Forward problem of electrocardiography based on cardiac source vector orientations.

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.

Machine learning to identify a composite indicator to predict cardiac death in ischemic heart disease.

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.

Diagnosing Coronary Artery Disease in the Patient Presenting with Stable Ischemic Heart Disease: The Role of Anatomic versus Functional Testing.

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.

Optimal Medical Therapy for Stable Ischemic Heart Disease: Focus on Anti-anginal Therapy.

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.

The Pathophysiologic Basis of Managing Chronic Atherosclerotic Cardiovascular Disease.

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.

Ischemic Heart Disease in Women.

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.

Medical Decision-Making and Revascularization in Ischemic Cardiomyopathy.

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.

Low HDL cholesterol and the eNOS Glu298Asp polymorphism are associated with inducible myocardial ischemia in patients with suspected stable coronary artery disease.

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.

Spectrum of Ischemic Heart Disease Throughout a Woman's Life Cycle.

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.

Association between preoperative frailty and myocardial injury after noncardiac surgery in geriatric patients: study protocol for a prospective, multicentre, real-world observational, cohort trial.

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.

Area-weighted unipolar voltage to predict heart failure outcomes in patients with ischaemic cardiomyopathy and ventricular tachycardia.

AIMS: Patients with ischaemic cardiomyopathy (ICM) referred for catheter ablation of ventricular tachycardia (VT) are at risk for end-stage heart failure (HF) due to adverse remodelling. Local unipolar voltages (UV) decrease with loss of viable myocardium. A UV parameter reflecting global viable myocardium may predict prognosis. We evaluate if a newly proposed parameter, area-weighted unipolar voltage (awUV), can predict HF-related outcomes [HFO; HF death/left ventricular (LV) assist device/heart transplant] in ICM. METHODS AND RESULTS: From endocardial voltage maps of consecutive patients with ICM referred for VT ablation, awUV was calculated by weighted interpolation of local UV. Associations between clinical and mapping parameters and HFO were evaluated and validated in a second cohort. The derivation cohort consisted of 90 patients [age 68 ±8 years; LV ejection fraction (LVEF) 35% interquartile range (IQR) (24-40)] and validation cohort of 60 patients [age 67 ± 9, LVEF 39% IQR (29-45)]. In the derivation cohort, during a median follow-up of 45 months [IQR (34-83)], 36 (43%) patients died and 23 (26%) had HFO. Patients with HFO had lower awUV [4.51 IQR (3.69-5.31) vs. 7.03 IQR (6.08-9.2), P < 0.001]. A reduction in awUV [optimal awUV (5.58) cut-off determined by receiver operating characteristics analysis] was a strong predictor of HFO (3-year HFO survival 97% vs. 57%). The cut-off value was confirmed in the validation cohort (2-year HFO-free survival 96% vs. 60%). CONCLUSION: The newly proposed parameter awUV, easily available from routine voltage mapping, may be useful at identifying ICM patients at high risk for HFO.

CineECG for visualization of changes in ventricular electrical activity during ischemia.

BACKGROUND: CineECG offers a visual representation of the location and direction of the average ventricular electrical activity throughout a single cardiac cycle, based on the 12­lead ECG. Currently, CineECG has not been used to visualize ventricular activation patterns during ischemia. PURPOSE: To determine the changes in ventricular activity during acute ischemia with the use of CineECG, and relating this to changes in the ECG. METHODS: Continuous ECG's during percutaneous coronary intervention with prolonged balloon inflation from the STAFF III database were analyzed with CineECG at baseline and every 10 s throughout the first 150 s of balloon inflation. The CineECG direction was determined for the initial QRS-complex, terminal QRS-complex, ST-segment and T-wave. Changes in the CineECG were quantified by calculating the Δangle between the direction at baseline and the direction at every 10 s of inflation. Additionally, the root mean square amplitude (rmsA) of the ST-segment was computed. RESULTS: 94 patients were included. At start inflation, the median Δangle was 14.7° [7.5-33.4], 21.8° [11.4-34.2], 20.6° [8.0-43.9], and 23.5° [11.8-48.0] for the initial QRS-complex, terminal QRS-complex, ST-segment and T-wave, respectively. Meanwhile, the median rmsA increased from 0.039 mV [0.027-0.058] at baseline to 0.045 mV [0.033-0.075] at start of inflation. CONCLUSIONS: CineECG was able to detect immediate changes in ventricular electrical activity during induced ischemia, while changes in the ST-segment of the ECG were still subtle. Therefore, CineECG might support the early detection of acute ischemia, even before distinct ECG changes become visible.

Harmony in Chaos: Deciphering the Influence of Ischemic Cardiomyopathy and Non-Cardiac Comorbidities on Holter ECG Parameters in Chronic Heart Failure Patients: A Pilot Study.

Background and Objective: In the landscape of heart failure, non-cardiac comorbidities represent a formidable challenge, imparting adverse prognostic implications. Holter ECG monitoring assumes a supplementary role in delineating myocardial susceptibility and autonomic nervous system dynamics. This study aims to explore the potential correlation between Holter ECG parameters and comorbidities in individuals with ischemic cardiomyopathy experiencing heart failure (HF), with a particular focus on the primary utility of these parameters as prognostic indicators. Materials and Methods: In this prospective inquiry, a cohort of 60 individuals diagnosed with heart failure underwent stratification into subgroups based on the presence of comorbidities, including diabetes, chronic kidney disease, obesity, or hyperuricemia. Upon admission, a thorough evaluation of all participants encompassed echocardiography, laboratory panel analysis, and 24 h Holter monitoring. Results: Significant associations were uncovered between diabetes and unconventional physiological indicators, specifically the Triangular index (p = 0.035) and deceleration capacity (p = 0.002). Pertaining to creatinine clearance, notable correlations surfaced with RMSSD (p = 0.026), PNN50 (p = 0.013), and high-frequency power (p = 0.026). An examination of uric acid levels and distinctive Holter ECG patterns unveiled statistical significance, particularly regarding the deceleration capacity (p = 0.045). Nevertheless, in the evaluation of the Body Mass Index, no statistically significant findings emerged concerning Holter ECG parameters. Conclusions: The identified statistical correlations between non-cardiac comorbidities and patterns elucidated in Holter ECG recordings underscore the heightened diagnostic utility of this investigative modality in the comprehensive evaluation of individuals grappling with HF. Furthermore, we underscore the critical importance of the thorough analysis of Holter ECG recordings, particularly with regard to subtle and emerging parameters that may be overlooked or insufficiently acknowledged.

Coronary microvascular dysfunction.

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.

Intracoronary electrocardiogram detects coronary microvascular dysfunction and ischemia in patients with no obstructive coronary arteries disease.

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.

NT-pro BNP level at dialysis initiation is a useful biomarker for predicting hospitalization for ischemic heart disease.

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.

Men with nonobstructive coronary disease have higher burden of ischemic heart disease detected by cardiopulmonary exercise test.

BACKGROUND: Nonobstructive coronary artery disease (NOCAD), characterized by the presence of myocardial ischemic symptoms and signs without obstructive coronaries, is a common clinical condition, but it is less well understood. Few studies have analyzed the gender differences in inducible myocardial ischemia assessed by cardiopulmonary exercise test (CPET) in NOCAD. METHODS: We conducted a study of 289 NOCAD patients (mean age 60, 56% women) with ischemic symptoms and confirmed ⫹50% coronaries stenoses by coronary angiography who underwent symptom-limited CPET. We assessed ischemic response using predicted % peak VO2 , O2 pulse trajectory, and exercise ECG test. RESULTS: Men with NOCAD had significantly lower predicted % peak VO2 (62% vs. 73%), higher proportions of flattening pattern (16% vs. 2%), and downward patterns of O2 pulse trajectory (2% vs. 0%) (p < .0001) compared with women. In contrast, women with NOCAD had a higher prevalence of shallow patterns of O2 pulse trajectory (21% vs. 6%, p < .0001). Men with NOCAD had a higher risk ischemic profile (medium risk: 63% vs. 54%, high risk: 18% vs. 4%, p < .0001). After adjustment, men with NOCAD had significantly lower predicted % peak VO2 (ß -27.4, 95% CI -30.74 to -24.07), higher risk for abnormal O2 pulse trajectories (OR 4.21, 95% CI 1.93 to 9.19), and myocardial ischemia risk per CPET parameters (OR 3.14, 95% CI 1.78 to 5.54) (p < .0001). CONCLUSION: Men with NOCAD had a higher risk profile for ischemic heart disease per CPET. Therefore, they should receive rigorous management and follow-up to prevent cardiovascular events.

Multimodality Risk Assessment of Patients with Ischemic Heart Disease Using Deep Learning Models Applied to Electrocardiograms and Chest X-rays.

Comprehensive management approaches for patients with ischemic heart disease (IHD) are important aids for prognostication and treatment planning. While single-modality deep neural networks (DNNs) have shown promising performance for detecting cardiac abnormalities, the potential benefits of using DNNs for multimodality risk assessment in patients with IHD have not been reported. The purpose of this study was to investigate the effectiveness of multimodality risk assessment in patients with IHD using a DNN that utilizes 12-lead electrocardiograms (ECGs) and chest X-rays (CXRs), with the prediction of major adverse cardiovascular events (MACEs) being of particular concern.DNN models were applied to detection of left ventricular systolic dysfunction (LVSD) on ECGs and identification of cardiomegaly findings on CXRs. A total of 2107 patients who underwent elective percutaneous coronary intervention were categorized into 4 groups according to the models' outputs: Dual-modality high-risk (n = 105), ECG high-risk (n = 181), CXR high-risk (n = 392), and No-risk (n = 1,429).A total of 342 MACEs were observed. The incidence of a MACE was the highest in the Dual-modality high-risk group (P < 0.001). Multivariate Cox hazards analysis for predicting MACE revealed that the Dual-modality high-risk group had a significantly higher risk of MACE than the No-risk group (hazard ratio (HR): 2.370, P < 0.001), the ECG high-risk group (HR: 1.906, P = 0.010), and the CXR high-risk group (HR: 1.624, P = 0.018), after controlling for confounding factors.The results suggest the usefulness of multimodality risk assessment using DNN models applied to 12-lead ECG and CXR data from patients with IHD.