Analytical Insights into Methods for Measuring Ischemia-Modified Albumin.

Ischemia-modified albumin (IMA) has emerged as a pivotal biomarker for the early detection of ischemic conditions, particularly myocardial ischemia, where timely diagnosis is crucial for effective intervention. This review provides an overview of the analytical methods for assessment of IMA, including Albumin Cobalt Binding (ACB), Albumin Copper Binding (ACuB), Enzyme-Linked Immunosorbent Assay (ELISA), new techniques such as liquid crystal biosensors (LCB), quantum dot coupled X-ray fluorescence spectroscopy (Q-XRF), mass spectrometry (MS), and electron paramagnetic resonance (EPR) spectroscopy. Each method was thoroughly examined for its analytical performance in terms of sensitivity, specificity, and feasibility. The ACB assay is the most readily implementable method in clinical laboratories for its cost-effectiveness and operational simplicity. On the other hand, the ACuB assay exhibits enhanced sensitivity and specificity, driven by the superior binding affinity of copper to IMA. Furthermore, nanoparticle-enhanced immunoassays and liquid crystal biosensors, while more resource-intensive, significantly improve the analytical sensitivity and specificity of IMA detection, enabling earlier and more accurate identification of ischemic events. Additionally, different biological matrices, such as serum, saliva, and urine, were reviewed to identify the most suitable for accurate measurements in clinical application. Although serum was considered the gold standard, non-invasive matrices such as saliva and urine are becoming increasingly feasible due to advances in technology. This review underscores the role of IMA in clinical diagnostics and suggests how advanced analytical techniques have the potential to significantly enhance patient outcomes in ischemic disease management.

Long-term outcomes of ischaemia with no obstructive coronary artery disease (INOCA): a systematic review and meta-analysis.

BACKGROUND: The prognosis of myocardial ischaemia with no obstructive coronary artery disease (INOCA) and its underlying vasomotor disorders, vasospastic angina (VSA) and microvascular angina (MVA), is not well defined. The aim of this study was to perform a systematic review and meta-analysis of studies evaluating the long-term prognosis of patients with INOCA. METHODS: We included studies evaluating the prognosis of patients with INOCA published between January 1984 and August 2023 in Medline, Embase, Web of Science and Cochrane databases. Studies were selected if they included patients who fulfilled the Coronary Vasomotor Disorders International Study Group (COVADIS) criteria for either possible or definitive VSA or MVA. The primary outcomes were composite of all-cause death and myocardial infarction (MI), and major adverse cardiovascular event (MACE) at annual intervals up to 5-year follow-up. The incidence of primary outcomes for INOCA, each INOCA endotype and by method used to determine the diagnosis was calculated using the random effects model. RESULTS: Fifty-four studies (17 302 patients) meeting the eligibility criteria were selected. The rate of all-cause death and MI with VSA was 0.7 (95% CI 0.4 to 1.0)/100 patient-years and with MVA was 1.1 (95% CI 0.7 to 1.5)/100 patient-years (p>0.05). The rate of MACE with VSA was 1.1 (95% CI 0.5 to 1.9)/100 patient-years and with MVA was 2.5 (95% CI 1.6 to 3.6)/100 patient-years (p=0.025). Patients with reduced coronary flow reserve (CFR) had higher all-cause death and MI rates than patients whose diagnosis of MVA was established based on an abnormal exercise or imaging stress test (4.7 (95% CI 2.0 to 8.4) vs 0.5 (95% CI 0.1 to 1.1) vs 1.1 (95% CI 0.5 to 2.0)/100 patient-years, p=0.001). CONCLUSIONS: Overall, patients with INOCA have a low rate of MACEs, but patients with MVA, especially those with reduced CFR, have a significantly higher rate of MACE than other subgroups, although there is high heterogeneity among the included studies. PROSPERO REGISTRATION NUMBER: CRD42021275070.

Development and Validation of Prognostic Models for Bleeding and Ischemia in Elderly Patients With Comorbid Acute Coronary Syndrome and Atrial Fibrillation.

BACKGROUND: Acute coronary syndrome and atrial fibrillation are common cardiovascular diseases in elderly individuals. Patients with comorbidities face increased risks of bleeding and ischemia; however, there is a lack of prognostic models for quantifying these risks in this special population. METHODS AND RESULTS: In this retrospective cohort study, 1851 patients (≥65 years old) with acute coronary syndrome and atrial fibrillation from 2 hospitals in China were included in the development cohort (1252 individuals) and 2 external validation cohorts (284 and 315 individuals). During 1-year follow-up, 96 Bleeding Academic Research Consortium type 3 or 5 bleeding events and 245 thromboembolic events were observed. In the development cohort, the concordance indexes for bleeding at 3, 6, and 12 mo ranged from 0.737 to 0.845 and for ischemia ranged from 0.723 to 0.777. The calibration curve and decision curve analysis indicated adequate calibration and clinical practicability. The concordance indexes varied from 0.679 to 0.809 in the validation cohorts. Subgroup analyses focusing on anticoagulant drugs and antithrombotic therapy were conducted, revealing similar discrimination and calibration. Kaplan-Meier curves demonstrated significant differences (log-rank P<0.001). Additionally, the models outperformed conventional models in concordance indexes, integrated discrimination improvement, and net reclassification improvement. CONCLUSIONS: Our study provides 2 robust prognostic models with easily available clinical factors for predicting bleeding and ischemia in elderly patients with acute coronary syndrome and atrial fibrillation. Furthermore, we provide online calculators to facilitate individualized risk evaluation and clinical decision-making. REGISTRATION: URL: www.chictr.org.cn/. Unique Identifier: ChiCTR2200067185.

Development and validation of a clinical diagnostic model for myocardial ischaemia in borderline coronary lesions based on optical pumped magnetometer magnetocardiography: a prospective observational cohort study.

OBJECTIVES: To develop and validate a clinical diagnostic model based on optical pumped magnetometer magnetocardiography (OPM-MCG) for the detection of myocardial ischaemia in patients with borderline coronary lesions prior to invasive coronary angiography (ICA). DESIGN: Prospective observational cohort study. SETTING: Single centre of the China National Clinical Research Centre for Cardiovascular Disease (NCCMRC). PARTICIPANTS: Adults with borderline coronary lesions on ICA (n=141). INTERVENTIONS: Underwent OPM-MCG before ICA and fractional flow reserve measurement. RESULTS: Five parameters were included in the final diagnostic model: MAgmax-TT, δDtsum-PN, δAgsum-C, δArsum-N and δArmin-N. 1000 bootstrap replications showed that the area under the receiver operating characteristic curve and 95% CI of the diagnostic model were 0.864 (0.803-0.925), with a sensitivity of 79.4%, specificity of 80.8%, positive predictive value of 79.4% and negative predictive value of 80.8%. Decision curve analysis showed a net benefit from the predictive model when the threshold probability of an ischaemic patient was >12%, suggesting the potential utility of the model in the real world. CONCLUSIONS: A nomogram based on five OPM-MCG parameters was developed to assess myocardial ischaemia in patients with borderline coronary lesions and has the potential to reduce the need for unnecessary ICA. TRIAL REGISTRATION NUMBER: China Clinical Trial Registry (ChiCTR2300072382).

Postmortem-Derived Exosomal MicroRNA 486-5p as Potential Biomarkers for Ischemic Heart Disease Diagnosis.

Exosomes are nanovesicles 30-150 nm in diameter released extracellularly. Those isolated from human body fluids reflect the characteristics of their cells or tissues of origin. Exosomes carry extensive biological information from their parent cells and have significant potential as biomarkers for disease diagnosis and prognosis. However, there are limited studies utilizing exosomes in postmortem diagnostics. In this study, we extended our initial research which identified the presence and established detection methodologies for exosomes in postmortem fluids. We analyzed exosomal miRNA extracted from plasma and pericardial fluid samples of a control group (n = 13) and subjects with acute myocardial infarction (AMI; n = 24). We employed next-generation sequencing (NGS) to investigate whether this miRNA could serve as biomarkers for coronary atherosclerosis leading to acute myocardial infarction. Our analysis revealed 29 miRNAs that were differentially expressed in the AMI group compared to the control group. Among these, five miRNAs exhibited more than a twofold increase in expression across all samples from the AMI group. Specifically, miR-486-5p levels were significantly elevated in patients with high-grade (type VI or above) atherosclerotic plaques, as per the American Heart Association criteria, highlighting its potential as a predictive biomarker for coronary atherosclerosis progression. Our results indicate that postmortem-derived exosomal microRNAs can serve as potential biomarkers for various human diseases, including cardiovascular disorders. This finding has profound implications for forensic diagnostics, a field critically lacking diagnostic markers.

Value of Ischemia and Coronary Anatomy in Prognosis and Guiding Revascularization Among Patients With Stable Ischemic Heart Disease.

BACKGROUND: The value of physiological ischemia versus anatomic severity of disease for prognosis and management of patients with stable coronary artery disease (CAD) is widely debated. METHODS: A total of 1764 patients who had rest-stress cadmium-zinc-telluride single-photon emission computed tomography myocardial perfusion imaging and angiography (invasive or computed tomography) were prospectively enrolled and followed for cardiac death/nonfatal myocardial infarction. The CAD prognostic index (CADPI) was used to quantify the extent and severity of angiographic disease. Prognostic value was assessed using Cox models, adjusted for pretest risk, known CAD, stressor, left ventricular ejection fraction, %ischemia and infarct, CADPI, and early (90-day) revascularization. Incremental prognostic value was evaluated using net reclassification index. RESULTS: The mean age was 69.7±9.5 years, 24.4% were women, and 29.3% had known CAD. Significant ischemia (>10%) was present in 28.4%. Nonobstructive, single, and multivessel disease was present in 256 (14.5%), 772 (43.8%), and 736 (41.7%), respectively. Early revascularization occurred in 579 (32.8%). Cardiac death/myocardial infarction occurred in 148 (8.4%) over a 4.6-year median follow-up. Both %ischemia and CADPI provided independent and incremental prognostic value over pretest clinical risk (P<0.001). In a model containing both ischemia and anatomy, ischemia was prognostic (hazard ratio per 5% ↑, 1.35 [95% CI, 1.11-1.63]; P=0.002) but CADPI was not (hazard ratio per 10-unit ↑, 1.09 [95% CI, 0.99-1.20]; P=0.07). Early revascularization modified the risk associated with %ischemia (interaction P=0.003) but not with CADPI (interaction P=0.6). %Ischemia and single-photon emission computed tomography variables added incremental prognostic value over clinical risk and CADPI (net reclassification index, 20.3% [95% CI, 9%-32%]; P<0.05); however, CADPI was not incrementally prognostic beyond pretest risk, %ischemia, and single-photon emission computed tomography variables (net reclassification index, 3.1% [95% CI, -5% to 15%]; P=0.21). CONCLUSIONS: Ischemic burden provides independent and incremental prognostic value beyond CAD anatomy and identifies patients who benefit from early revascularization. The anatomic extent of disease has independent prognostic value over clinical risk factors but offers limited incremental benefit for prognosis and guiding revascularization beyond physiological severity (ischemia).

Trends in deaths and disability-adjusted life-years of ischemic heart disease attributable to high body-mass index worldwide, 1990-2019.

BACKGROUND: The objective of this study is to evaluate the global burden of ischemic heart disease (IHD) attributable to High body mass index (HBMI) by utilizing data from Global Burden of Disease (GBD) 2019. METHODS: This study utilized data from the GBD 2019 to examine the impact of HBMI on deaths and disability-adjusted life years (DALYs). The analysis focused on age-standardized rates and considered a 30-year time frame. Trends were assessed using estimated annual percentage changes (EAPCs). RESULTS: Since 1990, a significant global increase in IHD attributable to HBMI has been observed. This increase is particularly notable among elderly males and in regions with low-middle Socio-Demographic Index (SDI), such as Central Asia and Eastern Europe. In 2019, IHD globally resulted in 1,662,339 deaths and 41,369,773 DALYs. Despite the high age-standardized death rate (20.73 per 100,000) and DALY rate (499.41 per 100,000), a declining trend was noted. This trend is reflected by the EAPCs of -0.35 for DALYs and - 0.67 for deaths. Notably, males and middle SDI countries exhibited higher rates of IHD, whereas high SDI regions such as High-income Asia Pacific and Western Europe showed decreasing trends in IHD. CONCLUSION: Over the past three decades, there has been a significant increase in IHD caused by HBMI, especially in low-middle and low SDI regions. This highlights the importance of targeted interventions in addressing this issue. Notably, regions including Central Asia, Eastern Europe, North Africa, and the Middle East have been heavily affected.

Myocardial ischaemic syndromes: a new nomenclature to harmonize evolving international clinical practice guidelines.

Since the 1960s, cardiologists have adopted several binary classification systems for acute myocardial infarction (MI) that facilitated improved patient management. Conversely, for chronic stable manifestations of myocardial ischaemia, various classifications have emerged over time, often with conflicting terminology-e.g. 'stable coronary artery disease' (CAD), 'stable ischaemic heart disease', and 'chronic coronary syndromes' (CCS). While the 2019 European guidelines introduced CCS to impart symmetry with 'acute coronary syndromes' (ACS), the 2023 American guidelines endorsed the alternative term 'chronic coronary disease'. An unintended consequence of these competing classifications is perpetuation of the restrictive terms 'coronary' and 'disease', often connoting only a singular obstructive CAD mechanism. It is now important to advance a more broadly inclusive terminology for both obstructive and non-obstructive causes of angina and myocardial ischaemia that fosters conceptual clarity and unifies dyssynchronous nomenclatures across guidelines. We, therefore, propose a new binary classification of 'acute myocardial ischaemic syndromes' and 'non-acute myocardial ischaemic syndromes', which comprises both obstructive epicardial and non-obstructive pathogenetic mechanisms, including microvascular dysfunction, vasospastic disorders, and non-coronary causes. We herein retain accepted categories of ACS, ST-segment elevation MI, and non-ST-segment elevation MI, as important subsets for which revascularization is of proven clinical benefit, as well as new terms like ischaemia and MI with non-obstructive coronary arteries. Overall, such a more encompassing nomenclature better aligns, unifies, and harmonizes different pathophysiologic causes of myocardial ischaemia and should result in more refined diagnostic and therapeutic approaches targeted to the multiple pathobiological precipitants of angina pectoris, ischaemia and infarction.

Enhancing Comprehensive Assessments in Chronic Heart Failure Caused by Ischemic Heart Disease: The Diagnostic Utility of Holter ECG Parameters.

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.

Volatilome: A Novel Tool for Risk Scoring in Ischemic Heart Disease.

Developing a novel risk score for accurate assessment of cardiovascular disease (CVD) morbidity and mortality is an urgent need in terms of early prevention and diagnosis and, thereafter, management, particularly of ischemic heart disease. The currently used scores for the evaluation of cardiovascular disease based on the classical risk factors suffer from severe limitations, including inaccurate predictive values. Therefore, we suggest adding a novel non-classical risk factor, including the level of specific exhaled volatile organic compounds that are associated with ischemic heart disease, to the SCORE2 and SCORE2-OP algorithms. Adding these nonclassical risk factors can be used together with the classical risk factors (gender, smoking, total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, diabetes mellitus, arterial hypertension, ethnicity, etc.) to develop a new algorithm and further program to be used widely.

Heterogeneous and overlapping mechanisms of ischemia and nonobstructive coronary arteries: in-hospital results of the MOSAIC-COR registry.

INTRODUCTION: Ischemia and nonobstructive coronary arteries (INOCA) remains a significant clinical issue. Recent guidelines underscore the importance of comprehensive coronary physiology assessment to make specific diagnoses and implement tailored treatment strategies. OBJECTIVES: Our primary objective was to implement comprehensive invasive diagnostics. The secondary objective was to determine the pathomechanism of INOCA in consecutive adult patients with symptomatic chronic coronary syndrome, noninvasive evidence of myocardial ischemia, and nonobstructive coronary artery disease included in the prospective MOSAIC­COR registry, and therefore, to define new INOCA subgroups. PATIENTS AND METHODS: All patients underwent comprehensive coronary physiological assessment, including resting full­cycle ratio, fractional flow reserve, index of microcirculatory resistance, and coronary flow reserve using a pressure wire and the thermodilution method. Coronary artery reactivity was assessed with acetylcholine in a provocative test. RESULTS: A total of 173 patients were enrolled (median [interquartile range] age, 66 [58-71] years; 66% women). A high prevalence of typical cardiovascular risk factors was registered. According to physiological assessment, the patients were divided into the following subgroups: epicardial vasospastic angina (EVSA; 19%), microvascular vasospastic angina (MVSA; 19%), coronary microcirculatory disease (CMD; 11%), EVSA+CMD (21%), MVSA+CMD (18%), and noncoronary disorders (12%). The diagnosis of MVSA and MVSA+CMD was more frequent in women (94% vs 76%, respectively). CONCLUSIONS: The patients diagnosed with INOCA in the MOSAIC­COR registry exhibit significant symptomatology and a high prevalence of typical cardiovascular risk factors. Myocardial ischemia in this population may be generated by various pathomechanisms that may overlap.

Ischemia with non-obstructive coronary artery (INOCA): Non-invasive versus invasive techniques for diagnosis and the role of #FullPhysiology.

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.

Screening Sportsmen and Sportswomen Over Age 35: The Relevance of an Exercise Electrocardiogram. Data From the SEEPRED Study.

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.

Assessment of Myocardial Viability in Ischemic Cardiomyopathy With Reduced Left Ventricular Function Undergoing Coronary Artery Bypass Grafting.

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.