Index Of Microcirculatory Resistance Research Articles

ST SEGMENT DEPRESSION: MUCH ADO ABOUT NOTHING

Abstract Introduction ST depression in ECG trace is classically used to assess the cardiac ischaemia. Several other causes of ST depression, like hypokalaemia, digoxin therapy, left ventricular hypertrophy, left bundle branch block can be easily excluded. Sometimes the ST segment depression during tachycardia is observed in young healthy people where ischemic background is rare. Case Report We present the case of an asymptomatic and without cardiovascular risk factors 29–years–old man who performed, during occasional sport visit, an ECG showing sinus tachycardia with diffuse ST segment depression. The ECG obtained at the presentation in Emergency Department of our hospital confirmed sinus tachycardia at 140 beats per minute and diffuse ST segment depression. This finding persisted during the following six hours and slowly regressed with normalization of the heart rate. The same ECG alteration was founded during an exercise test when the heart rate rised up to 90 bpm. A coronary angiography showed anatomically normal and angiographically free of stenosis coronaries; the functional study, using Fractional Flow Reserve (FFR), Coronary Flow Reserve (CFR) and Index of Microcirculatory Resistance (IMR), currently gold standard for the functional study of microcirculation, was normal. No alterations were founded at the cardiac magnetic resonance. Due to a previous resting ECG suspected of ventricular preexcitation, an electrophysiological study was performed and showed neither accessory pathways nor inducibility arrhythmias. The asymptomatic and hemodynamically stable patient was discharged and an ambulatorial follow–up was planned. Conclusion This case emphasizes the ever–present difficulty of attributing unequivocal etiological meanings to electrocardiographic alterations.

Prognostic Value of Microvascular Resistance Reserve Measured Immediately After PCI in Stable Coronary Artery Disease.

Microvascular resistance reserve (MRR) has been proposed as a specific metric to quantify coronary microvascular function. The long-term prognostic value of MRR measured in stable patients immediately after percutaneous coronary intervention (PCI) is unknown. This study sought to determine the prognostic value of MRR measured immediately after PCI in patients with stable coronary artery disease. This study included 502 patients with stable coronary artery disease who underwent elective PCI and coronary physiological measurements, including pressure and flow estimation using a bolus thermodilution method after PCI. MRR was calculated as coronary flow reserve divided by fractional flow reserve times the ratio of mean aortic pressure at rest to that at maximal hyperemia induced by hyperemic agents. An abnormal MRR was defined as ≤2.5. Major adverse cardiac events (MACEs) were defined as a composite of all-cause mortality, any myocardial infarction, and target-vessel revascularization. During a median follow-up of 3.4 years, the cumulative MACE rate was significantly higher in the abnormal MRR group (12.5 versus 8.3 per 100 patient-years; hazard ratio 1.53 [95% CI, 1.10-2.11]; P<0.001). A higher all-cause mortality rate primarily drove this difference. On multivariable analysis, a higher MRR value was independently associated with lower MACE and lower mortality. When comparing 4 subgroups according to MRR and the index of microcirculatory resistance, patients with both abnormal MRR and index of microcirculatory resistance (≥25) had the highest MACE rate. An abnormal MRR measured immediately after PCI in patients with stable coronary artery disease is an independent predictor of MACE, particularly all-cause mortality.

Prognostic Value of Microvascular Resistance Reserve After Percutaneous Coronary Intervention in Patients With Myocardial Infarction.

The microvascular resistance reserve (MRR) has recently been introduced as a novel index to assess the vasodilatory capacity of the microcirculation, independent of epicardial disease. The prognostic value of MRR in ST-segment elevation myocardial infarction (STEMI) is unknown. The aim of this analysis was to investigate the prognostic value of MRR in patients with STEMI and to compare MRR with cardiovascular magnetic resonance imaging parameters. From a pooled analysis of individual patient data from 6 cohorts that measured the index of microcirculatory resistance (IMR) directly after primary percutaneous coronary intervention in patients with STEMI (n=1,265), a subgroup analysis was performed in patients in whom both MRR and IMR were available. The primary endpoint was the composite of all-cause mortality or hospitalization for heart failure. Both MRR and IMR could be calculated in 446 patients. The optimal cutoff of MRR to predict the primary endpoint in this STEMI population was 1.25. During a median follow-up of 3.1 years (Q1-Q3: 1.5-6.1 years), the composite of all-cause mortality or hospitalization for heart failure occurred in 27.3% and 5.9% of patients (HR: 4.16; 95%CI: 2.31-7.50; P< 0.001) in the low MRR (≤1.25) and high MRR (>1.25) groups, respectively. Both IMR and MRR were independent predictors of the composite of all-cause mortality or hospitalization for heart failure. MRR measured directly after primary percutaneous coronary intervention was an independent predictor of the composite of all-cause mortality or hospitalization for heart failure during long-term follow-up.

OR8-2 | Intravenous vs Intracoronary Adenosine for the Determination of Coronary Flow Reserve and Index of Microcirculatory Resistance

OR8-2 | Intravenous vs Intracoronary Adenosine for the Determination of Coronary Flow Reserve and Index of Microcirculatory Resistance

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

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. 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. 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. URL: https://www.clinicaltrials.gov; Unique Identifier: NCT05406297.

Impaired coronary flow reserve in patients with poor type 2 diabetes control: Preliminary results from prospective microvascular dysfunction registry.

Type 2 diabetes (DM) is a common comorbidity associated with cardiovascular disease, especially when poor glucose control is present. Extracardiac microcirculatory complications prevalence is well documented, however coronary microcirculatory dysfunction (CMD) seem to be underreported in this group. The present study analyzed coronary physiology measurements (coronary flow reserve [CFR], index of microcirculatory resistance [IMR], resistance reserve ratio [RRR]) in 47 diabetic patients (21 subjects with poor glycemia control defined as fasting glucose levels > 7.2 mmol/L and 26 with normal fasting glucose), and compared to 54 non-diabetic controls, who had undergone coronary angiography due to symptoms of chronic coronary syndrome. The median age of patients was 65.5 [59.0; 73.0] years old, 74% male, similar in terms of cardiovascular risk factors and prior myocardial infarction. Insulin was used by 19% of diabetic patients with poor glucose control and by 15% of those with DM and low fasting glucose. Prevalence of CMD was 38% in poor glycemia control patients, 27% in DM-patients with proper glucose control and 31% of non-diabetics. Median CFR values were the lowest in poor DM control patients compared to both, normal fasting glucose (1.75 [1.37; 2.32] vs. 2.30 [1.75; 2.85], p = 0.026) and to non-diabetics (1.75 [1.37; 2.32] vs. 2.15 [1.50; 2.95], p = 0.045). Levels of IMR, RRR and MRR did not differ significantly between compared groups (p > 0.05 for all comparisons). Poor glycemia control in type 2 DM might be associated with a higher prevalence of CMD driven by decreased coronary flow reserve, however, further research in larger groups of patients should be performed to confirm this observation.

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.

Visual Estimates of Coronary Slow Flow Are Not Associated with Invasive Wire-Based Diagnoses of Coronary Microvascular Dysfunction.

Background: Coronary slow flow (CSF) by invasive coronary angiography is frequently understood to be an indicator of coronary microvascular dysfunction (CMD) in patients with ischemia with non-obstructive coronary arteries (INOCA). However, the relationship between visual estimates of CSF and quantitative wire-based invasive diagnosis of CMD is uncertain. Methods: We prospectively enrolled adults age ≥18 years with stable ischemic heart disease who were referred for invasive coronary angiography. Individuals with ≥50% epicardial coronary artery stenosis were excluded. Invasive coronary angiography was reviewed for CSF, defined as ≥3 cardiac cycles to opacify distal vessels with contrast. Coronary function testing was performed in the left anterior descending (LAD) coronary artery using bolus coronary thermodilution techniques to measure coronary flow reserve (CFR) and the index of microcirculatory resistance (IMR). Invasively determined CMD was defined as abnormal CFR (<2.5), abnormal IMR (≥25), or both. Results: Among 104 participants, the median age was 61.5 and 79% were female. The median CFR was 3.6 (IQR 2.5-4.7) and the median IMR was 21 (IQR 13.3-28.0). Overall, 24.0% of participants had abnormal CFR, 34.6% had abnormal IMR, and 48.1% had a final diagnosis of invasively determined CMD. CSF was present in 23 participants (22.1%). The proportions of patients with CMD (56.5% vs 45.7%, p=0.36), abnormal CFR (17.4% vs 25.9%, p=0.40) and abnormal IMR (43.5% vs. 32.1%, p=0.31) were not different in patients with versus without CSF. Conclusions: Among patients with INOCA, CSF was not associated with abnormal CFR, IMR, or either abnormal CFR or IMR. CSF is not a reliable angiographic surrogate of abnormal CFR or IMR as determined by invasive, wire-based physiology testing.

Smoking and Respiratory Diseases in Patients with Coronary Microvascular Dysfunction

BackgroundCoronary microvascular disease (CMD) is common in patients with and without obstructive coronary artery disease, and is associated with adverse clinical outcomes. Respiratory-related variables are associated with pulmonary and systemic microvascular dysfunction, while evidence about their relationship with CMD is limited. We aim to evaluate respiratory-related variables as risk factors of CMD. MethodsThis is an observational, single-center study enrolling consecutive patients undergoing invasive evaluation of coronary microvascular function in the catheterization laboratory. Patients with evidence of obstructive coronary artery disease or with missing data were excluded. Associations between respiratory-related variables and indices of CMD were assessed using univariate and multivariate regression models. ResultsOverall, 266 patients (mean age 67 ± 11 years, 59% females) were included in the current analysis. Of those, 155 (58%) had evidence of CMD. Among the respiratory variables, independent predictors of CMD were current smoking (adjusted odds ratio [AOR] 2.5; 95% confidence interval [CI], 1.2-5; P = .01) and obstructive sleep apnea (AOR 5.7; 95% CI, 1.2-26; P = .03), while chronic obstructive pulmonary disease was not. Among ever-smokers, higher smoking pack-years was an independent risk factor for CMD (median 35 vs 25 pack-years, AOR 1.09; 95% CI, 1.04-1.13; P < .01), and was associated with higher rates of pathologic index of microcirculatory resistance and resistive reserve ratio. ConclusionIn patients undergoing invasive coronary microvascular evaluation, current smoking and obstructive sleep apnea are independently associated with CMD. Among smokers, higher pack-years is a strong predictor for CMD. Our findings should raise awareness for prevention and possible treatment options.

Prognostic Implications of Microvascular Resistance Reserve in Symptomatic Patients With Intermediate Coronary Stenosis

BackgroundMicrovascular resistance reserve (MRR) is a novel index reflecting coronary microcirculatory function, irrespective of epicardial coronary artery stenosis. There is limited evidence regarding whether MRR can be an independent prognostic tool in patients with stable ischemic heart disease (IHD). ObjectivesThe aim of this study was to evaluate clinical outcomes according to MRR in patients with stable IHD accompanied with or without significant epicardial coronary artery stenosis. MethodsThe present study included 547 consecutive patients undergoing systematic echocardiographic and invasive physiological assessment for suspected stable IHD. Significant epicardial coronary artery stenosis was defined as fractional flow reserve (FFR) ≤0.80. Coronary microvascular dysfunction (CMD) was defined as MRR ≤3.0. The primary outcome was major adverse cardiovascular events (MACE), a composite of cardiovascular death, myocardial infarction, repeat revascularization, and admission for heart failure. ResultsAmong the study group, 172 patients (31.4%) had FFR ≤0.80, and 200 patients (36.6%) had CMD defined by MRR ≤3.0. MRR showed no significant correlation with FFR (R = −0.031; P = 0.469), but it was significantly correlated with the index of microcirculatory resistance (R = −0.353; P < 0.001), N-terminal pro–B-type natriuretic peptide (R = −0.296; P < 0.001), left ventricular filling pressure (E/e′ ratio) (R = −0.224; P < 0.001), and diastolic dysfunction grade (P < 0.001). During a median follow-up period of 3.3 years (Q1-Q3: 2.0-4.5 years), MRR was significantly associated with MACE risk (HR: 1.23 per 1-U decrease; 95% CI: 1.12-1.36; P < 0.001). CMD defined by MRR ≤3.0 was associated with an increased MACE risk for both FFR >0.80 (41.0% vs 26.0%; adjusted HR: 1.59; 95% CI: 1.07-2.35; P = 0.021) and FFR ≤0.80 (34.7% vs 14.8%; adjusted HR: 2.32; 95% CI: 1.12-4.82; P = 0.024). ConclusionsDecreased MRR was associated with the presence of cardiac diastolic dysfunction as well as increased left ventricular filling pressure. The presence of CMD defined by MRR was independently associated with the risk for a composite of cardiovascular death, myocardial infarction, repeat revascularization, and admission for heart failure in patients with stable IHD, irrespective of significant epicardial coronary artery stenosis. (Prognostic Impact of Cardiac Diastolic Function and Coronary Microvascular Function [DIAST-CMD]; NCT05058833)

Implementation of Microcirculation Examination in Clinical Practice-Insights from the Nationwide POL-MKW Registry.

Background and Objectives: The assessment of coronary microcirculation may facilitate risk stratification and treatment adjustment. The aim of this study was to evaluate patients' clinical presentation and treatment following coronary microcirculation assessment, as well as factors associated with an abnormal coronary flow reserve (CFR) and index of microcirculatory resistance (IMR) values. Materials and Results: This retrospective analysis included 223 patients gathered from the national registry of invasive coronary microvascular testing collected between 2018 and 2023. Results: The frequency of coronary microcirculatory assessments in Poland has steadily increased since 2018. Patients with impaired IMR (≥25) were less burdened with comorbidities. Patients with normal IMR underwent revascularisation attempts more frequently (11.9% vs. 29.8%, p = 0.003). After microcirculation testing, calcium channel blockers (CCBs) and angiotensin-converting enzyme inhibitors were added more often for patients with IMR and CFR abnormalities, respectively, as compared to control groups. Moreover, patients with coronary microvascular dysfunction (CMD, defined as CFR and/or IMR abnormality), regardless of treatment choice following microcirculation assessment, were provided with trimetazidine (23.2%) and dihydropyridine CCBs (26.4%) more frequently than those without CMD who were treated conservatively (6.8%) and by revascularisation (4.2% with p = 0.002 and 0% with p < 0.001, respectively). Multivariable analysis revealed no association between angina symptoms and IMR or CFR impairment. Conclusions: The frequency of coronary microcirculatory assessments in Poland has steadily increased. Angina symptoms were not associated with either IMR or CFR impairment. After microcirculation assessment, patients with impaired microcirculation, expressed as either low CFR, high IMR or both, received additional pharmacotherapy treatment more often.

The invasive investigation of INOCA in the coronary catheterization lab

Over half of all patients with angina have no angiographically demonstratable obstructive coronary disease, with a significant proportion of these patients having undiagnosed microvascular dysfunction and/or vasospastic angina. In chronic coronary syndrome, ischemia with non-obstructive coronary artery disease (INOCA) often remains undiagnosed, or uninvestigated. INOCAmay occur due to vasospastic angina and microvascular dysfunction and require invasive assessment in the coronary catheterization lab. To evaluate INOCA coronary flow reserve (CFR) and the index of microcirculatory resistance (IMR) are used to assess microvascular dysfunction before acetylcholine provocation testing for coronary spasm. This review provides an overview of the invasive investigation of INOCA in the coronary catheterization lab for patients with angina to be optimally managed.

Index of Microcirculatory Resistance to predict microvascular obstruction in STEMI: A systematic review and meta-analysis.

Microvascular obstruction (MVO) is an independent predictor of adverse cardiac events after ST-elevation myocardial infarction (STEMI). The Index of Microcirculatory Resistance (IMR) may be a useful marker of MVO, which could simplify the care pathway without the need for Cardiac Magnetic Resonance (CMR). We assessed whether the IMR can predict MVO in STEMI patients. We conducted a systematic review and meta-analysis, including articles where invasive IMR was performed post primary percutaneous coronary intervention (PCI) in addition to MVO assessment with cardiac MRI. We searched PubMed, Scopus, Embase, and Cochrane databases from inception until January 2023. Baseline characteristics, coronary physiology and cardiac MRI data were extracted by two independent reviewers. The random-effects model was used to pool the data. Among 15 articles identified, nine articles (n = 728, mean age 61, 81% male) contained IMR data stratified by MVO. Patients with MVO had a mean IMR of 41.2 [95%CI 32.4-50.4], compared to 25.3 [18.3-32.2] for those without. The difference in IMR between those with and without MVO was 15.1 [9.7-20.6]. Meta-regression analyses demonstrated a linear relationship between IMR and TIMI grade (β = 0.69 [0.13-1.26]), as well as infarct size (β = 1.18 [0.24-2.11]) or ejection fraction at 6 months (β = -0.18 [-0.35 to -0.01]). In STEMI, patients with MVO had 15-unit higher IMR than those without. IMR also predicts key prognostic endpoints such as infarct size, MVO, and long-term systolic function.

Influence of Trichosanthes pericarpium extract on improving microcirculation and outcomes of patients with acute myocardial infarction after percutaneous coronary intervention.

Microcirculatory dysfunction is an independent risk factor for a poor prognosis after percutaneous coronary intervention (PCI) in patients with acute myocardial infarction (AMI). Trichosanthes pericarpium is a well-known Chinese traditional herb described with the effect of activating blood circulation to dissipate blood stasis and improve blood circulation. However, its effects on microcirculation in patients with AMI after primary PCI remain unknown. This study aimed to investigate the effect of Trichosanthes pericarpium extract (TPE) on improving microcirculation and outcomes in patients with AMI after PCI. This study included 155 patients with a history of emergency PCI treatment. In this cohort, 31 patients received a course of TPE, defined as intravenous TPE infusion (12 ml TPE dissolved in 250 ml 5% Glucose Injection) once daily for 7 days on the background of standard treatment after PCI; 124 who did not receive TPE were regarded as the control group and received standard treatment after PCI. The corrected thrombolysis in myocardial infarction frame count (CTFC) and index of microcirculatory resistance (IMR) were used to evaluate myocardial microcirculation. Cardiac function was measured by echocardiography during hospitalization and follow-up. Major adverse cardiac events (MACEs) were recorded for prognostic analysis. At the 6-month follow-up, AMI patients who received TPE after primary PCI had significantly lower levels of CTCF (24.27 ± 2.40 vs. 21.88 ± 1.92, P < 0.001) and IMR (20.02 ± 2.20 vs. 17.80 ± 2.11, P < 0.001) than patients in the control group. Left ventricular ejection fraction and left ventricular internal dimension at systolic at 6-month follow-up in the TPE group significantly improved than in the control group (56.6 ± 4.5 vs. 62.1 ± 3.5, P < 0.001; 32.5 ± 1.5 vs. 30.2 ± 1.8, P < 0.001). Kaplan-Meier curve analysis indicated that patients with AMI who received TPE had significantly lower rates of MACEs than the control group at 6-month follow-up (P = 0.042). In the context of standard treatment, Trichosanthes pericarpium further improved coronary microcirculation, increased cardiac function, and reduced short-term MACEs rate. Our data suggest that TPE could be used in combination therapy for patients with AMI after primary PCI.

Enhanced External Counterpulsation for Management of Postacute Sequelae of SARS-CoV-2 Associated Microvascular Angina and Fatigue: An Interventional Pilot Study.

Postacute sequelae of SARS-CoV-2 infection (PASC) are a novel clinical syndrome characterized in part by endothelial dysfunction. Enhanced external counterpulsation (EECP) produces pulsatile shear stress, which has been associated with improvements in systemic endothelial function. To explore the effects of EECP on symptom burden, physical capacity, mental health, and health-related quality of life (HRQoL) in patients with PASC-associated angina and microvascular dysfunction (MVD). An interventional pilot study was performed, including 10 patients (male = 5, mean age 50.3 years) recruited from a tertiary specialized PASC clinic. Patients with angina and MVD, defined as index of microcirculatory resistance (IMR) ≥25 and/or diagnosed through stress perfusion cardiac magnetic resonance imaging, were included. Patients underwent one modified EECP course (15 one-hour sessions over five weeks). Symptom burden, six-minute walk test, and validated generic self-reported instruments for measuring psychological distress and HRQoL were assessed before and one month after treatment. At baseline, most commonly reported PASC symptoms were angina (100%), fatigue (80%), and dyspnea (80%). Other symptoms included palpitations (50%), concentration impairment (50%), muscle pain (30%), and brain fog (30%). Mean IMR was 63.6. After EECP, 6MWD increased (mean 29.5 m, median 21 m) and angina and fatigue improved. Mean depression scores showed reduced symptoms (-0.8). Mean HRQoL scores improved in seven out of eight subscales (+0.2 to 10.5). Patients with PASC-associated angina and evidence of MVD experienced subjective and objective benefits from EECP. The treatment was well-tolerated. These findings warrant controlled studies in a larger cohort.

Serial fractional flow reserve, coronary flow reserve and index of microcirculatory resistance after percutaneous coronary intervention in patients treated for stable angina pectoris assessed with PET.

Cardiac 15 O-water PET is a noninvasive method to evaluate epicardial and microvascular dysfunction and further quantitate absolute myocardial blood flow (MBF). The aim of this study was to assess the impact of revascularization on MBF and myocardial flow reserve (MFR) assessed with 15 O-water PET and invasive flow and pressure measurements. In 21 patients with single-vessel disease referred for percutaneous coronary intervention (PCI), serial PET perfusion imaging and fractional flow reserve (FFR), coronary flow reserve (CFR) and index of microcirculatory resistance (IMR) were performed during PCI and after 3 months. In the affected myocardium, stress MBF and MFR increased significantly from before revascularization to 3 months after revascularization: stress MBF 2.4 ± 0.8 vs. 3.2 ± 0.8; P < 0.001 and MFR 2.5 ± 0.8 vs. 3.4 ± 1.1; P = 0.004. FFR and CFR increased significantly from baseline to after revascularization and remained stable from after revascularization to 3-month follow-up: FFR 0.64 ± 0.20 vs. 0.91 ± 0.06 vs. 0.91 ± 0.07; P < 0.001; CFR 2.4 ± 1.2 vs. 3.6 ± 1.9 vs. 3.6 ± 1.9; P < 0.001, whereas IMR did not change significantly: 30.3 ± 22.9 vs. 30.1 ± 25.3 vs. 31.9 ± 25.2; P = ns. After revascularization, an increase in stress MBF was associated with an increase in FFR ( r = 0.732; P < 0.001) and an increase in MFR ( r = 0.499; P = 0.021). IMR measured before PCI was inversely associated with improvement in stress MBF, ( r = -0.616; P = 0.004). Recovery of myocardial perfusion after PCI was associated with an increase in FFR 3 months after revascularization. Microcirculatory dysfunction was associated with less improvement in myocardial perfusion.

Functional Assessment of Long-Term Microvascular Cardiac Allograft Vasculopathy.

Cardiac allograft vasculopathy (CAV) is a leading cause of death and retransplantation following heart transplantation (HTX). Surveillance angiography performed yearly is indicated for the early detection of the disease, but it remains of limited sensitivity. We performed bolus thermodilution-based coronary flow reserve (CFR) and index of microcirculatory resistance (IMR) and fractional flow reserve (FFR) measurements in HTX patients undergoing yearly surveillance coronary angiography without overt CAV. In total, 27 HTX patients were included who had 52 CFR, IMR, and FFR measurements at a mean of 43 months after HTX. Only five measurements were performed in the first year. CFR decreased significantly by 0.13 every year (p = 0.04) and IMR tended to increase by 0.98 every year (p = 0.051), whereas FFR did not change (p = 0.161) and remained well above 0.80 over time. After one year, CFR decreased significantly (p = 0.022) and IMR increased significantly (p = 0.015), whereas FFR remained unchanged (p = 0.72). The functional status of the epicardial coronary arteries of transplanted hearts did not deteriorate over time. On the contrary, a significant decrease in CFR was noted. In view of the increasing IMR, this is caused by the deterioration of the function of microvasculature. CFR and IMR measurements may provide an early opportunity to diagnose CAV.

Diagnostic value of computed tomography myocardial perfusion imaging to detect coexisting microvascular dysfunction in patients with obstructive epicardial coronary artery disease.

Computed tomography myocardial perfusion (CT-MP) has reported usefulness in assessing hemodynamically significant epicardial coronary artery lesions. However, the diagnostic ability of the absolute coronary flow using CT-MP to detect coronary microvascular dysfunction (CMD) remains elusive. This prospective cohort study aimed to assess the diagnostic value of CT-MP in evaluating coexisting CMD in patients with functionally significant epicardial coronary stenosis and to analyze the predictive factors of lesions with CMD. Sixty-eight patients with chronic coronary syndrome (CCS) and de novo single functionally significant stenosis [fractional flow reserve (FFR) ≤0.80] were studied. CMD was defined as an index of microcirculatory resistance ≥25. We compare clinical background and CT-MP findings between patients with and without CMD (CMD, n=29; non-CMD, n=39). CT-MP, and quantitative and qualitative plaque assessments were included in computed tomography angiography assessment. Logistic regression analysis was performed to predict CMD. FFR, invasive wire-derived coronary flow reserve (CFRwire) and index of microcirculatory resistance were 0.68 [interquartile range (IQR), 0.59-0.74], 1.71 (IQR, 1.24-2.88), and 22.6 (IQR, 15.1-34.5), respectively. The rest and hyperemic-myocardial blood flow (MBF) and CT-MP-derived CFR (CFRCT-MP) were 0.83 (0.64-1.03) mL/min/g, 2.14 (1.30-2.92) mL/min/g, and 2.19 (1.44-3.37), respectively. In the territories with CMD, hyperemic-MBF was significantly lower than in those without [1.68 (IQR, 0.84-2.44) vs. 2.31 (IQR, 1.67-3.34) mL/min/g, P=0.015] and the prevalence of CFRCT-MP <2.0 was higher in the lesions with CMD than in those without (62.1% vs. 28.2%, P=0.011), while FFR values were similar. Fibrofatty and necrotic core component volume was greater in the vessels with CMD than in those without [31.8 (IQR, 19.0-48.9) vs. 25.1 (IQR, 17.2-32.1) mm3, P=0.045]. Multivariable logistic regression analysis showed that hyperemic-MBF and fibrofatty and necrotic core component volume were independent predictors of CMD territories [odds ratio (OR) =0.583; 95% confidence interval (CI): 0.355-0.958; P=0.033 and OR =1.040; 95% CI: 1.010-1.070; P=0.011]. Quantitative assessment of absolute coronary flow using pre-percutaneous coronary intervention (PCI) CT-MP, and comprehensive plaque analysis using computed tomography angiography may help detect coexisting subtended microvascular dysfunction in territories with functionally significant epicardial coronary lesions. Further studies are required to elucidate the clinical significance of coexisting CMD in patients with CCS undergoing PCI.

Relation of Thrombolysis in Myocardial Infarction Frame Count to Invasively Measured Coronary Physiologic Indexes

In the international guidelines, higher thrombolysis in myocardial infarction frame count (TFC) is indicated as evidence of coronary microvascular dysfunction (CMD). However, the association of TFC with invasively measured coronary physiologic parameters such as coronary flow reserve (CFR) and index of microcirculatory resistance (IMR) remains unclear. Patients without significant epicardial coronary lesions underwent invasive coronary physiologic assessment using a thermodilution method in the left anterior descending artery. Corrected TFC (cTFC) was evaluated on coronary angiography. The cut-off values of CFR and IMR were defined as ≤2.0 and >25, and patients with abnormal CFR and/or IMR were defined as having CMD. This study aimed to assess whether cTFC >25, a cut-off value in the guidelines, was diagnostic of the presence of CMD. Of the 137 patients, 34 (24.8%) and 32 (23.3%) had cTFC >25 and CMD, respectively. The rate of CMD was not significantly different between patients with and without cTFC >25. cTFC was weakly correlated with at rest and hyperemic mean transit time and IMR, whereas no significant correlation was observed between cTFC and CFR. The receiver operating characteristic curve analysis showed the poor diagnostic ability of cTFC for abnormal CFR and IMR and the presence of CMD. In conclusion, in patients without epicardial coronary lesions, cTFC as a continuous value and with the cut-off value of 25 was not diagnostic of abnormal CFR and IMR and the presence of CMD. Our results did not support the use of cTFC in CMD evaluation.

The impact of primary percutaneous coronary intervention strategies during ST-elevation myocardial infarction on the prevalence of coronary microvascular dysfunction

Coronary microvascular dysfunction (CMD) is a common complication of ST-segment elevation myocardial infarction (STEMI) and can lead to adverse cardiovascular events. This is a non-randomized, observational, prospective study of STEMI patients with multivessel disease who underwent primary PCI, grouped based on whether they underwent balloon pre-dilatation stenting or direct stenting of the culprit lesion. Coronary physiology measurements were performed 3 months post-PCI including coronary flow reserve (CFR) and index of microcirculatory resistance (IMR) measurements at the culprit vessel. The primary endpoint was the prevalence of CMD at 3 months, defined as IMR ≥ 25 or CFR < 2.0 with a normal fractional flow reserve. Secondary endpoints included major adverse cardiovascular events (MACE) at 12 months. Two hundred ten patients were enrolled; most were men, 125 (59.5%), with a median age of 65 years. One hundred twelve (53.2%) underwent balloon pre-dilatation before stenting, and 98 (46.7%) underwent direct stenting. The prevalence of CMD at 3 months was lower in the direct stenting group than in the balloon pre-dilatation stenting group (12.24% vs. 40.18%; p < 0.001). Aspiration thrombectomy and administration of intracoronary glycoprotein IIb/IIIa inhibitors were associated with lower odds of CMD (OR = 0.175, p = 0.001 and OR = 0.113, p = 0.001, respectively). Notably, MACE in patients who underwent direct stenting was lower than in those who underwent balloon pre-dilatation before stenting (14.29% vs. 26.79%; p = 0.040). In STEMI patients with multivessel disease, direct stenting of the culprit lesion, aspiration thrombectomy and administration of intracoronary glycoprotein IIb/IIIa inhibitors were associated with a lower prevalence of CMD at 3 months and lower incidence of MACE at 12 months compared with balloon pre-dilatation stenting.This trial is registered at https://ichgcp.net/clinical-trials-registry/NCT05406297.