Index Of Microvascular Resistance Research Articles

Renal functional reserve assessment in patients with coronary microvascular dysfuntion and preserved renal function

Abstract Funding Acknowledgements None. Introduction Renal Functional Reserve (RFR) is a field of scientific debate and may be a valuable diagnostic tool for the early detection of subclinical renal disease. According to literature, chronic kidney disease is related to cardiovascular disease (CVD), however the available data on the association of early renal dysfunction and CVD are sparse. Aim The aim of the present study is to evaluate RFR in patients with coronary microvascular dysfunction (CMD) and preserved renal function [eGFR≥ 60 ml/min/1.73m2 (CKD-EPI) and proteinuria< 400mg/24h]. Methods This is a single-center, prospective study enrolling patients with CMD. We are presenting preliminary resuts. In the absence of significant coronary artery stenosis, functional coronary circulation assessment was performed for all patients. Coronary flow reserve (CFR) and index of microvascular resistance (IMR) were measured invasively. In all participants, RFR was estimated by endogenous creatinine clearance after oral protein load (cooked meal, 1.2gr/kg). Normal RFR was defined as ≥30 ml/min/1.73m2. Also, patients with CMD were offered 24-hour Ambulatory Blood Pressure Monitoring (ABPM). Results A total of 25 participants have been enrolled so far in study: 11 without CMD - non-CMD group [7 female, 64%, mean age: 52.9±8.8 years) and 14 with INOCA – CMD group (11 female, 79%, mean age : 53.5±10.3 years). CMD patients were classified into 2 groups, structural and functional endotype (CFR<2.5 and IMR≥25 were considered abnormal). The RFR value for CMD group is 7.4±6.3 ml/min/1.73m2, while for control group 36.3±5.8 ml/min/1.73m2 (p<0.005), This difference between groups was found to be statistically significant after controlling for confounding factors. It was found that RFR value for functional CMD endotype was 3.8±2.6 ml/min/1.73m2, while for patients with structural endotype 9.6±7,2 ml/min/1.73m2 (p=0.06). Furthermore, no statistical significance was found between RFR and IMR, CFR indices (p =0.35, p =0.23 respectively). According to data from 24hr ABPM , there were no significant differences in ambulatory blood pressure (systolic and diastolic) between the two endotypes of CMD (p=NS for all), as well as no relationship with RFR (p=0.6, p=0.6 respectively) was observed. However, the proportion of non-dippers (for both SBP and DBP) was significantly higher in functional CMD endotype (p<0.05). It was not found correlation between RFR and non-dipping phenotype, for both SBP and DBP (p=NS). Conclusion Abnormal RFR has been observed in all patients with microvascular dysfunction. In addition, patients with functional CMD show a lower RFR value compared to those with structural. RFR is not related to levels of BP or the non-dipping pattern. Given the hypothesis that the assessment of renal functional reserve is an early diagnostic tool for subclinical renal disease, the early identification of patients with specific phenotypes could contribute to the individualization of therapeutic interventions.

Microvascular dysfunction associated with reduced nailfold capillary density in patients with ischemia with no obstructive coronary artery disease

Abstract Funding Acknowledgements None. Introduction The impairment of microvascular function present in coronary microcirculation with chronic angina without obstructive coronary arteries. There are insufficient data in the literature regarding possible generalized microangiopathy in this population. Aim The aim of this study is to demonstrate whether patients with Angina with No Obstructive Coronary Artery Disease (ANOCA) compared to individuals without coronary microvascular dysfunction (CMD) are characterized by a different level of nailfold capillaroscopy abnormalities. Methods We examined 18 participants without CMD - non-CMD group [9 female, 50%, mean age: 54.4±8.1 years) and 26 patients with ANOCA - CMD group (22 female, 84,6%, mean age : 53.2±10.7 years). Functional coronary angiography was performed for the assessment of coronary microcirculation in all patients. Coronary flow reserve (CFR) and index of microvascular resistance (IMR) were measured in the left anterior descending coronary artery using a temperature/pressure sensor-tipped guidewire. In addition, the assessment of skin microcirculation was performed by capillaroscopy, a non-invasive technique to evaluate small vessels of the microcirculation in the nailfold, using stereomicroscope in all patients. Results In CMD group, mean CFR and IMR were 1.34±0.6 and 44.8±28, respectively. Out of the 26 MVD patients with abnormal CFR, 7 of them (27%) had a normal value of IMR, indicating functional microvascular dysfunction. On the other hand, 18 patients (69%) had an abnormal IMR, indicating structural microvascular dysfunction. Capillary density in patients with MVD was significantly decreased compared to the control group (7.6±2.2 vs 10.9±1.8 vessels/mm, p=0.04). The difference in capillary density between the two groups was statistically significant after adjustment for multiple comparisons (p<0.05). No significant difference was found in body mass index, renal function, medical history of dyslipidemia, diabetes mellitus and smoking status between the two groups (p<0.05). Conclusion Nailfold capillary density was reduced in ANOCA patients compared to control group. These data may provide new insights regarding possible generalized microangiopathy in CMD patients. These results suggest that there is an association between microcirculatory impairment at both heart and peripheral vascular bed level.

Intracoronary Adenosine-Derived Coronary Flow Reserve and Index of Microvascular Resistance.

Intracoronary Adenosine-Derived Coronary Flow Reserve and Index of Microvascular Resistance.

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

BackgroundMicrovascular resistance reserve (MRR) can characterize coronary microvascular dysfunction (CMD); however, its prognostic impact in ST-segment elevation myocardial infarction (STEMI) patients remains undefined. ObjectivesThis study sought to investigate the prevalence of CMD in STEMI patients and to elucidate the prognostic performance of MRR. MethodsThis 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. ResultsThe 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. ConclusionsThe 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)

C-20 | Assessing the Relationship between TIMI Frame Count and Index of Microvascular Resistance in Hemodynamically-Stratified Subgroups of Patients with Ischemia and Nonobstructive Coronary Arteries

C-20 | Assessing the Relationship between TIMI Frame Count and Index of Microvascular Resistance in Hemodynamically-Stratified Subgroups of Patients with Ischemia and Nonobstructive Coronary Arteries

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

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. To evaluate the predictive ability of caIMR of MVO after ST-segment elevation myocardial infarction (STEMI). 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. 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). 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 vessel volume on thermodilution measurements in patients with coronary microvascular dysfunction.

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. This study aimed to examine the influence of vessel volume on bolus thermodilution measurements. We prospectively included patients with angina with non-obstructive coronary arteries (ANOCA) undergoing bolus and continuous thermodilution assessments. All patients underwent coronary CT angiographyto 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. 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). 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.

Comparing planned versus ad hoc coronary microvascular assessment: Early findings from the Coronary Microvascular Disease Registry

BackgroundCoronary microvascular dysfunction (CMD) is an etiology for angina with non-obstructive coronary disease. However, the initial adoption of CMD assessment, whether planned or conducted ad hoc, is limited. We characterize planned and ad hoc CMD assessments and highlight evolving trends of a CMD referral center. MethodsWe analyzed outpatient data from the Coronary Microvascular Disease Registry from 2021 to 2023. Patients were categorized into planned or ad hoc CMD assessment groups, and baseline characteristics, hospital stay, medications, and physiological measurements were compared. Secondary analysis evaluated a CMD referral center's evolution. ResultsOf 101 included outpatients, 67.3 % underwent ad hoc procedures and 32.7 % planned procedures. Average age was 63.1 ± 10.1 years. The planned procedure group was 87.9 % female, and the ad hoc procedure group was 51.5 % female. There were no significant differences in index of microvascular resistance or coronary flow reserve between groups. Hospital stay duration was <1 day for both groups, and neither reported complications. Ad hoc patients were more frequently prescribed aspirin before (64.7 % vs. 36.4 %, p = 0.007) and after the procedure (66.2 % vs. 39.4 %, p = 0.01). CMD rates were higher for planned procedures (30.3 % vs. 10.3 %, p = 0.01). We observed that CMD referral centers have more planned procedures and a higher rate of positive results over time. ConclusionCMD referral centers' planned procedures, and subsequent positive cases, increased over time. This emphasizes the importance of planned procedures, appropriate patient selection, and increased awareness of CMD among healthcare providers. Clinical trial registrationCoronary Microvascular Disease (CMD) Registry, NCT05960474, https://clinicaltrials.gov/study/NCT05960474

The Role of Index of Microcirculatory Resistance in Left Anterior Descending Artery ST Segment Elevation Myocardial Infarction Patients after Primary Percutaneous Coronary Intervention.

Background: Our aim was to assess the relationship of the index of microvascular resistance (IMR) in left anterior descending (LAD) artery involved STEMI patients. Methods: Data of 316 STEMI patients who had undergone primary percutaneous coronary intervention (PCI) were collected from three cardiovascular centers from 2005 to 2015. In total, 246 patients with LAD STEMI were enrolled for IMR evaluation. Patients were divided into two groups respective of the cut-off IMR value of 30. All-cause mortality, left ventricular function, improvement of systolic function, and cardiac biomarkers were analyzed and compared. Results: A total of 246 patients were enrolled. The number of patients in the IMR above 30 group was 93 and below 30 was 153. The mean ages for each group were 57.91 ± 11.99 and 54 ± 10.63, respectively. The peak creatinine kinase (CK) (3936.85 ± 2827.32 IU/L vs. 2218.08 ± 2310.41 IU/L, p < 0.001) and CKmb (336.15 ± 195.08 mg/mL vs. 231.53 ± 179.53 mg/mL, p < 0.001) levels were higher for an IMR above the 30 group. The left ventricular ejection fraction (LVEF) (44.57 ± 6.685% vs. 47.35 ± 8.17%, p = 0.006) and improvement of LVEF (2.81 ± 7.135% vs. 5.88 ± 7.65%, p = 0.004) was lower in the IMR above 30 group. All-cause mortality (7.5% vs. 1.3%, p = 0.012) was higher in the IMR above 30 group, and a Cox regression analysis showed that an IMR above 30 was a poor prognostic factor regarding all-cause mortality (HR: 5.151, 95% CI 1.062-24.987, p = 0.042) even after adjusting for classical clinical risk factors. Conclusions: An elevated IMR value represented larger infarct size, more severe LV dysfunction, and higher mortality in LAD STEMI patients after successful PCI.

“The INOCA-IT: Rationale and design of a multicenter registry investigating ischemia in patients with non-obstructive coronary artery (INOCA) disease in Italy”

BackgroundIschemia with non-obstructive coronary artery (INOCA) disease is being progressively acknowledged as one of the pathophysiological mechanisms of chronic coronary syndrome (CCS) in an increasingly wide range of clinical pictures. Although the research has already begun to move towards a defined diagnostic pathway and a specific medical therapy for this disease, at present it remains a clinical challenge, especially if not thoroughly investigated. Methods and resultsThe INOCA IT Multicenter Registry RF-2019-12369486 is a prospective, multicentric, non-randomized, single-arm, open label clinical study which aims to evaluate the efficacy of a stratified diagnostic and therapeutic approach on adverse events prevention and symptom relief in Italian patients with INOCA disease. The study population includes patients with a clinical presentation of CCS for angina and/or positive stress test for myocardial ischemia and evidence of non-obstructive coronary artery disease (CAD) at coronary angiography. In these patients a complete invasive coronary physiology assessment is performed with the guidewire-based measurement of coronary flow reserve (CFR) and index of microvascular resistance (IMR), followed by acetylcholine (ACh) spasm provocation test. On the basis of the results of coronary function testing, patients are stratified into different INOCA endotypes (coronary microvascular disease, vasospastic angina, microvascular spasm, non-cardiac chest pain) and given a tailored medical therapy in accordance with the latest scientific evidence. At one year follow-up the impact of such a target therapy on angina class and quality of life, as well as on cardiovascular adverse events (hospitalization and coronary revascularization) is evaluated. ConclusionsThe INOCA-IT Multicenter Registry will inform clinicians on sex-specific prevalence of INOCA in Italy and will show the impact of a stratified diagnostic and therapeutic approach on symptoms burden and prognosis of INOCA patients.

An interventional sheep model of severe aortic valve stenosis hemodynamics for the evaluation of alterations in coronary physiology and microvascular function.

We aimed to develop a large animal model of subcoronary aortic stenosis (AS) to study intracoronary and microcirculatory hemodynamics. A total of three surgical techniques inducing AS were evaluated in 12 sheep. Suturing the leaflets together around a dilator (n = 2) did not result in severe AS. Suturing of a pericardial patch with a variable opening just below the aortic valve (n = 5) created an AS which was poorly tolerated if the aortic valve area (AVA) was too small (0.38-1.02 cm2), but was feasible with an AVA of 1.2 cm2. However, standardization of aortic regurgitation (AR) with this technique is difficult. Therefore, we opted for implantation of an undersized AV-bioprosthesis with narrowing sutures on the leaflets (n = 5). Overall, five sheep survived the immediate postoperative period of which three had severe AS (one patch and two bioprostheses). The surviving sheep with severe AS developed left ventricular hypertrophy and signs of increased filling-pressures. Intracoronary assessment of physiological indices in these AS sheep pointed toward the development of functional microvascular dysfunction, with a significant increase in coronary resting flow and hyperemic coronary resistance, resulting in a significantly higher index of microvascular resistance (IMR) and lower myocardial resistance reserve (MRR). Microscopic analysis showed myocardial hypertrophy and signs of fibrosis without evidence of capillary rarefaction. In a large animal model of AS, microvascular changes are characterized by increased resting coronary flow and hyperemic coronary resistance resulting in increased IMR and decreased MRR. These physiological changes can influence the interpretation of regularly used coronary indices.NEW & NOTEWORTHY In an animal model of aortic valve stenosis (AS), coronary physiological changes are characterized by increased resting coronary flow and hyperemic coronary resistance. These changes can impact coronary indices frequently used to assess concomitant coronary artery disease (CAD). At this point, the best way to assess and treat CAD in AS remains unclear. Our data suggest that fractional flow reserve may underestimate CAD, and nonhyperemic pressure ratios may overestimate CAD severity before aortic valve replacement.

Microvascular reperfusion of fibrinolysis followed by percutaneous coronary intervention versus primary percutaneous coronary intervention for ST-segment-elevation acute myocardial infarction.

Primary percutaneous coronary intervention (PPCI) has been widely recognized as the preferred treatment for ST-segment-elevation myocardial infarction (STEMI). However, substantial numbers of STEMI patients cannot receive timely PPCI. Early fibrinolysis followed by routine percutaneous coronary intervention (FPCI) has been proposed as an effective and safe alternative for eligible patients. To date, few studies have compared FPCI with PPCI in terms of microvascular reperfusion. This study aimed to evaluate the microvascular function of FPCI and PPCI. STEMI patients at the Peking University First Hospital and Miyun Hospital were enrolled in this retrospective study between January 2015 to December 2020. Microvascular function documented by the coronary angiography-derived index of microvascular resistance (caIMR) was measured at the final angiogram after revascularization. The primary end point was the caIMR of the culprit vessels. The secondary end points were in-hospital and follow-up major adverse cardiovascular events (MACE), including cardiovascular death, non-fatal recurrent myocardial infarction, target-vessel revascularization (TVR), and non-fatal stroke/transient ischemic attacks (TIA). Details of the adverse clinical events were obtained from telephone interviews and electronic medical record systems until January 2022. In total, 496 STEMI patients were enrolled in this cross-sectional retrospective study. Of these patients, 81 underwent FPCI, and 415 underwent PPCI. At the baseline, the PPCI patients had a higher-risk profile than the FPCI patients. The time from symptom onset to reperfusion therapy was significantly shorter in the FPCI group than the PPCI group (median 3.0 vs. 4.5 hours; P<0.001). The caIMR was significantly lower in the FPCI group than the PPCI group (median 20.34 vs. 40.33; P<0.001). The median follow-up duration was 4.1 years. During the follow-up period, the rate of MACE was lower in the FPCI group than the PPCI group [7 (10.1%) vs. 82 (20.8%), P=0.048]. After propensity score matching to adjust for the imbalances at the baseline, the caIMR remained significant and the clinical outcomes did not differ significantly between the two groups. In eligible STEMI patients, clinically successful FPCI may be associated with better microvascular reperfusion and comparable clinical outcomes as compared with PPCI.

Coronary microvascular resistance comparison of coronary arteries with and without considering vascular diameter: A retrospective, single‐center study

AbstractBackground and AimsMeasurement of coronary microvascular resistance (MR) is essential for diagnosing nonocclusive coronary artery ischemia, but whether coronary branches of different diameters can be similarly assessed using hyperemic microvascular resistance index (hMVRI) calculated from average peak velocity (APV) remains unclear. We investigated the relationship between coronary arteries of different diameters and hMVRI.MethodsThirty patients with suspected angina pectoris and nonobstructive coronary stenosis with fractional flow reserve &gt;0.8 underwent evaluation of all coronary arteries using a Doppler velocity and pressure‐equipped guidewire. Quantitative coronary angiography (QCA) was used to analyze vessel diameter (DQCA). Coronary blood flow (CBFQCA) was calculated as πDQCA2/4 (0.5 × APV) and hMVRIQCA as distal coronary pressure divided by CBFQCA during maximal hyperemia.ResultsThe hMVRI was significantly higher for the right coronary artery than for the left anterior descending artery, but no significant differences between arteries were seen for CBFQCA and hMVRIQCA. Although the correlation between CBFQCA and APV was weak, CBFQCA divided into three groups according to DQCA showed very strong correlations with APV. Slopes of the straight line between APV and CBFQCA for small‐, middle‐, and large‐diameter groups were 0.48, 0.30, and 0.21, respectively, with slope decreasing as diameter increased.ConclusionsComparative evaluation of MR in coronary branches with varying vessel diameters requires vessel diameter to be accounted for.

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

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. 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. 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%. 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.

Core laboratory comparative assessment of angiography-derived index of microvascular resistance (IMR) in patients with wire-based IMR

Abstract Background Coronary microvascular disease (CMD) is responsible for nearly half of angina in the general population. The index of microvascular resistance (IMR) is the gold standard for the diagnosis of CMD. Abnormal IMR is independently associated with adverse outcomes and persistent angina after percutaneous coronary intervention (PCI) regardless of the achieved fractional flow reserve (FFR). However, the implementation of IMR in clinical practice is low due to cost and the need for hyperemia. Thus, multiple software and formulas have been developed to calculate wireless IMR via angiography analysis. However, these angiography-derived IMRs have never been compared head-to-head by an independent core laboratory. Aim In this study, we aim to investigate the diagnostic accuracies of five angiography-derived IMR software/formulas by an independent core lab in a retrospective cohort undergoing follow-up angiograms after successful PCI. Methods We analyzed 43 patients from the FUNCOMBO trial and 34 patients from the RETROFI II trial. All patients have received successful PCI for STEMI, and wire-based IMR was measured at six months (for FUNCOMBO) and three years follow-up (for RETROFI II). Angiography-derived IMR was calculated with the QFR®2.1 software, the Flashangio CaIMR® software, and the AngioPlus software. In addition, using QFR-derived data, we calculated the angio-IMR using the formula of Escaned et al. [angio-IMR = (Pa–[0.1*Pa])*QFR*e-Tmn (where e-Tmn is an estimation of hyperaemic mean transit time)] and Scarsini et al. [NH-IMRangio=Pa(resting)x QFR x N frame(resting)/frame per second]. The threshold of CMD diagnosis is 25 for all five angiography-derived IMR methods. The correlation and agreement of the five methods were evaluated against wire-based IMR measurement. Results The wire-based IMR was significantly correlated with Medis IMR (r= 0.396, p=0.001) and NH-IMRangio (r=0.378, p=0.001). The agreements between IMR and the angiography-derived IMRs are demonstrated in figure 1. The sensitivity, specificity, positive predicted value, negative predicted value, and accuracy were demonstrated in figure 2, which showed that using the published criteria, the accuracy of diagnosis was 52%, 68%, 67%, 68%, and 49% for Medis IMR, CaIMR, AngioPlus IMR, angio-IMR, and NH-IMRangio, respectively. Comparison of all angiography-derived IMR with wire-based IMR yielded the AUC’s of 0.648, 0.561, 0.606, 0.674, 0.688 for Medis IMR, CaIMR, AngioPlus IMR, angio-IMR, and NH-IMRangio respectively. (Figure 2.) Conclusion In this small validation cohort, we found that all five angiography-derived IMR calculation methods had either poor or very poor diagnostic accuracy. Among the five methods, the Medis IMR, Angio-IMR, and NH-IMRangio may be viable options for wireless CMD diagnosis.Figure 1Figure 2

In vivo validation of intra-coronary absolute flow measurements and comparison of reliability between different microvascular indices and the microvascular resistance reserve

Abstract Background Coronary microvascular dysfunction plays a major role in patients with cardiac ischemia without flow limiting epicardial coronary stenosis, takotsubo cardiomyopathy, aortic valve stenosis and heart failure with preserved ejection fraction. In clinical practice, the index of microvascular resistance (IMR) and coronary flow reserve (CFR), and more recently the absolute coronary blood flow (ABF), absolute coronary resistance (ACR) and the microvascular resistance reserve (MRR) are used as parameters to measure resistance and flow using continuous coronary thermodilution. Purpose Firstly, to validate ABF measured with continuous coronary thermodilution in vivo against epicardial doppler-measured flow. Secondly, to assess reliability and reproducibility in-vivo of different microvascular indices. Methods For the purpose of this study coronary measurements were conducted in two large animal models and in patients, all with the appropriate ethical committee approval. For the first part of the study, fourteen sheep underwent repeated paired measurements of ABF and ACR (with use of continuous thermodilution) with different saline infusion speeds, as well as IMR, CFR and MRR in multiple coronary vessels. Seven additional sheep underwent these measurements while having simultaneous measurements with epicardial coronary flow probes (gold standard) in an open-chest model. The epicardial flow probes were placed on the proximal left anterior descending and circumflex artery. Maximal hyperemia was induced with adenosine (CFR and IMR) or infusion of saline at a rate of 30ml/min (ABF, ACR and MRR). For the second part of the study, in 41 patients receiving routine microvascular assessment, IMR and CFR measurements were duplicated by a single operator, after re-calibration, to assess the reproducibility of the measurement. The combined animal and human data resulted in the analysis of 408 coronary measurements made in 88 coronary vessels during 65 heart catheterizations. Results In sheep, ABF measured with continuous thermodilution (with saline infusion speeds from 5ml/min to 30ml/min) was accurate when compared with epicardial flow measurements. (Table 1, Fig 1A) Notably, the continuous thermodilution measurement had the tendency to slightly overestimate ABF. (Table 1, Fig 1B) The two methods were equivalent within 15% (Two one-sided test: mean difference: -8.73%; 95% CI: -14.40 to -3.06%, p= 0.016). When comparing test-retest reproducibility between the indices, CFR performed the worst while ACR and MRR performed the best. MRR had a significantly better reproducibility than the IMR. (Table 1, Fig 1C). Conclusion ABF can accurately be determined by continuous coronary thermodilution. MRR and ACR have a significantly superior reliability and reproducibility compared to IMR and CFR. Unlike ACR, MRR is not vessel or territory-size dependent and is therefore the index of choice for future research and clinical assessment of the microcirculation.

Invasive coronary function testing in patients with INOCA - a single center experience

Abstract Background Coronary vasomotion disorders (CVDs) represent a frequent cause of angina in patients with ischemia with non-obstructed coronary arteries (INOCA). Invasive coronary angiography (ICA) often fails to identify patients with vasospastic angina and/or microvascular dysfunction. Purpose Our aim was to describe and characterize CVDs in INOCA patients, using a multi-parametric, invasive, coronary function testing protocol. Methods Patients with INOCA that underwent our protocol for coronary function testing (CFT), between July 2021 and October 2022 were included in this single-center prospective study. The protocol consisted of an invasive assessment of coronary circulation vasorelaxation at rest and during hyperemia, as well as the propensity for coronary vasospasm using increasing doses of intra-coronary acetylcholine. Fractional flow reserve, coronary flow reserve (CFR), and index of microvascular resistance (IMR) were recorded. CVDs were diagnosed based on the criteria proposed by the Coronary Vasomotor Disorders International Study Group. Results A total of 56 patients were included, mean age was 64±12 years and 57.1% were female. At baseline, all patients had either typical angina (82.1%, n=46) or a positive ischemia test (67.9%, n=38). Twenty patients (35.7%) had a history of a previous ICA or computed tomography due to anginal symptoms, while only 8.9% of patients had known structural ischemic heart disease and were subjected to percutaneous coronary intervention. Our CFT protocol was completed in all patients without any serious complications. Isolated epicardial vasospasm was found in 16 (28.6%) patients, isolated coronary microvascular dysfunction (CMD) in 9 (16.1%), and a combination of CMD and coronary vasospasm in 9 (16.1%). Only 1 patient (1.8%) had isolated microvascular spasm. We were able to further identify two distinct endotypes of CMD, using a combined assessment of CFR and IMR, termed structural and functional CMD: Functional CMD - 7 patients (12.5%) had CFR &amp;lt; 2.0 and IMR &amp;lt; 25; Structural CMD - 6 patients (10.7%) had CFR &amp;lt; 2.0 and IMR &amp;gt; 25. Conclusion Coronary vasomotion disorders are a common cause of INOCA. A CFT protocol is safe, can be used in clinical practice, and can provide a definite diagnosis for the underlying cause of angina.

Increased arterial stiffness in patients with ischemia and no obstructive coronary artery disease

Abstract Introduction Recent studies have shown that patients with angina pectoris and no obstructive coronary artery disease are a heterogeneous population with an elevated risk of major adverse cardiovascular events. The current literature lacks evidence regarding the possible association between arterial stiffness and coronary microvascular dysfunction (CMD). Purpose The aim of this study is to determine whether arterial stiffness is increased among patients with CMD compared to hypertensive control group. Methods We examined 25 patients [10 female, 40%, mean age: 60.7±9.6 years, mean office blood pressure (BP) : 141/88±17/9 mmHg] and 35 CMD patients (22 female, 63%, mean age : 62.4±4.9 years, average office BP: 129/79±15/10 mmHg). In the group of patients with chronic angina, CMD was defined by a standardized systematic protocol in which coronary flow reserve (CFR) and index of microvascular resistance (IMR) were measured in the left anterior descending coronary artery using a temperature/pressure sensor-tipped guidewire. In addition, in all participants, arterial stiffness was assessed using aortic augmentation index (AIx), derived from the analysis of central pulse waveforms, recorded by applanation tonometry directly from the radial artery. Results In the CMD group, mean CFR and IMR were 1.3±0.9 and 45.7±35, respectively. Out of the 35 CMD patients with abnormal CFR 12 of them (34%) had a normal value of IMR, indicating functional microvascular dysfunction. On the other hand, 23 patients (66%) had an abnormal IMR, indicating structural microvascular dysfunction. In CMD group compared to asymptomatic controls, AIx was found significantly higher (35.6±10.5 vs 25.1±12.1%, p=0.03). This difference in AIx between groups was found to be statistically significant after adjustment for age, gender and levels of BP (p&amp;lt;0.05). Moreover, no significant differences were found in body mass index, renal function, history of dyslipidemia, diabetes mellitus and smoking status between the two groups (p=NS for all). Conclusion CMD patients are characterized by increased arterial stiffness in comparison with asymptomatic controls, independently of demographic and hemodynamic confounders. These results indicate that impairment of the microvasculature is associated with large artery stiffening. Thus, potential clinical benefit could be derived from specific therapies targeting AIx in patients with CMD.

Treatment of microvascular angina with the coronary sinus reducer: a first experience

Abstract The Coronary Sinus Reducer (CSR) is an hourglass-shaped device approved for the treatment of refractory angina. Its percutaneous implantation in the coronary sinus leads to a retrograde increase in venous pressure, which is thought to improve capillary recruitment and perfusion to the ischemic myocardium. No data is however available on the use of the CSR to treat microvascular angina, an increasingly recognized but still poorly understood condition. In this preliminary study, we evaluated the efficacy of the CSR in a small cohort of patients with non-obstructive disease. We screened consecutive patients from the prospective COMPLEX registry that received a CSR for refractory angina between June 2018 and November 2022. Inclusion criteria were the absence of obstructive coronary artery disease (&amp;lt;50% narrowing in all coronary arteries, or a negative intracoronary fractional flow reserve test) and no prior history of revascularization. Endpoints were angina and dyspnea symptoms, evaluated with the Canadian Cardiovascular Society (CCS) and the New York Hearth Association (NYHA) scores respectively, procedural success rate, and major adverse cardiovascular events (MACE), defined as a composite of all-cause mortality, cardiovascular death, acute coronary syndromes (ACS) and heart failure (HF) hospitalizations. We ultimately enrolled 8 patients; 6 (75%) were females and mean age was 67.8±9.9 years. Their baseline characteristics are further depicted in table 1. Microvascular dysfunction was invasively confirmed in 5 (62.5%) patients; mean index of microvascular resistance (IMR) was 32.8±15.7 and mean coronary flow reserve (CFR) was 1.7±0.7. In one patient, reduced global CFR (1.4) was evident on cardiac magnetic resonance examination. At baseline, mean CCS class was 2.9±0.6, NYHA class 2±0.9, and number of antianginal drugs 2.6±1.6. Procedural success was 100%, with only one patient experiencing a procedure-related complication (sternocleidomastoid muscle hematoma requiring no intervention). At a median follow-up of 647.5 days (IQR 132-732), mean CCS class was 1.5±0.8, NYHA class 1.9±0.9 and number of antianginal drugs 1.9±1.1. All patients improved by ≥1 CCS class and 3 (37.5%) by ≥2 CCS classes. No MACE was observed. To the best of our knowledge, we present the first report of CSR implantation for the treatment of microvascular angina. Our positive results are particularly promising given the paucity of treatment options currently available for the condition, but larger studies are needed to confirm these findings.table 1figure 1