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We retrospectively investigated the relationship between cardiopulmonary exercise testing (CPET) parameters and coronary microvascular dysfunction (CMD) using a novel angiography-based index of microcirculatory resistance (AccuIMR) in patients with ST-elevation myocardial infarction (STEMI) who underwent primary percutaneous coronary intervention (PCI) with complete revascularization. In 418 patients, the culprit vessel AccuIMR was calculated after successful primary PCI. CPET was conducted 44.04 ± 19.28 days after primary PCI. Overall, 157 patients (37.6%) showed elevated AccuIMR (> 40 U) in the culprit vessels. The LVEF was significantly lower in the CMD group than in the Non-CMD group. The CMD group showed worse results in VO2peak, peak O2-pulse, and VE/VCO2 slope than the Non-CMD group. Spearman correlation analysis suggested that VO2peak (r = -0.354), peak O2-pulse (r = -0.385) and VE/VCO2 slope (r = 0.294) had significant linear correlations with AccuIMR (P < 0.001). Multivariable logistic regression analysis showed that AccuIMR was the independent predictor of reduced VO2peak and elevated VE/VCO2 slope. The proportions of positive and equivocal ECG results and early O2-pulse flattening in the CMD group were significantly higher than those in the Non-CMD group, and AccuIMR was the only independent predictor of these ischemia-relating indicators, suggesting that patients with CMD had significant noninvasively detectable myocardial ischemia. [ABSTRACT FROM AUTHOR]

Abstract We retrospectively investigated the relationship between cardiopulmonary exercise testing (CPET) parameters and coronary microvascular dysfunction (CMD) using a novel angiography-based index of microcirculatory resistance (AccuIMR) in patients with ST-elevation myocardial infarction (STEMI) who underwent primary percutaneous coronary intervention (PCI) with complete revascularization. In 418 patients, the culprit vessel AccuIMR was calculated after successful primary PCI. CPET was conducted 44.04 ± 19.28 days after primary PCI. Overall, 157 patients (37.6%) showed elevated AccuIMR (> 40 U) in the culprit vessels. The LVEF was significantly lower in the CMD group than in the Non-CMD group. The CMD group showed worse results in VO2peak, peak O2-pulse, and VE/VCO2 slope than the Non-CMD group. Spearman correlation analysis suggested that VO2peak (r = -0.354), peak O2-pulse (r = -0.385) and VE/VCO2 slope (r = 0.294) had significant linear correlations with AccuIMR (P

Abstract Background Ischemia with non-obstructive coronary artery disease is a prevalent form of ischemic heart disease. The majority of ischemia with non-obstructive coronary artery disease cases are attributed to underlying factors such as coronary microvascular dysfunction (CMD) and/or coronary artery spasm. Ischemia with non-obstructive coronary artery disease can present with various clinical manifestations. Recurrent syncope is an atypical complaint in patients with ischemia with non-obstructive coronary artery disease. Case presentation This case report describes the presentation of a 58-year-old Chinese male patient who experienced repeated episodes of syncope. The syncope was found to be caused by concomitant coronary artery spasm and presumptive coronary microvascular dysfunctionc suggested by “slow flow” on coronary angiography. The patient was prescribed diltiazem sustained-release capsules, nicorandil, and atorvastatin. During the three-month follow-up conducted on our outpatient basis, the patient did not experience a recurrence of syncope. Conclusion This study highlights the importance of considering ischemia with non-obstructive coronary artery disease as a potential cause of syncope in the differential diagnosis. It emphasizes the need for early diagnosis of ischemia with non-obstructive coronary artery disease to facilitate more effective management strategies.

Background: Ischemia with non-obstructive coronary artery disease is a prevalent form of ischemic heart disease. The majority of ischemia with non-obstructive coronary artery disease cases are attributed to underlying factors such as coronary microvascular dysfunction (CMD) and/or coronary artery spasm. Ischemia with non-obstructive coronary artery disease can present with various clinical manifestations. Recurrent syncope is an atypical complaint in patients with ischemia with non-obstructive coronary artery disease. Case presentation: This case report describes the presentation of a 58-year-old Chinese male patient who experienced repeated episodes of syncope. The syncope was found to be caused by concomitant coronary artery spasm and presumptive coronary microvascular dysfunctionc suggested by "slow flow" on coronary angiography. The patient was prescribed diltiazem sustained-release capsules, nicorandil, and atorvastatin. During the three-month follow-up conducted on our outpatient basis, the patient did not experience a recurrence of syncope. Conclusion: This study highlights the importance of considering ischemia with non-obstructive coronary artery disease as a potential cause of syncope in the differential diagnosis. It emphasizes the need for early diagnosis of ischemia with non-obstructive coronary artery disease to facilitate more effective management strategies. [ABSTRACT FROM AUTHOR]

BackgroundMicrovascular resistance reserve (MRR) is a recently introduced specific index of coronary microcirculation. MRR calculation can utilize parameters deriving from coronary flow reserve (CFR) assessment, provided that intracoronary pressure data are also available. The previously proposed pressure-bounded CFR (CFRpb) defines the possible CFR interval on the basis of resting and hyperemic pressure gradients in the epicardial vessel, however, its correlation to the Doppler wire measurement was reported to be rather poor without the correction for hydrostatic pressure.PurposeWe aimed to determine the pressure-bounded coronary MRR interval with hydrostatic pressure correction according to the previously established equations of CFRpb adapted for the MRR concept. Furthermore, we also aimed to design a prediction model using the actual MRR value within the pressure-bounded interval and validate the results against the gold-standard Doppler wire technique.MethodsHydrostatic pressure between the tip of the catheter and the sensor of the pressure wire was calculated by height difference measurement from a lateral angiographic view. In the derivation cohort the pressure-bounded MRR interval (between MRRpbmin and MRRpbmax) was determined solely from hydrostatic pressure-corrected intracoronary pressure data. The actual MRR was calculated by simple hemodynamic equations incorporating the anatomical data of the three-dimensionally reconstructed coronary artery (MRRp−3D). These results were analyzed by regression analyses to find relations between the MRRpb bounds and the actual MRRp−3D.ResultsIn the derivation cohort of 23 measurements, linear regression analysis showed a tight relation between MRRpbmax and MRRp−3D (r2 = 0.74, p

Background: A guidewire‐free angiography‐derived microcirculatory resistance (AMR) derived from Quantitative flow ratio (QFR) exhibits good diagnostic accuracy for assessing coronary microvascular dysfunction (CMD), but there are no relevant studies supporting the specific application of AMR in patients with ST‐elevation myocardial infarction (STEMI). The study aims to evaluate CMD in patients with STEMI using the AMR index. Methods: This study included patients with STEMI who underwent percutaneous coronary intervention (PCI) from June 1, 2020 to September 28, 2021. All patients were divided into two groups: the CMD (n = 215) and non‐CMD (n = 291) groups. After matching, there were 382 patients in both groups.1‐year follow‐up major adverse cardiac events (MACEs) were evaluated. Results: After matching, the primary endpoint was achieved in 41 patients (10.7%), with 27 and 14 patients in the CMD and non‐CMD groups, respectively (HR 1.954 [95% CI 1.025–3.726]; 14.1% versus 7.3%, p =.042). Subgroup analysis revealed that 18 patients (4.7%) were readmitted for heart failure, with 15 and 3 in the CMD and non‐CMD groups, respectively (HR 5.082 [95% CI 1.471–17.554]; 7.9% versus 1.6%, p =.010). Post‐PCI AMR ≥ 250 was significantly associated with a higher risk of the primary endpoint and was its independent predictor (HR 2.265 [95% CI 1.136–4.515], p =.020). Conclusion: The retrospective use of AMR with a cutoff value of ≥250 after PCI in patients with STEMI can predict a significant difference in the 1‐year MACE rates when compared with a propensity score‐matched group with normal AMR. [ABSTRACT FROM AUTHOR]

Purpose: Coronary microvascular dysfunction (CMD) is emerging as an important cause of myocardial ischemia, but there is a lack of a non-invasive method for reliable early detection of CMD. Aim: To develop an electrocardiogram (ECG)-based machine learning algorithm for CMD detection that will lay the groundwork for patient-specific non-invasive early detection of CMD. Methods: Vectorcardiography (VCG) was calculated from each 10-second ECG of CMD patients and healthy controls. Sample entropy (SampEn), approximate entropy (ApEn), and complexity index (CI) derived from multiscale entropy were extracted from ST-T segments of each lead in ECGs and VCGs. The most effective entropy subset was determined using the sequential backward selection algorithm under the intra-patient and inter-patient schemes, separately. Then, the corresponding optimal model was selected from eight machine learning models for each entropy feature based on five-fold cross-validations. Finally, the classification performance of SampEn-based, ApEn-based, and CI-based models was comprehensively evaluated and tested on a testing dataset to investigate the best one under each scheme. Results: ApEn-based SVM model was validated as the optimal one under the intra-patient scheme, with all testing evaluation metrics over 0.8. Similarly, ApEn-based SVM model was selected as the best one under the intra-patient scheme, with major evaluation metrics over 0.8. Conclusions: Entropies derived from ECGs and VCGs can effectively detect CMD under both intra-patient and inter-patient schemes. Our proposed models may provide the possibility of an ECG-based tool for non-invasive detection of CMD.

Ischemia with no obstructive coronary arteries (INOCA) is defined as patients with evidence of myocardial ischemia without obstructive coronary artery disease. About 3–4 million people in the United States have INOCA, more commonly affecting women, and carries adverse morbidity, mortality, and relatively high healthcare costs. The pathophysiology of INOCA appears to be multi-factorial with a variety of contributing mechanisms. Diagnosis of INOCA is suggested by non-invasive or invasive testing consistent with myocardial ischemia. Due to the high prevalence of coronary risk factors and atherosclerosis in the INOCA population, current treatment strategies target angina, coronary atherosclerosis, and atherosclerotic risk factors, as well as burgeoning treatment of coronary microvascular dysfunction (CMD). Ongoing clinical trials are assessing different options.

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The aim is to investigate, by means of speckle tracking echocardiography, left ventricular (LV) contractile function at rest and during dipyridamole stress in patients with coronary microvascular dysfunction (CMD). 59 patients (39% women, mean age 65.6 ± 6.1 years) with history of chest pain and without obstructive coronary artery disease (CAD) underwent dipyridamole stress echocardiography. Coronary flow was assessed in the left anterior descending coronary artery. Coronary flow reserve (CFR) was determined as the ratio of hyperaemic to baseline diastolic coronary flow velocity. CMD was defined as CFR < 2. Global longitudinal strain (GLS) was measured at rest and at peak dose. Nineteen patients (32%) among the overall population showed CMD. Baseline GLS was significantly lower in patients with CMD (– 16.8 ± 2.7 vs. – 19.1 ± 3.1, p < 0.01). A different contractile response to dipyridamole infusion was observed between the two groups: GLS significantly increased up to peak dose in patients without CMD (from – 19.1 ± 3.1 to – 20.2 ± 3.1, p < 0.01), and significantly decreased in patients with CMD (from – 16.8 ± 2.7 to – 15.8 ± 2.7, p < 0.01). There was a significant inverse correlation between CFR and ∆GLS (r = – 0.82, p < 0.01). Rest GLS and GLS response to dipyridamole stress are markedly impaired among patients with chest pain syndrome, non-obstructive CAD and CMD, reflecting subclinical LV systolic dysfunction and lack of LV contractile reserve due to underlying myocardial ischemia. [ABSTRACT FROM AUTHOR]

Women with signs and symptoms of ischemia and no obstructive coronary artery disease (INOCA) often have coronary microvascular dysfunction (CMD). It can be diagnosed by coronary function testing (CFT), which is an invasive coronary angiogram procedure. Frequently, these women have persistent angina despite medical therapy, but it is not clear whether it is due to worsening or persistent CMD or inadequate therapy. In this brief report, we describe findings of repeat CFT in a case series of 12 women undergoing repeat CFT for the assessment of persistent angina in order to better understand the evolving pathology.

BackgroundCoronary microvascular dysfunction (CMD) has differences in prevalence and presentation between women and men; however, we have limited understanding about underlying contributors to sex differences in CMD. Myocardial perfusion reserve index (MPRI), as semi-quantitative measure of myocardial perfusion derived from cardiac magnetic resonance (CMR) imaging has been validated as a measure of CMD. We sought to understand the sex differences in the relations between the MPRI and traditional measures of cardiovascular disease by CMR.MethodsA retrospective analysis of a single-center cohort of patients receiving clinical stress CMR from 2015 to 2022 was performed. Patients with calculated MPRI and no visible perfusion defects consistent with obstructive epicardial coronary disease were included. We compared associations between MPRI versus traditional cardiovascular risk factors and markers of cardiac structure/function in sex-stratified populations using univariable and multivariable regression models.ResultsA total of 229 patients [193 female, 36 male, median age 57 (47–67) years] were included in the analysis. In the female population, no traditional cardiovascular risk factors were associated with MPRI, whereas in the male population, diabetes (β: −0.80, p = 0.03) and hyperlipidemia (β: −0.76, p = 0.006) were both associated with reduced MPRI in multivariable models. Multivariable models revealed significant associations between reduced MPRI and increased ascending aortic diameter (β: −0.42, p = 0.005) and T1 times (β: −0.0056, p = 0.03) in the male population, and increased T1 times (β: −0.0037, p = 0.006) and LVMI (β: −0.022, p = 0.0003) in the female population.ConclusionThe findings suggest different underlying pathophysiology of CMD in men versus women, with lower MPRI in male patients fitting a more “traditional” atherosclerotic profile.

Microvascular resistance (MR) is increased in takotsubo syndrome (TTS) and can be assessed by a validated pressure-wire-free tool called nonhyperemic angiography-derived index of microcirculatory resistance (NH-IMRangio). The authors aimed to study whether the degree and extent of an altered MR in TTS patients were associated with 1-year prognosis. The authors recruited 181 consecutive patients with TTS who underwent cardiac angiography. Impaired MR was defined as an NH-IMRangio ≥25. The degree and extent of impaired MR were assessed by the value of maximum NH-IMRangio in each major coronary artery and by the number of coronary arteries with an NH-IMRangio ≥25, respectively. Major adverse cardiac events (MACE) were a composite of cardiovascular death, heart failure event, acute myocardial infarction, and hospitalization for symptomatic arrhythmias. A total of 166 patients had NH-IMRangio available. The mean age was 74.8 years, and 83% were women. The rate of MACE at 1 year was 21.1%, mainly due to heart failure events that were generally mild. Kaplan-Meier curves showed higher rates of MACE in patients with higher NH-IMRangio (28.9% vs 13.3%; P = 0.019) and in those with 3 coronary arteries with increased MR compared to those with 2 or 1 affected arteries (33.3% vs 15.9% vs 9.5%; P = 0.040 and P = 0.040, respectively). After a multivariable Cox regression analysis, higher values of NH-IMRangio (HR: 3.41 [95% CI: 1.54-7.52]; P = 0.002) and the presence of 3 coronary arteries with increased MR (HR: 6.39 [95% CI: 1.46-27.87]; P = 0.014) were independent predictors of MACE in TTS patients. The degree and extent of an impaired MR assessed by a validated pressure-wire-free tool were independent predictors of MACE at 1-year follow-up in TTS patients. [Display omitted] [ABSTRACT FROM AUTHOR]

The prevalence of coronary microvascular dysfunction (CMD) beyond the spectrum of chronic coronary syndromes (CCS) is non-negligible, pertaining to pathophysiological and therapeutical implications. Thanks to the availability of accurate and safe non-invasive technique, CMD can be identified as a key player in heart failure, cardiomyopathies, Takotsubo syndrome, aortic stenosis. While CMD is widely recognized as a cause of myocardial ischemia leading to a worse prognosis even in the absence of obstructive coronary artery disease, the characterization of CMD patterns beyond CCS might provide valuable insights on the underlying disease progression, being potentially a "red flag" of adverse cardiac remodeling and a major determinant of response to therapy and outcomes. In this review, we aimed to provide an overview of the latest evidence on the prevalence, mechanistic and prognostic implications of CMD beyond the spectrum of CCS (i.e. heart failure, cardiomyopathies, Takotsubo syndrome, aortic stenosis)., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2024. Published by Elsevier Inc.)

BackgroundCoronary microvascular dysfunction (CMD) may play an important role in various cardiovascular diseases, including HFpEF and both obstructive and non-obstructive coronary artery disease (CAD). To date, there has been no bibliometric analysis to summarize this field. Here, we aim to conduct a bibliometric analysis of CMD to determine the current status and frontiers in this field.Materials and methodsPublications about CMD were taken from the Web of Science Core Collection database (WOSCC). WOSCC’s literature analysis wire, the VOSviewer 1.6.16, and CiteSpace 5.1.3 were used to conduct the analysis.ResultsA total of 785 publications containing 206 reviews and 579 articles are included in the sample. The leading authors are Iacopo Olivotto, Paolo G. Camici, and Carl J. Pepine. The most productive institutions are the University of Florence, Cedars Sinai Medical Center, and Harvard University. The most productive countries are the USA, Italy, and England. There are a total of 237 journals that contribute to this field, and the leading journals in our study were the International Journal of Cardiology, the European Heart Journal and the JACC. From 2012 to 2021, the top three most-cited articles focused on the association between HFpEF and CMD. The important keywords are heart failure, hypertrophic cardiomyopathy, chest pain, women, coronary flow reserve (CFR), endothelial dysfunction and prognostic value. “Positron emission tomography” shows the strongest burst strength, followed by “blow flow” and “artery.” The keywords that started to burst from 2015 are particularly emphasized, including “heart failure,” “coronary flow reserve,” and “management.”ConclusionStudies about CMD are relatively limited, and the largest contribution comes from the USA, Italy and England. More studies are needed, and publications from other countries should be enhanced. The main research hotspots in the CMD field include CMD in patients with HFpEF, sex differences, the new methods of diagnosis for CMD, and the effective treatment of CMD. Attention should be given to CMD in patients with HFpEF, and untangling the association between CMD and HFpEF could be helpful in the development of physiology-stratified treatment for patients with CMD and HFpEF.

BackgroundResting full-cycle ratio (RFR) is an alternative to fractional flow reserve (FFR) for the evaluation of borderline coronary artery lesions. Although FFR and RFR results are discordant in some cases, factors associated with the discordance remain unclear. The role of coronary microvascular dysfunction (CMD) is discussed as a potential mechanism to explain these discrepancies.AimThe study aimed to assess concordance between RFR and FFR in a real-life cohort from a high-volume center regarding the role of CMD.MethodsConsecutive patients with borderline coronary lesions undergoing coronary functional testing for chronic coronary syndromes were included in the study. Measurements of RFR and FFR were performed alongside additional coronary flow reserve (CFR), resistance reserve ratio (RRR), and an index of microcirculatory resistance (IMR) measurements. CMD was defined according to the current guideline by either IMR ≥25 or CFR ≤2.0 in vessels with no significant stenosis.ResultsMeasurements were performed in 157 coronary arteries, in 101 patients, with a median age of 66 y., 74% male, with prior history of arterial hypertension (96%), dyslipidaemia (91%), and diabetes (40%). The median value of vessel diameter stenosis was 45% according to QCA.Overall, FFR and RFR values were significantly correlated (r = 0.66, p < 0.001), where positive FFR/negative RFR and negative FFR/positive RFR were observed in 6 (3.8%) and 38 (24.2%) of 157 vessels. The RFR/FFR discrepancy was present in 44 (28%) of measurements. CMD was confirmed in 28 (64%) of vessels with discrepant RFR/FFR and in 46 (41%) of vessels with concordant results (p = 0.01). In discordant RFR/FFR vessels, as compared to concordant ones, significantly lower values of CFR [median 1.95 (IQR: 1.37, 2.30) vs. 2.10 (IQR: 1.50, 3.00), p = 0.030] and RRR [median 2.50 (IQR: 1.60, 3.10) vs. 2.90 IQR (1.90, 3.90), p = 0.048] were observed.Main predictors of RFR/FFR discrepancy in a univariate regression analysis were: higher age of patients [OR = 1.06 (1.01; 1.10), p = 0.010], presence of CMD [OR = 2.51 (1.23; 5.25), p = 0.012], lower CFR [OR = 1.64 (1.12; 2.56), p = 0.018], and lower RRR values [OR = 1.35 (95% CI: 1.03; 1.83), p = 0.038].ConclusionIn discrepant RFR/FFR vessels, CMD is more prevalent than in concordant RFR/FFR measurements, which can be driven by lower CFR or RRR values. Further research is needed to confirm this observation.

AimsWe set out to further develop reflectance spectroscopy for the characterisation and quantification of coronary thrombi. Additionally, we explore the potential of our approach for use as a risk stratification tool by exploring the relation of reflectance spectra to indices of coronary microvascular injury.Methods and resultsWe performed hyperspectral imaging of coronary thrombi aspirated from 306 patients presenting with ST-segment elevation acute coronary syndrome (STEACS). Spatially resolved reflected light spectra were analysed using unsupervised machine learning approaches. Invasive [index of coronary microvascular resistance (IMR)] and non-invasive [microvascular obstruction (MVO) at cardiac magnetic resonance imaging] indices of coronary microvascular injury were measured in a sub-cohort of 36 patients. The derived spectral signatures of coronary thrombi were correlated with both invasive and non-invasive indices of coronary microvascular injury. Successful machine-learning-based classification of the various thrombus image components, including differentiation between blood and thrombus, was achieved when classifying the pixel spectra into 11 groups. Fitting of the spectra to basis spectra recorded for separated blood components confirmed excellent correlation with visually inspected thrombi. In the 36 patients who underwent successful thrombectomy, spectral signatures were found to correlate well with the index of microcirculatory resistance and microvascular obstruction; R2: 0.80, p < 0.0001, n = 21 and R2: 0.64, p = 0.02, n = 17, respectively.ConclusionMachine learning assisted reflectance spectral analysis can provide a measure of thrombus composition and evaluate coronary microvascular injury in patients with STEACS. Future work will further validate its deployment as a point-of-care diagnostic and risk stratification tool for STEACS care.

With growing evidence in clinical practice, the understanding of coronary syndromes has gradually evolved out of focusing on the well-established link between stenosis of epicardial coronary artery and myocardial ischemia to the structural and functional abnormalities at the level of coronary microcirculation, known as coronary microvascular dysfunction (CMD). CMD encompasses several pathophysiological mechanisms of coronary microcirculation and is considered as an important cause of myocardial ischemia in patients with angina symptoms without obstructive coronary artery disease (CAD). As a result of growing knowledge of the understanding of CMD assessed by multiple non-invasive modalities, CMD has also been found to be involved in other cardiovascular diseases, including primary cardiomyopathies as well as heart failure with preserved ejection fraction (HFpEF). In the past 2 decades, almost all the imaging modalities have been used to non-invasively quantify myocardial blood flow (MBF) and promote a better understanding of CMD. Myocardial contrast echocardiography (MCE) is a breakthrough as a non-invasive technique, which enables assessment of myocardial perfusion and quantification of MBF, exhibiting promising diagnostic performances that were comparable to other non-invasive techniques. With unique advantages over other non-invasive techniques, MCE has gradually developed into a novel modality for assessment of the coronary microvasculature, which may provide novel insights into the pathophysiological role of CMD in different clinical conditions. Moreover, the sonothrombolysis and the application of artificial intelligence (AI) will offer the opportunity to extend the use of contrast ultrasound theragnostics.

Up to 4 million patients with signs of myocardial ischemia have no obstructive coronary artery disease (CAD). The absence of precise guidelines for diagnosis and treatment in non-obstructive CAD encourages the scientific community to fill the gap knowledge, to provide non-invasive and less expensive diagnostic tools. The aim of our study was to explore the biological profile of Ischemia with Non-Obstructive Coronary Arteries (INOCA) patients with microvascular dysfunction compared to patients presenting with obstructive chronic coronary syndrome (ObCCS) in order to find specific hallmarks of each clinical condition. We performed a gene expression array from peripheral blood mononuclear cells (PBMCs) isolated from INOCA (n = 18) and ObCCS (n = 20) patients. Our results showed a significantly reduced gene expression of molecules involved in cell adhesion, signaling, vascular motion, and inflammation in INOCA as compared to the ObCCS group. In detail, we found lower expression of Platelet and Endothelial Cell Adhesion Molecule 1 (CD31, p < 0.0001), Intercellular Adhesion Molecule-1 (ICAM1, p = 0.0004), Tumor Necrosis Factor (TNF p = 0.0003), Transferrin Receptor (TFRC, p = 0.002), and Vascular Endothelial Growth Factor A (VEGFA, p = 0.0006) in the INOCA group compared with ObCCS. Meanwhile, we observed an increased expression of Hyaluronidase (HYAL2, p < 0.0001) in INOCA patients in comparison to ObCCS. The distinct expression of molecular biomarkers might allow an early and non-invasive differential diagnosis between ObCCS and INOCA, improving clinical management and treatment options, in the era of personalized medicine. [ABSTRACT FROM AUTHOR]

Background: Patients with diabetes mellitus (DM) and heart failure (HF) have worse outcomes than normoglycemic HF patients. Cardiovascular magnetic resonance (CMR) can identify ischemic heart disease (IHD) and quantify coronary microvascular dysfunction (CMD) using myocardial perfusion reserve (MPR). We aimed to quantify the extent of silent IHD and CMD in patients with DM presenting with HF., Methods: Prospectively recruited outpatients undergoing assessment into the etiology of HF underwent in-line quantitative perfusion CMR for calculation of stress and rest myocardial blood flow (MBF) and MPR. Exclusions included angina or history of IHD. Patients were followed up (median 3.0 years) for major adverse cardiovascular events (MACE)., Results: Final analysis included 343 patients (176 normoglycemic, 84 with pre-diabetes, and 83 with DM). Prevalence of silent IHD was highest in DM 31% ( 26/83), then pre-diabetes 20% (17/84) then normoglycemia 17%, ( 30/176). Stress MBF was lowest in DM (1.53 ± 0.52), then pre-diabetes (1.59 ± 0.54) then normoglycemia (1.83 ± 0.62). MPR was lowest in DM (2.37 ± 0.85) then pre-diabetes (2.41 ± 0.88) then normoglycemia (2.61 ± 0.90). During follow-up, 45 patients experienced at least one MACE. On univariate Cox regression analysis, MPR and presence of silent IHD were both associated with MACE. However, after correction for HbA1c, age, and left ventricular ejection fraction, the associations were no longer significant., Conclusion: Patients with DM and HF had higher prevalence of silent IHD, more evidence of CMD, and worse cardiovascular outcomes than their non-diabetic counterparts. These findings highlight the potential value of CMR for the assessment of silent IHD and CMD in patients with DM presenting with HF., Competing Interests: Declaration of competing interests The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Microvascular resistance reserve (MRR) is a recently introduced specific index of coronary microcirculation. MRR calculation can utilize parameters deriving from coronary flow reserve (CFR) assessment, provided that intracoronary pressure data are also available. The previously proposed pressure-bounded CFR (CFRpb) defines the possible CFR interval on the basis of resting and hyperemic pressure gradients in the epicardial vessel, however, its correlation to the Doppler wire measurement was reported to be rather poor without the correction for hydrostatic pressure., Purpose: We aimed to determine the pressure-bounded coronary MRR interval with hydrostatic pressure correction according to the previously established equations of CFRpb adapted for the MRR concept. Furthermore, we also aimed to design a prediction model using the actual MRR value within the pressure-bounded interval and validate the results against the gold-standard Doppler wire technique., Methods: Hydrostatic pressure between the tip of the catheter and the sensor of the pressure wire was calculated by height difference measurement from a lateral angiographic view. In the derivation cohort the pressure-bounded MRR interval (between MRRpb min and MRRpb max ) was determined solely from hydrostatic pressure-corrected intracoronary pressure data. The actual MRR was calculated by simple hemodynamic equations incorporating the anatomical data of the three-dimensionally reconstructed coronary artery (MRR p-3D ). These results were analyzed by regression analyses to find relations between the MRRpb bounds and the actual MRR p-3D ., Results: In the derivation cohort of 23 measurements, linear regression analysis showed a tight relation between MRRpb max and MRR p-3D ( r 2  = 0.74, p  < 0.0001). Using this relation (MRR p-3D  = 1.04 + 0.51 × MRRpb max ), the linear prediction of the MRR was tested in the validation cohort of 19 measurements against the gold standard Doppler wire technique. A significant correlation was found between the linearly predicted and the measured values ( r  = 0.54, p  = 0.01). If the area stenosis (AS%) was included to a quadratic prediction model, the correlation was improved ( r  = 0.63, p  = 0.004)., Conclusions: The MRR can be predicted reliably to assess microvascular function by our simple model. After the correction for hydrostatic pressure error, the pressure data during routine FFR measurement provides a simultaneous physiological assessment of the macro- and microvasculature., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2024 Ágoston, Dorj, Üveges, Tar, Szabó, Barta, Szűk, Kest, Méhész, Komócsi, Czuriga, Csippa, Piróth, Barbato and Kőszegi.)

Background: A high proportion of coronary microvascular dysfunction (CMD) has been observed in patients with acute myocardial infarction (AMI) who have received primary percutaneous coronary intervention (PCI), which may affect their prognosis. This study used cadmium zinc telluride (CZT) single photon emission computed tomography (SPECT) to evaluate the prevalence and characteristics of CMD and myocardial area at risk (AAR) in AMI patients who had undergone primary PCI., Methods: We conducted a single-center cross-sectional retrospective study at TEDA International Cardiovascular Hospital from September 2021 to June 2022. A total of 83 patients received primary PCI for AMI. Subsequently, a rest/stress dynamic and routine gated myocardial perfusion imaging (MPI) were performed 1 week after PCI. The CMD group was defined as having a residual stenosis of infarct-related artery (IRA) <50% and myocardial flow reserve (MFR) <2.0 in this corresponding territory, whereas MFR ≥2.0 of IRA pertained to the normal control group. Rest-AAR of infarction (%) and stress-AAR (%) were expressed by the percentage of measured rest-defect-size and stress-defect-size in the left ventricular area, respectively. Logistic regression analyses were performed to identify significant predictors of CMD., Results: A total of 53 patients with a mean age of 57.06±11.99 years were recruited, of whom 81.1% were ST-segment elevation myocardial infarction (STEMI). The proportion of patients with CMD was 79.2% (42/53). The time of pain to SPECT imaging was 7.50±1.27 days in the CMD group and 7.45±1.86 days among controls. CMD patients had a higher body mass index (BMI) than controls (26.48±3.26 vs . 24.36±2.73 kg/m 2 , P=0.053), and a higher proportion of STEMI, thrombolysis in myocardial infarction (TIMI) 0 grade of IRA prior PCI than controls (88.1% vs . 54.5%, P=0.011; 61.9% vs . 18.2%, P=0.004, respectively). No significant difference was identified in the rest-myocardial blood flow (MBF) of IRA between the 2 groups, whereas the stress-MBF and MFR of IRA, rest-AAR, and stress-AAR in the CMD group were remarkably lowered. Higher BMI [odds ratio (OR): 1.332, 95% confidence interval (CI): 1.008-1.760, P=0.044] and stress-AAR (OR: 1.994, 95% CI: 1.122-3.543, P=0.019) were used as independent predictors of CMD occurrence., Conclusions: The prevalence of CMD is high in AMI patients who received primary PCI. Each 1 kg/m 2 increase in BMI was associated with a 1.3-fold increase in CMD risk. A 5% increase in stress-AAR was associated with a nearly 2-fold increase in CMD risk. Increased BMI and stress-AAR predicts decreased coronary reserve function., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://qims.amegroups.com/article/view/10.21037/qims-23-1260/coif). The authors have no conflicts of interest to declare., (2024 Quantitative Imaging in Medicine and Surgery. All rights reserved.)

Background: Coronary microvascular dysfunction (CMD) is an early feature of diabetic cardiomyopathy, which usually precedes the onset of diastolic and systolic dysfunction. Continuous intracoronary thermodilution allows an accurate and reproducible assessment of absolute coronary blood flow and microvascular resistance thus allowing the evaluation of coronary flow reserve (CFR) and Microvascular Resistance Reserve (MRR), a novel index specific for microvascular function, which is independent from the myocardial mass. In the present study we compared absolute coronary flow and resistance, CFR and MRR assessed by continuous intracoronary thermodilution in diabetic vs. non-diabetic patients. Left atrial reservoir strain (LASr), an early marker of diastolic dysfunction was compared between the two groups.Methods: In this observational retrospective study, 108 patients with suspected angina and non-obstructive coronary artery disease (NOCAD) consecutively undergoing elective coronary angiography (CAG) from September 2018 to June 2021 were enrolled. The invasive functional assessment of microvascular function was performed in the left anterior descending artery (LAD) with intracoronary continuous thermodilution. Patients were classified according to the presence of DM. Absolute resting and hyperemic coronary blood flow (in mL/min) and resistance (in WU) were compared between the two cohorts. FFR was measured to assess coronary epicardial lesions, while CFR and MRR were calculated to assess microvascular function. LAS, assessed by speckle tracking echocardiography, was used to detect early myocardial structural changes potentially associated with microvascular dysfunction.Results: The median FFR value was 0.83 [0.79–0.87] without any significant difference between the two groups. Absolute resting and hyperemic flow in the left anterior descending coronary were similar between diabetic and non-diabetic patients. Similarly, resting and hyperemic resistances did not change significantly between the two groups. In the DM cohort the CFR and MRR were significantly lower compared to the control group (CFR = 2.38 ± 0.61 and 2.88 ± 0.82; MRR = 2.79 ± 0.87 and 3.48 ± 1.02 for diabetic and non-diabetic patients respectively, [p < 0.05 for both]). Likewise, diabetic patients had a significantly lower reservoir, contractile and conductive LAS (all p < 0.05).Conclusions: Compared with non-diabetic patients, CFR and MRR were lower in patients with DM and non-obstructive epicardial coronary arteries, while both resting and hyperemic coronary flow and resistance were similar. LASr was lower in diabetic patients, confirming the presence of a subclinical diastolic dysfunction associated to the microcirculatory impairment. Continuous intracoronary thermodilution-derived indexes provide a reliable and operator-independent assessment of coronary macro- and microvasculature and might potentially facilitate widespread clinical adoption of invasive physiologic assessment of suspected microvascular disease.

Instantaneous wave-free ratio (iFR) has been proposed as a hemodynamic parameter that can reliably reflect the blood flow in stenosed coronary arteries. Currently, there are few investigations on the quantitative analysis of iFR in the patients regarding the variation of microcirculatory resistance (MR). The data aim to provide geometric (cross-section area of branches) and hemodynamic (flow rate and iFR of branches) parameters of normal and stenosed coronary arteries derived from CFD simulation. The CFD simulation was performed on the three-dimensional artery models reconstructed from computed tomography (CT) images of four subjects. The hemodynamic parameters were obtained in six situations of MR to simulate coronary microvascular dysfunction (CMD). This dataset could be used as the reference to estimate the iFR and flow rate in patients with CMD and stenosis in coronary arteries. The geometric parameters could be used in the modelling of coronary arteries.

Recently, the importance has emerged of ischemia with no obstructive coronary artery disease (INOCA), for which endothelial and vascular smooth muscle cell (VSMC) dysfunctions and alterations in coronary vasa vasorum are involved. Regarding endothelial vasodilator functions, both endothelium-derived nitric oxide and endothelium-derived hyperpolarizing factor play important roles in modulating vascular tone, especially in the microcirculation. Recent studies have suggested systemic endothelial dysfunction in INOCA. Regarding VSMC dysfunction, Rho-kinase has been identified as a key molecular mechanism of VSMC hyperconstriction in INOCA. Finally, recent advances of coronary imaging have demonstrated the important role of altered adventitial vasa vasorum functions in INOCA. [ABSTRACT FROM AUTHOR]

As a main etiology of myocardial ischemia, coronary microvascular dysfunction (CMD) can occur in patients with or without obstructive coronary artery disease. Currently, there is a lack of a non-invasive approach for early detection of CMD. We aim to develop a multilayer perceptron (MLP) algorithm to achieve non-invasive early detection of CMD based on vectorcardiography (VCG) and cardiodynamicsgram (CDG) features. Electrocardiograms of 82 CMD patients and 107 healthy controls were collected and synthesized into VCGs. The VCGs' ST-T segments were extracted and fed into a deterministic learning algorithm to develop CDGs. Temporal heterogeneity index, spatial heterogeneity index, sample entropy, approximate entropy, and complexity index were extracted from VCGs' ST-T segments and CDGs, entitled as STT - and CDG -based features, respectively. The most effective feature subsets were determined from CDG -based, STT -based, and the combined features (i.e., all features) via the sequential backward selection algorithm as inputs for CDG -, STT -, and CDG-STT -based MLP models optimized with an improved sparrow search algorithm, respectively. Finally, the classification capacity of the corresponding models was evaluated via five-fold cross-validations and tested on a testing dataset to verify the optimal one. The CDG-STT -based MLP model had significantly higher evaluated metrics than CDG - and STT -based ones on the validation dataset, with the accuracy, sensitivity, specificity, F1 score, and AUC of 0.904, 0.925, 0.870, 0.870, and 0.897 on the testing dataset respectively. The MLP model based on VCG and CDG features showed high efficiency in identifying CMD. The CDG-STT -based MLP model may afford a potential computer-aided tool for non-invasive detection of CMD. • Non-invasive early detection of coronary microvascular dysfunction (CMD). • Vectorcardiogram (VCG) and cardiodynamicsgram (CDG) features for CMD detection. • Our proposed multilayer perceptron model: accuracy of 0.904 and sensitivity of 0.925. • Temporal and spatial features of VCG and CDG are effective indicators of a CMD. [ABSTRACT FROM AUTHOR]

Background: Microvascular dysfunction in patients with nonobstructive coronary artery disease is increasingly being recognized as an important health issue. This systematic review and meta-analysis evaluated the effectiveness of ranolazine, an antianginal agent, in improving coronary microvascular function., Methods: We conducted a comprehensive literature search of the Cochrane Library, PubMed, Embase, China National Knowledge Infrastructure, the Chinese BioMedical Literature Database, and gray literature databases until September 30, 2023. The included studies were randomized controlled trials (RCTs) published in the English or Chinese languages that screened for eligibility using two independent investigators. Risk of bias was evaluated with the Cochrane Collaboration tool. Subgroup and sensitivity analyses were used to identify sources of heterogeneity. Meta-analysis was performed using RevMan version 5.4 (Cochrane) and Stata version 16.0 (StataCorp)., Results: From 1,470 citations, 8 RCTs involving 379 participants were included in this analysis. Our findings showed that ranolazine increased coronary flow reserve (CFR) over an 8 to 12-week follow-up period [standardized mean difference =1.16; 95% confidence interval (CI): 0.4-1.89; P=0.002]. Ranolazine increased the global myocardial perfusion reserve index (MPRI) [weighted mean difference (WMD) =0.18; 95% CI: 0.07-0.29; P=0.002] and the midsubendocardial MPRI (WMD =0.10; 95% CI: 0.02-0.19; P=0.02). Moreover, ranolazine improved 3 of the 5 Seattle Angina Questionnaire scores, namely, physical functioning (WMD =4.89; 95% CI: 0.14 to 9.64; P=0.04), angina stability (WMD =17.31; 95% CI: 7.13-27.49; P=0.0009), and quality of life (WMD =10.11; 95% CI: 3.57-16.65; P=0.0003). Trial sequential analysis showed that the meta-analysis of angina stability and quality of life scores had a sufficient sample size and statistical power., Conclusions: Our analysis suggests that ranolazine is associated with improvements in CFR, myocardial perfusion, and the Seattle Angina Questionnaire scores in patients with nonobstructive coronary artery disease. However, further large-scale RCTs with long-term follow-up are recommended to validate these findings and provide a more comprehensive understanding of the effects of ranolazine on coronary microvascular function., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://qims.amegroups.com/article/view/10.21037/qims-23-1029/coif). All authors reported that this work was supported by grants from the Beijing Municipal Natural Science Foundation (grant no. 7212068) and the National Natural Science Foundation of China (grant no. 81900747). The authors have no other conflicts of interest to declare., (2024 Quantitative Imaging in Medicine and Surgery. All rights reserved.)

Ischemia with no obstructive coronary arteries (INOCA) is defined as patients with evidence of myocardial ischemia without obstructive coronary artery disease. About 3-4 million people in the United States have INOCA, more commonly affecting women, and carries adverse morbidity, mortality, and relatively high healthcare costs. The pathophysiology of INOCA appears to be multi-factorial with a variety of contributing mechanisms. Diagnosis of INOCA is suggested by non-invasive or invasive testing consistent with myocardial ischemia. Due to the high prevalence of coronary risk factors and atherosclerosis in the INOCA population, current treatment strategies target angina, coronary atherosclerosis, and atherosclerotic risk factors, as well as burgeoning treatment of coronary microvascular dysfunction (CMD). Ongoing clinical trials are assessing different options., Competing Interests: Declaration of competing interest Dr. C. Noel Bairey Merz, serves as Board of Director for iRhythm, fees paid through CSMC from Abbott Diagnostics and Sanofi. Dr. Janet Wei served on an advisory board for Abbott Vascular.

Background: Computed tomography myocardial perfusion (CT-MP) has reported usefulness in assessing hemodynamically significant epicardial coronary artery lesions. However, the diagnostic ability of the absolute coronary flow using CT-MP to detect coronary microvascular dysfunction (CMD) remains elusive. This prospective cohort study aimed to assess the diagnostic value of CT-MP in evaluating coexisting CMD in patients with functionally significant epicardial coronary stenosis and to analyze the predictive factors of lesions with CMD., Methods: Sixty-eight patients with chronic coronary syndrome (CCS) and de novo single functionally significant stenosis [fractional flow reserve (FFR) ≤0.80] were studied. CMD was defined as an index of microcirculatory resistance ≥25. We compare clinical background and CT-MP findings between patients with and without CMD (CMD, n=29; non-CMD, n=39). CT-MP, and quantitative and qualitative plaque assessments were included in computed tomography angiography assessment. Logistic regression analysis was performed to predict CMD., Results: FFR, invasive wire-derived coronary flow reserve (CFR wire ) and index of microcirculatory resistance were 0.68 [interquartile range (IQR), 0.59-0.74], 1.71 (IQR, 1.24-2.88), and 22.6 (IQR, 15.1-34.5), respectively. The rest and hyperemic-myocardial blood flow (MBF) and CT-MP-derived CFR (CFR CT-MP ) were 0.83 (0.64-1.03) mL/min/g, 2.14 (1.30-2.92) mL/min/g, and 2.19 (1.44-3.37), respectively. In the territories with CMD, hyperemic-MBF was significantly lower than in those without [1.68 (IQR, 0.84-2.44) vs. 2.31 (IQR, 1.67-3.34) mL/min/g, P=0.015] and the prevalence of CFR CT-MP <2.0 was higher in the lesions with CMD than in those without (62.1% vs. 28.2%, P=0.011), while FFR values were similar. Fibrofatty and necrotic core component volume was greater in the vessels with CMD than in those without [31.8 (IQR, 19.0-48.9) vs. 25.1 (IQR, 17.2-32.1) mm 3 , P=0.045]. Multivariable logistic regression analysis showed that hyperemic-MBF and fibrofatty and necrotic core component volume were independent predictors of CMD territories [odds ratio (OR) =0.583; 95% confidence interval (CI): 0.355-0.958; P=0.033 and OR =1.040; 95% CI: 1.010-1.070; P=0.011]., Conclusions: Quantitative assessment of absolute coronary flow using pre-percutaneous coronary intervention (PCI) CT-MP, and comprehensive plaque analysis using computed tomography angiography may help detect coexisting subtended microvascular dysfunction in territories with functionally significant epicardial coronary lesions. Further studies are required to elucidate the clinical significance of coexisting CMD in patients with CCS undergoing PCI., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://qims.amegroups.com/article/view/10.21037/qims-23-618/coif). The authors have no conflicts of interest to declare., (2023 Quantitative Imaging in Medicine and Surgery. All rights reserved.)

Background: Coronary microvascular dysfunction (CMD) has been suggested to be one of the pathologic mechanisms contributing to heart failure with preserved left ventricular ejection fraction (LVEF) and left ventricular (LV) diastolic dysfunction. We therefore aimed to evaluate LV diastolic function in patients with CMD using cardiovascular magnetic resonance feature tracking (CMR-FT)., Methods: We prospectively enrolled 115 patients referred to cardiology clinics for chest pain assessment who subsequently underwent coronary computed tomography angiogram and stress perfusion CMR. CMD was defined as the presence of subendocardial inducible ischemia detected through visual assessment. LV diastolic function was evaluated using CMR-derived volume-time curves and CMR-FT parameters. The former included early peak filling rate (PFR) and time to PFR; the latter included LV global/regional peak longitudinal diastolic strain rate (LDSR), circumferential diastolic strain rate (CDSR), and radial diastolic strain rate (RDSR)., Results: A total of 92 patients with 1,312 segments were eventually included. Of these, 19 patients were classified as non-CMD (48.8±11.2 years; 63.2% male) and 73 as with CMD (52.3±11.9 years; 54.8% male). The LVEFs were similar and preserved in both groups (P=0.266). At the per-patient level, no differences were observed in PFR, time to PFR, or LV global diastolic strain rates between the two groups. At the per-segment level, 51% (665/1,312) of the myocardial segments were classified as CMD, whereas 49% (647/1,312) were classified as non-CMD. CMD segments showed significantly lower regional CDSR (P=0.019) and RDSR (P=0.006) compared with non-CMD segments., Conclusions: Despite normal LV ejection fraction in CMD patients, decreased LV diastolic function in CMD myocardial segments indicates early diastolic impairment., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://qims.amegroups.com/article/view/10.21037/qims-23-47/coif). The authors have no conflicts of interest to declare., (2023 Quantitative Imaging in Medicine and Surgery. All rights reserved.)

Purpose: Coronary microvascular dysfunction (CMD) is emerging as an important cause of myocardial ischemia, but there is a lack of a non-invasive method for reliable early detection of CMD., Aim: To develop an electrocardiogram (ECG)-based machine learning algorithm for CMD detection that will lay the groundwork for patient-specific non-invasive early detection of CMD., Methods: Vectorcardiography (VCG) was calculated from each 10-second ECG of CMD patients and healthy controls. Sample entropy (SampEn), approximate entropy (ApEn), and complexity index (CI) derived from multiscale entropy were extracted from ST-T segments of each lead in ECGs and VCGs. The most effective entropy subset was determined using the sequential backward selection algorithm under the intra-patient and inter-patient schemes, separately. Then, the corresponding optimal model was selected from eight machine learning models for each entropy feature based on five-fold cross-validations. Finally, the classification performance of SampEn-based, ApEn-based, and CI-based models was comprehensively evaluated and tested on a testing dataset to investigate the best one under each scheme., Results: ApEn-based SVM model was validated as the optimal one under the intra-patient scheme, with all testing evaluation metrics over 0.8. Similarly, ApEn-based SVM model was selected as the best one under the intra-patient scheme, with major evaluation metrics over 0.8., Conclusions: Entropies derived from ECGs and VCGs can effectively detect CMD under both intra-patient and inter-patient schemes. Our proposed models may provide the possibility of an ECG-based tool for non-invasive detection of CMD.

Background: To assess the diagnostic accuracy of AccuIMR, a newly proposed, pressure wire-free index, in identifying coronary microvascular dysfunction (CMD) among patients with acute coronary syndrome [including ST-segment elevation myocardial infarction (STEMI) and non-ST-segment elevation myocardial infarction (NSTEMI)] and chronic coronary syndrome (CCS)., Methods: A total of 163 consecutive patients (43 with STEMI, 59 with NSTEMI, and 61 with CCS), who underwent invasive coronary angiography (ICA) and for whom the index of microcirculatory resistance (IMR) was measured, were retrospectively enrolled at a single center. IMR measurements were made in 232 vessels. The AccuIMR based on computational fluid dynamics (CFD) was calculated from coronary angiography. The diagnostic performance of AccuIMR was assessed using wire-based IMR as a reference standard., Results: AccuIMR correlated well with IMR (overall r=0.76, P<0.001; STEMI r=0.78, P<0.001; NSTEMI r=0.78, P<0.001; CCS r=0.75, P<0.001) and had good diagnostic performance in detecting abnormal IMR [overall diagnostic accuracy, sensitivity, and specificity were 94.83% (91.14% to 97.30%), 92.11% (78.62% to 98.34%), and 95.36% (91.38% to 97.86%), respectively]. Using a cutoff value of IMR >40 U for AccuIMR in STEMI and IMR >25 U in NSTEMI and CCS, the area under the receiver operating characteristic (ROC) curve (AUC) of AccuIMR for predicting abnormal IMR value was 0.917 (0.874 to 0.949) in all patients, 1.000 (0.937 to 1.000) in patients with STEMI, 0.941 (0.867 to 0.980) in patients with NSTEMI, and 0.918 (0.841 to 0.966) in patients with CCS., Conclusions: The use of AccuIMR in the evaluation of microvascular diseases could provide valuable information and potentially increase the application of physiological assessment for microcirculation in patients with ischemic heart disease., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://qims.amegroups.com/article/view/10.21037/qims-22-961/coif). ZL reports grants from the National Natural Science Foundation of China (No. 82070425) and the Natural Science Foundation of Hubei Province of China (No. 2021CFA011). CL reports grants from the Chinese Cardiovascular Association-V.G. Fund (No. 2017-CCA-VG-006) and the Non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences (No. 2020-JKCS-003). YH and JH are employees of ArteryFlow. XL is a co-founder of ArteryFlow. JX is the CEO of ArteryFlow and receives a grant from Hangzhou Leading Innovation and Entrepreneurship Team Project (No. TD2022007). The other authors have no conflicts of interest to declare., (2023 Quantitative Imaging in Medicine and Surgery. All rights reserved.)

Background: The coronary angiography-derived index of microcirculatory resistance (caIMR) is a novel noninvasive method to assess coronary microvascular dysfunction (CMD). However, the association between caIMR and the prognosis of patients with dilated cardiomyopathy (DCM) is unclear. We aimed to explore the role of the caIMR in evaluating the outcome of patients with DCM., Methods: We consecutively and retrospectively enrolled patients with DCM in the Department of Cardiology, the First Affiliated Hospital of Nanjing Medical University, Nanjing, China, from January 2013 to January 2018. The caIMR was calculated for eligible patients. The primary end point in this study was composite events, including rehospitalization related to heart failure (HF), device implantation, heart transplantation, or cardiac death. Patients were categorized into groups based on whether they had composite events (the events and no-events groups), and differences in the baseline and end points between these two groups were analyzed., Results: A total of 95 eligible patients with DCM were enrolled in the study, 36 of whom had end point events. The best cutoff values of the caIMR for the left anterior descending (LAD) artery, left circumflex (LCX) artery, and right coronary artery (RCA) were >29.8 with an area under the curve (AUC) of 0.828, >25.5 with an AUC of 0.720, and >29.7 with an AUC of 0.717, respectively (all P values <0.001). Patients were then classified into the higher caIMR group and the lower caIMR group based on the cutoff value. Kaplan-Meier analyses showed that patients with a higher caIMR had increased cumulative risks of end point events regardless of the cutoff values for the LAD, LCX, and RCA (all log-rank P values <0.001). After adjustment for confounders, Cox regression analyses indicated that LAD-caIMR was an independent risk factor for end point events in patients with DCM [hazard ratio (HR) =1.11; 95% CI: 1.06-1.16]., Conclusions: A higher caIMR was significantly associated with the poor prognosis of patients with DCM., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://qims.amegroups.com/article/view/10.21037/qims-22-1060/coif). XK received funding from the Science Foundation of Gusu School (No. GSKY20220102); HW received funding from the Natural Science Foundation of Jiangsu Province (No. BK2012648). Zhi Zuo received funding from the Nanjing Science and Technology Innovation Projects for Overseas Graduates and the National Science Fund for Distinguished Young Scholars (No. 8220021578). Zhiyong Zhang received funding from the General Scientific Research Project of Jiangsu Provincial Health Commission (No. M2020083). The other authors have no conflicts of interest to declare., (2023 Quantitative Imaging in Medicine and Surgery. All rights reserved.)

Background: Coronary microvascular dysfunction (CMD) has differences in prevalence and presentation between women and men; however, we have limited understanding about underlying contributors to sex differences in CMD. Myocardial perfusion reserve index (MPRI), as semi-quantitative measure of myocardial perfusion derived from cardiac magnetic resonance (CMR) imaging has been validated as a measure of CMD. We sought to understand the sex differences in the relations between the MPRI and traditional measures of cardiovascular disease by CMR., Methods: A retrospective analysis of a single-center cohort of patients receiving clinical stress CMR from 2015 to 2022 was performed. Patients with calculated MPRI and no visible perfusion defects consistent with obstructive epicardial coronary disease were included. We compared associations between MPRI versus traditional cardiovascular risk factors and markers of cardiac structure/function in sex-stratified populations using univariable and multivariable regression models., Results: A total of 229 patients [193 female, 36 male, median age 57 (47-67) years] were included in the analysis. In the female population, no traditional cardiovascular risk factors were associated with MPRI, whereas in the male population, diabetes (β: -0.80, p = 0.03) and hyperlipidemia (β: -0.76, p = 0.006) were both associated with reduced MPRI in multivariable models. Multivariable models revealed significant associations between reduced MPRI and increased ascending aortic diameter (β: -0.42, p = 0.005) and T1 times (β: -0.0056, p = 0.03) in the male population, and increased T1 times (β: -0.0037, p = 0.006) and LVMI (β: -0.022, p = 0.0003) in the female population., Conclusion: The findings suggest different underlying pathophysiology of CMD in men versus women, with lower MPRI in male patients fitting a more "traditional" atherosclerotic profile., Competing Interests: JW served on an advisory board for Abbott Vascular, paid to institution. CM serves as Board of Director for iRhythm and Advisory Board member for SHL Telemedicine. DB serves as a consultant with Bayer Pharmaceuticals. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Kwan, Wei, Ouyang, Ebinger, Merz, Berman and Cheng.)

Background: Coronary microvascular dysfunction (CMD) may play an important role in various cardiovascular diseases, including HFpEF and both obstructive and non-obstructive coronary artery disease (CAD). To date, there has been no bibliometric analysis to summarize this field. Here, we aim to conduct a bibliometric analysis of CMD to determine the current status and frontiers in this field., Materials and Methods: Publications about CMD were taken from the Web of Science Core Collection database (WOSCC). WOSCC's literature analysis wire, the VOSviewer 1.6.16, and CiteSpace 5.1.3 were used to conduct the analysis., Results: A total of 785 publications containing 206 reviews and 579 articles are included in the sample. The leading authors are Iacopo Olivotto, Paolo G. Camici, and Carl J. Pepine. The most productive institutions are the University of Florence, Cedars Sinai Medical Center, and Harvard University. The most productive countries are the USA, Italy, and England. There are a total of 237 journals that contribute to this field, and the leading journals in our study were the International Journal of Cardiology, the European Heart Journal and the JACC. From 2012 to 2021, the top three most-cited articles focused on the association between HFpEF and CMD. The important keywords are heart failure, hypertrophic cardiomyopathy, chest pain, women, coronary flow reserve (CFR), endothelial dysfunction and prognostic value. "Positron emission tomography" shows the strongest burst strength, followed by "blow flow" and "artery." The keywords that started to burst from 2015 are particularly emphasized, including "heart failure," "coronary flow reserve," and "management.", Conclusion: Studies about CMD are relatively limited, and the largest contribution comes from the USA, Italy and England. More studies are needed, and publications from other countries should be enhanced. The main research hotspots in the CMD field include CMD in patients with HFpEF, sex differences, the new methods of diagnosis for CMD, and the effective treatment of CMD. Attention should be given to CMD in patients with HFpEF, and untangling the association between CMD and HFpEF could be helpful in the development of physiology-stratified treatment for patients with CMD and HFpEF., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Lin, Wu, Gao, Wang and Huang.)

Background: Resting full-cycle ratio (RFR) is an alternative to fractional flow reserve (FFR) for the evaluation of borderline coronary artery lesions. Although FFR and RFR results are discordant in some cases, factors associated with the discordance remain unclear. The role of coronary microvascular dysfunction (CMD) is discussed as a potential mechanism to explain these discrepancies., Aim: The study aimed to assess concordance between RFR and FFR in a real-life cohort from a high-volume center regarding the role of CMD., Methods: Consecutive patients with borderline coronary lesions undergoing coronary functional testing for chronic coronary syndromes were included in the study. Measurements of RFR and FFR were performed alongside additional coronary flow reserve (CFR), resistance reserve ratio (RRR), and an index of microcirculatory resistance (IMR) measurements. CMD was defined according to the current guideline by either IMR ≥25 or CFR ≤2.0 in vessels with no significant stenosis., Results: Measurements were performed in 157 coronary arteries, in 101 patients, with a median age of 66 y., 74% male, with prior history of arterial hypertension (96%), dyslipidaemia (91%), and diabetes (40%). The median value of vessel diameter stenosis was 45% according to QCA.Overall, FFR and RFR values were significantly correlated ( r = 0.66, p < 0.001), where positive FFR/negative RFR and negative FFR/positive RFR were observed in 6 (3.8%) and 38 (24.2%) of 157 vessels. The RFR/FFR discrepancy was present in 44 (28%) of measurements. CMD was confirmed in 28 (64%) of vessels with discrepant RFR/FFR and in 46 (41%) of vessels with concordant results ( p = 0.01). In discordant RFR/FFR vessels, as compared to concordant ones, significantly lower values of CFR [median 1.95 (IQR: 1.37, 2.30) vs. 2.10 (IQR: 1.50, 3.00), p = 0.030] and RRR [median 2.50 (IQR: 1.60, 3.10) vs. 2.90 IQR (1.90, 3.90), p = 0.048] were observed.Main predictors of RFR/FFR discrepancy in a univariate regression analysis were: higher age of patients [OR = 1.06 (1.01; 1.10), p = 0.010], presence of CMD [OR = 2.51 (1.23; 5.25), p = 0.012], lower CFR [OR = 1.64 (1.12; 2.56), p = 0.018], and lower RRR values [OR = 1.35 (95% CI: 1.03; 1.83), p = 0.038]., Conclusion: In discrepant RFR/FFR vessels, CMD is more prevalent than in concordant RFR/FFR measurements, which can be driven by lower CFR or RRR values. Further research is needed to confirm this observation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Legutko, Niewiara, Guzik, Szolc, Podolec, Nosal, Diachyshyn, Zmudka and Kleczynski.)

Background: The association between coronary slow flow (CSF) and coronary microvascular dysfunction (CMD) remains unclear. The objective of this study was to evaluate the correlation between the corrected thrombolysis in myocardial infarction (TIMI) frame count (CTFC) and the index of microcirculatory resistance (IMR)., Methods: We consecutively enrolled patients with CSF from January 2017 to March 2018. Concurrently, we randomly selected control participants with normal flow arteries at a ratio of 3:1. Two cardiologists performed the measurements of CTFC. Coronary angiography-derived IMR (caIMR) was used to assess CMD. The caIMR was analyzed by an independent agency, with CMD being defined as caIMR >40 U., Results: A total of 111 patients with CSF and 39 patients without CSF were enrolled in this retrospective study. Compared with the non-CSF group, the CSF group had a greater proportion of males (65.8% vs. 23.1%; P<0.001) and a lower prevalence of hypertension (47.7% vs. 67.7%; P=0.042). Additionally, the CSF group had higher CTFC, coronary angiography-derived fractional flow reserve (caFFR), and caIMR regardless of left anterior descending artery (LAD), left circumflex artery (LCX), and right coronary artery (RCA) (all P values <0.001). A strong correlation between CTFC and caIMR was observed for all arteries (all P values <0.001). In the univariate analysis, male sex [hazard ratio (HR) =2.63, 95% CI: 1.30-5.31], E/e' (HR =0.88, 95% CI: 0.78-0.99), CTFC (HR =1.12, 95% CI: 1.09-1.16), and caFFR (HR =1.81, 95% CI: 1.50-2.17) were significantly correlated with CMD. After adjusting for covariates, male sex (HR =2.72, 95% CI: 1.22-6.06), CTFC (HR =1.10, 95% CI: 1.07-1.14), and caFFR (HR =1.22, 95% CI: 1.00-1.50) were independent predictors for CMD. Additionally, the best cutoff value of CTFC of all arteries for predicting CMD was 38 frames, with an area under the curve of 0.873, a sensitivity of 92.8%, and a specificity of 63.8% (P<0.001). Moreover, the best cutoff value of CTFC of LAD, LCX, and RCA to identify CMD was 35 frames, 52 frames, and 50 frames, respectively (all P values <0.001)., Conclusions: CTFC correlated well with caIMR and had a strong predictive power to identify CMD., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://qims.amegroups.com/article/view/10.21037/qims-22-224/coif). The authors report that this research was funded by the Science Foundation of Gusu School (No. GSKY20220102), the Natural Science Foundation of Jiangsu Provincial (No. BK2012648 to HW), and the General Scientific Research Project of Jiangsu Provincial Health Commission (No. M2020083), with further support being provided by Suzhou RainMed Medical Technology Co., Ltd. The authors have no other conflicts of interest to declare., (2022 Quantitative Imaging in Medicine and Surgery. All rights reserved.)

Aims: We set out to further develop reflectance spectroscopy for the characterisation and quantification of coronary thrombi. Additionally, we explore the potential of our approach for use as a risk stratification tool by exploring the relation of reflectance spectra to indices of coronary microvascular injury., Methods and Results: We performed hyperspectral imaging of coronary thrombi aspirated from 306 patients presenting with ST-segment elevation acute coronary syndrome (STEACS). Spatially resolved reflected light spectra were analysed using unsupervised machine learning approaches. Invasive [index of coronary microvascular resistance (IMR)] and non-invasive [microvascular obstruction (MVO) at cardiac magnetic resonance imaging] indices of coronary microvascular injury were measured in a sub-cohort of 36 patients. The derived spectral signatures of coronary thrombi were correlated with both invasive and non-invasive indices of coronary microvascular injury. Successful machine-learning-based classification of the various thrombus image components, including differentiation between blood and thrombus, was achieved when classifying the pixel spectra into 11 groups. Fitting of the spectra to basis spectra recorded for separated blood components confirmed excellent correlation with visually inspected thrombi. In the 36 patients who underwent successful thrombectomy, spectral signatures were found to correlate well with the index of microcirculatory resistance and microvascular obstruction; R 2 : 0.80, p < 0.0001, n = 21 and R 2 : 0.64, p = 0.02, n = 17, respectively., Conclusion: Machine learning assisted reflectance spectral analysis can provide a measure of thrombus composition and evaluate coronary microvascular injury in patients with STEACS. Future work will further validate its deployment as a point-of-care diagnostic and risk stratification tool for STEACS care., Competing Interests: Author RK reports grants from Medtronic and Terumo Inc. outside the submitting work. Author AB reports grants from Boston Scientific and personal fees from Boston Scientific, Abbott, Medtronic, and Phillips outside the submitted work. Author GD reports consultancy fee from Miracor Medical SA, speaker fees from Miracor Medical SA and Abbott, and grants from Miracor Medical SA, Abbott, Philips, Medtronic, and Terumo outside the submitted work. In addition, Authors GD, KC, CV, RL, and MA have a patent PCT/US20/55240 pending relevant to this work. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Kotronias, Fielding, Greenhalgh, Lee, Alkhalil, Marin, Emfietzoglou, Banning, Vallance, Channon and De Maria.)

Objectives: The aim of this study was to ascertain whether coronary microvascular dysfunction (CMD) and inflammation are related in cardiac syndrome X (CSX). Background: CMD can lead to CSX, defined as typical angina and transient myocardial ischemia despite normal coronary arteriograms. Inflammation has been suggested to play a role in the pathogenesis of myocardial ischemia in CSX. Methods: We assessed 21 CSX patients (age 52 ± 10 years; 17 women) without traditional cardiovascular risk factors and 21 matched apparently healthy control subjects. Positron emission tomography was used to measure myocardial blood flow (MBF) and coronary flow reserve (CFR) in response to intravenous adenosine, whereas high-sensitivity C-reactive protein (CRP) was measured to assess inflammation. Patients were subdivided a priori into 2 groups according to CRP concentrations at study entry (i.e., ≤3 or >3 mg/l). Results: There were no differences in resting (1.20 ± 0.23 ml/min/g vs. 1.14 ± 0.20 ml/min/g; p = 0.32) or hyperemic MBF (3.28 ± 1.02 ml/min/g vs. 3.68 ± 0.89 ml/min/g; p = 0.18) between CSX patients and the control group, whereas CFR was mildly reduced in CSX patients compared with the control group (2.77 ± 0.80 vs. 3.38 ± 0.80; p = 0.02). Patients with CRP >3 mg/l had more severe impairment of CFR (2.14 ± 0.33 vs. 3.16 ± 0.76; p = 0.001) and more ischemic electrocardiographic changes during adenosine administration than patients with lower CRP, and a negative correlation between CRP levels and CFR (r = −0.49, p = 0.02) was found in CSX patients. Conclusions: CSX patients with elevated CRP levels had a significantly reduced CFR compared with the control group, which is indicative of CMD. Our study thus suggests a role for inflammation in the modulation of coronary microvascular responses in patients with CSX. [Copyright &y& Elsevier]

With growing evidence in clinical practice, the understanding of coronary syndromes has gradually evolved out of focusing on the well-established link between stenosis of epicardial coronary artery and myocardial ischemia to the structural and functional abnormalities at the level of coronary microcirculation, known as coronary microvascular dysfunction (CMD). CMD encompasses several pathophysiological mechanisms of coronary microcirculation and is considered as an important cause of myocardial ischemia in patients with angina symptoms without obstructive coronary artery disease (CAD). As a result of growing knowledge of the understanding of CMD assessed by multiple non-invasive modalities, CMD has also been found to be involved in other cardiovascular diseases, including primary cardiomyopathies as well as heart failure with preserved ejection fraction (HFpEF). In the past 2 decades, almost all the imaging modalities have been used to non-invasively quantify myocardial blood flow (MBF) and promote a better understanding of CMD. Myocardial contrast echocardiography (MCE) is a breakthrough as a non-invasive technique, which enables assessment of myocardial perfusion and quantification of MBF, exhibiting promising diagnostic performances that were comparable to other non-invasive techniques. With unique advantages over other non-invasive techniques, MCE has gradually developed into a novel modality for assessment of the coronary microvasculature, which may provide novel insights into the pathophysiological role of CMD in different clinical conditions. Moreover, the sonothrombolysis and the application of artificial intelligence (AI) will offer the opportunity to extend the use of contrast ultrasound theragnostics., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Zhan, Zhong and Wu.)

Background: Coronary microvascular dysfunction (CMD) and obstructive coronary artery disease (CAD) are likely to exist side-by-side, thereby probably inducing angina pectoris symptoms of some patients not effectively relieved after revascularization. We aimed to evaluate the prevalence and characteristics exhibited by CMD in patients with recurrent chest pain who received percutaneous coronary intervention (PCI) before., Methods: We conducted a single-center cross-sectional retrospective study. A total of 373 patients having received PCI were hospitalized for recurrent chest pain. Subsequently, they underwent coronary angiography and a rest/stress dynamic and routine gated myocardial perfusion imaging (MPI). At the vascular level, if any coronary artery stenosis <50% and myocardial flow reserve (MFR) <2.0 in the corresponding territory was considered to result from CMD. At the participant level, the CMD group was defined as one of the non-obstructive coronary arteries, in accordance with CMD at the vascular level., Results: A total of 102 patients were finally recruited. At the vascular level, 274 vessels were eligible for inclusion, and the proportion of CMD was 43.1% (118/274). At the participant level, 49.0% (50/102) post-PCI patients with recurrent chest pain were indicated as CAD coexisting with CMD. Body mass index (BMI), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) in CMD patients exceeded those in controls. The stress myocardial blood flow (MBF) of CMD patients was significantly decreased than controls (stress MBF of left ventricle in CMD vs. control: 1.36±0.43 vs. 2.50±0.70, P<0.01). After age adjustment, multivariate logistic regression analysis revealed that increased BMI (OR: 1.405, 95% CI: 1.048-1.882) and LDL-C (OR: 3.094, 95% CI: 1.044-9.173) showed independent correlations with CMD (P<0.05)., Conclusions: The prevalence of CMD could be relatively high in post-PCI patients suffering from recurrent angina with no need for revascularization, and increased BMI and LDL-C could be independent predictors of CMD., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://cdt.amegroups.com/article/view/10.21037/cdt-21-705/coif). The authors have no conflicts of interest to declare., (2022 Cardiovascular Diagnosis and Therapy. All rights reserved.)

Background: Coronary microvascular dysfunction (CMD) is an early feature of diabetic cardiomyopathy, which usually precedes the onset of diastolic and systolic dysfunction. Continuous intracoronary thermodilution allows an accurate and reproducible assessment of absolute coronary blood flow and microvascular resistance thus allowing the evaluation of coronary flow reserve (CFR) and Microvascular Resistance Reserve (MRR), a novel index specific for microvascular function, which is independent from the myocardial mass. In the present study we compared absolute coronary flow and resistance, CFR and MRR assessed by continuous intracoronary thermodilution in diabetic vs. non-diabetic patients. Left atrial reservoir strain (LASr), an early marker of diastolic dysfunction was compared between the two groups. Methods: In this observational retrospective study, 108 patients with suspected angina and non-obstructive coronary artery disease (NOCAD) consecutively undergoing elective coronary angiography (CAG) from September 2018 to June 2021 were enrolled. The invasive functional assessment of microvascular function was performed in the left anterior descending artery (LAD) with intracoronary continuous thermodilution. Patients were classified according to the presence of DM. Absolute resting and hyperemic coronary blood flow (in mL/min) and resistance (in WU) were compared between the two cohorts. FFR was measured to assess coronary epicardial lesions, while CFR and MRR were calculated to assess microvascular function. LAS, assessed by speckle tracking echocardiography, was used to detect early myocardial structural changes potentially associated with microvascular dysfunction. Results: The median FFR value was 0.83 [0.79-0.87] without any significant difference between the two groups. Absolute resting and hyperemic flow in the left anterior descending coronary were similar between diabetic and non-diabetic patients. Similarly, resting and hyperemic resistances did not change significantly between the two groups. In the DM cohort the CFR and MRR were significantly lower compared to the control group (CFR = 2.38 ± 0.61 and 2.88 ± 0.82; MRR = 2.79 ± 0.87 and 3.48 ± 1.02 for diabetic and non-diabetic patients respectively, [p < 0.05 for both]). Likewise, diabetic patients had a significantly lower reservoir, contractile and conductive LAS (all p < 0.05). Conclusions: Compared with non-diabetic patients, CFR and MRR were lower in patients with DM and non-obstructive epicardial coronary arteries, while both resting and hyperemic coronary flow and resistance were similar. LASr was lower in diabetic patients, confirming the presence of a subclinical diastolic dysfunction associated to the microcirculatory impairment. Continuous intracoronary thermodilution-derived indexes provide a reliable and operator-independent assessment of coronary macro- and microvasculature and might potentially facilitate widespread clinical adoption of invasive physiologic assessment of suspected microvascular disease., Competing Interests: CC reports receiving research grants from Biosensor, Coroventis Research, GE Healthcare, Medis Medical Imaging, Pie Medical Imaging, Cathworks, Boston Scientific, Siemens, HeartFlow Inc. and Abbott Vascular; and consultancy fees from Heart Flow Inc, Opsens, Pie Medical Imaging, Abbott Vascular and Philips Volcano. BD has a consulting relationship with Boston Scientific, Abbott Vascular, CathWorks, Siemens, and Coroventis Research; receives research grants from Abbott Vascular, Coroventis Research, Cathworks, Boston Scientific; and holds minor equities in Philips-Volcano, Siemens, GE Healthcare, Edwards Life Sciences, HeartFlow, Opsens, and Celiad. EB declares speaker's fees from Abbott Vascular, Boston Scientific and GE. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Gallinoro, Paolisso, Candreva, Bermpeis, Fabbricatore, Esposito, Bertolone, Fernandez Peregrina, Munhoz, Mileva, Penicka, Bartunek, Vanderheyden, Wyffels, Sonck, Collet, De Bruyne and Barbato.)

• Coronary microcirculatory dysfunction could be simulated using computational fluid dynamics. • MR variations in a branch with mild stenosis has limited hemodynamic effects on other branches. • Increased MR in a highly stenosed branch increases the blood flow and iFR of its cognate branches. The instantaneous wave-free ratio (iFR) has been proposed to estimate the hemodynamic severity of atherosclerotic stenosis in coronary arteries. The atherosclerotic stenosis in a proximal coronary artery could change its distal microcirculatory resistance (MR). However, there is a lack of investigation about the effect of MR variation on the blood flow and iFR of stenotic coronary arteries. We aim to investigate the changes of blood flow and iFR caused by distal MR variation. Four three-dimensional models of coronary arteries were reconstructed from the computed tomography images of two normal cases and two cases with 74.9% and 96.4% (in area) stenoses in a large branch of left anterior descending artery (LAD). Computational fluid dynamics simulation was performed on each model under 6 MR situations: hyperemia as the reference situation, resting when MR was multiplied by 8/3 in all outlet branches, h-one-1.5 and h-one-2 when MR was multiplied by 1.5 and 2.0 in one branch (the stenotic, or the corresponding branch in normal case) of LAD, h-branches-1.5 and h-branches-2 when MR was multiplied by 1.5 and 2.0 in the stenotic/corresponding and its cognate branches. Flow rate and iFR of each outlet branch were then calculated and compared between different MR situations to investigate the effect of MR variation on flow rate and iFR. In the 74.9% stenosed and normal cases, referring to the hyperemia situation, the increase of MR in any branch significantly decreased its flow rate and increased its iFR, with limited effect on the flow rate (<3%) and iFR (<0.01) of other branches. However, in the 96.4% stenosed case, the doubled MR in the stenosed branch (h-one-2) significantly increased the flow rate (>10%) and iFR (>0.05) of its cognate branches. The increase of MR in a normal or mildly stenosed branch of coronary artery decreases its blood flow and increases its iFR, with limited effect on other branches. Whereas, the increase of MR in a severely stenotic large branch could significantly increase the flow velocity and iFR of its cognate branches. [ABSTRACT FROM AUTHOR]

Competing Interests: None.

Background: Prognosis in pulmonary arterial hypertension (PAH) is largely dependent on right ventricular (RV) function. However, recent studies have suggested the presence of left ventricular (LV) dysfunction in PAH patients. The potential role of LV ischemia, as a contributor to progressive LV dysfunction, has not been systematically studied in PAH. We aim to assess the presence and extent of LV myocardial ischemia in patients with known PH and without obstructive coronary artery disease (CAD), using oxygen-sensitive (OS) cardiovascular magnetic resonance (CMR) and stress/rest CMR T1 mapping., Methods: We prospectively recruited 28 patients with right heart catheter-proven PH and no significant CAD, 8 patients with known CAD and 11 normal age-matched controls (NC). OS-CMR images were acquired using a T2* sequence and T1 maps were acquired using Shortened Modified Look-Locker Inversion recovery (ShMOLLI) at rest and adenosine-induced stress vasodilatation; ΔOS-CMR signal intensity (SI) index (stress/rest SI) and ΔT1 reactivity (stress-rest/rest T1 mapping) were calculated., Results: Global LV ΔOS SI index was significantly lower in PH patients compared with controls (11.1%±6.7% vs. 20.5%±10.5%, P=0.016), as was ΔT1 reactivity (5.2%±4.5% vs. 8.0%±2.9%, P=0.047). The ischemic segments of CAD patients had comparable ΔOS SI (10.3%±6.4% vs. 11.1%±6.7%, P=0.773) to PH patients, but lower ΔT1 reactivity (1.1%±4.2% vs. 5.2%±4.5%, P=0.036)., Conclusions: Decreased OS-CMR SI and T1 reactivity signify the presence of impaired myocardial oxygenation and vasodilatory response in PH patients. Given their unobstructed epicardial coronary arteries, this is likely secondary to coronary microvascular dysfunction (CMD)., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/cdt-20-698). Prof. JBS reports that he serves as a current Editorial Board Member. Dr. SP and Dr. JGW receive grants from Actelion, outside from submitted work. The authors have no other conflicts of interest to declare., (2020 Cardiovascular Diagnosis and Therapy. All rights reserved.)