Objective: The purpose of the study was to analyze the prevalence of hyponatremia and related 1-year outcomes of patients hospitalized for decompensated heart failure with reduced ejection fraction (HFrEF) in Turkish patients.
Methods: A total of 500 hospitalized patients with HFrEF were consecutively included in a retrospective study at 19 participating hospitals. Patients were categorized according to their serum sodium levels (sNa) on admission day as normonatremic (135–145 mEq/L) and hyponatremic (<135 mEq/L). One-year all-cause mortality, re-hospitalization rates, and the impact of the changes in sNa at the time of discharge to clinical outcomes were examined.
Results: Hyponatremia was observed in 29% of patients. Patients with hyponatremia had lower blood pressures, creatinine clearance, and left ventricular ejection fraction and higher serum creatinine and BUN levels on admission compared with those with normonatremia. Hyponatremia was associated with higher 1-year all-cause mortality (14% vs. 2.6%, p<0.001) and re-hospitalization rates (46.9% vs. 33.7%, p=0.005). After adjustment for covariates, hyponatremia was independently associated with 1-year all-cause mortality (adjusted HR, 4.762; 95% CI, 1.941–11.764; p=0.001). At discharge, only 50.8% of hyponatremic patients were corrected to normonatremia (≥135 mEq/L). Those with persistent hyponatremia had the highest all-cause mortality (p<0.001).
Conclusion: In this study, it is demonstrated that hyponatremia is relatively common and is associated with increased 1-year all-cause mortality and re-hospitalization rates among Turkish patients hospitalized with HFrEF. Approximately 50% of the patients with initial low sNa had persistent hyponatremia at discharge, and these patients had the worst clinical outcomes. (Anatol J Cardiol 2017; 17: 2-7)

Objective: In our study, sildenafil alone and everolimus or alagebrium in combination with sildenafil were investigated in terms of their additional therapeutic and anti-remodeling activity in monocrotaline-induced pulmonary hypertension (PH) model in rats. In particular, the inter-relation-ships between PH and matrix metalloproteinases (MMPs) were investigated.
Methods: The pulmonary artery responses of male Sprague Dawley rats were recorded using myography, and the quantities and activities of MMPs were analyzed in homogenates of the pulmonary arteries and lungs by enzyme-linked immunosorbent assays, activity assays, and gelatin zymography techniques.
Results: Our results indicated that the therapeutic effects of sildenafil were accompanied by its suppressor effects on MMP activity. It was also shown that everolimus or alagebrium in combination with sildenafil showed additional regulatory effects on MMPs as well as functional responses on pulmonary artery pressure. Therefore, the enzymes in the MMP superfamily are likely to be target molecules for the treatment of PH.
Conclusion: In conclusion, MMPs were involved in the pathogenesis of PH, and our results suggested that the addition of everolimus or alagebrium to sildenafil therapy may be beneficial in PH. Our results indicated that agents that limit pulmonary vascular hypertrophy and inflammation via their anti-remodeling effects significantly ameliorate mortality and morbidity in PH. (Anatol J Cardiol 2017; 17: 8-17)

Objective: Aquaporin (AQP) 1 and AQP 4 are expressed in human heart and several studies have been focused on these two aquaporins. For this purpose, the present study is aimed to research the effects of aging on AQP 1 and AQP 4 in heart tissue.
Methods: In this study, 14 Balb/C type white mice were used. Animals were divided into two equal groups. Group I consisted of 2-month-old young animals (n=7), and group II consisted of 18-month-old animals (n=7). To determine the AQP1 and AQP4 expression in the myocardium, the heart tissue was removed to perform western blotting and immunohistochemical and histopathological evaluations.
Results: Muscle fibers of the heart in aged animals were more irregular and loosely organized in hematoxylin–eosin (H&E) stained sections. H- score analysis revealed that AQP1 and AQP4 immunoreactivity significantly increased in heart tissues of old mice compared with those of young mice (p<0.001). In addition, AQP1 and AQP4 protein expressions in the tissues of old animals were increased significantly according to western blot analysis (p=0.018 and p<0.001 for AQP1 and AQP4, respectively).
Conclusion: Increased AQP1 and AQP4 levels in the heart tissue may be correlated with the maintenance of water and electrolytes balance, which decreases with aging. In this context, it might be the result of a compensatory response to decreased AQP4 functions. In addition, this increase with aging as demonstrated in our study might be one of the factors that increases the tendency of ischemia in elder people. (Anatol J Cardiol 2017; 17: 18-23)

Objective: Recent studies have shown that activation of the immune system, inflammatory cell infiltration, and activation of inflammatory mediators play an important role in the development of heart failure. The purpose of this study was to investigate whether cardiac function can be improved by regulating the balance of lymphocyte subsets and cytokines.
Methods: Ninety-six patients with chronic heart failure (CHF) who were older than 60 years were randomly divided into two groups: CHF testing group (CHFT) received regular therapy and thymopentin (2 mg thymopentin per day, 15th as a course, three courses in total). CHF control group (CHFC) received regular therapy. Forty-five healthy individuals older than 60 years were used as normal controls. The ejection fraction of left ventricle (LVEF), inner diameter of left ventricular end-diastole (LVEDD), inner diameter of left ventricular end-systole (LVESD), plasma high sensitive C-reactive protein (hsCRP), plasma brain natriuretic peptide (BNP), 6-min walking distance (6MWT), Minnesota Living with Heart Failure Questionnaire (MLHFQ) assessment, lymphocyte subsets, and inflammatory cytokines were tested.
Results: The levels of LVEF, 6MWT, CD 3+, CD4+T cells, natural killer cells, CD4+/CD8+ and IL-10 in CHFT were increased (p<0.01) compared with CHFC, while BNP, hsCRP, MLHFQ, CD8+, TNF-α, IL-1β, and TNF-α/IL-10 ratio in CHFT were decreased (p<0.01). LVEDD and LVESD were decreased, even though there was no significant difference between the two CHF groups.
Conclusion: These data suggest that immune modulation therapy improve cardiac function and regulate cytokines and lymphocyte subsets in older patients with CHF. (Anatol J Cardiol 2017; 17: 24-30)

Objective: By releasing mediators, like nitric oxide (NO), vascular endothelium is considered so significant in the process of atherosclerotic. In fact, the major functions of NO consist in inhibiting the activation of platelet, relaxing the muscles (vascular and smooth ones), and modulating the growth and the migration of cells (vascular and smooth ones). Therefore, this process makes the endothelial nitric oxide synthase (NOS3) considerably important because it possesses atheroprotective activity. Polymophisms, rs1808593 (10G/T) as well as rs891512 (G24943A) within NOS3 gene, play major role in the coronary artery disease (CAD) development. The aim of the study is to evaluate the relationship between the 10G/T and G24943A polymorphisms and the CAD among Tunisian individuals.
Methods: We included, in this survey, a set of 274 patients suffering from CAD together with 162 normotensive subjects. The PCR-RFLP was applied to analyze the polymorphism of intron 23 (10G/T) gene, while the ASA-PCR was used to analyze the intronic G24943A gene polymorphism. Overall and subgroup analyses were performed. Odds ratio (OR) and 95% confidence interval (CI) were used to evaluate the association between NOS3 10G/T and G24943A polymorphisms as well as CAD risk. Statistical analysis was performed with SPSS V.10.
Results: The genotype frequencies for G24943A polymorphism differed significantly between the CAD patients and the controls. The former had a frequency of 11.4% for the AA genotype, 34.7% for the GA genotype and 53.9% for the GG genotype. The latter had a frequency of only 2.5% for the AA genotype, 29.7% for the GA genotype and 67.7% for the GG genotype (χ2=7.62; OR=1.79; p=0.006). The CAD patient group showed a significantly-higher frequency of the A allele compared to the controls (0.28 vs. 0.16; χ2=15.20; p<0.001). The odds ratio of CAD for A vs. G allele frequency was statistically significant 1.99 (1.4–2.82) at 95% CI. The genotype distribution for the 3 investigated variants of 10G/T were not significantly different between CAD and control subjects (χ2=1.46; OR=1.72; p=0.22). Whereas, 10G/T has revealed barely allelic (χ2=4.45; OR=2.3; p=0.034) correlation with coronary artery disease
Conclusion: The present study was designed so that there would be an association between the CAD and NOS3 polymorphism (G24943A). However, these results have proven that the polymorphism of 10G/T is not associated with CAD in the Tunisian population. (Anatol J Cardiol 2017; 17: 31-6)

Objective: Subendocardial viability ratio (SEVR), defined as diastolic to systolic pressure-time integral ratio, is a useful tool reflecting the balance between coronary perfusion and arterial load. Suboptimal SEVR creating a supply–demand imbalance may limit favorable cardiac response to cardiac rehabilitation (CR). To explore this hypothesis, we designed a study to analyze the relationship between baseline SEVR and response to CR in patients with coronary artery disease (CAD).
Methods: In this prospectively study, after baseline arterial tonometry, echocardiography, and cardiopulmonary exercise tests (CPETs), patients undergone 20 sessions of CR. Post-CR echocardiographic and CPET measurements were obtained for comparison.
Results: Final study population was comprised of fifty subjects. Study population was divided into two subgroups by median SEVR value (1.45, interquartile range 0.38). Although both groups showed significant improvements in peak VO2, significant improvements in oxygen pulse (πO2) (from 16.1±3.4 to 19.1±4.8 mL O2.kg–1.beat–1; p<0.001) and stroke volume index (from 31±5 to 35±6 mL; p=0.008) were observed in only the patients in the above-median subgroup. The change in πO2 was also significantly higher in the above-median SEVR subgroup (2.9±3.3 vs. 0.5±2.4; p=0.007).
Conclusion: Our study shows that baseline supply–demand imbalance may limit systolic improvement response to CR in patients with CAD. (Anatol J Cardiol 2017; 17: 37-43)

Objective: Modified Limb Lead (MLL) ECG system may be used during rest or exercise ECG, or atrial activity enhancement. Because of modification in the limb electrode placement, changes are likely to happen in ECG wave amplitudes and frontal plane axis, which may alter the clinical limits of normality and ECG diagnostic criteria. The present study investigated the effects of the modified limb electrode position on the electrocardiographic waveforms, ST segment amplitudes (STa) and frontal plane axis.
Methods: The observational study included sixty sinus rhythm subjects of mean age 38.85±8.76 (SD) in the range 25 to 58 years. In addition to 12-lead ECG, MLL ECG was recorded with, the RA electrode placed in the 3rd right intercostal space to the right of the parasternal line, the LA electrode placed in the 5th right intercostal space to the right of the mid-clavicular line and the LL electrode placed in the 5th right intercostal space on the mid-clavicular line.
Results: The modification produced profound changes in ECG wave amplitudes and STa amplitudes in frontal plane leads. The QRS and T wave axis shifted on the average by –17o and 41o, respectively, with considerable individual variation, which altered the diagnostic criteria.
Conclusion: The ECG amplitudes and STa changes produced by the MLL system showed that all remains within the clinical limits, except the R wave amplitude in the modified lead I. It is evident that the MLL system produced deviations in frontal plane QRS axis which altered the diagnostic interpretation. (Anatol J Cardiol 2017; 17: 46-54)

Objective: Carotid intima-media thickness (CIMT) is reliable marker of subclinical atherosclerosis and cardiovascular events. Until today, there was no study that investigated whether epicardial adipose tissue (EAT), which is a surrogate for lipid depot in a special visceral tissue or circulating lipids, is more important for CIMT and atherosclerotic plaque.
Methods: Our study, having cross-sectional and prospective observational design, included 252 patients who were admitted to our outpatient clinic. EAT identified as an echo-free space under the pericardial layer on 2-dimensional echocardiography, was measured perpendicularly in front of the right ventricular free wall at end-systole.
Results: EAT significantly correlated with CIMT (r=0.623, p<0.001). CIMT was significantly increased with rising EAT thickness (0.72±0.15 mm, 0.85±0.16 mm, and 0.95±0.12 mm in patients with EAT <5 mm, 5–7, and >7 mm, p<0.001, respectively). Multiple linear regression analysis revealed that age (Beta: 0.406, p<0.001), male gender (Beta: 0.244, p<0.001), and EAT (Beta: 0.450, p<0.001) as independent correlates of CIMT. Otherwise, in logistic regression analysis, only EAT (OR, 1.386; 95% CI, 1.203–1.597, p<0.001) and LDL cholesterol (OR, 1.013; 95% CI, 1.002–1.013, p=0.02) were independent predictors for presence of carotid plaque.
Conclusion: Our study showed that EAT has a relationship with both CIMT and the presence of carotid plaque, but LDL is independently related to the plaque. This finding suggests that EAT thickness may be a risk factor and biomarker, playing an important role beginning from early stages of atherosclerosis, unlike LDL cholesterol, which appear to have a role in later stages of atherosclerosis. (Anatol J Cardiol 2017; 17: 56-63)

Objective: Psoriasis is associated with an increased frequency of cardiovascular risk factors. Metabolic syndrome (MS) and the Framingham risk score (FRS) are two different algorithms for evaluating cardiovascular risk. They include different features: waist circumference measurement is included in the MS criteria, whereas smoking, age, and gender are questioned in FRS. This study aimed to evaluate the frequency of MS and FRS in psoriasis patients compared with a control group and investigate the differences between MS and FRS.
Methods: This was a cross-sectional study involving 300 psoriasis patients and 177 controls. MS, FRS, and disease severity were evaluated.
Results: The frequency of MS was higher in females with psoriasis than in those in the control group (p=0.019). Females in the psoriasis group were more obese than those in the control group (p=0.036). FRS significantly differed between the patients and controls of age >60 years (p=0.006). The risk of hypertension in current and past smokers was higher in the psoriasis patients (OR=2.07 and 2.32–2.48, respectively) than in the control group. There was no statistically significant relationship among MS, FRS, and psoriasis severity (p>0.05).
Conclusion: The results of this study support the evaluation of cardiovascular risk assessment in female psoriasis patients with MS and in male and elderly psoriasis patients with FRS. (Anatol J Cardiol 2017; 17: 66-72)

A 31-year-old male patient with no medical history or medication use presented at emergency department with chest pain that had been ongoing for 2 hours. Electrocardiography indicator ST elevation in V2-V6 derivations, indicating acute anterior myocardial infarction. He was immediately taken to catheterization laboratory. Coronary angiography revealed thrombosed stenosis of left anterior descending artery. Drug-eluting stent was implanted in culprit lesion. Results of tests done prior to procedure revealed normal hemogram values [hemoglobin (Hb): 15.7 g/dL, hematocrit (Hct): 43.8%, platelet count: 297.000 per mm3]. After loading dose of ticagrelor 180 mg, patient was prescribed ticagrelor 90 mg twice a day and discharged without complication. Five weeks later, however, he was admitted to outpatient clinic with fatigue, dyspnea, headache, and hemiparesis of left extremities. Patient was taking acetylsalicylic acid (ASA) 100 mg, nebivolol 5 mg once a day, and ticagrelor 90 mg twice a day at the time. Laboratory results showed anemia (Hb: 8.4 g/dL, Hct: 25.0%), thrombocytopenia (platelet count: 20,000 per mm3), increase in LDH level (1074 U/L), and mild elevation of liver enzymes. Peripheral blood smear revealed schistocytes indicating fragmentation hemolysis. Patient had no fever, purpura, or renal failure. His prothrombin time (PT), activated partial thromboplastin time (aPTT), D-dimer, and fibrinogen levels were within normal limits. There was no sign of infection and HIV serology was negative. There was also no evidence of pathological fin- dings on cranial magnetic resonance imaging. He was diagnosed with TTP and referred to tertiary hematology clinic for further treatment. Plasma exchange and steroid therapy were administered. Ticagrelor was discontinued. Clinical improvement was observed and TTP went into complete remission after total of 5 plasma exchange treatments. Afterwards, patient used only ASA as an antiplatelet drug and was followed for 6 months. No further intervention or treatment was needed.