Overview of the Expert’s Meeting “Excellence in Croatian Hypertensiology and Cardiology – Selected Topics”

    Authors

    DOI

    https://doi.org/10.15836/ccar2018.207

    Full Text

    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 17 th , 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 <140/90mmHg, while in chronic kidney disease with albuminuria they are <130/80mmHg. Antihypertensive drugs of first choice in such patients in earlier stages are certainly ACE-inhibitors or angiotensin AT-1 receptor blockers, followed by diuretics and calcium channel blockers. In the next lecture, Dr. Ana Jelaković presented the results of the ESH Stroke study on secondary prevention of stroke, which was conducted in several European countries between 2009 and 2015 under the sponsorship of the European Society of Hypertension. Dr. Jelaković was the main researcher on the study conducted in Croatia. It must be pointed out that, according to the number of citizens, Croatia included the largest number of examinees in the study. According to the results of the study, after recovering from a stroke, 42% of patients in Croatia were released from hospitals with inadequately regulated values of BP, and such values persist even after 6-36 months from the event itself. Also, despite the fact that after recovering from an ischemic stroke 80% of patients were discharged with statin therapy, 66% of them reach values of LDL cholesterol lower than 2.6 mmol/L, and only 26% lower than 1.8 mmol/L. These results were examined from a neurological standpoint by Prof. Branko Malojčić, who emphasized their importance and said that, according to them, Croatia does not differ significantly from other European countries, but there is room for improvement in the regulation of arterial hypertension and dyslipidaemia in secondary prevention of stroke. The final lecture in this part on hypertensionology was dedicated to measuring the stiffness of major blood vessels. Dr. Tatjana Željković Vrkić, who has been recognized as a hypertensionologist by the European Society of Hypertension, reminded us that the stiffness of arteries is a marker of damage in target organs and an independent risk factor for cardiovascular morbidity and mortality. Arterial stiffness is most commonly evaluated by measuring pulse wave velocity, which is a simple, reproducible, and practical method which should be used more in clinical practice. Measuring arterial stiffness contributes to a better evaluation of total cardiovascular risk and, according to recent guidelines, this method should be used whenever possible. The next part contained a presentation of Co-Dalneva, a medication by the pharmaceutical company Krka. Co-Dalneva is a fixed triple combination of perindopril, amlodipine, and indapamide, a representative of three most commonly prescribed groups of antihypertensives. The availability of another fixed triple combination on our market is certainly welcome if we consider all that has been said on the need for a better regulation of our patients suffering from hypertension, as well as for simpler therapies with the goal of improving patient perseverance. The cardiological part of the symposium included presentations of Croatian experiences regarding the treatment of three key cardiac entities – acute myocardial infarction, arrhythmia, and heart failure. Regarding myocardial infarction, it is necessary to point out that ischemic heart disease is the leading cause of death in the world, including Croatia ( 1 ). In the last few decades there has been a reduction in the mortality of patients with acute myocardial infarction, which is primarily a result of the advancements in the use of primary percutaneous coronary intervention (pPCI) as a leading form of therapy in the treatment of such patients. Therefore, the total in-hospital mortality of patients treated for acute ST-elevation myocardial infarction (STEMI) in European countries is 3-10%, while in the group of patients with pPCI it is significantly lower and comes to 2.2-6.1% ( 2 ). The mortality of patients treated for STEMI in Croatia is within the aforementioned European average and comes to 4.4-6.3% ( 3 ). Although significantly financially constrained in comparison to other European countries, Croatia has been following trends from the very beginning and has started a network of cardiological centres for primary coronary intervention. In the last few years, 540-550 patients with acute STEMI per million population ( Figure 1 ) have been treated within the network, which positions our country alongside leading European countries ( 3 ). As a result of major efforts on the part of the Working Group for Acute Coronary Syndrome and the Working Group for Interventional Cardiology of the Croatian Cardiac Society, a prospective national Registry of invasive and intervention cardiology – STENOS was formed at the end of 2016, enabling direct monitoring of a large amount of data concerning the treatment of patients with acute coronary syndrome in Croatia. Total number of patients with ST-elevation myocardial infarction in Croatia treated with primary percutaneous coronary intervention per 1 million population per year. It is certainly necessary to point out that contemporary treatment of patients with acute non-ST segment elevation myocardial infarction (NSTEMI), based on contemporary guidelines, also includes timely and early percutaneous coronary revascularization. Therefore, it is very important to identify high-risk patients who must be provided this form of treatment as early as possible (within 2 hours from diagnosis) just like in the case of STEMI patients. Such patients are hemodynamically unstable, have continued and/or recurrent stenocardia refractory to drug treatment, are at arhythmologic risk, show signs of heart failure or mechanical complications of infarction ( 4 ). Such patients should be treated as though they were patients with STEMI and provide them with an immediate coronarography with the possibility of pPCI. Regardless of the need for further investment of human and financial resources into the development of the network of primary percutaneous coronary intervention, we must not forget the need for modern pharmacological treatment. Since the basis for pharmacological treatment of this group of patients is represented by a dual antiplatelet therapy (ticagrelor/prasugrel with aspirin), it is important to emphasize the fact that in Croatia patients with acute STEMI can receive treatment with ticagrelor without charge during twelve months following pPCI, and from March 1 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. 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. Number of atrial fibrillation ablations per year in Croatia. 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. 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. Number of veno-arterial extracorporeal membrane oxygenation implantations in University Hospital Centre Zagreb per year. 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 ). 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 . Cumulative survival rates in patients after heart transplantation in University Hospital Centre Zagreb.

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    Overview of the Expert’s Meeting “Excellence in Croatian Hypertensiology and Cardiology – Selected Topics”

    Professional Article
    Issue5-6
    Published
    Pages207-15
    PDF via DOIhttps://doi.org/10.15836/ccar2018.207

    Authors

    Jelena KosORCIDUniversity Hospital Centre Zagreb, Zagreb, Croatia
    Hrvoje Jurin*ORCIDUniversity Hospital Centre Zagreb, Zagreb, Croatia

    Full Text

    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 17 th , 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 <140/90mmHg, while in chronic kidney disease with albuminuria they are <130/80mmHg. Antihypertensive drugs of first choice in such patients in earlier stages are certainly ACE-inhibitors or angiotensin AT-1 receptor blockers, followed by diuretics and calcium channel blockers. In the next lecture, Dr. Ana Jelaković presented the results of the ESH Stroke study on secondary prevention of stroke, which was conducted in several European countries between 2009 and 2015 under the sponsorship of the European Society of Hypertension. Dr. Jelaković was the main researcher on the study conducted in Croatia. It must be pointed out that, according to the number of citizens, Croatia included the largest number of examinees in the study. According to the results of the study, after recovering from a stroke, 42% of patients in Croatia were released from hospitals with inadequately regulated values of BP, and such values persist even after 6-36 months from the event itself. Also, despite the fact that after recovering from an ischemic stroke 80% of patients were discharged with statin therapy, 66% of them reach values of LDL cholesterol lower than 2.6 mmol/L, and only 26% lower than 1.8 mmol/L. These results were examined from a neurological standpoint by Prof. Branko Malojčić, who emphasized their importance and said that, according to them, Croatia does not differ significantly from other European countries, but there is room for improvement in the regulation of arterial hypertension and dyslipidaemia in secondary prevention of stroke. The final lecture in this part on hypertensionology was dedicated to measuring the stiffness of major blood vessels. Dr. Tatjana Željković Vrkić, who has been recognized as a hypertensionologist by the European Society of Hypertension, reminded us that the stiffness of arteries is a marker of damage in target organs and an independent risk factor for cardiovascular morbidity and mortality. Arterial stiffness is most commonly evaluated by measuring pulse wave velocity, which is a simple, reproducible, and practical method which should be used more in clinical practice. Measuring arterial stiffness contributes to a better evaluation of total cardiovascular risk and, according to recent guidelines, this method should be used whenever possible. The next part contained a presentation of Co-Dalneva, a medication by the pharmaceutical company Krka. Co-Dalneva is a fixed triple combination of perindopril, amlodipine, and indapamide, a representative of three most commonly prescribed groups of antihypertensives. The availability of another fixed triple combination on our market is certainly welcome if we consider all that has been said on the need for a better regulation of our patients suffering from hypertension, as well as for simpler therapies with the goal of improving patient perseverance. The cardiological part of the symposium included presentations of Croatian experiences regarding the treatment of three key cardiac entities – acute myocardial infarction, arrhythmia, and heart failure. Regarding myocardial infarction, it is necessary to point out that ischemic heart disease is the leading cause of death in the world, including Croatia ( 1 ). In the last few decades there has been a reduction in the mortality of patients with acute myocardial infarction, which is primarily a result of the advancements in the use of primary percutaneous coronary intervention (pPCI) as a leading form of therapy in the treatment of such patients. Therefore, the total in-hospital mortality of patients treated for acute ST-elevation myocardial infarction (STEMI) in European countries is 3-10%, while in the group of patients with pPCI it is significantly lower and comes to 2.2-6.1% ( 2 ). The mortality of patients treated for STEMI in Croatia is within the aforementioned European average and comes to 4.4-6.3% ( 3 ). Although significantly financially constrained in comparison to other European countries, Croatia has been following trends from the very beginning and has started a network of cardiological centres for primary coronary intervention. In the last few years, 540-550 patients with acute STEMI per million population ( Figure 1 ) have been treated within the network, which positions our country alongside leading European countries ( 3 ). As a result of major efforts on the part of the Working Group for Acute Coronary Syndrome and the Working Group for Interventional Cardiology of the Croatian Cardiac Society, a prospective national Registry of invasive and intervention cardiology – STENOS was formed at the end of 2016, enabling direct monitoring of a large amount of data concerning the treatment of patients with acute coronary syndrome in Croatia. Total number of patients with ST-elevation myocardial infarction in Croatia treated with primary percutaneous coronary intervention per 1 million population per year. It is certainly necessary to point out that contemporary treatment of patients with acute non-ST segment elevation myocardial infarction (NSTEMI), based on contemporary guidelines, also includes timely and early percutaneous coronary revascularization. Therefore, it is very important to identify high-risk patients who must be provided this form of treatment as early as possible (within 2 hours from diagnosis) just like in the case of STEMI patients. Such patients are hemodynamically unstable, have continued and/or recurrent stenocardia refractory to drug treatment, are at arhythmologic risk, show signs of heart failure or mechanical complications of infarction ( 4 ). Such patients should be treated as though they were patients with STEMI and provide them with an immediate coronarography with the possibility of pPCI. Regardless of the need for further investment of human and financial resources into the development of the network of primary percutaneous coronary intervention, we must not forget the need for modern pharmacological treatment. Since the basis for pharmacological treatment of this group of patients is represented by a dual antiplatelet therapy (ticagrelor/prasugrel with aspirin), it is important to emphasize the fact that in Croatia patients with acute STEMI can receive treatment with ticagrelor without charge during twelve months following pPCI, and from March 1 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. 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. Number of atrial fibrillation ablations per year in Croatia. 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. 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. Number of veno-arterial extracorporeal membrane oxygenation implantations in University Hospital Centre Zagreb per year. 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 ). 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 . Cumulative survival rates in patients after heart transplantation in University Hospital Centre Zagreb.