Relationship of reduced cerebral blood flow and heart failure severity in elderly males.

INTRODUCTION: Brain detrimental effects are under-recognised complication of chronic heart failure (CHF). One of the major causes may be cerebral hypoperfusion. This study was designed to investigate the relationship between cerebral blood flow (CBF) and severity of CHF as well as to evaluate its determinants among different parameters of cardiac dysfunction. METHODS: Seventy-one CHF males with NYHA class II and III and 20 control subjects age ≥ 55 years were recruited. CBF was evaluated by colour duplex sonography of extracranial arteries. Echocardiography, 6-min walk test, quality of life and endothelial function were also assessed. Serum NT-pro-BNP and adipokines levels (adiponectin and leptin) were measured. RESULTS: CBF was significantly reduced in elderly patients with CHF compared to healthy controls (677 +/- 170 vs 783 +/- 128 ml/min, p=0.011). Reduced CBF was associated with reduced left ventricular ejection fraction (LVEF) (r=0.271, p=0.022), lower 6-min walk distance (r=0.339, p=0.004), deteriorated quality of life (r= -0.327, p=0.005), increased serum adiponectin (r= -0.359, p=0.002), and NT-pro-BNP levels (r= -0.375, p=0.001). In multivariate regression analysis, LVEF and adiponectin were independently associated with reduced CBF in CHF patients (R(2)=0.289). CONCLUSION: CBF was reduced in elderly males with mild-to-moderate CHF, and was associated with factors that represent the severity of CHF including high serum adiponectin and NT-pro-BNP levels, decreased LVEF, impaired physical performance, and deteriorated quality of life.

Comparison between carotid artery wall thickness measured by multidetector row computed tomography angiography and intimae-media thickness measured by sonography.

The increased thickness of the carotid wall >1 mm is a significant predictor of coronary and cerebrovascular diseases. The purpose of our study was to assess the agreement between multidetector row computed tomography angiography (MDCTA) in measuring carotid artery wall thickness (CAWT) and color Doppler ultrasound (CD-US) in measuring intimae-media thickness (IMT). Eighty-nine patients (aged 35-81) were prospectively analyzed using a 64-detector MDCTA and a CD-US scanner. Continuous data were described as the mean value ± standard deviation, and were compared using the Mann-Whitney U test. A p value <0.05 was considered significant. Bland-Altman statistics were employed to measure the agreement between MDCTA and CD-US. CAWT ranged from 0.62 to 1.60 mm, with a mean value of 1.09 mm. IMT ranged from 0.60 to 1.55 mm, with a mean value of 1.06 mm. We observed an excellent agreement between CD-US and MDCTA in the evaluation of the common carotid artery thickness, with a bias between methods of 0.029 mm (which is a highly statistically important difference of absolute values [t = 43.289; p < 0.01] obtained by paired T test), and limits of agreement from 0.04 to 0.104. Pearson correlation coefficient was 0.9997 (95% CI 0.9996-0.9998; p < 0.01). We conclude that there is an excellent correlation between CAWT and IMT measurements obtained with the MDCTA and CD-US.

Correlation of color Doppler with multidetector CT angiography findings in carotid artery stenosis.

The aim of this paper was to examine the correlation between the Color Doppler ultrasound (CD-US) and multidetector CT angiography (MDCTA) diagnostic methods, and to define the degree and extent of stenosis in patients with internal carotid artery stenosis. This was a cross-sectional study with a consecutive series of patients. All US examinations were always carried out by the same physician-angiologist, while all CT examinations were always carried out by the same physician-radiologist. Both worked independently from each other. The stenosis area was measured at the narrowest point by NASCET criteria for US/CT. Peak systolic velocity (PSV) over 210 cm/sec and end diastolic velocity (EDV) over 110 cm/sec criteria were applied for stenoses with lumen narrowed over 70%, while PSV under 130 cm/sec and EDV under 100 cm/sec criteria were applied for those with lumen narrowed under 70%. A total of 124 carotid arteries were observed; namely, 89 narrowed and 68 surgically treated. All patients were reviewed by US and then by MDCTA; patients with 70-99% stenosis underwent surgery. The correlation coefficient between stenosis degree measured by US and MDCTA was 0.922; p < 0.01. The average difference between US and MDCTA diagnostic methods was 3% (Z = -1.438, p > 0.05). The US and CT matching level for stenoses from 70 to 99% was very high (kappa = 0.778, p < 0.01). In conclusion, there is a highly significant statistical correlation among both diagnostic methods when measuring stenosis degree and extent. US is more dependent on the physician, while MDCTA is more objective and independent from the physician. We think it would be appropriate to undertake an MDCTA exam for those patients who are candidates for carotid endarterectomy.

The influence of various morphologic and hemodynamic carotid plaque characteristics on neurological events onset and deaths.

A group of 72 patients with 111 asymptomatic carotid stenoses (ACS), mean age 65.42 +/- 9.21, and a group of 36 patients with 58 symptomatic carotid stenoses (SCS), mean age 67.63 +/- 8.79, were analyzed prospectively during a 3-year follow-up period. All patients underwent color duplex scan sonography (CDS), carotid arteriography, computed tomography (CT) scan, and neurological examination. The aim of the study was to analyze the correlation between echo plaque morphology (degree and plaque quality), local hemodynamic plaque characteristics, ischemic CT findings, and onset of new neurological events and deaths. The results analysis showed significantly more ACS in the group of 30-49% stenosis (p < 0.001), but significantly more SCS in the group of 70-89% (p < 0.0001) and > or = 90% stenosis (p < 0.05). Fibrous plaque was more frequent in the ACS group (p < 0.001), while ulcerated and mixed plaques were more frequent in the SCS group (both p < 0.0001). In the SCS group, a significantly higher frequency of increased peak systolic and end diastolic velocities was noted at the beginning and end of the study (both p < 0.01), as well as for contralateral common (CCA) or internal carotid artery (ICA) occlusion (p < 0.05 and p < 0.01, respectively), but reduced carotid blood flow volume (p < 0.05) only at the end of the study. In the ACS group, the best correlation with new neurological events and deaths was shown with positive CT findings, peak systolic flow velocity over 210 cm/sec, end diastolic flow velocity over 110 cm/sec, plaque stenosis > or = 70%, plaque ulceration, mixed plaque (all p < 0.0001); stenosis > or = 50% (p < 0.001); and reduced carotid blood flow volume (p < 0.05).

Availability of Oral Formulations Labeled for Use in Young Children in Serbia, Germany and the USA.

BACKGROUND: The paucity of marketed drug products that have been adequately studied in infants and children and subsequently, licensed (or labeled) for pediatric use has caused abundant use of off-label and unauthorized products in this patient population. In those instances where insufficient pharmacologic or therapeutic information exists for children, the potential for off-label use of medicines to result in therapeutic misadventure does as well. In the USA, a series of regulatory measures have been introduced since 1997 which have increased both the number and scope of pediatric drug trials and also, fostered the development of ageappropriate drug formulations by pharmaceutical companies. Provisions of these regulations for previously marketed drugs include the potential for a company to be granted 6 months of marketing exclusivity, thereby providing them with a financial incentive. For new drugs being developed that have potential pediatric use, the regulations mandate the inclusion of children in the drug development process. In the EU comparable measures have been very recently (Jan 2007) signed into European law to overcome the therapeutic orphan status of the infants and children of Europe. METHOD: The aims of this study was to compare the availability of age-appropriate oral formulations labeled for use in children less than 12 years of age in Serbia, Germany and USA in 2007, and to investigate if certain drug groups of therapeutic importance to children had fewer medicines appropriately labeled for pediatric patients available. The primary sources of information for determining the ageappropriate oral dosage forms, and their licensing and labeling status were the official manuals on drug information and national formularies in 2007. FINDING: The general availability of oral drugs was the highest in the USA (304), followed by Germany (235) and Serbia (156). From all these oral drugs the availability of labeled age-appropriate pediatric dosage formulations was only between 21.2% and 47.7%. Moreover, there were striking differences between the three countries in the availability of labeled age-appropriate formulations for certain drug groups such as cardiovascular (absent in Serbia) and antiparasitic drugs (absent in Serbia and Germany). INTERPRETATION: Our data suggest that significant country-to-country differences continue to exist in both the number and type of oral drug formulations that have pediatric labeling. Potential contributing factors include country-specific differences in the drug regulatory process, capacity for pharmaceutical development and the regulatory lag time associated with the implementation of drug regulation specifically addressing pediatric product development and labeling. We hypothesize that the new European regulation concerning medicines and children will improve the current unacceptable situation.

Health-related quality of life in elderly patients hospitalized with chronic heart failure.

BACKGROUND: Chronic heart failure is a very common condition in the elderly, characterized not only by high mortality rates, but also by a strong impact on health-related quality of life (HRQOL). Previous studies of HRQOL in elderly heart failure subjects have included mostly outpatients, and little is known about determinants of HRQOL in hospitalized elderly population, especially in Serbia. In this study, we tried to identify factors that influence HRQOL in elderly patients hospitalized with chronic heart failure in Serbia. METHODS: The study population consisted of 136 patients aged 65 years or older hospitalized for chronic heart failure. HRQOL was assessed using the Minnesota Living with Heart Failure questionnaire. Predictors of HRQOL were identified by multiple linear regression analysis. RESULTS: Univariate analysis showed that patients with lower income, a longer history of chronic heart failure, and longer length of hospital stay, as well as those receiving aldosterone antagonists and digoxin, taking multiple medications, in a higher NYHA class, and showing signs of depression and cognitive impairment had significantly worse HRQOL. Presence of depressive symptoms (P<0.001), higher NYHA class (P=0.021), lower income (P=0.029), and longer duration of heart failure (P=0.049) were independent predictors of poor HRQOL. CONCLUSION: Depressive symptoms, higher NYHA class, lower income, and longer duration of chronic heart failure are independent predictors of poor HRQOL in elderly patients hospitalized with chronic heart failure in Serbia. Further, there is an association between multiple medication usage and poor HRQOL, as well as a negative impact of cognitive impairment on HRQOL. Hence, measures should be implemented to identify such patients, especially those with depressive symptoms, and appropriate interventions undertaken in order to improve their HRQOL.

[Gelatinases A and B activities in the serum of patients with various coronary artery disease stages].

BACKGROUND/AIM: The main characteristic of matrix metalloproteinases (MMPs) is the degradation of extracellular matrix. Synthesis of MMPs has been reported in coronary atherosclerotic lesions in patients with coronary disease (CD) suggesting a pathogenic role of MMPs in its development. Recently there is increasing evidence that gelatinase A (pro MMP-2) and gelatinase B (proMMP-9) play a pathogenic role in the development of the atherosclerotic plaques. The aim of the study was to determine, by the use of a gel image system, a possible presence of active gelatinases in the serum of the patients with CD, as well as if their activity is higher in these patients than in healthy people. METHODS: By gelatin zymography we analyzed the activity of proMMP-2 and proMMP-9 in the serum of 50 patients with various coronary artery disease stages and in the serum of 15 healthy controls. The activity was measured by using a gel image system (Kodak Image 1D 3.6.). RESULTS: ProMMP-2 and proMMP-9 activity was significantly higher in the serum of patients with CD compared to controls. There was higher activity of MMP-2 and MMP-9 in the serum of patients with acute myocardial infarction (AMI) compared to patients with stable angina pectoris, as well as higher proMMP-9 activity in patients with unstable angina pectoris compared to patients with stable angina pectoris. CONCLUSION: ProMMP-2 and proMMP-9 participate in processes associated with destabilizing plaques and understanding the processes of MMPs activation and regulation may have significant benefits in clinical interpretation. The reported higher proMMP-2 and proMMP-9 activity in the serum of patients with CD suggests a role of proMMP-2 and proMMP-9 in prognostic stratification of these patients and in designing new drugs.

[Correlation between morphologic carotid plaque findings based on color-Doppler and CT multidetector angiography with intraopertive findings in carotid artery stenosis].

BACKGROUND/AIM: Vast majority of patients with corotid arthery sclerosis do not have transitory ischemic attacs (TIA) as working to the persistent silent disease, but stroke is the first sign. Precise and early diagnosis of the carotid artery disease and plaques are very important. The aim of this study was to determine how the composition/identity of diagnostic methods, color-Doppler, ultrasonography (US) CT-multidetector angio (MDCTA) scan and intraoperative (IO) findings, as well as the morphology of plaques in patients with haemodynamic significant stenosis of the internal carotid artery. METHODS: Carotid plaques were observed by two diagnostic methods, US and MDCTA, and these findings were correlated with the IO findings. RESULTS: In 62 patients both carotid artheries were examined and 83 plaques were observed. There were 68 surgical interventions. The structure of plaques was divided into four types: lipid, fibrous, fibrocalcified and calcified plaque. US showed: lipid plaques 10.8%; fibrous 1.2%; fibrocalcified 44.6% and calcified 43.4%, and the MDCTA lipid plaques 8.4%; fibrocalcified 48.2% and calcified 43.4%. Intraoperative findings were: lipid plaques 10.3%; fibrocalcified 41.2% and calcified 48.5%. A statistically highly significant agreement between the US and MDCTA in the diagnosis of plaque morphology was obtained (Cramer's V = 0.919, p < 0.01; Lambda = 0.921, p < 0.01) and also statistically significant agreement between US and IO findings (Cramer's V = 0.831,p < 0.01; Lambda = 0.859, p < 0.01). A statistically highly significant agreement between MDCTA and IO findings in plaque morphology was found, as well (Cramer's V = 0.815, p < 0.01; Lambda = 0.829, p < 0.01). CONCLUSION: There is statistically highly significant correlation between US and MDCTA diagnostic methods in the evaluation of plaque morphology in surgically significant stenosis of internal carotid artery as well as their agreement with the intraoperative finding.

[Correlation between the inferior vena cava collapsibility and asymptomatic pericardial effusion in hemodialysis patients].

INTRODUCTION: The inferior vena cava collapsibility index is a sign of hypervolemia in hemodialysis patients. Asymptomatic pericardial effusion in these patients can be either a sign of hypervolemia or bad systolic function of the left ventricle, or both. The aim of this study was to assess the incidence of asymptomatic pericardial effusion and its correlation to collapsibility index in haemodialysis patients during 2-year follow-up. RESULTS: Of 115 consecutive hemodialysis patients, at the beginning of the study and on every 6 months we performed: clinical, ECG, echocardiography, laboratory assessment. There was 29 patients with asymptomatic pericardial effusion (25.21%) vs. 86 (74.79%) without asymptomatic pericardial effusion. There was no significant difference considering gender, age, vintage of HD between the groups. Colapsibillity index was statistically significantly lower among the patients with asymptomatic pericardial effusion: 0.39+/-0.09 vs. 0.69+/-0.21 in those without it; p<0.001. Asymptomatic pericardial effusion correlated inversely with colapsibillity index (r=-0.577; p<0.0001) and ejection fraction of left ventricle (r=-0.282; p<0.030) and positively with the dimension of left ventricle in diastole. The colapsibillity index had inverse correlation with asymptomatic pericardial effusion (r=-0.668; p<0.0001), end-diastolic dimension of the left ventricle (r=-0.464; p<0.0001), and only one positive correlation with Kt/V (r=0.294, p<0.002). During the follow-up, 16 pts (13.91%) died: 7 of them had a symptomatic pericardial effusion (43.75%). Factors with greatest relative risk for death were: persistent asymptomatic pericardial effusion (3.48); systolic dysfunction at the second examination (2.95): heart failure (2.88) at the third. CONCLUSION: Colapsibillity index and asymptomatic pericardial effusion are the closely correlated in inverse manner and both are the sign of hypervolemia. Asymptomatic pericardial effusion is also a sign of a bad systolic function and a very bad prognosis.

[Dilated cardiomyopathy associated with autoimmune disease of thyroid gland].

Congestive heart failure is the main cause of cardiovascular morbidity and mortality with more than one million hospitalizations per year. Dilated cardiomyopathy is one of the main causes of congestive heart failure characterized by diminished function of the left, right or both ventricles and ejection fraction less than 40%. Numerous studies reported that the diseases of thyroid gland among the patients with dilated cardiomiopathy were very frequent: with prevalence from 18% to 49%. The impaired thyroid gland function was found as primary cause of cardiomyopathy in 1% of patients. At the same time, among patients with terminal dilated cardiomyopathy, euthyroid sick syndrome was very frequent with low values of T3. According to our results, 29.4% of patients with dilated cardiomyopathy also had autoimmunity disorder of thyroid gland with present antithyroglobin and antimicrosomal antibodies. These patients had lower ejection fraction and worse prognosis. In American College of Cardiology/American Heart Association guidelines for the evaluation and treatment of the congestive heart failure, evaluation of thyroid gland function was recommended; but the evaluation of antitireoglobulin antibodies and free T3 and free T4 was also essential, as was calculation of their ratio. This is the way to discover the autoimmunity disorder of thyroid gland and/ or "euthyroid sick syndrome". In patients with dilated cardiomyopathy and low-T3 syndrome, short-term administration of thyroid hormones resulted in improvement of ejection fraction, diminishing of symptoms and better survival.