Cardiologia Croatica. 2017;12(9-10)

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

**Introduction**: Accounting for the largest number of hospitalizations, heart failure (HF) currently creates a large burden on the health systems in Europe. Myocardial diseases, one of the most frequent causes of HF, are predominantly represented by ischemic cardiomyopathy (ICM), while hypertrophic cardiomyopathy (HCM) is often recognized as the second most frequent form of cardiomyopathy. (1) The aim of this study was to describe the etiological characteristics and survival within our HF cohort. **Patients and Methods**: We performed a retrospective analysis of data from 200 patients (71% male, mean age 47.8±11.7 years) with mild to moderate chronic HF (NYHA II and IIIa) treated at our Department between December 2010 and December 2014. The mean follow-up period was 44.9±16.5 months and overall survival was defined as the primary outcome of the study. **Results**: The most frequent etiologies of HF included dilated cardiomyopathy (DCM) (25%), ICM (26.5%) and secondary cardiomyopathy (hypertensive, valvular, toxic) (19.5%), while HCM accounted for only 8% of the cohort (**Figure 1**). The overall survival in our cohort was 92%. No significant difference in the demographic parameters was noted among the surviving and deceased patients, except higher age and prevalence of diabetes in the deceased group. The majority of deceased patients were of DCM (8/15 deceased) and ICM (6/15) etiology. A trend towards higher overall mortality was noted in the DCM group compared to ICM, yet not reaching statistical significance (p=0.116) (**Figure 2**), while multivariate analysis revealed this to be due to significantly lower EF in the DCM group. There was no significant difference in the demographic parameters, except age, among the surviving and deceased patients. By log rank test and ROC analysis, NT-proBNP provided the strongest prediction of mortality in the entire HF cohort (area under the curve 0.702, p<0.05) (**Figure 3**). FIGURE 1. Distribution of cardiomyopathy etiologies. DCM = dilated cardiomyopathy, ICM = ischemic cardiomyopathy, Secondary CM = secondary cardiomyopathy, HCM = hypertrophic cardiomyopathy, RCM = restrictive cardiomyopathy, ARC = arrhythmogenic right ventricular cardiomyopathy, Myocarditis = cardiomyopathy after myocarditis, LVNC = left ventricular non-compaction cardiomyopathy FIGURE 2. Kaplan-Meier survival curves for the subgroups of patients with dilated and ischemic cardiomyopathy. FIGURE 3. Kaplan-Meier survival curves according to NTproBNP levels. **Conclusion**: Interestingly, the prevalence of DCM in our cohort is much higher than that described in European registries. NT-proBNP was confirmed to be a very reliable predictor of mortality in a diverse HF cohort. Our study suggests higher mortality in DCM patients (despite a younger age) compared to ICM, but a larger patient cohort and longer follow-up time is needed to confirm this trend.

Josip Varvodić, Savica Gjorgjievska, Marko Kušurin, Mislav Planinc, Daniel Unić, Davor Barić, Robert Blažeković, Željko Sutlić, Igor Rudež

**Objective**: Aortic valve replacement (AVR) is still the most commonly used therapeutic option for patients suffering from AR. Aortic valve repair (AVRep) is an attractive alternative method, since it avoids the risks of prosthesis-related complications. (1, 2) We would like to present our experience with the Yacoub root remodeling, valve sparing technique with the extraaortic expansible ring. **Patients and Methods**: Between November 2014 and August 2017, a total of 49 patients (52.1±12.5) years; 18.9% female, EuroScore II of (2.4%±1%) underwent AVRep, 6 due to isolated cusp malcoaptation and 43 with associated with aortic root dilatation. Recontruction was done with the Coroneo Extraaortic Ring (27 (25-31)) and the Gelweave graft (28 (26-32)). Concomitant procedures included MVRep in three patients with TVrep in two of them, CABG in two patents and replacement of aortic arch and placement of EVITA stent graft in two patients. Echocardiography was used to determine AR severity grade pre-operatively, during immediate post-operative period (within 7 days from operation) and at early follow-up. **Results**: In postoperative follow up no patients died. Freedom from reoperation was 94% (3/37) and there were 2 patients reoperated due to early postoperative regurgitation, and one because of early cardiac tamponade. A significant decrease in LV end-diastolic diameter was observed (LVEDD) (61.3/53.5 mm) with further decrease at early follow-up. At follow up none of the patients had major AR (AR 0=40, AR 1+=7, AR 2+=2). **Conclusions**: We have proved that AVRep is a good alternative for patients with aortic insufficiency and leads to LV reverse remodeling with comparable results in terms of LVEDD and LVEF immediately post-operatively and at early follow.

Ljiljana Banfić, Jasmina Hranjac, Majda Vrkić Kirhmajer, Zoran Miovski, Dražen Perkov, Savko Dobrota, Ana Marija Alduk, Ranko Smiljanić

This overview is related to one year diagnostic, treatment and follow up in patient with intermittent claudication. The patients presented with intermittent claudication were selected for investigation according to the clinical data, comorbidities, functional screening testing (pletismography, segmental pressures and ABI), arterial duplex scanning and finally submitted to CT angiography that could discriminate candidates for the best treatment options; angiointerventional or vascular surgery treatment. (1) In the group of 480 patient evaluated in one year period 119 were eligible for angiointerventional or surgical procedure according to the functional testing (pletismography and ABI, arterial duplex scanning) and 114 of them were referred to CT angiography. The patients evaluated on functional data ABI and pletismography before and after the treatment in the 48 hours period (100%), 3 months after (40%) and six months (14.9%) follow up time interval. The majority of patients were treated by angiointerventional techniques (71 patient, 62%), 17 patients (14%) with optimal medical treatment and, 16 (14%) as elective surgical candidates, and the rest as urgent surgical patients as 3 of them required amputation because of life threatening critical limb ischemia. According to the data 50% of the patients treated with percutaneous transluminal angioplasty (PTA) were treated with drug eluting balloons or balloons only, while the rest PTA was done with stents. Early results were determined 48 hours after the procedure and 85% had successful outcomes according to the angiography, ABI and pletismography data. 10% of patients had some complications such as 1 retroperitoneal hematoma that needed surgical interventions, 6 minor local dissections, 4 minor hematomas, and no fatal event. In conclusion: Patient candidates were selected on functional testing and CT angiography thereafter, as resulted in proper patient selection that generate successful early interventional results. We cannot assume long term 6 months results because of low number of patients submitted for follow up evaluation.

Diana Rudan

Cardiovascular diseases are the leading cause of death in the world with hyperlipidemia being one of the most important risk factors in their development. Therefore, numerous randomized controlled trials conducted, showed decrease morbidity and mortality from adverse cardiovascular events by effective lipid reduction. Statins are the most effective medications used in treatment of hyperlipidemia. Rosuvastatin represents a “new generation” statin. It is a synthetic statin that inhibits the enzyme 3-hydroxy-3-methylglutaryl coenzyme A reductase, and therefore reducing the synthesis of endogenous cholesterol. The major effect of rosuvastatin is the reduction of LDL-cholesterol, and total cholesterol in the blood. It is the only statin that has been shown to increase the levels of HDL-cholesterol up to 15%. The anti-inflammatory, anti-oxidative, and anti-thrombotic effects of the drug were demonstrated in various studies, causing further decrease in cardiovascular morbidity and mortality, that effect is beyond the one described only by the reduction in total cholesterol levels. The most common side-effect of statin treatment is myalgia, causing the non-adherence and discontinuation of the medication, leading to “alternative” drug treatment. However, the approach of alternative drug treatment often showed itself to be ineffective solution. Since treating hyperlipidemia is crucial in reducing cardiovascular risk, the importance of adherence to treatment, and achieving patient compliance to statin therapy must be emphasized. Rosuvastatin is available in 6 different doses from 5 to 40 mg, allowing the physician to adjust the dose of medication according to the patient’s needs, to maintain highest treatment effect while reducing unwanted side-effects at the minimum.

Mislav Puljević, Zoran Miovski, Majda Vrkić Kirhmajer, Krešimir Putarek, Ljiljana Banfić

The knowledge about the actual prevalence of the disease is only partially possible because it applies only to patients treated in hospital. We do not have epidemiologically relevant data about venous thrombosis prevalence in Croatia. The Working Group on Angiology and Peripheral Vascular Diseases of the Croatian Cardiac Society has an initiative for formation of a national registry in order to obtain an epidemiological data of population morbidity, mode of treatment and prevention of venous thrombosis. (1) We will present the results of a prospective epidemiological study in the University Hospital Centre Zagreb, which should represent a pilot study that could be a model for the formation of a national Registry “Venous Thrombosis”. Questionnaire includes the relevant data relating to the etiology of deep vein thrombosis, scope and localization of the disease, complications of disease, mode of mandatory and long-term treatment, as well as possible complications during treatment. Results of one center collected in period of 20 months during 2016 and 2017, included a total of only 142 patients. The data correspond to the world literature published so far.

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

**Introduction**: Implantation of extracorporeal membrane oxygenation (ECMO) as a bridge to recovery or decision is a widely accepted treatment. (1) We present our experience using VA ECMO for hemodynamic support of patients with cardiogenic shock. **Patients and Methods**: We supported 61 patients (72% males and 28% females) since 2011, with even 21 patients during the last year. The average age was 58 with 23% of pts of age ≥ 65. The average duration of ECMO was 6 days. Median SAVE score was -10 with significantly lower score among pts treated before then after 2015 (-11 vs -8, P=0.003). The etiology of cardiogenic shock was acute myocardial infarction (48%), cardiomyopathy (43%) and myocarditis (9%). New-onset heart failure (HF) was an indication in 57% while acute deterioration of chronic HF was present in 43%. ECMO was implanted during resuscitation in 28%. **Results**: Survival on ECMO support was 56%. Thirty-one percent (31%) were weaned from ECMO and 25% of patients continued on advanced HF therapies (8% were transplanted and 17% received LVAD). Survival at hospital discharge was 30%. Survival among pts that received ECMO during CPR was only 18%. The survival significantly improved since 2015. (46% vs 11%, P=0.003). Both mortality on ECMO as well as mortality at hospital discharge were significantly higher at age of ≥ 65 (62% vs 38%, P=0.029; 100% vs 62%, P=0.006). These two age groups, i.e. < 65 and ≥ 65 differed significantly only in the SAVE score with lower i.e. more unfavorable scores in older pts (P=0.01). Survival at hospital discharge strongly depended on renal function, with no survivors among pts who were already on or have started the dialysis on the very first day of ECMO support. Survival was higher in pts with new-onset HF than in pts with acute worsening of chronic HF, but this did not reach statistical significance (77% vs 68%, P=0.31). The predictors of better survival included lower serum creatinine, NT-proBNP and free hemoglobin, as well as higher, SAVE score (P=0.026, P=0.05, P=0.019 and P<0.001 respectively). **Conclusion**: Although results with ECMO support in cardiogenic shock steadily improve for last 7 years it still exhibits high short-term mortality. Our observations reinforce the need to start ECMO before the occurrence of irreversible multi-organ failure and to respect patient’s age and SAVE score before making such a difficult decision.

Ivana Jurin, Mirjana Kardum, Pejić, Vanja Ivanović, Mihajlović, Sandra Jakšić, Jurinjak, Irzal Hadžibegović

**Background**: Patients with primary aldosteronism as first described had a low incidence of cardiovascular complications however more recent investigations indicate that long term exposure to elevated aldosterone levels result in a substantial cardiac damage. (1) **Case report**: 61-year-old obese male with history of hypertension and paroxysmal atrial fibrillation was admitted to our department because of severe left-dominant heart failure. His heart rhythm was atrial fibrillation and echocardiographic exam revealed dilatation of both left atrium and ventricle with a severe reduction of left ventricular systolic function (EF LV 29% Simpson) and an abnormal pattern of left ventricular filling. Primary aldosteronism was diagnosed based on severe hypokalemia (2.4 mEq/L) and a low renin-high aldosterone state with hypertension and metabolic alkalosis. Etiology of this condition were expansive masses in right (9 mm in diameter) and in left suprarenal gland (13mm in diameter). Serum potassium was normalized and blood pressure was controlled well by a full dose of an aldosterone receptor blocker (spironolactone 100 mg/day). A diuretic (furosemide) was then added. Rate control of atrial fibrillation was obtained with a beta-adrenergic blocker, and anticoagulation therapy was started. Coronary arteries had no significant stenosis on coronary arteriograms. Twelve days after admission echocardiographic exam was repeated and it showed an excellent improvement in left ventricular systolic function (EF LV 60% Simpson). Follow up after six months revealed normal potassium levels, well controlled blood pressure and normal systolic function of left ventricle. **Conclusion**: We presented a case of a patient with hyperaldosteronism-induced cardiomyopathy. Left ventricular systolic function in primary aldosteronism does not generally differ from other types of hypertensive disease, but here in our case it was clear that elevated aldosterone levels induced systolic heart failure. Nevertheless, in primary aldosteronism abnormal pattern of ventricular filling is commonly detected (2, 3) which contributed to enlargement of left atrial size and atrial fibrillation development in this patient.

Irzal Hadžibegović, Ivana Jurin, Vanja Ivanović Mihajlović, Mario Sičaja, Boris Starčević

**Background**: Numerous prognostic indicators for acute pulmonary embolism (PE) have been proposed, with Pulmonary embolism severity index (PESI) being the most studied and most accepted risk score and predictor of mortality. (1, 2) We analyzed PESI and classical prognostic factors, and compared it with fast and simple blood count tests as predictors of mortality. **Patients and Methods**: We analyzed 299 patients treated for acute PE between 2013 and 2016. Median follow up time was 16 months (range 55 months). Multivariate Cox proportional hazard regression models for 30-day, 12-month and 48-months mortality were obtained, combining gender, age, malignancy history, PESI score, atrial fibrillation, positive troponin-I, C-reactive protein (CRP), main branch involvement on MSCT, red cell distribution width (RDW), mean platelet volume (MPV), and platelet to lymphocyte ratio. **Results**: Thirty-day survival was 82.3%, whereas 12-months and 48-months survival was 69.6% and 66.2%, respectively. Statistically significant effect on 30-day mortality was shown for higher PESI score (HR 1.027, CI 1.020-1.034; p=0.000), higher RDW (HR 1.301, CI 1.144-1.481; p=0.000), malignancy (HR 2.886, CI 1.366-6.101; p=0.006), higher CRP (HR 1.034, CI 1.006-1.062; p=0.016), and higher platelet to lymphocyte ratio (HR 1.001, CI 1.000-1.002; p=0.026). Statistically significant effect on 12-months mortality was shown for higher PESI score (HR 1.020, CI 1.015-1.025; p=0.000), higher RDW (HR 1.332, CI 1.225-1.449; p=0.000), and higher platelet to lymphocyte ratio (HR 1.001, CI 1.000-1.002; p=0.013). Statistically significant effect on 48-months mortality was shown for higher PESI score (HR 1.020, CI 1.015-1.025; p=0.000), higher RDW (HR 1.339, CI 1.234-1.453; p=0.000), malignancy (HR 1.713, CI 1.024-2.868; p=0.040), higher CRP (HR 1.021, CI 1.002-1.041; p=0.032), and higher platelet to lymphocyte ratio (HR 1.001, CI 1.000-1.002; p=0.006). **Conclusion**: Steep decline in survival rate was noted within first 12 months. PESI score above 111 and elevated RDW above 14.5 were the strongest and most consistent predictors of short term and long-term mortality. RDW outperformed PESI in predicting 12-months survival. Future prospective studies of simple blood count derived risk scores are warranted.

Duška Glavaš, Lovre Bojić, Ratko Ermacora, Bruna Bojić

**Introduction**: Cardiovascular illness are more often observed in glaucoma patients. (1) The purpose of the study was to assess the ultrasound measurements of the brachial artery flow-mediated dilation (FMD) in patients with glaucoma. **Patients and Methods**: Thirty-seven patients with glaucoma and thirty-one healthy controls were included in the study. All glaucoma patients and controls underwent ultrasound measurement of FMD of the brachial artery. **Results**: The mean values of brachial FMD were significantly lower among glaucoma group compared with control group (15.3 ± 9.5% vs 19.8 ± 9.3%; p=0.04). No significant difference was found in brachial artery diameter at rest (4.7 ± 0.6 vs. 4.9 ± 0.3; p=0.2) between glaucoma patients and controls. The significant difference in brachial artery diameter in hyperemia between patients with glaucoma and control group (5.4 ± 0.6 vs. 5.9 ± 0.4; p=0.002) was detected. A negative correlation among brachial FMD and brachial artery diameter at rest was found. **Conclusion**: Impaired brachial FMD could indicate presence of systemic vascular endothelial dysfunction in patients with glaucoma.

Filip Lončarić, Dora Fabijanović, Vedran Velagić, Nina Jakuš, Marijan Pašalić, Ivo Planinc, Davor Miličić, Maja Čikeš

**Background**: An advanced interatrial block (aIAB) is seen on the ECG as the combination of a P wave duration >120 ms and biphasic P wave morphology in the inferior leads. It is considered a marker of an electromechanically dysfunctional left atrium (LA) and hence a risk factor for supraventricular arrhythmias and heart failure (HF). (1) The aim of our pilot study is to explore aIAB as a potential marker for determining a clinically relevant subgroup of HF patients. **Patients and Methods**: An echocardiogram and a surface ECG were performed on a total of 51 HF patients in sinus rhythm (31 (61%) with HF with preserved ejection fraction (HFpEF), 20 (39%) with HF with reduced ejection fraction (HFrEF)) diagnosed per the current guidelines, and 20 sex-matched healthy controls. Echocardiographic parameters of LA structure and function were measured. ECG measurements were performed digitally with an electronic calliper. **Results**: Prevalence of aIAB was 11% (n=8) in the studied group, significantly greater in HFpEF patients, compared to HFrEF patients and healthy controls (88% vs. 0% vs. 12%, p=0.025, **Figure 1**). The HFpEF patients formed an aIAB HFpEF subgroup (n=7) that was compared to two control groups, both without P wave duration >120 ms or biphasic P wave morphology in the inferior leads: age- and sex- matched HFpEF patients (n=7) and sex-matched healthy controls (n=12). Based on this subanalysis, the aIAB patients had a significantly higher occurrence of paroxysmal atrial fibrillation (healthy controls vs. HFpEF controls vs. aIAB: 0% vs. 43% vs. 86%, p 120 ms | Biphasic P wave in inferior leads and P wave > 120 ms | Biphasic P wave in inferior leads and P wave > 120 ms | P values | P values | P values | | --- | --- | --- | --- | --- | --- | --- | | | Yes | No | | aIAB | aIAB | HFpEF controls | | | aIAB | HFpEF controls | Healthy controls | vs | vs | vs | | | (n=7) | (n=7) | (n=12) | HFpEF controls | Healthy controls | Healthy controls | | **Male sex – no. (%)** | 1 (14) | 1 (14) | 4 (33) | 1 | 0.603 | 0.603 | | **Age (IQR) –years** | 74 (71-81) | 75 (67-82) | 54 (51-55) | 1 | 2** | 46.4 (41.4-50.6) | 37.6 (32.7-54.1) | 26.6 (18.7-29.6) | 0.318 | 2** | 26.8 (23.9-32.0) | 21.6 (21.0-25.5) | 18.2 (15.0-20.3) | 0.073 | <0.0001 | 0.007 | | **LAEF (IQR) - %** | 34.6 (31.8-44.6) | 39.7 (31.0-41.3) | 57.8 (46.4-66.7) | 0.902 | 0.013 | 0.005 | | **V max (IQR) - ml** | 85.0 (81.0-109.0) | 71.0 (61.0-92.0) | 51.5 (35.5-59.5) | 0.259 | <0.0001 | 0.005 | | **V min (IQR) - ml** | 53.0 (35.0-75.0) | 42.0 (38.0-51.0) | 20.5 (12.3-28.8) | 0.456 | 0.001 | 0.0001 | | **preA volume (IQR) - ml** | 64.0 (52.0-86.0) | 59.0 (46.0-65.0) | 38.0 (22.2-28.8) | 0.456 | <0.0001 | 0.010 | [†] aIAB – advanced interatrial block; HFpEF – heart failure with preserved ejection fraction; IQR – interquartile range, AF – atrial fibrillation; LVEF – left ventricular ejection fraction; LAVI – left atrial volume index; LAA – left atrial area; LAEF – left atrial ejection fraction; V max – maximal volume of the left atrium; V min – minimal volume of the left atrium; preA volume – volume of the left atrium at start of P wave on ECG. Variables in the table are described with a percentage or with the median and interquartile range. **Conclusion**: This pilot study relates aIAB to the HFpEF part of the HF spectrum. Significant differences in LA structural and functional characteristics suggest that aIAB may be a useful parameter for determining a clinically relevant subgroup of HFpEF patients, however an analysis of a larger patient cohort would be required to further establish these findings.

Azra Durak-Nalbantić, Mirza Dilić, Faris Zvizdić, Alen Džubur, Marina Vučijak, Nerma Resić

**Introduction:** Up to 50% of patients with acute heart failure (AHF) have preserved left ventricular ejection fraction (HFPEF group) (1). Due to diverse activated pathophysiological pathways, there should be a difference in biomarkers release in heart failure with preserved ejection fraction (HFPEF) and reduced ejection fraction (HFREF). BNP is the best studied biomarker in AHF, but we want to investigate difference in release of troponin (marker of myocytes stress and injury), tumor marker CA125 (marker of congestion and volume overload om HF) and cystatin C (marker of interstitial fibrosis). **Patients and Methods:** In 222 patients hospitalized due to acute heart failure (138 with REF and 74 with PEF) were determined levels of BNP at admission („dry BNP“), BNP at discharge („wet BNP“), procentual change of BNP during hospitalization, high sensitive troponin I, cystatin C and CA125. **Results**: BNP at admission is lower in HFREF vs HFPEF group [1254.9 (732.7-2402.6) pg/ml vs 479.9 (240.7-865.7) pg/ml, p.**

Ivana Jurin, Mario Sičaja, Tomo Svaguša, Sandra Jakšić, Jurinjak, Diana Rudan, Irzal Hadžibegović, Boris Starčević

**Background**: Nonvalvular atrial fibrillation (AF) is the most common cause of systemic embolism. In rare cases, AF can cause coronary artery embolism which is a rare but important nonatherosclerotic cause of acute myocardial infarction. (1) **Case report**: We report the case of 81-years-old man with permanent atrial fibrillation who presented to our hospital with ST segment elevation myocardial infarction. Coronary angiography verified the embolic occlusion of distal posterolateral branch, which is a branch of the right coronary artery, unsuitable for percutaneous coronary intervention, and no significant atherosclerotic coronary artery disease was found. Transthoracic echocardiography showed a slightly reduced left heart systolic function (EF 45-50%), higher grade diastolic dysfunction and reduced longitudinal strain in inferoposterior segments of left ventricle (-2 to -7). The patient was treated according to the current guidelines. **Conclusion**: Proper anticoagulant therapy in patients with atrial fibrillation is extremely important in order to prevent thrombus formation, and consequently, the embolism commonly occurring in these conditions. Echocardiographic measurement of the longitudinal strain could indicate a greater possibility of forming the thrombus in patients with impaired cardiac contractility. At present, measurement of the ventricular strain is recommended as a better method for estimating the systolic function from the measurement of the ejection fraction. Using this method, it is better to examine segmental mobility of individual parts of the ventricle and to better evaluate contractility. Also, the strain may point to the hipo(a)contractility of the ventricle. In this case, there is a possibility that in this negligible part of the ventricle, conditions for the thrombus formation were created. Is this the case in this patient we cannot safely claim. Research is needed to confirm this assumption.

Rosanda Mulić, Iris Jerončić Tomić

Cardiovascular diseases (CVD) are the leading cause of death in Croatia with the highest mortality rate among European Mediterranean countries, with significant regional differences. (1-3) The hypothesis is that technological advances and transition changes have diminished the impact of Mediterranean lifestyle in Croatia, a country that has one third of its territory and one quarter of the population living in the Mediterranean area. As a possible indicator of the Mediterranean lifestyle we used standardized death rates of CVD per 100,000 inhabitants and compared these to the rates in some other Mediterranean countries. Furthermore, we also did an in-country comparison of the counties/regions. We used the data from Eurostat and from Croatian Health Statistics Yearbook. The EU-28’s standardized death rate for diseases of the circulatory system was 383 deaths per 100,000 inhabitants in 2013, with the rate for men being some 1.4 times higher than that for women. During 2014, among Mediterranean countries France had the lowest death rate from CVD (49.3 per 100,000 inhabitants), and Croatia the highest (306.5). Among Croatian counties, the lowest rates have been recorded in coastal areas (Šibenik-Knin County 264.3) and the highest among continental counties – such as Virovitica-Podravina County (475.4/100,000). In the 0-64 age group, rates range from as high as 48.5 in the continental Krapina-Zagorje County down to 16.3 in the littoral Šibenik-Knin County. In Croatia standardized death rates for CVD were systematically higher for men than for women. Over the last ten years we have seen a continuing downward trend in mortality caused by CVD, which is more pronounced for cerebrovascular diseases, than for ischemic heart disease and especially for the 0-64 age group, but CVD are still the major cause of mortality and morbidity. We concluded that in the coastal counties the mortality rate of CVD is lower than in the continental, and the probable cause is still the Mediterranean way of life in the coastal area. Public health needs to invest more efforts in preventing cardiovascular diseases in Croatia.

Majda Vrkić Kirhmajer, Ljiljana Banfić, Eduard Margetić, Irena Ivanac Vranešić, Milan Milošević

**Background**: Previous studies have found interaction between lower extremity artery disease (LEAD) and systemic vascular effects. (1-3) Little is known about association of LEAD and carotid artery stiffness (AS). The aim of this study is to investigate the correlation between carotid stiffness parameters, intima- media thickness (IMT) and severity of LEAD. **Patients and Methods**: Cross-sectional study of 120 patients with LEAD was performed (mean age 64.6 ± 8.6 years, 85 males, mean ABI 0.65 ± 0.15). The diagnosis of LEAD was defined as ABI ≤ 0.9. Patients were divided into two groups: mild LEAD (ABI from 0.9 to 0.71) and advanced LEAD (ABI ≤ 0.7). Local stiffness ß index, one-point pulse wave velocity (PWV-ß), elastic modulus (Ep), arterial compliance (AC), augmentation index (AI) and IMT were measured on common carotid artery by high-resolution ultrasonography and Echo-tracking technology. Patients with severe renal impairment and those with moderate and severe heart valve disease or reduced left ventricular ejection fraction (< 40%) were excluded from this study. **Results**: Out of 120 patients, 39 had mild LEAD (mean ABI 0.81 ± 0.07) and 81 had advanced LEAD (mean ABI 0.57 ± 0.11). Symptomatic LEAD was significantly more frequent in patients with advanced LEAD (59% vs. 93.8%, p < 0.001). No significant differences were found in demographic and laboratory findings (age, gender, body mass index, history of diabetes, smoking, hypertension and hyperlipidemia, fasting blood glucose, serum creatinine, total cholesterol, triglycerides, HDL and LDL cholesterol). Three arterial stiffness parameters: ß index, PWV-ß and Ep, were significantly higher in advanced forms of LEAD (ß index median: 8.1, interquartile range (IQR) [6.7-10.0] vs. 9.4 [7.9-11.1], p= 0.008; PWV-ß median: 6.4, IQR [5.9-7.2] vs. 6.9 [6.3-7.5] m/s, p =0.031; Ep median: 112, IQR [89-139] vs. 127 [107-154] kPa, p= 0.025). Augmentation index, arterial compliance and IMT did not significantly differ between groups (p= 0.862, p= 0.434 and p=0.060, respectively). **Conclusion**: In comparison with mild LEAD, patients with advanced forms of LEAD have higher carotid stiffness parameters (ß index, PWV-ß and Ep). Further studies are needed to assess the clinical importance of arterial stiffness in LEAD, targeting AS for potential therapies in order to improve management of LEAD.

Ersel Onrat, Sezgin Barlak, Serap Tutgun Onrat, İsmet Dogan, Hayri Demirbas, Serkan Gokaslan, Cigdem Gokaslan, Alaettin Avsar

**Introduction**: Carotid artery disease (CAD) is the narrowing of carotid arteries due to atherosclerosis. It can cause stroke. Some hereditary determinants can affect atherosclerosis formation. (1) In present study, we investigated the hereditary thrombophilia on the formation of CAD. **Patients and Methods**: We evaluated the effects of Factor V LEIDEN, Factor V H1299R, Prothrombin G20210A, Factor XIII V34L, B-Fibrinogen -455 G>A, PAI-1 4G/5G, HPA1, MTHFR C677T, MTHFR A1298C, ACE I/D, APO B R3500Q, and APO E polymorphisms on CAD formation by using a ViennaLab CVD Strip Assay. Group A includes 41 patients (70.2 ± 8.6 years, 30 men) with CAD and Group B includes 39 healthy controls (67.3 ± 9.2 years, 28 men). Twenty patients had transient ischemic attack or stroke, 21 had carotid artery stenosis, more than 50% in Group A. Hyperlipidemia is more frequent in Group A compared Group B (71%, 49%; pA, MTHFR C677T and MTHFR A1298C were more frequent in Group A compared with Group B significantly [(2.6%, 7.3% pA, MTHFR C677T and MTHFR A1298C heterozygous mutation seems to be determinant (p<0.05). We have some difficulty on the explication that why heterozygous form is significant even though homozygous form is not significant. This is a pilot study. We will go on working on the project to evaluate the hereditary thrombophilia.

Vedran Radonić, Damir Kozmar, Darko Počanić, Helena Jerkić, Ivan Bohaček, Tomislav Letilović

**Aim**: To compare the overall and disease-specific mortality of Croatian male athletes who won one or more Olympic medals representing Yugoslavia from 1948 to 1988 or Croatia from 1992 to 2016, and the general Croatian male population standardized by age and time period. While it is well known that regular physical activity improves general health and reduces the risk of premature mortality, effects of vigorous training are still unclear (1). Still, a large retrospective multinational study which included 15 174 Olympic medalists found that they have lower mortality than their general populations; however, that study did not examine causes of death of the athletes (2). **Methods**: All 233 Croatian male Olympic medalists were included in the study. Information about life duration and the cause of death for the Olympic medalists who died before January 1, 2017, was acquired from their families and acquaintances. For deceased Olympic medalists, medical documentation was requested. Croatian Bureau of Statistics (CBS) provided data about the overall and disease-specific mortality of the Croatian male population standardized by age and time period. Overall and disease-specific standard mortality ratios (SMR) with 95% confidence intervals (CI) were calculated to compare the mortality rates of Croatian Olympic medalists and the general population. **Results**: Among 233 Olympic medalists, 57 died before the study’s endpoint. Cardiovascular diseases were the most common main causes of death (33.3%), followed by neoplasms (26.3%) and external causes of death (17.6%). Overall mortality of the Olympic medalists was found to be significantly lower than that of the general population (SMR=0.73, CI=0.56-0.94, p=0.013). Regarding specific causes of death, athletes’ mortality from cardiovascular diseases was significantly reduced (SMR=0.61, CI=0.38-0.93, p=0.021) when compared with the general Croatian male population. **Conclusions**: Croatian male Olympic medalists benefit from lower overall and cardiovascular mortality rates in comparison to the general Croatian male population.

Jasmina Ćatić, Ivana Jurin, Marko Lucijanić, Sandra Jakšić, Jurinjak, Tomislava Bodrožić, Džakić, Poljak, Robert Blažeković

**Aim**: Red cell distribution width as an indicator of inflammation has been shown as a predictive and prognostic factor in coronary artery disease as well as in heart failure (1, 2). The aim of this study was to evaluate correlation between red cell distribution width (RDW) and echocardiographic parameters of systolic FUNCTION and atrial fibrillation occurrence in patients with acute ST segment elevation myocardial infarction (STEMI). **Patients and Methods**: We recruited 89 patients with acute myocardial infarction with ST elevation who were hospitalized in the Department of Cardiovascular Diseases, University Hospital Dubrava, Zagreb. Complete blood count was determined from blood samples prior to percutaneous coronary intervention (PCI). Echocardiographic exam was performed by two independent experts after PCI. **Results**: RDW was negatively correlated with ejection fraction (p=0.026, Rho=-0.24), patients with EF 14.5%, P=0.00, HR=3.99). **Conclusion**: Increased RDW values on admission in STEMI patients treated with PCI are associated with systolic dysfunction and atrial fibrillation occurrence in the follow -up period. These findings can guide further clinical practice but must be confirmed in future studies with more patients.

Lada Bradić, Marina Mihajlović, Arijana Crevar, Gregor Eder, Kristina Krželj, Tena Jukić, Ivan Bitunjac, Martina Lovrić Benčić

**Introduction**: Syncope is defined as transient, self-limited loss of consciousness due to temporary global cerebral hypoperfusion, resulting from low peripheral resistance and/or low cardiac output (1). Reported incidence of syncope is high; 18-40 per 1,000 patient-years in general population (2). Tilt-table testing enables reproduction and characterization of syncope in controlled settings, according to blood pressure and heart rate response to tilting. Modified VASIS classification to tilt testing distinguishes: reflex/vasodepressor syncope, cardioinhibitory syncope with/without asystole, mixed syncope, orthostatic hypotension and POTS (postural orthostatic tachycardia syndrome) (3). **Patients and Methods**: We retrospectively analyzed 708 patients (67% female, 33% male) who underwent tilt-table testing in our institution from 2013 to September 2017. Of the referred patients 47.6% were 15-30 y/o, 29.8% were 30-60 y/o, and 22.6% were >60 y/o. Patient history included syncope in majority of patients - 84.6%, 80.1% and 68.8% of patients 60 y/o, respectively. **Results**: Normal reaction to tilt-up testing was found in 49.3% of young (60 y/o). Tilt-up testing provoked syncope in 32.6% of patients 60 y/o (p60 y/o, p60 y/o) patients, p83% of elderly patients had normal reaction to testing, thus questioning widespread use of tilt-table testing in this age group. Mechanisms underlying syncope should be sought in order to properly diagnose and counsel patients for syncope avoidance. Only a minority of younger patients had cardioinhibitory syncope, and none during four analyzed years required pacemaker implantation. Elderly patients with syncope should be evaluated using alternative diagnostic algorithms.

Davor Miličić

Dear colleagues, We are happy and proud, as the Croatian Cardiac Society, to have the privilege of hosting and organizing Cardiology Highlights for the 5th time – the ESC Update Meeting in beautiful Dubrovnik, Croatia. The first Meeting was organized ten years ago, starting as a biannual congress endorsed by the European Society of Cardiology as a one of the three Update Meetings: Davos Cardiology Update, Rome Cardiology Forum, and Dubrovnik Cardiology Highlights. We are also honored by the fact that this time the Meeting is being held under the high patronage of the Croatian Academy of Sciences and Arts. Our Scientific Programme, lasting three and half days, has been composed to cover all the main topics of contemporary clinical cardiology, and special emphasis has been given to the newest ESC guidelines, according to the ESC Update Meetings’ mission and policy, defined by the ESC Committee on Education. The first day of the Meeting will be focused on Advanced Heart Failure, and the first day’s sessions are have been organized in collaboration with the Failure Association Board of the ESC. We have also organized a Session in collaboration with the ESC Working Group on Coronary Pathophysiology and Microcirculation, bringing some very challenging clinical and translational topics. Furthermore, the Zagreb-Zurich fellows’ interactive session already became a tradition, similarly as at the Davos Update in the Cardiology Meeting. The 5th ESC Highlights Meeting will host very prestigious international Faculty as well as the National Faculty composed of the leading Croatian cardiologists and cardiac surgeons. In addition to high quality interactive plenary lectures, we have once again included selected original communications and case presentations in the Programme as abstracts that have been published in the special issue of our national cardiology journal *Cardiologia Croatica*. The printed abstracts will be presented interactively at the Meeting in front of our distinguished peers, and the best of the abstracts are going receive awards. I really do hope that the scientific and educational purpose of the Meeting will provide a useful and enjoyable experience to all the attendees and be in accord with the high criteria of the ESC, as the world’s leading cardiovascular society. Sincerely yours,

Tomislava Bodrožić Džakić, Poljak, Diana Rudan, Miroslav Raguž, Jasmina Ćatić

**Introduction**: Ischemic heart disease is entity that involves structural atherosclerotic coronary artery disease (sCAD) and functional disorder of coronary circulation (**Figure 1**). Functional disorder of coronary artery is vasospastic angina (known as Prinzmetal’s, variant or inversa. This type of angina is rare, representing about 2% cases of angina. (1) We present the very rare case of a male patient who has coronary artery disease that involves both; structural -ectatic and functional-occlusive coronary artery disease (CAD). FIGURE 1. Schematic overview of coronary artery disease. **Case report**: 61-old male patient, with history of smoking (90pack per year) and arterial hypertension presented in emergency department with high blood pressure (240/130mmHg), epistaxis and headache. He complained that he has been suffering from severe chest pain in early mornings and after exposure to cold air. The chest discomfort lasted for five minutes with spontaneous resolving and was not precipitated by exercise. The initial electrocardiogram (ECG) did not show any signs of ischemia and laboratory parameters, including troponin were in normal range. Due to history of repeating chest pain, he was admitted to the Department of Cardiology for further investigation. Echocardiography showed moderate, symmetric, concentric hypertrophic myocardial muscle, preserved left ventricular systolic function and no valvular abnormalities. Coronarography was also performed. After contrast administration in left coronary artery patient complained of chest pain; ECG showed ST segment elevation up to 2 mm in all precordial leads and the occlusion of medial left anterior descendens branch (LAD) due to spasm could be seen (**Figure 2** and **3**Figure 3). After parenteral administration of nitrates the flow was established to the distal LAD (**Figure 4**). Right coronary angiography showed ectatic, dominant right coronary artery, with 50% stenosis in proximal segment (**Figure 5**). After contrast application patient had chest pain and ST segment denivelation in inferior ECG leads with no evident significant stenosis. We suggested treatment with calcium-channel blockers, angiotensin converting enzyme inhibitor, acetylsalicylic acid and statin. FIGURE 2. Occlusion of the medial segment of the left anterior descending branch during contrast application – right anterior oblique-cranial view. FIGURE 3. Occlusion of the medial segment of the left anterior descending branch during contrast application – “spider” projection. FIGURE 4. After parenteral administration of nitrates, the flow was established to the distal left anterior descending branch. FIGURE 5. Ectatic right coronary artery. **Conclusion**: It can be concluded that our patient has both: the vasospastic angina and the atherosclerotic coronary artery disease. Sometimes, it is hard to decide what kind of further diagnostic and therapeutic approach should be taken because of reasonable doubt which lesion (like in our patient) is “culprit” one.

Filip Lončarić, Dora Fabijanović, Nina Jakuš, Petra Mjehović, Dorja Sabljak, Antonija Mišković, Dominik Oroz, Maja Čikeš, Davor Miličić

**Background**: Women have poorer outcomes in acute coronary syndrome (ACS) due to older age, comorbidities, atypical presentation and delay in admission. (1) The aim is to consider gender differences in outcomes in the Croatian Branch of the ISACS-CT registry. **Methods**: From January 2012 to February 2017, 1808 patients were enrolled in the Croatian branch of the registry, 46% (n=844) presenting with acute ST segment elevation acute myocardial infarction (STEMI), 35% (n=637) with non-ST segment elevation myocardial infarction (NSTEMI) and 18% (n=327) with unstable angina. Sex ratio, male to female, was 2.2:1, the median age 65 (57-75) years. In-hospital mortality was defined as the primary outcome. **Results**: There was no sex difference in type of ACS at admission. Women were significantly older, generally more burdened with comorbidities and arrived to the hospital with more delay from symptom onset (women vs. men: in the first 2 h - 19% vs. 24%, p=0.02; in the first 6 h - 49% vs. 58%, p0.01) (**Figure 2**). There was no gender difference in undergoing percutaneous coronary intervention (PCI), but successful revascularization was less often achieved in women (92% vs. 97%, p<0.01). Moreover, female sex (OR = 4.7, CI 95% 1.5-14.7, p=0.021), together with creatinine levels (OR=1.01) and GB IIB/IIIA administration (OR=2.7), proved independently associated with in-hospital mortality in the PCI group, whereas this effect was not seen in the non-invasive treatment group. FIGURE 1. Sex differences in in-hospital mortality. STEMI = ST segment elevation acute myocardial infarction, NSTEMI = non-ST segment elevation myocardial infarction, PCI = percutaneous coronary intervention Figure 2. Sex differences in in-hospital mortality in patients with acute ST segment elevation myocardial infarction depending on time from onset of symptoms to admission. STEMI = ST segment elevation acute myocardial infarction **Conclusion**: Gender differences in patients presenting with STEMI are visible in the Croatian branch of the ISACS-CT registry. In this setting, female sex bears risk of worse outcome associated with delay in admission and invasive treatment.

Vedrana Baraban, Joško Bulum, Hrvoje Roguljić, Dražen Mlinarević, Livija Sušić, Zorin Makarović

**Introduction:** Acute aortic dissection is a life-threatening condition characterized with separation of the layers within the aortic wall. It is associated with high morbidity and mortality rates in spite of prompt medical treatment (1). **Case report**: 44-year-old man was admitted to the Coronary Care Unit from the Emergency Department with a diagnosis of acute myocardial infarction with ST elevation in precordial leads. The only chronic disease in his medical history was hypertension for which he was treated for the last three years. Due to the chest pain with ECG changes suggesting acute coronary syndrome and initially elevated troponin level (troponin I 0.165 ug/L) an urgent coronary angiography was performed. The angiogram showed no significant lesions of epicardial arteries. Due to the ongoing chest pain, persistent high blood pressure and elevated D-dimer levels (2.818 ug/L), a CT angiography of aorta was performed. CT angiogram revealed an acute Stanford type B dissection of the descending aorta. Due to the unavailability of endovascular treatment options in our hospital, the patient was immediately transferred to University Hospital Centre (UHC) Zagreb for thoracic endovascular aortic repair procedure which was successfully performed. During further hospitalization in UHC Zagreb the patient developed posterior reversible encephalopathy syndrome due to extremely high blood pressure levels. **Conclusion**: Aortic dissection has to always be included in the differential diagnosis of acute chest pain when it is associated with high blood pressure and elevated levels of D-dimer, especially when the patient has low serial troponin levels and a normal coronary angiogram. Interestingly, our patient had chest pain without propagation to any extremity or the to the neck and palpable, symmetrical arterial pulsations on all extremities. Therefore we conclude that atypical clinical presentation should not distract from making a correct diagnosis of acute aortic dissection.

Denis Došen, Dubravko Došen, Dejan Došen, Dora Fabijanović, Maja Čikeš, Davor Miličić

**Introduction**: Heart failure (HF) has been singled out as a staggering clinical and public health problem, associated with significant mortality, morbidity, and healthcare expenditures. Heart failure patients often experience a loss of productivity and quality of life. (1) This pilot study evaluated the effectiveness of a multidisciplinary, outpatient HF clinic during 6 months period. Our goal was to determine whether an intensive intervention at a HF clinic improves patient’s functional status (New York Heart Association (NYHA) class), echocardiographic parameters, and levels of NT-proBNP. Patients with optimal drug therapy at the start and at the end of the study were also evaluated. **Patients and Methods**: Our follow-up consisted of 8 scheduled patient contacts - initial visit at day 1, telephone contact at day 3, and visits to the clinic at weeks 1, 3, 5, 7 and at months 3 and 6. Verbal and written comprehensive education, optimization of treatment, easy access to the clinic, and advice for symptom monitoring and self-care were provided. Echocardiography study, six-minute walk test (6MWT) and levels of NT-proBNP were performed on an initial and the last visit. For group comparison Pearson chi-square, Fischer’s Exact test, Wilcoxon Signed Ranks Test and Paired Samples T-Test were used. **Results**: A total of 35 HF pts (mean age 76±6 years, 40% male) with various comorbidities (atrial fibrillation (57%), diabetes mellitus (32%), arterial hypertension (74%), chronic obstructive pulmonary disease (6%) diagnosed per the current guidelines were prospectively assessed in the period of 6 months. In follow-up period significant reduction of body mass index, average heart rate and systolic blood pressure was observed (**Table 1**). Echocardiography study showed improvements in systolic pulmonary pressure and left ventricular ejection fraction (**Table 2**). ### TABLE 1: Patients characteristics. | Segment | Visit 1 | Visit 6 months | P-value | | --- | --- | --- | --- | | **BMI (mean ± SD)** | 31.42 ± 5.45 | 30.70 ± 4.87 | **0.02** | | **SBP (mean ± SD)** | 127 ± 22 | 119 ± 9 | **0.02** | | **HR (mean ± SD)** | 76 ± 21 | 69 ± 11 | **0.03** | | **6MWT (median, IQR)** | 200 (82-280) | 270 (170-325) | **< 0.01** | | **NT-proBNP (median, IQR)** | 1873 (929-3301) | 1676 (434-4032) | 0.183 | | **NYHA (%)** **II** **III** | 20 (59) 14 (41) | 32 (97) 1 (3) | **< 0.01** | | **OMT** Beta-blockers (%) | 32 (94) | 31 (92) | 0.52 | | ACEI / ARBs (%) | 21 (62) | 23 (72) | 0.30 | | MRA (%) | 8 (24) | 23 (72) | **< 0.01** | | ARNI (%) | 3 (9) | 5 (16) | 0.46 | | Diuretics (%) | 33 (99) | 32 (97) | 1.0 | [†] BMI = body mass index, SBP = systolic blood pressure, HR = heart rate, 6MWT = 6 Minute Walk Test, NYHA = New York Heart Association, OMT = optimal medical therapy, ACEI = Angiotensin-converting-enzyme inhibitor, ARBs = Angiotensin receptor blockers, MRA = Mineralocorticoid receptor antagonist, ARNI = Angiotensin Receptor-Neprilysin Inhibitors ### TABLE 2: Echocardiographic parameters. | Segment | Visit 1 | Visit 6 months | P-value | | --- | --- | --- | --- | | **EDV (mean ± SD)** | 139 ± 62 | 131 ± 54 | 0.16 | | **LVEF (mean ± SD)** | 43 ± 14 | 48 ± 13 | **< 0.01** | | **E/E’ (mean ± SD)** | 12.3 ± 4.2 | 11.7 ± 4.2 | 0.34 | | **LAVI (mean ± SD)** | 60.2 ± 19.7 | 61.1 ± 16.1 | 0.74 | | **TAPSE (mean ± SD)** | 18 ± 4 | 20 ± 4 | **0.01** | | **sPAP (mean ± SD)** | 52 ± 15 | 27 ± 15 | **0.01** | [†] EDV = End-diastolic volume, LVEF = Left ventricular ejection fraction, LAVI = Left atrial volume index, TAPSE = Tricuspid annular plane systolic excursion, sPAP = Systolic pulmonary artery pressure **Conclusion**: A HF outpatient clinic involving an intensive intervention by a clinician, substantially improves patient’s functional status (NYHA class, 6MWT) as well as echocardiographic parameters. We also showed that mineralocorticoid receptor antagonists are still underutilized in the treatment of heart failure in our region and that further improvements in their prescribing are needed.

Ana Đuzel, Marin Pavlov, Zdravko Babić

Organization and outcome of health care in general, as well as, of cardiac intensive care units (CICU) highly depends on gross domestic product (GDP). We had been witnessing evolution of CICU from point of rapid resuscitation to intervention, and finally compendious critical care. (1) Authors analyze organization of CICU on national level in Croatia and compare it with economically more developed countries. Croatian GDP per capita is 35-40% of European (EU-28) average, which groups us among economically less developed European countries. (2) Data were collected from thirty-four Croatian hospitals, and analyzed during September and October 2016. (1) Croatia has 5 CICU per million inhabitants with mostly 5-6 beds (range of 1-9), on average one nurse on 2.7 patients (significant variation according to hospital size) and less than 4 beds per one physician (mostly cardiologists, lesser extent during night shifts). In addition, 76.5% of ICUs had 24/7 transthoracic echocardiography, 26.5% 24/7 transesophageal echocardiography, one third without therapeutic hypothermia, and 23.5% without ECMO as available treatment. This representative, nationwide sample of Croatian CICUs demonstrated considerable variation of key elements of structures with respect to hospital size and financial issues, what influenced following of present international guidelines. This kind of investigation revealed the space for improvement and has to be taken into account while proposing standards, reimbursement master plan, or quality assessment of national health system. (3)

Mario Stipinović, Sofiya Andreykanich, Darko Počanić, Tomislav Letilović, Bojana Aćamović Stipinović, Matija Marković, Ivica Premužić Meštrović, Helena Jerkić

**Objectives**: The indication for implantable cardioverter defibrillator (ICD) implantation is dilated cardiomyopathy (DCM), ischemic or nonischemic genesis, after three months of optimal medical therapy, with expected survival for more than one year (1). Available data from two large randomized trials show there was no effect of ICD implantation in patients with nonischemic DCM in total mortality, but there was a significant reduction of sudden cardiac death (SCD) (2, 3). The aim of ​​this study was to analyze real data from our center. **Patients and Methods**: During 2015 and 2016 we have implanted 35 ICDs in the primary prevention of SCD. The data were collected retrospectively and analyzed. **Results**: We analyzed 33 patients (2 lost from follow up), 4 females (12.1%) and 29 males (87.9%). The average follow-up was 22.7 months. In 20 patients (57.1%) the genesis of DCM was ischemic, and in 13 patients nonischemic (42.9%). Analyzing both groups, in the ischemic group, 3 deaths were recorded (15%), while in the nonischemic group 1 death was recorded (7.7%) (p = 0.48). All three deaths in ischemic group, as well as one in the nonischemic group, were the result of the terminal stage of cardiac insufficiency. Also, in the memory of the ICD in the ischemic group, malignant arrhythmias were recorded in 4 patients (20%), while malignant arrhythmias (p = 0.12) were not recorded in the nonischemic group. **Conclusion**: Comparing the obtained data from our center with data from large randomized trials we did not find benefit in total mortality in ischemic and nonischemic group (2, 3). In those trials there was significant reduction of SCD in nonischemic DCM due to successfully determination of malignant arrhythmias (2, 3), while our data suggested no benefit of ICD implantation in nonischemic group because there was no malignant arrhythmia in that group. Our data indicate a significant reduction in malignant arrhythmias in patients with nonischemic DCM. Because of the small number of patients, the results cannot be used for definitive conclusions without further investigation.

Ivana Jurin, Tomislav Letilović, Irzal Hadžibegović, Diana Rudan, Vanja Ivanović Mihajlović, Sandra Jakšić Jurinjak, Jasmina Ćatić, Petra Vitlov, Mario Sičaja, Boris Starčević

**Aim**: Principal aim of our prospective study was to evaluate aforementioned correlation of atrial fibrillation (AF) progression with inflammation. We tried to seek for inflammatory markers, that are readily available and could be related to AF progression (1). We compared the predictive power of those markers to the clinical tools specifically designed for AF progression prediction such as the HATCH score [hypertension, age > 75 years, previous transient ischemic attack (TIA) or stroke (doubled), chronic obstructive pulmonary disease, heart failure (doubled)]. Predictive power of those inflammatory markers was further compared to predictive power of CHA2DS2-VASc score, used for prediction of AF adverse events. Finally, it was compared to LADS score [left atrial diameter (0–2 points), age (0–2 points), diagnosis of stroke (0–1 point), and smoking status currently (0–1 point)] that was designed to identify acute stroke and transitory ischemic attack (TIA) patients with a greater chance of having AF. (2) **Patients and Methods**: The study included 579 consecutive patients of which 302 had paroxysmal atrial fibrillation, 107 had persistent atrial fibrillation and 170 had permanent atrial fibrillation. The study included patients who were hospitalized in our department between June 2012 and May of 2016. In the follow up period we enrolled only patients with paroxysmal and persistent atrial fibrillation. After a follow up period of 12-36 months of all 409 patients, 107 patients developed permanent atrial fibrillation. **Results**: Red cell distribution width (p= 0.036), MPV to platelet count ratio (p=0.011), lymphocytes (p= 0.004) and neutrophils to lymphocyte ratio (p=0.023) were found to be significant predictors of atrial fibrillation progression. In univariate analysis, age, platelets, mean platelet volume to platelet count ratio (MPV/platelet count), red cell distribution width (RDW) lymphocytes, neutrophils to lymphocyte ratio (N/L), CHA2DS2-VASc score, EF, LA size, HATCH and LADS score, and hypertension were significantly associated with AF progression. In multivariate analysis, only CHA2DS2-VASc score (P =0.024) and ejection fraction (P = 0.003) were shown to be independent risk factors for AF progression. **Conclusion**: These clinical and inflammatory markers could help us to determine which patients are at higher risk to develop permanent atrial fibrillation and therefore prevention of this progression remains an important target in the management of AF.

Miroslav Krpan, Marijan Pašalić, Jure Samardžić, Davor Miličić

**Introduction**: Patients with myocardial infarction (MI) are treated with percutaneous intervention (PCI) followed by dual antiplatelet treatment with ticagrelor and acetyl-salicylic acid (ASA). When ticagrelor is not available or poses a high risk for the patient clopidogrel and ASA are given (1). Interindividual variability of clopidogrel on platelet aggregation is widely recognized. Many studies have been conducted regarding individualized treatment with clopidogrel resulting in contradictory data. We designed a prospective, randomized study of individualized treatment with either clopidogrel or ASA or both in patients with acute MI and laboratory finding of high on treatment platelet reactivity (HOTPR). **Patients and Methods**: We investigated 73 patients with acute (MI) after PCI and standard loading doses of ASA and clopidogrel. Platelet reactivity was analyzed with Multiplate aggregometry. 43 patients comprised a therapeutic group with repeated daily loading doses of ASA and clopidogrel and then tailored treatment with up to 300 mg of ASA and 300 mg of clopidogrel daily. 30 patients were in the control group treated with standard treatment. **Results**: No significant difference in ischemic major adverse cardiovascular and cerebrovascular events (MACCE) (P=0.186) nor in overall mortality (0.521) was found when comparing the control group to the therapeutic one. However, further subanalysis revealed a higher tendency towards ischemic MACCE in the subgroup of patients with HOTPR ADP reactivity when compared to those with HOTPR ASPI reactivity (r=-0.376, P=0.013). Also, our data showed a tendency towards lower incidence of MACCE in the clopidogrel tailored subgroup (r=-0.244, P=0.078), something already shown in our previous research. When taking this into account, a significant difference in the incidence of MACCE among groups depending on all of the aforementioned therapeutic modalities is present (P=0.027). **Conclusion**: Our investigation showed that tailored antiplatelet therapy in patients with acute MI treated with clopidogrel and ASA and HOTPR showed no significant difference in MACCE. However, HOTPR in ADP reactivity carries greater impact on clinical outcome than HOTPR in ASPI reactivity showing tendency towards lower incidence of MACCE in patients with clopidogrel-only tailoring.

Daniel Lovrić, Marijan Pašalić, Vlatka Rešković, Lukšić, Kristina Gašparović, Dejan Došen, Jana Ljubas, Maček, Zvonimir Ostojić, Marija Brestovac, Davor Miličić, Jadranka Šeparović, Hanževački

**Background**: Visual assessment of regional wall motion abnormalities (RWMA) on echocardiography represents the current standard in assessing the coronary artery disease (CAD) induced changes in myocardial contractility. Although it has been proven to predict long-term outcomes it’s hard to rely on in acute situations due to the patient dependent variance in image acquisition quality and interoperator variability. It has been shown that 2D strain (2DS) is a sensitive indicator for sub-clinical myocardial injury.**1,2** The purpose of this study was to assess the value of regional 2DS performed early in patients with non-ST elevation acute coronary syndrome (NSTE-ACS) for predicting localization of ischemia-inducing stenosis and compare it with RWMA. **Patients and Methods**: We performed a retrospective analysis of patients admitted from January 2013 till December 2015 with the diagnosis of NSTE-ACS. Exclusion criteria were no coronary angiography, known prior CAD, no echo in 24 hours prior to angiography and image quality not adequate for 2DS analysis. Total of 123 patients were included. 4 clinicians blinded to laboratory and ECG results performed 2DS analysis of regional longitudinal peak systolic strain (LPSS) according to the 18-segment model, and RWMA were categorized according to the wall motion score guidelines, as interpreted by the clinician performing the original echo. **Results**: We found significant correlation of flow limiting stenosis, defined as a narrowing of >70% on angiography, with LPSS decrease for all three coronary vessels (**Table 1**). RWMA shows good predictive power of stenosis in LAD and LCx, but not in RCA (**Figure 1**). However, LPSS was more precise overall (mean sensitivity 75.6% vs 39.5%, P<0.001), and significant difference was present even after accounting for potentially confounding factors like arterial hypertension, smoking, alcohol, atrial fibrillation, valvular disease, age or prior medical therapy. ### TABLE 1: Regional visual wall motion assessment 2D longitudinal peak systolic strain values according to segments and location of coronary stenosis. | Segment | Lession location | *P* | | --- | --- | --- | | APLAX Basal anteroseptum | LAD | 0.098 | | APLAX Mid anteroseptum | LAD | <0.0001 | | APLAX Apical anteroseptum | LAD | <0.0001 | | APLAX Apical inferolateral | LCx | <0.0001 | | APLAX Mid inferolateral | LCx | 0.04 | | APLAX Basal inferolateral | LCx | 0.01 | | A4C Basal inferoseptal | RCA | 0.087 | | A4C Mid inferoseptal | LAD | 0.1 | | A4C Apical inferoseptal | LAD | <0.0001 | | A4C Apical anterolateral | LAD | 0.003 | | A4C Mid anterolateral | LCx | 0.366 | | A4C Basal anterolateral | LCx | 0.015 | | A2C Basal inferior | RCA | 0.133 | | A2C Mid inferior | RCA | 0.722 | | A2C Apical inferior | LAD | 0.15 | | A2C Apical anterior | LAD | <0.0001 | | A2C Mid anterior | LAD | 0.027 | | A2C Basal anterior | LAD | 0.032 | [†] LAD = left anterior descending coronary artery; LCx = left circumflex coronary artery; RCA = right coronary artery; APLAX – Apical long axis view; A4C – Apical four chamber view; A2C – Apical two chamber view. FIGURE 1. Comparison of sensitivity for detection of significant coronary artery stenosis of regional visual wall motion assessment (VWMA) vs 2D longitudinal peak systolic strain analysis (LSA). **Conclusion**: We have shown that there is significant correlation between a decrease in LPSS and localization of significant stenosis in patients with NSTE-ACS, and that it is significantly more accurate in detecting ischemia induced loss of myocardial contractility than the visual assessment of RWMA.

Jure Samardžić, Vedran Velagić, Boško Skorić, Saša Pavasović, Marijan Pašalić, Hrvoje Jurin, Ivo Planinc, Maja Čikeš, Davor Puljević, Davor Miličić

**Introduction**: Pulmonary vein isolation (PVI) procedures increase the potential thromboembolic risk (1). The aim of this study was to compare the effect of radiofrequency (RF) ablation and cryoablation on platelet reactivity (PR) in patients with atrial fibrillation (AF). **Patients and Methods**: We analyzed PR levels using Multiplate function analyzer in 63 consecutive patients undergoing PVI procedures in our institution. Blood samples were drawn just before the procedure and on the following day. Fourty six (46) and seventeen (17) patients underwent cryoablation and RF ablation, respectively. There was no difference in demographics and baseline platelet parameters (platelet count, MPV and PR) between patients in RF and cryo group. ASPI, ADP and TRAPtest were used to --assess multiple pathways of platelet activation. **Results**: One day after the procedure mean PR droped from baseline levels in both study groups. The observed delta was more expressed in the cryo group for all three PR tests but only ADPtest showed statistically significant difference in PR (**Figure 1**). FIGURE 1. Platelet reactivity before and after pulmonary vein isolation. RF = radiofrequency **Conclusion**: Our results show that PR after cryoablation is less pronounced compared to RF procedure. This affirms that thrombogenic burden of PVI is lower with cryoablation. We hypothesize that this could be a result of endocardial integrity preservation and decreased availability of platelet agonists during cryoablation. These results warrant further investigations with periinterventional PR measurements on a larger cohort of patients. ## Acknowledgments Aknowledgement: This study was funded by Croatian Science Foundation.

Saša Pavasović, Ana Reschner, Marijan Pašalić, Davor Miličić

**Background**: The ARB/neprilysin inhibitor sacubitril/valsartan reduced cardiovascular morbidity and mortality compared with enalapril in patients with HF and reduced left ventricular ejection fraction (LVEF) according to the PARADIGM-HF trial. (1, 2) The aim was to analyze several clinical parameters in patients with chronic systolic heart failure (CHF) after sacubitril/valsartan was introduced instead of ACEI/ARB. **Patients and Methods**: We have analyzed the medical history of 38 consecutive patients treated for HF with reduced ejection fraction hospitalized at the University Hospital Center Zagreb, Department of Cardiovascular Diseases, between October 2016 and March 2017., both before and 3 months after the introduction of sacubitril/valsartan therapy (**Figure 1**). Prior to the introduction of sacubitril/valsartan, all examined patients have been on therapy with ACE inhibitors/ARBs at least three months. LVEF, NT-proBNP and creatinine were analyzed with the Wilcoxon signed rank test to check for statistical significance before and 3 months after the introduction of sacubitril/valsartan. FIGURE 1. Inclusion/exclusion criteria. **Results**: Before the initiation of sacubitril/valsartan, these patients had a mean LVEF of 24%. After three months of therapy with sacubitril/valsartan, they had an increase of their average LVEF by 20% to 29%, which has been shown to be statistically significant with P=0.019. Also, accompanying this change, in the same group of patients we observed a decrease in the average NT-proBNP by 47% (before sacubitril/valsartan therapy mean value 3335 pg/ml to 1593 pg/ml after three months of therapy) which is a statistically significant decrease with P=0.031. We found no significant changes in NYHA category nor in the creatinine values (**Table 1**). ### TABLE 1: Left ventricular ejection fraction, NT-pro-BNP and creatinine values before introduction of sacubitril/valsartan and 3 months after. | Baseline | Baseline | Baseline | Baseline | 3 months follow-up | 3 months follow-up | 3 months follow-up | 3 months follow-up | | --- | --- | --- | --- | --- | --- | --- | --- | | | **Min.** | Max. | Mean | Min. | Max. | Mean | P-value | | **Left ventricular ejection fraction (%)** | **10** | 35 | 24 (± 6.5) | 20 | 42 | 29 (± 5.6) | 0.019* | | **NT-proBNP (pg/ml)** | **326.3** | 14491 | 4143 (± 4418) | 214 | 6785 | 1926 (± 1815) | 0.031* | | **Creatinine (umol/ml)** | **58** | 245 | 114.2 (± 40) | 74 | 197 | 123,3 (± 35.8) | 0.126 | **Conclusion**: In our patients with CHF after the introduction of sacubitril/valsartan instead of ACI/ARB there was a significant increase in LVEF and a drop of NT-proBNP in the period of 3 months after the introduction of sacubitril/valsartan.

Zvonimir Ostojić, Zoran Miovski, Marija Brestovac, Joško Bulum

**Introduction**: Contrast induced nephropathy (CIN) following invasive cardiovascular interventions (ICI) is associated with increased mortality and morbidity (1). Although, it occurs more frequently in high risk patients with renal failure (RF) and diabetes mellitus (DM), incidence up to 10% has been described in patients without DM (2). Some research suggest that urgent contrast requiring procedures elevate CIN incidence in overall population. Aim of this study was to compare CIN incidence in non-DM patients after ICI depending on the urgency of procedure. **Patients and Methods**: We retrospectively observed all patients undergoing ICI requiring contrast in 2015. From 2756 patients, we included 323 non-diabetic patients who had serum creatinine level (SCL) measured before ICI and at least one time between 24 and 72 hours following ICI. CIN was defined using grading system in two stages; 1. SCL increase ≥25% and 44 µmol/L above baseline. Patients were stratified accordingly in 3 groups no-CIN, CIN-1 and CIN-2. Complexity of ICI was assessed using total procedure duration (PD), fluoroscopy time (FT) and contrast volume (CV). **Results**: From total 323 patient (age 63.8±15.3) 101 (31.3%) were female. Compared with men they were significantly older (69.1±16.7 vs 61.5±19.9, p0.6). Interestingly, elective patients had lower baseline eGFR (70.6±25.9 vs. 78.6±24.6, p=0.006). There was no significant difference in other previously mentioned observed parameters. After comparison of all data between groups, we found significant difference only in gender, with women having higher rate of CIN in all groups (p<0.05). Also, between no-CIN and CIN-1 vs to CIN-2 group we observed lower baseline eGFR in CIN-2 (p<0.05). The same diversity was observed within each gender. **Conclusion**: Results of our study suggest high overall CIN incidence of 17%, with no difference considering urgency of procedure. All these results must be taken with caution due to potential selection bias in elective group. In our opinion, results here described, represent smaller, more morbid percentage of total elective patients (only 6.62% of totally screened elective patients were included). This might happened because elective ICI are usually one day procedures. Also, observation that CIN is commoner in female gender is probably influenced by confounding factor; older age and worse renal function in women. Just as previously described, our results suggest that low eGFR is important risk factor for CIN development, just as lower eGFR in connected with more sever stage of CIN.

Kristina Gašparović, Dora Fabijanović, Daniel Lovrić, Maja Čikeš, Boško Skorić, Hrvoje Jurin, Jana Ljubas, Maček, Jure Samardžić, Nina Jakuš, Davor Miličić

**Introduction**: Advanced heart failure is a devastating condition with mortality resembling those of the malignancies with the highest mortality. Nowadays, there is a growing employment of a left ventricular assist devices in the management of this lethal condition. (1, 2) We present a case of a patient with device malfunction (power spike, high flow alarms) successfully treated with early thrombolysis which led to fast recovery of the device function. **Case report**: 55-year old man with a history of ischemic cardiomyopathy presented with advanced heart failure in June 2016. He was diagnosed with biventricular cardiomyopathy with irreversible PVR, so we decided to implant a left ventricular assist device as a destination therapy. Our patient received a HeartWare System, Framingham, MA, USA, LVAD in July 2016. In January 2017, he presented to our Department with high flow alarms and Power spikes. At presentation, he was hemodynamically stable. Device settings had a pump flow rate of 9 liters/min and the power consummation was 4.0 watts at pumps speed of 2200 rpm. Turning the pump speed to 2400 and 2600 rpm made power consumption turn to 4.5 watts and flow rate to more than 10 liters/min suggesting the inability of the device to unload the left ventricle. Patient was, at the moment, asymptomatic but had laboratory signs of hemolysis suggesting thrombosis. File log analysis was indicative of thrombus formation, so our Heart Team decided to start thrombolytic therapy. The first step was to decrease INR below 2. We used fresh frozen plasma (250 ml) to reduce INR for 0.5 points. The next step was to use 10 mg of alteplase as a single shot. We repeated the same dose after 10 minutes because no changes in pump indices were noted. Then we continued infusion with a rate of 0.1 mg/kgBW/h for 5 hours to a total dose of 50 mg of alteplase. The result was normalization of all of the pump indices within this period. The pump hemodynamics showed a stable pump flow rate of 3.4 l/min with the power of 2.5 Watts. **Conclusion**: Left ventricular assist device thrombosis is a devastating condition that urges for immediate response. Despite having a risk of hemorrhagic complications, parenteral thrombolytic therapy can be used as a treatment with fast response and good results in clinically stable patients presenting with early stage of thrombus formation.

Ivana Lukić Milinković, Silvija Canecki-Varžić, Ivana Prpić-Križevac, Luka Švitek

**Introduction**: Myocites produce brain natriuretic peptide (BNP) or N-terminal pro-brain natriuretic peptide (NT-proBNP) in response to cardiac wall stretching. It is clinically used as a diagnostic and prognostic biomarker for heart failure. Since the mentioned peptide and its fragments, as well as their respective receptors, are located in the entire central nervous system, it seems that they could be involved in the regulation of the hypothalamic-pituitary-adrenocortical (HPA) axis. (1) **Case report**: We present the case of 21-year-old patient with clinical picture of severe adrenocortical insufficiency and hypogonadism. So, hydrocortisone replacement therapy was immediately introduced. Due to the suspicious ECG findings, cardiac testing was performed. The ECG changes were perceived as changes within the juvenile ECG findings. Initial value of NT-proBNP was elevated (4252 pg/ml). In the cardiac ultrasound, a discrete anterior mitral valve leaflet prolapse was found with trace mitral regurgitation and an EF of 76%. Since introduction of hydrocortisone replacement therapy, NT-proBNP values were being controlled repeatedly and they were gradually reduced (1534-706-338 pg/ml) within two week. With regard to the presence of hypogonadism, a testosterone replacement therapy was introduced two weeks later. After 3 weeks of combined replacement therapy the levels of NT-proBNP were completely normalized (40 pg/ml), and a general improvement of the patient’s state was observed. Amir et al. (2) showed in a group of male students that, in response to academic stress, the increase in plasma cortisol concentration is associated with the lowering of NT-proBNP levels. This data may indicate that mental stress implies an interaction between the HPA axis and the peripheral natriuretic peptide system, leading to reciprocal changes in the circulating levels of the corresponding hormones. Also, Chang et al. (3) is hypothesized that androgens suppress the secretion of the natriuretic peptide. The circulating levels of NT-proBNP are higher in women than in men. A study with young women without cardiac disease has shown, that free testosterone is independently inversely proportional to the levels of BNP or NT-proBNP. **Conclusion:** Secretion of NT-proBNP is not only influenced by cardiac function, but also by activation of neurohormonal function and vice versa.

Teodora Zaninović Jurjević, Štefica Dvornik, Nikolina Jurjević, Andrica Lekić, Luka Zaputović

**Introduction**: Recent studies have investigated the existence of so-called “obesity paradox” in heart failure (HF) patients, suggesting that obese patients might have a better prognosis than underweight and normal weight patients. (1) It seems that body mass index (BMI) may be an independent prognostic factor in patients with acute and chronic HF. **Patients and Methods**: We investigated the correlation between BMI, in-hospital survival and routine clinical and laboratory parameters in patients hospitalized for acutely decompensated HF. **Results**: Total number of 145 patients (mean age 76±10.2 years) were divided in three groups: 37 with normal body weight (20-24.9 kg/m2), 64 overweight (25-29.9 kg/m2), and 44 obese patients (≥30 kg/m2) patients. At the end of approximately 9 days of hospitalization, 24 of all patients died (16.5%). In-hospital mortality was significantly lower in obese patients (7%; p=0.05). Patients with normal body weight were older than obese patients: 80 (75-87) compared to 72 (65-80); p=0.001 and significant negative correlation between BMI and patients age existed (r=-0.383; p<0.001). There was no significant difference in left ventricular ejection fraction between three compared groups of patients. Obese patients had significantly lower NT-proBNP (pmol/l): 319 (182-758) compared to overweight 862 (342-3013) and compared to normal body weight 1209 (616-2378); p=0.001, hs-cTnT (ng/l): 23 (15-57) compared to overweight 38 (27-70) and compared to normal body weight 44 (29-60); p=0.009 and serum urea (mmol/l) concentration: 8.1 (6.2-12.3) compared to overweight 9.7 (6.6-12.3) and compared do normal body weight 11.3 (8.2-14.7); p=0.039. No significant difference in serum creatinine, uric acid and hemoglobin existed, but significant negative correlation between BMI and NT-proBNP was found (r=-0.22; p=0.013). **Conclusions**: In-hospital mortality was significantly lower in obese HF patients. Obese patients had significantly lower NT-proBNP, hs-cTnT and serum urea concentrations. There was significant negative correlation between BMI and NT-proBNP.

Bruno Lovreković, Mario Stipinović, Tomislav Letilović, Darko Počanić, Njetočka Gredelj Šimec, Helena Jerkić

**Objectives**: Port catheters are central venous catheters used as therapeutic devices in oncological patients. They are used for the administration of chemotherapeutic agents, antibiotics infusion, transfusion of blood products or parenteral nutrition (1). Their insertion and their use may be associated with serious complications. Port catheters insertion is usually performed by an oncologist, a radiologists or a surgeon (1). In our institution a cardiologist implants those devices. The purpose of this study is to determine early complications of port catheter insertion by cardiologists. **Patients and Methods**: Data from 76 patients with hematological malignancies, who had received a venous port catheter in University Hospital Merkur between October 2013 and May 2017, were collected and analyzed. The port catheter insertion procedure was performed by two cardiologists and all procedures were done through right subclavian venous access under fluoroscopy guidance. **Results**: Of the 76 patients, 42 (55.2%) were females and 34 (44.7%) males. Mean age was 51 years (range 21-65 years). Total catheter stay time was 897 months and mean time of catheter use was 402 days. A total of 76 port insertion were successful. Pneumothorax was observed in 4 patients (5.2%). Malposition (catheter tip in the left subclavian vein or internal jugular vein) was observed in 3 (3.9%) patients. Pocket hematoma was observed in 3 (3.9%) patients. None of these early complications required catheter extraction. Severe arrhythmia, cardiac perforation, thrombosis, hemothorax, catheter dysfunction, pocket infection were not observed in our study. **Conclusion**: The implantation of port catheters is a valuable method for long term treatment hematological malignancies. The rate of early complications in our study is comparable to the published data (1). So, venous port catheters placement can be performed safely by cardiologists.

Dario Dilber, Đivo Ljubičić, Mario Slatki, Jasna Čerkez Habek

**Introduction**: Chronic obstructive pulmonary disease (COPD), peripheral arterial disease (PAD) and ischemic heart disease are considered to be a smoking-related triad. PAD is a progressive, atherosclerotic process that indicates an increased risk for ischemic heart disease and can be assessed in clinical practice by calculating ankle-brachial index (ABI). COPD has been recognized as a systemic disease, and is associated with a markedly increased risk of cardiovascular disease independent of classical risk factors. (1, 2) Our goal was to examine the relationship between COPD and PAD using a prospective study. **Patients and Methods**: Total of 171 patients were included in this study, of which 75 were healthy non-smokers, 55 control smokers and 41 COPD subjects with smoking history. We measured ankle-brachial index (ABI) as a marker of atherosclerosis of the legs with a cutoff value of less than 0.9, pulmonary function with spirometry, calculated SCORE Risk chart and smoking pack-years. Spearman’s rank test was used to examine correlations between the variables. The differences in continuous variables were evaluated using two sampled Student’s t test. P-values < 0.05 were considered statistically significant. **Results**: ABI was significantly lower in the COPD patients than in the healthy control smokers (t=2.89, p < 0.01). The prevalence of ABI < 0.9 was significantly higher in the COPD group than in the control group (26.4% vs 12.8%). Smoking status and pack-year histories, age, sex distribution and total cholesterol levels were similar between the two groups. ABI correlated significantly with age (r = −0.23, p = 0.05), total cholesterol levels (r = 0.54, p = 0.05), systolic blood pressure (r=0.44, p=0.01) and smoking pack-years (r = −0.24, p = 0.05). **Conclusion**: The risk of leg atherosclerosis in COPD patients in our study was higher than in smokers without COPD. In this study we showed that the prevalence of undiagnosed PAD was high in COPD patients, a rate higher than that of matched healthy control smokers. Our study may indicate that COPD as a chronic inflammatory state promotes atherosclerosis and holds a greater risk for ischemic heart disease, ischemic stroke and death independent of classical risk factors. This study showed that attention should be paid to the risk of cardiovascular diseases in COPD patients.

Ivo Planinc, Dora Fabijanović, Jana Ljubas, Maček, Boško Skorić, Hrvoje Jurin, Jure Samardžić, Nina Jakuš, Hrvoje Gašparović, Maja Čikeš, Davor Miličić

**Introduction**: Age is one of the important factors when considering a patient for heart transplantation. Over the last decades there was a clear upper age limit when heart transplantation was not recommended due to shortage of donors and worse expected survival. However, more recently it has been increasingly shown that both ends of the age spectrum have different mortality rates, as well as incidence of specific post-transplantation complications. (1, 2) The aim of this study was to evaluate outcomes and complications of different age groups of heart transplant recipients from our Centre. **Patients and Methods**: We retrospectively collected data from 170 consecutive heart transplant recipients from our Centre in the period from January 2008. To August 2017. (median age 56 years, age distribution 15-70 years, 133 males, median follow-up 26 months, follow-up distribution 0-113 months). The patients were grouped by quartiles of age: 15-46 years (q1), 47-56 years (q2), 57-62 years (q3), 63-70 years (q4). The primary outcome of the study was overall survival; secondary outcomes were cellular and antibody-mediated rejection requiring treatment, graft vasculopathy, and infections. Pearsons χ2 test was used for group comparison, while for overall survival Kaplan-Meier curves were calculated. **Results**: As shown on **Figure 1** a significant difference in the primary outcome was found among the age groups, with the worst survival in the highest age quartile (p=0.01). Significant differences in the occurrence of several secondary outcomes were found as well: rejection episodes were more frequent in the lowest age quartile (p=0.01), while the occurrence of both fatal and non-fatal infections (p=0.04, and p<0.01), as well as the occurrence of neoplasms was higher in highest age quartile (p=0.04). Figure 1. Overall survival among quartiles of age presented as Kaplan-Meier curves. **Conclusion**: Our retrospective study confirms significant differences in outcomes and post-transplantation complications among patients of different age groups, warranting a more individualized treatment approach according to recipient age.

Karlo Golubić, Petra Angebrandt, Irena Ivanac Vranešić, Viktorija Ana Buljević, Josip Kuharić, Ivana Jonjić, Ivana Ježić, Nikola Bulj, Diana Delić-Brkljačić, Anton Šmalcelj, Martina Lovrić, Benčić

**Introduction**: The effectiveness and safety of treatment with warfarin are critically dependent on maintaining the international normalized ratio (INR) in the therapeutic range. Besides the dose of warfarin, many factors which interact with the metabolism of warfarin may influence the stability of treatment and the time in which patients’ INRs are in the therapeutic range. (1, 2) Aim: To establish whether there is a significant seasonal variation in effectiveness of warfarin therapy in adults with atrial fibrillation in a Croatian population. **Patients and Methods**: We conducted an observational study of a subgroup of patients enrolled in the AMACADo - Atrial fibrillation associated thromboembolic risk MAnagement in CroatiA national Database project, involving 2326 electronic medical records of patients with AF hospitalized in UHC Zagreb from 2010 until 2015. Out of 2326 patients we selected 1110 that were treated with warfarin as permanent anticoagulant therapy, prior to hospitalization, and the rest of patients we excluded from the research. Patient were divided in two categories based on INR values higher than 2.0 (INR > 2.0) and less or equal than 2.0 (INR ≤ 2.0). Furthermore, we analyzed seasonal variation in the INR value during four seasons: spring, summer, autumn and winter. The χ2 test was used for comparison of categorical variables. **Results**: Out of 239 patients admitted to hospital during summer 111 had an INR value > 2.0, (46.4%) in comparison with patients admitted during all other seasons (spring, autumn and winter) (324/871, 37.2%). Our results show that a larger proportion of patients was effectively anticoagulated during summer vs. other seasons (p=0.00950174, CI 95%). **Conclusion**: A seasonal variation in the INR values was observed among adults with atrial fibrillation, possibly due to many different factors such as variations in diet, hydration status and physical activity, and possibly therapy guidance. Seasonal variations in the intensity of warfarin therapy should always be considered in trials exploring thromboembolic complications of atrial fibrillation. The causes of this variations should be further investigated.

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

**Introduction**: Chronic heart failure (HF) has become one of the most prominent health issues of today and despite advances in treatment, HF mortality rates remain high. Echocardiography plays a crucial role in the diagnosis and management of HF patients. (1) The aim of this study was to reevaluate the role of „classic” echocardiographic parameters in predicting the mortality of patients with HF across various cardiomyopathies. **Patients and Methods**: We retrospectively analyzed data from 200 patients (71% male, 47.8±11.7y) with mild to moderate chronic HF (NYHA II and IIIa) treated at our Department from December 2010 until December 2014. All patients underwent a standardized echocardiographic examination. Left ventricular systolic/diastolic (LVIDs, LVIDd) and left atrial (LA) dimensions were determined using M-mode analysis in the long-axis parasternal view. Left ventricular ejection fraction (LVEF) was calculated using both 2D measurements and Simpson Biplane method. Right ventricular function was evaluated using tricuspid annular plane systolic excursion (TAPSE). The last patient follow-up was performed via telephone interview, with a mean follow-up period of 44.9±16.5 months. The primary outcome of the study was overall survival. **Results**: Most of our patients presented with HF due to ischemic and dilated cardiomyopathy (26.5% and 25% respectively). Overall patient survival was 92.5%. LVIDd, LVEF, LA and TAPSE differed significantly among the survival groups (**Table 1**). When comparing survival curves, LVEF lower than 35%, LA smaller than 4.6 cm and TAPSE lower than 16 mm were all found to be predictive of adverse outcome (**Figures 1**, **2**, and **3**Figure 2Figure 3). Regression analysis revealed LVIDd and LA to be the best predictors of mortality in our patient population (Exp(B)=1.8, P=0.038 and Exp(B)=2.0, P=0.037 respectively). ### TABLE 1: Comparison of echocardiographic parameters according to survival groups. | ECHO parameter | Patients without primary outcome | Patients with primary outcome | P-value | | --- | --- | --- | --- | | **LVIDd (cm)** | 6.6±1.1 | 7.3±0.6 | 0.022* | | **LVIDs (cm)** | 5.5±1.6 | 5.5±2.1 | 0.514 | | **LVEF (%)** | 32.3±14.8 | 23.9±8.8 | 0.033* | | **LA (cm)** | 4.6±1.0 | 5.2±0.7 | 0.032* | | **E/e’** | 19.1±13.0 | 16.0±5.8 | 0.970 | | **TAPSE (mm)** | 16.5±4.6 | 12.8±2.9 | 0.008* | [†] LVIDd = left ventricular internal diameter end-diastole, LVIDs = left ventricular internal diameter end-systole, LVEF = left ventricular ejection fraction, LA = left atrial diameter, EoEp = E over E prime, TAPSE = tricuspid annular plane systolic excursion. FIGURE 1. Survival curves according to left ventricular ejection fraction (LVEF). FIGURE 2. Survival curves according to left atrial diameter (LA). FIGURE 3. Survival curves according to tricuspid annular plane systolic excursion (TAPSE). **Conclusion**: Although sometimes considered obsolete in the modern era, „classical“, easily obtainable echocardiographic parameters of cardiac structure and function are still reliable predictors of patient mortality in chronic HF. As expected, enlarged LA and LV, as well as reduced systolic function of both ventricles were all associated with adverse outcome.

Jana Ljubas, Maček, Boško Skorić, Marijan Pašalić, Hrvoje Gašparović, Daniel Lovrić, Maja Čikeš, Jure Samardžić, Hrvoje Jurin, Ana Reschner, Davor Miličić

**Introduction**: To test the effect of pretransplant pulmonary vascular resistance (PVR) on posttransplant right ventricle (RV) size and function as well as to address the possible causes, except cardiotomy (1), affecting the RV function and its recovery trend after heart transplantation (2) (HTx). Also to compare invasive and echocardiographic RV function measurements and their impact on survival. **Patients and Methods**: PreHTx right heart catheterization (RHC) as well as postHTx ECG, echo and RHC were performed in 84 adult heart transplant pts. RV longitudinal function was assessed by tricuspid annular plane systolic excursion (TAPSE). Data on PVR, transpulmonary gradient (TPG), RV stroke work index (RVSWI) as well as graft ischemic time (GIT), extracorporeal circulation time (ECCT) and time on mechanical ventilation were collected. **Results**: The development of RBBB after HTx was not related with longer GIT or ECCT, and had no effect on posttransplant RV dilatation or function and survival. RV was dilated in 36% of pts in the 1st month after HTx with mean TAPSE 12±4 mm, which increased to 16±4 mm during the 2nd month. 63% of pts had reduced initial TAPSE with further recovery in only 44% (**Figure 1**). Longer GIT, ECCT and duration of mechanical ventilation had no influence on TAPSE or on the development of acute RV failure. Postransplant RV function assessed both by TAPSE or RVSWI had no influence on survival. RVSWI was significantly reduced in early postHTx period (5 gm-m/m2) but did not correlate with TAPSE. Pts with normal pretransplant PVR and TPG had similar posttransplant TAPSE and RVSWI in comparison to pts with reversibly increased PVR and TPG. PVR decreased for 43% after HTx (mean 203±102 to 116±45 dynes-sec-cm-5; p<0.001). Systolic pulmonary arterial pressure assessed by echo was mildly to moderately elevated in early postHTx period (39±11 mmHg) with trend to normalization within the first 6 months after HTx (**Figure 2**). FIGURE 1. Tricuspid annular plane systolic excursion - TAPSE (in millimeters) in follow-up after heart transplantation. The most pronounced recovery is present during the second month after heart transplantation. FIGURE 2. Systolic pulmonary artery pressure trend (by echocardiography) after heart transplantation. Significant decrease occurs during the first six months, with rise during the long-term follow-up. **Conclusion**: Posttransplant loss of the RV longitudinal systolic function was present in 60% of pts and recovered in almost half of them, but with no effect on patients’ survival. Higher and reversibly elevated pretransplant PVR and TPG did not add to the more pronounced decrease in RV longitudinal function posttransplant. Interestingly, post-transplant RVSWI as an invasive measure of RV function did not correlate with TAPSE.

Siniša Roginić, Krešimir Štambuk, Stanko Belina

**Introduction**: Aortic dissection is a devastating disruption of vessel wall caused in most cases by uncontrolled hypertension or intrinsic vessel weakness. Only minority of patients have typical clinical presentation. High clinical suspicion leads to diagnosis confirmation by CT (computed tomography) and/or transesophageal echocardiography (TEE). Although TTE in not the method of choice it can surprisingly diagnose dissection and acute complications in patients referred for other reasons like in presented cases. (1-3) **Case reports**: 71-year old lady treated for hypertension presented with neck pain, near fainting and transitory visual loss. Diagnosis of TIA (transient ischemic attack) was established and workup included TTE showing an aneurism of thoracic and abdominal aorta with dissection flap (**Figure 1**). Dissection caused moderate aortic regurgitation and propagated into brachiocephalic trunk causing neurologic symptoms. CT and TEE confirmed the diagnosis –Stanford A, DeBakey A type dissection (**Figure 2**). Aortic regurgitation subsided after aneurism repair so there was no need for aortic valve surgery. Postoperative recovery was prolonged by Dressler’s syndrome. FIGURE 1. Circular dissection of the aortic root (A) and ascending portion (B). FIGURE 2. 3D transesophageal echocardiography image of dissection flap rising above the right sinus of Valsalva. Second patient was 81-year old female with hypertension and diabetes admitted to Department of Neurology ward due to syncope. Troponin values were mildly elevated and TTE was indicated. Investigation found inferoposterior wall hypokinesia (patient has had an infarction five years ago) and preserved systolic function. There was a free floating calcified mass in ascending aorta. CT confirmed dissection of thoracic aorta starting above aortic valve and reaching origin of the left subclavian artery (Stanford A, DeBakey B). Aorta was tortuous and heavily calcified therefore dissection likely started as penetrated atherosclerotic ulcer. Patient was successfully operated with uneventful postoperative recovery. **Conclusion:** Both our patients were diagnosed aortic dissection with TTE conducted for other reasons. Aortic dissection is often a lethal disease, largely due to diverse clinical presentation and delayed diagnosis. TTE is a convenient and widely available tool which can make diagnosis and hasten further management. Detailed examination of all visible aortic segments using standard and atypical views is mandatory in every patient. Sometimes accidentally, unexpected findings make big difference like in these two cases.

Nina Jakuš, Ivo Planinc, Dora Fabijanović, Boško Skorić, Daniel Lovrić, Hrvoje Jurin, Jure Samardžić, Jana Ljubas, Maček, Hrvoje Gašparović, Bojan Biočina, Davor Miličić, Maja Čikeš

**Introduction**: Despite being a mainstay of modern advanced heart failure (AHF) therapy, more knowledge is to be gained on the effect of left ventricular assist device (LVAD) treatment on end organs, especially the possible differences between pulsatile and continuous blood flow. (1, 2) We have observed a clinically significant increase in diuresis in our HeartMate3 patient (pt) population, despite minimization/withdrawal of diuretic therapy, and have aimed to examine potential differences in postimplantation renal function (RF) and diuresis between patients treated with Heart MateII (HMII, axial) and Heart Mate3 (HM3, centrifugal) devices. **Patients and Methods**: 35 pts were implanted with a HeartMate LVAD during a 4-year period at our centre (2 pts who have expired in the first postoperative month and 8 with lacking data were excluded from further analysis) - 15 pts received HMII (15 men, mean age 62.73±4.15) and 10 pts received HM3 (8 men, mean age 55.8±10.69, p value for age=0.03). Most of the pts received the device for the treatment of AHF due to ischemic cardiomyopathy (60%), dilated cardiomyopathy (36%) and LVNC (4%) (etiology was similarly distributed between the groups). During the 2nd, 3rd and 4th postimplantation week, daily diuresis was measured, as well as fluid intake, diuretic therapy and estimated glomerular filtration rate (eGFR). **Results**: RF was preserved, even in the early postoperative period (1st postoperative month), in both pt populations (**Figure 1A**). Only one pt required intermittent hemodialysis during this period. There was no significant difference in fluid intake or diuretic therapy between the two groups. Despite having similar values of eGFR (centrifugal: 90.67±10.21 mL/min/SA, axial: 85.67±3.51 mL/min/SA, ns), we observed that the pt population receiving HM3 had greater absolute values of diuresis in the 3rd and 4th week compared to those receiving HMII, although not reaching statistical significance (**Figure 1B**). FIGURE 1A. Renal function expressed as estimated glomerular filtration rate (eGFR) was similar between the two groups during the follow up period. FIGURE 1B. Absolute values of diuresis differed between the two groups, especially in week 4, although not statistically significant. **Conclusion**: We have objectified an increase in postimplantation diuresis in our cohort of pts treated with continuous vs. axial HM LVADs, however without reaching statistically significant difference in these measurements, while having equally preserved RF. A study in a larger pt population is warranted to obtain better insight to this observation in the early postimplantation period.