Coronary Microvascular Dysfunction In Patients Research Articles

Invasive quantitative assessment of coronary microvascular dysfunction in patients with hypertrophic cardiomyopathy

Abstract Background Patients (P) with hypertrophic cardiomyopathy (HCM) commonly suffer from coronary microvascular dysfunction (CMD) - the affection of function/structure of the coronary microvasculature. Invasive assessment of CMD through thermodilution methods allows for the calculation of coronary flow reserve (CFR) and index of microvascular resistance (IMR). These methods, while extensively studied in the context of non-obstructive coronary artery disease and myocardial infarction, have not been thoroughly validated in HCM P. Objectives To invasively assess the presence of CMD in P with HCM and to determine clinical predictors of invasively assessed CMD. Methods In a prospective single-centre study, we opportunistically recruited consecutive adult P with an established diagnosis of HCM with or without LVOTO that had an indication to pursue elective coronarography – such as pre-procedural evaluation for alcoholic septal ablation (ASA) or exclusion of epicardial coronary artery disease. P characteristics and coronary hemodynamic invasive assessment data were extracted. CFR was calculated as the ratio between resting and hyperemia mean transit times (TmnRest;TmnHyper). IMR was calculated as the ratio between distal coronary pressure (Pd) and the inverse of TmnHyper (IMR=Pd/TmnHyper-1). A cutoff of ≤22.0 in IMR, an ≥d 2 in CFR was used. We excluded P with end-stage HCM (LV EF <50% and/or or left ventricular wall thinning), or with epicardial coronary artery disease. Continuous variables were reported as mean ± SD or median and IQR depending on data distribution pattern and categorical data as frequencies and percentages. A linear regression model was used to test predictors of IMR and CFR involvement. Results 25 HCM P with a mean age of 63±10 years were included, 14 (56%) were female. In 20 (80%) of the P the cause for coronary angiography was ASA. All P referred for ASA had LVOTO and were on beta-blocker therapy (Table 1.). Median CFR was 2.5 [1.5-3] and median IMR was 19 [14-22], both within normal range. A total of 13 (44%) P had a reduced CFR and 5 (20%) of P had an increased IMR. 14 P (56%) had an altered CFR or IMR value, with the presence of a functional CMD phenotype in 10 P (40%) (Table 2). Angina was associated with a higher IMR (5.3, 95% CI - 0.05-10, p=0.053) and for each +1 increase in CCS a larger increase in the likelihood of a higher IMR was observed (CCS 1, +7 (95%CI 0.68 – 14); CCS 2, +9 (95%CI 4 – 14); CCS 3, 10 (95%CI 2 – 18)). A similar but non significant trend was observed for higher CCS correlating with lower CFR (Table 3). Conclusion In a prospective cohort of HCM P submited to invasive angiographic evaluation 56% had at least one invasive measure compatible with CMD. Angina, and a higher degree of anginal symptoms correlated positively with the presence of higher IMR and therefore with a higher level of CMD. In the future, we intend to correlate these findings with multimodality imaging/clinical outcomes.Patient characteristics and LR results

Coronary microvascular dysfunction in patients with heart failure with reduced and mildly reduced ejection fraction: results from the PANACEA study

Abstract Aims Coronary microvascular dysfunction (CMD) is common and associated with impaired survival in patients with heart failure with preserved ejection fraction (HFpEF). In patients with heart failure with reduced ejection fraction (HFrEF) and mildly reduced ejection fraction (HFmrEF) the impact of CMD is not fully known. Purpose We aimed to investigate the prevalence of CMD and its association with phenotype, biomarkers, endothelial function and echocardiographic measurements in patients with HFrEF or HFmrEF. Method A prospective, exploratory bi-center study in patients with chronic stable heart failure, New York Heart Association (NYHA) Class II-IV, and ejection fraction (EF) <50% was performed. Study procedures included echocardiography, adenosine-based transthoracic Doppler echocardiography to assess coronary flow reserve (CFR), physical examination, fasting blood and urine sample, pulse wave velocity (PWV) and hemodynamic measurements. The cutoff of CFR<2.5 was used to diagnose CMD. A multivariable linear regression analysis with CFR as dependent variable, adjusted for age, sex, body mass index, smoking, atrial fibrillation and left ventricular mass, was performed to explore biomarkers, endothelial function, and echocardiographic measurements associated with CMD. Results Of 112 included patients, 87 (78%) were men, with a mean age of 73.3 (±7.5) years. Among patients with a successful CFR measurement (n=62), CMD was present in 40 (65%), mean age of 75.4 (±5.8) years (Table 1). Patients with CMD had higher N-terminal pro B-type natriuretic peptide (NTproBNP) and Troponin T (p<0.05), and more often HFrEF ( p=0.06). Patients with CMD had larger ventricles with greater left ventricular mass and larger end-diastolic volumes (p<0.05). In a linear regression analysis CMD was associated with higher NTproBNP, lower EF, PWV and global strain (table 2). Conclusion CMD was common and present in two thirds of patients with HFrEF or HFmrEF. Further CMD was associated with markers of more severe heart failure and systemic endothelial dysfunction indicating that CMD may be an important predictor of outcome in patients with HFrEF and HFmrEF.

The role of markers of endothelial dysfunction in the pathogenesis of coronary microvascular dysfunction in patients with non-obstructive coronary artery disease

Aim. To study the potential of non-invasive biomarkers in the diagnosis of coronary microvascular dysfunction (CMD) and prediction of the course of heart failure with preserved ejection fraction (HFpEF) in non-obstructive coronary artery disease.Materials and methods. The 12-month observational study included 118 consecutive patients (6 patients dropped out of the study due to contact loss) with non-obstructive coronary artery disease (CAD) and HFpEF (62 [59; 64]%). At the beginning of the study, serum levels of several biomarkers were assessed using the enzyme immunoassay: N-terminal pro-B-type natriuretic peptide (NT-proBNP), vascular endothelial growth factor (VEGF), and endothelin-1. Coronary flow reserve (CFR) was examined using dynamic single photon emission computed tomography. In the absence of obstructive CAD, CMD was defined as a global decrease in CFR ≤ 2. Echocardiography was used to determine parameters of hemodynamics, LV diastolic dysfunction, and myocardial stress. LV global longitudinal strain (GLS) was assessed using 2D speckle tracking.Results. The patients were divided into groups depending on the presence of CMD: group 1 included patients with CMD (n = 43), group 2 included those without it (n = 75). In patients in group 1, serum levels of endothelin-1 were 1.9 times higher (p = 0.012), levels of VEGF were 2.16 times higher (p = 0.008), and the concentration of NT-proBNP was 2.6 times higher (p = 0.004) than in patients in group 2. According to the ROC analysis, the concentrations of endothelin-1 ≥ 6.9 pg / ml (AUC = 0.711; p = 0.040) and VEGF ≥ 346.7 pg / ml (AUC = 0.756; p = 0.002) were considered as markers associated with the presence of CMD in patients with non-obstructive CAD. The multivariate regression analysis showed that only the presence of CMD (odds ratio (OR) 2.42; 95% confidence interval (95% CI) 1.26–5.85; p < 0.001) and an increase in NT-proBNP ≥ 760.5 pg / ml (OR 1.33; 95% CI 1.08–3.19; p = 0.023) were factors associated with adverse events, and their combination increased the risk of HFpEF progression by more than 3 times (OR 3.18; 95% CI 2.76–7.98; p < 0.001), whereas markers of endothelial dysfunction were not independent predictors. Conclusion. Endothelin-1 ≥ 6.9 pg / ml and VEGF ≥ 346.7 pg / ml can be used as non-invasive markers for the diagnosis of CMD. However, markers of endothelial dysfunction were not independent predictors of HFpEF progression in patients with non-obstructive CAD during 12-month follow-up.

TCT-675 Assessment of Coronary Microvascular Dysfunction in Patients With Diabetes Mellitus Presenting With Angina With Nonobstructive Coronary Arteries

TCT-675 Assessment of Coronary Microvascular Dysfunction in Patients With Diabetes Mellitus Presenting With Angina With Nonobstructive Coronary Arteries

TCT-679 Coronary Microvascular Dysfunction in Patients With Cancer Experiencing Angina With Nonobstructive Coronary Arteries

TCT-679 Coronary Microvascular Dysfunction in Patients With Cancer Experiencing Angina With Nonobstructive Coronary Arteries

TCT-604 Evaluation of Coronary Microvascular Dysfunction in Patients With Chronic Kidney Disease Presenting With Angina With Nonobstructive Coronary Arteries

TCT-604 Evaluation of Coronary Microvascular Dysfunction in Patients With Chronic Kidney Disease Presenting With Angina With Nonobstructive Coronary Arteries

Exercise-based cardiac rehabilitation effects on severity of angina, HRQoL and exercise capacity in patients with microvascular angina: systematic review and meta-analysis

Abstract Background Microvascular angina (MVA) is a clinical syndrome caused by coronary microvascular dysfunction in patients with angina symptoms and no flow limiting blockages in their main coronary arteries. Patients experience recurrent angina, low health related quality of life (HRQoL) and limited exercise tolerance, making them more likely to repeatedly present to healthcare services. Aim To establish the effects of exercise-based cardiac rehabilitation (CR) on the severity of angina, HRQoL and exercise capacity among adults with a diagnosis of MVA compared to a no-exercise group. Methods Searches were performed in 14 online databases. We included randomised controlled trials (RCTs) that assessed the independent effect of CR versus a no-exercise group in adults with a probable or definite diagnosis of MVA according to the COVADIS criteria. Risk of bias was assessed via the Cochrane RoB2 tool at outcome level and the quality of the evidence using the Grading of Recommendations, Assessment, Development and Evaluations framework. Meta-analysis using random effects models were used to estimate mean difference (MD) or standardised mean difference (SMD) with 95% confidence intervals (CI). Results Of the 15,873 reports identified, five studies (n=222) were included. Reasons for RoB judgements varied between studies and outcomes, however all were scored at either ‘high risk’ or ‘some concerns’. Participants were mostly female (97%), average ages ranged from 51 to 64 years. The CR programmes utilised aerobic exercise and resistance training. Meta-analysis of the effect of CR on severity of angina (2 RCTs; n=85) was not possible due to the limited data presented in one of the reports. The narrative synthesis concluded that there is no evidence of an effect of CR on severity of angina symptoms. Meta-analysis of the effects of CR versus no-exercise on HRQoL were conducted at domain level of the Short Form-36 (SF-36) questionnaire (2 RCTs; n=75), and exercise capacity as measured by peak VO2 (3 RCTs; n=101). The evidence of the effect of CR versus no-exercise intervention of the SF-36 domains from the meta-analyses was classified as ‘very low certainty’, meaning we have very little confidence in the effect estimates calculated. CR versus no-exercise intervention was estimated to result in a SMD of 1.06 (95% CI -0.7 to 2.19, low certainty of evidence) for measurements of peak VO2 in favour of CR. A SMD of 1.06 is estimated to be equivalent to a 4.42 ml/kg/min change in peak VO2, which is believed to represent a clinically meaningful difference. Conclusions CR may improve exercise capacity outcomes in patients with MVA compared to controls, however our confidence in the effect estimate is limited. We remain uncertain as to the effect of CR on the severity of angina symptoms and HRQoL. High-quality, well-reported RCTs are needed to more rigorously assess the benefits and harms of exercise-based CR for adults with MVA.

Factors Contributing to Coronary Microvascular Dysfunction in Patients with Angina and Non-Obstructive Coronary Artery Disease.

Coronary microvascular dysfunction (CMD), characterised by a reduced coronary flow reserve (CFR) or an increased index of microcirculatory resistance (IMR), has received considerable attention as a cause of chest pain in recent years. However, the risks and causes of CMD remain unclear; therefore, effective treatment strategies have not yet been established. Heart failure or coronary artery disease (CAD) is a risk factor for CMD, with a higher prevalence among women. However, the other contributing factors remain unclear. In this study, we assessed the risk in patients with angina and non-obstructive coronary artery disease (ANOCA), excluding those with heart failure or organic stenosis of the coronary arteries. Furthermore, we analysed whether the risk of CMD differed according to component factors and sex. This study included 84 patients with ANOCA (36 men and 48 women; mean age, 63 years) who underwent coronary angiography and functional testing (CFT). The CFT included a spasm provocation test (SPT), followed by a coronary microvascular function test (CMVF). In the SPT, patients were mainly provoked by acetylcholine (ACh), and coronary spasm was defined as >90% transient coronary artery constriction on coronary angiography, accompanied by chest pain or ischaemic changes on electrocardiography. In 15 patients (18%) with negative ACh provocation, ergonovine maleate (EM) was administered as an additional provocative drug. In the CMVF, a pressure wire was inserted into the left anterior descending coronary artery using intravenous adenosine triphosphate, and the CFR and IMR were measured using previously described methods. A CFR < 2.0 or IMR ≥ 25 was indicative of CMD. The correlations between various laboratory indices and CMD and its components were investigated, and logistic regression analysis was performed, focusing on factors where p < 0.05. Of the 84 patients, a CFR < 2.0 was found in 22 (26%) and an IMR ≥ 25 in 40 (48%) patients, with CMD identified in 46 (55%) patients. CMD was correlated with smoking (p = 0.020) and the use of EM (p = 0.020). The factors that correlated with a CFR < 2.0 included the echocardiograph index E/e' (p = 0.013), which showed a weak but positive correlation with the CFR (r = 0.268, p = 0.013). Conversely, the factors correlated with an IMR ≥ 25 included RAS inhibitor usage (p = 0.018) and smoking (p = 0.042). Assessment of the risk of CMD according to sex revealed that smoking (p = 0.036) was the only factor associated with CMD in men, whereas the left ventricular mass index (p = 0.010) and low glycated haemoglobin levels (p = 0.012) were associated with CMD in women. Our results indicated that smoking status and EM use were associated with CMD. The risk of CMD differed between the two CMD components and sex. Although these factors should be considered when treating CMD, smoking cessation remains important. In addition, CMD assessment should be performed carefully when EM is used after ACh provocation. Further validation of our findings using prospective studies and large registries is warranted.

CORONARY MICROVASCULAR DYSFUNCTION IN PATIENTS AFTER URGENT PERCUTANEOUS CORONARY INTERVENTION DUE TO ACUTE CORONARY SYNDROME

Background. Possible cause of residual myocardial ischemia after urgent PCI during ACS is coronary microvascular dysfunction. Aim: To study the frequency of coronary microvascular dysfunction in patients who underwent urgent PCI due to ACS. Materials and methods. The study included 38 participants with ACS. These patients underwent urgent PCI. After 28 days patients underwent echocardiography with intravenous dipyridamole. Coronary microvascular dysfunction was determined by an CFR less than 2. Quality of life was measured by the severity of angina using the SF-36 and SAQ questionnaires, respectively. To compare the results of the study, a cohort of 20 patients who underwent elective PCI without coronary microvascular dysfunction (CFR≥2) were selected. Results.About 2/3 of patients had complaints of shortness of breath, as the equivalent of angina pectoris, during routine physical exertion. In 83.3% patients presence of coronary microvascular dysfunction, was proven. Quality of life due to the SAQ and SF-36 questionnaires were significantly lower among patients, who underwent urgent PCI. Conclusion.The results of the work showed that 83.3% of patients after urgent PCI for ACS were diagnosed with coronary microvascular dysfunction.

Coronary microvascular dysfunction in patients with Takotsubo syndrome

BackgroundThe pathophysiology of Takotsubo syndrome (TTS) remains incompletely understood. While coronary microvascular dysfunction (CMD) is a potential pathophysiologic mechanism, evidence is limited. ObjectivesWe sought to evaluate CMD in patients with TTS. MethodsConsecutive patients diagnosed with TTS were included and underwent coronary angiography with invasive microvascular function evaluation, including fractional flow reserve, Coronary Flow Reserve (CFR), Index of Microcirculatory Resistance (IMR), and Resistive Reserve Ratio (RRR). Patients had an echocardiography evaluation during their index admission and at approximately 6 weeks. ResultsThirty patients were included (mean age 74 ±9, 90 % female). Twenty-five patients (83 %) had at least one abnormal coronary microvascular function parameter. Abnormal parameters included CFR<2.5 in 20 patients (67 %), IMR>25 in 18 patients (60 %), and RRR<3.5 in 25 (83 %). Longer time from symptoms to angiography correlated with a higher CFR (r = 0.51, P<0.01), and had an area under the receiver operating characteristic curve of 0.793 (95 % CI 0.60-0.98) for pathologic CFR. Patients with emotional trigger had a lower rate of pathologic IMR compared with non-emotional trigger (36 % vs 81 %, p = 0.01). Follow up echocardiography performed at a median of 1.5 months (IQR 1.15-6) showed an improvement in left ventricular ejection fraction for all patients (from mean of 40 % to 57 %). ConclusionCMD was present in most patients with TTS. The role of microvascular function in TTS may vary according to the clinical presentation and RRR may be more sensitive for the diagnosis of CMD in TTS.

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.

Occult coronary microvascular dysfunction and ischemic heart disease in patients with diabetes and heart failure

BackgroundPatients with diabetes (DM) and heart failure (HF) have worse outcomes than normoglycaemic HF patients. Cardiovascular magnetic resonance (CMR) can identify ischaemic heart disease (IHD) and quantify coronary microvascular dysfunction (CMD) using myocardial perfusion reserve (MPR). We aimed to quantify extent of silent IHD and CMD in patients with DM presenting with HF. MethodsProspectively recruited outpatients undergoing assessment into the aetiology of HF underwent inline quantitative perfusion CMR for calculation of stress and rest myocardial blood flow (MBF) and MPR. Exclusions included angina or history of IHD. Patients were followed up (median 3.0 years) for major adverse cardiovascular events (MACE). ResultsFinal analysis included 343 patients (176 normoglycaemic, 84 with pre-diabetes and 83 with DM). Prevalence of silent IHD was highest in DM (31%), then pre-diabetes (20%) then normoglycaemia (17%). Stress MBF was lowest in DM (1.53±0.52), then pre-diabetes (1.59±0.54) then normoglycaemia (1.83±0.62). MPR was lowest in DM (2.37±0.85) then pre-diabetes (2.41±0.88) then normoglycaemia (2.61±0.90). During follow up 45 patients experienced at least one MACE. On univariate Cox regression analysis MPR and presence of silent IHD were both associated with MACE. However, after correction for HbA1c, age and left ventricular ejection fraction the associations were no longer significant. ConclusionsPatients with DM and HF had higher prevalence of silent IHD, more evidence of CMD and worse cardiovascular outcomes than their non-diabetic counterparts. These findings highlight the potential value of CMR for assessment of silent IHD and CMD in patients with DM presenting with HF.

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