Hyperlactatemia and the Importance of Repeated Lactate Measurements in Critically Ill Patients.

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.

Comparison of two and three dimensional transthoracic versus transesophageal echocardiography in evaluation of anatomy and pathology of left atrial apendage.

OBJECTIVE: Our objective was the comparison of combined utility of two-dimensional (2D) transthoracic echocardiography (TTE) and three-dimensional (3D) TTE versus 2D and 3D transesophageal echocardiography (TEE) in evaluation of anatomy of the left atrium appendage (LAA) and for clot formation in LAA. BACKGROUND: 2DTEE as semi-invasive method has been for a long time used to visualize the LAA. Improved echocardiography technology has increasingly improved visualization of LAA by 2DTTE and 3DTTE in many patients and decreased the need for TEE performance. METHODS: We compared combined 2DTTE and 3DTTE with 2DTEE and 3DTEE in evaluating the LAA for anatomical features and thrombus. Eighty-six patients underwent 2DTTE, 3DTTE, 2DTEE and 3DTEE. RESULTS: LAA could be visualized in all patients. 31 % of patients had one lobe, 43% had 2 lobes and 26% had > 2 lobes. Of 86 patients studied, 79 had no thrombus and 7 had thrombus in the LAA by all modalities. Six patients, 3 with atrial fibrillation (AF), and 4 in sinus rhythm (SR) had a suspected thrombus by 2DTEE. Only in one patient 3DTEE cropping has been needed to clearly show thrombus which was suspected in short axis view on 2DTEE as rounded echo dense mass. CONCLUSIONS: Our preliminary study suggests that combined 2DTTE and 3DTTE has comparable accuracy to TEE in evaluating the LAA anatomy and pathology in terms of thrombus. Only in inappropriate (obese) patients 2TTE, but not 3DTTE, may misdiagnose pectinate musculature as thrombus.

Serum level of tumor marker carbohydrate antigen-CA125 in heart failure.

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.

Biphasic and monophasic pattern of brain natriuretic peptide release in acute myocardial infarction.

This study evaluated brain natriuretic peptide (BNP) release in acute myocardial infarction (AMI), absolute values as well as pattern of its release. There are two different patterns of BNP release in AMI; monophasic pattern--concentration in the first measurement is higher than in the second one, and biphasic pattern--concentration in the first measurement is lower than in the second one. We observed significance of biphasic and monophasic pattern of BNP release related to diagnostic and prognostic value. We included in this prospective observational study total of 75 AMI patients, 52 males and 23 females, average age of 62.3 +/- 10.9 years with range of 42 to 79 years. BNP was measured and pattern of its release was evaluated. In AMI group BNP levels were significantly higher than in controls (462.88 pg/mL vs. 35.36 pg/mL, p < 0.001). We found statistically significant real negative correlation (p < 0.05) between BNP concentration and left ventricle ejection fraction (LVEF) with high correlation coefficient (r = -0.684). BNP concentrations were significantly higher among patients in Killip class II and III compared to Killip class I; Killip class I BNP = 226.18 pg/mL vs. Killip class II 622.51 pg/mL vs. Killip class III 1530.28 pg/mL, p < 0.001. BNP concentrations were significantly higher in patients with; (i) myocardial infarction vs. controls; (BNP 835.80 pg/mL vs. 243.03 pg/mL); (ii) in pts with positive major adverse cardiac events (MACE) vs. negative MACE (BNP 779.08 pg/mL vs. 242.28 pg/mL, p < 0.001); (iii) in pts with positive compared to negative left ventricle (LV) remodelling (BNP 840.77 pg/mL vs. 341.41 pg/mL, p < 0.001). Group with biphasic pattern of BNP release had significantly higher BNP concentration compared to monophasic pattern group. In biphasic pattern group we found significant presence of lower LVEF, Killip class II and III, LV remodelling and MACE. We found that BNP is strong marker of adverse cardiac events in patients presenting with a myocardial infarction. In our AMI group we found significant elevation of BNP and it is suspected that second peak secretion is not only due to systolic dysfunction and subsequent remodeling of LV but also due to impact of ischaemia. Patients with biphasic pattern probably have worse prognosis due to severe coronary heart disease. Besides its diagnostic role as a simple blood marker of systolic function, BNP is also important prognostic marker who helps making clinical decision about early invasive vs. conservative management.

Effect of atorvastatin on systolic and diastolic function in patients with heart failure with reduced ejection fraction (HFrEF).

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.

Beta-blocker Use in Moderate and Severe Chronic Obstructive Pulmonary Disease.

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.

Therapeutic hypothermia as a treatment option after out-ofhospital cardiac arrest: our experience.

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.

Predictors of Hospitalization for Heart Failure Decompensation in 18-months Follow-up After Index Hospitalization for Acute Heart Failure.

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.

Significance of Nitric Oxyde Saliva Concentration of the Patients with Renal Failure on Hemodialysis.

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.

Impact of Different Types of Statins on Clinical Outcomes in Patients Hospitalized for Ischemic Heart Failure.

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.

Brain natriuretic peptide release in acute myocardial infarction.

Brain natriuretic peptide (BNP) is released from ventricular myocites due to their stretching and volume overload. In heart failure there is BNP release. Aim of this study was to observe BNP release in acute myocardial infarction (AMI). We measured BNP in 75 patients with AMI. Control group (n=61) was similar by age and gender to AMI group. We found statistically significant elevation of BNP compared to controls (462.875 pg/ml vs 35.356 pg/ml, p< 0.001). Patients with severe systolic dysfunction had the highest BNP levels, while patients with the preserved systolic function had the lowest BNP levels (Group with EF< 30% BNP= 1129.036 pg/ml vs Group with EF31-40 % BNP= 690.177 pg/ml vs Group with EF 41-50% BNP= 274.396 pg/ml vs Group with EF> 51% BNP= 189.566 pg/ml, p< 0.001). We found statistically significant light positive correlation between BNP and left ventricle end-diastolic diameter (LVDd) (r= 0.246, p<0.05). and real positive correlation between BNP and peak troponin levels (r= 0.441, p < 0.05). BNP levels were higher in anteroseptal allocation of AMI compared to inferior allocation (835.80 pg/ml vs 243.03 pg/ml, p< 0.001) and in patients who were treated with heparin compared to fibrinolitic therapy (507.885 pg/ml vs 354.73 pg/ml, p< 0.05). BNP is elevated in AMI and is a quantitative biochemical marker related to the extent of infarction and the left ventricle systolic dysfunction. Besides echocardiographic calculation, elevation of BNP could be used for quick and easy determination of the left ventricle systolic dysfunction.