Association between fibrinogen-to-albumin ratio and the presence and severity of coronary artery disease in patients with acute coronary syndrome

Objective Although the levels of plasma fibrinogen and albumin have been proven to be in relation to coronary heart disease (CHD), the association between fibrinogen-to-albumin ratio (FAR) and acute coronary syndrome (ACS) has not been adequately investigated. The aim of this study is to investigate the relationship between FAR and the presence and severity of CHD in patients with ACS. Methods and results A total of 1575 individuals who received coronary angiography (CAG) were enrolled. Patients were divided into the ACS group and the control group. The severity of ACS was determined by Gensini score, number of diseased coronary artery and the presence of myocardial infarction (MI). Data showed that the level of FAR in ACS group was higher than in the control group (81.20 ± 35.45 vs. 72.89 ± 20.24, P < 0.001). The results from subgroup analysis indicated that the values of FAR in the high Gensini score group, MI group and multiple-vessel stenosis group were higher than the matched subgroups. After adjustment for confounders, FAR was still independently related to the presence and severity of ACS (MI OR 2.097, 95%CI 1.430–3.076; High GS: OR 2.335, 95%CI 1.567–3.479; multiple-vessel disease: OR 2.088, 95%CI 1.439–3.030; P < 0.05). Conclusion The levels of FAR are independently associated with the presence and the severity of coronary artery disease in patients with ACS. Furthermore, FAR, as a more convenient and rapid biological indicator, may provide a new idea for predicting the presence and severity of ACS.

The Association Between Recurrence of Atrial Fibrillation and Revascularization in Patients With Coronary Artery Disease After Catheter Ablation

Aim: The connection between revascularization for coronary artery disease (CAD) and the incidence of recurrent events of atrial fibrillation (AF) after ablation is unclear. This study aimed to explore the relationship between coronary revascularization and AF recurrence in patients who underwent radiofrequency catheter ablation (RFCA).Methods: Four hundred and nineteen patients who underwent performed coronary angiography at the same time as RFCA were enrolled in this study. Obstructive CAD was defined as at least one coronary artery vessel stenosis of ≥75% and percutaneous coronary intervention (PCI) was recommended. Non-obstructive CAD was defined as coronary artery vessel stenosis of &lt;75%. The endpoint was freedom from recurrence from AF after RFCA during the 24-month follow-up.Results: In total, 102, 95, and 212 patients were undergone coronary angiography and diagnosed as having obstructive CAD, Non-obstructive CAD, and Non-CAD, respectively. During the 24-month follow-up period, patients without obstructive CAD were significantly more likely to achieve freedom from AF than patients with obstructive CAD (hazard ratio [HR]: 1.72; 95% confidence interval [CI]: 1.23–2.41; P = 0.001). The recurrence rate of AF was significantly lower in patients who underwent PCI than in those who did not (HR: 0.45; 95% CI: 0.25–0.80; P = 0.007). The multivariate regression analysis showed that the other predictors of AF recurrence for obstructive CAD were multivessel stenosis (HR: 1.92; 95% CI: 1.04–3.54; P = 0.036) and left atrial diameter (HR: 2.56; 95% CI: 1.31–5.00; P = 0.006).Conclusions: This study suggests that obstructive CAD is associated with a higher rate of AF recurrence. Additionally, For patients with CAD, coronary revascularization is related to a lower recurrence rate of AF after RFCA.

Structural Remodeling of the Extracellular Matrix in Arteriogenesis: A Review

Lower extremity arterial occlusive disease (AOD) results in significant morbidity and mortality for the population, with up to 10% of patients ultimately requiring amputation. An alternative method for non-surgical revascularization which is yet to be fully understood is the optimization of the body's own natural collateral arterial network in a process known as arteriogenesis. Under conditions of conductance vessel stenosis or occlusion resulting in increased flow, shear forces, and pressure gradients within collaterals, positive remodeling occurs to increase the diameter and capacity of these vessels. The creation of a distal arteriovenous fistula (AVF) will drive increased arteriogenesis as compared to collateral formation with the occlusion of a conductance vessel alone by further increasing flow through these arterioles, demonstrating the capacity for arteriogenesis to form larger, more efficient collaterals beyond what is spontaneously achieved after arterial occlusion. Arteries rely on an extracellular matrix (ECM) composed of elastic fibers and collagens that provide stability under hemodynamic stress, and ECM remodeling is necessary to allow for increased diameter and flow conductance in mature arterial structures. When positive remodeling occurs, digestion of lamella and the internal elastic lamina (IEL) by matrix metalloproteinases (MMPs) and other elastases results in the rearrangement and thinning of elastic structures and may be replaced with disordered elastin synthesis without recovery of elastic function. This results in transmission of wall strain to collagen and potential for aneurysmal degeneration along collateral networks, as is seen in the pancreaticoduodenal artery (PDA) after celiac occlusion and inferior mesenteric artery (IMA) with concurrent celiac and superior mesenteric artery (SMA) occlusions. Further understanding into the development of collaterals is required to both better understand aneurysmal degeneration and optimize collateral formation in AOD.

Early manifestations and differential gene expression associated with photoreceptor degeneration in Prominin-1-deficient retina

Retinitis pigmentosa (RP) and macular dystrophy (MD) are characterized by gradual photoreceptor death in the retina and are often associated with genetic mutations including those in the Prominin-1 (Prom1) gene. Prom1-knockout (KO) mice recapitulate key features of these diseases including light-dependent retinal degeneration and constriction of retinal blood vessels. The mechanisms underlying such degeneration have remained unclear, however. We here analysed early events associated with retinal degeneration in Prom1-KO mice. We found that photoreceptor cell death and glial cell activation occur between 2 and 3 weeks after birth. Whereas gene expression was not affected at 2 weeks, the expression of several genes was altered at 3 weeks in the Prom1-KO retina, with the expression of that for Endothelin-2 (Edn2) being markedly up-regulated. Expression of Edn2 was also induced by light stimulation in Prom1-KO mice reared in the dark. Treatment with endothelin receptor antagonists attenuated photoreceptor cell death, gliosis, and retinal vessel stenosis in Prom1-KO mice. Our findings thus reveal early manifestations of retinal degeneration in a model of RP/MD and suggest potential therapeutic agents for these diseases.

Pathogenesis and Molecular Mechanisms of Anderson–Fabry Disease and Possible New Molecular Addressed Therapeutic Strategies

Anderson–Fabry disease (AFD) is a rare disease with an incidenceof approximately 1:117,000 male births. Lysosomal accumulation of globotriaosylceramide (Gb3) is the element characterizing Fabry disease due to a hereditary deficiency α-galactosidase A (GLA) enzyme. The accumulation of Gb3 causes lysosomal dysfunction that compromises cell signaling pathways. Deposition of sphingolipids occurs in the autonomic nervous system, dorsal root ganglia, kidney epithelial cells, vascular system cells, and myocardial cells, resulting in organ failure. This manuscript will review the molecular pathogenetic pathways involved in Anderson–Fabry disease and in its organ damage. Some studies reported that inhibition of mitochondrial function and energy metabolism plays a significant role in AFD cardiomyopathy and in kidney disease of AFD patients. Furthermore, mitochondrial dysfunction has been reported as linked to the dysregulation of the autophagy–lysosomal pathway which inhibits the mechanistic target of rapamycin kinase (mTOR) mediated control of mitochondrial metabolism in AFD cells. Cerebrovascular complications due to AFD are caused by cerebral micro vessel stenosis. These are caused by wall thickening resulting from the intramural accumulation of glycolipids, luminal occlusion or thrombosis. Other pathogenetic mechanisms involved in organ damage linked to Gb3 accumulation are endocytosis and lysosomal degradation of endothelial calcium-activated intermediate-conductance potassium ion channel 3.1 (KCa3.1) via a clathrin-dependent process. This process represents a crucial event in endothelial dysfunction. Several studies have identified the deacylated form of Gb3, globotriaosylsphingosine (Lyso-Gb3), as the main catabolite that increases in plasma and urine in patients with AFD. The mean concentrations of Gb3 in all organs and plasma of Galactosidase A knockout mice were significantly higher than those of wild-type mice. The distributions of Gb3 isoforms vary from organ to organ. Various Gb3 isoforms were observed mainly in the kidneys, and kidney-specific Gb3 isoforms were hydroxylated. Furthermore, the action of Gb3 on the KCa3.1 channel suggests a possible contribution of this interaction to the Fabry disease process, as this channel is expressed in various cells, including endothelial cells, fibroblasts, smooth muscle cells in proliferation, microglia, and lymphocytes. These molecular pathways could be considered a potential therapeutic target to correct the enzyme in addition to the traditional enzyme replacement therapies (ERT) or drug chaperone therapy.

Analysis of Glomerular Filtration Rate in Ischemic Cerebrovascular Diseases under the Magnetic Resonance Angiography Image Segmentation Algorithm

In order to discuss the segmentation effect of the magnetic resonance angiography (MRA) image segmentation algorithm based on the fuzzy clustering algorithm and DR-CV model and the prognostic value of glomerular filtration rate (GFR) in the ischemic cerebrovascular disease (ICVD), a total of 178 patients who were admitted to the hospital and received MRA due to ICVD were selected as the research objects of this study. Blood vessel segmentation was performed on the MRA image by fuzzy clustering algorithm and DR-CV model, and all patients were divided into a control group (group A), a single-vessel stenosis group (group B), a two-vessel stenosis group (group C), and a multiple-vessel stenosis group (group D). The GFR was estimated by using the dietary modification equation for kidney disease, and the correlation between GFR and the severity of arterial stenosis in patients with ICVD was analyzed. It was found that the results of the Dice similarity index (DSI) of the MRA image blood vessel segmentation algorithm based on the fuzzy clustering algorithm and the integrated model of boundary and regional information (DR-CV model) were all above 85%. The age and GFR values of the four groups of patients were significantly different ( P < 0.05). The proportions of patients in groups C and D in the group with low DFR were significantly different from those in groups A and B ( P < 0.01); the proportions of patients in groups A and B in the high-level GFR group had extremely significant differences compared with group D ( P < 0.01). Age, GFR, total cholesterol (TC), and high-density lipoprotein-C (HDL-C) were correlated with the degree of arterial stenosis ( P < 0.05). It showed that the segmentation effect of MRA image blood vessel segmentation algorithm based on the fuzzy clustering algorithm and DR-CV model was better, and the GFR level can be used as an independent risk factor for the ICVD.

Retrospective Analysis of Surgical Treatment Results of Postinfarction Ventricular Septal Rupture

Ventricular septal rupture (VSR) is the most dramatic complication of acute myocardial infarction (MI). It manifests itself most often in the first week after infarction, with the maximum fatal complications occurring on day 1 and day 3–5 after MI. Patients receiving conservative treatment mostly die of progressive heart failure within few hours or days. Even now, in the era of endovascular interventions, surgical treatment remains the gold standard for the treatment of this pa-thology. Our research is mainly aimed at studying the factors of operative mortality, describing our methods of treatment and analyzing the survival rate and long-term outcomes after surgical treatment of this pathology. We studied 90 patients with postinfarction VSR who underwent surgical intervention in 2002–2019. Twelve of them were operated at the Central Clinical Hospital in Baku, and 78 at the National Amosov Institute of Cardiovascular Surgery in Ukraine. The mean age of the patients was 59.9 ± 9.59 years, 65 (72.2%) were men and 25 (27.8 %) were women. Fifteen (16.6%) patients were smokers, 31 (34.4%) were diabetic, 70 (77.7%) patients had arterial hypertension, 62% of patients had NYHA class III heart failure with average ejection fraction of 43.9 ± 10.4%. According to the results of coronary angiography, single vessel stenosis of the coronary arteries was detected in 18 (20%), two-vessel lesion in 32 (35.5%), and three-vessel lesion in 40 (44.4%) patients. There were no patients with left main coronary artery (LMCA) stenosis. Long-term results of surgical treatment were followed for 1 to 8 years, on average in 18 (28.6%) patients. Within 1, 3 and 8 years 17, 12 and 2 patients were examined, respectively. Good results within 5 and 10 years after surgical treatment were observed in 87.5% and 64.3% patients, respectively. Repeated complaints in our group and those observed in the literature are associated with worsening of heart failure after venticulotomy and changes in the geometry of the left ventricle. Recurrence of heart failure and coronary symptoms within 3 years and after 3 to 8 years were observed in 6 (33.3%) and 3 (25%) patients, respectively. Repeated endovascular revascularization was performed in 5 patients. ICD was im-planted in 4 patients, and in 2 patients CRT-D was implanted within 4 years 2 months and 7 years, respectively. There were no hemorrhagic complications within 8 years. Four (22.2%) patients died in the long-term period, the cause of death was unknown. In intensive care department the treatment strategy suggested hemodynamic stabilization with the help of conserva-tive therapy and IABP. The patients who underwent surgery in ≥ 3 weeks after the diagnosis of postinfarction VSR survived within 30 days after surgery. Delayed planned recovery is stipulated by the formation of scar tissue in the myocardium, which enables to facilitate the technical aspects of recovery. The time of the operation depends mainly on hemodynamic status of the patient. Patients with cardiogenic shock should undergo immediate surgical treatment.

Abstract P582: Accuracy of Transcranial Doppler in Detection of Intracranial Stenosis in Patients With Sickle Cell Disease

Background: Stroke is among the most devastating consequences of sickle cell disease (SCD). Most SCD strokes occur due to intracranial stenosis, that can be detected by increased flow velocities on Transcranial Doppler (TCD). However, increased velocities may also reflect anemia rather than arteriopathy and vessel stenosis. We aimed to assess the accuracy of TCD in detection of intracranial stenosis in SCD. Methods: Pediatric SCD patients with at least one TCD and MRA within one month apart were identified from a retrospectively collected database maintained at our institution from January 2000 to December 2016. Patient demographics, hemoglobin level, transfusion and hydroxyurea status were collected, along with mean flow velocities (mFV) and degree of stenosis from bilateral middle and anterior cerebral, and internal carotid arteries. A mFV of > 200 cm/s and vessel stenosis > 50% were considered abnormal. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were obtained to assess overall accuracy of TCD velocities in relation to vessel stenosis. Multivariate analysis was performed to identify independent factors associated with MRA stenosis. Results: A total of 164 patients were included in the database (median age 12 [IQR 8.9] years, 56% had ischemic strokes) and 64 of them had at least one TCD and MRA one month apart. Of these, 20% had ischemic strokes, 17% had MRA stenosis > 50% and 10% had TCD velocity > 200 cm/s. TCD mFV > 200 cm/s had a high specificity (95%) and NPV (87%) but low sensitivity (29%) and PPV (55%) when compared to MRA stenosis > 50%. As a continuous variable, TCD mFV 137.5 cm/s had the best balance between maximal specificity (77%) and sensitivity (72%). After adjustment for age, hemoglobin level, transfusion status, hydroxyurea, and vessel, for every increase in cm/sec on TCD, there was a 2% increase in the odds of > 50% stenosis on MRA (OR=1.02, 95% CI 1.01-1.03, p<0.001). Conclusion: Our study reports that TCD mFV is a positive predictor of MRA stenosis in SCD, independent of patient characteristics, including hemoglobin. A mFV > 200 cm/s is highly specific but less sensitive to detect stenosis > 50%. Lower mFV cut points may need to be considered for early detection of intracranial stenosis and risk of stroke.

Abstract P565: Influence of Thyroid Disease on Presentation and Outcomes of Moyamoya Disease

Introduction: The presence of thyroid autoantibodies may play a role in the pathogenesis of moyamoya-type angiopathy. However, the influence of thyroid disease on presenting characteristics and treatment outcomes of moyamoya disease (MMD) remains unclear. Methods: Consecutive patients with MMD prospectively treated at our institution from 2015-2018 were reviewed. Results: 264 MMD patients with MMD were identified, 33 (12.5%) of whom presented with concurrent thyroid disease (4 hyperthyroid, 28 hypothyroid, 1 unspecified). Comparing groups with and without thyroid disease, there were no differences in age of presentation (p=0.12), racial composition (p=0.38), or rates of diabetes (p=0.32), hypertension (p=1.0), and hyperlipidemia (p=0.71). There was a higher proportion of females (94% F vs. 74% F, p=0.02) and lower rates of smoking (p=0.04) and alcohol consumption (p=0.04) in the thyroid disease group. Despite lower rates of vascular risk factors, the thyroid disease group exhibited more severe angiographic MMD at presentation, with higher Suzuki grade (p=0.002), higher proportion of bilateral disease (91% vs. 67%, p=0.007), and a trend towards more posterior circulation involvement (39% vs. 24%, p=0.09). MMD patients with concurrent thyroid disease were also more likely to present with carotid occlusion as opposed to large vessel stenosis (39% vs 10%, p=0.03), resulting in increased collateral filling via the extracranial (3.5% vs. 2.8%, p=0.04) and posterior circulations (24% vs. 16%, p=0.002). Patients with thyroid disease trended towards having higher rates of ischemic complications (28% vs. 16.8%, p=0.06) perioperatively; however, there were no differences in rates of post-operative hemorrhage (p=1.0) or transient neurologic events (p=0.85). Conclusions: Patients with concurrent moyamoya and thyroid disease present with more advanced angiographic intracranial disease, which may be associated with higher rates of ischemic complications in the perioperative period.