Cardiologia Croatica. 2016;11(1-2)

Jadranka Šeparović, Hanževački

Adult congenital heart diseases (ACHD), in addition to complex heart defect diagnosed in childhood, also include very simple singular heat defects that are diagnosed only in adulthood due to their minor hemodynamic influence and severity. The indicators of simple ACHD on the left side of the heart and the aorta are signs the left ventricle (LV) has been remodeled by volume, pathological morphology of the valve (most commonly bicuspid aortic valve (BAV) disease and myxomatous mitral valve disease), and coarctation of the aorta. Volume load of the LV due to increased inflow into the left side of the heart leads to eccentric hypertrophy of the LV (normal wall thickness, increased volume, and ball-like shape) proportionate to the severity of the hemodynamic defect – the greater the regurgitation or shunt volume, the greater the dilation of the heart. Dilatation of the ascending aorta is also common in BAV. Volume load on the LV causes concentric hypertrophy (low systolic and diastolic volume, thickened walls). The most common natural causes of volume load on the LV are: congenital aortic stenosis, subaortic stenosis (isolated subaortic fibrous ring and subaortic membrane), coarctation of the aorta (more often associated with BAV), and conditions after previous surgical procedures. Other than the size of the cavities and the thickness of the walls and the left and right heart, the dynamic relationship of pressure changes during the cardiac cycle is important as well. When this relationship is disrupted, the ventricular or inter-atrial septum is displaced towards the area of lower pressure. Pressure load of the right ventricle (RV) causes the septum to be displaced towards the left in the systole and create a so-called D-shaped left ventricle. Volume load of the RV causes the septum to be displaced to the left in the diastole, causing a so-called D-shaped left ventricle in the diastole. In conclusion, we can group the echocardiographic indicators of simple and less severe ACHD into 5 basic categories: 1) size and morphology of the LV; 2) size of the right atrium, position of the inter-atrial septum; 3) size and morphology of the RV; 4) pulmonary hypertension; 5) flow pressure gradient across the aortic and pulmonary valve (AV/LVOT and PV/RVOT). Finding any of these indicators (with or without accompanying cardiologic signs and symptoms) should raise suspicion of the existence of ACHD, which should then be established or eliminated from the differential diagnosis.

Anton Šmalcelj, Maja Strozzi, Ivan Malčić, Darko Anić

A growing population of young heart failure (HF) patients with complex congenital heart disease, who have survived into adulthood owing to sophisticated cardiac surgery in infancy, emerges as a challenging quandary of contemporary cardiology. This new population primarily includes patients with: 1) repaired tetralogy of Fallot with consequent severe pulmonary valve regurgitation, 2) univentricular heart and Fontan circulation, 3) complete transposition of great arteries palliated by atrial switch surgery, 4) congenitally corrected transposition of great arteries, and 5) Eisenmenger syndrome. Right ventricular failure is a common denominator of all those entities, while in items 3 and 4, and often also in 2, the failing right ventricle is the systemic one. The grossly distorted anatomy of complex congenital heart disease, even if palliated by an early and often staged surgery, results in peculiar HF hemodynamics grossly aberrant from norm, but probably with similar systemic response. Time course of HF in congenital heart disease is much different from “ordinary” HF. It occurs much earlier and is heavily dependent on surgical and percutaneous interventions. Surgery, often more palliative than corrective, defers HF portending death from infancy into early or middle adulthood, but the real challenge is how to delay it further when the surgical and percutaneous interventional possibilities are used up. Heart failure in congenital heart disease defies standard concepts of medical HF treatment. The efficacy of renin-angiotensin-aldosterone antagonists and beta blockers has not been proven yet. Antiarrhythmic drugs are quite ineffective in grossly distorted hearts, but ablative antiarrhythmic interventions and hemodynamics improvement by pacing may be useful. Advanced pulmonary vasodilators have revived the treatment of Eisenmenger syndrome, previously deemed incurable. The diversity of congenital disease precludes unifying treatment concepts. Specific hemodynamic conditions have to be kept in mind in an individualized clinical approach, but new ways of treatment are clearly needed, medical, interventional, and surgical ones.

Maja Strozzi

It was a great pleasure to accept the invitation to be the guest editor for this issue of Cardiologia Croatica, which is dedicated to congenital heart disease in adults. This topic has been touched upon several times already in the journal from the organizational and epidemiological perspectives (1, 2). In this editorial, I would like to address other topics and inform the general cardiologic public in Croatia about some progress achieved over a short span of time in increasing awareness of the problem of adult patients with congenital heart disease. Acronym. For easier comprehension, two acronyms are generally used in the predominantly English language literature: GUCH (grown-up congenital heart disease), more common in the USA, and ACHD (adult congenital heart disease), more common in the UK and European Union. While deliberating on the best acronym to use in the Croatian language during the formation of the Working Group for Congenital Heart Disease of the Croatian Cardiac Society, we discussed this topic at the meeting of the Management Board and agreed on the acronym PSBO (“prirođene srčane bolesti odraslih” – congenital heart disease in adults). We expect more discussion on this topic and that this will be one of the points addressed at the round-table meeting at our next national congress. For easier comprehension, the Croatian language version of this Journal’s issue will be using PSBO as an acronym. Referral Center. Given the recommendations in relevant guidelines (3) as well as from the general consensus of experts in this field, we would like to announce the beginning of efforts to found a national care center for patients with ACHD at the University Hospital Centre Zagreb, since this institution is currently the only one with all the elements needed for a multidisciplinary approach to these patients. Based on demographics, Croatia can be expected to have 5-10 thousand such patients, and will need one or two such centers. A brief article in this issue describes the main characteristics of such a center. It is especially important to note that all patients with ACHD should register and receive the first evaluation at the center, after which they will continue treatment in their local institutions except in extremely complex or extraordinary cases. Registry. Establishing a patient registry is very important as well. Other cardiologic issues have shown how badly we lack national data, a problem that has been discussed several times (acute coronary syndrome registry, percutaneous coronary intervention registry, etc.). Due to the relatively limited number of patients with ACHD, we are presented with a unique opportunity to create a real registry for the first time in Croatia, which is especially important for ACHD, since these are “lifelong” patients with a complex disease that requires complex treatment due to differences in clinical presentation even under the same diagnosis. A registry would significantly improve communication among all physicians coming into contact with these patients. Despite great effort, the registry currently contains just over 350 patients we have had at the University Hospital Centre Zagreb for over a year. It is our hope that this issue of our Journal will encourage data-sharing. Education. It is well known that cardiologists lack education on congenital heart diseases, since most of us received our degrees at a time when the need for treatment of these diseases was small. Although we are behind other countries in the organization of care for patients with ACHD, the same problem is present in those countries as well, and guidelines (4) as well as other articles discuss the need for the education of cardiologists, subspecialists for ACHD. We believe it is important that some of our colleagues complete courses recommended by the European Society of Cardiology, but that it is even more important that we all become aware of the problem, recognize the patients, advise them appropriately, and treat cases of lower or moderate complexity by providing them with an adequate level of care either in our own institutions or by sending them to specialized ACHD centers. As a small contribution to this goal, we decided to dedicate this Journal issue to that topic. This Journal issue contains articles addressing topics discussed at the 1st meeting of the ACHD Working Group of the Croatian Cardiac Society, which took place in the Croatian Heart House in Zagreb on November 12, 2015 and was met with great interest. I can say with pleasure that the conference hall was full during the whole one-day meeting. We hope that readers will find the topics addressed in this issue of Cardiologia Croatica to be interesting reading; they are presented as review articles, case reports, and professional articles and are intended to convey the information and conclusions we arrived at during the meeting.

Nenad Lakušić

In spite of ample evidence supporting the direct effectiveness of statins in the reduction of total and low-density lipoprotein (LDL) cholesterol and long-term effects in primary and secondary prevention of cardiovascular diseases, in everyday practice we are still faced with various prejudices against the undesired effects of treatment and the possible adverse effects of statins, not only among patients, but among some physicians as well. The basic mechanism of action of statins is inhibiting 3-hydroxymethyl-3-methylglutaryl coenzyme A reductase (HMG-CoA), a key enzyme in cholesterol synthesis. Their other potential mechanisms are stabilization of atherosclerotic plaque and reduction of endothelial dysfunction, as well as inflammatory and post-thrombotic intravascular processes. The side effects of treatment with statins are generally mild, with a frequency comparable to placebo, and usually do not require the termination of treatment. It is necessary to emphasize that patients must always be encouraged to adopt an active, non-sedentary lifestyle that includes regular physical activity, due to its clear positive effects in the prevention and treatment of dyslipidemia and cardiovascular diseases.

Darko Anić

The number of patients with adult congenital heart disease (ACHD) is constantly increasing. In the University Hospital Centre Zagreb, a service was established in 2015 to treat such patients, including surgical treatment. We analyzed the database of patients with ACHD in the period between 2009 and 2015 to determine the number of patients as well as the most common diagnoses and outcomes, which we then compared to centers outside Croatia that are more experienced in treating ACHD. At our center, 111 surgical procedures were performed on 108 patients in that period, with an even ratio between women and men and a mean age of 35. Reoperations accounted for 44% of the procedures. Mortality and morbidity were low (0.9%). Since the establishment of the Working Group for ACHD of the Croatian Cardiac Society, the number of surgically treated patients has grown.

Margarita Brida, Maja Strozzi

Congenital heart disease makes up for one third of all serious congenital anomalies; the exact number of children born with congenital heart defects is hard to estimate due to differences in the availability and quality of health care and diagnosis in different parts of the world. Data indicate a prevalence of over 8 per 1000 newborns. (1) Survival rates for children born with congenital heart defects were very poor in the past, with only up to 20% of such children reaching adulthood in the 1940s. This has changed drastically. During the second half of the 20th century, pioneers of cardiac surgery came up with surgical solutions for almost all complex heart defects. With advancements in cardiac surgery and pediatric care, today over 90% of children with complex defects survives into adulthood. It is estimated that the number of adult patients is now twice as large as the number of children with congenital heart defects. (2) Although this is an outstanding success in the treatment of these patients, most cannot be considered cured, but rather palliated. This is supported by the fact that during last 15 years, the number of hospitalizations for these patients increased by over 80%. These are chronic conditions that require long-term monitoring and treatment, and commonly also re-interventions due to anatomical and functional abnormalities. Many of these patients are at high risk for the development of arrhythmia, heart failure, and endocarditis. (3) In Croatia we expect to have about 10,000 such patients of different complexity. This growing group of patients that was once exclusively under pediatric care, now requires the development of a new subspecialty in adult cardiology and presents new challenge in this field. The need for adequate care for this growing patient group has been recognize at the global and European levels, and guidelines have been issued by the European Society of Cardiology on the organization of care for adult patients with congenital heart disease (ACHD; or Grown-up Congenital Heart Disease, GUCH), as well as the education of cardiology subspecialists in Europe on that topic. (4) A specialized center must be located in a place with access to adult and pediatric cardiac care, as well as congenital heart surgery. Furthermore, due to the ageing of the population the whole spectrum of adult medicine must be available. In addition to a cardiologist specializing in ACHD, having an expert in echocardiography with knowledge of advanced techniques is also important, as well as a having an interventional cardiologist with expertise in structural heart disease and knowledge of complex interventional procedures. Access to electrophysiology and electrotherapy (pacemakers, cardiac resynchronization therapy, defibrillators, complex ablation) is of great importance because of the possibility of arrhythmia, which is a common cause of mortality and hospitalization in patients with ACHD. The team must also include a radiologist – imaging method specialist (magnetic resonance imaging, multislice computed tomography) and a specialist in gynecology and obstetricity regarding the care of women in generative age. Pregnancy is an additional risk factor in this group of patients and requires advisement and careful monitoring. A large contribution to such a center can be expected from medical nurses specializing in ACHD. Opening such centers has been shown to reduce mortality and morbidity (primarily hospitalization rates) in patients with ACHD. (5) The best care model is that in which patients undergo at least once examinations in a specialized center where a subspecialist for ACHD can give them further recommendations on the level of care and monitoring intervals depending on individual patient characteristics. In any case, a working network between the specialized center, the local general adult cardiology center, and the family physician is of critical importance. (6) Based on the estimated number of patients with ACHD, Croatia would need 1 to 2 such specialized centers. Pediatric cardiologists have a great knowledge and experience on congenital heart defects in children, but even their knowledge is limited when it comes to long-term monitoring and further treatment of adults, especially since that can include also the potential development of acquired heart diseases. Thus, a transitional period in the care of patients with congenital heart diseases is important. The best model is joint care in the period between 16 and 18 years of age. During that period, pediatric cardiologists can inform ACHD specialists on the course of treatment so far, and the patient will get to know and trust the physician that will be taking care of them in the next phase of their life. Despite the fact that the need for additional education in ACHD has been recognized among cardiologists, most still have little experience. According to European recommendations, a training period of two years is needed to complete subspecialty training in GUCH. During that period, 18 months must be spent in a specialized center, and 6 months at a pediatric cardiology department. In conclusion, a specialized ACHD center must be a supra-regional center serving as a center of excellence with the highest standard of care. It must also allow education in that field and promote research and innovation. (7)

Maja Strozzi

Pulmonary arterial hypertension (PAH) is a severe chronic, progressive disease. It affects the group of patients with congenital heart diseases (CHD); a high-profile example is Eisenmenger’s syndrome, the CHD with the greatest mortality and morbidity. Advanced PAH treatment for adult congenital heart diseases (ACHD) has significantly improved the outcome and clinical course for these patients, and endothelin receptor antagonist, primarily bosentan, are recommended as first-line treatment today. All case studies and registries show that bosentan improved the exercise tolerance, reduced pulmonary vascular resistance, and decreased the mortality of these patients. Other advanced therapy drugs (phosphodiesterase inhibitors and prostaglandins) are added in case of disease progression. Advanced PAH therapy can be administered long-term with good results and few side effects. Apart from Eisenmenger’s syndrome, other patients from the PAH group in ACHD can be treated through advanced therapy. In the treatment of surgical patients with ACHD who have developed or are developing a subsequent PAH, a different double endothelin inhibitor is indicated, macitentan. Therapy through a combination of drugs has not led to any further significant improvements in relation to treatment by a monotherapy of endothelin receptor inhibitors. It is possible that patients with Fontan circulation will be the target group for the treatment with these drugs.

Daniel Lovrić

Heart failure (HF) is the leading mortality cause in adult congenital heart disease patients, but this problem is very often overlooked in these patients due to good tolerance of symptoms as well as low expectations for functional capacity in many of those patients. Although neurohormonal activation follows the same pattern as does HF in acquired disease, the cornerstones of medical therapy have failed to provide significant benefits in mortality reduction, most probably due to a very diverse range of causes for HF that are present in different morphologies of congenital heart disease, as well as connected to specific surgical treatments. Heart transplantation can be performed in patients with terminal HF, but detecting those and determining the optimal moment for enlisting is problematic due to the low sensitivity of currently applied functional testing methods to detect change between a steady state of low functional capacity and deterioration. B-type natriuretic peptide blood test is a good marker of prognosis and deterioration and should be monitored on a regular basis in these patients.

Ksenija Pešek, Rajko Fureš

The sad news of the death of Dr. Stjepan Rogan comes as a heavy blow to all his colleagues, family, and patients that loved and respected him. He spent his short fifty five years in his family home in Poznanovac, in company of his loved ones. He went to work every day to the Zabok General Hospital and Croatian Veteran’s Hospital, which he did not leave even during his long and difficult illness. A consummate professional, and above all a diligent specialist in internal medicine, he was always available to all who needed his help and has left an indelible mark on all the hospital staff and all the patients of the Internal Medicine Department at the Zabok General Hospital and Croatian Veterans Hospital. Dr. Stjepan Rogan attended primary schools in the towns of Poznanovac and Bedekovčina. He graduated from secondary school in 1977 in Zabok, the health care medical school in Zabok in 1979, and graduated from the University of Zagreb School of Medicine in 1984. Professionally, Dr. Rogan held for many years the positions of department head at the Department of Intensive Medicine and Department of Internal Medicine, and was the Assistant Director for medical issues at the Zabok General Hospital. In all his work he was ever supportive of those in need, caring selflessly for the people around him, be they friends or people in trouble, and always had time for us all – other people were always most important to him. Stjepan Rogan was active in the Croatian association “Muži zagorskog srca”, the Bedekovčina Hunting Society, the “Bedekovčina” Fishing Society, and FC “Tondach” Bedekovčina. As a physician, he helped defend his country in the Croatian War of Independence. Our dear Štefek has left us, our Štefek who has left an indelible mark with his work, his thoughts, and his heart. A sudden void has opened with his passing and we are faced with a great loss, a loss that cannot be replaced. But we are still left with what is most beautiful, which is the remembrance of Štefek’s gentle spirit and all his good works and his big, unselfish heart. Štefek lived for love, for sincerity, for pure heartedness, and was loved for it by the colleagues and patients he dedicated himself to. The Zabok General Hospital and Croatian Veterans Hospital and the medical institutions of the whole Zagorje region have lost an exceptional man and a great doctor that gave his whole career to this hospital in his homeland of Zagorje. Until his last breath, he helped his patients and inspired his colleagues with his example, for which we are eternally grateful as colleagues, friends, and patients.

Irena Ivanac, Vranešić, Maja Strozzi

Patients with repaired tetralogy of Fallot (ToF), due to the development of complications in adulthood, need to attend regular follow-up at a tertiary adult congenital heart disease (ACHD) center. If disease progression is stable, the follow-up visits are most often indicated on a yearly basis. In addition to a detailed history of symptoms development, it is important to always look for possible complications. In case of a significant pulmonary regurgitation (PR), which is the most frequent late complication of repaired ToF, it needs to be quantified, and changes in right ventricular (RV) size and function need to be monitored. It is important not to postpone the re-intervention on the pulmonary valve (PV) for too long in order to preserve the RV function. It is also important to bear in mind the possible faster progression of prosthesis dysfunction if the operation was done at an earlier age. Since repaired ToF patients belong to the group of ACHD conditions with the highest risk of sudden cardiac death (SCD), it is necessary to stratify their risk by using currently available methods and to consider whether there are any indications for the implantation of a cardioverter defibrillator. In addition to the above, during each follow-up it is necessary to search for all other possible complications in order to better and more comprehensively monitor and treat these patients.

Vlatka Rešković, Lukšić

Bicuspid aortic valve is the most common congenital heart disease, although in the narrow sense it is not considered a disease but a predisposition for its development. The range of manifestations and the time of the onset of such a disease of the aortic valve vary greatly. In our practice, patients with manifestation at an early age, and especially those with accompanying anomalies (aortic aneurysm, coarctation, membrane), are classified under of congenital heart diseases due to the fact that, as is shown herein, such patients require constant monitoring and often multiple interventions. The patient described here is a good example of a combination of congenital disorder and coronary heart disease, which is characteristic for patients with congenital heart diseases under long-term monitoring.

Margarita Brida, Maja Strozzi, Darko Anić

Atrial septal defects (ASD) are the most common heart defect in adult patients and are often diagnosed late. This defect should be suspected whenever echocardiographic imaging finds an enlarged right ventricle. We report two cases of patients with newly-diagnosed ASD that were older than 50 years of age. In both cases the patients presented with arrhythmia (atrial fibrillation, i.e. total atrioventricular block), and a successful correction of the defect was performed. If there are no contraindications, that is primarily the development of significant pulmonary hypertension i.e. pulmonary vascular resistance, the active approach – defect closure – is recommended, since it significantly contributes to clinical improvement and reduction in mortality.

Dejan Došen, Maja Strozzi, Darko Anić

Ebstein’s anomaly is a rare congenital heart defect of the tricuspid valve and the right ventricle that presents at different ages and with different symptoms, depending on the anatomical variant and the severity of the tricuspid regurgitation. We report two cases of Ebstein’s anomaly discovered at an adult age when the patients presented with symptoms of heart failure. In both cases, echocardiography verified apical displacement of the tricuspid valve, severe tricuspid valve regurgitation, and significant dilatation of the right side of the heart. Since the patients remained symptomatic despite medication therapy, surgical correction of the tricuspid valve with bioprosthetic valve implantation was performed. At follow-up after 6 months, both patients showed significantly improved functional status.

Mirta Koželj, Katja Prokšelj, Jure Dolenc, Andraž Cerar, Tomaž Podnar

The management of 1623 adult patients with congenital heart disease in a 16-year follow-up period at the University Medical Centre Ljubljana is described herein. The mean patient age at the time of admission was 32±14.8 years (mean ± standard deviation; SD). The distribution of congenital heart disease, treatment, and mortality is presented. During the observation period, the mortality rate was 3.82%. The spectrum of congenital heart disease and the mortality rate in Slovenia correspond with data from the European Heart Survey. Care of pregnant women with heart disease is carried out by the same team of specialists as is care of patients with congenital heart disease.