Authors

• Maja Strozzi — University of Zagreb School of Medicine, University Hospital Centre Zagreb, Zagreb, Croatia — ORCID: 0000-0003-4596-8261
• Margarita Brida — University of Zagreb School of Medicine, University Hospital Centre Zagreb, Zagreb, Croatia — ORCID: 0000-0001-8754-8156
• Darko Anić — University of Zagreb School of Medicine, University Hospital Centre Zagreb, Zagreb, Croatia — ORCID: 0000-0002-7378-944X

Abstract

Due to the growing number of patients with adult congenital heart disease (ACHD), although their exact number and distribution in Croatia is not yet known, monitoring and treating these patients in specialized centers has become a necessity. Their number is estimated at 12 000, and in most cases these patients will require one or more surgical procedures due to complications later in life. The recommendations of the European Society of Cardiology include guidelines on the necessary number of specialized centers and their organization. Organization of such a center has begun in the Zagreb Clinical Hospital Center. This article describes the first steps being taken, which include setting up a clinic for ACHD, regular multidisciplinary councils, formation of a patient registry, and first steps towards educating the cardiologic community. A large number of patients were examined in the Center recently, providing insight into the specific problems in this patient population; we will present three cases here. The first is a woman with a surgically repaired tetralogy of Fallot but with an improperly diagnosed and treated case of arrhythmia, which can lead to serious clinical deterioration. The second patient is a woman with a case of corrected transposition that went undiagnosed due to a lack of experience on part of the cardiologist. Although the patient has not experienced significant difficulties, they are expected in the future, making a correct diagnosis extremely important. The third case is a typical ACHD patient, a woman that had undergone numerous surgeries in childhood in a constant search for a long-term solution, which in this case was a non-surgical valve replacement at aortic position. This overview also outlines specific challenges faced when treating young people who put especially high value on the quality of life.

Keywords

congenital heart diseases, adults, organization, registry, transposition of the great arteries, tetralogy of Fallot

DOI

Full Text

## Introduction Lately we have witnessed a growing population of patients with adult congenital heart disease (ACHD). Precise data on the size and composition of this patient population in Croatia is not yet available, but the growth trend, caused primarily due to greatly increased childhood survival rates of patients with congenital heart disease (CHD), is real. A population study encompassing children with CHD between 1985 and 1994 in Great Britain found that 78% of the children survived until 16 years of age, when they were classified as adults. Population analysis showed that as many as 82% of these congenital defects can be considered more or less hemodynamically significant, which necessitates serious long-term medical care. Most ACHD have been diagnosed in childhood, but some are diagnosed for the first time as adults. The prevalence of ACHD is estimated at 3-6.1 per 1000. (1) In Croatia this amounts to more than 12 000 patients. This approximation is based on epidemiological data from other developed countries and data from Croatian pediatric cardiologists. (2) In the review article on ACHD in Croatia published in this journal in 2012 (3), the authors presented all the known data on national CHD epidemiology in childhood and outlined the problems in the organization of ACHD medical care. They concluded there was a need for organized care for ACHD patients primarily through educations of internist-cardiologists, organizing a specialist center capable of pursuing the optimal multidisciplinary approach, and forming a patient registry. A review article in this issue of the journal (4) informs about the most important developments in ACHD treatment based on the literature published during the last two years. During that period, there has been little progress in Croatia. This review article describes the formation of an ACHD center in the Zagreb Clinical Hospital Center and presents three cases characteristic of the challenges faced in treating these patients in Croatia. ## Forming the Center and ACHD patient registry After the publication of the ACHD treatment guidelines in 1998, the organization of a center for the treatment of these patients was started, and a drop in mortality was noted already within three years, although the cases were increasingly complex. The 10% increase in patients monitored in specialized tertiary centers translated into a 5% drop in mortality within five years. (5) The most recent guidelines, published in 2010, also stress the need to provide organized special treatment for patients with ACHD. (6) The most common causes of poor medical treatment for patients with ACHD that necessitates the organization of specialized centers are as follows (7): - Patients with ACHD are lost to pediatric monitoring once they become adults, and this group of patients usually does not receive sufficient attention from the family doctor or internist-cardiologist; - The patients and their parents are not sufficiently informed of their condition, partly because they were children at the onset of the disease, and the parents often do not have a realistic approach. Partly to blame is the “short” history of successful surgeries of complex heart defects, with long-term results and late consequences only now becoming apparent; - Insufficiently educated cardiologists licensed for treating such cases in adult age. Although individual cardiologist in the University Hospital Centre Zagreb, University Hospital Centre "Sestre milosrdnice", and elsewhere expressed interest in this group of patients a long time ago, these were individual efforts. The organization of the ACHD center in the University Hospital Centre Zagreb in 2014 took several different directions: - Forming a patient registry (data has been collected on the first 200 patients within three months); - Founding an ACHD clinic, which operates once a week for now, and soon to be at new premises at the Daytime Hospital of the Cardiovascular Diseases Clinic; - Holding weekly ACHD meetings of a multidisciplinary team with constant membership, comprised of a number of cardiologists, a pediatric cardiologist, a cardiac surgeon specialized in congenital anomalies, and other experts as needed; - Acquiring additional equipment. The first few months provided better insight in the specific challenges in treating this group of patients. Due to the complexity of the cases, patients with ACHD require more time for clinical examination and ultrasound evaluation; invasive examinations are more difficult; and there are other issues to be addressed (questions about physical exertion, pregnancy, contraception, sports, etc.). In this short period we already encountered a number of patients who had been insufficiently evaluated and treated until now. We report three typical cases from the ACHD patient registry. ## Case one: Tetralogy of Fallot Patients with surgically treated tetralogy of Fallot (ToF) have increased morbidity and mortality, which can already manifest in early adulthood. According to most recent data, risk factors for sudden cardiac death and ventricular arrhythmia in these patients are hypertrophy and right ventricle (RV) dilation, ventricular dysfunction, and atrial tachyarrhythmias. (8) The most common cause of RV weakening are changes on the pulmonary valve, insufficiency being the most common. Although is well clinically tolerated, causing dilemmas on the need and time of corrective treatment, earlier treatment has been favored recently due to low procedural risk and to preserve RV functionality, avoiding unwanted cardiac events. (9) Atrial arrhythmias are also a risk factor for sudden cardiac death and ventricular tachycardia. Case report: Lj. P., born in 1962, underwent complete surgical correction of ToF at 15 years of age. She tolerated physical exertion well, and gave birth to nine healthy children. The first difficulties regarding lack of tolerance to exertion began to manifest in her forties, due to severe stenosis of the output flow of the RV as well as pulmonary stenosis. Reoperation was performed in 2009 and included closure of a small residual ventricular septal defect (VSD). This resulted in clinical improvement, but no regular follow-up was made. Three years before her presentation to the ACHD center, exertion intolerance began to reoccur. Repeated electrocardiogram (ECG) tests described sinus tachycardia at 120/min. Upon her arrival to the center, a clear atrial flutter at 130/min was found, and was constant on the ECG holter. Cardiac ultrasonography found hypocontractility of the RV, TAPSE 9, but also of the left ventricle (LV), EF 35%, with no residual VSD, as well as mild dilation of the ascending aorta, with no stenosis in the output pressure of the RV or the pulmonary valve. Despite the long duration of the undulation, the electroconversion was successful (Figure 1). Figure 1. 12-lead ECG before and after conversion. Due to beta-blockers and amiodarone, the patient is maintained on a stable sinus rhythm, with significant clinical improvement along with improved systolic function of the LV. A magnetic resonance imaging (MRI) test is scheduled to ascertain RV parameters. (10) Discussion: The clinical development is typical for patients operated for ToF. In her childhood and youth, the patient had no clinical difficulties and brought nine pregnancies to term with no complications, a rarity even in completely healthy women. (11) It is typical of ACHD patients in Croatia to forgo special examinations barring significant clinical deterioration. After the second surgery, the patient also discontinued tertiary center monitoring and treatment for arrhythmia. Atrial arrhythmia is common after ToF operations, and is associated with significant morbidity, including cardiac failure, serious disorders in ventricular rhythm, reoperation, and death. Atrial arrhythmia is common in patients with increase atrial volume and significant pulmonary regurgitation, which was not the case here. (12) A study indicates that pulmonary vein ablation is also a possible treatment for atrial flutter after ToF correction. (13) In our patient, sinus rhythm was achieved through electroconversion, despite the long duration of the arrhythmia. Conclusion: Neglecting regular follow up in a tertiary center led to relatively late repair of the pulmonary valve, only after serious symptoms had been manifested. Even after successful surgery, there was no proper follow up, and the patient suffered from atrial tachycardia for two years, resolved only after she presented at a specialized center. Cardiac ultrasonography indicates the reoperation six years ago was successful, despite reduced ventricular function. A magnetic resonance imaging (MRI) test is scheduled, as well as regular follow up in the ACHD center. ## Case two: Corrected transposition of the great arteries (L-TGA) Corrected transposition of the great arteries (L-TGA) involves switching the RV and LV as well as the aorta and pulmonary artery (double discordance). (14) If the patient has no other anomalies, it is not uncommon for it to be diagnosed later in life, usually when the first symptoms appear, which are most often heart failure, rhythm disturbances, or appearance of a new heart murmur. Sometimes it is discovered by accident. Long-term outcome is determined by the progressive weakening of the systemic (right) ventricle and tricuspid valve insufficiency, usually in the when the patient is in their forties or fifties. (15) Case report: M. B., born in 1979, healthy, gave birth to two children. Five years ago, during a routine checkup, ECG was pathological (pathological left axis, inferior scar pattern, interventricular conduction disorders). Despite the lack of clinical difficulties other than an intermittent feeling of the heart pounding, a detailed cardiologic examination was performed. Echocardiographic findings were repeatedly found to be within normal limits, other than a suspect minor apical aneurysm in the RV. MSCT coronarography was also within normal limits. Nuclear magnetic resonance (NMR) demonstrated cardiac rotation and moderate diastolic dysfunction, which was explained by the fact that the patient has a thoracic anomaly (pectus infundibuliforme). The cardiologist referred the patient to the ACHD center. An echocardiographic examination was performed, and L-TGA was diagnosed (Figure 2). The systemic ventricle was anatomically on the right. A reduction in systolic function of the systemic ventricle was also noted – EF 45% – as well as mild tricuspid regurgitation. Figure 2. Echocardiography image of the patient with corrected transposition. To the left of the image is the anatomically left ventricle (functionally the right ventricle), with a lower-placed AV valve insertion; to the right of the image the right ventricle is at the place of the systemic ventricle. Discussion: L-TGA is most commonly diagnosed using echocardiography, based on the anatomical characteristics of the ventricles and the insertion point on the atrioventricular valves. Descriptions of the “right” ventricle from earlier echocardiographic examinations mention an apical aneurysm, but the ventricle is actually perfectly normal for an anatomically left ventricle. This was a case of a lack of experience in ACHD diagnostics, as was the failure to establish a diagnosis after NMR imaging. The patient is 35 years old, and has had no subjective difficulties so far regarding exertion intolerance and arrhythmia, but difficulties can be expected to emerge in the following years due to the impaired function of the systemic ventricle. Long-term monitoring of such patients shows that mortality in such patients is caused by heart failure or sudden death. (16) The question of tricuspid regurgitation remains open. It has still not been determined whether it is a consequence of ventricle failure or vice-versa. It is clear that it is an issue with the treatment, since the results of operations, repair, and artificial valve implants are all poor. (17) Careful monitoring of such patients in a specialized center is recommended. Conclusion: In this case, establishing a correct diagnosis was very important for implementing lifestyle changes, including caution in physical exertion, and in life decisions such as a new pregnancy, which can cause hemodynamic changes. (18) The patient was recommended a yearly follow up in a specialized center, which would include a echocardiographic imaging to monitor the function of the systemic ventricle and the development of tricuspid regurgitation. ## Case three: Complete transposition of the great arteries (D-TGA) D-transposition of the great arteries is a cyanotic heart defect in which the pulmonary artery exits the morphologically left ventricle, and the aorta is attached to the morphologically right ventricle. Survival is possible only if there is mixing between the two parallel circulations in the form of a ventricular or atrial septal defect and an open ductus arteriosus. (19) Performing cardiac surgery as soon as possible is crucial to allow survival. The arterial switch operation which switches the arteries to their anatomical positions is the operation of choice today. Long-term monitoring is unavoidable due to possible later complications that are found in 5-25% of cases and often require reintervention, e.g. stenosis of the pulmonary artery, coronary artery insufficiency, dilation of the neo-aortic root, neo-aortic stenosis or insufficiency. (20) Case report: U. J., born in 1987 with D-TGA, underwent arterial switch surgery with correction of associated anomalies: closure of the atrial and ventricular septal defect and ductus arteriosus, as well as a commissurotomy of the pulmonary valve and correction of peripheral pulmonary stenoses. She underwent three more complex cardiac surgeries during childhood, including the replacement of the aortic valve with a biological prothesis (25 mm) in 2001 due to significant aortic insufficiency, and correction of aortic coarctation after unsuccessful dilatation in 2002. She experienced no further clinical difficulties, and gave birth naturally to a healthy boy in 2010. Soon after, she began experiencing progressively worse symptoms due to degeneration of the artificial aortic valve (maximal systolic gradient 110mmHg, mean 80mmHg, with preserved global systolic function of the left ventricle). A conventional cardiac surgical procedure, which would be her fifth, was proposed, but the patient was reluctant due to other alternative treatments being considered and the fact that she was a single mother. After detailed evaluation of the situation, in cooperation with a center outside the country, a decision was reached and a transcatheter aortic valve implantation (TAVI) procedure was performed:”valve in valve” with 26 mm balloon-expandable transcatheter valve (Sapien XT, Edwards Lifesciences Inc., Irvine, CA, USA). After the procedure, the patient is clinically fine, and after a year of follow up the maximal systolic gradient in ultrasound tests was 23 mmHg, mean 14 mmHg (Figure 3). The young mother could return to her son after only a brief absence. Figure 3. Echocardiographic image – Doppler of the aortic valve before and after the transcatheter aortic valve implantation procedure that indicates a significant gradient reduction. Discussion: As opposed to typical cardiologic cases, patients with ACHD come primarily from a young population, which places special emphasis on quality of life. This case illustrates the diversity of possible anomalies, as well as the constant possibility of deterioration leading to reintervention, either catheter-based or surgical. Our patient developed significant aortic insufficiency (the valve was originally pulmonary) and required valve implantation already at 14 years of age. (21) Despite numerous surgeries, this young woman has become a mother and considers her quality of life to be high. As expected, after 13 years since valve implantation, the biological implant began to degrade, causing serious stenosis. To accommodate the single mother’s request to delay the next surgery, we decided to perform a TAVI procedure despite very limited experience with percutaneous valves at the aortic position in CHD. (22) However, long-term outcomes are not yet known for young patients who underwent TAVI procedure, and there is a risk of early valve degeneration. Our patient is one of the youngest in the world to undergo a procedure otherwise intended for the elderly. Conclusion: Young patients with CHD are a unique patient population regarding the complexity of diagnosis and possible complications. They require a multidisciplinary approach not only from the specialist from our center, but occasionally also conferring with international centers to decide on the optimal treatment. The patient will receive regular follow up in the ACHD center, and several options are available in case of further valve degeneration, including reoperation and percutaneous reimplantation of ever-improving valves. ## Conclusion The aim of this review article was to inform the wider cardiologic public of the necessity of organizing a specialized ACHD center and of the efforts of the University Hospital Centre Zagreb to improve the treatment of these patients. We also described cases in which specialized care resulted in correct diagnosis and successful treatment or an improvement in overall health.

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