Turkish Real Life Atrial Fibrillation in Clinical Practice: TRAFFIC Study.

BACKGROUND: Atrial fibrillation (AF) is the most prevalent cardiac arrhythmia worldwide and is associated with an increased risk of thromboembolism, ischemic stroke, impaired quality of life, and mortality. The latest research that shows the prevalence and incidence of AF patients in Türkiye was the Turkish Adults' Heart Disease and Risk Factors study, which included 3,450 patients and collected data until 2006/07.The Turkish Real Life Atrial Fibrillation in Clinical Practice (TRAFFIC) study is planned to present current prevalence data, reveal the reflection of new treatment and risk approaches in our country, and develop new prediction models in terms of outcomes. METHODS: The TRAFFIC study is a national, prospective, multicenter, observational registry. The study aims to collect data from at least 1900 patients diagnosed with atrial fibrillation, with the participation of 40 centers from Türkiye. The following data will be collected from patients: baseline demographic characteristics, medical history, vital signs, symptoms of AF, ECG and echocardiographic findings, CHADS2-VASC2 and HAS-BLED (1-year risk of major bleeding) risk scores, interventional treatments, antithrombotic and antiarrhythmic medications, or other medications used by the patients. For patients who use warfarin, international normalized ratio levels will be monitored. Follow-up data will be collected at 6, 12, 18, and 24 months. Primary endpoints are defined as systemic embolism or major safety endpoints (major bleeding, clinically relevant nonmajor bleeding, and minor bleeding as defined by the International Society on Thrombosis and Hemostasis). The main secondary endpoints include major adverse cardiovascular events (systemic embolism, myocardial infarction, and cardiovascular death), all-cause mortality, and hospitalizations due to all causes or specific reasons. RESULTS: The results of the 12-month follow-up of the study are planned to be shared by the end of 2023. CONCLUSION: The TRAFFIC study will reveal the prevalence and incidence, demographic characteristics, and risk profiles of AF patients in Türkiye. Additionally, it will provide insights into how current treatments are reflected in this population. Furthermore, risk prediction modeling and risk scoring can be conducted for patients with AF.

Exercise Prevents Glucocorticoid-Induced Myocardial 4-Hydroxynonenal Production.

PURPOSE: Long-term administration of glucocorticoids (GCs) increases myocardial oxidative stress. 4-Hydroxynonenal (4-HNE) protein adducts, a marker of oxidative damage, have been associated with several cardiovascular diseases, including atherosclerosis, cardiac hypertrophy, cardiomyopathy, and ischemia-reperfusion injury. Exercise training has been shown to have a protective effect on the heart by lowering the level of oxidative stress in cardiomyocytes. Therefore, we aimed to investigate the effect of long-term dexamethasone treatment and exercise training on myocardial 4-HNE levels. METHODS: Twenty-four female Wistar albino rats were assigned to sedentary control-saline treated (C, n = 8), sedentary-dexamethasone treated (D, n = 8), and exercise training-dexamethasone treated (DE, n = 8) groups. Daily dexamethasone was injected for 28 days at a 1 mg kg-1 dose, while C animals were injected with the same volume of saline subcutaneously. DE animals underwent an exercise training protocol of 60 min/day, 5 days a week, at 25 m/min-1 (0% grade) for 28 days. Left ventricular 4-HNE, Hsp72 levels, and pHsp25/Hsp25 ratio were determined by Western blot. RESULTS: The administration of dexamethasone led to a significant elevation in 4-HNE levels in the myocardium of adult rats (p < 0.05; D vs. C). The concurrent implementation of exercise training impeded this increase (p > 0.05; DE vs. C). Exercise training induced a threefold increase in myocardial Hsp72 expression (p < 0.001; DE vs. C and D) and attenuated the dexamethasone-induced increase in Hsp25 phosphorylation (p < 0.05; C vs. D) (p < 0.001; DE vs. D). CONCLUSION: Our results indicate that long-term administration of dexamethasone is associated with an increase in cardiac 4-HNE levels, which is hindered by the addition of exercise training.

Long-term Dexamethasone Treatment Increases Cardiac Galectin-3 Levels.

PURPOSE: Glucocorticoids, which are widely prescribed around the world, cause cardiac remodeling in long-term treatment by triggering insulin resistance and increasing blood pressure. However, its role in cardiac remodeling remains unclear. Galectin-3 (gal-3) is a member of a beta-galactoside-binding animal lectins, upregulated as a result of insulin resistance and in the pressure-overloaded myocardium and regulate cardiac remodeling. We hypothesized that gal-3 may be upregulated in the myocardium with prolonged use of glucocorticoids and associated with cardiac hypertrophy. METHODS: To examine the involvement of glucocorticoids in gal-3 levels in rat myocardium, sixteen female Wistar Albino rats were assigned to control (C; n = 8) and dexamethasone (Dex; n = 8) groups. Daily dexamethasone was injected subcutaneously for 28 days at a dose of 1 mg.kg-1. Control animals were injected with the same volume of saline. The body weight and heart weights were determined. Gal-3 levels in myocardium were determined by Western blot. RESULTS: Our data shows that dexamethasone administration resulted in significant increase in heart weight (p < 0.05) and HW/BW ratios (p < 0.001) and 28 days of dexamethasone administration with the dose of 1 mg.kg-1 caused a twofold increase in the gal-3 expression in the left ventricle (p < 0.001). CONCLUSION: The finding of the current study is the first to show that dexamethasone causes an increase in gal-3 levels in myocardium. Our study provides an important step in the development of possible therapeutics by determining that dexamethasone causes an increase in gal-3 levels in the myocardium and raises awareness about the follow-up of patients receiving long-term glucocorticoid therapy.

Value of point-of-care neutrophil gelatinase associated lipocalin in early diagnosis of acute kidney injury in patients with left ventricular systolic dysfunction after coronary angiography.

BACKGROUND: Increased neutrophil gelatinase-associated lipocalin (NGAL) levels are associated with toxic or ischemic renal injury. OBJECTIVE: This study aimed to assess the usefulness of serial NGAL measurements with a point-of-care assay in patients with left ventricular systolic dysfunction (LVSD) for earlier detection of contrast-induced nephropathy (CIN). MATERIALS AND METHODS: A total of 84 patients with LVSD patients referred for coronary angiography were consecutively enrolled in the study. The study population was divided into two groups as the CIN and the non-CIN groups according to the CIN's determination. The serum creatinine levels were calculated 24 h before the procedure and at the 48th and 72nd h after the cardiac catheterization. The plasma NGAL concentration was measured before and at 4 and 24 h after the cardiac catheterization. RESULTS: Baseline and serial NGAL levels were significantly higher in patients with CIN compared to the patients without CIN. NGAL 24th h levels after the index procedure were found to be an independent and significant predictor of CIN in multivariate analysis. CONCLUSIONS: Serial point-of-care NGAL measurements might help earlier detection of CIN in patients with heart failure after coronary angiography.

Níveis de Tiol Sérico e Homeostase Tiol/Dissulfeto em Pacientes com Doença Valvar Mitral Reumatismal e em Sujeitos Saudáveis / Serum Thiol Levels and Thiol/Disulfide Homeostasis in Patients with Rheumatic Mitral Valve Disease and Healthy Subjects

Resumo Fundamento A doença valvar mitral reumatismal (DVMR) é a apresentação mais comum das doenças cardíacas reumáticas (DCR). Os processos de inflamação e fibrose também têm papéis significativos em sua patogênese. Estudos recentes demonstram que os tióis e o tiol-dissulfeto são marcadores de stress oxidativo inéditos e promissores. Objetivos O objetivo deste estudo foi avaliar diferenças entre os níveis de tiol sérico e de tiol-dissulfeto em pacientes com DVMR e no grupo de controle. Métodos Noventa e dois pacientes com DVMR foram cadastrados no estudo. Cinquenta e quatro sujeitos saudáveis, e com correspondência de sexo e idade em relação ao grupo de estudo, também foram incluídos no estudo como um grupo de controle. Foram investigados os níveis de tiol nos pacientes com DVMR e o grupo de controle. Os p-valores menores que 0,05 foram considerados estatisticamente significativos. Resultados Os pacientes com DVMR apresentaram pressão sistólica da artéria pulmonar (PSAP) e níveis de diâmetro do átrio esquerdo (AE) mais altos que os do grupo de controle. Os níveis de tiol nativo (407±83 μmol/L vs. 297±65 μmol/L, p<0,001) e tiol total (442±82 μmol/L vs. 329±65 μmol/L, p<0,001) são mais altos no grupo de controle. Níveis de dissulfeto (16,7±4,9 μmol/L vs. 14,8±3,7 μmol/L, p=0,011) são mais altos no grupo de pacientes com DVMR. Foi identificada uma correlação positiva entre as razões dissulfeto/tiol nativo e dissulfeto/tiol total com PSAP, diâmetro de AE, e gravidade da EMi. A razão dissulfeto/tiol total é significativamente mais alta em pacientes com EMi grave que em pacientes com EMi leve a moderada. Conclusões Até onde se sabe, este é o único estudo que avaliou a homeostase tiol/dissulfeto como um preditor inédito, que está relacionado de forma mais próxima à DVMR e à gravidade da EMi.

Abstract Background Rheumatic mitral valve disease (RMVD) is the most common presentation of rheumatic heart disease (RHD). Inflammation and fibrosis processes also play significant roles in its pathogenesis. Recent studies showed that thiols and thiol-disulfide are promising novel oxidative stress markers. Objectives The present study aimed to evaluate differences in the serum thiol and thiol-disulfide levels in patients with RMVD and the control group. Methods Ninety-two patients with RMVD were enrolled in the study. Fifty-four healthy subjects, age, and gender-matched with the study group, were also included in the study as a control group. This study investigated thiol levels in patients with RMVD and the control group. P-values lower than 0.05 were considered statistically significant. Results The patients with RMVD presented higher systolic pulmonary artery pressure (SPAP) and left atrial (LA) diameter levels than the control group. Native thiol (407±83 μmol/L vs. 297±65 μmol/L, p<0.001) and total thiol (442±82 μmol/L vs. 329±65 μmol/L, p<0.001) levels were higher in the control group. Disulfide (16.7±4.9 μmol/L vs. 14.8±3.7 μmol/L, p=0.011) levels were higher in the group of patients with RMVD. A positive correlation was found between disulfide/native and disulfide/total thiols ratio with SPAP, LA diameter, and MS severity. Disulfide/total thiols ratio was significantly higher in patients with severe MS than with mild to moderate MS patients. Conclusions To the best of our knowledge, this is the only study of its kind that has evaluated thiol/disulfide homeostasis as a novel predictor, which was more closely related to RMVD and the severity of MS.

Serum Thiol Levels and Thiol/Disulfide Homeostasis in Patients with Rheumatic Mitral Valve Disease and Healthy Subjects. / Níveis de Tiol Sérico e Homeostase Tiol/Dissulfeto em Pacientes com Doença Valvar Mitral Reumatismal e em Sujeitos Saudáveis.

BACKGROUND: Rheumatic mitral valve disease (RMVD) is the most common presentation of rheumatic heart disease (RHD). Inflammation and fibrosis processes also play significant roles in its pathogenesis. Recent studies showed that thiols and thiol-disulfide are promising novel oxidative stress markers. OBJECTIVES: The present study aimed to evaluate differences in the serum thiol and thiol-disulfide levels in patients with RMVD and the control group. METHODS: Ninety-two patients with RMVD were enrolled in the study. Fifty-four healthy subjects, age, and gender-matched with the study group, were also included in the study as a control group. This study investigated thiol levels in patients with RMVD and the control group. P-values lower than 0.05 were considered statistically significant. RESULTS: The patients with RMVD presented higher systolic pulmonary artery pressure (SPAP) and left atrial (LA) diameter levels than the control group. Native thiol (407±83 µmol/L vs. 297±65 µmol/L, p<0.001) and total thiol (442±82 µmol/L vs. 329±65 µmol/L, p<0.001) levels were higher in the control group. Disulfide (16.7±4.9 µmol/L vs. 14.8±3.7 µmol/L, p=0.011) levels were higher in the group of patients with RMVD. A positive correlation was found between disulfide/native and disulfide/total thiols ratio with SPAP, LA diameter, and MS severity. Disulfide/total thiols ratio was significantly higher in patients with severe MS than with mild to moderate MS patients. CONCLUSIONS: To the best of our knowledge, this is the only study of its kind that has evaluated thiol/disulfide homeostasis as a novel predictor, which was more closely related to RMVD and the severity of MS.

FUNDAMENTO: A doença valvar mitral reumatismal (DVMR) é a apresentação mais comum das doenças cardíacas reumáticas (DCR). Os processos de inflamação e fibrose também têm papéis significativos em sua patogênese. Estudos recentes demonstram que os tióis e o tiol-dissulfeto são marcadores de stress oxidativo inéditos e promissores. OBJETIVOS: O objetivo deste estudo foi avaliar diferenças entre os níveis de tiol sérico e de tiol-dissulfeto em pacientes com DVMR e no grupo de controle. MÉTODOS: Noventa e dois pacientes com DVMR foram cadastrados no estudo. Cinquenta e quatro sujeitos saudáveis, e com correspondência de sexo e idade em relação ao grupo de estudo, também foram incluídos no estudo como um grupo de controle. Foram investigados os níveis de tiol nos pacientes com DVMR e o grupo de controle. Os p-valores menores que 0,05 foram considerados estatisticamente significativos. RESULTADOS: Os pacientes com DVMR apresentaram pressão sistólica da artéria pulmonar (PSAP) e níveis de diâmetro do átrio esquerdo (AE) mais altos que os do grupo de controle. Os níveis de tiol nativo (407±83 µmol/L vs. 297±65 µmol/L, p<0,001) e tiol total (442±82 µmol/L vs. 329±65 µmol/L, p<0,001) são mais altos no grupo de controle. Níveis de dissulfeto (16,7±4,9 µmol/L vs. 14,8±3,7 µmol/L, p=0,011) são mais altos no grupo de pacientes com DVMR. Foi identificada uma correlação positiva entre as razões dissulfeto/tiol nativo e dissulfeto/tiol total com PSAP, diâmetro de AE, e gravidade da EMi. A razão dissulfeto/tiol total é significativamente mais alta em pacientes com EMi grave que em pacientes com EMi leve a moderada. CONCLUSÕES: Até onde se sabe, este é o único estudo que avaliou a homeostase tiol/dissulfeto como um preditor inédito, que está relacionado de forma mais próxima à DVMR e à gravidade da EMi.

Possible value of galectin-3 on follow-up of cardiac remodeling during glucocorticoid treatment.

Glucocorticoids are among the most prescribed drugs globally due to their potent anti-inflammatory and immunosuppressive properties. Although they have positive effects on the treatment of various disease states; long-term administration is associated with high blood pressure, insulin resistance, and susceptibility to type 2 diabetes. The heart attempts to cope with increased blood pressure and a decrease in glucose utilization by developing pathological cardiac remodeling. However, in this process, cardiac fibrosis formation and deterioration in heart structure and functions occur. Galectin-3, a member of the ß-galactoside binding lectins, is consistently associated with inflammation and fibrosis in the pathogenesis of various disease states including insulin resistance and heart failure. Galectin-3 expression is markedly increased in activated macrophages and a subset of activated fibroblasts and vascular cells. Also, failing and remodeling myocardium show increased Gal-3 expression and elevated Gal-3 levels are related to heart failure severity and prognosis. Furthermore, Gal-3-related pathways are recently suggested as therapeutic targets both pharmacologically and genetically to increase insulin sensitivity in vivo. The objective of this review is to provide a summary of our current understanding of the role of glucocorticoid-associated insulin resistance, which is important for some cardiac events, and the potential role of galectin in this pathophysiological process.

Whole blood viscosity predicts nondipping circadian pattern in essential hypertension.

Aim: We aimed to investigate the association between whole blood viscosity (WBV) and nondipping pattern in patients with essential hypertension. Materials & methods: A total of consecutive 530 patients who had been evaluated by ambulatory blood pressure monitoring were included. WBV was estimated by using hematocrit and plasma total protein levels for both WBV in low shear rate (0.5 s-1) and WBV in high shear rate (208 s-1) according to the de Simone's formula. Results: In the multivariate analysis, low shear rate and high shear rate of WBV were associated independently with nondipping pattern in patients with essential hypertension. Conclusion: As a simple, inexpensive and noninvasive tool, WBV seems to be a significant predictor of nondipping hypertension.

Transcatheter Self-Expandable Aortic Valve (Portico) Implantation in a Patient with Previous Mitral Valve Replacement: A Case Report.

Transcatheter aortic valve implantation (TAVI) has shown favorable outcomes in patients with severe symptomatic aortic valve stenosis who are at high surgical risk or who are unsuitable candidates for open-heart surgery. However, concerns exist over treating patients who have undergone previous mitral valve surgery due to the potential interference between the mitral prosthetic valve or ring and the TAVI device. In this case report, we present a case in which a patient with symptomatic severe aortic stenosis and previous mechanical mitral valve replacement was successfully treated with TAVI using a Portico valve, which is under-researched.

The role of thiol levels in predicting contrast-induced nephropathy in patients with ST-segment elevation myocardial infarction who underwent primary percutaneous coronary intervention.

OBJECTIVE: Contrast-induced nephropathy (CIN) is a common complication of diagnostic or interventional procedures that may arise from administration of intravascular contrast media. Recent studies have reported the thiol-disulfide ratio as a novel oxidative stress marker. Therefore, we investigated the role of thiol levels in predicting CIN in patients with ST-segment elevation myocardial infarction (STEMI) who had undergone primary percutaneous coronary intervention (PCI). METHODS: A total of 302 patients were enrolled in the study. CIN was defined as an increase in serum creatinine concentration ≥0.5 mg/dL compared with the admission value or a >25% relative rise during the first 48-72 hours after the procedure. To evaluate the relationship between thiol levels and CIN, the patients were divided into a CIN group and a non-CIN group. RESULTS: CIN occurred in 44 (15%) patients. Native thiol (274.8±84.7 µmol/L vs. 220.8±97.1 µmol/L, p=0.001) and total thiol (305.4±89.7 µmol/L vs. 260.1±102.1 µmol/L, p=0.009) levels were higher in patients within the non-CIN group. Disulfide (15.8±6.6 µmol/L vs. 19.6±8.4 µmol/L, p=0.002) levels, and mean disulfide/total thiol ratios (8.4±3.7 vs. 5.9±3.1, p=0.001) were higher in patients with CIN (+) group. In univariate analysis, the initial native thiol, total thiol, disulfide levels, and disulfide/total thiol ratio were found to have prognostic significance in the development of CIN. In the multivariate regression analysis, only the disulfide/total thiol ratio (OR=1.190; 95% CI: 1.090-1.300; p=0.001) was significantly and independently associated with CIN. The cutoff value of the disulfide/total thiol ratio to predict CIN on admission in patients with STEMI who underwent primary PCI was 7, with a sensitivity of 68.2% and a specificity of 79.8%. CONCLUSION: Our results suggest that thiol/disulfide homeostasis could be a good biochemical risk marker for CIN in STEMI patients who underwent primary PCI.

Percutaneous left atrial appendage closure in a patient with haemophilia and atrial fibrillation: a case report.

BACKGROUND: Atrial fibrillation (AF) is the most common cardiac arrhythmia and is a major cause of embolic stroke. In patients with hereditary bleeding disorders such as haemophilia, management of AF particularly anticoagulation can be quite challenging. Left atrial appendage (LAA) closure is an emerging option in AF patients who are not eligible for oral anticoagulation therapy because of contraindications or high bleeding risk. CASE SUMMARY: A 67-year-old man with permanent AF and haemophilia was referred for further evaluation of our cardiology clinic by his primary haematologist. The CHA2DS2-VASc score was estimated to be 3 and the HAS-BLED score was 3. Due to high risk of bleeding, we decided to perform percutaneous LAA closure instead of oral anticoagulation. Pre-procedural cardiac computerized tomography angiography and transoesophageal echocardiography were performed for measurements of LAA dimensions and exclude LAA thrombus. Percutaneous LAA occlusion was performed using a 28-mm AmplatzerTM AmuletTM device. The final result was excellent without significant residual leak, pericardial effusion, and embolic complication. Clopidogrel 75 mg/day and aspirin 81 mg/day for 1 month with adequate FVIII prophylaxis and then only aspirin 81 mg/day for 2 months were recommended. No antiplatelet was given after 3 months. The patient did not report any thrombotic or haemorrhagic adverse events and there were no complications related to implanted device after 1 year of follow-up. DISCUSSION: In patients with hereditary bleeding disorders such as haemophilia, management of AF particularly anticoagulation can be quite challenging. In this report, we present a case of percutaneous LAA occlusion using AmplatzerTM AmuletTM device in a patient who has haemophilia and permanent AF. LAA closure has the potential to be more cost effective as compared to oral anticoagulation therapy due to lesser necessity of clotting factor infusion.

Platelet to Lymphocyte Ratio on Admission and Prognosis in Patients with Acute Cardiogenic Pulmonary Edema.

BACKGROUND: Acute heart failure is a heterogenous syndrome defined by a number of factors, such as its physiopathology, clinical picture, time of onset, and relation to acute coronary syndrome. Acute cardiogenic pulmonary edema (ACPE) constitutes approximately 10-20% of acute heart failure syndromes, and it is the most dramatic symptom of left heart failure. Platelet to lymphocyte ratio (PLR) is a relatively novel inflammatory marker that can be utilized for prognosis in various disease processes. OBJECTIVE: In this study, we investigated the value of the PLR for the prediction of mortality in patients with ACPE. METHODS: A total of 115 patients hospitalized with a diagnosis of ACPE were included in this study. The patients were divided into tertile groups according to their PLR values: high (PLR > 194.97), medium (98.3-194.97), and low tertile (PLR < 98.3). RESULTS: We compared the PLR groups for in-hospital mortality and total mortality after discharge. Multivariate Cox regression analysis showed that PLR was independently associated with total mortality (hazard ratio 5.657; 95% confidence interval 2.467-12.969; p < 0.001). Survival analysis using the Kaplan-Meier curve showed that the high-PLR group had a significantly higher mortality rate than the other groups. CONCLUSIONS: We showed an association between high PLR and mortality in patients with ACPE. PLR, together with other inflammatory markers and clinical findings, may be used as an adjunctive parameter for the stratification of mortality risk, hospitalization, or discharge criteria scoring.

Can hemodialysis change QRS axis in patients without cardiovascular disease?

OBJECTIVE: Due to rapid changes in volume and electrolyte concentration during hemodialysis (HD), some electrocardiographic (ECG) changes or arrhythmias can be seen. The aim of this study was to assess ECG QRS axis changes and other ECG parameters after HD in patients with end-stage renal disease (ESRD). METHODS: A total of 46 patients (65% male, mean age 52±15 years) with a sinus rhythm and without cardiovascular disease who were undergoing chronic HD treatment were included to the study. Blood samples, 12-lead electrocardiograms, and echocardiograms were recorded immediately before and at the end of an HD session. The QRS axis and other electrocardiographic, echocardiographic, electrolyte parameter, and volume changes were analyzed. RESULTS: The serum urea, creatinine, potassium, and B-type natriuretic peptide concentrations significantly decreased after HD, and the serum calcium levels significantly increased after HD. Body weight significantly decreased after HD. There was no significant difference in the QRS duration, PR interval, P-wave axis, QRS axis, or QT and QTc interval following HD. Based on a comparison of variables according to the any QRS axis change after HD treatment, there was no significant difference in biochemical values, HD time, ultrafiltration volume, left ventricular ejection fraction, or other echocardiographic findings. CONCLUSION: ESRD and HD are complex and dynamic processes, and the change in the QRS axis is rarely emphasized in these patients. In our study, there was no significant change in the QRS axis with HD in patients without cardiovascular disease.

Combination of change in hematological parameters with exercise stress test to predict coronary artery disease.

OBJECTIVE: Treadmill exercise stress testing for identifying patients with a higher likelihood of coronary artery disease (CAD) before elective coronary angiography is recommended in the current guidelines. In this study, we aimed to evaluate the changes in the hematological parameters before and after exercise stress test in relation with the presence of CAD. METHODS: A total of 113 patients with chest pain who underwent treadmill exercise testing and coronary angiography were included in this study. RESULTS: Neutrophil count (4.38±0.99 vs 5.19±0.93, P<.001), and neutrophil to lymphocyte ratio (NLR) (2.04±0.63 vs 2.41±0.78, P<.001) were significantly elevated after treadmill exercise test in all the patients. Increase in the NLR after exercise test was significantly higher in patients with positive exercise test (n=68) than negative exercise test (n=45) (0.49±0.58 vs 0.19±0.44, P=.016). The sensitivity and specificity of treadmill exercise testing according to coronary angiography was 79% and 64%, respectively. A cut-off point of 0.2 for the change in the NLR in addition to positive treadmill exercise testing had 91% sensitivity and 92% specificity in predicting significant coronary artery stenosis (AUC:0.913, 95% CI: 0.805-1.000, P<.001). CONCLUSIONS: Neutrophil to lymphocyte ratio is an important inflammatory marker that can contribute to treadmill ECG testing in predicting CAD.

Pleiotrophin levels are associated with improved coronary collateral circulation.

OBJECTIVES: Elucidation of the underlying mechanisms of angiogenesis and arteriogenesis in coronary collateral formation is necessary for new therapies. Pleiotrophin is a secreted multifunctional cytokine and associated with the formation of functional cardiovascular neovascularization in a series of experimental animal models. We aimed to evaluate the serum levels of pleiotrophin in patients with chronic total coronary artery occlusion and poor or good collateral development. METHODS: We included 88 consecutive patients (mean age of the entire population: 63.7±12.1 years, 68 male patients) with stable angina pectoris who underwent coronary angiography and had chronic total occlusion in at least one major coronary artery. Collateral grading was performed according to the Rentrop classification. After grading, patients were divided into poor collateral circulation (Rentrop grade 0 and 1) and good collateral circulation (Rentrop grades 2 and 3) groups. Serum pleiotrophin levels were measured using a commercial human ELISA kit. RESULTS: Fifty-eight patients had good and 30 patients had poor coronary collaterals. The good collateral group had higher serum pleiotrophin levels than the poor collateral group (690.1±187.9 vs. 415.3±165.9 ng/ml, P<0.001). Pleiotrophin levels were higher with higher Rentrop grade (P<0.001). In multivariate analysis, increased pleiotrophin was associated independently with good collateral development (odds ratio: 1.007; confidence interval: 1.003-1.012; P=0.002). CONCLUSION: This study showed that increased serum pleiotrophin levels are associated with better developed coronary collateral circulation. Further studies are needed to better understand the relationship.

Homocysteine, visceral adiposity-related novel cardiometabolic risk factors, and exaggerated blood pressure response to the exercise treadmill test.

OBJECTIVE: Exaggerated blood pressure response to exercise is a risk factor for the development of future hypertension. In this study, we aimed to investigate the association between homocysteine, epicardial fat thickness, nonalcoholic hepatic steatosis, and exaggerated blood pressure response to exercise. PARTICIPANTS AND METHODS: We included 44 normotensive and 40 patients with exaggerated blood pressure response to exercise who have normal resting blood pressure and without a previous diagnosis of hypertension. All patients underwent treadmill exercise test and clinical, ultrasonographic, and echocardiographic evaluation. Exaggerated blood pressure response to exercise is defined as peak exercise systolic blood pressure of at least 210 mmHg in men and at least 190 mmHg in women. Homocysteine and other biochemical parameters were determined with standardized automated laboratory tests. RESULTS: Mean age of all participants is 47.9±8.5 years, and 36 of 84 participants were female. The frequency of diabetes mellitus in both groups was similar (P=0.250). Homeostasis model assessment index-insulin resistance had a statistically insignificant trend to be higher in a patient with exercise hypertension (P=0.058). The nonalcoholic fatty liver was more frequent in patients with exercise hypertension (13.6 vs. 47.5%, P=0.002). Epicardial fat thickness was increased in patients with exercise hypertension (5.5±1.5 vs. 7.3±1.1 mm; P=0.001). However, homocysteine levels did not significantly differ between normotensive and exercise hypertensive patients [12.3 µmol/l (5.7-16.9 µmol/l) vs. 13 µmol/l (5.9-28.3 µmol/l); P=0.883]. CONCLUSION: In our study, homocysteine levels were not associated with exaggerated blood pressure response to exercise; however, fatty liver and epicardial fat thickness as visceral adiposity-related cardiometabolic risk factors were significantly related with exaggerated blood pressure response to exercise in patients without a previous diagnosis of hypertension.

Clinically significant bleeding with low-dose rivaroxaban versus aspirin, in addition to P2Y12 inhibition, in acute coronary syndromes (GEMINI-ACS-1): a double-blind, multicentre, randomised trial.

BACKGROUND: Dual antiplatelet therapy (DAPT), aspirin plus a P2Y12 inhibitor, is the standard antithrombotic treatment following acute coronary syndromes. The factor Xa inhibitor rivaroxaban reduced mortality and ischaemic events when added to DAPT, but caused increased bleeding. The safety of a dual pathway antithrombotic therapy approach combining low-dose rivaroxaban (in place of aspirin) with a P2Y12 inhibitor has not been assesssed in acute coronary syndromes. We aimed to assess rivaroxaban 2·5 mg twice daily versus aspirin 100 mg daily, in addition to clopidogrel or ticagrelor (chosen at investigator discretion before randomisation), for patients with acute coronary syndromes started within 10 days after presentation and continued for 6-12 months. METHODS: In this double-blind, multicentre, randomised trial (GEMINI-ACS-1) done at 371 clinical centres in 21 countries, eligible patients were older than 18 years with unstable angina, non-ST segment elevation myocardial infarction (NSTEMI) or ST segment elevation myocardial infarction (STEMI), with positive cardiac biomarkers and either ischaemic electrocardiographic changes or an atherosclerotic culprit lesion identified during angiography. Participants were randomly assigned (1:1) within 10 days after admission for the index acute coronary syndromes event to either aspirin or rivaroxaban based on a computer-generated randomisation schedule. Randomisation was balanced by using randomly permuted blocks with size of four and was stratified based on the background P2Y12 inhibitor (clopidogrel or ticagrelor) intended to be used at the time of randomisation. Investigators and patients were masked to treatment assignment. Patients received a minimum of 180 days of double-blind treatment with rivaroxaban 2·5 mg twice daily or aspirin 100 mg daily. The choice of clopidogrel or ticagrelor during trial conduct was not randomised and was based on investigator preference. The primary endpoint was thrombolysis in myocardial infarction (TIMI) clinically significant bleeding not related to coronary artery bypass grafting (CABG; major, minor, or requiring medical attention) up to day 390. Primary analysis was by intention to treat. This study is registered with ClinicalTrials.gov, number NCT02293395. FINDINGS: Between April 22, 2015, and Oct 14, 2016, 3037 patients with acute coronary syndromes were randomly assigned; 1518 to receive aspirin and 1519 to receive rivaroxaban. 1704 patients (56%) were in the ticagrelor and 1333 (44%) in the clopidogrel strata. Median duration of treatment was 291 days (IQR 239-354). TIMI non-CABG clinically significant bleeding was similar with rivaroxaban versus aspirin therapy (total 154 patients [5%]; 80 participants [5%] of 1519 vs 74 participants [5%] of 1518; HR 1·09 [95% CI 0·80-1·50]; p=0·5840). INTERPRETATION: A dual pathway antithrombotic therapy approach combining low-dose rivaroxaban with a P2Y12 inhibitor for the treatment of patients with acute coronary syndromes had similar risk of clinically significant bleeding as aspirin and a P2Y12 inhibitor. A larger, adequately powered trial would be required to definitively assess the efficacy and safety of this approach. FUNDING: Janssen Research & Development and Bayer AG.