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.

Angiographic flow velocity predicts lower limb outcomes after endovascular therapy: Application of the frame count method.

INTRODUCTION: Several factors related to lesion characteristics and endovascular therapy (EVT) procedures have been reported to affect primary patency after EVT. However, it is unknown why these factors were associated with primary patency. We hypothesized patency failure was related to poor blood flow in affected arteries. METHODS: This retrospective study included 131 consecutive patients who had received EVT with bare metal stents for peripheral artery disease caused by femoropopliteal artery lesions. Based on the tertile post-EVT flow velocity of the superficial femoral artery (SFA), patients were divided into high (n = 43), middle (n = 44), and low (n = 44) flow velocity groups. Flow velocity was measured using the frame count method. We measured incidence of major adverse limb events (MALE), composed of target lesion revascularization (TLR), non-TLR, and major amputation. RESULTS: At a median follow-up period of 22.7 months, MALE had occurred in 7 (16.3%), 10 (22.7%), and 29 (65.9%) of patients from the high, middle, and low SFA flow velocity groups, respectively (p < 0.001). Kaplan-Meier analysis showed incidence of MALE was significantly higher in the patients of low SFA flow velocity (log-rank test χ2 = 38.8, p < 0.001). Multivariate analysis found low SFA flow velocity to be an independent predictor for MALE (hazard ratio: 4.42; 95% CI: 2.27 to 8.60; p < 0.001) as was ankle-brachial index. CONCLUSION: Post-EVT SFA flow velocity for femoropopliteal artery lesions treated with bare metal stents is an independent predictor of limb patency. The frame count method for assessing arterial flow velocity is convenient and has potential for wide applications in EVT.

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.

Assessment of triglyceride/glucose index with respect to coronary slow flow.

BACKGROUND: Coronary slow flow (CSF) is determined by delayed opacification of the epicardial coronary arteries without obstructive disease. The triglyceride glucose index (TGI) has been suggested as a useful marker of insulin resistance. Previous studies have shown that TGI is associated with cardiovascular disease, but no study has examined the relationship between TGI and CSF. OBJECTIVES: Therefore, the primary objective of the present study was to investigate the relationship between TGI and CSF. METHODS: This study retrospectively evaluated patients who were admitted to our clinic with complaints of chest pain and underwent coronary angiography between January and December 2018. A total of 1100 coronary angiography images were assessed, and 72 patients with CSF were detected. Coronary flow was quantified objectively using the TIMI (thrombolysis in myocardial infarction) frame count (TFC) method as described by Gibson et al. TGI was calculated as follows: ln [fasting triglycerides (mg/dL) × fasting glucose (mg/dL)/2]. RESULTS: The CSF group had significantly higher glucose levels (mg/dl) [ (114.92±30.92), (125.61±33.22), than the control and CSF groups, respectively, p=0.0001], TGI [ (9.02±0.56), (9.26±0.54), p=0.0001], and triglyceride levels (mg/dl) [ (170.67±110.81), (201.19±136.93), p=0.002]. There was no statistically significant correlation between TGI and left anterior descending artery TFC, circumflex artery TFC, right coronary artery TFC (r/p values; 0.24/0.06; 0.32/0.08; 0.18/0.36, respectively). TGI, HDL, HT, age, and sex were examined with a multiple logistic model, and TGI was found to be statistically significant for the risk of CSF (p=0.0001; O.R:7.459). CONCLUSION: TGI was statistically significantly higher in the CSF group than the control group. According to the multivariate logistic regression analysis, only TGI was independently associated with the risk of CSF, but higher TGI did not predict more slow coronary flow. Prospective studies are needed to clarify the prognostic relationship of TGI and CSF in terms of future cardiovascular events (Tab. 2, Fig. 1, Ref. 19).

To show the effect of intermittent fasting during ramadan on endothelial dysfunction via TIMI frame count.

BACKGROUND: Fasting and coronary functions are prestige fields for the study. There are a limited number of studies on these topics. The effect of Ramadan fasting on endothelial dysfunction, which can be manifested by loss of nitric oxide bioavailability, has been demonstrated via flow-mediated vasomotion in patients with the slow coronary flow in a small number of studies. To our knowledge, there is no study showing the relationship between TIMI frame count and Ramadan fasting. AIMS: We aimed to prove that Ramadan fasting can improve endothelial dysfunction which can be documented via the TIMI frame count method in angiography. METHOD: This retrospective study included 67 patients diagnosed with the coronary slow flow by coronary angiographic before Ramadan. All of them were evaluated again via TIMI frame count within a period of 1 to 3 months after Ramadan. We tested our hypothesis that fasting may improve endothelial dysfunction and it was proved by the TIMI frame count method in our study. RESULTS: TIMI frame counts measured angiographically from LAD, Cx, and RCA and they were significantly lower than the counts before fasting. All coronary frame count parameters showed significant improvement after Ramadan compared with the baseline values before the Ramadan fasting period (P < 0.001). CONCLUSION: Our results revealed that fasting and lifestyle changes during Ramadan may be beneficial for the improvement of endothelial dysfunctions in patients with the slow coronary flow and this can be showed easily using TIMI frame count. This is a practical and easy method for showing coronary functions.

Correlation between longitudinal strain analysis and coronary microvascular dysfunction in patients with heart failure with preserved ejection fraction.

OBJECTIVE: The aim of this study was to evaluate in patients with microvascular angina and heart failure with preserved ejection fraction, the speckle-tracking echocardiography, and longitudinal myocardial strain to evaluate the possible presence of alterations in heart failure with preserved ejection fraction patients compared with a control population. We also investigated the correlation between the longitudinal strain analysis and the TIMI frame count after coronary angiography. METHODS: Our study was performed on a population 41 patients with microvascular angina that underwent coronary angiography and speckle-tracking echocardiography. We divided the sample into two categories: patients with heart failure with preserved ejection fraction (n-21) and patients without heart failure with preserved ejection fraction (n-20). We calculated TIMI frame count indices for each patient based on angiographic images. RESULTS: Patients with heart failure with preserved ejection fraction had reduced global longitudinal strain values (-17.88) compared with the total control population, and this reduction was statistically significant (P = .028). This reduction was more marked in patients who had a significantly increased TIMI frame count. Therefore, a statistically significant correlation was observed between TIMI frame count and global longitudinal strain. CONCLUSION: Our results show that cardiac contractile mechanics are altered in patients with heart failure with preserved ejection fraction at a subclinical level hard to identifiable with conventional echocardiography. The dysfunction of the microcirculation and the consequent alteration of the TIMI frame count probably results in a reduction of myocardial performance.

Correlation of increased corrected TIMI frame counts and the topographical extent of isolated coronary artery ectasia.

BACKGROUND: The precise relationship between increased thrombolysis in myocardial infarction (TIMI) frame counts and the topographical extent of isolated coronary artery ectasia (CAE) has not been fully explained. New parameters of linear dimension (LD) and the estimated ectatic area (EEA) together with the diameter and ectasia ratio may be associated with the corrected TIMI frame count (CTFC) in isolated CAE patients. METHODS: The topographical parameters of ectatic coronary arteries and/or segments of 77 isolated CAE patients were consecutively studied. The CTFC for each coronary artery was determined by angiographic frame count. RESULTS: Right coronary artery (RCA) was the most frequently affected. The RCA and left circumflex (LCX) had significantly longer LD (p < 0.001 for both), and greater EEA (p < 0.001 for both) than those of left anterior descending artery (LAD). Similarly, the RCA and LCX have higher CTFCs (p = 0.001 and p = 0.008, respectively) than LAD. All topographic parameters and CTFCs were positively correlated with Markis classification. Linear regression analyses revealed that CTFCs were strongly correlated with diameter, LD, ectasia ratio and EEA, while EEA was the best predictor for the CTFC. Among multiple linear and nonlinear regression models, the cubic model between the CTFC and EEA exhibits the best Goodness-of-Fit. CONCLUSION: The severity of the topographical extent of CAE was significantly correlated with increased CTFCs. Both the linear dimension and ectatic diameter (combined as EEA) were important for evaluating decreased coronary flow in isolated CAE patients.

Evaluation of Plasma Thrombomodulin in Patients with Coronary Slow Flow.

BACKGROUND: It has been reported that coronary slow flow (CSF) is associated with acute myocardial infarction, ventricular tachycardia, ventricular fibrillation, and even sudden cardiac death. Although studies concerning the etiopathogenesis of CSF are scarce, diffuse atherosclerosis and endothelial dysfunction are thought to play important roles. It has been suggested that a high plasma thrombomodulin (TM) level seems to play an important role in the pathogenesis of atherosclerosis and endothelial dysfunction. OBJECTIVES: We hypothesized that a high plasma TM level might be associated with CSF and aimed to research the relationship between plasma TM level and CSF. METHODS: Fifty-two CSF patients with angiographically proven CSF and 44 cases with normal coronary flow were included in this study. Coronary flow velocity was determined by the thrombolysis in myocardial infarction (TIMI) frame count method. Plasma TM levels were measured in all the study subjects. RESULTS: Plasma TM levels were significantly higher in the CSF group compared to the control group (3.9 ± 0.5 vs. 3.6 ± 0.3 ng/mL, p = 0.01). There was a positive relationship (r = 0.31, p = 0.002) between plasma TM level and mean TIMI frame count (TFC). Factors associated with mean TFC were plasma TM level (ß = 0.206, p = 0.038) and red cell distribution width (ß = 0.088, p = 0.009) in multiple linear regression analysis. CONCLUSIONS: Patients with CSF have a higher plasma TM level, and this may play an important role in the pathogenesis of CSF. An elevated plasma TM level may be a predictor of CSF. Future studies are needed to confirm these results.

Coronary slow flow phenomenon: Not only low in flow rate but also in myocardial energy expenditure.

BACKGROUND AND AIM: Coronary slow flow phenomenon (CSFP) is a miscellaneous clinical entity leading to angina-like symptoms, and electrocardiographic and scintigraphic evidence of ischemia. The impact of this syndrome on myocardial performance has not been comprehensively evaluated. In this study, we sought to evaluate the myocardial energy expenditure (MEE) in patients with CSFP and its relationship with exercise capacity. METHODS AND RESULTS: A total of 64 patients (64.1% male, mean age 53.2 ± 10.3 years) with CSFP and 64 patients (60.9% male, mean age 52.2 ± 10.9 years) with normal coronary artery as control group were included. MEE was calculated by a validated formula that uses transthoracic echocardiography (TTE) parameters, including left ventricular circumferential end-systolic stress, stroke volume, and ejection time CSFP patients had significantly lower MEE (0.79 cal/systole ± 0.15 vs. 0.91 cal/systole ± 0.09, p < 0.001). In correlation analysis, MEE had a significant negative correlation with mean corrected TIMI frame count (mTFC) (ß = -0.523; p < 0.001) and positive correlations with metabolic equivalents (METs) (ß = 0.560; p < 0.001), rate pressure product (ß = 0.649; p < 0.001), and exercise duration (ß = 0.408; p < 0.001). At multivariate analysis, MEE was demonstrated as an independent predictor of CSFP (OR 1.863, CI 95% 1.485-2.338 p < 0.001). CONCLUSION: Myocardial energy consumption, as a calculation obtained from TTE parameters, was reduced in patients with CSFP, and it had a significant relationship with exercise capacity. Considering its significant correlation with exercise capacity, myocardial energy consumption seemed to use evaluation of myocardial performance and functional status in another cardiovascular disease.

Multimodality assessment of the coronary microvasculature with TIMI frame count versus perfusion PET highlights coronary changes characteristic of coronary microvascular disease.

Background: The diagnosis of coronary microvascular disease (CMVD) remains challenging. Perfusion PET-derived myocardial blood flow (MBF) reserve (MBFR) can quantify CMVD but is not widely available. Thrombolysis in Myocardial Infarction (TIMI) frame count (TFC) is an angiography-based method that has been proposed as a measure of CMVD. Here, we compare TFC and PET-derived MBF measurements to establish the role of TFC in assessing for CMVD. We use coronary modeling to elucidate the relationship between MBFR and TFC and propose TFC thresholds for identifying CMVD. Methods: In a cohort of 123 individuals (age 58 ± 12.1, 63% women, 41% Caucasian) without obstructive coronary artery disease who had undergone perfusion PET and coronary angiography for clinical indications, we compared TFC and perfusion PET parameters using Pearson correlation (PCC) and linear regression modeling. We used mathematical modeling of the coronary circulation to understand the relationship between these parameters and performed Receiver Operating Curve (ROC) analysis. Results: We found a significant negative correlation between TFC and MBFR. Sex, race and ethnicity, and nitroglycerin administration impact this relationship. Coronary modeling showed an uncoupling between TFC and flow in epicardial vessels. In ROC analysis, TFC performed well in women (AUC 0.84-0.89) and a moderately in men (AUC 0.68-0.78). Conclusions: We established an inverse relationship between TFC and PET-derived MBFR, which is affected by patient selection and procedural factors. TFC represents a measure of the volume of the epicardial coronary compartment, which is increased in patients with CMVD, and performs well in identifying women with CMVD.

Coronary Slow Flow Is Not Diagnostic of Microvascular Dysfunction in Patients With Angina and Unobstructed Coronary Arteries.

Background Guidelines recommend that coronary slow flow phenomenon (CSFP), defined as corrected thrombolysis in myocardial infarction frame count (CTFC) >$$ > $$27, can diagnose coronary microvascular dysfunction (CMD) in patients with angina and nonobstructed coronary arteries. CSFP has also historically been regarded as a sign of coronary endothelial dysfunction (CED). We sought to validate the utility of CTFC, as a binary classifier of CSFP and as a continuous variable, to diagnose CMD and CED. Methods and Results Patients with angina and nonobstructed coronary arteries had simultaneous coronary pressure and flow velocity measured using a dual sensor-tipped guidewire during rest, adenosine-mediated hyperemia, and intracoronary acetylcholine infusion. CMD was defined as the inability to augment coronary blood flow in response to adenosine (coronary flow reserve <2.5) and CED in response to acetylcholine (acetylcholine flow reserve ≤1.5); 152 patients underwent assessment using adenosine, of whom 82 underwent further acetylcholine testing. Forty-six patients (30%) had CSFP, associated with lower flow velocity and higher microvascular resistance as compared with controls (16.5±$$ \pm $$6.9 versus 20.2±$$ \pm $$6.9 cm/s; P=0.001 and 6.26±$$ \pm $$1.83 versus 5.36±$$ \pm $$1.83 mm Hg/cm/s; P=0.009, respectively). However, as a diagnostic test, CSFP had poor sensitivity and specificity for both CMD (26.7% and 65.2%) and CED (21.1% and 56.0%). Furthermore, on receiver operating characteristics analyses, CTFC could not predict CMD or CED (area under the curve, 0.41 [95% CI, 0.32%-0.50%] and 0.36 [95% CI, 0.23%-0.49%], respectively). Conclusions In patients with angina and nonobstructed coronary arteries, CSFP and CTFC are not diagnostic of CMD or CED. Guidelines supporting the use of CTFC in the diagnosis of CMD should be revisited.

Prognostic implication of coronary slow flow assessed by cTFC in patients with myocardial infarction with Non-obstructive coronary arteries.

BACKGROUND: Coronary slow flow (CSF) is common and linked to worse cardiovascular events and life-threatening arrhythmias. However, the clinical implication of CSF among myocardial infarction with the non-obstructive coronary artery (MINOCA) has never been studied. We aimed to evaluate the impact of CSF on the MINOCA population. METHODS: Patients diagnosed with MINOCA were consecutively selected. The corrected TIMI frame count (cTFC) was used to evaluate the coronary flow. CSF was defined as cTFC greater than 27 frames per second (FPS) in any of the three coronary arteries. Major adverse cardiovascular events (MACE) are the primary endpoint. Cox regression analysis was used to evaluate the association between CSF and MACE. RESULTS: A total of 158 patients with MINOCA were enrolled, of which 54 (34.2%) patients had CSF. Forty incidents of MACE occurred during the median 28 months of follow-up. The MACE incidence was higher among patients who presented with CSF than the normal coronary flow patients (35.2% vs. 20.2%, p = 0.040). In the Kaplan-Meier analysis, CSF patients had significantly higher rates of MACE (log-rank P = 0.034). Multivariate Cox regression analysis showed that CSF was an independent predictor linked to an increased hazard of MACE (adjusted HR, 2.76; 95% CI, 1.34-5.67; P = 0.006). CONCLUSION: The presence of CSF is associated with a higher risk of adverse events and is an independent predictor of clinical outcomes among patients with MINOCA. This result suggests that CSF might serve as a robust tool to stratify MINOCA patients.

Non-Dipper Blood Pressure Impact on Coronary Slow Flow in Hypertensive Patients With Normal Coronary Arteries.

OBJECTIVE: Coronary slow flow (CSF) is linked to myocardial ischemia, malignant arrhythmias, and cardiovascular mortality. On the other hand, hypertension (HTN) is an important risk factor for vascular disorders. There is limited research on the relationship between CSF and HTN. This study aimed to investigate TIMI frame count (TFC), which is an indicator of CSF, in dipper and non-dipper hypertensive individuals with normal coronary arteries. METHODS: The study was conducted as a retrospective observational study. Patients diagnosed with CSF and dipper or non-dipper hypertension were included in this study. Blood tests were routinely conducted for all patients. ECG was conducted for each patient, and echocardiography was performed. Coronary artery images were obtained in the CAG laboratory. Blood pressure (BP) measurements were obtained from the ambulatory Holter records. The patients were separated into two groups based on ambulatory Holter monitoring. The relationship between CSF and HTN was also examined. RESULTS: A total of 71 patients, comprising 25 women (37.2%) and 46 men (62.8%) with an average age of 52.75±9.42 years, were enrolled in the research. Based on ambulatory BP, the individuals were separated into two groups: non-dipper (n=36) and dipper (n=35). The pulse rate was significantly higher in the non-dipper group (p<0.001). In terms of mean systolic and diastolic blood pressure, there were no substantial differences across the groups (p = 0.326 and p = 0.654, respectively). The daytime mean systolic and diastolic BP did not significantly differ across the groups (p = 0.842 and p = 0.421). The dipper group had substantially lower nighttime systolic and diastolic BP values (p <0.001). The LAD, Cx, and RCA TIMI frame scores were significantly lower in the dipper group (p<0.001). CONCLUSION: In this study, non-dipper patients had a greater CSF rate than dipper.

Atrial fibrillation episode status and incidence of coronary slow flow: A propensity score-matched analysis.

Background: Previous studies have shown that patients with a history of atrial fibrillation (AF) have a higher risk of developing coronary slow flow (CSF). However, whether AF episode status affects the incidence of CSF has not been confirmed. This study investigated the correlation between AF episode status and the incidence of CSF. Methods: We enrolled patients with AF who underwent coronary angiography for symptoms of myocardial ischemia between January 1, 2017, and April 30, 2022, at our institution and classified them according to whether they had an episode of AF in the perioperative period. The outcomes were defined the occurrence of CSF overall and in each of the three coronary arteries. The analysis was repeated after adjusting the baseline information by the propensity score matching method in a 1:1 ratio. Results: 214 patients who met the inclusion and exclusion criteria were included in the study (AF episode group: 100 patients, AF non-episode group: 114 patients). Before matching, age, left atrial size, ejection fraction, heart rate, CSF incidence, and mean corrected thrombolysis in myocardial infarction frame counts were higher in patients with intraoperative AF episodes than in patients without episodes. To prevent the dependent variable (CSF incidence) from being confounded by confounding factors, we matched the two groups for age, left atrial size, and ejection fraction. In the logistic regression analysis, the incidence of CSF was significantly higher in the intraoperative AF episode group (P = 0.010, OR = 2.327, 95% CI: 1.226-4.416) than in the non-episode group. Conclusion: In patients with AF, AF episode status is significantly correlated with an increased overall incidence of CSF.

Impact of Coronary Microvascular Dysfunction on Myocardial Strain in Patients with Heart Failure and Preserved Ejection Fraction.

Background: This research aimed to evaluate the role of coronary microvascular dysfunction in alteration of left ventricular (LV) myocardial deformation. Materials and Methods: This observational study involved 50 patients with LV ejection fraction (LVEF) >50% and coronary microvascular dysfunction (diagnosed by coronary angiography). TIMI frame count (TFC) was calculated for each patient. They were classified into 2 groups: 30 patients with heart failure and preserved ejection fraction (HFpEF) (cases group) and 20 patients without HF (control group). Speckle tracking echocardiography was used to evaluate LV deformation. Results: The mean age of the studied patients was 58.8 ± 8 years. The frequency of diabetes mellitus, hypertension, and dyslipidemia were significantly higher in cases than controls. Cases had significant higher BMI (30 ± 4.48 vs. 27.3 ± 3.94 kg/m2, P=0.029). The total TFC in cases was 97.1 ± 22.9 and in controls was 79 ± 18.5, and this difference was statistically significant (P=0.005). Significantly decreased LV global strain was observed in HFpEF cases than in controls (-17.6 ± 2.14 % versus -19.5 ± 1.98%, P < 0.001). In cases with a higher TFC, the LV global strain decrease was more pronounced. There was a significant correlation between the LV global strain and total TFC (r=-0.470 and P=0.009). Conclusion: Patients with HFpEF exhibited higher total TFC reflecting more affected coronary microvasculature. Those patients had reduced LV global strain. Coronary microvascular dysfunction probably leads to alteration of myocardial performance.

Evaluation of serum nitric oxide synthase levels in patients with coronary slow flow based on corrected TIMI frame count.

Introduction: The coronary slow flow phenomenon (CSFP) finding in angiography is characterized by the delayed filling of the terminal vessels without significant epicardial coronary disease. The endothelium performs a vital role in cardiovascular homeostasis by releasing vasoactive substances. Endothelial cells produce nitric oxide (NO) as one of these essential compounds. Three isoforms of nitric oxide synthase (NOS) are endothelial nitric oxide synthase (eNOS), neuronal nitric oxide synthase (nNOS), and induced nitric oxide synthase (iNOS). We aimed to determine the role of NOS in the development of CSFP as the first human study. Material and methods: A total of 129 patients who met the inclusion criteria were enrolled in the study. The patients were classified into five groups based on the results of coronary angiography: Group 1 without coronary artery disease (CAD) and without CSF, group 2 without CAD and with CSF, group 3 with CAD (< 50%) and without CSF, group 4 with CAD (50-90%) and without CSF, and group 5 with CAD and CSF. The serum level of NOS was determined in the participants. Coronary flow was quantified in patients with CSFP using the corrected TIMI frame count (CTFC) method, and the correlation between the levels of this biomarker and CTFC was investigated. Results: In this study, the NOS serum levels were not significantly correlated with the mean CTFC. Since the total amount of NOS was measured as a result of 3 isoforms of this enzyme, the lack of correlation could be related to increased iNOS level and decreased eNOS concentration. Conclusions: These results should be confirmed by more human studies.

Positive Stress Electrocardiography in Patients With Non-obstructive Coronary Disease.

Introduction The episodes of myocardial ischemia in patients with non-obstructive coronary disease are extremely variable in provoking factors and presentation. Purpose We investigated the significance of coronary blood flow velocity and epicardial diameter as correlates of a positive electrocardiographic exercise stress test (ExECG) in hospitalized patients with unstable angina and non-obstructive coronary artery disease. Methods The study was a single-center cohort retrospective. ExECG was performed and analyzed in a group of 79 patients with non-obstructive coronary disease (coronary stenoses < 50%). Thirty-one percent of the patients (n=25) were diagnosed with slow coronary flow phenomenon, SCFP; 40.5% (n=32) - patients with hypertensive disease, left ventricular hypertrophy (LVH), and slow epicardial flow; 27.8% (n=22) with hypertension, left ventricular hypertrophy and normal coronary flow. The patients were hospitalized in University Hospital "Alexandrovska," Sofia in the period 2006-2008. Results The frequency of positive ExECG is increased as a trend was associated with smaller epicardial diameters and pronounced delay in epicardial coronary flow. In the subgroup with SCFP, the risk for a positive ExECG test was determined by slower coronary flow (36.5±7.7 frames vs. 30.3±4.4 frames, p=0.044) and borderline significant by epicardial lumen diameters (3.3±0.8 mm vs. 4.1±1.0 mm, p=0.051) and greater myocardial mass (92.8±12.6 g/m2 vs. 82.9±8.6 g/m2, p=0.054). In cases of left ventricular hypertrophy, which included both patients with the normal and slow epicardial flow, there were no statistically significant correlates of an abnormal exercise stress ECG test. Conclusions In patients with non-obstructive coronary atherosclerosis and predominantly slow epicardial coronary flow, the provoking of ischemia at an electrocardiographic exercise stress test is associated with the lower epicardial flow velocity at rest and with the smaller epicardial diameter. In SCFP, the risk for an abnormal stress test is determined by slower coronary flow, smaller epicardial lumen diameter, and greater myocardial mass. The presence and size of the plaque burden are not associated with a greater risk of a positive ExECG in these patients.

The effect of prior COVID-19 infection on coronary microvascular dysfunction.

BACKGROUND: Thrombolysis in Myocardial Infarction Frame Count (TFC) is an index that provides a quantitative evaluation of coronary microvascular dysfunction. In this study, we aimed to examine the effect of COVID-19 infection on TFC in patients admitted with chest pain and dyspnoea after COVID-19 disease and had abnormal findings in myocardial perfusion scintigraphy. METHODS: For this single-center retrospective study, patients with and without a history of COVID-19 who were underwent coronary angiography for abnormal findings in myocardial perfusion scintigraphy between January 1, 2021 and June 30, 2021 were analysed. Patients were divided into two groups as patients with COVID-19 history and those without. After exclusion criteria, patients with adequate angiographic monitoring and data were included in the study. RESULTS: A total of 210 patients, 48 with a history of COVID-19, were included in the study. The mean age was ±55 10 years, and 122 (58%) patients were women. In patients with a history of COVID-19, TFC was significantly higher in the LAD (p < 0.001) and LCx (p < 0.001) arteries and RCA TFC (p = 0.223) was similar in both groups. In the linear mix model, male gender (ß = 2.38, 95% CI = 1.26-3.51, p < 0.001) and history of COVID-19 (ß = 1.51, 95% CI = 0.49-2.53, p = 0.004) were significantly associated with TFC. CONCLUSION: TFC may be elevated due to coronary microvascular dysfunction in patients with a history of COVID-19.

Predictive value of thrombolysis in myocardial infarction frame count for coronary microvascular dysfunction evaluated with an angiography-derived index of microcirculatory resistance in patients with coronary slow flow.

Background: The association between coronary slow flow (CSF) and coronary microvascular dysfunction (CMD) remains unclear. The objective of this study was to evaluate the correlation between the corrected thrombolysis in myocardial infarction (TIMI) frame count (CTFC) and the index of microcirculatory resistance (IMR). Methods: We consecutively enrolled patients with CSF from January 2017 to March 2018. Concurrently, we randomly selected control participants with normal flow arteries at a ratio of 3:1. Two cardiologists performed the measurements of CTFC. Coronary angiography-derived IMR (caIMR) was used to assess CMD. The caIMR was analyzed by an independent agency, with CMD being defined as caIMR >40 U. Results: A total of 111 patients with CSF and 39 patients without CSF were enrolled in this retrospective study. Compared with the non-CSF group, the CSF group had a greater proportion of males (65.8% vs. 23.1%; P<0.001) and a lower prevalence of hypertension (47.7% vs. 67.7%; P=0.042). Additionally, the CSF group had higher CTFC, coronary angiography-derived fractional flow reserve (caFFR), and caIMR regardless of left anterior descending artery (LAD), left circumflex artery (LCX), and right coronary artery (RCA) (all P values <0.001). A strong correlation between CTFC and caIMR was observed for all arteries (all P values <0.001). In the univariate analysis, male sex [hazard ratio (HR) =2.63, 95% CI: 1.30-5.31], E/e' (HR =0.88, 95% CI: 0.78-0.99), CTFC (HR =1.12, 95% CI: 1.09-1.16), and caFFR (HR =1.81, 95% CI: 1.50-2.17) were significantly correlated with CMD. After adjusting for covariates, male sex (HR =2.72, 95% CI: 1.22-6.06), CTFC (HR =1.10, 95% CI: 1.07-1.14), and caFFR (HR =1.22, 95% CI: 1.00-1.50) were independent predictors for CMD. Additionally, the best cutoff value of CTFC of all arteries for predicting CMD was 38 frames, with an area under the curve of 0.873, a sensitivity of 92.8%, and a specificity of 63.8% (P<0.001). Moreover, the best cutoff value of CTFC of LAD, LCX, and RCA to identify CMD was 35 frames, 52 frames, and 50 frames, respectively (all P values <0.001). Conclusions: CTFC correlated well with caIMR and had a strong predictive power to identify CMD.

Diagnostic comparison of automatic and manual TIMI frame-counting-generated quantitative flow ratio (QFR) values.

Quantitative flow ratio (QFR) is a computational measurement of FFR (fractional flow reserve), calculated from coronary angiography. Latest QFR software automates TIMI frame counting (TFC), which occurs during the flow step of QFR analyses, making the analysis faster and more reproducible. The objective is to determine the diagnostic performance of QFR values obtained from analyses using automatic TFC compared to those obtained from analyses using manual TFC. This was a single-arm clinical trial that used the prospective analysis of the coronary angiographic image series of 97 patients who underwent evaluation of stable coronary artery disease with FFR/iFR at MedStar Washington Hospital Center in Washington, DC, USA. Automatic and manual TFC QFR values were obtained from the analyses of each of the 97 patients' image series, with manual TFC QFR values as the current gold standard for comparison. The diagnostic performance of automatic TFC QFR values was measured as follows: sensitivity was 0.87 (95% CI 0.66-0.97) and specificity was 1.00 (95% CI 0.9514-1.00), positive predictive value (PPV) was 1.00 (95%CI 1.00-1.00), while the NPV was 0.96 (95% CI 0.96-0.99). Overall accuracy was 96.91% (95% CI 91.23%-99.36%). The agreement as illustrated by the Bland-Altman plot shows a bias of 0.0023 (SD 0.0208) and narrow limits of agreement (LOA): Upper LOA 0.0573 and Lower LOA - 0.0528. The area under curve (AUC) was 0.996. QFR values generated from automatic TFC are comparable to those generated from manual TFC in diagnostic capability. The most recent software update produces values equivalent to those of the previous manual option, and can therefore be used interchangeably.