Milan Pavlovic

Frequency and significance of unrecognized chronic obstructive pulmonary disease in elderly patients with stable heart failure

Background and aims: Due to prolonged life-spans and modern therapeutic approaches, there has been an increase in the number of patients aged ≥65 years with chronic heart failure (CHF). The duration and quality of life in elderly patients with CHF also depend on accompanying diseases. Although frequency of chronic obstructive pulmonary disease (COPD) in patients with CHF is about 30%, it is hard to find similar data in the elderly population. COPD is defined as a spirometrically assessed ratio of a post-dilatory forced expiratory volume in the first second, divided by forced vital capacity (FEV1/FVC) <70%. The aims of our study were to assess the prevalence of previously undiagnosed COPD in outpatients (≥65 yrs) with stable CHF and to determine the effect of the combination of COPD and CHF on patients’ functional capacity as measured by a 6-minute walking test. Methods and Results: Of the 174 study patients, 126 (72.4%) were men. In 48 patients (27.6%) we found previously unrecognized COPD. They were significantly older (75.6±5.8 vs 73±4.5 years, p<0.01) and more frequently had abdominal obesity and a greater waist circumference (98.8±10.2 vs 94.9±9.1 cm, p<0.05). Patients with COPD had significantly shorter 6-min walking distance (275.5±112.9 vs 291.3±96.7 m, p<0.05). Only patient’s age had a positive prognostic association with unrecognized COPD (OR=1.16; 95% CI 1.01–1.34, p<0.01). Patients with COPD showed a significant correlation between actual/predicted FEV1 and the 6-min walking distance (r=0.39, p<0.01). Conclusions: We found a high prevalence of unrecognized COPD in elderly patients with CHF and central obesity. Chronic obstructive pulmonary disease influenced functional capacity in CHF patients, as determined by the 6-minute walking test. Closer co-operation between pulmonologists and cardiologists is necessary to optimize management of this large proportion of CHF patients.

Stress hyperglycemia in acute ST-segment elevation myocardial infarction is a marker of left ventricular remodeling.

Abstract Introduction: Stress hyperglycemia (SH) in STEMI is associated with high risk of in-hospital mortality. It is still controversial if SH is marker of high post-hospital risk. 
Objectives: The aim was to analyze in-hospital and one-year risk associated with SH in STEMI and to study if SH is marker of LV remodeling. 
Methods: We enrolled 275 patients who were admitted with first STEMI and reperfused. Patients were divided according to admission glycemia in three groups: (1) with diabetes mellitus (DM); (2) with SH, without DM and; (3) without both DM and SH. SH was defined as admission blood glucose level ≥ 8 mmol/l. 
Results: In-hospital mortality was higher in patients with known DM (5%) and highest in patients with SH without previous DM (9.3%), and only 1.6% in the third group, P < 0.05. In patients without known DM, SH was associated with 6.378-fold higher in-hospital mortality. Total mortality was double in group with SH without DM compared to the third group (13.9% versus 6.3%). EDV changed in patients with SH without DM from 126 ± 37 to 145 ± 30 ml after one year, P < 0.05. 
Conclusion: SH is associated with high in-hospital mortality risk and it could be marker of LV remodeling (significant increase of EDV during one year).

P-Glycoprotein Polymorphism C3435T Is Associated with Dose-Adjusted Clopidogrel and 2-Oxo-Clopidogrel Concentration

Background/Aims: One of the most common polymorphisms of ABCB1 gene, a synonymous mutation C3435T (rs1045642), is associated with increased in vivo activity. The main goal of this study was to determine the association of C3435T polymorphism with clopidogrel and 2-oxo-clopidogrel concentrations in plasma. Methods: The patients were recruited upon acute myocardial infarction diagnosis. They were all tested for ABCB1 C3435T polymorphism. In plasma, drawn 1 h after the drug administration, concentrations of clopidogrel and 2-oxo-clopidogrel were measured using UHPLC-DAD-MS analysis. Results: Due to differences in the maintenance doses, we have calculated the dose-adjusted concentrations of clopidogrel (0.2 ng/ml/mg (0.1-0.4)) and 2-oxo-clopidogrel (2.1 ng/ml/mg (0.5-4.6)). Patients carrying at least one C allele achieved significantly higher serum concentration of clopidogrel (p < 0.001), as well as dose-adjusted clopidogrel (p < 0.001) and 2-oxo-clopidogrel concentrations (p < 0.05). Conclusion: The ABCB1 3435CC genotype is associated with increased clopidogrel and 2-oxo-clopidogrel dose-adjusted concentrations. Therefore, the ABCB1 C3435T genotyping should be one of the parameters taken into account when deciding about the dosing regimen of clopidogrel.

The influence of stress hyperglycaemia on the prognosis of patients with acute myocardial infarction and temporary electrical cardiac pacing

INTRODUCTION Elevated glucose levels on admission in many emergency conditions, including acute myocardial infarction (AMI), have been identified as a predictor of hospital mortality. OBJECTIVE Since there are no data in the literature related to stress hyperglycaemia (SH) in patients with both AIM and temporary electrical cardiac pacing, we aimed to investigate the influence of stress hyperglycaemia on the prognosis of patients with AMI and temporary electrical cardiac pacing. METHODS The prospective study included 79 patients with diagnosed AMI with ST-segment elevation (STEMI), admitted to the Coronary Care Unit of the Clinic for Cardiovascular Diseases, Clinical Centre Nis, from 2004 to 2007, who were indicated for temporary electrical cardiac pacing. The blood was sampled on admission for lab analysis, glucose levels were determined (as well as markers of myocardial necrosis troponin I, CK-MB). Echocardiographic study was performed and ejection fraction was evaluated by using area length method. RESULTS The ROC analysis indicated that the best glycaemic level on admission, which could be used as a predictor of mortality, was 10.00 mmol/l, and the area under the curve was 0.82. In the group without SH, hospital mortality was 3-fold lower 11/48 (22.91%) compared to the group with SH 19/31 (61.29%), p < 0.0001. Patients with SH were more likely to have higher troponin levels, Killip >1, lower ejection fraction and heart rate, as well as systolic blood pressure. CONCLUSION The best cut-off value for SH in patients with AMI (STEMI) and temporary electrical cardiac pacing is 10 mmol/l (determined by ROC curve) and may be used in risk stratification; patients with glucose levels <10 mmol/l on admission are at 3-fold lower risk compared to those with glucose levels >10 mml/l. Our results suggest that SH is a more reliable marker of poor outcome in AMI patients with temporary pace maker, without previously diagnosed DM.

Prognostic utility of biomarker growth differentiation factor- 15 in patients with acute decompensated heart failure.

Objective Growth differentiation factor-15 (GDF-15) has established promising prognostic value in various cardiovascular diseases, although there is very little information available about it in patients with acute heart failure, particularly with regard to long-term outcomes. The aim of our study was to determine the prognostic value of GDF-15 in patients with acute decompensated heart failure (ADHF). Methods and results A total of 107 consecutive patients (median age 70 [interquartile range, IQR: 60-73.5]; 36% women), hospitalized for ADHF, were examined. The primary and secondary endpoints were to determine the differences in both mortality and rehospitalization due to heart failure after one year, depending on the GDF-15 plasma level. The control group consisted of 25 healthy people of a similar age. The patients with ADHF had significantly higher level of GDF-15 on admission (median 3481 [IQR: 2113-5090]), than the subjects in the control group (887.5 (IQR: 763.75-960.25] ng/L). A high GDF-15 level on admission remained a significant predictor for adverse clinical events, shown by a multivariable regression analysis (hazard ratio [HR], 3.08; 95% confidence interval [CI], 1.06-8.35, P< 0.05), together with left ventricle ejection fraction (P <0.05). Kaplan-Meier curve analysis showed a significantly higher probability of death and HF rehospitalization in patients with higher levels of GDF-15. Patients with both GDF-15 and BNP levels above the median on admission had the highest mortality rate. Conclusion In patients with ADHF, an elevated GDF-15 value on admission was a strong predictor of an adverse clinical outcome regarding mortality and HF rehospitalization 1-year after the initial hospitalization.

Regional differences among female patients with heart failure from the Cardiac Insufficiency BIsoprolol Study in ELDerly (CIBIS-ELD)

BACKGROUND The aim of our study was to examine regional differences in the demographics, etiology, risk factors, comorbidities and treatment of female patients with heart failure (HF) in the Cardiac Insufficiency BIsoprolol Study in ELDerly (CIBIS-ELD) clinical trial. METHODS AND RESULTS One hundred and fifty-nine female patients from Germany and 169 from Southeastern (SE) Europe (Serbia, Slovenia and Montenegro) were included in this subanalysis of the CIBIS-ELD trial. Women comprised 54% of the study population in Germany and 29% in SE Europe. German patients were significantly older. The leading cause of HF was arterial hypertension in German patients, 71.7% of whom had a preserved ejection fraction. The leading etiology in SE Europe was the coronary artery disease; 67.6% of these patients had a reduced left ventricular ejection fraction (34.64 ± 7.75%). No significant differences were found in the prevalence of traditional cardiovascular risk factors between the two regions (hypertension, diabetes, hypercholesterolemia, smoking and family history of myocardial infarction). Depression, chronic obstructive pulmonary disease and malignancies were the comorbidities that were noted more frequently in the German patients, while the patients from SE Europe had a lower glomerular filtration rate. Compared with the German HF patients, the females in SE Europe received significantly more angiotensin converting enzyme inhibitors, loop diuretics and less frequently angiotensin receptor blockers and mineralocorticoid receptor antagonists. CONCLUSIONS Significant regional differences were noted in the etiology, comorbidities and treatment of female patients with HF despite similar risk factors. Such differences should be considered in the design and implementation of future clinical trials, especially as women remain underrepresented in large trial populations.

VT/VF Detection Method Based On ECG Signal Quality Assessment

Artefacts which are present in electrocardiogram (ECG) recordings distort detection of life-threatening arrhythmias such as ventricular tachycardia and ventricular fibrillation. The method examines single ECG lead and exploits time domain signal parameters for real-time detection of severe cardiac arrhythmias. The method is dedicated to implementation in mobile ECG telemetry systems, which are designed by using low-power microcontrollers, operating more than a week on a single battery charge. The method has been validated on publicly available databases and the results are presented. We verified our method on ECG signals obtained without pre-selection meaning that the noisy intervals were not omitted from signal analysis.

ONE-YEAR CARDIOVASCULAR OUTCOME IN PATIENTS ON CLOPIDOGREL ANTI-PLATELET THERAPY AFTER ACUTE MYOCARDIAL INFARCTION

The aim of this study was to determine the risk factors in patients on clopidogrel anti-platelet therapy after acute myocardial infarction, for cardiovascular mortality, re-hospitalization and admission to emergency care unit. We followed 175 patients on dual antiplatelet therapy, with clopidogrel and acetylsalicylic acid, for 1 year after acute myocardial infarction, both STEMI and NSTEMI. Beside demographic and clinical characteristics, genetic ABCB1, CYP2C19 and CYP2C9 profile was analyzed using Cox-regression analysis. End-points used were: mortality, re-hospitalization and emergency care visits, all related to cardiovascular system. During the accrual and follow-up period, 8 patients (4.6%) died, mostly as a direct consequence of an acute myocardial infarction. Re-hospitalization was needed in 27 patients (15.4%), in nine patients (33.3%) with the diagnosis of re-infarction. Thirty-two patients (18.3%) were admitted to emergency care unit due to cardiovascular causes, up to 15 times during the follow-up. NSTEMI was an independent predictor of all three events registered (mortality OR=7.4, p<0.05; re-hospitalization OR=2.8, p<0.05); emergency care visit OR=2.4, p<0.05). Other significant predictors were related to kidney function (urea and creatinine level, creatinine clearance), co-morbidities such as arterial hypertension and decreased left ventricular ejection fraction, as well as clopidogrel dosing regimen. As a conclusion, it may be suggested that one of the most significant predictors of cardiovascular events (mortality, re-hospitalization and emergency care visits) is NSTEMI. Besides, clopidogrel administration according to up-to-date guidelines, with high loading doses and initial doubled maintenance doses, improves 1-year prognosis in patients with AMI.

The Association between Galectin-3 and hs-CRP and the Clinical Outcome after Non-ST-Elevation Myocardial Infarction with Preexisting Atrial Fibrillation

Increased galectin-3 plasma concentration has been linked to an unfavorable outcome in patients with heart failure or atrial fibrillation (AF). There are no published data about the prognostic utility of galectin-3 and high-sensitivity C-reactive protein (hs-CRP) for long-term clinical outcome in the Non-ST elevation acute myocardial infarction (NSTEMI) patients with preexisting AF. Thirty-two patients with the first acute NSTEMI and preexisting AF and 22 patients without preexisting AF, were prospectively followed for fifteen months. Patients with AF had significantly higher galectin-3 plasma levels (p < 0.05) and hs-CRP concentration (p < 0.01), compared with patients without AF. Galectin-3 plasma concentration was not a significant covariate of the composite outcomes (p = 0.913). Patients with high hs-CRP (above 4.55 mg/L) showed 2.5 times increased risk (p < 0.05) of the composite outcome occurrence (p < 0.05). Besides, three-vessel coronary artery disease, creatinine serum level, and creatinine clearance were significant covariates (p < 0.05; p < 0.05; p < 0.01) of the composite outcome, respectively. Creatinine clearance, solely, has been shown to be an independent predictor of unfavorable prognosis after a 15-month follow-up. Galectin-3 and hs-CRP plasma levels were elevated in NSTEMI patients with AF, but with differential predictive value for an unfavorable clinical outcome. Only hs-CRP was associated with increased risk of composite outcome occurrence.

The Factors Influencing Galectin-3 Levels in Acute Coronary Syndrome with Decreased Left Ventricular Function

Summary The aim of our study was to determine the factors influencing galectin-3 levels in patients with acute coronary syndrome and decreased left ventricular ejection fraction. We collected material from 37 successive patients with acute coronary syndrome and decreased left ventricular ejection fraction, of which 19 patients had atrial fibrillation, and 18 patients who were without atrial fibrillation constituted a control group. Blood samples used for the biochemical measurements were obtained on the third day from acute coronary syndrome. We used Statistical Package for Social Sciences for data analysis. A p-value less than 0.05 was considered to be a measure of statistical significance. Galectin-3 concentration is directly correlated with age and B-type natriuretic peptide level. Also, our results showed an inverse correlation between galectin-3 and total body weight, body mass index, body surface area and creatinine clearance. The following variables were found to be significant predictors of galectin-3 level: decreased left ventricular ejection fraction, total body weight, LDL concentration and body mass index. We identified factors that can predict a decrease in the left ventricular ejection fraction below 45% after acute coronary syndrome: atrial fibrillation increases the risk by almost six times, and urea concentration increases the risk by 1.2 times for each unit. Left ventricular ejection fraction below 45%, TBW, body mass index and LDL level are good predictors of galectin-3 concentration in patients with ACS and decreased left ventricular ejection fraction. Atrial fibrillation could be a predictive marker of decreased left ventricular ejection fraction.