Preface

This book presents some of the advances that have occurred in pediatric cardiology over the last 50 years for healthcare personnel involved in caring for infants, children, and adults with congenital heart disease (CHD).

The book is divided into seven sections. The first section introduces the book. In the introductory chapter, I review the evolution of pediatric cardiology over the last 50 years and summarize developments during this period. Then, I outline how this book is organized.

In Section 2 on fetal ultrasound, Dr. Russo et al. address the impact of fetal echocardiography on the prognosis of CHDs in Chapter 2. The authors state that CHD is one of the most common birth defects discovered both in utero and immediately following birth. They opine that current advances in the diagnosis and management improved the prognosis of babies born with CHD such that a large number of these babies are reaching adulthood. Then, they review historical aspects of fetal echocardiography since its early phases in the late 1980s. They assert that the diagnostic accuracy of fetal echocardiography is high, permitting the identification of most types of CHDs in the fetus. This facilitates fetal cardiac interventions when indicated; enables voluntary interruption of pregnancy, if necessary; simplifies pregnancy and delivery management; provides fetal and genetic counselling; identifies babies that need emergent neonatal management (ductal dependent lesions); and most importantly has a positive impact on improving long-term outcomes.

In Section 3 on echocardiography, Drs. Kojc and Varda review the clinical benefits of new echocardiographic methods in Chapter 3. The authors state that the chief objectives of echocardiography are the precise evaluation of myocardial function and accurate demonstration of cardiac morphology. The authors review some of the new echocardiographic approaches, including functional echocardiography, cardiac deformation imaging, and three-dimensional echocardiography with a focus on the key advantages, clinical utility, and chief limitations of each technique. Functional echocardiography, also called targeted echocardiography, is different in newborns compared to older children. It involves evaluation of cardiac function, assessment of the degree of pulmonary hypertension, detection of pericardial effusion and its adverse effects, and assessment of the magnitude of shunts (such as hemodynamically significant patent ductus arteriosus [hsPDA] in premature babies). Functional echocardiography permits real-time assessment of cardiac function recognizes the type of cardiovascular compromise, guides therapy, and monitors response to therapy. Myocardial deformation imaging includes assessment of strain and strain rate change, which helps evaluate both global and regional functions of both ventricles and helps circumvent disadvantages of load-dependent ventricular function parameters such as fractional shortening, ejection fraction, and fractional area shortening. Three-dimensional speckle-tracking offers an additional inclusive assessment of ventricular function. While strain imaging is well studied

in adult subjects, its use appears limited in pediatric patients. Three-dimensional echocardiography along with real time imaging (four-dimensional) is a relatively recent invention in ultrasound of the heart. It may be useful in subjects with CHD because it provides an appreciation of intricate spatial relationships. These new modalities may have advantages over the other existing imaging techniques such as magnetic resonance imaging (MRI) and computed tomography (CT), which are expensive, require anesthesia, or have increased radiation exposure. The disadvantages of three-dimensional imaging are low temporal and spatial resolution and the need for offline processing.

In Section 4, on the prevention of sudden cardiac death (SCD) in the athlete, I review in Chapter 4 issues related to sudden death associated with sports participation of athletes with a particular focus on pre-participation screening. SCD in sports, although rare, is a disastrous event. Sudden death in athletes often has a cardiac etiology and the most frequent causes are hypertrophic cardiomyopathy (HCM) and congenital coronary artery (CA) anomalies. I present a brief description of the anatomy, pathophysiology, and clinical features of HCM, aberrant CAs, Marfan's syndrome, arrhythmogenic right ventricle, and other entities responsible for SCD. The current recommendations are to perform a pre-spots participation screening consisting of complete personal and family history and a thorough physical examination. If abnormalities are detected during history or physical examination, further studies should be performed to define the etiology of the abnormalities. Using an electrocardiogram, echocardiogram, or MRI as a routine screening method is not recommended in the United States. I suggested that the pre-spots participation screening be undertaken at the primary care physicians' office as a part of routine annual physical (instead of mass screening but should include the fourteen-element history and physical examination. The justification of pre-participation screening is to allow as many athletes as feasible to take part in sports instead of being excluded from participation.

Section 5 consists of Chapters 5–8 on individual heart defects. Chapter 5 by Drs. Doshi and Wang-Giuffre discusses ventricular septal defect (VSD). The authors state that VSDs constitute up to 30% of all CHDs and that they are the most frequent heart defects seen in everyday clinical practice. The causation of CHDs, including VSDs, is largely explained based on multifactorial inheritance, although chromosomal abnormalities may sometimes be involved. Symptomatology is largely related to the magnitude of the shunt across the VSD. Echocardiographic studies are the chief modes of investigation to define the defects and their clinical significance. The natural history of VSDs involves spontaneous closure, development of pulmonary vascular obstructive disease (PVOD), onset of infundibular stenosis, and evolution to aortic insufficiency. Spontaneous closure is one of the main features of VSD; when that happens, no treatment is necessary. Hemodynamically significant shunts require surgical repair. Surgery is also recommended in patients with aortic valve leaflet prolapse and aortic insufficiency, irrespective of the degree of shunting across the VSD. The outcome following surgical correction is excellent, although an occasional patient may develop complete atrioventricular block or worsening aortic valve regurgitation. New methods of transcatheter and hybrid device closures are useful in patients with large muscular VSDs. Large, unrepaired VSDs may go on to develop irreversible PVOD, leading to Eisenmenger's syndrome, although this is uncommon in developed countries. Patients with Eisenmenger's syndrome may be

treated with endothelin receptor antagonists, phosphodiesterase 5 inhibitors, and prostacyclins; such treatment modalities appear to improve functional capacity. Patients with PVOD are not candidates for closure of VSD but may require eventual lung transplantation. In Chapter 6, Dr. Donthula and I review the issues related to atrioventricular septal defects (AVSDs). AVSDs are defects in the atrioventricular (AV) septum and AV valves. AVSD is the most common defect seen in patients with Down syndrome. They are classified into complete, intermediate, partial, and transitional forms. Complete forms of AVSDs are further divided into balanced and unbalanced defects. Echo-Doppler studies are the main imaging methods used for the diagnosis and assessment of AVSDs. Subjects with complete and intermediate types manifest early in infancy and surgical repair is needed, also in early infancy, while partial and transitional varieties develop symptoms in early childhood and need surgical intervention at that time. Babies who can't undergo complete surgical correction (because of their weight or comorbidities) are addressed by palliation with pulmonary artery banding. Surgical treatment of unbalanced AVSDs is more complicated. These patients are addressed with either single ventricle, one-and-a-half ventricle, or bi-ventricular repair, depending upon their anatomy and physiology. Prognosis following surgery is generally good for balanced AVSDs and residual mitral valve insufficiency is the most frequent reason for repeat surgery. For the unbalanced AVSDs, the selection of the type of procedure is more complex and the long-term outcome is less than ideal. In Chapter 7, Dr. Bell-Cheddar et al. tackle issues related to hypoplastic left heart syndrome (HLHS). The authors define HLHS as a complex CHD consisting of the hypoplastic left ventricle (LV), aorta (Ao), and mitral valve. This defect resulted in the uniformly fatal outcome prior to the description of the Norwood procedure in the early 1980s, but now, with the use of a three-stage surgery including Fontan, prognosis has improved remarkably. Nevertheless, a high morbidity and mortality still exist in 25% of babies with HLHS who either need heart transplantation or die within one year following the Norwood procedure. While the reasons for such high morbidity/mortality were not clearly defined, they appear to be related to cardiovascular/hemodynamic abnormalities. In the remaining part of the chapter, the authors focus on the studies of a mouse model of HLHS. The studies demonstrate metabolic dysfunction resulting in the arrest of cell cycle and defects in cardiomyocyte differentiation. It is hypothesized that these intrinsic cell defects contribute to cardiac abnormalities of HLHS. In addition, the association of HLHS with chromosomal anomalies and high recurrence rates support the genetic etiology of HLHS. Finally, Chapter 8 by Dr. Da Silva et al. is on Ebstein's anomaly. The authors characterize Ebstein's anomaly of the tricuspid valve (TV) as downward displacement of the septal and inferior leaflets of the TV. In addition, there is a redundancy of the anterior leaflet with a sail-like morphology, dilatation of the true right AV valve annulus, TV regurgitation, and dilation of the right atrium and right ventricle (RV). They also describe a similar abnormality of the left-sided morphologic tricuspid valve in patients with congenitally corrected transposition of the great arteries. Then they review the existing classifications and pathophysiology of Ebstein's anomaly. This is followed by a description of diagnostic studies such as echocardiography, cardiac MRI, and CT for evaluation of Ebstein's. The authors also examine the historical evolution of surgical management. They comment that the wide variability of anatomic and pathophysiologic characteristics of Ebstein's anomaly resulted in not securing uniformly good results following surgical repair; this resulted in the development of several surgical repair techniques. Then, they provide a detailed description of the cone procedure, which was developed by one of the authors of this

chapter. The Da Silva technique of cone reconstruction of the TV involves the creation of a cone-like structure from all available TV leaflet tissue; the result simulates normal TV structure. The authors contend that the cone procedure for Ebstein's anomaly has low mortality/morbidity with effective and long-lasting results in most patients. They also discuss the relative advantages of valved atrial septal defect (ASD) closure vs. bidirectional Glenn procedure in patients with inadequate RV to support pulmonary circulation. They then address surgical management of Ebstein's anomaly in the neonate. In the final section, they discuss post-operative management in detail. They conclude that given the advances in diagnostic techniques, surgical management, and peri-operative care, most Ebstein's anomaly patients are likely to have two-ventricle repair with good long-term results.

Section 6 reviews therapy. In Chapter 9, Dr. Surak reviews the pharmacological management of patent ductus arteriosus (PDA) in preterm infants. The author states that PDA is responsible for several morbidities in preterm infants and that there is an inclination toward a more conservative treatment of PDA instead of surgical therapy. He discusses the utility of targeted neonatal echocardiography in the detection of hsPDA. He then reviews the results of pharmacological therapy of PDA in preterm babies with non-steroidal anti-inflammatory drugs (NSAIDs) such as indomethacin and ibuprofen as well as acetaminophen. He also refers to the usefulness of combined therapy (ibuprofen and acetaminophen) in occluding the ductus. Finally, he mentions device closure of PDA and quotes safety and efficacy data of device occlusion of PDA. It is concluded that pharmacological therapy, while causing ductal constriction, does not guarantee the elimination of the shunt and that additional research is necessary to see if the device closure approach would produce added favorable outcomes in the premature. In chapter 10, Dr. Abqari discusses right ventricular outflow tract (RVOT) stenting. The standard management option in children with CHDs with diminished pulmonary blood flow is the creation of systemic-to-pulmonary artery shunt such as a modified Blalock-Taussig (BT) shunt. However, RVOT stenting has recently been used for palliation. The author asserts that RVOT stenting results in fewer complications and achieves physiological growth of pulmonary arteries (PAs). The latter may have a positive impact during final corrective surgery. Usually, RVOT stenting is undertaken in the neonate, but in some institutions, it is being used in older children. The author presents indications for RVOT stenting and provides a detailed description of RVOT stent procedure. The author also presents modifications, complications, challenges, and outcomes of the procedure. Two-point fixation of the stent guarantees the prevention of stent embolization. However, covering only the infundibular region, and sparing the pulmonary valve may prevent future trans annular patches, although removing the stent may be challenging. The author believes that RVOT stenting is a safer alternative in some pediatric cardiac programs, although several programs opt for primary surgical correction. The author concludes that RVOT stenting is expected to garner greater acceptance amongst other palliative procedures as larger experience with this procedure is gained. In Chapter 11, Dr. Wong et al. review the advances in the management of congenital malformations of the aortic valve. The authors state that congenital malformations of the aortic valve are life-long ailments that may need many catheters and/or surgical procedures. The bicuspid aortic valve may be seen in 1%–2% of live births, whereas aortic valve stenosis is much less common. The authors review management options, including balloon aortic valvuloplasty, surgical valvotomy, surgical repair of the aortic valve, and aortic valve replacement. The options of bicuspidization and tricuspidization

types of reconstruction and materials used for the reconstruction of the aortic valve are also reviewed in detail. Then, the authors address aortic valve replacement with mechanical valves and bioprosthetic valves (bovine or porcine valves, homografts, and allografts) or by Ross procedure (patient's own pulmonary valve is relocated to the aortic valve position and a tissue valve replaces the pulmonary valve). They also review the relative advantages of repair vs. replacement. In general, the described techniques carry their own benefits and have their own limitations regarding growth potential, longevity of repair, need for repeat surgery, anticoagulation requirement, risk of infection, and morbidity/mortality risks. The authors conclude by presenting a basic algorithm for the management of aortic stenosis.

Section 7 reviews international issues. In Chapter 12, Dr. Elshazali et al. discuss the management of CHD in low-income countries (LICs) and low-middle-income countries (LMICs). They review the epidemiology of CHD in the LICs and compare it with that in high-income countries (HICs). Although the overall prevalence of CHD is similar (8 to 9 per 1,000 live births), higher fertility and birth rates in LICs than in HICs result in 90% of babies with CHDs being born in countries with limited resources in caring for these babies. Pediatric cardiac services are considered to be a burden and a challenge in LICs and are a challenge as well in LICs. The currently available pediatric cardiac services in most LICs are difficult to access and not affordable for most and there is an absence of awareness of the necessity for quality pediatric cardiac services. Healthcare planners should recognize that pediatric cardiac services are essential services and are not a luxury. The authors recommend collaboration and partnerships among international organizations, national and local governments, and non-governmental organizations. They also assert that patient and family advocates are required to assure that children around the world have access to quality and dependable pediatric cardiac care. They quote some shining examples of countries such as Cuba, India, and China which accomplished providing pediatric cardiac services with strategic planning and leadership. They conclude that capacity building to accomplish the eventual objective of self-sufficient LIC and LMIC programs will necessitate a paradigm change by the leadership of the respective countries, better alliance among stakeholders, and facilitate data sharing and research expansion. In Chapter 13, Dr. Nwafor et al. review issues similar to those dealt with in the preceding chapter, but with a focus on Nigeria. They state that the delivery of cardiovascular services to children and adults with CHDs in Nigeria is grossly inadequate. They also opine that there is no accurate statistical data on CHD in Nigeria, but suggest that the prevalence of CHD is comparable to that reported in other countries (8 per 1,000 live births). They first review historical aspects of the development of surgery for CHD in Nigeria. The problems of inadequate surgical resources are presently improved by medical tourism and cardiac surgery missions from foreign countries, but the authors' assessment is that such services are still not adequate. They opine that there is a need for the government to share resources between non-communicable diseases such as CHD and communicable diseases. When this is accomplished with the help of international partners and humanitarian organizations, a sustainable pediatric cardiac surgery program is likely to be established. They conclude that such efforts will definitely improve the care of patients with CHD.

The last five decades have witnessed a great many advances in the diagnosis and management of CHD that have resulted in increased survival of children with heart disease. This book discusses some of these advances and is a useful resource on diagnostic and therapeutic methods for healthcare professionals in providing quality care to their patients with cardiac disease.

> **P. Syamasundar Rao, MD, DCH, FAAP, FACC, FSCAI** Children's Heart Institute, University of Texas at Houston McGovern Medical School, Children's Memorial Hermann Hospital, Houston, Texas, USA

> > Section 1

Introduction
