Coronary 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.

Impact of coronary microvascular dysfunction in heart failure with preserved ejection fraction: a meta-analysis.

Several mechanisms have been identified in the aetiopathogenesis of heart failure with preserved ejection fraction (HFpEF). Among these, coronary microvascular dysfunction (CMD) may play a key pathophysiological role. We performed a systematic review and meta-analysis to investigate the prevalence, echocardiographic correlates, and prognostic implications of CMD in patients with HFpEF. A systematic search for articles up to 1 May 2023 was performed. The primary aim was to assess the prevalence of CMD. Secondary aims were to compare key echocardiographic parameters (E/e' ratio, left atrial volume index [LAVi], and left ventricular mass index [LVMi]), clinical outcomes [death and hospitalization for heart failure (HF)], and prevalence of atrial fibrillation (AF) between patients with and without CMD. Meta-regressions according to baseline patient characteristics and study features were performed to explore potential heterogeneity sources. We identified 14 observational studies, enrolling 1138 patients with HFpEF. The overall prevalence of CMD was 58%. Compared with patients without CMD, patients with HFpEF and CMD had larger LAVi [mean difference (MD) 3.85 confidence interval (CI) 1.19-6.5, P<0.01)], higher E/e' ratio (MD 2.76 CI 1.54-3.97; P<0.01), higher prevalence of AF (odds ratio 1.61 CI 1.04-2.48, P=0.03) and higher risk of death or hospitalization for HF [hazard ratio 3.19, CI 1.04-9.57, P=0.04]. CMD is present in little more than half of the patients with HFpEF and is associated with echocardiographic evidence of more severe diastolic dysfunction and a higher prevalence of AF, doubling the risk of death or HF hospitalization.

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.

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.

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.

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...

Application of AMR in evaluating microvascular dysfunction after ST-elevation myocardial infarction.

A guidewire-free angiography-derived microcirculatory resistance (AMR) derived from Quantitative flow ratio (QFR) exhibits good diagnostic accuracy for assessing coronary microvascular dysfunction (CMD), but there are no relevant studies supporting the specific application of AMR in patients with ST-elevation myocardial infarction (STEMI). The study aims to evaluate CMD in patients with STEMI using the AMR index. This study included patients with STEMI who underwent percutaneous coronary intervention (PCI) from June 1, 2020 to September 28, 2021. All patients were divided into two groups: the CMD (n = 215) and non-CMD (n = 291) groups. After matching, there were 382 patients in both groups.1-year follow-up major adverse cardiac events (MACEs) were evaluated. After matching, the primary endpoint was achieved in 41 patients (10.7%), with 27 and 14 patients in the CMD and non-CMD groups, respectively (HR 1.954 [95% CI 1.025-3.726]; 14.1% versus 7.3%, p = .042). Subgroup analysis revealed that 18 patients (4.7%) were readmitted for heart failure, with 15 and 3 in the CMD and non-CMD groups, respectively (HR 5.082 [95% CI 1.471-17.554]; 7.9% versus 1.6%, p = .010). Post-PCI AMR ≥ 250 was significantly associated with a higher risk of the primary endpoint and was its independent predictor (HR 2.265 [95% CI 1.136-4.515], p = .020). The retrospective use of AMR with a cutoff value of ≥250 after PCI in patients with STEMI can predict a significant difference in the 1-year MACE rates when compared with a propensity score-matched group with normal AMR.

Diagnosis of coronary microvascular dysfunction using magnetocardiography

Abstract Background In patients with ischemia and non-obstructive coronary artery disease (INOCA), diagnosing coronary microvascular dysfunction (CMD) is limited to invasive, expensive, and/or difficult to access methods. Magnetocardiography (MCG) is a rest-based scan that measures weak magnetic fields generated by cardiac ionic currents and has been validated for diagnosing ischemia secondary to obstructive coronary artery disease (CAD). Objectives The goal of this study was to validate MCG for diagnosing CMD in patients with INOCA as compared to invasive coronary functional angiography (CFA), the gold-standard for evaluation of CMD by coronary flow reserve (CFR). Methods Forty-eight patients with INOCA (58 ± 10.5 years of age) underwent both CFA and a noninvasive 36-channel MCG scan. CFA diagnosed 21 patients with CMD (CFR &amp;lt;2 by Doppler wire method or CFR &amp;lt;2.5 by thermodilution method) and 27 patients were confirmed as negative for CMD. Using MCG, patients were classified as either CMD positive or CMD negative using an adaptive rules-based system, originally developed for evaluating ischemia secondary to obstructive coronary artery disease. These rules based on 5 features involve the analysis of depolarization and repolarization to observe regions where electrophysiological heterogeneity exists and action potentials in affected tissue are altered in amplitude and/or rate. Results Of the 21 patients confirmed positive for CMD by CFA, 15 had at least one abnormal finding on the MCG. Of the 27 patients confirmed negative for CMD by CFA, 19 had no abnormal findings in the MCG. Using gold standard invasive CFR as reference, MCG had a mean accuracy of 71%, sensitivity of 71% and specificity of 70% for the detection of CMD. Figure 1 shows an example of CMD negative and CMD positive patient. In patients that exhibited more than one abnormal finding on the MCG rules (n =5), accuracy was 80%, with 4 patients correctly characterized as CMD positive, and one patient being characterized as falsely positive. Conclusions In INOCA patients, MCG demonstrates ability to noninvasively assess for CMD. An MCG-based diagnostic pathway for CMD merits further clinical evaluation. Abbreviations and Acronyms: CMD, coronary microvascular dysfunction; MCG, magnetocardiography; CFR, coronary flow reserve; INOCA, ischemia and non-obstructive coronary artery disease; CFA, coronary functional angiographyFigure 1

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 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.

Abstract 17001: Enhancing Coronary Functional Angiography: Integrating Doppler-Based Left Circumflex Coronary Flow Reserve in Assessment

Background: Coronary microvascular dysfunction (CMD), predominantly affecting women is associated with poor outcomes and has limited diagnostic options. Coronary functional angiography (CFA) is used for diagnosing CMD in patients with refractory angina and no obstructive coronary artery disease (ANOCA). The assumption is that endothelial-independent CMD is a homogenous disease process, therefore current gold-standard for diagnosis is measure of coronary flow reserve (CFR) in the proximal left anterior descending artery (LAD). However, there is limited data on CFR in the left circumflex (LCx). Objective: Examine the benefits of measuring CFR using Doppler-tipped guide wire in LCx in addition to proximal LAD. Methods: Examined 191 ANOCA patients with Canadian Cardiovascular Society (CCS) class 3 or 4 angina despite optimal medical treatment who underwent CFA for assessment of CMD. CFR measurements were obtained using Doppler-tipped guidewire during the administration of 72 mcg of adenosine in both the proximal LAD and LCx and CFR of &lt;2.5 was used to define CMD. Results: 191 patients underwent CFA including 91% female with a median age of 59 years (IQR: 50, 67). The correlation in CFR measurements between the proximal LAD and LCx was 0.610 (p&lt;0.001). 149 (78%) patients had concordant results including 113 (59%) with abnormal CFRs and 36 (19%) with normal CFRs in both vessels. 12 (6%) had abnormal proximal LAD CFR and normal LCx CFR; and 30 (16%) had an abnormal LCx CFR and normal proximal LAD CFR and would have gone undiagnosed without measuring LCx CFR. Conclusion: The addition of LCx CFR measurement to the current standard CFA protocol using the Doppler guidewire improves diagnosis of CMD in patients. Further studies are needed to evaluate a comprehensive assessment of CMD including measurement of LCx CFR.

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.

The prevalence of coronary microvascular dysfunction (CMD) in heart failure with preserved ejection fraction (HFpEF): a systematic review and meta-analysis.

To date, studies on the prevalence of coronary microvascular dysfunction (CMD) in heart failure with preserved ejection fraction (HFpEF) have not been summarized and analyzed as a whole. We conducted this systematic review and meta-analysis to assess the prevalence of CMD in patients with HFpEF. The PubMed, Cochrane, and Embase databases were searched from dates of inception until May 1, 2023. The primary outcome was the prevalence of CMD in patients with HFpEF, and values of CMD prevalence were pooled using a random-effects model. In total, 10 studies involving 1267 patients, including 822 with HFpEF and 445 without HFpEF, were included. The pooled prevalence of CMD in patients with HFpEF was 71% (95% CI, 0.63-0.79). In the subgroup analysis, the prevalence of CMD was 79% (95% CI, 0.71-0.87) by invasive measurement and 66% (95% CI, 0.54-0.77) by noninvasive measurement and 67% (95% CI, 0.52-0.82) with CFR < 2.0 and 75.0% (95% CI, 0.71-0.79) with CFR < 2.5. The prevalence of endothelium-independent CMD and endothelium-dependent CMD was 62% (95% CI, 0.53-0.72) and 50% (95% CI, 0.19-0.81), respectively. The prevalence of CMD was 74% (95% CI = 0.69-0.79) and 66% (95% CI = 0.41-0.90) in prospective and retrospective studies, respectively. Compared with the control group, patients with HFpEF had a significantly lower CFR (MD = - 1.28, 95% CI = - 1.82 to - 0.74, P < 0.01) and a higher prevalence of CMD (RR = 2.21, 95% CI = 1.52 to 3.20, P < 0.01). Qualitative analysis demonstrated that CMD might be associated with poor clinical outcomes in patients with HFpEF. In conclusion, this is the first systematic review and meta-analysis of all studies reporting the prevalence of CMD in patients with HFpEF. Our study demonstrates that CMD is common in patients with HFpEF and might be associated with poor clinical outcomes in these patients. Clinicians should attach importance to CMD in the diagnosis and treatment of HFpEF. The number of studies in this field is relatively small. Therefore, more high-quality studies are needed to explore the diagnostic and prognostic value of CMD and the potential role of CMD as a therapeutic target in patients with HFpEF.

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

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

Coronary Microvascular Dysfunction in Asymptomatic Patients with Severe Psoriasis

Severe psoriasis is associated with an increased cardiovascular risk, which may be independent of the traditional risk factors. Coronary microvascular dysfunction (CMD) has been shown to predict a poor cardiovascular prognosis in the general population and in patients with psoriasis. In this study, we assessed the prevalence and predictors of CMD in a large cohort of patients with psoriasis without clinical cardiovascular disease. A total of 503 patients with psoriasis were enrolled and underwent transthoracic Doppler echocardiography to evaluate coronary microcirculation. Of these, 55 patients were excluded from the analyses because of missing data. Of the 448 patients in this study, 31.5% showed CMD. Higher PASI, longer disease duration, the presence of psoriatic arthritis, and hypertension were independently associated with CMD. An increase of 1 point of PASI and 1 year of psoriasis duration were associated with a 5.8% and 4.6% increased risk of CMD, respectively. In our study, CMD was associated with the severity and duration of psoriasis. This supports the role of systemic inflammation in CMD and suggests that the coronary microcirculation may represent an extracutaneous site involved in the immune-mediated injury of psoriasis. We should diagnose and actively search for CMD in patients with severe psoriasis.

Incremental value of non-invasive myocardial work for the evaluation and prediction of coronary microvascular dysfunction in angina with no obstructive coronary artery disease.

Evidence suggests that patients suffering from angina with no obstructive coronary artery disease (ANOCA) experience coronary microvascular dysfunction (CMD). We aimed to understand the diagnosis value of noninvasive myocardial work indices (MWIs) with left ventricular pressure-strain loop (LV PSL) by echocardiography in ANOCA patients with CMD. 97 patients with ANOCA were recruited. All subjects underwent standard echocardiography with traditional ultrasound parameters, two-dimensional speckle-tracking echocardiography with global longitudinal strain (GLS), LV PSL with MWIs include global work index (GWI), global constructive work (GCW), global waste work (GWW) and global work efficiency (GWE). In addition, all enrolled cases underwent high-dose adenosine stress echocardiography (SE) with coronary flow velocity reserve (CFVR). CMD was defined as CFVR <2.0. Of the 97 patients with ANOCA, 52 were placed in the CMD group and 45 in the control group. GWI and GCW were decreased significantly in the CMD group compared with the control group (P < 0.001 for both). GWI and GCW were moderately correlated with CFVR (r = 0.430, P < 0.001 and r = 0.538, P < 0.001, respectively). In the multiple logistic regression analyses, GCW was identified as the only independent echocardiography parameter associated with CMD after adjusting for age and baseline APV [OR (95%CI) 1.009 (1.005-1.013); P < 0.001]. Moreover, the best predictor of CMD in patients with ANOCA using receiver operating characteristic (ROC) curve was GWI and GCW, with an area under the curve (AUC) of 0.800 and 0.832, sensitivity of 67.3% and 78.8%, specificity of 80.0% and 75.6%, respectively. MWIs with LV PSL is a new method to detect LV systolic function noninvasively in ANOCA patients with CMD.

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.

Significance of inflammation markers in patients with coronary microvascular dysfunction and non-obstructive coronary artery disease

Aim. To study the relationship of coronary microvascular dysfunction (CMD) with the levels of pro- and anti-inflammatory biomarkers in patients with preserved ejection fraction (LVEF) and non-obstructive coronary artery disease (CAD).Material and methods. The study included 118 patients (70 men, mean age, 62,0 [58,0; 69,0] years) with preserved LVEF (62 [59; 64] %) and non-obstructive CAD. Serum levels of N-terminal pro-brain natriuretic peptide (NT-proBNP), high-sensitivity C-reactive protein (hsCRP), interleukin-1β, 6, and 10 were assessed initially by enzyme immunoassay. Coronary flow reserve (CFR) was assessed by dynamic single photon emission computed tomography. CFR ≤2 was a CMD marker.Results. Patients were divided into groups depending on CMD presence: group 1 included patients with CMD (n=45), and group 2 was the control group and included patients without CMD (n=73). HsCRP concentrations were 1,8 times higher (p=0,011) in group 1 compared to group 2. Interleukin-6 levels did not differ significantly between groups (p=0,842), while interleukin-10 concentrations were lower by 21,7 % (p=0,048), and interleukin-1β was 2,7 times higher (p=0,046) in group 1 compared to group 2. According to ROC analysis, hsCRP concentration ≥4,8 g/l (AUC=0,655; p=0,012), and NT-proBNP ≥950,6 pg/ml (AUC=0,792; p&lt;0,001) were identified as markers associated with CMD in patients with non-obstructive CAD, while levels of interleukin-1β, 6 and 10 showed no diagnostic significance. Multivariate regression analysis showed that diastolic dysfunction (odds ratio, 3,27; 95% confidence interval, 2,26-5,64; p&lt;0,001) and NT-proBNP ≥950,6 pg/ml (odds ratio, 2,07; 95% confidence interval, 1,56-4,12; p=0,023) were independent factors associated with CMD.Conclusion. We established that in patients with non-obstructive CAD, the pre­sence of CMD is associated with a higher expression of pro-inflammatory markers and a decrease in the expression of an anti-inflammatory marker, which may confirm the fact that chronic inflammation is one of CMD pathogenesis links.