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.

Pathogenesis, Assessment, and Treatment of Coronary Microcirculation Dysfunction. / Patogênese, Avaliação e Tratamento da Disfunção da Microcirculação Coronariana.

Cardiovascular disease is the predominant cause of mortality on a global scale. Research indicates that women exhibit a greater likelihood of presenting with non-obstructive coronary artery disease (CAD) when experiencing symptoms of myocardial ischemia in comparison to men. Additionally, women tend to experience a higher burden of symptoms relative to men, and despite the presence of ischemic heart disease, they are frequently reassured erroneously due to the absence of obstructive CAD. In cases of ischemic heart disease accompanied by symptoms of myocardial ischemia but lacking obstructive CAD, it is imperative to consider coronary microvascular dysfunction as a potential underlying cause. Coronary microvascular dysfunction, characterized by impaired coronary flow reserve resulting from functional and/or structural abnormalities in the microcirculation, is linked to adverse cardiovascular outcomes. Lifestyle modifications and the use of anti-atherosclerotic and anti-anginal medications may offer potential benefits, although further clinical trials are necessary to inform treatment strategies. This review aims to explore the prevalence, underlying mechanisms, diagnostic approaches, and therapeutic interventions for coronary microvascular dysfunction.

A doença cardiovascular é a causa predominante de mortalidade em escala global. A pesquisa indica que as mulheres, em comparação aos homens, apresentam maior probabilidade de apresentar doença arterial coronariana (DAC) não obstrutiva quando têm sintomas de isquemia miocárdica. Além disso, as mulheres tendem a apresentar uma maior carga de sintomas em relação aos homens e, apesar da presença de doença cardíaca isquêmica, são frequentemente tranquilizadas erroneamente devido à ausência de DAC obstrutiva. Nos casos de cardiopatia isquêmica acompanhada de sintomas de isquemia miocárdica, mas sem DAC obstrutiva, é imperativo considerar a disfunção microvascular coronariana como uma potencial causa subjacente. A disfunção microvascular coronariana, caracterizada por reserva de fluxo coronariano prejudicada resultante de anormalidades funcionais e/ou estruturais na microcirculação, está associada a desfechos cardiovasculares adversos. Modificações no estilo de vida e o uso de medicamentos antiateroscleróticos e antianginosos podem oferecer benefícios potenciais, embora sejam necessários mais ensaios clínicos para informar estratégias de tratamento. Esta revisão tem como objetivo explorar a prevalência, mecanismos subjacentes, abordagens diagnósticas e intervenções terapêuticas para disfunção microvascular coronariana.

Subdiaphragmatic activity-related artifacts in myocardial perfusion scintigraphy.

BACKGROUND: Myocardial perfusion imaging (MPI) with single photon emission computed tomography is an established non-invasive technique for assessing myocardial ischemia. This method involves the intravenous administration of a radiopharmaceutical that accumulates in the heart muscle proportional to regional blood flow. However, image quality and diagnostic accuracy can be compromised by various technical and patient-related factors, including high non-specific radiopharmaceutical uptake in abdominal organs such as the stomach, intestines, liver, and gall-bladder, leading to subdiaphragmatic artifacts. These artifacts are particularly problematic for evaluating inferior wall perfusion and often necessitate repeated imaging, which decreases gamma camera availability and prolongs imaging times. CONCLUSIONS: Despite numerous investigated techniques to reduce interfering gastrointestinal activity, results have been inconsistent, and current MPI guidelines provide scant information on effective procedures to mitigate this issue. Based on our experience, some possible approaches to reducing artifacts include choosing stress testing with an exercise stress test, when possible, late imaging, fluid intake, and consuming carbonated water immediately before imaging.

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).

Impact of epicardial fat on coronary vascular function, cardiac morphology, and cardiac function in women with suspected INOCA.

AIMS: Epicardial fat is a metabolically active adipose tissue depot situated between the myocardium and visceral pericardium that covers ∼80% of the heart surface. While epicardial fat has been associated with the development of atherosclerotic coronary artery disease, less is known about the relationship between epicardial fat and coronary vascular function. Moreover, the relations between excess epicardial fat and cardiac morphology and function remain incompletely understood. METHODS AND RESULTS: To address these knowledge gaps, we retrospectively analysed data from 294 individuals from our database of women with suspected ischaemia with no obstructive coronary disease (INOCA) who underwent both invasive coronary function testing and cardiac magnetic resonance imaging. Epicardial fat area, biventricular morphology, and function, as well as left atrial function, were assessed from cine images, per established protocols. The major novel findings were two-fold: first, epicardial fat area was not associated with coronary vascular dysfunction. Secondly, epicardial fat was associated with increased left ventricular concentricity (ß = 0.15, P = 0.01), increased septal thickness (ß = 0.17, P = 0.002), and reduced left atrial conduit fraction (ß = -0.15, P = 0.02), even after accounting for age, BMI, and history of hypertension. CONCLUSION: Taken together, these data do not support a measurable relationship between epicardial fat and coronary vascular dysfunction but do suggest that epicardial fat may be related to concentric remodelling and diastolic dysfunction in women with suspected INOCA. Prospective studies are needed to elucidate the long-term impact of epicardial fat in this patient population.

In a Canine Model of Septic Shock, Cardiomyopathy Occurs Independent of Catecholamine Surges and Cardiac Microvascular Ischemia.

BACKGROUND: High levels of catecholamines are cardiotoxic and associated with stress-induced cardiomyopathies. Using a septic shock model that reproduces the reversible cardiomyopathy seen over 10 days associated with human septic shock, we investigated the effects of catecholamines on microcirculatory perfusion and cardiac dysfunction. METHODS AND RESULTS: Purpose-bred beagles received intrabronchial Staphylococcus aureus (n=30) or saline (n=6). The septic animals were than randomized to epinephrine (1 µg/kg per minute, n=15) or saline (n=15) infusions from 4 to 44 hours. Serial cardiac magnetic resonance imaging, catecholamine levels, and troponins were collected over 92 hours. Serial adenosine-stress perfusion cardiac magnetic resonance imaging was performed on septic animals randomized to receive saline (n=8 out of 15) or epinephrine (n=8 out of 15). High-dose sedation was given to suppress endogenous catecholamine release. Despite catecholamine levels largely remaining within the normal range throughout, by 48 hours, septic animals receiving saline versus nonseptic animals still developed significant worsening of left ventricular ejection fraction, circumferential strain, and ventricular-aortic coupling. In septic animals that received epinephrine versus saline infusions, plasma epinephrine levels increased 800-fold, but epinephrine produced no significant further worsening of left ventricular ejection fraction, circumferential strain, or ventricular-aortic coupling. Septic animals receiving saline had a significant increase in microcirculatory reserve without troponin elevations. Septic animals receiving epinephrine had decreased edema, blunted microcirculatory perfusion, and elevated troponin levels that persisted for hours after the epinephrine infusion stopped. CONCLUSIONS: Cardiac dysfunction during sepsis is not primarily due to elevated endogenous or exogenous catecholamines nor due to decreased microvascular perfusion-induced ischemia. However, epinephrine itself has potentially harmful long-lasting ischemic effects during sepsis including impaired cardiac microvascular perfusion that persists after stopping the infusion.

[Compatibility mechanism of Qishen Yiqi Dripping Pills for treatment of myocardial ischemia based on UPLC-Q-Exactive Orbitrap-MS and network pharmacology].

Clinical efficacy and mechanism of Qishen Yiqi Dripping Pills(QSYQ) have been well researched, but the compatibility mechanism underlying its therapeutic effect still requires further analysis. This study aims to explore the compatibility mechanism of QSYQ in treating myocardial ischemia. UPLC-Q-Exactive Orbitrap-MS technique was used to obtain the absorbed blood components of QSYQ. Target proteins of the absorbed components were collected and screened using TCMSP, TCMIP, and SwissTargetPrediction databases. Disease proteins related to myocardial ischemia were obtained through GeneCards, OMIM, and DisGeNET databases. Core targets and core components were obtained using online plotting software Venny 2.1.0, STRING, and Cytoscape 3.9.1 software. David database was used for GO functional annotation and KEGG pathway enrichment of core targets, obtaining the main pathways of QSYQ in treating myocardial ischemia and drawing visualized network diagrams. The compatibility mechanism was analyzed based on "component-target", "drug-pathway", and "PI3K-AKT" characteristic pathways, and molecular docking was used for validation. This study obtained 42 absorbed blood components of QSYQ, 556 component targets, 1 980 disease targets, 69 core targets, and 15 core components. QSYQ can exert therapeutic effects on myocardial ischemia by regulating proteins such as MAPK1, RELA, SRC, JUN, and STAT3, acting on signaling pathways such as HIF-1, PI3K-AKT, Toll-like, MAPK, VEGF, etc. The interaction network diagrams of "component-target" and "drug-pathway" preliminarily elucidated the synergy among the four drugs in this prescription at the level of targets and pathways. The PI3K-AKT characteristic pathway indicated that the sovereign drug Huangqi(Astragali Radix) and minister drug Danshen(Salviae Miltiorrhizae Radix et Rhizoma) could regulate most targets in this pathway, while the assistant drug Sanqi(Notoginseng Radix et Rhizoma) cooperated with Huangqi and Danshen on IL6 and AKT proteins, and the envoy drug Jiangxiang(Dalbergiae Odoriferae Lignum) acted on AKT and RXRA proteins, with all drugs acting synergistically on proteins such as AKT, RXRA, NFKB to regulate cell survival and promote angiogenesis. Molecular docking indicated that hydrogen bonding and hydrophobic interactions might be the main forms of action, also validating the distribution of binding energy of the PI3K-AKT signaling pathway. This study analyzed the compatibility connotation of QSYQ from multiple dimensions including drugs, components, targets, and pathways, providing reference basis for the study of the mechanism of action and compatibility rules of QSYQ.

Myocardial ischemia caused by the synergistic effect of myocardial bridge and moderate stenosis: case report.

BACKGROUND: Clinical events such as angina pectoris, acute coronary syndrome, and sudden death caused by myocardial bridge (MB) have attracted increasing attention. It is still a challenge to diagnose whether MB can cause the symptoms of patients with MB. For most MB patients, medication remains the primary treatment. CASE PRESENTATION: This article reports a case of chest pain in a patient with MB in the middle segment of the left anterior descending artery (LADm) with moderate stenosis in the proximal segment (LADp). Through functional assessment, we found that neither MB nor fixed stenosis had sufficient effect on coronary blood flow to cause myocardial ischemia, but their synergistic effect resulted in myocardial ischemia. Finally, a stent was implanted in LADp and good clinical results were achieved. CONCLUSIONS: For symptomatic patients with MB combined with fixed stenosis, functional evaluation may be necessary, which has significant guiding significance for treatment strategy selection. For asymptomatic patients, early detection of myocardial ischemia may also improve the prognosis of patients.

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.

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.

Baduanjin for ischemic heart failure with mildly reduced/preserved ejection fraction (BEAR Trial): A randomized controlled trial.

AIM: While Baduanjin, a traditional Chinese mind-body exercise, has shown potential health benefits, its efficacy in improving outcomes for heart failure patients with mildly reduced or preserved ejection fraction (HFmrEF/HFpEF) has not been well documented. We aimed to investigate the adjunctive impact of Baduanjin on exercise capacity and quality of life for HFmrEF/HFpEF. METHODS: Patients with HFmrEF/HFpEF were enrolled in this multicenter randomized clinical trial. All participants were randomized to conventional cardiac rehabilitation with or without an additional 12-week Baduanjin exercise. The primary endpoint was the distance covered in a 6-min walk test (6MWD), while key secondary outcomes included quality of life measured by the Minnesota Living with Heart Failure Questionnaire (MLHFQ) and cardiopulmonary function including anaerobic threshold (VO2 AT). RESULTS: A total of 120 patients were enrolled, and 109 completed all session and tests. The mean age of the 120 patients was 60.5 years (SD, 9.21 years), and 23 (19.2%) were women. The Baduanjin group exhibited a 6.14% improvement in 6MWD compared to a 1.32% improvement in the control group (median improvement, 25.0 vs. 5.0 m; p < 0.001) at 12th week. The VO2 AT increased by 25.87% in the Baduanjin group versus 3.94% in the control group (p < 0.001). Quality of life also significantly improved in the Baduanjin group as indicated by MLHFQ score changes (-16.8% vs. -3.99%; p < 0.001). CONCLUSIONS: Adding Baduanjin to exercise-based cardiac rehabilitation for patients with ischemic HFmrEF or HFpEF are generally safe and could provide significant improvements in exercise capacity and quality of life.

Noninvasive and fast method of calculation for instantaneous wave-free ratio based on haemodynamics and deep learning.

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 iFRCT, which is calculated based on noninvasive coronary CT angiography (CTA) images and computational fluid dynamics (CFD). However, the existing methods for calculating iFRCT 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 iFRCT. 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 iFRCT 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 iFRCT 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 iFRCT calculation method based on haemodynamics and deep learning, which is important for noninvasive and rapid diagnosis of myocardial ischaemia.

Bone marrow cells contribute to seven different endothelial cell populations in the heart.

Understanding the mechanisms underlying vascular regeneration in the heart is crucial for developing novel therapeutic strategies for myocardial ischemia. This study investigates the contribution of bone marrow-derived cells to endothelial cell populations in the heart, and their role in cardiac function and coronary circulation following repetitive ischemia (RI). Chimeric rats were created by transplanting BM cells from GFP female rats into irradiated male recipients. After engraftment chimeras were subjected to RI for 17 days. Vascular growth was assessed from recovery of cardiac function and increases in myocardial blood flow during LAD occlusion. After sorting GFP+ BM cells from heart and bone of Control and RI rats, single-cell RNA sequencing was implemented to determine the fate of BM cells. Our in vivo RI model demonstrated an improvement in cardiac function and myocardial blood flow after 17 days of RI with increased capillary density in the rats subjected to RI compared to Controls. Single-cell RNA sequencing of bone marrow cells isolated from rats' hearts identified distinct endothelial cell (EC) subpopulations. These ECs exhibited heterogeneous gene expression profiles and were enriched for markers of capillary, artery, lymphatic, venous, and immune ECs. Furthermore, BM-derived ECs in the RI group showed an angiogenic profile, characterized by upregulated genes associated with blood vessel development and angiogenesis. This study elucidates the heterogeneity of bone marrow-derived endothelial cells in the heart and their response to repetitive ischemia, laying the groundwork for targeting specific subpopulations for therapeutic angiogenesis in myocardial ischemia.

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.

Personalized evaluation of the passive myocardium in ischemic cardiomyopathy via computational modeling using Bayesian optimization.

Biomechanics-based patient-specific modeling is a promising approach that has proved invaluable for its clinical potential to assess the adversities caused by ischemic heart disease (IHD). In the present study, we propose a framework to find the passive material properties of the myocardium and the unloaded shape of cardiac ventricles simultaneously in patients diagnosed with ischemic cardiomyopathy (ICM). This was achieved by minimizing the difference between the simulated and the target end-diastolic pressure-volume relationships (EDPVRs) using black-box Bayesian optimization, based on the finite element analysis (FEA). End-diastolic (ED) biventricular geometry and the location of the ischemia were determined from cardiac magnetic resonance (CMR) imaging. We employed our pipeline to model the cardiac ventricles of three patients aged between 57 and 66 years, with and without the inclusion of valves. An excellent agreement between the simulated and the target EDPVRs has been reached. Our results revealed that the incorporation of valvular springs typically leads to lower hyperelastic parameters for both healthy and ischemic myocardium, as well as a higher fiber Green strain in the viable regions compared to models without valvular stiffness. Furthermore, the addition of valve-related effects did not result in significant changes in myofiber stress after optimization. We concluded that more accurate results could be obtained when cardiac valves were considered in modeling ventricles. The present novel and practical methodology paves the way for developing digital twins of ischemic cardiac ventricles, providing a non-invasive assessment for designing optimal personalized therapies in precision medicine.