Cardiologia Croatica. 2018;13(5-6)

Jelena Kos, Hrvoje Jurin

An experts’ meeting entitled The Excellence of Croatian Cardiology and Hypertensionology – Selected Topics, organized by the Croatian Cardiac Society and the Croatian Society of Hypertension and sponsored by the pharmaceutical company Krka, was held on March 17th, 2018 in the Museum of Contemporary Art in Zagreb. The meeting was led by academician Davor Miličić and Prof. Bojan Jelaković. The first set of lectures, which focused on the unanswered questions in the field of hypertension, was initiated by Prof. Bojan Jelaković, who critically examined the latest American guidelines (AHA/ACC) from 2017. According to the guidelines, new limit values have been set and arterial hypertension is now defined by blood pressure (BP) values larger than 130/80 mmHg. This recommendation is predominantly based on the results of the SPRINT study. Prof. Jelaković warns that when interpreting the results of this study it is necessary to keep in mind a methodologically different measurement of BP in relation to previous research. Blood pressure was measured by an automated BP gauge without the presence of a physician or a nurse, and in such cases this method produces values of arterial pressure which are, on average, 14/8-10 mmHg lower than when measuring pressure using the usual method under the supervision of a physician or a nurse. With that fact in mind, it can be assumed that the values of BP in the SPRINT study would have been approximately 10 mmHg higher if the usual method had been applied, and the limit values for arterial hypertension would have remained at 140/90 mmHg. However, if we follow these guidelines, arterial pressure should be measured by automated devices without the presence of a physician. The new guidelines of the European Society of Hypertension will be presented at this year’s European congress on hypertension, which is to be held in June in Barcelona, and Prof. Jelaković suggested they will not bring about such radical changes in the diagnosis of arterial hypertension. This very interesting presentation, which reminded us of the need to read scientific articles and guidelines with a critical eye, was followed by a lecture on a major problem in the treatment of chronic non-contagious diseases, including hypertension – the perseverance of patients during treatment, held by Dr. Jelena Kos. Although numerous antihypertensive drugs of various classes are available, the percentage of patients suffering from hypertension who adequately regulate their condition is disappointingly low, in Croatia and in the rest of the world, and is approximately 20%. A certain number of patients never even begin their recommended therapies, and the number of those who do take the prescribed medications decreases over time. As expected, perseverance decreases with the increase in the number of prescribed drugs, and apart from the number of pills, perseverance is also affected by the complexity of the therapy, the ways of calculating the dosage of medications, the patient’s perception of taking medications as an additional effort, etc. In order to improve a patient’s perseverance, we should, whenever possible, simplify the recommendations for the therapy and continually work on the education of patients in cooperation with nurses and pharmacists. An increasingly important role is played by technology and other forms of reminding the patient, such as smartphone applications which include the patient in the process of treating hypertension. Dr. Krešimir Đapić presented My Pressure, a Croatian application developed through the cooperation of the Croatian Society of Hypertension and Ericsson Nikola Tesla, which is currently a part of a pilot project. The application will enable users to record and follow changes in BP over time, record medications and dosages, remind patients to take their pills and calculate the total cardiovascular risk, while also containing numerous educational materials and providing daily advice. We expect this application to help patients better regulate their BP. Dr. Josipa Josipović spoke about arterial hypertension in chronic renal patients. In such patients the prevalence of arterial hypertension is extremely high, from 60% to 90%. The target values of BP in chronic kidney disease without albuminuria are st, 2018 ticagrelor has been included on the Basic list of all medication of the Croatian Health Insurance Fund for the treatment of high-risk patients with NSTEMI. There are clear guidelines for the application of a dual antiplatelet therapy regarding the type of medication used and the duration of their usage. Although ticagrelor with aspirin is the basis of modern treatment, due to its availability and price clopidogrel remains one of the most prescribed antiplatelet medications in the world, including Croatia. Since clopidogrel is a drug that transforms into an active metabolite only after entering the body through processes in the liver, its weakened effect in a certain group of patients, determined by a weakened process of drug activation, has been recognized and described. Consequently, laboratory methods for determining the level of thrombocyte activity in a patient’s blood sample have been introduced into clinical use. We stress that the guidelines do not recommend a routine determination of thrombocyte reactivity or the quantification of the thrombocyte inhibition level conditioned by the application of anti-aggregational drugs, but they do enable the use of aforementioned tests in selected patients (5). This was the reason for the creation of a project of the Croatian Science Foundation which tests thrombocyte activity by measuring aggregability in the blood of patients treated with anti-aggregational drugs for a variety of indications, and especially in those with acute myocardial infarction. Research conducted as part of the project has shown that by adjusting clopidogrel dosage in patients with a measured elevated residual thrombocyte activity with a standard clopidogrel dosage can improve clinical outcomes, which is confirmed by the fact that in the aforementioned segment there is a need for additional research with the aim of determining the optimal treatment strategy for patients with acute myocardial infarction (6). Apart from antiplatelet therapy, it is also necessary to understand the need for the application of other drugs in the treatment of patients with acute myocardial infarction. Special attention should be paid to statins – drugs which, according to multicentric randomized studies, significantly improve clinical outcomes for this group of patients. We therefore wish to point out one large international and retrospective registry of patients with acute coronary syndrome: ISAC-TC (International Survey of Acute Coronary Syndromes in Transitional Countries). University Hospital Centre Zagreb also participates in this registry as the sole institution from the Republic of Croatia. ISACS-TC registry enables us to follow classic demographic and anthropometric data, numerous measured clinical variables, and a host of data on comorbidities of included patients. A subsequent sub-analysis of a Croatian group of patients in the registry found that an early application of statins in patients with STEMI (within 24 hours from admittance) significantly lowers in-hospital mortality in comparison with a later start of a therapy based on those drugs (**Figure 2**). Those results are the reason why an additional analysis of all patients included in the registry will be carried out with the aim of testing this very interesting hypothesis. Figure 2. Hospital mortality in Croatian subjects in the International Survey of Acute Coronary Syndromes in Transitional Countries (N=1788) regarding the time of statin administration. In the part of the symposium focusing on arrythmia the results of Croatian electrophysiological centres were presented, with a particular look at the development of the national ablation program. Thanks to significant technological improvements, modern arrhythmology has advanced considerably and raised the treatment strategy for atrium fibrillation, today’s most common clinical heart arrhythmia, to the level of a highly sophisticate treatment. Since the prevalence of this arrhythmia in adult population is approximately 3% (with significantly greater prevalence in the elderly, and especially in patients with diagnosed arterial hypertension, coronary heart disease and/or heart failure), every improvement that leads to a more successful treatment of this clinical entity has great direct implications for everyday clinical practice. After initial scientific articles proved that atrial fibrillation begins with the eruption of electrical impulses in the confluence of pulmonary veins in the left atrium, the development of numerous methods of electrophysiological ablation were initiated with the aim of isolating pulmonary veins and stopping the electrical eruption from spreading to the tissue of atrial myocardia, which interrupts the occurrence and sustention of arrhythmia. On the basis of numerous studies, we now know that catheter ablation of atrial fibrillation is a successful method of preserving sinus rhythm in patients with paroxysmal and persistent atrial fibrillation after an unsuccessful antiarrhythmic therapy. Moreover, new studies show a significant benefit of the invasive form of treatment as a type of primary treatment choice for patients with paroxysmal arrhythmia (7). Ablation treatment for atrial fibrillation has a longstanding tradition in Croatia, with a significant increase in the number of procedures in the last three years (**Figure 3**). In that period, due to an increase in the number of performed procedures, Croatia has surpassed the average of other countries in the region and come closer to leading European countries (**Figure 4**). This advancement represents one of the most significant national clinical cardiological improvements in recent medical history of our country and is surely a sign of similar future trends. Figure 3. Number of atrial fibrillation ablations per year in Croatia. Figure 4. Number of atrial fibrillation ablations per year in Europe. The syndrome of heart failure is certainly an epidemic of modern times. The prevalence of this condition is estimated at 1-2% of total population, while the frequency of this clinical entity among people above the age of 70 surpasses 10% (8). It is especially worrying that, despite the efforts of modern medicine, the 5-year survival rate of such patients remains low and is often significantly lower than in patients with malign diseases (**Figure 5**). However, in the last twenty years great scientific and technological efforts have resulted in a variety of currently available sophisticated pharmacological and non-pharmacological treatment options for this vulnerable group of patients. In the case of the latter, we are primarily referring to modern extracorporeal, short term and implanted, long-term pumps for circulatory support. In the area of treating patients with vital risk and acute heart failure, the short-term support pump V-A-ECMO (veno-arterial extracorporeal membrane oxygenation) that acutely replaces circulatory and respiratory functions is of special importance. At the University Hospital Centre Zagreb, the program for implanting ECMO devices has existed for several years. Although initially used only as surgical therapy (so-called postcardiotomic ECMO – the application of the pump in direct preoperational procedure for the optimization of surgical results), in recent times it is frequently used as a percutaneous cardiological method of ensuring acute stabilization of the hemodynamic and/or respiratory state of the patient, most commonly in the stage of cardiogenic shock following acute myocardial infarction or acute exacerbation of chronic cardiac insufficiency. In the period between the beginning of 2011 and the end of 2017, at the University Hospital Centre Zagreb the V-A-ECMO device was implanted in a total of 66 patients (average age 56.6 years, 47 men). In this period there was a continued increase in the yearly rate of implanted devices (**Figure 6**). The total success rate of the ECMO therapy (defined as a successful removal of the ECMO device due to a recovery in the cardiac function, an implantation of a long-term heart pump, or transplantation therapy) is 54.5%. These results place this program of short-term circulatory support at the University Hospital Centre Zagreb alongside foreign contemporary centres of excellence which, based on data from the ELSO registry (Extracorporeal Life Support Organization) show a success rate of 38-55% (9) for the ECMO therapy. On the other hand, the implantation of long-term, intracorporeal pumps for circulatory support is a method of treating terminal heart deficiency in patients who have, despite optimal medical therapy, acutely damaged functional status and are candidates for transplantation therapy (“bridge to transplantation”). It is also believed that this therapy is a good option in the treatment of patients who are not candidates for transplantation therapy and have a very high rate of mortality without advanced non-pharmacological therapy (“destination therapy”) (7). University Hospital Centre Zagreb is the leading Croatian centre for the implantation of long-term circulatory pumps that support the left ventricle (LVAD – left ventricle assist device). From 2010 to September 2017, a total of 64 patients received these devices, and the 4-year survival rate is 70% (**Figure 7**). Keeping in mind the results from LVAD – INTERMACS, the world’s largest patient registry, which shows the 4-year survival rate of 40%, it is clear that the data from the University Hospital Centre Zagreb represents excellence in the choice, preparation, treatment and monitoring of this group of extremely challenging patients. Figure 5. 5-year survival of chronic heart failure patients in regard to survival of patients with malignant diseases. Adapted from: Eur J Heart Fail. 2001 Jun;3(3):315-22. Figure 6. Number of veno-arterial extracorporeal membrane oxygenation implantations in University Hospital Centre Zagreb per year. Figure 7. Cumulative survival rates in patients with left ventricle assist device in University Hospital Centre Zagreb. Despite remarkable progress and development in the technology of implanted heart pumps, heart transplantation still represents the gold standard in the treatment of terminal heart failure. If we exclude the fact that there are decreasing numbers of donor organs, the main problems of modern heart transplantation lie in immunosuppressant therapy – the limited effectiveness of immunosuppressant drugs and the development of complications after their long-term use. The basis of modern immunosuppressant therapy is the so-called “triple therapy” which includes tacrolimus or cyclosporin, mycophenolic acid, and corticosteroid drugs, and the basis for monitoring after performed transplantation, apart from routine clinical, laboratory, echocardiographic, and functional testing, are certainly regular endomyocardial biopsies of the right ventricle and pathohistological analysis of samples with the aim of detecting cellular and humoral rejection. With this type of therapy and management, patients today have a respectable 5-year survival rate of over 70% (**Figure 8**). University Hospital Centre Zagreb is the larger cardiac transplant centre in Croatia, in which the first heart transplantation was performed long ago, in 1988. In the years after that, on average there were 5 transplantations performed each year at University Hospital Centre Zagreb, and this continued until 2007. That year Croatia became a member of Eurotransplant, which had a direct and significant influence on the transplantation program – the same year the number of performed transplantations increased to 11, and continued to rise in the following decade to at least 20 procedures yearly, which places University Hospital Centre Zagreb alongside leading transplantation centres in the world (**Figure 9**). Figure 8. Cumulative survival rates in pediatric and adult patients after heart transplantation. Adapted from the ISHLT International Registry for Heart and Lung Transplantation; https://www.ishlt.org/registries/slides.asp?slides=heartLungRegistry. Figure 9. Cumulative survival rates in patients after heart transplantation in University Hospital Centre Zagreb.

Krešimir Kordić, Nikola Kos, Nikola Bulj, Matias Trbušić, Ivo Darko Gabrić, Ozren Vinter, Igor Rudež, Diana Delić-Brkljačić

**Background**: Corynebacteria species are non-fermentous Gram-positive bacilli considered part of a human skin and mucos membranes flora and are commonly isolated in clinical specimens. They are not recognized as common cause of endocarditis. (1-3) We report a case of native mitral valve infective endocarditis caused by Corynebacterium spp. **Case report**: 45-year-old male with a history of spinal cord injury and paraplegia presented with a 20-day history of fever and fatigue. Before starting antibiotics, multiple blood samples were taken and Corynebacterium spp was isolated. Due to unknown source of infection and a new systolic heart murmur, a transesophageal echocardiography was performed, showing severe mitral regurgitation with two mobile hypoechogenic masses on the anterior and posterior mitral valve leaflets, 11x5 mm and 6x5 mm, respectively. According to antibiogram, vancomycin was administered, and the fever subsided. The patient was transferred to a Cardiac Surgery Department, where he underwent mitral valve replacement (On-X M 25/33). The resected vegetation was culture-negative. Postoperatively, pericardiocentesis was performed due to increasing pericardial effusion. Afterwards, the patient was discharged and presented free of infection and without pericardial effusion at the two-month follow up. **Conclusion**: According to available data, there is a growing incidence of non-diphtheriae Corynebacterium endocarditis, particularly as a part of nosocomial infections or in immunocompromised patients. In most of the cases the affected valve was mitral or aortic, mostly affecting native valves. There is high incidence of multiple résistance to standard antibiotics in Corynebacterium causing endocarditis. We presented a case of native mitral valve infective endocarditis caused by Corynebacterium spp.

Siniša Roginić, Krešimir Štambuk

**Introduction:** Mitral stenosis (MS) indicates elevation of transvalvular diastolic pressure gradient which is the most often caused by rheumatic heart disease. Congenital mitral stenosis is far less common, especially in adult population. (1-3) Management of those patients is challenging due to lack of data. **Clinical case**: We present a case of 29-year-old patient with known significant allegedly rheumatic mitral stenosis scheduled for percutaneous mitral balloon valvuloplasty (PMBV). After additional workup we have reclassified stenosis as moderate, caused by attachment of chordae to a single papillary muscle - defect known as a parachute mitral valve. It is the least common form of congenital MS, usually accompanied by the other left sided outflow lesions (Shone complex). Our patient had an isolated form. She was completely asymptomatic, although planning pregnancy which is hemodynamic challenge, even with a moderate MS. Patient was definitely discouraged from PMBV and referred to adult congenital heart disease center for another opinion. **Discussion:** We will discuss treatment options for women of child bearing potential with congenital mitral stenosis. Congenital form of MS in adult population is a very rare disease which challenges our knowledge based mainly on managing rheumatic MS. **Conclusion**: Define of etiology end severity of valvular lesion is essential, especially when invasive management is planned.

Petra Grubić Rotkvić, Jozica Šikić, Edvard Galić, Jasna Čerkez Habek, Zrinka Planinić

**Background**: Appropriate timing of surgery in asymptomatic severe primary mitral regurgitation (MR) remains challenging. According to the guidelines, surgery is recommended for patients with symptomatic severe primary MR or those with asymptomatic left ventricular (LV) systolic dysfunction, new-onset atrial fibrillation and pulmonary arterial hypertension (1). **Case report**: 40-year-old male came to our Echo Lab because of a heart murmur. He had no previous health problems and no disturbances in his daily activities. Myxomatous mitral valve degeneration with prolapse of the posterior leaflet and severe MR was found (**Figure 1**). No additional echo findings that would indicate surgical intervention were detected (LVESD was 34 mm, LVEF 65%, RVSP 30 mmHg, no significant LA enlargement). He was in sinus rhythm. We also measured left ventricular global longitudinal strain (LV-GLS) and preformed an exercise stress testing to assess his functional capacity with addition of echocardiographic measurement of RVSP during peak stress. He achieved 100% of predicted METs with no worsening of RVSP and LV-GLS was -24% (**Figure 2**). Based on the above-mentioned findings, we decided to follow-up the patient. Figure 1. Mitral regurgitation. Figure 2. Strain analysis. **Discussion:** Clinicians and patients often choose to postpone valve surgery as long as justified. This “watchful waiting” approach is dictated by a timely identification of LV dysfunction. Ejection fraction and end-systolic dimensions are affected by the altered loading conditions in MR and can remain falsely normal despite underlying myocardial dysfunction (2). New parameters capable of detecting onset of LV dysfunction earlier could help discriminate the higher risk patients. Current European guidelines state that the use of LV-GLS could be of potential interest and determination of functional capacity may be useful, but there are no exact recommendations (3). In the study of Mentias et al., reduced exercise capacity and worsening LV-GLS were associated with mortality providing additive prognostic utility (1). Maybe the detection of the relative change of GLS from baseline rather than an absolute cut-off value as in cardio-oncology could be helpful. **Conclusion**: We are still looking for an optimal timepoint when we should operate patients with asymptomatic severe primary MR. Further investigations are required.

Antun Lončarić, Valentina Kršić, Andrea Kresović, Alen Ružić, Luka Zaputović, Teodora Zaninović Jurjević

**Background**: Infective endocarditis (IE) is an infection of heart valves endocardium or an endocardial surface elsewhere, caused by microorganisms. The aim of our research was to present the clinical and epidemiological profile of patients with a diagnosis of the IE, hospitalized and treated at the University Hospital Centre Rijeka in the period from January 2012 to January 2017. **Methods**: We performed a retrospective study and 74 patients with the diagnosis of IE were identified in a five year period. Duke criteria were used for diagnosis. The study was based on data from the Department for Cardiovascular Diseases, Internal Medicine Clinic, University Hospital Centre Rijeka. All patients signed informed consent. **Results**: Out of a total of 74 identified patients, 29 were women (39.19%) and 45 men (60.81%). The average age of patients was 72 (32-88) years, while the average duration of hospitalization was 25 days. At admission, high fever was present in 52.70% of cases. Hemoculture was positive in 83.56% of cases. S. aureus (24.59%) and E. faecalis (24.59%) were most frequently isolated pathogens in blood cultures. 93.24% of patients had echocardiographic visible vegetation. Most common, the infection was located on aortic (40.54%) and mitral valve (40.54%). The tricuspid valve was affected by 4.05% (n = 3) cases, while simultaneous involvement of the aortic and mitral valve was present in 8.11% (n = 6) cases. The most commonly reported was mitral regurgitation 74.32% (n = 55), then tricuspid 70.27% (n = 52) and aortic regurgitation 55.41% (n = 41). In 28.38% of patients prosthetic heart valve was infected. The most common comorbidities were: arterial hypertension (64.86%), anemia (51.35%), and diabetes mellitus (36.49%). Hospital mortality rate was 12.16%. **Conclusion**: According to our research, patients were predominantly older (72 years), with numerous comorbidities. IE is a serious illness with high mortality. Given the large number of afebrile patients, IE should be considered even in those who do not show signs of infection, so we could diagnose it earlier, with the earliest start of proper treatment of this disease.

Mira Stipčević

The tricuspid valve (TV) is very often neglected in routine echocardiographic examination. It is important to understand that tricuspid value dysfunction is influential in patient outcomes (1). The most often seen TV pathology is tricuspid regurgitation (TR). The presence of mild TR is physiologic in 65-100% of the population (2). More than mild regurgitation is suspicious for tricuspid valve disease. Functional TR is the most frequent etiology. It is secondary to poor tricuspid leaflets coaptation due to dilatation of tricuspid annulus and right chambers secondary to left sided heart disease or pulmonary disease (3). Organic tricuspid valve disease (regurgitation or stenosis) can be due to rheumatic heart disease, endocarditis, carcinoid heart disease or congenital heart disease. The presence of pacemaker or intracardiac defibrillator, as well as repeated right ventricle biopsies in transplanted patients can lead to tricuspid trauma and TR**3**. Functional TR, resulting from left sided disease, can be significantly influenced by hemodynamic factors, and most often would not resolve after correction of the underlying pathology. It is essential to preform TV evaluation (morphology and function) in patients planed for cardiac surgery on a high quality transthoracic echocardiography and make decision whether TV warrants operative attention (4). Whilst the surgical management at the extremes of TR (mild or severe) is relatively clear, the ideal intervention in intermediate grades, especially during concurrent left sided surgery remains uncertain and is the subject of ongoing research.

Boško Skorić

Tricuspid valve regurgitation is the most frequent valve disease after heart transplantation (HTx) (1). Post-transplant tricuspid valve regurgitation ranges in different severity but the majority are of no clinical importance. There are many causes of tricuspid valve regurgitation and they are related to the time of diagnosis after the surgery. In the early post-transplant period, tricuspid valve regurgitation is usually secondary to pulmonary hypertension, i.e. increased pulmonary vascular resistance. Most of tricuspid valve regurgitation in the late phase is secondary to tricuspid annulus enlargement due to right ventricular remodeling and dilatation (2). Other frequent causes are lesions of valve apparatus during right ventricular endomyocardial biopsy, acute graft rejection and the alteration of right atrial morphology due to the surgical technique. Medical management of clinically significant tricuspid valve regurgitation in heart transplant patients is the standard therapy. Surgical correction is indicated in properly selected patients who are refractory to medical treatment alone.

Ivana Jurin, Dubravka Šušnjar, Josip Varvodić, Igor Rudež, Frane Paić, Irzal Hadžibegović

**Background**: Patients with preserved left ventricular ejection fraction (EF) and aortic stenosis have often increased global longitudinal strain as a sign of intrinsic left ventricular impairment. Heart failure due to left ventricular deformation is also shown to be predicted with simple blood count test like red cell distribution width (RDW). We evaluated the correlation of GLS and RDW patients with different severity stage of aortic stenosis and signs of left ventricular strain. **Methods**: We recorded relevant clinical, laboratory, and echocardiographic parameters, and measured global longitudinal strain (GLS) in 83 patients with EF > 45% and mild, moderate, and severe aortic stenosis (AS) in whom coronary artery disease was previously excluded. GLS was obtained using 2D speckle tracking echocardiography. RDW was easily obtained from full blood count that is routinely measured. **Results:** Mean velocity and aortic valve area was 2.73 m/s and 1.72 cm2, 3.37 m/s and 1,33 cm2, and 4.62 m/s and 0.74 cm2 in patients with mild, moderate and severe AS, respectively. Mean GLS was -18.82%, -17.7% and -16.85% in patients with mild, moderate and severe AS, and did not differ significantly. Patients with severe aortic stenosis had significantly higher left ventricular mass index and NT-pro BNP levels compared to patients with mild and moderate AS (186.66 g/m2 vs 133.57 and 169.57 g/m2, and 2644.69 pg/ml vs 312.71 vs 403.2 pg/ml, respectively). Among patients with mild aortic stenosis regression analysis showed significant positive correlation of GLS with RDW (beta 0.590, R square 0.34, p=0.005). That correlation was not confirmed for GLS and NT-pro BNP. **Conclusion**: GLS did not differ significantly among patients with different severity of AS, although patients with severe AS had highest values of GLS. Among patients with moderate AS, RDW showed to be a good predictor of impaired left ventricular function measured by GLS, and therefore it could be further evaluated as a tool in early selection for treatment of patients with moderate AS, preserved EF and no coronary artery disease.

Ivana Jurin, Dubravka Šušnjar, Josip Varvodić, Igor Rudež, Frane Paić, Irzal Hadžibegović

**Background**: Strain imaging is an established method for the accurate quantification of left ventricular function and left ventricular global longitudinal strain (GLS) has been shown to be a superior marker of contractility than ejection fraction (EF), and also a good marker for prognosis of patients with aortic stenosis (AS). We prospectively analyzed GLS in context to other relevant clinical parameters in patients with severe aortic stenosis and preserved EF. **Patients and Methods:** We preoperatively measured GLS in 42 patients with EF > 45% and severe AS. GLS was obtained using 2D speckle tracking echocardiography and patients were divided into four groups according to GLS quartiles. Relevant clinical and echocardiographic parameters were analyzed in relation to GLS, together with curve estimation regression analyses using GLS as independent variable. **Results:** In all, mean EF was 59.3% (SD 8.4%) and mean aortic valve area (AVA) was 0.74 cm2 (SD 0.17 cm2). Mean GLS was -16.85% (SD -3.58%) with four groups of patients according to quartiles. Group 1 consisted of 12 patients with mean GLS -20.46%, group 2 of 11 patients with mean GLS -18.85%, group 3 of 10 patients with mean GLS -15.43%, and group 4 represented 8 patients with mean GLS -10.67%. Among many clinical and echocardiographic parameters analyzed, groups differed significantly only by eGFR with group 3 having the lowest value (Kruskal Wallis, p=0.034). Curve estimation regression analysis using GLS as independent variable showed only statistically significant negative correlation of GLS with AVA (beta -0.347, R square 0.12, p=0.026). Left atrial volume index (LAVI) showed nearly significant positive correlation with GLS (beta 0.283, R square 0.08, p=0.06) whereas other parameters showed insignificant correlation. **Conclusions**: Almost one third of patients with preserved EF and severe AS have impaired left ventricular function measured with GLS. AVA and LAVI showed to be good predictors of impaired global ejection fraction. GLS should be used as an additional marker of left ventricular disfunction in all patients with severe aortic stenosis in order to select asymptomatic candidates for early treatment.

Mario Sičaja

Aortic valve stenosis is the rather common acquired valve disease in the developed world. As a conundrum in treatment of patients with severe aortic stenosis, classified as intermediate- and high-risk, transfemoral or transapical aortic valve implantation (TAVI) has emerged. The TAVI approach has been shown to be superior to standard medical treatment in patients classified as high-risk (Euroscore II and STS), and non-inferior to surgical aortic valve replacement in intermediate risk group (1). A successful program depends on multiple variables such as appropriate patient selection that is based on so-called ‘Heart Team’, careful planning and good quality control of maintaining high standards during and after the procedure (2). Once a TAVI program is in place, it is necessary to have performance monitoring measures in order to recognize weaknesses of the program as well as to improve procedure outcomes. This short lecture focuses on fundamentals of running a TAVI program with some reflections regarding the current situation in Croatia.

Valentina Faletar Živković, Petra Zebić-Mihić, Marul Ivandić, Lana Maričić, Kristina Selthofer-Relatić, Sandra Makarović

**Introduction**: Mitral valve prolapse (MVP) is a condition in which one or both mitral flaps of the mitral valve (MV) do not close smoothly or evenly, but instead bulge (prolapse) upward into the left atrium. It is relatively rare (frequency is 1-2%), and the highest percentage of patients is asymptomatic. Only a small number of patients reported palpitations, anxiety, tiredness, and atypical chest pain. An echocardiogram is a “gold standard” in diagnosing this disease. Complications are rare, and the most common and most important is mitral regurgitation. Asymptomatic patients should not be treated. Symptomatic patients need to be closely monitored clinically and ultrasonically, and surgical reconstruction of valves is considered in patients with severe mitral regurgitation (1, 2). **Case report**: 52-years-old female patient has heart murmur since childhood but so far has not been cardiologically treated. A few months ago, she felt chest pain spreading to her neck and intolerance of physical activity. The complete prolapse of the posterior MV has been diagnosed by echocardiography, with the suspected rupture of the chord, severe mitral insufficiency, consequently significant dilated left atrium, initially dilated left ventricle with still preserved left ventricular systolic function (LVEF 54%), and the signs of moderate pulmonary hypertension. Cardiac surgery was performed in our centre because of patient preference, and a mitral valve was replaced. Control echocardiography showed adequate position mechanical mitral valve with the non-parabolic flow and preserved systolic function of (LVEF 53%). On a follow-up visit the patient was subjectively well, without symptoms. **Conclusion**: Mitral valve prolapse is usually asymptomatic condition that requires no treatment and only needs to be monitored. It occasionally causes serious complications in form of mitral regurgitation that can lead to congestive heart failure. Those patients require medical treatment which includes oral medications or, in case of severe mitral regurgitation, mitral valve repair or surgical replacement. Early detection and periodic monitoring are recommended.

Tomislava Bodrožić Džakić Poljak, Jasmina Ćatić, Ivana Jurin

**Introduction:** Secondary, ischemic mitral regurgitation (MR) is still common complication of acute myocardial infarction (MI), and the definition of ischemic MR is MR that occurs after MI with consequent, segmental wall motion abnormalities with structurally normal valve leaflets and chordae tendineae. Most common reason of ischemic MR is posterior papillary muscle disfunction due its blood supply from only one artery – posterior descending branch. **Case report**: 60-years-old female with previous history of arterial hypertension presented to emergency department (ED) because of chest pain. She complained that she had chest pain for about 2 weeks, precipitated by exercise, lasting up to 10 minutes. The day she came to the ED she had severe chest pain, lasting for 16 hours continuously. Her initial electrocardiogram showed no signs of ischemia or infarction. Due to high levels of troponin, creatine kinase, lactate dehydrogenase and regression of chest pain she was, initially, treated medicamentously. At day first of hospitalization echocardiography showed mild mitral regurgitation, mild left atrial dilatation (43mm), akinetic posterior and inferior wall, hypokinetic lateral wall and ejection fraction (EF) about 45%. Few days later, patient presented with heart failure (HF) (Killip III), soon after and Killip IV. After initial stabilization with vasopressors and inotropes coronary angiography was performed. In subtotal stenosis of proximal segment of circumflex artery and subtotal stenosis of proximal segment of right coronary artery were implanted stents. Echo showed severe mitral regurgitation (**Figure 1**) with elements of elevated pressures in pulmonary circulation (**Figure 2**), and EF about 30%. After 45 days patient left home with medical therapy according to guidelines for heart failure treatment. In following months she became „frequent flyer“ HF patient, with rapid progression of left ventricular dysfunction (**Figure 3**) and consequent right ventricular dysfunction (**Figure 4**) and soon after she died. Figure 1. Severe mitral regurgitation, vena contracta 8mm, ERO 0.4 cm2. Figure 2. Indirect signs of elevated pressures in pulmonary circulation. Gradient across the tricuspid valve is about 60 mmHg, and right ventricular systolic pressure about 70 mmHg. Figure 3. Progression of left ventricular dysfunction (PLAX), dilatation of ventricle and EF about 25%. Figure 4. Progression of (indirect) pulmonary hypertension, gradient across the tricuspid valve above 100 mmHg. **Conclusion:** „Time is myocardium and myocardium is time“. If our patient came earlier in the hospital, percutaneous coronary intervention at the right time could prevent severe myocardial damage, ischemic MR with rapid progression of heart failure and death.

Kristina Marić Bešić, Maja Strozzi, Željko Baričević, Vlatka Rešković Lukšić, Jadranka Šeparović Hanževački, Margarita Brida

Congenital anomalies of the mitral valve may be isolated lesions or associated with other complex congenital heart defects. Each level of the mitral valve can be affected from the annulus, leaflets, chordae tendineae and papillary muscles. Isolated mitral stenosis is one of the rarest form of congenital heart disease (0.6%) but can be associated with other left side abnormalities (1). Most cases of mitral stenosis are diagnosed in early childhood leading to mitral valve repair or replacement. Unoperated congenital mitral stenosis in an adult will be limited to rather mild or moderately severe stenosis with symptoms and complications identical to rheumatic mitral valve disease. Mitral valve regurgitation due to primary mitral valve prolapse has a prevalence of 2.4% and is the most frequently diagnosed cardiac valvular abnormality. It occurs mostly as an isolated valve dysfunction but can be associated with connective tissue diseases or other cardiac abnormalities. Echocardiography is the definite diagnostic method for congenital mitral valve anomalies but in presence of multiple lesions, hemodynamic assessment by cardiac catheterization can be useful. To emphasize that the management of adult patients with congenital mitral valve disease can be challenging we present two patients. The first is 24-year-old female patient with a mechanical mitral valve who was operated in childhood because of mitral regurgitation. She has reduced left ventricular ejection fraction and her pregnancy was complicated with AV nodal reentry tachycardia requiring electrophysiology and catheter ablation before and after childbirth. The second patient is 30-year-old female with a parachute mitral valve. Stress echocardiography revealed severe mitral stenosis which presents a contraindication for her planned pregnancy. In conclusion, the decision for medical management or the need and timing of surgical intervention in these patients must be made according to clinical presentation, symptoms and noninvasive or invasive evaluation.

Jozica Šikić, Dario Gulin, Leon Adrović, Tomislav Mihaljević

**Background**: So far, no percutaneous nor cardiac surgical intervention did not present with significant and apparent long-term graft patency preventing and treating coronary artery bypass graft (CABG) restenosis at the site of the anastomosis (1). A process of restenosis, mainly driven by intimal hyperplasia, with abnormal migration and proliferation of smooth muscle cells, has many characteristics of inflammation like process. Proliferating tissue reaction after aortic valve replacement (AVR) at the site of coronary ostia may be due to traumatic consequence, debris embolization or edematous reaction (2, 3). Young patients are in undesirable position. **Case report**: 34-year-old man was admitted in 2007 in a local hospital due to bicuspid aortic valve endocarditis due to Streptococcus sp “D”, proceeding with biological AVR. One month after the surgery, due to recurrent endocarditis presenting with paravalvular leak and severe aortic regurgitation, reoperation was performed with the implantation of the mechanical valve. Two years later symptomatic severe paravalvular aortic regurgitation and severe mitral regurgitation due to the prolapse of the anterior cusp led to invasive diagnostic approach. Coronary angiography revealed subtotal restenosis of the left main coronary artery ostium. In September 2009, simultaneous third time redo was performed with replacement of the aortic root with the homograft, mitral valve repair with a pericardial patch of a perforation of the A2 segment, medial commissuroplasty with the insertion of Cosgrove ring, CABG with saphenous vein graft (SVG) to obtuse marginal (OM) and SVG to left anterior descending artery (LAD). Two years later, occluded anastomosis of a SVG to LAD and significant restenosis of a SVG to OM (both at the site of anastomosis), led to re-CABG of LAD with left internal mammary artery (LIMA) and repositioning of a SVG to OM. In 2017, coronary angiography showed significant restenosis of the LIMA-LAD graft anastomosis and SVG-OM graft. **Discussion**: Young patients present with intensive immunological reaction leading to CABG anastomosis or valvular junction stenosis. This patient demonstrates not only challenges in treating endocarditis, redo interventions and complications of valvular disease per se but also impediments in coronary artery supply.

Petar Pekić

**Background**: The incidence of bradyarrhytmias after cardiac surgery is approximately 15%. Approximately, 3-5% of patients undergoing a valvular surgical procedure require the installation of a permanent electrostimulator prior to hospital discharge (1). **Discussion**: Calcificating aortic valve disease is recognized as the cause of an atrioventricular (AV) block. Valvular interventions related to the repair of the perimembraneous septum represent the risk of AV block formation, which is therefore the most common bradyarrhythmia that can be associated to the surgical procedure. The block at or below the bundle of Hiss results in more permanent forms of the AV block which often implies the insertion of an electrostimulator. Surgical aspects that carry the risk of a persistent postoperative AV block are related to multiple valve operation at one and the same time, „re-do“ operations and prolonged time to the cardiopulmonary bypass (2). Of all valves, the replacement of the tricuspid valve alone or in combination with the intervention on the second valve carries the highest risk of the AV block. In one study, the pre-existing right branch block was a better predictor of the postoperative AV block than the left branch block. Preoperative PQ prolongation and age over 70 were additional predictive factors. A smaller percentage (about 10%) of bradyarrhytmias after valvular surgery is due to dysfunction of the sinus node and the „tachy-brady“ syndrome with atrial fibrillation episodes. Sinus node dysfunction has a better prognosis compared to the AV block. The fact that the conduction system in some cases still recovers has led to today’s practice of imaging an electrostimulator, which is delayed up to 10 days after the valve operation. Non-surgical, percutaneous valvular interventions do not benefit in the prevention of post-operative bradyarrhytmias. On the contrary, the transcutaneous aortic valve replacement (TAVR) has a higher incidence of AV block compared with the open-heart surgery. Approximately, 15-20% patients require implantation of the electrostimulator in the early postoperative period (3-5). **Conclusion**: Technological improvements in the artificial valves design and setting technique in relation to the root of the aorta could lead to a reduction in incidence of damage to the conduction system immediately after the operation. Regardless, the progressive nature of the congenital system disease associated with chronic valvular disease is unlikely to be slowed down by surgical relief of valve disease due to its multifactorial pathophysiology and progressive fibrosis.

Edvard Galić, Vera Slatinski, Ante Pašalić, Marko Perčić, Zrinka Planinić

**Background:** Mitral regurgitation (MR) represents the second most common valvular heart disease. It is classified as primary (organic) and secondary (functional) MR, with secondary being more frequent. Degenerative vavular disease, rheumatic fever, infective endocarditis and mitral valve prolapse are most common causes of primary MR. On the other hand, secondary MR is usually result of ischaemic heart disease or dilatative cardiomyopathy. Furthermore, according to haemodynamic echocardiographic parameters MR is classiffied as mild, moderate and severe (1). Treatment modalities include surgery and medications. Mitral valve repair and replacement represents the way of treating symptomatic severe MR, while medications have a role to prevent or slowing down the progression of mitral valve cusps degeneration and left ventricular remodelation (1). **Discussion:** Among medications, beta-blockers, angiotensin converting enzyme inhibitors, aldosterone antagonists, calcium channel blockers are widely used for treating patients who are symptomatic, have decreased left ventricle systolic function and waiting for surgery or have contraindication for surgery (2). It has been showed that beta-blockers reduce MR, prevent further deterioration of left ventricular systolic function in patients with primary MR**2**. Beta-blockers improve left ventricular function in chronic degenerative mitral regurgitation. Also, they improve NYHA functional class and left ventricular volumes in those with rheumatic mitral valve disease (3). Angiotensine converting enzyme inhibitors (ACEI) and angiotensin receptor blockers (ARBs) reduces regurgitant volume and left ventricular size, mass and volumes in patients with primary MR2. Renin-angiotensin system inhibitors improve survival rate in patients with secondary MR due to ischaemic heart disease (3). Nitrates reduce left ventricular end diastolic and systolic volumes thereby reducing ventricular dilatation, while calcium channel blockers reduce regurgitant volume (2). **Conclusion:** Optimal medication prevents left ventricular function worsening, improves NYHA functional class and survival rate. All above mentioned recommentadions are based on small studies, different patient populations, patients using other cardioactive drugs, so further investigations should be done.

Vera Slatinski, Ante Pašalić, Marko Perčić, Zrinka Planinić, Edvard Galić

**Background**: Mitral valve prolapse (MVP) is a common disorder, affecting 2-3% of general population, characterized by myxomatous degeneration of mitral valve cusps (1). It is a progressive disease which may lead to severe mitral regurgitation (MR), increase in the mitral annular diameter, left atrial enlargement, atrial fibrillation, thromboembolic events, left ventricular dysfunction, heart failure and sudden cardiac death (1). Therapeutic modalities for treating severe MR include mitral valve repair and replacement (2). Following surgical treatment possible complications include infective endocarditis, sepsis, thromboembolic events, hemorrhage, artificial valve failure, pericardiotomy syndrome etc. Mitral valve repair, when compared to mitral valve replacement, shows lower mortality rate, therefore guidelines recommend it as the method of treatment. It is also important to notice that mitral valve repair shows lower rate of infective endocarditis (3). **Case report**: In this article we present a case of young woman who had mitral valve prolapse with severe symptomatic MR. After mitral valve repair was performed, patient developed Staphylococcus epidermidis endocarditis (and consequential sepsis), which was verified via transthoracic and transesophageal echocardiography. After developing anaphylactic reaction to vancomycin and DRESS syndrome on teicoplanin and rifampicin, antibiotic therapy was changed to fosfomycin and ciprofloxacin. Additionally, postcardiotomy syndrome was present. Control echocardiography showed a loose, flotation mass with a thin pedicle, connected to the basis of anterior mitral cusp, on the atrial side, 12x8 mm in diameter. Due to its high embolic potential, in consultation with cardiac surgeon, mitral valve replacement was done, and mechanical artificial mitral valve was implanted. Following the procedure, patient fully recovered. **Conclusion**: MVP is progressive disease which can result in severe MR requiring surgical treatment. As mitral valve repair shows lower mortality rate in this case it was surgical treatment of choice. Unfortunately, our patient developed infective endocarditis, sepsis and postcardiotomy syndrome, which required prolonged hospitalization. Complex antibiotic therapy led to clinical recovery, but because of floating mass with high embolic potential, we opted for reoperation.

Ivana Lukić, Kristina Vučković, Marko Stupin, Lana Maričić, Kristina Selthofer-Relatić, Sandra Makarović

**Introduction**: Infective endocarditis is an acute condition with very high mortality. It is typically a bacterial infection and often affects heart valves. Duke criteria which should be fulfilled to establish the diagnosis of endocarditis, rely on echocardiography (1). **Case report 1:** 63-year-old patient with history of posterior mitral valve prolapse and, consequently, a severe mitral insufficiency, for which an operational treatment is planned, was hospitalized at the Clinic for Infectious Diseases for fever with characteristic features of sepsis. Staphylococcus aureus was isolated from blood culture and there was a suspicion of insufficient mitral valve endocarditis. A transthoracic ultrasound of heart was done and a mass which seemed to be vegetation on the prolapsed back mitral valve was verified and confirmed by a transesophageal echocardiography. The patient was treated parenterally with antibiotics according to the antibiogram, after which a clinical improvement followed. After the improvement of the inflammation and the preoperative treatment, the patient was subjected to cardiac surgical replacement of the mitral valve with a mechanical prosthesis. **Case report 2**: 58-year-old male patient was admitted to emergency room with severe pulmonary edema, fever, respiratory insufficiency and sepsis. Four months before, mitral valve was replaced by mechanical prostheses because of severe primary mitral regurgitation. A transthoracic echocardiogram showed prolapse of posterior cusp in left atrium and severe eccentric mitral regurgitation without clear vegetation on prosthetic mitral valve. Empirical antibiotic therapy was immediately started. Urgent reimplantation of mechanical mitral valve was done by the cardiac surgery team. Intraoperative mitral valve analysis showed a suture dehiscence of the prosthetic mechanical mitral valve. Microbiological samples and blood culture were sterile. During the postoperative monitoring, atrial fibrillation with total atrioventricular block was founded, and cardiac pacemaker was implanted. **Conclusion**: We presented endocarditis based on prolapse of mitral valve and endocarditis of artificial mechanical mitral valve. In both cases a surgical replacement of mitral valve was performed, while in second case urgent surgery was done.

Nikola Bulj

Echocardiography is the primary imaging method for diagnosing mitral regurgitation (MR) and determining the timing and method of treating this valve disorder. Modern techniques for treating MR are setting new challenges requiring echocardiographic assessment to define surgical or interventional treatment strategies, give clear insight in the anatomy and mechanism of MR, as well as the evaluation of pathophysiological and hemodynamic consequences (1). During echocardiogram, cardiologist has to determine a few important parameters not only to assess the severity of mitral regurgitation, but to describe the mechanism itself using well-known Carpentier’s functional classification, which categorizes MR into four types. Furthermore, in order to determine optimal timing for treating patients with MR, echocardiogram must contain information about the consequences of left atrial and left ventricle volume overload, along with the function of right ventricle and pulmonary circulation. It is important to note that standard transthoracic and Doppler echocardiography provides above mentioned information in the majority of patients. Transesophageal echocardiography should be used in addition to transthoracic echocardiography, primarily to get more details about the anatomy, reparability and functionality of mitral valve (2). In that regard, it is necessary to define all mitral leaflet segments, commissures and subvalvular apparatus, where three-dimensional transesophageal echocardiography can be of great help. Advanced echocardiographic techniques, including strain imaging, provide significant information, especially in patients with preserved left ventricular systolic function, but present subclinical myocardial injury, which can affect the decision about earlier surgical treatment.

Zrinka Planinić, Marko Perčić, Ante Pašalić, Tea Friščić, Dario Gulin, Leon Adrović, Dijana Bešić, Jozica Šikić

**Background**: Mitral regurgitation (MR) is often complicated with atrial fibrillation (AF), with estimated rate of 5% per year. Patients with both MR and AF have higher risk of cardiac events (1). The aim of our study was to investigate how many of patients with MR have AF, and is there any correlation with the severity of MR and AF occurrence. **Patients and Methods:** Retrospective study was conducted to investigate frequency of AF in patients with MR. A total number of 686 patients were included, 45% were female. The prevalence of arterial hypertension, diabetes mellitus, hyperlipidemia were similar between men and women. When compared to women, men smoke more frequently. On the other hand, women had higher serum uric acid levels. **Results**: Atrial fibrillation was found in 44% of patients with MR. Almost half of women (49.5%) and 39.5% of men with MR had AF. Paroxysmal AF was present in 38.7%, and permanent in 27.4% of patients with MR. 45% of patients had mild, 36.4% had moderate, and 18.6% had severe MR. 25.5% of men and 18.3% of women had concomitant AF and severe MR. Mitral regurgitation was associated with AF and coronary artery disease in 16.2% of cases, with 53% having mild MR. **Conclusion**: Atrial fibrillation can often be found in patients with mitral regurgitation. Mild MR was more often associated with AF occurrence, as well as in patients with both AF and CAD.

Ante Pašalić, Leon Adrović, Tea Friščić, Zrinka Planinić, Marko Perčić, Dario Gulin, Dijana Bešić, Jozica Šikić

**Background**: Mitral regurgitation (MR) represents the second most common valvular heart disease (VHD), with incidence of 24% (1). 10,4% of patients have two and 0.8% three or more concurrent valvular heart disease (1). MR can be isolated or associated with other valvular heart disease, most commonly with tricuspid regurgitation (2). In this article we represent data from our centre. **Patients and Methods:** Retrospective study was conducted to assess the relation between MR with other VHD. A total of 686 patients, with male predominance of 55%, were included in the study. The patients were divided into four groups according to the number of valvular diseases: two, three and four valvular diseases. **Results:** Among the patients with two valvular disease, the most common combination was MR and tricuspid regurgitation (TR) (50.58%). Among the patients with three valvular disease, the combination of MR, aortic regurgitation (AR) and TR was the most common. (17.78%). Finally, four valvular disease was found in 5.98% of patients. In both men and women with two valvular disease, MR and TR, was most frequently found (44.3 and 58.3%) in contrast to MR and AS which was least common combination (16.7 and 26.2%) in both men and women. When it comes to three valvular disease combination of MR, aortic stenosis (AS) and AR or MR, AS and TR was almost the same. **Conclusion**: Our results match the above-mentioned results in general population. MR was most commonly associated with TR. In three valvular disease combinations of MR, AR and TR was the most common in both gender.

Marko Perčić, Zrinka Planinić, Ante Pašalić, Tea Friščić, Dario Gulin, Leon Adrović, Dijana Bešić, Jozica Šikić

**Background**: Mitral regurgitation (MR) represents the second most common valvular heart disease (VHD) (1). It is classified as primary (organic) and secondary (functional) MR, with secondary being more frequent (2). Secondary MR is usually result of dilatative cardiomyopathy, ischemic heart disease, postmyocarditis and similar (2). Its prevalence is approximately 1.6% to 19.4%, and is associated with worse prognosis than primary (3). The aim of our study was to investigate the incidence of secondary MR according to gender. **Patients and Methods**: Retrospective study was conducted to assess the relation between MR with other VHD. A total of 686 patients, with male predominance of 55%, were included in the study. **Results**: Among all patients with MR 167 (24.3%) had secondary MR. The main cause was left ventricular enlargement with mitral annular dilatation, counting for 96 (57.5% of secondary MR patients and 14.0% of all MR patients). Other causes of secondary MR included ischemic and postmyocarditis causes, with frequency of 64 (38.3% of secondary MR patients and 9.3% of all MR patients) and 7 (4% of secondary MR patients and 1% of all MR patients), respectively. According to gender distribution, 99 (59.3%) males and 68 (40.7%) females had secondary MR. Dilatative cardiomyopathy was the main cause of secondary MR in both men and women (60.6% and 52.9%). Ischemic MR was present in 36 (36.4%) men, 28 (41%) women, while postmyocarditis MR was observed in 3 (3%) of men and 4(5.8%). **Conclusion**: Secondary MR presents high proportion of all MR causes. Dilatative cardiomyopathy was most common cause of secondary MR, regardless of gender groups, with men more affected. Ischemic cause was slightly more common in women than men.

Dario Gulin, Ante Pašalić, Zrinka Planinić, Marko Perčić, Tea Friščić, Leon Adrović, Dijana Bešić, Jozica Šikić

**Introduction:** Mitral regurgitation (MR) represents the second most common valvular heart disease (1). It is classified as primary (organic) and secondary (functional) MR, with secondary being more frequent (2). Degenerative valvular disease, rheumatic fever, infective endocarditis and mitral valve prolapse are most common causes of primary MR**2**. On the other hand, secondary MR is usually result of ischemic heart disease or dilatative cardiomyopathy (2). The aim of our study was to investigate the incidence of primary MR according to gender. **Patients and Methods:** Retrospective study was conducted to assess the relation between MR with other VHD. A total of 686 patients, with male predominance of 55%, were included in the study. **Results:** Among all patients with MR 519 (75.6%) had primary MR. Degenerative valvular heart disease was the main cause of primary MR, counting for 474 patients (91.3%). Other causes of primary MR included mitral valve prolapse, rheumatic valvular heart disease, and other causes, with frequency of 19 (3.6%), 5 (1%), 21 (4.1%), respectively. According to gender distribution, 290 (55.9%) males and 229 (44.1%) females had primary MR. Degenerative mitral valve disease was the main cause of primary MR in both men and women (90.3 and 92.5%), while the least frequent was infective endocarditis among men and rheumatic heart disease among women. **Conclusion:** Degenerative MR was most common cause of primary MR. Regardless of gender groups, with women slightly more affected.

Diana Rudan, Ivana Jurin

Mitral regurgitation (MR) is characterized by abnormal backflow of blood through the mitral valve during the systolic phase of cardiac cycle. Usually, it is the main indication for mitral valve repair or mitral valve replacement at the onset of symptoms of congestive heart failure. Although mitral valve repair is now frequently performed, especially for mitral regurgitation, valve replacement remains common (1). Echocardiography with Doppler is the method of choice for the non-invasive evaluation of prosthetic valve function and can provide a valuable information about functioning of operating valve and about medical management and considerations for reoperation on valvular complications (2). Because the assessment of prosthetic valve is more demanding, both to perform and to interpret, compared with native valves, transesophageal echocardiography (TEE) is preferable method for the evaluation of prosthetic valvular structure and associated complications (3, 4).

Iva Jurić, Hrvoje Roguljić, Dražen Mlinarević, Lana Maričić, Kristina Selthofer-Relatić, Sandra Makarović

**Introduction:** Prevalence of mitral regurgitation (MR) is still increasing in the western world despite the low incidence of rheumatic fever. Due to the complex structure of mitral apparatus pathology at any level can lead to valve dysfunction. Etiology of MR can be divided into primary, where the lesion is within the mitral apparatus, and secondary, which is caused by geometrical alteration of the left ventricle (1). Secondary or functional MR is considered a disease of the left ventricle which is dilated with distorted papillary muscles preventing normal systolic coaptation of the mitral valve leaflets. Echocardiography is paramount for the diagnosis and evaluation of MR (2, 3). Qualitative, semi-quantitative and quantitative methods should be used for evaluating the severity of MR. **Case presentation:** 70-year-old patient with a history of myocardial infarction several years ago, was admitted to our Department due to progression of chronic heart failure. He was complaining of shortness of breath at the slightest effort and leg swelling despite diuretics in his therapy. Echocardiogram revealed a dilated left ventricle (LVD 66 mm and 228 ml) with severely impaired systolic function (EF 18%). Due to the dilatation of mitral annulus a severe MR was present (PISA ERO 0.3 cm2). Furthermore, the patient had a trabeculated LV with a ratio of noncompacted/compacted myocardium >2 which is consistent with a noncompaction cardiomyopathy. With optimal medical therapy patients’ cardiorespiratory status was improved. After recompensation, he was scheduled for a cardiac resynchronization procedure. **Conclusion:** Secondary MR represents a significant problem for patients with cardiomyopathy. A slow progression of the symptoms is typical for this condition and often ends in irreversible left ventricular dysfunction. In contrast to primary MR which can be managed by surgery, optimal management for secondary MR is much less certain. Despite many surgical and percutaneous treatment options secondary MR is still accompanied by poor long-term survival and its treatment is both challenging and controversial.

Vjekoslav Radeljić

Pulmonary vein electrical isolation using radiofrequency RF energy or cryoablation is a standard in modern atrial fibrillation treatment. In the first place this method is a treatment of choice for those patients with paroxysmal pattern of this most frequent arrhythmia. Furthermore, patients with more prominent symptoms gain best response on the treatment considering quality of life in the first place. On the other side treatment of persistent and permanent forms of arrhythmia from the perspective of benefit from catheter ablation is still not well established (1). Mitral regurgitation changes atrial hemodynamics and structural characteristics. In case of functional mitral regurgitation this change in atrial architectonics with mitral annulus dilatation is obvious. Surgical mitral regurgitation treatment changes occurrence and appearance of atrial fibrillation. Surgical incision and a scar tissue creates slow conduction isthmuses as a new arrhythmia substratum, predominantly for re-entry arrhythmias. On the other side, reduction of mitral regurgitation has desirable effect (2). Mechanic mitral valve raises difficulties for cardiologist during the procedure since catheter can stuck in it. Since patients with mitral regurgitation and atrial fibrillation are often surgically treated there is a question whether surgical maze procedure or catheter ablation of atrial fibrillation is better (3). Earlier studies gave advantage to surgical treatment. However those studies were in time when modern ablation techniques have not been widely used. Atrial fibrillation and mitral regurgitations remain accompanied and we can expect more and more patients with two diseases. However, treatment requires special expertise and should be individualized by united efforts form arrhythmologists and valvular experts.

Matias Trbušić

Acute mitral regurgitation (MR) is a serious condition leading to acute heart failure and death if not recognized and treated on time. A targeted history and physical examination is important to recognize the new onset MR and its clinical consequences such as pulmonary congestion and cardiogenic shock. Organic causes of acute MR result in structural changes of the valve including leaflet perforation and paravalvular leakage from endocarditis, chordal rupture in myxomatous valvular disease, and papillary muscle rupture due to myocardial infarction (MI). Functional mitral regurgitation results from abnormalities of the left ventricle (LV). Examples are decompensated dilated cardiomyopathy, acute dilatation of the LV seen in Takotsubo, peripartal and toxic cardiomyopathy, but the most common is ischemic MR with multiple mechanisms such as posterior leaflet displacement, LV and annular dilatation, papillary muscle discoordination and impaired closing forces (1). Organic causes frequently require surgical repair or valve replacement; whereas functional causes may improve after the nonsurgical treatment of underlying myocardial ischemia, infarction, or cardiomyopathy. The electrocardiogram is usually nonspecific (except in ischemic MR) and the systolic murmur is often short, low pitched and hidden. Echocardiography is essential in diagnosing and can differentiate the etiology. The severity of the MR can be underestimated due to rapid equalization of left atrial (LA)–LV pressures and inadequate color flow visualization. Medical therapy incudes vasodilators (normotensive patients), inotrops (dobutamin and milrinon) and diuretics. Intraaortic ballon pump may be used in cardiogenic shock, but there are promising results with using venoarterial extracorporeal membranous oxygenation (ECMO) as in our case with chordal rupture in 73-year-old patient (**Figure 1**). There are some concerns about pulmonary congestion (white lungs) due to increased afterload produced by ECMO but it can be prevented by short ECMO support (urgent cardiac operation after initial stabilization), avoidance of positive fluid balance and high ECMO flow (2). FIGURE 1. Chordal rupture and flail posterior leaflet in 73-year-old woman admitted in emergency department because of acute heart failure (pulmonary edema and cardiogenic shock).

Jasna Čerkez Habek

Chronic, primary mitral regurgitation (MR) is a „pure“ volume overload, resulting in eccentric hypertrophy and LV dilation. Increased preload and low to- normal afterload, augments left ventricular ejection fraction, which is typically supranormal. Dilatation of left ventricle (LV), increased wall stress, myocardial dysfunction may occur due to the longstanding LV volume overload (1). Because ejection fraction is a load-dependent measure of LV function, it can be preserved even as myocardial contractile function becomes abnormal (1). Functional MR occurs as a consequence of LV dysfunction, either with coronary disease with myocardial infarction or either with primary dilated or hypertrophic cardiomyopathy or left atrial dilation in combination with mitral annular dilatation, papillary muscle displacement and reduced closing force (2). The central problem that drives outcome is LV dysfunction, not MR**2**. Mitral annular calcification (MAC) is a chronic process involving the fibrous annulus of the mitral valve. It is common asymptomatic, an incidental finding. But, more prominent MAC is conected with aging, atherosclerosis, altered mineral metabolism, or increased mechanical stress (3). In advanced cases, MAC may be significant, causing obstruction of left ventricular inflow and symptomatic mitral stenosis. Cohort studies have demonstrated an association of MAC with atherosclerotic disease, renal failure, adverse cardiovascular events, including stroke and increased mortality, arrhythmias, atrial fibrillation and conduction system disease. No surgical treatment is indicated for MAC unless correction of concomitant mitral regurgitation or mitral stenosis is needed. But, severe MAC makes valve surgery more difficult. Risks and benefits of surgery must be carefully assessed in patients with significant MAC, as increased surgical mortality has been observed in these patients. For patients with documented calcific emboli or repeated thromboembolism despite anticoagulation, valve replacement may be considered, but some complications are observed such as left ventricular rupture, acute posterior myocardial infarction, ventricular aneurysm, or hemorrhage from the left ventricle (4).

Dean Strinić, Tea Friščić

Mitral valve (MV) function depends on the coordinated action of the anatomic components of the mitral apparatus which is formed by two leaflets, annulus, chordae tendineae, and the papillary muscles (PM). The annulus is a saddle-shaped structure with a fixed portion (the anterior leaflet (AML) which is semilunar in shape) shared with the aortic annulus, and a dynamic portion (the quadrangular-shaped posterior leaflet (PML) composed of three scallops) that represents most of the circumference of the annulus (1). The surface area of the leaflets is twice the area of the mitral orifice which results in a large area of coaptation when the valve closes. The annulus to leaflet transition zone contains atrial myocytes with nerve fibres which extend from the mitral annulus, maintaining electrophysiological continuity with the rest of the heart (2). The commissures are a distinct area where the AML and PML come together. Along the free edge of the leaflets the chordae tendineae are inserted through multiple locations with the other end attached to the tips of the anterolateral and posteromedial PM (3). The PM and the adjacent wall attach the mitral apparatus to the left ventricle. Diseases of the MV are valvular stenosis (MS), regurgitation (MR) and prolapse. MS is usually caused by rheumatic heart diseases (RHD). The prevalence of RHD in the USA and Japan stands at 0.6–0.7/1,000, which contrasts with that in the developing countries of Africa and Asia where rates are 30/1,000. Congenital MS is rare and is typically diagnosed in infancy or early childhood. MR is the result of structural or functional abnormalities of the MV apparatus. Functional abnormalities causing MR include myxomatous MV diseases, leaflet prolapse, RHD, infective endocarditis, coronary artery diseases and cardiomyopathy. Degenerative disease is the most common form MR in Europe (with an estimated prevalence of 2–3%) and other developed countries. Ischemic MR affects 19% of patients after myocardial infarction.

Jozica Šikić

The Working Group on Valvular Diseases of the Croatian Cardiac Society is organizing the 4th Congress with international participation entitled “CROVALV 2018”, which will be held on June 8th and 9th, 2018, at the Sheraton Hotel in Zagreb. CroValv is a bi-annual Congress, designed not only for cardiologists but also for physicians in different specialties, cardiology residents, cardiac surgeons, anesthesiologists, general practitioners, and for all who are professionally involved in the treatment of valvular diseases. This year’s congress will cover an array of topics including valvular pathology, with an emphasis on mitral regurgitation in clinical practice, distinction between primary and secondary mitral regurgitation, criteria and treatment options for valve repair or replacement in primary and secondary mitral regurgitation, etc. In last two years, development of new, especially percutaneous interventions has brought new and improved treatment options. The congress aims to present everyday challenges in the approach, diagnosis, and selection of the most optimal way of treating patients with valvular diseases, implementing the latest research findings into clinical practice. In addition to invited lectures by reputable European and American speakers, leading national experts will bring their best. In this Supplement of the official journal of the Croatian Cardiac Society – *Cardiologia Croatic*a, we published summaries of original works that will be presented at the congress in the form of oral presentations or posters.