Endotrophin and matrix metalloproteinase-2 levels in bicuspid aortic valve and hypertension associated aortopathy and their relationship with strain parameters of the ascending aorta.

OBJECTIVE: Bicuspid aortic valve (BAV) is the most common congenital heart defect. Ascending aorta dilatation is related to BAV- and hypertension (HTN)-associated aortopathy. The aim of this study was to investigate aortic elasticity, as well as aortic deformation of the ascending aorta, using strain imaging, and to evaluate the possible relationship of biomarkers, such as endotrophin and matrix metalloproteinase-2 (MMP-2), with ascending aorta dilatation in patients with BAV- or HTN-associated aortopathy. PATIENTS AND METHODS: This prospective study included patients with ascending aorta dilatation with BAV (n = 33), or normal tricuspid aortic valve with HTN (n = 33), and 20 control subjects. The mean age of the total patients was 42.76 ± 10.4 years (67% male, 33% female). We calculated aortic elasticity parameters using the relevant formula by M-mode echocardiography and determined layer-specific longitudinal and transverse strains of the proximal aorta by speckle-tracking echocardiography. Blood samples of the participants were drawn for the analysis of endotrophin and MMP-2. RESULTS: Aortic strain and aortic distensibility were significantly decreased, whereas the aortic stiffness index was significantly increased in patient groups with BAV or HTN compared to the control group (p < 0.001). Moreover, longitudinal strain of both the anterior and posterior aortic walls of the proximal aorta were significantly impaired in BAV and HTN patients (p < 0.001). Serum endotrophin levels were significantly reduced in the patient cohort compared to the controls (p = 0.001). Endotrophin was noted to be significantly positively correlated with aortic strain and aortic distensibility (r = 0.37, p = 0.001; r = 0.45, p < 0.001, respectively), whereas inversely associated with aortic stiffness index (r = -0.402, p < 0.001). Furthermore, endotrophin was the single independent predictor of ascending aorta dilatation (OR = 0.986, p < 0.001). A cut-off value of endotrophin ≤ 82.38 ng/mL predicted ascending aorta dilatation with a sensitivity of 80.3% and specificity of 78.5% (p < 0.0001). CONCLUSIONS: The present study showed that aortic deformation parameters and elasticity are impaired in BAV and HTN patients, and strain imaging allows for a good analysis of ascending aorta deformation. Endotrophin could be a predictive biomarker of ascending aorta dilatation in BAV and HTN aortopathy.

Severe vitamin D deficiency is associated with endothelial inflammation in healthy individuals even in the absence of subclinical atherosclerosis.

OBJECTIVE: Vitamin D has beneficial effects, some of which involve the cardiovascular system. No study to date has investigated the association between serum endocan levels, as a biomarker of endothelial inflammation, and vitamin D levels in the absence of subclinical atherosclerosis detected by carotid intima-media thickness (CIMT) in healthy individuals. PATIENTS AND METHODS: Subjects were categorized into three groups based on vitamin D levels according to Endocrine Society guidelines. Mean CIMT was calculated from six measurements on two scans. Statistical significance was set at p < 0.05, and all testing was two-sided. RESULTS: The concentration of serum endocan was 802.8 ± 411.4 ng/L in the group with the lowest serum vitamin D level, 454.8 ± 334.3 ng/L in the mild/moderately low serum vitamin D level group, and 269.4 ± 180.2 ng/L in the group with normal serum vitamin D levels (p < 0.01). Receiver operating characteristics curve analysis revealed that a serum vitamin D concentration of 7.5 ng/mL had a 97% sensitivity and 81% specificity for the prediction of serum endocan level greater than 270 ng/L, which could be an indicator for endothelial inflammation. CONCLUSIONS: Demonstrating that vitamin D deficiency can cause endothelial damage in the early period of atherosclerosis without the development of clinical cardiovascular disease will have a pivotal role in the prevention of cardiovascular mortality and morbidity.

Endocan: a biomarker predicting successful reperfusion after coronary artery by-pass surgery of acute coronary syndrome patients.

OBJECTIVE: Endothelial specific molecule 1 (Endocan) is a biomarker of the inflammatory process occurring in endothelial cells. It was shown that endocan was increased in acute coronary syndromes. We aimed at investigating the endocan levels in acute coronary syndrome patients after coronary bypass surgery. PATIENTS AND METHODS: The study included 35 patients who presented with acute coronary syndrome to the Emergency Department. Serum endocan levels and other inflammatory markers were evaluated before and after coronary artery by-pass surgery. The correlation coefficients and their significance were calculated by Pearson's test and the difference in mean values before and after bypass surgery was calculated by paired sample t-test. Statistical analyses were performed using SPSS version 20.0 (SPSS Inc., Chicago, IL, USA). Statistical significance was taken as p<0.05. RESULTS: There was a significant change in serum hs-CRP and endocan levels and also LVEF before and after CABG operation (p<0.05). CONCLUSIONS: Serum endocan level was significantly decreased after successful reperfusion in our study. Thus, it may be an important biomarker in terms of clinical use as an indicator of successful reperfusion.

Type I cardiorenal syndrome in patients with acutely decompensated heart failure: the importance of new renal biomarkers.

OBJECTIVE: Type 1 cardiorenal syndrome (CRS) is an acute renal failure in patients with acute decompensated heart failure with an incidence of 24% to 45%. The aim of our study was to investigate the significance of new renal biomarkers to predict type 1 CRS. PATIENTS AND METHODS: The study included 111 patients with acute decompensated heart failure diagnosed at the Istanbul Medical Faculty Emergency Department between 2014 and 2016, and 24 healthy volunteers. All urine samples were stored at -80°C after centrifugation. Samples were run according to the instructions of TIMP-2, ILGF-7, KIM-1, and IGFBP-7 ELISA kits. Diuretic treatments were then administered with intravenous administration of at least 80 mg furosemide per day. Follow-up biochemical and spot urine specimens were taken after 72 hours. For statistical analysis, SPSS version 21.0 statistical software was used. Significance was evaluated at p<0.05. RESULTS: The baseline creatinine level was measured as 1.33 ± 0.39 mg/dL in the heart failure group. It was seen that 67% (75) of the patients had increased creatinine levels and developed type 1 CRS. ILGF-7, TIMP-2, and (ILGF-7 * TIMP-2) values were significantly higher in patients with cardiorenal syndrome when we separated the two groups as patients with and without cardiorenal syndrome (0.40 (0.25-0.71), p1: 0.049/2.40 (1.42-3.70), p2: 0.003/1.15 (0.29-2.43), p3: 0.001). CONCLUSIONS: Renal tubular markers reveal promising developments in the pathophysiology of cardiorenal syndrome in light of recently obtained data. Renal tubular biomarkers may have the potential to be a predictor of heart failure and cardiorenal syndrome.

A novel parameter for the diagnosis of acute pulmonary embolism: the T-wave peak-to-end interval.

OBJECTIVE: Acute pulmonary embolism (APE) is a very common disease that must be diagnosed and treated quickly and accurately to reduce significant morbidity and mortality rates. Acute pulmonary embolism is associated with numerous electrocardiographic (ECG) changes including prolonged QT interval with global T-wave inversion. The aim of the study was to investigate the relationship between the T-wave peak-to-end interval and diagnosis of APE, which has never been investigated in the literature. PATIENTS AND METHODS: Seventy-three patients who were suspected of having APE took part in the present study. The Local Ethics Committee of Istanbul University, Turkey, approved the study protocol. Forty-one of the patients were diagnosed as having APE using computed tomography. Surface ECGs were taken in the initial assessment at admission. The Tp-Te interval was identified as the interval from the peak of the T-wave to the end of the T-wave. The measurements of the Tp-Te interval were taken using precordial leads. All measurements were compared using appropriate statistical tests. Statistical analysis was performed using SPSS version 22.0. RESULTS: We enrolled 73 patients to the study, 41 of which were diagnosed as having APE. Men comprised 54% of the APE group. The mean ages in the APE (+) and APE (-) groups were 59.5 ± 14.5 years and 61±9.2 years, respectively. There was a significant increase in Tp-Te results in V1 (p<0.01). The Tp-Te interval was 74.21 ± 20.81 in the APE (+) group, whereas it was 59.73 ± 12.82 in APE (-) group (p<0.01). CONCLUSIONS: Acute pulmonary embolism (APE) is a mortal condition and as such, rapid and accurate diagnosis is very important. Surface ECG can be used to measure Tp-Te in patients admitted to the emergency room with suspected APE in the differential diagnosis as a fast and easily accessible tool.

Identification of gene variants related to the nitric oxide pathway in patients with acute coronary syndrome.

Dysfunction of vascular endothelium is known to have an essential role in the atherosclerotic process by releasing mediators including nitric oxide (NO). Nitric oxide maintains endothelial balance by controlling cellular processes of vascular smooth muscle cells. Evidence suggests that variations in the NO pathway could include atherosclerotic events. The objective of this study was to determine the possible effects of genes on the nitric oxide pathway in the development of acute coronary syndrome (ACS). The blood samples of 100 patients with ACS and 100 controls were collected at Istanbul University, Department of Cardiology. DNA samples were genotyped by using Illumina Cyto-SNP-12 BeadChip. The additive model and Correlation/Trend Test were selected for association analysis. Afterwards, a Q-Q graphic was drawn to compare expected and obtained values. A Manhattan plot was produced to display p-values that were generated by -log10(P) function for each SNP. The p-values under 1×10(-4) were selected as statistically significant SNPs while p-values under 5×10(-2) were considered as suspicious biomarker candidates. Nitric oxide pathway analysis was then used to find the single nucleotide polymorphisms (SNPs) related to ACS. As a result, death-associated protein kinase 3 (DAPK) (rs10426955) was found to be most statistically significant SNP. The most suspicious biomarker candidates associated with the nitric oxide pathway analysis were vascular endothelial growth factor A (VEGFA), methionine sulfoxide reductase A (MSRA), nitric oxide synthase 1 (NOS1), and GTP cyclohydrolase I (GCH-1). Further studies with large sample groups are necessary to clarify the exact role of nitric oxide in the development of disease.

The relationship between T-wave peak-to end interval and ST segment recovery on intracoronary ECG during primary PCI.

OBJECTIVE: T-wave peak to end interval (TPE) is a measure of repolarization dispersion, which has been reported as a major arrhythmogenic factor post acute myocardial infarction. The aim of our study was to investigate the changes in TPE in this patient population with regard to peri-procedural intracoronary ECG findings. PATIENTS AND METHODS: Forty-four patients (34 male and mean age of 54.9 ± 10.9 years) with acute STEMI were included. Intracoronary ECG was performed during primary PCI. TPE indices were calculated before and after the procedure. Measurement of the intracoronary ST-segment was carried out before and just after coronary blood flow was established in the infarct related artery. Intracoronary ST-segment resolution (IC-STR) was defined as ≥ 1 mm compared to baseline. RESULTS: There was no difference with respect to baseline characteristics when patients with IC-STR were compared with patients without IC-STR. TPE values decreased significantly after primary PCI in patients with IC-STR (80.9 ± 22.8 ms vs. 65.8 ± 14.4 ms; p < 0.001) whereas they did not change significantly after PCI in patients without IC-STR (79.2 ± 20.9 ms vs. 68.5 ± 16.3 ms; p = 0.18). CONCLUSIONS: TPE measured from surface ECG recordings is significantly reduced in STEMI patients with successful reperfusion after primary PCI, as determined by IC-ECG recordings.

Association of genetic polymorphisms with endothelial dysfunction in chronic heart failure.

OBJECTIVES: Endothelial dysfunction can be shown very early in the cardiovascular disease. In the present study the association between congestive heart failure (CHF), endothelial function and 3 gene polymorphisms was investigated. PATIENTS AND METHODS: In 104 healthy controls and 104 CHF patients, endothelial constitutive nitric oxide synthase (ecNOS), angiotensin converting enzyme (ACE) and angiotensin II type 1 receptor (AT1R) gene polymorphisms were assessed. The cause of CHF was ischemic in 68 patients and dilated cardiomyopathy (DCMP) in 36 patients. High resolution brachial artery ultrasound was used in 37 CHF patients and 37 healthy controls to assess the endothelial function. Endothelium-dependent vasodilation (EDD) and endothelium-independent vasodilation (EID) were determined. RESULTS: There no was difference between controls and CHF patients for the ACE, ecNOS, and AT1R genotype frequencies. Compared to controls CHF patients had significantly impaired EDD (9.0+5% vs 16±7%, p < 0.001) and EID (13±6% vs 19+8%, p = 0.001). EDD (7±4% vs 12+6%, p = 0.005), but not EID, was significantly impaired in ischemic CHF as compared to DCMP patients. In the CHF group ecNOS a allele and AT1R C allele influence the EDD. CONCLUSIONS: Endothelial dysfunction was present in CHF group and the presence of ecNOS a allele and AT1R C allele further impaired EDD.

Analgesic effects of rofecoxib in ear-nose-throat surgery.

UNLABELLED: In this study we evaluated the analgesic efficacy and the opioid-sparing effect of rofecoxib in ear-nose-throat surgery patients. Patients undergoing nasal septal or sinus surgery were randomized to receive either oral placebo or rofecoxib 50 mg 1 h before surgery. All patients received propofol 0.8 mg/kg, fentanyl 1 microg/kg, and local anesthesia at the operative site. Sedation was maintained by a continuous infusion of propofol adjusted to maintain sedation at a 2-3 level on the Ramsey scale. Additional fentanyl 0.5-1 microg/kg was administered at the patient's request or if the verbal rating scale score was >4. Patient sedation and pain scores were obtained at 5, 15, 30 45, and 60 min during surgery and 30 min and 2, 4, 6, 12, and 24 h after completion of the procedure. During the postoperative period, diclofenac 75 mg IM was administered for analgesia at the patient's request or if the visual analog scale (VAS) rating for pain was more than 4. VAS pain scores, intraoperative fentanyl, and postoperative diclofenac requirements were significantly smaller in the rofecoxib group compared with the placebo group (P < 0.001). The times to first analgesic request were also significantly less in the rofecoxib group. We conclude that the preoperative administration of oral rofecoxib provided a significant analgesic benefit and decreased the need for opioids in patients undergoing nasal septal and nasal sinus surgery. IMPLICATIONS: The aim of this study was to evaluate the analgesic efficacy and opioid-sparing effect of rofecoxib, a new selective cyclooxygenase-2 inhibitor drug, in ear-nose-throat surgery patients. Preoperative administration of oral rofecoxib provided a significant analgesic benefit and decreased the need for opioids in patients undergoing nasal septal and nasal sinus surgery.