Patients with angina and non-obstructive coronary arteries (ANOCA) or myocardial ischaemia with non-obstructive coronary arteries (INOCA) comprise a relatively large subgroup within those with ischaemic heart disease. Advances in the understanding of disease mechanisms, diagnostic tests and multidisciplinary care are improving awareness of the needs of affected individuals. However, practice variations and suboptimal management promulgate the health burden and increase health care resource consumption. Clinical standards represent a limited number of quality statements that describe the care patients should be offered by health professionals and providers for a specific clinical condition or defined clinical pathway in line with current best evidence. Clinical standards should address implementation of this evidence along with education of patients and healthcare professionals, multidisciplinary care networks, and research. In this consensus statement, we highlight contemporary evidence and stakeholder views, including clinicians and patients, to provide an international perspective for developing clinical standards for services involving ANOCA/INOCA patients. A clinical service for ANOCA/INOCA should "consider the whole patient" and provide a multidisciplinary, patient-centred service.

Electrocardiographic (ECG) abnormalities serve as important predictors of future cardiovascular events. However, the specific cardiac abnormalities that bridge the gap between ECG abnormalities and subsequent events remain poorly understood. This study aimed to evaluate the relationship between ECG abnormalities and the prevalence of coronary artery disease (CAD) in propensity score-matched patients with suspected CAD who underwent comprehensive cardiac computed tomography (CT).

A total of 357 patients suspected of CAD underwent ECG and cardiac CT assessments, including calcium scoring, stress dynamic CT perfusion (CTP), coronary CT angiography (CCTA), and CT late enhancement. Propensity score matching based on demographic parameters and CAD risk factors was performed, resulting in 286 matched patients (143 without ECG abnormalities and 143 with ECG abnormalities).

In both unadjusted and propensity score-matched analyses, ECG abnormalities were significantly associated with microvascular dysfunction and myocardial scarring (p < 0.05 for both analyses). However, no significant associations were observed between ECG abnormalities and coronary calcification severity or obstructive CAD (≥ 50% luminal narrowing) in the propensity score-matched patients. Among matched patients without obstructive CAD on CCTA, those with ECG abnormalities exhibited a higher prevalence (30%) of microvascular dysfunction, particularly in the diffuse-transmural pattern, compared to that (14%) of patients without ECG abnormalities (p < 0.01).

ECG abnormalities may not be reliable indicators of the presence of obstructive CAD. However, given their association with microvascular dysfunction, CAD evaluation with comprehensive cardiac CT, including dynamic CTP, is recommended for patients exhibiting ECG abnormalities, particularly to evaluate myocardial perfusion abnormalities.

Question We investigated whether ECG abnormalities in patients suspected of having CAD are linked to epicardial stenosis, microvascular dysfunction, or myocardial scarring. Findings After adjusting for traditional risk factors using propensity-score matching, ECG abnormalities were associated with microvascular dysfunction and myocardial scarring, but not with epicardial coronary stenosis. Clinical relevance These results suggest that ECG abnormalities may offer important insights into tissue-level changes and microvascular pathology, rather than simply reflecting epicardial stenosis, thereby underlining the need for comprehensive cardiac assessment in patients with ECG changes.

The occurrence of coronary microvascular dysfunction (CMD) after primary PCI in DM patients with STEMI and its impact on prognosis remains elusive.

This single-center retrospective observational study included 293 patients diagnosed with DM and STEMI. The caIMR was calculated using the measurement software FlashAngio, while cardiac magnetic resonance parameters were quantified using the post-processing software Cvi42. CMD was defined as caIMR ≥ 25 U. The primary endpoint was MACE, defined as all-cause mortality, non-fatal myocardial infarction, ischemia-driven revascularization, and heart failure.

MACE occurred in 86 patients (29.4%) during a median follow-up of 31 months. A significant correlation was identified between caIMR and both microvascular obstruction (MVO) (R = 0.61, P < 0.001) and infarct size (IS) (R = 0.39, P < 0.001). Furthermore, caIMR ≥ 25 was identified as an independent risk factor for MACE (HR, 2.99; 95% CI, 1.78-5.03; P < 0.001). Additionally, the integration of caIMR into risk modeling significantly improved MACE prediction (Net reclassification improvement 0.264, P<0.001; Integrated discrimination improvement 0.060, P<0.001). Lastly, the Kaplan-Meier survival curves displayed that patients with caIMR ≥ 25 were at a higher risk of MACE (log-rank P < 0.001).

The caIMR demonstrated a satisfactory correlation with CMR-determined MVO and IS in DM patients with STEMI. Elevated caIMR was independently linked to a higher risk of MACE in diabetic STEMI patients post-PCI, serving as an effective predictor for MACE.

Angio-based microvascular resistance (AMR) was proposed as a tool to quantitatively assess coronary microvascular based on single angiographic projection. The aims of this study are to assess the diagnostic accuracy and prognostic significance of AMR in ST-segment elevation myocardial infarction (STEMI) patients.

AMR was measured (Of these, 22 patients measured index of microvascular resistance (IMR)) in 70 STEMI patients after primary percutaneous coronary intervention (pPCI). ST-segment resolution (STR) was assessed 2 h after pPCI simultaneously. Transthoracic echocardiography was performed within 1 day and approximately 1 year after pPCI. STEMI patients underwent pPCI were followed up for 7.3 years and the primary endpoint was the major adverse cardiac and cerebral events (MACCEs).

AMR showed significant correlations with IMR (R = 0.334, P = 0.005). AMR has good predictive power for STR after pPCI (area under the curve: 0.889, sensitivity: 94.59%, specificity: 75.76%) in receiver operating characteristic (ROC) curve. Low-AMR patients showed markedly improved left ventricular ejection fraction (LVEF) 1 year after pPCI (42(40-49) vs. 41(39-44), P = 0.041). High-AMR patients showed higher risk for MACCEs than those with Low-AMR (HR = 3.90, P = 0.02). In multivariate cox regression analysis, AMR was considered an independent predictor of MACCEs (HR: 1.153, P = 0.020).

AMR is a reliable tool for the estimation of microvascular resistance and prognosis in the absence of intracoronary pressure-temperature sensor wire and adenosine based on single angiographic projection.

To examine the effects of fluctuations in fasting blood glucose (FBG) levels on left ventricular function in patients with T2DM and coronary microcirculation dysfunction (CMD).

A total of 290 patients with T2DM who received glucose-lowering therapy during hospitalization and were subsequently followed up for 18 months at the First Affiliated Hospital of Harbin Medical University, were enrolled in this study. 135 were diagnosed with CMD and were assigned to the CMD group, whereas 155 patients without CMD were allocated to the non-CMD group. The fasting blood glucose coefficient of variation (FBG-CV) was calculated for all participants. The CMD group was further stratified into three subgroups based on their FBG-CV values: CMD1 (FBG-CV > 25%), CMD2 (FBG-CV 15% ~ 25%), and CMD3 (FBG-CV < 15%). The left ventricular function, assessed by left ventricular ejection fraction (LVEF) and the E/e' ratio, was compared within each group before and after the follow-up period. This study was registered in the Chinese Clinical Trial Register, ChiCTR-ORC-16009800.

After the end of follow-up, the E/e' ratio in CMD1 was significantly higher than that in CMD2 and CMD3 (14.35 vs 8.57; p < 0.01; 14.35 vs 6.61; p < 0.01), and the E/e' ratio in CMD2 was significantly higher than that in CMD3 (8.57 vs 6.61; p < 0.01). Compared to the baseline measurements, the E/e' ratio in CMD1 showed a significant increase after an average 17.8 months of follow up (14.35 vs 8.44; p < 0.001). We found elevated E/e' ratio was associated with an increased FBG-CV level (odds ratio [OR]: 2.571; 95% CI 1.819-3.634; p < 0.001). In multivariate logistic analysis, course of diabetes (OR:1.062; 1.016-1.11; P = 0.007) and CMD (OR:2.231; 1.303-3.819; P = 0.003), were significantly associated with elevated E/e' ratio, while oral stains drugs (OR = 0.412 95% CI 0.237-0.715; P = 0.002) and insulin injections (OR = 0.536 95% CI 0.311-0.924; P = 0.025) behaved as a protective factor.

Our study clarified the association between FBG-CV levels and the E/e' ratio in a prospective cohort study. In T2DM patients with CMD, FBG-CV > 25% may adversely affect left ventricular diastolic function, whereas an optimal FBG-CV is considered to be less than 15%.

Sudden cardiac death is the most unpredictable and devastating consequence of hypertrophic cardiomyopathy, most often caused by persistent ventricular tachycardia or ventricular fibrillation. Although myocardial hypertrophy, fibrosis, and microvascular disorders are the main mechanisms of persistent reentrant ventricular arrhythmias in patients with advanced hypertrophic cardiomyopathy, the cardiomyocyte mechanism based on ion channel abnormalities may play an important role in the early stages of the disease.

Maximal oxygen uptake/consumption is an important variable determining exercise performance. It is generally considered to be limited largely, but not exclusively, by maximal cardiac output (CO), which limits the ability of heart to pump oxygen-rich arterial blood to working muscles. Cardiac output is a product of heart rate and stroke volume, which is the amount of blood ejected from the heart by one heart beat. Exercise training, especially of the endurance type, can increase maximal CO substantially. A straightforward way for the heart to increase maximal CO would be to increase maximal heart rate, but this does not happen; instead, maximal heart rate tends to be reduced after training. This is because heart rate is the most important determinant of myocardial oxygen consumption, and ventricular filling and myocardial blood flow (MBF) would be compromised by further increases in heart rate, given that MBF is blunted by contractions and occurs principally during diastole. Myocardial oxygen extraction is already high at rest and is increased further in endurance-trained athletes, making their hearts even more dependent on increases in MBF. The trained heart therefore also shows reduced MBF, enhanced blood mean transit time and higher myocardial vascular resistance at rest and during submaximal exercise, although MBF reserve is not improved. It follows logically that MBF is an important determinant of myocardial performance, and it is proposed in this review that cardiac afferent sensory nerves might contribute to controlling and limiting heart rate, hence maximal CO, in order to protect the heart from ischaemia.

Heart failure is a prevalent global health issue. Heart failure with preserved ejection fraction (HFpEF), which already represents half of all heart cases worldwide, is projected to further increase, driven by aging populations and rising cardiovascular risk factors. Effective therapies for HFpEF remain limited, particularly due to its pathophysiological heterogeneity and incomplete understanding of underlying pathomechanisms and implications. Coronary microvascular dysfunction (CMD), characterized by structural and functional changes in the coronary microcirculation, is increasingly recognized as a significant factor in HFpEF even though the exact nature of their causal relationship is still unclear. This review explores prevalence, prognostic implications, and potential therapeutic targets for CMD in HFpEF. CMD's role in HFpEF might involve impaired coronary blood flow regulation, leading to myocardial ischemia, impaired relaxation, and/or adverse remodeling. Vice versa, increased wall stress in patients with HFpEF might elevate coronary resistances, further worsening microvascular perfusion. Finally, abnormalities in substrate metabolism might cause both CMD and HFpEF. Current treatments, including pharmacotherapy and device-based therapies, show limited success, highlighting the need for more targeted approaches. New possible therapies, such as the coronary sinus reducer device, may show promise in improving myocardial perfusion and function. However, further large-scale studies are required to elucidate the mechanistic links between CMD and HFpEF and to develop specialized treatments for distinct heart failure phenotypes.

More than half of ST-segment elevation myocardial infarction (STEMI) patients have coronary microcirculatory dysfunction (CMD) after percutaneous coronary intervention (PCI). This study aimed to explore the role of CMD in the occurrence of contrast-induced acute kidney injury (CI-AKI) in patients with STEMI.

This was a single-centre retrospective clinical observational study. Coronary angiography-derived index of microcirculatory resistance (caIMR) was measured and used to assess CMD. Regression analysis was used to identify risk factors for CI-AKI. Restricted cubic splines (RCS) was employed to examine the dose-response relationship between caIMR and CI-AKI. The predictive accuracy of the models was assessed with net reclassification index (NRI), and integrated discrimination improvement (IDI).

This study included 745 patients, the incidence of CI-AKI was 10.6% (79/745). Multivariate logistic regression identified caIMR (OR = 1.072, 95% CI: 1.051-1.094) as an independent predictor of CI-AKI. RCS analysis indicated a linear dose-response relationship between caIMR and CI-AKI. Receiver operating characteristic (ROC) analysis demonstrated that the areas under the curve for caIMR was 0.725, the optimal cutoff value was 25.95 U. Integration of caIMR could significantly improve the risk model for CI-AKI in STEMI patients (NRI = 0.721, IDI = 0.102, P < 0.001).

Elevated caIMR is an independent risk factor for the development of CI-AKI after PCI in STEMI patients. Integrating caIMR significantly improves the risk model for CI-AKI.

Coronary microvascular disease (CMVD), marked by dysfunction of the small coronary vessels, poses significant diagnostic challenges due to the complexity and high cost of current procedures like the index of microcirculatory resistance (IMR). This study aimed to identify metabolomic biomarkers from coronary artery samples to facilitate CMVD diagnosis using advanced bioinformatics techniques-specifically, random forest algorithms and generalized linear models (GLMs)-to develop more cost-effective blood-based diagnostics.

In this prospective study, 68 patients scheduled for coronary angiography and IMR assessment were enrolled. Plasma samples obtained from their coronary arteries were analyzed using untargeted metabolomics with liquid chromatography-mass spectrometry. Advanced bioinformatics methods were applied: random forest algorithms were utilized for feature selection to identify significant metabolites, and GLMs were constructed for predictive modeling. The diagnostic performance of the models was evaluated through receiver operating characteristic (ROC) curve analysis.

The random forest analysis identified the top 10 metabolites that significantly contributed to the classification of CMVD. The GLM built using these metabolites demonstrated excellent diagnostic accuracy, achieving area under the ROC curve (AUC) values of 0.984 in the initial (discovery) cohort and 0.938 in the subsequent (validation) cohort. The use of mathematical modeling enhanced the robustness and interpretability of the biomarker selection process.

Advanced bioinformatics techniques, including random forest algorithms and GLMs, effectively identified key metabolites associated with CMVD. While the collection of coronary artery blood samples is invasive due to the necessity of coronary angiography, this method offers a more practical and cost-effective alternative to IMR measurement, potentially improving the diagnostic approach for CMVD.

Coronavirus disease 2019 (COVID-19) has been associated with impaired endothelial and vascular function. We investigated whether intervention with glycocalyx dietary supplement (GDS), containing glucosamine sulfate and fucoidan, improves endothelial glycocalyx and vascular function after COVID-19 infection.

Fifty-seven convalescent patients 14 days after mild-to-moderate COVID-19 infection managed in an outpatient setting were randomized to receive GDS (n = 29) or placebo (n = 28) for 4 consecutive months. We measured at baseline and at 4 months: (a) perfused boundary region (PBR) of the sublingual microvessels with a diameter range of 4-25 μm, as a marker of endothelial glycocalyx integrity, (b) pulse wave velocity and augmentation index, (c) coronary flow reserve using Doppler echocardiography, and (d) malondialdehyde and protein carbonyls as oxidative stress markers.

Four months after treatment, patients who received GDS showed a greater reduction in PBR 4-25 μm (-6.8% vs. -1.3%), pulse wave velocity (-13.2% vs. -3%), augmentation index (-28.5% vs. -2.5%), malondialdehyde (-26% vs. -2.9%), protein carbonyls (-31.3% vs. -1%) and a greater increase in coronary flow reserve (12.9% vs. 1.6%) compared to placebo (p < .05). In the GDS group, the reduction in PBR 4-25 μm was associated with the corresponding decrease in pulse wave velocity (r = .31, p = .047), malondialdehyde, and protein carbonyls, as well as with the increase in coronary flow reserve (r = -.59, p = .008) at follow-up. Post-treatment, none of the patients under GDS reported post-COVID symptoms compared to 21.4% of the patients under placebo.

Four-month treatment with GDS may improve endothelial glycocalyx and vascular function after COVID-19 infection.

URL: https://www.

gov. Unique identifier: NCT05185934.

Patients with angina and no obstructive coronary artery disease frequently have vasomotor dysfunction as the underlying mechanism for symptoms. Patients with vasomotor dysfunction have a high angina burden and their treatment frequently fails to reduce complaints sufficiently. Targeted therapies are currently unavailable due to heterogeneity in the patient population and incomplete understanding of the underlying pathophysiological mechanisms. One of the vasomotor dysfunction endotypes, epicardial spasm, is hypothesized to be a possible target for endothelin receptor antagonism treatment.

The EDIT-CAS trial is a registry based, double blind, randomised, placebo-controlled clinical trial and aims to compare the efficacy of 10 weeks of add-on bosentan treatment versus placebo to prevent epicardial spasm at repeat spasm provocation test. Secondary and explorative outcomes are the effect on anginal complaints, safety of bosentan treatment, changes in coronary reactivity and the relationship between baseline endothelin levels and treatment success. We will include 100 patients with previously diagnosed epicardial vasospasm on a maximal triggering dose of 100 micrograms of acetylcholine and continuing angina(-like) symptoms at least weekly despite optimal medical treatment.

The is registered in Clinical Trials Information System (2023-507782-25-00) and ClinicalTrials.gov (NCT06432452).

Type 2 diabetes is a stronger risk factor for cardiovascular disease (CVD) in women compared with men possibly due to higher susceptibility to develop myocardial microvascular dysfunction. We investigated sex-dependent effects of risk factors on myocardial blood flow (MBF) and myocardial flow reserve (MFR) in individuals with type 2 diabetes without overt CVD.

Cross-sectional analysis of a prospective study including 901 individuals recruited between 2020 and 2023. All participants underwent a cardiac 82-Rubidium positron emission tomography/computed tomography scan to quantify MBF at rest and during pharmacologically induced stress, allowing for calculation of MFR. Linear regression, with/without interaction terms for sex, was used to test whether sex modified the association between MFR/MBF and risk factors.

Mean (SD) age was 65 (8.9) years, diabetes duration was 14 (8.4) years, and 266 (29.5%) were women. Women had higher MBF at rest and stress but had lower MFR (mean (SD) 2.44 (0.67) vs. 2.59 (0.77), p = 0.003) than men. A similar proportion of men and women (21.1% vs. 23.7%) had an MFR < 2. The decline in predicted MFR with age differed between sexes. At age 55, women had a mean MFR that was 0.29 lower than men (95% CI: - 0.44 to - 0.14), but by age 75, this difference had nearly disappeared (- 0.04, 95% CI: - 0.19 to 0.11). However, after adjustment for other risk factors, the interaction between sex and age was not statistically significant (p = 0.057). No other risk factors exhibited significant sex-dependent interactions.

In individuals with type 2 diabetes without overt CVD, women exhibited lower MFR than men, primarily due to higher MBF at rest, suggesting sex-related differences. While MFR declined in both sexes, the sex difference was more pronounced in younger individuals and diminished over time. These findings underscore the need for further research into sex-specific thresholds for MFR in cardiovascular risk stratification.

More than 400 different types of post-translational modifications (PTMs), including O-GlcNAcylation and phosphorylation, combine to co-ordinate almost all aspects of protein function. Often, these PTMs overlap and the specific relationship between O-GlcNAcylation and phosphorylation has drawn much attention. In the last decade, the significance of this dynamic crosstalk has been linked to several chronic pathologies of cardiovascular origin. However, very little is known about the pathophysiological significance of this crosstalk for vascular smooth muscle cell dysfunction in cardiovascular disease. O-GlcNAcylation occurs on serine and threonine residues which are also targets for phosphorylation. A growing body of research has now emerged linking altered vascular integrity and homeostasis with highly regulated crosstalk between these PTMs. Additionally, a significant body of evidence indicates that O-GlcNAcylation is an important contributor to the pathogenesis of neointimal hyperplasia and vascular restenosis responsible for long-term vein graft failure. In this review, we evaluate the significance of this dynamic crosstalk and its role in cardiovascular pathologies, and the prospects of identifying possible targets for more effective therapeutic interventions.

Ischemic heart disease (IHD) is a leading cause of morbidity and mortality worldwide, presenting with acute and chronic coronary syndromes. Although coronary atherosclerosis is a major cause of IHD, many patients with angina or myocardial ischemia do not have obstructive coronary heart disease and impairment of the coronary microcirculation has been increasingly implicated as a relevant cause of IHD. Therefore, coronary microvascular dysfunction (CMD) refers to a term covering a wide spectrum of structural and functional alterations which affect the coronary microcirculation leading to myocardial ischemia and angina. The advent of non-invasive and invasive functional tests has exponentially broadened the ability to recognize CMD and delineate related clinical and biochemical features. Despite major advances in diagnosing and stratifying this condition, therapeutic strategies remain limited and poorly defined. In this review, we will provide an overview of the pathophysiology and the diagnostic evaluation of CMD across the spectrum of cardiovascular diseases. Furthermore, we will discuss the novel therapeutic strategies available for these patients in the perspective of a personalized medicine approach.

Obesity is a major cardiovascular risk factor associated with coronary microvascular dysfunction, which can be noninvasively assessed using myocardial flow reserve (MFR) on positron emission tomography (PET). As impaired MFR identifies high-risk patients, we assessed whether body mass index (BMI) modifies the association between MFR and cardiovascular outcomes.

Consecutive patients with no known coronary artery disease who had a clinically indicated PET were enrolled and followed prospectively for incident outcomes (all-cause death, major adverse cardiovascular events (MACE), and heart failure admissions). Multivariable-adjusted Cox proportional hazards models were used to study the association between MFR, and incident events stratified by BMI categories.

The study population consisted of 3397 patients; median (IQR) age 67 (59-74) years, 55.2% female, 63.9% White, 17.6% with a BMI of 18.5-<25 kg/m2, 27.5% with a BMI of 25-<30 kg/m2, 38.6% with a BMI of 30-<40 kg/m2, and 16.3% with a BMI of ≥40 kg/m2. The median (IQR) MFR was 2.35 (1.96-2.80). Over a median (IQR) follow-up time of 1.34 (.43-2.43) years, there were 125 incident events (56 MACE, 6 HF admissions, and 70 deaths). In adjusted analyses, a .1-unit increase in MFR was significantly associated with decreased incident outcomes; HR (95% CI):0.91 (95% CI .84-.99) for BMI 18.5-<25 kg/m2, .88 (.83-.94) for BMI 25-<30 kg/m2, .93 (.87-.99) for BMI 30-<40 kg/m2, and .88 (.76-1.01) for BMI ≥40 kg/m2. There was no significant interaction between MFR and BMI; P = .381.

PET-derived global MFR is inversely associated with subsequent cardiovascular outcomes in all BMI categories.

To determine the most important patient factors influencing quantitative MBF and to report the lower (LRL) and upper (URL) reference limits for 13N-ammonia positron emission tomography (PET) myocardial perfusion imaging (MPI).

Patients who underwent 13N-ammonia PET-MPI were screened, and those with evidence of myocardial ischemia or scar, known cardiomyopathy, impaired left ventricular function, non-response to vasodilators, and those who underwent a stress-rest protocol were excluded. Multiple linear regression analyses were performed to identify independent predictors of rest MBF (rMBF), stress MBF (sMBF), and myocardial flow reserve (MFR), and predictor importance was calculated. Finally, median, LRL, and URL for rMBF, sMBF, and MFR were calculated based on the presence of predictors.

Among 784 patients with a median coronary artery calcium score (CACS) of 69, median rMBF was 0.75mL∙min- 1∙g- 1 (LRL = 0.49 mL∙min- 1∙g- 1; URL = 1.33 mL∙min- 1∙g- 1), median sMBF was 2.41mL∙min- 1∙g- 1 (LRL = 1.42 mL∙min- 1∙g- 1; URL = 3.73 mL∙min- 1∙g- 1), and median MFR was 3.09 (LRL = 2.11; URL = 4.65). The body mass index (BMI) was the single most important independent predictor of rMBF, sMBF, and MFR (predictor importance of 72%, 87%, and 41%, respectively; standardized β=-0.434, -0.566 and - 0.174, respectively). Additional predictors were sex and hypertension for rMBF, sex for sMBF, and hypertension and CACS for MFR.

In patients without flow-limiting CAD, MBF is strongly influenced by the patient's habitus, whereby median and reference limits for sMBF and rMBF decrease with increasing BMI. Consequently, MFR exhibits stable lower reference limits across a wide range of BMI and may be considered the most robust quantitative parameter derived from 13N-ammonia PET-MPI.

Background: The soluble triggering receptor expressed on myeloid cells 2 (sTREM2) is linked to the progression of cardiovascular conditions, but its role in coronary microcirculation dysfunction (CMD) is not yet clear. Methods: A cross-sectional observational study from July 2023 to May 2024 was conducted in the China-Japan Friendship Hospital, after registration in the ClinicalTrials database (Registry Name: Coronary Microvascular Dysfunction in Angina Patients With Non-obstructive Coronary Artery Disease (ANOCA-CMD); Registry Number: NCT06503640; Registry Date: 23 September 2022). This cross-sectional study involved 76 subjects, including 55 patients with CMD and 21 without CMD, admitted to the China-Japan Friendship Hospital. CMD was defined by a coronary flow reserve (CFR) < 2.5 or index of microvascular resistance (IMR) ≥ 25. sTREM2 levels were measured using an enzyme-linked immunosorbent assay. Linear correlation analysis assessed the relationship between sTREM2 levels and CFR, IMR, microvascular resistance reserve (MRR), and the resistive reserve ratio (RRR). Univariate and multivariate regression analyses further examined the association between sTREM2 and CMD. Additionally, receiver operating characteristic (ROC) analysis was used to evaluate the diagnostic accuracy of plasma sTREM2 for identifying CMD patients. Results: Elevated sTREM2 levels were found in the CMD group. Correlation analysis showed a significant positive relationship with IMR and an inverse correlation with CFR, MRR, and RRR. After adjusting for confounders, sTREM2 was found to be an independent risk factor for CMD [OR = 1.003, 95% CI 1.001-1.007, p = 0.008]. ROC analysis revealed a sensitivity of 59.46%, specificity of 90.48%, and an AUC of 0.7677 (95% CI: 0.6481-0.8872, p = 0.008) for CMD diagnosis at a threshold of 595.5 pg/mL, indicating good diagnostic performance. Conclusions: Elevated sTREM2 levels in CMD patients indicate its potential as a biomarker.

Quantitative stress perfusion (qPerf) cardiac magnetic resonance (CMR) imaging is a noninvasive approach used to quantify myocardial blood flow (MBF). Compared with visual analysis, qPerf CMR has superior diagnostic accuracy in the detection of myocardial ischemia and assessment of ischemic burden. In the evaluation of epicardial coronary artery disease (CAD), qPerf CMR improves the distinction of single-vessel from multivessel disease, yielding a more accurate estimate of the ischemic burden, and in turn improving patient management. In patients with chest pain without epicardial CAD, the findings of lower stress MBF and myocardial perfusion reserve (MPR) allow the diagnosis of microvascular dysfunction (MVD). Given its accuracy, MBF quantification with stress CMR has been introduced into the most recent recommendations for diagnosis in patients who have ischemia with nonobstructive CAD. Recent studies have shown a greater decrease in stress MBF and MPR in patients with three-vessel CAD compared with those in patients with MVD, demonstrating an important role that quantitative stress CMR can play in differentiating these etiologies in patients with stable angina. In cases of hypertrophic cardiomyopathy and cardiac amyloidosis, qPerf CMR aids in early diagnosis of ischemia and in risk assessment. Ischemia also results from alterations in hemodynamics that may occur with valve disease such as aortic stenosis or in cases of heart failure. qPerf CMR has emerged as a useful noninvasive tool for detection of cardiac allograft vasculopathy in patients who have undergone heart transplant. The authors review the basic principles and current primary clinical applications of qPerf CMR. ©RSNA, 2025 Supplemental material is available for this article. See the invited commentary by Leung and Ng in this issue.

Coronary microvascular dysfunction (CMD) is a clinical syndrome of myocardial ischemia caused by structural and/or functional abnormalities of pre-coronary arterioles and arterioles. While genetics and other factors play a role in CMD etiology, the key pathogenic mechanism remains unclear. Currently, the diagnostic procedure for CMD is still cumbersome, and there is a lack of effective targeted interventions. Single nucleotide polymorphisms (SNPs) offer promise in addressing these issues. SNPs, reflecting common genetic variations, have garnered extensive investigation across multiple diseases. Several SNPs associated with CMD have been discovered, and some have the potential to be therapeutic targets. Nevertheless, studies on CMD-related SNPs are relatively nascent and limited in number. In this review, we summarize the previously reported CMD-associated SNPs, delineate their pathophysiological mechanisms, and predict potentially important CMD sites by analyzing the SNPs linked to diseases sharing similar pathogenetic mechanisms and risk factors, such as coronary artery disease. We aim to explore reliable genetic markers implicated in CMD risk and prognosis, thereby providing a novel approach for early diagnosis and gene-targeted interventions of CMD in subsequent studies.

Microvascular ischemia, especially in the heart and kidneys, is associated with inflammation and metabolic perturbation, resulting in cellular dysfunction and end-organ failure. Heightened production of adenosine from extracellular nucleotides released in response to inflammation results in protective effects, inclusive of adaptations to hypoxia, endothelial cell nitric oxide release with the regulation of vascular tone, and inhibition of platelet aggregation. Purinergic signaling is modulated by ectonucleoside triphosphate diphosphohydrolase-1 (NTPDase1)/CD39, which is the dominant factor dictating vascular metabolism of extracellular ATP to adenosine throughout the cardiovascular tissues. Excess levels of extracellular purine metabolites, however, have been associated with metabolic and cardiovascular diseases. Physiological estrogen signaling is anti-inflammatory with vascular protective effects, but pharmacological replacement use in transgender and postmenopausal individuals is associated with thrombosis and other side effects. Crucially, the loss of this important sex hormone following menopause or with gender reassignment is associated with worsened pro-inflammatory states linked to increased oxidative stress, myocardial fibrosis, and, ultimately, diastolic dysfunction, also known as Yentl syndrome. While there is a growing body of knowledge on distinctive purinergic or estrogen signaling and endothelial health, much less is known about the relationships between the two signaling pathways. Continued studies of the interactions between these pathways will allow further insight into future therapeutic targets to improve the cardiovascular health of aging women without imparting deleterious side effects.

Aims/Background Psoriasis is a chronic inflammatory condition associated with an elevated risk of cardiovascular diseases including coronary artery disease (CAD). This study assessed coronary microvascular dysfunction (CMD) in psoriasis patients using echocardiographic coronary flow parameters, controlling for traditional cardiovascular risk factors and atherosclerosis, to fill gaps identified in previous research. Methods A comprehensive literature search was performed using multiple electronic databases for studies on echocardiographic coronary flow parameters in patients with psoriasis. The outcomes of interest included the coronary flow velocity reserve (CFVR), hyperemic diastolic peak flow velocity (DPFV), and baseline DPFV. Data were extracted and analyzed using RevMan 5.4 (Nordic Cochrane Center, Copenhagen, Denmark), with pooled standard mean differences (SMDs) and 95% confidence intervals (CIs) were calculated. Statistical significance was set at p < 0.05. Results Four studies involving 557 patients were included in this analysis. Pooled analysis revealed a significant reduction in CFVR in patients with psoriasis compared to controls (SMD: -0.71; 95% CI: -0.97, -0.45; p < 0.00001). Hyperemic DPFV was significantly reduced (SMD: -0.71; 95% CI: -1.30, -0.12; p = 0.02), whereas baseline DPFV showed no signficant difference (SMD: 0.20; 95% CI: -0.92, 1.32; p = 0.73). Conclusion Psoriasis was associated with reduced CFVR and hyperemic DPFV, suggesting early CMD. CFVR could aid in early CMD detection in psoriasis patients, informing cardiovascular risk management and potential anti-inflammatory treatment benefits. Systematic Review Registration PROSPERO: CRD42024574085.

Mitochondrial dysfunction is increasingly recognized as a central contributor to the pathogenesis of cardiovascular diseases (CVDs), including heart failure, ischemic heart disease, hypertension, and cardiomyopathy. Mitochondria, known as the powerhouses of the cell, play a vital role in maintaining cardiac energy homeostasis, regulating reactive oxygen species (ROS) production and controlling cell death pathways. Dysregulated mitochondrial function results in impaired adenosine triphosphate (ATP) production, excessive ROS generation, and activation of apoptotic and necrotic pathways, collectively driving the progression of CVDs. This review provides a detailed examination of the molecular mechanisms underlying mitochondrial dysfunction in CVDs, including mutations in mitochondrial DNA (mtDNA), defects in oxidative phosphorylation (OXPHOS), and alterations in mitochondrial dynamics (fusion, fission, and mitophagy). Additionally, the role of mitochondrial dysfunction in specific cardiovascular conditions is explored, highlighting its impact on endothelial dysfunction, myocardial remodeling, and arrhythmias. Emerging therapeutic strategies targeting mitochondrial dysfunction, such as mitochondrial antioxidants, metabolic modulators, and gene therapy, are also discussed. By synthesizing recent advances in mitochondrial biology and cardiovascular research, this review aims to enhance understanding of the role of mitochondria in CVDs and identify potential therapeutic targets to improve cardiovascular outcomes.

Coronary microvascular dysfunction (CMD) is characterized by structural and functional abnormalities in the coronary microvasculature which can lead to ischaemia and angina and is increasingly recognized as a major contributor to adverse cardiovascular outcomes. Despite its clinical importance, the diagnosis of CMD remains limited compared with traditional atherosclerotic coronary artery disease. Furthermore, the historical lack of non-invasive methods for detecting and quantifying CMD has hindered progress in understanding its pathophysiology and clinical implications. This review explores advancements in non-invasive cardiac imaging that have enabled the detection and quantification of CMD. It evaluates the clinical utility, strengths and limitation of these imaging modalities in diagnosing and managing CMD. Having improved our understanding of CMD pathophysiology, cardiac imaging can provide insights into its prognosis and enhance diagnostic accuracy. Continued innovation in imaging technologies is essential for advancing knowledge about CMD, leading to improved cardiovascular outcomes and patient care.

Heart failure with preserved ejection fraction (HFpEF) represents a major clinical challenge with rising global prevalence. Women have a nearly double lifetime risk of developing HFpEF compared to heart failure with reduced ejection fraction (HFrEF). In HFpEF, sex differences emerge both in how traditional cardiovascular risk factors (such as hypertension, obesity, and diabetes) affect cardiac function and through distinct pathophysiological mechanisms triggered by sex-specific events like menopause and adverse pregnancy outcomes. These patterns influence not only disease development, but also therapeutic responses, necessitating sex-specific approaches to treatment. This review aims to synthesize existing knowledge regarding HFpEF in women including traditional and sex-specific risk factors, pathophysiology, presentation, and therapies, while outlining important knowledge gaps that warrant further investigation. The impact of HFpEF spans a woman's entire lifespan, requiring prevention and management strategies tailored to different life stages. While understanding of sex-based differences in HFpEF has improved, significant knowledge gaps persist. Through examination of current evidence and challenges, this review highlights promising opportunities for innovative research, therapeutic development, and clinical care approaches that could transform the management of HFpEF in women.

More than 60% of patients undergoing coronary angiography present no coronary artery disease (CAD). Angina and myocardial ischemia are classically determined by epicardial vascular obstruction, but coronary microvascular dysfunction (CMD) may also represent a possible cause for these phenomena. Two endotypes of CMD have been recognized, with two different pathophysiological mechanisms: structural CMD, characterized by low coronary flow reserve (CFR) and high microvascular resistance (MVR) values; and functional CMD, characterized by low CFR and normal MVR values. According to the present data, almost half of patients with non-obstructive CAD have shown signs of CMD. For this reason, further investigations for microvascular function assessment should be considered when evaluating no-CAD patients complaining of angina or presenting signs of myocardial ischemia. The thermodilution method is currently becoming a widespread invasive technique due to its feasibility and high reproducibility for coronary physiology evaluation. Furthermore, a recently introduced technique - called continuous thermodilution - allows for direct measurement of absolute coronary flow and resistances. The role of this brand-new technique in the clinical scenario is however still to be fully investigated and its use is at present limited to research purposes only. Among no-CAD patients, both structural and functional CMD are related to a worse prognosis in term of mortality and major adverse cardiovascular events (MACE). In this review, we will discuss the present evidence supporting the definition, prevalence and clinical implication of the different forms of CMD and the technical aspects of its invasive assessment.

Several methods for measuring IMR derived from angiography have been developed. AngioIMR is a novel method for the assessment of angiography-derived IMR with no requirement for a wire and hyperemia. The prognostic value of AngioIMR is unknown in STEMI patients. We aimed to provide the prognostic value of AngioIMR in patients with ST-elevation myocardial infarction (STEMI).

This study included patients with STEMI who underwent invasive coronary angiography and primary percutaneous coronary intervention (PPCI). AngioIMR was calculated using computational flow and pressure simulation immediately after PPCI. The presence of significant coronary microvascular dysfunction was defined as AngioIMR > 40. The primary outcome was a composite of all cause death or hospitalization for heart failure (MACE).

A total of 178 patients were included (65.0 ± 12.8 years on average, 74 % male gender). An AngioIMR > 40 was found in 72 patients. During a median follow-up of 2.9 (2.3-6.9) years, a primary endpoint was observed in 56 patients. By Kaplan-Meier analysis, the risk of MACE was significantly higher in patients with AngioIMR > 40 (log-rank P < 0.01). An Angio IMR > 40 was significantly associated with the occurrence of the primary endpoint in univariate (70 % vs 27 %; hazard ratio 4.519; 95 % CI: 2.550-8.009; p < 0.0001) and multivariate analysis (Hazard ratio 4.282; 95 % CI: 2.325-7.886; p < 0.0001). AngioIMR model showed incremental prognostic value compared to a model with clinical and imaging risk predictors (C-index 0.84 vs 0.79; p = 0.04).

Elevated AngioIMR showed a independent prognostic significance in STEMI patients. In addition to well-known risk factors, assessment of coronary microvascular dysfunction can be a feasible approach for early prevention and a therapeutic target in STEMI patients.

Lately, a large number of stable ischemic patients, with no obstructed coronary arteries are being diagnosed. Despite this condition, which is being described as angina with no obstructive coronary arteries (ANOCA), was thought to be benign, recent evidence report that it is associated with increased risk for adverse cardiovascular outcomes. ANOCA is more frequent in women and, pathophysiologically, it is predominantly related with microvascular dysfunction, while other factors, such as endothelial dysfunction, inflammation and autonomic nervous system seem to also play a major role to its development, while other studies implicate ANOCA and microvascular dysfunction in the pathogenesis of heart failure with preserved ejection fraction. For establishing an ANOCA diagnosis, measurement including coronary flow reserve (CFR), microvascular resistance (IMR) and hyperemic microvascular resistance (HMR) are mostly used in clinical practice. In addition, new modalities, such as optical coherence tomography (OCT) are being tested and show promising results for future diagnostic use. Regarding management, pharmacotherapy consists of a wide selection of drugs, according to the respected pathophysiology of the disease (vasospastic angina or microvascular dysfunction), while research for new treatment options including interventional techniques, is currently ongoing. This review, therefore, aims to provide a comprehensive analysis of all aspects related to ANOCA, from pathophysiology to clinical managements, as well as clinical implications and suggestions for future research efforts, which will help advance our understanding of the syndrome and establish more, evidence-based, therapies.

Coronary microvascular disease (CMD) is one of the commonest causes of cardiac chest pain. The condition is more prevalent in women, and incidence is known to increase with age, hypertension, and diabetes. The pathophysiological pathways are heterogenous and related to intrinsic vascular and endothelial dysfunction. Furthermore, this entity is known to be associated with adverse cardiovascular outcomes. Despite this, there is inertia amongst cardiologists to further evaluate patients with non-critical coronary artery disease and suspected CMD. With refinement in technology, we have now better understanding of CMD and invasive testing in the catheterization laboratory is a viable option for confirming the diagnosis of CMD. However, despite advances in diagnosing and stratifying this entity, therapeutic options remain limited and poorly defined. In this editorial, we will briefly focus on the pathophysiology and invasive assessment and therapeutic options available for CMD.

Coronary microvascular disease (CMD) comprises a spectrum of conditions characterized by the functional and structural abnormalities of coronary microcirculation, affecting vessels typically smaller than 500 μm. Despite its clinical significance as a contributor to myocardial ischemia, CMD frequently remains underdiagnosed due to the limitations of current diagnostic approaches. Invasive testing, including coronary reactivity assessment, is considered the gold standard, but it is resource-intensive and not always accessible. Non-invasive methods, such as positron emission tomography (PET) and transthoracic Doppler echocardiography (TTDE), offer alternatives but are limited by varying accuracy and accessibility. Amid these diagnostic challenges, there is increasing interest in circulating biomarkers as adjuncts in CMD evaluation. Biomarkers associated with endothelial dysfunction, inflammation, and oxidative stress, detectable through routine blood tests, may assist in CMD diagnosis, risk stratification, and therapeutic monitoring. These biomarkers can offer insights into CMD pathogenesis and enable early, non-invasive screening to identify patients who may benefit from more invasive investigations. This narrative review examines studies assessing biomarkers in CMD patients with diagnoses confirmed through invasive techniques. Our objective is to focus on circulating biomarkers linked to the invasive evaluation of coronary microcirculation, aiming to advance the understanding of the underlying mechanisms of this prevalent condition and enhance diagnostic accuracy and the clinical management of affected patients.

Coronary microvascular disease (CMD) is defined as impaired coronary flow reserve (CFR) and/or increased microvascular resistance (MR) without significant epicardial coronary stenosis. This definition allows for discordant CFR and MR values within patients with CMD. The aim of this meta-analysis is to characterise the prognostic value and pathophysiological backgrounds of CFR and MR con-/discordance.

A systematic search (PROSPERO CRD42024573004) identified studies determining CFR and MR in patients without significant epicardial coronary artery disease. Patients were divided into four groups: (1) normal CFR and MR, (2) abnormal CFR and MR, (3) abnormal CFR with normal MR and (4) normal CFR with abnormal MR and analysed for all-cause mortality and major adverse cardiovascular events (MACE).

We identified four studies representing 2310 total participants. Group B had the highest MACE (OR: 3.23; 95% CI 1.95 to 5.36) and mortality rate (OR: 2.27; 95% CI 1.12 to 4.58) compared with group A. Group C, associated with female sex, showed significantly higher MACE (OR: 2.07; 95% CI 1.25 to 3.45) but not mortality (OR: 1.89; 95% CI 0.92 to 3.88) compared with group A. In group D, associated with high body mass index, MACE and mortality rates did not differ significantly from group A (OR: 1.19; 95% CI 0.67 to 2.11 and OR: 0.55; 95% CI 0.16 to 1.90, respectively).

Abnormal CFR and MR are associated with a high risk of MACE and death. Abnormal CFR and normal MR are associated with an increased MACE-but not death. MACE and mortality risk in discordantly normal CFR and abnormal MR are low. Our findings show the need for tailoring CFR and MR diagnostic thresholds to patient characteristics and raise questions about the presence of CMD in patients with abnormal MR with normal CFR.

Wire-based index of microcirculatory resistance (IMR) utilizing pressure wires and thermodilution techniques for the assessment of coronary microcirculatory function, presents challenges for clinical routine use due to its complexity, time-consuming, and costly. This study introduces a novel multi-branch and wire-free method for IMR calculation based on coronary angiography. The diagnostic performance of CAG-IMR is validated within a retrospective single-center investigation.

In a retrospective single-center study, 139 patients with 201 vessels were evaluated using CAG-IMR for coronary microvascular dysfunction (CMD) detection, utilizing wire-based IMR as the reference standard. CMD was determined based on wire-based IMR ≥25U. CAG-IMR was independently calculated from diagnostic coronary angiography in a blinded fashion, employing the same diagnostic threshold of 25U for CMD identification.

CAG-IMR demonstrated significant correlation (r = 0.84, p < 0.001) and good diagnostic performance AUC = 0.97 (95% CI: 0.95-0.99) compared to wire-based IMR. It exhibited the overall diagnostic accuracy at 95.0% (95% CI: 92.0%-98.0%), alongside high sensitivity (92.7%) and specificity (95.6%). The positive predictive value (PPV) stood at 84.4%, and the negative predictive value (NPV) reached 98.1%.

This study introduces CAG-IMR, a novel, multi-branch and wire-free method for IMR calculation. The indicator demonstrates good diagnostic accuracy and correlation with wire-based IMR in a cohort of 139 patients and 201 vessels, with the potential to enhance clinical CMD assessment.

Coronary microvascular dysfunction (CMD) comprises a wide spectrum of structural and/or functional abnormalities of coronary microcirculation that can lead to myocardial ischemia. Emerging evidence has indicated that CMD is a relevant cause of morbidity and mortality and is associated with a high risk of major adverse cardiovascular events (MACEs) and heart failure with preserved ejection fraction as well as poor quality of life. This review aims to elucidate briefly the pathogenesis and diagnostic modalities of CMD and to shed light on contemporary evidence on the prognostic impact of CMD. Finally, we will provide an overview of novel emerging therapeutic strategies for CMD.

In patients with ischemic heart disease, coronary microvascular dysfunction is associated with cardiovascular risk factors and poor prognosis; however, data from healthy individuals are scarce.

The purpose of this study was to assess the impact of cardiovascular risk factors and subclinical atherosclerosis on coronary microvascular function in middle-aged asymptomatic individuals.

Myocardial perfusion was measured at rest and under stress using cardiac magnetic resonance in 453 individuals and used to generate myocardial blood flow (MBF) maps and calculate myocardial perfusion reserve (MPR). Subclinical atherosclerosis was assessed using 3-dimensional vascular ultrasound of the carotid and femoral arteries and coronary artery calcium scoring at baseline and at 3-year follow-up.

Median participant age was 52.6 years (range: 48.9-55.8 years), and 84.5% were male. After adjusting for age and sex, rest MBF was directly associated with the number of the metabolic syndrome components present (elevated waist circumference, systolic and diastolic blood pressure, fasting glucose, and triglycerides and low high-density lipoprotein cholesterol), insulin resistance (homeostatic model assessment for insulin resistance), and presence of diabetes. MPR was reduced in the presence of several metabolic syndrome components, elevated homeostatic model assessment for insulin resistance, and diabetes. Stress MBF was inversely associated with coronary artery calcium presence and with global plaque burden. Higher stress MBF and MPR were associated with less atherosclerosis progression (increase in plaque volume) at 3 years.

In asymptomatic middle-aged individuals free of known cardiovascular disease, the presence of cardiometabolic risk factors and systemic (poly-vascular) subclinical atherosclerosis are associated with impaired coronary microvascular function. Better coronary microvascular function reduces atherosclerosis progression at follow-up. (Progression of Early Subclinical Atherosclerosis [PESA]; NCT01410318).

Coronary microvascular disease (CMVD) affects the coronary pre-arterioles, arterioles, and capillaries and can lead to blood supply-demand mismatch and cardiac ischemia. CMVD can present clinically as ischemia or myocardial infarction with no obstructive coronary arteries (INOCA or MINOCA, respectively). Currently, therapeutic options for CMVD are limited, and there are no targeted therapies. Genetic studies have emerged as an important tool to gain rapid insights into the molecular mechanisms of human diseases. For example, coronary artery disease (CAD) genome-wide association studies (GWAS) have enrolled hundreds of thousands of patients and have identified > 320 loci, elucidating CAD pathogenic pathways and helping to identify therapeutic targets. Here, we review the current landscape of genetic studies of CMVD, consisting mostly of genotype-first approaches. We then present the hypothesis that CAD GWAS have enrolled heterogenous populations and may be better characterized as ischemic heart disease (IHD) GWAS. We discuss how several of the genetic loci currently associated with CAD may be involved in the pathogenesis of CMVD. Genetic studies could help accelerate progress in understanding CMVD pathophysiology and identifying putative therapeutic targets. Larger phenotype-first genomic studies into CMVD with adequate sex and ancestry representation are needed. Given the extensive CAD genetic and functional validation data, future research should leverage these loci as springboards for CMVD genomic research.

Women presenting with angina are more likely to have cardiac chest pain accompanied more frequently by associated symptoms like abdominal pain and lightheadedness. The evaluation of women with suspected coronary disease can be complex because many have microvascular dysfunction, coronary vasospasm, and altered coagulation that require specific testing protocols beyond the conventional stress testing and a coronary angiogram. Therefore, terms such as angina, ischemia, and myocardial infarction with no obstructive coronary disease have been introduced in recent years. More studies are required to elaborate guidelines on the diagnosis and management of these entities.

Ischaemic heart disease (IHD) and cerebrovascular disease are leading causes of morbidity and mortality worldwide. Cerebral small vessel disease (CSVD) is a leading cause of dementia and stroke. While coronary small vessel disease (coronary microvascular dysfunction) causes microvascular angina and is associated with increased morbidity and mortality. The vascular anatomy of the heart and brain is similar with conduit arteries distributed over the surface of these organs which in turn branch into a network of microscopic penetrating arteries which provide organ perfusion via an end-organ microcirculation. It has also been demonstrated that coronary microvascular dysfunction and CSVD share common vascular risk factors and pathophysiological mechanisms of disease. This has led to a link between the conditions being hypothesised, however, there is an evidence gap clearly demonstrating this relationship. The CorCMR (coronary microvascular angina cardiovascular magnetic resonance imaging) brain imaging study will provide novel insights into the associations between small vessel disease of the heart and brain and related clinical significance.

The CorCMR brain imaging study is a prospective, observational, multicentre cohort study including a blinded, central analysis and independent clinical trials unit; a prespecified study nested within the CorCMR trial. We will enrol patients with anginal symptoms who have undergone invasive coronary angiography which has demonstrated no obstructive coronary artery disease. The participants will then undergo brain MRI (to detect CSVD) immediately followed by a quantitative stress perfusion cardiac MRI (to detect coronary microvascular dysfunction). Participants will also undergo neurocognitive testing. The objectives of the study are to assess the prevalence of MRI features of CSVD in patients with angina and no obstructive coronary artery disease; to assess the association between coronary microvascular dysfunction and CSVD and to assess the association between CSVD and cognition.

The CorCMR study is approved by the UK National Research Ethics Service (Reference 20/WS/0159). Findings will be disseminated through peer-reviewed publications. All patients provided written informed consent.

ClinicalTrials.gov ID NCT04805814.

Epicardial stenosis and coronary microvascular dysfunction (CMD) may coexist in patients with chronic coronary syndrome (CCS). Microvascular resistance reserve (MRR) has been demonstrated to be a valid cross-modality metric using continuous saline infusion thermodilution and intracoronary Doppler flow velocity methods. This study aimed to investigate the prevalence and diagnostic concordance of CMD defined by MRR using two methods-stress transthoracic Doppler echocardiography (S-TDE) and the invasive bolus thermodilution method (B-Thermo)-in patients with functionally significant epicardial stenosis.

We retrospectively investigated 204 left anterior descending artery (LAD) territories in CCS. All patients underwent physiological assessment using a pressure-temperature wire and S-TDE before elective fractional flow reserve (FFR)-guided percutaneous coronary intervention. The concordance rate was evaluated using κ values.

In the final analysis, the median age was 72 years, and 72.5% of patients were male. The median FFR value was 0.69. MRRS-TDE and MRRB-Thermo were similar (3.41 vs 3.48, P = 0.877), whereas only a weak, albeit significant relationship was observed between these two metrics (r = 0.167, P = 0.017). CMD was diagnosed in 20.6% and 32.8% of patients using S-TDE and B-Thermo, respectively, when a cutoff MRR value of 2.7 was applied. The concordance rate of CMD diagnosis between the two methods was low (κ = 0.079).

MRRS-TDE and MRRB-Thermo showed a very weak correlation in the LAD territory with functionally significant stenosis in patients with CCS. The prevalence of CMD diagnosed using MRRS-TDE and MRRB-Thermo was not comparable, and the diagnostic concordance of CMD using these two methods was very low.

Coronary artery spasm (CAS) is a frequent finding in patients presenting with angina pectoris. Although the pathogenesis of CAS is incompletely understood, previous studies suggested a genetic contribution. Our study aimed to elucidate genetic variants in a cohort of European patients with angina and unobstructed coronary arteries who underwent acetylcholine (ACh) provocation testing.

A candidate association analysis of 208 genes previously associated with cardiovascular conditions was performed using genotyped and imputed variants in patients grouped in epicardial (focal, diffuse) CAS (n = 119) and microvascular CAS (n = 87). Patients with a negative ACh test result (n = 45) served as controls.

We found no association below the genome-wide significance threshold of p < 5 × 10-8, thus not confirming variants in ALDH2, NOS3, and ROCK2 previously reported in CAS patients of Asian ancestry. However, the analysis identified suggestive associations (p < 10-05) for the groups of focal epicardial CAS (CDH13) and diffuse epicardial CAS (HDAC9, EDN1). Downstream analysis of the potential EDN1 risk locus showed that CAS patients have significantly increased plasma endothelin-1 levels (ET-1) compared to controls. An EDN1 haplotype comprising rs9349379 and rs2070698 was significantly associated to ET-1 levels (p = 0.01).

In summary, we suggest EDN1 as potential genetic risk loci for patients with diffuse epicardial CAS, and European ancestry. Plasma ET-1 levels may serve as a potential cardiac marker.