Coronary Microvascular Function In Patients Research Articles

Coronary Sinus Reducer Improves Angina, Quality of Life, and CoronaryFlow Reserve in MicrovascularDysfunction.

Coronary microvascular dysfunction (CMD) is a common cause of angina with no obstructive coronary artery disease (ANOCA), and effective treatment options are limited. This study aims to assess the safety and efficacy of the coronary sinus (CS) Reducer (Neovasc, Inc/Shockwave Medical) for treatment of angina in patients with CMD. This Phase II trial enrolled 30 patients with ANOCA, invasively diagnosed CMD, and Canadian Cardiovascular Society (CCS) class 3 to 4 angina despite medical therapy. CMD was defined by coronary flow reserve (CFR)≤2.5 and/or≤50% increase in coronary blood flow (CBF) in response to intracoronary infusion of acetylcholine. Invasive coronary microvascular function testing was performed before and at 120days postimplantation. The primary endpoint was change in microvascular function at 120days. Secondary endpoints were changes in CCS angina class and Seattle Angina Questionnaire (SAQ) scores. Mean age was 54.8 ± 11.0 years; 67% (20/30) were women. In patients with low baseline CFR (endothelium-independent CMD), CFR increased significantly from 2.1 (1.95-2.30) to 2.7 (2.45-2.95) (n=19; P=0.0011). Patients with abnormal CBF response to acetylcholine at baseline (endothelium-dependent CMD) had an increase in CBF response to acetylcholine:-11.0% (-20.15% to 5.85%) to 11.5% (-4.82% to 39.29%) (n=11; P=0.042). There was a significant improvement in CCS angina class from 4.0 (3.25-4.0) to 2.0 (2.0-3.0) (P< 0.001) and increase in each domain of the SAQ questionnaire (P< 0.006 for all). This study demonstrates that the CS Reducer is associated with significant improvement in angina, quality of life, and coronary microvascular function in patients with CMD and may emerge as a novel therapy for patients with ANOCA.

The Impact of Bariatric Surgery on Coronary Microvascular Function Assessed Using Automated Quantitative Perfusion CMR

BackgroundCoronary microvascular function is impaired in patients with obesity, contributing to myocardial dysfunction and heart failure. Bariatric surgery decreases cardiovascular mortality and heart failure, but the mechanisms are unclear. ObjectivesThe authors studied the impact of bariatric surgery on coronary microvascular function in patients with obesity and its relationship with metabolic syndrome. MethodsFully automated quantitative perfusion cardiac magnetic resonance and metabolic markers were performed before and 6 months after bariatric surgery. ResultsCompared with age- and sex-matched healthy volunteers, 38 patients living with obesity had lower stress myocardial blood flow (MBF) (P = 0.001) and lower myocardial perfusion reserve (P < 0.001). A total of 27 participants underwent paired follow-up 6 months post-surgery. Metabolic abnormalities reduced significantly at follow-up including mean body mass index by 11 ± 3 kg/m2 (P < 0.001), glycated hemoglobin by 9 mmol/mol (Q1-Q3: 4-19 mmol/mol; P < 0.001), fasting insulin by 142 ± 131 pmol/L (P < 0.001), and hepatic fat fraction by 5.6% (Q1-Q3: 2.6%-15.0%; P < 0.001). Stress MBF increased by 0.28 mL/g/min (Q1-Q3: −0.02 to 0.75 mL/g/min; P = 0.003) and myocardial perfusion reserve by 0.13 (Q1-Q3: −0.25 to 1.10; P = 0.036). The increase in stress MBF was lower in those with preoperative type 2 diabetes mellitus (0.1 mL/g/min [Q1-Q3: −0.09 to 0.46 mL/g/min] vs 0.75 mL/g/min [Q1-Q3: 0.31-1.25 mL/g/min]; P = 0.002). Improvement in stress MBF was associated with reduction in fasting insulin (beta = −0.45 [95% CI: −0.05 to 0.90]; P = 0.03). ConclusionsCoronary microvascular function is impaired in patients with obesity, but can be improved significantly with bariatric surgery. Improvements in microvascular function are associated with improvements in insulin resistance but are attenuated in those with preoperative type 2 diabetes mellitus.

Coronary Microvascular Function Assessment using the Coronary Angiography-Derived Index of Microcirculatory Resistance in Patients with ST-segment Elevation Myocardial Infarction Undergoing Primary Percutaneous Coronary Intervention.

Studies reporting the status of coronary microvascular function in the infarct-related artery (IRA) after primary percutaneous coronary intervention (PCI) remain limited. This study utilized the coronary angiography-derived index of microcirculatory resistance (caIMR) to assess coronary microvascular function in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary PCI. We used the FlashAngio system to measure the caIMR after primary PCI in 157 patients with STEMI. The primary endpoint was the occurrence of a major adverse cardiovascular event (MACE), defined as a composite endpoint encompassing cardiac mortality, target vessel revascularization, and rehospitalization due to congestive heart failure (CHF), myocardial infarction (MI), or angina. Approximately 30% of patients diagnosed with STEMI and who experienced successful primary PCI during the study period had a caIMR in the IRA of 40. The caIMR in the IRA was significantly higher than in the reference vessel (32.9 15.8 vs. 27.4 11.1, p 0.001). The caIMR in the reference vessel of the caIMR 40 group was greater than in the caIMR 40 group (30.9 11.3 vs. 25.9 10.7, p = 0.009). Moreover, the caIMR 40 group had higher incidence rates of MACEs at 3 months (25.5% vs. 8.3%, p = 0.009) and 1 year (29.8% vs. 13.9%, p = 0.04), than in the caIMR 40 group, which were mainly driven by a higher rate of rehospitalization due to CHF, MI, or angina. A caIMR in the IRA of 40 was an independent predictor of a MACE at 3 months (hazard ratio (HR): 3.459, 95% confidence interval (CI): 1.363-8.779, p = 0.009) and 1 year (HR: 2.384, 95% CI: 1.100-5.166, p = 0.03) in patients with STEMI after primary PCI. Patients with STEMI after primary PCI often have coronary microvascular dysfunction, which is indicated by an increased caIMR in the IRA. An elevated caIMR of 40 in the IRA was associated with an increased risk of adverse outcomes in STEMI patients undergoing primary PCI.

Ranolazine for improving coronary microvascular function in patients with nonobstructive coronary artery disease: a systematic review and meta-analysis with a trial sequential analysis of randomized controlled trials.

Microvascular dysfunction in patients with nonobstructive coronary artery disease is increasingly being recognized as an important health issue. This systematic review and meta-analysis evaluated the effectiveness of ranolazine, an antianginal agent, in improving coronary microvascular function. We conducted a comprehensive literature search of the Cochrane Library, PubMed, Embase, China National Knowledge Infrastructure, the Chinese BioMedical Literature Database, and gray literature databases until September 30, 2023. The included studies were randomized controlled trials (RCTs) published in the English or Chinese languages that screened for eligibility using two independent investigators. Risk of bias was evaluated with the Cochrane Collaboration tool. Subgroup and sensitivity analyses were used to identify sources of heterogeneity. Meta-analysis was performed using RevMan version 5.4 (Cochrane) and Stata version 16.0 (StataCorp). From 1,470 citations, 8 RCTs involving 379 participants were included in this analysis. Our findings showed that ranolazine increased coronary flow reserve (CFR) over an 8 to 12-week follow-up period [standardized mean difference =1.16; 95% confidence interval (CI): 0.4-1.89; P=0.002]. Ranolazine increased the global myocardial perfusion reserve index (MPRI) [weighted mean difference (WMD) =0.18; 95% CI: 0.07-0.29; P=0.002] and the midsubendocardial MPRI (WMD =0.10; 95% CI: 0.02-0.19; P=0.02). Moreover, ranolazine improved 3 of the 5 Seattle Angina Questionnaire scores, namely, physical functioning (WMD =4.89; 95% CI: 0.14 to 9.64; P=0.04), angina stability (WMD =17.31; 95% CI: 7.13-27.49; P=0.0009), and quality of life (WMD =10.11; 95% CI: 3.57-16.65; P=0.0003). Trial sequential analysis showed that the meta-analysis of angina stability and quality of life scores had a sufficient sample size and statistical power. Our analysis suggests that ranolazine is associated with improvements in CFR, myocardial perfusion, and the Seattle Angina Questionnaire scores in patients with nonobstructive coronary artery disease. However, further large-scale RCTs with long-term follow-up are recommended to validate these findings and provide a more comprehensive understanding of the effects of ranolazine on coronary microvascular function.

Role of Protein Kinase C in Metabolic Regulation of Coronary Endothelial Small Conductance Calcium-Activated Potassium Channels.

Small conductance calcium-activated potassium (SK) channels are largely responsible for endothelium-dependent coronary arteriolar relaxation. Endothelial SK channels are downregulated by the reduced form of nicotinamide adenine dinucleotide (NADH), which is increased in the setting of diabetes, yet the mechanisms of these changes are unclear. PKC (protein kinase C) is an important mediator of diabetes-induced coronary endothelial dysfunction. Thus, we aimed to determine whether NADH signaling downregulates endothelial SK channel function via PKC. SK channel currents of human coronary artery endothelial cells were measured by whole cell patch clamp method in the presence/absence of NADH, PKC activator phorbol 12-myristate 13-acetate, PKC inhibitors, or endothelial PKCα/PKCβ knockdown by using small interfering RNA. Human coronary arteriolar reactivity in response to the selective SK activator NS309 was measured by vessel myography in the presence of NADH and PKCβ inhibitor LY333531. NADH (30-300 μmol/L) or PKC activator phorbol 12-myristate 13-acetate (30-300 nmol/L) reduced endothelial SK current density, whereas the selective PKCᵦ inhibitor LY333531 significantly reversed the NADH-induced SK channel inhibition. PKCβ small interfering RNA, but not PKCα small interfering RNA, significantly prevented the NADH- and phorbol 12-myristate 13-acetate-induced SK inhibition. Incubation of human coronary artery endothelial cells with NADH significantly increased endothelial PKC activity and PKCβ expression and activation. Treating vessels with NADH decreased coronary arteriolar relaxation in response to the selective SK activator NS309, and this inhibitive effect was blocked by coadministration with PKCβ inhibitor LY333531. NADH-induced inhibition of endothelial SK channel function is mediated via PKCβ. These findings may provide insight into novel therapeutic strategies to preserve coronary microvascular function in patients with metabolic syndrome and coronary disease.

Increased Coronary Contraction to Thromboxane A2 in Cardiac Surgery Patients With Poorly Controlled Hypertension

IntroductionCardioplegia and cardiopulmonary bypass (CP/CPB) alters coronary arteriolar response to thromboxane A2 (TXA2) in patients undergoing cardiac surgery. Comorbidities, including hypertension (HTN), can further alter coronary vasomotor tone. This study investigates the effects of HTN on coronary arteriolar response to TXA2 pre and post-CP/CPB and cardiac surgery. Materials and methodsCoronary arterioles pre and post-CP/CPB were dissected from atrial tissue samples in patients with no HTN (NH, n = 9), well-controlled HTN (WC, n = 12), or uncontrolled HTN (UC, n = 12). In-vitro coronary microvascular reactivity was examined in the presence of TXA2 analog U46619 (10−9-10−4M). Protein expression of TXA2 receptor in the harvested right atrial tissue samples were measured by immunoblotting. ResultsTXA2 analog U46619 induced dose-dependent contractile responses of coronary arterioles in all groups. Pre-CPB contractile responses to U46619 were significantly increased in microvessels in the UC group compared to the NH group (P < 0.05). The pre-CP/CPB contractile responses of coronary arterioles were significantly diminished post-CP/CPB among the three groups (P < 0.05), but there remained an increased contractile response in the microvessels of the UC group compared to the WC and NH groups (P < 0.05). There were no significant differences in U46619-induced vasomotor tone between patients in the NH and WC groups (P > 0.05). There were no differences in expression of TXA2R among groups. ConclusionsPoorly controlled HTN is associated with increased contractile response of coronary arterioles to TXA2. This alteration may contribute to worsened recovery of coronary microvascular function in patients with poorly controlled HTN after CP/CPB and cardiac surgery.

TCT-204 Effectiveness of Coronary Sinus Reducer Implantation on Coronary Microvascular Function in Patients With Angina and Nonobstructive Coronary Artery Disease

TCT-204 Effectiveness of Coronary Sinus Reducer Implantation on Coronary Microvascular Function in Patients With Angina and Nonobstructive Coronary Artery Disease

Gut microbiota-derived metabolite trimethylamine N-oxide and biomarkers of inflammation are linked to endothelial and coronary microvascular function in patients with inflammatory bowel disease.

Inflammatory bowel disease (IBD), which is an umbrella term used for ulcerative colitis (UC) and Crohn's disease (CD), is associated with an increased risk for atherosclerotic cardiovascular disease (CVD). We aimed to investigate the association of local and systemic biomarkers of inflammation and gut microbiota-derived metabolite trimethylamine N-oxide (TMAO) with endothelial and coronary microvascular dysfunction in IBD. A total of 56 patients with IBD (20 with UC and 36 with CD) and 34 age and gender matched controls were included. For all participants, samples were collected to analyze faecal calprotectin, and TMAO concentrations. Ultrasound-based examinations were done to measure flow-mediated vasodilatation (FMD) and coronary flow velocity reserve (CFVR). Patients with IBD had lower CFVR (2.07 (1.82-2.40)) and FMD (8.7±3.7) as compared to controls (2.30 (2.07-2.74), p=0.005 and 11.9±6.8, p=0.03). In patients with IBD, TMAO concentration (r=-0.30, p=0.03), C-reactive protein (r=-0.29, p=0.03) and WBC count (r=-0.37, p=0.006) had a significant negative correlation with CFVR, and TMAO (β=-0.27, 95% CI: -0.23 to -0.02) and WBC count (β=-0.31, 95% CI: -0.56 to -0.06) were significant predictors of CFVR after multivariate adjustment. None of the biomarkers of inflammation or TMAO showed significant correlations with FMD. In patients with UC, TMAO showed a significant correlation with both CFVR (r=-0.55, p=0.01) and FMD (r=-0.60, p=0.005) while only WBC count had a statistically significant correlation with CFVR (r=-0.49, p=0.004) in patients with CD. Gut microbiota-derived metabolite TMAO and biomarkers of systemic inflammation are associated with measures of endothelial/coronary microvascular dysfunction in patients with IBD.

Combining body mass index with waist circumference to assess coronary microvascular function in patients with non-obstructive coronary artery disease

BackgroundCoronary microvascular dysfunction (CMD) may precede clinically overt coronary artery disease (CAD). Overall and central obesity (CO) are major risk factors for CAD. This study sought to investigate the subclinical significance of body adiposity patterns based on the CMD risk. MethodsA total of 128 patients with non-obstructive CAD were prospectively enrolled. Patients were categorized into 4 anthropometric groups: normal weight and non-CO (NWNCO, n = 41), normal weight and CO (NWCO, n = 20), excess weight and non-CO (EWNCO, n = 26), and excess weight and CO (EWCO, n = 41). Patients underwent rest/stress electrocardiography-gated 13N-ammonia positron emission tomography to measure absolute myocardial blood flow (MBF), myocardial flow reserve (MFR), hemodynamic parameters, and cardiac function. ResultsResting MBF did not differ between groups (P = .36). Compared with the NWNCO group, hyperemic MBF and MFR were significantly lower in the NWCO and EWCO groups. Notably, patients with NWCO presented the lowest hyperemic MBF and MFR and the highest incidence of CMD. Waist circumference was an independent risk factor for CMD (OR 1.05, 95% CI 1.01 to 1.10, P = .02). ConclusionIn patients with non-obstructive CAD, CO may be associated with an increased risk of CMD to better fit the study findings which did not assess management or monitoring of MBF and MFR.

Association Between Insulin Resistance, Oxidative Stress, Sympathetic Activity and Coronary Microvascular Function in Patients With Early Stage Impaired Glucose Metabolism.

Although acute hyperglycemia and insulin resistance (IR) are risk factors for atherosclerosis development through oxidative stress and sympathetic activation in diabetes mellitus, the association of these factors with coronary microvascular function in the early diabetic stage remains controversial.Methods and Results: Using transthoracic echocardiography, coronary flow velocity (CFV) and its reserve (CFVR) as parameters of coronary microvascular function were measured before and 1 h after an oral glucose tolerance test (OGTT) in 40 patients (aged 59±12 years) without diagnosed diabetes mellitus or coronary artery disease. Plasma glucose, insulin and thiobarbituric acid reactive substance (TBARS; an oxidative stress marker) were measured during the OGTT. IR was evaluated as homeostasis model assessment of IR (HOMA-R). Sympathetic activity was evaluated by using plasma catecholamines after OGTT. CFVR decreased after an OGTT (P<0.0001) mainly because of an increased baseline CFV (P<0.0001). Although the change in CFVR was not associated with the change in TBARS and catecholamines, it was independently associated with HOMA-R on the multivariate regression analysis (β=-0.40, P=0.01). Another multivariate regression analysis revealed that change in baseline CFV was independently associated with HOMA-R (β=0.35, P=0.03). IR, rather than oxidative stress and sympathetic activity, was associated with an increase in baseline CFV and a decline in CFVR during acute hyperglycemia. IR might play an important role in increased myocardial oxygen demand and coronary microvascular dysfunction.

Doppler Echocardiography Assessment of Coronary Microvascular Function in Patients With Angina and No Obstructive Coronary Artery Disease.

Echocardiographic evaluation is an essential part of the diagnostic work-up in patients with known or suspected cardiovascular disease. Transthoracic Doppler echocardiography (TTDE) enables straightforward and reliable visualization of flow in the left anterior descending artery. In the absence of obstructive coronary artery disease, low TTDE-derived coronary flow velocity reserve (CFVR) is considered a marker of coronary microvascular dysfunction (CMD). TTDE CFVR is free from ionizing radiation and widely available, utilizing high-frequency transducers, pharmacologic vasodilator stress, and pulsed-wave Doppler quantification of diastolic peak flow velocities. European Society of Cardiology guidelines recommend TTDE CFVR evaluation only following preceding anatomic invasive or non-invasive coronary imaging excluding obstructive CAD. Accordingly, clinical use of TTDE CFVR is limited and CMD frequently goes undiagnosed. An evolving body of evidence underlines that low CFVR is an important and robust predictor of adverse prognosis and continuing symptoms in angina patients both with and without obstructive CAD. The majority of angina patients have no obstructive CAD, particularly among women. This has led to the suggestion that there may be a gender-specific female atherosclerotic phenotype with less epicardial obstruction, and a low CFVR signifying CMD instead. Nevertheless, available evidence indicates low CFVR is an equally important prognostic marker in both men and women. In this review, TTDE CFVR was evaluated regarding indication, practical and technical aspects, and interpretation of results. Association with symptoms and prognosis, comparison with alternative invasive and non-invasive imaging modalities, and possible interventions in angina patients with low CFVR were discussed, and key research questions were proposed.

Effect of SGLT2 inhibition on coronary microvascular function in patients with type 2 diabetes

Abstract Background Treatment with sodium-glucose cotransporter 2 (SGLT2) inhibitor reduces risk of cardiovascular death and heart failure but the underlying mechanisms remain poorly understood. It has been suggested that a shift in fuel source in the myocardium from glucose and free fatty acids to the more energy efficient ketogenesis reduces oxidative stress involved in coronary microvascular damage, leading to improved coronary microvascular function. Purpose To test the hypothesis that treatment with the SGLT2 inhibitor empagliflozin improves non-endothelial dependent coronary microvascular function. Methods We included 26 patients with type 2 diabetes in a double blinded, placebo-controlled cross-over study. Participants were treated with empagliflozin 25 mg and placebo for 12 weeks, interrupted by 2 weeks wash-out period. The primary outcome was change in coronary microvascular function, assessed as coronary flow velocity reserve (CFVR) and measured with transthoracic doppler echocardiography. Secondary endpoints were change in echocardiographic parameters of cardiac systolic function and 184 cardiovascular protein biomarkers. Results Nineteen patients completed both study periods according to protocol. There was a significant weight loss and reduction in Hba1c after empagliflozin treatment (table). We found no improvement in CFVR and parameters of cardiac systolic function. We observed a general tendency of reduction in level of cardiovascular biomarkers after empagliflozin treatment (figure) with significant difference between empagliflozin and placebo for 27 proteins, including IL18, ST2, YKL40, ACE2 and leptin. Conclusions Despite a significant weight loss and reduction in Hba1c after empagliflozin treatment, we found no effect on non-endothelial dependent coronary microvascular function in patients with type 2 diabetes mellitus. Improvement in multiple biomarkers may indicate underlying mechanisms but need confirmation in larger studies. Funding Acknowledgement Type of funding sources: Foundation. Main funding source(s): The Danish Council for Independent Research Table 1. Change in outcome parametersFigure 1. Change in biomarker levels

Coronary microvascular function in patients with angina with no obstructive coronary artery disease-What factors affect it clinically or angiographically?

Abstract Background In the clinical setting, we have often experienced patients with angina with no obstructive coronary artery disease (ANOCA), and it has been proposed that the presence of coronary microvascular dysfunction (CMD) play a pivotal role in the pathogenesis of ANOCA. Thus, it is important to assess coronary microvascular function (CMF). However, it has not been clarified what clinical factors or lesion characteristics on coronary angiography (CAG) affect CMF. Thus, we investigated the relationship between CMF and clinical factors or lesion characteristics on CAG in patients with ANOCA. Methods Thirty-four patients with chest pain, who underwent CAG, spasm provocation test (SPT) and CMF test, were enrolled. We excluded patients who had moderate coronary stenosis (% stenosis &amp;gt;30%). In the SPT with acetylcholine for left coronary artery and right coronary artery (RCA), the coronary spasm was defined as &amp;gt;90% narrowing of coronary artery on CAG accompanied with chest symptoms and/or ST-T changes on ECG during SPT, and coronary microvascular spasm (MVS) was defined as ≤90% narrowing of coronary artery on CAG with accompanied with chest pain and ST-T changes during SPT. In each coronary artery, the presences of atherosclerosis (20%≤%stenosis≤30%), focal spasm (spasm occurred within one segment of AHA classification), diffuse spasm (spasm occurred over two segments of AHA classification) and MVS, were checked. In the CMF test with a pressure-wire during adenosine triphosphate infusion, the index of microvascular resistance (IMR) was measured. IMR values were obtained in 34 of the left anterior descending coronary artery (LAD) and 12 in RCA. In each patient, conventional coronary risk factors, blood chemical parameters, peripheral endothelial function such as flow-mediated dilation (FMD) of brachial artery and left ventricular mass index (LVMI) were checked. Results In 34 patients, clinical factors including blood chemical parameters, FMD and LVMI, except for smoking status did not affect IMR values on LAD. Only the smoking status was associated with IMR values as follows: median IMR values were 44, 22 and 25 in current smokers (n=5), past smokers (n=8) and never smokers (n=21, p=0.03), respectively. In 46 coronary arteries, the presence of atherosclerosis, the type of the coronary spasm, such as focal and diffuse spasm and MVS, did not affect the IMR values, however, it was significantly higher in the RCA (median 38) than that in the LAD (median 26, p=0.02). Conclusion These results suggest that smoking status affected CMF in patients with ANOCA, suggesting the possibility of improvement of CMF by stop smoking in such patients. In addition, in the assessment of CMF, it may be important to take into account which coronary artery being evaluated. Funding Acknowledgement Type of funding sources: None.

Effects of Oral Drugs on Coronary Microvascular Function in Patients Without Significant Stenosis of Epicardial Coronary Arteries: A Systematic Review and Meta-Analysis of Coronary Flow Reserve

Objective: This study aims to investigate the impact of cardiovascular medications on the coronary flow reserve (CFR) in patients without obstructive coronary artery disease (CAD).Methods: We searched PubMed, EMBASE, and Cochrane databases from inception to 15 November 2019. Studies were included if they reported CFR from baseline to follow-up after oral drug therapy of patients without obstructive CAD. Data was pooled using random-effects modeling. The primary outcome was change in CFR from baseline to follow-up after oral drug therapy.Results: A total of 46 studies including 845 subjects were included in this study. Relative to baseline, the CFR was improved by angiotensin-converting enzymes (ACEIs), aldosterone receptor antagonists (ARBs) [standard mean difference (SMD): 1.12; 95% CI: 0.77–1.47], and statins treatments (SMD: 0.61; 95%CI: 0.36–0.85). Six to 12 months of calcium channel blocker (CCB) treatments improved CFR (SMD: 1.04; 95% CI: 0.51–1.58). Beta-blocker (SMD: 0.24; 95% CI: −0.39–0.88) and ranolazine treatment (SMD: 0.31; 95% CI: −0.39–1.01) were not associated with improved CFR.Conclusions: Therapy with ACEIs, ARBs, and statins was associated with improved CFR in patients with confirmed or suspicious CMD. CCBs also improved CFR among patients followed for 6–12 months. Beta-blocker and ranolazine had no impact on CFR.

Acute alterations in glucose homeostasis impact coronary microvascular function in patients presenting with ST-segment elevation myocardial infarction.

BackgroundMicrovascular dysfunction in the setting of ST-segment myocardial infarction (STEMI) is thought to be related to stress-related metabolic changes, including acute glucose intolerance. The aim of this study was to assess the relationship between admission glucose levels and microvascular function in non-diabetic STEMI patients.Methods92 consecutive patients with a first anterior-wall STEMI treated with primary percutaneous coronary intervention (PPCI) were enrolled. Blood glucose levels were determined immediately prior to PPCI. After successful PPCI, at 1‑week and 6‑month follow-up, Doppler flow was measured in culprit and reference coronary arteries to calculate coronary flow velocity reserve (CFVR), baseline (BMR) and hyperaemic (HMR) microvascular resistance.ResultsThe median admission glucose was 8.3 (7.2–9.6) mmol/l respectively 149.4 mg/dl [129.6–172.8] and was significantly associated with peak troponin T (standardised beta coefficient [std beta] = 0.281; p = 0.043). Multivariate analysis revealed that increasing glucose levels were significantly associated with a decrease in reference vessel CFVR (std beta = −0.313; p = 0.002), dictated by an increase in rest average peak velocity (APV) (std beta = 0.216; p = 0.033), due to a decreasing BMR (std beta = −0.225; p = 0.038) in the acute setting after PPCI. These associations disappeared at follow-up. These associations were not found for the infarct-related artery.ConclusionElevated admission glucose levels are associated with impaired microvascular function assessed directly after PPCI in first anterior-wall STEMI. This influence of glucose levels is an acute phenomenon and contributes to microvascular dysfunction through alterations in resting flow and baseline microvascular resistance.

Coronary microvascular dysfunction in patients with acute coronary syndrome and no obstructive coronary artery disease

Between 10 and 15% of patients admitted for non-ST-segment elevation acute coronary syndrome (NSTE-ACS) show no obstructive coronary artery disease (NO-CAD) at angiography. Coronary microvascular spasm is a possible mechanism of the syndrome, but there are scarce data about coronary microvascular function in these patients. To assess coronary microvascular function in patients with NSTE-ACS and NO-CAD. We studied 30 patients (67 ± 10years, 19 female) with NSTE-ACS and NO-CAD. Specific causes of NSTE-ACS presentation (e.g., variant angina, takotsubo disease, tachyarrhythmias, etc.) were excluded. Coronary blood flow (CBF) velocity response to IV ergonovine (6µg/kg up to a maximal dose of 400µg) was evaluated before discharge by transthoracic Doppler echocardiography. CBF response to IV adenosine (140μg/kg/min) and cold pressor test (CPT) was also assessed after 1month. Ten age- and sex-matched patients with non-cardiac chest pain served as controls. Vasoactive tests were repeated after 12months in 10 NSTE-ACS patients. The ergonovine/basal CBF velocity ratio was 0.79 ± 0.09 and 0.99 ± 0.01 in patients and controls, respectively (p < 0.001). The adenosine/basal CBF velocity ratio was 1.46 ± 0.2 and 3.25 ± 1.2 in patients and controls, respectively (p < 0.001), and the CPT/basal CBF velocity ratio was 1.36 ± 0.2 and 2.43 ± 0.3 in the 2 groups, respectively (p < 0.001). In 10 patients assessed after 12months, CBF velocity responses to ergonovine, adenosine, and CPT were found to be unchanged. Patients with NSTE-ACS and NO-CAD exhibit a significant coronary dysfunction, which seems to involve both an increased constrictor reactivity, likely mainly involving coronary microcirculation, and a reduced microvascular dilator function, both persisting at 12-month follow-up.

Lower Circulating Omega-3 Polyunsaturated Fatty Acids Are Associated with Coronary Microvascular Dysfunction Evaluated by Hyperemic Microvascular Resistance in Patients with Stable Coronary Artery Disease.

The consumption of omega-3 polyunsaturated fatty acids (PUFAs) reduces the incidence of cardiovascular events and sudden cardiac death. Coronary microvascular dysfunction (CMD) is a predictor of cardiac mortality, but little information is known on the relationship between CMD and omega-3 PUFAs. This study aimed to identify the relationship between the serum levels of omega-3 PUFAs and the CMD evaluated by the hyperemic microvascular resistance index (hMVRI) to assess coronary microvascular function in patients with stable coronary artery disease (CAD).Intracoronary physiological variables (fractional flow reserve (FFR), hMVRI, mean distal coronary pressure (Pd), and average peak velocity (APV)) were measured in 108 patients. These parameters were evaluated in 150 coronary arteries with stenosis of intermediate severity and without significant ischemia (FFR > 0.80). The PUFA levels and atherosclerotic risk factors were also measured. Univariate analysis shows that hMVRI was negatively correlated with eicosapentaenoic acid (EPA)/arachidonic acid (AA) ratio (β = -0.31, P = 0.001) and EPA (β = -0.25, P = 0.009) and was positively correlated with dihomo-γ-linolenic acid (β = 0.26, P = 0.006). Multivariate regression analysis shows that the EPA/AA ratio was the only independent determinant of hMVRI (β = -0.234, SE = 0.231, P = 0.024). Furthermore, hMVRI decreased significantly from the lowest to highest tertiles of the EPA/AA ratio (P = 0.007). The EPA/AA ratio was positively correlated with APV at hyperemia (β = 0.26, P = 0.008) but not with Pd at hyperemia.A lower serum EPA/AA ratio may cause CMD in patients with stable CAD.

RESULTS FROM THE MICROVASCULAR ASSESSMENT OF RANOLAZINE IN NON-OBSTRUCTIVE ATHEROSCLEROSIS (MARINA): A DOUBLE-BLINDED RANDOMIZED CONTROLLED TRIAL

We hypothesized that, by inhibiting myocardial late Na+ current, Ranolazine improves angina symptoms, exercise tolerance and coronary microvascular function in patients with microvascular ischemia. In this pilot randomized, double-blinded, placebo-controlled trial, 24 patients with angina symptoms

Impairment of coronary microvascular function in patients with Primary Biliary Cholangitis

Impairment of coronary microvascular function in patients with Primary Biliary Cholangitis

Effect of chronic inflammation on coronary arteries in renal amyloidosis: More than renal dysfunction

Effect of chronic inflammation on coronary arteries in renal amyloidosis: More than renal dysfunction