cooperative Studies Program data monitoring committee; and has received speaking honoraria from Amarin, Amgen, Janssen Pharmaceuticals, Pfizer, and Servier. Dr Marzilli lectures for Servier, Menarini, Degussa Pharma Group, Baldacci, Abbott, and AstraZeneca. Dr Crea has received personal speaker fees from Amgen, AstraZeneca, Servier, and BMS; and is a member of the advisory board for GlyCardial Diagnostics. Dr Mancini has received grants, advisory board appointments, and honoraria for educational lectures from Amgen, Sanofi, NovoNordisk, Lilly/Boehringer Ingelheim, and HLI Therapeutics; is on the advisory board for Esperion; and receives reports on grants from the National Institutes of Health (NIH) for the COURAGE and ISCHEMIA trials. Dr Weintraub has received research support from Amarin Corporation, NIH, and Centers for Disease Control and Prevention; and has served as a consultant for Amarin Corporation, AstraZeneca, Pfizer, Janssen, SC Pharma, Lexicon, Faraday, and The Medicines Company. Dr Taqueti is supported by NIH grant K23HL135438. Dr Pepine receives research grant support from NIH/NHLBI (R21AG063143, K08 HL130945, K01 HL138172, R01 HL146158, AG065141, R01 HL152162, R21 HL152264, R01 HL132448, UM1 HL087366, UM1 HL087318), NIH/National Center for Advancing Translational Sciences (UL1 TR001427), U.S. Department of Defense (W81XWH-17-2-0030, WARRIOR), Biocardia, Brigham and Women’s Hospital, CSL Behring, Cytori Therapeutics, DCRI, GE Healthcare, Mesoblast, and Pfizer; receives consultant fees/honoraria from Caladrius Biosciences, Slack, and Xylocor; and receives grant support from the Gatorade Foundation through the University of Florida Department of Medicine and from the McJunkin Family Foundation, Plantation, Florida. Dr Escaned has received speaker and advisory board honoraria from Abbott Laboratories and Philips. Dr Al-Lamee has received speaker honoraria from Philips Volcano, Abbott Vascular, and Menarini Pharmaceuticals. Dr Gowdak has received congress-related travel expenses from Servier; has participated in clinical trials sponsored by Servier and Angion Biomedica; has been a speaker for Servier, Boehringer-Lilly, and Abbott; is an advisory board member for Servier; and has prepared written scientific material for Servier and Abbott. Dr Berry is employed by the University of Glasgow, which holds consultancy and research agreements for his work with Abbott Vascular, AstraZeneca, Auxilius Pharma, Boehringer Ingelheim, Causeway Therapeutics, Coroventis, Genentech, GSK, HeartFlow, Menarini, Neovasc, Siemens Healthcare, and Valo Health; and receives research funding from the British Heart Foundation (grant RE/18/6134217), Chief Scientist Office, Engineering and Physical Sciences Research Council (EP/R511705/1, EP/S030875/1), European Union (754946-2), Medical Research Council (MR/S018905/1), and UKRI (MC/PC/20014). Dr Kaski has received speaker honoraria from A. Menarini Farmaceutica lnternazionale, Servier, and Bayer UK. Dr Escaned has reported that he has no relationships relevant to the contents of this paper to disclose., (Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Physicians are not always comfortable deferring treatment of a stenosis in the left anterior descending (LAD) artery because of the perception that there is a high risk of major adverse cardiac events (MACE). The authors describe, using the DEFINE-FLAIR (Functional Lesion Assessment of Intermediate Stenosis to Guide Revascularisation) trial, MACE rates when LAD lesions are deferred, guided by physiological assessment using fractional flow reserve (FFR) or the instantaneous wave-free ratio (iFR)., Objectives: The purpose of this study was to establish the safety of deferring treatment in the LAD using FFR or iFR within the DEFINE-FLAIR trial., Methods: MACE rates at 1 year were compared between groups (iFR and FFR) in patients whose physiological assessment led to LAD lesions being deferred. MACE was defined as a composite of cardiovascular death, myocardial infarction (MI), and unplanned revascularization at 1 year. Patients, and staff performing follow-up, were blinded to whether the decision was made with FFR or iFR. Outcomes were adjusted for age and sex., Results: A total of 872 patients had lesions deferred in the LAD (421 guided by FFR, 451 guided by iFR). The event rate with iFR was significantly lower than with FFR (2.44% vs. 5.26%; adjusted HR: 0.46; 95% confidence interval [CI]: 0.22 to 0.95; p = 0.04). This was driven by significantly lower unplanned revascularization with iFR and numerically lower MI (unplanned revascularization: 2.22% iFR vs. 4.99% FFR; adjusted HR: 0.44; 95% CI: 0.21 to 0.93; p = 0.03; MI: 0.44% iFR vs. 2.14% FFR; adjusted HR: 0.23; 95% CI: 0.05 to 1.07; p = 0.06)., Conclusions: iFR-guided deferral appears to be safe for patients with LAD lesions. Patients in whom iFR-guided deferral was performed had statistically significantly lower event rates than those with FFR-guided deferral., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Recently, the therapeutic benefits of percutaneous coronary intervention (PCI) have been challenged in patients with stable coronary artery disease (SCD)., Objectives: The authors examined the impact of PCI on exercise responses in the coronary circulation, the microcirculation, and systemic hemodynamics in patients with SCD., Methods: A total of 21 patients (mean age 60.3 ± 8.4 years) with SCD and single-vessel coronary stenosis underwent cardiac catheterization. Pre-PCI, patients exercised on a supine ergometer until rate-limiting angina or exhaustion. Simultaneous trans-stenotic coronary pressure-flow measurements were made throughout exercise. Post-PCI, this process was repeated. Physiological parameters, rate-limiting symptoms, and exercise performance were compared between pre-PCI and post-PCI exercise cycles., Results: PCI reduced ischemia as documented by fractional flow reserve value (pre-PCI 0.59 ± 0.18 to post-PCI 0.91 ± 0.07), instantaneous wave-free ratio value (pre-PCI 0.61 ± 0.27 to post-PCI 0.96 ± 0.05) and coronary flow reserve value (pre-PCI 1.7 ± 0.7 to post-PCI 3.1 ± 1.0; p < 0.001 for all). PCI increased peak-exercise average peak coronary flow velocity (p < 0.0001), coronary perfusion pressure (distal coronary pressure; p < 0.0001), systolic blood pressure (p = 0.01), accelerating wave energy (p < 0.001), and myocardial workload (rate-pressure product; p < 0.01). These changes observed immediately following PCI resulted from the abolition of stenosis resistance (p < 0.0001). PCI was also associated with an immediate improvement in exercise time (+67 s; 95% confidence interval: 31 to 102 s; p < 0.0001) and a reduction in rate-limiting angina symptoms (81% reduction in rate-limiting angina symptoms post-PCI; p < 0.001)., Conclusions: In patients with SCD and severe single-vessel stenosis, objective physiological responses to exercise immediately normalize following PCI. This is seen in the coronary circulation, the microcirculation, and systemic hemodynamics., (Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.)