Cardiologia Croatica. 2025;20(9-10)

Anica Milinković, Mia Dubravčić Došen, Petra Grubić Rotkvić, Tomislav Krčmar, Ivana Jurca, Sanda Huljev Frković, Majda Vrkić Kirhmajer

**Introduction**: Vascular Ehlers-Danlos syndrome (vEDS) is a rare genetic connective tissue disorder caused by pathogenic variants in COL3A1, a gene encoding type III collagen. Consequent tissue fragility manifests in a specific clinical phenotype, as well as possible life-threatening complications such as spontaneous arterial dissection or rupture, bowel perforation, and uterine rupture. Initial presentation typically occurs in early adulthood, whereas median life expectancy is estimated at 51 years (1). While diagnosis may be guided by clinical criteria, molecular confirmation is required (2). **Case report**: A 52-year-old man with arterial hypertension and bilateral renal cysts was incidentally diagnosed with a left external iliac artery dissection during a routine computed tomography (CT) scan (**Figure 1**). He reported no inguinal pain and showed no signs of limb ischemia. Further assessment revealed a family history of vascular events: his father died at 55 from a ruptured aortic aneurysm, and his paternal grandfather experienced sudden death at 50. Physical examination showed subtle features suggestive of vEDS, including micrognathia, keloids, varicose veins, and flat feet with piezogenic papules. A subsequent CT scan revealed bilateral saccular aneurysms at the renal artery bifurcations (**Figure 2**), in addition to the previously identified iliac artery dissection. Next-generation sequencing identified a heterozygous COL3A1 missense mutation, p.Gly237Arg. This variant was classified as pathogenic, confirming a diagnosis of vEDS. The patient was started on celiprolol and irbesartan, as these medications have been shown to reduce the incidence of major arterial events in patients with vEDS (3). Lifestyle modifications were advised, and cascade genetic testing was recommended for relatives. FIGURE 1. Contrast-enhanced CT angiography (maximum intensity projection reconstruction, oblique coronal plane) showing a dissected left external iliac artery with an intimal flap (white arrows). FIGURE 2. Contrast-enhanced CT angiography showing a right renal artery aneurysm. A) maximum intensity projection reconstruction (oblique coronal), black arrow. B) axial plane, white arrow. **Conclusion**: Although most vEDS patients develop major arterial complications by the age of 40, disease onset is variable and may present later, as observed in our patient. Despite appropriate management, these patients remain at high risk of morbidity and mortality. This case emphasizes the importance of considering vEDS in asymptomatic adults with incidental vascular findings, subtle connective tissue signs, and a relevant family history, in order to enhance clinical awareness and diagnostic accuracy.

Marija Doronjga, Marijan Pašalić, Maja Čikeš, Dora Fabijanović, Nina Jakuš, Hrvoje Jurin, Daniel Lovrić, Vedran Pašara, Ivo Planinc, Jure Samardžić, Željko Čolak, Joško Bulum, Hrvoje Gašparović, Davor Miličić, Boško Skorić

**Introduction**: Cardiac allograft vasculopathy (CAV) remains a leading cause of late graft loss after heart transplantation (HTx) and results from complex immune- and non-immune-mediated pathways, each contributing to endothelial dysfunction. (1-3) **Patients and Methods**: We performed a retrospective registry-based analysis of HTx recipients who underwent CAV assessment by coronary angiography between January 2010 and January 2018 at the University Hospital Centre Zagreb. Baseline donor and recipient characteristics were collected, along with recipient clinical parameters at 1 and 3 years following HTx. The objective was to identify risk factors for CAV at 3 years. **Results**: Among 126 heart transplant recipients, CAV was present in 38 patients (30%) at 3 years; 25 (65.8%) were male. The CAV group had a higher mean donor age (46.7 ± 8.7 years). Recipient history of coronary artery disease (CAD) and donor age >45 years were independently associated with increased CAV risk. CAD history conferred a 3.6-fold higher risk (HR = 3.61, 95% CI: 1.59–8.22, p = 0.002), and donor age >45 was associated with a 3.7-fold increased risk (HR = 3.72, 95% CI: 1.64–8.45, p = 0.002) (**Figure 1**). No other baseline characteristics or recipient cardiovascular risk factors at 1 and 3 years were significantly different between groups (**Figures 2** and **3**Figure 3). FIGURE 1. Forest plot illustrating the association between baseline donor and recipient characteristics and detection of coronary allograft vasculopathy at 3 years. AMCS = acute mechanical circulatory support, BMI = body mass index, CAD = coronary artery disease, CAV = coronary allograft vasculopathy, CMV = cytomegalovirus, DMCS = durable mechanical circulatory support, eGFR = estimated Glomerular Filtration Rate, HDL = high-density lipoprotein, HTx = heart transplantation, LDL = low density lipoprotein, MCS = mechanical circulatory support, PRA = panel reactive antibodies, SD = standard deviation. FIGURE 2. Recipient 1-year characteristics based on ≥1 coronary allograft vasculopathy at 3 years. ACEi = angiotensin-converting enzyme inhibitor, ARB = angiotensin II receptor blockers, CCB = calcium channel blocker, CyA = cyclosporine, eGFR = estimated Glomerular Filtration Rate, HDL = high-density lipoprotein, DL = low-density lipoprotein, MMP = mycophenolate mofetil. FIGURE 3. Recipient 3-year characteristics based on ≥1 coronary allograft vasculopathy at 3 years. ACEi = angiotensin-converting enzyme inhibitor, ARB = angiotensin II receptor blockers, CCB = calcium channel blocker, CyA = cyclosporine, eGFR = estimated Glomerular Filtration Rate, HDL = high-density lipoprotein, LDL = low-density lipoprotein, MMP = mycophenolate mofetil. **Conclusion**: Recipient CAD history and donor age >45 years were significantly associated with CAV development at 3 years after HTx. These results are consistent with prior studies and underscore the importance of donor-recipient risk profiling to improve prediction of post-HTx outcomes and may warrant more intensive prevention measures.

Ana Reschner Planinc, Marija Doronjga, Maja Čikeš, Dora Fabijanović, Nina Jakuš, Hrvoje Jurin, Daniel Lovrić, Marijan Pašalić, Ivo Planinc, Jure Samardžić, Renata Žunec, Marija Burek Kamenarić, Željko Čolak, Hrvoje Gašparović, Davor Miličić, Boško Skorić

**Introduction**: Human leukocyte antigen (HLA) sensitization limits donor availability and increases the risk of waitlist mortality, antibody-mediated rejection (AMR), cardiac allograft vasculopathy, and reduced survival after heart transplantation (HTx). Management often requires complex crossmatch strategies and intensified immunosuppression such as rATG, IVIG, plasmapheresis, rituximab, or complement inhibitors, which may increase complications. (1-3) **Case report**: 21-year-old woman with arrhythmogenic right ventricular cardiomyopathy and high sensitization (cPRA 70%) underwent orthotopic HTx. She received immunoadsorption, rATG, corticosteroids, IVIG, and maintenance with tacrolimus and mycophenolate. On POD 4 she developed dyspnea with bilateral infiltrates, progressing to ARDS by week 2 and requiring mechanical ventilation. Lung CT showed diffuse ground-glass opacities and consolidation. Infection was excluded and graft function remained normal. Despite treatment, donor-specific antibodies rose (A3 900 MFI, B27 21,200 MFI, Cw2 6,200 MFI). Lung injury was suspected from IVIG or rATG. Further IAS/IVIG were withheld, and eculizumab introduced. Corticosteroid pulses were given for ARDS. She was extubated after 7 days with rapid clinical recovery, though infiltrates persisted for 4 weeks (**Figure 1**). At 12 months she was asymptomatic, rejection-free, and had low DSA (B27 2,300 MFI) (**Figure 2**). FIGURE 1. The patient's clinical course with treatment. *Luminex before the 5th immunoadsorption, ** Corticosteroid dose was intravenous methylprednisolone 125mg for 5 days. A29, B27, CW2- HUMAN LEUKOCYTE ANTIGENS, MFI- MEAN FLUORESCENCE INTENSITY, BX- ENDOMYOCARDIAL BIOPSY, IVIG- INTRAVENOUS IMMUNOGLOBULIN, IGM- IMMUNOGLOBULIN M, IAS- IMMUNOADSORPTION, CTS- CORTICOSTEROIDS. FIGURE 2. Temporal evolution of Donor Specific Antibodies (DSA) Mean Fluorescence Intensity (MFI). **Discussion**: Pulmonary toxicity after IVIG or rATG is rare. IVIG-related lung injury is usually reversible, including pneumonitis or diffuse alveolar damage via hypersensitivity or immune-complex deposition. rATG more often causes severe complications such as ARDS, often during first infusions, through cytokine release or TRALI-like reactions involving complement activation, direct toxicity, or hypersensitivity. Eculizumab has not been associated with acute lung injury and may mitigate complement-mediated endothelial injury and capillary leak. **Conclusion**: In highly sensitized HTx recipients, complex immunotherapy entails substantial risk. Flexibility in therapeutic strategies is essential to reduce the high risk of rejection and graft dysfunction. In this case, eculizumab may have contributed not only to rejection prevention but also to pulmonary recovery.

Mirna Momčilović, Vanja Nedeljković, Dora Meštrović, Marijan Pašalić, Vedran Pašara, Ana Marinić, Hrvoje Jurin, Dora Fabijanović, Ivo Planinc, Nina Jakuš, Jure Samardžić, Davor Miličić, Daniel Lovrić

**Introduction**: To report our center’s initial experience with intravenous (IV) landiolol for acute heart rate control in critically ill cardiac patients, focusing on hemodynamic stability and tissue perfusion markers. **Patients and Methods**: This retrospective study included all patients treated with IV landiolol in the Cardiac Intensive Care Unit (CICU) at the University Hospital Centre Zagreb between September 2024 and September 2025. Administrations separated by ≥24 hours were defined as distinct episodes. Baseline demographics and laboratory data were collected. During the first 24 h heart rate (HR), mean arterial pressure (MAP), vasoactive drugs, and urine output were recorded every 2 h when available. Categorical variables are presented as counts, and continuous variables as medians (minimum-maximum). Statistical significance was set at 2) received landiolol, yielding 14 episodes (11 supraventricular tachyarrhythmias, 3 ventricular tachycardia). Cardiogenic shock occurred in 11 episodes, sepsis in 8, septic shock in 4, and mechanical circulatory support was required in 4. Landiolol was started at 18.5 (1–92) days after CICU admission, with a duration of 37.5 (6.8–634.9) h and mean dose 5.1 ± 3.4 µg/kg/min. HR decreased significantly at 2 h (145 [85–190] vs. 105 [70–135] bpm; p = 0.003) and over 24 h (103 [75–130]; p = 0.002). MAP remained stable (73.5 [40–99] vs. 75.5 [55–87] at 2 h, p = 0.22; 75.3 [60–88] 24 h/average, p = 0.27). Lactates showed no change (1.4 [0.3–3.9] vs. peak 1.4 [0.3–7.2]; p = 0.11). Urine output before and after initiation was 2700 [0–4230] vs. 2100 [0–3310] mL/24 h, p = 0.07 (**Figure 1**). No patients required vasoactive support at initiation, but 5/14 episodes required it during therapy, all in sepsis or septic shock. FIGURE 1. Hemodynamic and perfusion dynamics following landiolol initiation in 14 treatment episodes. Bpm – beats per minute; AVG – average; MAP – mean arterial pressure **Conclusions**: In this initial single-centre experience since the national introduction of landiolol, the drug achieved rapid and sustained rate control in critically ill CICU patients, including those with cardiogenic shock and sepsis. HR reduction was not associated with MAP or lactate deterioration, while urine output before and after did not differ significantly. Landiolol may be a safe and effective option for rate control in the CICU, but larger studies are warranted. (1-3)

Sara Varga, Ivan Zeljković, Fran Šaler, Ivana Jurin

**Introduction**: Cardiac implantable electronic devices (CIEDs), including implantable cardioverter-defibrillators (ICDs) and cardiac resynchronization therapy devices (CRTs), alongside optimal medical therapy (OMT), have been a cornerstone of treatment of heart failure with reduced ejection fraction (HFrEF) (1). Up-titration of OMT, which includes beta-blockers (BB), is an irreplaceable step in treatment and prevention of sudden cardiac death SCD (2). However, previous studies have shown that HFrEF patients often fail to reach target doses of OMT (3). This study aimed to assess whether patients with ICDs and CRTs reach maximal doses of BB. **Patients and Methods**: This was an observational, registry-based study that included patients with HFrEF who had ICD or CRT implanted in our institution from January 2021 to September 2024. Data was extracted from the CaRD registry (NCT06090591). **Results:** This registry-based study included 166 patients with a median age of 64 (IQR 59-68), 81% male. All patients had BB prescribed, most often bisoprolol (74% and 59% in the ICD and CRT groups, respectively), followed by carvedilol in the ICD group (10%) and nebivolol in the CRT group (17%). Maximal doses of BB were reached in only 13% of patients prior to ICD implantation and in 12% of patients before CRT implantation. After the implantation of CIEDs, up-titration of BBs to maximal doses has not improved significantly (13 vs. 16% patients in the ICD group, p=0.206; 12 vs. 22% of patients in the CRT group, p=1.404). Most common reasons for lack of up-titration of BBs were clinician inertia (44% of patients in the ICD group and 35% of patients in the CRT group) and intolerance of higher doses (36% of patients with ICD and 38% of patients with CRTs), mostly due to arterial hypotension. In only 4% of patients in both groups, the maximal dose of BBs was not reached due to patient non-adherence. **Conclusion**: Our findings highlight the need for continuing efforts in titrating BBs to their target doses, especially in order to minimize clinician inertia.

Petra Radić, Krešimir Kordić, Diana Delić-Brkljačić, Matias Trbušić

**Introduction**: Constrictive pericarditis is a chronic inflammatory process, often characterised by scarring, fibrosis and calcification associated with diastolic heart failure, which might potentially be curable. (1) **Case report**: 56-year-old male patient was brought to the Emergency Department because he noticed swelling of both lower legs. Upon arrival to the hospital, he was hypotensive, and the ECG showed a rapid atrial fibrillation and microvoltage. Chest X-ray revealed diffuse pericardial calcifications. Echocardiography showed a thickened, hyperechoic and calcified pericardium around the entire heart. Septal bounce and higher septal E’ velocity values than lateral were recorded. Thoracic CT scan calcification along the lower inferior wall of the myocardium. Right heart catheterization described constrictive hemodynamics, more pronounced in the right ventricle. Square root sign was recorded as well as pronounced ventricular interdependence. Coronary angiography a dynamic mid LAD stenosis. In January 2024, a pericardiectomy was performed, without LAD aortocoronary bypass. Intraoperatively, the pericardium was almost completely calcified and attached to the epicardium. Caseous necrosis was also verified in the front wall. The surgical recommendation was to perform functional coronary angiography with the aim of assessing the degree of LAD stenosis. The patient was re-hospitalized in March 2024 for evaluation of the LAD stenosis. Coronary angiography showed 70% stenosis of mid LAD. IFR was performed and it measured 0.94. Microbiological analysis of the intraoperative pericardial contents that was subsequently received was sterile. After six months of follow-up, the patient was clinically stable, without angina or signs of heart failure. **Conclusion**: The most common cause of constrictive pericarditis worldwide is tuberculosis, while in developed countries it is most often idiopathic or post-viral. Pericardiectomy is still considered the gold standard of treatment.

Emilija Katarina Lozo, Marija Doronjga, Filip Lončarić, Dubravka Šipuš, Nina Jakuš, Davor Miličić, Maja Čikeš, Ivo Planinc

**Introduction**: Peripheral eosinophilia is defined as an absolute eosinophil count (EC) exceeding 500/µL (1). Clinical manifestations range from asymptomatic cases and hypersensitivity reactions, such as skin eruptions to severe presentations mimicking sepsis with end-organ involvement, including myocarditis. **Case report**: We present a case of a 56-year-old male with biventricular dilated cardiomyopathy and a history of mitral and tricuspid valve annuloplasty, who had remained clinically stable 18 months following surgery. He gradually developed worsening heart failure (HF) and required recurrent HF hospitalizations. During one of those, in January 2025 his echocardiogram showed severely dilated left ventricle with poor left and right ventricular function. Right-heart catheterization demonstrated increased filling pressures and severely reduced cardiac index. Intravenous furosemide was administered initially, and dobutamine infusion (4 mcg/kg/min) two weeks later with initial improvement in haemodynamics. Fourteen days later, a continuous rise in EC and leukocytes was observed with a peak EC of 10,350/µL (reference range 0–430 /µL) (**Figure 1****)**, while liver function tests remained normal. The patient also developed a rash with vesicles on the lower extremities (**Figure 2**). Dermatologic examination revealed plaques, macules, and papules, and histopathology of skin biopsy confirmed eosinophilic infiltrates. Combination of eosinophilic infiltrates in skin lesions with blood eosinophilia raised suspicion of drug-induced hypersensitivity, and careful investigation of the recently started medications revealed dobutamine as the most likely cause. Discontinuation of dobutamine and transition to milrinone led to complete resolution of both cutaneous manifestations and eosinophilia. FIGURE 1. Progression of eosinophil and leukocyte count after dobutamine initiation. WBC: white blood cell count FIGURE 2. Cutaneous manifestations of dobutamine-induced eosinophilia. **Conclusion**: This case underscores the possibility of dobutamine-induced eosinophilia, potentially related to the drug or its sulfite preservatives, which can aggravate the clinical course in patients with advanced decompensated heart failure. Due to its nonspecific presentation, clinicians should monitor complete blood count and skin changes closely. Early recognition and prompt discontinuation of the offending agent are crucial for rapid resolution and prevention of further clinical deterioration.

Martina Gregur, Marija Brestovac, Matilda Coga, Martina Lovrić Benčić, Blanka Glavaš Konja, Sandra Jakšić Jurinjak, Vlatka Rešković Lukšić, Joško Bulum, Zvonimir Ostojić, Davor Radić, Richard Matasić, Antonio Hanžek, Jadranka Separovic Hanzevacki

**Introduction**: The purpose of this case report is to highlight the diagnostic pitfalls in a patient with recurrent Emergency Room (ER) visits presenting with signs of heart failure (HF) due to non-calcified pericardial constriction (ncPC). **Case report**: 78-year-old man with a history of arterial hypertension presented in February 2024 to the ER with fever, chills, perineal pain and dysuria. He was treated for urosepsis (S. aureus), prostatic abscess and aortic valve (AV) endocarditis which was diagnosed using focused ultrasound (FoCUS) in the ER. Using eyeballing method a mild aortic stenosis (AS), normal left ventricle ejection fraction (LVEF), normal pericardium and inferior vena cava (VCI) were described. The patient was treated with antibiotics for 6 weeks. Since April 2025 the patient was examined five times in the ER with symptoms of right-sided HF, bilateral leg edema, ascites, dyspnea and progressive decline of renal function. In April and May transthoracic echocardiography (TTE) was not performed due to convincing symptoms. Pulmonary embolism and congestion were ruled out using CT but a small pericardial effusion (PE) was described. No signs of malignancy were found, and thyroid function was normal. In June, a FoCUS revealed LVEF 35%, no PE while the AV was not described. Each subsequent ER visit and management relied on the previous FoCUS resulting in continuous diuretic therapy uptitration and the patient was repeatedly discharged from the ER. The patient presented to our ER in August 2025 with syncope, in normal sinus rhythm, hypotensive with ascites (4.5 L were evacuated). Comprehensive TTE revealed severe AS, preserved LVEF and thickened pericardium no PE with typical signs of constriction also proven by right heart catheterization (**Figure 1**). Cardiac CT confirmed diffuse thickening of the pericardium without calcifications, consistent with ncPC (**Figure 2****).** Patient is referred for AV replacement and pericardiectomy. FIGURE 1. Signs of non-calcified constrictive pericarditis: A) parasternal long axis view B) M-mode showing thickened pericardium (yellow arrow), severe aortic calcification (blue arrow), inspiratory leftward shift of the interventricular septum (green arrow); C) "square root sign" during heart catheterization. FIGURE 2. A computed tomography scan of the heart showing non-calcified thickened pericardium. **Conclusion**: The diagnosis of ncPC is often challenging and may be established only after irreversible organ damage has occurred. Even when one diagnosis appears likely, additional causes must be considered. (1-3) Although well established, FoCUS should be used and interpreted with caution. Dependence on partially interpreted findings led to suboptimal and delayed therapeutic management.

Merljinda Ljušaj, Danijela Grizelj, Ivana Jurin, Jasmina Ćatić, Branko Ostrički, Tea-Terezija Cvetko

**Introduction**: Mitral stenosis (MS) is shifting from rheumatic to prosthetic and calcific causes in developed regions. The 2025 ESC guidelines stress individualized, Heart Team–based care. Echocardiography, particularly transesophageal echocardiography (TEE) with 3D imaging, is pivotal for defining valve anatomy, hemodynamics, and guiding intervention. (1, 2) **Case presentations**: Through presented cases we discuss two different etiologies of mitral stenosis. First, a 35-year-old severely symptomatic woman with prior bioprosthetic mitral valve replacement for prolapse developed combined prosthetic stenosis and regurgitation 15 years later. Comprehensive TEE evaluation demonstrated a valve area of 1.0 cm2 (3D), mean transmitral gradient of 12 mmHg, effective regurgitant orifice area 0.4 cm2, regurgitant volume 66 ml, and moderately reduced LVEF at 45%. Two leaflets were immobile, consistent with structural valve degeneration (**Figure 1**). Second patient (**Figure 2**) is a 47-year-old man with longstanding rheumatic MS and prior surgical commissurotomy (2007) who presented with dyspnea. TTE and TEE revealed classical commissural fusion, severe annular calcification, valve area 0.7 cm2 (3D), mean gradient 11 mmHg, mild MR, moderate functional TR, and preserved LVEF at 50%. Both patients were discussed at the multidisciplinary Heart Team for definitive management planning. FIGURE 1. A) Transesophageal echocardiography (TEE) apical 4-chamber view showing severe turbulence during mitral valve opening. B) TEE long axis view showing the PISA radius for mitral regurgitation. C) TEE long axis view showing the PISA VTI for mitral regurgitation. D) TEE 3D reconstruction of the prosthetic mitral valve and depiction of immobile leaflets of the prosthesis. FIGURE 2. A) Transesophageal echocardiography (TEE) apical 4-chamber view showing severe mitral valve calcifications and thickening of the leaflet tips. B) TEE 3D reconstruction of severe mitral stenosis; the valve is heavily calcified, with commissural fusion and restricted mobility of both mitral valve leaflets. **Discussion**: The ESC 2025 guidelines recommend percutaneous mitral commissurotomy (PMC) as first-line therapy in suitable rheumatic MS. However, in prosthetic degeneration and heavily calcific, non-rheumatic stenosis, PMC is ineffective and either surgical redo or transcatheter mitral valve replacement is favored. These cases underscore the pivotal role of TEE and 3D echocardiography in diagnosis and workup. This comprehensive imaging framework informs not only severity grading but also intervention feasibility, procedural strategy, and perioperative risk assessment. **Conclusion**: MS in contemporary practice represents two distinct entities—rheumatic and non-rheumatic/prosthetic. Advanced echocardiographic workup, particularly TEE with 3D modalities, is indispensable for accurate diagnosis, mechanism delineation, and intervention planning. Alongside structured Heart Team review, imaging serves as the cornerstone of individualized patient management.

Jozica Šikić

Percutaneous coronary intervention (PCI) for left main (LM) coronary artery disease with bifurcation or trifurcation involvement remains one of the most challenging settings in interventional cardiology. The large myocardial territory at risk, complex vessel geometry, and prognostic importance of side branches complicate procedural decision-making. (1-3) The introduction of drug-eluting stents (DES) has reduced restenosis and repeat revascularization compared with bare-metal stents, supporting PCI as a valid alternative to coronary artery bypass grafting in selected patients, as demonstrated in the EXCEL and NOBLE trials. However, LM bifurcation and trifurcation PCI remain associated with increased risks of restenosis and stent thrombosis. Intravascular imaging with intravascular ultrasound (IVUS) and optical coherence tomography (OCT) has become essential to optimize LM PCI. IVUS-guided PCI improves vessel sizing, lesion characterization, and stent expansion, with clinical benefit demonstrated in IVUS-XPL and ULTIMATE. OCT offers superior resolution for strut apposition and edge dissections, though its penetration is limited in large LM vessels. Current guidelines advocate routine imaging guidance in LM interventions. Stenting strategies include provisional and planned two-stent approaches. The DKCRUSH V trial established the efficacy of double-kissing crush in true LM bifurcations, but simplified methods remain desirable. The single stent over bifurcation lesion or drug eluting ballon in side branch or both branches may be at least good enough as two-stent implantation. Combining DES with DCB, or DCB only strategy with IVUS or OCT guidance may enhance procedural safety and long-term efficacy in LM bifurcation and trifurcation lesions. We do not still enough data for quadrifurcation. Further randomized trials are needed to validate this approach and refine patient selection.

Sara Dolički, Zvonimir Ostojić, Anamaria Ostović, Luka Perčin, Hrvoje Jurin, Tomislav Krčmar, Joško Bulum

**Introduction**: Access site-related vascular injury (ASRVI) following percutaneous transfemoral transcatheter aortic valve implantation (TAVI) remains a notable complication. Most ASRVI cases can be effectively treated percutaneously using balloon dilatation or stent graft (SG) implantation (1). Device sizing is typically based on angiographic imaging of the common femoral artery (CFA) at the procedure’s start. This study aimed to compare angiographic CFA dimeter with those derived from computed tomography (CT) to evaluate whether CT-based measurements could guide device sizing for ASRVI treatment. **Patients and Methods**: This single-center analysis included all TAVI patients who developed ASRVI and were treated with balloon dilatation or SG implantation. CFA dimensions from pre-TAVI CT scans were compared to angiography performed at the beginning of the procedure. Diameter differences were calculated to assess percentage of the correspondence. **Results:** Among 54 patients with ASRVI post-TAVI, all underwent balloon or SG treatment. Device diameter was determined using angiography. Mean CFA diameter via angiography was 8.01 ± 1.24 mm, significantly larger than CT-based mean diameter (7.16 ± 1.60 mm, p=0.003), but not different from CT-based maximal diameter (7.93 ± 1.42 mm, p=0.75). Case-by-case comparison between maximal CT and angiography derived CFA diameter showed: good accordance ( 0.9 mm) in 20 cases (37.4%). In the moderate group, CT overestimated CFA in 10 cases by mean of 0.57 mm, and underestimated in 8 by mean of 0.47 mm. In the discordant group, CT overestimated CFA in 7 cases (mean 1.5 mm) and underestimated in 13 (mean 1.23 mm). **Conclusion**: CT-based CFA measurements show poor agreement with angiography and should not be used for device sizing in ASRVI treatment post-TAVI.

Ana Reschner Planinc, Antonio Hanžek, Marija Doronjga, Anica Milinković, Andrija Nekić, Filip Lončarić, Dora Fabijanović, Dubravka Šipuš, Luka Perčin, Denis Došen, Marijan Pašalić, Ivica Šafradin, Joško Bulum, Daniel Lovrić, Davor Miličić, Hrvoje Jurin

**Introduction**: In spite of advances in percutaneous coronary interventions and short term mechanical circulatory support (MCS), cardiogenic shock (CS) complicating acute coronary syndrome still carries high mortality risk. (1) **Case report**: A 62-year-old male with arterial hypertension and nicotinism presented hypotensive with a 24h progressive back pain and sinus tachycardia with diffuse ST denivelation. Upon admission to Coronary Care Unit he was in refractory CS. Urgent hemodynamic (HD) stabilization was achieved with peripheral venoarterial extracorporeal membrane oxygenation (VA-ECMO) and he was rushed to catheterization laboratory. Coronary angiography revealed chronic total occlusion (CTO) of subostial left anterior descending artery, CTO of mid hypoplastic right coronary artery and acute thrombotic occlusion of dominant proximal circumflex artery (LCX). Drug-coated balloon delivery was used for successful revascularization of the LCX. For the purpose of left ventricular (LV) unloading, the procedure was ultimately completed by implantation of an Impella CP pump via the left femoral artery (FA). Initial echocardiography revealed severely reduced LV ejection fraction (EF) of only 10%. Invasive HD showed mPAP of 26 mmHg, PCWP 19 mmHg and CI under HD support of 2.3 ml/min/m2. Echocardiography two days later showed slight improvement of EF to 30%. On the 3rd day VA-ECMO was successfully percutaneously extracted. However, attempt to wean off Impella CP was unsuccessful due to immediate clinical deterioration, so the micro-axial pump was repositioned with immediate HD stabilization. Given there was no appropriate percutaneous option of further revascularization, the patient underwent successful surgical revascularization of the LAD along with escalation to Impella 5.5. Inotropic and vasopressor support was discontinued by post-operative day (POD) 4 followed by levosimendan loading. On POD 5 guideline-directed medical therapy (GDMT) including eplerenone, sacubitril/valsartan, dapagliflozin, bisoprolol was carefully initiated. MCS with Impella 5.5 was gradually weaned off and removed on POD 7. Ultimately, the patient clinically recovered, and pre-discharge echocardiography showed LVEF of 40%. Patient was discharged from hospital 22 days after admission with GDMT. **Conclusion**: This case demonstrates that appropriate early implementation and subsequent escalation of MCS optimizes survival and functional recovery in this patient population.

Davor Miličić

## Dear Colleagues, The 8th Cardiology Highlights – the International Update Meeting initiated by the ESC Committee on Education from 2009 as a biennial meeting, is awaiting you to join, present, discuss, network, and enjoy the selected hottest topic in cardiovascular medicine in Dubrovnik, October 23-26, 2025. Our on-site audience will be up to 300 participants, ranging from cardiology fellows to top, world-renowned experts. As the entire Meeting will be recorded, many more interested people will have the opportunity to view the Programme recordings posted to the web page of the Croatian Cardiac Society - www.kardio.hr. We have tried to compose our sessions to be diverse, attractive, and to provide inspirational lectures, education on guidelines and other essential novelties for daily practice, as well as selected cutting-edge science in cardiology. As is tradition, there will be some time devoted to original contributions and challenging case presentations, to set the stage for our young cardiologist community. In addition to that, our young cardiologists have prepared a Cardiology Quiz for the first time, which I am sure we are going to enjoy. Despite many congresses and meetings taking place in parallel, we have gathered impressive international faculty from 21 countries, from neighboring Slovenia, Italy, Hungary, and Bosnia and Herzegovina, as well as Romania, Bulgaria, Slovakia, France, Spain, the Netherlands, Germany, UK, and Baltic and Nordic countries, and also from the USA and Canada. This makes us very proud and grateful to all who will join us – both to our Founding Directors and other old friends who have experienced Dubrovnik Meetings before and to our distinguished guests coming here for the first time. As a reminder, Cardiology Highlights has remained the only ongoing congress from the ESC Update Meetings family (Davos, Rome, Rotterdam, Dubrovnik). It is organized by the Croatian Cardiac Society under the high auspices of the Croatian Academy of Sciences and Arts. We are also grateful to the ESC President, Prof. Thomas Luescher, who has continuously supported our Meeting since its very beginning. I hope you will enjoy the Meeting and its atmosphere, and take home some wonderful memories. Sincerely, Professor Davor Miličić, MD, PhD, FESC, FHFA, FACC Vice President, Croatian Academy of Sciences and Arts President Croatian Cardiac Society Director, 8th Cardiology Highlights – The International Update Meeting

Zvonimir Ostojić, Nino Petroci, Hrvoje Jurin, Luka Perčin, Joško Bulum

**Introduction**: Transcatheter aortic valve implantation (TAVI) carries a risk of coronary artery occlusion (CAO) in selected patients, particularly those with low coronary ostia. Several methods have been developed to prevent CAO, with chimney stenting being widely adopted due to its simplicity. However, long-term outcomes of this technique are lacking. (1) The aim of this study was to assess outcomes in patients who underwent coronary protection during TAVI using the chimney technique. **Patients and Methods**: This was a single-centre retrospective study that included all patients undergoing TAVI with coronary protection using the chimney technique. Patients were stratified into two groups: Group 1 (stent implanted) and Group 2 (no stent implantation). Procedural and clinical data were collected from the hospital’s digitalized database. All patients were contacted for follow-up outcome assessment. **Results**: Of 810 patients undergoing TAVI, 16 (1.98%) were deemed at high risk for CAO based on pre-TAVI CT. Clinical and procedural data are presented in **Tables 1** and **2**Table 2. In all cases, a stent was positioned in the coronary artery at risk before valve deployment. After implantation, coronary artery patency was assessed, and the decision regarding definitive stent implantation was made at that time. This resulted in seven stent implantations (0.86% of all TAVI cases, 43.75% of those at high risk of CAO), comprising Group 1. The mean follow-up was 13.7 ± 7.5 months. One patient (Group 2) was lost to follow-up. There were two deaths, both in Group 1: one due to complications (sepsis) following transapical TAVI, and one non-cardiac death 1.5 years post-procedure. In Group 1, a P2Y12 inhibitor was prescribed for either 3 months (50%) or 6 months (50%). All patients reported clinical improvement, with no reports of chest pain. There were no cases of late CAO or need for percutaneous coronary intervention. ### TABLE 1: Clinical characteristics of patients. | | **All patients** | **Group 1 (n=7)** | **Group 2 (n=9)** | | --- | --- | --- | --- | | Age – mean ± SD | 80.6 ± 4 | 80.6 ± 2.1 | 80.6 ± 4.9 | | Female gender – n(%) | 14 (87.5) | 6 (85.7) | 8 (88.9) | | Arterial hypertension – n(%) | 15 (93.8) | 6 (85.7) | 9 (100) | | Hyperlipidemia – n(%) | 12 (75) | 6 (85.7) | 6 (66.7) | | Diabetes mellitus | 7 (43.8) | 4 (57.1) | 3 (33.3) | | Chronic renal insufficiency – n(%) | 11 (68.8) | 6 (85.7) | 5 (55.6) | | Coronary artery disease – n(%) | 10 (62.5) | 5 (71.4) | 5 (55.6) | | Percutaneous coronary intervention – n(%) | 0 | 0 | 0 | | Coronary artery bypass graft – n(%) | 2 (12.5) | 2 (28.6) | 0 | | Peripheral artery disease – n(%) | 4 (25) | 2 (28.6) | 2 (22.2) | | Chronic obstructive pulmonary disease – n(%) | 1 (6.25) | 1 (14.3) | 0 | | Malignancy – n(%) | 3 (18.8) | 2 (28.6) | 1 (11.1) | | Oral anticoagulation – n(%) | 8 (50) | 5 (71.4) | 3 (33.3) | ### TABLE 2: Procedural characteristics. | | **All patients** | **Group 1 (n=7)** | **Group 2 (n=9)** | | --- | --- | --- | --- | | Transfemoral approach – n(%) | 15 (93.8) | 6 (85.7) | 9 (100) | | Valv-in-valve – n(%) | 5 (31.3) | 3 (42.9) | 2 (22.2) | | Balloon expanding valve – n(%) | 8 (50) | 3 (42.9) | 5 (55.6) | | Valve size - mean ± SD | 26 ± 3.3 | 26.3 ± 4.4 | 25.8 ± 2.1 | | Left main coronary artery protection – n (%) | 15 (93.8) | 6 (85.7) | 9 (100) | | Coronary artery ostia height - mean ± SD | 7.62 ± 1.51 | 7.46 ± 1.92 | 7.74 ± 1.03 | | Stent diameter - mean ± SD | / | 3.71 ± 0.52 | / | | Stent length - mean ± SD | / | 35.3 ± 4.3 | / | **Conclusion**: The chimney technique appears to be a safe and effective strategy for the prevention and management of CAO during TAVI. Notably, fewer than 50% of patients in the high-risk group ultimately required stent implantation.

Antonio Hanžek, Vlatka Rešković Lukšić, Joško Bulum, Zvonimir Ostojić, Sandra Jakšić Jurinjak, Denis Došen, Kristina Marić-Bešić, Ivica Šafradin, Marija Brestovac, Jadranka Šeparović Hanževački

**Introduction**: Paravalvular leak (PVL) is a common problem after cardiac surgery, which independently increases morbidity and mortality (1). Based on the literature, percutaneous closure devices are a viable option in the treatment of the PVL, to defer repeat surgery and improve the overall prognosis (2). **Case report**: 66-year-old female previously underwent implantation of a mechanical mitral prosthesis (SJM Masters 33 mm) in October of 2024 for severe mitral regurgitation with secondary valvular cardiomyopathy. Her past medical history was significant for papillary thyroid carcinoma and lung carcinoid, treated with thoracic surgery and everolimus. Preoperative echocardiography revealed prolapse of both mitral cusps, with considerable calcification extending to the mitral anulus. Those findings were confirmed intraoperatively, and extensive mitral annular calcification (MAC) limited adequate prosthesis sealing, resulting in two considerable PVLs, superomedial and inferolateral (**Figure 1**). At first, it was decided to follow the patient without intervention as the early repeat surgery was deemed futile due to MAC. During follow-up, the patient exhibited laboratory results consistent with intravascular hemolysis, without significant anemia. Of note, there was a progressive dilatation of the left ventricle, with further deterioration of the systolic function that correlated with gradual clinical worsening. During follow-up, the Heart Team indicated that percutaneous closure was necessary, with heart CT for preprocedural planning. In May 2025, the patient was hospitalized for the closure of PVLs. Due to difficulty passing the catheter through the calcified lateral PVL, the leak was initially dilated with an Xtreme OTW balloon; subsequently, an Amplatzer Valvular plug (Abbott, 5x10 mm) was implanted. The medial leak was more easily passed, using the same closing device (**Figure 2**). Angiography after the procedure showed an optimal result. During follow-up, the patient is doing well, with only mild residual regurgitation. FIGURE 1. Paravalvular leaks shown on transesophageal echocardiography (marked with arrows). FIGURE 2. Paravalvular leak ocluder in position on transesophageal echocardiography. **Conclusion**: Proper preprocedural planning before PVL closure, utilizing multimodality imaging, is crucial for achieving optimal results. In an aging and polymorbid population where severe MAC is expected, PVL closure offers an alternative solution to addressing this challenge (3).

Petra Grubić Rotkvić, Mia Dubravčić Došen, Mislav Puljević, Sanda Huljev Frković, Anica Milinković, Darko Anić, Majda Vrkić Kirhmajer

**Introduction**: Disease of the aortic root and ascending aorta is commonly linked to hereditary or congenital factors. Genetic disorders affecting the thoracic aorta are known as heritable thoracic aortic disease, which can present as syndromic and non-syndromic, with underlying gene defects encoding three major groups: the extracellular matrix, TGF-β signaling pathway, and the smooth muscle cell contractile apparatus. (1) **Case report**: A 34-year-old female was referred for cardiologic evaluation due to elevated blood pressure and periodic chest pain. Echocardiography revealed mild to moderate aortic regurgitation with combined root and ascending aorta dilation (**Figure 1**). MR and CT aortography confirmed dilation of the ascending aorta up to 50 mm, with sinuses of Valsalva and sinotubular junction measuring up to 49 mm (**Figure 2**). Due to extra-aortic features (short stature, wide and short neck, short fourth and fifth metacarpal bones, scoliosis, small breasts), mosaic Turner syndrome was initially suspected but her karyotype analysis was normal. Further genetic testing using the Aorta Panel identified a heterozygous duplication of 7q11.23 encompassing the ELN gene, which encodes the elastin protein. 7q11.23 duplication has been associated with thoracic aneurysms, presumably due to increased ELN expression and elastin excess (2). Interpreting the clinical relevance of 7q11.23 duplications is challenging, as phenotypic variability is wide. There are no specific prediction models that can estimate the risk of rupture or dissection in these patients. Nevertheless, considering her short stature (her height was 154 cm), we calculated the aortic size index: 30 mm/m2, aortic height index: 32 mm/m, and the z-score: 7 - all markedly elevated. She underwent a successful valve-sparing “Florida sleeve” procedure (**Figure 3**), with uneventful postoperative course. Subsequently, her parents were tested using a molecular karyotype test (array-based comparative genomic hybridization) and the results were normal, indicating that the mutation in our patient occurred de novo. Nevertheless, we performed an echocardiographic screening in both of her siblings, which confirmed normal aortic dimensions. FIGURE 1. Echocardiographic image of the dilated aortic root and ascending aorta (yellow arrow). FIGURE 2. A) MR image of the dilated aortic root (blue arrow); B) dilated ascending aorta on CT scan (red arrow). FIGURE 3. Echocardiographic image of the ascending aorta (purple arrow) after the „Florida sleeve” procedure. **Conclusion**: There is a need for better characterization and risk stratification models in rare genetic aortopathies.

Ana Reschner Planinc, Kristina Marić Bešić, Boško Skorić, Eduard Margetić, Luka Perčin, Denis Došen, Davor Radić, Zvonimir Ostojić, Marijan Pašalić, Tomislav Krčmar, Davor Miličić, Joško Bulum, Hrvoje Jurin

**Introduction**: Pullback pressure gradient (PPG) is a novel, emerging method in distinguishing coronary artery disease (CAD) patterns, as either beeing focal, intermediate or diffuse. (1-3) In this small retrospective observational study we aimed to show the role of PPG in tailored decision-making (OMT vs PCI). **Patients and Methods**: We included stable CAD patients who underwent PPG measurements in order to recognize CAD patterns as either focal or diffuse. In all patients the manual Fractional Flow Reserve (FFR) pullbacks were used for PPG measurements. The FFR was performed on Abbott™ CoroFlow‡v3.6 Cardiovascular System. Besides demographics, we collected data on comorbidities, laboratory parameters (LDL cholesterol, creatinine, glomerular filtration rate), medications, and symptoms. FFR index, PPG, coronary anatomy and significance of lesions was reported from coronary angiography reports. Descriptive statistics were used for characterization of the patient cohort. **Results**: In total, 13 patients with stable CAD were included (mean age 66.7 ± 10.2 years, 62% males). Nearly all had arterial hypertension (12/13) and hyperlipidemia (11/13), while less than half reported smoking (5/13). Only 6/13 patients had haemodinamically significant stenosis according to FFR (positive FFR <0.80). Three out of six patients with positive FFR had diffuse pattern of CAD according to PPG (<0.5) and were managed conservatively with further optimization of their medical therapy. Out of the remaining patients with positive FFR, 2 had focal, and 1 had mixed CAD pattern, and all underwent PCI. Post-PCI FFR varied by disease pattern. Patient with mixed pattern CAD achieved a final FFR of 0.65, while patients with focal disease obtained optimal revascularization with final FFR 0.84 and 0.91 clearly confirming the positive predictive value of PPG. Medical therapy was further optimised in 7 patients with negative FFR, among which PPG showed focal disease in 3, while remaining patients had diffuse disease. **Conclusion**: In our cohort, combined FFR and PPG prevented potentially unnecessary interventions in half of the patients that were managed conservatively despite positive FFR. This small observational study supports emerging data that optimal decision making in PCI should incorporate both ischemic burden (FFR) and disease pattern (PPG).

Luka Perčin, Hrvoje Jurin, Zvonimir Ostojić, Tomislav Krčmar, Kristina Marić, Mirna Momčilović, Joško Bulum

**Introduction**: The coronary sinus reducer (CSR) is a novel percutaneous device developed for patients with refractory angina pectoris (RAP) who are not candidates for surgical or percutaneous revascularization. By creating a controlled narrowing in the coronary sinus, the CSR aims to improve myocardial perfusion and reduce angina symptoms (1). We report the first institutional experience with CSR implantation at the University Hospital Centre (UHC) Zagreb and evaluate its clinical impact. **Patient and Methods**: This retrospective study included all patients with RAP who underwent CSR implantation at the UHC Zagreb between October 2022 and November 2025. Demographic and clinical data were collected, including sex, age, and Canadian Cardiovascular Society (CCS) angina class. CCS class was assessed at baseline and during follow-up visits. Continuous variables are presented as mean ± standard deviation (SD). The primary endpoint was improvement by at least one CCS class. Statistical significance was defined as p < 0.05. **Results:** A total of 35 patients underwent CSR implantation (23 males [65.7%], mean age 69 ± 7.6 years, range 51–83). Procedural success was achieved in all patients. One major peri-procedural complication, a coronary sinus perforation, was successfully managed with stent-graft implantation. Follow-up CCS data were available for 25 patients; 10 were excluded due to loss to follow-up (n=3), insufficient follow-up duration (n=3), death from sepsis (n=1), acute coronary syndrome (n=1), and percutaneous coronary intervention for disease progression (n=2). At baseline, the mean CCS class was 2.44 ± 0.51 (56% class II, 44% class III). At a mean follow-up of 15.8 ± 8.7 months, the mean CCS class significantly improved to 1.36 ± 0.57 (p < 0.001). Overall, 21 patients (84%) improved by at least one CCS class, including 6 patients (24%) with a reduction of ≥2 classes; 4 patients (16%) remained unchanged, and none worsened (**Figure 1**). FIGURE 1. Distribution of Canadian Cardiovascular Society (CCS) angina class at baseline and follow-up. **Conclusion**: Our initial single-centre experience suggests that CSR implantation is a feasible and safe procedure in patients with refractory angina. The intervention was associated with significant symptomatic improvement, consistent with previously published studies, and supports CSR as an effective therapeutic option in the management of refractory angina.

Antun Zvonimir Kovač, Irena Ivanac Vranešić, Petar Martinčić, Denis Došen, Goran Međimurec, Darko Anić, Kristina Marić Bešić

**Introduction**: Pulmonary arterial hypertension (PAH) in atrial septal defects (ASDs) develops variably but atrioventricular (AV) canal abnormalities confer a higher and earlier risk (1). Current guidelines recommend ASD closure when pulmonary vascular resistance (PVR) falls ≤ 5 Wood units (WU) after pulmonary vasodilator therapy, with still significant left-to-right shunt (Qp/Qs > 1.5) (2). Individual treatment approach should be applied and these patients need assessment in a tertiary center with experience in adult congenital heart disease and PAH. **Case report**: 26-year-old man with a history of cardiac murmur and severely reduced functional capacity (5.4 METs) on exercise testing was referred for further evaluation. Echocardiography and cardiac MRI demonstrated a large primum-type ASD with Qp/Qs 4.5:1 and severe left AV valve regurgitation with pulmonary hypertension. Ventricular septal defect (VSD) was mostly closed by right AV valve tissue and there was suspicion of residual restrictive inlet VSD. Right heart catheterization confirmed severe PAH (mean pulmonary artery pressure (mPAP) of 58 mmHg and PVR of 5.1 WU), precluding surgical septal defect closure. Targeted therapy with sildenafil and bosentan was initiated. Over the next 12 months, serial catheterizations showed a marked reduction in mPAP (45 mmHg) and PVR (3.3 WU), allowing reconsideration for surgery. Intraoperatively, a transitional AV canal defect was confirmed with description of small indirect Gerbode type VSD. Complete repair was successfully performed, including fenestrated primum ASD closure, VSD closure and both AV valves cleft repair. Recovery was uneventful, and follow-up echocardiography showed smaller RV with mildly reduced systolic function and residual mPAP of 38mmHg which persisted over the follow-up period of 3 years. Dual PAH therapy was continued postoperatively. Last excercise stress test showed markedly improved physical capacity (11 METs) and NTproBNP was normal. **Conclusion**: Targeted pulmonary vasodilator therapy can reduce PVR and convert initially inoperable ASD (or transitional atrioventricular septal defect) into surgically correctable lesion. Optimal outcomes of “treat and repair strategies” require advanced imaging, expert interpretation and multidisciplinary management with repeated hemodynamic reassessment.

Nikolina Jupek, Mia Dubravčić Došen, Ivana Jurca, Mislav Puljević, Dražen Perkov, Nino Tičinović, Majda Vrkić Kirhmajer

**Introduction:** Acute limb ischemia (ALI) carries substantial mortality risk and frequent severe complications. Intra-arterial catheter-directed thrombolysis (CDT) offers high short-term clinical and technical success in selected patients. However, long-term outcomes after CDT remain insufficiently explored (1). **Patients and Methods**: We retrospectively analyzed consecutive adult patients with acute limb ischemia who underwent catheter-directed thrombolysis at the University Hospital Centre Zagreb between 2012 and 2022. Eligible patients had symptoms ≤14 days and viable extremities. Outcomes, including amputation-free survival (AFS), major adverse limb events (MALE), major adverse cardiovascular events (MACE), ankle-brachial index (ABI) trends, and mortality, were assessed at 1 year, 3 years, and at the final follow-up. **Results**: The study cohort comprised 48 patients (60.4% men; median age 68 years, IQR 57.3–75.5), predominantly presenting with lower limb ischemia (94%). Initial clinical success was achieved in 81.3% of cases. Median ankle-brachial index (ABI) improved from 0.33 before thrombolysis to 0.85 after therapy. During long-term follow-up, major amputation occurred in three patients (9.4%), and overall mortality reached 27.1% by the end of the observation period. This corresponded to AFS of 89.3% in one year, 79.1% in three years, and estimated AFS of 64.2% at 72 months. Recurrent ALI was documented in 5.1%, and critical limb ischemia developed in 15.4%. MACE occurred in 13.8% of patients, while MALE affected 28.2%. Patients achieving initial clinical success maintained significantly higher ABI values during follow-up (median ABI 0.98 vs 0.59 at final assessment), confirming sustained perfusion benefits (**Figure 1**). Continued anticoagulation use was more common in these patients, suggesting a potential protective role against re-occlusion. FIGURE 1. Ankle-brachial index before and after thrombolysis, after one year follow-up and at the end of follow-up. CDT = catheter-directed thrombolysis **Conclusions**: CDT provides durable limb salvage with acceptable long-term safety. Preserved ABI over several years highlights its effectiveness. Careful patient selection and vigilant follow-up are essential for optimizing long-term results.

Matias Trbušić, Matej Nedić, Ozren Vinter, Ivan Turalija

**Introduction**: Tuberculosis is uncommon in Croatia (≈6/100,000), and tuberculous pericarditis (TBP) occurs in only ~1% of cases, making it exceptionally rare. By contrast, in endemic areas such as North Africa, TBP accounts for up to 90% of effusive pericarditis. (1-3) The rarity in low-incidence countries often delays diagnosis and increases complications and mortality. Establishing the diagnosis is particularly challenging because the clinical presentation is atypical and not accompanied by the usual indicators of active tuberculosis, as in our patient. In this context, echocardiography and computed tomography (CT) play a key role in raising the initial suspicion. **Case report:** We report a 78-year-old patient admitted with pericardial effusion after three months of progressive fatigue and exertional dyspnea, without fever or chest pain. Past history included arterial hypertension. Multislice CT revealed pericardial thickening with fat stranding, mediastinal lymphadenopathy, calcified hilar nodes, and fibrotic lung changes. Echocardiography confirmed pericardial thickening with extensive deposits, mild effusion, and impaired filling. Pericardiocentesis yielded cloudy yellow fluid, exudative and lymphocytic (LDH per/ser 16.4; protein per/ser 0.8). The adenosine deaminase (ADA) test was markedly elevated (78.1 U/L), and polymerase chain reaction (PCR) test for Mycobacterium tuberculosis confirmed TBP. Standard anti-tuberculous therapy (isoniazid, rifampicin, pyrazinamide, ethambutol) was initiated. We decide to start with corticosteroids to reduce the risk of constriction despite unclear guidelines and the conflicting position in literature. Workup excluded active pulmonary disease, indicating reactivation of latent infection without obvious risk factors beyond advanced age. **Conclusion**: TBP remains a rare but potentially underrecognized diagnosis in Croatia. Isolated forms can be subtle, with nonspecific symptoms and no overt pulmonary disease. Clinical suspicion is essential, particularly as immigration from high-incidence countries rises. Pericardiocentesis is the cornerstone of diagnosis, allowing rapid confirmation through ADA and PCR, while culture provides definitive proof. Early recognition and timely treatment are critical to prevent progression to constrictive pericarditis and improve patient outcomes.

Karlo Gjuras, Dijana Bešić, Iva Saraja, Marija Križanović, Kristina Marić Bešić, Ivana Jurin

**Introduction**: Data on the association between unprovoked pulmonary embolism (PE) and subsequent diagnosis of occult malignancy remain limited and heterogeneous. Whether an unprovoked thromboembolic event should be considered a clinical warning sign for underlying cancer is still debated. (1, 2) **Patients and Methods**: We conducted a prospective observational study based on a pulmonary embolism registry from two tertiary care centers, covering the period December 2013 to December 2024. Patients with an index PE were included, while those with active cancer at baseline or a history of malignancy were excluded. Participants were classified into two groups: unprovoked PE (UPE) and non-malignancy-provoked PE (NMPE). The primary aim was to compare the incidence of newly diagnosed malignancies during follow-up between groups, with prespecified subgroup analyses according to age and sex. **Results**: A total of 656 patients were enrolled (median age 73 years [IQR 60–80], 56.4% female). During a median follow-up of 3.3 years [IQR 0.9–6.3], malignancy was diagnosed in 11/193 (5.7%) in the UPE group and 19/463 (4.1%) in the NMPE group, a difference that was not statistically significant (OR 1.41, 95% CI 0.66–3.03). Age-stratified analysis revealed a significantly higher cancer incidence among patients >60 years with UPE (OR 2.41, 95% CI 1.09–5.31). This association was most pronounced in women over 60 years, where the risk of subsequent malignancy was nearly fourfold higher (OR 3.89, 95% CI 1.29–11.7). **Conclusion**: In the overall population, UPE was not associated with an increased incidence of malignancy compared with NMPE. However, older women with UPE demonstrated a markedly higher risk, suggesting that this subgroup may benefit from closer clinical follow-up. Further research is warranted to confirm these observations.

Anja Boc, Mojca Božič Mijovski, Vinko Boc, Kevin Pelicon, Ula Dobovičnik, Maja Glogovšek

**Introduction**: Peripheral arterial disease of the lower limb (PAD) is one of the most common clinical manifestations of atherosclerosis,which is an inflammation-driven process. Patients with PAD exhibit elevated baseline levels of inflammatory markers compared to the healthy population (1). Revascularisation interventions cause an additional, acute increase in circulating inflammatory markers due to arterial wall injury. These markers mediate inflammatory and coagulation responses and are considered an early indicator of potential restenosis (2). Successful revascularisation restores limb perfusion and can lead to a mid- and long-term reductions in inflammatory markers (3). In this observational prospective pilot study, we aimed to investigate the dynamics of circulating inflammatory biomarkers in the first three months after revascularisation. **Patients and Methods**: The study was conducted in the Catheterisation Laboratory of the Department of Vascular Diseases, University Medical Centre Ljubljana, Slovenia. Patients with successful percutaneous femoropopliteal revascularisation due to limiting intermittent claudication were included. Levels of interleukins 6 (IL-6), 8 (IL-8), and 10 (IL-10), C-reactive protein (CRP), and tumour-necrosis factor alpha (TNFα) were determined one hour before the procedure, one day after the procedure, and three months after the procedure. **Results**: Among 28 participants, aged 50-79 years (median 69 years), 18 (64.3%) were male. Statistically significant differences among the three blood samples were observed for IL-6 (p<0.001), IL-10 (p=0.012), and TNFα (p=0.016). For IL-6, differences were present between all three time points: 1st vs 2nd (p=0.011), 2nd vs 3rd (p<0.001), and 1st vs 3rd (p<0.001). A difference between the 2nd and 3rd time point was also observed for IL-10 (p=0.004) and TNFα (p=0.026). **Conclusion**: Restoration of blood flow appears to modulate systemic inflammatory activity and may potentially slow both local and systemic progression of atherosclerosis. More research is needed to determine implications of revascularisation procedures on short- and long-term biomarker levels and their correlation with clinical outcomes.

Petra Radić, Martina Čančarević, Ognjen Čančarević, Siniša Car

**Introduction**: Myocarditis is a rare but serious complications of tick-borne infections, particularly those caused by Rickettsia rickettsii and Rickettsia conorii. (1, 2) **Case report**: 32-year-old patient presented to the Emergency Department due to shortness of breath and exercise intolerance. He reported an erythematous skin rash and swelling of his right ankle. In the physical status, a hyperemic pharynx and petechiae on the soft palate were described. Heart rate was tachyarrhythmic and a holosystolic murmur was present. The electrocardiogram showed a rapid form of atrial fibrillation. Laboratory showed elevated troponin and NT-proBNP levels. Echocardiography showed a dilated left ventricle, severely reduced ejection fraction (LVEF 15%, GLS -2.2%) and mitral valve annulus dilatation with consequent severe mitral regurgitation. Synchronized cardioversion was performed and sinus rhythm was achieved. Due to hypotension, inotropic support with dobutamine was started. A cardiac magnetic resonance imaging was performed, which confirmed biventricular cardiomyopathy and described a non-ischemic zone of fibrosis. Because of the amnestic information on rash and swelling of the ankle, a microbiological testing was performed, which revealed a positive finding of IgM antibodies to Rickettsia conorii and Rickettsia typhi. An infectious disease specialist was consulted, and it was established that the patient had been in contact with people who were in an area with a known endemic rickettsia infection. Doxycycline was administered for 14 days. Two months after the first presentation of heart failure NT-proBNP values were normal. Echocardiography showed a marginally dilated left ventricle with an ejection fraction of 55% and a mild mitral regurgitation. **Conclusion**: In myocarditis, patients usually develop tiredness, chest discomfort and dyspnoea which may progress to cardiogenic shock or development of arrhythmias. If timely diagnosed myocarditis caused by rickettsiosis is treatable with favorable outcomes.

Vedrana Baraban, Nika Srb, Ninoslava Vonić

**Introduction**: Studies show that even though the prevalence of depressive disorders varies worldwide, patients who have experienced heart failure (HF), have higher rates of depressive and anxious disorders than in the general population. (1) However, this made us wonder is the reverse also true. Therefore, the aim of our study was to find if depressive disorders lead to higher incidence of heart failure, since therapy for depressive disorders is prescribed often and without a psychiatrist’s recommendation. **Patients and Methods**: Patients who came into the emergency department of the University Hospital Centre Osijek, were included in this study. The inclusion criteria was heart failure as the primary diagnosis. Data was collected about their gender, age, chronic therapy, diabetes mellitus (DM) and whether this was their first heart failure. Data on therapy for depressive (F32-F33), anxious (F40-F41) disorders and insomnias (F51) were analyzed. The study was conducted from January 2024. to March 2025. **Results**: The overall number of examinees, included in this study was 146, out which most were male 74 (50.68%). Therapy for depressive disorders was taken in 41 (28%) of all the examinees and the most common drug was alprazolam. Diabetes mellitus was prevalent in 63 (43.15%) examinees. This was the first heart failure for 59 (41.78%) of them and 20 (33.89%) of those examinees were diabetics. Therapy for depressive disorders was taken by 24 (40.67%) of the first time HF examinees, and there were 11 (7.53%) first-time heart failure patients with diabetes mellitus. **Conclusion**: The incidence of depressive disorders rises after experiencing heart disorders, therefore after heart failure as well. We aimed to prove that taking medication for depressive disorders, with or without comorbidities, leads to higher incidence of HF. However, we did not find higher levels of depressive and anxious disorders among first time heart failure patients in our study. This could also be because not all the examinees admitted to taking therapy, since social stigmas around these medications still exist. Therefore, a bigger study that would include more examinees and over a longer period, should be conducted to get a better insight into these disorders.