Ability of the coronary angiography-derived index of microcirculatory resistance to predict microvascular obstruction in patients with ST-segment elevation.

Background: The coronary angiography-derived index of microvascular resistance (caIMR) correlates well with the index of microcirculatory resistance (IMR), which predicts microvascular obstruction (MVO). However, the relationship between caIMR and MVO remains unclear. Aim: To evaluate the predictive ability of caIMR of MVO after ST-segment elevation myocardial infarction (STEMI). Methods: CaIMR was calculated using computational flow and pressure simulation in patients with STEMI in whom MVO status had been assessed by cardiac magnetic resonance (CMR) after successful primary percutaneous intervention at Peking University First Hospital between December 2016 and August 2019. The clinical, biochemical, echocardiographic, and CMR characteristics were assessed according to MVO status. The predictive value of the clinical parameters and caIMR was evaluated. Results: Fifty-three eligible patients were divided into an MVO group (n = 32) and a no-MVO group (n = 21). The caIMR tended to be higher in the MVO group (41.6 U vs. 30.1 U; p = 0.136). CaIMR and peak cardiac troponin-I (cTNI) were independent predictors of MVO (per 1-U increment in caIMR: odds ratio [OR] 1.044, 95% confidence interval [CI] 1.004-1.086, p = 0.030; per 1 ng/L increase in peak cTNI: OR 1.018, 95% CI 1.003-1.033, p = 0.022). In receiver-operating characteristic curve analysis, when a cut-off value of 45.17 U was used, caIMR had some ability to predict MVO (area under the curve 0.622, 95% CI 0.478-0.752, p = 0.127). Conclusions: CaIMR and peak cTNI were independent predictors of short-term MVO in patients with STEMI who had undergone successful primary percutaneous coronary intervention and may help to identify those at high risk of MVO.

Deferred revascularization in diabetic patient according to combined invasive functional and intravascular imaging data: A case report.

BACKGROUND: Invasive functional evaluation by fractional flow reserve (FFR) is considered as a gold standard for the evaluation of intermediate coronary stenosis. However, in patients with diabetes due to accelerated progression of atherosclerosis the outcome may be worse even in the presence of negative functional testing. CASE SUMMARY: We present a case of 55-year-old male diabetic patient who was admitted for chest pain. Diagnostic coronary angiography disclosed 2 intermediate stenoses of the obtuse marginal branch with no evidence of restenosis on previously implanted stent. Patient undergone invasive functional testing of intermediate lesion with preserved FFR (0.88), low coronary flow reserve (1.2) and very high index of microvascular resistance (84). Due to discrepancy in invasive functional parameters, intravascular imaging with optical coherence tomography showed fibrotic stenoses without signs of thin-sup fibroatheroma. Because of the preserved FFR and no signs of vulnerable plaque, the interventional procedure was deferred and the patient continued with optimal medications. CONCLUSION: Combined functional and anatomic imaging of intermediate coronary stenosis in diabetic patients represent comprehensive contemporary decision pathway in the management of the patients.

Diagnostic and prognostic value of angiography-derived index of microvascular resistance: a systematic review and meta-analysis.

Background: The angiography-derived index of microvascular resistance (A-IMR) is a novel tool for diagnosing coronary microvascular dysfunction (CMD) addressing limitation of unavailability. However, the clinical value of A-IMR remains controversial. Methods: A systematic review and meta-analysis was conducted. PubMed, EMBASE, Cochrane Library and Web of Science were searched for relevant studies. Studies that reported estimates of A-IMR's diagnostic accuracy (with thermodilution-based IMR as the reference test) and/or predictions of adverse cardiovascular events were selected. Pooled sensitivity, specificity, area under the summary receiver operating characteristic curve (sROC) were calculated to measure diagnostic performance; pooled hazard/risk ratio (HR/RR) and 95% confidence interval (95% CI) of major adverse cardiovascular events (MACE) or other independent adverse events were calculated to measure prognostic effect. This study was registered with PROSPERO (CRD42023451884). Results: A total of 12 diagnostic studies pooling 1,642 vessels and 12 prognostic studies pooling 2,790 individuals were included. A-IMR yielded an area under sROC of 0.93 (95% CI: 0.91, 0.95), a pooled sensitivity of 0.85 (95% CI: 0.79, 0.89) and a pooled specificity of 0.89 (95% CI: 0.83, 0.93) for the diagnosis of CMD. CMD diagnosed using A-IMR was associated with higher risks of MACE (HR, 2.73, 95% CI: 2.16, 3.45), CV death (RR, 2.39, 95% CI: 1.49, 3.82) and heart failure hospitalization (HR, 2.30, 95% CI: 1.53, 3.45). Conclusion: A-IMR demonstrated high diagnostic accuracy for CMD and showed a strong prognostic capability in predicting the risk of adverse CV outcomes. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023451884, PROSPERO (CRD42023451884).

Impact of Coronary Microvascular Dysfunction on Functional Left Ventricular Remodeling and Diastolic Dysfunction.

BACKGROUND: Coronary microvascular dysfunction (CMD) is a common complication of ST-segment-elevation myocardial infarction (STEMI) and can lead to adverse cardiovascular events. Whether CMD after STEMI is associated with functional left ventricular remodeling (FLVR) and diastolic dysfunction, has not been investigated. METHODS AND RESULTS: This is a nonrandomized, observational, prospective study of patients with STEMI with multivessel disease. Coronary flow reserve and index of microcirculatory resistance of the culprit vessel were measured at 3 months post-STEMI. CMD was defined as index of microcirculatory resistance ≥25 or coronary flow reserve <2.0 with a normal fractional flow reserve. We examined the association between CMD, LV diastolic dysfunction, FLVR, and major adverse cardiac events at 12-month follow-up. A total of 210 patients were enrolled; 59.5% were men, with a median age of 65 (interquartile range, 58-76) years. At 3-month follow-up, 57 patients (27.14%) exhibited CMD. After 12 months, when compared with patients without CMD, patients with CMD had poorer LV systolic function recovery (-10.00% versus 8.00%; P<0.001), higher prevalence of grade 2 LV diastolic dysfunction (73.08% versus 1.32%; P<0.001), higher prevalence of group 3 or 4 FLVR (11.32% versus 7.28% and 22.64% versus 1.99%, respectively; P<0.001), and higher incidence of major adverse cardiac events (50.9% versus 9.8%; P<0.001). Index of microcirculatory resistance was independently associated with LV diastolic dysfunction and adverse FLVR. CONCLUSIONS: CMD is present in ≈1 of 4 patients with STEMI during follow-up. Patients with CMD have a higher prevalence of LV diastolic dysfunction, adverse FLVR, and major adverse cardiac events at 12 months compared with those without CMD. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique Identifier: NCT05406297.

In-vitro validation of coronary physiology assessment with 5 French guiding catheters.

BACKGROUND: The trans-radial approach for cardiac catheterization led to an increasing adoption of 5 French (F) catheters. We aim to evaluate reliability and reproducibility of coronary physiology assessment performed with 5F guiding catheter (GC). METHODS: Physiological measurements were performed in a coronary flow simulator, which provides two pulsatile flows, the baseline and hyperaemic flows. Two screws, positioned proximally and distally to the distal sensor of a pressure-temperature guidewire, were used to determine various combinations of stenoses and distal obstructions, simulating different pathophysiological conditions. For each setting, 5 measurements of fractional flow reserve (FFR), coronary flow reserve (CFR) and index of microvascular resistance (IMR) were performed with 6F and 5F GCs. RESULTS: A total amount of 190 measurements were performed, 95 with 6F GC and 95 with 5F GC. Minimal differences between 6F and 5F GCs were detected for FFR [0.91 (IQR: 0.87-0.94) and 0.87 (IQR: 0.82-0.92) respectively, p < 0.001] and IMR (16.5 ± 8.8 and 15.4 ± 8.3 respectively, p = 0.001). Mean CFR was comparable between 6F and 5F GCs (3.6 ± 1.1 and 3.5 ± 0.7 respectively, p = 0.38). Misclassification rates were 1.0 %, 1.0 % and 0 % for FFR, CFR and IMR, respectively. According to Passing-Bablok analysis, an excellent agreement between 6F and 5F GCs was demonstrated for FFR and IMR, and a modest agreement for CFR. All measurements with 5F GC showed high reproducibility. CONCLUSIONS: In our in-vitro model, a complete physiological assessment including FFR, CFR and IMR resulted substantially comparable between 6F and 5F GCs. Further in-vivo analysis is required to support these findings.

Hemodialysis-induced Myocardial Stunning with No Obstructive Coronary Artery Disease: Pathophysiological Significance of Coronary Microvascular Dysfunction.

Hemodialysis (HD)-induced myocardial stunning, characterized by transient left ventricular systolic dysfunction during HD, has been reported to be common and associated with a poor prognosis. However, the pathophysiology is not fully understood. We herein report a case of HD-induced myocardial stunning without obstructive coronary artery disease complicated by coronary microvascular dysfunction (CMD), suggesting that CMD plays a crucial role in the pathophysiology of this disease.

Possible Involvement of Coronary Microvascular Dysfunction in Painful Left Bundle Branch Block.

Cases of painful left bundle branch block syndrome have been reported; however, the pathophysiology of chest pain remains unclear. Here, we report a patient with left bundle branch block and chest pain. We evaluated coronary microvascular dysfunction using guide wire-based thermodilution. (Level of Difficulty: Intermediate.).

Angiography-based coronary microvascular assessment with and without intracoronary pressure measurements: a systematic review.

BACKGROUND: In recent years, several indices have been proposed for quantifying coronary microvascular resistance. We intended to conduct a comprehensive review that systematically evaluates indices of microvascular resistance derived from angiography. OBJECTIVE: The objective of this study was to identify and analyze angiography-derived indices of microvascular resistance that have been validated against an invasive reference method. We aimed to compare their limits of agreement with their reference methods and explore their advantages and inherent limitations. METHODS AND RESULTS: We searched PubMed from inception until 2022 for studies on different techniques for quantifying microvascular resistance. Seven studies met the inclusion criteria. Five studies included techniques that applied calculations based solely on invasive angiography, and were validated against invasively measured thermodilution-derived index of microvascular resistance. The remaining two studies combined angiography with invasively measured intracoronary pressure data, and were validated against invasive Doppler measurements. We converted the ± 1.96 standard deviation limits of agreement with the reference method from the seven studies into percentages relative to the cut-off value of the reference method. The lower limits of agreement for angiography-based methods ranged from - 122 to - 60%, while the upper limits ranged from 74 to 135%. The range of the limits of agreement was considerably lower for the two combined angiography- and pressure-based methods, standing at - 52 to 60% and - 25 to 27%. CONCLUSION: Our findings suggest that combined angiography- and pressure-based methods provide a more reliable assessment of microvascular resistance compared to methods relying solely on angiography. Central illustration. Comparative assessment of image-based methods quantifying microvascular resistance with and without intracoronary pressure measurements. Angiography-based methods rely on angiography alone to calculate the microvascular resistance by utilizing angiographic frame counting to extrapolate coronary flow (Q) and subsequently deriving distal coronary pressure using fluid dynamic equations. Combined angiography- and pressure-based methods utilize invasive intracoronary pressure gradients measured during rest and maximal vasodilation to determine coronary flow in their calculation of microvascular resistance. The combined methods showed more acceptable levels of agreement with their reference methods compared to angiography-based methods alone.

Microvascular function and inflammatory activation in Takotsubo cardiomyopathy.

AIMS: The aim of this study was to determine microvascular function in the acute phase of Takotsubo syndrome (TTS) and to identify inflammatory mediators that could reflect TTS-induced pathology. METHODS AND RESULTS: The study included 20 females [median age 65 years; interquarile range (IQR) = 58-70 years] with TTS according to the Mayo diagnostic criteria. During heart catheterization, we determined the index of microvascular resistance (IMR) and drew blood samples almost simultaneously from the aorta and coronary sinus. Cardiac magnetic resonance imaging (MRI) was done in the acute phase. We present descriptive coronary physiology and cardiac MRI data and compare inflammatory biomarkers between samples from the aorta, coronary sinus, and venous samples after 3 months using the Wilcoxon signed-rank test. For comparison, we also analysed the actual biomarkers in venous blood from 15 healthy female controls. A supplementary analysis explored Spearman's rank correlation between the inflammatory biomarkers, IMR, MRI data, and cardiac biomarkers. The median IMR was 16.5 mmHg·s (IQR = 10.5-28.2 mmHg·s), which was only slightly higher than that in the reference populations. Seven (35%) of the study subjects had IMR > 25 mmHg·s, suggesting a microvascular dysfunction. IMR was not affected by time from symptom onset. According to MRI, the apical region of the left ventricle was affected in 65% of the subjects. The median ejection fraction was 41% (IQR = 31-48%). Biomarker analyses revealed elevation of markers for extracellular matrix remodelling and fibrosis, inflammation, immune activation, and upstream inflammation as compared with healthy controls. Only the levels of interleukin (IL)-1 receptor antagonist and soluble T-cell immunoglobulin mucin domain-3 (sTIM-3) were higher in the coronary sinus than in the aorta. No variable was significantly correlated with IMR. The IL-6 level in the aorta was inversely correlated with the left ventricular ejection fraction. Growth differentiation factor-15, osteoprotegerin, and von Willebrand factor levels in both aorta and coronary sinus were positively correlated with N-terminal-pro-brain-natriuretic peptide, while the correlations of IL-6 and sTIM-3 with N-terminal-pro-brain-natriuretic peptide were restricted to the aorta and coronary sinus, respectively. While most of the markers were within normal limits after 3 months, matrix metalloproteinase-9 increased during follow-up to reach levels higher than those in the healthy controls. CONCLUSION: The median IMR was only slightly elevated in this study, but about one-third of the patients had values indicating microvascular dysfunction. The present study supports the involvement of several inflammatory pathways in TTS, including monocyte/macrophage activation, with sTIM-3 as a potential novel marker.

A systematic review and meta-analysis of the effect of high-intensity statin on coronary microvascular dysfunction.

OBJECTIVE: The purpose of this meta-analysis is to evaluate the role of high-intensity statin pretreatment on coronary microvascular dysfunction in patients with coronary heart disease undergoing percutaneous coronary intervention (PCI). METHODS: PubMed, Cochrane, and Embase were searched. This meta-analysis selection included randomized controlled trials (RCTs), involving high-intensity statin pretreatment as active treatment, and measurement of thrombolysis in myocardial infarction (TIMI), myocardial blush grade (MBG) or index of microvascular resistance (IMR) in coronary heart disease (CHD) patients undergoing PCI. I2 test was used to evaluate heterogeneity. Pooled effects of continuous variables were reported as Standard mean difference (SMD) and 95% confidence intervals (CI). Pooled effects of discontinuous variables were reported as risk ratios (RR) and 95% confidence intervals (CI). Random-effect or fix-effect meta-analyses were performed. The Benefit was further examined based on clinical characteristics including diagnosis and statin type by using subgroup analyses. Publication bias was examined by quantitative Egger's test and funnel plot. We performed sensitivity analyses to examine the robustness of pooled effects. RESULTS: Twenty RCTs were enrolled. The data on TIMI < 3 was reported in 18 studies. Comparing with non-high-intensity statin, high-intensity statin pretreatment significantly improved TIMI after PCI (RR = 0.62, 95%CI: 0.50 to 0.78, P < 0.0001). The data on MBG < 2 was reported in 3 studies. The rate of MBG < 2 was not different between groups (RR = 1.29, 95% CI: 0.87 to 1.93, P = 0.21). The data on IMR was reported in 2 studies. High-dose statin pretreatment significantly improved IMR after PCI comparing with non-high-dose statin (SMD = -0.94, 95% CI: -1.47 to -0.42, P = 0.0004). There were no significant between-subgroup differences in subgroups based on statin type and diagnosis. Publication bias was not indicated by using quantitative Egger's test (P = 0.97) and funnel plot. Sensitivity analyses confirmed the robustness of these findings. CONCLUSIONS: Comparing with non-high-intensity statin, high-intensity statin pretreatment significantly improved TIMI and IMR after PCI. In the future, RCTs with high quality and large samples are needed to test these endpoints.

Angiography-based index of microcirculatory resistance (AccuIMR) for the assessment of microvascular dysfunction in acute coronary syndrome and chronic coronary syndrome.

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.

The Impact of Trimethylamine N-Oxide and Coronary Microcirculatory Dysfunction on Outcomes following ST-Elevation Myocardial Infarction.

INTRODUCTION: Persistent coronary microcirculatory dysfunction (CMD) and elevated trimethylamine N-oxide (TMAO) levels after ST-elevation myocardial infarction (STEMI) may drive negative structural and electrical cardiac remodeling, resulting in new-onset atrial fibrillation (AF) and a decrease in left ventricular ejection fraction (LVEF). AIMS: TMAO and CMD are investigated as potential predictors of new-onset AF and left ventricular remodeling following STEMI. METHODS: This prospective study included STEMI patients who had primary percutaneous coronary intervention (PCI) followed by staged PCI three months later. Cardiac ultrasound images were obtained at baseline and after 12 months to assess LVEF. Coronary flow reserve (CFR), and index of microvascular resistance (IMR) were assessed using the coronary pressure wire during the staged PCI. Microcirculatory dysfunction was defined as having an IMR value ≥25 U and CFR value <2.5 U. RESULTS: A total of 200 patients were included in the study. Patients were categorized according to whether or not they had CMD. Neither group differed from the other with regards to known risk factors. Despite making up only 40.5% of the study population, females represented 67.4% of the CMD group p < 0.001. Similarly, CMD patients had a much higher prevalence of diabetes than those without CMD (45.7% vs. 18.2%; p < 0.001). At the one-year follow-up, the LVEF in the CMD group had decreased to significantly lower levels than those in the non-CMD group (40% vs. 50%; p < 0.001), whereas it had been higher in the CMD group at baseline (45% vs. 40%; p = 0.019). Similarly, during the follow-up, the CMD group had a greater incidence of AF (32.6% vs. 4.5%; p < 0.001). In the adjusted multivariable analysis, the IMR and TMAO were associated with increased odds of AF development (OR: 1.066, 95% CI: 1.018-1.117, p = 0.007), and (OR: 1.290, 95% CI: 1.002-1.660, p = 0.048), respectively. Similarly, elevated levels of IMR and TMAO were linked with decreased odds of LVEF improvement, while higher CFR values are related to a greater likelihood of LVEF improvement. CONCLUSIONS: CMD and elevated TMAO levels were highly prevalent three months after STEMI. Patients with CMD had an increased incidence of AF and a lower LVEF 12 months after STEMI.

Myocardial Infarction with Non-Obstructive Coronary Arteries (MINOCA): Focus on Coronary Microvascular Dysfunction and Genetic Susceptibility.

Among the most common causes of death worldwide, ischemic heart disease (IHD) is recognized to rank first. Even if atherosclerotic disease of the epicardial arteries is known as the leading cause of IHD, the presence of myocardial infarction with non-obstructive coronary artery disease (MINOCA) is increasingly recognized. Notwithstanding the increasing interest, MINOCA remains a puzzling clinical entity that can be classified by distinguishing different underlying mechanisms, which can be divided into atherosclerotic and non-atherosclerotic. In particular, coronary microvascular dysfunction (CMD), classifiable in non-atherosclerotic mechanisms, is a leading factor for the pathophysiology and prognosis of patients with MINOCA. Genetic susceptibility may have a role in primum movens in CMD. However, few results have been obtained for understanding the genetic mechanisms underlying CMD. Future studies are essential in order to find a deeper understanding of the role of multiple genetic variants in the genesis of microcirculation dysfunction. Progress in research would allow early identification of high-risk patients and the development of pharmacological, patient-tailored strategies. The aim of this review is to revise the pathophysiology and underlying mechanisms of MINOCA, focusing on CMD and actual knowledge about genetic predisposition to it.

Association between the triglyceride-glucose index and the presence and prognosis of coronary microvascular dysfunction in patients with chronic coronary syndrome.

BACKGROUND: Coronary microvascular dysfunction (CMD) is a strong determinant of prognosis in patients with chronic coronary syndrome (CCS). The triglyceride-glucose index (TyG index), an alternative method to evaluate insulin resistance, is positively correlated with the incidence and adverse outcomes of cardiovascular diseases. However, the relationship between the TyG index and the presence and prognosis of CMD in CCS patients has not been investigated. Therefore, we aimed to evaluate the association between the TyG index and the presence and clinical outcomes of CMD among CCS patients. METHODS: CCS patients who underwent coronary angiography between June 2015 to June 2019 were included. The TyG index was calculated as Ln[fasting triglycerides (mg/dL) × fasting blood glucose (mg/dL)/2]. Coronary angiography­derived index of microvascular resistance (caIMR) was used to measure microvascular function, and CMD was defined as caIMR ≥ 25U. Patients with CMD were divided into three groups (T1, T2, and T3 groups) according to TyG tertiles. The primary endpoint was major adverse cardiac event (MACE). RESULTS: Of 430 CCS patients, 221 patients had CMD. CMD patients had significantly higher TyG index than those without CMD. Sixty-three MACE was recorded during the follow-up duration among CMD patients, and the incidence rate of MACE was higher in the T3 group compared to T1/T2 groups (39.2% vs. 20.5% vs. 25.7%; P = 0.035). Multivariable logistic regression analysis showed that the TyG index was an independent predictor of CMD (OR, 1.436; 95% CI, 1.014-2.034; P = 0.042). Compared to the T1 group, the T3 group strongly correlated with the risk of MACE in CMD patients even after adjusting for additional confounding risk factors (HR, 2.132; 95%CI, 1.066-4.261; P = 0.032). CONCLUSION: TyG index is significantly associated with the risk of CMD, and it is an independent predictor of MACE among CMD patients with CCS. This study suggests that the TyG index has important clinical significance for the early prevention and risk stratification of CMD.

The Influence of Microcirculatory Dysfunction on the Resting Full Cycle Ratio Compared to Fractional Flow Reserve.

BACKGROUND: The relation between the resting full cycle ratio (RFR) and fractional flow reserve (FFR) is not fully understood. This study aims to investigate the influence of coronary microvascular dysfunction, assessed by the index of microvascular resistance (IMR), on RFR compared to FFR in patients undergoing functional assessment for coronary stenosis. MATERIALS AND METHODS: Two-hundred patients with borderline stenosis underwent functional assessment of RFR, FFR, coronary flow reserve (CFR) and IMR. Retriever operator curve analysis was performed to assess the diagnostic value of RFR in patients with (IMR ≥ 24) and (IMR < 24). RESULTS: Median RFR did not differ significantly in patients with IMR ≥ 24 compared to patients with IMR < 24: 0.89 (interquartile range (IQR) 0.84, 0.95) vs. 0.90 (IQR 0.84, 0.92), p = 0.29). FFR was significantly higher in patients with IMR ≥ 24 compared to patients with IMR < 24: median FFR 0.85 (IQR (0.76, 0.92)) vs. 0.82 (IQR 0.73, 0.86), p = 0.009, and median CFR was significantly lower 1.80 (IQR 1.40, 2.55) vs. 2.70 (IQR 1.80, 3.95), p < 0.001. The diagnostic value of RFR was high (Area under the curve (AUC) 0.89 95 % Confidence Interval: [0.85, 0.93]) and AUC did not differ between patients with IMR ≥ 24 compared to patients with IMR < 24: 0.89 vs. 0.90, p = 0.89. An overall optimal cut off of 0.88 was identified. The cut off did not differ significantly between patients with IMR ≥ 24 compared to patients with IMR < 24: 0.88 vs. 0.90, p = 0.397. CONCLUSION: In patients with coronary borderline stenosis, the coronary microvascular function did not influence on the cut off values or AUC of RFR compared to FFR.

Angiography-derived index of microvascular resistance in takotsubo syndrome.

Coronary microvascular dysfunction (CMD) has been proposed as a key driver in the etiopathogenesis of Takotsubo syndrome (TTS), likely related to an "adrenergic storm" upon a susceptible microvascular circulation. The aim of our manuscript was to assess CMD in patients with TTS through the computation of the angiography-derived index of microcirculatory resistance (IMR) and its correlation with clinical presentation. Coronary angiograms of 41 consecutive TTS patients were retrospectively analyzed to derive angiography-based indices of CMD. Three indices (NH-IMRangio, AngioIMR and A-IMR) were calculated based on quantitative flow ratio. CMD was defined as an IMRangio value ≥ 25 units. The correlation between CMD and clinical presentation was then assessed. Median age was 76 years, 85.7% were women and mean left ventricular ejection fraction (LVEF) at first echocardiogram was 41.2%. Angiography-derived IMR was higher in left anterior descending artery (LAD) than circumflex and right coronary artery with either NH-IMRangio (53.9 ± 19.8 vs 35.8 ± 15.4 vs 40.8 ± 18.5, p-value < 0.001), AngioIMR (47.2 ± 17.3 vs 31.8 ± 12.2 vs 37.3 ± 13.7, p-value < 0.001) or A-IMR (52.7 ± 19 vs 36.1 ± 14.1 vs 41.8 ± 16.1, p-value < 0.001). All patients presented CMD with angiography-derived IMR ≥ 25 in at least one territory with each formula. Angiography-derived IMR in LAD territory was significantly higher in patients presenting with LVEF impairment (≤ 40%) than in those with preserved ventricular global function (NH-IMRangio: 59.3 ± 18.1 vs 46.3 ± 16.0 p-value = 0.030; AngioIMR: 52.9 ± 17.8 vs 41.4 ± 14.2, p-value = 0.037; A-IMR: 59.2 ± 18.6 vs 46.3 ± 17.0, p-value = 0.035). CMD assessed with angiography-derived IMR is a common finding in TTS and it is inversely correlated with LV function. The available formulas have a substantial superimposable diagnostic performance in assessing coronary microvascular function.

One-year results from the Assessing MICRO-vascular resistances via IMR to predict outcome in ST-elevation myocardial infarction patients with multivessel disease undergoing primary PCI (AMICRO) trial.

Background: In ST-elevation myocardial infarction (STEMI) patients undergoing primary percutaneous coronary angioplasty (PPCI) the index of microcirculatory resistance (IMR) correlates to the extent of myocardial damage and left ventricular (LV) function recovery. Data on the IMR time-course and impact on clinical outcome in STEMI patients with multi-vessel disease (MVD) are scarce. Aims: We designed a prospective, multicenter clinical trial to assess the infarct-related artery (IRA)-IMR in STEMI patients with MVD undergoing PPCI and to explore its potential in relationship with outcome and LV remodeling. Methods: The study enrolled 242 STEMI patients with MVD. Both fractional flow reserve (FFR) and IMR of the IRA were assessed after successful PPCI. Then, FFR/IMR measurements were repeated in the IRA at a staged angiography, and FFR-guided angioplasty was performed in non-IRA lesions. The primary endpoint was the composite of cardiovascular death, re-infarction, re-hospitalization for heart failure, resuscitation or appropriate ICD shock at 1-year follow-up. Results: A significant improvement of IRA-IMR values (from 47.9 to 34.2, p < 0.0001) was observed early after PPCI. Staged FFR-guided angioplasty was performed in 102 non-IRA lesions. We failed to find a correlation between IRA-IMR, clinical events and LV remodeling. Notwithstanding, in patients with anterior STEMI an inverse correlation between initial IMR values and LV function at follow-up was observed. Conclusion: After successful PPCI, a significant proportion of patients with STEMI and MVD had coronary microvascular dysfunction as assessed by IMR that recovered early after reperfusion. Higher IMR values predicted lack of improvement of LV function only in anterior STEMI. Clinical trial registration: https://clinicaltrials.gov/, identifier [NCT02325973].

Coronary microvascular dysfunction as assessed by angiography-derived index of microvascular resistance co-localizes with and may explain the presence of ischemia in stress-cardiac magnetic resonance imaging in the absence of coronary artery disease.

Introduction: Ischemia with no obstructive coronary disease (INOCA) is a frequent phenomenon in the cath lab. A possible cause is coronary microvascular dysfunction (CMD), which may be assessed by invasive testing with possible complications; therefore, less invasive approaches have emerged, such as the angiography-derived index of microvascular resistance (aIMR). The aim of our study was to investigate the association of single-vessel aIMR as a measure of CMD with areas of INOCA in stress testing. Methods: We measured aIMR in 286 vessels from 102 patients undergoing both stress cMRI and coronary angiography. Groups were (a) INOCA group (93 vessels, 32 patients); (b) coronary artery disease (CAD) control group (116 vessels, 42 patients) with ischemia due to relevant stenosis; and (c) control group (77 vessels, 28 patients) without ischemia or relevant stenosis. Results: INOCA patients presented higher mean aIMR (28.3 ± 5.7) compared to both CAD patients (17.4 ± 5.7, p < 0.001) and controls (22.1 ± 5.9, p < 0.001). Furthermore, in INOCA patients aIMR was significantly increased (33.0 ± 8.1 vs. 25.8 ± 6.3, p = 0.021) in vessels with vs. without ischemia. Single vessel aIMR presented a very good diagnostic efficiency in detecting INOCA [AUC 0.865 (0.804-0.925), optimal cut-off 27.1, p < 0.001]. Conclusion: CMD, as assessed by 3-vessel aIMR, co-localizes with and may explain the presence of ischemia in stress-cMRI in INOCA.