Background/Objectives: Postural orthostatic tachycardia syndrome (POTS) is a form of dysautonomia characterized by excessive tachycardia during orthostatic stress. It is frequently observed in patients with syncope, Chronic Fatigue Syndrome (CFS), and post-COVID-19 syndrome (PCS), yet the underlying mechanisms may differ across these conditions. This study aimed to assess autonomic nervous system (ANS) function in patients with syncope, CFS of insidious onset, and CFS post-COVID-19 who presented with POTS, and to compare them with age- and sex-matched patients without POTS. Methods: In this retrospective cross-sectional study, 138 patients over 18 years of age were included following head-up tilt testing (HUTT). Patients were divided into six groups: syncope with and without POTS, CFS with insidious onset with and without POTS, and CFS post-COVID-19 with and without POTS. All participants underwent HUTT, cardiovascular reflex testing (CART) by Ewing, five-minute resting ECG with short-term Heart Rate Variability (HRV) analysis, and 24 h Holter ECG monitoring. Results: The prevalence of POTS across groups ranged from 5% to 7%. Female predominance was consistent across all subgroups. In syncope with POTS, hypertensive responses during HUTT, lower rates of normal Valsalva maneuver results, and reduced HF values in short-term HRV suggested baroreceptor dysfunction with sympathetic overdrive. In both CFS subgroups with POTS, CART revealed higher rates of definite parasympathetic dysfunction, along with more frequent extreme blood pressure variation during HUTT and reduced vagally mediated HRV parameters (rMSSD, pNN50). Across groups, no significant differences were observed with regard to long-term HRV across groups. Conclusions: Distinct autonomic profiles were identified in POTS patients depending on the underlying condition. Syncope-related POTS was associated with baroreceptor dysfunction and sympathetic predominance, whereas CFS-related POTS was characterized by parasympathetic impairment and impaired short-term baroreflex regulation. Evaluating dysautonomia patterns across disease contexts may inform tailored therapeutic strategies and improve management of patients with POTS.

Background and Clinical Significance: Concomitant severe aortic stenosis (AS) and abdominal aortic aneurysm (AAA) in elderly patients presents a significant therapeutic challenge. While transcatheter aortic valve replacement (TAVR) and endovascular aneurysm repair (EVAR) have become established minimally invasive treatments for high-risk patients, simultaneous management of both conditions remains rare. Case Presentation: We report the first documented case in Serbia of a simultaneous TAVR and EVAR in a 75-year-old male with severe symptomatic AS and AAA. The patient had a history of hypertension, diabetes mellitus, atrial fibrillation, prior radiofrequency pulmonary vein ablation, and pacemaker implantation. Echocardiography demonstrated severe AS with a transvalvular gradient of 116/61 mmHg, an aortic valve area of 0.6 cm2, and a left ventricular ejection fraction of 30–35%. Coronary angiography revealed 50–60% stenosis of the right coronary artery. Following evaluation by a multidisciplinary Heart and Vascular Team, a combined procedure was performed under general anesthesia via bilateral femoral access. TAVR with a Medtronic Evolut R valve was successfully deployed, followed by EVAR with satisfactory stent graft positioning and angiographic results. The patient’s postoperative course was uneventful, and he was discharged on the ninth day. At six-month follow-up, echocardiography showed optimal valve function, and CT identified a type II endoleak, which was managed conservatively. Conclusions: This case demonstrates the feasibility and safety of simultaneous TAVR and EVAR in a high-risk elderly patient, emphasizing the importance of careful preoperative planning and a coordinated multidisciplinary approach. Further studies are warranted to establish standardized guidelines for the management of patients with coexisting severe AS and AAA.

Autonomic nervous system (ANS) dysfunction has emerged as a central feature of post-infectious syndromes, including post-COVID syndrome (PCS), chronic fatigue syndrome (CFS), and late-stage Lyme disease. This cross-sectional study included 1036 patients evaluated in the Neurocardiological Laboratory of the Institute for Cardiovascular Diseases “Dedinje,” divided into four groups: PCS, CFS after COVID-19, CFS of insidious onset, and Lyme disease. All patients underwent head-up tilt testing (HUTT), and serological testing was performed in accredited institutions. The Lyme disease group demonstrated the highest prevalence of positive HUTT responses and a significantly greater frequency of orthostatic hypotension and syncope. Approximately 50–65% of patients in the PCS and Lyme groups were positive for IgM antibodies against at least one microorganism, with more than 10% showing positivity for three or more pathogens. Logistic regression analysis revealed that, beyond classical hemodynamic parameters, antibody status served as a significant predictor of HUTT outcomes, with specific associations identified for HSV-1, HHV-6, Coxiella burnetii, Toxoplasma gondii, and Borrelia spp. Multinomial regression further indicated that negative IgG antibodies, particularly to HSV-1 and VZV, predicted Lyme disease group membership. These findings support the hypothesis that ANS dysfunction in post-infectious syndromes may be driven by persistent or prior infections, highlighting the need for integrative diagnostic approaches.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.