CHAPTER 56: CONGENITAL HEART DISEASE IN ADOLESCENTS AND ADULTS

The incidence of moderate and severe forms of congenital heart disease (CHD) is 6 per 1000 live births. If bicuspid aortic valves (BAVs) are included, the incidence increases to 19 per 1000 live births.¹ Without early medical or surgical treatment, the majority of patients with complex CHD would not survive to adulthood.² Surgical and medical advances over the past 60 years have dramatically altered the once bleak prognosis of patients with CHD. In the current era, more than 85% of patients with CHD survive to reach adulthood, and most live productive and functional lives.^3,4 Many patients have undergone surgical interventions that were once thought to be curative. However, with the exception of early surgical ligation of a patent ductus arteriosus (PDA), a surgical “cure” for complex CHD without operative sequelae or need for reoperation does not exist.⁵

Adults with operated and unoperated CHD require long-term follow-up. This long-term care should include cardiologists with experience in or who specialize in adult CHD (ACHD). Standardized diagnostic and treatment guidelines have emerged from the American College of Cardiology (ACC) and American Heart Association (AHA).⁶ Cardiologists trained and experienced in patients with complex CHD can minimize diagnostic and treatment errors with a strong knowledge base in pathophysiology, cardiovascular hemodynamics, and prognosis of congenital lesions.

These patients may also face a variety of psychosocial issues, including self-image problems; difficulties in acquiring and maintaining health and life insurance; exercise and activity limitations; and issues of sexuality, contraception, and reproduction. Patient referral to a regional team of experts in a recognized ACHD center is encouraged to facilitate specialized counseling and management.

Specialized ACHD centers have developed in North America and Europe, but there remains a need for more specialized centers even in these regions.⁷ Requirements for comprehensive ACHD care centers include dedicated ACHD clinics, ACHD cardiologists, congenital cardiac surgeons, nurse specialists, and consultants. Training and research are of pivotal importance. The development of management, research, and training guidelines over the past two decades is a major step forward for the field of ACHD.^6,8,9,10,11 Another encouraging development is the establishment of the Adult Congenital Heart Association (ACHA) in the United States. This nonprofit patient-initiated association seeks to improve the quality of life and extend the lives of adults with CHD by leading legislative efforts, sponsoring patient and physician conferences, and identifying and certifying comprehensive ACHD centers in the United States. Multicenter and prospective clinical research in ACHD has increased in frequency and variety.¹² A dedicated multicenter research network, the Association for Adult Research in Congenital Cardiology, was established in 2007 in North America to foster and implement multicenter research.¹³ A recent collaboration between the ACHA and the National Heart, Lung, and Blood Institute also strives to identify and promote key areas of research in ACHD.

Many adults with CHD have not had, or may never require, surgical intervention. The most common defects incidentally encountered in adulthood are small ventricular septal defects (VSDs) or atrial septal defects (ASDs), mild pulmonary stenosis, BAVs, and mitral valve prolapse. Less common, but more complex, conditions include nonrestrictive central shunts with right-to-left shunt reversal resulting in the cyanotic Eisenmenger syndrome and pulmonary hypertension. Most patients require long-term follow-up to monitor for disease progression, appropriately treat possible sequelae or complications, and reinforce the need for a healthy lifestyle and diligent dental care.⁶ Women of childbearing age and men wishing to father children should be informed of the risks of pregnancy and the increased risk of CHD in their biological children.¹⁴

An increasing number of patients who underwent childhood palliative procedures, such as Glenn or Fontan cavopulmonary shunts, or corrective operations, such as intracardiac repair of tetralogy of Fallot (TOF), are reaching adulthood. Many patients are under the false impression that they are “cured” and are lost to follow-up until symptoms bring them back to medical attention. Uncorrected, corrected, and palliated patients often require repeat operations, interventional catheterizations, and electrophysiologic therapies in adulthood. All adults with CHD should have a consultation with an ACHD center at least once to determine optimal frequency and center for follow-up. Performance of advanced diagnostic studies and interventions at experienced centers is highly recommended given the potential complexity and rarity of some conditions.⁶

Hemodynamics

Progressive myocardial dysfunction with resultant heart failure is a leading cause of morbidity and mortality in patients with CHD. Patients may present with left, right, biventricular, and, at times, univentricular failure. The etiology of systolic or diastolic heart failure is often multifactorial and may include pressure or volume overload, chronic hypoxia, and/or pulmonary vascular disease. Intrinsic myocardial abnormalities may result in restrictive diastolic properties, leading to a chronic low cardiac output state, volume overload, congestive hepatopathy or nephropathy, ascites, and protein-losing enteropathy. Complications of restrictive cardiomyopathy are often progressive and difficult to manage; cardiac transplantation is the ultimate therapeutic option.

Physical examination includes a thorough assessment of volume status with specific attention to the jugular venous filling pressure and waveform. Pulmonary hypertension or ventricular filling abnormalities are often accompanied by an amplified A wave in the jugular venous pulse. Right-sided atrioventricular (AV) valve regurgitation may result in an amplified jugular venous V wave proportional to the severity of regurgitation. Percussion and palpation of the liver to evaluate for pulsatility and degree of hepatomegaly are recommended. Doppler echocardiography is indispensable for noninvasive evaluation of hemodynamics and shunt fractions.^15,16 Exercise testing is helpful to evaluate for exertional symptoms and, when combined with echocardiography, is also useful for correlating symptoms with exercise-induced gradients in obstructive lesions. Invasive cardiac catheterization is important for patients with inadequate acoustic windows that limit the utility of transthoracic echocardiography (TTE) or in those in whom pulmonary vascular resistance, shunt fractions, or chamber pressures cannot be gleaned from noninvasive methods and must be measured directly. Cardiac magnetic resonance imaging (MRI) is an important adjunct modality for quantification of biventricular function, calculation of systemic and pulmonary flow, and quantification of valvular regurgitation.¹⁷

Operations to palliate or repair congenital cardiovascular lesions were originally devised to address physiologic issues, specifically to increase or diminish the supply of blood to the pulmonary circulation. The early era of congenital cardiac surgery was marked by giant leaps forward in the physiologic treatment of lesions. In the 1940s, the development of aortopulmonary shunts, such as the famed Blalock-Taussig shunt, allowed palliation of patients with pulmonary atresia or a functional single ventricle¹⁸ (Fig. 56–1). Another major surgical development was the atrial switch operation, also known as the Mustard or Senning procedure, for correction of complete or dextro-transposition of the great arteries (TGA; Fig. 56–2), in which deoxygenated blood is redirected by the atrial baffle from the cavae to the left ventricle (LV) and thereafter to the pulmonary arterial circulation. The oxygenated pulmonary venous blood returns to the systemic right ventricle (RV). These operations are successful in diverting blood flow to improve or correct physiology, but do not normalize anatomy or optimize hemodynamics. Patients with systemic RVs or those with functional single ventricles are especially susceptible to deteriorating ventricular function. The heterogeneous morphology and loading conditions for these ventricles suggest that standard indices of ventricular function, namely echo or other imaging-derived ejection fraction, may not be as useful in identifying the highest risk subsets. Use of echocardiographic strain is helpful in diagnosing early myocardial dysfunction and carries important prognostic value in hypertrophic cardiomyopathy or acquired cardiomyopathy, and is being studied in the ACHD population.^19,20 Cardiac MRI has been studied and demonstrated to be superior to echocardiography for quantification of RV volumes and ejection fraction in patients with transposition.²¹ Elevations of serum brain natriuretic peptide (BNP) may help identify patients with increased ventricular wall tension often accompanied by ventricular enlargement and dysfunction.²² Atrial and ventricular arrhythmias increase in frequency and severity as ventricular function deteriorates and themselves lead to further decreases in cardiac output. Medical and surgical interventions are aimed at preservation of function and prevention of arrhythmias.

Postoperative residual defects may be a major cause of progressive deterioration decades after surgery. Severe chronic pulmonary regurgitation may be well tolerated for decades after surgery.²³ Eventually, progressive RV dilatation and elevated filling pressures, particularly if ventriculotomy scars coexist, may create the substrate for ventricular arrhythmias. Medical therapy for heart failure in patients with CHD is adapted from the guidelines for patients with ischemic and nonischemic cardiomyopathies.²⁴ There is a paucity of prospective randomized data evaluating heart failure therapies in patients with CHD. The renin-angiotensin system may not play as deleterious a role in certain subsets of patients with CHD compared with those with ischemic and nonischemic cardiomyopathies. For example, patients with systemic RVs with depressed systolic function do not demonstrate increased angiotensin levels and, therefore, do not appear to derive demonstrable intermediate-term benefit from the use of angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs).^25,26 Selective β-blockers may delay the progression of ventricular dysfunction and decrease the likelihood of arrhythmias.²⁷ Diuretics have not been rigorously evaluated in patients with CHD, but are frequently used to regulate volume status in patients with chronic volume-loaded conditions, such as Fontan patients.

Cyanosis

Adults with CHD may be cyanotic because of decreased pulmonary blood flow or mixture of desaturated systemic venous blood with pulmonary venous blood. Decreased pulmonary blood flow may occur in the presence or absence of pulmonary vascular disease. The latter is exemplified by unrepaired TOF with pulmonary atresia, in which pulmonary vasculature is supplied by aortopulmonary collaterals. Cyanosis in the presence of pulmonary vascular disease may be secondary to unrepaired central shunts (Eisenmenger syndrome) or the coincidence of idiopathic pulmonary hypertension in the presence of an ASD.²⁸

In 1897, Victor Eisenmenger described the autopsy findings of a 32-year-old man who had been cyanotic from infancy; findings included a large VSD, pulmonary arteriosclerosis, and pulmonary artery thrombosis. The cause of death was pulmonary hemorrhage. The Eisenmenger complex, coined by Maude Abbott, specifically refers to a reversed shunt (right to left) in the presence of a nonrestrictive VSD²⁹ (Fig. 56–3). The term Eisenmenger syndrome also refers to a reversed central shunt, but is used more broadly to encompass a heterogeneous series of congenital lesions in which the pulmonary vasculature is exposed to elevated or even systemic pressures, eventually leading to this physiology. During the first few years of life, the small muscular pulmonary artery branches are capable of relaxing, and the defect can be closed with a subsequent gradual decrease in pulmonary vascular resistance. After 2 to 3 years, reactive intimal fibrosis begins to obliterate the lumen of the muscular arteries, and they no longer respond to vasodilating agents such as acetylcholine, adenosine, or nitric oxide.³⁰ This obliterative process represents a fixed obstruction to flow; the shunt reverses, and surgical correction is contraindicated. Patients with trisomy 21 (Down syndrome) are especially susceptible to developing pulmonary vascular disease.³¹ Patients with cyanosis secondary to pulmonary vascular disease and shunt reversal experience significantly decreased maximal and submaximal exercise capacity compared with other patients with complex CHD (Fig. 56–4).^32,33

Survival in patients with Eisenmenger syndrome is reduced by approximately 20 years compared with healthy control subjects; nearly 50% of patients survive to the sixth decade of life.^34,35 Decreased functional capacity, heart failure, renal dysfunction, and arrhythmias are predictors of decreased survival. Patients with unrepaired truncus arteriosus and those with single-ventricle morphology have a poorer prognosis than patients with nonrestrictive VSD (Eisenmenger complex).³⁶ With single-ventricle morphology, especially RV morphology, progressive ventricular dysfunction is a concern. Causes of death include pulmonary hemorrhage, pulmonary arterial thrombosis, pulmonary artery dissection, ventricular arrhythmias, and ventricular failure.³⁶

Interestingly, patients with cyanotic CHD demonstrate an antiatherogenic substrate and are less susceptible to atherosclerotic heart disease than noncyanotic control subjects.^37,38,39 The coronary arterial circulation in cyanotic patients is characterized by markedly dilated and tortuous extramural coronary arteries and a well-developed microcirculation within the myocardium.^38,39 Serum lipid levels are low in cyanotic patients and remain low years after correction of cyanosis, suggesting the modulation of as-yet unidentified operator genes by cyanosis. The antiatherogenic state of these patients is further characterized by elevated bilirubin levels; increased nitrous oxide production by vascular endothelial cells because of increased shear stress from hyperviscosity; and low platelet levels, incurring less thrombotic risk.^37,40 Patients with chronic cyanosis also develop defective hemostasis from abnormalities in platelet function and in the coagulation and fibrinolytic systems.^41,42 Interestingly, the pulmonary arterial circulation is not spared from atherosclerosis and thrombosis. Indeed, these patients often demonstrate an aggressive atherosclerotic process within the pulmonary arterial tree that correlates with the duration of pulmonary hypertension.⁴³ Cardiac computed tomography (CT) may be used to quantify calcium deposition within the pulmonary arterial tree, as calcium is a surrogate marker for atherosclerosis (Fig. 56–5). Histologic examination of necropsy or autopsy pulmonary artery specimens demonstrates a mix of typical calcified lipid-rich atherosclerotic plaques and dystrophic intimal calcification. Pulmonary arterial thrombosis is common, especially in older patients, those with biventricular dysfunction, and those with decreased pulmonary blood flow velocity.^44,45 Unlike pulmonary emboli, in situ pulmonary arterial thrombosis is challenging to treat and may not respond to anticoagulation. Chronic anticoagulation increases the risk of life-threatening pulmonary hemorrhage, particularly in patients with thrombocytopenia, and is of unclear mortality benefit. As such, it should be avoided unless the patient has other definitive indications (eg, atrial fibrillation or deep venous thrombosis).³⁶

Chronic cyanosis leads to secondary erythrocytosis and, if uncompensated, may result in hyperviscosity. The risk of symptomatic hyperviscosity is low in patients with a hemoglobin level below 20 g/dL who are not dehydrated. Symptoms of hyperviscosity include headache, dizziness, fatigue, and blurry vision. Judicious phlebotomy may improve these symptoms, but should be reserved for patients who do not respond to aggressive hydration.⁴⁶ Regular phlebotomies should be strictly avoided, regardless of the hemoglobin level, because the resultant iron deficiency leads to microcytic and less deformable red blood cells that do not pass through the microcirculation as readily as more deformable iron-replete cells.⁴¹ As a result, the paradoxical anemia of erythrocytotic patients with iron deficiency may increase the risk of stroke.^42,47 Iron repletion in these patients should be instituted with care because of the tendency for excessive erythrocytosis. Hyperuricemia is common because of increased red blood cell turnover and decreased renal excretion of uric acid; however, urate crystal nephropathy is rare despite the elevated serum uric acid levels. Patients with elevated uric acid levels rarely develop tophaceous deposits within the soft tissue of the elbows or digits; these can be painful and tender (Fig. 56–6). Arthralgia is well recognized, and frank gouty arthritis is rare.⁴⁸

Cyanotic patients with right-to-left shunts are at risk for “paradoxical” emboli from the venous to the systemic arterial circulation, leading to cerebrovascular accidents, renal impairment, or myocardial infarction. Air filters should be used with all intravenous (IV) lines, and chronic indwelling venous catheters should be avoided. Anticoagulation may be considered in patients who must have chronic indwelling lines (eg, patients with infective endocarditis who require prolonged IV antibiotic therapy). All cyanotic patients are at a heightened risk for infective endocarditis, and antibiotic prophylaxis for bacterial endocarditis is mandatory prior to bacteremic procedures, including dental work. Septic emboli may cause cerebral abscesses and must always be considered in cyanotic patients with fever and neurologic symptoms.

Promising advances have occurred over the past decade in the treatment of patients with pulmonary hypertension. The Bosentan Randomized Trial of Endothelin Antagonist Therapy-5 (BREATHE-5) is the first prospective and randomized clinical trial performed solely in patients with Eisenmenger syndrome randomized to either a nonselective endothelin inhibitor (bosentan) or placebo.⁴⁹ Patients receiving bosentan had a significant decrease in pulmonary vascular resistance and systemic vascular resistance, resulting in increased pulmonary and systemic blood flow, respectively. They also had a significant increase in 6-minute walk distance (51 m). Patients were followed for 16 weeks. Long-term follow-up of patients placed on endothelin blockers suggests an attenuation of the benefits over time.⁵⁰ Phosphodiesterase-5 inhibitors are also effective in the treatment of patients with Eisenmenger syndrome and result in a similar improvement in functional capacity and lowering of pulmonary vascular resistance as endothelin blockade.⁵¹ IV prostacyclin use is generally avoided because of the requirement for chronic indwelling venous catheters, which increases the risk of thrombosis and paradoxical embolism across the right-to-left shunt. Moreover, the presence of a central right-to-left shunt results in much of the IV-administered drug bypassing the pulmonary bed and resulting in systemic hypotension. Inhaled prostacyclin may be more efficacious in this patient population; however, at this time, there is a paucity of data on the use of this agent in patients with Eisenmenger syndrome. Serum BNP is a diagnostically and prognostically important marker in various forms of systolic and diastolic heart failure as well as primary and secondary forms of pulmonary hypertension. Serum BNP is elevated in most patients with Eisenmenger syndrome; however, an outpatient level 250 pg/mL or above in clinically euvolemic patients predicts impending heart failure admission or death.⁵²

Infective Endocarditis

Patients with CHD (corrected or uncorrected) are at risk for developing infective endocarditis.⁵³ Certain subgroups are considered at higher risk for infective endocarditis. Guidelines from the European Society of Cardiology (ESC) and the AHA/ACC on prevention of infective endocarditis place patients with prosthetic valves, cyanosis, and systemic or pulmonary artery conduits, as well as patients with previous endocarditis, into a high-risk subgroup.^53,54,55 Most other congenital cardiac conditions are in a moderate-risk category, except for patients who have undergone surgical or transcatheter repair of ASD, VSD, or PDA (without residua beyond 6 months) who are considered low risk provided there are no sequelae (eg, aortic valve prolapse, aortic regurgitation). In patients at high risk, the ESC and AHA/ACC recommend antibiotic prophylaxis for dental procedures associated with significant bleeding from hard or soft tissues, periodontal surgery, scaling, and professional teeth cleaning. Other procedures requiring prophylaxis include respiratory, genitourinary, and gastrointestinal procedures. Poor dental hygiene may produce bacteremia, even in the absence of dental procedures. Individuals who are at risk for developing bacterial endocarditis should establish and maintain the best possible oral health to reduce potential sources of bacterial seeding. Optimal oral health is maintained through regular professional care and diligent brushing and flossing on the part of the patient. High-risk patients are advised to use a minimally abrasive soft bristle toothbrush to minimize bleeding. In 2008, the National Institute for Health and Clinical Excellence of the United Kingdom recommended complete cessation of antibiotics for endocarditis prophylaxis, resulting in a 90% decrease in antibiotic prescriptions. A study of endocarditis cases from 2000 to 2013 in the United Kingdom observed a significant increase in endocarditis cases after the 2008 recommendations.⁵⁶ Despite this increase, the National Institute for Health and Clinical Excellence has not recommended any changes to the 2008 recommendations, pending further study. A structured questionnaire mailed to 515 dentists and 85 cardiologists in Ireland revealed that most cardiologists are familiar with the cardiac conditions that pose a risk for dental patients, but did not educate their patients on the importance of dental health. On the other hand, dentists were good at identifying dental procedures that place patients at risk, but less informed about which cardiac conditions warranted prophylaxis, choice of prophylaxis, and appropriate treatment intervals.⁵⁷ A survey questionnaire of 102 adults with CHD found that patients’ knowledge of their underlying condition, endocarditis risk, and prevention measures was sorely lacking.⁵⁸

There is an under-recognized risk of bacteremic infective endocarditis in patients who acquire tattoos or body piercings.⁵⁹ Patient education is of paramount importance, and patients should carry an information card with them that clearly identifies their endocarditis risk category.

The symptoms of infective endocarditis are often subtle and nonspecific, including low-grade fever, malaise, fatigue, and headache. The diagnosis of endocarditis should be entertained in any patient with unexplained fever or malaise and should prompt blood cultures and echocardiographic imaging. Echocardiography is an integral tool in the diagnosis and follow-up of patients with infective endocarditis.⁶⁰ The use of transesophageal echocardiography (TEE) is recommended in cases with high clinical suspicion and equivocal or negative findings on TTE or when a prosthetic valve or conduit is involved⁶¹ (Fig. 56–7). Injudicious use of antibiotics without prior blood cultures often makes the culprit organism more difficult to identify by culture, making appropriate treatment more difficult.

Electrophysiologic Problems

Arrhythmias and conduction defects are common in operated and unoperated patients with CHD, and have a major impact on survival and quality of life. Although the principles for diagnosis and treatment of arrhythmias are similar to those used in patients with anatomically normal hearts, there are some notable exceptions. Atrial rhythm disturbances that may be well tolerated with a rate control strategy in a structurally normal heart may be poorly tolerated in complex CHD. Patients with functional single-ventricle or tricuspid atresia who have undergone total cavopulmonary (Fontan) connection exemplify this in that atrial tachyarrhythmias frequently result in deleterious hemodynamics, a decrease in cardiac output, and functional deterioration despite adequate rate control.⁶² Atrial arrhythmias occur in 15% of adults with CHD. The lifetime incidence increases exponentially with advancing age, and atrial arrhythmias affect more than 50% of adults with complex CHD.^63,64 Bradyarrhythmias are common in certain subsets of patients, such as those with TGA. Special consideration must be given to the use of therapies that have negative chronotropic and inotropic properties. The clinical significance of arrhythmias depends greatly on the hemodynamic context in which they occur.

The 2014 ACC/AHA guidelines on the management of atrial fibrillation recommends use of the CHA₂DS₂-VASc scoring system to risk stratify patients with nonvalvular atrial fibrillation for stroke.⁶⁵ This risk stratification scheme assigns a score based on the presence of congestive heart failure or systemic LV systolic dysfunction, hypertension, age ≥ 75 years (doubled), diabetes, stroke (doubled), vascular disease, younger age (65-74 years), and sex (female). Considering these scores and the recommendation to consider anticoagulation in patients with a risk score ≥ 1, anticoagulation is thus recommended for most patients with atrial fibrillation or flutter. However, such risk scoring systems do not consider the presence of CHD. Patients with CHD may be more predisposed to thrombus formation as a result of chamber dilation with slow flow, presence of prosthetic material including valves, intracardiac shunts, and associated hypercoagulable states. Patients with a Fontan circulation are at particularly high risk for thrombotic complications. Long-term anticoagulation is therefore recommended in patients with CHD of severe complexity and is reasonable in those with moderate forms of CHD.⁶⁶ In patients requiring anticoagulation, oral vitamin K antagonists are widely used. However, use of the non–vitamin K novel oral anticoagulants is increasing quickly on the basis of clinical trials in patients with atrial fibrillation demonstrating noninferiority in stroke prevention, as well as decreased incidence of intracranial bleeds.^67,68,69,70 Further study of safety of novel oral anticoagulants in the CHD population is ongoing.

Abnormalities of sinus node function are common in adults with CHD, especially in patients who have undergone atrial surgery. Patients with surgically corrected ASD, specifically those with superior sinus venosus defects, are at a heightened risk of developing postoperative sinus node dysfunction (SND) because of the proximity of the defect to the sinus node.⁷¹ Patients with uncorrected atrial shunts causing chronic right atrial volume overload and right atrial stretch undergo a process of electrical remodeling with increases in effective refractory period, conduction delay at the crista terminalis, and SND. Conduction delay at the crista terminalis persists beyond ASD closure and may contribute to the long-term atrial arrhythmia substrate in this condition.⁷² Patients who have undergone surgeries that involve extensive atrial reconstruction are particularly prone to SND. A retrospective follow-up study of 137 patients who had undergone the Mustard or Senning operation for complete TGA (see Fig. 56–2) demonstrated that nearly 50% of patients had SND; however, the presence of SND did not influence mortality.⁷³ Frequency of SND is also increased after surgery for correction of TOF, placement of cavopulmonary shunt (Glenn or Fontan), and numerous other congenital heart operations. High-grade AV node block is a well-recognized problem in patients with unoperated congenitally corrected TGA; many patients are initially diagnosed in adulthood when they present with signs and symptoms of bradycardia from high-grade heart block. Injury to the AV node and ventricular conduction tissue may result from surgery for lesions such as VSD, TOF, and mitral or tricuspid valve repair or replacement. Transient complete AV block in the postoperative period has been shown to have prognostic significance, especially if the induced block is below the bundle of His.⁷⁴ Postoperative right bundle branch block is frequent after right ventriculotomy and is likely secondary to transection of distal Purkinje fibers and postsurgical scarring, creating an area of slowed conduction and a substrate for reentrant ventricular arrhythmias.^75,76 Although bradycardia has been postulated as the cause of death in some conditions, evidence indicates that tachyarrhythmia is the more likely culprit. However, the presence of underlying bradycardia as a substrate for initiation of tachycardia is well recognized.⁷⁷ Indications for pacemaker implantation in asymptomatic patients with SND or conduction system disease are controversial because the arrhythmia is benign in the majority of cases. Patients who are asymptomatic at rest or with low levels of activity may become more fatigued and dyspneic with greater levels of exertion. Electrocardiographic stress testing identifies patients with chronotropic incompetence leading to decreased exercise capacity.

Pacemaker implantation may be challenging in patients with complex underlying or postoperative anatomy.⁷⁸ The choice of pacemaker depends on the specific indication. In patients who have isolated SND, a single atrial lead should suffice. Patients who require chronic ventricular pacing often develop progressive cardiomyopathy and ventricular dyssynchrony if a single ventricular pacing is performed, which is a problem that may be ameliorated by multisite ventricular pacing.⁷⁹ Cardiac resynchronization therapy (CRT) is indicated in CHD patients with a systemic LV ejection fraction ≤ 35%, sinus rhythm, left bundle branch block with a QRS duration ≥ 150 milliseconds, and New York Heart Association (NYHA) class II to ambulatory IV heart failure. The available data suggest a potential role for CRT in patients with systemic RV anatomy, but studies of CRT in patients with systemic RV have largely been small retrospective studies with limited follow-up.⁶⁶

Tachyarrhythmias occur in patients with operated and unoperated forms of CHD. Atrial tachyarrhythmias are common in patients who have undergone atrial surgery (eg, Senning or Mustard operations) and those in whom AV valve disease or shunts lead to atrial volume or pressure overload. Scar-mediated reentrant atrial flutter is a common theme in the majority of patients who have undergone some form of atrial reconstruction. The various modifications of the Fontan operation were developed to decrease the very high incidence of poorly tolerated atrial tachyarrhythmias seen with the right atrial–to–pulmonary artery Fontan repair that was initially performed in 1971^62,80 (Fig. 56–8). Medical or electrical cardioversion should be carried out promptly to restore sinus rhythm; antiarrhythmic medications may be necessary to help maintain it. Surgical cryoablation and transvenous catheter ablation aided by three-dimensional electroanatomic mapping can be used as a therapeutic intervention in atrial tachyarrhythmias.^81,82,83 Electroanatomic mapping and radiofrequency ablations in patients with CHD represent some of the most challenging electrophysiologic procedures because of the complex pre- and post-surgical anatomy, chamber dilatation, variable anatomy of the conduction system, and presence of intracardiac scars leading to multiple reentrant circuits. An experienced congenital electrophysiology team, including operators and technicians familiar with the complexity of the anatomy, arrhythmias, and substrates, is key in the management of patients with CHD.

Ventricular arrhythmias may occur in a variety of settings, particularly after repair of TOF.⁸⁴ First-generation intracardiac repairs were performed via a large anterior ventriculotomy and frequently included incision of the pulmonary valve annulus and placement of a transannular patch made of pericardium or synthetic material (eg, Gore-Tex or Dacron). This technique successfully relieved the outflow tract obstruction but inevitably resulted in pulmonary valvar incompetence and pulmonary regurgitation (Fig. 56–9). Pulmonary regurgitation was thought to have minimal adverse clinical consequences, an assertion that held generally true for the first two decades after transannular patch repair. However, with time, the adverse hemodynamic effects of severe low-pressure pulmonary regurgitation become evident. The RV gradually dilates and becomes hypokinetic, and wall stress invariably increases. Ventricular tachycardia is likely to occur under such conditions and often arises from the region of the transannular patch or ventriculotomy suture lines. Programmed ventricular stimulation resulting in monomorphic or polymorphic ventricular tachycardia is of prognostic importance in these patients.⁸⁵ In a cohort of 793 patients with repaired TOF followed for a mean 21.1 years, ventricular tachycardia occurred in 4.2% and sudden cardiac death occurred in 2% of patients.¹⁹ Transventricular and transannular repairs were associated with ventricular tachycardia and sudden cardiac death. QRS width on the surface electrocardiogram (ECG) has additive prognostic value.⁸⁶ Gatzoulis and colleagues²³ reported that 88% of such patients with ventricular tachycardia and 63% of patients with sudden death had a QRS duration of ≥ 180 ms (see Fig. 56–15A). Patients invariably have a right bundle branch block that results from early injury because of surgical VSD closure and ventriculotomy followed by subsequent QRS lengthening secondary to RV dilatation. The presence of ventricular tachycardia (spontaneous or induced; monomorphic or polymorphic) in a patient with moderate or severe pulmonary regurgitation is an indication for surgical pulmonary valve replacement and ventricular scar excision. Transvenous radiofrequency ablation may be deferred in favor of surgical cryoablation in patients requiring surgical valve replacement. Transvenous radiofrequency ablation is feasible in patients with repaired TOF who have ventricular tachycardia originating from ventriculotomy or transannular patch scar sites and should be attempted in patients who do not require surgical valve or conduit replacement.^87,88,89 Defibrillator placement may be considered in patients who continue to have inducible ventricular arrhythmias or spontaneous symptomatic ventricular arrhythmias despite radiofrequency ablation or surgical repair. Subcutaneous defibrillator systems allow ICD placement in patients whose anatomy is not conducible to a transvenous system, such as patients with single-ventricle anatomy.⁹⁰ There is a disparity between the high frequency of ventricular arrhythmia and the much lower incidence of sudden death in this population.⁹¹ Prophylactic antiarrhythmic therapy has not demonstrated efficacy in asymptomatic patients, and there is insufficient evidence to advocate prophylactic antiarrhythmic therapy in these patients. Identification of asymptomatic individuals who are at risk for ventricular tachycardia or sudden cardiac death remains a challenge. A very wide QRS (> 180 ms) on the surface ECG is a marker for increased risk, but has low predictive accuracy in individual cases.⁹² LV diastolic dysfunction and elevated LV filling pressure are predictors of ventricular arrhythmias and appropriate defibrillation in adults with repaired TOF.^93,94 Further refinements in risk stratification are necessary and may involve electrophysiologic testing, exercise testing, evaluation of ventricular late potentials using signal averaged ECG, heart rate variability, and presence of repolarization abnormalities.^95,96,97

Pregnancy

An increasing number of women with complex CHD are surviving to reproductive age because of the surgical advances of the past five decades. Pregnancy counseling is mandatory for all patients, whether operated or unoperated. Counseling should begin when the patient reaches menarche and continue well into adulthood. The maternal and fetal risks of pregnancy and transmitted risk of CHD should be discussed in women with CHD who are of childbearing age, preferably before pregnancy. Evaluation should include a detailed medical and social history with specific attention paid to functional capacity, which is an important prognostic determinant of maternal and fetal outcomes.^98,99,100 Among risk factors for adverse outcomes, advanced NYHA functional class and history of heart failure are well recognized. The detrimental effects of smoking include arrhythmias and increases in systemic vascular resistance, systemic blood pressure, pulmonary artery pressure and vascular resistance, atrial pressures, and heart rate.^101,102 TTE determines ventricular and valvar function as well as pulmonary artery pressure. Impaired subpulmonary or subaortic ventricular function is associated with adverse maternal and fetal outcomes.^98,100 Exercise echocardiography further assesses functional capacity, ventricular function, and valvar function.

The maternal cardiovascular system undergoes a myriad of changes during pregnancy that include a doubling of intravascular volume and cardiac output accompanied by a decrease in systemic vascular resistance. Obstructive lesions are less well tolerated than regurgitant lesions or left-to-right shunts. Severe aortic valve stenosis may be well tolerated if LV function is not impaired.¹⁰⁰ When LV systolic function deteriorates, pregnancy becomes hazardous for the mother and the fetus. The maternal mortality for patients with a depressed ejection fraction and severe aortic stenosis is 5.9%.¹⁰⁰ In general, women with valvular regurgitation and left-to-right shunts tolerate pregnancy well. However, patients with severe pulmonary regurgitation who have depressed subpulmonary ventricular function are at increased risk for adverse outcomes during pregnancy and at delivery.⁹⁸ Heart failure followed by arrhythmia is the main complication of pregnancy in patients with various CHDs.

Patients with univentricular hearts or tricuspid atresia who have undergone the Fontan operation with normal systolic function tolerate pregnancy well but have an increased risk of miscarriage.¹⁰³ The outcomes may also be affected by single-ventricle morphology, specifically the decreased capacity of a morphologic RV to adapt to the volume and pressure changes that face the heart during pregnancy and the peripartum period. Thus, Fontan patients with an RV are at higher risk of developing congestive heart failure than those with an LV. Patients with repaired TOF, specifically those with depressed RV function and severe pulmonary regurgitation as a result of surgical valvotomy or transannular patch repair, are at an increased risk of adverse events.¹⁰⁴ Thirteen percent of patients had cardiac complications in a study by Veldtman and colleagues.¹⁰⁴ Decreased LV systolic function and pulmonary hypertension were similarly correlated with poor maternal and fetal outcomes. Six percent of infants in this study had CHD.

Patients with cyanosis face the most problems in carrying fetuses to term, and pregnancy is strongly advised against (Table 56–1).¹⁰⁵ There is a high incidence of early spontaneous abortion inversely related to the degree of cyanosis. In a study by Presbitero et al,¹⁰⁵ only 12% of pregnancies in women with an oxygen saturation lower than 85% resulted in live births. The maternal complication rate has improved with close monitoring and meticulous care during pregnancy and delivery, but is still considerable (32%). There are scant data on management strategies for patients seen late in pregnancy when safe termination is not feasible. Vaginal delivery is generally preferable because it results in less blood loss than cesarean section. Many maternal deaths occur after successful delivery when maternal intravascular volume and systemic vascular resistance increase, exceeding the capacity of the patient’s cardiovascular system to adapt. It is the practice of established ACHD centers to counsel and advise our cyanotic patients against becoming pregnant and to advise pregnancy termination if it is acceptable to the patient.

Maternal mortality in patients with Eisenmenger syndrome has been reported to be as high as 50%.¹⁰⁶ Despite advances in medical therapy, pregnancy outcomes in patients with pulmonary hypertension remain poor. Parental or inhaled prostaglandins are recommended in pregnant patients with severe RV impairment and/or significant symptoms of heart failure. Oral phosphodiesterase inhibitors may be considered in pregnant patients with normal RV function who are minimally symptomatic. Endothelin receptor blockers and soluble guanylate cyclase stimulators are pregnancy category X and should be avoided. At the time of delivery, close monitoring with a central venous catheter and arterial line are recommended.¹⁰⁷

Patients with connective tissue abnormalities of the aorta, particularly Marfan syndrome, are at increased risk of aortic dissection or rupture if the ascending aorta is dilated (> 40 mm).^108,109 Patients with BAVs, independent of the degree of valvular stenosis, demonstrate a medial abnormality of the ascending aorta that places them at increased risk as well. Therapy with β-blockers in the peripartum period may decrease the risk of aortic dissection and rupture and is usually well tolerated. Severe valvular aortic stenosis places both the mother and fetus at risk because the decrease in systemic vascular resistance and large volume shifts during pregnancy and the postpartum period result in exaggerated valve gradients and increased filling pressure.^110,111 Minimization of vascular volume and resistance alterations can be accomplished by avoidance of large IV volume infusions, avoidance of anesthetics known to decrease systemic vascular resistance, and use of adequate pain control to blunt increases in systemic blood pressure. Patients with severe aortic stenosis and congestive heart failure may require balloon valvuloplasty. The literature on aortic valvuloplasty in pregnancy consists of case reports and small case series. Balloon dilatation of a calcified aortic valve can tear the valve leaflets and cause severe poorly tolerated aortic regurgitation. Pregnant patients with heavily calcified valves and significant aortic regurgitation who are in congestive heart failure or are hemodynamically unstable may require surgical valve placement and cesarean delivery of the fetus.¹¹²

The management of pregnant women with mechanical valve prostheses is challenging for a number of reasons. Pregnant women are inherently hypercoagulable, and their risk of valve thrombosis is increased, thus necessitating appropriate anticoagulation.^113,114 Oral warfarin accomplishes this task well and is associated with a lower maternal risk, but it is teratogenic to fetuses, especially in the first trimester; the risk of teratogenicity is low after the eighth week of gestation.¹¹⁵ Therefore, warfarin is recommended by the ACC/AHA guidelines in the second and third trimesters of pregnancy. Given the low risk of teratogenicity with warfarin doses < 5 mg, warfarin may be used in the first trimester if the baseline dose is < 5 mg. If the baseline warfarin dose is > 5 mg, then heparin may be used in the first trimester. Unfractionated heparin can be given subcutaneously twice a day or as a continuous IV infusion; even with meticulous control, there is still an increased risk of valve thrombosis.^113,116 Subcutaneous low-molecular-weight heparin is more effective, but requires frequent anti–factor Xa level monitoring.¹¹³ Because warfarin crosses the placental barriers and results in anticoagulation of the fetus and the mother, warfarin should be discontinued and IV heparin initiated prior to planned vaginal delivery. Cesarean section may be considered as an alternative to vaginal delivery in order to minimize interruption in therapeutic anticoagulation.¹¹³

The hemodynamic deteriorations during and after labor can be minimized by avoidance of rapid volume and pressure shifts. Planned induction 1 to 2 weeks before the expected term minimizes the risk of spontaneous labor and delivery. Invasive hemodynamic monitoring has not been shown to favorably affect outcomes and is often reserved for the highest risk subsets of patients (eg, those with critical valvular stenosis, severely depressed ventricular function with heart failure, or severe pulmonary hypertension). Vaginal delivery is recommended unless there are obstetric indications for cesarean section, such as a fetus in the breach position. The use of antibiotics for endocarditis prophylaxis after rupture of the membranes is controversial given the absence of randomized controlled trials addressing this topic. The 2014 ACC/AHA valvular heart disease guidelines do not recommend antibiotics for genitourinary procedures in the absence of infection, whereas the 2008 ACC/AHA ACHD guidelines and the American College of Obstetrics and Gynecology favor use of antibiotics for endocarditis prophylaxis in the highest risk patients undergoing vaginal delivery.^6,113,117 In this situation, each patient must be individualized, and the proper medical management should be addressed by the ACHD team.

Genetics and Genetic Counseling

CHD is the leading cause of birth defects and noninfectious mortality in the first year of life.¹ The cause of CHD is multifactorial. Genetic and environmental factors each play an important role in the development of CHD. Environmental insults such as chemical teratogens (eg, retinoic acid, lithium) and viral infections (eg, rubella) are known to increase the risk of CHD. Genetic factors also play a role in the development of CHD, as demonstrated by the increased incidence of CHD in patients with chromosomal abnormalities such as microdeletions of chromosome 22q11 and trisomy 21. Most defects are not part of a syndrome, and patients have no family history of CHD. Even in seemingly sporadic cases of CHD, epidemiologic evidence demonstrates an increased likelihood of recurrence of CHD in subsequent pregnancies, supporting the existence of a genetic predisposition to CHD. It has been estimated that approximately 8% of CHD cases are caused by inherited genetic abnormalities.¹¹⁸ In an analysis of 6640 pregnancies in patients with a first-degree family history of CHD, the observed incidence of CHD in pregnancies referred because of sibling CHD and paternal CHD was 2% to 3%.¹¹⁹ There was a similar incidence of CHD for pregnancies referred because of maternal CHD (2.9%) or paternal CHD (2.2%). A study of a 1094 patients with CHD demonstrated an increased risk of CHD in the offspring of mothers with CHD (5.7%) versus fathers with CHD (2.2%).¹²⁰ This study did challenge the polygenic basis for all forms of CHD by demonstrating that AV septal defect is a single-gene defect and TOF is a polygenic disorder with a small number of interacting genes. Isolated TGA is likely a sporadic defect. The risk of recurrence of CHD increases with the number of affected siblings or relatives, and genetic counseling should be provided for potential parents.¹²¹

The molecular mechanisms leading to CHD are complex, and the causes of the cardiac malformations observed in humans are still unclear. Furthermore, most patients do not have family history of CHD; thus, the mutations are likely spontaneous. The combining of expertise in cardiac anatomy, pathology, and molecular genetics is essential to adequately comprehend CHD. CONgenital CORvitia (CONCOR), a national DNA bank and registry of patients with CHD, will help facilitate research on the genetic contribution to CHD and allow investigation into the molecular basis of CHD.¹²²

Diagnostic Catheterization and Imaging

Cardiac catheterization with angiocardiography has long been the gold standard for making and confirming hemodynamic and anatomic findings in patients with CHD. This position of preeminence is being challenged in the current era by an array of noninvasive imaging techniques, each with certain strengths and weaknesses, yet together capable of almost complete noninvasive anatomic and functional cardiovascular assessment. TTE with Doppler is the most widely used and cost-effective tool for diagnostic imaging in patients with CHD. Two-dimensional and, more recently, three-dimensional echocardiography provides a plethora of anatomic and functional data in a matter of minutes at low cost and without any radiation or contrast exposure (Fig. 56–10). Continuous-wave, pulsed-wave, and color-flow Doppler have added incremental value and are the most widely used techniques for quantifying valvar pathology and estimating intracardiac pressure. Tissue Doppler, a form of pulsed-wave Doppler, allows quantification of myocardial velocities and determination of ventricular electromechanical synchrony. The various Doppler-based methods may be used together to estimate atrial pressures, pulmonary artery pressure, and ventricular diastolic function.¹²³ For example, the ratio of the early diastolic ventricular filling velocity (E) to the early diastolic annular velocity (E′) provides an accurate estimate of atrial pressure.¹²⁴ Tissue Doppler and speckle tracking for determination of ventricular strain and torsion provide a plethora of information regarding ventricular systolic and diastolic function.¹²⁵

The Achilles heel of TTE is the difficulty of image acquisition in patients with poor acoustic windows. Obesity, chest wall deformities, lung disease, or breast implants may adversely impact image quality. Moreover, posterior cardiac structures, such as pulmonary veins and atrial appendages, are often inadequately visualized. TEE traverses many of the previously mentioned hurdles of TTE and is ideal for the visualization of pulmonary venous anatomy, atrial anatomy, AV valve morphology, ventricular outflow tract lesions, and vegetations or thrombi. Intraoperative TEE is particularly helpful during repair of congenital defects.

In parallel with the decreasing need for diagnostic catheterization, there has been a dramatic increase in the number of transcatheter cardiac interventions in patients with CHD.¹²⁶ The majority of secundum ASDs can now be closed via transcatheter delivery of a closure device (Fig. 56–11). The success of percutaneous transcatheter closure of ASDs is contingent upon proper patient selection.¹²⁷ TEE is widely used to assess the size, shape, and rim adequacy of ASDs and to exclude the presence of atrial thrombi or an anomalous pulmonary venous connection. Intracardiac echocardiography can also be used to guide ASD closure.¹²⁸

Cardiovascular MRI provides important incremental anatomic and functional data in patients with CHD. Ultrasound waves are not propagated through air; therefore, echocardiography (transthoracic or transesophageal) is of limited utility for imaging the extracardiac pulmonary vasculature, the site of frequent pathology in certain subsets of CHD. Magnetic resonance angiography (MRA) is invaluable in identifying the size, course, and degree of obstruction of medium to large vascular structures. Velocity mapping and flow quantification provide hemodynamic data such as the volume of pulmonary valve regurgitation per cardiac cycle.¹²⁹ Gradient-echo cine-MRI provides incremental information regarding ventricular systolic and diastolic wall motion, segmental strain, and ventricular volumes (Fig. 56–12).^130,131 Four-dimensional phase-contrast MRI is in clinical use and has been demonstrated to have improved sensitivity for and depiction of hemodynamically significant shunts and valvular regurgitation.¹³² Myocardial fibrosis detected by late gadolinium enhancement MRI is common in patients with repaired TOF.¹³³ The degree of late gadolinium enhancement is related to adverse clinical markers, including ventricular dysfunction, exercise intolerance, neurohormonal activation, and arrhythmia. MRA of the coronary arteries is feasible, but imaging beyond the proximal coronary tree is suboptimal. Metallic structures, such as stents and valves, alter the local magnetic field and result in artifacts, thus limiting the utility of cardiac MRI in a significant subset of patients. The presence of a permanent pacemaker or defibrillator is considered a relative contraindication for cardiac MRI. The issues surrounding pacemakers are complex. Various generations of pulse generators and leads make generalizations regarding suitability for MRI problematic. Therefore, patients with pacemakers should not be scanned unless special circumstances arise and then only in centers with special cardiac MRI experience.

Cardiac CT has developed into a widely used noninvasive method for defining anatomy. ECG-gated multidetector CT provides tomographic two-dimensional data that can be sculpted into three-dimensional images, thus clarifying complex anatomy and enhancing the understanding of structure and form (Fig. 56–13).¹³⁴ MRI tomographic images can similarly be reconstructed into three-dimensional structures. CT angiography (CTA) allows visualization of the coronary arterial tree, with a high sensitivity, specificity, and negative predictive value for identifying obstructive coronary disease.¹³⁵ CT has outperformed MRA in this respect as a result of superior spatial resolution and faster acquisition time. CTA has another advantage in that it does not require as much specialized training and technical knowledge as MRI.^136,137 For these reasons, CTA is set to become the method of choice for noninvasive cardiovascular angiography in community practice, while cardiac MRI remains confined to specialized regional centers despite certain advantages of MRI over CT (eg, the lack of radiation exposure and superiority in the provision of functional information). Moreover, cardiac CT can be performed in the presence of metallic structures or pacemakers, a relative contraindication for MRI.¹³⁸

Cardiac catheterization with angiocardiography remains the gold standard method for identifying anatomy, quantifying shunts, and measuring hemodynamics. Although the less invasive methods described earlier often obviate the need for invasive evaluation, numerous circumstances necessitate invasive evaluation. These include cases in which the noninvasive techniques give inconsistent or conflicting data or cases in which exact pressures and resistances must be measured. For example, patients with single-ventricle physiology may be candidates for the Fontan operation if certain hemodynamic and functional criteria are met (Table 56–2). Direct invasive measurement of pulmonary artery pressure and calculation of resistance must be performed to make the decision to proceed or not proceed with the Fontan operation.

Stress Testing

Exercise and pharmacologic stress testing provide important prognostic information regarding exercise capacity, cardiopulmonary reserve, and chronotropic response.^32,33 Exercise capacity is generally decreased in adults with CHD, and drastically so in patients with Eisenmenger syndrome (see Fig. 56–4). The decreased exercise capacity in patients with CHD is comparable to patients with ischemic and nonischemic cardiomyopathy. Chronotropic incompetence is common in certain subsets of patients, specifically those with previous operations or taking β-blockers. Lack of a heart rate response to exercise, pulmonary arterial hypertension, and impaired ventilatory function are correlates of maximum exercise capacity. A blunted heart rate response to exercise identifies patients at increased risk of dying.¹³⁹ Cardiopulmonary exercise testing adds incremental diagnostic and prognostic information in patients with CHD. Maximum oxygen consumption is decreased in patients with CHD (see Fig. 56–4). Poor exercise capacity identifies ACHD patients at risk for hospitalization or death. Cyanotic patients with right-to-left shunts (eg, Eisenmenger syndrome) fail to demonstrate a normal increase in pulmonary blood flow with exercise. The systemic arterial resistance decreases with no appreciable change in pulmonary arterial resistance; therefore, more deoxygenated blood is shunted away from the pulmonary arterial bed, and patients desaturate with exercise. The carotid chemoreceptors located at the bifurcation of the internal and external carotid arteries detect this hypoxia and, via a complex feedback mechanism involving the respiratory control centers of the brain stem, increase the minute ventilation, resulting in hyperventilation during exercise (Table 56–3). Ventilatory response to exercise is abnormal across the spectrum of CHD, but is most markedly abnormal in cyanotic patients irrespective of pulmonary arterial hypertension. An increased ratio of minute ventilation to CO₂ production (VE/VCO₂ slope) is a strong exercise predictor of death in noncyanotic CHD patients.²⁶ Oxygen uptake (VO₂) slowly increases in the later stages of exercise yet remains markedly reduced in patients with cyanotic heart disease (see Fig. 56–4). Submaximal exercise capacity, as measured by 6-minute walk distance, is used widely and is of prognostic importance in patients with pulmonary arterial hypertension and correlates closely with peak VO₂.¹⁴⁰

Reoperations

Reoperations in adults with CHD are common and provide particular challenges.¹⁴¹ The risks of reoperation are often greater than for the primary procedures, often requiring careful entry into the chest with extensive dissection of scar tissue and longer cardiopulmonary bypass times and greater use of blood products.¹⁴² Careful preoperative planning should include an in-depth understanding of the underlying cardiovascular anatomy and the alterations caused by previous surgical intervention. CT or MRA may be used to determine the anatomic relationships and quantify the proximity of the heart to the sternum. Sternal entry is particularly risky when a high-pressure ventricle, great artery, or conduit lies immediately posterior to the sternum. Moreover, these imaging modalities help identify arterial and venous collateral vessels that may need to be ligated during the course of reoperation. The need for reoperation may come as a surprise to patients and their families, who frequently have a misconception that the previously performed operation was curative.

Inevitable Reoperation

Childhood repair of CHDs that involved insertion of prosthetic valves or conduits often requires reoperation. The prostheses used in infants and children are often too small for adult patients or have undergone degeneration, resulting in stenosis or regurgitation. Development of conduit obstruction is influenced by the type and size of the conduit as well as the timing of the original operation.¹⁴³ In the minority of patients with TOF and pulmonary atresia, transannular patch placement is usually not possible; instead, a valved conduit is placed from the RV to the distal pulmonary trunk or confluence of the right and left pulmonary arteries. The early conduits consisted of Dacron into which a bioprosthetic valve was sewn. However, these conduits tend to develop obstruction or regurgitation, requiring replacement in the majority of patients older than 10 to 15 years, and have generally been abandoned in favor of allograft (pulmonary or aortic) conduits.¹⁴⁴ For all conduits, calcification and obstruction remain significant complications. The signs of severe obstruction may be subtle, and patients should be evaluated with this in mind. TTE with Doppler is an invaluable tool for monitoring ventricular size and function as well as flow velocity through the conduit with estimation of a peak instantaneous and mean pressure gradient.

Right-sided and anterior conduits are often not well visualized by TTE and may require further imaging with CT or MRA. Diagnostic cardiac catheterization and angiography may be needed if the degree of stenosis is unclear or there are conflicting data from the noninvasive studies. The consequences of chronic pressure overload, specifically on the RV, are chamber dilatation, decreased systolic function, and diastolic dysfunction. These changes increase the risk of surgery and may not be fully reversible. Careful monitoring of ventricular size and function by TTE is paramount in identifying these processes early in their course to avoid irreversible damage. Serial stress echocardiography is especially useful in estimating exercise-induced gradients, determining ventricular function with exercise, and quantifying functional capacity. Reoperation is usually indicated if the RV pressure is 75% of the systemic pressure, or if there is evidence of deteriorating ventricular function or declining functional capacity.

Residual and Recurrent Defects

Residual or recurrent defects can affect long-term prognosis in patients with CHD, so attention should be paid to their presence after operative repair. Patients with TOF who have undergone early intracardiac repair with placement of a transannular patch inevitably develop chronic low-pressure pulmonary regurgitation. This represents the most common indication for reoperation in adults.¹⁴⁵ Chronic pulmonary regurgitation was thought to have minimal adverse clinical consequences, an assertion that held true for the first two decades after transannular patch repair. However, with time, the adverse hemodynamic effects of severe low-pressure pulmonary regurgitation became evident. The RV gradually dilates and becomes hypokinetic, and wall stress invariably increases. The RV outflow tract (RVOT) in the region of the transannular patch becomes dyskinetic, thus causing turbulence and energy loss. The tricuspid annulus frequently dilates, and tricuspid regurgitation often occurs. Therefore, the RV suffers under an additive source of volume overload in the presence of tricuspid regurgitation. Ventricular arrhythmias are more likely to occur under such conditions and often arise from the region of the transannular patch or ventriculotomy suture lines. In a cohort of 793 patients with repaired TOF followed for a mean 21.1 years, ventricular tachycardia occurred in 4.2%, and sudden cardiac death occurred in 2% of patients.²³ Transventricular and transannular repairs with subsequent severe pulmonary regurgitation were associated with ventricular tachycardia and sudden cardiac death. Indications for pulmonary valve replacement include progressive RV dilatation, decreasing systolic function, the presence of arrhythmias, and decreasing exercise tolerance.^146,147

Staged Repair

In patients with complex CHD, specifically those with cyanotic lesions, definitive “correction” may not be possible until the anatomy and physiology have been optimized by one or more “palliative” procedures. This course is often necessary in patients with extreme forms of TOF with pulmonary atresia, hypoplastic or discontinuous pulmonary arteries, and multiple aortopulmonary collaterals. These patients frequently require complex “unifocalization” of aortopulmonary collaterals, consisting of incorporation of these collaterals into a pericardial tube that receives arterial blood via a surgically created arterial shunt.¹⁴⁸ Unifocalization alone has failed to show a mortality benefit; however, it is used as the first step in a staged repair that subsequently leads to surgical pulmonary artery connection and insertion of a conduit from the RV to the pulmonary artery with concomitant VSD closure.^149,150 A one-stage repair including unifocalization and total intracardiac repair has been described and may become a preferable option as various centers accrue more experience with this procedure.¹⁵¹

Other situations in which definitive repair is delayed while palliative procedures are performed include patients with single-ventricle physiology (LV or RV morphology) who often undergo early placement of palliative arteriopulmonary shunts and pulmonary artery banding. Thereafter, these patients often undergo partial (Glenn) or total (Fontan) cavopulmonary connection if they fulfill the stringent criteria for this operation (see Table 56–2).

Heart and Heart-Lung Transplantation

Heart and heart-lung (block) transplantation are ultimate therapeutic options in patients who continue to deteriorate with optimal medical therapy and have no other good reparative surgical options. Despite the often complex anatomy, multiple previous thoracotomies, adhesions, and often coexistent pulmonary vascular disease, orthotopic heart transplantation has been associated with good outcomes.^152,153 Patients with Eisenmenger syndrome may be offered lung transplantation with repair of the cardiac defect or heart-lung transplantation. The success of either approach in these patients has been limited.^47,154 Given the advancements in the management of patients with pulmonary hypertension and the limited success of these operations, mainly the sickest patients who fail to stabilize or improve on pulmonary arterial vasodilator therapy are referred for transplantation.

Noncardiac Surgery

An awareness of the significance of various repaired or unrepaired congenital lesions in adults is imperative to the safe management of patients during and after noncardiac surgery. All of the anesthetic and bleeding risks encountered for cardiovascular operations also apply to noncardiac surgery. Many patients with CHD are at increased risk for arrhythmias that may be exacerbated by sympathomimetic agents and elevated catecholamine levels. Moreover, anesthetic agents that depress ventricular function must be used with care. Patients with poor cardiac function and those with Fontan connections often have a prolonged circulation time and may not respond as quickly to IV agents as other patients. This should be taken into account when monitoring the effect of anesthetics and titrating medication doses. The surgeon must also be aware of the potential presence of a pacemaker or defibrillator and pacing leads that may affect the safety of electric cautery. In patients with pulmonary vascular disease, general anesthesia may result in a sudden decrease in systemic vascular resistance and hypotension.¹⁵⁵ Avoidance of vasodilating anesthetic agents is recommended. Cyanotic patients often have impaired hemostasis, and bleeding may be increased. Use of particle filters on all IV lines in patients with intracardiac shunts is imperative in preventing systemic embolization. The safety of noncardiac surgery is greatly increased when the procedures are performed by physicians and staff who are familiar with these issues with concomitant consultation by an ACHD specialist.

Transcatheter Interventions

Major advances in percutaneous transcatheter interventions have been made over the past 25 years in the field of CHD.¹⁵⁶ In 1976, Mills and King¹⁵⁷ published the first report of transcatheter closure of an ASD using a double umbrella device. Since then, improvements in device, imaging, and catheterization technologies and procedural techniques have brought interventional cardiology to the forefront as a therapeutic intervention that may delay or obviate surgery. The advances in noninvasive cardiovascular imaging, specifically echocardiography, MRI, and CTA, have made diagnostic cardiac catheterization and angiocardiography necessary in a shrinking pool of patients. These include patients who have undergone the Fontan operation and those in whom noninvasive evaluation has resulted in ambiguous or conflicting results. Adult congenital cardiac catheterizations today are often performed solely for reparative or palliative transcatheter interventions. Interventional catheterization has largely replaced surgery as the treatment of choice for a number of congenital cardiovascular conditions, including secundum ASD, coarctation of the aorta, PDA, and pulmonary artery or valve stenosis.^156,158 Technologies for percutaneous valve replacement are under intense clinical evaluation, and results are encouraging.^{159,160,161,162} Careful patient selection and imaging are imperative to the safety and success of transcatheter procedures. Noninvasive imaging helps clarify anatomy before intervention, and can be used as a means of monitoring for sequelae or complications. MRA and CTA are excellent tools for defining two- and three-dimensional vascular anatomy, and are ideal for imaging of the aorta after transcatheter stent deployment (Fig. 56–14). The preprocedural images are key to defining lesion anatomy and precisely identifying neighboring structures that may be affected by the intervention.¹³⁴ MRI or CT images may be used to develop three-dimensional models unique to individual patients, allowing for testing of devices ex vivo.

Electrophysiologic and Device-Based Therapies

The past two decades have seen the explosive growth of electrophysiology as a major diagnostic and interventional field in cardiology. Adults with CHD are often plagued by a plethora of electrophysiologic problems, namely, supraventricular tachyarrhythmias, ventricular tachycardia, and various forms of bradycardia. Therefore, the technical advancements in invasive electrophysiologic diagnostics and interventions have been of enormous benefit to patients with operated and unoperated CHD. Diagnostic electrophysiologic testing is recommended in symptomatic patients and in those in whom arrhythmias can be detected by ECG monitoring.⁶⁶ Transcatheter radiofrequency ablation is successful in the treatment of many supraventricular tachycardias, but may be deferred in favor of surgical cryoablation in patients requiring surgical intervention for other reasons (eg, pulmonary valve replacement in a patient with TOF). Transcatheter radiofrequency ablation is less successful in the treatment of ventricular tachycardia originating from ventriculotomy or transannular patch scar sites, but should be attempted in patients who do not require surgical valve or conduit replacement.^88,89 Transvenous defibrillator placement should be considered in patients who continue to have inducible ventricular arrhythmias or spontaneous symptomatic ventricular arrhythmias despite radiofrequency ablation or surgical repair (Fig. 56–15).⁶⁶

Electrical resynchronization via multisite ventricular pacing has demonstrated efficacy in patients with various forms of cardiomyopathy and dyssynchronous ventricular contraction. Approximately 4% to 9% of patients with complete or congenitally corrected TGA are eligible for resynchronization therapy based on degree of heart failure symptoms, ventricular systolic function, and QRS duration.¹⁶³ Initial clinical results have been favorable, but the small number of studies and the heterogeneous patient populations make definitive conclusions difficult; however, resynchronization therapy in appropriate candidates appears to improve ventricular function and clinical status.^164,165,166

Atrial Septal Defect

ASDs are commonly encountered and occur in one-third of adults with CHD (Fig. 56–16; see also Figs. 56–11 and 56–13). Various types exist, but secundum ASD present in the area of the fossa ovalis is the most common, accounting for 75% of defects.¹⁶⁷ Ostium primum defects associated with endocardial cushion defects and inlet-type VSDs occur in 20% of cases. Sinus venosus defects (usually superiorly located) occur in 5% of patients. The rarest type is unroofed coronary sinus. Associated lesions may occur and include pulmonary stenosis, VSD, mitral valve abnormalities (regurgitation or stenosis), and syndromic problems such as Down syndrome and Holt-Oram syndrome. Most cases of ASD are sporadic, but familial cases of ASD have been reported, especially in patients with coexistent prolongation of the PR interval.¹⁶⁸

Natural History

ASDs often go unrecognized for the first two decades because of the indolent clinical course and benign findings on physical examination. Careful inspection of the ECG usually demonstrates a characteristic RSR′ complex in the anterior precordial leads with a rightward QRS axis in patients with secundum-type defects and left-axis deviation in those with primum-type ASD (Fig. 56–17). Initial diagnosis in adulthood is common, and survival into adulthood is the rule. However, life expectancy is not normal in unrepaired patients, with mortality increasing by 6% per year after 40 years of age.^169,170 Progressive symptoms of dyspnea on exertion and palpitations frequently occur in adulthood and are caused by increasing right-sided chamber enlargement, pulmonary hypertension, RV failure, tricuspid regurgitation, and atrial arrhythmias. Patients with large ASDs causing left-to-right shunts develop RV volume overload, which is relatively well tolerated for the first two decades but thereafter results in right heart failure and arrhythmias. The subsequent increase in serum BNP levels and decrease in exercise capacity are correlated with the magnitude of left-to-right shunting.¹⁷¹ The degree of left-to-right shunt may increase with age as LV compliance decreases and systemic arterial resistance increases after the fourth decade of life. Paradoxical embolism may occur, but is a rare complication. The risk of infective endocarditis is low unless the patient has coexistent valvular disease (eg, cleft mitral valve).

Management and Results

Surgical repair via direct suture of small defects and patch closure of larger defects has been performed for more than 40 years and has been efficacious and safe provided the pulmonary arterial resistance is not severely elevated.^167,172 Closure of small defects (< 1 cm) in asymptomatic patients diagnosed after 25 years of age is controversial, with no significant difference in clinical outcomes between medically and surgically treated patients followed for over 20 years.¹⁷³ A retrospective study by Konstantinides et al¹⁷⁴ of 179 patients diagnosed after the age of 40 years with a Qp:Qs ratio of 1.5:1 or greater demonstrated a relative risk of 0.31 for patients who underwent surgical closure, as compared with patients treated medically (P = .02). Estimated probability of survival was 95% at 10 years for surgically treated patients and 84% for patients treated medically. Predictors of increased mortality in the surgical group included older age at operation, advanced heart failure (NYHA class III or IV), Qp:Qs ratio of 2.5:1, pulmonary artery systolic pressure above 40 mm Hg, and pulmonary vascular resistance above 1.6 Wood units. Nonfatal clinical outcomes such as supraventricular arrhythmias occurred with similar frequency between the two groups. However, the operations carried out in this study did not include atrial arrhythmia surgery (maze or Cox-maze procedures), which is known to decrease arrhythmia recurrence in patients undergoing surgical ASD closure.¹⁷⁵ A prospective, randomized study by Attie et al¹⁷⁶ of surgical versus medical management of ASD in 241 patients older than 40 years of age did not demonstrate similar survival advantages over a median follow-up of 7 years. However, a significantly lower percentage of patients in the surgical group reached the composite end point of heart failure, recurrent pneumonia, peripheral or pulmonary embolism, or death (P = .0046), leading the authors to conclude that surgical closure should be performed in all patients with an ASD and pulmonary artery systolic pressure below 70 mm Hg and Qp:Qs ratio above 1.6:1.

Pulmonary artery vasodilator therapy with prostaglandins, endothelin blockers, and phosphodiesterase-5 inhibitors may reduce pulmonary arterial pressure and resistance to a level that allows consideration of shunt closure in these patients, but this should only be considered at centers experience in the management of such patients.¹⁷⁷ Current ACC/AHA guidelines recommend consideration of closure if pulmonary artery pressure is less than two-thirds of systemic level, pulmonary vascular resistance is less than two-thirds of systemic vascular resistance, or there is a positive response to either pulmonary vasodilator therapy or test occlusion of the defect.⁶ Pulmonary vasoreactivity testing and a trial of pulmonary vasodilators for several months may help risk stratify patients with borderline pulmonary pressures for closure. In a study by Balint et al,¹⁷⁸ many patients with ASDs and pulmonary arterial hypertension continued to have elevated pulmonary artery pressures after closure, and 15% had persistent severe pulmonary hypertension. Closure is contraindicated in patients with severe irreversible pulmonary arterial hypertension and no evidence of left-to-right shunt.⁶ Severe pulmonary hypertension in patients with ASD usually represents the coincidence of idiopathic pulmonary hypertension or pulmonary hypertension secondary to another process (eg, scleroderma) and ASD.²⁸ Unlike patients with large, unoperated, nonrestrictive central shunts (eg, VSD) who experience pulmonary hypertension from birth and develop pulmonary vascular disease within the first few years, patients with large ASDs of similar shunt magnitude do not necessarily develop severe pulmonary hypertension, and right-to-left shunting or the onset of pulmonary hypertension is delayed into late adulthood.¹⁷⁹ However, a large ASD may well contribute to the development of pulmonary hypertension, but may not be the sole cause of the underlying pulmonary vascular disease in a cyanotic patient. Patients with trisomy 21 (Down syndrome) may develop accelerated pulmonary vascular disease in the presence of ASD (primum or secundum).

Transcatheter device closure of secundum-type ASD was first performed in 1976 by Mills and King.¹⁵⁷ Advancements in device design and catheterization technology have led to the availability of a variety of occlusion devices (see Fig. 56–11).^180,181,182 Transcatheter device closure compares favorably with surgical closure in terms of efficacy and is associated with shorter hospital stays and fewer postprocedural complications.^181,183 Appropriate patient selection is imperative and may be accomplished via a variety of noninvasive and invasive imaging methods.^{184,185,186,187} Transcatheter device closure techniques have supplanted surgery at many institutions as the method of choice for ASD closure in properly selected patients; complications are rare. Short-term complications have included device embolization, aortic root or atrial wall perforation, and cardiac tamponade.¹⁸⁸ Mid- and long-term complications include thrombus formation, device erosion into the aortic root, atrial dysrhythmias, and infective endocarditis. The use of platelet inhibitors for at least 6 months after device closure is recommended to decrease the risk of device thrombosis.¹⁸⁹ The long-term outcomes of device closure using the Amplatzer septal occluder are excellent, as evidenced by no deaths and minimal complications in 151 patients followed for 6.5 years after ASD closure.¹⁹⁰

Ventricular Septal Defect

Isolated VSD is the most commonly encountered form of CHD in the pediatric population (see Fig. 56–16). This is not the case in the adult population for a number of reasons.^191,192

1. Most children with hemodynamically significant defects are diagnosed and undergo repair in childhood because they develop signs and symptoms of LV enlargement and failure. Children growing up in developing countries often go undiagnosed and unrepaired well into adulthood because of absent or intermittent medical attention.

2. Small unrepaired perimembranous or muscular VSDs often spontaneously decrease in size or close with age. However, small VSDs initially encountered in adulthood (in patients older than 20 years of age) are unlikely to close spontaneously.

3. Large nonrestrictive defects that are not surgically corrected within the first 2 years of life result in incompletely reversible pulmonary vascular disease and are associated with increased mortality in childhood (see Fig. 56–3).

Therefore, the spectrum of isolated residual VSD encountered in the adult patient usually consists of:

1. Small restrictive defects or defects that have closed partially with time. The pulmonary vascular resistance is not significantly elevated, and the left-to-right shunt magnitude is mild (Qp:Qs ratio ≤ 1.5:1). The intensity of the precordial holosystolic murmur is inversely related to the size of the defect; therefore, a disturbingly loud and harsh precordial holosystolic murmur in a patient with VSD should be viewed as a reassuring sign, not a cause for alarm.

2. Large nonrestrictive defects in cyanotic patients who have developed the Eisenmenger complex, with systemic pulmonary vascular resistance and shunt reversal (right to left).

3. Patients with moderately restrictive defects (Qp:Qs ratio ≥ 1.6:1 and ≤ 2:1) who have not undergone closure for some reason. These patients often have mild to moderate pulmonary hypertension.

4. Patients who have had their defects closed in childhood. These patients may have small, but generally inconsequential, VSD patch leaks that may be identified by careful color and two-dimensional Doppler scanning of the entire interventricular septum during echocardiographic examination.

Natural History

Small restrictive defects of the muscular or membranous septum may be watched conservatively without the need for operative intervention. Patients are at increased risk for endocarditis as a result of the turbulent, high-velocity jet impinging on the septal leaflet of the tricuspid valve that partially closes many perimembranous defects. Six percent of patients with small perimembranous defects may develop aortic valve prolapse and resultant aortic regurgitation that may be progressive.¹⁹³ The prolapsing aortic valve cusp (usually the right coronary cusp) may partially or completely close the VSD. Aortic valve repair or replacement may be necessary in patients with aortic regurgitation who develop exertional symptoms or progressive LV dilatation.^113,194 In a long-term follow-up registry, the overall survival rate was 87% for all patients with unoperated VSD.¹⁷⁹ For patients with small defects (Qp:Qs ratio < 1.5 and low pulmonary artery pressure), the survival rate was 96% at 25 years. Patients with moderate and large defects fare worse, with 25-year survival rates of 86% and 61%, respectively. Those with cyanosis (Eisenmenger complex) had a much lower 25-year survival rate of 41.7%.

In patients with large nonrestrictive VSD, pulmonary vascular disease begins at or soon after birth with abnormal vascular remodeling; if the VSD is not surgically repaired, patients eventually develop obliterative pulmonary vascular disease.¹⁹² Systemic pulmonary vascular resistance results in a balanced bidirectional shunt or shunt reversal and cyanosis, a condition first described by Eisenmenger in 1897 and coined “the Eisenmenger complex” by Maude Abbott in 1927.¹⁹⁵ Survival is generally decreased in these patients, although with proper medical care and protection against certain risks (eg, dehydration, endocarditis), survivors have been reported into the seventh decade of life.^47,196 Patients develop compensatory erythrocytosis, which is an appropriate response to the decreased systemic oxygen saturation from right-to-left shunting of deoxygenated blood. Phlebotomy is not warranted unless patients develop symptoms of hyperviscosity (headache, visual changes) that are refractory to hydration. As a matter of fact, routine phlebotomy does not reduce cerebral complications and leads to iron deficiency anemia. Microcytic iron-deficient red blood cells carry less oxygen and are less deformable in the microcirculation than iron-replete red blood cells, thus resulting in worsening cyanosis and increased cerebral complications, which are properly treated by judicious iron repletion.⁴⁷

Management and Results

Patients with small restrictive defects (Qp:Qs ratio ≤ 1.5:1 and low pulmonary artery pressure) are generally asymptomatic and should be managed conservatively and followed up regularly.¹⁷⁹ Although antibiotics for endocarditis prophylaxis are no longer recommended by the ACC/AHA guidelines, patients are at increased risk for endocarditis.¹¹³ Patients should be instructed in dental and skin care. Small defects with aortic valve prolapse and aortic regurgitation may be repaired to avoid progressive aortic regurgitation.¹⁹⁷ Larger defects may be repaired in the absence of severe pulmonary hypertension and severely elevated pulmonary vascular resistance (> 10 Wood units × m²), which incurs a high perioperative risk.^198,199 Postoperative life expectancy is not normal, but has improved over the past 50 years with improved surgical techniques and experience. Postoperative conduction defects are common, but complete heart block is rare in the current era. The postoperative risk of infective endocarditis is low. Transcatheter device occlusion of muscular and perimembranous VSD is feasible, and trials demonstrate a good safety and efficacy profile.^{200,201,202,203} Complete heart block has been noted to occur in up to 6% of children and 1% of adults.^200,202

Atrioventricular Septal Defects

Atrioventricular septal defect is an umbrella term used to describe endocardial cushion defects representing a spectrum of lesions involving the atrial and ventricular septum, AV valves, and LV outflow tract (LVOT). The defects are classified into “partial” or “complete” forms. In the partial form, patients have a primum ASD but no VSD (see Fig. 56–16). The complete form includes both a primum ASD and an inlet VSD (see Fig. 56–16). The deficiency of the inlet ventricular septum along with abnormalities of the AV valves (overriding, straddling, or cleft) produces an elongated LVOT that has characteristically been described as having a “goose neck” appearance on left ventriculography. Subaortic stenosis (SAS) is a common association often caused by chordal attachments of the cleft anterior mitral valve to the LV outflow septum (Fig. 56–18). SAS may also occur de novo after surgical repair because of a discrete fibrous membrane.²⁰⁴

Natural History

Approximately 5% of infants with CHD have AV septal defect, with two-thirds of patients having the complete form.²⁰⁵ Trisomy 21 and other chromosomal abnormalities are frequently associated, and these patients usually have the complete form. The natural history of partial AV septal defect patients depends on the size of the defect and, in many ways, these primum ASDs behave in a similar manner to secundum ASD (see earlier). Patients with Down syndrome may have accelerated pulmonary vasculopathy, resulting in pulmonary hypertension at an earlier age. Mitral valve regurgitation, secondary to the presence of a common AV valve and “cleft” (see Fig. 56–18), if present, leads to greater left-to-right shunt magnitude and earlier signs of pulmonary hypertension and heart failure. Patients with complete defects that are unrepaired in infancy or childhood frequently develop severe pulmonary hypertension and eventual shunt reversal, characteristic of Eisenmenger syndrome (see earlier).

Management and Outcomes

Surgical repair involves patch closure of the primum ASD and VSD closure in patients with the complete form of AVSD. “Cleft” mitral valve repair should be attempted to restore valvar competence, the assessment of which can be made using intraoperative TEE.^206,207 Percutaneous ASD closure of a primum defect is contraindicated given the close proximity of the defect to the tricuspid and mitral valves as well as the ostium of the coronary sinus. Surgical mortality is 15% within the first 30 days after surgery.²⁰⁸ Adverse predictors of mortality include the complete type of AV septal defect, the presence of pulmonary hypertension, and the absence of cleft mitral valve repair. Survival late after operation in a study of 121 patients demonstrated that survival was 80% at 1 year, 78% at 10 years, and 65% at 20 years. Freedom from reoperation was 91% at 1 year, 79% at 10 years, and 76% at 20 years. Mitral valve regurgitation necessitating valve repair or replacement was the most frequent indication for reoperation.

Tetralogy of Fallot

TOF is the most common cyanotic congenital heart malformation and one of the first complex lesions to be successfully repaired. TOF occurs in 7% to 10% of children with CHD. The four characteristic findings in TOF are (1) a malaligned VSD, (2) RV outflow or pulmonary valve or artery stenosis or atresia, (3) a dextraposed over-riding aorta, and (4) RV hypertrophy (see Fig. 56–1A). In the modern era, early surgical repair consisting of VSD closure and alleviation of RV outflow obstruction has gained favor over early palliation with an aortopulmonary shunt followed by intracardiac repair. Surgical outcomes are excellent and dramatically improve prognosis. However, these patients are not “cured” and are at significant risk of developing subsequent electrical and hemodynamic problems. Operated patients with TOF should be evaluated at regular intervals by a cardiologist trained in CHD; any symptoms suggestive of hemodynamic or electrical compromise should spur further investigation. Advances in imaging, medical therapy, electrophysiology, device and resynchronization therapy, and percutaneous intervention provide clinicians with a number of therapeutic options.

Natural History

The natural history of unoperated patients is in large part determined by the severity of obstruction to RV outflow. A total of 66% of unoperated patients live to 1 year of age, 49% live to 3 years of age, 24% live to 10 years of age, and only 3% of patients reach 40 years of age.²⁰⁹ The chance of survival is greatly diminished when complete pulmonary atresia, instead of a variable degree of pulmonary stenosis, is present. Complications of right-to-left shunting across a nonrestrictive VSD include cyanosis, erythrocytosis, thrombocytopenia, and an increased risk of paradoxical emboli and cerebral abscess formation. Patients are at high risk for developing infective endocarditis. Malignant ventricular arrhythmias and congestive heart failure are major causes of death.

Management and Results

Since Blalock and Taussig performed a successful clinical palliative shunt in 1945, the survival and quality of life for patients with TOF has improved dramatically, truly one of the great accomplishments for cardiovascular medicine in the 20th century (see Fig. 56–1). Surgical palliation consists of systemic arterial–to–pulmonary arterial shunts designed to increase blood flow to the pulmonary arteries. Palliative surgery was followed subsequently by intracardiac repair that included VSD closure and relief of the RV outflow obstruction (see Fig. 56–1). Surgical techniques have changed significantly since the early intracardiac repairs of the 1960s and 1970s. The deleterious hemodynamic and electrical effects of pulmonary regurgitation and ventriculotomy scars have spurred efforts to ensure pulmonary valvar competence and minimize the extent of ventricular incisions. Advancements in surgical repair now confer an 85% survival into adulthood in the United States.²¹⁰ The technique used for repair depends on the level and extent of outflow obstruction. Simple pulmonary valvar stenosis with a nondysplastic well-developed pulmonary valve requires the least extensive surgery, which consists of VSD and pulmonary valvotomy. More extensive or more severe outflow tract stenoses necessitate a more extensive reconstruction of the RVOT or complete bypass of the RV outflow tract by placement of a valved conduit. The first generation of intracardiac repairs was performed via a large anterior ventriculotomy and frequently included incision of the pulmonary valve annulus and placement of a transannular patch made of pericardium or synthetic material. This technique successfully relieved the outflow tract obstruction but resulted in pulmonary valvar incompetence and severe pulmonary regurgitation (see Fig. 56–9). Pulmonary regurgitation was thought to have minimal adverse clinical consequences, which may be true for the first two decades after transannular patch repair. However, with time, the adverse hemodynamic effects of severe low-pressure pulmonary regurgitation results in RV dilation and increased wall stress. The RVOT in the region of the transannular patch becomes dyskinetic, causing turbulence and energy loss. The tricuspid annulus frequently dilates, and tricuspid regurgitation often occurs. Therefore, the RV suffers under an additive source of volume overload in the presence of tricuspid regurgitation. Additionally, the RV develops “restrictive” diastolic properties that further compromise energy-efficient hemodynamics²¹¹ (see Fig. 56–9). Ventricular arrhythmias are more likely to occur under such conditions and often arise from the region of the transannular patch or ventriculotomy suture lines.²¹² Programmed ventricular stimulation resulting in monomorphic or polymorphic ventricular tachycardia is of prognostic importance in these patients.⁸⁵ In a cohort of 793 patients with repaired TOF followed for a mean of 21 years, ventricular tachycardia occurred in 4.2%, and sudden cardiac death occurred in 2% of patients.²³ Transventricular and transannular repair were associated with ventricular tachycardia and sudden cardiac death. QRS width on the surface ECG has additive prognostic value; 88% of patients with ventricular tachycardia and 63% of patients with sudden death had a QRS duration of ≥ 180 ms.²³ Patients invariably have a right bundle branch block that results from early injury caused by surgical VSD closure and ventriculotomy followed by subsequent QRS lengthening secondary to RV dilatation. Therefore, severe pulmonary regurgitation leads to RV dilatation, which in turn leads to systolic and diastolic functional deterioration and increasing QRS duration, creating a vicious cycle; all of these factors combine to increase the risk of malignant ventricular arrhythmias. LV systolic and diastolic dysfunction are additional high-risk markers.^93,213,214

Patients with an RV–to–pulmonary artery valved conduit may develop progressive conduit stenosis, but do not usually develop significant pulmonary regurgitation. Atrial arrhythmias are a cause of morbidity and confer a worse prognosis in patients with repaired TOF, especially in patients with tricuspid valve regurgitation and right atrial enlargement.^23,215 AV block may occur after initial repair and VSD closure and is usually the result of damage to the conduction system at or below the bundle of His incurred during VSD closure. These patients require implantation of a permanent pacemaker (usually dual chamber) and are often pacemaker dependent. Chronic RV pacing is known to lead to deterioration of biventricular function and dyssynchronous ventricular contraction.²¹⁶ Biventricular resynchronization may improve dyssynchrony and increase cardiac output.^217,218 LV systolic and diastolic dysfunction may occur in the presence of severe pulmonary regurgitation. The interventricular septum bows leftward during diastole, resulting in impaired LV diastolic filling and asynchronous septal contraction. A decrease in LV ejection fraction is ominous.²¹⁹ Abnormal strain patterns by cardiac MRI are associated with adverse clinical outcomes.^20,220 Approximately one in 10 patients will require subsequent reoperation for RV outflow repair, conduit replacement, or pulmonary valve replacement.²²¹ Additional tricuspid valve annuloplasty and right atrial maze cryoablation are often performed in patients with severe tricuspid regurgitation and atrial arrhythmias. In patients with mild or moderate tricuspid regurgitation and dilated tricuspid annular size, tricuspid regurgitation improves after pulmonary valve replacement, regardless of whether tricuspid annuloplasty was performed.^222,223 Every effort should be made by the surgeon to excise the ventriculotomy scar tissue that serves as the source of reentrant ventricular arrhythmias. Reoperation carries a low perioperative risk of death.¹⁴⁵

Transcatheter pulmonary valve (TCPV) replacement can alleviate RVOT conduit dysfunction whether caused by stenosis, regurgitation, or both, thereby delaying the need for open heart surgery and essentially decreasing the number of operations with their associated morbidities.²²⁴ The Melody (Medtronic, Dublin, Ireland) TCPV was the first valve to receive US Food and Drug Administration (FDA) approval, initially under humanitarian device exemption in 2010 and thereafter for clinical use in 2014. The Melody valve is widely used for the treatment of dysfunctional RV–to–pulmonary artery conduits and bioprosthetic valves, and more recently has been used to treat dysfunctional native RVOT lesions. The various Sapien transcatheter bovine pericardial stent valves (Edwards, Irvine, CA; Sapien, Sapien XT, and Sapien 3) are FDA approved for use in the aortic position and are being used by multiple centers for off-label implantation in the pulmonary position. The larger diameter Sapien valves (26 and 29 mm) allow for implantation in large dysfunctional native RVOTs. Short-term follow-up after Melody valve implantation has been promising, with hemodynamic and clinical improvement and acceptable durability of the valve.²²⁵ Greater improvement in exercise capacity is seen in patients with both RVOT stenosis and regurgitation, compared with those with only RVOT regurgitation.²²⁶ Favorable longer term outcomes were seen after a median follow-up of 4.5 years in 148 patients in the US Melody valve investigational device exemption trial, with a 5-year freedom from reintervention of 76% and a 5-year freedom from explant of 92%.²²⁷ Stent fracture and endocarditis have been the primary causes for reintervention.^{228,229,230,231,232}

Stent fracture often occurs in patients with conduits or native RVOT dysfunction, and is likely caused by repetitive stress on the platinum iridium frame (Fig. 56–19). Prestenting before Melody valve placement has significantly reduced the incidence of stent fracture. Also, valve-in-valve implantation is a successful treatment option for Melody valve stent fracture. As for endocarditis, adherence with subacute bacterial endocarditis prophylaxis is imperative; however, data suggest there is an increased risk of infective endocarditis with implanted Melody valves.^230,231,233 Other complications, such as conduit or pulmonary artery dissection or rupture, are life threatening but rare and can be treated with covered stent placement. There is a 5% risk of coronary artery compression, but this risk can be reduced by performing simultaneous balloon inflation in the RVOT with coronary or aortic root angiography to test for coronary artery compression. TCPV replacement has also been successfully performed within failed bioprosthetic valves, not as part of RV–to–pulmonary artery conduits, with excellent outcomes. In the subset of CHD patients with native RVOT or RVOT patch repairs, there is a growing body of literature on the utility of commercially available valves used off label.

The timing of pulmonary valve replacement in asymptomatic patients remains controversial, especially in the repaired TOF patient. Severe RV dilation or dysfunction and the development of atrial arrhythmias are the most common indications for pulmonary valve replacement in the otherwise asymptomatic patient, although the RV volume threshold for pulmonary valve replacement varies by ACHD center. Therrien et al¹⁴⁷ demonstrated that patients with TOF and severe pulmonic regurgitation had normalization of RV end-diastolic volumes after pulmonic valve replacement if the preoperative indexed RV end-diastolic volume was ≤ 170 mL/m². An indexed RV end-diastolic volume of ≥ 160 mL/m² or an indexed RV end-systolic volume ≥ 65 mL/m² has therefore been suggested as an indication for pulmonary valve replacement.¹⁴⁶ However, the advent of transcatheter valve therapies may be lowering the threshold for pulmonary valve replacement. Some experts argue that all patients with severe pulmonary regurgitation should undergo pulmonary valve replacement prior to the development of RV dilation or dysfunction.²³⁴ This aggressive early intervention approach must be weighed against the procedural risks, the potential for infective endocarditis, and the potential decrease in the internal orifice diameter of surgically placed conduits or bioprosthetic valves with multiple transcatheter pulmonary valve implants over a patient’s lifetime.²³⁵

Pulmonary Stenosis

Isolated pulmonary valve stenosis is commonly seen in adults with CHD. The valvar stenosis is typically characterized by a trileaflet valve with fused commissures, as opposed to the more rare dysplastic valve without commissural fusion. The exception is Noonan syndrome, in which a dysplastic and stenotic pulmonary valve is commonly present. RV hypertrophy, including excessive hypertrophy of the infundibulum, occurs in response to RV pressure overload from the stenotic valve. Isolated infundibular stenosis is rare, as is isolated supravalvar stenosis.

Natural History

Survival into adulthood is usual. Severe pulmonary stenosis that is uncorrected may result in progressive RV hypertrophy, dilatation, and symptoms of right heart failure. Moderate or mild pulmonary stenosis generally does not progress and is well tolerated.

Management and Outcomes

Mild and moderate degrees of pulmonary stenosis (peak gradient ≤ 50 mm Hg) are well tolerated and generally do not require surgical or percutaneous intervention.⁹³ Infective endocarditis of the pulmonary valve is rare; endocarditis prophylaxis during bacteremic procedures is not recommended.⁶ Asymptomatic patients with severe pulmonary stenosis and a peak gradient ≥ 60 mm Hg or a mean gradient ≥ 40 mm Hg should undergo intervention to reduce the severity of the stenosis. Symptomatic patients with a peak gradient ≥ 50 mm Hg or a mean gradient ≥ 30 mm Hg should undergo intervention.⁶

Surgical valvotomy for isolated pulmonary stenosis has been successfully and safely performed for 50 years. Perioperative and late results are excellent, especially if surgery is performed in the first two decades of life.²³⁶ Various degrees of pulmonary regurgitation occur and are well tolerated in the short and medium term. Severe pulmonary regurgitation is more common when pulmonary valvectomy or transannular patching is performed, usually for dysplastic valves or narrowed annulus. Severe chronic regurgitation results in progressive RV dilatation and dysfunction with an increased rate of coexistent ventricular and supraventricular arrhythmias (see earlier section Tetralogy of Fallot). The advent and widespread use of transcatheter balloon valvuloplasty in the past three decades have made surgical valvotomy unnecessary in most cases of isolated valvar stenosis (Fig. 56–20).^156,237,238 The immediate and midterm results of balloon valvuloplasty in mobile nondysplastic pulmonary valvar stenosis are favorable.²³⁹ Subvalvar infundibular hypertrophy often results in a dynamic subvalvar gradient across the infundibulum that often increases after valvuloplasty because of the relief of downstream obstruction. β-Blocker therapy before and after valvuloplasty helps decrease this dynamic gradient and avoid the rare, but catastrophic, severe infundibular stenosis characterizing the “suicide ventricle."²⁴⁰

Left Ventricular Outflow Tract Obstruction

LVOT obstruction (LVOTO) may occur at the subvalvar, valvar, or supravalvar levels.²⁴¹ These obstructions to forward flow may present alone or in association with other levels of obstruction, as in the frequent association of a BAV with coarctation of the aorta. LVOTO imposes increased afterload on the LV and, if severe and untreated, results in hypertrophy and eventual dilatation and failure of the LV and life-threatening arrhythmias.

LVOTO is congenital in the majority of patients younger than 50 years of age in the United States; some variants of subaortic obstruction are the exception (eg, subaortic membranes). Patients with LVOTO are at risk for developing infective endocarditis. Fixed SAS may be caused by a discrete fibrous membrane, a muscular narrowing, or a combination of the two. The obstruction may be focal or more diffuse, resulting in a tunnel leading out of the LV. The discrete form of fibromuscular SAS is most frequently encountered (90%), but the tunnel-type lesions are associated with a greater degree of stenosis.²⁴² In some patients with AV septal defects and cleft mitral valve, abnormal accessory mitral valve tissue or chords may cause SAS (see Fig. 56–20B). SAS may be a congenital isolated lesion, but may also be acquired. A BAV is present in 23% of patients.²⁴² SAS may also present as part of a complex of obstructive lesions, as in the Shone complex, which frequently includes parachute mitral valve, mitral stenosis, BAV, and coarctation of the aorta. A total of 37% of patients with SAS may also have concomitant VSDs of the perimembranous type.²⁴²

BAV is one of the most common congenital cardiovascular malformations with an estimated incidence of 1% to 2%.²⁴³ BAV is sometimes inherited, and family clusters have been studied. Inheritance patterns are autosomal dominant with variable penetrance.²⁴⁴ Variants of BAV range from a nearly trileaflet bicommissural valve with mild cuspal inequality to a unicuspid unicommissural valve. The aortic root tissue structure is abnormal. The histology of the ascending aortic wall demonstrates medial abnormalities that are similar to, but less advanced than, those of the Marfan syndrome.²⁴⁵ Although aortic dilatation above a stenotic BAV has previously been attributed to “poststenotic” turbulence, several studies have clearly demonstrated that dilatation and histologic abnormalities of the ascending aorta in BAV occur irrespective of the degree of valvar stenosis or regurgitation.²⁴⁶

Supravalvar aortic stenosis (SVAS) is the rarest type of LVOTO and is defined by a focal or diffuse narrowing starting at the sinotubular junction and often involving the entire ascending aorta.²⁴⁷ SVAS is frequently associated with Williams-Beuren syndrome, a multisystem disorder with an autosomal dominant inheritance pattern that occurs in 1 in 20,000 births.²⁴⁸

Natural History

In the absence of LV hypertrophy, dilatation, or failure, intervention in patients with SAS may be safely deferred; however, there should be careful lifelong follow-up for symptoms and stenosis progression. Aortic regurgitation may result from damage to the valve by the turbulent flow caused by SAS. The clinical course of SAS is usually progressive with increasing obstruction and progression of aortic regurgitation in the majority of untreated patients.^249,250 The primary hemodynamic effect on the LV is one of increased afterload, resulting in increased intracavitary pressure and wall stress. Patients may present with one of the triad of symptoms associated with severe valvar aortic stenosis (ie, angina, heart failure, or syncope). Patients with SAS are at increased risk for developing infective endocarditis, which frequently involves the aortic valve and often leads to aortic regurgitation.²⁵¹ Even in the absence of endocarditis, when the Doppler-derived LVOT peak instantaneous gradient reaches 50 mm Hg or above, there is an increased risk of moderate-to-severe aortic regurgitation.²⁵²

BAV disease is gradually progressive in the majority of cases. Abnormal folding and creasing of the valve leaflets throughout the cardiac cycle, extended areas of valve contact, turbulent flow, and restricted motion of the leaflets lead to valve damage, scarring, calcification with resultant stenosis, and regurgitation.²⁵³ Turbulent flow into the ascending aorta added to the medial abnormalities discussed above may lead to progressive dilatation and an increased likelihood of rupture or dissection.^253,254 Atherosclerotic changes have been identified in BAV and are similar to those seen with calcific degenerative stenosis of trileaflet aortic valves. The presence of dyslipidemia may be associated with accelerated progression of BAV stenosis.^255,256 Aortic stenosis is the most common complication of BAV. Patients with a mobile BAV have a systolic ejection sound after the first heart sound best heard at the LV apex. This ejection sound is present until valve calcification restricts mobility. Concomitant aortic regurgitation results in an early diastolic decrescendo murmur; when well heard at the right mid sternal border, it suggests the presence of a dilated ascending aorta. Evidence of echocardiographic sclerosis can be seen as early as the second decade of life. Thickening and calcification often occur in the fourth decade of life, and only 15% of patients with BAV have a normally functioning valve in the fifth decade.²⁵⁷ Moreover, a BAV predisposes patients to the development of aortic regurgitation. Progression of aortic regurgitation may occur via several mechanisms and, in most cases, is directly correlated with the degree of aortic root and annular dilatation.²⁵⁸ Other mechanisms include leaflet prolapse, degeneration, and retraction. Infective endocarditis of the BAV may cause leaflet destruction and perforation along with intimal dissection leading to a sudden worsening of aortic regurgitation that is poorly tolerated hemodynamically and is a surgical emergency. Aortic dissection is an infrequent, but deadly, complication. Asymptomatic patients with a peak transvalvar systolic velocity of 4 m/s or above are likely to develop symptoms related to stenosis (dyspnea, chest pain, syncope) within 5 years.^113,259 The ascending aorta in patients with BAV gradually dilates at a mean of 0.9 mm/year.^260,261 The risk of dissection in patients with BAV is estimated to be five to nine times that of the general population, and is highest in patients with concomitant coarctation.^262,263 Patients with a BAV and ≥ 55-mm aortic root diameter should be referred for surgical aortic root wrapping or replacement.¹¹³

Fifty percent of patients with SVAS may have concomitant aortic valve abnormalities, most commonly a BAV.²⁶⁴ Fatigue stress and shear forces are increased on the aortic valve leaflets in the setting of a poorly distensible sinotubular junction and may result in leaflet thickening and damage with resultant regurgitation, stenosis, or both.²⁶⁵ SAS occurs in 16% of patients and may contribute to aortic valve damage.²⁶⁶ Impaired coronary perfusion may occur because of varying degrees of aortic valve leaflet adhesion to the narrowed sinotubular junction, restricting diastolic filling of the coronary arteries.²⁶⁷ Furthermore, the coronary arteries are subjected to elevated systolic pressures in SVAS, which leads to dilatation, tortuosity, and accelerated atherosclerosis.²⁶⁸

Management and Results

Surgical resection is the intervention of choice for treatment of SAS and is usually done via a transaortic approach. Surgical mortality is low, and complications are generally minimal.²⁶⁹ Surgical management consists of discrete membrane excision or blunt dissection (or both) in focal SAS with focal septal myotomyectomy. Tunnel-type SAS is more surgically challenging and often necessitates application of the Konno-Rastan procedure to reconstruct the LVOTO.²⁷⁰ Concomitant repair of the aortic valve is performed if the severity of the aortic regurgitation is more than mild. SAS recurs in up to 37% of cases after surgical resection.²⁴² In this series, tunnel-type SAS recurred in 71% of patients versus a 14.7% recurrence rate for discrete SAS over 6 years of follow-up. The presence of an immediate postoperative gradient above 10 mm Hg led to progressive recurrent SAS in 75% of patients; therefore, attention must be paid to the excision of all abnormal tissue and removal of the membrane from the anterior mitral leaflet. Progressive aortic regurgitation may develop despite relief of SAS. Percutaneous balloon dilatation of a fixed focal stenosis causes short-term improvement in the gradient and may be considered for palliation of SAS.²⁷¹ In one case series, 25-year freedom from reintervention was 77%.²⁷²

There are currently no proven medical therapies that alter the course of aortic stenosis or regurgitation in patients with BAV. β-Blockers may delay the progression of ascending aortic dilatation.¹¹³ Patients with hypertension and aortic regurgitation may benefit from afterload reduction with ACE inhibitors, hydralazine, or calcium channel blockers. However, a randomized, prospective trial of enalapril or nifedipine versus placebo in patients with severe aortic regurgitation revealed no differences in regurgitant volume, LV size, or ejection fraction over 7 years of follow-up.²⁷³ Aortic valve replacement should be performed in patients with severe symptomatic aortic valve stenosis. Aortic valve replacement is also recommended in asymptomatic patients with severe aortic stenosis if the LV ejection fraction is < 50% or if the patient is undergoing other cardiac surgery. Surgery may be considered in asymptomatic patients with very severe stenosis with a peak velocity ≥ 5 m/s if patients are assessed to be low surgical risk.¹¹³ Because stenosis is secondary to bicuspid commissural fusion, balloon valvuloplasty may safely decrease the gradient and improve symptoms in those without a calcified valve.^274,275 Surgical repair or replacement is indicated for patients with severe stenosis (peak instantaneous Doppler velocity of ≥ 4 m/s) who are symptomatic.¹¹³ Surgery should also be considered in those with less severe stenosis who have concomitant moderate or severe aortic valve regurgitation or a dilated ascending aorta. Asymptomatic patients with severe BAV stenosis who want to become pregnant or to exercise more vigorously should also be considered for surgery. Severe aortic regurgitation, if associated with symptoms, severe aortic root enlargement, or LV dilatation and decreased ejection fraction, should be surgically corrected.¹¹³ Numerous surgical techniques have been used to repair or replace the aortic valve. Valve repair has shown promising results and should be considered if the valve is not calcified.^113,276 If valve replacement is needed, bioprosthetic valves are generally preferred in patients older than 65 years, women of childbearing age wishing to avoid warfarin, and patients refusing to take or who are allergic to warfarin. These bioprosthetic valves generally deteriorate over 10 to 20 years and require replacement. Mechanical prostheses have superior durability in patients who can tolerate warfarin. The Ross procedure has been used successfully in patients with BAV and is favored in the pediatric population. However, after the Ross procedure, patients are at risk for developing neoaortic dilatation, progressive aortic regurgitation, neopulmonary homograft regurgitation, and myocardial ischemia.²⁷⁷

Patients with SVAS may undergo surgical enlargement of the narrowed sinotubular region and adjacent ascending aorta if they have symptoms of angina, dyspnea, syncope, or heart failure, or a mean pressure gradient of 50 mm Hg or above. Surgical relief of obstruction consists of excision of a focal stenosis with end-to-end anastomosis of the ascending aorta, patch enlargement of the sinotubular junction, or more complex aortoplasty involving patch placement into two or more sinuses of Valsalva. The Ross procedure has also been used to replace the aortic root in patients with concomitant aortic valve disease. Balloon angioplasty of SVAS does not result in relief of obstruction and risks aortic dissection or rupture.

Coarctation of the Aorta

Coarctation of the aorta in adults is usually a discrete narrowing in the region of the ligamentum arteriosum (Fig. 56–21). More diffuse forms of the disease may involve the arch or isthmus. Coarctation of the aorta occurs in 7% of patients with CHD, and there is a small male predominance of 1.5:1. Coarctation is a diffuse arteriopathy characterized by cystic changes in the aortic media.²⁷⁸ The descending aorta immediately distal to the segment of coarctation is often aneurysmal. A BAV is present in about half of cases. Intracranial aneurysms, often in the circle of Willis, have been detected in up to 10% of patients.²⁷⁹ Adult unoperated patients present with systemic arterial hypertension in the upper extremities. A normal patient should have a 5- to 10-mm Hg increase in systolic blood pressure in the lower extremities compared with the upper extremities. Absence of this increase or presence of a decrease in the lower extremities should arouse suspicion of coarctation.

Natural History

Unoperated survival is poor, and median survival is only 35 years.²⁸⁰ Patients die of congestive heart failure, aortic dissection or rupture, complications of infective endocarditis, and intracranial hemorrhage from ruptured aneurysms in the circle of Willis.

Management and Results

Excision of the narrowed segment and end-to-end anastomosis of the para-coarctation aorta is the preferred method for initial repair (Fig. 56–22). Subsequent modifications in surgical technique include the use of prosthetic overlay grafts, subclavian patch aortoplasty, and prosthetic tube grafts from the ascending to the descending aorta in patients with complete interruption (see Fig. 56–22). Percutaneous balloon angioplasty with stenting for primary coarctation has gained popularity and has displayed encouraging results. Stent implantation is preferable to angioplasty alone and has excellent long-term outcomes (see Fig. 56–14).^281,282

Patients with successfully treated coarctation often continue to have systemic arterial hypertension despite the absence of significant residual coarctation.^283,284 Patients who undergo repair in childhood demonstrate very good long-term survival up to 60 years.²⁸⁵ Late repair (> 14 years of age) is associated with higher rates of hypertension and decreased survival.²⁸⁶ Patients with hypertension after late repair are at an increased risk of developing heart failure, atherosclerosis, stroke, and progressive aortic disease.

Complete Transposition of the Great Arteries

Complete TGA refers to a ventriculoarterial discordance characterized by medial transposition of the aorta, which arises anteriorly and rightward from a morphologic RV, and the pulmonary artery arises posteriorly and leftward from a morphologic LV. Simply, the aorta is anteriorly dextraposed and emerges from a normally located RV, and the pulmonary artery is posteriorly levoposed to emerge from the LV (see Fig. 56–2). As a result, the systemic and pulmonary arterial circulations run in parallel, not in series. Therefore, poorly oxygenated blood enters the aorta, and survival depends on the delivery of oxygenated blood to the systemic circulation via a left-to-right shunt. Atrial balloon septostomy (Rashkind procedure) may need to be urgently performed within the first few hours of life to create an intracardiac shunt. Other anomalies often coexist, including VSD (30%), LVOTO (10%), and more rarely, PDA and coarctation of the aorta.²⁰⁵

Natural History

Surgical intervention in infancy is imperative for survival, and almost all adult patients with this condition have undergone prior correction. However, patients with large nonrestrictive shunts at the atrial, ventricular, or pulmonary arterial levels who may survive into adulthood often develop congestive heart failure in childhood and pulmonary vascular disease thereafter.

Management and Results

The use of balloon atrial septostomy in the infant with TGA, initially described by Rashkind and Miller²⁸⁷ in 1966, allows enough left-to-right shunting of oxygenated blood to palliate the patient. The Senning operation, a description of which was initially published in 1959, followed by the Mustard operation in 1964, involved redirection of atrial blood via baffles to deliver oxygenated pulmonary venous blood to the systemic RV and deoxygenated systemic venous blood to the pulmonary LV (see Fig. 56–2).^288,289 The major difference between these two operations is that whereas the earlier Senning operation uses atrial and septal tissue to create the baffles described earlier, the Mustard operation uses extrinsic materials (ie, pericardium) for this purpose. These surgeries were performed in the majority of operated infants and children (usually between 1 and 12 months of age) until the late 1970s and early 1980s. Long-term follow-up demonstrates an 80% 28-year survival rate, with the majority of survivors in NYHA class I.²⁹⁰ Atrial tachyarrhythmias and bradyarrhythmias occur over time, with SND and incisional reentrant atrial arrhythmias being frequent long-term complications. Loss of sinus rhythm is progressive, but usually asymptomatic at rest. Patients often demonstrate evidence of chronotropic incompetence with exercise and may benefit from pacemaker insertion. Reentrant atrial tachyarrhythmias are a worrisome development and are notoriously difficult to treat and may require life-long anticoagulation. These arrhythmias often result in deleterious and poorly tolerated hemodynamic consequences and increase the risk of sudden cardiac death, especially in the presence of RV dysfunction.²⁹¹ Sudden death is a well-documented occurrence in up to 15% of patients and usually occurs during exercise.^290,292 Patients at increased risk for sudden cardiac death are older, have worse systemic RV function, and have a widened QRS complex (> 140 ms).²⁹³ Obstruction of the pulmonary or systemic venous baffles (usually the superior vena cava baffle) occurs in a minority of patients and can usually be treated with transcatheter angioplasty and stenting. Baffle leaks are more common than obstruction, and the majority are not hemodynamically significant; only 1% to 2% require intervention because of cyanosis or volume overload. Progressive systemic RV failure does not usually occur in the short and intermediate term, but may be a problem beginning in early adult life. ACE or angiotensin receptor inhibition does not improve exercise performance or decrease serum BNP levels.^25,26,294 This may be explained by a lack of activation of the renin-angiotensin system and the presence of another yet unidentified mechanism for progressive systemic RV dysfunction and impaired exercise capacity. β-Blocker therapy, on the other hand, may be beneficial in halting adverse ventricular remodeling, decreasing the risk of life-threatening arrhythmias, and improving exercise capacity.^291,295

The late complications sited earlier for atrial switch operations led to the increasing acceptance of the arterial switch (Jatene operation) as the operation of choice.²⁹⁶ This procedure consists of anatomic correction by transection of the aorta and pulmonary artery at a level above the valve sinuses with detachment of the coronary arteries from the aorta. Thereafter, the positions of the transected great arteries are reversed so that the “neo-aorta” emerges from the LV and the “neopulmonary” artery emerges from the RV. The coronary arteries are sutured into place in the neo-aorta. This is a technically challenging surgery but has certain advantages over the atrial switch operations, namely, the LV is the systemic ventricle and the incidence of arrhythmias is lower.²⁹⁷ Some authors have advocated performing the arterial switch operation after “conditioning” the LV with pulmonary artery banding in patients with a previous Mustard or Senning repair. The existing literature indicates a significant surgical mortality and inconsistent LV response to “conditioning” if the arterial switch is performed after childhood.^298,299 The long-term outcomes of the arterial switch operation are now becoming available, and the results are encouraging. The 10-year survival rate is 88% in patients without associated lesions such as VSD, in whom the operative mortality is higher and the 10-year survival is decreased to 80%.³⁰⁰ Neo-aortic valve regurgitation occurs in approximately 15% of patients; however, only a minority of patients require reoperation for this problem.³⁰¹ Neopulmonary artery stenosis or branch pulmonary artery stenosis occurs in a minority of patients and may require transcatheter or operative intervention. Myocardial ischemia related to reimplantation, surgical manipulation, and distortion has been reported, and late deaths because of coronary events may occur in a minority of patients.³⁰⁰

Congenitally Corrected Transposition of the Great Arteries

Congenitally corrected TGA is characterized by AV and ventriculoarterial discordance. From a circulatory oxygenation standpoint, these patients are “congenitally corrected,” essentially “two wrongs make a right,” and the pulmonary and systemic circulations run in series, not in parallel, as with dextro-TGA. There is ventricular inversion, and the respective AV valves follow the ventricles. Therefore, the systemic RV is transposed to the left, and the tricuspid valve goes with it. The left atrium empties into the RV, which then pumps to the leftward and usually anterior aorta (Fig. 56–23). The LV and mitral valve are dextraposed, and the pulmonary artery emerges posteriorly from the LV. Fewer than 10% of patients are free of associated abnormalities, which include VSD (membranous or muscular) in up to 80%, pulmonic stenosis (valvar or subvalvar) in up to 70%, and tricuspid valve abnormalities (usually Ebstein anomaly) in 33%.³⁰²

Natural History

In the minority of patients without associated defects, unoperated survival into adulthood is common, and survival into the eighth and ninth decades of life has been reported.³⁰² Most patients remain undiagnosed until early adulthood. However, these patients have an increased incidence of AV conduction problems and complete heart block with age.³⁰³ Complete heart block may be present from birth (in ~10%) and has been reported to develop in 2% of patients per year.³⁰⁴ Systemic morphologic RV dysfunction and congestive heart failure occur in more than 50% of patients with associated lesions by the time they are 45 years of age.³⁰³ Ebstein anomaly of the systemic AV valve is common, and regurgitation occurs in over 80% of adults with congenitally corrected TGA. Pulmonary morphologic LV dysfunction occurs less often, but may be present in up to 20% of patients. Aortic regurgitation of some degree is present in 25% of adults, but seldom requires surgical intervention.

Management and Results

Systemic AV (tricuspid) valve regurgitation is a common and progressive problem in these patients that can lead to morphologic RV dilatation and dysfunction if the valve is not replaced.^288,305 Early surgical intervention in patients with more than mild tricuspid regurgitation, to prevent systemic ventricular dysfunction, is warranted and is associated with improved intermediate- and long-term outcomes. Patients with a combination of pulmonic stenosis and VSD may be cyanotic because of the right-to-left shunt at the ventricular level. Surgical repair in these patients consists of VSD closure and pulmonary valvotomy or replacement, frequently accompanied by subinfundibular muscle bundle resection. Alternative surgical strategies involving the “double-switch” operation have been described. This surgery involves a Mustard- or Senning-type atrial redirection along with a Jatene-style great arterial switch, thus leaving the patient with a systemic LV after this complex surgery.³⁰⁶ Patients with pulmonic stenosis or atresia and a VSD may undergo a modification of the double-switch operation by baffling of morphologic LV outflow through the VSD to the leftward and anterior aorta and placement of a conduit from the morphologic RV to the pulmonary artery.³⁰⁷ Long-term follow-up after these surgical interventions is limited. Pacemaker placement is indicated for patients with Mobitz type II or complete heart block.

Ebstein Anomaly of the Tricuspid Valve

Ebstein anomaly is characterized by apical displacement of the septal (and often the posterior) leaflet of the tricuspid valve into the RV cavity (Fig. 56–24). The RV is therefore divided into a proximal “atrialized” portion and a distal “functional” portion. The effective volume of the functional RV is often small.³⁰⁸ The anterior leaflet is usually excessively long and may have attachments to the RV free wall. The “atrialized” portion of the RV is usually thin because of a congenital absence of myocardium. The effective right atrium (including the atrialized portion of the RV) is invariably large and becomes more so in the presence of tricuspid regurgitation, which is a very common occurrence. An ASD or patent foramen ovale is present in more than one-third of cases. Other associated lesions are far less common and may include pulmonary stenosis, VSD, and PDA. Ebstein anomaly is commonly found in patients with congenitally corrected TGA (see earlier discussion).

Natural History

The clinical spectrum is variable and is heavily dependent on the severity of the deformity and the presence of associated defects. Patients presenting in infancy represent the worst end of the spectrum, with severe tricuspid regurgitation and a high incidence of associated abnormalities such as pulmonary stenosis or atresia.^309,310 Patients surviving into adulthood without surgical valve repair or replacement may develop a variety of signs and symptoms, including cyanosis (because of right-to-left shunting across an ASD or patent foramen ovale), dyspnea and fatigue (as a result of decreased preload and cardiac output), or palpitations. In adolescents and adults, palpitations secondary to atrial arrhythmia are the most common clinical presentation. Ebstein anomaly is often associated with ventricular pre-excitation, which may involve more than one accessory pathway that may be endocardial or epicardial in location and often is challenging to map and ablate from an intravascular approach. Up to 20% of unoperated patients may die from heart failure, and approximately 5% may die suddenly, presumably from atrial or ventricular arrhythmias.³¹¹ Heart failure results from RV dysfunction and tricuspid regurgitation, and may be exacerbated by LV fibrosis and dysfunction.

Management and Results

There are numerous variations on the surgical management of Ebstein anomaly.³¹² Most surgical approaches consist of some form of repair (or replacement if repair is not feasible) of the tricuspid valve, often accompanied by atrial or atrialized ventricle plication, and closure of an interatrial communication.^313,314 Eventual reoperation for recurrent tricuspid regurgitation after tricuspid valve repair is expected, and a tricuspid valve replacement is typically undertaken after failure of a repaired valve. With recent advancements in transcatheter valve replacement, valve repair with an annular ring or valve replacement is an increasingly attractive option in adults.^315,316 Valve repair may not be feasible in the most severe forms of Ebstein anomaly in which the long anterior leaflet of the tricuspid valve is adherent to the RV endocardium and there is almost complete atrialization of the RV; valve replacement is a good option in this subset of patients. The results of surgery in patients with poor RV function can be improved considerably if the RV is unloaded by a concomitant cavopulmonary (Glenn) shunt, also known as the one-and-a-half ventricle repair.^312,317 Furthermore, in the most severe cases with near complete absence of a functioning RV, a univentricular repair leading to a Fontan palliation may be necessary.^318,319 Intraoperative radiofrequency ablation or cryoablation (modified maze) and division of accessory pathways that are usually located in the posteroseptal or RV free wall are recommended at the time of valve repair or replacement.³²⁰ Overall surgical mortality was 13% in a multicenter analysis, with young age at the time of operation as the only multivariate risk factor.³¹² The long-term survival and functional capacity of operated patients are very good.³²¹

As patients with CHD make the transition from adolescence to adulthood, it is imperative that they come to understand the nature and implications of their heart problem and what interventions must and may need to be performed. Appropriate advice and guidance should be available regarding employment, insurance, socialization, contraception, and exercise.

Employment

The majority of operated and unoperated patients can be and are gainfully employed. Patients with simple forms of CHD, such as isolated VSD, pulmonary stenosis, or aortic valve stenosis, often achieve higher levels of education then the national standards.³²² A cross-sectional study from Holland, in which CHD patients were asked to complete a questionnaire focusing on employment issues, demonstrated that adults with complex CHD have reduced job participation compared with patients with mild CHD (59% vs 76% employed).³²³ Many receive disability benefits or experience career problems or job handicaps. Career counseling focusing on physical abilities and level of education may help increase appropriate employment in this population. Adults with CHD are at a disadvantage when applying for employment because of the tendency of some employers to consider the potential for future deterioration of an applicant with a “known heart problem.” In the United States, the National Rehabilitation Act of 1973 obliges employers to consider only the present capacity of a prospective employee to perform a given job.

Restrictions for employment do exist for certain jobs in which the safety of others is the direct responsibility of the patient with CHD. The clearest example of this is commercial airline pilots. It is the task of CHD specialists to estimate the risk of acute disability or sudden cardiac death in such patients. Low-risk rates are defined in only a small subset of patients with CHD.³²⁴

Insurance

Adults with CHD are significantly more likely to have difficulty obtaining life insurance.³²⁵ Refusal rates appear to be independent of the type or severity of CHD, suggesting that the label of CHD has a negative impact by itself. This problem is compounded by the limited long-term survival data for specific CHD subtypes. An article by Vonder Muhll et al³²⁶ discusses the scope of this problem and provides a summary of mortality data and predictors of adverse outcomes in various subsets of CHD along with practical tips for patients and physicians to assist with the insurance application process.³²⁶ In general, insurance policies are restrictive, and patients with CHD are frequently insured at higher rates or not insured at all.³²⁷ As a result, the patient must seek to obtain a new policy, which often excludes benefits for medical or surgical treatment of the congenital cardiovascular condition. In 2010, a health care bill was passed by the Congress of the United States that included extension of parental coverage until 26 years of age, expanded the government insurance programs for low-income individuals, and prohibited insurers from refusing to insure patients as a result of pre-existing conditions.

Despite a call for near universal health care coverage, it remains unclear how such an initiative will be funded at the federal and state level. In a pilot study by Moons et al³²⁸ and in a subsequent study by Mackie et al,³²⁹ patients with CHD, particularly severe CHD, incurred considerably higher expenses than age- and gender-matched control subjects. Further data are clearly needed to predict the potential health care expenditure in various subsets of patients with CHD.

Psychosocial Development

Most adults with CHD appear well adjusted. Utens et al³³⁰ assessed the occurrence of a wide range of behavioral and emotional problems in 166 young adults long term after surgical correction compared with age-matched control subjects using the Young Adult Self-Report.³³⁰ On most Young Adult Self-Report scales, no differences were found between the mean problem scores of the CHD patients and control subjects, except for small differences in two scales (Somatic Complaints and Strange). No significant relationship was found between cardiac diagnosis and problem behaviors in CHD adults. Moreover, no relationship was found between IQ scores and problem behaviors. Psychosocial problems can occur in patients with CHD, manifesting in excessive psychologic stress that is unrelated to the clinical severity of the original cardiac defect.³³¹ In a study by Ternestedt et al,³³² two cohorts of patients operated on before the age of 15 years, one for TOF and the other for ASD, were queried 20 and 30 years after surgical repair regarding quality of life. There was no connection between quality of life and functional capacity. Interestingly, fewer patients in the TOF than in the ASD group considered that their lives were affected by their heart disease. Therefore, multiple questionnaire-based studies have demonstrated that the severity of the heart disease is not necessarily congruent with estimated quality of life, suggesting that patients develop coping strategies during childhood and adolescence.

Although most patients with CHD appear well adjusted, many have the feeling that they are different from their peers and experience isolation and low self-esteem, feelings that are compounded by exercise limitations, surgical scars, and parental overprotection. These factors, when added to the challenges of adolescence and young adulthood, can adversely affect psychosocial development. A number of large longitudinal series of patients with repaired TOF have demonstrated that suicide is a common cause of late death, ranging in frequency from 4.8% to 10%.^333,334,335 Psychosocial anxiety and neurotic behavior may be avoided by early repair in childhood.³³⁶ Anxieties about sexuality, relationships, and reproduction are common and often prove difficult to adequately discuss with the physician in a busy clinic setting; such issues are more thoroughly dealt with by a multispecialty team that may include a psychologist, social worker, and nurse practitioner. Psychological support should be considered as one of the most important aspects in the long-term care of patients with CHD.

The impact of CHD on intellectual development appears more dependent on lesion type and severity than are psychosocial issues. Studies of intellectual development and capacity mostly exclude patients with genetic syndromes or overt neurologic defects. Cyanosis is associated with mild intellectual impairment; however, it is unclear that early repair of cyanotic lesions such as TOF results in improved intellectual function.^337,338 Neurodevelopmental outcomes in patients with single-ventricle physiology who have undergone the Fontan operation are in the normal range, but performance on examinations of IQ are lower than the general population.³³⁹

Contraception

Advice regarding contraception should be available to adolescent and adult patients with CHD.³⁴⁰ Unfortunately, contraceptive advice to patients with CHD is often inadequate or incorrect.^340,341 Cardiologists are often reluctant to discuss issues of contraception, partly because this is an area that is often outside their realm of expertise. When giving family planning advice to patients with CHD, it is important to review the risk of pregnancy for women, risk of CHD in the fetus, and risks and benefits of different modes of contraception for the individual patient. Therefore, understanding the normal physiology of pregnancy and its impact on various CHD subtypes is essential (refer to the section on pregnancy). Contraceptive advice should be tailored to the individual patient in terms of his or her medical, social, and educational conditions. Surgical tubal ligation and hysteroscopic tubal coil occlusion are highly effective and permanent forms of contraception that are reserved for women who are at very high risk of adverse events with pregnancy, such as those with Eisenmenger syndrome. Traditional laparoscopic sterilization requires general anesthesia, placing cyanotic patients at significant risk for operative mortality.⁴⁷ However, hysteroscopic coil occlusion of the fallopian tubes may be performed under local anesthesia in the office setting or under moderate sedation, avoiding the anesthesia risks associated with laparoscopic procedures.

For women in long-term monogamous relationships, vasectomy for the male partner is also effective in preventing pregnancy. Hormonal contraception with low-dose estrogen is generally safe and effective³⁴²; however, in a minority of patients, exacerbation of systemic hypertension may occur with such formulations.³⁴³ Combined estrogen and progesterone formulations have a lower contraceptive efficacy and carry a well-documented risk of thromboembolic complications; they are best avoided in patients with previous thromboembolic events, those at high risk of thromboembolic events (eg, patients with Fontan connection and sluggish venous flow), and those who would tolerate thromboembolism poorly.^344,345 They are also inappropriate for patients with congestive heart failure because of the tendency for fluid retention. Barrier methods, such as diaphragms or condoms, are generally safe and effective, but can only be relied upon in the most motivated patients; even then, there is a risk of contraceptive failure. Intrauterine contraceptive devices are effective, but they are associated with an increased risk of pelvic inflammatory disease. This is worrisome in patients with CHD because of the potential risk of infective endocarditis, although the actual occurrence of endocarditis in this setting is exceedingly rare.^346,347

Exercise and Sports

The physical and mental benefits of exercise are well established.^348,349 Participation in sports is also important for the normal socialization of children and adolescents. However, unoperated and operated patients with CHD often have diminished exercise capacity (see Fig. 56–4).³² Reduced exercise capacity may reflect both the limitations set upon the individual by the underlying cardiovascular condition and the deconditioning that occurs from adopting a sedentary lifestyle. Inappropriate avoidance of exercise is often reinforced by protective parents or recommended by physicians who are unsure of the cardiovascular risk associated with a specific condition and choose to err on the side of short-term caution.³⁵⁰ The long-term cost of this approach is that many patients with CHD do not reap the immense benefits of exercise.

The 36th Bethesda Conference focused on issues concerning exercise in patients with cardiovascular disease and provided exercise recommendations for this population.³⁵¹ In some patients with simple repaired CHD (eg, ligated PDA), exercise capacity is normal, and the risk of exercise is minimal. On the other extreme are patients with pulmonary vascular disease and cyanosis in whom exercise capacity is severely limited. Exercise results in almost immediate worsening of hypoxemia because of the decrease in systemic arterial resistance and increased shunting of deoxygenated blood away from the pulmonary alveolar bed. These patients should be advised to avoid isometric exercise and confine themselves to mild isotonic exercise.³⁵¹ Between these extremes, the recommendations should take into account the individual patient’s underlying operated or unoperated cardiovascular defect, functional capacity, hemodynamic status, and form of exercise contemplated. Formal exercise testing can help delineate functional capacity. Walking protocols of 6 or 12 minutes can be used to determine the safety of submaximal exercise. Treadmill or bicycle protocols can determine the maximal exercise capacity, coronary artery ischemia, blood pressure response and, importantly, chronotropic response to exercise. Cardiopulmonary exercise testing adds incremental diagnostic and prognostic value, and is highly recommended in patients with CHD.³² Combining the exercise protocol with echocardiographic imaging is useful in determining ventricular function and valvar function and estimating pressure changes with exercise.