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Publikacije (42)

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S. Veljković, Jovana Lakčević, A. Peruničić, Armin Šljivo, M. Babic, Slobodan Tomić, Jelena Kljajević, Sanja Vučinić et al.

Anomalous origin of the Left Coronary Artery from the Pulmonary Artery (ALCAPA), also known as Bland-White-Garland syndrome, is a rare congenital coronary anomaly with an estimated incidence of 1 in 300,000 live births. While commonly diagnosed in infancy, adult presentations are exceedingly rare and pose significant diagnostic challenges. Delayed diagnosis may result in progressive myocardial ischemia, heart failure, arrhythmias, or sudden cardiac death. Surgical correction is the definitive treatment, with the goal of restoring a dual coronary artery system and preventing irreversible myocardial damage. We present the case of a 30-year-old male with a prior history of non–ST-elevation myocardial infarction who was referred for evaluation of exertional angina and symptoms of heart failure. Transthoracic echocardiography revealed a dilated left ventricle with an ejection fraction (LVEF) of 35%. Coronary angiography and cardiac MDCT identified an anomalous origin of the left circumflex artery (LCx) from the right pulmonary artery (RPA) and a coronary–pulmonary artery fistula involving the LAD. The patient underwent successful surgical correction with reimplantation of the LCx into the ascending aorta. Postoperative recovery was uneventful. At 3-month follow-up the patient was symptom-free, though echocardiography revealed persistent LV dilation and reduced LVEF, necessitating continued pharmacologic therapy and monitoring. This case highlights the importance of maintaining a high index of suspicion for ALCAPA in adult patients with unexplained cardiomyopathy or ischemic symptoms. Early diagnosis and surgical intervention remain crucial for improving long-term outcomes and preventing life-threatening complications.

B. Hadžić, Nebojša Romčević, N. Marković, Maša Petrović, Milovan Bojic, B. Milovanović

Background/Objectives: Syncope is a common clinical problem often requiring pharmacological treatment, yet evidence-based therapies remain limited. Midodrine, a vasopressor agent, is frequently used, though its autonomic effects over time remain unclear. This study aimed to assess autonomic nervous system changes and blood pressure response in syncope patients treated with Midodrine, placebo, or their combination. Additionally, the structural properties of the Midodrine placebo were analyzed using nanotechnological methods. Methods: A total of 67 patients with syncope were randomized to receive Midodrine, sucrose placebo, or their combination over three weeks. All participants underwent 24 h Holter ECG with heart rate variability (HRV) analysis and ambulatory blood pressure monitoring before and after therapy. Structural analysis of Midodrine tablets, sucrose, and Midodrine placebo was performed using Raman spectroscopy and X-ray diffraction (XRD). Results: Patients receiving the Midodrine–placebo combination showed a significant reduction in HRV markers of parasympathetic activity (RMSSD, pNN50, HF) and an increase in sympathetic dominance (LF/HF ratio) compared to the other groups. Only this group showed a statistically significant rise in average systolic and diastolic blood pressure. Raman and XRD analyses revealed structural alterations in the sucrose-based placebo compared to its original form, indicating subtle changes in crystalline structure. Conclusions: In this exploratory study, the combination of Midodrine and placebo was associated with autonomic imbalance and modest increases in blood pressure, which may indicate a potential effect in patients with hypotensive syncope phenotypes. These preliminary findings should be interpreted with caution, and the structural modifications observed in the placebo formulation are presented as hypotheses requiring further investigation rather than established mechanisms.

Maja Milošević Marković, B. Anicic, M. Lazarević, Milica Jakšić Karišik, Dijana D Mitić, B. Milovanović, Stefan Ivanović, I. Pećinar et al.

This study investigated the potential of Thymus serpyllum L. and Mentha × piperita L. essential oils (EOs), known for their bioactive properties, as adjunctive treatments targeting Basal cell carcinoma cancer stem cells (BCC CSCs). Primary cultures were established from ten BCC tumor samples and their distant resection margins as controls. The chemical composition of the EOs was analyzed by gas chromatography–mass spectroscopy (GC-MS) and attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR). The biological effects were evaluated via colony and spheroid formation, scratch assays, MTT and neutral red cytotoxicity assays, and qRT-PCR for Hh (SHH, PTCH1, SMO, and GLI1) and Notch (Notch1 and JAG1) gene expression. GC analysis identified thymol, p-cymene, and linalool as the main components of the EO of T. serpyllum L., and menthone and menthol in the EO of M. × piperita L. IC50 values were 262 µg/mL for T. serpyllum L. and 556 µg/mL for M. × piperita L. and were applied in all experiments. Both EOs significantly reduced CSC clonogenicity and migration (p < 0.05). The EO of T. serpyllum L. downregulated SMO and GLI1, while the EO of M. × piperita L. upregulated PTCH1, Notch1, and JAG1 (p < 0.05). These findings suggest that both EOs exhibit anticancer effects in BCC CSCs by modulating key oncogenic pathways, supporting their potential in BCC therapy.

N. Milošević, Bogdan Okiljević, S. Mićović, Milovan Bojic, Igor S Zivkovic

Parkes-Weber Syndrome is a rare congenital vascular abnormality characterized by aneurismatic illness of blood arteries in the afflicted limb, as well as hypertrophy, ulceration, ischemia, and high-output heart failure. Imaging investigations are required to provide a diagnosis, with contrast arteriography being the gold standard. The majority of treatment options are endovascular, with surgical excision for arteriovenous malformations and limb amputation as alternatives. We describe a 73-year-old male patient with mainly asymptomatic PWS, coronary disease, and borderline EF (45%) who had CABG surgery. In individuals with established CAD and other cardiac disorders, it is critical to identify additional diseases or syndromes that might have a compounding effect on the heart, such as PWS and high-output heart failure.

A. Peruničić, Matija Furtula, S. Veljković, Jovana Lakčević, Armin Šljivo, Valentina Balint, Slobodan Tomić, Sanja Vučinić et al.

Anomalous origin of the right coronary artery from the pulmonary artery (ARCAPA) is a rare congenital coronary anomaly, with an uncertain prevalence and often diagnosed incidentally. This case report presents a 62-year-old male with ARCAPA diagnosed during an evaluation for chest surgery. The patient had a history of colon cancer and active tuberculosis, complicating the clinical management. He reported chest pain, shortness of breath, and palpitations, with atrial fibrillation observed on a 24 h Holter ECG. Coronary angiography revealed robust collateral circulation and a suspected anomalous origin of the right coronary artery, confirmed by CT imaging. The patient’s stress MRI showed mildly reduced left and right ventricular ejection fractions and perfusion deficits in the apical segments (2/17) of the septal and inferior walls. Given the patient’s comorbidities, including active tuberculosis, the Heart team decided on a non-operative management approach, focusing on careful monitoring and pharmacological management rather than immediate surgery. This case emphasizes the complexity of managing ARCAPA in the context of significant comorbidities, highlighting the importance of individualized, multidisciplinary treatment strategies. Early diagnosis using advanced imaging techniques is crucial, and a non-operative approach can be considered in patients with preserved left ventricular function and no significant ischemia, as demonstrated in this case.

B. Milovanović, N. Marković, Maša Petrović, V. Žugić, M. Ostojic, Milica Dragicevic-Antonic, Milovan Bojic

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.

Aleksandra Nikolić, S. Veljković, Jovana Lakčević, A. Peruničić, Armin Šljivo, M. Babic, M. Nikolić, Slobodan Tomić et al.

Background/Objectives: Congenital heart disease (CHD), affecting approximately 1% of live births, has transitioned to a chronic condition due to advances in diagnostics and surgery, resulting in an increasing adult congenital heart disease (ACHD) population. This study characterizes the clinical and demographic profiles of ACHD patients in Serbia, focusing on congenital anomalies, mortality rates, and key clinical factors to identify opportunities for improving care and outcomes. Methods: This observational single-center study was conducted at the Cardiovascular Institute “Dedinje” in Belgrade, Serbia, involving patients diagnosed or treated for CHD between 2006 and 2022. Results: A total of 1532 patients were included in the study, with common diagnoses including atrial septal defects (ASD) (47.65%) and ventricular septal defects (VSD) (13.19%). The mean patient age was 48.31 years, with a slight predominance of females (57.21%). The complexity of CHD was categorized as mild (54.6%), moderate (36.5%), and severe (6.3%). The mortality rate was 4.2%, with higher rates observed in conditions like Ebstein anomaly (17.78%) and congenital aortic stenosis (11.76%). Conclusions: This study provides a comprehensive overview of the current state of ACHD management in Serbia, highlighting the high prevalence of ASD and VSD among patients, the challenges associated with moderate and severe CHD, and the notable mortality rates for certain conditions. The findings underscore the importance of improving early detection, individualized treatment plans, and multidisciplinary care to enhance patient outcomes in this growing population.

B. Milovanović, N. Marković, Maša Petrović, V. Žugić, M. Ostojic, Milovan Bojic

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.

B. Milovanović, N. Marković, Maša Petrović, V. Žugić, M. Ostojic, L. Ranković-Ničić, Milovan Bojic

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.

Valentina Balint Jovanovic, M. Farkić, Darko Boljević, Milovan Bojic, Matija Furtula, Dragan Topić, M. Dobric, A. Ielasi et al.

The natural progression of bioprosthetic valve degeneration over time requires further interventions for those experiencing symptomatic prosthesis dysfunction. Transcatheter aortic valve replacement (TAVR) emerges as a promising therapeutic option to alleviate symptoms in such patients. The valve-in-valve (ViV) technique eliminates the necessity for repetitive open-heart surgical procedures, offering particular advantages for individuals with higher surgical risks. In this report, we describe the case of a 78-year-old female patient presenting with severe symptomatic aortic restenosis of a biological aortic valve implanted 5 years prior. Given the patient’s high surgical risk, a transcatheter ViV implantation was chosen as the treatment approach. Utilizing a balloon-expandable valve, the intervention resulted in the successful implantation of a functional TAVR, resulting in symptom relief and enabling a fast discharge from the hospital.

Slobodan Tomić, S. Veljković, Armin Šljivo, D. Radoicic, Goran Lončar, Milovan Bojic

Background and Objectives: Left ventricular aneurysm (LVA) causes geometric changes, including reduced systolic function and a more spherical shape, which is quantified by the sphericity index (SI), the ratio of the short to long axis in the apical four-chamber view. This study aimed to assess SI’s value in A-LVA and B-LVA, identify influencing factors, and evaluate its clinical relevance. Materials and Methods: This clinical study included 54 patients with post-infarction LVA and used echocardiography to determine LVA locations (A-LVA near the apex and B-LVA in the basal segments), with SI and other echocardiographic measures assessed in both systole and diastole for the entire cohort and stratified by A-LVA and B-LVA groups. Results: Among the 54 patients, 41 had A-LVA and 13 had B-LVA. The mean SI was 0.55 in diastole and 0.47 in systole for the cohort. Patients with A-LVA had a mean SI of 0.51 in diastole and 0.44 in systole, while B-LVA patients exhibited significantly higher SI values, with 0.65 in diastole and 0.57 in systole, due to lower long-axis (L) values in both phases. The mean left ventricular ejection fraction (EF) was 23.95% in A-LVA and 30.85% in B-LVA, with no significant difference. However, apical aneurysms were larger (greater LVAV and LVAA) and more significantly reduced functional myocardium. LVEDV, LVESV, LVEDA, and LVESA did not differ significantly between A-LVA and B-LVA. In cases of severe mitral regurgitation (MR), SI was notably higher (0.75 in diastole) due to a marked reduction in the L axis. Conclusions: SI is key in differentiating A-LVA and B-LVA on echocardiography. B-LVA has lower volume and area values, but similar aneurysm and left ventricular volumes and EF. Higher SI in B-LVA is due to a reduced L-axis, and is worsened by severe mitral regurgitation (MR). Surgical ventricular reconstruction (SVR) compensates for L-axis reduction, with preservation of the L axis critical for achieving a more physiological shape. SI thus serves as a marker for left ventricular geometry and surgical outcomes.

S. Veljković, A. Peruničić, Jovana Lakčević, Armin Šljivo, D. Radoicic, M. Farkić, Darko Boljević, Jelena Kljajević et al.

Coronary artery fistulas (CAFs) are rare congenital anomalies, presenting in 0.05–0.9% of cases, characterized by an aberrant connection between a coronary artery and a cardiac chamber or great vessel. Clinical manifestations can include heart failure, myocardial ischemia due to coronary steal, arrhythmias, or infective endocarditis. We report a case of a 39-year-old man initially evaluated in 2016 for peripheral edema and suspected right ventricular (RV) abnormality. Earlier assessments indicated a left anterior descending (LAD) coronary artery–RV fistula, but initial catheterization was nondiagnostic. Transthoracic echocardiography (TTE) revealed a dilated left coronary artery (LCA) and an RV apex aneurysm, confirmed by CT and coronary angiography, showing a 14 mm LAD fistula with large aneurysmal sacs (45.6 × 37.3 mm). Cardiac MRI demonstrated a tortuous LAD fistula draining into RV aneurysmal sacs with preserved biventricular function. Surgical intervention was recommended, but the patient declined and was lost to follow-up until 2022, being asymptomatic. Re-evaluation showed progression in aneurysm size (47 × 45 mm and 16 × 18 mm) without ventricular functional change. Follow-up TTE in 2023 indicated stable findings. This case emphasizes the necessity of multimodal imaging (TTE, CT, MRI, angiography) for CAF diagnosis and management planning. Given the variability in CAF presentation and outcomes, individualized management—including surgical, percutaneous, or conservative strategies—is crucial. Persistent follow-up is essential for monitoring potential complications and guiding treatment, even in asymptomatic patients refusing intervention.

Medical professionals have a responsibility to inform the public about contemporary research on alcohol consumption. Earlier health recommendations focused primarily on the link between alcohol and cardiovascular diseases. Over time, these guidelines have expanded to consider the broader impact of alcohol on all-cause morbidity and mortality. Unlike the tobacco industry, which remains profitable but faces strict regulations on marketing and lobbying, the alcohol industry benefits from fewer regulations. This allows alcohol manufacturers to freely promote their products and influence both federal and state policies. Clear emphasis on the importance of ceasing alcohol consumption is crucial, particularly in primary and secondary prevention efforts. Keywords: cardiovascular diseases, alcoholics, prevention.

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