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Background: Left ventricular (LV) thrombus is not common but poses significant risks of embolic stroke or systemic embolism. However, the distinction in embolic risk between nonischemic cardiomyopathy (NICM) and ischemic cardiomyopathy (ICM) remains unclear., Methods and Results: In total, 2738 LV thrombus patients from the JROAD-DPC (Japanese Registry of All Cardiac and Vascular Diseases Diagnosis Procedure Combination) database were included. Among these patients, 1037 patients were analyzed, with 826 (79.7%) having ICM and 211 with NICM (20.3%). Within the NICM group, the distribution was as follows: dilated cardiomyopathy (DCM; 41.2%), takotsubo cardiomyopathy (27.0%), hypertrophic cardiomyopathy (18.0%), and other causes (13.8%). The primary outcome was a composite of embolic stroke or systemic embolism (SSE) during hospitalization. The ICM and NICM groups showed no significant difference in the primary outcome (5.8% vs. 7.6%, p = 0.34). Among NICM, SSE occurred in 12.6% of patients with DCM, 7.0% with takotsubo cardiomyopathy, and 2.6% with hypertrophic cardiomyopathy. Multivariate logistic regression analysis for SSE revealed an odds ratio of 1.4 (95% confidence interval [CI], 0.7-2.7, p = 0.37) for NICM compared to ICM. However, DCM exhibited a higher adjusted odds ratio for SSE compared to ICM (2.6, 95% CI 1.2-6.0, p = 0.022)., Conclusions: This nationwide shows comparable rates of embolic events between ICM and NICM in LV thrombus patients, with DCM posing a greater risk of SSE than ICM. The findings emphasize the importance of assessing the specific cause of heart disease in NICM, within LV thrombus management strategies., Competing Interests: Declaration of competing interest Masashi Fujino has supported by the grant from the Bristol-Myers Squibb KK and the Japan Heart Foundation. Yu Kataoka has received research support from Kowa, Nipro and Abbott, and honoraria from Nipro, Abbott, Kowa, Amgen, Sanofi, Astellas, Takeda and Daiichi-Sankyo. Stephen J Nicholls has received research support from AstraZeneca, Amgen, Anthera, CSL Behring, Cerenis, Eli Lilly, Esperion, Resverlogix, New Amsterdam Pharma, Novartis, InfraReDx and Sanofi-Regeneron and is a consultant for Amgen, Akcea, AstraZeneca, Boehringer Ingelheim, CSL Behring, Eli Lilly, Esperion, Kowa, Merck, Takeda, Pfizer, Sanofi- Regeneron, Vaxxinity, CSL Sequiris, Cyclarity and Novo Nordisk. Other authors have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Ischemia with non-obstructive coronary arteries (INOCA) is an increasingly recognized entity. It encompasses different pathophysiological subtypes (i.e., endotypes), including coronary microvascular dysfunction (CMD), vasospastic angina (VSA) and mixed entities resulting from the variable combination of both. Diagnosing INOCA and precisely characterizing the endotype allows for accurate medical treatment and has proven prognostic implications. A breadth of diagnostic technique is available, ranging from non-invasive approaches to invasive coronary angiography adjuvated by functional assessment and provocative tests. This review summarizes the strength and limitations of these methodologies and provides the rationale for the routine referral for invasive angiography and functional assessment in this subset of patients., Competing Interests: Conflict of interest statement Prof. Porto reports consultant or speaker fees from Medtronic, Abbott Vascular, Edwards, ABIOMED, GE, Siemens Healthcare, Sanofi, Amgen, Daiichi-Sankyo, Astra Zeneca, Bayer, and PIAM, not related to this work. Prof. Gianluca Campo reports research grants from SMT, Siemens Healthcare, GADA, Abbott Vascular, Insight Lifetech. Dr. Benenati reports speaker fees from Amgen. Other authors have nothing to disclose., (Copyright © 2024 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.)

Background: The occurrence of transient myocardial ischemia (TMI) is an important pathology in patients with non-ST elevation acute coronary syndrome (NSTE-ACS), yet studies are scarce regarding when TMI occurs during hospitalization, particularly in relation to invasive coronary angiography (ICA). This study examined: (1) TMI before or after ICA; (2) patient characteristics and ischemic burden by TMI group (before or after ICA); and (3) major in-hospital complications (transfer to critical care, death) and length of stay by TMI group (before or after ICA)., Methods: Secondary data analysis in hospitalized NSTE-ACS patients with TMI event(s) identified from 12-lead electrocardiographic Holter. Patient records were reviewed to assess ischemic burden [TMI time (min) ÷ hours recording duration], outcomes, and TMI timing, before or after ICA., Results: In 38 patients, 3 (8%) had TMI before and after ICA. Of the remaining 35 patients (92%), TMI occurred before ICA (16; 46%), and after ICA (9; 26%), and 10 (28%) did not have ICA. Patient characteristics, untoward outcomes, and TMI duration (minutes) did not differ by group. Ischemic burden was higher in patients with TMI after ICA (7.29 ± 8.82 min/h) compared to before ICA (2.54 ± 2.11 min/h), P = 0.039. Hospital length of stay by TMI group was 113 ± 113 (before), 226 ± 244 (after), and 85 ± 65 hours (no ICA); P = 0.172., Conclusions: Almost half of the sample had TMI before ICA; one-third had TMI but did not have ICA. Patients with TMI after an ICA had a higher ischemic burden. Future studies with larger sample sizes are needed to investigate further the short- and long-term clinical significance of TMI among NSTE-ACS patients., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Dysfunction of the coronary microvasculature has become increasingly recognized as an important mechanism of myocardial ischemia in patients without obstructive coronary artery disease. The causes and management of coronary microvascular dysfunction remain poorly understood and are still largely based on extrapolation of epicardial coronary artery disease data. Quantification of myocardial blood flow and flow reserve have improved diagnosis, though important questions remain. In this review, we explain current understanding of the spectrum of pathophysiology of coronary microvascular dysfunction, summarize current diagnostic techniques to assess for coronary microvascular dysfunction, and appraise the limited data on management options specifically for patients with coronary microvascular dysfunction., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background and Objectives : Chronic heart failure (CHF) caused by ischemic heart disease (IHD) is the leading cause of death worldwide and presents significant health challenges. Effective management of IHD requires prevention, early detection, and treatment to improve patient outcomes. This study aims to expand the diagnostic utility of various 24 h Holter ECG parameters, such as T-wave alternans (TWA), late ventricular potentials (LVPs), and heart rate variability (HRV) in patients with CHF caused by IHD. Additionally, we seek to explore the association between these parameters and other comorbid conditions affecting the prognosis of CHF patients. Materials and Methods : We conducted a prospective case-control study with 150 patients divided into two subgroups: 100 patients with CHF caused by IHD, and 50 patients in the control group. Data included medical history, physical examination, laboratory tests, echocardiography, and 24 h Holter monitoring. Results : Our comparative analysis demonstrated that both TWA and LVPs were significantly higher in patients with CHF compared to the control group ( p < 0.01), indicating increased myocardial electrical vulnerability in CHF patients. Both time and frequency-domain HRV parameters were significantly lower in the CHF group. However, the ratio of NN50 to the total count of NN intervals (PNN50) showed a borderline significance ( p = 0.06). While the low-frequency (LF) domain was significantly lower in CHF patients, the high-frequency (HF) domain did not differ significantly between groups. Acceleration and deceleration capacities were also significantly altered in CHF patients. Categorizing CHF patients by left ventricular ejection fraction (LVEF) revealed that the mean of the 5-min normal-to-normal intervals over the complete recording (SDNN Index) was significantly higher in patients with LVEF ≥ 50% compared to those with CHF with reduced EF and CHF with mildly reduced EF ( p < 0.001), whereas the other HRV parameters showed no significant differences among the groups. Conclusions : Holter ECG parameters can become a reliable tool in the assessment of patients with CHF. The integration of multiple Holter ECG parameters, such as TWA, LVPs, and HRV, can significantly enhance the diagnostic assessment of CHF caused by IHD. This comprehensive approach allows for a more nuanced understanding of the patient's condition and potential outcomes.

Background: Angina with no obstructive coronary disease (ANOCA) and ischemia with no obstructive coronary disease, prevalent yet underrecognized conditions, mostly affect women. Previous studies rarely distinguished between them. We aimed to compare the prevalence of objective ischemia through various examinations in women with ANOCA and assess the impact of objective and subjective ischemia on their mental health., Methods and Results: A total of 84 eligible women with ANOCA and 42 controls underwent mental stress, pharmacological stress, exercise stress, and Holter testing. Objective evidence of myocardial ischemia was assessed by positron emission tomography-computed tomography and ECG, and subjective symptoms were graded using the Canadian Cardiovascular Society scale (CCS). Psychological assessments were conducted using 6 scales. Among 84 women with ANOCA, 37 (44%) received a diagnosis of ischemia with no obstructive coronary disease following mental stress testing, 20 (28.6%) through pharmacological stress testing, 14 (21.2%) via exercise stress testing, and 24 (32.9%) from Holter. Mental stress-induced myocardial ischemia was more prevalent ( P <0.05). Among 54 patients with ANOCA who completed all tests, 30% showed no ischemia, and only 1 (1.9%) showed ischemia in all tests. In addition, patients with ANOCA had higher psychological scores than controls ( P <0.01). No significant differences was observed in psychological scores between ANOCA with positive and negative ischemia test results ( P >0.05). However, ANOCA with milder angina (CCS I) exhibited higher scores across the Hospital Anxiety and Depression Scale, State-Trait Anxiety Inventory, Perceived Stress Scale, and Posttraumatic Stress Disorder Checklist-Civilian Version and a higher prevalence of Type D personality traits ( P <0.05)., Conclusions: In patients with ANOCA, the positive rate of myocardial ischemia exhibits variability among several noninvasive tests. A worsened psychological state is more closely linked to milder angina symptoms than to ischemia performance, highlighting the importance of focusing on symptom management in their psychological care., Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03982901.

Ischemic heart disease (IHD) affects more than 20 million adults in the United States. Although classically attributed to atherosclerosis of the epicardial coronary arteries, nearly half of patients with stable angina and IHD who undergo invasive coronary angiography do not have obstructive epicardial coronary artery disease. Ischemia with nonobstructive coronary arteries is frequently caused by microvascular angina with underlying coronary microvascular dysfunction (CMD). Greater understanding the pathophysiology, diagnosis, and treatment of CMD holds promise to improve clinical outcomes of patients with ischemic heart disease., Competing Interests: Disclosure Dr N.R. Smilowitz serves on an advisory board for Abbott Vascular. The remainder of the authors report no financial relationships or conflicts of interest regarding the content herein., (Published by Elsevier Inc.)

Background and Aims: A heart-healthy diet is an important component of secondary prevention in ischemic heart disease. The Danish Health Authority recommends using the validated 19-item food frequency questionnaire HeartDiet in cardiac rehabilitation practice to assess patients' need for dietary interventions, and HeartDiet has been included in national electronic patient-reported outcome instruments for cardiac rehabilitation. This study aims to evaluate challenges and benefits of its use. The objectives are to: 1) describe HeartDiet responses of patients with ischemic heart disease and discuss HeartDiet's suitability as a screening tool, 2) discuss whether an abridged version should replace HeartDiet., Methods and Results: A cross-sectional study using data from a national feasibility test. HeartDiet was sent electronically to 223 patients with ischemic heart disease prior to cardiac rehabilitation. Data were summarised with descriptive statistics, and Spearman's rank correlations, explorative factor analysis, and Cohen's kappa coefficient were used to derive and evaluate abridged versions. The response rate was 68 % (n = 151). Evaluated with HeartDiet, no respondents had a heart-healthy diet. There was substantial agreement between HeartDiet and an abridged 9-item version (kappa = 0.6926 for Fat Score, 0.6625 for FishFruitVegetable Score), but the abridged version omits information on milk products, wholegrain, nuts, and sugary snacks., Conclusion: With the predefined cut-offs, HeartDiet's suitability as a screening tool to assess needs for dietary interventions was limited, since no respondents were categorised as having a heart-healthy diet. An abridged version can replace HeartDiet, but the tool's educational potential will be compromised, since important items will be omitted., Competing Interests: Declaration of competing interest None declared., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Introduction: Perioperative myocardial ischemia (PMI) is a serious postoperative complication. Aortic operations represent an especially high-risk surgery concerning cardiac complications. This aim of this study was to analyse the clinical features of PMI after elective aortic aneurysm surgery., Patients and Methods: This study is a retrospective analysis of 863 patients who underwent elective aortic aneurysm surgery between 2005 and 2012 in the Department of Vascular and Endovascular Surgery of Heidelberg University Hospital with regard to PMI. The PMI diagnosis was based on a positive serum troponin diagnostic test. We evaluated the clinical course, time point of the diagnosis and features of diagnostics to characterise PMI. Moreover, we analysed the treatment options and management of the patients' discharge., Results: Thirty-one patients (3.6% of 863) with PMI after elective aortic aneurysm surgery were identified. Of these, 21 patients (67.7%) underwent open surgery and 10 patients (32.3%) received endovascular treatment. PMI was diagnosed in 24 patients (77%) during the first 3 days. More than half of these patients (16/31) were clinically asymptomatic. Electrocardiogram did not show pathological findings in 24 cases (77.4%). The first troponin measurement was not elevated in eight patients (25.8%). Drug therapy alone was used in 17 cases (54.8%) of PMI, coronary catheterisation was performed in 12 patients (38.7%) and two patients (6.5%) received aortocoronary bypass. Fourteen patients (45.1%) were discharged home and another 14 patients (44.1%) were transferred to another hospital or to a rehabilitation institution. Two patients died because of multi-organ failure., Conclusion: PMI is not a rare complication after elective aortic surgery. The diagnosis of PMI can be challenging because of occult symptoms especially in a perioperative setting. Due to the potentially serious consequences, cardiac enzyme diagnostics should be initiated immediately if there is suspicion of PMI or routinely in defined at-risk patients after aortic surgery., Competing Interests: Die Autorinnen/Autoren geben an, dass kein Interessenkonflikt besteht., (Thieme. All rights reserved.)

The adult heart is a complex, multicellular organ that is subjected to a series of regulatory stimuli and circuits and has poor reparative potential. Despite progress in our understanding of disease mechanisms and in the quality of health care, ischaemic heart disease remains the leading cause of death globally, owing to adverse cardiac remodelling, leading to ischaemic cardiomyopathy and heart failure. Therapeutic targets are urgently required for the protection and repair of the ischaemic heart. Moreover, personalized clinical biomarkers are necessary for clinical diagnosis, medical management and to inform the individual response to treatment. Non-coding RNAs (ncRNAs) deeply influence cardiovascular functions and contribute to communication between cells in the cardiac microenvironment and between the heart and other organs. As such, ncRNAs are candidates for translation into clinical practice. However, ncRNA biology has not yet been completely deciphered, given that classes and modes of action have emerged only in the past 5 years. In this Review, we discuss the latest discoveries from basic research on ncRNAs and highlight both the clinical value and the challenges underscoring the translation of these molecules as biomarkers and therapeutic regulators of the processes contributing to the initiation, progression and potentially the prevention or resolution of ischaemic heart disease and heart failure., (© 2024. Springer Nature Limited.)

Background: Early recognition, which preferably happens in primary care, is the most important tool to combat cardiovascular disease (CVD). This study aims to predict acute myocardial infarction (AMI) and ischemic heart disease (IHD) using Machine Learning (ML) in primary care cardiovascular patients. We compare the ML-models' performance with that of the common SMART algorithm and discuss clinical implications., Methods and Results: Patient-level medical record data (n = 13,218) collected between 2011-2021 from 90 GP-practices were used to construct two random forest models (one for AMI and one for IHD) as well as a linear model based on the SMART risk prediction algorithm as a suitable comparator. The data contained patient-level predictors, including demographics, procedures, medications, biometrics, and diagnosis. Temporal cross-validation was used to assess performance. Furthermore, predictors that contributed most to the ML-models' accuracy were identified. The ML-model predicting AMI had an accuracy of 0.97, a sensitivity of 0.67, a specificity of 1.00 and a precision of 0.99. The AUC was 0.96 and the Brier score was 0.03. The IHD-model had similar performance. In both ML-models anticoagulants/antiplatelet use, systolic blood pressure, mean blood glucose, and eGFR contributed most to model accuracy. For both outcomes, the SMART algorithm was substantially outperformed by ML on all metrics., Conclusion: Our findings underline the potential of using ML for CVD prediction purposes in primary care, although the interpretation of predictors can be difficult. Clinicians, patients, and researchers might benefit from transitioning to using ML-models in support of individualized predictions by primary care physicians and subsequent (secondary) prevention., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Salet et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Aims: Large outcome trials have demonstrated cardiovascular benefits of selected glucagon-like peptide-1 (GLP-1) receptor agonists. We examined coronary disease outcomes in the Harmony Outcomes trial of the GLP-1 receptor agonist albiglutide., Methods and Results: Harmony Outcomes was an event-driven, multicenter, double-blind, and placebo-controlled trial involving 9463 patients >40 years of age with type-2 diabetes and established atherosclerotic cardiovascular disease. It tested the effects of albiglutide on the occurrence of a composite primary endpoint, consisting of cardiovascular death, myocardial infarction (MI), or stroke. Within this post-hoc analysis, the effects of albiglutide on MI subtypes and other ischaemic endpoints were analysed.During the median-follow up of 1.6 years, a total of 421 patients (4.5%) experienced at least one MI, with 72 patients having more than one event. Treatment with albiglutide reduced both first events [hazard ratio (HR) 0.75 (0.62-0.91)] and overall events [HR 0.75 (0.61-0.91)] as well as first type 1 [HR 0.73 (0.57-0.92)] and type 2 myocardial infarctions [HR 0.65 (0.46-0.92)]. The effect of albiglutide treatment was consistent for ST-segment elevation [HR 0.69 (0.38-1.26)] and non-ST elevation (HR 0.86 (0.66-1.2) MI., Conclusion: Treatment with the GLP-1 receptor agonist albiglutide resulted in a 25% relative risk reduction in MI that was consistent for type of infarction and presence or absence of ST elevation. Our findings add novel information about the effects of GLP-1 receptor agonists on ischaemic events in patients with type 2 diabetes., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Competing Interests: Dr Fleg reports employment by the National Heart, Lung, and Blood Institute during the conduct of the study. Drs O’Brien, Berger, Kwong, and Maron and Z. Huang report grants from the National Heart, Lung, and Blood Institute during the conduct of the study. Dr Reynolds reports grants from the National Heart, Lung, and Blood Institute during the conduct of the study. She receives support from Abbott Vascular (donation of optical coherence tomography catheters for an unrelated research study) and Biotelemetry Inc (donation of telemetry monitors for an unrelated research study). Dr Reynolds is also a consultant for HeartFlow. Dr Chaitman reports grants from the National Heart, Lung, and Blood Institute, and personal fees from Merck, NovoNordisk, Sanofi, Lilly, Johnson and Johnson, Daiichi Sankyo, Tricida, Relypsa, Imbria, and Xylocor outside the submitted work. Dr Berman receives software royalties from Cedars-Sinai Medical Center outside the submitted work. Dr Min reports grants from the National Heart, Lung, and Blood Institute during the conduct of the study; other from Cleerly Inc, grants and other from GE Healthcare, and other from Arineta outside the submitted work. Dr Bangalore reports grants from the National Heart, Lung, and Blood Institute during the conduct of the study; grants and personal fees from Abbott Vascular; and personal fees from Biotronik, Pfizer, Amgen, and Reata outside the submitted work. Dr Hochman is principal investigator for the ISCHEMIA trial for which, in addition to support by the National Heart, Lung, and Blood Institute grant, devices and medications were provided by Abbott Vascular, Medtronic, Inc, Abbott Laboratories (formerly St Jude Medical, Inc), Royal Philips NV (formerly Volcano Corporation), Arbor Pharmaceuticals, LLC, AstraZeneca Pharmaceuticals, LP, Merck Sharp & Dohme Corp, and Omron Healthcare, Inc, and financial donations were provided by Arbor Pharmaceuticals LLC and AstraZeneca Pharmaceuticals LP. Dr Hochman is also the PI of ISCHEMIA-EXTEND. The other authors report no conflicts. The content of this article is solely the responsibility of the authors and does not necessarily represent the views of the National Heart, Lung, and Blood Institute, the National Institutes of Health, or the United States Department of Health and Human Services.

Introduction: The importance of exercise electrocardiogram (ECG) is still controversial in the prevention of cardiovascular events among sportsmen and sportswomen. The aim of this study was to assess the relevance of exercise ECG as a screening tool to prevent cardiovascular events when any cardiovascular disease (CVD) risk factors are present., Methods: The study included leisure time asymptomatic sportsmen and sportswomen over age 35 evaluated from 2011 to 2016 at the University Hospital of Saint-Etienne (France). Major adverse cardiovascular events (MACE) and atrial fibrillation were collected at 3 years., Results: Of the cohort of 2457 sportsmen and sportswomen (mean age 50.2 ± 9.4 years), 50 (2%) had a high-risk SCORE2. A total of 256 exercise ECGs (10%) were defined as positive, most of them due to silent myocardial ischemia (SMI) (n = 196; 8%). These 196 SMI cases led to 33 coronary angiograms (1%), which revealed 23 significant coronary stenoses requiring revascularization. In multivariate logistic regression analysis, having at least two CVD risk factors was independently associated with (1) positive exercise ECG (OR = 1.80 [95% CI: 1.29-2.52], p = 0.0006), with (2) suspected SMI (OR = 2.57 [95% CI: 1.10-6.02], p = 0.0304), with (3) confirmed SMI (OR = 8.20 [95% CI: 3.46-19.46], p < 0.0001) and with (4) cardiovascular events (MACE or atrial fibrillation) (OR = 6.95 [95% CI: 3.49-13.81], p < 0.0001) at 3 years (median)., Conclusions: The study supports the European recommendations for the use of exercise ECG in evaluation of asymptomatic leisure time sportsmen over age 35. Having at least two CVD risk factors was the best predictor for presence of coronary artery stenosis that may increase the risk for adverse events., Trial Registration: ClinicalTrials.gov Identifier: NCT06024863., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: We aim to provide a comprehensive review of the current state of knowledge of myocardial viability assessment in patients undergoing coronary artery bypass grafting (CABG), with a focus on the clinical markers of viability for each imaging modality. We also compare mortality between patients with viable myocardium and those without viability who undergo CABG., Methods: A systematic database search with meta-analysis was conducted of comparative original articles (both observations and randomized controlled studies) of patients undergoing CABG with either viable or nonviable myocardium, in EMBASE, MEDLINE, Cochrane database, and Google Scholar, from inception to 2022. Imaging modalities included were dobutamine stress echocardiography (DSE), cardiac magnetic resonance (CMR), single-photon emission computed tomography (SPECT), and positron emission tomography (PET)., Results: A total of 17 studies incorporating a total of 2317 patients were included. Across all imaging modalities, the relative risk of death post-CABG was reduced in patients with versus without viability (random-effects model: odds ratio: 0.42; 95% confidence interval: 0.29-0.61; p < 0.001). Imaging for myocardial viability has significant clinical implications as it can affect the accuracy of the diagnosis, guide treatment decisions, and predict patient outcomes. Generally, based on local availability and expertise, either SPECT or DSE should be considered as the first step in evaluating viability, while PET or CMR would provide further evaluation of transmurality, perfusion metabolism, and extent of scar tissue., Conclusion: The assessment of myocardial viability is an essential component of preoperative evaluation in patients with ischemic heart disease undergoing surgical revascularization. Careful patient selection and individualized assessment of viability remain paramount., (© 2024 The Author(s). Clinical Cardiology published by Wiley Periodicals LLC.)

AbstractTesting for cardiac ischemia, or for the obstructive coronary artery disease (CAD) that causes cardiac ischemia, is common among hospitalized patients. Many testing options exist. Choosing an appropriate test can be challenging and requires accurate risk stratification. Two major categories of testing are available: stress testing (also known as functional testing) and anatomical testing. Stress testing evaluates specifically for ischemia and can be conducted with or without imaging. Anatomical testing visualizes the obstructive CAD that causes ischemia. This article reviews how to choose an appropriate test for the evaluation of cardiac ischemia in the inpatient setting, using case examples to illustrate the considerations involved.

Background: Functional assessment using fractional flow reserve (FFR) and anatomical assessment using optical coherence tomography (OCT) are used in clinical practice for patients with intermediate coronary stenosis. Moreover, coronary computed tomography angiography (CTA) is a common noninvasive imaging technique for evaluating suspected coronary artery disease before being referred for angiography. This study aimed to investigate the association between FFR and plaque characteristics assessed using coronary CTA and OCT for intermediate coronary stenosis., Methods: Based on a prospective multicenter registry, 159 patients having 339 coronary lesions with intermediate stenosis were included. All patients underwent coronary CTA before being referred for coronary angiography, and both FFR measurements and OCT examinations were performed during angiography. A stenotic lesion identified with FFR ≤0.80 was deemed diagnostic of an ischemia-causing lesion. The predictive value of plaque characteristics assessed using coronary CTA and OCT for identifying lesions causing ischemia was analyzed., Results: Stenosis severity and plaque characteristics on coronary CTA and OCT differed between lesions that caused ischemia and those that did not. In multivariate analysis, low attenuation plaque on coronary CTA (odds ratio [OR]=2.78; P=0.038), thrombus (OR=5.13; P=0.042), plaque rupture (OR=3.25; P=0.017), and intimal vasculature on OCT (OR=2.57; P=0.012) were independent predictors of ischemic lesions. Increasing the number of these plaque characteristics offered incremental improvement in predicting the lesions causing ischemia., Conclusions: Comprehensive anatomical evaluation of coronary stenosis may provide additional supportive information for predicting the lesions causing ischemia., Competing Interests: Declaration of competing interest J.-S.K. has received proctoring fees from Abbott Vascular. All other authors declare no conflicts of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background and Objectives: Instantaneous wave-free ratio (iFR) is a new invasive indicator of myocardial ischaemia, and its diagnostic performance is as good as the "gold standard" of myocardial ischaemia diagnosis: fractional flow reserve (FFR). iFR can be approximated by iFR CT , which is calculated based on noninvasive coronary CT angiography (CTA) images and computational fluid dynamics (CFD). However, the existing methods for calculating iFR CT fail to accurately simulate the resting state of the coronary artery, resulting in low computational accuracy. Furthermore, the use of CFD technology limits its computational efficiency, making it difficult to meet clinical application needs. The role of coronary microcirculatory resistance compensation suggests that microcirculatory resistance can be adaptively reduced to compensate for increases in coronary stenotic resistance, thereby maintaining stable myocardial perfusion in the resting state. It is therefore necessary to consider this compensation mechanism to establish a high-fidelity microcirculation resistance model in the resting state in line with human physiology, and so to achieve accurate calculation of iFR CT ., Methods: In this study we successfully collected clinical data, such as FFR, in 205 stenotic vessels from 186 patients with coronary heart disease. A neural network model was established to predict coronary artery stenosis resistance. Based on the compensation mechanism of coronary microcirculation resistance, an iterative solution algorithm for microcirculation resistance in the resting state was developed. Combining the two methods, a simplified single-branch model combining coronary stenosis and microcirculation resistance was established, and the noninvasive and rapid numerical calculation of iFR CT was performed., Results: The results showed that the mean squared error (MSE) between the pressure drop predicted by the neural network value for the coronary artery stenosis model and the ground truth in the test set was 0.053 %, and correlation analysis proved that there was a good correlation between them (r = 0.99, p < 0.001). With reference to clinical diagnosis of myocardial ischaemia (using FFR as the gold standard), the diagnostic accuracy of the iFR CT calculation model for the 205 cases was 88.29 % (r = 0.71, p < 0.001), and the total calculation time was < 8 s., Conclusions: The results of this study demonstrate the utility of a simplified single-branch model in an iFR CT calculation method based on haemodynamics and deep learning, which is important for noninvasive and rapid diagnosis of myocardial ischaemia., Competing Interests: Declaration of competing interest We have not identified any conflict of interest to be disclosed regarding publication of this study., (Copyright © 2024. Published by Elsevier B.V.)

Objective: The primary objective of this study was to assess the diagnostic potential of galectin-3 (Gal-3), fractalkine (FKN), interleukin (IL)-6, microRNA(miR)-21, and cardiac troponin I (cTnI) in patients with ischemic cardiomyopathy (ICM)., Method: A total of 78 ICM patients (Case group) and 80 healthy volunteers (Control group) admitted to our hospital for treatment or physical examination from Aug. 2018 to Feb. 2020 were included in the current study. The serum concentration of Gal-3, FKN, IL-6, miR-21, and plasma expression of cTnI of both groups were determined. The severity of ICM was classified using New York Heart Association (NYHA) scale., Results: When compared with the control group, the case group had a significantly high blood concentration of Gal-3, FKN, IL-6, miR-21, and cTnI ( P < 0.001). NYHA class II patients had lower blood levels of Gal-3, FKN, IL-6, miR-21, and cTnI than that in patients of NYHA class III and IV without statistical significance ( P > 0.05). However, statistical significance could be achieved when comparing the above-analyzed markers in patients classified between class III and IV. Correlation analysis also revealed that serum levels of Gal-3, FKN, IL-6, miR-21, and cTnI were positively correlated with NYHA classification (R = 0.564, 0.621, 0.792, 0.981, P < 0.05)., Conclusion: Our study revealed that up-regulated serum Gal-3, FKN, IL-6, miR-21, and cTnI levels were closely related to the progression of ICM. This association implies that these biomarkers have diagnostic potential, offering a promising avenue for early detection and monitoring of ICM progression.

Objectives: Ischemic heart disease (IHD) is a significant contributor to global mortality and disability, imposing a substantial social and economic burden on individuals and healthcare systems. To enhance the efficient allocation of medical resources and ultimately benefit a larger population, accurate prediction of healthcare costs is crucial., Methods: We developed an interpretable IHD hospitalization cost prediction model that integrates network analysis with machine learning. Specifically, our network-enhanced model extracts explainable features by leveraging a diagnosis-procedure concurrence network and advanced graph kernel techniques, facilitating the capture of intricate relationships between medical codes., Results: The proposed model achieved an R 2 of 0.804 ± 0.008 and a root mean square error (RMSE) of 17,076 ± 420 CNY on the temporal validation dataset, demonstrating comparable performance to the model employing less interpretable code embedding features (R 2 : 0.800 ± 0.008; RMSE: 17,279 ± 437 CNY) and the hybrid graph isomorphism network (R 2 : 0.802 ± 0.007; RMSE: 17,249 ± 387 CNY). The interpretation of the network-enhanced model assisted in pinpointing specific diagnoses and procedures associated with higher hospitalization costs, including acute kidney injury, permanent atrial fibrillation, intra-aortic balloon bump, and temporary pacemaker placement, among others., Conclusion: Our analysis results demonstrate that the proposed model strikes a balance between predictive accuracy and interpretability. It aids in identifying specific diagnoses and procedures associated with higher hospitalization costs, underscoring its potential to support intelligent management of IHD., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Mental stress-induced myocardial ischemia (MSIMI) is associated with adverse cardiovascular outcomes in individuals with coronary artery disease, but the mechanisms underlying this phenomenon are unknown. We examined the relationship between stress-induced autonomic dysfunction, measured by low heart rate variability (HRV) in response to stress, and MSIMI in patients with stable coronary artery disease. We hypothesized that stress-induced autonomic dysfunction is associated with higher odds of MSIMI., Methods: In 735 participants with stable coronary artery disease, we measured high- and low-frequency HRV in 5-minute intervals before and during a standardized laboratory-based speech stressor using Holter monitoring. HRV at rest and stress were categorized into low HRV (first quartile) versus high HRV (second to fourth quartiles); the low category was used as an indicator of autonomic dysfunction. Multivariable logistic regression models were used to examine the association of autonomic dysfunction with MSIMI., Results: The mean age was 58 (SD, ±10) years, 35% were women, 44% were Black participants, and 16% developed MSIMI. Compared with high HRV during stress, low HRV during stress (both high and low frequencies) was associated with higher odds of MSIMI after adjusting for demographic and clinical factors (odds ratio for high-frequency HRV, 2.1 [95% CI, 1.3-3.3]; odds ratio for low-frequency HRV, 2.1 [95% CI, 1.3-3.3]). Low-frequency HRV at rest was also associated with MSIMI but with slightly reduced effect estimates., Conclusions: In individuals with coronary artery disease, mental stress-induced autonomic dysfunction may be a mechanism implicated in the causal pathway of MSIMI., Competing Interests: Disclosures None.

Purpose To investigate whether right ventricular (RV) myocardial strain ratio (RVMSR) assessed using nitrogen 13 ammonia ( 13 N-NH 3 ) PET can predict cardiovascular events in patients with ischemic heart disease (IHD). Materials and Methods This retrospective study included 480 consecutive patients (mean age, 66 years ± 12 [SD]; 334 males and 146 females) with IHD who underwent 13 N-NH 3 PET. RVMSR was defined as the ratio of RV strain during stress to that at rest. The primary end point was major adverse cardiac events (MACEs), defined as cardiac death or heart failure hospitalization. The ability of RVMSR to predict MACE was assessed using receiver operating characteristic (ROC) curve and Kaplan-Meier analyses. Cox proportional hazards regression analysis was used to calculate hazard ratios (HRs) with 95% CIs. Results ROC curve analysis identified a sensitivity and specificity of 84% and 82%, respectively, for predicting MACE from RVMSR. Patients with reduced RVMSR (<110.2) displayed a significantly higher rate of MACE than those with a preserved RVMSR (34 of 240 vs four of 240; P < .001). Cox proportional hazards regression analysis of imaging parameters, including myocardial flow reserve, indicated that RVMSR was an independent predictor of MACE (HR, 0.94 [95% CI: 0.92, 0.97]; P < .001). Conclusion RVMSR was an independent predictor of MACE and has potential to aid in the risk stratification of patients with IHD. Keywords: Right Ventricular Myocardial Strain Ratio, Myocardial Flow Reserve, Ischemic Heart Disease, 13 N-Ammonia Positron Emission Tomography Supplemental material is available for this article. © RSNA, 2024.

Background: Machine learning (ML) employs algorithms that learn from data, building models with the potential to predict events by aggregating a large number of variables and assessing their complex interactions. The aim of this study is to assess ML potential in identifying patients with ischemic heart disease (IHD) at high risk of cardiac death (CD)., Methods: 3987 (mean age 68 ± 11) hospitalized IHD patients were enrolled. We implemented and compared various ML models and their combination into ensembles. Model output constitutes a new ML indicator to be employed for stratification. Primary variable importance was assessed with ablation tests., Results: An ensemble classifier combining three ML models achieved the best performance to predict CD (AUROC of 0.830, F1-macro of 0.726). ML indicator use through Cox survival analysis outperformed the 18 variables individually, producing a better stratification compared to standard multivariate analysis (improvement of ∼20%). Patients in the low risk group defined through ML indicator had a significantly higher survival (88.8% versus 29.1%). The main variables identified were Dyslipidemia, LVEF, Previous CABG, Diabetes, Previous Myocardial Infarction, Smoke, Documented resting or exertional ischemia, with an AUROC of 0.791 and an F1-score of 0.674, lower than that of 18 variables. Both code and clinical data are freely available with this article., Conclusion: ML may allow a faster, low-cost and reliable evaluation of IHD patient prognosis by inclusion of more predictors and identification of those more significant, improving outcome prediction towards the development of precision medicine in this clinical field., Competing Interests: Declaration of competing interest there is no conflict of interest to declare by all authors., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Cardiovascular disease is the leading cause of death among women in the United States. It is well established that gestational diabetes mellitus is associated with an overall lifetime increased risk of cardiometabolic disease, even among those without intercurrent type 2 diabetes. However, the association between gestational diabetes mellitus and short-term risk of cardiovascular disease is unclear. Establishing short-term risks of cardiovascular disease for patients with gestational diabetes mellitus has significant potential to inform early screening and targeted intervention strategies to reduce premature cardiovascular morbidity among women., Objective: This study aimed to compare the risk of cardiovascular disease diagnosis in the first 24 months postpartum between patients with and without gestational diabetes mellitus., Study Design: Our longitudinal population-based study included pregnant individuals with deliveries from 2007 to 2019 in the Maine Health Data Organization's All Payer Claims Database. We excluded records with gestational age <20 weeks, non-Maine residence, multifetal gestation, no insurance in the month of delivery or the 3 months before pregnancy, an implausibly short interval until next pregnancy (<60 days), pregestational diabetes mellitus, and any prepregnancy diagnosis of the cardiovascular conditions being examined postpartum. Gestational diabetes mellitus and cardiovascular disease (heart failure, ischemic heart disease, arrhythmia/cardiac arrest, cardiomyopathy, cerebrovascular disease/stroke, and new chronic hypertension) were identified by International Classification of Diseases 9/10 diagnosis codes. Cox proportional hazards models were used to estimate hazard ratios, adjusting for potential confounding factors. We assessed whether the association between gestational diabetes mellitus and chronic hypertension was mediated by intercurrent diabetes mellitus., Results: Among the 84,746 pregnancies examined, the cumulative risk of cardiovascular disease within 24 months postpartum for those with vs without gestational diabetes mellitus was 0.13% vs 0.20% for heart failure, 0.16% vs 0.14% for ischemic heart disease, 0.60% vs 0.44% for cerebrovascular disease/stroke, 0.22% vs 0.16% for arrhythmia/cardiac arrest, 0.20% vs 0.20% for cardiomyopathy, and 4.19% vs 1.83% for new chronic hypertension. After adjusting for potential confounders, those with gestational diabetes had an increased risk of new chronic hypertension (adjusted hazard ratio, 1.56; 95% confidence interval, 1.32-1.86) within the first 24 months postpartum compared with those without gestational diabetes. There was no association between gestational diabetes and ischemic heart disease (adjusted hazard ratio, 0.75; 95% confidence interval, 0.34-1.65), cerebrovascular disease/stroke (adjusted hazard ratio, 1.13; 95% confidence interval, 0.78-1.66), arrhythmia/cardiac arrest (adjusted hazard ratio, 1.16; 95% confidence interval, 0.59-2.29), or cardiomyopathy (adjusted hazard ratio, 0.75; 95% confidence interval, 0.40-1.41) within the first 24 months postpartum. Those with gestational diabetes appeared to have a decreased risk of heart failure within 24 months postpartum (adjusted hazard ratio, 0.45; 95% confidence interval, 0.21-0.98). Our mediation analyses estimated that 28% of the effect of gestational diabetes on new chronic hypertension was mediated through intercurrent diabetes mellitus., Conclusion: Patients with gestational diabetes mellitus have a significantly increased risk of new chronic hypertension as early as 24 months postpartum. Most of this effect was not due to the development of diabetes mellitus. Our findings suggest that all women with gestational diabetes need careful monitoring and screening for new chronic hypertension in the first 2 years postpartum., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Echocardiography has been used clinically to assess regional myocardial wall motion for the diagnosis of acute myocardial ischemia or stress-induced ischemia, but it is often difficult to distinguish hypokinetic motion from normal motion. Myocardial wall motion is affected by loading conditions as well as intrinsic contractility, making it challenging to define a normal range of wall motion. Therefore, hypokinesis is usually diagnosed by comparing target areas with other areas of myocardium considered normal (relative hypokinesis). Myocardial strain analysis by tissue Doppler echocardiography and speckle-tracking echocardiography has enabled objective and quantitative evaluation of regional myocardial wall motion. Peak systolic strain decreases during acute ischemia, but subtle and invisible myocardial motion, such as early systolic lengthening (ESL) and postsystolic shortening (PSS), also occurs, and the analysis of these subtle motions can improve the diagnostic accuracy of ischemia. However, the diagnosis of ischemic myocardium by strain analysis is not widely performed in clinical practice at this time due to several limitations. This article reviews the features of myocardial motion during acute ischemia, the mechanisms of ESL and PSS, the diagnosis of ischemic myocardium using strain analysis, and current approaches and future challenges to overcome the limitations in the detection of relative hypokinesis. This article also explains the use of ESL and PSS to detect myocardial ischemic memory that remains after brief ischemia., (© 2024. Japanese Society of Echocardiography.)

Background: Ischemia and no obstructive coronary artery disease (INOCA) is increasingly recognized and associated with poor outcomes. The triglyceride-glucose (TyG) index is a reliable alternative measure of insulin resistance significantly linked to cardiovascular disease and adverse prognosis. We investigated the association between the TyG index and myocardial ischemia and the prognosis in INOCA patients., Methods: INOCA patients who underwent both coronary angiography and myocardial perfusion imaging (MPI) were included consecutively. All participants were divided into three groups according to TyG tertiles (T1, T2, and T3). Abnormal MPI for myocardial ischemia in individual coronary territories was defined as summed stress score (SSS) ≥ 4 and summed difference score (SDS) ≥ 2. SSS refers to the sum of all defects in the stress images, and SDS is the difference of the sum of all defects between the rest images and stress images. All patients were followed up for major adverse cardiac events (MACE)., Results: Among 332 INOCA patients, 113 (34.0%) had abnormal MPI. Patients with higher TyG index had a higher rate of abnormal MPI (25.5% vs. 32.4% vs. 44.1%; p = 0.012). Multivariate logistic analysis showed that a high TyG index was significantly correlated with abnormal MPI in INOCA patients (OR, 1.901; 95% CI, 1.045-3.458; P = 0.035). During the median 35 months of follow-up, 83 (25%) MACE were recorded, and a higher incidence of MACE was observed in the T3 group (T3 vs. T2 vs. T1: 36.9% vs. 21.6% vs. 16.4%, respectively; p = 0.001). In multivariate Cox regression analysis, the T3 group was significantly associated with the risk of MACE compared to the T1 group (HR, 2.338; 95% CI 1.253-4.364, P = 0.008)., Conclusion: This study indicates for the first time that the TyG index is significantly associated with myocardial ischemia and poor prognosis among INOCA patients., (© 2024. The Author(s).)

Background: Interleukin-17 (IL-17) has been hypothesized to be involved in ischemic cardiovascular disease (ICVD). However, the association of IL-17 with ICVD remained unclear. The aim of this study was to systematically analyze the available evidence regarding the association between IL-17 and ICVD., Methods: We searched the PubMed, Web of Science, Cochrane Library, and Embase databases up to October 2023 to identify publications on the association between IL-17 and ICVD. The merged results were analyzed using a random effects model for meta-analysis and subgroup analysis., Results: A total of 955 publications were initially identified in our search and screened; six studies were eventually included in the analysis. The average age of study participants was 60.3 ± 12.6 years and 65.5% were men. There was a high degree of heterogeneity among studies. The results showed that IL-17 level were higher in the case group than those in the control group (standardized mean difference, SMD = 1.60, 95% confidence interval (95% CI): 0.53-2.66, P = 0.003). In sensitivity analysis, the merged results showed good robustness. Additionally, subgroup analysis showed that race and ethnicity, sample size, and detection methods were significant factors influencing heterogeneity in the published studies., Conclusion: Our finding revealed that increased IL-17 level contributed to the development of ICVD, suggesting IL-17 as a potential risk marker. Further research is needed to establish IL-17 as a therapeutic biomarker of ICVD., (© 2024. The Author(s).)

Objective: To investigate the contributions of low-grade inflammation measured by C-reactive protein (CRP), hyperglycaemia, and type 2 diabetes to risk of ischemic heart disease (IHD) and cardiovascular disease (CVD) death in the general population, and whether hyperglycaemia and high CRP are causally related., Research Design and Methods: Observational and bidirectional, one-sample Mendelian randomization (MR) analyses in 112,815 individuals from the Copenhagen General Population Study and the Copenhagen City Heart Study, and bidirectional, two-sample MR with summary level data from two publicly available consortia, CHARGE and MAGIC., Results: Observationally, higher plasma CRP was associated with stepwise higher risk of IHD and CVD death, with hazard ratios and 95% confidence intervals (95%CI) of 1.50 (1.38, 1.62) and 2.44 (1.93, 3.10) in individuals with the 20% highest CRP concentrations. The corresponding hazard ratios for elevated plasma glucose were 1.10 (1.02, 1.18) and 1.22 (1.01, 1.49), respectively. Cumulative incidences of IHD and CVD death were 365% and 592% higher, respectively, in individuals with both type 2 diabetes and plasma CRP ≥ 2 mg/L compared to individuals without either. Plasma CRP and glucose were observationally associated (β-coefficient: 0.02 (0.02, 0.03), p = 3 × 10 - 20 ); however, one- and two-sample MR did not support a causal effect of CRP on glucose (-0.04 (-0.12, 0.32) and - 0.03 (-0.13, 0.06)), nor of glucose on CRP (-0.01 (-0.08, 0.07) and - 0.00 (-0.14, 0.13))., Conclusions: Elevated concentrations of plasma CRP and glucose are predictors of IHD and CVD death in the general population. We found no genetic association between CRP and glucose, or vice versa, suggesting that lowering glucose pharmacologically does not have a direct effect on low-grade inflammation., (© 2024. The Author(s).)

Cardiac electrical changes associated with ischemic heart disease (IHD) are subtle and could be detected even in rest condition in magnetocardiography (MCG) which measures weak cardiac magnetic fields. Cardiac features that are derived from MCG recorded from multiple locations on the chest of subjects and some conventional time domain indices are widely used in Machine learning (ML) classifiers to objectively distinguish IHD and control subjects. Most of the earlier studies have employed features that are derived from signal-averaged cardiac beats and have ignored inter-beat information. The present study demonstrates the utility of beat-by-beat features to be useful in classifying IHD subjects (n = 23) and healthy controls (n = 75) in 37-channel MCG data taken under rest condition of subjects. The study reveals the importance of three features (out of eight measured features) namely, the field map angle (FMA) computed from magnetic field map, beat-by-beat variations of alpha angle in the ST-T region and T wave magnitude variations in yielding a better classification accuracy (92.7 %) against that achieved by conventional features (81 %). Further, beat-by-beat features are also found to augment the accuracy in classifying myocardial infarction (MI) Versus control subjects in two public ECG databases (92 % from 88 % and 94 % from 77 %). These demonstrations summarily suggest the importance of beat-by-beat features in clinical diagnosis of ischemia., (© 2024 IOP Publishing Ltd.)

Chronic coronary disease (CCD) is a major cause of morbidity and mortality worldwide. The most common symptom of CCD is exertional angina pectoris, a discomfort in the chest that commonly occurs during activities of daily life. Patients are dismayed by recurring episodes of angina and seek medical help in preventing or minimizing episodes. Angina occurs when the coronary arteries are unable to supply sufficient blood flow to the cardiac muscle to meet the metabolic needs of the left ventricular myocardium. While lifestyle changes and aggressive risk factor modification play a critical role in the management of CCD, management of angina usually requires pharmacologic therapy. Medications such as beta-blockers, calcium channel blockers, nitrates, ranolazine, and others ultimately work to improve the mismatch between myocardial blood flow and metabolic demand. This manuscript briefly describes the pathophysiologic basis for symptoms of angina, and how currently available anti-anginal therapies contribute to preventing or minimize the occurrence of angina., Competing Interests: Disclosures All authors have no conflicts of interest., (Copyright © 2023 Elsevier Inc. All rights reserved.)

There are unique advantages and disadvantages to functional versus anatomic testing in the work-up of patients who present with symptoms suggestive of obstructive coronary artery disease. Evaluation of these individuals starts with an assessment of pre-test probability, which guides subsequent testing decisions. The choice between anatomic and functional testing depends on this pre-test probability. In general, anatomic testing has particular utility among younger individuals and women; while functional testing can be helpful to rule-in ischemia and guide revascularization decisions. Ultimately, selection of the most appropriate test should be individualized to the patient and clinical scenario., Competing Interests: Disclosure M D. Kelsey reports consultation/advisory panels for Bayer, Heartflow. The remaining authors report nothing to disclose., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Previous studies showed that exercise may increase cardiac troponin serum levels; whether the occurrence of myocardial ischemia influences the changes of exercise-induced troponin raise, however, remains debatable., Methods: We prospectively enrolled consecutive patients undergoing for the first time an elective stress myocardial perfusion scintigraphy (MPS) because of clinical suspicion of obstructive coronary artery disease (CAD). Patients were divided into 3 groups based on the evidence and degree of stress-induced myocardial ischemia at MPS: 1) group 1, no myocardial ischemia (≤4 %); 2) group 2, mild myocardial ischemia (5-10 %); 3) group 3, moderate-to-severe myocardial ischemia (≥10 %). High-sensitivity cardiac troponin I (cTnI) was measured immediately before (T 0 ) and 1 hour (T 1 ) and 4 h (T 2 ) after the stress test., Results: One hundred-seven patients (71 males; age 65.6 ± 9.4 years) were enrolled in the study. Serum hs-cTnI concentrations (logarithmic values) significantly increased after MPS, compared to baseline, in the whole population, from 1.47±1.26 ng/L at T 0 , to 1.68±1.12 ng/L at T 1 (p<0.001) and 2.15±1.02 ng/L at T 2 (p<0.001 vs. both T 0 and T 1 ). The increase in hs-cTnI did not significantly differ between the 3 groups (p = 0.44). The heart rate achieved during the test was the strongest determinant of cTnI increase (p < 0.001) after the stress test., Conclusions: In patients with suspected CAD, stress MPS induces an increase of cTnI that is independent of the induction and extension/severity of myocardial ischemia and is mainly related to myocardial work, as indicated by the heart rate achieved during the test., (Copyright © 2023. Published by Elsevier B.V.)

Coronary microvascular dysfunction (CMD) is a key mechanism underlying ischemic heart disease (IHD), yet its diagnosis and treatment remain challenging. This article presents a comprehensive overview of CMD research, covering its pathogenesis, diagnostic criteria, assessment techniques, risk factors, and therapeutic strategies. Additionally, it highlights the prospects for future CMD research. The article aims at advocating early and effective intervention for CMD and improving the prognosis of IHD., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024. Published by Elsevier Inc.)

Ischemic cardiomyopathy (ICM) is the most common underlying etiology of heart failure in the United States and is a significant contributor to deaths due to cardiovascular disease worldwide. The diagnosis and management of ICM has advanced significantly over the past few decades, and the evidence for medical therapy in ICM is both compelling and robust. This contrasts with evidence for coronary revascularization, which is more controversial and favors surgical approaches. This review will examine landmark clinical trial results in detail as well as provide a comprehensive overview of the current epidemiology, diagnostic approaches, and management strategies of ICM., Competing Interests: Disclosures Dr A.P. Ambrosy has received relevant research support through grants to his institution from the National Heart, Lung, and Blood Institute, United States (K23HL150159), the American Heart Association, United States (2nd Century Early Faculty Independence Award), The Permanente Medical Group, Northern California Community Health Program, Garfield Memorial Fund, Abbott Laboratories, Amarin Pharma, Inc., Edwards Lifesciences LLC, Esperion Therapeutics, Inc., and Novartis. All other authors have no relevant financial disclosures., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Patients with end-stage kidney disease (ESKD) are at high risk of cardiovascular disease including stroke, heart failure, and ischemic heart disease (IHD). To prevent the occurrence and progression of CVD, a reliable prognostic cardiac biomarker is essential. We investigated the prognostic value of NT-proBNP for each incident type of CVD., Methods: Male patients from the Ibaraki Dialysis Initiation Cohort (iDIC) study with preserved serum samples from dialysis initiation day (n = 212) were analyzed. Patients were classified into four groups according to quartiles of baseline NT-pro BNP levels. The relationship between NT-proBNP levels at the initiation of dialysis and the subsequent incidence of hospitalization events due to IHD, heart failure, and stroke was analyzed., Results: The incidence rate for hospitalization due to IHD was significantly higher in the highest NT-proBNP category (Log rank p = 0.008); those of stroke and heart failure showed no significant differences among quartiles. Cox proportional hazards regression analysis revealed that serum NT-proBNT was the only prognostic factor for hospitalization for IHD after adjustment by major known IHD risk factors. (HR, 1.008; 95% confidence interval, 1.002-1.014; p = 0.01) The ROC curve analysis for the incidence of hospitalization due to IHD showed that NT-proBNP had an area under the curve (AUC) of 0.759 (95% CI 0.622-0.897; p = 0.004) at a cut-off value of 956.6 pg/mL., Conclusion: NT-proBNP measurement at the initiation of dialysis therapy is useful to predict later hospitalization for IHD., Trial Registration: UMIN000010806., (© 2024. The Author(s), under exclusive licence to Japanese Society of Nephrology.)

Chronic coronary heart disease encompasses a broad spectrum of disorders that range in severity from trivial to imminently life-threatening. The primary care physician encounters coronary disease at all stages. The number of available diagnostic and therapeutic options for evaluating and treating coronary disease is vast, presenting a complex selection strategy challenge when making choices for the individual patient. The primary care physician is responsible to tailor evaluation and management strategies to each individual patient based on his/her particular disease characteristics. There are many categories of diagnostic studies and therapeutic interventions that have been shown at the population level in clinical trials to improve patient outcomes. Blindly applying the findings of all demonstrated studies and therapies to a patient with coronary disease would saddle him/her with an unsustainable burden of diagnostic tests and therapies. The core principle of the approach outlined in this article is to tailor diagnostic and therapeutic choices to the operative pathophysiology that drives a particular patient's disorder. This introductory article is intended to provide a conceptual framework for studying and applying the specialized topics discussed in the articles that follow., (Copyright © 2023 Elsevier Inc. All rights reserved.)

This review synthesizes the current understanding of ischemic heart disease in women, briefly discussing differences in risk factors, presentation, and treatment. We have underscored the unique clinical phenotype of IHD in women with a higher prevalence of ischemia with non-obstructive coronary arteries. Further research is needed to elucidate the complexities of ischemic heart disease in women, understand the discordance between ischemic burden and clinical symptoms, and optimize treatment strategies., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objective: To compare baseline characteristics of participants in the Women's IschemiA TRial to Reduce Events In Non-ObstRuctive CAD (WARRIOR) trial by qualification by Coronary Computed Tomography Angiography (CCTA) or Invasive Coronary Angiography (ICA)., Methods: The WARRIOR trial (NCT03417388) is an ongoing multicenter, prospective, randomized, blinded outcome evaluation of intensive medical therapy vs. usual care in women with suspected Ischemia and No Obstructive Coronary Artery Disease (INOCA) identified by either CCTA or ICA on the outcome of major adverse cardiovascular events (MACE). No obstructive coronary artery disease is defined as <50% luminal stenosis and normal coronary arteries is defined as no evidence of atherosclerosis including calcified and non-calcified plaque. Data presented was extracted on May 27, 2020. No clinical outcomes were assessed., Results: An initial sample cohort of 797 women was included. The majority were younger than 65 years, White participants (73.3%), 159 had diabetes (19.9%), and 676 had angina (84.8%) with the remainder having symptoms of suspected ischemic heart disease. Over 50% of randomized participants had normal coronaries without luminal irregularities by ICA or CCTA. Participants randomized to ICA were more likely to have worse baseline clinical risk profiles with older age, higher burden of cardiac risk factors and poor quality of life with disabling angina., Conclusions: Among this initial sample of women with suspected INOCA randomized in the WARRIOR trial, there is a differential baseline cardiac risk of participants enrolled after CCTA or ICA. However, the majority had no evidence of atherosclerotic plaque or obstructive stenosis, after evaluation by ICA or CCTA. These results suggest that non-invasive evaluation with CCTA is likely to be associated with lower risk of MACE., Competing Interests: Declaration of competing interest CNBM serves as Board of Director for iRhythm and receives personal fees paid to CSMC bySHL Telemedicine. CJP receives research grants from GE Healthcare, Merck, Sanofi, CLS Behring, BioCardia, McJunkin Family Foundation Trust, Brigham & Women's Hospital, Gatorade Trust through the University of Florida Department of Medicine, and Mesoblast, Inc.; has received consultant fees/honoraria from Verily Life Sciences. LLC Project Baseline OSMB (Google), Ironwood, XyloCor, Slack Inc., Elsevier, Imbria Pharmaceuticals, Milestone Pharmaceuticals Inc., AstraZeneca Pharmaceuticals, and Sanofi-Aventis. SL has no disclosures. MB has received grant support from NIH and GE. GC has no disclosures. LS has received honoraria for speaking from Elucid Bioimaging and Heartflow., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

To localize the unusual cardiac activities non-invasively, one has to build a prior forward model that relates the heart, torso, and detectors. This model has to be constructed to mathematically relate the geometrical and functional activities of the heart. Several methods are available to model the prior sources in the forward problem, which results in the lead field matrix generation. In the conventional technique, the lead field assumed the fixed prior sources, and the source vector orientations were presumed to be parallel to the detector plane with the unit strength in all directions. However, the anomalies cannot always be expected to occur in the same location and orientation, leading to misinterpretation and misdiagnosis. To overcome this, the work proposes a new forward model constructed using the VCG signals of the same subject. Furthermore, three transformation methods were used to extract VCG in constructing the time-varying lead fields to steer to the orientation of the source rather than just reconstructing its activities in the inverse problem. In addition, the unit VCG loop of the acute ischemia patient was extracted to observe the changes compared to the normal subject. The abnormality condition was achieved by delaying the depolarization time by 15ms. The results involving the unit vectors of VCG demonstrated the anisotropic nature of cardiac source orientations, providing information about the heart's electrical activity., (Creative Commons Attribution license.)

Background: Coronary microvascular dysfunction (CMD) is the leading cause of ischemia with no obstructive coronary arteries disease (INOCA) disease. Diagnosis of CMD relies on surrogate physiological indices without objective proof of ischemia., Objectives: Intracoronary electrocardiogram (icECG) derived hyperemic indices may accurately and objectively detect CMD and reversible ischemia in related territory., Methods: INOCA patients with proven ischemia by myocardial perfusion scan (MPS) and completely normal coronary arteries underwent simultaneous intracoronary electrophysiological (icECG) and physiological (intracoronary Doppler) assessment in all 3 coronary arteries during rest and under adenosine induced hyperemia., Results: Sixty vessels in 21 patients were included in the final analysis. All patients had at least one vessel with abnormal CFR. 41 vessels had CMD (CFR < 2.5), of which 26 had increased microvascular resistance (structural CMD, HMR > 1.9 mmHg.cm -1 .s) and 15 vessels had CMD (CFR < 2.5) with normal microvascular resistance (functional CMD, HMR <= 1.9 mmHg.cm -1 .s). Only one-third of the patients (n = 7) had impaired CFR < 2.5 in all 3 epicardial arteries. Absolute ST shift between hyperemia and rest (∆ST) has shown the best diagnostic performance for ischemia (cut-off 0.10 mV, sensitivity: 95%, specificity: 72%, accuracy: 80%, AUC: 0.860) outperforming physiological indices (CFR: 0.623 and HMR: 0.653 DeLong's test P = .0002)., Conclusions: In INOCA patients, CMD involves coronary artery territories heterogeneously. icECG can accurately detect CMD causing perfusion abnormalities in patients with INOCA outperforming physiological CMD markers, by demonstrating actual ischemia instead of predicting the likelihood of inducible ischemia based on violated surrogate thresholds of blunted flow reserve or increased minimum microvascular resistance., Condensed Abstract: In 21 INOCA patients with coronary microvascular dysfunction (CMD) and myocardial perfusion scan proved ischemia, hyperemic indices of intracoronary electrocardiogram (icECG) have accurately detected vessel-specific CMD and resulting perfusion abnormalities & ischemia, outperforming invasive hemodynamic indices. Absolute ST shift between hyperemia and rest (∆ST) has shown the best classification performance for ischemia in no Obstructive Coronary Arteries (AUC: 0.860) outperforming Doppler derived CMD indices (CFR: 0.623 and HMR: 0.653 DeLong's test P = .0002).icECG can be used to diagnose CMD causing perfusion defects by demonstrating actual reversible ischemia at vessel-level during the initial CAG session, obviating the need for further costly ischemia tests., Clinicaltrials: GOV: NCT05471739., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: The endothelial nitric oxide synthase (eNOS) gene deficiency is known to cause impaired coronary vasodilating capability in animal models. In the general clinical population, the eNOS gene polymorphisms, able to affect eNOS activity, were associated with cardiometabolic risk features and prevalence of coronary artery disease (CAD)., Aim: To investigate the association of eNOS Glu298Asp gene polymorphism, cardiometabolic profile, obstructive CAD and inducible myocardial ischemia in patients with suspected stable CAD., Methods: A total of 506 patients (314 males; mean age 62 ± 9 years) referred for suspected CAD was enrolled. Among these, 325 patients underwent stress ECG or cardiac imaging to assess the presence of inducible myocardial ischemia and 436 patients underwent non-invasive computerized tomography or invasive coronary angiography to assess the presence of obstructive CAD. Clinical characteristics and blood samples were collected for each patient., Results: In the whole population, 49.6% of patients were homozygous for the Glu298 genotype (Glu/Glu), 40.9% heterozygotes (Glu/Asp) and 9.5% homozygous for the 298Asp genotype (Asp/Asp). Obstructive CAD was documented in 178/436 (40.8%) patients undergoing coronary angiography while myocardial ischemia in 160/325 (49.2%) patients undergoing stress testing. Patients with eNOS Asp genotype (Glu/Asp + Asp/Asp) had no significant differences in clinical risk factors and in circulating markers. Independent predictors of obstructive CAD were age, gender, obesity, and low HDL-C. Independent predictors of myocardial ischemia were gender, obesity, low HDL-C and Asp genotype. In the subpopulation in which both stress tests and coronary angiography were performed, the Asp genotype remained associated with increased myocardial ischemia risk after adjustment for obstructive CAD., Conclusion: In this population, low-HDL cholesterol was the only cardiometabolic risk determinant of obstructive CAD. The eNOS Glu298Asp gene polymorphism was significantly associated with inducible myocardial ischemia independently of other risk factors and presence of obstructive CAD., (© 2024. The Author(s).)

Introduction: Frailty has become a worldwide health burden that has a large influence on public health and clinical practice. The incidence of frailty is anticipated to increase as the ageing population increases. Myocardial injury after noncardiac surgery (MINS) is associated with short-term and long-term mortality. However, the incidence of MINS in frail geriatric patients is unknown., Methods and Analysis: This prospective, multicentre, real-world observational cohort study will be conducted at 18 designated centres in China from January 2023 to December 2024, with an anticipated sample size of 856 patients aged 65 years and older who are scheduled to undergo noncardiac surgery. The primary outcome will be the incidence of MINS. MINS is defined as a fourth-generation plasma cardiac troponin T (cTnT) concentration ≥ 0.03 ng/mL exhibited at least once within 30 days after surgery, with or without symptoms of myocardial ischaemia. All data will be collected via electronic data acquisition., Discussion: This study will explore the incidence of MINS in frail patients. The characteristics, predictive factors and 30-day outcomes of MINS in frail patients will be further investigated to lay the foundation for identifying clinical interventions., Clinical Trial Registration: https://beta., Clinicaltrials: gov/study/NCT05635877 , NCT05635877., (© 2024. The Author(s).)

Coronary artery stenosis (CAS) may affect up to 27% of patients with Williams syndrome (WS), which may lead to myocardial ischemia. Patients with WS face a 25- to 100-fold greater risk of sudden cardiac death, frequently linked to anesthesia. Assessing CAS requires either imaging while under general anesthesia or intraoperative assessment, with the latter considered the gold standard. Our study aimed to identify electrocardiogram (ECG) markers of myocardial ischemia in patients with WS or nonsyndromic elastin arteriopathy and documented CAS. We retrospectively reviewed patients with WS/elastin arteriopathy who underwent supravalvar aortic stenosis surgery and CAS assessment from January 1, 2006 to April 30, 2021. A pediatric electrophysiologist, not aware of the patients' CAS status, reviewed their preoperative ECGs for markers of ischemia. We assessed associations of study parameters using Wilcoxon rank-sum and Fisher's exact tests. Of 34 patients, 62% were male, with a median age of 20 months (interquartile range: 8 to 34). CAS was present in 62% (21 of 34), 76% of whom (16 of 21) were male. There were no ECG indicators of myocardial ischemia in patients with CAS. In conclusion, CAS was present in >1/2 the children with WS/elastin arteriopathy who underwent repair of supravalvar aortic stenosis. CAS in WS/nonsyndromic elastin arteriopathy does not appear to exhibit typical ECG-detectable myocardial ischemia. ECGs are not a useful screening tool for CAS in WS/elastin arteriopathy. Given the high anesthesia-related cardiac arrest risk, other noninvasive indicators of CAS are needed., Competing Interests: Declaration of competing interest The authors have no competing interests to declare., (Published by Elsevier Inc.)

Ischemic heart disease (IHD) is the leading cause of morbidity and mortality in both genders; however, young women fare the worst, likely reflecting the more complex spectrum of IHD in women when compared to men. Substantial sex-based differences exist in the underlying risk factors, risk enhancers, presentation, diagnosis, and pathophysiology of IHD that are mainly attributed to the influence of female sex hormones. This article reviews the spectrum of IHD including obstructive epicardial coronary artery disease (CAD), myocardial infarction with no obstructive coronary artery disease, ischemia with no obstructive coronary artery disease, spontaneous coronary artery dissection, coronary microvascular dysfunction, vasospastic angina, and coronary thrombosis/embolism that occur in women throughout various stages of their life cycle. We aim to update clinicians on the diagnosis and management of these various types of IHD and highlight where further randomized controlled studies are needed to determine optimal treatment and inform guideline-directed medical therapy., Competing Interests: The authors have no competing interests to declare., (Copyright: © 2024 The Author(s).)

Background: Chest pain is responsible for millions of visits to the emergency department (ED) annually. Cardiac ultrasound can detect ischemic changes, but varying accuracy estimates have been reported in previous studies. We synthetized the available evidence to yield more precise estimates of the accuracy of cardiac ultrasound for acute myocardial ischemia in patients with chest pain in the ED and to assess the effect of different clinical characteristics on test accuracy., Methods: A systematic search for studies assessing the diagnostic accuracy of cardiac ultrasound for myocardial ischemia in the ED was conducted in MEDLINE, EMBASE, CENTRAL, CINAHL, LILACS, Web of Science, two trial registries and supplementary methods, from inception to December 6th, 2022. Prospective cohort, cross-sectional, case-control studies and randomized controlled trials (RCTs) that included data on diagnostic accuracy were included. Risk of bias was assessed with the QUADAS-2 tool and a bivariate hierarchical model was used for meta-analysis with paired Forest and SROC plots used to present the results. Subgroup analyses was conducted on clinically relevant factors., Results: Twenty-nine studies were included, with 5043 patients. The overall summary sensitivity was 79.3% (95%CI 69.0-86.8%) and specificity was 87.3% (95%CI 79.9-92.2%), with substantial heterogeneity. Subgroup analyses showed increased sensitivity in studies where ultrasound was conducted at ED admission and increased specificity in studies that excluded patients with previous heart disease, when the target condition was acute coronary syndrome, or when final chart review was used as the reference standard. There was very low certainty in the results based on serious risk of bias and indirectness in most studies., Conclusions: Cardiac ultrasound may have a potential role in the diagnostic pathway of myocardial ischemia in the ED; however, a pooled accuracy must be interpreted cautiously given substantial heterogeneity and that important patient and test characteristics affect its diagnostic performance., Protocol Registration: PROSPERO (CRD42023392058)., (© 2024. The Author(s).)