ORIGINAL ARTICLE Braz J Cardiovasc Surg 2020;35(5):683-8 Serum Elabela Level Significantly Increased in Patients with Complete Heart Block Armağan Acele1, MD; Atilla Bulut1, MD; Yurdaer Donmez1, MD; Mevlut Koc1, MD DOI: 10.21470/1678-9741-2019-0461 Abstract Objective: To investigate the change in serum Elabela level, (NT-proBNP) levels, but negatively correlated with heart rate, a new apelinergic system peptide, in patients with complete high-density lipoprotein cholesterol, and cardiac output. In linear atrioventricular (AV) block and healthy controls. regression analysis, it was found that these parameters were only Methods: The study included 50 patients with planned cardiac closely related to heart rate and NT-proBNP. Serum Elabela level pacemaker (PM) implantation due to complete AV block and 50 was determined in the patients with AV block independently; healthy controls with similar age and gender. Elabela level was an Elabela level > 9.5 ng/ml determined the risk of complete AV- measured in addition to routine anamnesis, physical examination, block with 90.2% sensitivity and 88.0% specificity. and laboratory tests. Patients were divided into two groups, with Conclusion: In patients with complete AV block, the serum and without AV block, and then compared. Elabela level increases significantly before the PM implantation Results: In patients with AV block, serum Elabela level was procedure. According to the results of our study, it was concluded significantly higher and heart rate and cardiac output were that serum Elabela level could be used in the early determination significantly lower than in healthy controls. Serum Elabela of patients with complete AV block. level was found to be positively correlated with high-sensitive Keywords: Atrioventricular Block. Pacemaker Artificial. C-reactive protein and N-terminal pro-brain natriuretic peptide Cardiac Output. C-Reactive Protein. Cholesterol, HDL. Abbreviations, acronyms & symbols INTRODUCTION AT1 = Angiotensin II receptor type 1 The cardiovascular system, cardiac myocytes, and cardiac AV = Atrioventricular conduction system are under the influence of many systemic and local bioactive peptides and the neural and hormonal systems. HDL = High-density lipoprotein The renin-angiotensin-aldosterone (RAA) system, sympathetic Hs-CRP = High-sensitive C-reactive protein nervous system, parasympathetic nervous system, and natriuretic LDL = Low-density lipoprotein peptide system are well known and previously researched. These LV = Left ventricular systems are interrelated and are often activated for the purpose NT-proBNP = N-terminal pro-brain natriuretic peptide of protecting the cardiovascular condition, and they can be used PM = Pacemaker in the diagnosis and treatment of cardiovascular diseases. The RAA = Renin-angiotensin-aldosterone apelinergic system has been reported to play an important role in the modulation of the cardiovascular system via apelin peptide ROC = Receiver operating characteristic and APJ receptor[1,2]. The APJ receptor has 31% similarity to the 1Department of Cardiology, University of Health Sciences – Adana Health Practice Correspondence Address: and Research Center, Adana, Turkey. Yurdaer Donmez https://orcid.org/0000-0003-4745-7801 This study was carried out at the Adana City Training and Research Hospital, Department of Cardiology, University of Health Sciences – Adana Health Practice Adana, Turkey. and Research Center Dr. Mithat Özsan Bulvarı Kışla Mah. 4522 Sok. No: 1 Yüreğir, Adana, Turkey Zip Code: 01230 E-mail: [email protected] Article received on December 10th, 2019. Article accepted on January 7th, 2020. 683 Brazilian Journal of Cardiovascular Surgery Acele A, et al. - Elabela and Heart Block Braz J Cardiovasc Surg 2020;35(5):683-8 final receptor of the RAA system, the angiotensin II receptor type filtration rate < 60 mL/min/1.73m2 or > 30 mg/L of proteinuria 1 (AT1)[3]. Elabela and apelin antagonize the RAA system and, were excluded. Patients with secondary hypertension, renal artery therefore, play a crucial role in the prevention of cardiovascular stenosis, familial hyperlipidemia, moderate or severe valvular disease and slowing disease progression[3]. In recent studies, heart disease, known heart failure, and nephrectomy were also apelin and these related peptide receptors have been shown to excluded. This study followed the recommendations of the ethics have cardioprotective effects in atherosclerosis and myocardial principles published in the Declaration of Helsinki, developed infarction, heart failure, and pulmonary arterial hypertension[4-6]. by the World Medical Association – WMA and approved by the Recently, a peptide called Elabela, which binds to the local ethics committee. The clinical information for the informed same receptor as apelin and has similar effects, has been consent was explained to the patients in detail, and patients were found[7]. Elabela's cardiac positive effect is more effective than included in the study after consent was obtained. Anamnesis apelin. The effects of these peptides begin in the embryonic was taken and detailed physical examinations were performed. stage and are associated with angiogenesis. In the literature, Heart rate, systolic blood pressure, and diastolic blood pressure studies have reported that Elabela is associated with many were measured. The demographic data were recorded including cardiovascular conditions and diseases[3]. Apelinergic system age, sex, hypertension, and the presence of diabetes mellitus. activity is increasing especially in cases of remodeling, heart The weight and height of all cases were measured. failure, and arterial hypertension after myocardial infarction and it has positive effects by blocking the RAA system[3]. In a study Ethical Approval on conscious rats, intravenous, intracoronary, or intraperitoneal The study was approved by the Çukurova University School administration of apelin or Elabela showed a significant increase of Medicine Local Ethics Committee (approved at October 5th in heart rate[8-11]. This effect is not related to the AT1 receptor and 2018, decision number 81), and the requirement for informed may be associated with a positive chronotropic effect on the consent was waived. cardiovascular system. However, to the best of our knowledge, in the literature, there is no study investigating the serum Elabela or Laboratory Parameters apelin levels in patients with cardiac conduction system disease or third-degree atrioventricular (AV) block who require cardiac Routine laboratory parameters of all subjects (glucose, pacemaker implantation. We hypothesized that an increase in high-sensitive troponin I, N-terminal pro-brain natriuretic the activity of the apelinergic system may occur in response to peptide [NT-proBNP], renal functions, lipid parameters, high- bradycardia and, therefore, an increase in serum apelin or Elabela sensitive C-reactive protein [Hs-CRP], and complete blood levels may be considered. count) were analyzed. Serum Elabela levels were determined Hence, in our study, we aimed to investigate whether there using commercial kits (Sunred Biological Technology, Shanghai, is a change in serum Elabela level, a new apelinergic system China). Elabela-32 isoform was measured. The kit used a double- peptide, in patients with third-degree AV block compared to antibody sandwich enzyme-linked immunosorbent assay – healthy controls. ELISA to assay the level of Elabela in blood samples. According to the manufacturer, this assay has inter-assay coefficients of METHODS variation < 12% and intra-assay coefficients of variation < 10%. All of the abovementioned tests were performed from blood Subjects Identification samples that were taken at the 24th hour of hospital admission. This cross-sectional study included 50 patients (24 males, 26 females, mean age 52.7±6.8 years) who were diagnosed with a Echocardiographic Evaluation third-degree AV block and, therefore, underwent conventional Doppler and two-dimensional echocardiographic pacemaker implantation and 50 healthy individuals (22 males, 28 evaluations were performed using an echocardiography device females, mean age 51.6±6.0 years). The study was conducted in (EPIQ 7; Philips Healthcare, Andover, Massachusetts, United a single center between October 2018 and March 2019 at the States of America). The standards of the American Society of Adana City Training and Research Hospital, Turkey. The duration Echocardiography were used for all measurements. Biplane of bradycardia before AV block was unknown. All patients Simpson’s method was used for the calculation of left ventricular with complete and permanent AV block were included in this ejection fraction[13]. Cardiac output measurement was calculated study before pacemaker implantation. Pacemaker implantation with the stroke volume ´ heart rate/1000 formula[13]. indication was decided according to the European Society of Cardiology Cardiac Pacing and Cardiac Resynchronization Statistical Analysis Guidelines[12]. After the diagnosis of complete AV block, all patients were evaluated in terms of secondary reasons for a All analyses were performed using the IBM SPSS Statistics complete algorithm (laboratory tests, medical treatment history, (Chicago, Illinois, United States of America) statistical software echocardiography, and ischemia evaluation) to determine the package, version 22.0. The distribution of continuous variables causes of reversible complete AV block. Patients who received was evaluated by the Kolmogorov-Smirnov test. Continuous medications