Cardiologia Croatica. 2018;13(1-2)

Sonja Frančula-Zaninović

The prevalence of arterial hypertension (AH) is still high. Hypertension is the most important changeable cardiovascular (CV) risk factor and is significantly associated with high morbidity and mortality from cardiovascular and cerebrovascular (CBV) diseases. AH thus represents a significant healthcare problem. It is multifactorial, and the treatment approach is based on combination treatment. Combination treatment consist of two or more antihypertensives of different groups with different mechanisms, which results in faster achievement of target blood pressure (BP) values. According to the guidelines for the treatment of arterial hypertension published by the European Society of Hypertension (ESH) and the European Society of Cardiology (ESC), it is recommended to introduce the combination therapy already in the first stage of the disease as the first line of treatment in case of high CV risk and comorbidity or in case of failed treatment with a single medication. Unfortunately, prescribing multiple tablets to be taken during the day reduces treatment adherence. The goal of modern AH treatment is to use fixed-dose combinations of antihypertensives with complementary and synergistic effects in order to achieve the most effective treatment. Management of BP is significantly improved even at smaller doses of the active components in the combination, which also reduces the incidence of side-effects. Receiving a treatment which is effective, does not burden the patient, and is taken once per day significantly increases patient adherence. The ultimate goal of such successful treatment of AH is the reduction of CV and CBV morbidity and mortality. According to the ESH/ESC guidelines for the treatment of hypertension, the optimal combination is that of three groups of antihypertensives: renin-angiotensin-aldosterone system inhibitors, calcium channel antagonists, and diuretics.

Tomislav Šipić

In the recent years, the cardiovascular patient became the focus of cardiovascular experts. Because the vessels in our body are made of the same material, the vascular problem could emerge from head to toe, so it is logical that, in the best interest of patient, the decision how to optimally treat the cardiovascular patient is often made by the team of experts - interventional cardiologists, vascular surgeons, interventional radiologists, anesthesiologists and sometimes many others expert. Some patients require combination of interventional and surgical treatment. According to this, there is a lot of overlapping between the professions. It is obvious that one new profession is emerging - endovascular medicine. (1) In last 7 years, in our institution, our peripheral vascular team (2 interventional cardiologists and vascular surgeon), performed more than 330 peripheral interventions (on femoral, iliac and subclavian arteries) and more then 50 endovascular aneurysm repair and thoracic endovascular aneurysm repair procedures. In this presentation we will show our work and results during the recent period and some thoughts considering the development of endovascular medicine.

Romana Palić, Daniela Šmalcelj, Irena Ošlaj, Marija Matoš, Joško Bulum, Maja Strozzi, Ivica Šafradin

**Introduction**: In the beginning, Thoracic Endovascular Aortic Repair (TEVAR) procedure with the insertion of an endovascular stent-graft in the aorta was used for the repair of degenerative aneurysms of the descending aorta, but afterwards the indications for the procedure include the whole spectrum of descending aorta pathology, and traumatic rupture. (1-3) **Case report**: 28-years-old male driver of a family car, who was injured in a car crash, was brought into the surgical emergency department by first aid medical team. The patient was conscious, in a stable circulatory and respiratory condition and immobilized. Diagnostic procedures including a CT scan revealed the following diagnoses: the rupture of the aortic arch descending part, the right occipital condyle fracture, the fracture of the atlas vertebra, multiple rib fractures on the both sides, right-sided lung contusion with a small pneumothorax and contusion of the right adrenal gland. The consultant interventional cardiologist decided to perform a percutaneous closure of a tear in the aortic wall which was life threatening injury with impeding exsanguination. An emergency interventional team was summoned and in the Cath lab of our clinic a TEVAR graft measuring 28/28X157 cm was successfully implanted. During the procedure the patient was intubated and sedated. After the procedure, the patient was transferred to intensive care unit in clinically stable condition.

Mario Sičaja

In the light of recent publications regarding patent foramen ovale (PFO) closure in patients with cryptogenic stroke, specifically regarding the results of trials CLOSE, REDUCE and RESPECT, there is an increasing need for optimal treatment of these patients. (1, 2) The aim of this presentation is to propose a multidisciplinary program regarding the diagnosis, treatment, and follow-up of patients with PFO-mediated stroke based on a Heart-Brain team decision making. It is our aim to analyze necessary steps in everyday clinical practice, describe procedure work-flow together with tips-and-tricks regarding the procedure, and to review the activities during the first year of implementation in our practice. In conclusion, the first year of implementation of the above described program allowed us a quick implementation of published trial results in every day clinical practice together with high level of confidence, a short learning curve for a dedicated interventional cardiologist and with a superior patient safety. Furthermore, it allowed us to indicate the potential flaws in the protocol and practice, especially regarding reimbursement for healthcare insurance.

Biljana Šego, Kristijana Radić, Zoran Marić

Patent foramen ovale (PFO) is a defect of interatrial septum, mostly without any clinical repercussions. Its incidence is 25%, and it is associated with cryptogenic stroke, migraine, platypnea-orthodeoxia syndrome and decompression illness. (1-3) One of therapeutic strategies for secondary prevention of such incidents is percutaneous closure of defects. The closure procedure requires teamwork of invasive cardiologist, echocardiographer, anesthesiologist and operating room nurse. Transcatheter closure of PFO is a safe procedure with long term efficacy in preventing paradoxical embolism. Procedure itself requires nurse interventions, which include patient preparation and its monitoring until the placement of the occluder. Procedure protocol is closely followed from the start until the discharge of the patient. All patients receive antibiotic prophylaxis 1 h prior to the procedure and before discharge from the hospital a post-interventional transthoracic echocardiography is performed. Here we report a case of a patient with prior ischemic stroke, who was diagnosed with PFO, and therefore underwent a successful PFO occluder placement. In conclusion, the success of the procedure, with the goal of complete occlusion without any residual shunt, is dependent both on anatomy of the atrial septum and on cooperation within the interventional team.

Marina Pavletić, Željka Roginić, Patricia Kakarigi

Alcohol in the heart can indeed be a cure. Percutaneous transluminal septal myocardial ablation or alcohol septal ablation (ASA) is one of the methods of treating hypertrophic cardiomyopathy. Hypertrophic cardiomyopathy is the most common genetic transmissible heart disease. Since 1994, alcohol septal ablation (ASA) has been used as a minimally invasive treatment of patients with hypertrophic obstructive cardiomyopathy, resistant to conservative medical therapy. This catheter-based intervention is performed by injecting alcohol into the septal branch to induce an infarction of the hypertrophied septum and thus reduce the obstruction of the left ventricle. This gradient reduction is associated with decreased symptoms and left ventricular remodeling. While surgical myomectomy was a gold standard by the end of the 1990s, alcohol septal ablation (ASA) has achieved rapid popularity and acceptance, especially in Europe. (1) This review presents the process of preparation, performing the procedure and describing postprocedural care and potential procedural complications. If done in an experienced institution, ASA has a high rate of success and a low rate of complications. The procedure provides relief of symptoms and gives a similar longevity to patients as in the general population.

Marina Pavletić, Siniša Blažon, Ivana Barun

Ballon aortic valvuloplasty (BAV) was introduced more than three decades as an alternative to replacement of aortic valve in older patients who are considered unsuitable for surgery. (1) Because of the high rate of early restenosis and without affecting long-term survival, the development of the procedure has stopped. However, with recent technological advances, especially with the appearance of a TAVI, there was a revival of this technique. Balloon aortic valvuloplasty is a percutaneous therapeutic option for patients with severe aortic stenosis but the effectiveness of this procedure depends on the morphology of the stenotic aortic valve and the respective dilation mechanism. In younger patients with congenital aortic stenosis, there are good acute and mid-term results. In this paper, we describe and present the preoperative course, the performance of balloon aortic valvuloplasty and postprocedural process. BAV allows patients with severe aortic stenosis to safely survive to surgery, to TAVI or to relieve symptoms by conservative therapy.

Morena Kvaternik, Pavica Stanišić, Ružica Višnjovski

Paravalvular leak after artificial valve implantation is rare but serious complication. The patients are usually older, with a lot of comorbidities and surgical approach is connected with large perioperative risk and possible failure. Percutanous closure is minimally invasive method and very efficient. As the number of patients with implanted valves is growing, there will be increased need for these interventions. (1, 2) We are presenting a case of percutaneous closure of aortic paravalvular leak in a younger female patient, using Occlutech’s nitinol mesh occluder (PLD Occluder 63PLD07T).

Krešimir Gabaldo, Božo Vujeva, Ivica Dunđer, Katica Cvitkušić Lukenda, Marijana Knežević Praveček, Irzal Hadžibegović, Martina Menegoni, Domagoj Mišković, Ana Marija Palenkić, Đeiti Prvulović

The acute coronary syndrome (ACS) network is a complex system of concern for patients with acute coronary syndrome. In order to provide adequate patient care, reduce total mortality and irrational costs of treatment, we need varied algorithms and a patient concern protocols. Outhospital emergency medical services, intrahospital emergency rooms, and coronary care units in percutaneous coronary intervention (PCI) and nonPCI centers participate in the care of ACS patients. (1) Therefore, only algorithms adapted to each of these levels can improve the protocol for patient care. By standardized protocol implementation since January 2016, we compared the results with respect to the total number of patients before the protocol was applied. We analyzed the total number of patients, the relationship between the number of transferred and non-transferred patients, the intra-hospital mortality as well as the total mortality for ST-elevation myocardial infarction (STEMI) and non-ST elevation myocardial infarction patients (NSTEMI). The results show that the standardized protocol increases the total number of PCIs in patients with ACS, namely 36% for STEMI and 20% for NSTEMI. However, the total mortality of STEMI patients has increased from 5.2% to 6.9%, which is a consequence of an increased number of patients with cardiogenic shock (2.5% to 7.8%), as well as inappropriately high rates of transfer time from nonPCI hospitals (average time was 160min). In patients with NSTEMI we recorded an increase in the total number of patients by 20%, while total mortality rate has not been changed. However, we should point out a favorable trend in the increase of PCI within 72 hours in NSTEMI patients. The standardized protocol, along with other organizational improvements, has led to the primary goal of increasing the number of primary PCIs in STEMI and PCI at ACS-NSTEMI at an early stage. It has also revealed the need for additional effort to increase the quality of treatment in terms of reducing patient delay time, proper recognition of STEMI by the outhospital emergency services, as well as the need to reduce transport time for transferred patients. If a transfer within 120 minutes cannot be provided we recommend pharmacoinvasive approach to be applied.

Benjamin Koren, Jelena Mikulan

The right heart catheterization (RHC) enables measurement of pressure in the right ventricle, pulmonary artery and pulmonary capillaries. It is important to take blood samples for analysis and determine oxygen saturation, which allows us to determine the intracardial level. With the help of Fick principle, it is possible to calculate the heart rate index. The catheterization is performed by the puncture of femoral, subclavian, internal jugular or cervical veins. A balloon-tipped flotation catheter-originally designed by Swan and Ganz is the most commonly used balloon catheter. The balloon tip allows the catheter to float through the right side of the hearth safely and easily. The balloon “wedges” in the distal side of catheter helps to measure the pulmonary artery pressure. Right-sided heart catheterization is indicated for patients with a history of dyspnea, valvular heart disease, or intracardiac shunts. It is most commonly used for measuring right atrium, right ventricular, pulmonary artery and pulmonary capillary pressure. The right heart catheterization is also useful for assessing pulmonary vascular resistance, tricuspidal and pulmonary function, and right ventricular pressure. (1) The patient’s preparation for RHC is the same as preparation for other heart catheterizations. The nurse must know the RHC protocol and must take part in the catheterization performance. It must know the normal values and appearance of the pressure curves in the heart cavities and ECG. The nurse needs to have knowledge of hemodynamic patient monitoring system and record, mark and analyze the pressure values. The nurse takes care of proper blood sampling during catheterization and proper labeling and transport of samples to the laboratory. The nurse has the skill to recognize and observe artefacts and pathological changes in vital function monitoring and timely and properly respond to them. (2)

Kristina Pavlović, Katija Haklička

**Introduction**: Coronary intervention complications refer to ischemic complications and bleeding after intervention. Ischemic are related to a thrombosis in the stent, myocardial infarction in the artery area where the stent is placed and sudden cardiac deaths. Acute thrombosis in the stent is a very serious and fatal complication of percutaneous coronary intervention. It is relatively rare, up to 3% of patients are affected after the intervention on the coronary artery and occurs within 24 hours. (1) **Case report**: We present the case of a 78-year-old man treated in the Coronary Unit of the Dubrovnik General Hospital, who comes to emergency care in the clinical present of unstable angina pectoris, and during treatment develops an acute ST infarction. After admitting in the Coronary Unit, the patient is subjected to an emergency coronary angiography and we diagnosed atherothrombotic occlusion of proximal RCA. With the balloon propagation, the stent is placed over the entire length of the lesion and the control angiogram shows the optimal result. The patient is placed in the Coronary Unit, but within 12 hours the angina occurs with ST-segment elevation, and soon comes a cardiorespiratory arrest. After the patient’s intubation and stabilization, we approach to re-coronarography that shows the large thrombotic mass at the RCA and in the pre-set stent is made. PTCA is performed three times, using fibrinolysis and aspirated by aspiration catheter. In the further course of treatment, the condition of the patient is complicated by anemia, renal dysfunction and atrial fibrillation. The patient is released after three weeks in a stable state with recommendations. **Conclusion**: Acute thrombosis in the stent, a rare and dangerous complication of primary percutaneous intervention and requires rapid diagnosis and rapid revascularization of the coronary artery.

Maja Strozzi

**Introduction**: Percutaneous coronary intervention (PCI) is a best choice of treatment when a surgical graft fails (1). Left internal mammary artery (LIMA) graft sometimes needs intervention, mostly early and on anastomosis site. Historical data revealed balloon angioplasty as best method, but drug-eluting stent (DES) seems to be good solution in contemporary studies (2). **Case report**: We present a case of 70-years-old men with NSTEMI, 12 years after CABG. Echocardiography revealed ejection fraction of 40%. On coronary angiography, the left anterior descending (LAD) and the right coronary artery (RCA) and two saphenous vein graft (SVG) were occluded; LIMA was patent with a significant anastomosis stenosis. Significant stenosis of the left coronary artery (LCA) and the circumflex (Cx) coronary artery were found. A PCI with DES implantation in LCA/CX was done, with good result. Patient came back soon for angina. Result of previous procedure was unchanged, and LIMA/LAD lesion was recognized as culprit. Patient refused re-operation; a high-risk intervention was performed. Via femoral artery, the LIMA was passed to the distal LAD with a hydrophilic wire, balloon dilatation with several balloon sizes was done, with immediate recoil. A short DES could not passed the tortuotic vessel, so a second wire was attempted, and caused a dissection and occlusion of middle portion of LIMA. Angina, ST-segment elevation and hypotension followed. With repeated balloon dilatation, flow was established. In new attempt a second wire was introduced and two DES 3.0mm implanted. The result was optimal with TIMI 3 flow. On angiographic control 3 month later, a re-stenosis was present, with a non-expanded stent. In a re-intervention an improvement was achieved after 3.5mm HP balloon dilatation (up to 24 atm), with acceptable, but not perfect result. The patient is in follow-up for 2 years, without complains. **Discussion**: This case illustrates several problems of LIMA PCI: technical difficulties, high risk in case of complication, what in our case was fortunately resolved. It seems that LIMA react similar to stent as native coronary arteries (3). In our case the lesion was not completely dilatable, and stent not fully expanded, what can be explained with the fact the stenosis was on surgically crated anastomosis 12 years old. **Conclusion**: PCI of LIMA is rarely necessary, it is technically demanding, high risk, and with questionable long-term result. In our case, despite procedural complication and not optimal angiographic appearance a long-term clinical result was good.

Vanja Hulak-Karlak, Tomislava Bodrožić Džakić Poljak, Boris Starčević, Mario Sičaja, Ante Lisičić, Irzal Hadžibegović

**Introduction**: Rare complication of percutaneus coronary intervention is coronary stent dislodgement (incidence between 0.32 and 8%) and it is more common in severely calcified lessions. This complication may lead to more severe complication: myocardial infarction (MI), cerebral and peripheral embolizations, sometimes even death. (1) We report a case of stent dislodgement in ostial right coronary artery (RCA) after rotablation, that is after all, successfully retrieved through 12 french (Fr) femoral artery sheath. **Case report**: 68-old-male patient was admitted to the cardiology department because of unstable angina pectoris. This patient had MI 13 years ago and he had coronary stent in left anterior descendent artery (LAD), he has diabetes mellitus and arterial hypertension. He complained that he has been suffering from severe chest pain in rest, up to 10 minutes with spontaneous resolving and it was precipitated by exercise. Electrocardiography (ECG) showed biphasic T waves in inferior leads, but laboratory parameters, including troponin were in normal range. Due to his symptoms and ECG, coronarography was performed. LAD and circumflex artery had diffuse calcifications but no significant stenosis, in proximal RCA, which arises atypical in right coronary sinus, was shown significant calcified stenosis. After rotablation, percutaneous angioplasty with semicomplient balloons was done and just after stent was partially inserted into ostial RCA, it detached from the stent balloonsit, with consequent stent dislodgement. Despite a small balloon technique and a double wire technique, stent could not be retrieved, so we used loop snare, femoral 8Fr sheath was replaced with 12Fr and after adequate technique it was successfully removed. The patient was discharged in great condition fourth day after. **Conclusion**: Although losing stent a rare situation, it is necessary to know how to solve this complication; every interventional cardiologist should be familiar with it and every catheterization laboratory should be adequately equipped.

Željko Baričević, Kristina Marić Bešić, Maja Strozzi, Joško Bulum

**Background:** Making final decisions to perform percutaneous coronary intervention (PCI) based on angiographic results, without taking into consideration objective physiologic parameters that are not subject to misinterpretation, is a major issue in many cardiac catheterization laboratories. Despite numerous studies indicating their weakness, far too many operators still rely on visual angiography estimates or quantitative coronary angiography (QCA) for treatment guidance. This may be especially problematic in technically demanding lesions, bifurcation or multivessel disease, in which case a misinterpreted stenosis severity may lead to over- or undertreatment and possibly worse outcomes. Game-changing technology of instantaneous wave-free ratio (iFR) (**Figure 1**), which is performed with high fidelity pressure wire that is passed distal to the lesion to determine whether a stenosis is causing a limitation of flow with subsequent ischemia, is very feasible in daily clinical practice (1). In terms of cost-effectiveness with the adoption of iFR, although there is still a large reimbursement issue to be accounted for in Croatia, there are also some obvious benefits rising from elimination of unnecessary treatments and reduction in hospital readmissions. To support the concept, we are presenting a series of clinical decision-making cases from our institution, using iFR-guided assessment of angiographically intermediate coronary artery stenoses in different clinical settings. FIGURE 1. The physiological principle of the instantaneous wave-free ratio. **Case 1 – Angiographically non-significant right coronary artery (RCA) lesion:** 77-year-old female with the history of arterial hypertension and dyspnea on exertion was referred for coronary angiography, following inconclusive treadmill exercise stress test. A long proximal to mid-segment RCA stenosis of borderline angiographic appearance was noted; however, iFR of 0.71 demonstrated true lesion severity. PCI RCA with a single drug-eluting stent (DES) implantation and high-pressure balloon postdilatation was performed. **Case 2 – Multivessel disease:** 59-year-old male smoker with newly diagnosed arterial hypertension, diabetes and old anteroseptal myocardial infarction was admitted due to unstable angina. Coronary angiography showed old ostial left anterior descending artery (LAD) occlusion, culprit subocclusive stenosis of the proximal circumflex artery (Cx) with the plaque extending from the left main coronary artery (LMCA) and severely ectatic RCA with multiple aneurysms, angiographically intermediate stenosis of the mid-segment and calcified stenosis of the posterior descending (PD) branch. PCI LMCA/Cx was performed with 2 DES implanted, followed by iFR of the RCA one month later, in a staged manner. PD stenosis was found positive (0.85) and treated with DES implantation, but the prognostically challenging mid-RCA stenosis was iFR negative (0.94) and subsequently left untreated. **Case 3 – Diffuse LAD disease:** 60-year-old male patient with previous PCI RCA for myocardial infarction was referred for second-look coronary angiography due to residual diffuse LAD disease beginning at the ostium level and angiographically significant Cx stenosis (QCA 75%). By means of iFR, Cx lesion was found negative (0,91) and the LAD was positive (0.85), which was confirmed by fractional flow reserve finding of 0.75. Using iFR pullback method (**Figure 2**) a jump was demonstrated at the level of LAD/2nd diagonal (D) bifurcation (Medina classification 0,1,0) that led to PCI with 1 drug-coated balloon applied to treat the lesion. Due to localized dissection, an additional DES was implanted proximally. Myocardial SPECT was performed 4 months later showing no inducible ischaemia. FIGURE 2. Instantaneous wave-free ratio pullback assessment. **Case 4 – Unstable angina with bifurcation LAD/D1 stenosis:** 57 year-old woman was hospitalized due to single episode of angina at rest, with ischaemic ECG changes in leads I and aVL. Coronary angiography showed bifurcation lesion involving subocclusion of the small D1 as a culprit lesion and angiographically intermediate LAD stenosis (Medina classification 1,0,1). The patient had been free of chest pain from the time of the admission. iFR was done revealing that the LAD stenosis was not flow-limiting (0.98) and the patient was discharged with optimal medical therapy only. **Conclusion:** Physiological assessment of angiographically intermediate coronary artery lesions using iFR is feasible and should be performed on a regular basis to improve patient treatment and outcomes.

Ivica Benko, Gordana Hursa, Sanja Keleković, Dorotea Vuk

Transseptal catheterization is a procedure that allows transvenous access to the structures of the left heart but percutaneously and mostly via femoral veins. Transseptal catheterization has been primarily developed for the evaluation of valvular disease and mitral valvuloplasty, while today, transseptal approach is widely used in various interventions in invasive cardiology like left atrial appendage occluders, mitral balloon valvuloplasty, MitraClip, invasive evaluation of left atrial pressure, electrophysiology procedures, etc. Transseptal catheterization is performed by using specially designed needles, sheaths and dilatators. (1-3) In University Hospital Centre “Sestre milosrdnice”, transseptal catheterization is most frequently performed with Brockenbrough needle and Mullins sheath, and with help of coronary sinus catheter as an orientation for the transseptal puncture (TSP). Further orientation and control are performed wit use of fluoroscopy (in left anterior oblique – LAO 45, and right anterior oblique – RAO 30 projection) and use of invasive blood pressure. Like in any other invasive procedure, a thorough preparation is important to minimize the risk for complications. TSP is one of the procedures where nursing staff has a major influence on the rate of complications, from material preparation to assisting physician and monitoring of anticoagulant parameters. In this paper, we are showing 5-year follow-up, where in 629 patients (441 male, 190 female) 1040 TSP were performed. Transseptal catheterization was mostly indicated for electrophysiology procedures. 90.4% of procedures were only guided with fluoroscopy and invasive pressure, while 9.6% needed additional guidance with transesophageal echocardiography. In these 629 patients, 3 perforations/tamponade (0.4%) occurred, and were treated with percutaneous drainage. There were 4 (0.6%) thromboembolic events: 2 transient ischemic attacks and 2 coronary events with changes in ST-segment. Since there is a constant increase in a number of transseptal catheterizations and it is becoming a standard procedure in catheterization labs, nursing staff must therefore be trained in for this kind of procedure and its complications.

Tomislav Letilović, Damir Kozmar, Darko Počanić, Mario Stipinović, Maro Dragičević, Vedran Radonić, Helena Jerkić

**Introduction**: Coronary collaterals (CC) are anastomotic connections that can provide an alternative blood supply. They are especially important in the case of the vessel occlusion as they are prerequisite of viability. Collaterals have an indispensable role in any type of chronic total occlusion (CTO) intervention. (1) Aim of our study was to analyze angiographic characteristics and clinical relations of collaterals in CTO patients. **Patients and Methods**: Consecutive patients, in whom at least one attempt of CTO intervention in our institution was attempted, were enrolled. Data from 133 patients were collected from the beginning of the 2015 to the June of 2017. Angiographic characteristics were analyzed using Rentrop and Werner classifications. Possible relation of those angiographic characteristics to coronary risk factors were sought. Association of CC angiographic characteristics and individual components of the so called optimal medical therapy (OMT) was also investigated. 79 (59.4%) had a CTO of right coronary artery (RCA), 36 (27.1%) of left anterior descending (LAD) and 18 (13.5%) of circumflex artery. Mean age was 63.6±9.2 years. Mean Rentrop score was 2.1±0.84 and mean Werner score was 1.37±0.51. 99 patients (74.4%) had heterocollaterals. Collaterals were frequently (58 patients - 44%) of multiple locations i.e. both septal and bridging. Further analyses showed no relation between angiographic characteristics of CC and coronary disease risk factors. No association of any individual component of OMT and CC angiographic characteristics was found. There was a trend of higher Werner class in men as opposed to women (1.42±0.53 vs 1.25±0.43; p=0.07). **Conclusion**: Our results show that most of the patients have heterocollaterals and frequently from different localizations. We found no connection between angiographic characteristics of CC and coronary disease risk factors as well as medical therapy.

Marijan Pašalić, Boško Skorić, Maja Čikeš, Daniel Lovrić, Jana Ljubas Maček, Hrvoje Jurin, Jure Samardžić, Joško Bulum, Davor Miličić

**Introduction**: Benefits of venovenous extracorporeal membrane oxygenation (VV-ECMO) in patients with severe acute respiratory failure (RF) have been identified in different trials (1). Due to surfactant washout, drowning often results in acute respiratory distress syndrome (ARDS), which remains the most important cause of death in those patients surviving the transfer to hospital. **Case report**: 32-year-old male patient with no prior medical history presented to our Emergency Department following drowning and a successful resuscitation. He was found submerged in the pool just a couple of minutes after being seen conscious and swimming. Lifeguard on duty pulled him out of the pool and started cardiopulmonary resuscitation. Upon the arrival of Emergency Medical Service, patient had a pulse and was breathing spontaneously, but was exhibiting grand mal seizures and not recovering consciousness. In the emergency department he was put on mechanical ventilation (MV) due to global RF and in the Coronary Care Unit therapeutic hypothermia (TH) was started. Urgent diagnostics was performed and no signs of stroke, coronary artery disease, pulmonary embolism or significant electrolyte imbalance were detected. 12-lead ECG and echocardiography showed no abnormal findings despite severe respiratory acidosis. Due to signs of ARDS (**Figure 1**) and worsening RF in spite of increasing MV support, VV ECMO implantation was indicated. It was successfully conducted in the early period (th day) and of MV (8th day). He exhibited no signs of neurologic deficit and was rapidly mobilized. Finally, on the 21st day he was discharged home. FIGURE 1. MSCT findings showing diffuse pulmonary (parenchimal) infiltrates and radiologic signs of acute respiratory distress syndrome. FIGURE 2. X-ray findings before and after methylprednisolone and cefepime therapy. **Conclusion**: Our case report recognizes the potential life-saving role of VV-ECMO in treating drowning patients with severe ARDS. Hence, the use of ECMO should be beared in mind as a treatment modality in all drowning victims.

Kristijana Radić, Biljana Šego, Mirjana Slanc

Rotational atherectomy is used in patients with highly calcified coronary arteries where it is very hard to perform percutaneous transluminal coronary angioplasty (PTCA) procedures. (1, 2) Operating nurses have to know all phases of the procedure, anatomy and physiology, usage of aseptic methods. Importance of the work process in the operating room, high level of professional education, knowing skills of high-quality maintain high quality of health care is a must-have in these procedures. Rotablation represents an addition to the standard PTCA procedure, it makes treatment of calcified vessels easier and less risky. Nurse is responsible for assembling and material integrity. She needs to cooperate and support the interventional cardiologist, notify and check for ECG changes. Important responsibilities of nurse before rotablation are: 1. System set-up: Connect foot pedal to console Connect air hose to air supply Connect air supply to console Open gas tank to pressurize system 2. Rotablation flushing cocktail: verapamil, nitrates and heparin in saline 3. Component set-up: Attach advancer to the console Attach saline infusion port to IV pressure bag Open irrigation line Backload burr catheter into guidewire Connect wire clip torquer 4. Pre-procedure system test - DRAW test: D – Drip = Verify irrigation at distal tip of burr catheter R – Rotation = set burr speed to desired RPM level and verify Dynaglyde speed A – Advancement = Confirm advancer knob and burr move freely W – Wire = Verify brake is holding guidewire while burr is spinning, and wire clip is fixed

Anita Miljas, Ivan Šakić, Tomislav Krčmar

**Introduction**: In our Laboratory for the catheterization of the heart and coronary arteries greatest number of procedures is performed via transradial vascular access. Anomalies of the origin of supraaortic arteries are more frequently encountered when using right transradial vascular access. Three different types of anomalies of the aorta and its branch vessels are defined in referral to the distance of brachiocephalic trunc and aortic arch itself. The most frequent variant is so called bovine arch, when brachiocephalic trunc debranches into the left and the right common carotid artery as well as into the right subclavian artery. This variant has the prevalence of 7-10% in general population and makes no technical problem during heart catheterization. Aberant right subclavian artery (a. lusoria) is present in general population with the prevalence of 1-2%. In this variant the origin of right subclavian artery is positioned distally to the origin of the left subclavian artery. A. lusoria in this variant runs retroesophageally. Due to this course some of the patients have difficulties with swallowing of the food, while majority of the patients is completely symptom-free. Diagnostic methods for precise definition of aortic arch anomalies, i.e. a. lusoriae are CT and MRI angiography. (1) **Case report**: We present 75-year-old patient who was admitted to CCU in Dubrovnik General Hospital due to the acute coronary syndrome of inferoposterior localization. Urgent coronary arteriography was performed, and right radial artery was used as vascular access. Due to tortuosity of the artery that fulfilled criteria of a. lusoria there were difficulties in placement of the catheter in orifices of both left and right coronary artery. Standard JL 4.0 5Fr catheter was used for the left coronary artery, and AL1 6Fr catheter was used for right coronary artery. Culprit lesion was thrombotic occlusion of distal segment of the right coronary artery, so primary percutaneous coronary intervention was performed with one DES (4.0x13 mm) implanted in the lesion. On the third day of the treatment MSCT angiography of the aortic arch was performed and diagnosis of a. lusoria variant was confirmed. This variant makes right transradial vascular access challenging but with the proper manipulations with the catheter, coronary intervention can be successfully performed.

Kristina Marić Bešić

Burnout is a psychological and behavioral syndrome with emotional exhaustion as a hallmark. According to data from the literature (1) the percentage of physicians experiencing burnout is rising in the past few years, but the medical society still seems not to recognize it as a significant problem. Especially in medical specialties where diseases are acute and life-threatening, like in cardiology, burnout rates are higher as a result of great responsibility and expectations and little control in the outcome of our patients. Long and unpredictable hours, less direct patient contact, too much administrative work and the growing requirements for maintaining of certification are also contributing to burnout among physicians. The „hamster wheel medicine“ that we are practicing today where the health care system stimulates high volume vs high quality care is becoming more and more present also in Croatia. Interventional cardiology is not an exception. Interventional cardiologists are facing more and sicker patients with complex coronary artery and structural heart diseases and treating these patients despite technology improvement becomes a great challenge. Although there are data about the burnout rates among cardiologists (2, 3), there are no data about interventional cardiologists. Because of negative implications of burnout on private (alcohol and drug abuse, depression, suicide) and professional lives of physicians (decreased quality of care, increased medical errors, decreased productivity and patients satisfaction) we need to address this issue in interventional cardiology.

Tomislav Krčmar

Over 40 years have gone since first percutaneous intervention on left main (LM PCI) and we still deal with many controversies. Guidelines for LM PCI have evolved through time. First “green light” for LM PCI was in American guidelines from 2009: LM PCI may be considered in patients with anatomic conditions that are associated with a low risk of PCI procedural complications and clinical conditions that predict an increased risk of adverse surgical outcomes. Last American and European guidelines from 2014 gave PCI and coronary artery bypass graft (CABG) surgery IB recommendation for treatment of low SYNTAX patients mostly because of data driven from sub-analysis of SYNTAX trial. Two studies presented and published in late 2016 on the treatment of unprotected left main coronary came up with conflicting results. In the EXCEL trial published in the New England Journal of Medicine (1), patients with low- or intermediate-SYNTAX scores treated with an everolimus-eluting metallic stent had comparable rates of death, stroke, or myocardial infarction (MI) at 3 years when compared with patients treated with CABG surgery. Investigators also saw more periprocedural MI and ST-segment elevation MI in the CABG-treated patients at 30 days. In contrast, in the NOBLE trial (2), published in the Lancet treatment with PCI using predominantly a biolimus-eluting stent was associated with a significantly higher rate of major adverse cardiac and cerebrovascular events at 5 years when compared with CABG surgery. Individually, all-cause mortality was comparable between the two treatments, while nonprocedural MI and the need for a repeat coronary revascularization were higher among those treated with PCI. Stroke rates were higher among the CABG patients at 30 days but numerically higher among PCI patients at 5 years. Two large meta-analysis from 2017 concludes that all-cause mortality is similar from PCI or CABG treatment. When we consider all new data from 2016. and 2017, PCI with new-generation DES confers similar outcomes as CABG in terms of mortality throughout 5 years, but still it suffers from increased need for repeat revascularization after PCI and less protection for non-procedural MI. In conclusion, probably is time to change the guidelines on LM treatment towards IA grade recommendation for LM PCI and CABG for low to intermediate SYNTAX patients.

Mihajlo Kovačić, Marko Hranilović

**Introduction**: Dobutamine stress echocardiography is based on the causal relationship between induced myocardial ischemia and left ventricular regional wall motion abnormalities. Strain and strain rate imaging have been applied to stress echocardiography as the most recent advancement striving to provide a more quantitative approach. (1) The lumen diameter reduction after percutaneous coronary intervention (PCI) is known as “restenosis”. In the era of bare metal stents (BMS) the occurrence of restenosis ranged between 17–41%. Two strategies should be considered for treatment of any type of coronary in-stent restenosis (ISR): PCI with second or third generation drug eluting stents (DES) and drug coated balloons (DCB). (2) We will present a case report of successful PCI for in stent restenosis of BMS of mid segment left anterior descending artery (LAD) with third generation DES after verification of ischemia with dobutamine stress echocardiography. **Case report:** 75-years-old male patient with hypertension and dyslipidemia, who suffered anteroseptal ST-segment elevation myocardial infarction in January 2017, was treated with PCI of mid segment LAD with implantation of two BMS. One year after procedure he started to complain of mild exercise induced dyspnea. Standard treadmill ECG stress testing was performed up to a maximum predicted heart rate for his age and was without electrocardiographic evidence of cardiac ischemia. In further evaluation of symptoms, in January 2018 dobutamine stress echocardiography was performed, with maximal dose of 40 μg/kg/min. In rest setting, there was no visible regional akinesia of left ventricular wall, but in peak stress, test has clearly shown apicoseptal akinesia to dyskinesia. Both settings were quantitatively analyzed with strain and strain rate methods (**Figure 1**). After a positive stress echocardiography test, reevaluation with coronary catheterization was indicated due to suspected in stent restenosis of BMS in mid segment of LAD. Cardiac catheterization was performed on 24th of January 2018 and significant (90%) ISR was determined (**Figure 2**). Using right transradial approach, vessel was cannulated with AL 1.0 6F catheter due to anomalous left coronary artery. Lesion was predilated with NC balloon 2.75x20mm, after which third generation DES 2.75x33mm was implanted (Ultimaster). Procedure was terminated after postdilatation with NC balloon 3.0x15mm, with finally TIMI 3 coronary flow (**Figure 3**). FIGURE 1. Curved anatomical M-mode of strain rate analysis in peak stress shows clearly apicoseptal akinesia with marked postsystolic shortening. FIGURE 2. Coronary angiogram before intervention shows significant in-stent restenosis in the mid segment of the left anterior descending artery. FIGURE 3. Coronary angiogram after intervention shows no stenosis and TIMI 3 flow in the left anterior descending artery. **Conclusion**: In reevaluation of post myocardial infarction patients due to occlusive coronary disease in LAD region treated with PCI, stress ECG treadmill testing is not sufficient for analysis of left ventricular ischemia and possible target lesion failure detection. Stress imaging should be applied and stress echo with strain rate analysis can match sensitivity and specificity of single photon emission computed tomography or cardiovascular magnetic resonance imaging stress testing. PCI of ISR with second or third generation DES or DCB are methods of choice for treatment.

Irzal Hadžibegović, Mario Sičaja, Ognjen Čančarević, Ante Lisičić, Boris Starčević

Complex, high risk and indicated patients (CHIP) for percutaneous coronary intervention have gained a lot of interest in the last several years, and revascularization strategies for complex multivessel and patients with chronic total occlusion (CTO) are being currently scrutinized beyond SYNTAX trial. (1) It appears that in complex multivessel disease percutaneous coronary intervention (PCI), coronary artery bypass grafting or hybrid strategy selection does not matter if revascularization strategy is both indicated and total. CHIP group mostly comprises of patients selected for conservative treatment because of high risk after a heart team meeting, but it has been found that total revascularization of hemodynamically significant lesions improves survival in those patients. In fact, it seems that outside myocardial infarction, this subset of patients is the one where interventional cardiology treatment dramatically shows benefit in the terms of survival and quality of life. Interventional cardiology teams that plan to embark into CHIP have to be equipped, experienced, and educated in fractional flow reserve (FFR), intravascular ultrasound, CTO intervention techniques, plaque modification techniques, thrombus burden solutions and at last hemodynamic protection. However, results with the intra-aortic balloon pump or extracorporeal membrane oxygenation (ECMO) in CHIP subset did not prove beneficial. Currently, Impella 2.5 or Impella CP are temporary ventricular support devices preferred for protected PCI in hemodynamically stable high-risk patients, but it has not yet been used in our clinical setting. We analyzed our center experience with complex high-risk patients indicated for revascularization from 2012 to 2017. We observed a notable increase in CTO and plaque modification procedures, without significant increase in complications. However, reimbursement issues disabled the growth in number of FFR and IVUS procedures in complex patients. Although hemodynamic protection with ECMO had a relatively good reimbursement policy, initial clinical experience did not show promising results in CHIP subset, as compared to acute setting. In conclusion, Croatian interventional cardiology centers entering CHIP territory need integrated heart team education, adequate equipment and adequate reimbursement for complex high-risk patients, while appropriate hemodynamic support still remains an unresolved issue.

Lovel Giunio, Anteo Bradarić, Jakša Zanchi, Mislav Lozo, Dino Mirić, Lada Giunio

**Aims**: What are clinical, angiographic and procedural characteristics of the interventionally treated patients with left main coronary artery disease in the hospital that does not routinely use percutaneous coronary intervention (PCI) for left main disease (1, 2), and how do they fare? **Patients and Methods**: All patients treated with PCI for left main coronary artery disease between January 2007 and 2017 were enrolled. The group consisted of patients who refused coronary artery bypass graft (CABG) surgery, were refused by surgeons or severity of their clinical condition did not allow transfer to cardiac surgery. **Results**: Out of 525 (6.3%) patients with left main disease 467 (88.9%) were treated surgically. Fifty-eight (11.1%) patients were treated with PCI. Mean age of patients was 66.9±11.9 years, and 48 (82.7%) were male. The mean SYNTAX score was 25.6±8.8 and logistic Euro SCORE was 14.95%. Fifteen patients (25.9%) had unstable angina pectoris, 28 (48.2%) had non–ST-segment elevation myocardial infarction and 15 (25.9%) had ST-segment elevation myocardial infarction. Twelve (20.7%) patients were obese (body mass index >30), 7 (12%) had diabetes, 39 (67.2%) had arterial hypertension, 12 (20.7%) had hypercholesterolemia and 28 (48.3%) were smokers. Thirty (51.7%) patients have already had a myocardial infarction and 16 (27.6%) have already had CABG. Right transradial approach was used in 25 (43.1%) cases, right transfemoral in 26 (44.8%), left transradial in 5 (8.6%) and left transfemoral in 2 (3.5%) cases. In 52 (89.6%) patients 6F guiding catheter was used. Seven patients (12%) had only isolated left main disease, 12 (20.7%) had also accompanying single, 16 (27.6%) double, and 23 (39.7%) triple vessel disease. Nine (15.5%) patients had occlusion, and 49 (84.5%) had significant stenosis of left main. Only 5 (8.6%) patients underwent balloon angioplasty alone and the rest were stented, nine (15.5%) with bare-metal stents and 44 (75.8%) drug-eluting stents. Average stent diameter was 3.86±0.69 mm and length was 18.5±6.45 mm. Twenty nine (50%) patients underwent additional intervention in another coronary artery during the same procedure. There was 4.9% procedural mortality, and in-hospital mortality was 9.8%. **Conclusions**: In a hospital that routinely uses CABG for left main disease, PCI has been demonstrated as an effective treatment when surgical treatment was not feasible or refused by the patient.

Boris Starčević, Mario Udovičić, Hrvoje Falak, Aleksandar Blivajs, Vanja Ivanović Mihajlović, Petra Vitlov

Cardiac allograft vasculopathy (CAV) is a major cause of morbidity and mortality after the first year of heart transplantation. It is characterized by progressive, concentric intimal hyperplasia and has a prevalence approaching 50% within the first 10 years after transplantation (1). We report a case of a male patient who in 2007 at the age of 30 years underwent a heart transplantation due to dilated cardiomyopathy. Seven years later, during routine coronary angiography he was diagnosed with diffuse CAV. In follow-up angiographies successive progression of CAV was observed, despite modification of medical treatment, and it mandated percutaneous coronary intervention (PCI) with implantation of 3 drug-eluting stents (DES) in the left anterior descending artery, the circumflex coronary artery and the right coronary artery, culminating with a successful PCI with implantation of a further DES in left main coronary artery in 2016. Finally, in April 2017 he underwent a successful cardiac retransplantation. PCI is a feasible bridging strategy for coronary lesions associated due to CAV (1), which includes unprotected PCI for the left main coronary artery stenosis, however the only definitive treatment for CAV is retransplantation.

Đeiti Prvulović, Martina Menegoni, Božo Vujeva, Krešimir Gabaldo, Irzal Hadžibegović, Ognjen Čančarević

We can calculate that 2 million interventions worldwide are performed on bifurcation lesions per year. Publication of the 12th consensus document from the European Bifurcation Club (EBC) (1) confirms that we are still looking for perfect bifurcation treatment. Analyzing eight general consensus statements and a number of consensus documents dedicated to specific topics published by EBC, the most important question in treating bifurcation lesion (BL) is the decision whether to implant one stent or two stents (simplicity or complexity). (2) This decision depends mostly on the operator’s subjective judgment of the true clinical relevance of a side branch. We will review the present literature on how to differentiate simple from complex BL and critical analysis of clinical studies comparing provisional vs two stent techniques. We will present real world data from our medium volume center. We conclude and suggest: 1. our reality differs from randomized controlled trials (RCT): there is a disconnection between RCT and patient-centered decision-making; 2. EBC consensus is based on the data from RCTs done by top experts. The decision how to treat BL is largely based on the comfort and experience of the operator. Every day less experienced operators are faced with the challenge of treating complex bifurcation lesions in real world; 3. We need data in the standard of real-world clinical practice: detailed clinical data of the patient, anatomical lesion details, all of the details of the performed procedure and wide spectrum of clinical and angiographic outcomes. These facts must be kept in mind in our search for holy grail in treating BL: technique that is fast, simple, easy, with less contrast and radiation, high success rates, low complications and good long-term results.

Iva Ladić, Majda Vrkić Kirhmajer, Krešimir Putarek, Ljiljana Banfić, Nada Božina

**Background**: Dual antiplatelet therapy and statins are the cornerstone of acute coronary syndrome (ACS) treatment. Interaction between these drugs can be affected by differences in inter-individual pharmacokinetics/pharmacogenetics. Rhabdomyolysis is adverse reaction of statins. Previous reports suggested that concomitant use of ticagrelor may add an additional risk in developing statin induced rhabdomyolysis. (1, 2) We present a case of rosuvastatin and ticagrelor induced rhabdomyolysis. **Case report**: 87-year-old female patient was admitted in the Department of Cardiovascular Diseases because of symptoms and signs of rhabdomyolysis. Her medical history revealed hypertension, chronic renal failure and acute coronary syndrome with percutaneous coronary intervention performed a month before. Her therapy at admission included aspirin 100 mg, ticagrelor 2 x 90 mg, furosemide 40 mg, potassium 1 gr, rosuvastatin 20 mg, pantoprazole 40 mg, amiodarone 200 mg and bisoprolol 2.5 mg. Physical examination showed no major abnormalities except muscle pain and weakness. Laboratory parameters were: serum creatinine kinase (CK) 19182 U/L, creatinine 306 μmol/L, mild hepatic lesion and red cells in urine analysis, suggesting that patient had developed rhabdomyolysis and progression of chronic renal failure. Despite rosuvastatin and amiodarone discontinuation CK rose further to 23974 U/L. On 5th day of hospitalization a mild decrease of CK values was noticed while clinical symptoms remained unchanged. On 7th day ticagrelor was discontinued and shortly after a rapid normalization of CK was recorded with mild renal function improvement. The patient declared regression of symptoms with complete recovery in few days. Real-time PCR based pharmacogenetic analyses indicated that the patient was carrier of low activity alleles of metabolic enzymes (CYP3A4*22, CYP2C9*3, UGT2B7-161C/T) and ABCB1 drug transporter which could prolong ticagrelor and rosuvastatin dispositions. **Conclusion**: Our patient had several risk factors for rhabdomyolysis: old age, renal and hepatic impairment, drug interactions and genetic predisposition. Pharmacogenetic analysis can provide additional information about mechanism of this interaction and help in tailoring an individual statin and antiplatelet therapy.

Jozica Šikić, Dario Gulin

In the last 30 years women have a worse outcome after acute coronary syndrome (ACS) than men, but unfortunately women are not well represented in the studies. Women with ACS are “older and sicker” and are on average about 10 years older than men for the 1st ACS. Younger women with ACS (<55 years) have more comorbidity (diabetes, heart failure, stroke, peripheral artery disease, chronic obstructive pulmonary disease), differences in comorbidities are decreasing with age. Women with diabetes have a 4.3x higher risk for myocardial infarction (MI) than women without diabetes. In men, the risk is 2.7x higher. Smoking increases the risk for MI 3.3x in women and by 1.9x in men. In women, under the age of 45, the difference is more pronounced (7.1: 2.3). Women have smaller coronary artery lumen. Plaque characteristics are different (smaller necrotic nucleus, less calcium) and more frequently endothelial dysfunction, vasospasm due transitional sympathetic-vagal imbalance, plaque erosion and spontaneous coronary artery dissection. Non-obstructive coronary disease (microvascular disease) is more often in women, 10% women with ACS have not the pathological substrate. Women have more frequent periprocedural complications (mortality, major adverse cardiac events, need for blood derivatives, stroke) higher mortality risk after acute MI and 22% higher risk for rehospitalization within 30 days. After ST-segment elevation MI they have a worse 30-day outcome than the man. Reasons for later appearing in the late hospitalization, higher comorbidities rate, small coronary vessels, restenosis, “in-stent” thrombosis and distal embolization. Women have a lower troponin level (including hsTn) than men (a lower myocardial mass) and a smaller implementation of new drug eluting stents after the onset of the market. Optimal medical therapy has the same efficacy in women and men, but women are rarely treated with aspirin, GP IIb/IIIa inhibitors and beta blockers. They have a better response to statins in terms of atheroma reduction. They are less referred to cardiologic rehabilitation and less frequently remain on it. Education of women in the term of ACS is essential with the aim to prevent it and reduce risk factors especially diabetes and smoking. (1-3)

Jozica Šikić, Dario Gulin, Ana Marija Slišković, Ante Pašalić, Jasna Čerkez Habek

**Introduction**: Coronary artery disease (CAD) is common among elderly patients and may have certain characteristics that are different from those in younger age. (1-3) The aim of this study is to determine the presented risk factors, clinical presentation and angiographic findings in elderly patients. **Patients and Methods**: This retrospective observational study included all patients referred for coronary angiography at our department in eight-month period. The cutoff of 75 years was used to determine characteristics and outcomes of patients older than 75 years (OP) vs. younger than 75 (YP). **Results**: Among the 942 patients referred for coronary angiography, 178 (18.9%) were OP. 46 patients (25.8%) of OP had acute coronary syndrome (ACS) and 22.6% of YP. Female/male ratio was 46.7% in OP and 31% in YP. OP had the higher prevalence of previous myocardial infarction (32% vs. 24.4%) and similar rate of previous PCI (25.8% vs. 26.7%). Cerebrovascular disease was present in 10.1 vs. 6.6% and peripheral artery disease in 10.1 vs. 7.6%. Previous cardiovascular risk factors were present in OP: smoking 6.7% vs. 25.7%; hypertension 88.7% vs. 82.4%; diabetes 30.8% vs. 26.7%; hyperlipidemia 67.4% vs. 69.7%. Beta blockers were used in 64.4%, ACE inhibitors in 57.8% and statins in 45.5% of OP, while 55.9%, 51.1% and 45.8% in YP. Mean hospitalization stay was 5.97 days in OP and 5.56 in YP (both median 4 days). Culprit coronary artery was in OP RCA in 39.5%, LAD in 38.4% and ACx in 22.1%, while in YP RCA in 35.7%, LAD in 42.6% and ACx in 21.6%. In OP, type A lesion was present in 10.5%, type B in 57%, type C in 15.1% and coronary occlusion in 17.4%; while in YP 21.2%, 51.3%, 11.7% and 15.8%. OP had more coronary segments involved (2.86 vs. 2.57). A median value of percent of luminal stenosis was 99% in OP and 90% in YP (mean values - 90.8% and 85.9%). The mean number of stents implanted was higher in OP (0.73 vs. 0.67). GpIIb/IIIa inhibitor was used more in YP (3.9% vs. 5.3%). **Discussion and Conclusion**: Patients older than 75 show specific group characteristics. This group presented more with ACS, higher female/male ratio, prevalence rates of arterial hypertension, diabetes, previous myocardial infarction, cerebrovascular and peripheral artery disease, and drug intake. More diffused CAD was also observed with more severe types of coronary lesions and higher luminal stenosis.

Jozica Šikić, Dario Gulin, Ana Marija Slišković, Jasna Čerkez Habek, Edvard Galić

**Introduction**: Women with the acute coronary syndrome (ACS) have higher short and long-term mortality rates than similarly aged men. (1, 2) **Patients and Methods**: This retrospective observational study was conducted in the cardiovascular department in an eight-month period. Patients over 26 years of age with ACS were enrolled in this study. **Results**: Among the 219 included patients, 65 (29.6%) were female. Compared with men, women had higher prevalence of previous myocardial infarction (21.5% vs. 12.9%), while the previous percutaneous coronary intervention (PCI) was performed in 6.1% of women and 12.9% of men. Cerebrovascular disease was present in 4.6% of women and 5.1% of men, while peripheral artery disease was present in 9.2% of women and 4.5% of men. Previous cardiovascular risk factors were present in women: smoking 29.2% vs. 35.7%; arterial hypertension 78.4% vs. 71.4%; diabetes 27.7% vs. 22.7%; hyperlipidemia 66.6% vs. 56.5%. Beta blockers were used in 32.3%, ACE inhibitors in 41.5% and statins in 26.2% of women, while 24.6%, 25.3% and 22.1% in men. Hospitalization stay was similar for both sexes (6.96 days for women vs. 7.19 days for men). At the time of ACS, women were older than men (average age 68.03 vs. 61.24). Culprit coronary artery was in women RCA in 32.6%, LAD in 50% and ACx in 17.4%, while in men RCA in 34.7%, LAD in 42.7% and ACx in 22.6%. According to the type of the lesion in women, type A was present in 25.6%, type B in 30.2%, type C in 11.6% and coronary occlusion in 32.6%; while in men 19.5%, 35%, 12.2% and 33.3%. Regarding the severity of coronary artery disease, measured as a number of diseased coronary segments, women had fewer segments involved (3.09 vs. 3.52). The number of stents implanted was less in women (1.01 vs. 1.28). GpIIb/IIIa inhibitor was used in 13.8% of women vs. 18.1% of men. **Discussion and Conclusion**: Women with ACS present seven years later than men. The higher rate of previous myocardial infarction and a lower rate of previous PCIs were observed in women. Regarding cardiovascular risk factors, women had higher rates of diabetes, arterial hypertension, and hyperlipidemia, as well as higher rates of using optimal medical therapy. It seems that more complex coronary artery disease was present in men, mainly seen as a shift type A and B lesions, but also as more coronary segments involved, more stents implanted and more antiplatelet GpIIb/IIIa inhibitors used.

Dean Strinić, Jasna Čerkez Habek, Tea Blažević

**Introduction**: Controversy exists regarding the safety of testosterone replacement therapy following recent report of an increased risk of adverse cardiovascular events. A total of 7 population-based studies analyzed the association between cardiovascular disease and levels of total testosterone. Although 3 of these studies found statistically significant higher cardiovascular mortality associated with lower levels of total testosterone, the others 4 studies did not confirm these results. In both medical and lay literature, one of the principal adverse effects generally associated with anabolic steroid use is the increased risk for myocardial infarction. However, direct evidence showing cause and effect between anabolic steroid administration and myocardial infarction is limited. Many of the case studies reported normal coronary arterial function in anabolic steroid users who experienced myocardial infarction, while others have shown occluded arteries with thrombus formation. (1-3) **Case report**: 53-year-old male patient without standard risk factors for cardiovascular disease, had taken i.m. testosterone once a month during a period of 15 years and was admitted in August 2017 with ST-segment elevation myocardial infarction (STEMI) of the anteroseptal wall. Primary percutaneous coronary intervention (pPCI) of the proximal left anterior descending coronary artery (LAD) with implantation of the drug-eluting stent (3.5x18 mm) was performed immediately. One hour later, patient had chest pain with ST-segment elevation localized in anteroseptal leads which was induced by early coronary stent thrombosis and rePCI of previously treated LAD was performed with an implantation of a second drug-eluting stent (3.5x15 mm). One hour later, transitory ST-segment denivelation of the inferior wall was reported in ECG. Echocardiography showed non-dilated left ventricle with mild reduction in systolic function (EF 45%) with hypokinesis of anterior wall and apex. Level of testosterone in patient was above reference value. **Conclusion**: The use of testosterone with known coronary artery disease is yet controversial.

Đeiti Prvulović

There is no mandated retirement age for physicians in the United States, and physicians 65 and older currently represent 23 percent of physicians in the United States (1). It is estimated that 5-10% of people age 65 and older have dementia. (2) Older physicians have deep knowledge, well-honed interpersonal skills, better judgement than young ones and more balanced perspective. To perform demanding and challenging job of interventional cardiologist, physician must have the physical and mental ability. Health, physical ability, and cognition decline with age, but with significant variability in the cognitive aging process across older adults. (2) Is there an age limit for interventional cardiologist? Is it everything in the age? If there is physical or cognitive decline, who is going to make an assessment and how to measure it? Who is responsible to act in this situation? What are impediments to stop catheterization laboratory activity? In Croatia there is a lack of experienced interventional cardiologist. Mandatory retirement age is 65. „For many of us, cardiology is not only a career but a lifetime endeavor“. (3) We must think about opportunities of advantages of older colleagues and their possible contribution to the health care environment as potent knowledge and experience resources, in practical work in catheterization laboratory, in advocacy and in education.

Dario Gulin, Jozica Šikić, Ana Marija Slišković, Edvard Galić, Jasna Čerkez Habek, Tea Blažević

**Introduction**: Acute coronary syndrome (ACS) mainly occurs in patients over 50 years of age, but younger patients can also be affected. (1, 2) **Patients and Methods**: This retrospective observational study was conducted in our cardiovascular department in an eight-month period. The cutoff of 50 years was used to determine clinical characteristics and outcomes of patients younger than 50 years (YP) comparing them with older than 50 years (OP). **Results**: Among the 219 patients with ACS, 26 (11.8%) were YP. Women were affected in 11.5% in YP and 32.1% in OP group. There were no female patients younger than 46 years. Compared to OP, YP had the lower prevalence of previous myocardial infarction (3.8% vs. 17.1%) and previous PCI (3.8% vs. 11.9%). Cerebrovascular disease was present in 5.7% and peripheral artery disease in 6.7% of OP, while in YP both were not observed. Previous cardiovascular risk factors were present in YP: smoking 65.4% vs. 29.4% in OP; arterial hypertension 57.7% vs. 75.6%; diabetes 26.9% vs. 23.8%; hyperlipidemia 42.3% vs. 61.6%. Beta blockers were used in 19.2%, ACE inhibitors in 3.8% and statins in 11.5% of YP, while 27.9%, 33.6% and 24.8% in OP. Mean hospitalization stay was 5.26 days in YP (median 4 days) and 7.38 in OP (median 5 days). Culprit coronary artery was in YP RCA in 42.8%, LAD in 28.6% and ACx in 28.6%, while in OP RCA in 37.7%, LAD in 41.3% and ACx in 21.0%. In YP, type A lesion was present in 19%, type B in 42.8%, type C in 4.8% and coronary occlusion in 33.4%; while in OP 21.4%, 32.4%, 13.1% and 33.1%. YP had fewer coronary segments involved (2.92 vs. 3.46). A median value of percent of luminal stenosis was 99% in both groups (mean value of 91% in YP and 94.7% in OP). The mean number of stents implanted was higher in YP (1.46 vs. 1.17). GpIIb/IIIa inhibitor was used in 30.7% of YP vs. 15% of OP. **Discussion and Conclusion**: Patients younger than 50 years present smaller percentage of ACS patients. Our study showed no differences between the percentage of complete vessel occlusion in YP and OP. Among cardiovascular risk factors, greatest difference was seen in smoking. YP had less documented arterial hypertension, hyperlipidemia, and rate of previous drug use. RCA and ACx were more frequent culprit in YP and LAD in OP. YP had less coronary segments affected but higher rates of implanted stents and more need for antiplatelet GpIIb/IIIa therapy.

Petra Grubić Rotkvić, Jozica Šikić, Jasna Čerkez Habek, Dean Strinić, Zdravko Babić, Marin Pavlov

**Background**: Broken heart syndrome or Takotsubo syndrome (TTS) is considered a type of acute and usually reversible heart failure episode, often indistinguishable from acute coronary syndromes, characterized by the lack of significant obstructive coronary artery disease. The most characteristic wall motion pattern is apical ballooning. Reversible LV dysfunction affects more than one coronary territory and timelines of recovery is variable. It is believed that enhanced sympathetic stimulation induces transient myocardial stunning through a variety of mechanisms associated with emotional or physical stress. To the best of our knowledge, there is only one published case report of TTS resulting from the exacerbation of chronic pancreatitis (1). **Case report**: We report the case of a 69-year-old lady with four-year history of chronic pancreatitis who came to our emergency room with acute epigastric pain and vomiting associated with ST-elevation in precordial leads (**Figure 1**) and elevated troponin (troponin I 1496 ng/L). Moreover, serum amylase (315 U/L) and lipase (249 U/L) were increased. Echocardiography revealed a dilated and hypokinetic apex with reduced left ventricle ejection fraction (LVEF 40%). The abdominal ultrasound showed inhomogeneous pancreas with calcifications. Obstructive lesions of coronary arteries were absent on the angiogram and apical ballooning was demonstrated on left ventriculography (**Figure 2**).The findings were consistent with TTS and acute exacerbation of chronic pancreatitis. The patient was managed with intravenous crystaloids, analgesics, anti-emetics, beta blockers, ACE inhibitors. Over the next 2-3 days she was able to tolerate an oral diet. The ECG typically evolved with T wave inversion and QT interval prolongation (**Figure 3**) without significant arrhythmia. Echocardiography at discharge showed normalization of LVEF (55%) with mildly hypokinetic apical segment of the interventricular septum FIGURE 1. ECG on admission showing ST elevation in leads V1-V3. FIGURE 2. Left ventriculography demonstrating apical ballooning. FIGURE 3. ECG on day 3 demonstrating T-wave inversions and QT prolongation. **Conclusion**: Acute pancreatitis as well as the exacerbation of chronic pancreatitis are stressors that increase sympathetic stimulation of the heart and are associated with distributive shock that leads to transient myocardial ischemia and microvascular hypoperfusion (1, 2). Our case highlights the rare association of exacerbation of chronic pancreatitis with TTS.

Ana Gluhak, Renata Čosić, Mihaela Fekonja, Ivana Benković, Sandra Benković, Valentina Šimunović, Ivica Benko, Jadranka Daskijević

In this case report we present a case of 73-year-old male (year of birth 1945), urgently admitted to the Cardiac intensive care unit (CICU) of University Hospital Centre “Sestre milosrdnice” on 11th January 2018 due to the multiple implantable cardioverter defibrillator (ICD) activations/shocks at home (for most of which he did not lose consciousness at that time). On the day of admission to the CICU, ten additional shocks were delivered by ICD (also, with no loss of consciousness). The attending physician applied a dose of intravenous magnesium sulphate. Regardless of its application, the ICD storm continued, and 10 more shocks were delivered. Magnet application on the skin and reprogramming of ICD parameters to a more aggressive anti-tachycardia pacing (ATP) and ramp mode was performed by physician. Despite this, in the further course of the hospitalization, there were episodes of both ventricular tachycardia (VT) and ventricular fibrillation (VF) that led to the activation of the ICD (shocks were delivered), but thanks to reprogramming to the more aggressive ATP mode, additional shocks were delivered while the patient was unconscious, causing him to regain sinus rhythm and recover consciousness. On the 5th day, coronary angiography was performed with a placement of one stent in the stronger septal branch of left anterior descending artery. On the 7th day, an electrophysiology study with Carto 3 system was performed during which clinical VT was induced and mapped in the anterolateral part of the left ventricle. The radiofrequency ablation was performed, thus resolving arrhythmia permanently. On the 9th day the patient was transferred to the Post Coronary Care Unit and Arrhythmia Department. During the rest of the patient’s stay he reported no pain or discomfort and no malignant ventricular arrhythmias were recorded via telemetry system or ICD memory. On the 13th day, after the treatment was successfully completed, the patient was discharged for further rehabilitation. Goal of this case report was to present the complexity of the treatment of a patient with ICD storm and the importance of multidisciplinary care in interventional cardiology for favorable treatment outcome. (1) All together represents an extremely demanding need for highly educated nursing staff for various aspects of invasive and interventional cardiology.

Jasna Čerkez Habek, Jozica Šikić, Petra Grubić, Dean Strinić, Dario Gulin

**Background**: Myocardial infarction with ST elevation has incidence rate ranged from 43 to 144 per 100 000 per year (1). Differentiation of arterial thrombosis from most common causes of myocardial infarction, rupture or erosion of atherosclerotic plaque, especially in younger patients without or less cardiovascular risk factors and atherosclerosis, can be challenging. **Case report**: 47-years-old lady was admitted to our clinic 1 hour after onset of a chest pain. Risk factors for cardiovascular disease were positive family history, dyslipidemia and nicotinism. ECG revealed ST elevation from V1-V4 to 3 mm. Just after ECG was performed, the patient was defibrillated with 120J because of ventricular fibrillation. An emergency coronary angiography pointed out a thrombotic occlusion of the proximal left anterior descending coronary artery, treated with implantation of the drug-eluting stent (3.0x18 mm). Before discharge echocardiography showed non-dilated left ventricle with mild reduction in systolic function (EF 45-50%). Hypokinesis of apical segment of anterior wall and apex was noted with unexpected two prominent sessile thrombi. Initial therapy with ticagrelor and aspirin was changed in clopidogrel, aspirin, nadroparin initially until the therapeutic range was achieved with warfarin. During the triplet therapy due to a menorrhagia severe anemia occurs, treated with intrauterine levonorgestrel release device. Thrombophilia test showed that lady is homozygous for MTHFR and heterozygous for the PAI1 mutation. **Discussion**: Inherited thrombophilia is a genetic disorder predisposing thrombosis which may occasionally manifest, usually in the presence of trigger factors (2). It induces a hypercoagulable state, which, together with other cardiovascular risk factors, may explain the arterial thrombosis in this younger patient and thrombus formation in the ventricle, although time to balloon time was less than two hours and without aneurysmal formation of the left ventricle. It seems like thrombophilia may favor myocardial infarction, but is not able to cause it per se (3). **Conclusion**: Inherited thrombophilia is responsible for a small percentage of acute myocardial infarctions, and should be suspected mostly in younger patients. An absence of diagnosis leads to inadequate therapy and poor prognosis.

Joško Bulum

In the last decade, cardiac catheterization with transradial access is increasingly being used and become a golden standard for performing percutaneous coronary interventions, especially in patients with acute myocardial infarction with ST elevation, primarily because of the few and easiest possible complications than the transfemoral access. One of the disadvantages of the transradial approach is the relatively high incidence of catheterization failure (from 1% to 5%) which can be reduced by routine angiography of radial artery and by modification of the technique in the case of anatomic variations of the radial artery. (1) According to the results of our retrospective research, the incidence of anatomical variations of the radial artery was 8.8%, excluding the tortuosities with the incidence of 12.7% The most common complication of the transradial approach we want to avoid is the radial artery occlusion which is mostly asymptomatic and the frequency with the routine Doppler is about 5%. Procedures that reduce the incidence of radial artery occlusion include routine use of heparin and vasodilators, the use of hydrophilic sheaths such as smaller diameter and the closure of the puncture point for neocclusive hemostasis devices.

Boris Starčević, Mario Sičaja, Ognjen Čančarević, Jasmina Ćatić, Mario Udovičić, Irzal Hadžibegović, Petra Vitlov, Hrvoje Falak, Aleksandar Blivajs

**Case report**: 43-year old male patient, with a positive family history for coronary artery disease, was admitted to hospital in Jul 2017 with acute ST-segment elevation myocardial infarction presenting with rhythmic instability (VT/VF) and cardiogenic shock. Angiography revealed occlusion of the proximal left anterior descending artery as the culprit lesion and intermediate stenoses of the distal segment of the right coronary artery (RCA) and OM branch of the circumflex artery. Percutaneous coronary intervention (PCI) of the culprit lesion was performed with an optimal angiographic result. Echocardiography showed dilation of the left ventricle with significant reduction of ejection fraction (EFLV 35%) and mild mitral regurgitation. He was discharged with optimal medical therapy. In Oct 2017 repeat angiography was performed to evaluate the aforementioned residual coronary lesions. Intravascular ultrasonography showed nonsignificant lumen stenosis of the left main artery (MLA 8 cm2), RCA and OM branch. Medical therapy was modified with introduction of sacubitril/valsartan. In Dec 2017 the patient was admitted to hospital with rhythmic instability (VT/VF) and elevated cardiac biomarkers. Angiography revealed significant ostial stenosis of left main artery with ventriculization of blood pressure curves and fall in BP during catheterization. After stabilization, an implantable cardioverter defibrillator was implanted for secondary prevention followed by PCI of the left main with implantation of one everolimus-eluting stent. On follow up visits the patient remains symptom-free, without clinical signs of heart failure or evidence of malignant ventricular arrhythmias. **Conclusion**: This was a case of rapid coronary artery disease progression involving the left main coronary artery in a patient with ischemic cardiomyopathy with low ejection fraction in spite of optimal medical therapy and repeat angiographic studies using advanced intravascular imaging. (1, 2) It also remains uncertain when is the optimal timing of ICD implantation in patients with malignant arrhythmias in the early acute phase of myocardial infarction.

Željko Baričević

**Background**: Acute myocardial infarction complicated by cardiogenic shock is associated with high early mortality of 40 to 50%, with many of these patients known to have multivessel coronary artery disease. Although current guidelines recommend multivessel revascularization if feasible (1), the findings of the recent CULPRIT-SHOCK trial show that non-culprit vessel percutaneous coronary intervention (PCI) in this setting increases all-cause mortality (2). However, the clinical scenarios may differ significantly and there is still room to debate whether a straightforward infarction-related artery PCI only is the correct approach in every single case. **Case report**: A 50-year-old male non-smoker with history of arterial hypertension was admitted to the hospital complaining of upper abdominal pain radiating toward the neck that had begun 5 hours before, followed by general weakness, malaise and somnolence. At the time of admission cardiogenic shock was noted with a blood pressure of 60/40 mmHg and ECG revealing sinus bradycardia of 45/min with right bundle branch block. Bedside echocardiogram showed severely reduced left ventricular systolic function (LVEF 20%) with hypokinesia of anteroseptal, apical, anterior and inferior wall segments, together with severely hypokinetic right ventricle. Urgent coronary angiography demonstrated acute thrombotic occlusion of the ostial left anterior descending artery (LAD) and short chronic total occlusion (CTO) of the mid-right coronary artery (RCA) segment. Due to profound shock despite high-dose inotropic and vasopressor therapy, the percutaneous peripheral veno-arterial extracorporeal membrane oxygenation (VA-ECMO) support was initiated. A successful provisional stenting of the left main coronary artery and LAD using 2 drug eluting stents was then performed, followed by the LAD/circumflex artery bifurcation optimization using standard proximal optimization technique (POT), side-branch inflation, kissing balloons inflation and re-POT sequence (**Figure 1A**). Being aware of the large amount of affected myocardium in a latecomer with uncertain potential for recovery and expected detrimental hemodynamic side effects of the prolonged VA-ECMO support, an ad hoc anterograde PCI CTO RCA was done to recruit myocardial contractility reserve to help promote early weaning from ECMO (**Figure 1B**). The mechanical support was successfully removed 8 days after the implantation, with full RV recovery noted, coupled with LVEF increase to 35% due to inferior wall contractility restitution, but showing no improvement in the LAD territory. The patient was transferred to rehabilitation facility with uneventful course. Figure 1. Multivessel percutaneous coronary intervention protocol. Provisional left main coronary artery/left anterior descending artery stenting (A) followed by revascularization of the chronically occluded mid-right coronary artery (B). **Conclusion**: Immediate non-culprit vessel PCI may be considered in certain patients with acute myocardial infarction complicated by cardiogenic shock, especially with ongoing mechanical circulatory support counterbalancing potential drawbacks of prolonged intervention.

Eduard Margetić

## Dear Colleagues, The Working Group on Invasive and Interventional Cardiology of the Croatian Cardiac Society is organizing the 8th Croatian Conference on Interventional Cardiology – CROINTERVENT 2018, which will take place in Hotel Westin, Zagreb, Croatia, on March 8-10, 2018. Since the last Conference, new diagnostic and interventional procedures emerged or have been established. New drugs have been introduced in routine clinical practice, and the value of some existing drugs for improving primary outcomes or preventing cardiovascular complications of cardiovascular interventions has been additionally confirmed. The aim of this event, in addition to demonstrating current clinical practice in interventional cardiology, is to discuss concerns and difficulties encountered in our daily practice. Apart from cardiology and cardiology specialists, the CROINTERVENT 2018 is intended for cardiac surgeons, anesthesiologists, doctors of other specialties, and everyone else who is professionally associated with this important part of modern medicine. The conference program will contain invited lectures and oral and moderated poster presentations. As before, a significant part of the conference will be dedicated to the practical side of interventional cardiology, both through transmitted “live cases” and presentation of already completed interventions with analysis and evaluation. This Supplement of Cardiologia Croatica – the official journal of the Croatian Cardiac Society, consists of selected original contributions from our participants in the form of abstracts, which will be presented at the meeting in the form of oral presentations and moderated posters. Sincerely yours,

Zdravko Babić

Modern sports have shown a trend of greater and greater stresses being placed on young athletes with the goal of achieving top results, which sometimes overcome the capacities of the organism’s functional reserves. On the other hand, mechanization, urbanization, and other technological advances in the modern world increase the prevalence of sedentary lifestyles. Awareness of severe deleterious effects of such a lifestyle, especially in the most developed countries, has led to efforts to increase recreational physical activity among the general population. Congenital and acquired heart and vascular diseases represent a risk factor in sports, recreation, and work-related physical activity that can lead to an increase in morbidity and mortality. This textbook, to be published in the spring of 2018, represents a multidisciplinary approach to cardiology in sports, physical, and work-related activity, in which authors with many years of experience in professional and scientific work in the fields of kinesiology, sports cardiology, occupational medicine and dietetics, attempted to clearly and extensively cover the physiology of exercise and physical activity, as well as the pathophysiology, etiology, and diagnostics of clinical entities in sports cardiology. The book comprehensively describes the risks and benefits of exercise and physical activity in general, as well as the assessment of functional status and morphology, with the goal of establishing fitness for work and athletic activity. The specifics and importance of cardiologic examination in sports cardiology are described in detail, along with the procedures of functional diagnostics and the assessment of cardiovascular risk in athletes, which is very important for the everyday practice of all professionals working with athletes and recreational sport participants. The chapter on sports cardiology describes clinical entities from arrhythmology, heart valve diseases, and cardiomyopathy, as well as less common clinical entities found in athlete populations. The textbook delineates various aspects of recreational physical activity both in healthy participants in recreational sports and in persons with cardiovascular diseases and related risk factors. It also covers the work capacity and rehabilitation in cardiovascular patients with arrhythmias and heart failure, coronary disease, and after surgical procedures. The topics address important issues for both healthy persons and those with cardiovascular diseases – diet, sex life, driving motor vehicle capacity, physical activity at an advanced age, and resuscitation or cardiopulmonary reanimation in case of sudden cardiac death. The textbook is intended for graduate and postgraduate students of the Faculty of Kinesiology, graduate and postgraduate students of the School of Medicine, as well as all participants in training, competition, and health care of professional and recreational athletes. The basic goals of the book are to facilitate better recognition and understanding of the specifics of the field of sports cardiology and physical and work-related activities for kinesiologists, physicians, and other sports and health care professionals. This is the first Croatian textbook of this type in the field of sports cardiology, physical and work-related activities, and cardiovascular patients, and is a welcome addition to the Croatian professional and medical literature.

Maja Strozzi, Darko Anić, Željko Baričević, Margarita Brida, Irena Ivanac Vranešić, Kristina Marić Bešić, Jadranka Šeparović Hanževački

We recently informed the general cardiologic public in Croatia about the increasing problem of adult patients with congenital heart disease (ACHD) (1, 2). With this thematic issue of the Cardiologia Croatica journal, we hoped to increase the awareness of the problem and present some progress we have achieved over time. In this article, we will focus on one specific aspect of the issue: the problem of pregnancy in women with ACHD, including our experiences with these patients. It is not hard to see why pregnancy is full of risk for patients with ACHD. Pregnancy in any women is associated with significant hemodynamic changes. Due to hormonal changes, there is a very early drop in systemic vascular resistance (SVR), leading to compensatory renin-angiotensin reaction on pre- and afterload drop, with a correspondent rise in blood volume and heart rate. This results in increased cardiac output (CO), which can be almost doubled at the end of the pregnancy. Extra-cardiac anatomy can also have a negative effect on hemodynamics. In patients with already decreased cardiac function, this can have a severe impact (3). Maternal cardiac mortality during pregnancy is very low. Based on data from the British statistical office, it was 2.3 per 100 000 pregnancies in 2011 (4). The good news is that patients with ACHD only make up a small portion of this group, but other problems occur during pregnancy that can influence later mortality and morbidity (5). Pregnancies in patients with ACHD should be managed according to a precise plan that includes: - Evaluation before pregnancy - Avoidance of drugs harmful to the baby - Cardiac and obstetric care prior to delivery - Fetal development care - Cardiac and obstetric care during labor - Post-delivery care - Future contraception - Genetic counseling (if needed) - Antibiotic prophylaxis (if needed) According to this algorithm, the first rule is pre-conception counseling. Our goal is to establish and optimize the future mother’s heart condition, and discuss the following issues: immediate and late effects of pregnancy on the mother’s cardiac condition and risk to the baby. The pre-pregnancy examination includes history and clinical status, ECG, echocardiography (ECHO) to establish ventricular function, valves, vessels (conduits), shunts, and pulmonary pressure. If necessary, alternative imaging or other methods such as nuclear magnetic resonance (MR), exercise capacity testing, and heart catheterization in suspected high pulmonary vascular resistance (PVR), should be performed. In some cases, genetic counseling is advised. Unfortunately, patients sometimes come to our outpatient clinic already pregnant! Pregnancy risk should be determined, which is best done according to **WHO risk stratification during pregnancy** (ESC Guidelines on the management of cardiovascular diseases during pregnancy) (6). All patients with ACHD can be stratify into four groups (I-IV). ## Low who risk stratification group - In patients with surgically corrected atrial septal defect (ASD) and ventricular septal defect (VSD) without complication, a normal pregnancy can be expected (I). - In un-operated ASD and small VSD with good left ventricular function and no pulmonary hypertension (PH), normal pregnancy is expected (II). The left-to-right shunt can decrease because of the fall in SVR. There is a small risk of atrial arrhythmias and a theoretical risk of paradoxical embolization in ASD. (7) - Pulmonary stenosis (PS) with a gradient lower than 60 mmHg is also not a high risk for pregnancy (I). ## Intermediate WHO risk stratification group - It is recommended to treat severe PS before pregnancy (RVP>75 mmHg, P gradient >60 mmHg). Untreated PS caries high risk for right heart failure (II-III). - Repaired Tetralogy of Fallot (TOF) is a moderate risk for pregnancy (II). - Marfan syndrome can cause dissection during pregnancy, but the risk is not so high if the dimensions of the ascending aorta are less than 4.0-4.5 cm (II-III). ## High WHO risk stratification group - Transposition of the great arteries (TGA) after atrial switch (Senning-Mustard procedure); changes in RVEF and systemic valve competence can be permanent! (III). - Mechanical valves carry a great pregnancy risk. There is no consensus on the best anticoagulation regime in pregnancy (risk for pregnancy termination, thrombosis risk, teratogenicity risk for the baby) (III). - Un-operated TOF, rare today, carries a risk of cyanosis (III). - Pregnancy problems are common in Fontan patients (III). ## Case 1 ## MD, 1981, “murmur” known from childhood - Effort intolerance in the last two years, pregnancy planed. - Valvular pulmonary stenosis (PS) diagnosed (gradient 94 mmHg, annulus 21 mm) (**Figure 1**).Figure 1Echo finding of a congenital valvular pulmonary stenosis. - Pre-pregnancy intervention recommended. - PTA successful with two balloons 16+13 mm (**Figure 2**)Figure 2Percutaneous balloon dilatation of stenotic pulmonary valve: A) Pulmonary angiography before dilatation; B) Simultaneous inflation with two balloons; C) Pressure gradient before dilatation; D) After dilatation. - Pregnant, so far without complication, a normal vaginal delivery is expected. **This case is a good example of pre-pregnancy evaluation and optimized pregnancy outcome due to the advised intervention.** ## Case 2 ## JS, 1989, healthy - Mother died at 47 years of age (sudden death from aortic rupture, previous operation of cerebral aneurysm). - 2015: sister successfully operated for ascending aortic aneurysm (9 cm). - Accompanying her sister for postoperative ECHO control, somebody of echo staff she was pregnant (23 weeks) and offered her ECHO control as well. - ECHO revealed 4.5 cm of sinus Valsalva, Cesarean section recommended (**Figure 3**).Figure 3Dilatation of sinus Valsava in pregnant patient with suspected Marfan syndrome. - Birth was uneventful, and the patient is in regular follow-up; small progression of aortic dimension (4.7 cm) after 1.5 years. **The case is an example of the importance of screening. Marfan syndrome with aortic dilatation carries high risk for aortic dissection during pregnancy or delivery!** ## Case 3 ## PH, 1995, transposition of great arteries (TGA) - Senning-Mustard operation was performed at 4 months, in regular pediatric FU. Last pediatric control was 12/2012; **37 months pregnant**. ECHO description: normal tricuspid valve (systemic) function, good systemic right ventricular function. In ECG, a sinus tachycardia 140/min was described. - 3 weeks later, (1/2013) gave normal vaginal birth to a healthy girl. - 3/2013: hospitalization for severe heart failure, referred to our center (5/2013). - Atrial flutter at first presentation, low max oxygen consumption on spiroergometry (20 vol %O2), low EF, and significant systemic valve insufficiency on ECHO found (**Figure 4**).Figure 4Echo finding of patient with systemic right ventricle (transposition of great vessels after Senning Mustard operation): A) Dilatation and systolic function reduction of systemic right ventricle; B) Significant systemic (tricuspid) valve regurgitation. - Electrocardioversion was done, on beta-blocker therapy without without significant arrhythmia, on regular follow-up. Improvement of clinical and ECHO findings (**Figure 5**).Figure 5Improvement of systolic function of systemic right ventricle after pregnancy. **In this case, the question is whether EF deterioration was associated with pregnancy and was arrhythmia unrecognized. After pregnancy and conversion to sinus rhythm, fortunately, improvement of systolic function and reduction of systemic valve regurgitation was observed.** In the literature (8) on patients with TGA after Senning-Mustard operation, RV dilatation progressed in 1/3 of patients and with no recovery in 31%. RV systolic dysfunction progressed in 25% of patients, in the majority with no recovery. Tricuspid regurgitation progressed in 50%, and 1/3 of patients did not recover! The mother should be informed about the risk, and if she is willing to take it, careful follow-up is needed. ## Case 4 ## KS, 1994, congenital mitral valve disease - ×2 mitral valve repair in childhood. - 2009: mechanic valve implantation for severe mitral regurgitation was performed (parents’ decision). - 2015: first pregnancy, miscarriage in the 8th week (fetal death). - Last year: frequent SVT, electrophysiology was scheduled, but in the meantime there was second pregnancy; the patient presented at our center after 6 weeks: warfarin stopped, fractionated heparin introduced, beta blocker continued. - High warfarin dose needed (10.5 mg), so fractionated heparin continued, aspirin 75 mg introduced (from 14 to 32 weeks), regular anti-Xa level control (0.35-0.7 IU/mL). - New onset of SVT 220/min, stopped with verapamil (introduced instead of beta blocker for regular therapy) (**Figure 6**).Figure 612-lead ECG in pregnant patient with mechanical mitral valve; A) Supraventricular tachycardia 194/min; B) Sinus rhythm, after conversion with verapamil. - Ablation was planed after delivery, but for increase in arrhythmia frequency, the procedure was done in the 6-th month of pregnancy, with maximal radiation protection. In regular FU, so far with no complication, Cesarean section planed. **The case is a good example of the need to discuss the treatment strategy with patients (parents). Mechanical valves represent a high risk for future pregnancy, and this should be explained to patients (parents) before surgery!** In meta-analysis of studies (9) examining the best anticoagulation strategy in pregnant women with mechanical valves, different anticoagulation regimes had different impacts on maternal death, thromboembolism risk, valve failure, but also fetal spontaneous abortion, death, and congenital defects. Warfarin is the best drug for the prevention of valve thrombosis (only 5% risk for the mother) but has a high impact on congenital defect incidence in the fetus (up to 45%). There is also a risk of fetal hemorrhage (the drug is crossing placental membrane). Low-dose warfarin (if it is sufficient for good coagulation control) carries a much smaller risk. It should be avoided in the first trimester. Heparin carries approximately 15% risk for the child but also for the mother as well. Fractionated heparin is easier to use. The following combination can be recommended in some patients: fractionated heparin in the first 3 and last 2 months with warfarin in between; however, there is no a perfect anticoagulation regime for pregnancy! ## Case 5 ## MI, 1973, AV canal (large VSD and single atrium), severe PS - Cyanotic from childhood, rejected for reconstruction due to complexity. - 1998: Kawashima operation at 25 years of age (Fontan circulation). - 2000: normal pregnancy, gave birth to a small but healthy girl by vaginal delivery. - 2003 and 2006: pulmonary AV fistula closure. - Last 2 years: ascites, moderate reduction of EF, no systemic valve regurgitation, no conduits stenosis, no evidence of PLE, chronic hepatic lesion, suspect ovarian disease (Meigs syndrome?); adnexectomy 7/2017, ascites still present, but clinical status is stable. **This case represents the only Fontan patients with a successful pregnancy in our ACHD registry. The uncomplicated pregnancy may be result of late initial operation (at 25 years of age). The majority of our Fontan patients, are burdened with the usual complications occurring 20 years after the operation, when they reach the age for pregnancy.** Pregnancy after Fontan operation is associated with a high miscarriage rate. Older (10) and more recent (11) studies all reached the same conclusions: miscarriage occurs in 1/3 pregnancies in Fontan patients, and 70% pregnancies end with premature delivery, which has an impact on infant mortality and morbidity. Cardiac events are rare, and maternal mortality was not recorded. Group of patients with ACDH strongly discouraged from pregnancy (WHO IV) 1. Eisenmenger syndrome (50% maternal mortality). 2. Marfan’s syndrome with dilated aortic root (>4.5cm). 3. Severe aortic stenosis/coarctation. 4. Systemic ventricular ejection fraction <35%. 5. Severe pulmonary hypertension. The risks for the baby in pregnant women with ACHD includes: - Fetal growth restriction (Fontan circulation, cyanosis, beta-blockers users). - Preterm delivery (spontaneous, sometimes iatrogenic). - Teratogenicity (drugs). - Recurrence of congenital heart disease is rare (3-5%, including paternal disease). Medication during pregnancy is of great concern. There are **safe drugs** (digoxin, Ca-channel blockers, beta-blockers, thiazide and furosemide, heparin, sildenafil, low dose aspirin). Some of these drugs should be given with caution in the first trimester, some can reduce fetal growth, and for some, drug concentration monitoring is recommended. Some drugs are **not safe drugs** or at least not proven to be safe (ACE and ARB inhibitors, warfarin in the first trimester, spironolactone, bosentan, amiodarone, etc.). In peripartal care, the emphasis is on delivery planning and timing (and careful induction if necessary). In intermediate and high-risk patients, delivery should take place in a tertiary center, and the mode of delivery should be discussed with the obstetrician. In general, vaginal delivery is recommended. The birth position, analgesia, and time control must be considered. Antibiotic prophylaxis is not recommended in vaginal delivery. Cesarean section should be chosen for obstetric indications and selective cardiac states: Marfan syndrome, heart failure, mechanical valves. Complications in post-partal care can be expected, such as hemodynamic changes (heart failure and pulmonary edema, hypertension, shunting changes, and cyanosis), hemorrhagic complication (careful anticoagulation therapy monitoring); thromboembolic incidents are possible (pulmonary, systemic in patients with shunts), and incidence of infection is higher after section. ## Conclusion - The number of patients with ACHD is growing; more pregnancies in these patients are expected. - Pregnancy is possible in most women with ACHD, but there is an increased risk for the mother and fetus. - Strategy, potential risks, and therapy choices if necessary, should be discussed with the patient. - The risk can be diminished with proper care in a specialized ACHD center, with a multidisciplinary team available. - In our experience, the most vulnerable period is the transition from pediatric to adult care.

Tatjana Cikač, Kristina Sambol

Arterial hypertension is a leading public health problem and a risk factor for the development of cardiovascular and cerebrovascular diseases. Most patients suffering from hypertension are monitored by family medicine physicians that have the requisite knowledge and skills needed to diagnose and treat this disease. This is greatly facilitated by 24-hour ambulatory blood pressure monitoring (ABPM), which has more diagnostic value for arterial hypertension than clinical measurement of blood pressure (BP) values and is also used for monitoring disease management and deciding on the therapy of choice. This article assesses the utility of 24-hour ABPM in family medicine clinics for establishing the diagnosis of arterial hypertension and monitoring patients with a previously established diagnosis. We included 52 patients in a cross-sectional study over a period of 4 months. BP values measured using 24-hour ABPM were compared with values initially measured at the clinic on the examination date. The difference in the percentage of uncontrolled hypertension diagnosed by clinical BP measurement in comparison with 24-hour ABPM was tested by applying the χ 2 test. The association between BP values measured at the clinic and those measured by ABPM was tested using Spearman’s rank correlation coefficient. The study comprised 18 men and 34 women. The average age of the participants was 56.06 years. Average 24-hour systolic pressure was 156.13 mmHg, and average diastolic pressure was 89.81 mmHg. The average values of systolic and diastolic pressure measured in the clinic were 141.98 mmHg and 84.52 mmHg, respectively. Uncontrolled systolic pressure demonstrated by ABPM was found in 47/52 patients, while 36/52 patients had uncontrolled diastolic pressure. In clinical measurements, uncontrolled systolic and diastolic BP values were registered in 29/52 and 9/52 patients, respectively. The measurement results demonstrate a positive correlation between BP values measured at the clinic and those measured using 24-hour ABPM. The application of ABPM contributes to correctly establishing the diagnosis of arterial hypertension and improved BP management.