The role of coronary microcirculation in heart failure with preserved ejection fraction: An unceasing odyssey.

Heart failure with preserved ejection fraction (HFpEF) represents an entity with complex pathophysiologic pathways, among which coronary microvascular dysfunction (CMD) is believed to be an important orchestrator. Research in the field of CMD has highlighted impaired vasoreactivity, capillary rarefaction, and inflammation as potential mediators of its development. CMD can be diagnosed via several noninvasive methods including transthoracic echocardiography, cardiac magnetic resonance, and positron emission tomography. Moreover, invasive methods such as coronary flow reserve and index of microcirculatory resistance are commonly employed in the assessment of CMD. As far as the association between CMD and HFpEF is concerned, numerous studies have highlighted the coexistence of CMD in the majority of HFpEF patients. Additionally, patients affected by both conditions may be facing an adverse prognosis. Finally, there is limited evidence suggesting a beneficial effect of renin-angiotensin-aldosterone system blockers, ranolazine, and sodium-glucose cotransporter-2 inhibitors in CMD, with further evidence being awaited regarding the impact of other pharmacotherapies such as anti-inflammatory agents.

Microvascular resistance reserve: impact on health status and myocardial perfusion after revascularization in chronic coronary syndrome.

BACKGROUND AND AIMS: The microvascular resistance reserve (MRR) is a novel invasive index of the microcirculation, which is independent of epicardial stenoses, and MRR has both diagnostic and prognostic implications. This study investigates whether MRR is associated with health status outcomes by revascularization in patients with moderate coronary stenoses. METHODS: Consecutive patients with stable chest pain and moderate (30-90% diameter) stenoses on invasive coronary angiography (n=222) underwent invasive physiology assessment. Revascularization was performed by guideline recommendations. At baseline and follow-up, health status and myocardial perfusion were assessed by Seattle Angina Questionnaire (SAQ) and positron emission tomography. The primary endpoint was freedom from angina at follow-up with secondary endpoints including changes in health status by SAQ domains and myocardial perfusion by MRR and revascularization status. Low MRR was defined as ≤3.0. RESULTS: Freedom from angina occurred in 38/173 patients. In multivariate analyses, MRR was associated with freedom from angina at follow-up (odds ratio 0.860, 95% confidence interval 0.740-0.987). By MRR and revascularization groups, patients with normal MRR who did not undergo revascularization, and patients with abnormal MRR who underwent revascularization, improved health status of angina frequency (mean difference SAQ angina frequency score 8.5 [3.07-13.11] and 13.5 [2.82-23.16], respectively). For both groups, health status of physical limitation (mean difference in SAQ physical limitation score 9.7 [4.79-11.93] and 8.7 [0.53-13.88], respectively) and general health status (mean difference in SAQ summary score 9.3 [5.18-12.50] and 10.8 [2.51-17.28], respectively) also improved. Only patients with abnormal MRR who underwent revascularization improved myocardial perfusion. CONCLUSIONS: In patients with moderate coronary stenoses, MRR seems to predict symptomatic and perfusion benefit of revascularization.

Vascular Remodeling in Coronary Microvascular Dysfunction.

BACKGROUND: Approximately half of the patients with angina and nonobstructive coronary artery disease (ANOCA) have evidence of coronary microvascular dysfunction (CMD). OBJECTIVES: This study aims to characterize patients with ANOCA by measuring their minimal microvascular resistance and to examine the pattern of vascular remodeling associated with these measurements. METHODS: The authors prospectively included patients with ANOCA undergoing continuous thermodilution assessment. Lumen volume and vessel-specific myocardial mass were quantified using coronary computed tomography angiography (CTA). CMD was defined as coronary flow reserve <2.5 and high minimal microvascular resistance as >470 WU. RESULTS: A total of 153 patients were evaluated; 68 had CMD, and 22 of them showed high microvascular resistance. In patients with CMD, coronary flow reserve was 1.9 ± 0.38 vs 3.2 ± 0.81 in controls (P < 0.001). Lumen volume was significantly correlated with minimal microvascular resistance (r = -0.59 [95% CI: -0.45 to -0.71]; P < 0.001). In patients with CMD and high microvascular resistance, lumen volume was 40% smaller than in controls (512.8 ± 130.3 mm3 vs 853.2 ± 341.2 mm3; P < 0.001). Epicardial lumen volume assessed by coronary CTA was independently associated with minimal microvascular resistance (P < 0.001). The predictive capacity of lumen volume from coronary CTA for detecting high microvascular resistance showed an area under the curve of 0.79 (95% CI: 0.69-0.88). CONCLUSIONS: Patients with CMD and high minimal microvascular resistance have smaller epicardial vessels than those without CMD. Coronary CTA detected high minimal microvascular resistance with very good diagnostic capacity. Coronary CTA could potentially aid in the diagnostic pathway for patients with ANOCA.

Novel diagnostic approaches and management of coronary microvascular dysfunction.

The mechanism underlying ischaemic heart disease (IHD) has been primarily attributed to obstructive coronary artery disease (CAD). However, non-obstructive coronary arteries are identified in >50% of patients undergoing elective coronary angiography, recently leading to growing interest in the investigation and management of angina/ischaemia with non-obstructive coronary arteries (ANOCA/INOCA). INOCA is an umbrella term encompassing a multiple spectrum of possible pathogenetic entities, including coronary vasomotor disorders which consist of two major endotypes: coronary microvascular dysfunction (CMD) and vasospastic angina. Both conditions can coexist and be associated with concomitant obstructive CAD. Particularly, CMD refers to myocardial ischaemia due to reduced vasodilatory capacity of coronary microcirculation secondary to structural remodelling or impaired resting microvascular tone (functional) or a combination of both. CMD is not a benign condition and is more prevalent in women presenting with chronic coronary syndrome compared to men. In this setting, an impaired coronary flow reserve has been associated with increased risk of major adverse cardiovascular events. ANOCA/INOCA patients also experience impaired quality of life and associated increased healthcare costs. Therefore, research in this scenario has led to better definition, classification, and prognostic stratification based on the underlying pathophysiological mechanisms. The development and validation of non-invasive imaging modalities, invasive coronary vasomotor function testing and angiography-derived indices provide a comprehensive characterisation of CMD. The present narrative review aims to summarise current data relating to the diagnostic approach to CMD and provides details on the sequence that therapeutic management should follow.

The coronary angiography-derived index of microcirculatory resistance predicts perioperative myocardial injury in stable coronary artery disease patients undergoing PCI.

Background: Coronary microvascular dysfunction (CMD) assessed by the index of microcirculatory resistance (IMR) is associated with perioperative myocardial injury (PMI).The angiographically derived index of microcirculatory resistance (caIMR) represents a novel and accurate alternative to IMR. Objective: This study aims to evaluate the predictive ability of caIMR for PMI in patients with stable coronary artery disease (CAD) undergoing percutaneous coronary intervention (PCI). Methods: Consecutive patients with stable CAD undergoing elective PCI of a single lesion were recruited. caIMR was measured before and after revascularisation, and total creatine kinase-MB (CK-MB) and high-sensitivity troponin T (hsTnT) levels were measured before and within 24 h after PCI. Results: A total of 65 patients were enrolled and 26 patients fulfilled the diagnostic criteria for PMI. Post-PCI caIMR values were significantly higher in the PMI group than in the control group (27.02 ± 3.70 vs. 15.91 ± 3.43U, P < 0.001). Pearson correlation analysis showed that increased post-PCI caIMR values had a significant positive correlation with peak hsTnT (r = 0.803, P < 0.001) and peak CK-MB (r = 0.512, P = 0.001). Multivariate logistic regression analysis showed that post-PCI caIMR was an independent predictor of PMI (OR,1.731; 95 % CI:1.348-2.023; P < 0.001).ROC analysis suggested that the best cut-off value of post-PCI caIMR was 25.17U to diagnose PMI (AUC = 0.951, sensitivity 88.5 %, specificity 97.1 %). During a median follow-up 16 months, patients with PMI had a higher incidence of major adverse cardiovascular events (MACE) (42.31 % vs 5.13 %, P = 0.04). Conclusions: Post-PCI caIMR can accurately predict PMI and clinical outcomes in stable CAD patients undergoing elective PCI, which supports the use of caIMR in clinical practice.

Mixing properties of coronary infusion catheters assessed by in vitro experiments and computational fluid dynamics.

Aims: Continuous infusion thermodilution is an established technique for the assessment of absolute coronary blood flow and microvascular resistance due to its proven accuracy and reproducibility. However, for this technique to yield reliable measurements, direct and homogenous mixing of injected saline and blood is mandatory. This study aimed to assess and compare the mixing properties of two different microcatheters, namely the Rayflow® (with sideholes for infusion) and the Finecross® catheter (single end-hole for infusion), which are commonly used in the catheterization laboratory. Methods and results: The study employed three different methods to evaluate the mixing properties of the catheters. Firstly, a qualitative assessment of mixing was performed using ink injections in an in vitro bench model of a coronary artery. Secondly, in analogy to the human catheterization laboratory, mixing properties over the length of the coronary artery were assessed semi-quantitatively by temperature measurements in the bench model. Lastly, a quantitative assessment was performed by 3D computational fluid dynamics, where the standard deviation and entropy ratio of the temperature over the cross-section in the coronary artery model were calculated for both catheters. Conclusion: All three evaluation methods demonstrated that the Rayflow catheter's specific design leads to a more optimal, homogeneous mixture of blood and saline over both the cross-section and length of a coronary vessel, as compared with the standard end-hole catheter.

Ischemia with non-obstructive coronary artery (INOCA): Non-invasive versus invasive techniques for diagnosis and the role of #FullPhysiology.

Ischemia with non-obstructive coronary arteries (INOCA) is an increasingly recognized entity. It encompasses different pathophysiological subtypes (i.e., endotypes), including coronary microvascular dysfunction (CMD), vasospastic angina (VSA) and mixed entities resulting from the variable combination of both. Diagnosing INOCA and precisely characterizing the endotype allows for accurate medical treatment and has proven prognostic implications. A breadth of diagnostic technique is available, ranging from non-invasive approaches to invasive coronary angiography adjuvated by functional assessment and provocative tests. This review summarizes the strength and limitations of these methodologies and provides the rationale for the routine referral for invasive angiography and functional assessment in this subset of patients.

Basal Coronary Microvascular Resistance Predicting Death and Heart Failure in Patients Without Functional Coronary Stenosis.

BACKGROUND: Abnormal coronary microcirculation is linked to poor patient prognosis, so the aim of the present study was to assess the prognostic relevance of basal microvascular resistance (b-IMR) in patients without functional coronary stenosis.Methods and Results: Analyses of 226 patients who underwent intracoronary physiological assessment of the left anterior descending artery included primary endpoints of all-cause death and heart failure, as well as secondary endpoints of cardiovascular death and atherosclerotic vascular events. During a median follow-up of 2 years, there were 12 (5.3%) primary and 21 (9.3 %) secondary endpoints. The optimal b-IMR cutoff for the primary endpoints was 47.1 U. Kaplan-Meier curve analysis demonstrated worse event-free survival of the primary endpoints in patients with a b-IMR below the cutoff (χ2=21.178, P<0.001). b-IMR was not significantly associated with the secondary endpoints (P=0.35). A low coronary flow reserve (CFR; <2.5) had prognostic value for both endpoints (primary endpoints: χ2=11.401, P=0.001; secondary endpoints: (χ2=6.015; P=0.014), and high hyperemic microvascular resistance (≥25) was associated only with the secondary endpoints (χ2=4.420; P=0.036). Incorporating b-IMR into a clinical model that included CFR improved the Net Reclassification Index and Integrated Discrimination Improvement for predicting the primary endpoints (P<0.001 and P=0.034, respectively). CONCLUSIONS: b-IMR may be a specific marker of the risk of death and heart failure in patients without functional coronary stenosis.

The pressure-derived microvascular resistance reserve and its correlation to Doppler MRR measurement-a proof of concept study.

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 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. Results: In the derivation cohort of 23 measurements, linear regression analysis showed a tight relation between MRRpbmax and MRRp-3D (r 2 = 0.74, p < 0.0001). Using this relation (MRRp-3D = 1.04 + 0.51 × MRRpbmax), 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.

Beyond Coronary Artery Disease: Assessing the Microcirculation.

Ischemic heart disease (IHD) affects more than 20 million adults in the United States. Although classically attributed to atherosclerosis of the epicardial coronary arteries, nearly half of patients with stable angina and IHD who undergo invasive coronary angiography do not have obstructive epicardial coronary artery disease. Ischemia with nonobstructive coronary arteries is frequently caused by microvascular angina with underlying coronary microvascular dysfunction (CMD). Greater understanding the pathophysiology, diagnosis, and treatment of CMD holds promise to improve clinical outcomes of patients with ischemic heart disease.

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.

The Impact of Microvascular Resistance Reserve on the Outcome of Patients With STEMI.

BACKGROUND: Microvascular resistance reserve (MRR) can characterize coronary microvascular dysfunction (CMD); however, its prognostic impact in ST-segment elevation myocardial infarction (STEMI) patients remains undefined. OBJECTIVES: This study sought to investigate the prevalence of CMD in STEMI patients and to elucidate the prognostic performance of MRR. METHODS: This prospective cohort study enrolled 210 STEMI patients with multivessel disease who underwent successful revascularization and returned at 3 months for coronary physiology assessments with bolus thermodilution. The prevalence of CMD (MRR <3) and the association between MRR and major adverse cardiovascular and cerebrovascular events (MACCEs) at 12 months were investigated. RESULTS: The median age of patients was 65 years, and 59.5% were men. At the 3-month follow-up, 56 patients (27%) had CMD (MRR <3.0). The number of MACCEs at 12 months was higher in patients with vs without CMD (48.2% vs 11.0%; P < 0.001). MRR was independently associated with 12-month MACCEs (HR: 0.45 per unit increase; 95% CI: 0.31-0.67; P < 0.001) and with stroke, heart failure, and poorer recovery in left ventricular systolic function. The areas under the receiver-operating characteristic curves for predicting MACCEs at 12 months with fractional flow reserve, coronary flow reserve (CFR), the index of microvascular resistance (IMR), and MRR were 0.609, 0.762, 0.781, and 0.743, respectively. The prognostic performance of CFR, IMR, and MRR were all comparable. CONCLUSIONS: The novel parameter MRR is a prognostic marker of MACCEs in STEMI patients with a comparable performance to CFR and IMR. (Impact of TMAO Serum Levels on Hyperemic IMR in STEMI Patients [TAMIR]; NCT05406297).

Microvascular resistance reserve before and after PCI: A serial FFR and [15O] H2O PET study.

BACKGROUND AND AIMS: Microvascular Resistance Reserve (MRR) has recently been introduced as a microvasculature-specific index and hypothesized to be independent of coronary stenosis. The aim of this study was to investigate the change of MRR after percutaneous coronary intervention (PCI). METHODS: In this post-hoc analysis from the PACIFC trials, symptomatic patients underwent [15O]H2O positron emission tomography (PET) and invasive fractional flow reserve (FFR) before and after revascularization. Coronary flow reserve (CFR) from PET and invasive FFR were used to calculate MRR. RESULTS: Among 52 patients (87 % male, age 59.4 ± 9.4 years), 61 vessels with a median FFR of 0.71 (95 % confidence interval: 0.55 to 0.74) and a mean MRR of 3.80 ± 1.23 were included. Following PCI, FFR, hyperemic myocardial blood flow (hMBF) and CFR increased significantly (all p-values ≤0.001). MRR remained unchanged after PCI (3.80 ± 1.23 before PCI versus 3.60 ± 0.97 after PCI; p=0.23). In vessels with a pre-PCI, FFR ≤0.70 pre- and post-PCI MRR were 3.90 ± 1.30 and 3.73 ± 1.14 (p=0.56), respectively. Similar findings were observed for vessels with a FFR between 0.71 and 0.80 (pre-PCI MRR 3.70 ± 1.17 vs. post PCI MRR 3.48 ± 0.76, p=0.19). CONCLUSIONS: Our study indicates that MRR, assessed using a hybrid approach of PET and invasive FFR, is independent of the severity of epicardial stenosis. These findings suggest that MRR is a microvasculature-specific parameter.

The Influence of Epicardial Resistance on Microvascular Resistance Reserve.

BACKGROUND: The optimal index of microvascular function should be specific for the microvascular compartment. Yet, coronary flow reserve (CFR), despite being widely used to diagnose coronary microvascular dysfunction (CMD), is influenced by both epicardial and microvascular resistance. Conversely, microvascular resistance reserve (MRR) adjusts for fractional flow reserve (FFR), and thus is theoretically independent of epicardial resistance. OBJECTIVES: The authors tested the hypothesis that MRR, unlike CFR, is not influenced by increasing epicardial resistance, and thus is a more specific index of microvascular function. METHODS: In a cohort of 16 patients who had undergone proximal left anterior descending artery stenting, we created 4 grades of artificial stenosis (no stenosis, mild, moderate, and severe) using a coronary angioplasty balloon inflated to different degrees within the stent. For each stenosis grade, we calculated CFR and MRR using continuous thermodilution (64 measurements of each) to assess their response to changing epicardial resistance. RESULTS: Graded balloon inflation resulted in a significant sequential decrease in mean FFR (no stenosis: 0.82 ± 0.05; mild: 0.72 ± 0.04; moderate: 0.61 ± 0.05; severe: 0.48 ± 0.09; P < 0.001). This translated into a linear decrease in mean hyperemic coronary flow (no stenosis: 170.5 ± 66.8 mL/min; mild: 149.8 ± 58.8 mL/min; moderate: 124.4 ± 53.0 mL/min; severe: 94.0 ± 45.2 mL/min; P < 0.001). CFR exhibited a marked linear decrease with increasing stenosis (no stenosis: 2.5 ± 0.9; mild: 2.2 ± 0.8; moderate: 1.8 ± 0.7; severe: 1.4 ± 0.6), corresponding to a decrease of 0.3 for a decrease in FFR of 0.1 (P < 0.001). In contrast, MRR exhibited a negligible decrease across all stenosis grades (no stenosis: 3.0 ± 1.0; mild: 3.0 ± 1.0; moderate: 2.9 ± 1.0; severe: 2.8 ± 1.0), corresponding to a decrease of just 0.05 for a decrease in FFR of 0.1 (P < 0.001). CONCLUSIONS: MRR, unlike CFR, is minimally influenced by epicardial resistance, and thus should be considered the more specific index of microvascular function. This suggests that MRR can also reliably evaluate microvascular function in patients with significant epicardial disease.

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.

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.

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 vessel volume on thermodilution measurements in patients with coronary microvascular dysfunction.

BACKGROUND: Two invasive methods are available to estimate microvascular resistance: bolus and continuous thermodilution. Comparative studies have revealed a lack of concordance between measurements of microvascular resistance obtained through these techniques. AIMS: This study aimed to examine the influence of vessel volume on bolus thermodilution measurements. METHODS: We prospectively included patients with angina with non-obstructive coronary arteries (ANOCA) undergoing bolus and continuous thermodilution assessments. All patients underwent coronary CT angiography to extract vessel volume. Coronary microvascular dysfunction was defined as coronary flow reserve (CFR) < 2.0. Measurements of absolute microvascular resistance (in Woods units) and index of microvascular resistance (IMR) were compared before and after volumetric adjustment. RESULTS: Overall, 94 patients with ANOCA were included in this study. The mean age was 64.7 ± 10.8 years, 48% were female, and 19% had diabetes. The prevalence of CMD was 16% based on bolus thermodilution, while continuous thermodilution yielded a prevalence of 27% (Cohen's Kappa 0.44, 95% CI 0.23-0.65). There was no correlation in microvascular resistance between techniques (r = 0.17, 95% CI -0.04 to 0.36, p = 0.104). The adjustment of IMR by vessel volume significantly increased the agreement with absolute microvascular resistance derived from continuous thermodilution (r = 0.48, 95% CI 0.31-0.63, p < 0.001). CONCLUSIONS: In patients with ANOCA, invasive methods based on coronary thermodilution yielded conflicting results for the assessment of CMD. Adjusting IMR with vessel volume improved the agreement with continuous thermodilution for the assessment of microvascular resistance. These findings strongly suggest the importance of considering vessel volume when interpreting bolus thermodilution assessment.