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S. Zivkovic, Vojko V. Misevic, K. Krupnikovic, Aleksa D. Obradovic, M. Babic, B. Saroskovic, Andjelka M. Isakovic, Vedrana Pavlovic et al.

Introduction: Acute ST-segment elevation myocardial infarction (STEMI) remains a major cause of cardiovascular morbidity and mortality. Despite successful primary percutaneous coronary intervention (pPCI), early myocardial injury and stress may contribute to left ventricular dysfunction. The optimal timing of biomarker assessment after STEMI remains uncertain. Objective: To characterize the early kinetics of soluble suppression of tumorigenicity-2 (sST2), galectin-3 (Gal-3), mid-regional pro-adrenomedullin (MR-proADM), and growth differentiation factor 15 (GDF-15) during the first 96 h after STEMI and identify potentially informative sampling time points for future prognostic assessment. Secondary, exploratory objectives were to evaluate differences in biomarker concentrations according to symptom duration, left ventricular ejection fraction (LVEF), and infarct-related artery. Methods: In this prospective, single-center, exploratory pilot study, patients aged 18–75 years with first STEMI treated with pPCI within 6 h of symptom onset were enrolled between September 2024 and November 2025. Blood samples were collected at admission and 12 ± 4, 24 ± 4, 48 ± 8, and 96 ± 8 h after pPCI. Biomarkers were measured by ELISA, with high-sensitivity cardiac troponin I (hs-cTnI) as a reference marker of myocardial injury. Results: Of 46 enrolled patients, 16 were excluded, mostly due to early discharge, and 30 patients with complete samples at all five time points were included in the analysis (mean age 57.9 ± 11.1 years; 66.7% male). sST2, MR-proADM, and hs-cTnI showed significant temporal variation (all p < 0.001), with the highest measured concentrations of sST2 at 12 h and of MR-proADM at 24 h. No significant change over time was found for Gal-3 and GDF-15. In exploratory analyses, sST2 and MR-proADM concentrations were higher in patients with LVEF < 40%, and sST2 concentrations were higher in patients with left anterior descending artery (LAD) infarction. Symptom duration was not associated with biomarker concentrations. Conclusions: sST2 and MR-proADM show distinct early post-STEMI kinetics, suggesting potentially informative sampling windows for future prognostic studies. Larger prospective studies are needed to confirm these kinetics and the exploratory differences according to left ventricular function and infarct location, and to evaluate the prognostic value of these sampling windows with echocardiographic and clinical follow-up.

B. Milovanović, N. Marković, Nada Petrović, Slobodan Petrović, Masa G. Petrovic, Aleksa Korugić, Milovan Bojić

<p style="text-align: justify;"><span class="a_GcMg font-feature-liga-off font-feature-clig-off font-feature-calt-off text-decoration-none text-strikethrough-none">Dysautonomia, reflecting autonomic nervous system dysfunction, is frequently observed in patients with syncope, particularly those with orthostatic hypotension. </span><em><span class="a_GcMg font-feature-liga-off font-feature-clig-off font-feature-calt-off text-decoration-none text-strikethrough-none">Thymus serpyllum </span></em><span class="a_GcMg font-feature-liga-off font-feature-clig-off font-feature-calt-off text-decoration-none text-strikethrough-none">L. (wild thyme) has demonstrated antioxidant, anti-inflammatory, and cardiometabolic properties in preclinical studies. This study aimed to evaluate the effects of </span><em><span class="a_GcMg font-feature-liga-off font-feature-clig-off font-feature-calt-off text-decoration-none text-strikethrough-none">T. serpyllum </span></em><span class="a_GcMg font-feature-liga-off font-feature-clig-off font-feature-calt-off text-decoration-none text-strikethrough-none">essential oil on autonomic function and selected biochemical markers in patients with syncope. This prospective, single-center study included 15 patients with a history of syncope who received a capsule formulation of </span><em><span class="a_GcMg font-feature-liga-off font-feature-clig-off font-feature-calt-off text-decoration-none text-strikethrough-none">T. serpyllum</span></em><span class="a_GcMg font-feature-liga-off font-feature-clig-off font-feature-calt-off text-decoration-none text-strikethrough-none"><em> </em>essential oil for three months. Autonomic function was assessed using beat-to-beat heart rate and blood pressure variability analysis, 24-hour Holter ECG monitoring, and ambulatory blood pressure monitoring. Biochemical parameters were evaluated at baseline and after treatment. After three months, the beat-to-beat analysis showed increased LFnu values and a higher LF/HF ratio, along with decreased HF values, indicating a shift toward sympathetic predominance. No significant changes were observed in 24-hour heart rate or blood pressure parameters. Biochemical analyses revealed significant reductions in AST and C-reactive protein levels after treatment. In this pilot study, three-month supplementation with </span><em><span class="a_GcMg font-feature-liga-off font-feature-clig-off font-feature-calt-off text-decoration-none text-strikethrough-none">T. serpyllum </span></em><span class="a_GcMg font-feature-liga-off font-feature-clig-off font-feature-calt-off text-decoration-none text-strikethrough-none">essential oil was associated with changes in autonomic balance and favorable reductions in selected inflammatory and biochemical markers in patients with syncope. Further and larger placebo-controlled studies are required to confirm these findings and clarify their clinical significance.</span></p>

B. Milovanović, N. Marković, Masa G. Petrovic, V. Žugić, M. Ostojic, A. Grbović, Smiljana Stojanovic, Dragisa Radovanovic et al.

Lyme disease, caused by Borrelia burgdorferi sensu lato, may lead to persistent complications, including autonomic nervous system dysfunction. Although postural orthostatic tachycardia syndrome is frequently associated with orthostatic intolerance in Lyme disease, broader autonomic impairment remains insufficiently characterized. This cross-sectional study included 324 participants: 233 patients with late-stage Lyme disease and 91 healthy controls. All participants underwent cardiovascular autonomic reflex testing, beat-to-beat heart rate variability analysis, baroreflex assessment, 24-hour Holter electrocardiography, and ambulatory blood pressure monitoring. Compared with controls, patients with Lyme disease demonstrated significantly higher rates of sympathetic and parasympathetic dysfunction (p<0.05). Heart rate variability spectral parameters, including very low frequency, low frequency, and high frequency components, were significantly reduced, while baroreflex sensitivity and baroreflex effectiveness index were also impaired (p<0.05). Holter monitoring additionally revealed reduced time-domain heart rate variability parameters and an elevated low-frequency/high-frequency ratio, suggesting relative sympathetic predominance in patients with Lyme disease (p<0.05). These findings support the presence of cardiovascular autonomic dysfunction in patients with late-stage Lyme disease and highlight the importance of comprehensive autonomic evaluation in this population. Keywords: Autonomic Dysfunction; Lyme disease; Heart rate variability; Neurocardiology.

Goran Lončar, Milovan Bojić, Jelena Repac, Natasa Cvetinovic, Marija Rakić, Tamara Nedeljkovic, Tanja M. Lunić, D. Obradovic et al.

Background/Objectives: In heart failure with preserved ejection fraction (HFpEF), the gut–heart axis has emerged as a potential contributor to inflammation and cardiometabolic stress. We characterised gut microbiota composition, diversity, and predicted metabolic potential in HFpEF to assess their associations with disease status and clinical heterogeneity. Methods and Results: Faecal samples from 30 HFpEF patients and 28 healthy controls were profiled by means of bacterial ribosomal RNA gene sequencing. The groups were comparable in age (74 years in both groups) and sex (female: 60% vs. 60.7%). HFpEF patients exhibited lower community evenness (p = 0.04) and a trend toward lower diversity (p = 0.08), but no detectable shift in global community structure. The tested clinical and demographic variables explained only a modest proportion of the observed variation in community structure, with substantial residual variation across the beta-diversity analyses. No taxa were differentially abundant between groups at the predefined thresholds. Among clinical stratifications, New York Heart Association (NYHA) class showed the most consistent family-level associations, including stepwise depletion of Lachnospiraceae, Butyricicoccaceae, and Ruminococcaceae and enrichment of Akkermansiaceae; Enterobacteriaceae peaked in milder disease. These severity-associated taxonomic trajectories were accompanied by predicted functional shifts consistent with microbial adaptation to increasing metabolic constraints, including enrichment of stress-adaptation traits and, with increasing functional limitation, depletion of core metabolic and fermentative pathways and relative enrichment of oxidative stress-response pathways. Conclusions: HFpEF is associated with subtle gut microbiota alterations that appear to reflect severity- and context-dependent ecological reorganisation rather than uniform dysbiosis. These findings support severity-informed approaches targeting microbial metabolic function and ecological context rather than broad compositional changes.

Jelena Lesanovic, Milan Milojevic, Djordje L. Nikolic, Ivan Soldatović, D. Unić-Stojanović, Igor S. Zivkovic, M. Miličić, P. Vukovic et al.

Background and Objectives: Myocardial protection during on-pump coronary artery bypass grafting (CABG) limits ischaemic injury, particularly in patients with left main coronary artery disease (LMCAD), in whom severe proximal stenosis may compromise antegrade cardioplegia delivery. We investigated whether combined antegrade–retrograde blood cardioplegia reduces postoperative high-sensitivity cardiac troponin I (hs-cTnI) concentrations, a marker of perioperative myocardial injury. Materials and Methods: We conducted a prospective, single-centre, randomised trial involving 60 adults undergoing elective isolated on-pump CABG for significant LMCAD. Patients were assigned (1:1) to antegrade-only or combined antegrade–retrograde blood cardioplegia. Cardiac biomarkers were measured after induction and at 4, 12, 24, and 48 h after ICU admission. The primary endpoint was peak hs-cTnI within 48 h; key secondary endpoints included the hs-cTnI area under the concentration–time curve, CK-MB, immediate myocardial electrical recovery and 30-day outcomes. Results: All patients received the assigned cardioplegia strategy, with no crossover. Peak hs-cTnI did not differ significantly between the antegrade-only and combined groups (median 529.1 [IQR 829.9] vs. 394.1 [503.4] ng/L; p = 0.21), nor did the hs-cTnI area under the concentration–time curve from 4 to 48 h (12,910.6 [23,127.4] vs. 8112.2 [11,686.2] ng·h/L; p = 0.16). Serial hs-cTnI, CK-MB, total creatine kinase, serum creatinine, immediate myocardial electrical recovery, and 30-day outcomes also did not differ significantly. No deaths, coronary sinus injuries, or other cardioplegia-related complications occurred. Conclusions: In patients undergoing isolated on-pump CABG for significant LMCAD, combined antegrade–retrograde blood cardioplegia did not significantly decrease peak hs-cTnI levels compared to the antegrade-only method. The combined approach was feasible with no cardioplegia-related complications, suggesting that an individualised strategy may be preferable to a routine one. Larger prospective studies are needed to determine whether higher-risk patients may derive greater benefit.

Milos Banjanac, D. Unić-Stojanović, Milica Stojicic Miljkovic, Mia Vukotic, Tamara Nehez, Jovana Kostić, Sanja Djokić, Nikola Stankovic et al.

Maja Milošević Nale, D. Ušjak, Martina Mia Mitic, Milovan Bojić, P. Otašević, Ivana Petrović, S. Mićović, Sofija Dunjic Manevski et al.

Unicuspid aortic valve (UAV) is a rare congenital malformation with severe clinical consequences, and its genetic background remains poorly defined. We present an exploratory genomic resource for UAV, generated from whole-exome sequencing (WES) of nine families (including probands and 19 unaffected relatives) and integrated with single-cell RNA sequencing (scRNA-seq) data from human embryonic hearts. The scRNA-seq dataset enabled the identification of genes expressed in valve-forming cell populations during development, providing a biologically informed filter for candidate variant prioritisation. Further prioritisation identified 81 candidate variants across 68 genes with enrichment in extracellular matrix (ECM) organisation and developmental signalling pathways, particularly transforming growth factor-β-mediated signalling. Complementary exome-wide family segregation analysis further supported this pattern, again highlighting ECM organisation and developmental signalling as recurrently enriched biological themes. By establishing a preliminary genomic dataset, this study provides a resource for further validation, expansion to larger cohorts, and exploration of the molecular architecture underlying this rare disorder.

S. Borović, D. Kosevic, Jelena Stefanovic Neskovic, Jelena Lešanovic, Goran Lončar, Jelena Miladinović, B. Milovanović, Petar Dabić et al.

PURPOSE To evaluate the feasibility of telemetry-guided optimization of guideline-directed medical therapy (GDMT) and continuous arrhythmic surveillance in ambulatory patients with heart failure with reduced ejection fraction (HFrEF). METHODS TELEMETRIC-HF was a single-center, randomized, open-label pilot study including 30 patients with HFrEF assigned to telemetry-guided management (n=15) or standard outpatient care (n=15). Patients in the telemetry group underwent 8 weeks of continuous ambulatory monitoring using the CPC12 CE MDR Class IIb wearable system, providing continuous electrocardiographic and physiological monitoring with clinician oversight. The primary endpoint was the between-group difference in beta-blocker (BB) target-dose achievement at 8 weeks. Secondary endpoints included optimization of other GDMT classes, ventricular arrhythmia detection, clinical status, quality of life, safety, and healthcare utilization. RESULTS Telemetry-guided management was associated with significantly greater BB target-dose achievement at 8 weeks than standard care (60.0% vs. 39.2% of the guideline-recommended target dose; absolute difference 20.8 percentage points, 95% CI 2.7-39.2; p=0.028). Target-dose achievement for angiotensin receptor-neprilysin inhibitors, mineralocorticoid receptor antagonists, and sodium-glucose cotransporter-2 inhibitors did not differ significantly between groups. Recurrent non-sustained ventricular tachycardia was detected only in the telemetry group, prompting additional clinical evaluation, antiarrhythmic therapy, and primary prevention implantable cardioverter-defibrillator implantation in one patient. Hemodynamic, laboratory, and echocardiographic parameters remained stable throughout follow-up, and telemetry was well tolerated. No heart failure hospitalizations or deaths occurred during the 8-week study period. CONCLUSION In this pilot randomized study, telemetry-guided remote monitoring was feasible and was associated with earlier BB optimization and improved detection of clinically relevant ventricular arrhythmias without compromising safety. These exploratory findings support further evaluation of telemetry-guided outpatient heart failure management in larger, adequately powered multicenter randomized trials.

D. Kojić, A. Radunović, Sladjana Božović-Ogarević, Ivan Ilic, V. Niković, M. Tomović, Milovan Bojić

Background Holt–Oram syndrome (HOS) is a rare autosomal-dominant genetic disorder caused by mutations in the TBX5 gene. It is characterized by skeletal abnormalities of the upper limbs and congenital heart defects, most frequently atrial septal defect (ASD) and ventricular septal defect. Middle-aged individuals often develop conduction disorders and atrial arrhythmias, most commonly atrial fibrillation and atrial flutter, while focal atrial tachycardia (AT) remains relatively rare. We present the successful catheter ablation of a right anteroseptal focal AT in a patient with HOS and a history of surgical ASD closure. Case report A 22-year-old man was admitted due to recurrent episodes of supraventricular tachycardia, refractory to drug therapy. He has a history of HOS, patch closure of ASD at age three, and three hand surgeries. A 12-lead electrocardiogram showed narrow QRS complex tachycardia at 171 beats/min, regular RR intervals, and RP < PR interval. Transthoracic echocardiography revealed mostly normal findings, with mildly reduced left ventricle function and intact ASD patch with no residual shunt. Electrophysiology study showed no retrograde conduction over an accessory pathway. Programmed stimulation from the left atrium induced tachycardia with cycle length 280 ms, narrow QRS complexes, regular RR intervals, initial 1:1 AV (atrio-ventricular) ratio, and short VA interval (34 ms). Using the Carto 3 3D mapping system, activation mapping of the right atrium identified the earliest atrial activation near the His-Bundle area (5.9 mm distance from His bundle cloud). Radiofrequency ablation terminated AT within 2.5 s of the first application. Postablation tachycardia was not-inducible at baseline and under Isoproterenol. The patient was discharged from the hospital 1 day after ablation without antiarrhythmic therapy. After 21 months of follow-up, there were no recurrences of AT. Conclusion This case demonstrates that catheter ablation is a feasible, safe, and effective treatment option for focal AT patients with HOS and surgical ASD closure.

S. Tanasković, A. Milačić, Nikola Ružić, Stefan Graovac, Jovan Petrović, Milovan Bojić, Bojan Božić

Background/Objectives: Peripheral arterial disease (PAD) and diabetes mellitus (DM) may produce different and overlapping plantar thermal patterns. This study descriptively characterized whole-foot temperature-distribution patterns in clinically defined healthy, PAD, DM, and combined PAD_DM cohorts. Methods: This single-center, exploratory, cross-sectional observational study included 73 participants: healthy controls (n = 21), isolated PAD (n = 13), isolated DM (n = 19), and combined PAD_DM (n = 20). Right- and left-foot temperature distributions were processed separately for each participant and interpreted as one paired bilateral thermal footprint using patient-level histograms, representative bilateral kernel density estimation (KDE) profiles, and a cohort-derived deterministic rule-based model. The model was developed from the present cohort and was not evaluated as an independent diagnostic classifier. Results: Among healthy controls, 11 of 21 participants (52.4%) were assigned to healthy and 8 of 21 (38.1%) to borderline healthy categories. In the DM cohort, 7 of 19 participants (36.8%) were assigned to DM, 3 of 19 (15.8%) to borderline healthy/suspected DM or controlled DM, 3 of 19 (15.8%) to DM suspected PAD, and 5 of 19 (26.3%) to PAD_DM. In the combined PAD_DM cohort, 15 of 20 participants (75.0%) were assigned to PAD_DM. The isolated PAD cohort was the most heterogeneous: 6 of 13 participants (46.2%) were assigned to PAD_DM, while none were assigned to the isolated PAD output. Conclusions: This exploratory, cross-sectional study demonstrated that whole-foot plantar temperature distributions can descriptively characterize differences among healthy individuals, patients with isolated DM, and those with combined PAD and DM. While healthy controls generally demonstrated symmetric thermal footprints, the DM cohort frequently exhibited globally elevated and compact temperature-distribution profiles, while mixed asymmetric patterns were common in participants with combined PAD and DM. In contrast, the isolated PAD cohort was characterized by pronounced thermal heterogeneity.

S. Younas, N. Okwose, A. Fuller, R. Stefanetti, S. Charman, Fatima Bano, M. Dobric, Milovan Bojić et al.

Heart failure with preserved ejection fraction (HFpEF) is more prevalent in women, whereas heart failure with reduced ejection fraction (HFrEF) predominates in men. Despite these well-established epidemiological differences, sex-specific alterations in vascular function in heart failure (HF) remain poorly characterised. This systematic review, using a narrative synthesis approach, evaluated sex-related differences in vascular function in individuals with HF. The review was prospectively registered with PROSPERO (CRD42024617745). MEDLINE and CINAHL were searched from inception to 26th November 2024 for studies reporting sex-stratified measures of arterial stiffness among individuals with HF. Nine studies met the eligibility criteria for inclusion (n = 2820; men: n = 1390, women: n = 1430). Of the included studies, 78% were characterised as HFpEF. Compared with men, women exhibited a higher pulsatile arterial load and lower arterial compliance. Representative findings from individual studies showed that women exhibited a higher augmentation index (28.9 ± 13.7% vs 21.7 ± 11.9%, p < 0.001) and augmentation pressure (19.1 ± 12.4 vs 13.7 ± 10.1 mmHg, p = 0.003). Body mass index (BMI) showed variable relationships with arterial stiffness indices, including positive associations with pulse wave velocity (r = 0.24, p < 0.01), central pulse pressure (r = 0.33, p < 0.001), and augmentation index (r = 0.23, p = 0.01), but an inverse relationship was found with cardio-ankle vascular index (r = −0.204, p < 0.001). Importantly, sex differences in HFpEF remained significant after adjustment for BMI. Women with HF exhibit higher pulsatile arterial load and reduced arterial compliance compared with men, which remain after adjustment for BMI. Sex-specific vascular dysfunction contributes to HF pathophysiology and supports the need for sex-informed assessment.

B. Milovanović, N. Marković, E. Ristanović, Nikoleta Đorđevski, Sonja Atanasievska Kujović, Sulin Bulatović, V. Žugić, Masa G. Petrovic et al.

Background: Bartonella henselae infection has been associated with a broad spectrum of neurological and autonomic manifestations, although its impact on autonomic nervous system function remains insufficiently characterized, and the aim of this study was to evaluate autonomic function in patients with polymorphic symptoms and Bartonella henselae IgM seroreactivity. Methods: In this cross-sectional study, 75 patients were compared with 75 age- and sex-matched healthy controls, and all participants underwent cardiovascular autonomic reflex testing, short-term (5 min) and long-term (24 h) heart rate variability analysis, and 24 h ambulatory blood pressure monitoring, while head-up tilt testing was performed in the Bartonella group. Results: Abnormal autonomic reflex tests were significantly more frequent in the Bartonella IgM-seroreactive group, particularly those reflecting parasympathetic function, while heart rate variability analysis demonstrated reduced high-frequency components and lower long-term variability indices, and head-up tilt testing revealed heterogeneous hemodynamic responses including orthostatic hypotension and pronounced blood pressure variability, with ambulatory monitoring additionally showing higher nighttime blood pressure values and reduced nocturnal dipping. Conclusions: These findings indicate a consistent pattern of autonomic imbalance characterized predominantly by parasympathetic impairment and altered blood pressure regulation in patients with Bartonella henselae IgM seroreactivity, although further studies are required to clarify underlying mechanisms and clinical implications.

Maja Milošević Nale, Bojan Božić, Ivan Soldatović, L. Ranković-Ničić, Goran Lončar, Milica Milošević, Nikola Mitović, Vladimir Mihajlović et al.

Background/Objectives: Hypertrophic cardiomyopathy (HCM) is a complex myocardial disease in which structural remodeling extends beyond conventional parameters such as maximal wall thickness (MWT). This study aimed to evaluate isoperimetric analysis as a geometry-based approach for characterizing left ventricular (LV) morphology and to compare its performance with fractal analysis in distinguishing HCM from non-HCM subjects. Methods: This retrospective study included 120 subjects (60 HCM and 60 controls) who underwent clinically indicated CMR. Endocardial contours were delineated on short-axis cine images at end-diastole. The isoperimetric index (IPI), cavity-corrected IPI (CC-IPI), and fractal dimension (FD) were calculated. Group comparisons, correlations, and receiver operating characteristic analyses were performed. Results: Patients with HCM showed significantly higher IPI and CC-IPI values than controls (p < 0.001), including in sex-stratified analyses. IPI and CC-IPI correlated strongly with MWT (r = 0.867) and LV mass index (r = 0.807 and 0.803, respectively), moderately with native T1 (r = 0.567), and weakly with end-diastolic volume index (r = 0.256 and 0.253, respectively) and stroke volume (r = 0.237 and 0.229, respectively). No association was observed with late gadolinium enhancement. IPI and CC-IPI showed a strong linear correlation (R2 = 0.997), with both indices demonstrating high discriminatory performance (AUC = 1.00). Conclusions: HCM is associated with notable alterations in LV endocardial geometry beyond myocardial hypertrophy alone. IPI and CC-IPI provide simple, size-normalized, and physiologically interpretable morphologic descriptors that complement conventional CMR parameters and FD-based contour complexity analysis.

Jovana Gavrilović, Bojan Božić, M. Dobric, Milovan Bojić, T. Lončar-Turukalo

This case study proposes a multi-stage deep learning-based system for an automated inventory analysis of stent boxes cabinets in angiography rooms. The proposed pipeline integrates cabinet image segmentation, vendor classification, detection of region-of-interest (ROI) with numerical features, and character recognition enabling extraction of stent boxes’ attribute triples (vendor, diameter, length). Experimental results show that the system achieves high performance across individual stages: mAP@0.5 of 0.995 in box segmentation task, top-1 accuracy of 99.3% in the stent vendor classification and mAP@0.5 of 0.991 in ROI detection. The overall F1 score at the system level for stent box attribute triples is 0.811. The error analysis indicates that system performance is strongly influenced by camera-to-cabinet distance determining the scale of segmented ROI, and can be improved to F1=0.984 by partial standardization of image acquisition step.

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