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F. Zvizdić, E. Begić, A. Mujaković, E. Hodžić, B. Prnjavorac, Omer Bedak, F. Čustović, Haris Bradaric et al.

Introduction: The most appropriate choice of pharmacological treatment of heart rhythm disorders occurring in patients with chronic obstructive pulmonary disease (COPD) and cardiovascular comorbidity is often a topic of debate between pulmonologists and cardiologists in clinical practice, although numerous studies and clinical trials have demonstrated evidence to support the use of selective beta-blockers (BBs) in these patients. Aim: To examine the difference in the number of exacerbations in patients treated with a combination of verapamil and digoxin or BB alone in patients with different COPD stages. Patients and methods: The study included 68 patients (n = 68) diagnosed with COPD who were followed-up during a 12-month period, and the number of exacerbations were analyzed. The patients were divided into two groups according to the stage of COPD: GOLD II (moderate), and GOLD III (severe), and in each group a subdivision was established in relation to the use of either a combination of verapamil and digoxin or the use of BBs alone in pharmacological treatment. The inclusion criteria for patients were defined as following: a) established diagnosis of COPD according to present or deteriorated relevant clinical symptoms and signs, b) the ejection fraction (EF) of a left ventricle (LV) >35%, and c) spirometric cut-points classified as GOLD II (FEV1 / FVC <0.7, FEV1 predicted 50-80%), or GOLD III (FEV1/FVC <0.7, FEV1 predicted 30-50%) stage of the COPD. The exclusion criteria were EF of LV <35% and a lethal outcome during a follow-up period (2 patients were encountered). Exacerbation was defined as functional deterioration of the COPD symptoms verified by spirometric functional testing, frequency of hospitalizations according to GOLD stage assignment or verified clinical symptoms deterioration. Results: Regardless the pharmacological treatment, there is a statistically significant increase in the number of COPD exacerbations, in a 12-month period follow-up, in the GOLD III group (severe) compared to the GOLD II group (moderate). In the group of patients taking verapamil and digoxin, a two-tailed t-test was used to analyze the results between the GOLD II and GOLD III stage groups, p = 0.01, and 2. In the group of patients taking BBs, a two-tailed t-test was also used to analyze the results between the GOLD II and GOLD III stage groups, p = 0.003). Within the COPD GOLD II stage group, there appears to be no statistically significant difference in the number of exacerbations between the patients taking verapamil and digoxin (n = 24) and the patients taking BBs alone (n = 15), although, in patients taking BBs alone, there appears to be a trend towards a decrease in the exacerbations compared to the number of exacerbations in patients taking verapamil and digoxin (p = 0.007). Within the COPD GOLD III stage group, there is no difference in the number of exacerbations between the patients taking verapamil and digoxin (n = 20), and the patients taking BBs alone (n = 9), as analyzed by a two-tailed t-test, p = 0.577. Conclusion: Use of selective BBs in the treatment of cardiovascular comorbidity in patients with COPD represents a far better choice of pharmacological approach in the treatment of patients diagnosed with COPD GOLD II (moderate) stage.

Alzheimer's disease represents the most common age-related neurodegenerative disorder and a leading cause of progressive cognitive impairment. Predicting cognitive decline is challenging but would be invaluable in an increasingly aging population which also experiences a rising cardiovascular risk. In order to examine whether plasma measurements of one of the established biomarkers of heart failure, brain natriuretic peptide (BNP), reflect a decline in cognitive function, associated with Alzheimer's disease neurodegeneration, BNP levels were analysed, by using a novel assay called a SOMAscan, in 1. cognitively healthy, control subjects; 2. subjects with mild cognitive impairment, and 3. subjects with Alzheimer's disease. The results of our study show that the levels of the BNP were significantly different between the three types of diagnoses (p < 0.05), whereby subjects with mild cognitive impairment had the lowest mean BNP value, and healthy subjects had the highest BNP value. Importantly, our results show that the levels of the BNP are influenced by the presence of at least one APOE4 allele in the healthy (p < 0.05) and in the Alzheimer's disease groups of subjects (p < 0.1). As the levels of the BNP appear to be independent of the APOE4 genotype in subjects with mild cognitive impairment, the results of our study support inclusion of measurements of plasma levels of the BNP in the list of the core Alzheimer's disease biomarkers for identification of the mild cognitive impairment group of patients. In addition, the results of our study warrant further investigations into molecular links between Alzheimer's disease-type cognitive decline and cardiovascular disorders.

Aim To investigate a correlation between resistive index (RI) level changes following extracorporeal shock wave lithotripsy (ESWL) in treated and non-treated kidneys depending on the ESWL treatment intensity. The study was conducted on 60 subjects, which were divided in two groups according to age and treatment protocol. Results In the group of patients younger than 55 years of age there was a significant increase in mean RI values, on the first (p=0.001) and second day after the treatment (p=0.007). In the group older than 55 years of age, the resulting increase in mean RI levels was also significant on the first (p=0.003) and second (p=0.011) day following the treatment. The RI values in the non-treated kidney on the first day after the treatment grew significantly (p=0.033). In the group older than 55, RI values in the non-treated kidney grew significantly on the first day after the treatment (p=0.044). In the group who received 2000 SWs, RI levels grew significantly (p=0.044) as well as in the group who received 4000 SWs during the treatment, where the significance was more pronounced (p=0.007). Conclusion There is a correlation between RI changes and the degree and localization of changes in vascular elements of the kidney. Post-ESWL treatment changes are existent and reversible, over a period of one week after the treatment.

E. Hodžić, Adnan Durek, E. Begić, N. Šabanović Bajramović

Aim To investigate etiological link between acute myocardial infarction (AMI) and the accompanying impotence/erectile dysfunction (ED). Methods Study included 99 male patients (48 who had AMI - patient group, and 51 healthy examinees without previous cardiovascular disease - control group). All patients completed a standardized questionnaire, the International Index of Erectile Function (IIEF-5). Results Older patients had significantly lower IIEF-5 score (negative correlation) (p<0.05), but higher ED degree (significant positive correlation) (rho=0.522; p=0.0001). In the patient group, 37 (77.1%) patients had ED, while in the control group it was found in 26 (51%) examinees (p<0.05). A clear correlation was found between incidence of ED and diabetes, dyslipidaemia, hypertension and positive family history (they were more common in patients with ED, with no statistically significant difference). There was no statistically significant difference between patients with ED and patients without ED according to the beta-blocker usage (p=0.824): ED was reported in 11 (68%) patients in the group who used carvedilol, 14 (82.3%) in the group who used metoprolol, and nine (81.8%) who used nebivolol. Conclusion Myocardial infarction as well as age are directly related to the occurrence of ED. Cardiovascular risk factors are in direct correlation for the occurrence of erectile dysfunction after myocardial infarction.

Lafora progressive myoclonus epilepsy (Lafora disease, LD) is a fatal autosomal recessive neurodegenerative disorder (with an onset in teenage years in previously normal adolescents). This paper represents a view of a patient diagnosed with Lafora progressive myoclonus epilepsy, over a course of seven years. A description of the initial manifestation of symptoms, doctors' attempts to combat the symptoms with drug treatment, further attempts towards reaching the correct diagnosis, the final confirmation of the Lafora diagnosis (mutation in the NHLRC1 gene), and the current state of the patient is presented. The absence of a positive family history, the lack of staff specialized in dealing with this or similar pathology, and the diagnostic inability to characterize this type of disorder in Bosnia and Herzegovina have led to a fair delay in diagnosing and beginning of an adequate pharmacological treatment. Overall, recent identification of LD cases in Bosnia and Herzegovina warrants an establishment of a Centre for Genetic Testing in order to ensure more humane counseling of an entire family whose family member(s) might be diagnosed with this devastating and currently an incurable disorder.

Title of Days of AMNuBiH 2018” and “SWEP 2018” is “Ethical Dilemmas in Science Editing and Publishing”. Why? If one wants to create a scientific work, must have on his mind that creating a scientific work requires creativity and openness, honesty, trust, and obeying the ethical principles for writing a scientific paper. While working on a an biomedical research involving human subjects medical workers should have on mind that it is the duty of the physician to remain the protector of the life and health of that person on whom biomedical research is being carried out. The World Medical Association (WMA) has developed the Declaration of Helsinki as a statement of ethical principles to provide guidance to physicians and other participants in medical research involving human subjects.

S. Trnačević, Amer Mujkanovic, Edin Nišlić, E. Begić, Zenaida Karasalihovic, Adnan Cickusic, Alma Trnačević, Mirna Aleckovic Halilovic

Aim: Aim of the article was to present a case of post transplantation invasive aspergillosis, successfully treated with conservative and surgical treatment. Case report: Patient, male, 44 years old, with second kidney transplant, required special preparation therapy, because he was sensitized, with concentration of Panel Reactive Antibody (PRA) class I 11% and PRA class II 76%. On the day of transplantation, induction was done with anti-thymocyte globulin (ATG) and glucocorticosteroids. After transplantation, plasmapheresis with ATG was performed. On the fourth day patient was anuric. Fine-needle biopsy of the graft was performed and showed positive CD4 antibodies for peritubular capillaries and humoral rejection. 14 plasmaphereses through 14 days, were negative and ATG treatment was suspended completely. Full therapeutic dosage of tacrolimus and mycophenolate mofetil were given during treatment. Four days after treatment patient was stable, but next day clinical status had worsened with dyspnea and fever. In sputum, spores of Aspergillus species were microscopically found, and radiologically by computerised tomography. Caspofungin was administered for seven days. Voriconazole therapy was given for first ten days by intravenous route and after then orally. Even with this treatment, there was no improvement in clinical picture, while CT scan of the lungs showed abscess collection in right lung. Lobectomy was performed and pus collection was found. After graft-nephroctomy, patient was treated with continous veno-venous hemodiafiltration (CV-VHDF) dialyses, with constant voriconazole therapy for the next three months (200mg two times per day). After one month of diagnosis, Galactomannan (GM) test was negative. Conclusion: Although highly sensitized patients, those who are on hemodialysis, in preparation for transplantation, receive intensive immunosuppressive therapy that suppress the immune system. Occurrence of secondary fungal infections especially infection by aspergillosis, is cause of high mortality of infected. Application GM test that detects existence of antibodies against Aspergillus antigens and usage of different type of immunosuppressive preparation can increase longevity of graft and patients in solid organ transplantation program. Aspergillosis is treated with voriconazole and surgery, and sometimes graft-nephrectomy if needed. Recommendation is that in all immunocompromised hosts and organ transplant recipient should have been tested with GM test.

Introduction: In patients with acute myocardial infarction (AMI) early risk assessment of development of complications is of great importance. It is proven that aldosterone level has a major role in progression of cardiovascular pathology. Aim: Determination of influence of aldosterone plasma level in the progression of heart disease in patients without signs of heart failure after AMI. Material and Methods: Research included 207 patients, hospitalized in the acute phase of myocardial infarction, and who were divided into two groups: 127 patients with no clinical signs of heart failure and 60 patients with heart failure. Results: The serum aldosterone concentration was 73.4% higher in the group of decompensated patients, 128 pg/mL (75.4-236 pg/mL) in decompensated and 73.7 pg/mL (42.7 -115.25 pg/mL) in compensated. In the group of compensated patients, changes in aldosterone levels showed a statistically significant effect on the incidence of post-infarction angina (p=0.0001) as well as reinfarction (p=0.009). There is a connection between changes in aldosterone plasma level and positive stress test (p=0.012). Conclusion: In patients with AMI, elevated serum aldosterone level can be prognostic factor of the progression of coronary heart disease, development of heart failure, as well of development of post-infarction angina, myocardial reinfarction and pathological finding on the stress test.

1Sarajevo School of Science and Technology, Sarajevo, Bosnia and Herzegovina 2University Clinical Center Sarajevo, Sarajevo, Bosnia and Herzegovina KeYWORdS: natriuretic peptides, brain natriuretic peptide, biomarker of myocardial infarction, Alzheimer’s disease. citAtiON: Cardiol Croat. 2018;13(11-12):435. | https://doi.org/10.15836/ccar2018.435 *AddReSS fOR cORReSpONdeNce: Edin Begic, Sarajevo School of Science and Technology, Sarajevo Medical School, Department of Pharmacology, Hrasnicka cesta 3a, 71000 Sarajevo, Bosnia and Herzegovina. / Phone: +38761303375 / E-mail: edinbegic90@gmail.com ORcid: Edin Begic, https://orcid.org/0000-0001-6842-262X • Suncica Hadzidedic, https://orcid.org/0000-0001-9026-8737 Ajla Kulaglic, https://orcid.org/0000-0003-3410-7079 • Belma Ramic-Brkic, https://orcid.org/0000-0002-8205-0137 Zijo Begic, https://orcid.org/0000-0002-1863-5755 • Mirsada Causevic, https://orcid.org/0000-0002-6099-6415

E. Begić, E. Hodžić, Z. Begić

Introduction: Brugada syndrome (BS) is a dominantly inherited arrhythmogenic disease caused by a mutation in the SCN5A gene. It accounts for 20% of cases of sudden death, without structural heart abnormalities1. Diagnosing the BS is achievable by electrocardiography (ECG), ST segment elevation in V1 to V3, with the right bundle branch block pattern as a hallmark of the syndrome2. BS is divided into three types. However, only type 1 can be verified with an ECG2,3. BS manifests as a syncope that is caused by ventricular tachycardia, which, if converted to ventricular fibrillation, leads to a fatal outcome. An implantable cardioverter defibrilator (ICD) implantation is indicated, while pharmacological therapy on its own is not sufficiently effective. Aim: To present a diagnostic and therapeutic approach towards suspected BS in a younger patient. Case report: 24-years-old patient was admitted to a hospital, after a cardiac arrest and a prolonged cardiopulmonary resuscitation with intubation. ECG findings verified sinus rhythm, with heart rate of 94 beats per minute, normal heart axis with PQ interval of 0.16 s, and right bundle branch block (RBBB) with an ST elevation from V1 to V3. An ajmalin provocation test was performed, and ECG changes (J-wave elevation of >2 mm with ST elevation from V1 to V3 with RBBB) were recorded, but without induced ventricular arrhythmia. Patent foramen ovale was suspicious as a cause, but after transesophageal echocardiography it was excluded. According to electrocardiographic changes, the BS was diagnosed as the cause of malignant ventricular heart rhythm. Genetic testing for Brugada syndrome was not performed and in consultations with the Centre for Electrophysiology in Sarajevo (Bosnia and Herzegovina) and Zadar (Croatia), the implantation of an ICD was indicated, and subsequently performed. The patient was discharged under pharmacological therapy consisting of metoprolol 25 mg twice per day, amiodarone 100 mg per day, with magnesium, and aspirin once per day. Conclusion: In daily clinical work, in all conditions of syncope occurring in younger patients, in order to prevent sudden death, an existence of the BS should be considered. An overall clinical status of a patient, including positive ajmaline test with specific ECG changes, can verify BS, even when information on the presence of the SCN5A gene is not available.

E. Hodžić, Amira Drakovac, E. Begić

Introduction: Heart rhythm disorders are quite common in the clinical course of acute myocardial infarction and have a significant influence on the prognosis of the disease. Aim: To investigate the type and frequency of ventricular arrhythmias in patients with acute myocardial infarction (AMI) by sex and age, according to localization of myocardial infarction, and correlated with troponin and C reactive protein (CRP). Material and Methods: A prospective, analytical, comparative clinical study was performed. A total of 100 patients was included who were hospitalized at the Clinic for Heart Disease and Rheumatism at the Clinical Center University of Sarajevo for a period of 6 months, of both sexes, aged from 20 to 90 years. The occurrence of ventricular arrhythmias, CRP and troponin, were observed in relation to the localization (anterior and inferior myocardial wall). Results: It was found that men are more represented in comparison to women and that the largest number of males were in the age group of 51-60 years of life and women in the age group of 71-80 years. It has been established that there is no significant difference between ventricular arrhythmia according to localization of AMI. By determining the mean CRP and troponin levels, a positive correlation was found between CRP and troponin values and recorded ventricular arrhythmias. Conclusion: There is a positive correlation between the troponin and CRP values and ventricular arrhythmias, not related to the localization of AMI, which is important in prevention and planning the treatment of complications of potentially malignant ventricular arrhythmias and fatal outcome at AMI.

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