Cardiologia Croatica. 2023;18(11-12)

Dominik Buljan, Anđela Jurišić, Marin Viđak, Šime Manola, Ivana Jurin

**Introduction**: Urinary tract infections (UTIs) can contribute to adverse cardiovascular events due to systemic inflammation process. Patients with heart failure (HF) represent fragile population with increased risk of heart failure accutization as well as cardiovascular death. (1) Sodium glucose cotransporter-2 (SGLT-2) inhibitors have been proven to reduce adverse cardiovascular events among patients with chronic heart failure with reduced ejection fraction (HFrEF), chronic renal disease as well as patients with diabetes mellitus type 2 (T2D). Otherwise SGLT-2 inhibitor-induced glycosuria is hypothesized to increase the risk of UTIs so we assessed the risk of UTIs associated with SGLT-2 inhibitors depending on used SGLT-2 inhibitor, dapagliflozin or empagliflozin. **Patients and Methods**: We conducted a prospective cohort study using data from register of our patients treated with SGLT-2 inhibitors. From a base cohort of patients with UTIs we constructed two comparative cohorts wherein the exposure contrast was defined as usage of SGLT-2 inhibitors type. For comparison we used chi-squared distribution. **Results**: There were 75 patients with diagnosed UTIs during the study and 23 of them had UTIs in medical history before initiation of SGLT-2 inhibitor. Patients were elderly, predominantly female (56%) and with T2D or prediabetes in anamnesis (72%). 44 patients were treated with dapagliflozin while 31 were treated with empagliflozin. Among 30 patients SGLT-2 inhibitors were discontinued during the study, mostly due to UTIs (80%). Median of time between initiation and discontinuation of SGLT-2 inhibitors was 113 days. **Conclusion**: There is not statistically significant difference of UTIs among patients depending on which of two compared SGLT-2 inhibitors they are treated with (p=0.1659).

Nikola Škreb, Filip Lončarić, Anne Bonnin, Hector Dejea, Ivana Ilić, Hrvoje Gašparović, Boško Skorić, Bart Bijnens, Davor Miličić, Ivo Planinc, Maja Čikeš

**Background**: Endomyocardial biopsy (EMB) is the gold standard in heart transplantation (HTx) follow-up, with samples commonly fixed with formalin, and then embedded in paraffin for histology analysis. Recently, EMB samples have been scanned with synchrotron X-ray phase-contrast imaging (X-PCI) to assess graft rejection. (1) We aim to compare imaging time efficiency and image quality between formalin-fixed and paraffin-embedded samples to determine the optimal scanning methodology. **Methods**: Three adult patients undergoing EMB after HTx were included. EMB samples were initially stored in formalin and imaged by X-PCI at the Paul Scherrer Institute TOMCAT beamline (Villigen, Switzerland). On site samples were scanned in glass tubes in deionised, degassed water, and then embedded in paraffin, positioned on a holder, and scanned again using a multi-scale beamline set-up. Imaging time efficiency was measured by on-site sample preparation and scan time, and image quality was assessed with signal-to-noise ratio (SNR) and pixel resolution. Post-processing comparison included fibrosis quantification (using Ilastik for segmentation and Fiji for calculating the average percentage of collagen in 3 selected areas) and graft-rejection grading (assessed by two blinded observers based on the ISHLT 2004. criteria) (2). **Results**: Scanning F1-F3 and P1-P3 samples produced the same imaging resolution, while F1-F3 samples exhibited higher SNR values (clearer sample visibility) (**Table 1**). On site preparation and scan time were shorter with P1-P3 samples. Fibrosis quantification produced similar results in all samples, with F1-F3 showing slightly higher collagen percentage compared to the corresponding P1-P3 samples (**Table 1** and **Figure 1**). Samples F1 and F2 were graded as 1R, with others classified as 0R (ISHLT 2004.) (**Table 1**). ### TABLE 1: Imaging time (including preparation and scanning), technical parameters and imaging data analysis between the two sample preparation methodologies. | | | **Imaging time efficiency** | **Imaging time efficiency** | **Technical image quality** | **Image post-processing analysis** | **Image post-processing analysis** | | --- | --- | --- | --- | --- | --- | --- | | Sample | Methodology | On-site preparation time (min:sec) | Scan time (min:sec) | SNR (dB) | Average percentage of collagen in 3 selected areas (%) | Rejection grading (ISHLT 2004. criteria) | | F1 | Formalin | 3:58 | 49:08 | 112,16 | 0.34 | 1R | | P1 | Paraffin | 0:17 | 6:34 | 72,86 | 0.21 | 0R | | F2 | Formalin | 4:13 | 37:24 | 119,39 | 0.16 | 1R | | P2 | Paraffin | 0:20 | 12:03 | 54,65 | 0.11 | 0R | | F3 | Formalin | 4:21 | 49:08 | 112,19 | 0.37 | 0R | | P3 | Paraffin | 0:32 | 12:08 | 56,72 | 0.12 | 0R | FIGURE 1. Left side of the figure showing X-PCI images of formalin samples and the right side of the figure showing X-PCI images of the same samples in paraffin. Both set of samples are marked with the corresponding tissue areas for the collagen segmentation and quantification (collagen shown in light blue). **Conclusion**: Embedding EMB samples in paraffin is more time efficient in terms of on-site sample preparation and imaging. Results showed similar fibrosis quantification regardless of preparation methods, whereas rejection grading did not differ in clinically meaningful way. In conclusion, in initial testing using small sample number, no significant difference was found between the preparation methods. Supported by the Croatian Science Foundation (project no. UIP-2020-02-5572).

Jerko Arambašić, Dražen Mlinarević, Marko Stupin, Petra Zebić Mihić, Iva Jurić

**Introduction**: Primary heart tumors are rare, with the majority being benign. The most prevalent malignant cardiac tumor is angiosarcoma. It is characterized by aggressive growth and broad spectrum of clinical manifestations. The primary treatment approach for cardiac angiosarcoma primarily involves surgical excision, as it tends to exhibit significant resistance to chemo and radiation therapy. (1, 2) **Case report**: We present a 63-year-old female who reported chest discomfort three days prior to her hospital admission. An echocardiogram unveiled a tumor mass in the left atrium, measuring 37x74 mm, which extended into the left ventricle. Additionally, there were two smaller tumor masses located at the apex of the left ventricle and an additional mass in the left ventricular outflow tract, measuring 22x13 mm. Initially, there was no compromise in circulation. However, during initial hospitalization and subsequent evaluation, the patient developed obstructive shock due to the tumor masses. Urgent surgical resection was performed, which involved the removal of the masses. The pathology examination confirmed that the masses were consistent with cardiac angiosarcoma. The initial recovery was promising as echocardiography indicated the absence of intracavitary masses. However, a subsequent CT scan unveiled secondary lesions within the mesenteric soft tissue. Following a multidisciplinary consensus, chemotherapy involving paclitaxel was promptly initiated. Despite intensive treatment efforts, on the eleventh day following the surgical procedure, an echocardiogram revealed a tumor mass in the left atrium that extended into the left ventricle, closely resembling the original mass in size, causing the mitral stenosis with a mean pressure gradient of 22 mmHg. Regrettably, the patient chose to discontinue treatment, which ultimately resulted in a fatal outcome shortly after being discharged from the hospital. **Conclusion**: Cardiac angiosarcomas are exceptionally rare tumors, often displaying diverse clinical presentations. Despite diligent diagnostic and therapeutic efforts, their rapid growth and destructive nature can be challenging to grasp, acting discouraging for both physicians and patients. Nevertheless, it remains crucial to report cases of angiosarcoma to achieve improved treatments in the future.

Petra Radić, Krešimir Crljenko, Iva Klobučar, Zdravko Babić

**Introduction**: Sudden cardiac death (SCD) is a term that refers to the sudden cessation of cardiac activity. According to the literature, in the European Union the average annual incidence of out-of-hospital cardiac arrest (OHCA) ranges from 47.8 to 57.9 per 100,000 inhabitants. (1) **Case report**: 43-year-old female was hospitalized after an OHCA with initial rhythm of pulseless electrical activity. Resuscitation was performed by ambulance personnel. According to witnesses, the arrest took place in a church full of bystanders, but no appropriate cardiopulmonary resuscitation (CPR) was conducted. Upon arrival to the hospital, a brain CT scan and a CT pulmonary angiography were performed and there were no pathological findings. An emergency coronary angiography followed, which established normal epicardial coronary arteries. Echocardiography showed normal-size left ventricle, with a hypokinetic mid- and apical septum, and moderately reduced systolic function. Patient was admitted to the Cardiac Intensive Care Unit, where targeted temperature management was started. After withdrawal of analgosedation, the level of neuron specific enolase was determined, which was 201.3 µg/L. Neurological status-maintained Glasgow Coma Scale 3. For additional quantification of the neurological status, a control brain CT scan was performed, followed by a CT angiography of the cerebral arteries, which described the absence of arterial flow. An anesthesiologist was consulted, who declared the patient brain dead. An interview was conducted with family members who agreed on organ explantation. In view of the unexplained cause of the patient’s cardiac arrest, a pathohistological analysis of the heart was performed, in which no pathological substrate was found at the macroscopic or microscopic level. Considering that the patient was a mother of four, a genetic analysis was performed with a target screening panel for arrhythmias. The findings of the analysis are in process. **Conclusion**: Bystander CPR is of great importance for increasing survival from OHCA. However, the percentage of cases in which an individual receives bystander CPR is only 40% globally. (2) Systematic education of lay people on how to recognize sudden cardiac arrest and perform CPR should become one of the most important goals of public health actions.

Krešimir Crljenko, Petra Radić, Zdravko Babić

**Introduction**: Community acquired methicillin-resistant Staphylococcus aureus (MRSA) is a microbiological agent that can lead to life-threatening infections. MRSA infection is most often associated with people who have been in a hospital environment, but in recent years there has been an increase in infections caused by community acquired MRSA. MRSA is a frequent cause of skin infections, pneumonia, and osteomyelitis. However, only half a dozen cases of pericarditis caused by MRSA have been reported in the literature so far (1, 2). **Case report**: 65-year-old patient was hospitalized due to a significant circumferential pericardial effusion followed by elevated inflammation markers and fever (**Figure 1****)**. At the admission, severe microcytic anemia (Hb 78 g/L), compensated respiratory alkalosis (pH 7.49), acute renal insufficiency with elevated lactates (5 mmol/L), inflammatory parameters (CRP 262 mg/L) and troponin (hsTnI 3673 ng/L) were monitored in laboratory findings. Upon arrival at Cardiac Intensive Care Unit, a diagnostic pericardiocentesis was performed via apical access (**Figure 2**). Hemorrhagic-purulent content was obtained, in total 750 ml of liquid. Microbiological analysis was performed, and community acquired MRSA was isolated from the punctate. In the further course of treatment, a significant left-sided pleural effusion developed, for which a Rocket drain was placed, while MRSA was also isolated from the punctate. Given that MRSA was also isolated from the blood culture, a transesophageal ultrasound was performed, and endocarditis was ruled out. Targeted antimicrobial therapy with vancomycin and linezolid was started with complete recovery after 3 weeks of therapy. FIGURE 1. Chest CT scan showing large circumferential pericardial effusion. FIGURE 2. Chest CT scan after the pericardiocentesis. **Conclusion**: Perimyocarditis caused by MRSA is a rare condition especially in absence of recent in-hospital treatments. An infection like this often leads to a high patient mortality rate, especially if cardiac tamponade occurs. Community acquired MRSA has so far not been recognized as a frequent cause of community-acquired infections, but due to the increase in incidence, it is certainly a cause that we should keep in mind when treating patients with a clinical presentation of sepsis that occurred outside the hospital.

Josip Anđelo Borovac, Jelena Stipanović, Duška Glavaš

**Background**: The initiation and titration of guideline-directed medical therapies for heart failure with reduced ejection fraction (HFrEF) are essential for improving prognosis. However, data from several global registries indicate suboptimal adherence to these guidelines. (1, 2) This study aims to assess the utilization of pharmacologic and device therapies at discharge for HFrEF patients at the University Hospital Centre Split (UHC Split) and compare it with prescription patterns documented in the robust U.S.-based hospital registry known as Get With The Guidelines-HF (GWTG-HF). **Patients and Methods**: We conducted a cross-sectional observational study, comparing a consecutive sample of patients hospitalized with chronic HFrEF at the Cardiovascular Diseases Department of UHC Split in the year 2022-2023 with data published from the GWTG-HF Registry. (3) **Results**: **Figure 1** illustrates that the use of beta-blockers and ACE inhibitors/ARBs/ARNi medications was similar between the two registries, with the UHC Split HF registry reporting numerically higher prescription rates at discharge (95% vs. 89% and 78% vs. 68%, respectively). Significantly higher rates of MRAs and SGLT2 inhibitors were prescribed at discharge in the UHC Split HF Registry compared to GWTG-HF (80% vs. 41% and 78% vs. 20%, p<0.001). In terms of device therapies, cardiac resynchronization therapy was similarly utilized in both registries (13% vs. 10%, respectively), while a significantly greater rate of ICD implantations was observed in GWTG-HF compared to the UHC Split HF registry (23% vs. 8%, respectively). FIGURE 1. A proportion (%) of guideline-directed medical therapy and device therapies at discharge among patients with heart failure and reduced ejection fraction: comparison between the Get With The Guidelines Heart Failure Registry and University Hospital Centre Split Heart Failure Registry. ACE-I = angiotensin-converting enzyme inhibitor; ARB = angiotensin receptor blocker; ARNi = angiotensin receptor neprilysin inhibitor: GWTG = Get With The Guidelines; HF = heart failure; SGLT2 = sodium-glucose co-transporter 2; MRA = mineralocorticoid receptor antagonist; ICD = implantable cardioverter-defibrillator; CRT = cardiac resynchronization therapy; UHC = University Hospital Centre. **Conclusions**: The use of fundamental pharmacologic therapies for HFrEF at UHC Split is high and appears to exceed what is reported in the contemporary GWTG-HF registry. Conversely, the utilization of device therapies for HFrEF is relatively low at UHC Split and should be improved in the coming years.

Antonio Hanžek, Zvonimir Ostojić, Ivica Šafradin, Hrvoje Jurin, Tomislav Krčmar, Joško Bulum

**Introduction:** Percutaneous transfemoral transcatheter aortic valve implantation (pTF-TAVI) is an established method for the treatment of aortic stenosis in elderly patients. Despite improvements in this approach, access site-related vascular injury (ASRVI) remains a common complication (1). Although the implantation of a stent-graft (SG) in the common femoral artery (CFA) is not recommended, it is used to treat ASRVI despite the lack of clinical evidence (2). The aim is to evaluate the clinical outcomes in patients undergoing peripheral intervention for ASRVI related to pTF-TAVI. **Patients and Methods**: This single-center retrospective analysis included all patients undergoing pTF-TAVI who experienced ASRVI treated with either balloon angioplasty or SG implantation in the CFA. Patient demographics, comorbidities, as well as procedural data during TAVI were collected. Patient clinical follow-up (FUP) data was collected during FUP interviews. **Results**: A total of 197 patients underwent pTF-TAVI with MANTA as the primary vascular closure device. A total of 31 patients (15.7%) had ASRVI, the majority of whom (N=30, 96.7%) were successfully treated percutaneously and included in the study. The general patient and procedural characteristics are shown in **Table 1**. Of the 30 patients, 8 (26.6%) underwent balloon angioplasty and 22 (73.4%) underwent SG implantation. The mean FUP was 11 ± 6.3 months. The mean diameter of the balloon or SG used was 8.04 ± 1.13 mm. In the cases in which SG was implanted, most were balloon-expanding SG (N=19, 86.36). At FUP, 2 (6.67%) patients reported intermittent claudication, 6 (20%) had nonspecific limb pain, and the majority (N=23, 76.67%) had a walking distance of > 500 m. One patient initially treated with balloon angioplasty developed limiting claudication and underwent stent implantation. A comparison of clinical outcomes between patients treated with BD or SG is shown in **Table 2**. ### TABLE 1: General and procedural characteristics of patients undergoing percutaneous treatment of access site-related vascular injury after transfemoral transcatheter aortic valve implantation. | | **N=30** | | --- | --- | | Female - n (%) | 16 (53.33) | | Age – mean ± SD | 81.38 ± 6.55 | | Coronary artery disease*, n (%) | 17 (56.67) | | Atrial fibrillation, n (%) | 8 (26.67) | | Chronic obstructive pulmonary disease, n (%) | 4 (13.33) | | Chronic renal insufficiency**, n (%) | 13 (43.33) | | Peripheral artery disease, n (%) Occlusive PAD***, n (%) | 17 (56.67) 8 (26.67) | | Aortic valve replacement before TAVI, n (%) | 3 (10) | | Mean left ventricular ejection fraction ± SD | 51.72 ± 12.41 | | Self-expanding valve, n (%) | 20 (66.6) | | Mean valve size ± SD | 29.27 ± 6.23 | [†] *defined with coronary angiography; **defined as estimated glomerular filtration rate 2; ***Occlusive peripheral artery disease defined with CT angiography; SD standard deviation ### TABLE 2: Comparison of clinical outcomes of patients treated with balloon angioplasty or stent-graft implantation. | **Clinical outcome** | **General (N=30)** | **Balloon angioplasty (N=8)** | **Stent-graft implantation (N=22)** | | --- | --- | --- | --- | | **Intermittent claudication**, n (%) | 2 (6.66) | 1 (12.5) | 1 (4.54) | | **Non-specific limb pain**, n (%) | 6 (20) | 0 (0) | 6 (27.27) | | **Additional vascular procedure***, n (%) | 1 (3.33) | 1 (12.5) | 0 (0) | | **Walking distance** (m), n (%) < 100 100 – 200 – 500 500 or more | 1 (3.33) 2 (6.66) 3 (10) 23 (76.66) | 1 (12.5) 0 (0) 0 (0) 7 (87.5) | 0 (0) 2 (9.09) 3 (13.63) 16 (72.72) | | **Mortality****, n (%) | 4 (13.33) | 1 (12.5) | 3 (13.63) | | **CVI*****, n (%) | 1 (3.33) | 1 (12.5) | 0 (0) | | **Permanent pacemaker implantation**, n (%)**** | 1 (3.33) | 0 (0) | 1 (4.54) | [†] *Need for additional vascular intervention (percutaneous or surgery) during clinical follow-up, at the access site-related vascular injury site; **Mortality during clinical follow-up; ***Cerebrovascular insult during transcatheter aortic valve implantation procedure; ****Need for permanent pacemaker implantation after the transcatheter aortic valve implantation procedure. **Conclusion**: The results of our single-center analysis demonstrate that peripheral vascular interventions, including implantation of SG in CFA, provide satisfactory 1-year clinical outcomes in elderly patients undergoing pTF-TAVI and thus can be considered as a bailout method for the treatment of ASRVI. Patients initially treated with SG did not need reintervention as they had no lifestyle-limiting claudication.

Dubravka Šipuš, Mia Dubravčić Došen, Petra Mjehović, Dora Fabijanović, Nina Jakuš, Ivo Planinc, Marijan Pašalić, Hrvoje Jurin, Jure Samardžić, Daniel Lovrić, Maja Čikeš, Hrvoje Gašparović, Renata Žunec, Davor Miličić, Vesna Elveđi Gašparović, Boško Skorić

**Background**: Pregnancy in heart transplant (HT) recipients with episodes of rejection or positive donor specific antibodies (DSA) is discouraged by all recommendations due to higher risk of complications. Although there is paucity of data for DSA trend during pregnancy in HT recipients, there is evidence of improvement of symptoms during pregnancy in some autoimmune diseases (1-3). **Case report**: 23-year-old female who underwent HT due to post-myocarditis cardiomyopathy in June 2014, reported unplanned pregnancy in June 2022. She had a history of acute cellular (3R/3B) and humoral rejection (DSA major histocompatibility complex (HLA) class I, specificity A11, A30, B13, B35 and HLA class II, specificity DR3, DR15, DR51, DR52, DQ2, mean fluorescent intensity (MFI) 1000-13 300) in August 2017 which required mechanical circulatory support due to severe heart failure with multiorgan damage. She underwent pulse corticosteroid treatment, and 12 cycles of plasmapheresis with administration of rituximab, intravenous immunoglobulins, and thymoglobulin. After that she had persistent positive DSA, predominantly DQ2 (MFI up to 12200), and because of that was on quadruple immunosuppression (tacrolimus, mycophenolate (MMF), everolimus, prednisone) from October 2019 to July 2020 when MMF was discontinued due to gastrointestinal side effects. She had one more cellular rejection episode (2R/3A) in March 2022 which was treated with pulse corticosteroids. During pregnancy she was on tacrolimus, everolimus, and prednisone combination with closely monitoring of immunosuppressants concentrations. Echocardiography controls showed normal left ventricle function and mildly reduced right ventricle function, NT-proBNP was slightly elevated (493-823 ng/L) and DSA were in a downward trend which is shown in **Figure 1**. At 32+3 weeks of pregnancy, she was hospitalized due to early labor. The following day male baby was delivered by Caesarean section due to pathological cardiotocography (Apgar score 8/9). After delivery DSA remained weakly positive. FIGURE 1. Trend in donor specific antibodies (DSA) detected by the Luminex method from September 2017 to May 2023 expressed in mean fluorescent intensity (MFI). The patient had her first episode of humoral and cellular rejection in August 2017, and the second in March 2022. She was on quadruple immunosuppression (tacrolimus, mycophenolate, everolimus, prednisone) from October 2019 to July 2020. She was pregnant from June 2022 to February 2023. **Conclusion**: Although pregnancy in HT recipients with history of rejection and positive DSA is discouraged, positive outcome is possible with close monitoring of multidisciplinary team. Furthermore, we described a rare case of downward trend of positive DSA during pregnancy.

Petar Samardžić, Marijan Pašalić, Laura Rudelj, Hrvoje Jurin, Ivo Planinc, Maja Čikeš, Boško Skorić, Vedran Velagić, Jure Samardžić, Davor Miličić

**Introduction**: Direct oral anticoagulants (DOACs) are recommended in preference to vitamin K antagonists (VKA) in patients with atrial fibrillation (Afib) (1). There is no direct comparison between DOACs and substantial share of patients are still treated with VKAs due to certain comorbidities or financial reasons. Pulmonary vein isolation (PVI) is an established procedure to treat paroxysmal and persistent Afib but it increases thromboembolic risk (2). The aim of this study was to compare periinterventional platelet reactivity (PR) in Afib patients undergoing PVI on different chronic oral anticoagulation. **Patients and Methods**: PR was analyzed with Multiplate function analyzer in 136 patients undergoing PVI procedures in our institution. Blood samples were drawn before the procedure and on the following morning. ASPItest, ADPtest and TRAPtest were used as assays for the quantitative in vitro determination of PR triggered by arachidonic acid, adenosine diphosphate and thrombin receptor activating peptide-6, respectively. Fourty three patients (31.6%) were taking VKA, while 38 (27.9%), 29 (21.3%) and 26 (19.1%) patients were treated with dabigatran, rivaroxaban and apixaban, respectively. Edoxaban was not available during the investigation. **Results**: There was no significant difference in demographics between the groups. Patients on VKA had lower mean platelet volume (MPV) compared to patients on DOACs (9.9 vs 10.7-10.8 fL; p=0.020). Patients on xabans (rivaroxaban and apixaban) had lower baseline PR compared to VKA and dabigatran (**Table 1**). One day after PVI, there was no significant change from PR baseline in all four groups (**Figure 1**). ### TABLE 1: Study patient characteristics. | **Patients’ characteristics** | **VKA** **(n=43)** | **Dabigatran** **(n=38)** | **Rivaroxaban** **(n=29)** | **Apixaban (n=26)** | **p** | | --- | --- | --- | --- | --- | --- | | Age, years, mean (min-max) | 58.2 (36-73) | 61.7 (45-76) | 59.3 (42-77) | 60.1 (45-76) | 0.659 | | Men, n (%) | 31 (72.1) | 27 (71.1) | 22 (75.9) | 15 (57.7) | 0.487 | | BMI, kg/m2, mean (min-max) Paroxysmal Afib, n (%) | 29.2 (22.0-37.6) 32 (74.4) | 28.96 (21.4-38.1) 31 (81.6) | 27.68 (22.1-34.7) 20 (68.9) | 28.67 (23.1-38.3) 23 (88.5) | 0.560 0.307 | | Arterial hypertension, n (%) Hyperlipidemia, n (%) | 33 (76.7) 22 (51.2) | 30 (78.9) 23 (60.5) | 20 (68.9) 14 (48.3) | 24 (92.3) 12 (46.2) | 0.206 0.654 | | Diabetes mellitus, n (%) CrCl2DS2-VASc, mean (min-max) HAS-BLED, mean (min-max) | 1 (2.3) 2 (4.6) 1.72 (0-5) 0.77 (0-4) | 3 (7.9) 6 (15.8) 1.94 (0-6) 1.12 (0-3) | 4 (13.8) 4 (13.8) 2.07 (0-4) 1.00 (0-3) | 3 (11.5) 3 (11.5) 2.54 (0-5) 1.15 (0-4) | 0.310 0.343 0.095 0.238 | | Platelets, x109/L, mean (min-max) MPV, fL, mean (min-max) PR before PVI ASPItest, mean (U) ADPtest, mean (U) TRAPtest, mean (U) Periinterventional UFH administration, mean (IU) (min-max) | 227.8 (134-379) 9.9 (7.8-12.2) 35.4 28.9 37.5 11952 (7000-24000) | 214.8 (126-318) 10.7 (8.2-12.8) 29.1 23.6 37.4 13844 (7000-30000) | 214.8 (126-318) 10.7 (8.6-13.2) 14.2 16.9 24.3 11944 (5000-26000) | 217.6 (119-308) 10.8 (8.4-13.1) 20.1 13.4 22.1 13650 (9000-23000) | 0.896 0.020 0.022 0.049 0.251 0.203 | [†] Afib = atrial fibrillation; ASPItest = assay for determination of platelet function triggered by arachidonic acid; ADPtest = assay for determination of platelet function triggered by adenosine diphosphate; BMI = body mass index; MPV = mean platelet volume; PR = platelet reactivity; PVI = pulmonary vein isolation; TRAPtest = assay for determination of platelet function triggered by thrombin receptor activating peptide-6; UFH = unfractionated heparin FIGURE 1. Platelet reactivity change one day after pulmonary vein isolation in patients on different oral anticoagulation. ASPItest = assay for determination of platelet function triggered by arachidonic acid; ADPtest = assay for determination of platelet function triggered by adenosine diphosphate; VKA = vitamin K antagonist; TRAPtest = assay for determination of platelet function triggered by thrombin receptor activating peptide-6 **Conclusion**: Our results show that there is no significant effect of PVI on PR one day after the procedure regardless of chronic oral anticoagulation that was used. Lower basal PR was noted in patients on xabans compared to direct thrombin inhibitor and VKA. This antiplatelet mechanism is not fully understood but might be associated with multiple direct and indirect pathways which could contribute to potential differences in events between patients on certain DOACs. This warrants further investigation in seeking optimal DOAC choice for each patient. **Acknowledgement**: This study was part of SPARELIFE-CVD project funded by the Croatian Science Foundation.

Mihovil Santini, Lana Nikše, Pavao Mioč, Kristijan Đula, Siniša Car, Vjekoslav Radeljić, Nikola Bulj, Ivan Zeljković

**Introduction**: Spontaneous pneumomediastinum (SPM) is an uncommon entity mainly affecting young adult males with a tall, thin body habitus which can be rarely complicated with spontaneus pneumopericardium (SPP) (1, 2). **Case report**: 22-year-old female patient was examined in the Emergency Department (ED) due to an acute onset of dyspnoea and severe pain in the left side of the neck, chest and left arm, notably when leaning forward. She denied trauma, physical exertion, coughing, aspiration of foreign body, drug abuse or emesis. On admission, she was afebrile and physical examination revealed symmetric, clear breath sounds and inaudible heart beats without murmur or Hamman’s sign. An arterial blood gas analysis revealed mild hypocapnia: pH 7.443, PaO2 13.09 kPa, PaCO2 4.34 kPa, and SaO2 97%. The complete blood analysis was within normal range apart from lactate dehydrogenase (LDH= 333 U/L). The 12-lead ECG showed sinus tachycardia with normal axis, intervals within the normal range and no sign of low voltage (**Figure 1**). A chest X-ray showed pneumomediastinum and pneumopericardium (**Figure 2**), and subsequent chest multi-slice computed tomography confirmed extensive pneumomediastinum with pneumopericardium up to 5 mm in thickness, no signs of pulmonary bullae, or any structural abnormalities in the bronchi or the oesophagus. Echocardiography was done using subxiphoid projection showing no pathology and no hemodynamic repercussions due to pneumopericardium. She was hospitalized and the therapy was absolute bed rest, peroral analgesia and nasal oxygen supply (4 L/min). During hospitalization she was hemodynamically stable and afebrile, therefore no antibiotics were prescribed. The follow-up chest X-ray done 7 days after, showed a complete resolution of SPM and SPP. Thus, she was discharged with a recommendation to avoid physical activity for the next 2 months. At 2-month follow-up visit she was symptom free, with no signs of SMP or SPP (**Figure 3**). FIGURE 1. 12-lead electrocardiogram recorded sinus tachycardia with no signs of low voltage. FIGURE 2. The chest X-ray finding indicating suspected pneumomediastinum and pneumopericardium. FIGURE 3. The follow-up chest X-ray after 2 months showed no signs of pneumomediastinum or pneumopericardium. **Conclusion**: SPM and SPP are benign diseases with low incidences in a young, otherwise healthy adults. When evaluating a young adult in the ED, who presents with chest pain and dyspnoea, it is important to include SPM and SPP in the differential diagnosis if there is reasonable clinical doubt, in order to establish an early diagnosis and avoid potential complications.

Petra Grubić Rotkvić, Lucija Jedvajić, Nino Tičinović, Mislav Puljević, Majda Vrkić Kirhmajer

**Introduction**: Buerger disease or thromboangiitis obliterans (TAO) is non-atherosclerotic segmental inflammatory and occlusive vessel disease of unknown etiology. It affects small and medium-sized arteries and veins of the limbs, typically occurring in young male smokers. Involvement of visceral arteries is rare. The diagnosis relies on clinical presentation, radiological findings and exclusion of other clinical entities. The main treatment approach is smoking cessation (1-3). **Case report**: 34-year-old-man, smoker, was admitted to due to recent abdominal pain, mainly postprandial, without signs of peritonitis. During the period of several weeks he has lost about 5 kg. He noticed a spontaneous appearance of small wounds on his big toes that did not heal and reported intermittent claudication for the last couple of years that now progressed to rest pain. Upon physical examination, we observed a lividity on the soles of both feet and small areas of necrosis on big toes. Distal arterial pulsations were absent. Computed tomography angiography (CTA) of abdominal aorta branches showed a thrombotic occlusion of the celiac trunk and the proximal section of the lienal artery without intestinal infarction while CTA of leg arteries revealed a segmental occlusion of both-sided peroneal and tibial arteries (**Figure 1** and **2**Figure 2). No significant abnormality was found in blood tests, thrombophilia screening was negative, while potential cardioembolism was ruled out. Considering the patient’s history of smoking, younger age, clinical presentation and angiographic findings of segmental occlusions of the lower leg arteries along with the presence of corkscrew collateral vessels, we made a diagnosis of TAO. The patient has immediately been started on heparinization and antiaggregation, statins, analgesics and a customized diet plan. Balloon angioplasty of both legs was performed in two stages. During follow-up, we observed favorable outcomes: reduction in leg and abdominal pain, spontaneous recanalization of the splenic artery and stable body weight (**Figure 3**). Due to involvement of the splanchnic circulation, the patient was maintained on warfarin. FIGURE 1. Computed tomography angiography of abdominal aorta branches showing the occlusion of the celiac trunk. FIGURE 2. Digital subtraction angiography of lower extremities showing corkscrew collateral vessels (yellow arrows), the fibular artery (blue arrow) and the anterior tibial artery (red arrow). FIGURE 3. Ankle-brachial index before (a) and after (b) percutaneous revascularization showing improvement. **Conclusion**: Abdominal angina in young smokers should raise suspicion of TAO. Anticoagulants in visceral involvement could improve the prognosis of TAO patients.

Zdravko Babić, Krešimir Crljenko, Dorijan Babić, Marin Pavlov

**Goal**: Determination of 20-year trends in demographic characteristics, frequencies of main and other diagnoses, risk factors, type and number of admissions, Cardiac Intensive Care Unit (CICU) and hospital stay, employed therapeutic agents and procedures, as well as outcomes including mortality. **Patient and Methods**: Data from medical records and electronic hospital information system on all patients hospitalized in CICU University Hospital Centre „Sestre milosrdnice“, Zagreb, Croatia during March 2003, March 2013 and March 2023 were investigated. Descriptive data are presented as medians and interquartile ranges or counts and frequencies. Chi-square test was used for categorical variables, Kruskal-Wallis H test for continuous variables. Two-tailed significance tests were performed, and p<0.05 was considered significant. **Results**: In investigated period, a total of 304 patients were hospitalized in CICU, 64.8% were male, median age was 68 years (59-78). Number of admissions (74 vs. 87 vs. 143 per month), especially from referral hospitals (1.4 vs. 28.7 vs. 34.3%, p<0.01) and patients with ST-elevation myocardial infarction (STEMI) (6.8 vs. 31.0 vs. 28.7%, p<0.01) increased over time. Use of echocardiography, mostly bedside, increased (33.9 vs. 56.5 vs. 65.7%, p<0.01), as well as utilization of percutaneous coronary intervention (PCI) (35.6 vs. 61.2 vs. 67.8%, p<0.01). The use of drugs depended on contemporary international guidelines and drug availability (eptifibatide 0.0 vs. 10.6 vs. 7.0%, p<0.05, LWMH 11.9 vs. 69.6 vs. 72.0%, p<0.01). For antibiotics (3.4 vs. 18.8 vs. 22.9%, p<0.01), an increase followed the frequency of infections. Median time CICU (59 vs. 43 vs. 22 hours, p<0.01) and in-hospital stay (10 vs. 7 vs. 3 days, p<0.01) decreased during investigated period (**Figure 1** and **2**Figure 2), similar to mortality (9.5 vs. 5.7 vs 2.8%, p<0.01). FIGURE 1. Trends in Cardiac Intensive Care Unit length of stay over time. 1 – MARCH 2003; 2 – MARCH 2013; 3 – MARCH 2023; CICU – CARDIAC INTENSIVE CARE UNIt FIGURE 2. Trends in hospital length of stay of Cardiac Intensive Care Unit patients over time. 1 – MARCH 2003; 2 – MARCH 2013; 3 – MARCH 2023 **Conclusion**: The results indicate an increasing trend in the number of patients hospitalized in the CICU (especially those with STEMI) with a shortening of stay, and a decrease in mortality. The number of patients who underwent echocardiographic diagnostics and PCI, as well as those treated with antibiotics, increased. As for trends in the use of mechanical circulatory and respiratory support, and continuous renal replacement therapy, a larger number of examined patients is required to reach statistical significance. (1-3)

Dora Gašparini, Igor Klarić, Viktor Ivaniš, Dijana Travica Samsa, Viktor Peršić, Tamara Turk Wensveen

**Introduction**: Synthetic anabolic androgenic steroids (AAS), compounds mimicking the action of endogenous testosterone in enhancing training performance, have been extensively studied during the last century. AAS abuse has become a major public health concern with an estimated worldwide lifetime prevalence of 1–5% (1). Long-term administration of AAS in supraphysiological doses may have detrimental effects on the cardiovascular system, presumably through direct action on cardiac myocyte androgen receptors. In severe cases, life-threatening conditions such as myocardial infarction, aortic dissection or cardiomyopathy, particularly dilated cardiomyopathy as the most common form, may occur. Hereby, we report a rare case of AAS-induced cardiomyopathy with an emphasis on the multidisciplinary approach. **Case report**: 46-year-old male bodybuilder presented with exercise intolerance unrelated to maximum training load and post-workout water retention 6 weeks before the visit. History revealed previous administration of testosterone enanthate 500 mg every 8 to 12 days during the period of 4 years. After a month-long cessation, he started taking testosterone undecanoate 1000 mg in 6-week intervals. The cardiorespiratory part of the physical examination showed normal findings and blood pressure of 125/80 mmHg. The patient was of athletic build with no signs of increased hairiness and no palpable testicular mass. An electrocardiogram showed a normal electrical axis and sinus bradycardia. Laboratory assessment (**Table 1**) was followed by echocardiography which was in accordance with the diagnosis of AAS-induced cardiomyopathy (**Figure 1**). Further diagnostic assessment of osteoporosis, hepatic, renal and psychological complications was performed. Conclusion: Long-term administration of AAS with unknown pharmacokinetic and pharmacodynamic properties should be considered as a cause of newly diagnosed cardiomyopathy, especially in previously healthy individuals with an athletic background. ### TABLE 1: Laboratory evaluation revealed unmeasurably high testosterone levels with a subsequent suppression of the pituitary-testicular axis. | **Pituitary-testicular axis** | **Pituitary-testicular axis** | **Cardiac markers** | **Cardiac markers** | **Liver markers** | **Liver markers** | | --- | --- | --- | --- | --- | --- | | Testosterone | > 52.05 nmol/l | Troponin I | 18 ng/l | AST | 57 U/l | | SHBG | 65.54 nmol/l | hs-Troponin T | 13 ng/l | ALT | 71 U/l | | FSH | <0.1 IU/l | NTproBNP | 48 ng/l | | | | LH | <0.1 IU/l | CK; CK-MB | 317 U/l; 7.9 μg/l | | | [†] ALT, alanine aminotransferase; AST, aspartate aminotransferase; CK, creatine kinase; FSH, follicle-stimulating hormone; hs, high sensitivity; LH, luteinizing hormone; MB, myocardial band; SHBG, sex-hormone binding globulin. FIGURE 1. Echocardiographic assessment of anabolic steroid-induced cardiomyopathy. Representative echocardiogram images for the left ventricle (upper panel), and the right ventricle (lower panel) with corresponding values. Transthoracic echocardiography was performed using Vivid E95 Cardiac Ultrasound (GE Healthcare, Chicago, IL, USA). 3D-LVEF, three-dimensional left ventricular ejection fraction; E/E’, early mitral inflow velocity to early diastolic mitral annulus velocity ratio; FAC, fractional area change; GLS, global longitudinal strain; LVEDd, left ventricular end-diastolic diameter; MAPSE, mitral annular plane systolic excursion; RVTD, right ventricular transverse diameter; TAPSE, tricuspid annular plane systolic excursion.

Mihovil Santini, Sandra Jakšić Jurinjak, Vlatka Rešković Lukšić, Jadranka Šeparović Hanževački, Martina Lovrić Benčić

**Introduction:** Sarcoidosis is a multisystem granulomatous disease of unknown etiology. Cardiac involvement is present in 20-30% of all patients (1). In cardiac sarcoidosis myocardium and endocardium are typically affected, while pericardial involvement and supraventricular arrhythmias are less common (1-3). **Case report:** 55-year-old female patient was diagnosed in June 2022 with mediastinal and hilar lymphadenopathy as an incidental finding during evaluation for dyspnea and episode of paroxysmal supraventricular tachycardia. Radiological findings, bronchoscopy and further workup confirmed the diagnosis of sarcoidosis. Quantiferon test was negative and was done to ruled out tuberculosis. Echocardiography verified the hyperechogenic calcified pericardium with “septal bounce” sign and constrictive hemodynamics (**Figure 1**). In the June 2023, a CT coronary angiography was performed, which revealed an almost completely thickened (up to 15 mm) and diffusely calcified pericardium, sparing the posterior contour of both atria and the apex of both ventricles, which compresses the ventricles with a clear disturbance of the diastolic function of the heart (**Figure 2**). There was no pericardial effusion or coronary artery calcification. Due to heart failure, a right-sided heart catheterization was performed, confirming the ventricular interdependence phenomenon and the diagnosis of constrictive pericarditis. Magnetic resonance of the heart did not prove a clear signs of myocardial sarcoidosis, but showed signs of constrictive pericarditis, with potential pericardial sarcoidosis (**Figure 2**). Metabolically active lymph nodes of the neck, mediastinum, lung hilum, axilla, retroperitoneum and inguinal were observed with a subsequent PET-CT. There were no focal or diffuse pathological accumulation of activity along the calcified pericardium. Based on the performed diagnostic workup, an elective partial pericardiectomy was indicated. FIGURE 1. A. The four-chamber view of the heart showed calcified pericardium with a septal bounce phenomenon B. Three chamber view of the heart showed calcified pericardium. C. Doppler ultrasound showed reverse flow in the hepatic veins. FIGURE 2. A. CT coronary angiography showed an almost completely thickened (up to 15 mm) and diffusely calcified pericardium. B. Magnetic resonance of the heart showed signs of constrictive pericarditis, with potential pericardial sarcoidosis. **Conclusion:** We report a rare case of systemic sarcoidosis, presented with constrictive pericarditis and paroxysmal supraventricular tachycardia. The most likely etiology of constrictive pericarditis is pericardial sarcoidosis. Determining the etiology of constrictive pericarditis is challenging, indicating in some cases partial or total pericardiectomy.

Petra Mjehović, Mia Dubravčić Došen, Andrija Nekić, Dora Fabijanović, Nina Jakuš, Ivo Planinc, Marijan Pašalić, Hrvoje Jurin, Jure Samardžić, Daniel Lovrić, Maja Čikeš, Davor Miličić, Hrvoje Gašparović, Željko Čolak, Boško Skorić

**Introduction**: Immune mediated vascular damage is a major risk for cardiac allograft vasculopathy (CAV). Anti-thymocyte globulin (rATG) provides intense immunosuppression early after HTx. The role of rATG on CAV prevention still remains controversial. (1, 2) While lymphopenia reflects the therapeutic effect of rATG, a decrease in platelet count is deemed as an adverse effect. We hypothesize that lower lymphocyte and platelet counts following rATG induction may be associated with less risk for the development of CAV. **Patients and Methods**: We performed a retrospective single-centre study in patients transplanted between 2010 and 2017. All pts received rATG induction therapy for 5 days. Absolute lymphocyte count (ALC) and platelet count were assessed on days 0, 7, 14, and 21 following HTx. The primary outcome was the diagnosis of CAV grade ≥1, during 3 years of follow-up. **Results**: A total of 133 pts were transplanted in this period. During first three years after HTx 18.8% of pts developed CAV≥1. Those pts had significantly older donors (47 (IQR 40-49) vs 37 (IQR 28-49), p=0.02), higher median platelet count on day 7 (140 x 109/L (IQR 103-156 X 109/L) vs 105 x 109/L (IQR 68-147 x 109/L), p=0.04), higher median lymphocyte count on day 14 (335 x 109/L (IQR 184-314 x 109/L vs 215 x 109/L (IQR 105-401 x 109/L), p=0.02), higher median leukocyte count on day 21 (810 x 103/µL (IQR 600-960 x 103/µL) vs 660 x 103/µL (IQR 500-794 x 103/µL), p=0.03), and higher median platelet count on day 21 post HTx (237 x 109/L (IQR 195-278 x 109/L) vs 193 x 109/L (IQR 148-226 x 109/L), p=0.03) than the pts without CAV. Univariate binary logistic regression showed that CAV was associated with older donor age, lymphocyte count ≥200 x 109/L on day 7, higher platelet count on day 7 and 21, and higher leukocyte count on day 21. In multivariable binary logistic regression, the adjusted risk of CAV was significantly higher for pts with older donors (p=0.027), and higher platelet count on day 21 (p=0.04). **Conclusion**: Lower platelet count after induction with rATG was associated with lower incidence of CAV. Association with lower lymphocyte count in univariate logistic regression did not reach significance in multivariable analysis. The controversial reports on clinical benefit from rATG induction on CAV prevention could be explained by variable platelet response of the recipients to the therapy.

Vedran Pašara, Luka Perčin, Ivan Prepolec, Borka Pezo-Nikolić, Davor Puljević, Davor Miličić, Vedran Velagić

**Background**: Ventricular tachycardia (VT) commonly occurs in patients with structural heart disease, either of ischemic or non-ischemic nature. Treatment options include various antiarrhythmic drugs (AADs) and implantable cardioverter-defibrillators (ICDs). When AADs fail, radiofrequency (RF) catheter ablation is a valuable treatment option for patients with recurrent VT. (1) This single-center ten-year retrospective study aimed to assess acute and chronic success rates of RF catheter ablation and to identify predictors of VT recurrence and patient survival. **Patients and Methods**: We analyzed all consecutive patients with structural heart disease who underwent RF catheter ablation of VT in our institution from 2011 to 2021. Data were collected from existing hospital electronic medical records. **Results**: A total of 72 patients (89% male, mean age 62 years, 28% with non-ischemic cardiomyopathy, mean LVEF 35%) were included. Non-inducibility was achieved in 64.7% of cases. One year VT recurrence rate was 41.6%. Substrate ablation significantly reduced the frequency of ICD shocks (14% vs. 60%, p = 0.001). The overall one-year survival was 86%. In multivariate analysis, VT inducibility was an independent predictor of VT recurrence (p = 0.02; OR = 13.5; 95% CI = 1.46-124.7). Female gender was an independent negative risk factor for patient survival (p = 0.03; OR = 7.19; 95% CI = 1.22-42.6). **Conclusion**: Our data show that RF catheter ablation of VT can be a feasible treatment option for patients with frequent AAD-refractory VTs with acceptable acute and chronic success rates, even in mid-volume centers like ours. VT ablation can reduce the frequency of ICD shocks and improve patients’ quality of life. Institutional registry can help monitor and improve outcomes and provide valuable feedback.

Andrija Nekić, Ivan Prepolec, Vedran Pašara, Jakov Emanuel Bogdanić, Jurica Putrić Posavec, Domagoj Kardum, Zvonimir Katić, Borka Pezo Nikolić, Mislav Puljević, Davor Puljević, Davor Miličić, Vedran Velagić

**The goal:** The goal was to show results of a long-term follow-up following the cryoballoon pulmonary vein isolation in patients with atrial fibrillation (AF). **Patients and Methods**: A total of 126 patients were included in the study of which 77.0% had paroxysmal atrial fibrillation (PAF). Successful treatment outcome was defined as AF recurrence- free survival with stabile sinus rhythm during a 5-year period after the procedure. A treatment failure was defined as symptomatic AF recurrence with ECG verification (12 lead ECG or AF lasting >30s by Holter EKG). The patients on antiarrhythmic therapy and those that underwent a redo pulmonary vein isolation procedure were also included. **Results**: Following cryoballon pulmonary vein isolation in a 5-year period 52.4% of patients were in stable synus rhythm without AF recurrence. With redo pulmonary vein procedures a total of 61.9% of patients was without AF recurrence. Together with antiarrhythmic drugs 57.9% of patients was in sinus rhythm without AF recurrence in a 5-year period. With redo pulmonary vein isolation and antiarrhytmic drugs a total of 73.8% of patients were without AF recurrence. There was statistically significant difference regarding AF recurrence between patients that underwent redo pulmonary vein isolation and those that did not (p=0.006). In patients with PAF, 62.9% remained without AF recurrence and 79.4% who underwent redo procedure. In patients with persistent atrial fibrillation (PersAF), 41.4% was without AF recurrence and 55.1% that underwent a redo procedure. The difference between PAF and PersAF was statistically significant (p=0.009). **Conclusion**: Data from our centre show good long-term results of cryoballoon pulmonary vein isolation in patients with atrial fibrilation. The procedure is especially successful in patients with PAF. (1) The use of redo procedures is justified as it increases long-term success rate.

Antonio Hanžek, Boško Skorić

**Introduction:** Psoriasis has been reported as an unusual cause of high-output heart failure (HF), and high mixed venous oxygen saturation (SvO2) due to changes in the skin microcirculation, including vasodilatation and functional arterio-venous shunting that may increase cutaneous blood flow up to 10 times (1, 2). We hypothesize that due to abnormal redistribution of blood flow between skin and other organs, using SvO2 may represent an obstacle to an accurate measurement of cardiac index (CI) by the Fick principle in patients with a combination of severe psoriasis and HF with reduced ejection fraction (HFrEF). **Case report**: 54-year-old male patient was admitted in February of 2023 with acute decompensated biventricular HF, caused by dilated cardiomyopathy. The patient had signs and symptoms of volume overload and low cardiac output, and a skin exam revealed severe psoriasis. He was treated with intravenous diuretics, inotropes, and continuous hemofiltration. Right heart catheterization (RHC) showed pulmonary hypertension with elevated filling pressures of both ventricles and normal pulmonary vascular resistance. Unexpectedly, SvO2 was around 80%, and the calculated CI using the Fick formula was high (4.4 L/min/m2). Diagnostic work-up excluded an intracardial shunt. As the calculated CI was assumed to be inaccurate due to a sampling blood error, the RHC was repeated. Again, CI was high (5.5 L/min/m2). Systemic vascular resistance (SVR) was surprisingly normal even though patient presented with low output symptoms. We hypothesized that the redistribution of blood from vasoconstricted areas in hypoperfused organs toward vasodilated psoriatic skin with functional arterio-venous shunting was responsible for both the total sum of normal SVR and high SvO2. The RHC was repeated, but this time by using the thermodilution method which finally confirmed low CI (1.8 L/min/m2). **Conclusion**: This report shows that in the case of a combination of HFrEF and severe psoriasis, the Fick principle is inaccurate for the calculation of CI. It also highlights the importance of using alternative methods in the case of contradictory results, given the fact that each method uses different physical principles that become useful in situations when these principles are compromised by the nature of the underlying disease.

Aleksandar Trbović

Atherosclerotic cardiovascular diseases (ASCVD) present a global public health challenge with potentially fatal consequences. The key factor in the prevention of ASCVD is the control of LDL cholesterol (LDL-C) levels. Herein we present two important agents for the reduction of elevated LDL-C levels: rosuvastatin and ezetimibe. Rosuvastatin is a potent HMG-CoA reductase inhibitor that considerably lowers LDL-C, increases HDL cholesterol, and reduces triglyceride levels. Ezetimibe, on the other hand, inhibits the intestinal absorption of cholesterol. The combination of these drugs enables achieving target cholesterol levels. Although statins are the cornerstone therapy for LDL-C reduction, they often need to be combined with ezetimibe, especially in high-risk patients. Research shows that this combination can significantly reduce the risk of cardiovascular events. Despite the guidelines, achieving target LDL-C levels is often challenging in practice. A statin/ezetimibe combination may be key to achieving set targets and improving cardiac health. Control of LDL-C levels is key in the prevention of ASCVD. An integrated approach, including healthy diet, exercise, and pharmacotherapy, is crucial in fighting this global public health challenge.

Davor Miličić

## Dear Colleagues, Welcome to the 7th Cardiology Highlights – International Update Meeting in Cardiology. It was first held in 2009, as the youngest in the family of ESC Update Meetings (Davos, Rotterdam, Rome, Dubrovnik). Now, after the COVID outbreak, it seems the Dubrovnik Cardiology Highlights is the last to remain from the ESC Update Meetings family. The Congress is aimed at being an update on contemporary cardiology, primarily setting the stage for the European Society of Cardiology, by presenting the newest guidelines, position papers, and ESC policies toward reducing the burden of cardiovascular disease. The current Cardiology Highlights present many important updates on contemporary cardiology as well as some intriguing topics. Additionally, selected original contributions have been published in the newest issue of Cardiologia Croatica, some of which are going to be presented as oral communications. The best of those will receive awards, as in our previous Highlights Meetings. Furthermore, two special sessions have been organized: The Lancet Regional – Europe – Session and the ACC Georgia – Croatia Chapter. The Lancet Session will discuss regional differences in cardiovascular health status in Europe, and the Georgia Chapter will interactively elucidate the consensus and controversies of the hottest topics in cardiovascular imaging. The WALTZ Session will bring together young cardiologists from Vienna, Athens, Ljubljana, Timișoara, and Zagreb. We will also cover some extremely interesting topics such as inflammation and atherosclerosis, biomarkers in cardiology now and in the future, the role of registries in contemporary cardiology, newest advances in heart failure, interventional cardiology, and interventional arrhythmology. This Meeting, in addition to providing an attractive overview of modern cardiology, should serve as an opportunity for interactive discussions and international networking. You will really enjoy the Meeting, the professional networking, and the beauty of Dubrovnik. Last but not least, we are proud that the Meeting is held, once again, under the patronage of the Croatian Academy of Sciences and Arts – the leading institution of Croatian scientific and cultural excellence. Thank you for joining us! With kindest regards, Prof. **Davor Miličić**, MD, PhD, FESC, FHFA, FACC Director, 7th Cardiology Highlights – International Update Meeting in Cardiology Vice President, Croatian Academy of Sciences and Arts President, Croatian Cardiac Society

Martina God, Marin Viđak, Ivana Jurin, Šime Manola

**Introduction**: The coexistence of heart failure (HF) with type 2 diabetes (T2D) is common and T2D is considered one of the risk factors for adverse outcomes in HF patients (1-3). Studies found conflicting results in terms of HF outcomes with some studies showing lower rates of HF hospitalization among glucagon-like peptide-1 (GLP1) receptor agonists users and others showing neutral effects on HF hospitalizations. We aimed to evaluate whether adding semaglutide to sodium-glucose cotransporter-2 (SGLT2) inhibitors benefits HF patients with T2D. **Patients and Methods**: This was a prospective observational study conducted at University Hospital Dubrava, Zagreb. We recruited patients presented with HF symptoms from May 2021 to August 2023. We collected data on gender, age, prescribed medications, body mass index, comorbidities, NT-proBNP, lipid and HbA1c levels, ejection fraction and number of hospitalizations. Categorical variables are presented as frequencies and percentages and continuous variables are presented as median and interquartile range (IQR). P values <0.05 were considered as statistically significant. Statistical analysis was performed using JASP software. **Results**: We collected data of 850 participants in total. 121 (14.2%) participants already had DM2 at the time of the study initiation, 42 (5%) were diagnosed with DM2 during the checkup and 145 participants had prediabetes (17%). Semaglutide was started in 72 participants. There was a reduction in BMI in both groups with more significant decrease in semaglutide group (0.3 in the non-semaglutide group and 2.2 in the semaglutide group, P < 0.0001). NT-proBNP levels were lower in the semaglutide group (881 vs 1945.4pg/mL, P<0.001) and HbA1c was reduced by 1.11 points (95% CI 0.55-1.69) in the semaglutide group and 0.35 (95% CI 0.26-0.44) in the non-semaglutide group. There was no change in the cholesterol, LDL levels or HF hospitalizations. **Conclusion**: Semaglutide offers significant metabolic advantages in patients with HF and TD2 by reducing glucose levels and body weight. Use of semaglutide should be facilitated in patients with TD2 as it decreases NT-proBNP and HbA1c levels. While yielding no difference in hospitalizations, adding semaglutide provides better control of cardiovascular risk factors. Future studies are needed to assess long term impact of semaglutide in HF and T2D patients.

Marin Viđak, Jasmina Ćatić, Jelena Kursar, Petar Lišnjić, Tomislav Šipić, Šime Manola, Ivana Jurin

**Background**: Heart failure (HF) societies classify LVEFs of 41–49% as mildly reduced ejection fraction (HFmrEF) (1, 2). HFmrEF is an intermediate HF type between HF with preserved EF (HFpEF) and HF with reduced EF (HFrEF), as it shares characteristics from both ends of the spectrum. HFmrEF is controversial due to LVEF changes and inter-rater variability (3, 4). Studies on HFmrEF are inconsistent and it is not clear whether HFmrEF is a transition or an independent clinical entity. No prospective studies have assessed the effect of therapy in patients with HFmrEF. Current evidence in patients with HFmrEF is based on post-hoc analyses of studies (3). **Patients and Methods**: This was a prospective observational study conducted at University Hospital Dubrava, Zagreb. We recruited patients presenting with HF symptoms from May 2021 to August 2023. We collected data on gender, age, drugs and adherence, comorbidities, NT-proBNP and HbA1c levels and EF. Categorical variables are presented as frequencies and percentages and continuous variables are presented as medians and interquartile ranges. P value 50% in 21 and decreased to <40% in 4 participants. EF has not changed in 26 participants. Level of NT-proBNP was 1.834pg/mL (95% CI 66-32,127) during initial visit and 651pg/mL (95% CI 44-12,555) at 12 months (p<0.001). HbA1c levels decreased from 6.3% (95% CI 5.3- 10.9) at the initial visit to 5,85% (95% CI 4.9-8.3) at 12 months (p<0.001). **Conclusion**: HFmrEF remains a mystery. Optimal medical treatment might improve EF or prevent it from deteriorating further in some patients, but long-term real-world data is needed.

Aleksandar Blivajs, Barbara Radovani, Lovorka Đerek, Diana Rudan, David Visentin, Gordan Lauc, Ivan Gudelj

**Introduction:** Coronary artery disease (CAD) is the most common cardiovascular disease (CVD), resulting from chronic inflammation of the coronary arteries due to the formation of atherosclerotic plaques, and its presence is a significant marker of adverse cardiovascular events. A growing body of research suggests that alterations in protein N-glycosylation are involved in the development of CVD through various mechanisms and have significant biomarker potential because of their sensitivity to changes that occur in the organism during inflammation-related conditions such as CVD (1-3). Our aim was to determine whether the N-glycome of total plasma proteins is associated with CAD, because N-glycans are known to alter the effector functions of proteins, which may enhance their inflammatory response in CAD. **Patients and Methods**: In this study, we analysed the N-glycome of plasma proteins isolated from patients who underwent coronary angiography and classified into patients with confirmed coronary atherosclerosis and patients with clean coronaries. Proteins were denatured and enzymatically deglycosylated, and the released and fluorescently labelled N-glycans were analysed by ultra-high performance liquid chromatography based on hydrophilic interactions with fluorescence detection (HILIC-UHPLC-FLR) (**Figure 1**). Because previous studies have shown evidence of sexual dimorphism in CVD and significant sex differences in the association of N-glycans with CVD risk, we performed sex-stratified analysis of plasma N-glycans. FIGURE 1. Representative chromatogram of 2-AB labelled plasma protein N-glycans separated by HILIC–UHPLC-FLR. The integration areas together with a major structure presented in each glycan peak are shown. **Results:** The results showed significant differences in plasma N-glycome composition in CAD. Lower abundance of complex biantennary galactosylated N-glycans with core fucose and, conversely, a higher abundance of highly branched (tri- and tetra-antennary) sialylated N-glycan structures with terminal fucose was shown to be associated with CAD. **Conclusion:** The obtained chromatograms shed light on the composition of plasma protein N-glycans in CAD and provided new insights into N-glycosylation changes in CAD. Overall, because of their sensitivity to changes that occur in an organism, protein N-glycosylation emerges as a significant factor in CAD and holds potential as a diagnostic tool, with glycan-based biomarkers showing promise for predicting cardiovascular health.

Petar Samardžić, Laura Rudelj, Ivo Planinc, Hrvoje Jurin, Vedran Velagić, Maja Čikeš, Boško Skorić, Davor Puljević, Jure Samardžić, Davor Miličić

**Introduction**: Pulmonary vein isolation (PVI) is an established procedure to treat atrial fibrillation (Afib) but it increases periinterventional thromboembolic burden (1). Literature provides ambiguous results about ablation effects on different hemostatic markers. The aim of this study was to assess the difference between two used PVI methods (cryoablation and radiofrequency ablation (RFA)) in postinterventional platelet reactivity (PR). **Patients and Methods**: We analyzed PR in 168 consecutive patients undergoing PVI due to Afib in our institution using Multiplate function analyzer. Blood samples for PR measurements were drawn prior to the procedure and the on the following morning. In total, 123 and 45 patients underwent cryoablation and RFA, respectively. There was no difference in demographics and baseline platelet parameters between the groups (**Table 1**). ASPItest, ADPtest and TRAPtest were used as assays for the quantitative in vitro determination of PR triggered by arachidonic acid, adenosine diphosphate and thrombin receptor activating peptide-6, respectively. ### TABLE 1: Baseline patient characteristics. | **Patients’ characteristics** | **Cryoablation (n=123)** | **Radiofrequency ablation (n=45)** | **p** | | --- | --- | --- | --- | | Age, mean years (min-max) | 58.3 (27-77) | 60.8 (45-78) | 0.17 | | Men, n (%) | 89 (72.3) | 27 (60.0) | 0.12 | | BMI, kg/m2, mean (min-max) Paroxysmal Afib, n (%) | 28.36 (22.0-38.2) 100 (81.3) | 28.96 (23.5-37.2) 38 (84.4) | 0.48 0.64 | | Arterial hypertension, n (%) Hyperlipidemia, n (%) | 86 (69.9) 61 (49.6) | 33 (73.3) 21 (46.7) | 0.67 0.74 | | Diabetes mellitus, n (%) Renal dysfunction, n (%) CHA2DS2-VASc, mean (min-max) HAS-BLED, mean (min-max) | 8 (6.5) 12 (9.7) 1.82 (0-6) 0.97 (0-3) | 3 (6.7) 4 (8.9) 1.91 (0-5) 0.82 (0-3) | 0.97 0.86 0.70 0.34 | | Platelets, x109/L, mean (min-max) MPV, fL, mean (min-max) PR before PVI ASPItest, U, mean ADPtest, U, mean TRAPtest, U, mean | 220.1 (108-339) 10.44 (8.2-13.2) 29.3 23.9 35.4 | 222.1 (138-379) 10.25 (8.1-12.4) 32.1 28.9 38.3 | 0.82 0.42 0.66 0.36 0.71 | **Results**: Postprocedurally, PR was significantly lower in both groups after 24 hours. There were no statistically significant differences in PR values between the groups on the next day in all three tests (ASPItest 23U v 25U p=0.75; ADPtest 20U v 25U p=0.24; TRAPtest 29U v 34U p=0.47) (**Figure 1**). FIGURE 1. Platelet reactivity change one day after pulmonary vein isolation. ASPItest - assay for determination of platelet function triggered by arachidonic acid; ADPtest - assay for determination of platelet function triggered by adenosine diphosphate; PVI – pulmonary vein isolation; RFA – radiofrequency ablation; TRAPtest - assay for determination of platelet function triggered by thrombin receptor activating peptide-6 **Conclusion**: Our results show that PR after PVI is lower after 24 hours regardless of the type of ablation. Insignificantly lower PR in cryo group might be due to less myocardial necrosis done with cryo compared to RFA. We hypothesize that the general similarity in PR drop could be predominantly a result of successful restoration of sinus rhythm in both groups which might be the prevailing factor in determining PR level in patients with Afib one day after ablation. These results should be confirmed with studies which would encompass early and late periinterventional PR measurements on a larger cohort of patients. ## Acknowledgments This study was funded by the Croatian Science Foundation.

Luka Antolković, Petar Lišnjić, Nikola Pavlović, Šime Manola, Ivana Jurin

**Introduction**: Patients with heart failure and reduced ejection fraction (HFrEF) and concomitant chronic obstructive pulmonary disease (COPD) have historically been undertreated across the spectrum of care, including medical and device therapy (1). The aim of this study was to evaluate implementation of quadruple therapy in patients with HFrEF and COPD as well as outcomes in terms of hospitalizations in patients with optimal medical therapy in real life conditions. **Results**: We identified 525 patients with HFrEF in our Registry, 59 of which also have COPD. Mean age of patients with COPD and HFrEF was 69.89±8.3 years, 81.5% were males, 69.5% had ischemic cardiomyopathy, 30.5% were NYHA II functional class and 67.8% were NYHA III of IV functional classes. Mean age of HFrEF patients but without COPD was 67.8±12 years, 74% were males and 52.3% had ischemic cardiomyopathy, 46.9% were NYHA II functional class and 47.6 were NYHA III or NYHA IV functional classes. 33.9% of patients with COPD and HFrEF were taking optimal medical therapy while 42.1% patients without COPD were taking quadruple medical therapy (OR 0.71, 95% CI 0.4-1.22). Of note is that patients with HFrEF and COPD despite optimal medical therapy were more likely to be hospitalized during follow-up (RR 1.7; 0.9239-2.93, P=0.06) of 743.84 days. **Conclusion**: Despite established benefits of quadruple medical therapy, including beta-blockers in COPD patients with HFrEF, data from our Registry suggest that optimal medical therapy, including beta-blockers is still underutilized in this fragile population.

Vjekoslav Radeljić

Both non-ischemic cardiomyopathy and extensive atherosclerosis are common diseases. Differentiating between causal and bystander coronary artery disease (CAD) can occasionally be quite difficult. Although treating CAD in patients with severe cardiomyopathy makes a lot of sense, there are currently no reliable data to back it up. Separate studies on surgical and percutaneous revascularization have been conducted. It is challenging to compare one revascularization technique to another because those trials were carried out at various points in history and with patients who varied in their patient characteristics. The most current large-scale trial investigating the impact of coronary artery bypass graft (CABG) surgery on prognosis in ischemic heart failure is called the Surgical Treatment for Ischemic Heart Failure (STICH) trial. The rate of all-cause death did not significantly differ after a five-year follow-up period. Only after a lengthy 9.8-year follow-up period did CABG demonstrate a benefit in terms of death rate. The low incidence of ICD implantation, younger patient age than in most other comparable trials, low ICD implantation rate, and absence of contemporary therapy were just a few of the trial’s severe flaws. All the aforementioned may have had a significant impact on the trial’s outcome. The REVIVED-BCIS2 investigated possible other advantages that PCI might have over conventional medical treatment. (1) This well-designed multicentric trial randomly assigned individuals to receive either PCI or the best medical care. There was no difference in death or hospitalization rates between these two groups after 3.4 years of follow-up. These two studies serve as the primary source of evidence supporting revascularization in patients with poor ejection fractions. Although trials had similar patient populations, there were still big disparities. We can infer from these two trials that patients won’t benefit from either of these two treatments in the initial stages up to five years following therapy. After five years, with modern medical therapy and an ICD, it is still questionable if any benefit might be realized.

Tomislav Čikara, Marko Lucijanić, Marin Pavlov, Irzal Hadžibegović, Nikola Pavlović, Šime Manola, Ivana Jurin

**Introduction**: Sodium-glucose co-transporter 2 (SGLT-2) inhibitors are the latest addition to guideline-directed medical therapy in heart failure (HF) (1). It has been documented that SGLT-2 inhibitors significantly increase hemoglobin (Hgb) and hematocrit (Hct) levels via several supposed mechanisms (2). We analyzed SGLT-2 inhibitors treated HF patients and dynamics of Hgb and Hct levels in follow-up period of 12 months. **Metods**: We consider all of patients with or developing Hgb levels >160 g/L for females or >165 g/L for males to represent secondary polycythemia (SP). **Patients and Results**: We analyzed a total of 848 SGLT-2 inhibitor treated HF patients. At the baseline, median Hgb was 136 g/L, IQR (124-147). A total of 31 (3.7%) patients fulfilled WHO criteria for polycythemia. At 6 months, median Hgb was 140 g/L, IQR (127-150) and was significantly higher in comparison to baseline (P0.05 for both analyses). However, structure of the patient cohort presenting with SP significantly differed over time (P<0.001) as shown in **Figure 1**. About 1% of patients had persistent SP at both 6 months in comparison to baseline and at 12 months in comparison to baseline and 6 months milestone. However, during first 6 months 4% of patients developed de-novo SP in comparison to baseline, whereas 2% of patients experienced SP resolution. At subsequent 6 months, 3% of new patients developed SP and 3% of new patients experienced SP resolution in comparison to first 6 months period. Overall, during 12 months similar proportion of patients developed SP and experienced SP resolution, whereas 1% of patients had persisting SP. FIGURE 1. Dynamics of secondary polycythemia in a heart failure patients over 6 and 12 months of follow-up. SP = secondary polycythemia **Conclusion**: These observations shed novel light on phenomenon of erythrocytosis developing in association with SGLT-2 inhibitor use in HF patients. As our data show, there is continuous exchange of patients who develop and resolute SP over time with only a fraction of them (1%) experiencing persistent polycythemia, and therefore probably require further hematologic workup.