Milan Petrovic

High output heart failure in patients with newly diagnosed acromegaly

PURPOSE We sought to determine the prevalence and characteristics of heart failure in patients with newly diagnosed acromegaly. SUBJECTS AND METHODS We assessed 102 consecutive patients who had acromegaly (44 men; age range, 22 to 71 years) for signs and symptoms of heart failure. We included a control group of 33 nonobese healthy subjects (13 men; age range, 26 to 70 years). Cardiac morphologic parameters, left ventricular mass index, ejection fraction, end-systolic wall stress, and cardiac index were measured by echocardiography. Endocrinological assessment was performed in all participants. RESULTS Of the 102 patients, 10 (10%) had overt heart failure at the time of diagnosis of acromegaly, 9 of whom were men (P <0.01). Patients with acromegaly and heart failure had an increased mean (+/- SD) left ventricular end-diastolic diameter (76 +/- 11 mm) compared with those without heart failure (53 +/- 6 mm, P <0.001) and control subjects (49 +/- 5 mm, P <0.001). Patients with heart failure had higher left ventricular mass index (230 +/- 56 g/m2 vs. 118 +/- 40 g/m(2), P <0.001) and end-systolic wall stress (237 +/- 79 x 10(3) dyn/cm2 vs. 111 +/- 42 x 10(3) dyn/cm2, P <0.001), but lower ejection fraction (42% +/- 17% vs. 66% +/- 9%, P <0.001), in comparison with patients without heart failure. The mean cardiac index was significantly higher in patients with heart failure (4.3 +/- 1.8 L/min-m2) than in those without heart failure (3.5 +/- 0.8 L/min-m2, P = 0.04) or in control subjects (3.1 +/- 0.6 L/min-m2, P = 0.002). Two factors were independently associated with heart failure in acromegalic patients: cardiac index (odds ratio [OR] per SD of 1.0 L/min-m2 = 16; 95% confidence interval [CI]: 1.8 to 135) and ejection fraction (OR per SD of 12% = 0.7; 95% CI: 0.6 to 0.9). CONCLUSION High output heart failure with a modest decline in ejection fraction is frequently detected at the time of diagnosis of acromegaly. Left ventricular hypertrophy in these patients is characterized by a dilated ventricle and an increased left ventricular mass that is primarily due to the enlarged chamber diameter.

Regional difference of microcirculation in patients with asymmetric hypertrophic cardiomyopathy: transthoracic Doppler coronary flow velocity reserve analysis.

OBJECTIVE To evaluate, by noninvasive coronary flow velocity reserve (CFVR), whether patients with asymmetric hypertrophic cardiomyopathy (HC), with or without left ventricular outflow tract obstruction, demonstrate significant regional differences of CFVR. METHODS We evaluated 61 patients with HC (27 men; mean age 49 ± 16 years), including 20 patients with hypertrophic obstructive cardiomyopathy (HOCM) and 41 patients without obstruction (HCM). The control group included 20 age- and sex-matched subjects. Transthoracic Doppler echocardiography CFVR of the left anterior descending coronary artery (LAD) and the posterior descending coronary artery (PD) were performed, including calculation of relative CFVR as the ratio between CFVR LAD and CFVR PD. RESULTS Compared with the controls, all the patients with HC had lower CFVR LAD (2.12 ± 0.53 vs 3.34 ± 0.67; P < .001) and CFVR PD (2.29 ± 0.49 vs 3.21 ± 0.65; P < .001). CFVR LAD in HOCM group in comparison with the HCM group was significantly lower (1.93 ± 0.42 vs 2.22 ± 0.55; P = .047), due to higher basal diastolic coronary flow velocities (0.40 ± 0.09 vs 0.33 ± 0.07 m/sec; P = .002), with similar hyperemic diastolic flow velocities (0.71 ± 0.16 vs 0.76 ± 0.19 m/sec; P = .330), respectively. There was no significant difference in CFVR PD between patients with HOCM and those with HCM (2.33 ± 0.46 vs 2.27 ± 0.50; P = .636), respectively. Relative CFVR was lower in the HOCM group compared with the HCM group (0.84 ± 0.16 vs 0.98 ± 0.14; P = .001). By multivariable regression analysis, left ventricular outflow tract gradient was the independent predictor of CFVR LAD (B = -0.24; P = .008) and relative CFVR (B = -0.34; P = .016). CONCLUSIONS CFVR LAD and relative CFVR were significantly lower in patients with HOCM compared with patients with HCM. Regional differences of CFVR are present only in patients with significant left ventricular outflow tract obstruction, which suggests that obstruction per se, by increasing wall stress in basal conditions, leads to higher basal diastolic coronary flow velocities and results in lower CFVR in LAD compared with PD.

Predictors of diabetic cardiomyopathy in asymptomatic patients with type 2 diabetes

Jelena P. Seferovic Mitrovic , Petar M. Seferovic ⁎, Bosiljka Vujisic Tesic , Milan Petrovic , Arsen D. Ristic , Katarina Lalic , Aleksandra Jotic , Milorad Tesic , Vojislav Giga , Natasa Milic , Sandra Singh , Nebojsa M. Lalic a,d a Clinic for Endocrinology, Diabetes and Metabolic Diseases, Clinical Center of Serbia, Belgrade, Serbia b Clinic of Cardiology, Clinical Center of Serbia, Belgrade, Serbia c Institute for medical statistics and informatics, Faculty of Medicine, University of Belgrade, Serbia d Belgrade University Faculty of Medicine, Belgrade, Serbia

Diagnostic value of NT-proBNP in identifying impaired coronary flow reserve in asymptomatic moderate or severe aortic stenosis

AIM NT-proBNP has been shown to be a reliable biochemical marker for left ventricular wall stress. The relationship between NT-proBNP and coronary flow reserve (CFR) was evaluated in patients with significant asymptomatic aortic stenosis (AS). METHODS A total of 74 patients with moderate or severe AS, mean age 66.68 ± 10.02 years (56.75% males), were enrolled in this prospective study. All patients underwent coronary angiography and had no obstructive coronary disease (defined as having no stenosis >50% in diameter). They had all undergone standard transthoracic Doppler-echo study and adenosine stress transthoracic-echo for CFR measurement and laboratory analysis for NT-proBNP measurement. RESULTS The median NT-proBNP value was significantly increased (417.0 pg/ml; interquartile range [IQR]: 176.8-962.2 pg/ml). NT-proBNP was significantly higher in the group with CFR ≤2.5 (median: 549.0 pg/ml; IQR: 311.5-1131.0 pg/ml; as opposed to median: 291.5 pg/ml; IQR: 123.0-636.2 pg/ml; W = 452; p = 0.012). NT-proBNP showed significant negative correlation with CFR (ρ = -0.377, p = 0.001). There was also significant correlation between NT-proBNP and E/E´, S´ and aortic valve resistance. The NT-proBNP value of 334.00 pg/ml was determined as the best cut-off value for the diagnosis of CFR ≤2.5 (area under the curve: 0.67; 95%CI: 0.54-0.79; p < 0.01) and the sensitivity and specificity were 74 and 64%, respectively. CONCLUSION Elevated NT-proBNP can indicate patients with impaired CFR in asymptomatic moderate or severe AS patients with preserved ejection fraction and nonobstructive coronary arteries.

The interface of hypothalamic–pituitary–adrenocortical axis and circulating brain natriuretic peptide in prediction of cardiopulmonary performance during physical stress

Brain natriuretic peptide (NT-pro-BNP) was implicated in the regulation of hypothalamic-pituitary-adrenocortical (HPA) responses to psychological stressors. However, HPA axis activation in different physical stress models and its interface with NT-pro-BNP in the prediction of cardiopulmonary performance is unclear. Cardiopulmonary test on a treadmill was used to assess cardiopulmonary parameters in 16 elite male wrestlers (W), 21 water polo player (WP) and 20 sedentary age-matched subjects (C). Plasma levels of NT-pro-BNP, cortisol and adrenocorticotropic hormone (ACTH) were measured using immunoassay sandwich technique, radioimmunoassay and radioimmunometric techniques, respectively, 10min before test (1), at beginning (2), at maximal effort (3), at 3rdmin of recovery (4). In all groups, NT-pro-BNP decreased between 1 and 2; increased from 2 to 3; and remained unchanged until 4. ACTH increased from 1 to 4, whereas cortisol increased from 1 to 3 and stayed elevated at 4. In all groups together, ΔNT-pro-BNP2/1 predicted peak oxygen consumption (B=37.40, r=0.38, p=0.007); cortisol at 3 predicted heart rate increase between 2 and 3 (r=-0.38,B=-0.06, p=0.005); cortisol at 2 predicted peak carbon-dioxide output (B=2.27, r=0.35, p<0.001); ΔACTH3/2 predicted peak ventilatory equivalent for carbon-dioxide (B=0.03, r=0.33, p=0.003). The relation of cortisol at 1 with NT-pro-BNP at 1 and 3 was demonstrated using logistic function in all the participants together (for 1/cortisol at 1 B=63.40, 58.52; r=0.41, 0.34; p=0.003, 0.013, respectively). ΔNT-pro-BNP2/1 linearly correlated with ΔACTH4/3 in WP and W (r=-0.45, -0.48; p=0.04, 0.04, respectively). These results demonstrate for the first time that HPA axis and NT-pro-BNP interface in physical stress probably contribute to integrative regulation of cardiopulmonary performance.

Gender influence on left ventricular structure and function in metabolic syndrome. Are women at greater risk

The aim of this study was to investigate the influence of metabolic syndrome (MS) on left ventricular (LV) structure and function depending on gender.

Prediction of a good response to cardiac resynchronization therapy in patients with severe dilated cardyomyopathy: could conventional echocardiography be the answer after all?

Objectives: The aim of this study was to assess the performance of echocardiographic parameters to predict response to cardiac resynchronization therapy (CRT). Background: CRT reduces morbidity and mortality due to the proper selection of candidates for CRT. Methods: The 12‐month trial was performed on 70 optimally medicated patients with standard inclusion criteria: NYHA class III or IV heart failure, left ventricular ejection fraction (LVEF) ≤ 35%, and QRS ≥ 120 ms. All parameters were evaluated by conventional and tissue Doppler‐based methods. Indicator of positive CRT response was more than 20% in improvement of LVEF. Results: LVEF increased >20% in 42 patients. Out of 43 tested baseline echocardiographic parameters, 12 showed statistical difference between responders and nonresponders. Out of these 12 parameters, six (LVSV, LVSI, LVFS, RVd, VPMR, and PISA) had modest to moderately good ability to predict LVEF response with sensitivity ranging from 62.2% to 82.4%, and specificity ranging from 56.5% to 81.2%. For those parameters, the area under the receiver‐operating characteristic curve for positive response to CRT was ≤0.76. Multivariate regression analysis resulted in selection of LVSI and LVFS as possible predictive independent parameters for a good response. The cutoff value for LVSI was 38.7 mL/m2 (P = 0.045) and for LVFS was 13% (P = 0.032). Conclusions: Contribution of LVSI and LVFS is to be confirmed in larger trials. Simplicity of their assessment by conventional echocardiography could be an argument for adding them to the inclusion criteria for CRT in severe heart failure patients. (Echocardiography 2012;29:267‐275)

Is gender responsible for everything? The relationship between sex and right ventricular remodeling in metabolic syndrome.

The aim of this study was to examine the impact of metabolic syndrome (MS) on right ventricular (RV) remodeling in different genders.

Assessment of the left ventricular chamber stiffness in athletes.

Since diastolic dysfunction is an early sign of the heart disease, detecting diastolic disturbances is predicted to be the way for early recognizing underlying heart disease in athletes. So‐called chamber stiffness index (E/e′)/LVDd was predicted to be useful in distinguishing physiological from pathological left ventricular hypertrophy, because it was shown to be reduced in athletes. It remains unknown whether it is reduced in all athletic population. Standard and tissue Doppler were used to assess cardiac parameters at rest in 16 elite male wrestlers, 21 water polo player, and 20 sedentary subjects of similar age. In addition to (E/e′)/LVDd index, a novel (E/e′)/LVV, (E/e′)/RVe′lat indices were determined. Progressive continuous maximal test on treadmill was used to assess the functional capacity. VO2 max was the highest in water polo players, and higher in wrestlers than in controls. LVDd, LVV, LVM/BH2.7 were higher in athletes. Left ventricular early diastolic filling velocity, deceleration and isovolumetric relaxation time did not differ. End‐systolic wall stress was significantly higher in water polo players. RV e′ was lower in water polo athletes. Right atrial pressure (RVE/e′) was the highest in water polo athletes. (E/e′lat)/LVDd was not reduced in athletes comparing to controls (water polo players 0.83 ± 0.39, wrestlers 0.73 ± 0.29, controls 0.70 ± 0.28; P = 0.52), but (E/e′s)/RVe′lat better distinguished examined groups (water polo players 0.48 ± 0.37, wrestlers 0.28 ± 0.15, controls 0.25 ± 0.16, P = 0.015) and it was the only index which predicted VO2 max. In conclusion, intensive training does not necessarily reduce (E/e′lat)/LVDd index. A novel index (E/e′s)/RVe′lat should be investigated furthermore in detecting diastolic adaptive changes. (Echocardiography 2011;28:276‐287)

POTENTIALS OF SERBIAN LIVESTOCK PRODUCTION - OUTLOOK AND FUTURE

The paper describes the state of the livestock production in the Republic of Serbia including preliminary results from the 2012 census: according to preliminary data, 908.990 heads of cattle, 3.403.288 pigs, 1.729.278 sheep and 235.576 goats are reared in Serbia. Structural and institutional measures, and measures of credit support should be the main instruments for achieving the goals of progress in animal husbandry. Activities in the breeding-selection work should be carried out in accordance with the recommendations of international organizations (ICAR, INTERBULL, EAAP). One of the most important outcome of these activities should result in a level of over 80% of the total population of cattle, pigs, sheep and other species of domestic farm animals in Serbia included in the control of production performance (presently between 25 and 30%). Genetic improvement of cattle, sheep and pigs (milk, meat) is very complex. More efficient use of reproductive technologies (AI - artificial insemination and embryo transfer ET, etc.), also of methods for evaluation of breeding value of farm animals through new methods of evaluation of breeding value of cows and breeding bulls will contribute to faster genetic improvement of production traits of these species of domestic animals. New knowledge in mapping and gene transfer, marker assisted selection, in vitro embryo development, embryo cloning, sexing, etc., are improving rapidly, with new technologies being developed permanently. Breeding/improvement of cattle, sheep and pigs in through breeding - selection work should facilitate further improvement of fertility traits, growth rate, feed efficiency, carcass quality (higher percentage of muscle tissue in the body), the quality of milk and meat, resistance to disease and stress, etc.. [Projekat Ministarstva nauke Republike Srbije, br. TR-31053]