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Aim To investigate the benefit of high-dose lipophilic statin therapy on cardiac remodelling, function and progression of heart failure (HF) in patients with ischemic heart disease. Methods A total of 80 patients with ischemic HF diagnosis were followed during 6 months, and they were divided in two groups. First group (n=40) was treated by high-dose lipophilic statin therapy (atorvastatin 40 mg) and conventional therapy for HF, while the second group (n=40) had no atorvastatin in the therapy. Results In the beginning of study, from all of the observed parameters, only the ratio of flow rates in early and late diastole (E/A ratio) differed between the test groups (p=0.007). After six months, a statistically significant increase in left ventricular end-diastolic diameter (LVIDD) in patients who had not been treated with atorvastatin was found. In the patients treated with atorvastatin, there was a significant reduction in basal right ventricle diameter in diastole and systole (p<0.001 and p<0.001, respectively), and in tricuspid annular plane systolic excursion (TAPSE) (p<0.001); there was a reduction in LVIDD (p<0.001), and an increase of ejection fraction of the left ventricle according to Teicholtz and Simpson (p<0.001 and p<0.001, respectively). Also, there was an increase of deceleration time of early diastolic velocity (DTE) (p<0.05) and a decrease of isovolumic relaxation time (IVRT) (p<0.001). Conclusion The reduction in the right and left ventricle diameters was noted after the six-month atorvastatin therapy. Atorvastatin in the therapy resulted in increased EFLV and better systolic function and should be a part of a therapeutic modality of HF.

A. Iglica, Amina Godinjak, E. Begić, E. Hodžić, F. Zvizdić, N. Kukavica, K. Aganović, N. Šabanović-Bajramović et al.

Aim To examine the effects of therapeutic hypothermia on the outcome of patients with the diagnosis of out-of-hospital cardiac arrest (OHCA). Methods The study included 76 patients who were hospitalised at the Medical Intensive Care Unit (MICU) of the Clinical Centre University of Sarajevo, with the diagnosis of out-of-hospital cardiac arrest, following the return of spontaneous circulation. Therapeutic hypothermia was performed with an average temperature of 33oC (32.3 - 34.1o C) on the patients who had coma, according to the Glasgow Coma Scale (GCS). Results Multiple organ dysfunction syndrome (MODS) significantly affected survival (p=0.0001), as its presence reduced patients' survival by 96%. In addition, ventricular fibrillation (VF) as the presenting rhythm, also significantly affected survival (p=0.019). A degree of patient's coma, as measured by the GCS, significantly affected survival (p=0.011). For each increasing point on the GCS, the chance for survival increased twice. Moreover, other physiological factors such as the pH and the lactate serum levels significantly affected patients' survival (p=0.012 and p=0.01, respectively). Conclusion In patients with the diagnosis of OHCA who underwent to the treatment with therapeutic hypothermia, verified VF as a presenting rhythm was a positive predictive factor for their outcome. Therefore, therapeutic hypothermia represents an option of therapeutic modality for this type of patients.

G. De Backer, P. Jankowski, K. Kotseva, E. Mirrakhimov, Ž. Reiner, L. Rydén, L. Tokgözoğlu, D. Wood et al.

G. De Backer, P. Jankowski, K. Kotseva, E. Mirrakhimov, Ž. Reiner, L. Rydén, L. Tokgözoğlu, D. Wood et al.

F. Zvizdić, E. Begić, A. Mujaković, E. Hodžić, B. Prnjavorac, O. 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.

Introduction: An increase in nitric oxide (NO) synthesis concentration could help alleviate some pathological changes directly related to uremia. Aim: To investigate the concentration of nitric oxide in saliva of patients with terminal stage of chronic renal failure on hemodialysis and to investigate the effect of hemodialysis on concentration of nitric oxide in saliva of the patients with terminal stage of chronic renal failure on hemodialysis. Material and Methods: The study had a prospective character and included 60 respondents of both sexes, at age between 20 and 60 years. The control group included 30 healthy volunteers of both sexes (15 men and 15 women) of the same age, who were based on subjective and objective health status without any manifestations of pathophysiological changes. The group of patients with terminal stage of chronic renal failure on hemodialysis involved 30 patients of both sexes (15 men and 15 women). Inclusion criteria: hemodialysis duration more than 6 months and age between 20 and 60 years. Results: The amount of non-stimulated saliva collected during 15 minutes in patients with chronic renal failure was lower by 31.3% compared to the control group of healthy subjects (p<0.0001). Concentration of NO in saliva in patients with chronic renal failure was higher by 121% than in the control group (p<0.001). Concentration of NO in saliva in patients with chronic renal failure after hemodialysis was 121% lower than in the same subjects prior to hemodialysis (p<0.001). A statistically significant negative correlation (r=-0.381, p<0.05) was found between the hemodialysis duration in months and the level of NO in saliva of the patients with chronic renal failure prior to hemodialysis. There was no statistically significant correlation (r=-0.167, NS) between the hemodialysis duration in months and NO levels in saliva of the patients with chronic renal failure after hemodialysis treatment. Conclusion: Concentration of NO in saliva of the patients on hemodialysis was statistically significantly higher in relation to NO concentration in the saliva of healthy subjects and after hemodialysis was statistically significantly lower in relation to NO values prior to hemodialysis. Monitoring of changes in NO concentration dynamics in saliva of hemodialysis patients will probably be helpful in monitoring hemodialysis efficacy.

Introduction: The effect of statins on risk of heart failure (HF) hospitalization and lethal outcome remains dubious. Aim: To investigate whether statin therapy improves clinical outcomes in patients hospitalized for ischemic heart failure (HF), to compare the efficacy of lipophilic and hydrophilic statins and to investigate which statin subtype provides better survival and other outcome benefits. Material and Methods: Total amount of 155 patients in the study were admitted to the Clinic for Cardiology, Rheumatology and Vascular diseases in Clinical Center University of Sarajevo in the period from January 2014- December 2017. Inclusion criteria was HF caused by ischemic coronary artery disease upon admission. For each patient the following data were obtained: gender, age, comorbidities and medications on discharge. New York Heart Association (NYHA) class for heart failure was determined by physician evaluation and left ventricle ejection fraction (LVEF) was determined by echocardiography. The patients were followed for a period of two years. Outcome points were: rehospitalization, in-hospital death, mortality after 6 months, 1 year and 2 years. All-cause mortality included cardiovascular events or worsening heart failure. Results: Overall, 58.9% of HF patients received statin therapy, with 33.9% patients receiving atorvastatin and 25.0% rosuvastatin therapy. The most frequent rehospitalization was in patients without statin therapy (66.7%), followed by patients on rosuvastatin (64.1%), and atorvastatin (13.2%), with statistically significant difference p = 0.001 between the groups. Mortality after 6 months, 1 year and 2 years was the most frequent in patients without statin therapy with a statistically significant difference (p = 0.001). Progression of HF accounted for 31.7% of mortality in patients without statin therapy, 12.8% in patients on rosuvastatin therapy and 3.8% in patients on atorvastatin therapy (p = 0.004). Conclusion: Lipophilic statin therapy is associated with substantially better long-term outcomes in patients with HF.

Introduction: Heart failure (HF) has very high rate of repeat hospitalizations due to HF decompensation (HHFD), sometimes very shortly after discharge for acute HF. Aim: The aim of this paper is to investigate rate of HHFD and to identify their possible predictors. Patients and Methods: Total amount of 222 patients hospitalized at Clinic for heart and vessel disease and rheumatism in acute HF were followed for next 18 months for occurrence of HHFD. During hospitalization were collected demographic data, risk factors, routine laboratory tests and admission BNP (brain natriuretic peptide), discharge BNP, percentage change of BNP during hospitalization, high sensitive troponin I, CA125 (cancer antigen125) and cystatin C. Results: In next 18 months 129 patients (58.11%) reached end-point HHFD- mean time of its occurrence was 2.2 (95% CI=1.67-2.7) months. Patients with HHFD had more often arterial hypertension (HTA) (p=0.006), had higher BMI (p=0.035) and had higher values of bilirubin, admission BNP (p=0.031), discharge BNP (p <0.001), CA125 (p=0.023) and cystatin C (p=0.028). There was no difference in troponin values (p=0.095), while % reduction of BNP during hospitalization was lower (p<0.001) in group with HHFD. In univariate Cox hazard analysis HTA was positively and BMI negatively correlated with HHFD, while in multivariate Cox hazard analysis independent predictors were HTA (HR 1.6; 95% CI=1.1-2.2; p=0.018) and BMI<25 (HR 1.6; 95% CI=1.1-2.3; p=0.007). In univariate Cox hazard analysis admission BNP, discharge BNP, rise of BNP during hospitalization, CA125 and bilirubin were positively correlated, while sodium was negatively correlated with HHFD. In multivariate Cox hazard analysis there was only one independent predictor of HHFD - discharge BNP (HR 6.05; 95% CI=1.89-19.4; p=0.002). Conclusion: Arterial hypertension, BMI>25 and discharge BNP are independent predictors of HHFD. This could help us to identify high-risk patients for readmission who should be monitored more frequently and treated with sophisticated drug and device therapy.

Amina Godinjak, Selma Jusufović, A. Rama, A. Iglica, F. Zvizdić, A. Kukuljac, Ira Tančica, Šejla Rožajac

Objective The aim of the study was to describe the prevalence of hyperlactatemia and emphasis on repeated lactate measurements in critically ill patients, and the associated mortality. Materials and methods The study included 70 patients admitted in the Medical Intensive Care Unit at the Clinical Center, University of Sarajevo, in a 6-month period (July - December 2015). The following data were obtained: age, gender, reason for admission, Simplified Acute Physiology Score II, Acute Physiology and Chronic Health Evaluation, lactate concentrations upon admission, after 24 and 48 hours, and outcome (discharge from hospital or death). Results Upon admission,hyperlactatemia was present in 91.4% patients with a mean concentration of lactate 4.13 ±1.21 mmol/L. Lactate concentration at 48 hours was independently associated within creased in-hospital mortality (P = 0.018). Conclusion Persistent hyperlactatemia is associated with adverse outcome in critically ill patients. Lactate concentration at 48 hours is independently associated within creased in-hospital mortality and it represents a statistically significant predictive marker of fatal outcomes of patients. Blood lactate concentrations > 2.25 mmol/L should be used by clinicians to identify patients at higher risk of death.

Introduction: Up to 50% of patients with acute heart failure (AHF) have preserved left ventricular ejection fraction (HFPEF group)1. Due to diverse activated pathophysiological pathways, there should be a difference in biomarkers release in heart failure with preserved ejection fraction (HFPEF) and reduced ejection fraction (HFREF). BNP is the best studied biomarker in AHF, but we want to investigate difference in release of troponin (marker of myocytes stress and injury), tumor marker CA125 (marker of congestion and volume overload om HF) and cystatin C (marker of interstitial fibrosis).

OBJECTIVE To assess serum levels of tumor marker carbohydrate antigen 125 (CA125) in patients with heart failure (HF) and to investigate possible correlation with echocardiographic parameters and level of brain natriuretic peptide (BNP). PATIENTS AND METHODS We included 76 patients with different cardiac symptoms hospitalized at Clinic for heart disease and rheumatism. Control group (n = 26) was consisted of patients without signs and symptoms of HF, normal left ventricle ejection fraction (LVEF) and normal BNP level. Patients with diagnosis of HF (n = 50) were subdivided into 2 group depending on signs and symptoms of fluid overload: compensated (compHF, n = 10) and decompensated group (decompHF, n = 40). Serum CA125 and BNP were measured on admission and all patient underwent ECG recording and trans thoracic echocardiographic examination. RESULTS The median CA125 level in HF group was significantly higher compared to control group (71.05 [30.70-141.47]U/ml vs 10.75 [8.05- 14.32] U/ml, p < 0.0005). Higher CA125 levels were found in decompHF group compared to compHF group (94.90 [49.75-196.75]U/ml vs 11.90 [10.25-15.80]U/ml, p < 0.0005). In decompHF group 13 of patients had pleural and/or pericardial effusion- their CA125 levels were significantly higher compared to patients without serosal effusion (n = 27) (205.10 [106.50-383.90]U/ml vs. 71.50 [47.30-109.55] U/ml, p < 0.002). We found significant difference in CA125 levels between patients with atrial fibrillation and sinus rhythm (98.40 [48.20-242.70] U/ml vs. 47.30 [12.95-99.05] U/ml, p = 0.015). There was no significant difference in CA125 levels in group with enlarged left atrium compared to normal sized atrium (p = 0.282), as well as in group with moderate/severe mitral regurgitation compared to group with no/mild mitral regurgitation (p = 0.99). Finally, levels of serum CA125 positively correlated with serum level of BNP (r = 0.293, p = 0.039), but not with LVEF (p = 0.369) and left atrium diameter (p = 0.636). CONCLUSION Serum CA125 is elevated in decompensated HF patients: more pronounced elevation was found in patients with pleural and/or pericard effusion compared to patients with no serosal effusion. CA125 level correlated with BNP, but not with left atrium diameter nor with LVEF. Tumor marker CA125 could be used as a marker of systemic congestion and volume overload in decompensated HF. We hypothesized that high CA125 level indicates that measured high BNP is actually wet BNP.

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