Investigation of the markers of sudden cardiac death and arrhytmia, and relationship of gene mutation KCNJ8-S422l in the population with early repolarization pattern on ECG

İstanbul Bilim Üniversitesi, Tıp Fakültesi, Kardiyoloji Anabilim DalıGiriş: Erken repolarizasyon (ER), EKG’de J noktasının izoelektrik hatta göre ardışık 2 derivasyonda en az 1 mm (0.1mV) yükselmesi olarak tanımlanmaktadır. Çoğunlukla yapısal kalp hastalığı bulunmayan kişilerde görülen Erken Repolarizasyon Sendromu (ERS), günümüzde Brugada Sendromu (BS) ile olan benzerlikleri nedeniyle ‘J Dalga Sendromları’ başlığı altında incelenmeye başlanmıştır. Yayınlanan çok merkezli çalışmalar sonucunda ERS ile ani kardiyak ölüm (AKÖ) arasındaki ilişkinin ortaya konmasıyla beraber hayatı tehdit edici ventriküler aritmilere neden olabileceği bilinmektedir. Amaç: ERS tanısı alan kişilerde aritmi belirteçleri olan testler ile riskli hasta grubunu belirleyebilmek ve son yıllarda literatürde AKÖ gerçekleşmiş ERS tanısı alan kişilerde bildirilen KCNJ8 geni S422L mutasyonunun varlığını araştırmaktır. Gereç ve Yöntem: Kardiyak açıdan semptomatik ya da asemptomatik 50 erken repolarizasyon tanısı almış bireyler ile 50 normal EKG özelliğine sahip kontrol grubu çalışmaya alındı. Koroner arter hastalığı (KAH) bulunmayan ve ekokardiyografi sonucu normal olan kişiler çalışmaya dahil edildi. Çalışmaya alınan bireylerin yaş ortalaması hasta grubunda 33.1±9.7, kontrol grubunda 45.8±9.9 idi. Holter monitörizasyonu ile aritmi varlığı, kalp hızı değişkenliği ve geç potansiyellerin varlığına ER bulunan grupta bakıldı. Her iki grupta ‘allel spesifik PCR yöntemi’ ile KCNJ8 geni S422L mutasyonu genotiplendirildi. Bulgular: Çalışmamızda ER bulunan kişilerde ‘ER EKG paterni’ tiplendirmesinde %54’ünde tip l, %42’sinde tip 2, %4’ünde ise tip 3 ER EKG paterni izlendi. Kontrol grubu ile karşılaştırıldığında düzeltilmiş QT mesafesi (QTc)’nin, ER grubunda daha kısa olduğu görüldü. Fakat sonuç istatiksel anlamlılığa ulaşmadı (ER bulunanlarda ortalama QTc; 371±28.7 msn, kontrol grubunda ise 381±31.4 msn, p =0.08). ERS grubunda bakılan ritm holter kayıtlarında hiçbir hastada couplet, triplet prematür ventriküler kompleks (PVC) ya da süreksiz VT atağı izlenmedi. Kalp hızı değişkenliği (KHD) zaman alanlı metodlar kullanılarak bakıldığında hastaların %26’sında azalmış olarak izlendi. Hastaların sinyal ortalamalı EKG (SOEKG) ile %14’ünde geç potansiyeller (LP) izlendi. Yakın zamanda yapılmış çalışmalardaki rakamlarına benzer sonuçlar elde edildi. Nörolojik değerlendirmeleri normal bulunan sadece 2 hastada açıklanamayan senkop öyküsü bulunmaktaydı ve senkop ile ERS ilişkisi değerlendirildiğinde ise istatistiksel anlamlılığa ulaşmadı (p=0.15). Her iki grupta bakılan KCNJ8-S422L mutasyonu ise hasta grubunda değil kontrol grubundan bir hastada bulundu. Böylece KCNJ8-S422L mutasyonu ile ERS ilişkisi istatiksel olarak anlamsız bulundu. Fakat belirtmek gerekir ki çalışmamıza dahil ettiğimiz ERS hastalarının hiçbirisinde ve ailelerinde AKÖ öyküsü bulunmamakta idi ve yalnızca 50 ER bulunan kişi çalışmaya dahil edilmişti. Sonuç: Primer aritmojenik sendromlar ve kanolopatiler başlığı altında incelediğimiz ve önceleri tamamen benign bir EKG bulgusu olarak değerlendirilen ERS, son zamanlarda BS ile olan benzerliği ve AKÖ ilişkisinin ortaya konması nedeniyle ilgi çekmektedir. Biz de bu hastalarda aritmi belirteci testler ile riskli hastaları belirleyebilmek amacıyla bu çalışmayı planladık ve KCNJ8-S422L mutasyonu varlığı ile ERS arasındaki ilişkiyi inceledik. AKÖ geçiren ERS hastalarında sekonder korumada tek tedavinin implante edilebilen kardiyoverter defibrilatör (ICD) olduğu bilinmektedir. Asıl problem özellikle de gençlerde yaklaşık %5 gibi yaygın gözlenen bu EKG paternininin primer koruma açısından hangi hastalarda ölümcül aritmilere neden olabileceğinin belirlenmesidir. Klinikte literatürde bildirilen kriterlere uygun riskli hastaların belirlenmesi gereklidir. ER paterni bulunan kişilerde açıklanamayan senkopun varlığı veya ailede açıklanamayan AKÖ öyküsünün bulunması, inferior/inferolateral (tip2) veya tüm derivasyonlarında (tip3) >0,2 mv J noktası elevasyonu bulunması ve EKG’de ST segment elevasyonunun yatay/inen tarzda olması, ER paterni ile birlikte kısa QT’nin varlığı, son olarak da couplet PVC’lerin görülmesi birer risk işareti olarak değerlendirilmelidir. Yüksek risk işareti bulunan her hastada primer tedavinin gerekliliği konusunda ve bu hastaların nasıl takip edileceği ile ilgili sorular ise ilerleyen yıllarda genetik çalışmaların da ışığı altında yapılan çalışmalar ile yanıt bulacaktır.Introduction: Early repolarization (ER) is defined as the elevation of J point at least 1mm (0.1mV) in 2 consequent derivations on ECG. Early Repolarization Syndrome (ERS) which is usually seen in people without structural heart disease is considered under the title of ‘J wave syndromes’ because of its similarities with Brugada syndrome (BS). As a result of multi-center studies, the association of ERS with sudden cardiac death (SCD) established and its now known that ERS is a cause of life threatening ventricular arrhytmias. Purpose: Aim of the study to detect the individuals at risk among the patients with ERS using the arrhytmia markers and investigate the existence of reported S422L mutation in the KCNJ8 gene, that are detected in the patients with SCD an diagnosed ERS. Methods: Study included 50 symptomatic or asymptomatic patients with diagnosed ERS and 50 people with normal ECG as the control group. People without coronary artery disease and with normal echocardiography results are included. Mean age was 33.1±9.7 in the study group and 45.8±9.9 in the control group. The existence of arrhytmia, heart rate variability and late potentials is examined in ER group. In both groups S422L mutation in the KCNJ8 gene is genotyped using allele specific PCR. Results: In our study using the ‘ER ECG pattern typing’ 54% of the patients with ER are defined as type l, 42% type 2 and 4% are type 3 ER pattern. It is found that corrected QT distance (QTc) is shorter in the ER group than in the control group, but in the level of statistical significance (In the ER group mean QTc; 371±28.7 ms, in the control group mean QTc; 381±31.4 ms, p =0.08). No couplet/trıplet VPC or nonsustained ventricular tachycardia is detected in the holter recordings of ERS group. Heart rate variability is found to be decreased 26% in the patients, using the time domain methods. By using signal averaged ECG.in late potentials are detected in 14% of the patients. These finding is consistent with the results of contemporary studies. History of unexplained syncope is found in 2 patients with normal neurologic assessment and the association of syncope with ERS was not statistically significant ( p=0.15). The S422L- KCNJ8 gene mutation which is investigated in both groups, is detected in the control group, but not in the study group, making the association of mutation with ERS statistically insignificant. Neverthless, it should be stressed that no ERS patients in the study has sudden cardiac death in themselves and their families and only 50 patients with ER are included in the study. Conclusion: ERS which is included under the title of primary arrthytmogenic syndromes and channelopaties and considered as a completely benign ECG finding, has drawn attention due to its similarities with BS and association with SCD. We planed this study to detect the susceptible population with arrhytmia markers,and investigate the relationship of KCNJ8-S422L mutation with ERS. It is known that the only treatment secondary prevention in ERS patients with SCD implantable cardioverter defibrilator (ICD). The emerging problem is to detect which individuals with this ECG finding is susceptible to SCD, and could be protected by primary prevention. In clinical practise, patients at risk should be detected using the criteria proposed in literature. In patients with ER pattern, history of unexplained syncope or SCD in family, >0,2mV J point elevation in inferior/inferolateral (type 2) or all derivations (type 3), existence of horizontal/downslopping ST segment elevation or short QT with ER pattern, and finally detection of couplet VPC are cosidered at risk factors. The question regarding the need of primary treatment and follow up and all patients with high risk factors will find an answer light of future genetic investigations

Recurrent Takotsubo Cardiomyopathy

Stress-induced cardiomyopathy or takotsubo syndrome is a transient cardiac dysfunction which is precipitated by intense emotional or physical stress. It mimics acute coronary syndrome clinically (chest pain and dyspnea) and has specific echocardiographic findings in the absence of significant coronary stenosis. The underlying pathophysiologic mechanism is mostly due to stress-induced catecholamine release. This syndrome is more commonly seen in females especially in the postmenopausal period. The prognosis of stress-induced cardiomyopathy is usually favorable with a prevalence of in-hospital mortality of less than 2%. Reports of a single episode of stress-induced cardiomyopathy are common in the literature, but recurrence of stress-induced cardiomyopathy is rare. Herein, we present an uncommon case of recurrent stress-induced cardiomyopathy in order to provide an explanation of the pathophysiology of this unique syndrome

Nötrofil Lenfosit ve Platelet Lenfosit Oranlarının Göğüs Ağrısı Olan Hastalarda Kanada Kardiyovasküler Cemiyeti Angina Sınıflaması ile Olan İlişkisi

Yolcu, Mustafa (Arel Author)Amaç: Bu çalışmada polikliniğe başvuran ve göğüs ağrısı olan hastalarda nötrofil lenfosit (NLO) ve platelet lenfosit oranlarının (PLO) Kanada Kardiyovasküler Cemiyeti (KKC) anjina sınıflaması ile ilişkisi incelenmiştir. Materyal ve Metot: Çalışma hastaları polikliniğimize göğüs ağrısı ile başvuran hastaları içermektedir. Çalışma grupları, kardiyak olmayan göğüs ağrısı ve atipik anjina (grup 1), KKC sınıf 1 ve sınıf 2 (grup 2), KKC sınıf 3 ve sınıf 4 (grup 3) hastalardan oluşmuştur. Bulgular: NLO koroner arter hastalığının yaygınlığı ve anjina derecesi ile pozitif korelasyon göstermiştir. (p 0,05)Sonuç: NLO, ucuz ve pratik bir enflamatuar belirteç olup poliklinik koşullarında hastaların KKC anjina dereceleri ile ilişkili bulunuştur.Objectives: We examined the association between neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte ratio (PLR) with the Canadian Cardiovascular Society (CCS) angina grade of patients in outpatient setting. Materials and Methods: The study population included patients with chest pain who had admitted to our outpatient clinic. The study group consisted of noncardiac chest pain and atypical angina (group 1), CCS class 1 and class 2 angina (group 2) and CCS class 3 and class 4 (group 3) patients. Results: The neutrophil lymphocyte ratio was positively correlated with extent of CAD and angina grade (p<0.001). To test the power of neutrophil lymphocyte ratio for distinguishing group 1 and group 2+3, and group 1+2 and group 3, ROC analysis was performed. The NLR had AUC values of 0.714 and 0.698 (p<0.001), which demonstrate its sufficiency to distinguish patients in group 1 from individuals in group 2+3 and patients in group 1+2 from individuals in group 3, respectively. The platelet lymphocyte ratio did not differ among groups (p>0.05). Conclusion: The NLR is a cheap and practical inflammatory marker and is associated with CCS angina grade of patients in outpatient setting

Epidemiologic features of inflammatory bowel disease in Western Blacksea region of Turkey for the last 10 years: retrospective cohort study

Can, Guray/0000-0002-6054-9244WOS: 000466334400008PubMed: 29695147Background/Aims: There are only a few epidemiological study about inflammatory bowel disease in the last 10 years in Turkey, especially in Western Blacksea region. In our study, we aimed to identify the changes in the incidence and the prevalence of inflammatory bowel disease in Western Blacksea region at the last 10 years. Methods: Totally 223 patients with inflammatory bowel disease (160 ulcerative colitis, 63 Crohn's disease) were enrolled in the study followed up between 2004 to 2013 years. The epidemiological characteristics of patients were recorded. Results: The prevalences were 12.53/10(5) and 31.83/10(5) for Crohn's disease and ulcerative colitis respectively. Mean annual incidences increased from 0.99/10(5) and 0.45/10(5) for ulcerative colitis and Crohn's disease (2004 to 2005 years) to 4.87/10(5) and 2.09/10(5) for ulcerative colitis and Crohn's disease respectively (2011 to 2013 years). While the prevalence was higher in urban areas in Crohn's disease (12.60/10(5)), it was higher in rural areas in ulcerative colitis (36.17/10(5)). In ulcerative colitis, mean annual incidences were 2.91/10(5) and 2.86/10(5) for urban and rural areas respectively. In Crohn's disease, they were 1.37/10(5) and 1.08/10(5) for urban and rural areas respectively. Conclusions: The incidence of inflammatory bowel disease seems to increase in Western Blacksea region at the last 10 years. This increment is more prevalent in rural areas

The importance of speckle tracking echocardiography in the early detection of left ventricular dysfunction in patients with polycystic ovary syndrome

PubMed ID: 26614851Polycystic ovary syndrome (PCOS) is characterized by hormonal and metabolic abnormalities and is thought to increase a risk for cardiovascular diseases. In this study we use speckle tracking echocardiography (STE) to evaluate left ventricular (LV) dysfunction in the early period of the disease. We enrolled 31 patients with PCOS and 32 healthy volunteers as a control group. The participants’ ages ranged between 18 and 40 years. PCOS was diagnosed according to the Rotterdam criteria. LV strain (LS) and strain rate (SR) were evaluated using apical two-chamber (2C), three-chamber (3C), and four-chamber (4C) imaging. Global LS and SR were calculated as average of three apical views. The waist-to-hip ratio, homeostasis model assessment-insulin resistance (HOMA-IR), and fasting insulin and triglyceride levels were higher in the PCOS group than in the controls (p = 0.001, p = 0.001, p = 0.001, and p = 0.005, respectively). In the PCOS group, the mitral A wave, deceleration time (DT), and isovolumetric relaxation time (IVRT) were significantly higher than in the controls (all p < 0.05). The LV global longitudinal strain (GLS) and global longitudinal SR systolic (GLSRS) were significantly lower in the PCOS patient group (both p = 0.001). There were strong negative correlations between GLS and both fasting insulin (r = -0.64) and DT (r =-0.62) (both p < 0.05). The study demonstrated that PCOS patients had decreased LV function using STE. Therefore, STE imaging appears to be useful for the early detection of subclinical LV dysfunction in patients with PCOS. © 2015 ABMSFBIH

Suboptimal use of non-vitamin K antagonist oral anticoagulants: Results from the RAMSES study

WOS: 000384041400052PubMed ID: 27583892This study aimed to investigate the potential misuse of novel oral anticoagulants (NOACs) and the physicians' adherence to current European guideline recommendations in real-world using a large dataset from Real-life Multicenter Survey Evaluating Stroke Prevention Strategies in Turkey (RAMSES Study).RAMSES study is a prospective, multicenter, nationwide registry (ClinicalTrials.gov identifier NCT02344901). In this subgroup analysis of RAMSES study, patients who were on NOACs were classified as appropriately treated (AT), undertreated (UT), and overtreated (OT) according to the European Society of Cardiology (ESC) guidelines. The independent predictors of UT and OT were determined by multivariate logistic regression.Of the 2086 eligible patients, 1247 (59.8%) received adequate treatment. However, off-label use was detected in 839 (40.2%) patients; 634 (30.4%) patients received UT and 205 (9.8%) received OT. Independent predictors of UT included >65 years of age, creatinine clearance 50mL/min, urban living, existing dabigatran treatment, and HAS-BLED score of <3, whereas that of OT were creatinine clearance <50mL/min, ongoing rivaroxaban treatment, and HAS-BLED score of 3.The suboptimal use of NOACs is common because of physicians' poor compliance to the guideline recommendations in patients with nonvalvular atrial fibrillation (NVAF). Older patients who were on dabigatran treatment with good renal functions and low risk of bleeding were at risk of UT, whereas patients who were on rivaroxaban treatment with renal impairment and high risk of bleeding were at risk of OT. Therefore, a greater emphasis should be given to prescribe the recommended dose for the specified patients