Asymmetric Dimethylarginine Is Associated with the Phenomenon of Coronary Slow Flow in Patients with Nonvalvular Atrial Fibrillation.

INTRODUCTION: Coronary slow flow phenomena (CSFP) are associated with endothelial and blood component abnormalities in coronary arteries. Asymmetric dimethylarginine (ADMA) can damage the endothelium of the heart or blood vessels in patients with non-valvular atrial fibrillation (NVAF), causing changes in levels of biological indicators. Our aim was to analyze the relationship between ADMA and CSFP in NVAF patients. METHODS: We consecutively enrolled 134 patients diagnosed with NVAF and underwent coronary angiography, 50 control patients without a history of atrial fibrillation and with normal coronary angiographic flow were included at the same time. Based on the corrected TIMI frame count (CTFC), the NVAF patients were categorized into two groups, CTFC ≤27 frames and CTFC >27 frames. Plasma ADMA, P-selectin (p-sel), von Willebrand factor (vWF), D-dimer (D-Di), plasminogen activator inhibitor 1 (PAI-1), and nitric oxide (NO) were detected by ELISA in the different groups. RESULTS: We found that plasma ADMA levels were significantly higher among NVAF patients in the CTFC >27 grade group compared with the control or CTFC ≤27 group. In addition, the levels of blood cells and endothelium-related biomarkers (NO, P-selectin, vWF, D-Di, and PAI-1) were significantly altered and correlated with ADMA levels. Multifactorial analysis showed that plasma ADMA (odd ratio [OR; 95% CI]: 1.65 [1.21-2.43], p < 0.001) and left atrial internal diameter (OR [95% CI]: 1.04 [1.02, 1.1], p < 0.001) could be used as independent risk factors for the development of CSFP in patients with NVAF. The ROC curves of ADMA can predict the development of CSFP in NVAF patients. The minimum diagnostic concentration for the development of CSFP in patients was 2.31 µmol/L. CONCLUSION: Our study demonstrated that CSFP in NVAF patients was associated with high levels of ADMA and left atrial internal diameter. Therefore, aggressive preoperative detection and evaluation of ADMA and left atrial internal diameter can help deal with the intraoperative presence of CSFP.

Epicardial fat volume is associated with primary coronary slow-flow phenomenon in patients with severe aortic stenosis undergoing transcatheter valve implantation.

BACKGROUND: Primary coronary slow flow (CSF) is defined as delayed opacification of the distal epicardial vasculature during coronary angiography in the absence of relevant coronary artery stenoses. Microvascular disease is thought to be the underlying cause of this pathology. Epicardial fat tissue (EFT) is an active endocrine organ directly surrounding the coronary arteries that provides pro-inflammatory factors to the adjacent tissue by paracrine and vasocrine mechanisms. The aim of the present study was to investigate a potential association between EFT and primary CSF and whether EFT can predict the presence of primary CSF. METHODS: Between 2016 and 2017, n = 88 patients with high-grade aortic stenosis who were planned for transcatheter aortic valve implantation (TAVI) were included in this retrospective study. EFT volume was measured by pre-TAVI computed tomography (CT) using dedicated software. The presence of primary CSF was defined based on the TIMI frame count from the pre-TAVI coronary angiograms. RESULTS: Thirty-nine of 88 TAVI patients had CSF (44.3%). EFT volume was markedly higher in patients with CSF (142 ml [IQR 107-180] vs. 113 ml [IQR 89-147]; p = 0.009) and was strongly associated with the presence of CSF (OR 1.012 [95%CI 1.002-1.021]; p = 0.014). After adjustment, EFT volume was still an independent predictor of CSF (OR 1.016 [95%CI 1.004-1.026]; p = 0.009). CONCLUSION: Primary CSF was independently associated with increased EFT volume. Further studies are needed to validate this finding and elucidate whether a causal relationship exists.

Uric acid to albumin ratio as a novel predictor for coronary slow flow phenomenon in patients with chronic coronary syndrome and non-obstructive coronary arteries.

BACKGROUND: The plasma uric acid to albumin ratio (UAR) is considered as a novel indicator for Inflammation. However, the association between UAR and coronary slow flow phenomenon (CSFP) remains unclear. METHODS: A total of 1328 individuals with chronic coronary syndrome (CCS) receiving coronary angiography (CAG) and found no obvious obstructive stenosis (< 40%) were included in this study. 79 individuals developed CSFP and were divided into CSFP group. The 1:2 age-matched patients with normal coronary blood flow were allocated to the control group (n = 158). The clinical characteristics, laboratory parameters including uric acid, albumin ratio, UAR and the angiographic characteristics were compared between the two groups. RESULTS: Patients with CSFP had a higher level of uric acid (392.3 ± 85.3 vs. 273.8 ± 71.5, P < 0.001), UAR (10.7 ± 2.2 vs. 7.2 ± 1.9, P < 0.001), but a lower level of plasma albumin (36.9 ± 4.2 vs. 38.5 ± 3.6, P = 0.003). Moreover, UAR increased as the numbers of vessels involved in CSFP increased. The logistic regression analysis demonstrated that UAR was independent predictors for CSFP. The Receiver operating characteristic (ROC) curve analysis showed that when UAR was more than 7.9, the AUC was 0.883 (95% CI: 0.840-0.927, p < 0.001), with the sensitivity and specificity were 78.2% and 88.2% respectively. CONCLUSION: Combined uric acid with plasma albumin, UAR could serve as an independent predictor for CSFP.

Predictors of non-obstructive coronary slow flow in poorly controlled type 2 diabetes mellitus: a cross-sectional study.

BACKGROUND: Coronary slow flow (CSF) can occur due to various factors, such as inflammation, small vessel disease, endothelial dysfunction, and inadequate glucose control. However, the exact pathological mechanisms behind CSF remain incompletely understood. The objective of this study was to identify the risk factors associated with slow coronary flow in individuals with Type 2 Diabetes Mellitus (T2DM) who have non-obstructive coronary artery disease (CAD) and experience CSF. METHODS: We conducted a prospective cohort study involving 120 patients with T2DM who were referred for invasive coronary angiography due to typical chest pain or inconclusive results from non-invasive tests for myocardial ischemia. Using a 2 × 2 design, we categorized patients into groups based on their glycemic control (adequate or poor) and the presence of CSF (yes or no), defined by a TIMI frame count > 27. All patients had non-obstructive CAD, characterized by diameter stenosis of less than 40%. We identified many variables associated with CSF. RESULTS: Our investigation revealed no significant differences in age, sex, family history of coronary artery disease, ECG ischemia abnormalities, or echocardiographic (ECHO) data between the groups. In patients with adequate glycemic control, hypertension increased the risk of CSF by 5.33 times, smoking by 3.2 times, while dyslipidemia decreased the risk by 0.142. Additionally, hematocrit increased the risk by 2.3, and the platelet-to-lymphocyte ratio (PLR) increased the risk by 1.053. Among patients with poor glycemic control, hematocrit increased the risk by 2.63, and the Neutrophil-to-Lymphocyte Ratio (NLR) by 24.6. Notably, NLR was positively correlated with glycemic control parameters in T2DM patients with CSF. CONCLUSIONS: In T2DM patients with CSF, various factors strongly correlate with glycemic control parameters and can be employed to predict the likelihood of CSF. These factors encompass hypertension, smoking, increased body mass index (BMI), elevated platelet count, hematocrit, NLR, PLR, and C-reactive protein (CRP). TRIAL REGISTRATION: Registry: ZU-IRB (ZU-IRB#9419-3-4-2022), Registered on: 3 April 2022, Email: IRB_123@medicine.zu.edu.eg.

Coronary Slow-Flow Phenomenon in Takotsubo Syndrome: The Prevalence, Clinical Determinants, and Long-Term Prognostic Impact.

Patients with takotsubo syndrome (TTS) may present coronary slow flow (CSF) in angiography performed in the acute myocardial infarction (MI). However, the detailed clinical relevance and its long-term impact remain poorly understood. Among 7771 MI patients hospitalized between 2012 and 2019, TTS was identified in 82 (1.1%) subjects. The epicardial blood flow was assessed with thrombolysis in myocardial infarction (TIMI) scale and corrected TIMI frame count (TFC), whereas myocardial perfusion with TIMI myocardial perfusion grade (TMPG). CSF was defined as TIMI-2 or corrected TFC > 27 frames in at least one epicardial vessel. CSF was identified in 33 (40.2%) TTS patients. In the CSF-TTS versus normal-flow-TTS group, lower values of left ventricular ejection fraction on admission (33.5 (25-40) vs. 40 (35-45)%, p = 0.019), more frequent midventricular TTS (27.3 vs. 8.2%, p = 0.020) and the coexistence of both physical and emotional triggers (9.1 vs. 0%, p = 0.032) were noted. Within a median observation of 55 months, higher all-cause mortality was found in CSF-TTS compared with normal-flow TTS (30.3 vs. 10.2%, p = 0.024). CSF was identified as an independent predictor of long-term mortality (hazard ratio 10.09, 95% confidence interval 2.12-48.00, p = 0.004). CSF identified in two-fifths of TTS patients was associated with unfavorable long-term outcomes.

A Cautionary Tale of Hypertrophic Cardiomyopathy-From "Benign" Left Ventricular Hypertrophy to Stroke, Atrial Fibrillation, and Molecular Genetic Diagnostics: A Case Report and Review of Literature.

This case report concerns a 48-year-old man with a history of ischemic stroke at the age of 41 who reported cardiac hypertrophy, registered in his twenties when explained by increased physical activity. Family history was positive for a mother with permanent atrial fibrillation from her mid-thirties. At the age of 44, he had a first episode of persistent atrial fibrillation, accompanied by left atrial thrombosis while on a direct oral anticoagulant. He presented at our clinic at the age of 45 with another episode of persistent atrial fibrillation and decompensated heart failure. Echocardiography revealed a dilated left atrium, reduced left ventricular ejection fraction, and an asymmetric left ventricular hypertrophy. Cardiac magnetic resonance was positive for a cardiomyopathy with diffuse fibrosis, while slow-flow phenomenon was present on coronary angiography. Genetic testing by whole-exome sequencing revealed three variants in the patient, c.309C > A, p.His103Gln in the ACTC1 gene, c.116T > G, p.Leu39Ter in the PLN gene, and c.5827C > T, p.His1943Tyr in the SCN5A gene, the first two associated with hypertrophic cardiomyopathy and the latter possibly with familial atrial fibrillation. This case illustrates the need for advanced diagnostics in unexplained left ventricular hypertrophy, as hypertrophic cardiomyopathy is often overlooked, leading to potentially debilitating health consequences.

Emerging Predictors by Non-HDL-C/HDL-C Ratio and Novel Biomarkers for Coronary Slow Flow Phenomenon.

The coronary slow-flow (CSF) phenomenon is a condition characterized by delayed coronary opacification during diagnostic angiography without the presence of epicardial coronary artery disease. This mini-review explores various emerging predictors and biomarkers associated with CSF, aiming to address the potential diagnostic tools. A comprehensive analysis of recent studies has investigated different biomarkers, including growth differentiation factor 15, galectin 3, microRNA (miRNA)-22, miRNA-155, interleukin 34, soluble vascular cell adhesion molecule-1, long non-coding RNA, plasma choline, adropin, and lipid markers non-high-density lipoprotein cholesterol (HDL-C)/HDL-C ratio to enhance understanding and predict CSF. Additionally, we have summarizes the major findings and significant limitations observed in various studies on CSF biomarkers. The implications of these findings suggest significant advancements in personalized treatment strategies and improved prognostic outcomes for patients exhibiting CSF.

Comparison of the Effect of Non-HDL-C/HDL-C Ratio on Coronary Slow Flow with Other Non-Traditional Lipid Markers.

Background: Coronary slow flow (CSF) is a microvascular disease characterized by delayed opacification of the epicardial coronary arteries during angiography. The main pathogenesis of CSF is endothelial dysfunction caused by diffuse atherosclerosis. Dyslipidemia is one of the primary factors raising the risk of atherosclerosis. Compared to conventional lipid profiles, non-traditional lipid profiles more accurately reflect dyslipidemic status. In this work, we compared the non-high density lipoprotein-cholesterol (HDL-C)/HDL-C ratio (NHHR) with other conventional and non-conventional lipid profiles in order to determine its impact on CSF. Methods: A total of 9112 subjects who underwent coronary angiography were screened retrospectively, of whom 130 subjects with CSF and 130 subjects with normal CF were included. Multivariate regression analysis was used to identify independent predictors of CSF. Additionally, in order to predict CSF, the diagnostic accuracies of NHHR and other non-traditional lipid profiles were examined. Results: There were significantly higher non-traditional lipid profiles in the CSF group (all p < 0.001). Compared to other non-traditional lipid profiles, NHHR had a stronger association with thrombolysis in myocardial infarction frame count (r = 0.3593, p < 0.0001). In addition to NHHR, non-HDL-C, Castelli's risk index-II, atherogenic index of plasma, plasma glucose, dyslipidemia, smoking, and body mass index were identified as independent predictors of CSF. The ability of NHHR to detect CSF was superior to other non-traditional lipid profiles (area under the curve: 0.785; confidence interval: 0.730-0.840; p < 0.001). Conclusions: NHHR was found to be a potent and reliable predictor of CSF. This indicates that NHHR can be used as a reliable biomarker for risk stratification of CSF.

Long-Term Change in Flow Rates in Patients with Coronary Slow Flow.

INTRODUCTION: Coronary slow flow (CSF) is a condition characterized by impaired blood flow rates in the coronary arteries. It can result in severe cardiovascular outcomes. There is no sufficient evidence regarding the certain etiology and reversibility of slow flow patterns and changes in frame counts with long-term management. METHODS: We retrospectively enrolled 48 patients with chronic coronary syndrome and CSF who underwent a second angiography. A corrected coronary frame rate (CFR) >27 was defined as CSF. We created 3 groups according to the change in CSF status as the improved, not changed, and worsened groups. We compared the CFR and CSF status of the patients between the first and second angiographies within a median of 2.6 years. RESULTS: We determined a nonsignificant change in cCFR in left anterior descending (LAD) artery (34.4 [18.9] vs. 31.59 [10.3], p = 0.35), circumflex (Cx) artery (42.84 [12.56] vs. 40.66 [13.2], p = 0.35), and right coronary artery (RCA) (57.80 [30.13] vs. 50.32 [19.5], p = 0.11). In the comparison of CSF status of LAD (75% vs. 63%, p = 0.27), Cx (96% vs. 83%, p = 0.09), RCA (94% vs. 94%, p = 1.0) between first and second angiographies, there was no significant change. In the comparison of the 3 groups according to the improvement of CSF status, there was no significant difference in demographic features, change in laboratory parameters, and time between the groups. CONCLUSION: There was no significant change in the median CFR and CSF status in the overall group between the two angiographies after 3 years.

Relationship between quantitative epicardial adipose tissue based on coronary computed tomography angiography and coronary slow flow.

BACKGROUND: The purpose of this study was to explore the relationship between quantitative epicardial adipose tissue (EAT) based on coronary computed tomography angiography (CCTA) and coronary slow flow (CSF). METHODS: A total of 85 patients with < 40% coronary stenosis on diagnostic coronary angiography were included in this retrospective study between January 2020 and December 2021. A semi-automatic method was developed for EAT quantification on CCTA images. According to the thrombolysis in myocardial infarction flow grade, the patients were divided into CSF group (n = 39) and normal coronary flow group (n = 46). Multivariate logistic regression was used to explore the relationship between EAT and CSF. Receiver operating characteristic (ROC) curve was plotted to evaluate the diagnostic value of EAT in CSF. RESULTS: EAT volume in the CSF group was significantly higher than that of the normal coronary flow group (128.83± 21.59 mL vs. 101.87± 18.56 mL, P < 0.001). There was no significant difference in epicardial fat attenuation index between the two groups (P > 0.05). Multivariate logistic regression analysis showed that EAT volume was independently related to CSF [odds ratio (OR) = 4.82, 95% confidence interval (CI): 3.06-7.27, P < 0.001]. The area under ROC curve for EAT volume in identifying CSF was 0.86 (95% CI: 0.77-0.95). The optimal cutoff value of 118.46 mL yielded a sensitivity of 0.80 and a specificity of 0.94. CONCLUSIONS: Increased EAT volume based on CCTA is strongly associated with CSF. This preliminary finding paves the way for future and larger studies aimed to definitively recognize the diagnostic value of EAT in CSF.

Relationship between inflammatory markers and coronary slow flow in type 2 diabetic patients.

BACKGROUND: Diabetes is a serious and quickly expanding global health problem. Cardiovascular disease is the leading cause of mortality in type 2 diabetes mellitus (T2DM) patients. Coronary slow flow (CSF) is characterised by delayed distal perfusion during coronary angiography with normal coronary arteries. This study aimed to investigate the correlation between CSF and inflammatory markers regarding glycemic status in T2DM. METHODS: This cross-sectional study included 120 patients who were divided equally into 4 groups according to their glycemic control and presence or absence of coronary slow flow: Group I included patients with T2DM with good glycemic control without CSF; Group II included patients with T2DM with good glycemic control and CSF; Group III included patients with T2DM with poor glycemic control without CSF; and Group IV included patients with T2DM with poor glycemic control and CSF. The neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), C-reactive protein (CRP), platelets, hematocrit, and haemoglobin were also evaluated as risk factors for coronary slow flow. RESULTS: This study showed that body mass index (BMI), hematocrit level, NLR, and CRP demonstrated a moderate but significant correlation (r = 0.53) with CSF in poorly controlled T2DM. NLR cutoff > 2.1 could predict CSF in poorly controlled T2DM with a modest sensitivity and specificity. A 1.9 increase in HbA1c increases the likelihood of coronary slow flow. Dylipidemia increases the likelihood of coronary slow flow by 0.18 times. Other predictors for coronary slow flow include NLR, PLR, CRP, platelets, hematocrit, and hemoglobin. The effect of the predictors is still statistically significant after being adjusted for glycemic status, age, and sex (p < 0.001). CONCLUSIONS: Poor glycemic control increases the incidence of CSF. This supports the hypothesis that CSF is related to endothelial dysfunction as poor glycemic control causes endothelial dysfunction due to inflammation. TRIAL REGISTRATION: ZU-IRB#9419-3-4-2022 Registered 3 April 2022, email.  IRB_123@medicine.zu.edu.eg .

The effect of coronary slow flow on ventricular repolarization parameters.

INTRODUCTION: Ischemia due to microvascular dysfunction may be responsible for the heterogeneity of ventricular repolarization in coronary slow flow. To our knowledge, there is no study in which QT interval, Tp-Te interval, index of cardiac-electrophysiological balance (iCEB), and frontal QRS-T angle were evaluated together in patients with CSF. In this study, we examined for the first time the relationship between all these myocardial repolarization parameters and CSF. MATERIALS AND METHODS: The study group included 178 patients (99 female, mean age: 50.6 ± 8.6 years) with isolated CSF without stenotic lesions and with angiographically proven normal coronary arteries. The control group included 120 patients (71 female, mean age: 49.3 ± 9.4 years) with normal coronary angiography. QRS duration, QT interval, QTc interval, Tp-Te interval, Tp-Te/QT, Tp- Te/QTc, iCEB score, and frontal QRS-T angle were calculated from 12­lead ECGs. RESULTS: There was no significant difference in demographic parameters between the two groups. Compared with the control group, patients with CSF had significantly longer QTmax duration, QT dispersion, Tp-Te interval, and higher iCEB score, wider frontal QRS-T angle. CONCLUSION: In our study, we found that many of the ventricular repolarization parameters were adversely affected in patients with CSF. Impaired parameters may be associated with the risk of malignant ventricular arrhythmias.

Evaluation of cardiac chamber functions by speckle-tracking echocardiography in the presence of coronary artery flow disturbances other than stenosis: A review.

Conditions other than stenosis also disturb the coronary flow. Such conditions include the coronary slow flow phenomenon, coronary artery ectasia, and coronary artery tortuosity. Evidence exists regarding myocardial dysfunction in these conditions. In this review, we present studies that have used speckle-tracking echocardiography to determine whether coronary flow disturbances are accompanied by myocardial dysfunction. Additionally, we seek to show the gaps in knowledge concerning this issue and the dimensions that future studies should consider.

Predictors of Long-Term Mortality in Patients with Stable Angina Pectoris and Coronary Slow Flow.

Background and Objectives: Coronary slow flow (CSF) is an angiographic phenomenon characterized by the slow progression of an injected contrast agent during diagnostic coronary angiography in the absence of significant stenosis. Although CSF is a common angiographic finding, the long-term outcomes and mortality rates are still unknown. This study aimed to investigate the underlying causes of mortality over a 10-year period in patients diagnosed with stable angina pectoris (SAP) and CSF. Materials and Methods: This study included patients with SAP who underwent coronary angiography from 1 January 2012 to 31 December 2012. All patients displayed CSF despite having angiographically normal coronary arteries. Hypertension (HT), diabetes mellitus (DM), hyperlipidaemia, medication compliance, comorbidities, and laboratory data were recorded at the time of angiography. Thrombolysis in myocardial infarction (TIMI) frame count (TFC) was calculated for each patient. The cardiovascular (CV) and non-CV causes of long-term mortality were assessed. Results: A total of 137 patients with CSF (93 males; mean age: 52.2 ± 9.36 years) were included in this study. Twenty-one patients (15.3%) died within 10 years of follow-up. Nine (7.2%) and 12 (9.4%) patients died of non-CV and CV causes, respectively. Total mortality in patients with CSF was associated with age, HT, discontinuation of medications, and high-density lipoprotein cholesterol (HDL-C) levels. The mean TFC was associated with CV mortality. Conclusion: Patients with CSF exhibited a notable increase in cardiovascular-related and overall mortality rates after 10 years of follow-up. HT, discontinuation of medications, HDL-C levels, and mean TFC were associated with mortality in patients with CSF.

Evaluation of Arterial Stiffness and Subfoveal Choroidal Thickness in Patients with Coronary Slow Flow.

Background: Coronary slow flow may not only affect the coronary arteries, but it may also be a vascular problem affecting the rest of the arterial system. Objective: The aim of this study was to determine peripheral arterial stiffness and the thickness of the choroid layer in patients with slow coronary flow. Methods: Fifty consecutive patients (age, 54.3 ± 11.4 years, 38 male) with coronary slow flow and 25 consecutive patients (age, 50.5 ± 9.9 years, 16 male) with normal coronary arteries both documented by coronary angiography were included. Arterial stiffness parameters were measured noninvasively using a Mobil-O-Graph arteriography system. The choroidal thickness was assessed using the enhanced depth imaging optical coherence tomography method. Results: The patients with coronary slow flow had significantly higher peripheral systolic blood pressure, peripheral pulse pressure, central pulse pressure, and pulse wave velocity (PWV) and significantly thinner choroidal thickness compared to the controls. Thrombolysis in myocardial infarction frame count was positively correlated with PWV (r: 0.237, p = 0.041) and negatively correlated with choroidal thickness (r: -0.249, p = 0.031). There was also a negative correlation between PWV and mean choroidal thickness (r: -0.565, p < 0.001). Linear regression analysis showed that coronary slow flow was an independent predictor of both PWV and choroidal thickness when adjusted by age and sex. Conclusions: The acceleration of average peripheral arterial PWV with a thinning of choroidal thickness in patients with coronary slow flow may support the idea that this phenomenon may be a coronary presentation of a systemic microvascular disorder.

Association between Serum Galectin-3 and Growth Differentiation Factor-15 Levels and Coronary Slow Flow Phenomenon.

Background: Coronary slow flow phenomenon (CSFP) is characterized by delay in the progression of contrast material in the coronary tree that is not accompanied by significant coronary artery narrowing. Pathophysiologic pathways underpinning CSFP still remain poorly understood. Objectives: To evaluate the relationship between serum galectin-3 (GAL-3) and growth differentiation factor-15 (GDF-15) levels with CSFP. Methods: Fifty CSFP patients and 40 subjects with normal coronary arteries were included in this retrospective study. The patients' serum GDF-15 and GAL-3 concentration levels were measured using relevant kits. Thrombolysis in myocardial infarction frame count (TFC) of each patients was determined. Results: We did not find any differences with respect to clinical and demographic features between the two groups. GDF-15 and GAL-3 concentration levels were significantly higher in the patients with CSFP. Moreover GDF-15 and GAL-3 concentration levels were positively correlated with TFC (GDF-15; r = 0.448, GAL-3; r = 0.642, p < 0.001 for both). Multivariate logistic regression showed that GAL-3 and GDF-15 were predictors of the CSFP. Similarly, GDF-15 and GAL-3 were the only predictors of TFC. More specifically, GDF-15 and GAL-3 concentration levels of 182.18 pg/mL and 8.58 ng/mL predicted CSFP with sensitivities of 76% and 87.5%, respectively, and specificities of 84% and 75%, respectively. Conclusions: GDF-15 and GAL-3 levels were increased in the CSFP patients and predicted the presence and severity of CSFP. Thus, these two biomarkers might prove useful in relation to the diagnosis of CSFP.

The Proportion of Circulating CD45RO+CD8+ T Cells is Associated with the Coronary Slow Flow.

Background: Circulating memory CD8+ T cells have been shown to be a crucial mediator of chronic inflammation. This study investigated whether the baseline proportion of circulating CD45RO+CD8+ T cells was associated with the coronary slow flow (CSF) phenomenon. Methods: A total of 160 consecutive patients [mean (standard deviation (SD)) age, 67.86 (9.55) years; 51.25% male] who were admitted to our hospital between August 2020 and October 2020 for chest pain and underwent coronary angiography with the absence of coronary stenosis were enrolled in this cross-sectional analysis. The patients' admission CD45RO+ CD8+ T cell plasma levels were measured using flow cytometry. Angiographic CSF was defined as thrombolysis in myocardial infarction (TIMI) flow of ≤ 2 without coronary stenosis, and non-CSF was defined as coronary arteries (< 50% stenosis) with TIMI 3 flow. Results: The incidence of angiographic CSF was 22.5%. Patients with angiographic CSF had higher levels of CD45RO+CD8+ T cells than those without CSF [56.18 (13.93) vs. 45.26 (16.45); p < 0.001]. After multivariable adjustment, the risk of incident CSF was 2.41 [95% confidence interval (CI) 1.46-3.97] per SD change in CD45RO+ CD8+ T cells. Further, coronary microvascular resistance was significantly higher in patients with CSF than in those without CSF. A positive linear relationship between CD45RO+CD8+ T cells and coronary microvascular resistance was observed. Conclusions: The proportion of circulating CD45RO+CD8+ T cells is an independent indicator of CSF. This observation may provide insights into the pathophysiological mechanism of CSF.

Relationship between increased systemic immune-inflammation index and coronary slow flow phenomenon.

BACKGROUND: Systemic immune-inflammation index (SII, platelet × neutrophil/lymphocyte ratio), a new marker of inflammation, is associated with adverse cardiovascular events, but its relationship with coronary slow flow phenomenon (CSFP) is unclear. Therefore, we aimed to investigate the relationship between SII and CSFP. METHODS: We enrolled consecutive patients who presented with chest pain, with normal/near-normal coronary angiography findings (n = 89 as CSFP group; n = 167 as control group). The baseline characteristics, laboratory parameters and angiographic characteristics of the two groups were compared. RESULTS: SII levels were significantly higher in the CSFP group than in the control group (409.7 ± 17.7 vs. 396.7 ± 12.7, p < 0.001). A significant positive correlation between SII and the mean thrombolysis in myocardial infarction frame count (mTFC) was found (r = 0.624, p < 0.001). SII increased with the number of coronary arteries involved in CSFP. In multivariate logistic regression analysis, SII/10 was an independent predictor of CSFP (odds ratio: 1.739, p < 0.001). In addition, the SII level > 404.29 was a predictor of CSFP with 67.4% sensitivity and 71.9% specificity. CONCLUSIONS: SII can predict the occurrence of CSFP.

Endothelial nitric oxide synthase Asp298Glu (894G/T) gene polymorphism as a possible risk factor for the coronary slow flow phenomenon among Iranians.

BACKGROUND: Mounting evidence indicates an association between endothelial dysfunction and the coronary slow flow phenomenon (CSFP). In the present study, we aimed to evaluate the possible role of endothelial nitric oxide synthase (eNOS) 894G/T and interleukin-1ß (IL-1ß) 315C/T polymorphisms as possible risk factors for CSFP. METHODS: This prospective study enrolled patients with CSFP and individuals with normal coronary arteries. Genotypes were assessed using regular polymerase chain reaction and direct Sanger-sequencing techniques. RESULTS: The study population consisted of 267 individuals: 180 patients with CSFP (49 women [27.2%]) at a median age of 55 (48-62) years and 87 controls with normal coronary arteries (56 women [64.4%]) at a median age of 47 (41-58) years. The allelic distribution of eNOS 894G/T was significantly associated with CSFP (odds ratio [OR], 1.58; 95% confidence interval (CI), 1.04-2.42; P = 0.03). This polymorphism increased the risk of CSFP under the dominant model (OR 1.73; 95% CI I.02-2.95; P = 0.04). However, the allelic frequencies (1.05; 95% CI 0.68-1.59; P = 0.83) and genotypic frequencies (0.88; 95% CI 0.52-1.49; P = 0.63) of the IL-1ß 315C/T polymorphism were not associated with the incidence of CSFP in the Iranian population. CONCLUSIONS: The CSFP and control groups were statistically different regarding the eNOS 894G/T polymorphism. Our findings also demonstrated that the IL-1ß 315C/T polymorphism was not a risk factor for CSFP.

The Application of Coronary Contrast Emptying Time in Diagnosing Coronary Slow Flow Phenomenon: A Serial Case Report.

The Coronary Slow Flow Phenomenon doesn't achieve as much attention as its counterpart Coronary Arterial Disease because it is considered a rather benign entity. But now it is proven that coronary slow flow phenomenon can also manifest as an acute coronary syndrome, myocardial ischemia, malignant arrhythmia, and even sudden cardiac death.This entity is usually diagnosed from coronary angiography study when a delayed coronary contrast filling time is found without the presence of significant epicardial narrowing of the related arteries. But, in our center's years of experience, we frequently found cases in which myocardial ischemia or infarction was suggested or proven clinically, on the other hand, angiography study showed no significant epicardial coronary artery narrowing neither delayed coronary contrast filling time. Furthermore, we observed that this group of patients exhibited a rather prolonged coronary contrast emptying time instead.In this serial case report, we presented some of our cases where microvascular disorders were suspected. We demonstrated that not all coronary contrast filling times in ischemic or infarction-related arteries were prolonged, on the other hand, prolongation of coronary contrast emptying time showed a more consistent result.