Browsing by Author "Milovanovic, Branislav (23474625200)"

Background/Objectives: Syncope is a common clinical occurrence, with neurally mediated and orthostatic types accounting for about 75% of cases. The exact pathophysiological mechanisms remain unclear, with recent evidence suggesting autonomic nervous system damage and a potential infectious etiology. This study aimed to examine the role of infection in the development of syncope and orthostatic hypotension (OH). Methods: The cross-sectional study included 806 patients from the Neurocardiological Laboratory of the Institute for Cardiovascular Diseases “Dedinje”. Patients were divided into three groups: unexplained recurrent syncope (n = 506), syncope with OH during the head-up tilt test (HUTT) (n = 235), and OH without a history of syncope (n = 62). All participants underwent the HUTT, and 495 underwent serological testing for various microorganisms. Data were analyzed using chi-squared tests and binary and multinomial logistic regression. Results: The HUTT was positive in 90.6% of patients with syncope and OH, compared with 61.6% with syncope alone (p < 0.001). Serological testing revealed that 57.85% of syncope patients, 62.9% of syncope with OH patients, and 78% of OH patients had positive IgM antibodies to at least one microorganism. Multivariate analysis indicated that IgM antibodies to Coxsackievirus and Epstein–Barr virus were significant predictors of OH. Conclusions: This study demonstrated a potential association between infections and syncope/OH. Further investigation into the role of infectious agents in autonomic dysfunction is warranted to clarify the underlying mechanisms of syncope and OH. © 2025 by the authors.

Background/Objectives: Syncope is a common clinical occurrence, with neurally mediated and orthostatic types accounting for about 75% of cases. The exact pathophysiological mechanisms remain unclear, with recent evidence suggesting autonomic nervous system damage and a potential infectious etiology. This study aimed to examine the role of infection in the development of syncope and orthostatic hypotension (OH). Methods: The cross-sectional study included 806 patients from the Neurocardiological Laboratory of the Institute for Cardiovascular Diseases “Dedinje”. Patients were divided into three groups: unexplained recurrent syncope (n = 506), syncope with OH during the head-up tilt test (HUTT) (n = 235), and OH without a history of syncope (n = 62). All participants underwent the HUTT, and 495 underwent serological testing for various microorganisms. Data were analyzed using chi-squared tests and binary and multinomial logistic regression. Results: The HUTT was positive in 90.6% of patients with syncope and OH, compared with 61.6% with syncope alone (p < 0.001). Serological testing revealed that 57.85% of syncope patients, 62.9% of syncope with OH patients, and 78% of OH patients had positive IgM antibodies to at least one microorganism. Multivariate analysis indicated that IgM antibodies to Coxsackievirus and Epstein–Barr virus were significant predictors of OH. Conclusions: This study demonstrated a potential association between infections and syncope/OH. Further investigation into the role of infectious agents in autonomic dysfunction is warranted to clarify the underlying mechanisms of syncope and OH. © 2025 by the authors.

[No abstract available]

Background/Objectives: Chronic fatigue syndrome and post-COVID-19 syndrome are associated with dysfunction of the autonomic nervous system, which may manifest as syncope and orthostatic intolerance. This study aimed to compare autonomic nervous system function in patients with chronic fatigue syndrome of unknown etiology and those with chronic fatigue syndrome secondary to post-COVID-19 syndrome using multiple diagnostic modalities, and to assess the prevalence and characteristics of syncope in these populations. Methods: This cross-sectional study included 440 patients examined at the Neurocardiological Laboratory of the Institute for Cardiovascular Diseases “Dedinje”. Patients were divided into three groups: chronic fatigue syndrome of unknown etiology (Group 1, n = 210), chronic fatigue syndrome secondary to post-COVID-19 syndrome (Group 2, n = 137), and healthy controls (Group 3, n = 91). Diagnostic modalities included cardiovascular reflex tests, the head-up tilt test, beat-to-beat analysis, 24 h Holter electrocardiogram monitoring, and 24 h ambulatory blood pressure monitoring. Statistical analyses were performed using analysis of variance, Tukey’s honestly significant difference test, and the Mann–Whitney U test. Results: Both chronic fatigue syndrome groups demonstrated significant autonomic nervous system dysfunction compared to healthy controls (p < 0.05), including reduced baroreceptor sensitivity and impaired heart rate variability parameters. Syncope prevalence was high in both chronic fatigue syndrome groups, with extreme blood pressure variability observed in 45–47% of patients during the head-up tilt test. Patients with post-COVID-19 chronic fatigue syndrome exhibited greater blood pressure increases during the head-up tilt test than those with chronic fatigue syndrome of unknown etiology (p < 0.05). Conclusions: Patients with chronic fatigue syndrome, irrespective of etiology, exhibit significant autonomic nervous system dysfunction and a high prevalence of syncope. Post-COVID-19 chronic fatigue syndrome demonstrates distinct hemodynamic patterns, suggesting unique pathophysiological mechanisms that warrant further investigation. © 2025 by the authors.

Background and aim: Reduced baroreflex sensitivity (BRS), decreased heart rate variability (HRV) and increased blood pressure (BP) variability have serious consequences for target organ damage in patients with hypertension, beside the BP level. The study was aimed to evaluate acute and long-term effects of enalapril, on BRS and HRV in individuals with prehypertension and mild essential hypertension. Methodology: We enrolled in the study 85 patients (male 53%, age 42-67) with prehypertension and mild hypertension (systolic blood pressure ≥120 mmHg or diastolic blood pressure ≥80 mmHg). All patients were tested before, 30 minutes after first oral enalapril dose and three weeks after monotherapy with enalapril. The methodology included: beat to beat HRV analysis, BRS measurements with sequence technique, ECG with short term and 24-hour HRV analysis, 24-hour ambulatory blood pressure monitoring with systolic and diastolic BP variability analysis. Patients were divided into groups with sympathetic or vagal predominance based on Autonomic Nervous System Adjustment (ANSA) method. Results: 1) 30 min after initial dose enalapril significantly and effectively reduced systolic BP with shift towards the parasympathetic predominance as reflected in decreased heart rate and low frequency (LF) to high frequency (HF) ratio (LF/HF ratio); 2) chronic enalapril therapy effectively reduced BP, including both systolic BP, diastolic BP and pulls pressure, had positively influence on dipping status, but did not significantly change BP variability; 3) in the whole patient group chronic enalapril therapy did not significantly change HRV, but it significantly decreased LF(nu) in the patient with high basal sympathetic activity, and significantly increased LF(nu) in patients with high basal vagal activity; enalapril also significantly decreased HF (nu) in patients with high basal parasympathetic activity; 4) despite initial, transit changes in maximal and minimal slope of BRS enalapril did not significantly affect sensitivity of spontaneous baroreflex activation. Conclusion: Initial enalapril dose significantly reduced systolic BP and had beneficial effects on autonomic tone and baroreflex sensitivity. Chronic enalapril therapy effectively reduced BP without significant influence on BRS, but had significant autonomic effects on HRV when initial autonomic profile in each patient was analyzed by ANSA. Analyzed by ANSA method chronic enalapril therapy managed to retrieve disturbed sympathovagal balance and established autonomic equilibrium. © 2011 Akadémiai Kiadó, Budapest.

Objectives Personalised monitoring in health applications has been recognised as part of the mobile crowdsensing concept, where subjects equipped with sensors extract information and share them for personal or common benefit. Limited transmission resources impose the use of local analyses methodology, but this approach is incompatible with analytical tools that require stationary and artefact-free data. This paper proposes a computationally efficient binarised cross-approximate entropy, referred to as (X)BinEn, for unsupervised cardiovascular signal processing in environments where energy and processor resources are limited. Methods The proposed method is a descendant of the cross-approximate entropy ((X)ApEn). It operates on binary, differentially encoded data series split into m-sized vectors. The Hamming distance is used as a distance measure, while a search for similarities is performed on the vector sets. The procedure is tested on rats under shaker and restraint stress, and compared to the existing (X)ApEn results. Results The number of processing operations is reduced. (X)BinEn captures entropy changes in a similar manner to (X)ApEn. The coding coarseness yields an adverse effect of reduced sensitivity, but it attenuates parameter inconsistency and binary bias. A special case of (X)BinEn is equivalent to Shannon's entropy. A binary conditional entropy for m =1 vectors is embedded into the (X)BinEn procedure. Conclusion (X)BinEn can be applied to a single time series as an auto-entropy method, or to a pair of time series, as a cross-entropy method. Its low processing requirements makes it suitable for mobile, battery operated, self-attached sensing devices, with limited power and processor resources. © 2016

Objectives Personalised monitoring in health applications has been recognised as part of the mobile crowdsensing concept, where subjects equipped with sensors extract information and share them for personal or common benefit. Limited transmission resources impose the use of local analyses methodology, but this approach is incompatible with analytical tools that require stationary and artefact-free data. This paper proposes a computationally efficient binarised cross-approximate entropy, referred to as (X)BinEn, for unsupervised cardiovascular signal processing in environments where energy and processor resources are limited. Methods The proposed method is a descendant of the cross-approximate entropy ((X)ApEn). It operates on binary, differentially encoded data series split into m-sized vectors. The Hamming distance is used as a distance measure, while a search for similarities is performed on the vector sets. The procedure is tested on rats under shaker and restraint stress, and compared to the existing (X)ApEn results. Results The number of processing operations is reduced. (X)BinEn captures entropy changes in a similar manner to (X)ApEn. The coding coarseness yields an adverse effect of reduced sensitivity, but it attenuates parameter inconsistency and binary bias. A special case of (X)BinEn is equivalent to Shannon's entropy. A binary conditional entropy for m =1 vectors is embedded into the (X)BinEn procedure. Conclusion (X)BinEn can be applied to a single time series as an auto-entropy method, or to a pair of time series, as a cross-entropy method. Its low processing requirements makes it suitable for mobile, battery operated, self-attached sensing devices, with limited power and processor resources. © 2016

AIM: To investigate autonomic nervous function in patients with a diagnosis of gastroesophageal reflux disease (GERD). METHODS: The investigation was performed on 29 patients (14 men), aged 18-80 years (51.14 ± 18.34). Who Were Referred to Our Neurocardiology Lab. at the Clin. and Hosp. Ctr. bezanijska Kosa with A Diagn. of GERD. One Hundred Sixteen Healthy Volunteers Matched in Age and Sex with the Examinees Served As the Contr. Grp.. the Stud. Protocol Included the Eval. of Autonomic Funct. and Hemodynamic Status, Short-term Heart Rate Variability Anal., 24 H Ambulatory ECG Monitoring with Long-term HRV Anal. and 24 H Ambulatory Blood Pressure Monitoring. RESULTS: Pathologic Results of Cardiovasc. Reflex Test Were More Com. among Patients with Reflux Compared to the Contr. Grp.. Severe Autonomic Dysfunction Was Detected in 44.4% of Patients and in 7.9% of Controls . Parameters of Short-term Anal. of RR Variability, Which Are the Indicat. of Vagal Activ., Had Lower Values in Patients with GERD Than in the Contr. Grp.. Long-term HRV Anal. of Time-domain Parameters Indicated Lower Values in Patients with Reflux Dis. When Compared to the Contr. Grp.. Pwr. Spectral Anal. of Long-term HRV Revealed Lower Low-and High-frequency Values. Detailed 24 H Ambulatory Blood Pressure Anal. Showed Significantly Higher Values of Systolic Blood Pressure and Pulse Pressure in the Reflux Grp. Than in the Contr. Grp.. CONCLUSION: Patients with GERD Have Distortion of Sympathetic and Parasympathetic Components of the Autonomic Nerv. Syst., but Impaired Parasympathetic Funct. Appears More Congruent to GERD. 2015 Baishideng Publ. Grp. Inc. All Rights Reserved.

This paper introduces a set of formulae for automatic evaluation of threshold level rTEOR for which the cross-entropy of systolic blood pressure (SBP) and pulse interval (PI) (Cross-ApEn) reaches its maximum. A mathematical method for estimating the level of consistency of entropy estimates is established as well. These two methods jointly determine a steady working point for consistent entropy estimates. © 2013 CCAL.

This paper introduces a set of formulae for automatic evaluation of threshold level rTEOR for which the cross-entropy of systolic blood pressure (SBP) and pulse interval (PI) (Cross-ApEn) reaches its maximum. A mathematical method for estimating the level of consistency of entropy estimates is established as well. These two methods jointly determine a steady working point for consistent entropy estimates. © 2013 CCAL.

Background/Objectives: Post-infectious syndromes, including Post-COVID syndrome, Chronic Fatigue Syndrome, and late-stage Lyme disease, are associated with overlapping clinical features and autonomic dysfunction. Despite shared symptoms such as fatigue and orthostatic intolerance, the underlying pathophysiology and specific patterns of autonomic dysfunction may differ. This study aimed to evaluate and compare autonomic nervous system function in these syndromes using multiple diagnostic modalities to identify unique characteristics and improve differentiation between these conditions. Methods: This cross-sectional study included 758 patients, which were divided into four groups: Post-COVID syndrome, Chronic Fatigue Syndrome following Post-COVID syndrome, Chronic Fatigue Syndrome unrelated to COVID-19, and late-stage Lyme disease. Autonomic nervous system function was assessed using cardiovascular reflex tests, the Head-Up Tilt Test, beat-to-beat analysis, five-minute electrocardiogram recordings, 24 h Holter electrocardiogram monitoring, and 24 h ambulatory blood pressure monitoring. Statistical analyses compared parameters across the groups, focusing on patterns of sympathetic and parasympathetic dysfunction. Results: The patients with Lyme disease showed distinct autonomic patterns, including a higher prevalence of orthostatic hypotension (53.4%) and changes in heart rate variability during the Head-Up Tilt Test suggestive of adrenergic failure. Compared to the other groups, patients with Lyme disease exhibited reduced baroreceptor sensitivity and diminished changes in frequency domain heart rate variability parameters during orthostatic stress. Parasympathetic dysfunction was less prevalent in the Lyme disease group, while the Post-COVID syndrome and Chronic Fatigue Syndrome groups showed more pronounced autonomic imbalances. Conclusions: The patients with Post-COVID syndrome, Chronic Fatigue Syndrome, and late-stage Lyme disease exhibited varying degrees and types of autonomic dysfunction. Late-stage Lyme disease is characterized by adrenergic failure and distinct hemodynamic responses, differentiating it from other syndromes. The functional assessment of autonomic nervous system function could aid in understanding and managing these conditions, offering insights for targeted therapeutic interventions. © 2025 by the authors.

Background/Objectives: Post-infectious syndromes, including Post-COVID syndrome, Chronic Fatigue Syndrome, and late-stage Lyme disease, are associated with overlapping clinical features and autonomic dysfunction. Despite shared symptoms such as fatigue and orthostatic intolerance, the underlying pathophysiology and specific patterns of autonomic dysfunction may differ. This study aimed to evaluate and compare autonomic nervous system function in these syndromes using multiple diagnostic modalities to identify unique characteristics and improve differentiation between these conditions. Methods: This cross-sectional study included 758 patients, which were divided into four groups: Post-COVID syndrome, Chronic Fatigue Syndrome following Post-COVID syndrome, Chronic Fatigue Syndrome unrelated to COVID-19, and late-stage Lyme disease. Autonomic nervous system function was assessed using cardiovascular reflex tests, the Head-Up Tilt Test, beat-to-beat analysis, five-minute electrocardiogram recordings, 24 h Holter electrocardiogram monitoring, and 24 h ambulatory blood pressure monitoring. Statistical analyses compared parameters across the groups, focusing on patterns of sympathetic and parasympathetic dysfunction. Results: The patients with Lyme disease showed distinct autonomic patterns, including a higher prevalence of orthostatic hypotension (53.4%) and changes in heart rate variability during the Head-Up Tilt Test suggestive of adrenergic failure. Compared to the other groups, patients with Lyme disease exhibited reduced baroreceptor sensitivity and diminished changes in frequency domain heart rate variability parameters during orthostatic stress. Parasympathetic dysfunction was less prevalent in the Lyme disease group, while the Post-COVID syndrome and Chronic Fatigue Syndrome groups showed more pronounced autonomic imbalances. Conclusions: The patients with Post-COVID syndrome, Chronic Fatigue Syndrome, and late-stage Lyme disease exhibited varying degrees and types of autonomic dysfunction. Late-stage Lyme disease is characterized by adrenergic failure and distinct hemodynamic responses, differentiating it from other syndromes. The functional assessment of autonomic nervous system function could aid in understanding and managing these conditions, offering insights for targeted therapeutic interventions. © 2025 by the authors.

[No abstract available]

In most of the guidelines by various agencies, a widespread belief exists that underlying usual blood pressure can alone account for all blood pressure related risk of vascular events and for the benefits of anti-hypertensive drugs. This view may not be correct because it does not consider total risk. Around-the-clock ambulatory blood pressure monitoring is necessary for at least 7 days to better assess risk related to blood pressure and blood pressure variability. Reference limits for blood pressure are currently based mostly on cohort studies and on controlled drug trials conducted among hypertensive patients. This must be changed. Using fixed limits for all adults 18 years and older (or in just 2 age groups) should be replaced by time-specified limits qualified by gender, age, and ethnicity, to be derived from clinically healthy populations, as done on too small a scale within the project on The Biosphere and the Cosmos (BIOCOS). This special paper highlights Vascular Variability Disorders (VVDs), which include, with MESOR-hypertension, Circadian Hyper-Amplitude-Tension (CHAT), ecphasia, ecfrequentia, excessive pulse pressure, excessive pulse pressure product, and a deficient heart rate variability. Anti-hypertensive drugs with their bioavailability as well as bioactivity have to be optimized by chronotherapy to improve benefit and reduce side effects, as documented by a great scientist and human being, Professor Franz Halberg, an exceptional, remarkable man, the father of chronobiology, who introduced the concepts of chronopharmacology and chronotherapy. © 2016 Nova Science Publishers, Inc.

INTRODUCTION: Numerous studies were focused on coronary artery disease, most of them in the male population and it seems that data on gender differences in CAD were extrapolated from these studies. GOAL: The multi-center prospective study was designed to analyze gender differences in features, clinical presentation, and early in-hospital mortality in patients with acute coronary syndrome (ACS) admitted to coronary units in 50 hospitals in Serbia, during a 12 month-period. METHODS: The data were collected from the central register of ACS, analyzed with respect to gender differences. The study protocol included all consecutive patients with diagnosis of ACS. In the study 12,094 patients were analyzed, 7639 men and 4455 women. Women were significantly older than men in all ACS manifestations (p < 0.001). RESULTS: Incidence of myocardial infarction (MI) in women was the highest between the 7th and 8th life decade, while in men the highest incidence is observed between their sixties and seventies. Equalization in the incidences of MI in men and women is observed between the sixth and seventh life decades. There were significant differences in the incidence of fibrinolytic therapy and heart failure (p < 0.001) in favor of women. Women with unstable angina and NSTEMI had higher in-hospital mortality (2.4% vs. 1.7% and 9.0% vs. 7.1%, respectively), without statistical significance, while in STEMI the difference was highly statistically significant (16.1% compared to men 10.1), p < 0.001. DISCUSSION: The mean age of the greatest frequency of occurrence of MI has been shifted five years earlier in the population of women, different from other studies related to the analysis of MI by gender differences. CONCLUSION: Female mortalitywas significantly higher compared to the male population, thus more aggressive therapy should be administrated.

[No abstract available]

[No abstract available]

>Objective Antiphospholipid syndrome (APS) may manifest itself as a primary (PAPS) or secondary disease, most commonly in the context of systemic lupus erythematosus (SLE) with various neurological and cardiac manifestations in its occurrence. The objective of this study was to investigate the relationship between cerebrovascular (stroke and transient ischaemic attack (TIA)) and valvular manifestations in a Serbian cohort of APS patients. Methods This is cross sectional study of 508 APS patients: 360 PAPS and 148 APS patients associated with SLE (SAPS). aPL analysis included detection of anticardiolipin antibodies (aCL: IgG/IgM), anti-ß2glycoprotein I (ß2GPI: IgG/IgM), and LA. Results The prevalence of valvular manifestations (valvular vegetations and valvular thickening and dysfunction not related to age) in our cohort was significantly higher in SAPS group. (28.4% vs. 8.6%, p=0.0001). Age was strong predictor for stroke and TIA occurrence in both groups as well as gender (stroke more likely occurred in male SAPS and TIA in male PAPS patients). Presence of ß2GPI IgG in SAPS patients was significantly related to stroke (p=0.018), whereas ß2GPI IgG negative PAPS patients were more prone to TIA. Valvular manifestations were significantly related to TIA in both groups of patients and were independent risk factors for TIA in PAPS (OR 3.790 CI 1.597-8.998 p=0.003). Conclusion In this cross-section analysis of a large cohort of Serbian APS patients, there was a strong relationship between valvular and cerebrovascular manifestations, suggesting a more cautious approach regarding neurological symptoms, especially in PAPS patients with valvular vegetations present. © Copyright CliniCal and ExpErimEntal rhEumatology 2018.

>Objective Antiphospholipid syndrome (APS) may manifest itself as a primary (PAPS) or secondary disease, most commonly in the context of systemic lupus erythematosus (SLE) with various neurological and cardiac manifestations in its occurrence. The objective of this study was to investigate the relationship between cerebrovascular (stroke and transient ischaemic attack (TIA)) and valvular manifestations in a Serbian cohort of APS patients. Methods This is cross sectional study of 508 APS patients: 360 PAPS and 148 APS patients associated with SLE (SAPS). aPL analysis included detection of anticardiolipin antibodies (aCL: IgG/IgM), anti-ß2glycoprotein I (ß2GPI: IgG/IgM), and LA. Results The prevalence of valvular manifestations (valvular vegetations and valvular thickening and dysfunction not related to age) in our cohort was significantly higher in SAPS group. (28.4% vs. 8.6%, p=0.0001). Age was strong predictor for stroke and TIA occurrence in both groups as well as gender (stroke more likely occurred in male SAPS and TIA in male PAPS patients). Presence of ß2GPI IgG in SAPS patients was significantly related to stroke (p=0.018), whereas ß2GPI IgG negative PAPS patients were more prone to TIA. Valvular manifestations were significantly related to TIA in both groups of patients and were independent risk factors for TIA in PAPS (OR 3.790 CI 1.597-8.998 p=0.003). Conclusion In this cross-section analysis of a large cohort of Serbian APS patients, there was a strong relationship between valvular and cerebrovascular manifestations, suggesting a more cautious approach regarding neurological symptoms, especially in PAPS patients with valvular vegetations present. © Copyright CliniCal and ExpErimEntal rhEumatology 2018.