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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

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.

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.

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.