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Item Current clinical practice of cardiac resynchronization therapy in Turkey: Reflections from Cardiac Resynchronization Therapy Survey-II(TURKISH SOC CARDIOLOGY, 2020-01-01) Kocyigit, Duygu; Sarigul, Nedim Umutay; Altin, Ali Timucin; Cay, Serkan; Polat, Veli; Saygi, Serkan; Gumrukcuoglu, Hasan Ali; Gemici, Kani; Ikitimur, Baris; Akyol, Ahmet; Bilge, Ahmet Kaya; Basarici, Ibrahim; Ozcan, Emin Evren; Demir, Mesut; Kabul, Hasan Kutsi; Ornek, Ender; Normand, Camilla; Linde, Cecilia; Dickstein, KennethObjective: Cardiac resynchronization therapy (CRT) has been shown to reduce mortality in selected patients with heart failure with reduced ejection fraction (HFrEF). CRT Survey-II was a snapshot survey to assess current clinical practice with regard to CRT. Herein, we aimed to compare Turkish data with other countries of European Society of Cardiology (ESC). Methods: The survey was conducted between October 2015 and December 2016 in 42 ESC member countries. All consecutive patients who underwent a de novo CRT implantation or a CRT upgrade were eligible. Results: A total of 288 centers included 11,088 patients. From Turkey, 16 centers recruited 424 patients representing 12.9\% of all implantations. Compared to the entire cohort, Turkish patients were younger with a lower proportion of men and a higher proportion with ischemic etiology. Electrocardiography (ECG) showed sinus rhythm in 81.5\%, a ORS duration of <130 ms in 10.1\%, and >= 150 ms in 63.8\% of patients. Left bundle branch block (LBBB) was more common. Median left ventricular ejection fraction (LVEF) was 25\%, lower than in the overall ESC cohort, but NYHA class was more often II. Most common indication for CRT implantation was HF with a wide ORS (70.8\%). Almost 98.3\% of devices implanted were CRT-D, in contrast to the overall cohort. Fluoroscopy time was longer, but duration of overall procedure was shorter. LV lead implantation was unsuccessful in 2.6\% patients. Periprocedural complication rate was 6.3\%. The most common complication was bleeding. Remote monitoring was less utilized. Conclusion: These are the first observational data reflecting the current CRT practice in Turkey and comparing it with other countries of Europe. Findings of this study may help detect gaps and provide insights for improvement.Item Predictive Value of Endoplasmic Reticulum Stress Markers in Low Ejection Fractional Heart Failure(INT INST ANTICANCER RESEARCH, 2019-01-01) Sabirli, Ramazan; Koseler, Aylin; Mansur, Nesteren; Zeytunluoglu, Ali; Sabirli, Gizem Tukenmez; Turkcuer, Ibrahim; Kilic, Ismail DoguBackground/Aim: Endoplasmic reticulum (ER) stress plays a critical role in the development of cardiac hypertrophy and heart failure. Heart failure is a crucial health problem that affects 23 million people worldwide, causes approximately 2.4 million people to be hospitalized every year in the USA, and leads to the death of more than 300,000 people. In this study, we aimed to investigate the clinical significance of ER stress markers and the predictive value of acute decompensated heart failure in patients with low ejection fraction heart failure (ADHF). Patients and Methods: This is a prospective case control study. The data included laboratory parameters pertaining to patients with ADHF in the emergency service and lipid parameters obtained during their admission to the hospital. In addition, the same parameters obtained from the control group patients with chronic heart failure (CHF) during their routine polyclinic control were recorded in the data set. Admission time to the hospital and length of hospital stay were included in the data. The levels of glucose regulated protein (GRP78), protein kinase RNA-like endoplasmic reticulum kinase (PERK), and C/EBP homologous protein (CHOP) in peripheral blood serum obtained from the patients and the control group were measured using the ELISA method. Results: Serum GRP78 concentration was lower in the HF group (p=0.003) compared to the control. The median value of serum PERK concentration in the HF group was higher than that of the control group (573 pg/ml, IQR=477.5-650 vs. 495.5 pg/ml, IQR=294-648, respectively) (p=0.001). However, there were no statistically significant differences in GRP78 and PERK serum concentrations between ADHF and CHF subgroups. Receiver operating characteristic (ROC) curve analysis showed greater area under the curve (AUC) for the serum GRP78 levels of the healthy individuals (AUC=0.748, 95\% CI=0.681-0.814, p=0.0003). The serum GRP78 level was found to be 80\% sensitive and 70\% specific at 147.5 pg/ml (p=0.0003) for distinguishing healthy individuals from HF patients. In the ADHF subgroup, there was a moderate correlation between hospitalization time and serum CHOP concentrations (Spearman rho=0.586 and p=0.001). Conclusion: High GRP78 serum concentration may protect the patient from ER stress. In addition, the serum PERK level is high in patients with HF, whereas it is insufficient in predicting acute decompensation. CHOP may be useful in predicting the length of hospital stay in patients with ADHF.Item Increased free Zn2+ correlates induction of sarco(endo)plasmic reticulum stress via altered expression levels of Zn2+-transporters in heart failure(WILEY, 2018-01-01) Olgar, Yusuf; Durak, Aysegul; Tuncay, Erkan; Bitirim, Ceylan Verda; Ozcinar, Evren; Inan, Mustafa Bahadir; Tokcaer-Keskin, Zeynep; Akcali, Kamil Can; Akar, Ahmet Ruchan; Turan, BelmaZn2+-homoeostasis including free Zn2+ ({[}Zn2+](i)) is regulated through Zn2+-transporters and their comprehensive understanding may be important due to their contributions to cardiac dysfunction. Herein, we aimed to examine a possible role of Zn2+-transporters in the development of heart failure (HF) via induction of ER stress. We first showed localizations of ZIP8, ZIP14 and ZnT8 to both sarcolemma and S(E)R in ventricular cardiomyocytes (H9c2 cells) using confocal together with calculated Pearson's coefficients. The expressions of ZIP14 and ZnT8 were significantly increased with decreased ZIP8 level in HF. Moreover, {[}Zn2+](i) was significantly high in doxorubicin-treated H9c2 cells compared to their controls. We found elevated levels of ER stress markers, GRP78 and CHOP/Gadd153, confirming the existence of ER stress. Furthermore, we measured markedly increased total PKC and PKC alpha expression and PKC alpha-phosphorylation in HF. A PKC inhibition induced significant decrease in expressions of these ER stress markers compared to controls. Interestingly, direct increase in {[}Zn2+](i) using zinc-ionophore induced significant increase in these markers. On the other hand, when we induced ER stress directly with tunicamycin, we could not observe any effect on expression levels of these Zn2+ transporters. Additionally, increased {[}Zn2+](i) could induce marked activation of PKC alpha. Moreover, we observed marked decrease in {[}Zn2+](i) under PKC inhibition in H9c2 cells. Overall, our present data suggest possible role of Zn2+ transporters on an intersection pathway with increased {[}Zn2+](i) and PKC alpha activation and induction of HF, most probably via development of ER stress. Therefore, our present data provide novel information how a well-controlled {[}Zn2+](i) via Zn2+ transporters and PKC alpha can be important therapeutic approach in prevention/treatment of HF.