Coronary Resistance Research Articles

Prognostic utility of longitudinal quantification of PET myocardial blood flow early post heart transplantation

BackgroundMyocardial blood flow (MBF) quantification by Rubidium-82 positron emission tomography (PET) has shown promise for cardiac allograft vasculopathy (CAV) surveillance and risk stratification post heart transplantation. The objective was to determine the prognostic value of serial PET performed early post transplantation. Methods and ResultHeart transplant (HT) recipients at the University of Ottawa Heart Institute with 2 PET examinations (PET1 = baseline, PET2 = follow-up) within 6 years of transplant were included in the study. Evaluation of PET flow quantification included stress MBF, coronary vascular resistance (CVR), and myocardial flow reserve (MFR). The primary composite outcome was all-cause death, re-transplant, myocardial infarction, revascularization, allograft dysfunction, cardiac allograft vasculopathy (CAV), or heart failure hospitalization. A total of 121 patients were evaluated (79% male, mean age 56 ± 11 years) with consecutive scans performed at mean 1.4 ± 0.7 and 2.6 ± 1.0 years post HT for PET1 and PET2, respectively. Over a mean follow-up of 3.0 (IQR 1.8, 4.6) years, 26 (22%) patients developed the primary outcome: 1 death, 11 new or progressive angiographic CAV, 2 percutaneous coronary interventions, 12 allograft dysfunction. Unadjusted Cox analysis showed a significant reduction in event-free survival in patients with PET1 stress MBF < 2.1 (HR: 2.43, 95% CI 1.11-5.29 P = 0.047) and persistent abnormal PET1 to PET2 CVR > 76 (HR: 2.19, 95% CI 0.87-5.51 P = 0.045). There was no association between MFR and outcomes. ConclusionLow-stress MBF and persistent increased CVR on serial PET imaging early post HT are associated with adverse cardiovascular outcomes. Early post-transplant and longitudinal assessment by PET may identify at-risk patients for increased surveillance post HT.

Pathophysiologic Basis and Diagnostic Approaches for Ischemia With Non-obstructive Coronary Arteries: A Literature Review

Ischemia with non-obstructive coronary arteries (INOCA) has gained increasing attention due to its high prevalence, atypical clinical presentations, difficult diagnostic procedures, and poor prognosis. There are two endotypes of INOCA—one is coronary microvascular dysfunction and the other is vasospastic angina. Diagnosis of INOCA lies in evaluating coronary flow reserve, microcirculatory resistance, and vasoreactivity, which is usually obtained via invasive coronary interventional techniques. Non-invasive diagnostic approaches such as echocardiography, single-photon emission computed tomography, cardiac positron emission tomography, and cardiac magnetic resonance imaging are also valuable for assessing coronary blood flow. Some new techniques (e.g., continuous thermodilution and angiography-derived quantitative flow reserve) have been investigated to assist the diagnosis of INOCA. In this review, we aimed to discuss the pathophysiologic basis and contemporary and novel diagnostic approaches for INOCA, to construct a better understanding of INOCA evaluation.

Low- versus high-concentration intravenous immunoglobulin for children with Kawasaki disease in the acute phase.

Few studies have compared the effects of low-concentration (5%) and high-concentration (10%) intravenous immunoglobulin (IVIG) preparations for patients with Kawasaki disease (KD) in the acute phase. The purpose of this study was to compare outcomes between low- and high-concentration IVIG preparations in children with KD, using a national inpatient database in Japan. We used the Diagnostic Procedure Combination database to identify patients with KD treated with IVIG from April 2012 to March 2020. We identified those receiving high- and low-concentration IVIG preparations as an initial treatment. The outcomes included the proportions of patients with coronary artery abnormalities (CAAs) and IVIG resistance, length of stay, and medical costs. Propensity score-matched analyses were conducted to compare the outcomes between the 2 groups. Instrumental variable analyses were performed to confirm the results. We identified 48046 patients with KD and created 4:1 propensity score-matched pairs between the low- and high-concentration IVIG groups. There was a significant difference in the percentage with IVIG resistance between the 2 groups (20.6% vs 24.1%; risk difference, 3.5% [95% confidence interval, 2.3-4.7]; P<.001). However, there was no significant difference in CAAs (1.6% vs 1.6%; risk difference, 0.013% [95% confidence interval, -0.34 to 0.37]; P=.953). The instrumental variable analyses showed similar results. The proportion of CAAs did not differ significantly between those receiving low- and high-concentration IVIG. To confirm the results of this study, prospective studies adjusting for duration of IVIG administration and duration of observation are needed.

Patient-specific fluid-structure simulations of anomalous aortic origin of right coronary arteries.

ObjectivesAnomalous aortic origin of the right coronary artery (AAORCA) may cause ischemia and sudden death. However, the specific anatomic indications for surgery are unclear, so dobutamine-stress instantaneous wave-free ratio (iFR) is increasingly used. Meanwhile, advances in fluid–structure interaction (FSI) modeling can simulate the pulsatile hemodynamics and tissue deformation. We sought to evaluate the feasibility of simulating the resting and dobutamine-stress iFR in AAORCA using patient-specific FSI models and to visualize the mechanism of ischemia within the intramural geometry and associated lumen narrowing.MethodsWe developed 6 patient-specific FSI models of AAORCA using SimVascular software. Three-dimensional geometries were segmented from coronary computed tomography angiography. Vascular outlets were coupled to lumped-parameter networks that included dynamic compression of the coronary microvasculature and were tuned to each patient's vitals and cardiac output.ResultsAll cases were interarterial, and 5 of 6 had an intramural course. Measured iFRs ranged from 0.95 to 0.98 at rest and 0.80 to 0.95 under dobutamine stress. After we tuned the distal coronary resistances to achieve a stress flow rate triple that at rest, the simulations adequately matched the measured iFRs (r = 0.85, root-mean-square error = 0.04). The intramural lumen remained narrowed with simulated stress and resulted in lower iFRs without needing external compression from the pulmonary root.ConclusionsPatient-specific FSI modeling of AAORCA is a promising, noninvasive method to assess the iFR reduction caused by intramural geometries and inform surgical intervention. However, the models’ sensitivity to distal coronary resistance suggests that quantitative stress-perfusion imaging may augment virtual and invasive iFR studies.

Peripheral Coronary Artery Circulatory Dysfunction in Remote Stage Kawasaki Disease Patients Detected by Adenosine Stress 13N-Ammonia Myocardial Perfusion Positron Emission Tomography.

Coronary peripheral circulatory disturbances in the remote stage of Kawasaki disease have been reported. In this study, of the 50 patients in the remote stage of Kawasaki disease who underwent coronary perfusion evaluation using adenosine-loaded 13N-ammonia positron emission tomography, 28 patients who did not have stenosis of ≥75% in the left coronary artery underwent an evaluation for myocardial flow reserve (MFR) of the left anterior descending artery (LAD) and left circumflex artery (LCx). Clinical findings were compared between patients with normal (≥2.0) and abnormal (<2.0) MFRs. In the group with an abnormal MFR in the LAD, the responsiveness of the coronary vascular resistance to adenosine stress decreased even in the LCx (3.50 ± 1.23 vs. 2.39 ± 0.25, p = 0.0100). In the group with an abnormal MFR in the LCx, the responsiveness of the coronary vascular resistance in the LAD also decreased (3.27 ± 1.39 vs. 2.03 ± 0.25, p = 0.0105), and the age of onset of Kawasaki disease tended to be younger in the group with abnormal MFR in the LAD and LCx. We found that the peripheral coronary circulation was extensively impaired in the remote stage of Kawasaki disease, suggesting that an early onset of Kawasaki disease may affect the peripheral coronary circulation in later years.

Mitophagy alleviates ischemia/reperfusion-induced microvascular damage through improving mitochondrial quality control

ABSTRACT The coronary arteries mainly function to perfuse the myocardium. When coronary artery resistance increases, myocardial perfusion decreases and myocardial remodeling occurs. Mitochondrial damage has been regarded as the primary cause of microvascular dysfunction. In the present study, we explored the effects of mitophagy activation on microvascular damage. Hypoxia/reoxygenation injury induced mitochondrial oxidative stress, thereby promoting mitochondrial dysfunction in endothelial cells. Mitochondrial impairment induced apoptosis, reducing the viability and proliferation of endothelial cells. However, supplementation with the mitophagy inducer urolithin A (UA) preserved mitochondrial function by reducing mitochondrial oxidative stress and stabilizing the mitochondrial membrane potential in endothelial cells. UA also sustained the viability and improved the proliferative capacity of endothelial cells by suppressing apoptotic factors and upregulating cyclins D and E. In addition, UA inhibited mitochondrial fission and restored mitochondrial fusion, which reduced the proportion of fragmented mitochondria within endothelial cells. UA enhanced mitochondrial biogenesis in endothelial cells by upregulating sirtuin 3 and peroxisome proliferator-activated receptor gamma coactivator 1-alpha. These results suggested that activation of mitophagy may reduce hypoxia/reoxygenation-induced cardiac microvascular damage by improving mitochondrial quality control and increasing cell viability and proliferation.

Characterization of quantitative flow ratio and fractional flow reserve discordance using doppler flow and clinical follow-up.

The physiological mechanisms of quantitative flow ratio and fractional flow reserve disagreement are not fully understood. We aimed to characterize the coronary flow and resistance profile of intermediate stenosed epicardial coronary arteries with concordant and discordant FFR and QFR. Post-hoc analysis of the DEFINE-FLOW study. Anatomical and Doppler-derived physiological parameters were compared for lesions with FFR+QFR- (n = 18) vs. FFR+QFR+ (n = 43) and for FFR-QFR+ (n = 34) vs. FFR-QFR- (n = 139). The association of QFR results with the two-year rate of target vessel failure was assessed in the proportion of vessels (n = 195) that did not undergo revascularization. Coronary flow reserve was higher [2.3 (IQR: 2.1-2.7) vs. 1.9 (IQR: 1.5-2.4)], hyperemic microvascular resistance lower [1.72 (IQR: 1.48-2.31) vs. 2.26 (IQR: 1.79-2.87)] and anatomical lesion severity less severe [% diameter stenosis 45.5 (IQR: 41.5-52.5) vs. 58.5 (IQR: 53.1-64.0)] for FFR+QFR- lesions compared with FFR+QFR+ lesions. In comparison of FFR-QFR+ vs. FFR-QFR- lesions, lesion severity was more severe [% diameter stenosis 55.2 (IQR: 51.7-61.3) vs. 43.4 (IQR: 35.0-50.6)] while coronary flow reserve [2.2 (IQR: 1.9-2.9) vs. 2.2 (IQR: 1.9-2.6)] and hyperemic microvascular resistance [2.34 (IQR: 1.85-2.81) vs. 2.57 (IQR: 2.01-3.22)] did not differ. The agreement and diagnostic performance of FFR using hyperemic stenosis resistance (> 0.80) as reference standard was higher compared with QFR and coronary flow reserve. Disagreement between FFR and QFR is partly explained by physiological and anatomical factors. Clinical Trials Registration https://www.clinicaltrials.gov ; Unique identifier: NCT01813435.

Prolonged (24-hour) Normothermic ex vivo Heart Perfusion Facilitated by Perfusate Hemofiltration.

Currently, normothermic ex vivo heart perfusion (NEVHP) is limited to 6-12 hours. NEVHP for 24 hours or more would allow organ treatment, assessment of organ function, and near-perfect recipient matching. We present a model of NEVHP using continuous hemofiltration (HFn) with sustained myocardial viability up to 24 hours. Twenty hearts from 6-10 kg piglets were procured and maintained on our NEVHP circuit. HFn hearts (n = 10) underwent NEVHP with HFn, whereas controls (n = 10) used NEVHP alone. All HFn vs. four controls were viable at 24 h (p = 0.004). At end perfusion, HFn hearts had higher left ventricular systolic pressure (51.5 ± 6.8 mm Hg, 38.3 ± 5.2 mm Hg, p = 0.05), lower coronary resistance (0.83 ± 0.11 mm Hg/mL/min, 1.18 ± 0.21mmHg/mL/min, p &lt; 0.05), and lower serum lactate levels (2.9 ± 0.4 mmol/L, 4.1 ± 0.6 mmol/L, p &lt; 0.0001) when compared to control hearts. HFn hearts also had less extensive myocardial damage and significantly less edema than control hearts with lower weight gain and wet-dry ratios. Using our circuit, NEVHP for 24 hours is possible with HFn and allows for preservation of myocardial function, improved tissue viability, decreased tissue edema, and less myocardial injury.

The Role of Coronary Microvascular Disease in Cardiomyophaties

Coronary microvascular disease (CMD) makes reference to the anatomically and functionally disorders affecting vascular compartments (&lt;400 mm diameter), covering a broad range of clinical conditions in which the structure and function of the coronary microcirculation is affected. CMD is characterized by an impaired coronary flow reserve (cut-off values of 2.0-2.5) or an abnormally index of coronary microvascular resistance (IMR &gt;25) and/or focal or diffuse vasoconstriction during acetylcholine challenge, with an important role in myocardial perfusion. The aim of this work is to review CMD, definition, clinical manifestations, diagnosis method (non invasive and invasive approach) and the role of CMD in the main cardiomiophaties, such as Hypertrophic cardiomiopathy, none idiomatic dilated cardiomiopathy and infiltrative miocardiophaty.

Correlation between the Level of Inflammatory Cytokines and Prognosis in Children with IVIG-sensitive Kawasaki Disease and IVIG-resistant Kawasaki Disease.

Objectives:To investigate whether the levels of interleukin 1β (IL-1β), interferon γ (IFN-γ), tumor necrosis factor α (TNF-α) in children with Kawasaki disease (KD) are correlated with coronary artery lesion (CAL) and resistance to intravenous immunoglobulin (IVIG) treatment.Methods:A total of 216 children in line with KD diagnostic criteria were continuously included as subjects, and 50 healthy children at the same period were selected as the control group, and their levels of IL-1β, IFN-γ, and TNF-α were detected.Results:Subjects were subdivided according to the presence or absence of CAL: 42 cases (19.4%) of 216 children with KD developed CAL and were subdivided into the CAL group, while 174 (80.6%) of those who did not develop CAL were subdivided into the NCAL group. The levels of IL-1β, IFN-γ, and TNF-α in the CAL group and the NCAL group were higher than those in the control group (P<0.05), and the levels of those in the CAL group were higher than those in the NCAL group (P<0.05). Subjects were subdivided according to the effect of IVIG treatment: 194 cases (89.8%) of 216 children with KD had a good control of inflammation after the initial IVIG treatment, and were considered to have IVIG-sensitive KD and divided into the IVIG-sensitive group; 22 cases (10.2%) could not get good control of inflammation after the initial IVIG treatment, and were considered to have IVIG-resistant KD and divided into the IVIG-resistant group. The levels of IL-1β, IFN-γ, and TNF-α in the IVIG-sensitive group and the IVIG-resistant group were higher than those in the control group; The levels of IL-1β, IFN-γ, and TNF-α in the IVIG-resistant group were higher than those in the IVIG-sensitive group (P<0.05), while the fever time of the IVIG-sensitive group was lower than that of the IVIG-resistant group (P<0.05).Conclusion:Children with KD may experience changes in IL-1β, IFN-γ, and TNF-α levels in the acute phase. Such a significant increase in levels may be a risk factor for CAL and resistance to IVIG treatment in children with KD, while the prolonged fever time is a risk factor for resistance to IVIG treatment in children with KD.

СТЕНОКАРДИЯ БЕЗ ОБСТРУКТИВНОГО ПОРАЖЕНИЯ КОРОНАРНЫХ АРТЕРИЙ (Часть 2). МЕТОДЫ ДИАГНОСТИКИ В КЛИНИЧЕСКОЙ ПРАКТИКЕ

Coronary vasomotor disorders are a common cause of angina pectoris without obstructive lesion of the coronary arteries (CA). Over the past decade, various non-invasive and invasive diagnostic methods have made it possible to comprehensively assess coronary vasomotor function and determine the endotypes of epicardial and microvascular dysfunction, which is important for stratification of cardiovascular risk and individualization of patient treatment. The basis for the diagnosis of the complex interaction of vasodilation and vasoconstriction of various parts of the coronary bed is a comprehensive intracoronary functional testing, which is recommended if the angina symptoms are persisting against the background of angiographically unchanged or moderately stenosed, blood flow non-limiting coronary arteries. The established parameters characterizing adequate vasodilation are coronary blood flow reserve and microvascular resistance. Increased vasoconstriction potential is diagnosed by intracoronary provocation test with acetylcholine, which allows verification of epicardial and/or microvascular vasospasm. The article discusses standardized criteria, non-invasive imaging methods and modern invasive examination algorithms used in the diagnosis of microvascular and vasospastic angina.

389 Microvascular dysfunction in patients with Type II diabetes mellitus: invasive assessment of absolute coronary blood flow and microvascular resistance reserve

Abstract Aims Coronary microvascular dysfunction (CMD) is an early feature of diabetic cardiomyopathy, which usually precedes the onset of diastolic and systolic dysfunction. Continuous intracoronary thermodilution allows an accurate and reproducible assessment of absolute coronary blood flow and microvascular resistance thus allowing the evaluation of coronary flow reserve (CFR) and Microvascular Resistance Reserve (MRR), a novel index specific for microvascular function, which is independent from the myocardial mass. In the present study we compared absolute coronary flow and resistance, CFR and MRR assessed by continuous intracoronary thermodilution in diabetic vs. non-diabetic patients. Left atrial reservoir strain (LASr), an early marker of diastolic dysfunction was compared between the two groups. Methods In this observational retrospective study, 108 patients with suspected angina and non-obstructive coronary artery disease (NOCAD) consecutively undergoing elective coronary angiography (CAG) from September 2018 to June 2021 were enrolled. The invasive functional assessment of microvascular function was performed in the left anterior descending artery (LAD) with intracoronary continuous thermodilution. Patients were classified according to the presence of DM. Absolute resting and hyperaemic coronary blood flow (in mL/min) and resistance (in WU) were compared between the two cohorts. FFR was measured to assess coronary epicardial lesions, while CFR and MRR were calculated to assess microvascular function. LAS, assessed by speckle tracking echocardiography, was used to detect early myocardial structural changes potentially associated with microvascular dysfunction. Results The median FFR value was 0.83 (0.79–0.87) without any significant difference between the two groups. Absolute resting and hyperaemic flow in the left anterior descending coronary were similar between diabetic and non-diabetic patients. Similarly, resting and hyperaemic resistances did not change significantly between the two groups. In the DM cohort the CFR and MRR were significantly lower compared to the control group [CFR = 2.38 ± 0.61 and 2.88 ± 0.82; MRR = 2.79 ± 0.87 and 3.48 ± 1.02 for diabetic and non-diabetic patients respectively, (P &amp;lt; 0.05 for both)]. Likewise, diabetic patients had a significantly lower reservoir, contractile and conductive LAS (all P &amp;lt; 0.05). Conclusions Compared with non-diabetic patients, CFR and MRR were lower in patients with DM and non-obstructive epicardial coronary arteries, while both resting and hyperaemic coronary flow and resistance were similar. LASr was lower in diabetic patients, confirming the presence of a subclinical diastolic dysfunction associated to the microcirculatory impairment. Continuous intracoronary thermodilution-derived indexes provide a reliable and operator-independent assessment of coronary macro- and microvasculature and might potentially facilitate widespread clinical adoption of invasive physiologic assessment of suspected microvascular disease.

197 Angio-based index of microcirculatory resistance for the assessment of the coronary resistance: a proof of concept study

Abstract Aims The study of coronary microcirculation has gained increasing consideration and importance in cath-lab. Despite the increase of evidence its use still remains very limited. QFR is a novel angio-based approach for the evaluation of coronary stenosis. The aim of our study was to use the QFR assessment in stable patients to recreate the IMR formula and to correlate the result of the two techniques. Methods and results From 1 June 2019 to 29 February 2019, 200 patients with CCS and indication of coronary artery angiography and referred to the cath-lab of the University Hospital of Ferrara (Italy) were enrolled. After baseline coronary angiogram, quantitative flow ratio, fractional flow reserve and index of microcirculatory resistance evaluation were performed. Pearson correlation (r) between Angio-based index of microcirculatory resistance (A-IMR) and IMR 0.32 with R2 = 0.098, P = 0.03: McNemar test showed a difference between the two test of 6.82% with 95% CI from −12.05% to 22.89%, which is not significant (P = 0.60). Bland and Altman plot showed a mean difference of 23.3 (from −26.5 to 73.1). Sensitivity, specificity, NPV and PPV were 70%, 83.3%, 75% and 70% for A-IMR value &amp;gt; 44.2. The area under the ROC curve for A-IMR was 0.76 (95% CI: 0.61–0.88, P = 0.0003). Conclusions We have validated for the first time the formula of the A-IMR, a tool for the calculation of microvascular resistance which does not require the use of pressure guides and the induction of hyperemia

Physiologically personalized coronary blood flow model to improve the estimation of noninvasive fractional flow reserve.

Coronary outlet resistance is influenced by the quantification and distribution of resting coronary blood flow. It is crucial for a more physiologically accurate estimation of fractional flow reserve (FFR) derived from computed tomography angiography (CTA), referred to as FFRCT. This study presents a physiologically personalized (PP)-based coronary blood flow model involving the outlet boundary condition (BC) and a standardized outlet truncation strategy to estimate the outlet resistance and FFRCT. In this study, a total of 274 vessels were retrospectively collected from 221 patients who underwent coronary CTA and invasive FFR within 14 days. For FFRCT determination, we have employed a PP-based outlet BC model involving personalized physiological parameters and left ventricular mass (LVM) to quantify resting coronary blood flow. We evaluated the improvement achieved in the diagnostic performance of FFRCT by using the PP-based outlet BC model relative to the LVM-based model, with respect to the invasive FFR. Additionally, in order to evaluate the impact of the outlet truncation strategy on FFRCT, 68 vessels were randomly selected and analyzed independently by two operators, by using two different outlet truncation strategies at 1-month intervals. The per-vessel diagnostic performance of the PP-based outlet BC model was improved, based on invasive FFR as reference, compared to the LVM-based model: (i) accuracy/sensitivity/specificity: 91.2%/90.4%/91.8% versus 86.5%/84.6%/87.6%, for the entire dataset of 274 vessels, (ii) accuracy/sensitivity/specificity: 88.7%/82.4%/90.4% versus 82.4%/ 76.5%/84.0%, for moderately stenosis lesions. The standardized outlet truncation strategy showed good repeatability with the Kappa coefficient of 0.908. It has been shown that our PP-based outlet BC model and standardized outlet truncation strategy can improve the diagnostic performance and repeatability of FFRCT.

Early Hyperdynamic Sepsis Alters Coronary Blood Flow Regulation in Porcine Fecal Peritonitis.

Background: Sepsis is a common condition known to impair blood flow regulation and microcirculation, which can ultimately lead to organ dysfunction but such contribution of the coronary circulation remains to be clarified. We investigated coronary blood flow regulatory mechanisms, including autoregulation, metabolic regulation, and endothelial vasodilatory response, in an experimental porcine model of early hyperdynamic sepsis.Methods: Fourteen pigs were randomized to sham (n = 7) or fecal peritonitis-induced sepsis (n = 7) procedures. At baseline, 6 and 12 h after peritonitis induction, the animals underwent general and coronary hemodynamic evaluation, including determination of autoregulatory breakpoint pressure and adenosine-induced maximal coronary vasodilation for coronary flow reserve and hyperemic microvascular resistance calculation. Endothelial-derived vasodilatory response was assessed both in vivo and ex vivo using bradykinin. Coronary arteries were sampled for pathobiological evaluation.Results: Sepsis resulted in a right shift of the autoregulatory breakpoint pressure, decreased coronary blood flow reserve and increased hyperemic microvascular resistance from the 6th h after peritonitis induction. In vivo and ex vivo endothelial vasomotor function was preserved. Sepsis increased coronary arteries expressions of nitric oxide synthases, prostaglandin I2 receptor, and prostaglandin F2α receptor.Conclusion: Autoregulation and metabolic blood flow regulation were both impaired in the coronary circulation during experimental hyperdynamic sepsis, although endothelial vasodilatory response was preserved.

Endothelium in Coronary Macrovascular and Microvascular Diseases.

:The endothelium plays a pivotal role in the regulation of vascular tone by synthesizing and liberating endothelium-derived relaxing factors inclusive of vasodilator prostaglandins (eg, prostacyclin), nitric oxide (NO), and endothelium-dependent hyperpolarization factors in a distinct blood vessel size–dependent manner. Large conduit arteries are predominantly regulated by NO and small resistance arteries by endothelium-dependent hyperpolarization factors. Accumulating evidence over the past few decades has demonstrated that endothelial dysfunction and coronary vasomotion abnormalities play crucial roles in the pathogenesis of various cardiovascular diseases. Structural and functional alterations of the coronary microvasculature have been coined as coronary microvascular dysfunction (CMD), which is highly prevalent and associated with adverse clinical outcomes in many clinical settings. The major mechanisms of coronary vasomotion abnormalities include enhanced coronary vasoconstrictive reactivity at epicardial and microvascular levels, impaired endothelium-dependent and endothelium-independent coronary vasodilator capacities, and elevated coronary microvascular resistance caused by structural factors. Recent experimental and clinical research has highlighted CMD as the systemic small artery disease beyond the heart, emerging modulators of vascular functions, novel insights into the pathogenesis of cardiovascular diseases associated with CMD, and potential therapeutic interventions to CMD with major clinical implications. In this article, we will summarize the current knowledge on the endothelial modulation of vascular tone and the pathogenesis of coronary macrovascular and microvascular diseases from bench to bedside, with a special emphasis placed on the mechanisms and clinical implications of CMD.

Intraoperative Assessment of Coronary Resistances: A New Quality Marker and Potential Tool to Predict Early Graft Failure after Coronary Artery Bypass Grafting?

Intraoperative assessment of graft patency is pivotal for successful coronary revascularization. In the present study we aimed to propose a new, easy to perform tool to assess anastomotic quality intraoperatively, and to investigate its potential reliability in predicting early graft failure. Intraoperative graft flowmetry of 63 consecutive patients undergoing CABG were prospectively collected. Transit time flowmetry and its derivatives were recorded. Coronary resistances were calculated according to Hagen–Poiseuille equation both during cardioplegic arrest and after withdrawal from cardiopulmonary bypass. Angiographic evidence of graft occlusion at follow-up was cross-checked with intraoperative recordings. After a mean follow-up of 10.4 ± 6.0 months, 22 grafts were studied, and occlusion was documented in five (22.7%). Occluded grafts showed lower flows and higher resistances recorded during aortic cross-clamping. Coronary resistances, recorded during aortic cross-clamping, greater than 2.0 mmHg/mL/min, showed a sensitivity of 80% and a specificity of 100% to predict graft failure. We propose the routine recording of coronary resistances during aortic cross-clamping as an additional tool to overcome the acknowledged limitation of TTF to predict graft occlusion at 1 year.

Abstract 13341: Enhanced External Counterpulsation Attenuates Coronary Microcirculation Dysfunction in Coronary Artery Disease With Diabetes: Primary Results of EECP-CMD Study

Introduction: Coronary microcirculation dysfunction (CMD) is recognized as a pivotal pathophysiological change of coronary artery disease (CAD) with diabetes, however, there is little evidence for CMD medication treatment. Though enhanced external counterpulsation (EECP), a non-invasive therapy to increase shear stress of coronary flow, has been proved to release angina and restore endothelial capacities, whether EECP could attenuate CMD remains unknown. Hypothesis: EECP could attenuate CMD in patients of CAD with diabetes. Methods: This is a single center, prospective, randomized, single blind, control clinical trial (ChiCTR1800019060). Forty-eight patients [age: (57.7±8.5) yrs, 30 males] diagnosed with CAD and diabetes were enrolled during March 2019 and October 2020 in the Eighth Affiliated Hospital of Sun Yat-sen University, Shenzhen, China. The main exclusion criteria are as follows: type 1 diabetes or diabetes history≤3 years; ≥ 70 years old; acute coronary syndrome; chronic total occlusion lesions and contraindications for EECP. All accepted coronary angiography and index of microcirculation resistance (IMR) test with pressure wire, then were randomized to EECP (n=24) or control (n=24) group. All followed standard medication therapy as guidelines recommended, EECP group took 35 times of EECP (60 minutes per time, 5 times a week and 7 weeks for whole procedure) after IMR test. Another IMR test would be done at the end of 12-week follow-up, the occurrence of angina and the metabolic parameters, FMD, PWV, CPET and TTE would also be evaluated. Results: The baseline IMR displayed no significant difference in both groups [EECP: (26.56±3.70) vs. Control: (26.91±4.22), P =0.74], while IMR markedly decreased in the EECP group than control at the end of follow-up [(24.02±3.15) vs. (26.78±4.63), P =0.02]. After multivariate linear regression analysis, FMD and PWV were found to independently correlated with IMR change [FMD: (β=0.45, P =0.014); PWV: (β=-0.27, P =0.038)]. Apart from above, EECP reduced angina occurrence and improved exercise tolerance, early diastolic function of left ventricular. Conclusion: EECP attenuates CMD in CAD with diabetes through coronary microcirculation resistance decrease.

TCT-478 Thermodilution-Derived Coronary Absolute Flow and Resistance in Patients With and Without Epicardial Stenosis

TCT-478 Thermodilution-Derived Coronary Absolute Flow and Resistance in Patients With and Without Epicardial Stenosis

Microvascular Dysfunction in Patients With Type II Diabetes Mellitus: Invasive Assessment of Absolute Coronary Blood Flow and Microvascular Resistance Reserve.

Background: Coronary microvascular dysfunction (CMD) is an early feature of diabetic cardiomyopathy, which usually precedes the onset of diastolic and systolic dysfunction. Continuous intracoronary thermodilution allows an accurate and reproducible assessment of absolute coronary blood flow and microvascular resistance thus allowing the evaluation of coronary flow reserve (CFR) and Microvascular Resistance Reserve (MRR), a novel index specific for microvascular function, which is independent from the myocardial mass. In the present study we compared absolute coronary flow and resistance, CFR and MRR assessed by continuous intracoronary thermodilution in diabetic vs. non-diabetic patients. Left atrial reservoir strain (LASr), an early marker of diastolic dysfunction was compared between the two groups.Methods: In this observational retrospective study, 108 patients with suspected angina and non-obstructive coronary artery disease (NOCAD) consecutively undergoing elective coronary angiography (CAG) from September 2018 to June 2021 were enrolled. The invasive functional assessment of microvascular function was performed in the left anterior descending artery (LAD) with intracoronary continuous thermodilution. Patients were classified according to the presence of DM. Absolute resting and hyperemic coronary blood flow (in mL/min) and resistance (in WU) were compared between the two cohorts. FFR was measured to assess coronary epicardial lesions, while CFR and MRR were calculated to assess microvascular function. LAS, assessed by speckle tracking echocardiography, was used to detect early myocardial structural changes potentially associated with microvascular dysfunction.Results: The median FFR value was 0.83 [0.79–0.87] without any significant difference between the two groups. Absolute resting and hyperemic flow in the left anterior descending coronary were similar between diabetic and non-diabetic patients. Similarly, resting and hyperemic resistances did not change significantly between the two groups. In the DM cohort the CFR and MRR were significantly lower compared to the control group (CFR = 2.38 ± 0.61 and 2.88 ± 0.82; MRR = 2.79 ± 0.87 and 3.48 ± 1.02 for diabetic and non-diabetic patients respectively, [p < 0.05 for both]). Likewise, diabetic patients had a significantly lower reservoir, contractile and conductive LAS (all p < 0.05).Conclusions: Compared with non-diabetic patients, CFR and MRR were lower in patients with DM and non-obstructive epicardial coronary arteries, while both resting and hyperemic coronary flow and resistance were similar. LASr was lower in diabetic patients, confirming the presence of a subclinical diastolic dysfunction associated to the microcirculatory impairment. Continuous intracoronary thermodilution-derived indexes provide a reliable and operator-independent assessment of coronary macro- and microvasculature and might potentially facilitate widespread clinical adoption of invasive physiologic assessment of suspected microvascular disease.