Cardiologia Croatica. 2021;16(1-2)

Boško Skorić

The most recent Guidelines for the management of dyslipidemias of the European Society of Cardiology and the European Atherosclerosis Society arrived after two major studies that demonstrated the efficiency of proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i), as well as the key fact that every additional reduction of LDL cholesterol reduces increased cardiovascular risk, i.e. that there is no lower limit of target blood concentration of LDL cholesterol. The latter was reflected in the recommendation of significantly lower target values of LDL cholesterol, especially for people with high and very high cardiovascular risk, resulting in the recognition of the need to combine statins with other hypolipemic agents, primarily ezetimibe followed by PCSK9i. Omega-3 fatty acids are recommended for the treatment of high-risk patients with hypertriglyceridemia despite statin treatment. Some modifications were made to cardiovascular risk categories, primarily for patients with diabetes mellitus and familial hypercholesterolemia, and more importance has been assigned to determining apolipoprotein B and lipoprotein(a) for more precise assessment of cardiovascular risk. We are now tasked with investing significant efforts into implementing these recommendations in our daily clinical practice in order to further reduce the population burden of cardiovascular diseases.

Marina Vučijak-Grgurević, Edin Begić, Azra Durak-Nalbantić, Faris Zvizdić

**Case report**: 39-years-old male patient was admitted to Clinic for Cardiology due to high blood pressure (180/105 mmHg) and epigastric pain which started 24 hours before. Patient was also febrile, he denied previous history of high blood pressure and had a hepatitis B (received blood transfusion during the war time). He is smoker and a heavy manual worker on the road. On electrocardiogram (ECG) there were signs of left ventricular hypertrophy. On the chest X-ray there were no signs of heart and large vessels enlargement and no lung infiltration. On echocardiography mild left ventricular hypertrophy were found, while all other parameters, including dimension of ascending aorta were normal. In laboratory results aspartate aminotransferase (AST) was 105 IU/mL, alanine aminotransferase (ALT) was 88 IU/mL, creatine kinase (CK) was 584 IU/mL, lactate dehydrogenase (LDH) was 1232 IU/mL, while high-sensitive cardiac troponin T was within normal limits. Patient had high C-reactive protein (CRP) 79 mg/L, increased leukocytes 12.0x109 /L, high D-dimer 4.37 µg/mL and low platelets count 99x109/L. Two days after levels of AST, ALT and CK normalized, LDH was lower but still elevated (999 IU/mL), while D-dimer raised (4.74 µg/mL) as well as CRP (180 mg/L) although antibiotics were administrated: first cefazolin and after ciprofloxacin and clarithromycin. Because high D-dimer and persistently elevated LDH patient was sent to perform computed tomography (CT) of thorax due to high clinical suspicion of pulmonary thromboembolism. CT scan result was completely unexpected: aortic dissection of descending aorta (Stanford type B) with normal dimension of aorta. Next day thoracic endovascular aortic repair (TEVAR) was performed. During further hospitalization the patient as electrically and hemodynamically stable. During a three-year follow-up, a patient without new acute cardiovascular incidents. **Conclusion**: Aortic dissection is life-threatening condition whose late diagnosis is main reason for high mortality. Combination of high LDH (marker of tissue necrosis) and high D-dimer could be a clue to the early diagnosis of aortic dissection. (1)

Filip Puškarić, Nikolina Maglić, Zvonimir Ostojić, Ivo Planinc, Joško Bulum, Davor Miličić, Maja Čikeš

**Introduction:** Acute coronary syndrome (ACS), including ST-segment elevation myocardial infarction (STEMI), non-ST-elevation myocardial infarction (NSTEMI) and unstable angina pectoris (UA), has been less researched in the subpopulation of young patients. Sex differences in discharge therapy after ACS have been described in older patients as favouring the male sex (1), and we decided to test this hypothesis in young patients. The term “young” (with regard to ACS) is not uniquely defined, but according to multiple sources, the proposed cut-off age is 45 years (2). **Patients and Methods:** A total of 361 young patients (with an age cut-off of 45 years for men and 55 years for women) with ACS and percutaneous coronary intervention (PCI) performed at the University Hospital Centre Zagreb (UHCZG) between Jan 1st 2012 and Jan 1st 2020 were enrolled. The patients were divided into the UHCZG group (241 patients discharged home after ACS) and the PCI network group (120 patients transferred to another medical facility after ACS). We explored statistically relevant associations between sex and discharge therapy using the Pearson chi-square test in the UHCZG group, due to the completeness of this dataset. **Results:** The mean patient age in the UHCZG group was 44±7 years, and 148 (61.4%) were men. 139 (57.9%) patients had STEMI, 72 (30.0%) NSTEMI, and 29 (12.1%) had UA (**Table 1**, **Figure 1**). Female patients had a higher prevalence of hypothyroidism, lower diastolic blood pressure at admission and higher LDL values (**Table 1**). A significantly higher proportion of male patients were prescribed with angiotensin-converting enzyme inhibitors (ACEi) (82.4% versus 65.6%, p=0.003). There were no sex differences in the prescription of other cardiovascular drugs (**Table 2**). ### TABLE 1: Baseline patient characteristics by sex in the University Hospital Centre Zagreb group. | **Characteristic** | **UHCZG group - women (n = 93)** | **UHCZG group - men (n = 148)** | **p-value** | | --- | --- | --- | --- | | Age, years | 50 ± 5 | 41 ± 4 | **2 | 27.9 ± 6.6 | 29.9 ± 5.4 | **0.018** | | ACS type | | | | | STEMI | 50 (53.8) | 89 (60.5) | 0.298* | | NSTEMI | 29 (31.2) | 43 (29.3) | 0.749* | | Unstable angina | 14 (15.1) | 15 (10.2) | 0.263* | | Arterial hypertension | 53 (57.0) | 78 (52.7) | 0.516 | | Diabetes mellitus | 16 (17.2) | 14 (9.5) | 0.077 | | Hypothyroidism | 7 (7.6) | 2 (1.4) | **0.013** | | Dyslipidemia | 47 (50.5) | 77 (52.0) | 0.818 | | Family history of CVD | | | | | CVD at younger age | 10 (18.2) | 15 (15.6) | 0.682** | | CVD at older age | 8 (14.5) | 10 (10.4) | 0.453** | | CVD at unknown age | 11 (20.0) | 11 (11.5) | 0.153** | | Previous myocardial infarction | 12 (12.9) | 16 (10.9) | 0.638 | | Previous TIA or CVA | 1 (1.1) | 2 (1.4) | 0.849 | | Previous angina pectoris | 32 (34.8) | 38 (25.7) | 0.131 | | Smoking status | | | | | Non-smoker | 20 (22.2) | 20 (14.3) | 0.121* | | Former smoker | 6 (6.7) | 11 (7.9) | 0.734* | | Current smoker | 64 (71.1) | 109 (77.9) | 0.246* | | Number of significant coronary stenoses | | | | | 0 | 0 (0.0) | 5 (3.4) | 0.073** | | 1 | 58 (63.0) | 95 (65.1) | 0.749** | | 2 | 17 (18.5) | 36 (24.7) | 0.263** | | 3 | 17 (18.5) | 10 (6.8) | 0.006** | | Culprit vessel | | | | | LAD | 36 (39.1) | 64 (44.1) | 0.447* | | LCX | 17 (18.5) | 28 (19.3) | 0.873* | | RCA | 39 (42.4) | 48 (33.1) | 0.147* | | Dominant coronary artery | | | | | Right | 65 (83.3) | 102 (78.5) | 0.390* | | Left | 7 (9.0) | 20 (15.4) | 0.184* | | Co-dominance | 6 (7.7) | 8 (6.2) | 0.667* | | Systolic BP at admission, mmHg | 138 ± 29 | 142 ± 25 | 0.265 | | Diastolic BP at admission, mmHg | 85 ± 16 | 90 ± 17 | **0.011** | | Heart rate at admission, beats/min | 77 ± 18 | 80 ± 17 | 0.369 | | Total cholesterol, mmol/L | 5.15 ± 1.34 | 5.07 ± 1.35 | 0.706 | | Triglycerides, mmol/L | 1.77 ± 0.88 | 2.04 ± 1.33 | 0.094 | | HDL, mmol/L | 1.17 ± 0.39 | 0.96 ± 0.27 | **< 0.001** | | LDL, mmol/L | 3.19 ± 1.26 | 3.23 ± 1.19 | 0.809 | [†] If not otherwise marked, significance determined at p-value of 0.05. *significance of p-value = 0.008 (due to Bonferroni correction) ** significance of p-value = 0.006 (due to Bonferroni correction). UHCZG – University Hospital Centre Zagreb; BMI – body mass index; ACS – acute coronary syndrome; STEMI – ST-segment elevation myocardial infarction; NSTEMI – non-ST-elevation myocardial infarction; CVD – cardiovascular disease; TIA – transient ischemic attack; CVA – cerebral vascular accident; LAD – left anterior descending artery; LCX – left circumflex artery; RCA – right coronary artery; BP – blood pressure; HDL – high-density lipoprotein; LDL – low-density lipoprotein. FIGURE 1. Pie chart showing the distribution of types of acute coronary syndrome in the University Hospital Centre Zagreb group. STEMI – ST-segment elevation myocardial infarction; NSTEMI – non-ST-elevation myocardial infarction. ### TABLE 2: Sex differences in discharge therapy in the University Hospital Centre Zagreb group. | **Drug class** | **UHCZG group - women (n = 93)** | **UHCZG group - men (n = 148)** | **p-value** | | --- | --- | --- | --- | | Acetylsalicylic acid | 88 (94.6) | 144 (97.3) | 0.287 | | Anti-platelet therapy | | | | | Ticagrelor | 40 (43.0) | 63 (42.6) | 0.944* | | Clopidogrel | 51 (54.8) | 79 (53.4) | 0.826* | | Beta-blocker | 81 (87.1) | 129 (87.2) | 0.988 | | RAAS inhibitor | | | | | ACE inhibitor | 61 (65.6) | 122 (82.4) | **0.003*** | | ARB | 8 (8.6) | 6 (4.1) | 0.142* | | MRA | 10 (10.8) | 24 (16.2) | 0.236 | | Nitrate | 29 (31.2) | 37 (25.0) | 0.295 | | Statin | | | | | Atorvastatin | 81 (87.1) | 135 (91.2) | 0.308** | | Rosuvastatin | 7 (7.5) | 11 (7.4) | 0.976** | | Simvastatin | 0 (0) | 1 (0.7) | 0.430** | | Antiischemic drug | 15 (16.1) | 22 (14.9) | 0.791 | | Calcium channel blocker | 24 (25.8) | 24 (16.2) | 0.070 | | Antiarrhythmic drug | 4 (4.3) | 9 (6.1) | 0.552 | | Diuretic | 20 (21.5) | 23 (15.5) | 0.239 | | Fibrate | 3 (3.2) | 6 (4.1) | 0.741 | | Omega-3-fatty acid | 13 (14.0) | 29 (19.6) | 0.263 | [†] If not otherwise marked, significance determined at p-value of 0.05. * - significance of p-value = 0,008 (due to Bonferroni correction) ** - significance of p-value = 0,006 (due to Bonferroni correction). UHCZG – University Hospital Centre Zagreb; RAAS – renin-angiotensin-aldosterone system; ACE – angiotensin-converting enzyme; ARB – angiotensin II receptor blocker; MRA – mineralocorticoid receptor antagonist. **Conclusion:** In a group of young patients with ACS, we found a statistically significant difference between male and female patients regarding the prescription of ACEi, despite a lack of significant difference in systolic blood pressure. Results similar to ours, regarding sex differences in optimal medical therapy, have been described in the literature, including young ACS patients (3).These results raise concerns regarding potentially negative consequences on the health of young women treated for ACS.

Alen Džubur, Edin Begić, Alden Begić, Mirza Babić, Azra Durak-Nalbantić

**Aim**: To connect the values of systolic and diastolic blood pressure at the admission of a patient with a diagnosis of pulmonary embolism (PE) with the values of the degree of pulmonary artery obstruction index (PAOI score). **Patients and Methods**: Patients were hospitalized under a diagnosis of pulmonary embolism, which was confirmed on the basis of the following criteria: clinical picture, changes in the electrocardiogram (ECG), serum D-dimer values and computed tomography (CT) angiography with contrast. The PAOI score was determined according to CT findings. On admission, systolic, diastolic and pulse pressure were measured. **Results**: The mean systolic blood pressure was 124.4 ± 27.75 mmHg, and there was a statistically significant correlation between the PAOI score and the systolic blood pressure (p = 0.004), with a significant negative correlation between the values of the PAOI score and the values of systolic blood pressure (r = -0.328, p = 0.018) (**Figure 1**). The mean value of diastolic blood pressure was 78.5 ± 14.06 mmHg. A statistically non-nsignificant negative correlation between PAOI score and diastolic blood pressure value was verified (r = -0.149, p = 0.293). The mean value of pulse pressure was 45.21 ± 19.09 mmHg, with statistical significance between PAOI score and the value of pulse pressure (p = 0.001). A statistically significant negative correlation between PAOI score and pulse pressure value was verified (r = -0.366, p = 0.008). FIGURE 1. Systolic blood pressure values and pulmonary artery obstruction index score. **Conclusion**: Lower systolic blood pressure values are associated with more extensive pulmonary embolism. (1)

Ivan Jerković, Maja Mizdrak, Josip Anđelo Borovac, Joško Božić, Vedran Kovačić, Tina Tičinović Kurir

**Introduction**: Acute elevations of biomarkers reflecting myocardial injury, thrombosis, systemic inflammation, and heart dysfunction are associated with poor prognosis among hospitalized patients with COVID-19. (1-3) In this study, we aimed to determine levels of these biomarkers in patients that were hospitalized with COVID-19 pneumonia at our institution during the first pandemic wave. Secondly, we aimed to determine if these biomarkers correlate with risk assessment tools such as MEWS (Modified Early Warning Score) and SOFA (Sequential Organ Failure Assessment) scores that reflect disease severity and clinical deterioration of patients. **Patients and Methods**: Data of 40 consecutive hospitalized patients with PCR-confirmed SARS-CoV-2 infection and pneumonia verified by imaging methods were considered for the analysis. **Results**: The mean age was 80.5 ± 9.9 years and 25 (78.1%) were women. Of these patients, 9 (22.5%) had a significant renal insufficiency (eGFR 14 pg/mL) while 10 patients (32.3%) satisfied acute heart failure rule-in criteria according to natriuretic peptide cut-off values adjusted for age. The mean hs-cTnT value was 28.9 ± 42.7 pg/mL while mean NT-proBNP value was 2481 ± 4662 pg/mL. One-third of patients (32.3%) had C-reactive protein values >41.1 mg/L (mean 33.7 ± 39.1 mg/L), highly predictive of severe disease. Nearly two-thirds of patients (N=19, 61.3%) had D-dimer levels >2.1 mg/L that was highly predictive of in-hospital death in previous studies (**Figure 1**). The mean MEWS and SOFA scores were 2.5 ± 1.6 and 3.1 ± 2.3 points, respectively. In decreasing order of relationship, CRP, D-dimer, and NT-proBNP values significantly correlated with both MEWS and SOFA scores as shown in **Table 1**. Troponin values had a borderline association with both risk scores. FIGURE 1. Prevalence of abnormal cardiovascular biomarkers reflecting myocardial injury, ventricular overload, systemic inflammation and thrombotic risk among patients hospitalized with COVID-19 pneumonia. CRP - C-reactive protein; hs-cTnT - high-sensitivity cardiac troponin T; NT-proBNP - N-terminal of proBrain Natriuretic Peptide ### TABLE 1: Correlation of cardiovascular laboratory parameters with the risk of clinical deterioration (MEWS score) and estimated rate of organ failure (SOFA score). | **Laboratory parameter** | **MEWS score** | **MEWS score** | **SOFA score** | **SOFA score** | | --- | --- | --- | --- | --- | | | **r-value** | **p-value** | **r-value** | **p-value** | | NT-proBNP | 0.360 | 0.047* | 0.360 | 0.047* | | hs-cTnT | 0.304 | 0.096 | 0.306 | 0.094 | | CRP | 0.802 | <0.001* | 0.710 | <0.001* | | D-dimer | 0.449 | 0.011* | 0.439 | 0.013* | [†] CRP-C-reactive protein; hs-cTnT-high-sensitivity cardiac troponin T; MEWS-Modified Early Warning Score for Clinical Deterioration; NT-proBNP-N-terminal of proBrain Natriuretic Peptide; SOFA-sequential organ failure assessment score *denotes significant result at p<0.05; r-Pearson’s correlation coefficient; p-statistical significance **Conclusions**: Our data show that a significant number of patients hospitalized due to COVID-19 were elderly and with a high risk of thrombotic events and cardiac insufficiency. Likewise, a high inflammatory burden was observed in one-third of patients. CRP correlated the most with MEWS and SOFA score, followed by D-dimer levels and NT-proBNP while no significant interaction was observed with cardiac troponin values.

Mislav Vrsalović, Tonći Batinić, Nikola Kos, Ksenija Vučur, Boris Car

**Aim**: Patients with peripheral artery disease (PAD) are at very high risk of cardiovascular events. (1-3) The first Croatian Prospective Peripheral Artery Disease Registry (CRO-PAD) was created in 2010, with the aim to collect, organize and present data about patients with PAD. The purpose was to evaluate risk factors, prognosticators, longitudinal outcomes, and therapeutic development in order to improve patients’ healthcare and disease outcomes. **Patients and Methods**: The occurrence of major adverse cardiovascular events (MACE), defined as composite endpoint of acute myocardial infarction, stroke, and death was assessed in 1084 symptomatic PAD patients admitted to the University Hospital between January 2010 and January 2020 (65% men, age 70±10 years). Multivariate Cox regression analysis adjusted for age, gender, traditional cardiovascular risk factors, polyvascular disease, chronic limb threatening ischemia (CLTI), atrial fibrillation (AF), anemia, statin treatment, and impaired renal function was applied to assess the independent predictors of MACE. **Results**: During median follow-up period of 44 months (interquartile range, 23-59 months), 370 patients (34%) experienced MACE. Compared to patients without MACE, these patients were older, more likely to have diabetes, hypertension, CLTI, polyvascular disease, AF, anemia, and renal impairment. In multivariate regression analysis, age (HR 1.03, 95% CI 1.02-1.04), polyvascular disease (HR 1.42, 95% CI 1.15-1.77), CLTI (HR 1.91, 95% CI 1.54-2.36), AF (HR 1.54, 95% CI 1.18-2.01) and anemia (HR 1.65, 95% CI 1.31-2.06) remained independent predictors of MACE. Patients with both polyvascular involvement and CLTI were four times more likely to experience MACE compared to those with PAD alone (**Figure 1**). FIGURE 1. Cumulative major adverse cardiovascular events (MACE) free survival in 1084 symptomatic PAD patients according to polyvascular involvement (POLYVASC) and chronic limb threatening ischemia (CLTI). **Conclusion**: Polyvascular involvement, critical limb ischemia, anemia, and AF were independent predictors of MACE in symptomatic PAD patients during long-term follow-up.

Ana Marija Slišković, Ana Šutalo, Sanda Huljev Frković, Andrea Crkvenac Gregorek, Ljiljana Banfić, Majda Vrkić Kirhmajer

**Introduction**: Vascular Ehlers-Danlos syndrome (vEDS) is considered the most severe form of EDS because of its typical life-threatening complications in young adults: spontaneous rupture of arteries, uterus or intestine (1). The prevalence of vEDS is at least 1:200.000. It is associated with autosomal dominant mutation in COL3A1 gene, which encodes pro-alpha 1 chains of type III collagen. The median life expectancy is 48 to 51 years. The beneficial role of celiprolol in reduction of arterial complications has been described, and the mechanisms may be related to reduction of hemodynamic stress and by upregulation of collagen synthesis via transforming growth factor-β (2, 3). **Case report**: A 26-year-old man was referred with long history of serious vascular complication. From early childhood he was prone to spontaneous bruising. At the age of 7, after minor trauma, he had a duodenal hematoma. Hemophilia was ruled out. In 2014, urgent nephrectomy was done because of spontaneous rupture of right renal artery. Calf varicose veins were treated with foam sclerotherapy in 2016. In 2017, urgent femoro-femoral bypass was performed due to spontaneous rupture of the left common iliac artery (CIA) and failure to repair extremely vulnerable CIA wall. Several months later hybrid vascular procedure was done due to spontaneous dissection of right external iliac artery. Early postoperative course was complicated by spontaneous pneumothorax. His physical appearance was also suggestive to vEDS: thin skin, characteristic facial appearance (thin lips, small chin, thin nose, prominent eyes with dark circles), small joints hypermobility. Molecular genetic testing in 2019 confirmed vEDS: our patient is heterozygous for COL3A1c.1149+2_1149+51del. His current medical therapy includes vitamin C and tolerable dose of celiprolol. For the last three years he is without new adverse vascular events. **Conclusion**: Accurate diagnosis, genetic consulting, avoiding high risk activities and procedures are crucial in patients with vEDS. Endovascular or surgical intervention are mainly reserved for urgent complications of arterial or organ rupture. Celiprolol, a beta blocker with a unique pharmacologic profile, demonstrated a promising role in reduction of vascular complication in vEDS.

Igor Tagasovski, Andrea Crkvenac Gregorek, Sanda Huljev Frković, Dražen Perkov, Majda Vrkić Kirhmajer

**Introduction**: Klippel-Trenaunay Syndrome (KTS) is rare syndrome characterized by a presence of capillary and venous malformation, limb overgrowth, with or without lymphatic anomalies (1). KTS is related to mutations in the PIK3CA gene. Complications of KTS include clotting disorder, bleeding, lymphedema, soft tissue infection and pain. Treatment is individualized; it may include endovascular or surgical procedures and supportive care (management of coagulopathy, infection, pain). The use of mammalian target of rapamycin (mTOR) inhibitor sirolimus shows promising results in complex vascular malformations (2, 3). **Case report**: We present a 45 years old patient, currently living out of Croatia. Vascular malformation of the left arm was noticed a few months after his birth. During his childhood an angiography of the left arm lead to confirmation of KTS without further specific treatment. During the last 15 years he was undergoing regular hematology controls and treatment of consumptive coagulopathy as complication of KTS. In 2010 at age 35, he suffered a fracture on the left arm, but he was declared inoperable on basis of vascular malformation which extended the healing process. From 2018 further proliferation of vascular malformation was noticed on his left hemithorax. In 2020 he was presented to multidisciplinary vascular team, MR angiography was performed Unfortunately, due to extreme extension of vascular malformation with soft tissue hypertrophy and osseous deformation the patient is not suitable for any surgical or endovascular procedure. We suggested a treatment with sirolimus which is delayed due to patient’s temporary relocation. Genetic panel testing covering PIK3CA gene is in progress. **Conclusion**: By presenting this case, our objective is to increase the awareness of KTS, related complications and the role of sirolimus which can improve the prognosis of vascular anomalies. Additionally, we wish to emphasize the importance of multidisciplinary vs specialty focused approach in management patients with KTS.

Ana Šutalo, Ana Marija Slišković, Mislav Puljević, Ante Bosnić, Ljiljana Banfić, Majda Vrkić-Kirhmajer

**Introduction**: Compared with the general population, cancer patients with venous thromboembolism (VTE) have higher rates of both VTE recurrence and bleeding. Low molecular weight heparins (LMWH) are the standard of care for the treatment of cancer-associated venous thromboembolism (CAT). Direct oral anticoagulants (DOACs) have recently emerged as a new therapeutic option, but optimal duration of therapy is still unclear. Decision for prolonged anticoagulation treatment is made individually as it depends on disease activity, current antineoplastic regime and patient risk-benefit profile (1-3). **Patients and Methods**: A single center retrospective analysis of patients with CAT was conducted. The aim was to investigate type and duration of anticoagulation therapy. From our database of patients with VTE collected between 2016 and 2020, we included those with cancer associated deep venous thrombosis and/or pulmonary embolism. **Results**: The cohort consisted of 44 patients (40% women and 60% male), aged 20 to 91 years. Therapeutic options at discharge were LMWH in 60% cases (enoxaparin and dalteparin equally represented), VKA in 25% and DOAC in 15%. One patient was dismissed without anticoagulation because of an end-stage gastric carcinoma which manifested as acute gastrointestinal bleeding. In follow-up period we observed that 20 patients (45%) had extended anticoagulation beyond 6 months: 50% LMWH, 30% rivaroxaban, 20% VKA. Among them, four patients initially treated with LMWH, were transited to rivaroxaban because of reduced tolerability of parenteral drug. One case of major bleeding occurred (hematuria) but there were no fatal or intracranial bleeding episodes in CAT patients on extended anticoagulant therapy in follow up period. **Conclusion**: Treatment of VTE in patient with cancer remains a clinical challenge. Guidelines recommend at least 6 months of therapy for CAT and longer if the patient has active cancer or is receiving antineoplastic therapy. Extended anticoagulation may include LMWH or transition to an oral anticoagulant. Since carcinoma carries both thromboembolic and bleeding risk, the decision should be made on a case-by-case basis. From our experience, that assumes regular clinical reassessments.

Ana Marija Slišković, Mislav Puljević, Ana Šutalo, Ante Bosnić, Ljiljana Banfić, Majda Vrkić Kirhmajer

**Background**: In March 2020 formally declared pandemic of coronavirus disease (COVID-19) caused a global impact on public health. Venous thromboembolism (VTE) encompassing pulmonary embolism (PE) and deep venous thrombosis (DVT) is frequently observed in patients with COVID-19 (1), while the pandemic influence on non COVID-19 VTE prevalence remains unknown. Previous meta -analysis supported an association between regular physical activity and lower risk of VTE when compared with a sedentary or less active lifestyle (2). Aim: to investigate the influence of pandemic circumstances on the prevalence of non COVID-19 patients hospitalized due to VTE. **Patients and Methods**: Single centre retrospective analysis of consecutive non COVID-19 patients admitted for VTE was performed. We compared demographic characteristics and diagnostics findings in patients hospitalized for VTE between 1st of March and 31st of October 2019 and non COVID-19 VTE patients hospitalized between the same period in 2020. All patients underwent laboratory tests, venous ultrasonography of the lower limbs and/or CT pulmonary angiography and had negative swab test for SARS-CoV2 at admission. One patient had previously recovered from COVID-19. **Results**: During the period of 8 months 70 VTE patients (female 48%, mean age 60.8 ± 17.2 years) were admitted in 2019, while 86 non COVID-19 VTE patients (female 50%, mean age 68.5± 16.8 years) were admitted in 2020. There was no significant difference in prevalence of VTE hospitalization (4.1% vs 5.4%, p=0.106), but patients in 2020 were significantly older (p=0.002). Dividing the VTE cases into isolated PE, isolated DVT and combined DVT+PE we found a significant increase in prevalence of DVT+PE during pandemic (34 vs 36, p=0.23; 23 vs 25, p=0.24 and 13 vs 25, p=0.03, respectively). **Conclusion**: During COVID 19 pandemic we observed significant increase in prevalence of hospitalized non COVID-19 patients with combined DVT+ PE but not with isolated PE or isolated DVT. Possible explanation could be a less active lifestyle due to pandemic social restriction recommendation and delaying treatment for initial DVT.

Josip Figl, Tomislav Meštrović, Ivan Brižić, Damir Halužan, Dino Papeš, Predrag Pavić, Andrea Crkvenac Gregorek, Irena Šnajdar, Ivan Škorak

**The goal**: To compare the results of most distal femoral bypasses in our institution with results in literature. **Patients and Methods**: A single centre retrospective analysis of femoral to crural and distal-leg bypass performed in University Hospital Centre Zagreb between 2014 and 2018. **Results**: Primary one-year patency is even a bit better in our hospital than in literature (80% vs 77% respectively) and secondary patency is in the range of the world literature (54% vs 68% respectively). **Conclusion**: Surgical revascularization in form of the most distal bypasses, performed in this institution observed, although reserved for a smaller number of patients, is very good and reliable method of treatment, and its results are at the level of world standards and percentages. (1-3)

Ljiljana Banfić

COVID-19 is systemic disease that affects human cells by binding to angiotensin converting enzyme 2 (ACE2) receptor and is considered as mild disease for the most patients affected by virus. About 15% of patients could develop severe symptoms and 5% of them require intensive care unit treatment. The pathogenesis of disease is characterized as immunothrombosis with proinflammatory and procoagulant state. Hypercoagulability, microangiopathy, venous thromboembolism (VTE) and arterial thrombosis affects patients with underlying cardiovascular risk and vascular disease as they are more likely to require critical care because of increased likelihood for severe and very severe forms of COVID-19 infection. Thromboprophylaxis with DOACs or LMWH is recommended because of increased vascular patient vulnerability. Compared to the patient with a history or actual deep vein thrombosis and pulmonary embolism arterial thrombosis occur less frequently and has lower mortality rate. The VAS-European Independent Foundation in Angiology/Vascular Medicine (1) published guidance for the management of COVID patients with vascular diseases and cardiovascular risk factors. VAS recommendation clarifies the need for identification of patients with vascular diseases in COVID-19 infection and preventive measures in hospital and outpatient setting. The important role of primary health care network and eHealth technology is to recognize and identify vascular patients with COVID. Family doctors should promote adherence to the antithrombotic therapy (Aspirin, Clopidogrel, Prasugrel, Ticagrelor), statins and antihypertensive drugs because of their protective potential during COVID-19 infection. The great attention is focused on thromboprophylaxis with intermediate doses of LMWH in hospitalized patients. DOACs or LMWH are recommended in postdischarged period for up to 40 days if IMPROVE-D-dimer score is >4. The scoring is suggested as useful tool in patients selection for possible prolonged prophylaxis with DOACs: rivaroxaban 10 mg OD, and betrixaban 80 mg OD, or LMWH at weight adjusted prophylactic dose. Guidance document published by VAS is useful frame for care of vascular patient and COVID-19 infection, although proposed recommendations has a low grade of evidence as randomized clinical trials are still lacking.

Vjeran Nikolić-Heitzler

**The goal**: In everyday practice, we doctor often prescribe aspirin. The question arises whether this is always justified. It is necessary to discern the use of aspirin in primary prevention in people with no signs of cardiovascular disease from use in secondary prevention in at-risk individuals with previous heart attacks and strokes or known cardiovascular diseases (CVD). Coronary heart disease and stroke, the principal manifestations of CVD, are the first and second most common causes of death worldwide. The World Health Organization predicts that, by 2020, coronary heart disease will become the world’s most important cause of death and disability and, further, the most important cause of premature death, “if the victims of the COVID-19 pandemic do not overtake them” (authors comment). Low doses of aspirin were considered indispensable in the prevention of heart attack and stroke and other CVD. New guidelines, though, suggest that aspirin should not be prescribed to most adults who are in good cardiovascular health and that the risk of internal bleeding often outweighs the benefit. According to the European Guidelines for Cardiovascular Diseases and Prevention in 2016, using the experience of older historical trials, aspirin is recommended for the primary prevention of people with high CVD risk (especially those with a ten-year mortality risk of over 10%). The Antiplatelet Trialists Collaboration meta-analysis demonstrated the benefits of antithrombotic therapy (mainly aspirin) in patients with type 1 or type 2 DM with clinically established CAD, cerebrovascular disease or other forms of thrombotic disease, with a 25% reduction in risk of CV events. (1) The use of aspirin for the primary prevention of CVD has been a subject of intense debate since the publication of three large, randomized clinical trials in 2018 (ASCEND, ARRIVE, and ASPREE). The American College of Cardiology and American Heart Association released the new guidelines in 2019 and one of the mayor changes is recommendation against the broad use of aspirin in primary prevention. (2) Low-dose aspirin 100 milligrams or less did not help older adults who do not have CVD. The new trials published 2019, meta-analysis of aspirin effects in primary prevention of CVD comprising 13 randomized-controlled trials in 164.225 patents comparing aspirin versus placebo/control during a mean follow-up period of 6.4 years suggested that the benefit of aspirin for primary prevention has been neutralized, perhaps due to the use of other modern preventive therapies, such as statins, and general improvements in the population prevalence of smoking and hypertension. The authors of the new guidelines said low-dose aspirin should not be routinely given as a preventive measure to adults 70 years and older or to any adult who has an increased risk of bleeding. Aspirin did reduce CVD by a modest 11%, with a number needed to treat to prevent 1 event of 265, but it also increased major bleeding, such as serious GI bleed, intracranial bleed or bleed needing hospitalization or transfusion by 43%. That is a number needed to harm of 210. Among major bleeding events, intracranial hemorrhage is associated with high mortality rates and functional dependency. (3) **Conclusion**: Aspirin remains an important medication for acute management of vascular events; for use after certain procedures; for secondary prevention; and, only after careful selection of the right patients, for primary prevention.

Ivana Jurin, Marko Lucijanić, Anđela Jurišić, Aleksandar Blivajs, Boris Starčević, Irzal Hadžibegović

**Introduction**: Randomized controlled trials of direct oral anticoagulant therapy (DOAC) included limited number of obese patients providing uncertainty about their efficacy in this population. (1) Since DOACs are expected to be increasingly used, more information about efficacy and safety, especially among obese patients which might be exposed to suboptimal drug levels, is urgently needed. Therefore, we aimed to investigate in the real-life setting whether DOAC anticoagulated patients with atrial fibrillation stratified according to the different body mass index (BMI) subgroups experience different risks of unwanted outcomes. **Patients and Methods**: We retrospectively investigated a real-life cohort of 325 DOAC anticoagulated patients with atrial fibrillation [179 receiving dabigatran (55%), 74 apixaban (23%) and 72 rivaroxaban (22%)]. Patients were stratified according to the body mass index (BMI) into non-obese (233 with BMI 2), class I obesity (71 with BMI 30-34.9 kg/m2) and class II + obesity (21 with BMI ≥35 kg/m2). **Results**: Patients with higher BMI receiving DOACs were more likely to experience stroke/systemic embolism sooner (P = 0.043), experience major bleeding sooner (P < 0.001) and have shorter time to composite event consisting of thrombosis, bleeding or death (P < 0.001) whereas there was no significant association with overall survival (P = 0.470). BMI was significantly associated with thrombosis but not bleeding among dabigatran treated patients, and significantly associated with bleeding but not thrombosis among patients treated with factor Xa inhibitors. Associations of higher thrombotic, bleeding and composite endpoint risks with higher BMI remained statistically significant in multivariate Cox regression models adjusted for age, gender, eGFR, CHA2DS2VASC and HAS-BLED. **Conclusion**: Our findings indicate that obese patients receiving DOACs, especially ones with class II + obesity, might be under higher risks of stroke/bleeding depending on DOAC subtype. Loss of efficacy might be associated with dabigatran, whereas higher risk of major bleeding might be associated with factor Xa inhibitors.

Almin Handanagić, Edin Begić, Alma Handanagić

**Case Report**: A 73-year-old patient was hospitalized at the Department of Internal medicine, Cantonal Hospital Bihać, due to chest pain and dyspnea. He stated that he had a myocardial infarction 15 years ago. Coronarography verified triple-vessel coronary artery disease and he underwent surgical revascularization. Since then, he received antiaggregation therapy, angiotensin-converting enzyme (ACE) inhibitor, beta-blocker, amiodarone, nitroglycerin, diuretic and statin. By echocardiography, preserved systolic function was verified, along with hypokinesis of the mediobasal segment of the inferior and basal segment of the posterior wall. He pointed out that in the past 3-4 years he got an ashy color of his facial skin (**Figure 1**). Dermatologist suspected on phototoxic reaction of amiodarone and recommended to exclude amiodarone from therapy, along with the administration of antihistamines and local photoprotection with Sun Creme Sensitive Protect SPF 50+. After two months, the patient has undergone stress testing and new coronarography was indicated. In the control findings of a dermatovenerologist, the previously described changes on the facial skin were in regression. FIGURE 1. Amiodarone-induced phototoxic reaction. **Conclusion**: The occurrence of facial pigmentation is associated with long-term use of amiodarone (1), and in case of its occurrence, the consequences of the therapeutic modality should be taken into account.

Mario Udovičić, Danijela Grizelj, Mariam Samara, Hrvoje Falak, Ana Jordan, Petra Vitlov, Diana Rudan

**Goal**: The aim of this study was to evaluate the community-based prevalence of atrial fibrillation (AF) in a geographically well-defined population in the central part of Croatia. **Methods**: We searched hospital electronic health records of Clinic of Internal Medicine (IMD) and Emergency Department (ED) of University Hospital Dubrava (UHD) for patients older than 20 years of age diagnosed with AF in the period from January 1, 2007 to January 1, 2017. We then eliminated all the patients who have died before 2017 or did not have residence within the official catchment area. **Results**: Of the 125 596 patients analyzed, 14 781 were diagnosed with AF; of these 5 086 were alive on January 1, 2017 and residing within the official catchment area of UHD, which meant that the overall prevalence of AF was 2.0%. The prevalence increased with age from 4.3% in patients over 50 years of age to 13.0% in those over 80 years. It was higher in men than in women in all age groups, while 90.8% of the population were at high risk of stroke (≥2 points) according to CHA2DS2-VASc score. **Conclusion**: Within our population, we identified a very high community-based prevalence of AF, and a very large portion of patients with indication for OAC prophylactic therapy of AF. The prevalence was strongly associated with increasing age and male gender. (1)

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

Arrhythmias are the main cause of morbidity and hospital visits for grown-up congenital heart (GUCH) patients. Supraventricular arrhythmias are the most frequent problem. Although usually not harmful in the general population, they can be severely compromising in GUCH patients. The low success rate of antiarrhythmic drugs in GUCH patients is well-recognized. Therefore, electrophysiologists play an important role in the diagnostics and treatment of rhythm disturbances in GUCH patients. (1, 2) In our centre, 13 GUCH patients underwent catheter ablation procedures from January 2015 to December 2020. There were six patients with atrial septal defect (ASD), two patients with tetralogy of Fallot (ToF), two with Ebstein anomaly, one with transposition of the great arteries, one with ventricular septal defect (VSD), and one with dextrocardia. A successful radiofrequency (RF) ablation of the cavotricuspid isthmus (CTI) was performed in five ASD patients, one patient with ToF, and eventually in a patient with VSD. The same procedure was unsuccessful in a patient with transposition of the great arteries. RF ablation for AVNRT was successfully performed in one patient with ASD, one patient with Ebstein anomaly, and a patient with dextrocardia. RF ablation of atrial tachycardia in another patient with Ebstein anomaly was discarded due to the high risk of iatrogenic AV node ablation. Another patient with ToF underwent only an electrophysiology study. In conclusion, the most common arrhythmia in our GUCH patients was CTI-dependent atrial flutter which was easily treated with a high success rate.

Vedran Pašara, Ivan Prepolec, Richard Matasić, Borka Pezo-Nikolić, Miroslav Krpan, Mislav Puljević, Davor Puljević, Martina Lovrić Benčić, Davor Miličić, Vedran Velagić

His bundle pacing activates the ventricles physiologically by direct stimulation of the His-Purkinje cardiac conduction system. (1) It was first described in the 1970s, first studies were reported in the early 2000s followed by technological advances that led to its widespread uptake and growing evidence base. (1, 2) This retrospective study aimed to evaluate His-bundle lead implantation program in our centre. A total of 116 consecutive patients (63.8% male, 65.4 ± 13.6 years) who underwent His-bundle lead implantation in our centre from November 2018 until November 2020 were analyzed. Among these patients, over two-thirds (69.8%) had arterial hypertension, 43.1% had dyslipidemia and 29.3% had diabetes. Nearly half of patients (49.1%) had chronic heart failure, 26.7% had coronary artery disease and 8.6% had prior myocardial infarction. 40.5% of patients had atrial fibrillation. His-bundle lead implantation was achieved in 105 (90.5%) of all patients, while the rest of the procedures were aborted and ended with right ventricle lead placement. Ten (8.6%) patients had postprocedural complications, six of which were resolved without lead extraction. Only one patient had a device-associated infection. With this analysis, we showed that the results of our His-bundle lead implantation program, regarding success and complication rates, are similar to available literature data. (1, 2)

Lana Maričić, Dražen Mlinarević, Jerko Arambašić

Thromboembolic events are the leading cause of morbidity and mortality in the world. Over a three-year period of the initial 193 patients, 124 patients (64.2%) survived. A recurrence of VTE was documented in 2.36% of patients, and the same percentage of patients developed a newly diagnosed malignant disease. After three years, 4.72% of patients were still treated with low molecular weight heparin, warfarin therapy was continued in 29.9% of patients, direct oral anticoagulant therapy was continued in 31.5%, and anticoagulant therapy was excluded in 31.5% of patients. Of patients receiving direct oral anticoagulant, rivaroxaban was the most commonly prescribed (65%), dabigatran in 27.5%, apixaban in 7.5%. Current guidelines in the treatment of thromboembolic incident allow free assessment in the choice and duration of anticoagulation therapy, depending on the presence or absence of risk factors, active malignancy, or other patient related factors. The aim of this register is to monitor patients, compare with data from world registries, and analyze the therapeutic approach. After examining the results, we can conclude that there are many similarities between our patients and those from other registries (1, 2).

Ivana Jurin, Marko Lucijanić, Vedran Radonić, Tomislav Letilović, Diana Rudan, Tomislava Bodrožić Džakić-Poljak, Irzal Hadžibegović

**Objective**: To investigate predictors of falling requiring visit to emergency department in patients with non-valvular atrial fibrillation (AF) receiving different types of anticoagulants, as well as to investigate clinical consequences of falling in the same population. **Patients and Methods**: A total of 1,217 patients with non-valvular AF from two institutions were retrospectively evaluated. Physical examination, clinical history and medications profile were obtained from each patient at baseline. **Results**: Median age of our cohort was 71 years. There were 52.3% males and 86.1%patients were receiving anticoagulation at the study baseline. Freedom-from-falling 5-year rate was 81.6%. Use/type of anticoagulation was not significantly associated with the risk of falling (P=0.222), whereas higher Morse-Fall-Scale (MFS), CHA2DS2-VASC and HAS-BLED scores were significantly associated with the higher hazard of the first fall in univariate analyses. In the multivariate Cox-regression model MFS, older age, osteoporosis, higher HDL-cholesterol, higher diastolic-blood-pressure, use of amiodarone, use of diuretics, and use of short and medium-acting benzodiazepines were identified as mutually independent predictors of the first fall. A total of 93/163(57%) patients suffered a bone fracture during the fall. Type of anticoagulation significantly affected survival after the first fall (P<0.001) with patients inadequately anticoagulated with warfarin experiencing worse and patients receiving apixaban and dabigatran experienced best survival after the first fall. **Conclusion**: Older patients with comorbidities, taking amiodarone, diuretics, and short and medium acting benzodiazepines are under highest risk of falling. (1) Type and quality of anticoagulation do not seem to affect the risk of falling but significantly affect survival after the first fall.

Ivana Jurin, Marko Lucijanić, Vedran Radonić, Tomislav Letilović, Jasmina Ćatić, Ana Jordan, Petra Vitlov, Irzal Hadžibegović

**Objective**: Atrial fibrillation (AF) has been associated with dementia, even in patients without prior stroke and the pathogenesis that correlates the two entities is multifactorial. Imaging studies have shown that structural cerebral changes are common in patients with AF so it was thought that treatment with oral anticoagulants should protect against small emboli which causes microinfarctions that eventually lead to cognitive deterioration. Patients with dementia are less likely to receive anticoagulant treatment although previous studies have reported that AF patients on anticoagulant treatment at baseline had a 29% lower risk of dementia. (1) To investigate prescription patterns of anticoagulation therapy in patients with AF and dementia as well as incidence of dementia in the patient cohort. **Patients and Methods**: A total of 1217 patients with non-valvular AF from two institutions were retrospectively evaluated. Physical examination, clinical history and medication profile were obtained at baseline. **Results**: Median age of our cohort was 71 years. A total of 162/1217 (13.3%) patients were diagnosed with dementia. Patients with dementia were significantly older, were more likely to be of female gender, more likely to have diabetes mellitus, prior stroke/TIA, heart failure, peripheral artery disease, osteoporosis, thyroid disease, lower eGFR, lower height, lower weight, lower LVEF, lower hemoglobin, higher CRP, higher leukocytes, to take higher number of drugs in general and higher number of psychiatric drugs. Median follow-up of our cohort was 53 months. In univariate analyses among unselected AF patients, patients with dementia were significantly more likely to experience inferior overall survival (HR=15.3; P<0.001), shorter time to thrombosis (HR=8.4; P<0.001), shorter time to major bleeding (HR=4.13; P<0.001) and shorter time to first fall (HR=2.36; P<0.001). **Conclusion**: Our findings speak in support of increased thrombotic and mortality risks in patients with dementia, possibly due to inadequate anticoagulation and higher number of comorbidities. Therefore, our suggestion is that physicians should prescribe more often DOACs in patients have dementia or higher risk of developing dementia.

Ivana Jurin, Marko Lucijanić, Anđela Jurišić, Zrinka Šakić, Sanda Sokol Tomić, Irzal Hadžibegović

**Introduction**: The risk of thromboembolism in patients with atrial fibrillation becomes higher if they have comorbidities such as ischemic heart disease, hypertension, and diabetes. (1) The risk for cardio-embolic complications has been linked to a reduced ejection fraction (rEF) in several studies and has been well known for decades. An ejection fraction of 40–49% is neither normal/pre- served (pEF) nor reduced, and it is termed mid-range EF (mrEF). It is increasing in prevalence and is associated with older age, non-cardiac comorbidities and higher rates of AF. This category was separated in recent guidelines, although associated risks and the potential therapy remain poorly understood. We aimed to assess stroke/systemic embolism, major bleeding and mortality risks in our cohort of non-valvular AF patients based on the presence of mrEF in comparison to rEF and pEF. **Patients and Methods**: We studied 1000 consecutive patients who were admit- ted to our hospital due to non-valvular AF between 2013 and 2018. **Results**: Patients with mrEF presented with older age (P < 0.001) and a higher frequency of arterial hypertension (P = 0.001) in comparison to both pEF and rEF patients. In comparison to pEF, mrEF patients were more likely to have diabetes mellitus (P = 0.004), lower HDL-cholesterol (P < 0.001) and lower estimated glomerular filtration rate (P < 0.001), significantly higher CHA2DS2-VASC score (P < 0.001), significantly higher HAS-BLED score (P = 0.002) and had a higher likelihood of receiving anticoagulant therapy, mostly warfarin (P = 0.001). In addition, mrEF patients had a significantly higher risk of thrombotic events (HR = 2.22; P = 0.015), death (HR = 1.71; P = 0.005) and composite endpoint of thrombosis, bleeding or death (HR = 1.65; P = 0.003) in comparison to pEF patients but did not significantly differ in comparison to rEF patients. There was no significant difference regarding major bleeding risk. Associations with clinical outcomes remained statistically significant in multivariate models independently of CHA2DS2-VASC. **Conclusion**: Our findings support defining AF patients with mrEF as a subgroup with distinct clinical characteristics and increased risk for thrombotic events and death, irrespective of predetermined CHA2DS2-VASC risk.

Irzal Hadžibegović, Ivana Jurin, Marko Lucijanić, Anđela Jurišić, Ana Jordan, Boris Starčević

**Background**: Patients with atrial fibrillation (AF) and high thrombotic risk should be protected from thromboembolic events with adequate oral anticoagulation therapy. In Croatia, direct oral anticoagulant drugs (DOACs) are only partially reimbursed whereas optimal dosing of vitamin K antagonist (VKA) is hard to obtain. (1) Aim: To investigate differences in characteristics and clinical outcomes of patients with AF exposed to different types of anticoagulant drugs. **Patients and Methods**: We retrospectively analyzed 1000 consecutive patients with non-valvular AF hospitalized in our institution in a period from 2013 to 2018. Patients were followed-up for a median time of 42 months. **Results**: DOAC penetration as initial anticoagulation therapy increased from 37% to 58% (P=0.002 for trend). Patients anticoagulated with VKA had more unfavorable thromboembolic and bleeding risk factors than DOAC patients, whereas risk factors were similarly distributed among three DOAC subgroups. Only 37% of patients using VKA had optimal dosing control, whereas three groups of DOAC patients had optimal dosing in >92% of cases. There were significantly more thromboembolic and bleeding events among patients with poorly controlled VKA therapy in comparison to patients exposed to DOACs or optimal VKA (15% vs 3% thrombotic events, and 14% vs 4% bleeding events, respectively). After adjusting for all factors unbalanced at baseline and for optimal dosing, significant difference in thrombotic and bleeding events between VKA and DOACs was lost. However, patients who received VKA at baseline, irrespective of optimal dosing, had higher mortality even after adjusting for all factors unbalanced at baseline. Permanent discontinuation of therapy was very rare, whereas 18% of patients experienced therapy switch. Only 46% of patients with poorly controlled VKA therapy, and only 24% of patients who experienced a thrombotic event while actively taking VKA, experienced a therapy switch immediately after the event. **Conclusion**: Despite a steady trend of increased DOAC use in AF, higher risk patients still receive VKA relatively more often possibly due to socio-economic reasons. They also rarely obtain optimal dosing control, rarely switch therapy after events, and have significantly shorter survival compared to patients on DOACs.

Robert Mujkić, Darija Šnajder Mujkić, Ivana Ilić, Anđela Grgić, Edi Rođak, Dalibor Divković, Kristina Selthofer-Relatić

**Introduction**: Extracellular matrix (ECM) is essential for adipogenesis, adipose tissue growth and architecture. ECM processes are deregulated in obesity, related to immune cell accumulation in adipose tissue and impaired metabolic functions. Soluble CD163 is a new macrophage-specific serum marker elevated in inflammatory and related with obesity and diabetes mellitus II, called obesity-related insulin resistance. (1-3) The study aimed to investigate the occurrence of collagen deposition and CD163+ accumulation in the subcutaneous (SAT) and visceral (VAT) adipose tissue of male children. **Patients and Methods**: This research included 30 young male children, age in range 3.88 [3.10-9.71] years old, hospitalized for elective abdominal surgery at the Department of Pediatric Surgery of the University Hospital Osijek, divided into two groups depending on their body mass index score (BMI) Z-score: normal weight (NW) group, (N=13) and overweight/obese (OO) group, (N=17). SAT and VAT samples were gained during the surgical procedure. Before the beginning of the research, patients’ parent gave written consent. Immunohistochemistry for CD163+ cells was performed, and the number of positive cells was counted per mm2 of adipose tissue. Histological staining for extracellular components with standard Masson’s trichrome stain method was also performed and histomorphometric analysis was conducted using the free online image analysis program Fiji, a distribution of ImageJ. **Results**: The OO group were significantly older (5.75[3.65-10.30] vs. 3.20[2.40-4.25] years old; p=0.025) and they had higher BMI, Z-score, waist and hip circumference. In the group of OO, there was an increased collagen deposition in SAT compared to NW group (5.54 vs 3.89%; p=0.048). In the same OO group, a larger adipocyte surface area in SAT when compared with NW group was observed (980.47 vs 604.77µm2; p<0.001). In VAT more CD163+ cells were counted in the group of OO children (178.00 vs 93.00; p<0,001). **Conclusion**: In healthy young male children increased collagen deposition and adipocyte hypertrophy is related to their weight status. Independent of age, more accumulation of CD163+ cells was observed in VAT of overweight/obese children. Early childhood fat tissue changes can present a future adult risk for metabolic-related diseases.

Mario Ivanuša

The COVID-19 pandemic and the that hit Zagreb in March not only reduced the availability of health care and caused higher morbidity and mortality in the population of the Republic of Croatia, but also limited the use of secondary prevention measures in cardiovascular (CV) patients. These high-risk patients were faced with a drastic change in the quantity and quality of daily activities, quarantine and isolation as a result of COVID-19, and fear of the consequences and uncertainty from a sudden earthquake, all leading to a health disruption. These rapid and significant changes in everyday life, especially in those who can marshal less mental resilience, have resulted in a deterioration of lifestyle habits and impairment of the quality of life. (1) To adequately respond to the emerging conditions, the program of outpatient CV rehabilitation of the Srčana Institute for Cardiovascular Prevention and Rehabilitation in Zagreb embraced digitalization and reorganized its traditional patterns (2) to implement a fully virtual program for the first time. The virtual program has been running for 60 days, and we will outline the full scope of adjustments made to the program since March until the end of 2020. During the period from March 23 to May 28, 2020, we used easy-to-reach methods of communication, such as telephone-delivered or text messaging interventions that we accompanied with structured therapeutic education and digital materials sent to CV patients by e-mail. Additionally, we dedicated a section on our web portal to publishing all digital content (PDF, mp4) with recorded medical exercises for CV patients and advice from psychologists and other members of the CV rehabilitation team, covering topics such as nutrition and other important information. (3) To maintain patient engagement after the earthquake, 80 patients who remained virtually involved in the program were also included in the weekly newsletter program. (4) Despite our focus on maintaining high engagement, five patients opted out of the program, which is still in line with our expectations. Having restored conditions for the safe implementation of the program, we recommenced performing the traditional form of rehabilitation in our center (12 weeks, 36 sessions), starting with previously enrolled patients and followed by newly admitted patients two weeks after. In order to reduce the possibility of accidental infection of CV patients and healthcare professionals with COVID-19, we have adapted the organization and protocols of all therapeutic interventions, ensured the application of hygienic procedures and social distancing, and, in addition to the use of personal protective equipment, we have installed protective glass on reception desks (**Figure 1**). All visits to the Institute are recorded, and after measuring body temperature at the entrance and checking for negative epidemiological history, we acquaint visitors movement limitations that are currently in force in the institution. The program of outpatient CV rehabilitation, in accordance with the experience of other countries, has been adapted by focusing on the most important components of secondary prevention: risk stratification, correction of variable risk factors, psychosocial support, therapeutic education, and medical exercises. In this way, we strive to ensure the high quality of health care among high-risk CV patients. FIGURE 1. Organization of a medical gymnastics hall before (A, B) and after (C, D) the COVID-19 pandemic.

Drago Rakić, Zrinka Jurišić, Cristian Bulat, Ivana Cvitković, Zvonko Rumboldt

**Introduction**: Accounting for 50% of all primary cardiac tumors, myxomas are the most common; some 75% are located in the left atrium, the rest occur in other heart chambers, encroaching occasionally even the valves. Three quarters are pedunculated, mostly originating from the atrial septum. These tumors are often gelatinous and friable, increasing the risk of embolism. Their diameter varies from a few millimeters to several centimeters. (1) The aim of this case presentation is to underscore the role of echocardiography in prompt detection and early surgical treatment of such tumors, particularly among young patients. **Case report**: In November 2019 a 60-year-old cashier suddenly experienced at her counter “discomfort all over her body” followed by right hand drop. After some 5-10 minutes of “massage” she felt much better and the hand recuperated its strength so that she continues to serve the customers. Only a week later she consulted her physician: the physical examination was within normal limits, her blood pressure was 140/80 mmHg, and ECG disclosed sinus rhythm, 76 bpm/min. However, echocardiography unveiled an oval, 20x20 mm, pedunculated, mobile mass stemming from the atrial septum, presumably myxoma. The patient was immediately referred to and hospitalized where the clinical suspicion was confirmed. Except for an elevated CRP (72.6 mg/l) the rest of her data were within normal limits, including coronarography. She was operated on the fifth day after the initial visit and 12 days after the initial symptoms. Histological examination of the excised tumor confirmed the clinical impression of gelatinous myxoma. The patient was observed for a couple of days because of the nodal rhythm and discharged with no symptoms. Up to this moment she is free of any symptoms or signs. **Conclusion**: Since left atrial myxomas may cause stroke and other embolic events, echocardiographic examination in case of TIA is warmly advised because of its wide availability, noninvasiveness and high sensitivity. As this case illustrates, it offers fast diagnostic detection and prompt surgical cure of atrial myxoma, preventing future embolism and eliminating anticoagulant therapy.

Mladen Jukić

Main role of coronary computed tomography angiography (CCTA) is to rule out obstruction in patients with suspected coronary artery disease (but no ST-elevation myocardial infarction), and to alleviate invasive cardiology of unnecessary diagnostic procedures. This is especially useful in situation of COVID-19 pandemic, since CCTA can be performed in outpatient setting, with very short times of personnel to patient exposure. (1) In 2020 we had 1393 patients on CCTA (a 30% increase from 2019), and in 69% we excluded obstructive coronary artery disease. We believe this shows that CCTA as first line strategy can, when appropriate, relieve invasive cardiology, and comparatively reduce COVID-19 transmission channels.

Diana Rudan, Miroslav Raguž, Ivana Jurin, Hrvoje Falak, Tomislav Svaguša, Jelena Kursar, Danijela Grizelj, Mario Udovičić, Irzal Hadžibegović

**Background**: Outpatient non-invasive and invasive diagnostic and therapeutic procedures and outpatient follow-up in cardiology are definitely going to increase in near future. (1) Aim: To analyze diagnostic and therapeutic procedures performed within outpatient cardiology clinic in University Hospital Dubrava in 2019 and 2020 and to observe future opportunities and threats. **Methods**: We analyzed and compared data on non-invasive and invasive diagnostic and therapeutic procedures performed in outpatient clinic during 2019 (12-month active period including renovation and dislocation period was analyzed) and 2020. (4.5 months active period between the two waves of the COVID-19 pandemic in Croatia was analyzed). **Results**: During the 12 months period in 2019 there were 205 coronary angiographies, 30 cardioversions, 146 MSCT coronary and aortic (TAVI assessment) angiographies, 81 LVAD controls, and 325 administered intravenous therapies. In the year 2020. outpatient clinic was closed during the pandemic and reorganization of University Hospital Dubrava as a dedicated COVID-19 hospital. During the 4,5 months active period in 2020 there were 136 coronary angiographies, 18 cardioversions, 192 MSCT coronary and aortic (TAVI assessment) angiographies, 17 LVAD controls, and 186 administered intravenous therapies. During both observed periods there were only 4 documented hospitalizations due to complications after invasive outpatient procedures (1 contrast induced nephropathy, 2 bleeding events and 1 minor vascular complication). **Conclusion**: Outpatient non-invasive and invasive diagnostic and therapeutic procedures increased in the period between the two waves of the COVID-19 pandemic, showing the importance of outpatient cardiology clinic in providing needed health care for patients with cardiovascular diseases during and after the pandemic. In future, hospitalization and prolonged hospital stay will most probably be avoided, with growing opportunities for outpatient clinics, but also with growing needs for changing our everyday habits in diagnostic and therapeutic procedures.

Fatmir Ferati, Anida Ferati, Ardian Preshova, Mentor Karemani, Nexhbedin Karemani

**Introduction**: Left ventricular (LV) pseudoaneurysm (PA) are rare but rare complications after myocardial infarction (MI), caused by the partial rupture or defect on LV wall, with intact pericardium. (1-3) **Case report 1**: Patient RSH, 57 years old, male, with anamnesis of old MI of the inferior wall, was admitted to the hospital for angina pectoris. Coronarography was performed without significant stenosis of coronary arteries. On the echocardiography (January 18, 2017) defect in the inferior wall of the LV was confirmed, together with a small pericardial effusion (**Figure 1**). 10 days after, enlargement of the PA was noticed (1.52 cm) without symptoms (**Figure 2**). The patient refusing surgical treatment. On February 28, enlargement of the PA was noted. But due to congestive heart failure on March 28, further PA enlargement was spotted – the size of the PA was 16,5 cm2 (**Figure 3**). The operation was done with Dor’s approach. On the echocardiography done one month after the operation the patient was hemodynamically stable without rhythm changes, and symptom free. FIGURE 1. Small pericardial effusion. FIGURE 2. Enlargement of the pseudoaneurysm. FIGURE 3. Further pseudoaneurysm enlargement. **Case report 2**: Patient LH aged 70, was admitted to the hospital due to an anterior STEMI on July 3, 2019. The urgent PCI was performed. Echocardiography on July 5 noted small discontinuities in of apical segment. Another examination was scheduled for July 12, but the patient did not show up. On July 23, the patient was admitted like an urgent case with atrial fibrillation and congestive heart failure. In the echocardiography the rupture of myocardium in apical region was noted, 2 cm long, with large pseudoaneurysm formation (**Figure 4**). Urgent cardiac surgery was done. On the check conducted on August 15, 2019, optimal reconstruction of LV has been noted, with very good EF from 62% on basal region with akinetic apical segment, due to a reconstruction of this part. FIGURE 4. A 2 cm long rupture of the myocardium in the apical region was observed, with large pseudoaneurysm formation. **Conclusion**: 1. PA are rare but very serious complications; 2. Hemodynamic and rhythmical instability are present in both cases; 3. Surgical intervention is necessary option in cases of PA with acute rupture and in those with the tendency of their increase; 4. Cardiosurgical interventions of the PA should be conducted timely, before the damages of LV, which disables their optimal treatment.

Ana Fabris

**Introduction**: A more quantitative method for evaluation of stress echocardiography is introduced by measuring deformation (1-3). **Case report**: A 69-year old woman, formerly fitted with a double CABG, presents to the Polyclinic as a result of a new chest pain and shortness of breath on exertion. Exercise stress echocardiography with cardiac function parameters is performed: during the exercise, no cardiac arrhythmias and ECG signs of myocardial ischemia are shown, but testing is interrupted due to the leg pain at 71% of the theoretical maximum frequency. Immediate postpeak color Doppler derived long-axis systolic strain rate significantly decreases in midanteroseptal and basal posterior segment and insignificantly decreases in midinferior segment. Immediate postpeak parameters of diastolic function are borderline. MSCT coronary angiography: LIMA-LAD is flowing smoothly, with adequate flow through the distal LAD and collateral opacification of PD and PL. Long-lasting plaques with abundant calcifications are evident in the proximal segment ACx, therefore it is impossible to determine the degree of stenosis. The venous graft (VSM-RCA) is occluded. Coronary angiography: LAD at the beginning of the middle segment is suboccluded (99%), and then the competitive flow from the LIMA-LAD is seen. LIMA-LAD is in good condition and connection. After the attachment of the LIMA-LAD, LAD is diffusely altered with long, borderline (70%) stenosis. Borderline (50%) stenosis in the middle ACx segment is followed by a series of marginal changes. RCA is occluded at the end of the proximal segment. VSM-RCA bypass is of the proper flow and connection. **Conclusion**: Exercise stress echocardiography with the cardiac function parameters may reveal the alterations in the CABG function.

Ana Fabris

**Introduction**: Small coronary vessel disease may be related to a functional and/or organic factor. **Case report**: A 60-year-old man with the history of the arterial hypertension and type 2 diabetes, presents to the Polyclinic with a significant number of VES and nsVT in the 24 h ECG monitoring. Slightly enlarged LV, moderately enlarged LA and mild MR are shown in the transthoracic echocardiography. Systolic and diastolic functions of the LV are found within normal limits. Exercise stress echocardiography with parameters of the cardiac function is interrupted at achieved 83% of the theoretical maximum frequency due to arrhythmia, without the ST depression. WMSI 1.25 is registered at the baseline and 1.13 immediate postpeak. Significant postpeak color Doppler derived strain rate decrease is registered in midanteroseptal, basal inferolateral and midinferior segment. Coronary angiogram reveals no organic stenosis of the main epicardial coronary arteries, but diffuse tightening of the lowest segments of the coronary macrocirculation, which might be related to the diffuse microvascular disease in diabetes and arterial hypertension. **Conclusion**: Exercise stress echocardiography with the cardiac function parameters might be useful in detection of the small coronary vessel disease. (1, 2)

Luka Perčin, Maja Strozzi, Darko Anić, Mislav Planinc, Goran Međimurec, Tomislav Tokić, Kristina Marić Bešić

**Introduction**: An anomalous aortic origin of the left main coronary artery (LMCA) with an inter-arterial or intramural course is a rare but dreadful congenital condition that carries a substantial risk of sudden cardiac death (1, 2). It can present with syncope, myocardial infarction, and arrhythmias that can lead to cardiac arrest. Coronary computed tomography angiography (CCTA) is a commonly used imaging method in detecting the anomaly while cardiac surgery is the treatment of choice (3). **Case report**: We present a case of a 19-year old female with a medical history of intermittent chest pain and presyncope who was hospitalized at the University Hospital Centre Zagreb due to an out of hospital cardiac arrest followed by successful cardiopulmonary resuscitation. At the admission, she was sedated, intubated, mechanically ventilated and hemodynamically stable. After the conduction of an induced hypothermia protocol, the patient was extubated and awakened without signs of neurological deficit. While both echocardiography exam and the magnetic resonance scan confirmed a structurally normal heart, CCTA showed an anomalous origin of the LMCA from the right coronary sinus with an inter-arterial narrow course between the wall of the ascending aorta and pulmonary artery (**Figure 1**). Since this finding identified the underlying reason for cardiac arrest, the cardiothoracic surgeon was consulted. The patient subsequently underwent cardiac surgery where it was verified that LMCA courses within the anterior aortic wall (**Figure 2**). A successful „unroofing procedure“ was performed which consisted of an incision of the intramural segment of LMCA with neo-ostium formation at the left coronary cusp (**Figure 3**). The patient had an uneventful postoperative period and was discharged without complications. On follow-up, control CCTA confirmed the normal origin and course of LMCA (**Figure 4**) which correlated with the patient`s excellent performance on cardiac exercise stress testing. FIGURE 1. Computed tomography coronary angiogram, axial plane. Anomalous origin of left main coronary artery from the right coronary sinus (black arrow). FIGURE 2. Intraoperative photograph. The right coronary sinus as seen after the aortotomy with the ostium of the right coronary artery (black arrow). The coronary probe is placed inside the intramural course of left main coronary artery (black arrow with interrupted lines). FIGURE 3. Intraoperative photograph. Left main coronary artery (LMCA) after the unroofing of the intramural portion with neo-ostium of the LMCA in the left coronary sinus (black arrow). FIGURE 4. Computed tomography coronary angiogram, axial plane. Neo-ostium of the left main coronary artery in the left coronary sinus (black arrow). **Conclusion**: The main aim of this case report was to emphasize anomalous LMCA origin as an important cause of chest pain, syncope and arrhythmias that can lead to cardiac arrest in young, otherwise healthy patients. Furthermore, we wanted to point out the „unroofing procedure“ as an effective method of anomalous LMCA origin treatment.

Irena Ivanac Vranešić, Lea Jerkić, Maja Hrabak Paar, Jadranka Šeparović Hanževački, Martina Lovrić Benčić

**Introduction**: Congenital pericardial agenesis (CPA) is a rare cardiac condition with an incidence of < 1 in 10000. It can be found in isolation or associated with other congenital cardiac abnormalities. The most common form is complete left-sided CPA and patients are usually asymptomatic. On the other hand, patients with partial CPA may be more symptomatic and at higher risk for complications due to cardiac herniation. (1, 2) **Case report**: A 54-year-old lady with history of hypertension was referred to our outpatient clinic because of dyspnea on exertion and palpitations. Physical examination revealed BP of 180/85mmHg and mild systolic murmur. An EKG showed normal sinus rhythm, with a heart rate of 65 bpm, vertical heart axis, Q waves from V1-V3 and slow R wave progression in precordial leads. A 24-hour Holter EKG and a treadmill exercise stress test were unremarkable. During the echocardiography study a marked leftward and posterior displacement of the apical 4-chamber window was noted. Impression of cardiac hypermobility, left ventricular bulbous appearance and elongated, compressed atria were observed. Parasternal LAX window was also shifted more laterally and from this view right ventricle appeared dilated. All these findings raised the suspicion of complete CAP. The CMR confirmed the diagnosis by showing typical indirect signs of complete left-sided CAP. Pericardial continuity was only seen on the right side, close to atria (**Figure 1**). FIGURE 1. A) Axial thoracic half-Fourier acquisition single-shot turbo spin-echo (HASTE) image depicts levorotation of the heart with posterolateral shift of the left ventricular apex. Pericardial continuity on the right side close to atria is preserved (arrow); B) 3D non-contrast MR angiography. Interposition of lung tissue (arrow) between the ascending aorta (A) and the main pulmonary artery (PA) is typical for complete left-sided pericardial agenesis; C) Two-chamber steady-state free precession (SSFP) view of the heart. Interposition of the lung parenchyma (arrow) between the left hemidiaphragm and the inferior cardiac surface. **Conclusion**: Complete CPA is usually incidentally diagnosed on cardiac imaging, cardiac surgery or postmortem. Marked leftward and posterior shift of the heart, as the most prominent sign on chest X-ray or echocardiography, should raise suspicion of this entity and CMR or cardiac CT should be performed in order to confirm the diagnosis. Although majority of patients with complete CPA are asymptomatic with good long-term prognosis, some may experience debilitating symptoms and may require surgery.

Zijo Begić, Nedim Begić, Edin Begić

**Introduction**: Exercise stress test (ergometry) in pediatric cardiology practice is used to examine the condition and functional ability of the heart in children. It is performed using a bicycle ergometer or treadmill, estimating and measuring the amount of physical activity, heart rate, blood pressure values and electrocardiogram. (1, 2) The aim of article was to present the role and importance of exercise stress test in everyday clinical pediatric cardiac practice. **Patients and Methods**: Based on data from medical histories and the Register of Exercise stress test from the Pediatric Clinic, Clinical Center of the University of Sarajevo in the period from April 2008 to January 2020, we conducted a retrospective and descriptive study. **Results**: During mentioned period, 840 exercise stress tests were performed on a treadmill according to the Naughton protocol. There were 474 boys (56.4%) and 366 girls (43.6%). According to age, 375 (44.6%) patients were aged 15-19, and 465 (55.3%) aged 5-15. Indications for the test were congenital heart defects (CHD), before and after surgery in 321 (38.2%) cases, significant or insignificant arrhythmias (incisiona) in 269 (32%) patients, assessment of the possibility of playing sports and performing physical activity in 86 (10.2%) patients, chest pain in 64 (7.6%) patients, arterial hypertension in 51 (6.1%) patients, transient loss of consciousness in 36 (4.3%) patients, while other indication were in 13 (1.6%) patients. Positive test was in 126 patients (15%), while control ergometry was indicated in 49 patients (6%). **Conclusion**: Exercise stress test has a significant place in examining the causes of pain in children with CHD before or after surgery, detection and treatment of arrhythmias, as well as assessment of physical activity and ability of doing sport for the child.

Zvonimir Ostojić, Klara Klarić, Marijan Pašalić, Kristina Marić Bešić, Maja Strozzi, Ivan Škorak, Hrvoje Jurin, Bosko Skorić, Eduard Margetić, Joško Bulum

**Introduction**: Smaller stent diameter represents risk factor for target lesion failure (TLF). Drug coated balloons (DCB) could represent valid substitution for stents in selected patients. (1) The aim of the study was to assess clinical and angiographic outcomes after percutaneous coronary interventions (PCI) using DBC in treatment of coronary arteries ≤ 2.5 mm. **Patients and Methods**: Study included 222 patients treated with DCB between January 2012 and June 2019. All baseline procedures and consecutive coronary angiographies were reviewed to determine indication, lesion complexity, vessel size and procedural success. Baseline and follow up clinical data were extracted from hospital digital database. **Results**: Mean patient age was 63.8±10.6 years, with the majority being men (N=162, 73%). In total 108 (48.6%) patients were hospitalized due to acute coronary syndrome (ACS), of which 28 (12.6%) had ST segment elevation myocardial infarction. Altogether, 107 (48.2%) patients had multivessel disease and 84 (37.8%) had bifurcation stenosis. DCB was most often used (59%, N=131) in the treatment of side branches. Mean DCB diameter and length were 2.18±0.23 mm and 20.4±5.4 mm, respectively. Overall, procedural success was 92.8%, with 16 (7.2%) cases requiring “bail out” stent implantation. Regarding angiographic follow up, 111 (50%) patients underwent repeated coronary angiography (21 (19%) due to ASC). Mean time to repeated coronary angiography was 12.4±15.9 months. TLF was observed in 14 (12.6%) patients, of which 9 (8.2%) underwent target lesion PCI. After multivariable analysis, longer baseline procedure and fluoroscopy duration, higher volume of contrast administered and total Kerma air exposure were in positive correlation with TLF. Mean time of clinical follow up was 30.3±25.8 months, with 43 (19.4%) patients lost in follow up. Regarding clinical outcomes, angina improvement was observed in 149 (28.2%) of cases. Out of 53 (29.6%) patients examined in emergency department, 36 (20.1) were urgently hospitalized and 4 (2.2%) died. **Conclusion**: Utilization of DCB in treatment of coronary arteries ≤ 2.5 mm, when stent implantation is not feasible, provides good angiographic and clinical long-term outcome. More complex interventions represent risk factor for TLF. Further studies are needed to confirm presented results.

Petra Mjehović, Ana Reschner Planinc, Dubravka Šipuš, Maja Čikeš, Hrvoje Jurin, Joško Bulum, Davor Miličić, Boško Skorić

**Introduction**: Congenital coronary artery fistulas (CAFs) are coronary artery anomaly characterized by a direct connection between one or more coronary arteries and any of the 4 chambers or any of the great vessels. The incidence is approximately 0.08-0.3% of patients undergoing coronary angiography. (1) Coronary angiography is the gold standard for detecting the presence of coronary artery fistulas and estimation of their hemodynamic significance. CAFs that drain into the LV may cause myocardial ischemia due to coronary steal syndrome but rarely lead to hemodynamic impairment, due to high pressure in the LV. (2) Ageing increases the risk of their dilatation, thereby increasing the risk of complications. **Case report**: 72-year-old female with a history of arterial hypertension, dyslipidemia, and chronic obstructive pulmonary disease was hospitalized for anginal symptoms. She reported anginal symptoms during minimal physical activity and relieved by nitroglycerine. Echocardiography showed preserved systolic function with a discrete hypocontractility of the apical segment of the anterolateral and anterior wall. Coronary angiography showed coronary arteries without angiographically significant stenosis. However, intensive opacification of myocardial walls after contrast injection and contrast drainage into the ventricles through extensive multiple microfistulas were observed. Due to multiple and small-sized CAFs our patient was not suitable for interventional or surgical closure. The antianginal therapy was upgraded with trimetazidine (2x35 mg) and ranolazine (2x500 mg) with favorable response. **Conclusion**: Although a rare cause of angina pectoris, the coronary steal syndrome caused by the coronary arterial-ventricular fistulas should be considered during diagnostic work-up. Besides myocardial ischemia, CAFs may cause arrhythmias, heart failure, and infective endocarditis.

Irzal Hadžibegović, Mario Sičaja, Ivana Jurin, Jasmina Ćatić, Sandra Jakšić Jurinjak, Neven Čače

**Background**: In April 2019 SCAI published the first consensus document on patent foramen ovale (PFO) closure after cryptogenic stroke, driven by the positive results of CLOSE, REDUCE, and DEFENSE-PFO trials. (1) Aim: To analyze referral and indication for PFO closure in our institution before and after April 2019. **Methods**: We analyzed clinical characteristics, imaging data, referral information and follow-up data of patients that underwent PFO closure before and after the publication of 2019 consensus document. **Results**: From 2016 to 2020 a total of 26 patients underwent PFO closure (14 patients before, and 12 patients after the 2019 consensus paper). There were no significant differences in patient’s demographic and clinical characteristics. Patients in both groups were all referred by a neurologist after stroke/TIA and underwent CT or MRI brain scan, 24-h ECG monitoring and TEE exam before the procedure. All patients treated after the 2019 consensus had subcortical lesions on CT or MRI. Only 1 patient in pre-consensus group with history of TIA had no imaging evidence of subcortical ischemia before the procedure. All patients had and at least 1 TEE high risk feature. There were more patients on direct oral anticoagulation drugs after stroke after the 2019 consensus. All patients were treated with Amplatzer device and received dual antiplatelet therapy for at least 3 months, with additional ASA continued indefinitely in selected high-risk patients. There were no documented recurrent ischemic events or new onset atrial fibrillation within 1 year after PFO closure in both groups. **Conclusion**: There were no significant differences in referral and indications for PFO closure before and after the 2019 consensus. Very careful patient selection, in concordance with the consensus, relates to procedure safety and long-term outcomes. Neurologists remain the gatekeepers, whereas cardiologists plan and perform the procedure, and tailor postprocedural antithrombotic therapy. We observed an increase in annual volume after the consensus, most probably because of increased awareness after 2018, and facilitation of the decision to perform PFO closure after cryptogenic stroke brought by the consensus document.

Lara Gudelj, Matias Trbušić

**Introduction**: Transradial access (TRA) is well established approach but there is a possibility of a failure due to anatomic vascular anomalies, radial artery spasm or stenosis. Secondary approach is needed, and most clinicians tend to use transfemoral access (TFA). Some believe that transbrachial approach (TBA) is an obsolete catheterization route due to high risk of complications. (1-3) Our hypothesis is that for TR cardiologists with high success rate, TBA is easier and more suitable first alternative. In TRA era complications of TFA are relatively more common because trainees have no experience in femoral artery compression nor staff with care around puncture site. We have decided to investigate outcomes of TBA for coronary angiography and intervention. The aim of this study was to demonstrate effectiveness and feasibility of TBA for percutaneous coronary intervention in patients in whom TRA is not possible. **Patients and Methods**: We collected all cases that underwent diagnostic coronary angiography and intervention from August 2012 to February 2020, with total of 116 patient. Arterial sheath was removed 6 hours (hrs) after procedure if coronary intervention was performed or 3 hrs after coronary angiography. Direct manual pressure was applied to brachial artery for 10 min, after hemostasis was secured, further local pressure with elastic bandages for 2 hrs. Patients were advised to restrict movements of hand, especially elbow and best rest for 6 hrs. **Results**: Median patient age of patients was 69 yrs., with 70 male patients (63%). There was only 1 case of major complications of arterial thrombosis due to intensive elastic bandage compression and 1 minor complication of hematoma that resolved in few weeks. Our low complication rate could be since we used material intended for radial artery puncture and accurate puncture technique was performed with gentle, delicate maneuver of catheter. Since P< 0.05 we consider these results statistically significant. **Conclusion**: Results we have presented show that TBA is effective and feasible alternative to TRA with many advantages in comparison to TFA such as early ambulation, positive feedback from patients and availability in aortoiliac disease if performed by operators experienced in arm approaches. However, more caution is needed that with TRA to avoid complications such as thrombosis.

Rea Levicki, Martina Lovrić Benčić, Martina Matovinović, Lada Bradić, Kristina Gašparović, Tamara Božina, Nada Božina, Jadranka Sertić, Bojan Jelaković

**Introduction**: Region near the gene encoding methylenetetrahydrofolate reductase (MTHFR) is associated with blood pressure. CT and TT genotype of the C677T MTHFR gene are more common in obese hypertensive patients with BMI>29 kg/m2. (1, 2) The aim of this study was to prove the connection between C667T polymorphism of MTHFR gene and non-dipping pattern in 24h ambulatory blood pressure monitoring (ABPM) in obese patients. **Patients and Methods**: We included 33 patients from a multidisciplinary weight management program in which genetic analysis on MTHFR gene polymorphism was tested and 24h ABPM was performed. Patients were divided into 3 groups: 12 patients with MTHFR C677T healthy genotype CC (9 W, 3 M, age 48.83±9.82y, BMI 44.39±9.69 kg/m2), 14 patients with MTHFR C677T heterozygous mutation CT (11 W, 3 M, age 47.93±8.74y, BMI 40.9±5.96 kg/m2), 7 patients with MTHFR C677T homozygous mutation TT (6 W, 1 M, age 43.43±12.22y, BMI 37.46±5.79 kg/m2). In each group 24h ABPM results were analyzed, and dipping status was determined according to percentage of night systolic blood pressure drop and divided into 4 groups: inverse dipper (20%). **Results**: Patients with MTHFR C677T: CT had the lowest average night blood pressure drop (8.51±5.9%), comparing to MTHFR C677T: TT (10.17±4.72%) and MTHFR C677T: CC (10.53± 6.07%). Patients with MTHFR C677T:CT (**Figure 1**) were the only group with inverse dipper pattern present, but also with significant non-dipping pattern (inverse dipper 7.1%, non-dipper 35.7%, dipper 57.1%) comparing to patients with MTHFR C677:TT (non-dipper 28.6%, dipper 71.4%) (**Figure 2****)**. Patients with MTHFR C677T:CC (**Figure 3**) had the highest level of dipper pattern, but also extreme dipper patter was present (non-dipper 25%, dipper 66.7%, extreme dipper 8.3%). FIGURE 1. Dipping status distribution in patients with MTHFR C677T heterozygous CT mutation. FIGURE 2. Dipping status distribution in patients with MTHFR C677T homozygous TT mutation. FIGURE 3. Dipping status distribution in patients with MTHFR C677T healthy CC genotype. **Conclusion**: MTHFR C677T:CT polymorphism is the most associated with pathological patterns in dipping status; non-dipper and inverse dipper status, more than MTHFR C677T:TT, what indirectly indicates higher cardiovascular risk.

Besim Memedi, Agron Zuferi

**Introduction**: The metabolic syndrome over recent years is being actively studied and is in the focus of experimental and clinical studies. Insulin resistance cause major problem in metabolism and is related not only to obesity but also to the pathogenesis of type 2 diabetes, cardiovascular disease, etc. (1-3) Purpose: The effect of fructose on body weight in experimental adult rats and the effect of fructose on the content of glucose, triglycerides, uric acid, insulin, adiponectin and leptin in the blood of experimental animals. **Material and Methods**: The study was performed on 12 adult male rats divided into two groups: control group and fructose group. Experimental animals were treated daily in a period of 8 weeks with 10% fructose solution, 1ml/100g by mouth (per os). While, the control group of animals was treated with a vehiculum (physiological digestion). **Results**: **Table 1** are presented the changes in body weight of experimental animals under the influence of fructose. Statistically significant (p<0.05) is the weight of fructose-treated experimental animals compared to the control group at the end of the experiment. **Table 2** presents the results from the definition of other indicators. The animal blood glucose levels are elevated treated with glucose compared to the control group. Statistically significant is the increase in blood of the triglyceride levels after 8 weeks of glucose treatment. ### TABLE 1: Influence of fructose on body weight of adult male mice. | **Group** | **Weight at the beginning of the experiment (g)** | **Weight at the end of the experiment (g)** | | --- | --- | --- | | K (n=6) | 130.0 ± 30.0 | 180.0 ± 33.0 | | H (n=6) | 132.0 ± 25.0 | 250.0 ± 40.0* | ### TABLE 2: Impact of fructose on glucose, triglyceride, uric acid, insulin, adiponectin and leptin contents in experimental animal blood. | **Group** | **Group** | **Glucose** **(mmol/L)** | **Triglycerides** **(mmol/L)** | **Uric acid** **(mg/dL)** | **Uric acid** **(mg/dL)** | **Uric acid** **(mg/dL)** | **Insulin** **(ng/ml)** | **Adiponektin** **(ng/ml)** | **Leptin** **(ng/ml)** | | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | | K (n=6) | 6.0 ± 0.4 | | 1.2 ± 0.03 | | 3.7 ± 0.2 | 2.8 ± 0.3 | | 6.0 ± 2.1 | 28.7 ± 3.1 | | H (n=6) | 18.2 ± 1.2* | | 4.6 ± 0.3* | | 6.5 ± 1.1* | 3.5 ± 1.8* | | 2.4 ± 0.05* | 35.9 ± 4.0* | **Conclusions**: The analysis of insulin elevation and blood sugar rise gives us reasons for the development of “insulin resistance” under the influence of fructose. At the experimental animals cannot be demonstrated the effect of insulin elevation, and fasting blood sugar is elevated after 8-week treatment with fructose.

Irzal Hadžibegović, Danijel Unić, Ivana Jurin, Nikola Bradić, Boris Starčević, Igor Rudež

**Background**: Transcatheter aortic valve implantation (TAVI) was proved to be a preferred method of severe aortic stenosis treatment in patients with medium and high surgical risk. However, that significant superiority over surgery is maintained only if femoral approach is possible. (1) Aim: We analyzed changes of approach to TAVI implantation before and after the introduction of percutaneous transfemoral implantation, together with data on 12-months survival, complications and hospital stay. **Results**: Among a total of 149 patients who received TAVI in our center, there were 94 implantations before and 55 implantations after the introduction of routine percutaneous implantation when it is feasible (with surgical cut-down reserved only for patients with peripheral artery disease). There were no significant differences in patients’ characteristics and risk factors among patients operated during two different periods. All 82 femoral procedures during the first period were performed with surgical cut-down, in addition to 9 transapical and 2 transaortic implantations. In the second period, there were 54 femoral implantations (30 with surgical cut down and 24 full percutaneous) and 1 transapical implantation. 12-month mortality (16% vs 7%), and median duration of hospitalization (10 vs 8 days) were lower among patients treated in the second period. However, there were more vascular complications in the second period (2% vs 9%), that were mostly resolved during the procedure, or within one day. **Conclusions**: After the introduction of full percutaneous approach to TAVI we observed a decrease in postoperative mortality, and reduction of hospital stay length, most probably due to significant decrease in relative proportion of transapical approach and routine surgical cut-down. Relative increase in vascular complications due to persistent selection of transfemoral approach in patients with challenging vascular access did not result in prolonged hospital stay or excess mortality. Future strategies for TAVI, especially during and after the pandemic era, will most probably favor fast-track approach, leaving hospital resources readily and longer available mainly for the most complicated patients.

Dario Dilber

**Introduction**: Sinus of Valsalva aneurysm (SOVA) is an abnormal dilatation of the aortic root located between the aortic valve annulus and the sinotubular junction. The function of the sinuses is to prevent occlusion of the coronary artery ostia during systole when the aortic valve opens. The estimated rate of Sinus of Valsalva aneurysm is approximately 0.09% of the general population (1). Sinus of Valsalva aneurysm can be either congenital, associated to connective tissue disorders, BAV, hypoplastic left heart syndrome or acquired, associated to atherosclerosis, chest injury or infective diseases. Sinus of Valsalva aneurysms usually affect the right coronary sinus (65–85%), followed by the noncoronary sinus (10–30%), and the left (< 5%) coronary sinus (2). Males are four times more likely to be affected than females (1). Patients that have sinus of Valsalva aneurysm may be asymptomatic or may present with dyspnea, chest pain, palpitations or syncope. Non-ruptured Sinus of Valsalva aneurysm thrombosis can lead to coronary ostia occlusion. Rupture of the right and noncoronary sinuses typically results in communication between the aorta and either the right atrium or the right ventricular outflow tract, thus creating a left to right shunt and requires surgical management. Non-ruptured sinus of Valsalva aneurysm should be surgically or percutaneously repaired with aneurysms greater than 5.5 cm without comorbidities and should be considered when there is a growth rate of more than 0.5 cm/year with beta-blocker in therapy. (1-3) **Case report**: A 52-year- old male with past medical history of a fall from height in 2004 presented to a cardiologist with complaints of shortness of breath and chest pain. He was sent for exercise stress test which demonstrated a reduced functional capacity with ECG changes in inferior leads at rest (**Figure 1**) He was referred for a transthoracic echocardiogram, which showed aortic root dilation to 5.8 cm and aneurysmal dilatation of the right sinus of Valsalva with moderate aortic regurgitation (**Figure 2**, **Figure 3**) and hypocontractility and fibrotic changes of inferoposterior wall of the left ventricle. Coronarography showed no significant disease (**Figure 4**). Finally, cardiac computed tomography angiography was performed (**Figure 5**), which confirmed dilation at the right coronary cusp, and patient was referred to a heart surgeon. FIGURE 1. Electrocardiogram showing changes in inferior leads. FIGURE 2. Echocardiogram showing dilatation of the right sinus (the parasternal short-axis view). FIGURE 3. Echocardiogram showing dilatation of the right sinus (the parasternal long axis view). FIGURE 4. Coronarography findings, right coronary artery with enlarged right sinus. FIGURE 5. Dilation at the right coronary cusp confirmed by a computerized tomography coronary angiogram.

Mario Udovičić, Danijela Grizelj, Vanja Ivanović Mihajlović, Hrvoje Falak, Ana Jordan, Igor Rudež, Davor Barić, Daniel Unić, Robert Blažeković, Josip Varvodić, Dubravka Jonjić, Boris Starčević

Heart transplantation (HTx) remains the gold standard and treatment of choice for advanced heart failure refractory to other methods (1, 2). In this study we report a single center experience and outcomes of patients referred to HTx by the Department of Cardiology, University Hospital Dubrava (UHD). All patients underwent HTx at the Department of Cardiac and Transplantation Surgery UHD, and were subsequently referred for follow up in close collaboration of two departments. We retrospectively examined the outcomes from 108 HTx recipients between 1995 and October 2020. The mean recipient age was 52.9 years, and 83.3% were male. Dilated cardiomyopathy was present in 56%, ischemic in 37% and 7% were other causes. 26 recipients (24.1%) were placed either on high urgent list of Eurotransplant or on national high urgent list. Survival was studied using Kaplan-Meier curves. Early in-hospital mortality was 10.2%. The global survival rates at 1, 5, and 10 years are 85.2%, 77.5% and 62.0% respectively. The mean survival is 141.5 months (95% CI, 117.2-165.1). Including patients referred from other centers, there have been 208 HTx in UHD in total since 1995. Annual HTx number peaked in 2019 when 21 HTx were performed, while in 2020 due to the COVID-19 lockdown only 12 HTx have been done so far. Three HTx recipients have been diagnosed with COVID-19 by now, two of which required hospitalization and high flow oxygen therapy, but all eventually recovered. Post-HTx survival rates at 1, 5, and 10 years remain high in UHD, while the program is currently facing challenges due to COVID-19 pandemic.

Dubravka Šipuš, Ivo Planinc, Boško Skorić, Vedran Velagić, Marijan Pašalić, Hrvoje Jurin, Daniel Lovrić, Jure Samardžić, Jana Ljubas Maček, Hrvoje Gašparović, Bojan Biočina, Davor Miličić, Maja Čikeš

**Background**: Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) is widely used in refractory cardiogenic shock and cardiac arrest but is characterized by increased left ventricular (LV) afterload and consequent development of pulmonary oedema (ECMO lungs). The ProtekSoloTM (LivaNova, IT) cannula is inserted via the right femoral vein to the left atrium, by a trans-septal puncture (under the guidance of transesophageal echocardiography and fluoroscopy). This bypasses the LV by draining blood from the left atrium to a paracorporeal pump (eg Rotaflow pump (Maquet, DE)) and returning it via a femoral artery cannula, thus providing direct unloading of LV. (1-3) We aimed to demonstrate our experience with the paracorporeal LV assist device using the ProtekSolo cannula and Rotaflow pump (PSp-LVAD). **Patients and Methods**: 7 adult patients underwent PSp-LVAD placement in UHC Zagreb from January to December 2020. We divided the patients in two groups: those who required PSp-LVAD to treat ECMO lungs (n=4) and those who received PSp-LVAD implantation prior to developing ECMO lungs (n=3). In addition to the description of the treated patients, we also assessed 30-day all-cause mortality. **Results**: The baseline characteristics of patients are shown in **Table 1**. All patients were male, mean age 56±9.3 years. 57.1% of patients underwent PSp-LVAD placement due to worsening of chronic heart failure and 42.9% due to acute coronary syndrome. Concurrent infection was present in 57.1% of patients. 71.4% were first on VA-ECMO support, of those 80% developed ECMO lungs. Laboratory tests (**Figure 1**) show improvement in kidney and liver function after PSp-LVAD placement. Outcomes are shown in **Table 2**; patients in prophylactic group have lower observed 30-day mortality rate (33% vs 75%) and longer VA-ECMO support duration due to lower mortality. Besides 2 patients who are still in active treatment, all others died during initial hospitalization due to infective complications, predominantly those that had a concurrent infection upon institution of the PSp-LVAD. ### TABLE 1: Baseline characteristics. | **N** | **7** | **N** | **7** | | --- | --- | --- | --- | | **Mean age (years)** | 56±9.3 | **Heart rate (beats/min)** | 90 (85-125) | | **Sex (male %)** | 7 (100%) | **Urinary output hourly (ml/h)** | 100 (15-180) | | **Mean BMI (kg/m2)** | 25.5±2.9 | **Laboratory values** | | | **Aetiology of cardiogenic shock** | | Lactate (mmol/L) | 2.1 (0.4-4.8) | | Worsening of chronic heart failure | 4 (57.1%) | BUN (mmol/L) | 11.5 (1.9-19.7) | | Acute coronary syndrome | 3 (42.9%) | Creatinine (umol/L) | 91 (61-133) | | **Duration of disease** | | AST (IU/L) | 193 (19-2132) | | Cardiomyopathy (years) | 8±5.3 | ALT (IU/L) | 75 (17-566) | | Acute coronary syndrome (days) | 5±6 | NTproBNP (ng/L) | 8118 (41-26245) | | **SAVE score** | -3 (-13, 6) | **Inotropic or vasopressor therapy before PSp-LVAD placement** | | | **VA-ECMO prior to PSp-LVAD** | 5 (71.4%) | Dobutamine | 4 (57.1%) | | **ECMO lungs** | 4 (57.1%) | Milrinone | 3 (42.9%) | | **Infection prior to VA-ECMO** | 4 (57.1%) | Levosimendan | 4 (57.1%) | | **Mean arterial pressure (mmHg)** | 76 (60-79) | Norepinephrine | 5 (71.4%) | [†] BMI: body mass index, SAVE: Survival After Veno-arterial Ecmo, VA-ECMO: veno-arterial extra corporeal membrane oxygenation, PSp-LVAD: Protek Solo paracorporeal left ventricular assist device, BUN: blood urea nitrogen, AST: aspartate transaminase, ALT alanine transaminase, NTproBNP: N-terminal prohormone of brain natriuretic peptide. FIGURE 1. Laboratory values before and after Protek Solo paracorporeal left ventricular assist device placement. BUN: blood urea nitrogen, NTproBNP: N-terminal prohormone of brain natriuretic peptide, AST: aspartate transaminase. ### TABLE 2: Outcomes. | | **ECMO lungs before PSp-LVAD (N=4)** | **No ECMO lungs before PSp-LVAD (N=3)** | | --- | --- | --- | | **30-day mortality** | 3 (75%) | 1 (33%) | | **Survival to decannulation** | 1 (25%) | 1 (33%) | | **Mean PSp-LVAD days** | 11±5 | 32.5±12 | | **VA-ECMO prior to PSp-LVAD** | 4 (100%) | 1 (33%) | | **Removal of oxygenator** | 2 (50%) | 3 (100%) | | **Durable LVAD implantation** | 0 (0%) | 1 (33%) | | **Complications** | | | | Infective | 4 (100%) | 1 (33%) | | Bleeding | 2 (50%) | 1 (33%) | [†] VA-ECMO: veno-arterial extra corporeal membrane oxygenation, PSp-LVAD: Protek Solo paracorporeal left ventricular assist device, LVAD: left ventricular assist device. **Conclusion**: Pulmonary edema (ECMO lungs) due to increased LV afterload is a major complication of VA-ECMO. Prophylactic LV unloading by PSp-LVAD seems associated with lower 30-days mortality.

Dubravka Šipuš, Ivo Planinc, Boško Skorić, Marijan Pašalić, Hrvoje Jurin, Daniel Lovrić, Jure Samardžić, Jana Ljubas Maček, Hrvoje Gašparović, Bojan Biočina, Davor Miličić, Maja Čikeš

**Background**: Right ventricular (RV) failure is a common complication of left ventricular assist devices (LVAD). (1, 2) We describe two cases of durable LVAD carriers requiring acute RV mechanical support provided using the ProtekDuo (LivaNova, IT) cannula, implanted via the right jugular internal vein, bypassing the RV by draining blood from the right atrium to an extracorporeal blood pump (Rotaflow pump, Maquet, DE) and returning it to the pulmonary artery (**Figure 1**). FIGURE 1. A) Chest X-ray after HM3 and ProtekDuo placement. B) Transthoracal echocardiography subcostal 4-chamber view. Red arrows indicate ProtekDuo cannula, red arrowhead indicates the tip of the cannula in the pulmonary artery. Yellow arrows indicate implantable-cardioverter defibrillator electrode. **Case report 1**: A 37-year-old male following LVAD implantation in 2016 due to dilated cardiomyopathy, was diagnosed with chronic RV failure in 2018. During a subsequent episode of of acute RV failure parenteral furosemide, dobutamine and intermittent levosimendan were started. Due to ensuing cardiogenic shock, veno-arterial extracorporeal membrane oxygenation (VA-ECMO) was placed. Three days later, an upgrade to a paracorporeal RVAD (p-RVAD) by placement of a ProtekDuo cannula and Rotaflow pump providing a flow of 4.15 litres/minute was performed. An improvement of hemodynamic parameters was obtained with the p-RVAD, but while awaiting the high-urgent heart transplantation, multiorgan failure and repetitive infections ensued, leading to the patients’ death. **Case report 2**: In April 2020, a 28-year-old male earlier diagnosed with dilated cardiomyopathy was admitted for acute heart failure. Echocardiography showed a predominant left ventricular cardiomyopathy with significantly reduced LV ejection fraction of 15%. One week after admission, ventricular fibrillation occurred, terminated by implantable cardioverter-defibrillator. Due to hemodynamic compromise, dobutamine and norepinephrine were started, but VA-ECMO was required soon thereafter. Three days later, a durable LVAD (HeartMate 3, Abbott, USA) implantation was performed, however the patient was not weanable from cardiopulmonary bypass due to acute RV failure, and promptly received a p-RVAD with the ProtekDuo cannula. Two weeks later, the p-RVAD was successfully weaned and he was discharged a month later and is currently in regular follow-up. **Conclusion**: We present two cases of acute and chronic RV failure in LVAD carriers. In both cases, the ProtekDuo cannula enabled acute RV support. Early institution of RV mechanical circulatory support, when needed, should improve patient outcomes.

Anto Stažić, Mirna Doknjaš, Jerko Arambašić, Kristina Kralik, Kristina Selthofer-Relatić

**Introduction**: The aim of the study was to establish pharmacotherapy application in the treatment of HFrEF (heart failure with reduced ejection fraction) patients in regular clinical practice, according to the European Society of Cardiology guidelines for acute and chronic heart failure 2016 (1). **Patients and Methods**: The study included 127 patients of both sexes (41% female, mean age 80; 59% male, mean age 68, p=0.001), hospitalized in 2019 at the Department for Heart and Vascular Diseases, Osijek University Hospital, due to HFrEF NYHA IV. It follows their first, second, and third hospitalizations. All the patients’ data, including HFrEF etiology; biochemical, hemodynamic, and echocardiographic parameters; and pharmacotherapy data, were collected from the hospital database. **Results**: Crucial comorbidities for HFrEF, such as arterial hypertension, were present in 83% of patients. Diabetes mellitus type II was found in 39% patients, and coronary heart disease in 57.5% of patients. In the first hospitalization (median NT-proBNP value 4276 pg/ml), discharge therapy included 54% BB, 60% ACEI, 52% MRA (50% 50mg), 32% ARNI (25% 49/51mg twice daily), 49% statins. In the second hospitalization (median NT-proBNP 5636 pg/ml), discharge therapy included 26% BB, 22% ACEI, 25% MRA (25% 50mg), 29% ARNI (50% 49/51mg twice daily), 24% statins. In the third hospitalization (median NT-proBNP 8998 pg/ml), discharge therapy included 10% BB, 10% ACEI, 12% MRA (25% 50mg), 21% ARNI (25% 49/51mg twice daily), 14% statins. A negligible number of patients were treated with ATII blockers and SGLT2 inhibitors. **Conclusion**: HFrEF patients were already treated in outpatient clinics because of comorbidities and established HFrEF during stabile phase of disease. After the first hospitalization, they had the best pharmacologic profile for HFrEF treatment (except ARNI group, higher dose in the second hospitalization). HFrEF worsening in each next hospitalization that followed, resulting in lower quality pharmacotherapy, probably as a result of patients’ worse clinical, hemodynamic, and biochemical condition. Early medication of HFrEF treatment in stabile phase of the disease is crucial for HFrEF prognosis.

Ivo Planinc, Dubravka Šipuš, Nina Jakuš, Dora Fabijanović, Boško Skorić, Hrvoje Jurin, Jure Samardžić, Jana Ljubas, Marijan Pašalić, Daniel Lovrić, Fran Borovečki, Maja Čikeš, Davor Miličić

**Background**: Current guidelines recommend genetic counselling and testing in patients with familial non-ischemic idiopathic cardiomyopathies with hypertrophic, dilated, restrictive or arrhythmogenic phenotype. (1, 2) We aimed to investigate genotype features of patients with non-ischemic cardiomyopathies in advanced stage of heart failure in University Hospital Centre Zagreb. **Methods**: Genetic testing (single variant and multiple variant testing) was performed in part using the in-house genetics laboratory, and also in a collaborating genetics laboratory in Helsinki, Finland (Blueprint Genetics). Pathogenic and likely pathogenic variants that established a molecular diagnosis were confirmed by Sanger sequencing. **Results**: From September 2016 to December 2020, we have performed genetic testing in 66 patients. Of this number, 14 patients (8 males, 41.5±14.3 years) had advanced heart failure as evidenced by either having undergone heart transplantation, mechanical circulatory support implantation, or were currently listed for heart transplantation. Before genetic testing, clinically observed phenotypes indicated dilated cardiomyopathy in 6 patients, restrictive cardiomyopathy in 6 patients, and arrhythmogenic cardiomyopathy in 2 patients. Diagnostic yield of the performed genetic tests was relatively high, only one test did not identify any mutations, and 4/14 identified mutations that can currently be classified only as variants of uncertain significance. Pathogenic and likely pathogenic mutations predominantly affected genes coding proteins of the sarcomere, cellular and nuclear membrane, or pathologic protein such as transthyretin (**Table 1**). Genetic testing lead to change in the clinically determined diagnosis in 4/14 patients. Results of genetic testing in this group of patients warranted further family clinical screening in all of the patients, and family genetic screening in 5 eligible patients. ### TABLE 1: Genotypes associated with clinically observed phenotypes. | **Clinical phenotype** | **DCM (N=6)** | **RCM (N=6)** | **ACM (N=2)** | | --- | --- | --- | --- | | **Gender (males)** | 3/6 | 4/6 | 1/2 | | **Age (years)** | 34.6±11.9 | 49.9±14.4 | 36.9±12.7 | | **Genotype** | | | | | **- pathogenic** | 1/6 | 1/6 | 1/6 | | | TNNT2 | FLNC | PKP2 | | **- likely pathogenic** | 2/6 | 3/6 | 1/6 | | | FLNC | TTR | LMNA | | | DSP | MYH7 | | | **- VUS** | 3/6 | 1/6 | 0/6 | | | DMD, DES, DYSF, SGCB | KCNA5 | | | | MYH7, PRDM16 | | | | | FLNC | | | | **- negative** | 0/6 | 1/6 | 0/6 | [†] DCM: dilated cardiomyopathy, RCM: restrictive cardiomyopathy, ACM: arrhythmogenic cardiomyopathy, TNNT2: cardiac troponin T, FLNC: filamin C, PKP2: plakophilin 2, TTR: transthyretin, LMNA: lamin A/C, DSP: desmoplakin, MYH7: myosin heavy chain 7, DMD: dystrophin, DES: desmin, DYSF: dysferlin, SGCB: sarcoglycan beta, KCNA5: potassium voltage-gated channel subfamily A member 5, PRDM16: PR/SET Domain 16, VUS: variant of uncertain significance. **Conclusion**: Genetic testing in our advanced heart failure population yields important information on etiology of the diseases, and indicates further family screening.

Petra Mjehović, Maja Čikeš, Mia Dubravčić, Dora Fabijanović, Nina Jakuš, Hrvoje Jurin, Daniel Lovrić, Jana Ljubas Maček, Marijan Pašalić, Ivo Planinc, Jure Samardžić, Boško Skorić, Davor Miličić

**Introduction**: Data on heart transplant (HTx) patients and infection with acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are very limited. There is significant heterogeneity in the clinical presentation. (1) Immunosuppression-related issues are of the main concern because of an increased risk for viral replication and superimposed infections. There is no evidence-based recommendation for the management of these patients. Some authors suggest modification in immunosuppression, i.e. discontinuation of mycophenolate mofetil (MMF) and calcineurin inhibitor (CNI) reduction in patients with more severe clinical presentation. (2) **Patients and Methods**: This is a case series of 5 HTx recipients from our center who tested positive for COVID-19 infection and were treated in different COVID-19 specialized units. **Results**: There were 4 male and one female patients, 62-75 years old. Four of them were symptomatic and hospitalized, while one remained self-quarantined at home. The clinical presentation was mild to moderate, with symptoms including mild fever, dyspnea, and myalgia. X-ray signs of pneumonia were present in 3 patients, but none needed ICU care nor mechanical ventilation. Both a reduction of CNI dose with lower target serum concentration and MMF was discontinued in all patients. One patient was treated with hydroxychloroquine, one with remdesivir and one with steroid therapy. Antibiotics prophylaxis was administered in 2 patients. None of the patients experienced overt graft rejection and all patients have successfully recovered (**Table 1**). ### TABLE 1: Main characteristics of the 5 heart transplant patients with COVID-19. | | **Patient 1** | **Patient 2** | **Patient 3** | **Patient 4** | **Patient 5** | | --- | --- | --- | --- | --- | --- | | **Age (years)** | 63 | 57 | 62 | 75 | 66 | | **Gender** | Female | Male | Male | Male | Male | | **Time from HTx (years)** | 3 | 3 | 3 | 10 | 5 | | **Imumunosuppressive therapy (mg/day)** | | | | | | | **Tacrolimus** | 1.5 | 2 | - | 1.5 | - | | **Cyclosporine** | - | - | 160 | - | 160 | | **Mycophenolate mofetil** | 1500 | - | 3000 | 2000 | 2000 | | **Everolimus** | - | 0.5 | - | - | - | | **COVID-19 onset** | | | | | | | **Presenting symptoms** | | | | | | | **Cough** | - | + | - | - | - | | **Shortness of breath** | + | + | + | - | + | | **Myalgia** | + | + | + | - | + | | **Anosmia** | + | + | - | - | - | | **Headache** | + | - | - | - | + | | **Sinusitis** | - | - | - | - | - | | **Gastrointestinal symptoms** | - | - | - | - | + | | **NPS test** | + | + | + | + | + | | **X-ray pneumonia signs** | - | + | + | - | + | | **Fever peak (°C)** | 37.9 | 38 | 37.6 | 36.6 | 37.8 | | **Hospitalization** | - | + | + | + | + | | **SpO2 at admission (%)** | / | 90 | 95 | 96 | 96 | | **Worst SpO2 during hospitalization** | / | 90 | 94 | 91 | 96 | | **Laboratory results at admission** | | | | | | | **WBC count (cells per 109/l)** | 4.0 | 5.5 | 5.3 | 2.8 | 7.5 | | **Hb (g/l)** | 121 | 139 | 139 | 105 | 149 | | **Platelets (cells per 109/l)** | 283 | 124 | 192 | 111 | 140 | | **Lymphoyte (cells per 109/l)** | 0.60 | 1.70 | 0.55 | 0.62 | / | | **CRP (mg/l)** | 0.9 | 57.4 | 6.8 | 0.4 | 20 | | **Creatinine (umol/l)** | 107 | 126 | 72 | 136 | 169 | | **Troponin I (ug/l)** | / | / | 4 | / | / | | **Treatment and outcomes** | | | | | | | **Hydroxychloroquine** | - | - | - | - | + | | **Remdesivir** | - | - | + | - | - | | **Corticosteroid therapy** | - | + | - | - | - | | **Discontinuation of mycophenolate mofetil** | + | + | + | + | + | | **Antibiotics prophylaxis** | - | + | - | - | + | | **ICU stay** | - | - | - | - | - | | **Mechanical ventilation** | - | - | - | - | - | | **Complications** | - | - | - | - | - | | **In-hospital length of stay (days)** | / | 5 | 9 | 21 | 11 | | **Outcome** | Alive | Alive | Alive | Alive | Alive | [†] NPS- nasop haryngeal swab test, SpO2 - oxygen saturation, CRP- C-reactive protein, ICU - intensive care unit **Conclusion**: Lacking any evidence-based recommendation for the treatment of HTx patients infected with SARS-CoV-2, we are challenged to modify maintenance immunosuppression carefully balancing between the risk of uncontrolled viral replication with a superimposed infection on one side, and the increased risk of graft rejection on the other side. Further studies are needed to determine the optimal management of COVID-19 infection in these patients.

Anita Jukić, Katarina Kutleša, Damir Fabijanić

**Introduction**: The objective of this study was to analyze characteristics of the patients hospitalized because of heart failure according to their left ventricular ejection fraction (EF). **Patients and Methods**: We retrospectively analyzed data on 293 HF patients hospitalized at the Department of Cardiology of the University Hospital of Split between January 1st and December 31st, 2019. The patients were divided according to left ventricular ejection fraction (EF) into 3 categories: 1) HF with preserved EF (HFpEF), 2) HF with midrange EF (HFmrEF) and 3) HF with reduced EF (HFrEF). Categorical variables were described as absolute or relative prevalence and assessed by χ2 test; analysis of variance (ANOVA) was used to compare normally distributed quantitative variables; Kruskal-Wallis ANOVA was used to compare non-normally distributed quantitative variables. **Results**: Among 293 HF patients, 125 (43%) had HFrEF, 61 (21%) had HFmrEF and 107 (36%) had HFpEF. Patients with HFrEF were mostly men (72%), younger than 70 years (62%), most commonly with arterial hypertension (54.4%) and revascularized coronary artery disease (36%). Patient with HFmrEF were mostly men (59%), older than 70 years (60.66%), with arterial hypertension (80.33%), permanent atrial fibrillation (63.93%) and revascularized coronary artery disease (31%). Patients with HFpEF were mainly women (61.68%), older than 70 years (61.68%), with arterial hypertension (80.37%), atrial fibrillation (60.75%), valvular heart diseases (25.23%) and chronic obstructive pulmonary disease (12,15%). **Conclusion**: The largest number of hospitalized patients diagnosed with HF had a reduced EF. These patients were more likely to be younger men with previously revascularized coronary artery disease, whereas HFpEF patients were predominantly elderly females with arterial hypertension and permanent atrial fibrillation. Despite the fact that they were mostly men, according to clinical characteristics, the patients with HFmrEF were significantly more similar to patients with HFpEF. (1)

Mila Jakovljević

**Introduction**: The aim of the study was to assess the effect of complementary supportive therapy (CST) on the quality of life and functional capability in patients with heart failure and reduced ejection fraction (HFrEF). **Patients and Methods**: We investigated 33 patients with left ventricular dilatation (LVIDd> 60 mm) and reduced ejection fraction (EF <40%) in 76 complementary supportive therapy (CST) periods. Prior to each CST period, therapy was optimized (OMT) for one month. CST consists of a 10-day session. In addition to OMT, the patients were treated with carnitine, L-arginine, magnesium, thiamine, riboflavin, pantothenic acid, niacin, pyridoxal, biotin, lipoic acid, coenzyme Q-10, vitamin E, vitamin C, selenium while lying for 30 minutes inside a pulsating electromagnetic field with intensity up to 30 microteslas and inhaling negatively ionized oxygen. Before and after each CST period, patients were asked to evaluate the quality of life using the Minnesota Living with Heart Failure Questionnaire (MLHFQ) and the visual analogue scale and EF, LVIDd and NYHA classes were determined. Statistical analysis was based on the t-test, Spearman’s rank correlation coefficient and Wilcoxon’s signed-ranks test. The longest observation period was 122 months. **Results**: After administering the complementary supportive therapy, a statistically significant improvement (p<0.05) was noticed in the particular items of the MLHFQ, in emotional and physical dimensions. The values of VAS and EF increased whereas NYHA and LVIDd decreased significantly (p<0.001). **Conclusion**: CST significantly improved the quality of life and functional capacity in patients with HFrEF. (1, 2)

Mia Dubravčić, Dubravka Šipuš, Dora Fabijanović, Hrvoje Jurin, Daniel Lovrić, Jure Samardžić, Jana Ljubas Maček, Ivo Planinc, Marijan Pašalić, Nina Jakuš, Maja Čikeš, Davor Miličić, Boško Skorić

**Background**: Venoarterial extracorporeal membrane oxygenation (VA-ECMO) is increasingly used in patients during cardiac arrest and cardiogenic shock and is associated with increased survival rate (1). Since mortality on ECMO is still rather high, SAVE (Survival after Veno-Arterial ECMO) score can be used to predict survival from refractory cardiogenic shock requiring ECMO (2). **Patients and Methods**: We performed a retrospective analysis of 121 patients (78% male) who underwent VA-ECMO implantation in our Department from January 2011 till November 2020 (**Figure 1** and **Table 1**). FIGURE 1. Number of venoarterial extracorporeal membrane oxygenation implantations from January 2011 to November 2020. ### TABLE 1: Clinical characteristics and laboratory values prior to venoarterial extracorporeal membrane oxygenation implantation. | Age, years (Mdn, IQR) | 58 (49-64) | | --- | --- | | Gender male (N, %) | 94 (78) | | BMI, kg/m2 (Mdn, IQR) | 27 (24-30) | | Creatinine, qmol/L (Mdn, IQR) | 130 (87-173) | | Bilirubin, qmol/L (Mdn, IQR) | 16 (10-34) | | INR (Mdn, IQR) | 1.2 (1.05-1.52) | | NT-proBNP, ng/L (Mdn, IQR) | 7654 (2834-15582) | | TnT, ng/L (Mdn, IQR) | 292 (43-2620) | | LDH, U/L (Mdn, IQR) | 755 (293-1817) | | CRP, mg/L (Mdn, IQR) | 20 (4-74) | | SAVE score (Mdn, IQR) | -8 (-12- -4) | | ECMO, days (Mdn, IQR) | 6 (3-10) | | ECMO during CPR (N, %) | 44 (37) | **Results**: Median age was 58 years with 21% of patients older then 65 years. Median of ECMO duration was 6 days. The most common causes of cardiogenic shock were acute myocardial infarction and cardiomyopathy (53% and 37%, respectively) (**Figure 2**), and 37% patients were implanted during cardiopulmonary resuscitation (eCPR). Overall survival on ECMO support was 59%, but in patients after CPR only 34%. Furthermore, of all patients, 34% were successfuly weaned and the rest who survived continued on advanced heart failure therapies (**Figure 3**), but overall survival in follow-up was only 26%. Median SAVE score was -8 with significantly less negative values in patients younger than 65 and treated after 2015. Also, patients treated before 2015 had significantly higher values of creatinine, free hemoglobine and international normalized ratio (INR) and their survival rate was only 39%, in comparison to those who were implanted after 2015 whose survival rate was 62%. FIGURE 2. Etiology of cardiogenic shock. CMP = cardiomyopathy; AMI = acute myocardial infarction FIGURE 3. Outcomes of patients on venoarterial extracorporeal membrane oxygenation implantation. LVAD = left ventricular assist device **Conclusion**: Although results with ECMO support in cardiogenic shock in our Department improved throughout 10-years experience, they still exhibit high long-term mortality. Our observations reinforce the need for thorough assessment of each ECMO candidate, especially in respect to patient’s age, end-organ failure and SAVE score as key steps to ensure optimal outcomes.

Mia Dubravčić, Maja Čikeš, Hrvoje Jurin, Daniel Lovrić, Jure Samardžić, Jana Ljubas Maček, Ivo Planinc, Marijan Pašalić, Nina Jakuš, Dora Fabijanović, Davor Miličić, Boško Skorić

**Background**: The number of transplant patients of childbearing age has increased. Decisions regarding the pregnancy management are challenging. Close monitoring includes screening for complications including rejection, graft dysfunction, and infection. First pregnancy in a post-cardiac transplant patient was reported in 1988 in a female patient who conceived less than 2 years post-transplant. Since then, there are many case reports that have demonstrated successful pregnancies in solid organ transplant recipients. (1-3) **Case report**: We present a case of 42-years-old female patient who underwent heart transplant 2016. In 2018 the patient expressed wishes for pregnancy and childbirth. A multidisciplinary team of cardiologists and gynecologists was formed and preconception and genetic counseling given. Before pregnancy we adjusted standard immunosuppressant therapy – mycophenolate mofetil was excluded, prednisone was continued in dose of 5 mg daily, and tacrolimus titrated to achieve concentration of 10-15 ng/ml. One month later, myocardial biopsy excluded graft rejection and 6 months later patient conceived naturally. Graft function was assessed by regular monthly NT-proBNP check. Echocardiography performed at 4th and 35th week of pregnancy showed normal graft function. In 36th week of pregnancy patient was admitted to our Department due to renal failure and hyperkalemia and was treated conservatively. Due to labor contractions on the 7th day of hospitalization, urgent caesarean section was performed in general anesthesia. Our patient gave birth to a healthy male newborn, without post-partal complications. Standard immunosuppressant therapy with mycophenolate mofetil, tacrolimus and prednisone was introduced immediately after birth. Repeated myocardial biopsy performed in the follow-up showed no signs of graft rejection. **Conclusion**: Pregnancy and childbirth in post-cardiac transplant patient is feasible and should be managed by multidisciplinary team of healthcare providers.

Faruk Čustović, Edin Begić, Denis Mačkić, Sanko Pandur

**Aim**: To present a therapeutic modality of peripartum cardiomyopathy (PPCM). **Case report**: A 24-year-old female patient, with no prior known diagnosis, was admitted to the Department of Cardiology with signs of acute heart failure. A 45 days prior to admission she delivered a healthy baby (first pregnancy) via cesarean section, while 20 days before hospitalization she developed symptoms like dyspnea, orthopnea, fatigue, weakness and extremely low tolerance to effort. Upon admission on X-ray, heart shadow was enlarged and, while on electrocardiogram (ECG) there was a sinus tachycardia with negative T waves from V1-V5. Echocardiography on admission showed initial dilatation of cardiac chambers, reduced ejection fraction of left ventricle (EFLV; estimated about 25%) with global hypokinesia, signs of moderate to severe mitral and tricuspid regurgitation with mild pulmonary hypertension, along with hemodynamically nonsignificant circumferential pericardial effusion (diastolic separation of 8mm). Laboratory findings were as follows: NT-pro BNP 1810.0 pg/mL; signs of anemia, while inflammatory parameters, cardiac necrosis markers, urea, creatinine, D-dimer and thyroid hormones values remained in reference values. Testing for known cardiotropic viruses was not positive and PPCM was diagnosed. The patient was treated with cardio selective beta blocker (metoprolol), angiotensin-converting enzyme (ACE) inhibitor (ramipril), diuretics (furosemide), spironolactone, and digoxin along with supportive therapy. After twelve days of hospital treatment, there was significant improvement of the clinical status of our patient. Her symptoms were notably ameliorated. EFLV before discharge improved to 40%, heart chambers dimensions were in referral values, while mitral and tricuspid regurgitation were significantly reduced into a mild grade, while pericardial effusion was also in regression. Follow-up examination after two and six months showed further improvement of patients’ conditions while after six months only beta-blocker and acetylsalicylic acid were prescribed in therapy. **Conclusion**: PPCM can occur during the end of pregnancy or within five months after delivery with no determinable etiology and with absence of cardiac disease in anamnesis. (1)

Josip Anđelo Borovac, Joško Božić, Darko Duplančić, Zora Sušilović Grabovac, Duška Glavaš

**Introduction**: Heart failure (HF) is a complex clinical syndrome associated with high mortality, morbidity, and healthcare expenditures. (1, 2) We sought to determine temporal trends concerning baseline characteristics and treatment modalities of patients enrolled at our Center during two periods: 2008-2012 and 2018-2019 for which data were available. **Patients and Methods**: Patients admitted with the chief diagnosis of HF were stratified into two groups for the statistical analysis. The historic cohort comprised patients admitted during the period 2008-2012 (N=356) while the contemporary cohort (2018-2019) consisted of 108 patients. **Results**: Patients in the contemporary cohort were younger, had a significantly higher prevalence of non-ischemic cardiomyopathy, diabetes mellitus, more preserved renal function, higher hemoglobin, higher uric acid, and lower potassium levels compared to the historic cohort. On the other hand, distribution of sex, blood pressure at admission, the prevalence of atrial fibrillation, NYHA functional class, left ventricular ejection fraction and left end-diastolic diameters were similar in both groups (**Table 1**). As shown in **Figure 1A**, we observed a significant decline in the prevalence of HF with midrange ejection fraction in a contemporary cohort compared to a historic one (p2* | 49 ± 23 | 58 ± 25 | **<0.001*** | | **Uric acid**, *mmol/L* | 486 ± 172 | 535 ± 166 | **<0.001*** | | **Hemoglobin**, *g/L* | 126 ± 20 | 134 ± 20 | **<0.001*** | | Sodium, *mmol/L* | 138 ± 4.4 | 138 ± 3.7 | 0.762 | | **Potassium**, *mmol/L* | 4.5 ± 0.8 | 4.1 ± 0.5 | **<0.001*** | | Systolic blood pressure, *mmHg* | 137 ± 28 | 137 ± 29 | 0.145 | | Diastolic blood pressure, *mmHg* | 81 ± 15 | 81 ± 13 | 0.204 | [†] LVEDd-left ventricular end-diastolic diameter; LVEF-left ventricular ejection fraction; NYHA-New York Heart Association; eGFR-estimated glomerular filtration rate *denotes statistically significant result at p<0.05 level (Chi-square analysis or Student t-test were used for comparisons between two groups) FIGURE 1. A) Change in heart failure clinical phenotypes over time in two compared cohorts; B) Trends in pharmacotherapy use over time in two compared cohorts. ACE-Angiotensin-converting enzyme; ARB-angiotensin receptor blocker; HFmrEF-heart failure with midrange ejection fraction; HFpEF-heart failure with preserved ejection fraction; HFrEF-heart failure with reduced ejection fraction **Conclusions**: After the approximately 10-year timespan, we observed several changes in baseline characteristics of HF patients treated at our center. The most prominent change is the highest relative growth in the prevalence of HF with preserved ejection fraction. Likewise, the proportional use of life-prolonging pharmacotherapies and anticoagulation coverage (nowadays mostly direct oral anticoagulants) significantly improved over time.

Barbara Rubinić, Mia Dubravčić, Hrvoje Jurin, Daniel Lovrić, Borka Pezo-Nikolić, Mislav Puljević, Vedran Velagić, Davor Puljević

**Introduction**: Atrial fibrillation can lead to heart failure with reduced ejection fraction (HFrEF) by reducing cardiac output due to irregular rhythm, high frequency of the ventricles, reducing diastole time and loss of atrial contraction. HFrEF could also potentiate the onset of atrial fibrillation due to the increase of pressure in the left atrium, enlargement of the left atrium, activation of the sympathetic nervous system which in turn can potentiate automatic triggers and functional mitral regurgitation. (1) **Case report**: We present 47-year old male who was physically active, playing amateur football. On routine check-ups persistent normofrequent atrial fibrillation was found along with dilation of all four chambers. Patient complained of exertion fatigue, dyspnea on exertion and feeling of an irregular heart rhythm. Transthoracic echocardiography revealed diffuse hypocontractility and severe reduction in systolic function of the left ventricle, with ejection fraction (EF) of 35%. Coronary artery disease was excluded. Automatic cardioverter defibrillator (AICD) was implanted in primary prevention of sudden cardiac death. Two and a half years later systolic function has improved (EF 50%) and there was a spontaneous conversion to sinus rhythm. AICD was explanted on patient request. Less than a year after, systolic function has once again declined (EF 20%) and a recurrence of persistent atrial fibrillation with average heart rate obtained in Holter ECG 90/min was observed. After the recurrence of arrhythmia post electrocardioversion, pulmonary vein isolation with cryoablation was performed. Eight and 17 months after the ablation no recurrence of atrial fibrillation was found. Patient is again physically active (jogging) and ejection fraction returned to normal. **Conclusion**: Atrial fibrillation and heart failure with their pathophysiological mechanisms can make the “circulus vitiosus”. This case report shows how removal of arrhythmogenic triggers, normalization of the heart rhythm and heart rate could significantly contribute to the improvement of heart function. That could be explained by halting, and possibly even reverting, the structural and electrical heart remodeling.

Drago Rakić, Leo Luetić, Velimir Pivac, Ivana Cvitković, Zvonko Rumboldt

**Introduction**: Sudden cardiac death (SCD) is mostly defined as a natural death due to cardiovascular cause that occurs within one hour of the onset of symptoms. (1) Out-of-hospital SCD frequency is underestimated because it reflects the cases treated by emergency medical services (EMS) only, which amounts to some 50-60% of the global incidence. Moreover, it is highly variable, ranging from 38 to over 84.7 per 100,000 inhabitants per year; in Croatia 62/100,000 (2) or some 9000 victims per year. SCD survival to hospital discharge is also widely variable, ranging from 0.3% to 20.4%. (1, 2) The aim of this study was to assess the SCD incidence and survival rate among the victims resuscitated by EMS in Split-Dalmatian County. **Methods**: From the Split-Dalmatian County EMS electronic data base analyzed were all SCD case reports (Utstein forms) from January 1, 2017 to December 31, 2017. Data on etiology and outcome for hospitalized SCD individuals were extracted from patients’ files, discharge letters and/or autopsy notes. **Results**: During the investigated period there were 291 EMS treated victims of presumed SCD (69/100,000). Sudden death mostly (68%) happened at home, lay CPR on the spot was performed in 12 cases (4.1%) only, with no instance of lay defibrillation. Hospitalized were 32 (11%) such individuals, 21 surviving to hospital discharge (7.2%). **Conclusion**: The identified weak links in the survival chain must be improved, e.g. for low SCD survival rate - assure public access to lay defibrillation, such as “Start the Heart - Save the Life” program in Croatia; for lay defibrillation lack - provide as many AEDs as possible, form a network of devices, and educate a large number of volunteers; for the prevalent SCD occurrence at home - train family members of patients at elevated risk in CPR.

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

**Introduction**: There is a variety of approaches to pre-procedural imaging of pulmonary veins (PV) and left atrium (LA) in order to facilitate atrial fibrillation (AF) ablation, including CT angiography, cardiac MRI and intra-procedural three-dimensional rotational angiography (3DRA). Data supporting different practices is still evolving and there is an open question whether LA imaging could improve safety and outcomes of cryoballoon ablation (CB) ablation. (1, 2) Here we present the preliminary data from a single-centre unblinded randomized clinical trial. **Patients and Methods**: So far, we recruited 82 patients (68.3% male, 59.0±11.6 years) with paroxysmal (92.8%) and early-persistent AF. Patients were randomized to no imaging or 3DRA which was performed intra-procedurally after trans-septal puncture. Angiographic images were segmented and overlaid to the fluoroscopy screen to guide the ablation procedure. All patients are followed for 1 year and data concerning procedural characteristics, safety outcomes and AF recurrence are being collected. **Results**: Of 82 patients recruited so far, 40 (48%) underwent 3DRA. In patients who received no imaging (non-3DRA group) all PVs were successfully isolated while in 3DRA group isolation of one PV could not be achieved in 1 patient. Procedure time was significantly longer when 3DRA was performed (89.4±29.7 min compared to 69.4±21.4 in non-3DRA group, p<0.001). Total radiation dose (146.9±186.1 vs 399.8±216.5 mGy, p<0.001) and contrast administration (44.2±27.6 vs 136.8±28.4 ml) were significantly lower in the control group. Only minor complications were reported in both groups. Three patients developed large hematoma (2 in 3DRA group vs 1 in control group). In each group there was one incident of transient phrenic nerve palsy. **Conclusion**: 3DRA is a safe and efficient intra-procedural imaging method to guide CB ablation for AF. However, it significantly increases procedure duration, total radiation dose and contrast expenditure. In our trial it did not have any impact on the acute success rate of PV isolation. One-year follow up data is still being collected and will subsequently be presented.

Ivan Prepolec, Vedran Pašara, Borka Pezo-Nikolić, Maja Čikeš, Boško Skorić, Davor Puljević, Davor Miličić, Vedran Velagić

Supraventricular tachycardias (SVT) are increasingly recognized late complications after cardiac transplantation (CTX). The most commonly described arrhythmias include cavotricuspid isthmus (CTI)-dependent atrial flutter (AFL), other macroreentrant atrial tachycardias (MRAT) and focal atrial tachycardias (AT). Although surgical substrate can be important, the effect of the surgical technique on the mechanism and the occurrence of arrhythmia remains unclear. (1-3) We describe characteristics of CTX patients who presented with SVT for electrophysiological studies (EPS) at our centre from 2017 to 2020. Among 6 patients (mean age 48 ± 18 years, 4 of 6 were men), 2 presented during the first year after CTX, while 4 patients presented after a long follow-up (13.3 ± 2.8 years). Cardiac rejection was ruled out in all patients. In 3 patients significant graft vasculopathy was present. Initially, the conventional EPS was performed in all patients. In 5 cases, the initial diagnosis was CTI-dependent AFL and a successful radiofrequency ablation of CTI was performed. In one case, the arrhythmia was due to the non-CTI-dependent MRAT and rate-control strategy was adopted. During the follow-up (29.2 ± 10.2 months), 3 patients remained without recurrences. In two patients early recurrence was noted (after 1 and 3 months) and a second EPS was performed (conventional or electroanatomical mapping) which demonstrated the multiple MRAT unsuitable for ablation. These patients were managed conservatively while one of them received second CTX due to advanced graft vasculopathy. During the follow-up one patient died due to graft rejection. In our group of patients typical AFL and other non-CTI-dependent MRAT were observed. In CTI-dependent AFL, conventional radiofrequency ablation was effective, while recurrences were more difficult to treat. Extensive scarring of the atria is the substrate for multiple MRAT circles that are not easily amenable with ablation.

Ekrema Mujarić, Edin Begić, Samed Djedović

**Case report**: Severe mitral regurgitation due to rupture of the chordae tendineae and mitral valve prolapse (Barlow’s disease), with a left atrial volume of 37.6 mL/m2 was verified in 43-year old patient. He was admitted for an examination due to frequent palpitations and fast and irregular heartbeats. In the anamnestic data, thrombosis of the veins of the right leg was verified (thrombosis of popliteal, posterior tibial and great saphenous vein during previous years). He carries mutations: heterozygote of factor V Leiden, with MTHFR C677T heterozygote (CT), PAI- 1 heterozygote (4G⁄5G) and MTHFR A1298C heterozygote. The surgical treatment was done, and mechanical valve was implanted. In the following months, the patient complained on frequent dizziness, with crises of consciousness, and a shortness of breath. He was not suitable for beta-blocker therapy, as well as propafenone and amiodarone, which had been prescribed in therapy in the meantime. The 24-hour ECG Holter monitoring described various arrhythmias, most of the time AV block of the first degree with PQ interval up to 320 msec, occasionally second-degree atrioventricular block Mobitz II, polymorphic ventricular extrasystoles and one attack of non-sustained ventricular tachycardia (6 ventricular extrasystoles in row), with intermittent nodal rhythm, junctional tachycardia and atrial flutter with AV ratio 2:1. An electrophysiological study was performed, and the cavotricuspid isthmus (CTI) dependent atrial flutter was verified, and radiofrequent ablation was done. After the procedure patient was in sinus rhythm. During the next follow up visits, the patient was in sinus rhythm, on therapy with a low dose of nebivolol (inability to tolerate beta blockers) and ivabradine, along with vitamin K antagonists. **Conclusion**: Although it is associated with surgical treatment, electrophysiological examination can be option in the therapeutic modality of post-incisional arrhythmias. (1)

Ante Lisičić, Sanda Sokol Tomić, Nikša Bušić, Petra Vitlov, Irzal Hadžibegović

**Background**: Case of “missing patients” with coronary artery disease and myocardial infarction during the COVID-19 pandemic is widespread. Implantable devices procedures and ablation procedures have also been affected, however reports are few. (1) Aim: To compare the numbers of implantable cardiac devices procedures between 2019 and 2020. **Patients and Methods**: Numbers and complications of single-chamber (VVI) and dual-chamber pacemakers (DDD), implantable cardiac defibrillators (ICD), and cardiac resynchronization devices (CRT) implantations were analyzed and compared between the period from Jan 2019 to Dec 2019 and Jan 2020 to Dec 2020. **Results**: In a 12-month operating period in 2019, there were 88 VVI, 103 DDD, 25 ICD, and 16 CRT implantations. In comparison, during a 7-months working period in 2020, there were 53 VVI, 88 DDD, 36 ICD, and 15 CRT implantations. The remaining 5 months of 2020 we worked as a COVID-19 dedicated hospital with no non-urgent and elective procedures, and performed only 1 urgent VVI and 1 urgent DDD implantation in COVID-19 positive patients. In addition, invasive electrophysiology and ablation of cardiac arrhythmias has been introduced in December 2019, with 33 invasive EP procedures with ablation performed by the sole interventional electrophysiologist in 2020. There were 15 AF ablations using cryoballoon technology, 6 SVT ablations (focal AT and AVNRT) using 3D electroanatomical mapping system (4 of which were “zero fluoro” procedures), and the rest were miscellaneous SVT ablations (mostly AVNRT and CTI dependent atrial flutter) using conventional approach. There were no differences in complications or duration of hospitalization between the two periods. **Conclusion**: COVID-19 pandemic reduced the number of VVI and DDD implantations, that are more frequently urgent in the elderly population. However, in 2020, CRT and ICD implantations increased absolutely and relatively (respectively), and would probably increase even more without the pandemic situation, ensuring optimal treatment for more heart failure patients with appropriate indications. Also, we expected that the numbers of ablations would probably increase over time without the pandemic situation. However, there was probably a negative impact on patients’ consent to be ablated in a COVID-19 dedicated hospital.

Edin Begić, Amer Iglica, Zijo Begić, Nedim Begić, Ada Đozić, Faruk Čustović

**Goal**: Indicate the prognostic significance of non-sustained ventricular tachycardia (NSVT) in the recovery phase of stress testing. **Patients and Method**s: From total of 584 findings, 14 patients who developed an episode of NSVT (3 beats of ventricular origin and more) in the recovery phase of stress testing (according to the Bruce protocol) were analyzed. Patients who did not have a significant finding during exercise stress testing (without significant ST-segment changes and significant heart rhythm disorders) were included. **Results**: After 247 ± 53 seconds (4 minutes and 11 seconds) in average patients developed NSVT, and were referred for coronary angiography. Of total number, 4 had a significant finding on coronary angiography; 3 patients had single-vessel coronary disease (one received a stent on right coronary artery (RCA), two on left anterior descending artery (LAD)), and one had triple-vessel coronary disease (received a stent on circumflex artery (CX) and LAD). **Conclusion**: The prognostic significance of NSVT is quite unclear, and the origin of NSVT can be ischemic or idiopathic. (1, 2) Regardless, patients with NSVT are candidates for additional evaluation of ischemic heart disease (stress echocardiography, multi-slice computed tomography (MSCT) or invasive coronary angiography).

Ines Vinković, Mihajlo Kovačić

**Background**: According to the latest European Society of Cardiology (ESC) guidelines for patients with non ST elevation myocardial infarction (NSTEMI), the time to invasive treatment is divided into an immediate invasive strategy within two hours for very high-risk patients, an early invasive strategy within 24 hours for high-risk patients, and a selective invasive strategy within 72 hours for low-risk patients, although the time interval that is most optimal for high-risk patients has not yet been determined (1). Our goal was to examine in what time interval patients were treated in County Hospital Čakovec after acute coronary syndrome (ACS) - NSTEMI in the previous 3 years. **Patients and Methods**: Included were patients with ACS - NSTEMI from January 2018 to November 2020. The time of the first contact with the medical staff and the time of the beginning of the invasive treatment was recorded, then the time interval was calculated. **Results**: Total number of included NSTEMI patients was 203, patients with incomplete documentation were excluded. There were 137 (67%) men and 66 (33%) women, median age was 67 years, women were older than men (71 vs 63 years). 118 (58%) patients were from primary PCI (percutaneous coronary intervention) centre and 85 (42%) patients were from local hospitals. 89 patients (44%) were treated within 24 hours, while 149 patients (73%) were treated within 72 hours. Patients treated within 24 hours were younger than those treated after 24 hours (62 vs 70 years), women were treated at a slightly lower percentage within the first 24 hours compared to men (41% vs 45%), (**Figure 1**). More patients were treated within 24 hours from the primary PCI center than from local hospitals (60% vs 23%). Over the past three years, there has been an increase in the number of patients treated within 24 hours, 31% of patients during 2018, 29% during 2019, while this year, the percentage was 40% (**Figure 2**). FIGURE 1. Men and women treated within and after 24 hours (44% vs 56%). PCI = percutaneous coronary intervention; h = hours. FIGURE 2. Number of patients treated within 24 hours through years. PCI = percutaneous coronary intervention. **Conclusion**: A large number of patients diagnosed with NSTEMI are at high risk, and only one in ten receives an invasive treatment strategy within the recommended timeframe (2). Our goal is to treat as many patients as possible within the first 24 hours.

Jozica Šikić, Edvard Galić, Jasna Čerkez Habek, Dean Strinić, Zrinka Planinić

**Aim**: To study the impact of age and sex-related differences in patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI). **Methods and Results**: From March 2017 to November 2019, 9106 patients (6309 men and 2797 women) with ACS from 13 PCI centers were enrolled in this study (STENOS Registry). Among enrolled patients, men (69%) were younger than women (63y vs. 68y, P = 0.001), with a higher prevalence of previous myocardial infarction (15% vs 9.5% P < 0.001), previous PCI (15.9 vs. 9.7%, P = 0.003), and similar frequency of previous cerebrovascular insult and peripheral artery disease (PAD). The most affected coronary artery was proximal and mid left anterior descending (LAD) in both gender and all ages. PCI on coronary artery bypass (CABG) was performed in 0.3% (0.3% in men vs 0.18% in women). In patients under age 55, 25% of men vs 11% of women (p<0.001) have had ACS. Radial approach has been done in 81%, and in 89% (87.7% in men and 88.9% in women) stent has been implanted. Average stent length was 22.01x2.99 mm in men vs 20.7x3.17 mm in women. Women have had 3% of unsuccessful procedures, in comparison to 2.3% in men. Restenosis rate was 3.9%, and more often in men (4.8% vs 2.7%, p<0.001). The highest restenosis rate was between 55-80 y in men, and between 66-80 y in women. Clopidogrel was the drug of choice in 56.49%. There was no difference in blood complications. In-hospital mortality rate for patients with ST-segment elevation myocardial infarction was 5.2%, without gender differences. **Conclusion**: Although there were no differences between men and women in management and in-hospital outcomes, gender was shown to be predictor of earlier occurrence of ACS, higher restenosis and re-ACS rate. (1, 2)

Irzal Hadžibegović, Ante Lisičić, Mario Udovičić, Miroslav Raguž, Ilko Vuksanović, Ognjen Čančarević, Vanja Hulak-Karlak, Ivana Jurin, Aleksandar Blivajs, Petra Vitlov, Boris Starčević

**Background**: COVID-19 pandemic has caused a worldwide situation of “missing patients” with acute myocardial infarction (AMI) suitable for a timely percutaneous coronary intervention (PCI). (1) We aimed to investigate the impact of COVID-19 pandemic on PCI in AMI (ST elevation + non ST elevation MIs) in a hospital included in the national primary PCI network and dedicated for COVID-19 patients from Mar 2020. **Patients and Methods**: We compared numbers, characteristics and outcomes of patients presenting with AMI and receiving timely percutaneous intervention in our hospital between two periods: Jan 2019 – Jan 2020 (“pre-COVID-19” era) and Mar 2020 – Dec 2020 (“COVID-19” era - 9 months period with mixed hospital organization: 4 months dedicated COVID-19 only hospital, and 5 months both non-COVID-19 and COVID-19 hospital). **Results**: In the pre-COVID-19 era we performed 434 PCIs in 505 patients with AMI who received urgent/early coronary angiography after admission (average monthly number of AMI suitable for revascularization: 42 patients), with in-hospital mortality of 3.7%. During the COVID-19 era there were 137 PCIs in 186 patients with AMI and urgent/early coronary angiography (average monthly number of AMI suitable for revascularization: 18 patients), with in-hospital mortality of 8%. During the COVID-19 era, there were 14 COVID-19 positive patients with acute AMI who underwent urgent angiography (8 received PCI and 6 were treated conservatively) and had in-hospital mortality of 28%. **Conclusion**: We found an astonishing 40% reduction in monthly rates of patients with AMI suitable for revascularization presenting to our hospital during the COVID-19 pandemic. AMI patients that were treated with PCI during the pandemic era had significantly higher mortality, mostly influenced by a very high mortality rate of COVID-19 positive patients presenting with AMI. Comprehensive analysis of national primary PCI network organization and patient awareness of AMI during COVID-19 pandemic in Croatia is warranted.

Faruk Čustović, Edin Begić, Anela Šubo, Bilal Oglečevac, Denis Mačkić

**Aim**: To present a therapeutic modality of rhabdomyolysis after acute myocardial infarction (AMI). **Case report**: A 45-year-old patient was admitted to Urgent Care Center due to chest pain. Due to repeated attacks of ventricular fibrillation (11 direct-current cardioversion defibrillation was done), and after successful cardiopulmonary resuscitation (CPR) he was intubated. Computed tomography (CT) of the head was without pathological findings. At admission laboratory findings were as follows: urea 17.5 mmol/L, creatinine 143 μmol/L, AST 584 IU/L, ALT 162 IU/L, creatine kinase 6220 IU/L, C-reactive protein 249.5 mg/L, troponin I 0.12 ug/L (in two days increased to 6.31 ug/L). In the resuscitation procedure, gastric contents were aspirated, and shadowing of the right lung was radiographically verified. Patient from admission was febrile up to 40° Celsius despite received therapy (positive finding on Haemophilus influenzae B was received subsequently). Ejection fraction of left ventricle was reduced (estimated about 30-35%) along with anteroseptal medioapical akinesia, while stroke volume was 46 mL. Hypokinesia of right ventricular free wall was verified. Tricuspid annular plane systolic excursion was 15mm, along with moderate tricuspid regurgitation. On the fourth day deep vein thrombosis of the left leg was verified. On the ninth day of hospitalization, a high increase in creatine kinase was verified (up to 127.100 IU/L) with consecutive renal failure (urea 38.1 mmol/L, creatinine 620 μmol/L) and rhabdomyolysis with acute renal failure was diagnosed. The patient was included in the acute hemodialysis program (six hemodialysis were performed, diuresis was up to a maximum of 250 mL/day). The patient’s condition gradually stabilized, and the patient was taken of mechanical ventilation after 16 days. During next twenty days, kidney function was improving, and the patient was discharged home. Follow-up examination after two months verified anteroseptal and medioapical akinesia of left ventricle, with satisfactory renal function. Percutaneous coronary intervention was indicated. **Conclusion**: Rhabdomyolysis may accompany AMI, especially after CPR, and a multidisciplinary approach to the patient is required, with optimized pharmacological treatment. (1)

Admira Bilalić, Josip Anđelo Borovac, Tina Tičinović Kurir, Marko Kumrić, Andrija Matetić, Joško Božić

**Introduction**: Previous studies showed an increased likelihood and risk of acute myocardial infarction (AMI) and hospitalizations for cardiovascular events among patients exposed to chronic use of proton pump inhibitors (PPIs). (1-3) In this study we aimed to compare parameters reflecting disease burden and cardiometabolic profile among patients treated for AMI with respect to the chronic exposure to PPIs. **Patients and Methods**: Data of 143 adult consecutive patients hospitalized for ST-elevation myocardial infarction (STEMI) or non-ST-segment elevation myocardial infarction (NSTEMI) during the 2019-2020 period were analyzed. All continuous variables had a normal distribution. **Results**: The mean age was 64.8 ± 11.3 years and 79.7% were men. Two-thirds (65.7%) of patients had STEMI while 34.3% had NSTEMI. The mean GRACE score in the whole cohort was 117 ± 26 points while 12.6% of patients were at high risk of in-hospital death, after adjustment for the ACS type. A total of 19 IPP+ patients were identified. Patients in the IPP+ group were significantly older and had a higher prevalence of NSTEMI compared to IPP- group while both groups did not significantly differ in terms of sex, body mass index, waist-to-hip ratio, the mean number of diseased vessels at angiography, and left ventricular ejection fraction. Patient IPP+ group had a significantly higher high-sensitivity cardiac troponin I rise from 1st to 2nd measurement compared to IPP- group (4726 ± 5938 vs. 2554 ± 3480 ng/L, p=0.025, **Table 1**). Furthermore, C-reactive protein, blood glucose, and serum creatinine levels at admission were significantly higher in IPP+ vs. the IPP- group. Finally, patients in the IPP+ group had a significantly higher risk of in-hospital and 6-month post-discharge death compared to IPP- group, as adjudicated by the GRACE score (132 ± 23 vs. 114 ± 26 points, p=0.008). ### TABLE 1: Comparison of consecutive patients with acute myocardial infarction exposed to chronic inhibitor of proton pump (IPP) use (IPP+ group) with those not exposed (IPP-group). | **Variable** | **IPP+ group (N=19)** | **IPP- group (N=124)** | **p-value** | | --- | --- | --- | --- | | Age, *years* | 71.9 ± 9.6 | 63.3 ± 11.2 | 0.003* | | Body mass index, *kg/m2* | 26.2 ± 1.7 | 27.3 ± 3.4 | 0.201 | | Waist-to-hip ratio | 1.03 ± 0.07 | 1.12 ± 0.88 | 0.644 | | Male sex | 64.7% | 81.9% | 0.100 | | NSTEMI as a type of ACS | 47.4% | 33.1% | 0.224 | | Mean Killip class | 1.11 ± 0.33 | 1.10 ± 0.40 | 0.890 | | Mean number of diseased vessels | 1.20 ± 0.44 | 1.17 ± 0.50 | 0.823 | | Left ventricular ejection fraction, *%* | 50.8 ± 12.7 | 52.1 ± 9.8 | 0.656 | | Δcardiac Troponin I value, *ng/L¶* | 4726 ± 5938 | 2554 ± 3480 | 0.025* | | C-reactive protein, *mg/L* | 27.4 ± 48.5 | 11.7 ± 20.0 | 0.015* | | Glucose, *mmol/L* | 9.5 ± 4.8 | 7.7 ± 3.0 | 0.037* | | Creatinine, μmol*/L* | 110 ± 56 | 89 ± 26 | 0.012* | | Sodium, *mmol/L* | 138 ± 2.9 | 137 ± 3.0 | 0.146 | | Potassium, *mmol/L* | 4.04 ± 0.43 | 4.08 ± 0.40 | 0.724 | | GRACE score, *points* | 132 ± 23 | 114 ± 26 | 0.008* | [†] ACS-acute coronary syndrome; AMI-acute myocardial infarction; GRACE-Global Registry of Acute Coronary Events; NSTEMI-Non-ST-segment elevation myocardial infarction. *result significant at a two-tailed p-value st to 2nd measurement **Conclusions**: Our study showed that AMI patients with chronic exposure to IPPs are older, mostly male, and tend to present with NSTEMI. These patients exhibit a larger magnitude of myocardial injury and systemic inflammation accompanied by worse renal function, and also seem to be at an increased risk of poor in-hospital and post-discharge outcomes. However, potential confounding of underlying comorbidities and age must be taken into account when interpreting these results.

Davor Miličić

## Dear colleagues, The year 2020 has changed our lives dramatically. In spring, when we faced the first wave of the coronavirus pandemic, the world stopped, and so did our domestic and foreign gatherings. Early in the summer it seemed that the worst had passed, so we started planning our professional meetings, symposiums and congresses, as well as our central event organized every two years, the 13th Congress of the Croatian Cardiac Society. Already in August it became clear that the second pandemic wave would be worse than the first one and that we had to postpone all our gatherings to better times. However, in spite of everything, our cardiology lives and makes progress, and we haven’t stopped our quite lively cooperation with the European Society of Cardiology and other international cardiology associations, with our colleagues and their teams in Europe and worldwide. Quite a successful communication through electronic channels has been established, including advisory board meetings, online seminars, and congresses too. The Croatian Cardiac Society has made excellent adjustments to new circumstances and during the past moths it held numerous virtual meetings on a wide range of topics and with exemplary attendance. Since, unfortunately, our cardiology congress planned for December cannot be held in its previous form which involves gathering around one thousand participants — members of our society, foreign and domestic guests, we have decided to organize the 13th Congress of the Croatian Cardiac Society in a virtual form. As the 12th Congress was held in 2018, it was logical not to skip the two-year overview of the Croatian cardiology developments, but also to show important novelties in European and global cardiology. Of course, one of the topics will be special conditions of cardiovascular pathology in the coronavirus pandemic, both in general and in our specific circumstances. The Congress will be organized in two parts, in December and in January, since participants will not be able to request paid leave. For this reason, the Congress will be held in afternoon hours. Also, as it is known that the attention span for virtual content is much lower than it is during classical congresses, this Congress will be structured around scientific sections with comments and discussions from invited lecturers on selected topics in cardiology, original communications as an equivalent of moderated poster sections, and sponsored content in the form of satellite symposiums or separate lectures. There will also be time and space for our sponsors’ virtual showrooms and advertisements. It is a great honour that this year’s Congress will also be held under the auspices of the Croatian Academy of Sciences and Arts, that is the Academy Department of Medical Sciences. I hereby invite you to actively join the Congress in large numbers, especially with your original communications that will be published on the electronic platform of the Congress and printed in the special edition of our journal Cardiologia Croatica. With warm regards and best wishes, Yours sincerely,