Arrhythmology is among the most complex and most demanding parts not only of cardiology, but also the entire clinical medicine. All the better understanding of the pathophysiological mechanisms of arrhythmias and the use of new technological advancements have significantly improved the treatment options for patients with heart rhythm disorders.

Despite many problems, and owing to great efforts and enthusiasm of physicians who deal with rhythmology in the Republic of Croatia, we have seen a significant advancement in the field of cardiac electrophysiology (hereinafter electrophysiology) and cardiac pacing in recent years. In accordance with the article that accompanies this review article (1), we shall show the current state of rhythmology and electrostimulation in the Republic of Croatia, primarily based on official data published in the EHRA White Book from 2011 to 2013 (the Report European Heart Rhythm Association) and the still unofficial data collected from personal communications in 2013 (2, 3).

Electrophysiology is a part of rhytmological portfolio which has seen the greatest progress in the last few years, being reflected in a significant increase in the number of performed electrophysiological procedures throughout the Republic of Croatia, resulting in a partial reduction of the huge disproportion in comparison with other countries in the region (4).

Table 1 presents the relevant data of electrophysiological procedures in the Republic of Croatia from 2010 to 2013. Currently there are five electrophysiological laboratories, out of which four in the region of Zagreb and one in Zadar. Every year we can see a substantial increase in the number of procedures performed and it is estimated that during the year 2013 some 700 electrophysiological procedures were performed. The increase in complex procedures using three-dimensional (3D) navigation systems, in particular in the number of atrial fibrillation (AF) catheter ablations is significant, which is in line with global trends.

The main problems preventing further development of this branch of medicine are the lack of required financial resources for the purchase of supplies, particularly more expensive catheters for more complex procedures using navigation systems and the lack of adequate diagnosis-related group (DRG) in the Croatian hospital system, which would be used for calculation and valuation of the performed clinical work in a proper way.

An additional problem is still a lack of awareness about this treatment option among the patients, family physicians and a certain number of medical specialists leading to a lack of sufficient referrals of patients to specialized institutions. In this way, due to non-compliance with the guidelines of the European Society of Cardiology (ESC), the patients are denied an efficient method which in many cases can lead to a complete cure, they are exposed to long-term antiarrhythmic therapy with their potential side-effects and the entire health system is unnecessarily burdened.

AF is the most common persistent cardiac arrhythmia, which occurs in about 1-2% of the general population. In accordance with these data, probably more than 60,000 patients suffer from AF in Croatia. AF confers a double increase in mortality and fivefold increase in the risk of stroke, and one in five of all strokes is attribuited to this arrhythmia. Ischemic stroke associated with AF is often fatal, and those patients who survive are left more disabled by their stroke and more likely to suffer a recurrence than patients with other causes of stroke. Due to the foregoing, the basic and the only therapy that has proven to reduce mortality in patients with AF is the stroke prevention by using anticoagulant therapy (5, 6).

Another great advancement with catheter ablation in the treatment of patients with AF which has been present in the last few years in our region is the availability of new oral anticoagulants (NOAC) (6, 7). In Croatia, two NOACs are currently available: dabigatran and rivaroxaban, and this year the registration of apixaban is expected. NOACs are divided into two groups: direct thrombin inhibitors (dabigatran), which has been added to the supplemental list of Croatian Health Insurance Fund since June 2013 and inhibitors of activated factor X (rivaroxaban and apixaban). Unlike vitamin K antagonists (VKA) which have an effect on a number of factors of the coagulation cascade, NOACs block the activity of one single step in coagulation. Large randomized trials and meta- analyses have demonstrated non-inferiority of NOACs compared with VKA in reducing thromboembolic events and a better safety profile in terms of reducing the incidence of bleeding, especially intracranial bleeding. The main problems that still limit a greater penetration of NOACs among patients with AF are a higher price than the price of VKA, non-coverage or partial coverage of the costs by health insurance in the Republic of Croatia and still insufficient education of physicians and patients in respect to the efficacy and safety of this type of anticoagulant therapy.

Given the aforementioned advancements in the treatment of AF, the availability of new European guidelines, the need has arisen for systematic collection of contemporary data on the treatment and management of patients with AF in ESC member countries. For this reason, ESC has launched a program of creating a AF registry in order to collect contemporary data as to determine whether the diagnostic and therapeutic procedures in patients with AF are in compliance with contemporary guidelines, to evaluate the use of rhythm control strategies such as catheter ablation AF, symptoms, quality of life, morbidity and mortality in patients with AF.

As well as the ESC, the Working Group on Arrhytmias and Cardiac Pacing of the Croatian Cardiac Society has launched a project of a national AF registry in order to obtain suitable data on incidence, prevalence, morbidity and mortality of patients with AF, treatment trends, pharmacoeconomics, all in order to develop better treatment strategies in patients with AF in the Republic of Croatia.

Progress in the field of electrostimulation is reflected not only in reducing the cost of devices for electrotherapy, but also the availability of more quality data from large randomized clinical trials that better show what patients can benefit from the above therapy compared to the groups of patients who are not likely to have much benefit from such a therapy (while harmful consequences can be significant). In that respect, once relatively rare treatment methods such as cardiac resynchronization therapy (CRT) devices and implantable cardioverter defibrillators (ICD) have become ubiquitous in the Republic of Croatia, where the most significant difference compared to most European countries remains relatively insufficient number of implanted devices compared to the real needs of our population. The main limiting factor, unfortunately, is still a lack of financial resources available for the use of this treatment option. Mitigating factors, such as the enthusiasm and interest of colleagues, constantly present education and a growing number of centers where these procedures can be performed, had only a limited effect on the number of these procedures (data on the most typical procedures in electrotherapy are detailed in Table 2). Furthermore, in order to be able to compare the existing situation in the Republic of Croatia with the situation we faced a few years ago, we draw the reader’s attention to an article published in Cardiologia Croatica in 2011, which will give you a complete insight into the current situation and trends as well (4).

The presented data shows that a certain maximum in the number of implanted pacemakers has been achieved, whereas we still expect a further increase considering the evolution of some diagnostic methods. However, this increase has not occurred for the above reasons. There is a certain increase in the implantation of CRT and ICD devices, but unfortunately, this increase is still insufficient compared to the most of countries in the region, which was also recorded in 2011 (2, 3).

Certainly the most significant innovation in the field of cardiac pacing is publishing of long awaited ESC Guidelines for pacing and cardiac resynchronization therapy published during Europace Congress in June 20138. Considering the fact that the previous Guidelines were published in 2007 (with additional update in the field of treatment by using CRT devices in 2010), it is clear why the new edition is welcome (9, 10).

The main novelty in these Guidelines is the result of numerous studies in the field of applying cardiac resynchronization therapy in patients with heart failure. The publication of the results of several large randomized controlled clinical studies which showed that the use of CRT devices brings substantial benefit to patients with severe heart failure — in terms of better survival, but also improvement of symptoms — was followed by a series of studies in which emphasis was placed on defining the variables that closely determine subgroups of patients which are most likely to benefit from this therapy. The foregoing primarily applies to the appropriate selection of patients who are considered to undergo the treatment by a CRT device as well as to determination of clinical characteristics that lead to a favorable response to such a treatment. New insights from these studies are incorporated in the new Guidelines, which primarily relate to the variables for the selection of patients who are most likely to benefit from the use of CRT devices and predicting the response to CRT application.

Ever greater attention is paid to the infection of electrical stimulation system, since the number of such infections is constantly in rise. Considering the increasing number of patients who are the carriers of such systems, the foregoing is not surprising; however, it has significant implications for the healthcare system, since such infections are a significant cause of morbidity, mortality and a significant increase in medical costs. Also, considering an increasing number of patients who will need a replacement of the existing pacemaker (primarily due to the generator depletion, but also due to inspection of electrodes), we can expect an increasing number of such infections. According to the data shown in Table 2, the methods of extraction of the pacing systems started to be implemented in the Republic of Croatia.

The new guidelines for the implantation of a CRT device include for the first time the clear recommendations for the perioperative treatment of patients with antiplatelet and/or anticoagulant therapy. Pocket hematomas are a common complication, occurring in about 2.9% to 9.5% of cases and are usually treated conservatively. Evacuation is required in about 0.3% to 2% of cases and increases risk for occurrence of infection by 15 times. Most of the hematoma and bleeding can be avoided by proper preoperative patient preparation and adequate regulation of antiplatelet and anticoagulant therapy. The new guidelines recommend that in the majority of patients on antiplatelet therapy, the therapy may be discontinued perioperatively for a period of 5-7 days, especially if these drugs were introduced for primary prevention. In higher-risk patients with dual antiplatelet therapy, discontinuation of clopidogrel in a length of 4 days prior to implantation is recommended. Dose reduction of VKA is recommended in patients on anticoagulant therapy with low thromboembolic risk, achieving an INR of 1.5-2 or discontinuation of anticoaganticoagulant therapy for 3-5 days prior to implantation. In high thromboembolic risk patients implantation of devices with an INR between 2-2.5 is recommended. The use of heparin perioperatively as a "bridge" for anticoagulant therapy is no longer recommended due to a significant increase in the risk for the development of hamstring hematoma (incidence 15-20%) (8).

Although the preparation of the new Guidelines in the area of treatment of ventricular arrhythmias and prevention of sudden cardiac death (SCD) is in progress (where the publishing of these guidelines is expected in 2015), it is important to note that a number of new insights are present in this area, which are mostly incorporated in the Guidelines for cardiac pacing and cardiac resynchronization therapy, since the previous guidelines in this area were published in 2006. (11). One of the significant novelties is an additional presentation of the role of heart MRI scan, which can be performed in a few centers in the Republic of Croatia. New insights in this area are related to a better understanding of the incidence and causes of ventricular arrhythmias and SCD, as well as the selection of patients that are benefit the most from ICD therapy.

Finally, we should mention the breakthroughs made in regard to the cardiopulmonary resuscitation procedures. Several types of cardiopulmonary resuscitation courses have taken place in the last few years in the Republic of Croatia in accordance with the Guidelines of the European Society for Resuscitation (ALS, ILS, EPLS, AED; the latest guidelines date back to 2010), organized by the Croatian Society of Resuscitation of the Croatian Medical Association (12). During the year 2013, major breakthroughs have been made in the availability of defibrillators in public places, not only in the City of Zagreb, but also throughout the Republic of Croatia; with an aim to help as many lay persons to successfully perform resuscitation and, if necessary, external defibrillation using the AED devices. The role of the Croatian Cardiac Society and the Croatian Heart House foundation is to be emphasized. The main challenge in this area is certainly the need for continuous and comprehensive education of as many lay persons as possible, but also the medical staff.

Inherited arrhythmogenic heart diseases are an important cause of malignant cardiac arrhythmias. They often occur in young people, and usually manifest in the form of palpitations, syncopes, and at worst, SCD. They are characterized by an increased incidence of supraventricular and ventricular cardiac rhythm disorders and are considered the most common cause of SCD in young athletes.

The group of congenital arrhythmogenic diseases include long QT syndrome (LQTS) and short QT syndrome (SQTS), the Brugada syndrome (BrS), catecholaminergic Polymorphic Ventricular Tachycardia (CPVT), arrhythmogenic right ventricular cardiomyopathy (ARVC) and hypertrophic cardiomyopathy (HCM) (Figures 1-4). They are inherited predominantly autosomally, while closer relatives are at increased risk of developing the same disease (13, 14).

At the moment, there is no possibility of a systematic genetic testing of congenital arrhythmogenic heart disease in the Republic of Croatia. In June 2012, the cooperation was established between the Institute for Cardiovascular Diseases University Hospital Centre Rijeka and Statens Serum Serum Institute (Copenhagen, Denmark) as part of the joint project in order to conduct a systematic trial of all the patients with a clinical diagnosis of congenital arrhythmogenic diseases and their close relatives (15, 16). The aim of this trial was to conduct a systematic genetic analysis of patients with congenital arrhythmogenic diseases and their close relatives, in order to obtain genetic characterization of populations for the first time in our region, to attempt to identify patients at an increased risk for SCD and providing them with prompt advice and treatment.

85 patients and their relatives were genetically analyzed, and genetic mutation was detected in 35 patients (41%). The control group was composed of 200 healthy Croatian volunteers whose genetic material will be deposited, so that it could be used for further trials in the future and to exclude any characteristic and frequent mutations in our population.

Table 3 shows the characteristics of patients with established genetic mutation. The most interesting result is 17 new mutations described so far (48%), which is to be expected taking into account the population that has been so poorly genetically characterized in the past (17, 18).

Genetic trial of arrhythmologic patients and discovery of new mutations is an important contribution necessary for a better understanding of the diversity of arrhythmia, and allows us earlier diagnosis, better quality treatment and preventive action. The basic problems are high prices of these tests, the inability to perform the above tests in Croatia, the inability to refund the costs from the health insurance and lack of education in the field of genetic counseling.

To conclude, we can say that the greatest advancement in the area of arrhythmology has been made in the field of electrophysiology and AF catheter ablation in the Republic of Croatia in recent years, primarily due to the great enthusiasm of physicians that engage in this area of medicine. There are also significant advancements in new insights in the field of electrical stimulation. A further increase in a number of centers where such procedures are performed has been recorded in the Republic of Croatia, and there is also an increasing number of performed procedures where education keeps up with new insights and trends, all with an aim to enable our patients prolonged survival and a better quality of life. However, some major challenges we are facing have not significantly changed compared to the previous years, and the basic one is finding additional resources to ensure better prevention of SCD by a necessary increase in the number of ICD and CRT implantats. The room for improvement is great, whereas we can not sufficiently emphasize the importance of persistent activities of the professional society in this area.