Effects of Ticagrelor on Ionic Currents and Contractility in Rat Ventricular Myocytes.

PURPOSE: Antiplatelet therapy has been widely used for management of patients with ischaemic heart diseases or thrombotic events. Experimental studies have shown that ticlopidine and clopidogrel decreased L-type Ca(2+) currents (ICaL), altered action potential (AP) duration and thence exerted negative inotropic effects. In this study we tested if ticagrelor, a non-thienopyridine agent, has any influence on contractile and electrical properties of isolated ventricular myocytes. METHODS: Cardiomyocytes were isolated from male rat hearts with an enzymatic dissociation procedure and left ventricular myocytes were used for experiments. The effects of ticagrelor (1 µM) on sarcomere shortening, ionic currents and action potentials were measured at 36 ± 1 °C. RESULTS: Ticagrelor significantly reduced ICaL density (~18%, p < 0.01) of ventricular myocytes and this effect was reversible. In consistence, it also decreased sarcomere shortening of electrically stimulated cardiomyocytes (13%, p < 0.05), while it did not change relaxation rates. Repolarizing K(+) currents and AP duration were unaffected by 1 µM ticagrelor application. CONCLUSIONS: Ticagrelor exerts a significant influence on contractile properties and membrane currents of ventricular myocytes similarly to thienopyridine agents. The impact of ticagrelor on cardiac excitation-contraction coupling elements is important, since it is widely used for the treatment of patients with heart diseases.

An epidemiological study to evaluate the use of vitamin K antagonists and new oral anticoagulants among non-valvular atrial fibrillation patients in Turkey- AFTER-2 study design.

OBJECTIVES: Atrial fibrillation (AF) is one of the most common causes of preventable ischemic stroke and is related to increased cardiovascular morbidity and mortality. There is a lack of data in Turkey on the use of new oral anticoagulants (NOACs), and time in therapeutic INR range (TTR) in vitamin K antagonist users and AF management modality. In this multi-center trial, we aimed to analyze, follow and evaluate the epidemiological data in non-valvular AF patients. STUDY DESIGN: Four thousand one hundred consecutive adult patients from 42 centers with at least one AF attack identified on electrocardiography will be included in the study. Patients with rheumatic mitral valve stenosis and prosthetic valve disease will be excluded from the study. At the end of one year, the patients will be evaluated in terms of major cardiac end points (death, transient ischemic attack, stroke, systemic thromboembolism, major bleeding and hospitalization). RESULTS: First results are expected in June 2015. Data about major cardiovascular end-points will be available in January 2016. CONCLUSION: The rates and kind of oral anticoagulant use, TTR in vitamin K antagonist users and main management modality applied in non-valvular AF patients will be determined by AFTER-2 study. In addition, the rate of major adverse events (MACEs) and the independent predictors of these MACEs will be detected (AFTER-2 Study ClinicalTrials.gov number, NCT02354456.).

Can lipid mediators and free fatty acids guide acute coronary syndrome diagnosis and treatment?

OBJECTIVE: The aim of this study was to investigate fatty acids, lipid mediator levels, and the desaturase index rates on different acute coronary syndrome types and their possible relationship with routine lipid parameters. METHODS: The study included 81 patients with myocardial infarction (MI), 20 patients with unstable angina pectoris, and 31 healthy people. Fatty acids, CD59, lipoxin A4, 8-isoprostane, serum lipids, albumin, C-reactive protein (CRP), and high sensitive troponin levels were measured in all participants. RESULTS: When the fatty acid groups were evaluated as a ratio of albumin, MUFA/albumin and SFA/albumin ratios were significantly higher in the MI group compared to the control group. Although CD59 and lipoxin A4 levels were higher in the control group, there was no significant differences between the groups. When lipoxin A4/CRP and CD59/CRP ratios were evaluated, the results were significantly lower than those in the control group. CONCLUSION: Lipid mediators may be useful in treating atherosclerosis by contributing to the resolution of inflammation.

Patient Perception, Knowledge and Adaptation in The Management of Heart Failure: A Multicenter, Cross-Sectional, Observational, Questionnaire-Based Study: ADAPTATION HF.

OBJECTIVE: The aim of this study is to reveal the perception levels of heart failure (HF) patients about the disease, their adaptation to the disease process, their compliance with the treatment, and their knowledge and thoughts about the disease from the patient's perspective. METHOD: Patients with a diagnosis of HF for at least 6 months who applied to the cardiology clinics of 10 different centers were included in this cross-sectional, multicenter and questionnaire-based study. A questionnaire consisting of sections that included demographic information, evaluation of the patient's symptoms, knowledge and experience of clinical follow-up, knowledge of HF, compliance and awareness of treatment was applied to the patients. RESULTS: 504 patients with a mean age of 59.8 ± 14.9 years (M/F: 360/144, 71.4%/28.6%) were included in the study. 61.2% of the patients stated that they knew about HF disease before. Most of the patients knew that the complaints of shortness of breath, fatigue and palpitation could develop due to HF (95.4%; 92.7%; 89.7%, respectively). The patients reported that they were mostly worried about not being able to provide their own self-care without the support of another person (67.5%). While the majority of patients (37.6%) thought that the worst disease was to have a cerebrovascular disease; only 10.9% stated that HF was the worst disease. While 98.8% of the patients stated that they used HF drugs regularly, a relatively large part of the patients did not know that the drugs were effective on kidney functions (68.5%) and blood pressure (76.9%). In the daily practice of the patients, the rate of weight follow-up was 35.5%, the rate of blood pressure monitoring was 26.9%, and the rate of patients who exercised was 27%. Among the patients, 73.3% said that they pay attention to the amount of salt they take with diet, and 33.5% have a completely salt.free diet. There was no difference between the groups with low and high knowledge scores in terms of Pittsburgh Sleep Quality Index (P > 0.005). The knowledge level score was significantly higher in patients with previous myocardial infarction (P = 0.002). CONCLUSION: Most of the HF patients participating in the study are aware of the signs and symptoms of HF, follow the recommendations of their physicians, and use drugs regularly. These patients should have more information about blood pressure monitoring, weight monitoring, diet and sodium restriction, exercise, which are included in the non-pharmacological part of treatment management.

[Percutaneous treatment of a ruptured sinus Valsalva aneurysm with double orifices]. / Çift agizli yirtilmis Valsalva sinüsü anevrizmasinin perkütan yolla tedavisi.

An aneurysm of the sinus of Valsalva (SVA) may rupture into the cardiac cavities and cause abnormal connections between these cavities and the aorta. The right atrium and/or right ventricle are the cavities into which the SVA is most commonly observed to rupture. A 30-year-old patient presented to our cardiology clinic with the complaint of dyspnea. His physical examination revealed a thrill localized in the 5th intercostal space on the right edge of the sternum and systolic-diastolic murmur beginning from the aortic focus and spreading to the neck and back along the right edge of the sternum. The echocardiographic and invasive examinations revealed two defects leading to a passage from the right sinus Valsalva to the right ventricle. While the left-to-right shunt ratio was calculated as 3.8, the anatomic locations and dimensions of the defects were found to be eligible for percutaneous closure. Using the Amplatzer Duct Occluder I device, the defects were closed in two sessions. Although the classical treatment method of ruptured SVA is surgical repair, percutaneous closure devices may be used as a reliable alternative method in suitable patients.

Association between mean platelet volume and severity of disease in patients with obstructive sleep apnea syndrome without risk factors for cardiovascular disease.

OBJECTIVES: Obstructive sleep apnea syndrome (OSAS) is associated with increased cardiovascular morbidity and mortality. Platelet activation and aggregation are central processes in the pathophysiology of atherothrombosis. Mean platelet volume (MPV), a determinant of platelet activation, is a newly-emerging risk factor for atherothrombosis. Therefore, we have investigated the possible association between OSAS and MPV. STUDY DESIGN: We selected 30 mild, 32 moderate, and 31 severe OSAS patients and 31 healthy control subjects matched for age, sex, and body mass index. MPV was measured using an automated blood cell counter. RESULTS: The MPV levels were significantly higher in the severe OSA group than in the control group (8.6±1.1 vs. 7.8±0.7 fl, p=0.03). There were no significant differences in respect to MPV between controls and patients with mild and moderate OSA (7.8±0.7 vs. 8.3±1.2 fl, p=0.2; 7.8±0.7 vs. 8.4±1.3 fl, p=0.08) and between patients with mild, moderate, and severe OSA (8.3±1.2 vs. 8.4±1.3 vs. 8.6±1.1 fl, p=0.9). Significant correlations were seen between MPV and apnea-hypopnea index (r=0.347, p?0.001), minimal oxygen saturation (r=-0.224, p=0.03), and the percentage of recording time spent at a oxygen saturation less than 90% (r=0.240, p=0.02). CONCLUSION: Our results suggest that OSAS patients tend to have relatively increased platelet activation andatherothrombotic risk.

Evaluation of the left ventricular regional function using two-dimensional speckle tracking echocardiography in patients with end-stage renal disease with preserved left ventricular ejection fraction.

OBJECTIVE: It is known that patients with end-stage renal disease (ESRD) more frequently develop a wide range of left ventricular (LV) structural and functional abnormalities. The aim of our study is to evaluate the left ventricular regional function using two-dimensional speckle tracking echocardiography (2D-STE) in ESRD patients with preserved left ventricular ejection fraction (PLVEF) undergoing haemodialysis treatment. METHODS AND RESULTS: In total 61 healthy individuals and 87 ESRD patients were enrolled. Using the 2D-STE method, the strain (S) and strain rate (SR(S): systolic, SR(E): early diastolic, SR(A): late diastolic) values belonging to the radial (R), circumferential (C), and longitudinal (L) functions of the LV have been measured and the SR(E/A) values were calculated. While the LVEF values in the ESRD group were found to be lower than in the healthy control group (64.39 +/- 5.7 vs. 65.49 +/- 3.95, P = 0.033; R(S) = 45.17 +/- 17.28 vs. 53.97 +/- 14.29, P = 0.001; L(S) = -19.71 +/- 3.1 vs. -30.13 +/- 2.1, P < 0.001; RSRE(E/A) = 1.55 +/- 0.85 vs. 2.04 +/- 0.96, P = 0.001; LSR(E/A) = 1.42 +/- 0.51 vs. 1.88 +/- 0.7, P < 0.001), no difference was observed in terms of the C(S) (19.42 +/- 7.14 vs. 18.57 +/- 4.12, P = 0.155) and CSR(E/A) (2.5 +/- 1.34 vs. 2.56 +/- 1.35, P = 0.869) values. The C(S) was observed as an independent predictor related to the LVEF (beta = 0.2, 95% CI: 0.126-0.207, P = 0.015). CONCLUSION: In patients with ESRD, although the longitudinal and radial systolic functions are reduced, the LVEF may remain within normal limits due to the preservation of the circumferential functions. 2D-STE has the potential to detect the severity of uraemic cardiomyopathy in the early stages of the disease and might provide useful information for the risk stratification in ESRD patients with PLVEF.

Angiotensin receptor neprilysin inhibitor for patients with heart failure and reduced ejection fraction: Real-world experience from Turkey (ARNi-TR).

OBJECTIVE: Heart failure (HF) is a growing public health problem with high morbidity and mortality. Recently, angiotensin receptor neprilysin inhibitor (ARNi) has emerged as a promising treatment for HF with reduced ejection fraction (HFrEF). Here, we shared our experience with the use of ARNi in HFrEF from multiple centers in Turkey. METHODS: The ARNi-TR is a multicenter, noninterventional, retrospective, observational study. Overall, 779 patients with HF from 22 centers in Turkey who were prescribed sacubitril/valsartan were examined. Initial clinical status, biochemical and echocardiographic parameters, and New York Heart Association functional class (NYHA-FC) values were compared with follow-up values after 1 year of ARNi use. In addition, the effect of ARNi on number of annual hospitalizations was investigated, and the patients were divided into 2 groups, depending on whether ARNi was initiated at hospitalization or under outpatient clinic control. RESULTS: N-terminal pro-brain natriuretic peptide (NT-proBNP), left-ventricle ejection fraction (LV-EF), and NYHA-FC values improved significantly in both groups (all parameters, p<0.001) within 1-year follow-up. In both groups, a decrease in hemoglobin A1c (HbA1c) values was observed in ARNi use (p<0.001), and a decrease in daily diuretic doses and hospitalizations owing to HF were observed after ARNi use (all comparisons, p<0.001). Hypotension (16.9%) was the most common side effect in patients using ARN. CONCLUSION: The ARNi-TR study offers comprehensive real-life data for patients using ARNi in Turkey. The use of ARNi has shown significant improvements in FC, NT-proBNP, HbA1c levels, and LV-EF. Likewise, reductions in the number of annual hospitalizations and daily furosemide doses for HF were seen in this study.

Effects of prasugrel on membrane potential and contractile activity of rat ventricular myocytes.

BACKGROUND: Though prasugrel is one of the important P2Y12 inhibitors currently in use for antiplatelet therapy, its potential effects on contractility and electrical activity of ventricular myocytes have not yet been investigated. Hence this study was designed to study the impact of prasugrel on contractile function and membrane potential of isolated ventricular myocytes. METHODS: Freshly isolated rat ventricular myocytes were used in this study. Myocyte contraction was measured during electrical stimulation of cardiomyocytes and the action potential (AP) recordings were obtained with current clamp mode of the patch-clamp amplifier. RESULTS: AP duration and fractional shortening of ventricular myocytes did not show any change with the administration of 1µM of prasugrel. However, remarkable depolarization of resting membrane potential followed by apparent fibrillation episodes was detected in the cardiomyocytes. Similar events were observed in the contractile activity of myocytes during field stimulation. Also, a higher concentration of prasugrel (10µM) elicited repeated fibrillations, which disappeared after washout or nitric oxide synthase (NOS) inhibition with L-NAME. In contrast, the same concentration of ticagrelor, another P2Y12 inhibitor did not induce fibrillation events though it decreased the contractility of ventricular myocytes significantly. The perfusion of ventricular myocytes with L-NAME did not alter the negative inotropic effect of ticagrelor. CONCLUSIONS: Prasugrel, a widely used antithrombotic agent, may induce depolarization in the membrane potential of myocytes as well as fibrillation via NO mediated pathway.

Assessment of left atrial function using speckle tracking echocardiography in ankylosing spondylitis: a case-control study.

The aim of this study is to assess the left atrium (LA) deformation parameters by using 2D speckle tracking echocardiography (2D-STE) in ankylosing spondylitis (AS) patients and to evaluate the relationship between these parameters and AS clinical indexes. 30 patients with AS (22 males, 8 females) and 30 healthy individuals (19 males, 11 females) were enrolled in this study. Transthoracic echocardiography was performed to both groups. Besides the conventional echocardiographic parameters, the LA strain parameters; including systolic-reservoir (LA S-S), early diastolic-conduit (LA S-E), late diastolic-contraction (LA S-A) were measured. No significant difference was found between two groups in terms of conventional echocardiographic parameters except mean deceleration time (DT). Mean DT was prolonged in the AS patients compare with the control group (173.5 ± 22.5 vs. 155.3 ± 36.7, p = 0.025). In the AS patients, LA S-S (48.3 ± 9.4 vs. 56.9 ± 10.1, p = 0.001), LA S-E (26.4 ± 6.4 vs. 31.6 ± 7.3, p = 0.005) and LA S-A (21.9 ± 4.7 vs. 25.4 ± 5.7, p = 0.013) values were statistically lower than the control group. Also a negative correlation was observed between the Bath Ankylosing Spondylitis Metrology Index (BASMI) and LA S-S (r = - 0.509, p = 0.004), LA S-E (r = - 0.501, p = 0.005). Our study demonstrated that 2D-STE is a useful method to determine the left atrial involvement in AS patients without the clinical evident of cardiovascular disease.

Type 1 neurofibromatosis complicated by pulmonary arterial hypertension: A case report.

Neurofibromatosis type I (NF1) is a rare genetic disease caused by mutations in the NF1 gene, which encodes the tumor suppressor neurofibromin. Precapillary pulmonary hypertension is a severe complication of NF1, initially described in patients with advanced parenchymal lung disease, which may complicate the course of NF1. Presently described is a case of neurofibromatosis complicated by pulmonary hypertension.

Swimming exercise reverses aging-related contractile abnormalities of female heart by improving structural alterations.

BACKGROUND: The objective of this study was to examine the effect of swimming exercise on aging-related Ca2+ handling alterations and structural abnormalities of female rat heart. METHODS: For this purpose, 4-month and 24-month old female rats were used and divided into three following groups: sedentary young (SY), sedentary old (SO), and exercised old (Ex-O). Swimming exercise was performed for 8 weeks (60 min/day, 5 days/week). Myocyte shortening, L-type Ca2+ currents and associated Ca2+ transients were measured from ventricular myocytes at 36 ± 1°C. NOX-4 levels, aconitase activity, glutathione measurements and ultrastructural examination by electron microscopy were conducted in heart tissue. RESULTS: Swimming exercise reversed the reduced shortening and slowed kinetics of aged cardiomyocytes. Although the current density was similar for all groups, Ca2+ transients were higher in SO and Ex-O myocytes with respect to the SY group. Caffeine-induced Ca2+ transients and the integrated NCX current were lower in cardiomyocytes of SY rats compared with other groups, suggesting an increased sarcoplasmic reticulum Ca2+ content in an aged heart. Aging led to upregulated cardiac NOX-4 along with declined aconitase activity. Although it did not reverse these oxidative parameters, swimming exercise achieved a significant increase in glutathione levels and improved structural alterations of old rats' hearts. CONCLUSIONS: We conclude that swimming exercise upregulates antioxidant defense capacity and improves structural abnormalities of senescent female rat heart, although it does not change Ca2+ handling alterations further. Thereby, it improves contractile function of aged myocardium by mitigating detrimental effects of oxidative stress.

Evaluation of Subclinical Left Ventricular Systolic Dysfunction in Chronic Asymptomatic Alcoholics by Speckle Tracking Echocardiography.

By using two-dimensional speckle tracking echocardiography, we aimed to investigate the structural and functional changes on myocardium in chronic asymptomatic alcoholics without any cardiovascular disease. Forty-one consecutive asymptomatic male alcoholics who were admitted to the outpatient alcoholism unit and 30 age matched healthy male volunteers selected as the control group were enrolled in the study. The study group were investigated by using standard two-dimensional echocardiography and speckle tracking echocardiography. The left ventricular (LV) global longitudinal strain and LV global circumferential strain were significantly lower in alcoholics when compared with control subjects. There was no difference in global radial strain between the two groups. To demonstrate the effect of total life time dose of ethanol (TLDE) on echocardiographic abnormalities, we assessed the correlation analysis. There was a nonsignificant weak correlation between global LV circumferential strain and TLDE (r = 0.27, p = 0.083). Speckle tracking echocardiography derived left ventricular systolic function was impaired in chronic alcoholic patients when compared with healthy controls.

Relation between serum sodium levels and clinical outcomes in Turkish patients hospitalized for heart failure: a multi-center retrospective observational study.

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.

Pulmonary Endarterectomy For Large Vessel Pulmonary Arteritis Mimicking Chronic Thromboembolic Disease.

Takayasu's arteritis is a chronic, non-specific primary and inflammatory disease of large vessels, especially the aorta and its branches. Although pulmonary artery involvement is common, clinical signs of pulmonary artery involvement as the initial presentation is rare. Considering Takayasu's arteritis in the early diagnosis is important. In this article, we report a 23-year-old female patient of Takayasu's arteritis who was treated with successful surgery combined with medical therapy.

The significance of the left atrial volume index in cardioversion success and its relationship with recurrence in patients with non-valvular atrial fibrillation subjected to electrical cardioversion: a study on diagnostic accuracy.

OBJECTIVE: The aim of this study was to assess the predictive value of the left atrial volume index (LAVI) in electrical cardioversion (ECV) and observe the recurrence rate of atrial fibrillation (AF) after a successful ECV in patients with non-valvular atrial fibrillation. METHOD: This study was designed as a diagnostic accuracy and prospective cohort study. Eighty patients (mean age 62±12 years; 52.5% female) were enrolled in study. LAVI was measured using the area-length method and the indexed body surface area. Patients in whom the sinus rhythm (SR) was established following the ECV were assessed according to the clinical and electrocardiography (ECG) findings at the first month and grouped as those with continued SR or recurrent AF. The Student's t, Mann-Whitney U, Fisher's exact, Chi-square tests, ROC and logistic regression analyses were used for statistical analysis. RESULTS: Subsequent to the ECV, SR was achieved in 62.5% (n=50) of the patients. In those where SR was established, the AP-Lad (4.32±0.62 vs. 4.77±0.4 cm/p=0.002) and LAVI (35.3±11.5 vs. 53.1±10.1 mL/m2/p<0.001) values were observed to be lower. ECV success was found to be associated only with the LAVI (OR:1.122, 95%CI: 1.058-1.191, p<0.001). The AUC was found as 0.892±0.041 for the LAVI (95% CI:0.075-0.285, p<0.001). During the controls at the end of the 1st month, SR was maintained in 72% (n=36) of the successful ECV group. Among the patients with maintained SR, the antero-posterior left atrial dimension (4.17±0.62 vs. 4.72±0.5 cm/p=0.004) and LAVI (30.8±6.2 vs. 46.8±13.9 mL/m2/p<0.001) values were also observed to be lower. Only the LAVI was found to be associated with the recurrence of the AF (OR:1.355, 95% CI: 1.154-1.591, p<0.001). The AUC was found as 0.950±0.029 for the LAVI (95% CI:0.063-0.313, p=0.003) CONCLUSION: Lower LAVI values before the ECV are strong and independent predictors of the success of the ECV and the maintenance of SR after a successful ECV.