Microvascular Dysfunction In Patients Research Articles

Prognostic impact of coronary microvascular dysfunction in patients with atrial fibrillation

BackgroundCoronary microvascular dysfunction (CMD) is frequently observed in atrial fibrillation (AF), the most commonly sustained arrhythmia. Nevertheless, an in-depth prognostic significance of CMD in AF is lacking. We aimed to provide insight into the predictive impact of CMD assessed by a novel non-invasive coronary angiography-derived index of microcirculatory resistance (caIMR) for major adverse events (MACE) in AF patients. MethodThis study included patients with AF who underwent invasive coronary angiography due to suspected cardiac ischemia and did not exhibit obstructive epicardial coronary artery disease (≤50 % stenosis). The caIMR was prospectively evaluated, and the optimal cutoff value for predicting MACE was determined through ROC analysis. ResultA total of 463 patients with AF were enrolled. During a median of 33 months of follow-up, 111 (23.97 %) patients had MACE endpoints. The best caIMR cutoff value was 39.28. In patients with MACE, both the mean caIMR and the prevalence of elevated caIMR (caIMR>39.28) were significantly higher compared to those without MACE. An elevated caIMR was linked to a higher risk of MACE (log-rank P < 0.001) and emerged as an independent predictor of clinical outcomes (HR: 4.029; 95 % CI: 2.529–6.418; P < 0.001). In addition, the risk of MACE was higher in high caIMR patients with non-paroxysmal AF (log-rank P < 0.001) and no catheter ablation (log-rank P < 0.001). ConclusionElevated caIMR is common and showed a vital independent prognostic significance in AF patients. In addition to well-known risk factors, assessment of microvascular function can be a feasible approach for early prevention and a therapeutic target in AF patients.

Prevalence of Coronary Microvascular Dysfunction in Patients after Coronary Artery Bypass Grafting

The aim. To analyze the prevalence of coronary microvascular dysfunction (CMD) in patients with coronary artery disease after coronary artery bypass grafting (CABG).&#x0D; Materials and methods. The study was conducted in compliance with the provisions of the Declaration of Helsinki and was approved by the local ethics committee during 2018-2021. Due to recurrent complaints of discomfort/pain behind the sternum or shortness of breath during physical exertion in patients after CABG (average time of occurrence 18 ± 6 months after surgery), as well as positive or doubtful result of the stress testing, 31 patients were re-hospitalized for further examination. To diagnose CMD, echocardiography was performed with intravenous dipyridamole in order to determine the coronary flow reserve. The patency of the grafts was confirmed and newly formed hemodynamically significant coronary artery lesions were excluded during invasive coronary angiography.&#x0D; Results. The mean age was 61.2 ± 2.3 years, the majority of the patients were male (20 [64.5%]). The most common comorbid pathologies in the patients were: hypertension in 29 patients (93.5%), impaired glucose metabolism (diabetes/prediabetes) in 17 (54.8%) subjects, 13 (41.9%) patients had a history of myocardial infarction. Left ventricular ejection fraction according to echocardiography was reduced (less than 55%) in 5 (16.1%) of 31 patients, in others it was preserved. After CABG, there was a trend towards the coronary flow reserve increase, but no significant difference was found (1.89 ± 0.08 vs. 2.11 ± 0.13; p &gt; 0.05). The presence of CMD before and after CABG did not change significantly (13 [41.9%] vs. 12 [38.7%]; p &gt; 0.05).&#x0D; Conclusion. According to the results of the study, CMD is a common pathology in patients with obstructive coronary artery disease and is found in about 40% of patients with repeated myocardial ischemia after CABG. CABG did not affect the frequency of detection of CMD in patients with coronary artery disease before and after the operation.

Cardiometabolic biomarker patterns associated with cardiac MRI defined fibrosis and microvascular dysfunction in patients with heart failure with preserved ejection fraction.

Heart failure with preserved ejection fraction (HFpEF) is a complex disease process influenced by metabolic disorders, systemic inflammation, myocardial fibrosis, and microvascular dysfunction. The goal of our study is to identify potential relationships between plasma biomarkers and cardiac magnetic resonance (CMR) imaging markers in patients with HFpEF. Nineteen subjects with HFpEF and 15 age-matched healthy controls were enrolled and underwent multiparametric CMR and plasma biomarker analysis using the Olink® Cardiometabolic Panel (Olink Proteomics, Uppsala, Sweden). Partial least squares discriminant analysis (PLS-DA) was used to characterize CMR and biomarker variables that differentiate the subject groups into two principal components. Orthogonal projection to latent structures by partial least squares (OPLS) analysis was used to identify biomarker patterns that correlate with myocardial perfusion reserve (MPR) and extracellular volume (ECV) mapping. A PLS-DA could differentiate between HFpEF and normal controls with two significant components explaining 79% (Q2 = 0.47) of the differences. For OPLS, there were 7 biomarkers that significantly correlated with ECV (R2 = 0.85, Q = 0.53) and 6 biomarkers that significantly correlated with MPR (R2 = 0.92, Q2 = 0.32). Only 1 biomarker significantly correlated with both ECV and MPR. Patients with HFpEF have unique imaging and biomarker patterns that suggest mechanisms associated with metabolic disease, inflammation, fibrosis and microvascular dysfunction.

Characterisation of coronary microvascular dysfunction in patients with severe aortic stenosis undergoing TAVI.

Microvascular resistance reserve (MRR) is a validated measure of coronary microvascular function independent of epicardial resistances. We sought to assess whether MRR is associated with adverse cardiac remodelling, a low-flow phenotype and extravalvular cardiac damage (EVCD) in patients with severe aortic stenosis (AS) undergoing transcatheter aortic valve implantation (TAVI). Invasive thermodilution-based assessment of the coronary microvascular function of the left anterior descending artery was performed in a prospective, multicentre cohort of patients undergoing TAVI. Coronary microvascular dysfunction (CMD) was defined as the lowest MRR tertile of the study cohort. Haemodynamic measurements were performed at baseline and then repeated immediately after TAVI. EVCD and markers of a low-flow phenotype were assessed with echocardiography. A total of 134 patients were included in this study. Patients with low MRR were more frequently females, had a lower estimated glomerular filtration rate and a higher rate of atrial fibrillation. MRR was significantly lower in patients with advanced EVCD (median 1.80 [1.26-3.30] vs 2.50 [1.87-3.41]; p=0.038) and in low-flow, low-gradient AS (LF LG-AS) (median 1.85 [1.20-3.04] vs 2.50 [1.87-3.40]; p=0.008). Overall, coronary microvascular function tended to improve after TAVI and, in particular, MRR increased significantly after TAVI in the subgroup with low MRR at baseline. However, MRR was significantly impaired in 38 (28.4%) patients immediately after TAVI. Advanced EVCD (adjusted odds ratio 3.08 [1.22-7.76]; p=0.017) and a low-flow phenotype (adjusted odds ratio 3.36 [1.08-10.47]; p=0.036) were significant predictors of CMD. In this observational, hypothesis-generating study, CMD was associated with extravalvular cardiac damage and a low-flow phenotype in patients with severe AS undergoing TAVI.

Coronary Microvascular Dysfunction in Patients With Heart Failure: Characterization of Patterns in HFrEF Versus HFpEF.

Coronary microvascular dysfunction (CMD) is involved in heart failure (HF) onset and progression, independently of HF phenotype and obstructive coronary artery disease. Invasive assessment of CMD might provide insights into phenotyping and prognosis of patients with HF. We aimed to assess absolute coronary flow, absolute microvascular resistance, myocardial perfusion, coronary flow reserve, and microvascular resistance reserve in patients with HF with preserved ejection fraction and HF with reduced ejection fraction (HFrEF). Single-center, prospective study of 56 consecutive patients with de novo HF with nonobstructive coronary artery disease divided into HF with preserved ejection fraction (n=21) and HFrEF (n=35). CMD was invasively assessed by continuous intracoronary thermodilution and defined as coronary flow reserve <2.5. Left ventricular and left anterior descending artery-related myocardial mass was quantified by echocardiography and coronary computed tomography angiography. Myocardial perfusion (mL/min per g) was calculated as the ratio between absolute coronary flow and left anterior descending artery-related mass. Patients with HFrEF showed a higher left ventricular and left anterior descending artery-related myocardial mass compared with HF with preserved ejection fraction (P<0.010). Overall, 52% of the study population had CMD, with a similar prevalence between the 2 groups. In HFrEF, CMD was characterized by lower absolute microvascular resistance and higher absolute coronary flow at rest (functional CMD; P=0.002). CMD was an independent predictor of a lower rate of left ventricular reverse remodeling at follow-up. In patients with HF with preserved ejection fraction, CMD was mainly due to higher absolute microvascular resistance and lower absolute coronary flow during hyperemia (structural CMD; P≤0.030). Continuous intracoronary thermodilution allows the definition and characterization of patterns with distinct CMD in patients with HF and could identify patients with HFrEF with a higher rate of left ventricular reverse remodeling at follow-up.

Coronary microvascular dysfunction in patients undergoing transcatheter aortic valve implantation

ObjectivesThis study aimed to evaluate the prognostic value of coronary microvascular dysfunction (CMD) at long term after transcatheter aortic valve implantation (TAVI) and to explore its relationship with extravalvular cardiac...

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.

Non-hyperaemic coronary flow velocity acceleration indices correlate with hyperaemic microvascular resistance in patients with INOCA

Abstract Background Coronary microvascular dysfunction (CMD) is associated with an overall worse prognosis. While the diagnosis and endo-typing of CMD currently rely on hyperaemic physiological indices, the search for accurate non-hyperaemic techniques continues. Flow velocity acceleration pattern is mechanistically associated with changes in shear stress, endothelial function, arterial stiffness and pressure in pulsatile flow systems (1-3). Purpose We aim to interrogate whether resting flow velocity acceleration indices correlate with hyperaemic microvascular resistance (HMR) in patients with Ischemia and no obstructive coronary artery disease (INOCA). Methods In 21 Patients with INOCA (all of whom had presented with typical angina pectoris, had no significant epicardial stenoses but positive myocardial perfusion scan test for ischemia) invasive physiological assessment was performed by means of intracoronary Doppler. Hyperaemia was induced with intracoronary adenosine administration. Coronary flow reserve (CFR) and HMR were calculated per their definitions. Flow velocity acceleration indices were derived from the first derivative of the averaged resting flow velocity waveforms with respect to time. We have defined 6 wave peaks of interest in all patients (peak diastolic acceleration (initial prominent peak with ventricular relaxation, referred as A), early diastolic deceleration (B), early re-acceleration wave (C), peak presystolic deceleration (seen just before initial systolic acceleration peak, J), initial systolic acceleration peak (X) and pre-diastolic deceleration nadir (Z)) and calculated the ratios between them as well as adjusted them with respect to resting mean flow velocity (Figure 1). Results The mean age was 59 ± 8 years and the majority of the study group was female (%81). Cardiovascular risk factors were common amongst the study group.All patients had CFR &amp;lt; 2.5. Mean CFR and HMR were 2.05 ± 0.32 and 2.20 ± 0.60 mmHg.cm.sec-1 respectively. Raw C peak magnitude was significantly correlated with APVh (rho:-0.457 p:0.037) and HMR (rho:0.612 p:0.004). Adjusting the C magnitudes with APVb at patient level yielded better correlations (APVh rho:-0.496 p:0.022 ; HMR:0.642 p:0.002). The ratio between diastolic reacceleration peak (C) and presystolic peak deceleration (J), C/J , adjusted with the APVb ((C/J)/APVb) showed the most pronounced correlation with HMR (rho: 0.758 p &amp;lt; 0.001) (unadjusted C/J – HMR rho: 0.718 p&amp;lt;0.001)(Figure 2). Conclusion(s) Acceleration characteristics of resting coronary flow velocity correlate with hyperaemic microvascular resistance indicating structurally impaired coronary microcirculation, hence their utilisation may aid developing non-hyperaemic physiological markers for coronary microvascular dysfunction in patients with INOCA.Derived Acceleration WaveformsCorrelations between HMR and C/J Ratio

Endotypes of coronary microvascular dysfunction in patients with and without Diabetes Mellitus

Abstract Background Coronary microvascular dysfunction (CMD) is an early feature of diabetic cardiomyopathy, which usually precedes the onset of ventricular 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). Recently, two different endotypes of CMD, structural and functional were identified, based on CFR and minimal resistance (Rm-hyp) values. Purpose To compare the patterns of CMD among patients with and without diabetes mellitus by continuous intracoronary thermodilution. Methods Consecutive patients with angina and non-obstructive coronary artery disease undergoing absolute flow measurement with continuous intracoronary thermodilution between 2020 and 2022 were included. Considering a CFR threshold of 2.5, patients were divided into 4 groups, CMD with and without diabetes (DM-CMD and NDM-CMD respectively), and two control groups with and without diabetes (DM-Control and NDM-Control group, respectively). Rm-hyp threshold of 390 (median value) was used to divide structural and functional endotypes (Rm-hyp above or below the threshold respectively). Results 204 patients were included (NDM-CMD=62 vs NDM-Control=77 and dm-CMD=38 vs dm-Control=27). The prevalence of CMD among diabetic patients was 58%. Both CFR and MRR were significantly reduced in both CMD groups compared to the control groups. DM-CMD and NDM-CMD patients had both lower Rm-hyp and higher Rm-rest as compared to the control groups. Among patients with CMD, DM-CMD had higher Rm-hyp compared to NDM-CM patients (480±163 vs 420±124 WU, respectively, p=0.04) and had a higher prevalence of structural endotype (78% vs 58%), p=0.03) which was higher among patients with insulin-dependent diabetes than in those without. Conclusions In patients with DM structural microvascular dysfunction is the most prevalent endotype. Functional endotype is more frequent among those with non-insuline dependent DM. Therefore, CMD in diabetic patients appears to be a continuum, evolving from a functional pattern to a structural one as the disease progresses.

Abstract 15954: The Impact of Lipid Rich Plaque on Microvascular Dysfunction Evaluated by Angiography-Derived Index of Microcirculatory Resistance After Percutaneous Coronary Intervention

Introduction: Microvascular damage due to distal embolization during percutaneous coronary intervention (PCI) is an important cause of periprocedural myocardial infarction (PMI). Microcirculatory resistance index using pressure wires (invasive IMR) has been used to assess microvascular dysfunction, but recently angiography-derived microcirculatory resistance index (IMRangio) as a noninvasive method has received increasing attention. There have been few reports examining the relationship between noninvasive IMR and LRP assessed by near-infrared spectroscopy (NIRS). The purpose of this study was to investigate the impact of LRP assessed by NIRS on noninvasive IMRangio before and after PCI. Hypothesis: The purpose of this study was to investigate the impact of LRP assessed by NIRS on noninvasive IMRangio before and after PCI. Methods: We retrospectively evaluated consecutive patients admitted for coronary artery disease without ST elevated myocardial infarction (STEMI) who underwent coronary angiography at our hospital from November 2021 to January 2023. We analyzed 50 patients who performed NIRS before and after PCI and IMRangio available. The maximum value of LCBI for any of the 4-mm segments at the culprit lesion (maxLCBI4mm) was calculated at the culprit lesion. We divided the patients into 2 groups using a cutoff of culprit maxLCBI4mm ≥600. On the other hand, the value of IMRangio in culprit vessels was evaluated before and after PCI. The IMRangio values were compared between those two groups. Results: Mean pre-maxLCBI4mm was 529±260 and mean pre and post-PCI IMRangio were 17.5±9.00 and 22.1±10.2, respectively. Mean ΔIMRangio (=IMRangio after PCI–IMRangio before PCI) was 4.63±9.34. ΔIMRangio values were significantly higher in patients with high maxLCBI4mm than in those with low maxLCBI4mm (7.46±1.74 vs 2.23±1.74, P=0.047).The incidence of microvascular dysfunction (IMR ≥25 U) was higher in the high maxLCBI4mm group (52.2% vs. 22.2%, p=0.027). Furthermore, patients with elevatedΔIMRangio were significantly more likely to have a maxLCBI4mm ≥ 600 (59.3% vs. 87.0%, P=0.025). Conclusions: IMRangio is a valid alternative to invasive IMR to detect microvascular dysfunction in patients with lipid rich plaque assessed by NIRS.

Abstract 17927: Acipimox Does Not Improve Endothelial Function and Insulin-Stimulated Vasodilation in Patients With Metabolic Syndrome

Introduction: Insulin resistance increases circulating free fatty acid (FFA) concentrations, which causes the release of inflammatory cytokines and induces endothelial dysfunction. Acipimox reduces FFA efflux and may improve insulin sensitivity and endothelium-dependent microvascular vasodilation. Hypothesis: We hypothesize that acipimox treatment will improve insulin-stimulated forearm blood flow (FBF) compared to placebo in volunteers with metabolic syndrome. Methods: We conducted a randomized, double-blind, placebo-controlled crossover trial (NCT00759291) evaluating 1-week of acipimox 250 mg QID on insulin-stimulated FBF in patients with and without metabolic syndrome. Results: Sixteen patients received acipimox (6 metabolic syndrome and 10 healthy controls). Patients with metabolic syndrome were older (63.8 vs 49.9 years old, p&lt;0.001) with higher baseline insulin levels (15.9 vs 3.5 μU/mL, p=0.002), and trended towards higher BMIs (30.9 vs 24.6 kg/m 2 , p=0.083). Baseline insulin sensitivity by Homeostatic Model Assessment for Insulin Resistance (HOMA IR) differed between controls and those with metabolic syndrome (0.68 vs 3.28, p=0.001) but did not change with acipimox (p=0.540, Panel A). Insulin stimulation increased FBF in patients treated with placebo (p=0.01, Panel B) and acipimox (p=0.03, Panel C) but was not augmented by acipimox in participants with metabolic syndrome or healthy controls (Panel D and E). In multivariable-adjusted regression analysis, acipimox did not increase FBF, even after adjusting for baseline FBF and key baseline differences, including metabolic syndrome. Conclusion: Acipimox did not improve insulin sensitivity and had no effect on microvascular endothelial dysfunction assessed by insulin-stimulated FBF. This suggests that FFA modulation does not reverse microvascular dysfunction in patients with metabolic syndrome.

Abstract 14662: What Factors Contribute to the Presence of Coronary Microvascular Dysfunction in Patients With Non-Obstructive Coronary Artery Disease?

Introduction: In recent years, there has been growing interest in coronary microvascular dysfunction (CMD). Several risk factors have been discussed as causes of CMD, but there are still many unknowns. Hypothesis: In this study, we evaluated clinical risk factors for CMD in patients with chest pain with non-obstructive coronary artery disease (INOCA). Methods: Sixty-two patients who were able to undergo comprehensive coronary angiography at the time of chest pain screening were included in the study. Patients with a history of heart failure were excluded. Comprehensive angiography excluded patients with organic coronary artery stenosis (%stenosis&gt;50%) and was performed with the spasm provocation test using acetylcholine (ACh) to induce coronary spasm and with a pressure wire to evaluate CMD. Positive coronary spasm was defined as the presence of usual chest pain or electrocardiographic changes and &gt;90% coronary artery constriction on angiograms in response to ACh provocation. In addition, a coronary spasm within one section of the American Heart Association’s classification was defined as a focal spasm. CMD was defined as the presence of coronary flow reserve (CFR) &lt; 2.0 or an index of microcirculatory resistance (IMR) ≥ 25 obtained from a pressure wire. The clinical background leading to CMD was investigated and evaluated by logistic analysis. Results: Of 62 patients with INOCA, 26 (42%) had CMD. The results are shown in the table. Conclusions: These results suggested that factors contributing to CMD in INOCA patients were diverse: women, smoking, focal spasm, and elevated NTproBNP level. It is necessary to identify the cause of CMD before treatment in such patients.

Prognostic value of coronary microvascular dysfunction in patients with aortic stenosis and nonobstructed coronary arteries.

Patients with aortic valve stenosis have been postulated to have coronary microvascular dysfunction (CMD) contributing to the clinical symptoms and adverse outcomes. The coronary angiography (CAG)-derived index of microcirculatory resistance (caIMR) is proposed as a novel, less invasive and pressure-wire-free index to assess CMD. This study aimed to quantify CMD assessed by caIMR and investigate its prognostic impact in patients with aortic valve stenosis. This study included 77 moderate or severe aortic valve stenosis patients with no obstructive coronary disease (defined as having no stenosis more than 50% in diameter) who underwent caIMR measurement. CMD was defined by caIMR at least 25. Major adverse cardiovascular events (MACE) were the clinical outcomes during the median 40 months of follow-up. The incidence of CMD was 47.7%. Seventeen MACE occurred during the follow-up duration. CMD was associated with an increased risk of MACE (log-rank P < 0.001) and an independent predictor of clinical outcomes [hazard ratio 5.467, 95% confidence interval (CI) 1.393-21.458; P = 0.015]. The receiver-operating characteristic (ROC) curve analysis demonstrated that caIMR could provide a significant predictive value for MACE in aortic valve stenosis patients (AUC 0.785, 95% CI 0.609-0.961, P < 0.001). In addition, the risk of MACE was higher in CMD patients with severe aortic valve stenosis (log-rank P < 0.001) and no aortic valve replacement (log-rank P = 0.003) than in other groups. Aortic valve stenosis patients demonstrated markedly impaired caIMR. CMD assessed by caIMR increases the risk of MACE and is an independent predictor of adverse outcomes in aortic valve stenosis patients. This finding suggests that using caIMR in the clinical assessment may help identify high-risk groups and stimulate earlier intervention.

A Comparison of Dynamic SPECT Coronary Flow Reserve with TIMI Frame Count in the Treatment of Non-Obstructive Epicardial Coronary Patients.

Microvascular dysfunction in patients with non-obstructive epicardial coronary may aggravate patient's symptoms or lead to various clinical events. To investigate the correlation between dynamic single photon emission computed tomography (D-SPECT) derived coronary flow reserve (CFR) and TIMI frame count (TFC) in patients with non-obstructive epicardial coronary patients. Patients with suspected or known stable CAD who were recommended to undergo invasive coronary angiography were prospectively enrolled in this study. Those who had non-obstructive coronary received TIMI frame count (TFC) and D-SPECT. A cut-off value of >40 was defined as slow flow referred to TFC. A total of 47 patients diagnosed with non-obstructive coronary were enrolled. The mean age of patients was 66.09 ± 8.36 years, and 46.8% were male. Dynamic SPECT derived coronary flow reserve (CFR) was significantly correlated with TIMI frame count in 3 epicardial coronary (LAD: r=-0.506, P = 0.0003; LCX: r= -0.532, P = 0.0001; RCA: r= -0.657, P < 0.0001). The sensitivity and specificity of CFR in identifying abnormal TIMI frame count < 40 was 100.0% and 57.6% in LAD, 62.5% and 87.0% in LCX, 83.9% and 75.0% in RCA, respectively. The optimal CFR cut-off values were 2.02, 2.47, and 1.96 among the three vessels. In patients with non-obstructive coronary, CFR derived from D-SPECT was strongly correlated with TFC. This study demonstrates that that CFR may be an alternative non-invasive method for identifying slow flow in non-obstructive coronary.

TCT-735 Coronary Microvascular Dysfunction in Patients With Discordant RFR and FFR

TCT-735 Coronary Microvascular Dysfunction in Patients With Discordant RFR and FFR

Reduced reactive hyperemia of the brachial artery in diabetic patients assessed by repeated measurements: The FMD-J B study.

Type 2 diabetes mellitus (T2DM) is a major cause of microvascular dysfunction. However, its effect on blood flow patterns during ischemic demand has not been adequately elucidated. In this study, we investigated the hypothesis that microvascular dysfunction in patients with T2DM manifests as brachial reactive hyperemia (BRH), defined as the ratio of peak blood flow velocities in a brachial artery before and after forearm cuff occlusion. The study enrolled 943 subjects (men, n = 152 [T2DM] and n = 371 [non-T2DM]; women, n = 107 [T2DM] and n = 313 [non-T2DM], respectively) with no history of cardiovascular disease. Semiautomatic measurements were obtained three times at 1.5-year intervals to confirm the reproducibility of factors involved in BRH for each sex. An age-adjusted mixed model demonstrated attenuated BRH in the presence of T2DM in both men (p = 0.022) and women (p = 0.031) throughout the study period. Post hoc analysis showed that the estimated BRH was significantly attenuated in patients with T2DM regardless of sex, except at baseline in women. In multivariate regression analysis, T2DM was a negative predictor of BRH at every measurement in men. For women, BRH was more strongly associated with alcohol consumption. Repeated measurements analysis revealed that T2DM was associated with attenuated postocclusion reactive hyperemia.

Integrin β5 subunit regulates hyperglycemia-induced vascular endothelial cell apoptosis through FoxO1-mediated macroautophagy.

Hyperglycemia frequently induces apoptosis in endothelial cells and ultimately contributes to microvascular dysfunction in patients with diabetes mellitus (DM). Previous research reported that the expression of integrins as well as their ligands was elevated in the diseased vessels of DM patients. However, the association between integrins and hyperglycemia-induced cell death is still unclear. This research was designed to investigate the role played by integrin subunit β5 (ITGB5) in hyperglycemia-induced endothelial cell apoptosis. We used leptin receptor knockout (Lepr-KO) ( db / db ) mice as spontaneous diabetes animal model. Selective deletion of ITGB5 in endothelial cell was achieved by injecting vascular targeted adeno-associated virus via tail vein. Besides, we also applied small interfering RNA in vitro to study the mechanism of ITGB5 in regulating high glucose-induced cell apoptosis. ITGB5 and its ligand, fibronectin, were both upregulated after exposure to high glucose in vivo and in vitro . ITGB5 knockdown alleviated hyperglycemia-induced vascular endothelial cell apoptosis and microvascular rarefaction in vivo.In vitro analysis revealed that knockdown of either ITGB5 or fibronectin ameliorated high glucose-induced apoptosis in human umbilical vascular endothelial cells (HUVECs). In addition, knockdown of ITGB5 inhibited fibronectin-induced HUVEC apoptosis, which indicated that the fibronectin-ITGB5 interaction participated in high glucose-induced endothelial cell apoptosis. By using RNA-sequencing technology and bioinformatic analysis, we identified Forkhead Box Protein O1 (FoxO1) as an important downstream target regulated by ITGB5. Moreover, we demonstrated that the excessive macroautophagy induced by high glucose can contribute to HUVEC apoptosis, which was regulated by the ITGB5-FoxO1 axis. The study revealed that high glucose-induced endothelial cell apoptosis was positively regulated by ITGB5, which suggested that ITGB5 could potentially be used to predict and treat DM-related vascular complications.

Microvascular dysfunction in patients with heart failure with preserved ejection fraction: A meta-analysis.

Although microvascular dysfunction (MVD) is considered an essential pathophysiology in patients with heart failure with preserved ejection fraction (HFpEF), the frequency and prognostic impact of MVD are not fully understood. This meta-analysis evaluated the frequency of MVD in patients with HFpEF and its utility in risk stratification. On May 26, 2022, a literature search was performed on PubMed, Web of Science, the Cochrane library, and Embase using the search terms such as "Heart failure with preserved ejection fraction," "HFpEF," "microvascular dysfunction," and "MVD." The prevalence of MVD in patients with HFpEF was calculated using the general inverse variance method. A comprehensive literature review was conducted to examine the association between MVD and prognosis in patients with HFpEF. Data pertaining to a total of 941 patients diagnosed with HFpEF were extracted from the collective pool of 9 studies. The results of the meta-analysis revealed that the frequency of MVD among patients with HFpEF was found to be 55.5% (95% CI: 34.8%-76.2%), with a substantial degree of heterogeneity (I2  = 98%, p for heterogeneity <.001). Among the five studies that provided data on the association between MVD and prognosis, a significant statistical association was observed in four of them. This meta-analysis revealed that approximately 50% of patients diagnosed with HFpEF exhibited MVD. Moreover, the presence of MVD demonstrated significant prognostic implications in multiple studies conducted on patients with HFpEF. These findings strongly suggest that MVD plays a crucial role in the underlying pathophysiology of patients with HFpEF.

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

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

Prognostic Significance of Coronary Microvascular Dysfunction in Patients With Heart Failure With Preserved Ejection Fraction.

The prognostic impact of coronary microvascular dysfunction (CMD) has been scarcely addressed in heart failure with preserved ejection fraction (HFpEF). This study investigated the prevalence and prognostic significance of CMD as measured by a novel pressure wire-free coronary angiography-derived index of microcirculatory resistance (caIMR) on clinical outcomes. Patients diagnosed with HFpEF from 2019 to 2021 were enrolled retrospectively. caIMR was used to quantify microvascular function, and patients were categorised into 2 groups based on their caIMR. The primary end points were composite of all-cause death and heart failure rehospitalisation. Of 137 HFpEF patients, CMD (defined as caIMR ≥ 25) was present in 88 patients (64.2%). Forty-five patients (32.8%) experienced composite events during a mean follow-up of 15 months. Compared with patients with caIMR < 25, those with caIMR ≥ 25 had a notably higher incidence of composite events (16.3% vs 42.0%; P= 0.002). On survival analysis, patients with caIMR ≥ 25 demonstrated a worse prognosis than those with caIMR < 25 for composite events (P= 0.006). Patients with caIMR ≥ 25 in multiple coronary arteries showed a trend to worse outcome than those with caIMR ≥ 25 in a single coronary artery (log-rank P= 0.056). In adjusted analysis, caIMR ≥ 25 was independently predictive of adverse outcomes (adjusted hazard ratio 2.93, 95% confidence interval [CI] 1.28-6.70; P= 0.010). caIMR displayed a significant predictive power for adverse event prediction (area under the receiver operating characteristic curve 0.767, 95% CI 0.677-0.858; P < 0.001). CMD is highly prevalent and is an independent predictor of adverse outcomes in HFpEF patients. Assessment of CMD may identify high-risk patients early for intensified treatment and risk-factor management.