ACC/AHA 2008 Guidelines for the Management of Adults With Congenital Heart Disease

A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Develop Guidelines on the Management of Adults With Congenital Heart Disease) Developed in Collaboration With the American Society of Echocardiography, Heart Rhythm Society, International Society for Adult Congenital Heart Disease, Society for Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons

Class I

• 1. The focus of current healthcare access goals for ACHD patients should include the following:

  • a. Strengthening organization of and access to transition clinics for adolescents and young adults with CHD, including funding of allied healthcare providers to provide infrastructure comparable to that provided for children with CHD. (Level of Evidence: C)

  • b. Organization of outreach and education programs for patients, their families, and caregivers to recapture patients leaving pediatric supervisory care or who are lost to follow-up. Such programs can determine when and where further intervention is required. (Level of Evidence: C)

  • c. Enhanced education of adult cardiovascular specialists and pediatric cardiologists in the pathophysiology and management of ACHD patients. (Level of Evidence: C)

  • d. A liaison with regulatory agencies at the local, regional, state, and federal levels to create programs commensurate with the needs of this large cardiovascular population. (Level of Evidence: C)

• 2. Health care for ACHD patients should be coordinated by regional ACHD centers of excellence that would serve as a resource for the surrounding medical community, affected individuals, and their families (Table 2).⇓

  • a. Every academic adult cardiology/cardiac surgery center should have access to a regional ACHD center for consultation and referral. (Level of Evidence: C)

  • b. Each pediatric cardiology program should identify the ACHD center to which the transfer of patients can be made. (Level of Evidence: C)

  • c. All emergency care facilities should have an affiliation with a regional ACHD center. (Level of Evidence: C)

• 3. ACHD patients should carry a complete medical “passport” that outlines specifics of their past and current medical history, as well as contact information for immediate access to data and counsel from local and regional centers of excellence. (Level of Evidence: C)

• 4. Care of some ACHD patients is complicated by additional special needs, including but not restricted to intellectual incapacities or psychosocial limitations that necessitate the inclusion of designated healthcare guardians in all medical decision making. (Level of Evidence: C)

• 5. Every ACHD patient should have a primary care physician. To ensure and improve communication, current clinical records should be on file with the primary care physician and a local cardiovascular specialist, as well as at a regional ACHD center; patients should also have copies of relevant records. (Level of Evidence: C)

• 6. Every cardiovascular family caregiver should have a referral relationship with a regional ACHD center so that all patients have geographically accessible care. (Level of Evidence: C)

The need for delivery of appropriate healthcare to ACHD patients largely remains unmet. The 32nd Bethesda Conference report in 2000 recommended organizing ACHD care within a regional and national system of specialized adult CHD centers of excellence that would disseminate care, provide education, orchestrate research and innovation, and serve as a general resource for the region within this model (3) (Table 2). Such a system has been demonstrated to improve care for adults with similar chronic severe illness, such as severe heart failure, for which measures of improvement surrounding uniformity of care within a guidelines framework, medical and surgical outcomes, decreased visits, improved patient quality of life, cost containment, data collection and knowledge dissemination, trials of new therapeutics, and enhanced insurability have been achieved.

A detailed integration of caregivers and support was suggested by the 32nd Bethesda Conference, from primary care to patient advocacy groups to the highest levels of subspecialty resources. The pediatric cardiology team should be paired with adult cardiologists to facilitate transition of care for affected individuals. It was recommended that all ACHD patients have a provider who constitutes the medical “home,” as well as at least 1 overreaching visit with a cardiologist with advanced training and experience with ACHD patients (4). A pattern of visits, follow-up, surgical care, subspecialty (catheterization, electrophysiology) cardiac and noncardiac care, emergent medical access, data coordination and dissemination, referral guidance, and education (with recognized regional variation) was suggested for ACHD patients and their caregivers based on the degree of medical complexity. Improvement in patient outcome was stressed via extension of physician caregiving by team-based clinical care associates (midlevel practitioners) with expertise in the management of ACHD patients.

The 32nd Bethesda Conference described 3 levels of training of adult cardiovascular specialists in terms of experience in ACHD (5). Task Force 9 covered training in the care of adult patients with CHD and differentiated 3 levels of training and expected expertise. These levels were subsequently incorporated into the COCATS (Core Cardiology Training Symposium) III document (6). Level 1 training consists of basic exposure to CHD patients and organized educational material on CHD. To enable proper recognition of the problems of adults with CHD and to be cognizant of when specialized referral is needed, all medical cardiology fellows should achieve level 1 training in CHD. Level 1 trainees should be instructed by a faculty member with level 2 or 3 training or its equivalent. A pediatric cardiologist should also be involved in these training programs.

Level 2 training represents additional training for fellows who plan to care for adult patients with CHD so that they may acquire expertise in the clinical evaluation and management of such patients. Level 2 training generally requires 1 year of training in ACHD: either a 1-year formal program at a regional or tertiary care ACHD center or cumulative experience of 12 months through repetitive rotations or electives as a cardiology fellow with experienced ACHD cardiologists. This training should prepare the individual to be well-equipped for the routine care of even moderate to complex ACHD and to recognize when more advanced consultation or referral is advisable.

Level 3 training represents the level of knowledge needed by those graduates who wish to make a clinical and academic/research commitment to this field and not only become competent in the care of the entire spectrum of adult patients with CHD but also participate in the teaching and research of ACHD. Level 3 trainees generally require 2 years of training. These 24 months may either be consecutive or cumulative experience, and some recognition can be given to overall experience in CHD, be it pediatric, adolescent, or adult (eg, prior pediatric cardiology training or rotations). Such level 3 training would be sufficient to clinically manage the most complex ACHD patient in a regional or tertiary care center, to pursue an academic career, to train others in the field, or to direct an ACHD center program (6).

The 32nd Bethesda Conference report in 2000 highlighted the need for healthcare professionals, patients, and their families, together with regulatory agency representatives, to develop a strategic plan for organized advocacy for ACHD patients (3,4). This ACC/AHA Guideline Committee, working in parallel with but independently of a workgroup of the National Heart, Lung, and Blood Institute charged with recommending key research opportunities in ACHD patients, recognizes key actions that are currently and urgently required to improve care access for ACHD patients.

1.5.1. Recommendations for Access to Care

1.5.2. Recommendations for Psychosocial Issues

1.5.3. Transition of Care

Physical and emotional maturity is the primary requirement for transfer of adolescent or young adult patients into adult care environments. The age at which this occurs varies and may range from the mid-teens to the mid-20s, depending on the patient. However, the process of transitioning, that is, preparing young patients for successful transfer to an adult healthcare provider at a later time, should begin by the age of 12 years (43).

Strategies for transfer of patients with CHD into adult care settings are well described (44,45) and use a stepwise approach to establishing autonomy and understanding one's cardiac problem and lifestyle issues important to long-term stability of CHD. Pediatric clinicians can reinforce autonomy by focusing their communication on the patient, so that the teen years serve as an ongoing “workshop” in which the ultimate goal is accepting ownership of and responsibility for one's cardiac disease. Parents should take an active role in fostering independence in their teenagers. The use of support groups and educational meetings geared toward parents and ACHD patients offers a prime opportunity for parents to discuss their fears and openly communicate reality-based strategies for approaching difficult topics with their children. National support organizations for CHD and ACHD patients now exist and provide resources for families (eg, the Congenital Heart Information Network and the Adult Congenital Heart Association). Regional tertiary centers for the care of ACHD patients may also provide conferences that serve this purpose. Some centers provide transitional support meetings so that adolescents and parents can familiarize themselves with the goals of ACHD care. Despite the availability of structured resources for parents, patients, and families with CHD, the ultimate responsibility still rests with clinicians to meet the educational needs of their young patients. Topics that should be discussed early in childhood and repeatedly through the teens, 20s, and beyond include a description of the cardiac defect and surgeries (including use of diagrams); medications; exercise prescription; risk modification; health maintenance and follow-up recommendations; vocational and educational recommendations; insurance information; and information about genetics, contraception, and pregnancy. This information should be given in verbal and written form and provided to the patient in an electronic or paper format (45,46). This is a reference tool that can be a constant resource for the patient long term and can assist healthcare providers who are not familiar with the patient. The use of advanced practice nurses and physician assistants in pediatric and ACHD settings optimizes the facilitation of the transition process from pediatrics to adult cardiology, identification of patient needs, screening and referral for psychosocial problems, and education and counseling of patients and families (47).

Pertinent medical records, including diagrams of cardiac defects and operations, operative and procedural reports, recent physical examination, electrocardiograms (ECGs), and echocardiograms, should be provided to all cardiologists involved in the care of a patient with CHD. In addition, once patients are properly educated and aware of basic terminology pertaining to their own cardiac status, they should be offered copies of their medical reports, which implies and imparts responsibility and autonomy regarding their condition.

1.5.4. Exercise and Athletics

Exercise restrictions correlate with internalization of fear in young people with CHD (48). The ability to exercise is a fundamental measure of quality of life, perceived capacity for social acceptance, employment, sexual relations, and procreation. Young people with CHD may experience exercise limitations for many reasons, including their underlying cardiac reserve, physical deconditioning, and lack of exercise experience in childhood; poor coordination related to coexisting disabilities; misperceptions about restrictions; lack of interest; and anxiety (43,44). Current symptoms only account for approximately 30% of all barriers to exercise. Recommendations regarding physical training, exercise, and athletics are core to the comprehensive patient education that should begin by early adolescence. An individual exercise prescription (one that accounts for physical limitations, developmental challenges, risk modification, health concerns such as obesity, and personal preferences) needs to be provided and updated regularly so that the beneficial utility of exercise is not lost among a list of restrictions. Guidelines for physical activity and exercise in patients with CHD are outlined in the 36th Bethesda Conference in “Eligibility: Recommendations for Competitive Athletes with Cardiovascular Abnormalities.” (49) Currently, however, there are few data concerning activity guidelines for the nonathlete.

The finding of diminished aerobic capacity in all groups with CHD (50–58) validates the importance of comparative testing over time in patients until reference values can be researched further (54). However, improved oxygen uptake during exercise is only 1 parameter of the effect of training and cannot be used alone to determine whether the main goals of exercise have been achieved (59). Beyond improved oxygen consumption and tolerance of physical activity, physical training of children and adolescents can also result in decreased withdrawal and somatic complaints (60,61). This supports the need for organized exercise programs for young people with CHD, particularly adolescents who view physical activity as the defining focus of a healthy lifestyle despite restrictions from competitive athletics.

1.5.5. Employment

Entering the job market and establishing a career is arguably the most important developmental milestone of a young adult's life (30). Careful consideration of the individual's physical, mental, and psychological disposition will help in identifying the right career choice. This is a discussion that should include the cardiologist, so that realistic limitations are explored and misconceptions eliminated. Vocational planning should take place early in adolescence so that appropriate educational options can be pursued long before the patient enters the work force. Ideally, cognitive evaluation should be performed at or before 5 years of age so that the appropriate educational track can be determined. Early childhood intervention has been shown to result in improved employment status during adult life (62). The goal of clinicians caring for those with CHD should be to view every patient as employable and avoid the temptation to accept the status quo when a patient is receiving social security disability income or other disability assistance through Medicaid or Medicare. Governmental assistance programs may perpetuate long-term disability for those fearful of losing their health insurance coverage (63). Reports from more than a decade ago projected that approximately 10% of ACHD patients would be totally disabled (64). Furthermore, 8% to 13% of ACHD patients were receiving public assistance or living as a dependent with relatives (64,65). Important legislation has focused on bringing individuals with disabilities into the work force. Ultimately, with improving longevity in patients with CHD and better surgical outcomes, the proportion of physically disabled ACHD patients is expected to decrease.

Seeking assistance from the state employment development department (the names of these programs vary from state to state) can be an important step in finding jobs for adults with disabilities. These programs offer job and training referrals, counseling, and job search assistance and workshops. Federal programs provide for vocational rehabilitation for disabled individuals, as well as hiring and placement into jobs appropriate for their level of disability.

The Americans With Disabilities Act of 1990 prohibits discrimination with respect to hiring, promotion, or termination of employees on the basis of disability. Therefore, ACHD patients are not required to disclose their cardiac condition to a prospective employer unless physical restrictions imposed by their cardiac disease would limit their ability to satisfy the job description (63). The Family and Medical Leave Act of 1993 states that covered employers must grant eligible employees up to a total of 12 workweeks of unpaid leave during any 12-month period when the employee is unable to work because of a serious health condition or to take care of an immediate family member with a serious health condition (66).

The Work Incentives Improvement Act of 1999 (also known as the Medicaid Buy-In Program) is designed to promote employment and economic self-sufficiency for individuals with disabilities. Under this federal legislation, states can amend their Medicaid programs to enable individuals with disabilities to obtain coverage under Medicaid while giving incentives for these individuals to seek and maintain employment. Advocates in each ACC and AHA chapter should work with state Medicaid programs and state legislators to define appropriate health disabilities eligible for coverage (10).

1.5.6. Insurability

In the 1990s, studies indicated that up to 20% of ACHD patients were uninsured and that most health insurance policies were individual plans rather than group policies. The heterogeneity of CHD over the life span contributes to the difficulties faced by insurers when assigning risk. Regional tertiary centers specializing in the care of ACHD patients must collaborate in multicenter studies to define and publish survival data in a format amenable to life-table analysis (67). In addition, the use of clinical practice guidelines, such as those outlined in this ACC/AHA document, will further direct insurers, primary care providers, and cardiologists on the appropriate use of diagnostic testing, as well as the appropriate time for referral.

Today, the most affordable way to obtain health insurance is via a group policy, through one's employer, or with health management organizations. With national attention now focused on the need for regional tertiary care for patients with complex CHD, health maintenance organizations are being held accountable for finding appropriate specialized care for ACHD patients. Patients, with their physician's support, need to be their own advocates within the health maintenance organization system and demand referrals if they believe their cardiologist is ill equipped to manage their complex cardiac care. National patient support organizations such as the Adult Congenital Heart Association have made it their mission to educate adults via newsletters, the Internet, and the like about the need for specialized cardiac care in ACHD patients with moderate to severe disease, and they provide an extensive referral network of ACHD specialists.

Currently, at least 30 states offer high-risk health insurance plans through “risk pools.” This provides a safety net for individuals who are denied health insurance because of a preexisting medical condition. More than 250 000 enrollees have been able to obtain comprehensive health insurance protection via these risk pools since the first pools were started in 1976. Risk pools are state created, are nonprofit, and usually do not require tax dollars for operational purposes. Eligible individuals must prove state residency and prove they have been rejected for similar health insurance with similar premiums by at least 1 insurer. Healthcare providers caring for ACHD patients should be aware of options available in their state. Healthcare providers need to give accurate health information to insurers in a prompt fashion so that a fair evaluation of the patient's risk status can be made.

Health and life insurance can be elusive to ACHD patients. Regardless of severity, ACHD patients face a significantly higher risk of being denied life insurance than their peers without CHD (10,40,68). Recent studies found that more than one third of ACHD patients were refused life insurance compared with 4% of age-matched peers without CHD, with no regard to severity of defect (40). A useful resource for state-by-state consumer guidelines about getting and keeping health insurance can be accessed via the Internet at www.healthinsuranceinfo.net.

1.5.7. Congenital Syndromes

Congenital syndromes, including coexisting neurological and cognitive deficits, can further complicate the psychological and social adjustment of ACHD patients. Approximately 18% of congenital heart defects are associated with a congenital syndrome or chromosomal abnormality (69). Among chromosomal abnormalities in infants with cardiovascular defects, 81% are Down syndrome, which has a CHD prevalence of 40%. Adults with Down syndrome represent a growing number of the patients seen in tertiary ACHD clinics and require careful attention to coexisting diseases and special care issues. Hypothyroidism, leukemia, Alzheimer's disease, depression, atlantoaxial subluxation, obesity, and sleep apnea are common in Down syndrome, and regular screening for these ailments should be performed. Often, sedation or general anesthesia is necessary for routine procedures, such as dental cleaning, Pap smears, or prolonged diagnostic procedures that require immobility. The risks of anesthesia and procedures need to be carefully reviewed by CHD specialists and discussed with the patient.

Approximately 15% of patients with tetralogy of Fallot and other conotruncal defects have chromosome 22q11.2 deletion, most commonly manifested as DiGeorge syndrome but also presenting as velocardiofacial (Shprintzen) syndrome and conotruncal anomaly face (Takao) syndrome (70). Patients with a history of type B interrupted aortic arch or truncus arteriosus also have a high incidence of DiGeorge syndrome. Many patients with this chromosome deletion show impairment in social function. Coexisting diseases associated with these overlapping syndromes include schizophrenia, mental disability, deafness, immune deficiencies, endocrinopathies, and clubbed foot (70).

Williams syndrome is a developmental disorder that involves connective tissue, the central nervous system, and supravalvular AS (SupraAS); it has been associated with a chromosome deletion in band 7q11.23 (70). Most Williams syndrome patients have a lack of social inhibition and some degree of mental disability that complicates planning and self-management. Adults with other syndromes, including Noonan and Turner syndromes, have varying degrees of cognitive deficits. Patients with Turner syndrome have a variety of noncardiovascular problems, including ovarian and thyroid disorders, inflammatory bowel disease, pigmented and melanotic nevi, and sensorineural deficits.

Because the cardiologist may be the only regular healthcare provider for adults who have congenital syndromes and chromosomal abnormalities in association with their CHD, careful screening and appropriate referrals (such as endocrinology, genetic counseling, psychiatry, and vocational rehabilitation) should take place. Because of the multiplicity of comorbidities and the potential for impact on cardiovascular management, there should be clarity about which healthcare provider is serving as the medical “home.” Whenever possible, the ACHD specialist should work closely with a primary physician who accepts this responsibility. Although many of these patients are dependent on others for long-term care, some are able to live independently and require sensitive counseling regarding healthcare maintenance and risks. Advice regarding sexual activity and contraception is essential, even if the patient does not request it. Genetic counseling should be offered to all patients.

1.5.8. Medical/Ethical/Legal Issues

Some ACHD patients, especially those with associated syndromes, may be incapable of providing informed consent to the degree that meets ethical and legal standards of understanding their situation, understanding the risks associated with the decision at hand, and communicating a decision based on that understanding. Adults who may require a legal surrogate to facilitate informed consent are those who are cognitively impaired, such as those with Down syndrome, and those with impaired consciousness due to severe illness. If an adult's mental competency is in question, and no appointed adult surrogate is available, a psychological evaluation should be requested (63). The issue of legal guardianship in adults with significant mental disability becomes an ethical and legal challenge when 1 or both parents die or become incapacitated by illness with no accommodation for transfer of guardianship. Guidance in addressing these issues should be included as part of the transition education and reinforced thereafter.

Advance directives can assist family members and healthcare providers in understanding a patient's wishes if they are incapable of speaking for themselves (71). All ACHD patients should be encouraged to complete an advance directive, ideally at a time during which they are not morbidly ill or hospitalized, so that they can express their wishes in a less stressful setting.

Class I

• 1. ACHD patients must be informed of their potential risk for IE and should be provided with the AHA information card with instructions for prophylaxis. (Level of Evidence: B)

• 2. When patients with ACHD present with an unexplained febrile illness and potential IE, blood cultures should be drawn before antibiotic treatment is initiated to avoid delay in diagnosis due to “culture-negative” IE. (Level of Evidence: B)

• 3. Transthoracic echocardiography (TTE) should be performed when the diagnosis of native-valve IE is suspected. (Level of Evidence: B)

• 4. Transesophageal echocardiography (TEE) is indicated if TTE windows are inadequate or equivocal, in the presence of a prosthetic valve or material or surgically constructed shunt, in the presence of complex congenital cardiovascular anatomy, or to define possible complications of endocarditis (eg, sepsis, abscess, valvular destruction or dehiscence, embolism, or hemodynamic instability). (72) (Level of Evidence: B)

• 5. ACHD patients with evidence of IE should have early consultation with a surgeon with experience in ACHD because of the potential for rapid deterioration and concern about possible infection of prosthetic material. (Level of Evidence: C)

Class IIa

• 1. Antibiotic prophylaxis before dental procedures that involve manipulation of gingival tissue or the periapical region of teeth or perforation of the oral mucosa is reasonable in patients with CHD with the highest risk for adverse outcome from IE, including those with the following indications:

  • a. Prosthetic cardiac valve or prosthetic material used for cardiac valve repair. (Level of Evidence: B)

  • b. Previous IE. (Level of Evidence: B)

  • c. Unrepaired and palliated cyanotic CHD, including surgically constructed palliative shunts and conduits. (Level of Evidence: B)

  • d. Completely repaired CHD with prosthetic materials, whether placed by surgery or by catheter intervention, during the first 6 months after the procedure. (Level of Evidence: B)

  • e. Repaired CHD with residual defects at the site or adjacent to the site of a prosthetic patch or prosthetic device that inhibits endothelialization. (Level of Evidence: B)

• 2. It is reasonable to consider antibiotic prophylaxis against IE before vaginal delivery at the time of membrane rupture in select patients with the highest risk of adverse outcomes. This includes patients with the following indications:

  • a. Prosthetic cardiac valve or prosthetic material used for cardiac valve repair. (Level of Evidence: C)

  • b. Unrepaired and palliated cyanotic CHD, including surgically constructed palliative shunts and conduits. (Level of Evidence: C)

Class III

• 1. Prophylaxis against IE is not recommended for nondental procedures (such as esophagogastroduodenoscopy or colonoscopy) in the absence of active infection. (Level of Evidence: C)

The clinical setting and presentation of endocarditis have changed over the last 50 years, in part owing to technical advances (eg, cardiac surgery, hemodialysis), the use of prosthetic devices and indwelling lines, the increasing prevalence of intravenous drug abuse, the emergence of resistant organisms, and the continued development of increasingly potent antibiotics (73–78). True surgical cures of congenital cardiovascular disorders are infrequent, and almost all patients who have undergone surgery are left with some form of residua or sequelae, many of which predispose to IE (73,74,77–82).

Epidemiological studies of IE have reported underlying CHD in 11% to 13% of cases (83,84). Li and Somerville reported that IE accounted for 4% of admissions to a specialized adult congenital heart service (85). Including pediatric data, certain unoperated and operated cardiac lesions may be more susceptible to infection (Table 6). Tetralogy of Fallot, TGA, unrepaired ventricular septal defect (VSD), patent ductus arteriosus (PDA), and bicuspid aortic valves (BAVs) with aortic valve stenosis or aortic regurgitation (AR) are susceptible to IE.(73,74,79,81,86–102) Patients who have had surgical palliation of CHD (eg, systemic–to–pulmonary artery shunts) or various types of reparative surgery (often requiring prosthetic materials or valves, conduit insertion, or conduit replacement) have major predisposing conditions for IE (74,79,81,103).

The Second Natural History Study of Congenital Heart Defects reported on the incidence of IE in young adults with aortic stenosis (AS), pulmonary stenosis (PS), and VSD (104). The incidence rate was nearly 35-fold the population-based rate; viridans streptococcus was the predominant organism. The stenotic pulmonary valve was rarely affected, with only 1 case in this series. For VSDs, the risk of IE before surgical closure was more than twice that for the surgically closed VSD. In addition, the presence of AR independently increased the risk of IE in patients with VSD, whether managed medically or surgically. Of those with a surgically repaired VSD who developed IE, at least 22% were known to have a residual VSD leak.

Li and Somerville (85) reported IE in the grown-up congenital heart population comprising 185 patients (214 episodes) during 2 periods, 1983 to 1993 and 1993 to 1996, divided into unoperated or palliated (group I) and operated definitive repair or valve repair/replacement (group II). They noted no IE in atrial septal defect (ASD), closed VSD, patent ductus, isolated PS, or unrepaired Ebstein's anomaly or after Fontan-type or Mustard operations. IE in group I was most commonly represented by VSD (24%), left ventricular outflow tract (LVOT) lesions (17%), and mitral valve disorders (13%) and in group II by LVOT lesions (35%), repaired tetralogy of Fallot (19%), and atrioventricular (AV) defects (14%). Of the 185 patients, 87 (47%) had a known predisposing event (dental procedure or sepsis in group I, 33%; cardiovascular surgery in group II, 50%). Diagnosis was delayed (from onset of symptoms to time of diagnosis) in group I by 60 days and in group II by 29 days.

Niwa et al in 2005 (105) reported IE in 170 pediatric and 69 adult patients from 1997 to 2001. They noted prior cardiac surgery in 199 patients with IE, 88 of whom had surgery for cyanotic cardiovascular malformations. IE was left-sided in 46% and right-sided in 51%; the most common organisms were streptococci (50%) and staphylococci (37%). Surgery during IE was needed in 26% for large vegetations (45%) and heart failure (29%). Complications were seen in 48.5%. Mortality was 8% for medical treatment alone and 11.1% for those who also required surgery. In 33.3% of patients, conditions and procedures associated with IE were identified that preceded IE; the most common were dental manipulation (37.2%) and cardiovascular surgery (25.6%), followed by pneumonia (14.1%). Of these cases, only 28.2% had received antibiotic prophylaxis.

Di Filippo et al reported in 2006 (106) on 153 episodes of IE in CHD diagnosed with the revised Duke criteria, showing an increasing rate with 81 episodes from 1966 to 1989 (3.5 per year) and 72 episodes from 1990 to 2001 (6 per year). During the second period, there were more adults (40% later versus 9% earlier). Of interest, CHD was known in 122 patients before IE but was unrecognized in 31. Of the 153 episodes of IE, 39 occurred in patients who had repaired lesions, 35 in patients who had palliation (usually complex disease), and 79 in patients who had unoperated CHD. Tetralogy of Fallot with IE decreased from 12% to 3%, and complex cyanotic disease increased from 14% to 28%; the proportion of aortic valve anomalies and small VSDs increased. Dental procedures as a presumed cause of IE were more common during the later period (33% versus 20% earlier), cutaneous infection rose to 17% (from 5% earlier), and postoperative infection appeared less frequently later (11%) than earlier (21%). The streptococcus group continued to represent the most prevalent organisms, followed by staphylococci. Their data emphasized that current targets of prevention of IE should include complex cyanotic lesions, lesions repaired with prosthetic material, and small VSDs.

The pathogenesis of IE in part requires damaged or traumatized endothelium and a portal of entry of bacteria into the bloodstream. Bacteria may bind to platelets in the blood pool and then be deposited at the site of vascular endothelial damage. The infective lesion usually occurs at the low-pressure end of a high-gradient lesion at the site of impact of a high-velocity jet. For example, vegetations in conjunction with aortic coarctation may occur in the downstream descending aorta. With aortic valve disease, not only may vegetations occur on the ventricular surface of the valve, but the regurgitant jet impacting on the mitral valve may cause secondary vegetation. Usual sites of vegetations with a restrictive VSD occur where the high-velocity left-to-right jet impacts on the right side of the heart (ie, tricuspid valve septal leaflet or mural RV endocardium). The consequences of the infective vegetation depend on the site or structure involved and the virulence of the organism. Valvular destruction with significant valvular regurgitation or fistulous connections can cause heart failure. Endarteritis (as with patent ductus and coarctation) can cause aneurysm formation with potential for rupture. Embolization of vegetative material can cause arterial obstruction (eg, stroke) and possible abscess formation, and right-sided embolization to the lung can mimic pneumonia. Immunologic reactions can trigger glomerulonephritis or vasculitis as a result of the deposition of circulating immune complexes in the small vessels in skin (Janeway lesion and Osler node) (75).

Many cases of clinically suspected IE are difficult to diagnose with certainty because of altered immune response, prior antibiotic exposure, or indolent organisms and in some patients with acute right-sided IE in whom the systemic and immune responses have not developed (73,75,76,80,81). Now widely accepted, Durack et al incorporated 2-dimensional echocardiography as a means of demonstration of vegetations (77,107). The Duke criteria defined 2 major criteria (positive blood culture with typical microorganisms and evidence of endocardial involvement, eg, a typical vegetation on an echocardiogram) and 6 minor criteria (ie, predisposition, fever, vascular phenomena, immunologic phenomena, suggestive microbiological evidence, and echocardiographic findings consistent with endocarditis but not meeting major echocardiographic criteria), with categories defined as definite, possible, and rejected (107). Echocardiography is crucial in the diagnosis of IE. In general, a TTE study is useful in confirming the presence of vegetation, but often, the sensitivity is too low to rule out its absence. If a TTE study is equivocal, or in the presence of a prosthetic valve or complex congenital cardiovascular anatomy in which transthoracic windows may be inadequate, TEE is indicated (73 to 79, 81, 108 to 112). TEE is particularly important in the search for IE in the adolescent and adult for evaluation of the thoracic aorta, ventricular outflow tracts, and valved conduits and for visualization of the entire ventricular septum. Given the complexity of many of the malformations and the wide array of surgical palliations and repairs, however, performance and interpretation of echocardiography must be done by those with expertise in the native and altered postoperative (109) anatomy (103,108,110–112).

A delay in diagnosis of IE carries the risk of significant morbidity and mortality. A high index of suspicion for IE in any patient with operated or unoperated CHD is a key to early diagnosis (74,78,79,81,103,113–115). Cardiac lesions and their relative risk of developing IE are listed in Table 7.

An antecedent event is identified in a minority of cases with IE (74,79). Awadallah et al identified predisposing events in 56%, with unprotected dental work, recent open heart surgery, and skin infections being the most common (116). Gersony et al found that an antecedent event could be identified in 32% of cases; these events included dental work, previous bacterial infection (ie, pharyngitis, sinusitis, enteritis, or pelvic inflammatory disease), and cardiac catheterization (101).

Additional issues more specific for patients with CHD and risk for IE may not be well recognized by many practitioners (72,74,78–80). Patients with unoperated cyanotic heart disease frequently have acne or have spongy, friable gums; appropriate care is necessary to diminish the risk of bacteremia. Epistaxis and hemoptysis are frequent in the cyanotic patient; nasal cautery may be a risk factor for IE. Nail biting is a problem, with the possibility of local infection being a focus for bacteremia. High-risk behaviors (eg, intravenous drug abuse, body piercing, or tattoos) not uncommon in adolescents and young adults in particular are well-known risk factors, especially for acute staphylococcal IE on the right side of the heart, and the patient should be informed of the risks of these activities. The use of intrauterine devices for female contraception is somewhat controversial because of concern about endocarditis, although the rate of infection is only approximately 1.4 times normal, provided that sexual relationships are monogamous. The AHA recommendations do not advise antibiotic prophylaxis for patients before genitourinary procedures, but because of the high risk for adverse outcome in patients with prosthetic cardiac valves and those with cyanotic CHD and the potential for infection in the setting of a complex vaginal delivery, this committee proposed that antibiotics might be considered in those high-risk patients at the time of membrane rupture (recognizing that proof of efficacy of prophylaxis is not available) (117).

In all cases of IE, cultures should be obtained to try to establish the causative organism before antibiotics are initiated (73,75,78,82,112). CHD patients who present with fever and potential IE should have blood cultures drawn before antibiotic therapy is initiated to avoid subsequent false-negative blood cultures (78,103,118). Recognizing that initial therapy is usually parenteral and usually intravenous, one should recall that cyanotic patients with right-to-left shunts have the possibility of “paradoxical” systemic embolization and, as such, risk of stroke. Air filters should be used on the line with meticulous attention to avoiding injection of air bubbles. Details of all aspects of medical and antimicrobial management of IE are beyond the scope of this review and are addressed by a separate AHA working group, as well as other authors (78,81,99,119,120). Collaboration with an infectious disease specialist is invaluable. Prompt referral of the adult patient with CHD to a specialized center is usually indicated because hemodynamic deterioration may be rapid, and surgical treatment of often complicated anatomy and/or reoperation may be required (78,82). Early consultation with a cardiac surgeon with experience treating adults with CHD is appropriate. Surgical intervention is considered in patients with uncontrolled congestive heart failure, continued emboli, medically uncontrolled infection, prosthetic material infection, and development of heart block (73,75,78,80,112–114,121). Management decisions regarding infected prosthetic valves or conduits in which the duration of preoperative antibiotic therapy must be balanced against the risk of reoperation must be made in collaboration with the surgeon. Ultimately, to reduce costs without risking efficacy, prolonged home parenteral antibiotics may be required after the initial inpatient hospitalization.

Prevention of IE includes nonchemotherapeutic and chemotherapeutic methods (74,75,78,80,81,103). Clinical judgment and discretion are required. It is always worthwhile to strive to provide evidence-based medical care. However, the Cochrane Collaboration did not provide evidence proving whether or not penicillin prophylaxis is effective protection against bacterial endocarditis in those with lesions considered at risk for development of IE and who were about to undergo an invasive dental procedure. They also noted that there is lack of evidence to support published guidelines in this area or to show whether the potential harm or cost of penicillin outweighs the benefit (122).

On the basis of a “revised” assessment regarding the risk of bacteremia-induced endocarditis, new guidelines for the prevention of endocarditis were published in 2006 by the Working Party of the British Society for Antimicrobial Chemotherapy (123). The 2006 guidelines recommend that antimicrobial prophylaxis for dental procedures be confined to those with (1) previous IE, (2) prosthetic cardiac valves, or (3) surgically constructed pulmonary shunts or conduits. In contrast, for bacteremic nondental procedures, the 2006 group expanded the “dental risk” list to also include (4) complex CHD (except not secundum ASD, which is presumably isolated and uncomplicated), (5) complex LVOT obstruction, including AS and BAVs, (6) acquired valvulopathy, and (7) mitral valve prolapse in the presence of echocardiographic “substantial leaflet pathology and regurgitation.” The British Society for Antimicrobial Chemotherapy justifies its decisions by shifting the emphasis from “procedure-related bacteremia” to “cumulative bacteremia.”

The 2007 AHA guidelines for the prevention of endocarditis have substantially changed the recommendations for antibiotic prophylaxis on the basis of a consensus of expert opinions (72). The new, simplified recommendations are based on the proposition that most bacteremia occurs during activities of daily living, that IE is more likely to result from long-term cumulative exposure to these daily random bacteremias than from procedural bacteremias, and that proof is lacking that prophylaxis prevents any (or at most a very small number) cases of IE. They posit that the risks of antibiotic adverse events in the patient (allergic reactions) and the emergence of resistant organisms exceed any proven benefit of antibiotic prophylaxis against IE.

The new AHA guidelines appropriately emphasize maintenance of oral health and hygiene to reduce daily bacteremia and underscore that this is more important than any dental antibiotic prophylaxis. Accordingly, the 2007 AHA writing committee for the updated guidelines on prevention of endocarditis concluded that antibiotic prophylaxis for dental procedures likely to induce procedural bacteremia (those that involve manipulation of gingival tissue or the periapical region of the teeth or perforation of the gingival mucosa) should be confined to cardiac conditions associated with the most significant adverse outcomes should IE develop (72). They included in this group those with previous IE; those with prosthetic cardiac valves or surgically constructed conduits or shunts; those with unrepaired cyanotic CHD or CHD repaired with prosthetic material or devices (until 6 months after the procedure); those with repaired CHD with residual defects at or adjacent to the site of a prosthetic patch or device; and cardiac transplant patients who develop valvulopathy. They specifically recommend no IE prophylaxis before gastrointestinal or genitourinary procedures, a major departure from previous guidelines. The new AHA guidelines have engendered some considerable controversy and may violate long-standing patient and provider expectations and practice. Concern has been expressed that changes in preexisting recommendations were not based on new data or randomized trials and that absence of proof of efficacy and safety cannot be used as proof of absence of efficacy and safety of antimicrobial prophylaxis (124). The present ACHD Guideline Committee understands that there may be reluctance to deviate from prior recommendations for patients with some forms of CHD. This reluctance may be especially true for patients with BAV or coarctation of the aorta. In select circumstances, the committee understands that some clinicians and some patients may still feel more comfortable continuing with IE prophylaxis. Accordingly, this committee recommends that healthcare providers discuss the rationale for these new changes with their patients, including the lack of scientific evidence demonstrating proven benefit for IE prophylaxis. In those settings, the clinician should determine that the risks associated with antibiotics are low before continuing a prophylaxis regimen. Over time, and with continuing education, the committee anticipates growing acceptance of the new guidelines among both provider and patient communities.

This ACHD writing committee proposes that the “high-risk” group in whom it is reasonable to give antibiotic prophylaxis before dental procedures would include the following: (1) those with a prosthetic cardiac valve; (2) those with prior IE; (3) those with unrepaired and palliated cyanotic CHD, including surgically constructed palliative shunts and conduits; (4) those with repaired CHD with prosthetic material or device, whether placed by surgery or by catheter intervention, during the first 6 months after the procedure; and (5) those with repaired CHD with residual defects at the site or adjacent to the site of a prosthetic patch or prosthetic device that inhibit endothelialization.

We emphasize that nonchemotherapeutic methods are particularly important in the adolescent or young adult patient with CHD, among whom nail biting, acne, and problems with dental health are common. Oral prevention starts with meticulous oral care and routine preventive care by a dentist or oral hygienist. A patient with cyanotic heart disease often has spongy, friable gums, and a soft-bristle toothbrush must be used. Female contraception should be planned with the risks and benefits of intrauterine devices kept in mind.

The patient's knowledge of the need for and the type of IE prophylaxis is also an important issue (77,103,125). Caldwell et al noted that fewer than 50% of families knew about endocarditis prevention or precautions, and even fewer understood why prophylaxis was considered indicated (91). Cetta and Warnes reported in 1995 from their specialized ACHD clinic that those with CHD had inadequate knowledge about their cardiac lesion, about IE, and about prophylaxis (125). With aggressive education in their clinic, patient knowledge improved, but they emphasized that educational efforts need to be reinforced regularly. A patient should be given a detailed explanation of his or her diagnosis and the rationale for IE prevention, and the patient's specific regimen for dental procedures should be provided. Information about the signs and symptoms of IE should also be provided. At every subsequent visit, it should again be verified that the patient knows what is required for dental care and prophylaxis (74).

Class I

• 1. Basic preoperative assessment for ACHD patients should include systemic arterial oximetry, an ECG, chest x-ray, TTE, and blood tests for full blood count and coagulation screen. (Level of Evidence: C)

• 2. It is recommended that when possible, the preoperative evaluation and surgery for ACHD patients be performed in a regional center specializing in congenital cardiology, with experienced surgeons and cardiac anesthesiologists. (Level of Evidence: C)

• 3. Certain high-risk patient populations should be managed at centers for the care of ACHD patients under all circumstances, unless the operative intervention is an absolute emergency. High-risk categories include patients with the following:

  • a. Prior Fontan procedure. (Level of Evidence: C)

  • b. Severe pulmonary arterial hypertension (PAH). (Level of Evidence: C)

  • c. Cyanotic CHD. (Level of Evidence: C)

  • d. Complex CHD with residua such as heart failure, valve disease, or the need for anticoagulation. (Level of Evidence: C)

  • e. Patients with CHD and malignant arrhythmias. (Level of Evidence: C)

• 4. Consultation with ACHD experts regarding the assessment of risk is recommended for patients with CHD who will undergo noncardiac surgery. (Level of Evidence: C)

• 5. Consultation with a cardiac anesthesiologist is recommended for moderate- and high-risk patients. (Level of Evidence: C)

Performance of any surgical procedure in ACHD patients carries a greater risk than in the normal population. Certain surgical procedures are frequently required in cyanotic patients, such as intervention for gallstones, scoliosis, and, less commonly, cerebral abscess. The risk for noncardiac surgery depends on the nature of the underlying CHD, the extent of the procedure, and the urgency of intervention. Table 7 lists lesions at moderate and high risk for noncardiac surgery.

A thorough evaluation of the patient with CHD should be undertaken before anticipated noncardiac surgery. Basic preoperative assessment includes an ECG, chest x-ray, TTE, and blood tests for full blood count and coagulation screen. It is recommended, when possible, that the preoperative evaluation and surgery be performed in an ACHD center by experienced surgeons and cardiac anesthesiologists. This allows close perioperative follow-up by an ACHD specialist. The specialist team should always be involved in the care of the complex and cyanotic adult patient with CHD, because this minimizes avoidable errors that can cause important morbidity or even death (126).

Select high-risk patient populations should be managed at centers for the care of ACHD patients under all circumstances, unless the operative intervention is an absolute emergency. These patients include those with prior Fontan procedure, severe PAH, cyanotic CHD, or complex CHD with residua such as heart failure, valve disease, or the need for anticoagulation.

Patients with cyanotic CHD, especially when associated with PAH, are at highest risk from noncardiac surgery (126). The bleeding risk can be reduced by preoperative phlebotomy if the hematocrit is more than 65% (127). Anesthetic management is critical, because a fall in systemic vascular resistance can worsen hypoxia, resulting in hemodynamic collapse. Long operations associated with hemodynamic instability and that require large-volume fluid replacement are associated with increased perioperative mortality. Fluid balance is critical in cyanotic and single-ventricle patients and those with heart failure because of occult renal failure in these patients.

Postoperatively, patients with CHD may need intensive care unit monitoring facilities even for relatively minor procedures. Nursing staff should be informed about the specific issues related to the CHD. Special issues that should be considered include administration of endocarditis prophylaxis, the need for anticoagulation around the time of the procedure, anticipation of special problems related to the underlying hemodynamics, filters for intravenous lines in cyanotic patients, prevention of venous thrombosis, monitoring of renal function, special care with drug administration, and the reduced arm blood pressure measurement in patients with prior classic Blalock-Taussig shunts. There is no evidence that cyanotic heart disease per se leads to liver disease (refer to Section 10, Tetralogy of Fallot, and Section 14, Tricuspid Atresia/Single Ventricle, for information regarding long-standing central venous hypertension leading to cardiac cirrhosis). There is increased prevalence of hepatitis C infection in adult patients who underwent CHD surgery before screening in 1992, and therefore these patients should be screened (128).

Class I

• 1. Patients with CHD should have consultation with an ACHD expert before they plan to become pregnant to develop a plan for management of labor and the postpartum period that includes consideration of the appropriate response to potential complications. This care plan should be made available to all providers. (Level of Evidence: C)

• 2. Patients with intracardiac right-to-left shunting should have fastidious care of intravenous lines to avoid paradoxical air embolus. (Level of Evidence: C)

• 3. Prepregnancy counseling is recommended for women receiving chronic anticoagulation with warfarin to enable them to make an informed decision about maternal and fetal risks. (129–131) (Level of Evidence: B)

Class IIa

• 1. Meticulous prophylaxis for deep venous thrombosis, including early ambulation and compression stockings, can be useful for all patients with intracardiac right-to-left shunt. Subcutaneous heparin or low-molecular-weight heparin is reasonable for prolonged bed rest. Full anticoagulation can be useful for the high-risk patient. (Level of Evidence: C)

Class III

• 1. The estrogen-containing oral contraceptive pill is not recommended for ACHD patients at risk of thromboembolism, such as those with cyanosis related to an intracardiac shunt, severe PAH, or Fontan repair. (Level of Evidence: C)

Congenital malformations now represent the most common cause of maternal morbidity and mortality from heart disease in North America. Better assessment and management of this group of patients is likely to make a substantial improvement in outcomes for mother and baby (132).

Both men and women with ACHD should have a thorough understanding of the risks of transmitting CHD to their offspring. Counseling by an ACHD expert before pregnancy is important and should include genetic evaluation and, specifically for women, assessment of potential fetal risk, risk of prematurity or low birth weight in the offspring, review of medications that may be deleterious to the fetus, appropriate management of anticoagulation, and discussion of potential maternal complications (132). If pregnancy occurs, fetal echocardiography should be obtained and its consequences discussed (132).

The outcome of pregnancy is favorable in most women with CHD provided that functional class and systemic ventricular function are good. PAH presents a serious risk during pregnancy, particularly when the pulmonary pressure exceeds 70% of systemic pressure, irrespective of functional class. Events often occur after delivery (133). The need for full anticoagulation during pregnancy, although not a contraindication, poses an increased risk to both mother and fetus (134). The relative risks and benefits of the different anticoagulant approaches need to be discussed fully with the prospective mother. There is a small group of patients with complex CHD or high-risk disorders in whom pregnancy is either dangerous or contraindicated owing to the risk to mother or fetus. If pregnancy occurs and continues with any of these disorders, these high-risk patients should be managed and delivered in specialized centers with multidisciplinary expertise and experience in CHD, obstetrics, anesthesiology, and neonatology. A coordinated care pathway for supervision of delivery and the postpartum period needs to be developed and in place by the third trimester and made available to all caregivers and to the patient. A normal vaginal delivery or an assisted delivery is usually feasible and may be preferable for patients with CHD. Cesarean delivery is recommended in patients with CHD for obstetric reasons and for women fully anticoagulated with warfarin at the time of delivery due to the risk of fetal intracranial hemorrhage.

Medications should be used only when necessary in any pregnant patient. Certain medications are contraindicated during pregnancy; these medications include angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers. These medications cause congenital and renal disorders in the fetus when given during pregnancy; therefore, they should be discontinued before pregnancy occurs or early during pregnancy if possible (135). Warfarin should be used only after full discussion with the patient about the risks of using warfarin during pregnancy (136).

Although endocarditis is a recognized risk for maternal morbidity and mortality, endocarditis prophylaxis around the time of delivery is not universally recommended for patients with structural heart disease, because some believe that the risk of bacteremia is low. Others routinely administer antibiotics because it is not known in advance whether or not instrumentation will be required. Thus, there is no consensus on this point (117). Antibiotics should be considered for those at highest risk of an adverse outcome and, when appropriate, given as the membranes rupture. Intravenous amoxicillin and gentamicin should be considered for women with high-risk anatomy or previous history of endocarditis (see Section 1.6, Recommendations for Infective Endocarditis).

1.8.1. Contraception

It is the duty of the ACHD specialist to provide or otherwise make available informed advice on contraception, including discussion of risks. There are limited data on the safety of various contraceptive techniques in ACHD patients. The estrogen-containing oral contraceptive pill is generally not recommended in ACHD patients at risk of thromboembolism, such as those with cyanosis, prior Fontan procedure, atrial fibrillation, or PAH. In addition, this form of contraceptive therapy may upset anticoagulation control. However, medroxyprogesterone, the progesterone-only pills, and levonorgestrel may also cause fluid retention and should be used with caution in patients with heart failure. Depression and breakthrough bleeding may prevent the use of the progesterone-only pills, and there is a higher failure rate than with combined oral contraceptives.

Levonorgestrel, barrier methods, or tubal ligation are the recommended contraceptive methods for women with cyanotic CHD and PAH. The potential complications of the “morning after pill” (levonorgestrel “plan B”) should be explained to those at risk of acute fluid retention. Tubal ligation, although the most secure method of contraception, can be a high-risk procedure in patients with complex CHD or those with PAH. Hysteroscopic sterilization (Essure) may be reasonable for high-risk patients (137). Sterilization of a male partner of a woman with CHD should only occur after full explanation of the prognosis to the patient. The specialist in the ACHD clinic needs to interact with both the general practitioner and the gynecologist to provide optimal advice regarding contraception. The risk of endocarditis with intrauterine devices in women with CHD is controversial, and recommendations should be individualized on the basis of discussions between the cardiologist and gynecologist.

Breast-feeding is safe in women with CHD. Women requiring cardiovascular medications should be aware that many of the medications will cross into breast milk and should clarify the potential effect of medications on the infant with a pediatrician.

Class I

• 1. Complete and appropriate noninvasive testing, as well as clear knowledge of the specific anatomy and review of all surgical and procedural records, is recommended before electrophysiological testing or device placement is attempted in ACHD patients. (Level of Evidence: C)

• 2. Decisions regarding tachycardia management in ACHD patients should take into account the broad cardiovascular picture, particularly repairable hemodynamic issues that might favor a surgical or catheter-based approach to treatment. (Level of Evidence: B)

• 3. Catheter ablation procedures for ACHD patients should be performed at centers where the staff is experienced with the complex anatomy and distinctive arrhythmia substrates encountered in congenital heart defects. (Level of Evidence: B)

• 4. Pacemaker and device lead placement (or replacement) in ACHD patients should be performed at centers where the staff is familiar with the unusual anatomy of congenital heart defects and their surgical repair. (Level of Evidence: B)

• 5. Epicardial pacemaker and device lead placement should be performed in all cyanotic patients with intracardiac shunts who require devices. (Level of Evidence: B)

Class IIa

• 1. It is reasonable to recommend the use of an implantable cardioverter defibrillator for any patient who has had a cardiac arrest or experienced an episode of hemodynamically significant or sustained ventricular tachycardia (VT). (Level of Evidence: C)

• 2. Pacemaker implantation can be beneficial in ACHD patients with bradyarrhythmias and may be helpful in overdrive pacing in patients with difficult-to-control tachyarrhythmias (see ACC/AHA/HRS 2008 Guidelines for Device-Based therapy of Cardiac Rhythm Abnormalities). (138) (Level of Evidence: B)

Class IIb

• 1. Pacemaker implantation may be beneficial for asymptomatic adult patients with resting heart rates of less than 40 beats per minute or abrupt pauses in excess of 3 seconds. (Level of Evidence: C)

Cardiac arrhythmias are a major source of morbidity and mortality for ACHD patients. Although rhythm disorders can often be observed in adults with unrepaired or palliated defects, the most difficult cases usually involve patients who have undergone prior intracardiac repairs, especially when this reparative surgery was performed relatively late in life (139,140). In this setting, the electrical pathology stems from the unique and complex myocardial substrates created by septal patches and suture lines in combination with cyanosis and abnormal pressure/volume status of variable duration. Virtually the entire spectrum of rhythm disturbances is manifested in these patients, including some disorders that are specific to the anatomic defect or the surgical technique used for repair (Table 8).

The optimal management strategy for many of these arrhythmias is as yet undetermined. The dramatic evolution of interventional electrophysiology in recent years, including techniques such as catheter or surgical ablation and implantation of antitachycardia devices, has broadened the list of therapeutic options significantly, but much of the literature in this field is still limited to small institutional series and anecdotal case reports. In the absence of large prospective outcome trials, current policies for arrhythmia treatment often involve extrapolation from studies of more conventional types of adult heart disease, such as ischemic myopathy. This approach, although a useful starting point, can underestimate the unique anatomic and physiological challenges of the ACHD patient. More organized multicenter research is needed in this area, as is more aggressive cross-training of electrophysiologists from both pediatrics and internal medicine to meet the special needs of these patients. Furthermore, until knowledge of these conditions is more widely disseminated, it is reasonable to recommend that interventional arrhythmia procedures be performed at centers where the staff is experienced with the complex anatomy and distinctive arrhythmia substrates encountered in congenital heart defects.

1.9.1. Management of Tachyarrhythmias: Wolff-Parkinson-White Syndrome

Accessory pathways can complicate certain forms of CHD, especially Ebstein's anomaly of the tricuspid valve (141). Tachycardia symptoms may begin in childhood but become increasingly problematic in adult years, when atrial dilation or surgical scars predispose the patient to atrial flutter or atrial fibrillation with potential for rapid conduction over an accessory pathway. An attempt at definitive therapy with catheter ablation has become the standard of care for these patients. However, compared with simple accessory pathway ablation in a structurally normal heart, the acute success rates are reported to be lower and the risk of recurrence higher in patients with anatomic defects (141–143). These differences appear to relate to the challenges of distorted anatomic landmarks, abnormal location for the AV node, and a high incidence of multiple pathways in the CHD population. Intraoperative accessory pathway ablation can be considered in the patient with Ebstein's anomaly referred for operative intervention for tricuspid valve disease. This approach has been demonstrated to be safe and effective (144).

1.9.2. Intra-Atrial Reentrant Tachycardia or Atrial Flutter

The most common form of tachycardia seen in the ACHD patient population is macroreentry within atrial muscle. This arrhythmia usually surfaces as a late postoperative disorder, and in children, it has been associated with chronotropic incompetence. Although it may arise after nearly any procedure that involves a right atriotomy (even simple closure of an ASD), the incidence is clearly highest after the Mustard, Senning, and Fontan operations, in which as many as 30% to 50% of patients can be expected to develop a symptomatic episode during extended follow-up (144,145). The term “intra-atrial reentrant tachycardia” (IART) has become the customary designation for this arrhythmia to distinguish it from classic atrial flutter seen in structurally normal hearts (146–148). Whereas typical atrial flutter involves a very predictable circuit around the tricuspid annulus that results in the familiar ECG appearance of sawtooth flutter waves at a rate of 300 beats per minute, IART can involve novel circuits around surgical scars and patches that generate a much wider spectrum of atrial rates and P-wave contours. Generally, IART tends to be slower than typical flutter, with atrial rates in the range of 170 to 250 beats per minute (144). In the setting of a healthy AV node, these rates will frequently allow a pattern of 1:1 AV conduction that may result in hemodynamic instability, syncope, or possibly death (149–151). Even if the ventricular response rate is safely titrated, sustained IART of long duration can be responsible for thromboembolic events.

Once IART is recognized, acute interruption is easily accomplished with either electrical cardioversion, overdrive pacing (150), or administration of certain class I or class III antiarrhythmic drugs (152). The far more difficult challenge is prevention of recurrence and adequate assessment of hemodynamic status that might predispose to recurrent tachycardia. Chronic antiarrhythmic drugs are still used in many cases, but the general experience with pharmacological therapy for this condition has been discouraging (149,153), which has led to a growing preference for nonpharmacological options at most centers.

Pacemaker implantation can be useful for those patients who have concomitant sinus node dysfunction as a prominent component of their clinical picture. Simply increasing the atrial rate to an appropriate level for the hemodynamic status can often result in marked reduction in IART frequency (150), while at the same time making it safer to prescribe medications that might aggravate bradycardia (138). Pacemakers with advanced programming features that incorporate atrial tachycardia detection and automatic burst pacing may also be beneficial in select cases (150,155) but carry the risk of accelerating the atrial rate and must thus be used cautiously in patients with robust AV conduction. Newer-generation implantable cardioverter defibrillators equipped with algorithms for both atrial tachycardia and VT detection and treatment, including atrial antitachycardia pacing and low-energy shocks for atrial tachycardia, have also been used successfully in a small number of ACHD patients with recurrent IART.

Catheter ablation has been adopted by many institutions as an early intervention for recurrent IART. The technique has evolved rapidly in terms of mapping accuracy and effectiveness, particularly since the introduction of 3-dimensional mapping technology for improved circuit localization (156,157) and irrigated-tip or large-tip ablation catheters for more effective lesion creation (158). With current technology, acute success rates of nearly 90% can be achieved with catheter ablation, although later tachycardia recurrence is still disappointingly common (159). The recurrence risk appears to be particularly high in the Fontan population of patients, who tend to have multiple IART circuits and the thickest/largest atrial dimensions. Although still far from perfect, ablation results for IART are likely to improve with continued advances in technology and even now are superior to the degree of control obtained with medications alone.

If the above measures fail to prevent IART recurrence, or if a patient with IART is returning to the operating room for hemodynamic reasons, consideration should be given to surgical ablation during a right atrial Maze operation. This procedure is used most commonly for the Fontan population with the most refractory variety of IART and is usually combined with revision of the Fontan connection or conversion from an older atriopulmonary anastomosis to a cavopulmonary connection. Results are encouraging, with very low rates of IART recurrence (160), but the surgical risks must be weighed against the electrophysiological benefit.

1.9.3. Atrial Fibrillation

Although far less common than IART in ACHD patients, atrial fibrillation is no less difficult to treat. It occurs most often in patients with congenital AS, mitral valve disease, or palliated single ventricles (161). Management principles are similar to atrial fibrillation encountered in other forms of heart disease, beginning with medical therapy for anticoagulation and ventricular rate control as needed, followed by electrical cardioversion. Class III antiarrhythmic agents may offer protection against recurrence of atrial fibrillation for some patients, but as in the case of IART, drug therapy has been only marginally successful for this group. Also similar to IART, pacemaker implantation may reduce atrial fibrillation episodes in patients with concomitant sinus node dysfunction. Successful elimination of atrial fibrillation has also been reported after combined right and left atrial Maze operations, which may be reasonable to consider if a patient requires cardiac surgery to address hemodynamic issues. Catheter ablation has not yet been extended in any systematic way to atrial fibrillation in the ACHD patient population.

1.9.4. Ventricular Tachycardia

There are several scenarios in which high-grade ventricular arrhythmias may develop in the ACHD patient. The most familiar involves macroreentrant VT as a late complication in postoperative patients who have undergone ventriculotomy and/or patching of a VSD, such as tetralogy of Fallot repair. In such cases, the reentry circuit is typically caused by narrow conduction corridors around regions of scar in the RV outflow tract (RVOT). The incidence of late VT or sudden death for repaired tetralogy has been estimated between 0.5% and 6.0% in various series (140,162,163). Some patients with slow organized VT may be hemodynamically stable at presentation, but VT tends to be rapid for the majority, producing syncope or cardiac arrest as the presenting symptom. The clinical picture is often confounded by the fact that symptomatic atrial tachycardias are also common in ACHD patients (164), which makes it difficult at times to tell whether an event was caused by VT, IART, or both.

Predicting which CHD patients will develop VT in advance of an episode remains a challenge. Studies seeking risk factors in the population with tetralogy of Fallot have identified older age at time of reparative surgery, advanced degrees of RV dilation, and prolonged QRS duration greater than 180 milliseconds as independent variables (140,165–167), although the predictive accuracy for each of these factors is imperfect. Holter monitoring and exercise testing have also been examined as screening tools with some degree of correlation between spontaneous ectopy and future VT events, but because ectopy on ambulatory monitoring is nearly ubiquitous in this population, the positive predictive value is diluted. Formal ventricular stimulation study can discriminate between high- and low-risk CHD patients (168,169) but remains too imperfect and too impractical to be recommended as a general screening tool. Intracardiac electrophysiology testing is usually reserved for selected patients with concerning symptoms or Holter findings when VT is suspected but not yet proven. At present, there is no generally accepted scheme for rhythm surveillance in asymptomatic patients with tetralogy of Fallot. Some combination of the above tests must be viewed in the context of the individual patient's history and general hemodynamic status to guide testing and treatment decisions whenever symptoms are minimal or absent. Symptoms of palpitations, dizziness, or unexplained syncope would obviously heighten the index of suspicion and should trigger a thorough and prompt diagnostic evaluation, which probably should include formal electrophysiological testing.

Although tetralogy of Fallot is typically cited as the archetypal lesion when VT in the ACHD patient population is discussed, serious ventricular arrhythmias may also develop in a number of other malformations, even in the absence of direct surgical scarring to ventricular muscle. Examples include congenital AS, dextro- or levo-TGA when the right ventricle supports the systemic circulation, severe Ebstein's anomaly, certain forms of single ventricle, and VSD with PAH. The appearance of ventricular arrhythmias in these cases commonly coincides with deterioration in overall hemodynamic status (165).

Therapy for VT in ACHD patients is complex and evolving. Similar to VT treatment in ischemic heart disease, sole reliance on pharmacological management has now been largely abandoned. Empirical beta blockade and class I or class III agents might still be prescribed in rare cases when the clinician remains ambivalent about a patient's VT risk after thorough testing, but no data support this approach once sustained VT or cardiac arrest has occurred. Drug therapy has now been replaced at most centers by more definitive interventions, such as implantable cardioverter defibrillator placement, catheter ablation, or arrhythmia surgery. Before deciding among these options, hemodynamic catheterization combined with comprehensive electrophysiology study should be obtained. Reparable hemodynamic issues may be identified that would favor a surgical strategy for therapy, such as closure of a residual septal defect or relief of valve regurgitation, combined with intraoperative VT mapping and ablation (170). In addition, IART may be identified as either a contributing or confounding factor for a patient's symptoms and can be addressed with either catheter or surgical ablation at the same setting. Finally, if VT can be induced that is slow enough to support the circulation during mapping, catheter ablation of the VT circuit may be considered on the basis of the risks and benefits to the individual patient (171,172). Although reports of ablation for VT in ACHD patients are still limited to small series, it appears that it can be accomplished with a reasonable degree of acute success (173,174); however, the risk of VT recurrence after ablation is now being more clearly defined and may exceed 20% (174). It seems wise to reserve ablation as isolated VT therapy for those CHD patients with superior hemodynamics and single circuits of slow tachycardia, and even then, to perform follow-up stimulation studies to ensure that the same or different circuits cannot be induced before dismissing the need for an implantable cardioverter defibrillator. Perhaps a more important role for catheter ablation may be as supplemental therapy to reduce the shock burden in patients with frequent VT recurrences who already have an implantable cardioverter defibrillator in place.

Most ACHD patients with documented or highly suspected VT are now managed with an implantable cardioverter defibrillator (175). Transvenous systems are possible in most cases, with the notable exceptions of single-ventricle patients, those with obstructed venous channels, and those with significant intracardiac shunts who would be at risk for systemic embolic events from an intravascular lead. Acute defibrillation thresholds in CHD patients are comparable to those encountered in acquired heart disease. What may differ during follow-up is the need for lead revision. There is now growing evidence that lead failure from insulation or conductor breaks is relatively high in this group (175), which possibly reflects a more active lifestyle for young ACHD patients than for an older population with ischemic disease.

1.10.1. Sinoatrial Node Dysfunction

Although some rare forms of heterotaxy syndrome can be associated with congenital dysfunction or absence of the sinoatrial node, pathological sinus bradycardia in ACHD patients is more often an acquired problem related to cardiac surgery. Direct trauma to the sinoatrial node or its arterial supply occurs fairly frequently after the Mustard, Senning, Glenn, and Fontan operations (139,144,176,177). The likelihood of a patient developing IART or atrial fibrillation becomes significantly increased in this setting. Furthermore, patients with suboptimal hemodynamics may become symptomatic owing to chronotropic incompetence and the loss of AV synchrony. The updated guidelines for antibradycardia pacemaker implantation developed by the ACC and AHA (138) include information pertinent to CHD under the heading of “children and adolescents.” These same guidelines can be applied reasonably well to ACHD patients. Implantation of an atrial or dual-chamber pacing system with activity responsiveness is recommended as a Class I indication in any symptomatic patient with sinoatrial node dysfunction. This will include most of those with tachy-brady syndrome and symptoms from recurrent atrial tachycardias, as well as any patient who is shown to have pause-dependent VT. Pacemaker implantation is also recommended as a Class IIb indication for asymptomatic adult patients with resting heart rates of less than 40 beats per minute or abrupt pauses in excess of 3 seconds. The possibility of developing ventricular dysfunction with apical ventricular pacing exists. Although dual-chamber pacing systems may be implanted, manipulation of pacing programming to maintain atrial pacing with intact AV conduction is desirable.

There are a number of unique technical considerations during pacemaker implantation in ACHD patients. Transvenous lead positions, for example, will often have to be modified in response to the cardiac lesion and vascular redirection imposed by surgical patches or anastomotic stenosis, as occurs after the Mustard or Senning operations. Transvenous leads may be impossible or ill advised in other CHD lesions, including in some postoperative Fontan patients or patients with intracardiac shunting, thereby necessitating epicardial lead placement. With either the endocardial or epicardial approach, it can be challenging to locate lead anchor points with proper pacing and sensing function due to fibrosis and patching, particularly for an atrial lead. Clear knowledge of the specific anatomy and review of all surgical records are essential before device placement is attempted in these patients.

1.10.2. Atrioventricular Block

Surgical repair of CHD may result in direct trauma to the AV conduction tissues. Although improved knowledge of the anatomy of the AV node and His bundle in various CHD lesions has lessened its occurrence (178), closure of some VSDs, surgery for left-sided heart outflow obstruction, and replacement or repair of an AV valve may still be complicated by AV block. Fortunately, in more than half of cases, this injury is a transient phenomenon, and conduction recovers within 7 to 10 days of the operation (179). Permanent pacemaker implantation is advised (138) as a Class I indication for any patient with postoperative advanced second- or third-degree AV block that is not expected to resolve or persists at least 7 to 10 days after cardiac surgery. A pacemaker is also recommended by some as a Class IIb indication when surgical AV block recovers but the patient is left with permanent bifascicular block.

The AV conduction tissues may also be congenitally abnormal in terms of their location and function in specific forms of CHD, notably congenitally corrected TGA (CCTGA), as well as AV septal defect (AVSD), particularly those with Down syndrome (180–182). These patients may be more susceptible to surgical or catheter-induced AV block but may also develop AV block spontaneously at any point in time ranging from fetal life to adulthood. Patients with these particular anatomic defects merit periodic assessment of AV conduction with serial ECGs and Holter monitoring, even if AV conduction was not directly affected by surgery.

1.11.1. Recommendations for Hematologic Problems

Class I

• 1. Cyanotic patients should drink nonalcoholic and noncaffeinated fluids frequently on long-distance flights to avoid dehydration. (Level of Evidence: C)

Class IIb

• 1. Supplemental oxygenation may be considered for cyanotic patients during long-distance flights. (Level of Evidence: C)

Cyanotic patients should use only pressurized commercial airplanes. Oxygen therapy, although often unnecessary, may be suggested for prolonged travel. Similarly, residence at high altitude is detrimental for patients with cyanosis. Dehydration should be avoided by frequent fluid intake on long flights and during sports activities.

Competitive sports should be avoided in cyanotic patients (187). Cyanosis is a recognized handicap to fetal growth and development, and pregnancy outcome is impacted, with an increased risk of congestive heart failure, preterm delivery, intrauterine growth retardation, and miscarriage. Increased maternal and fetal mortality are also noted and correlate with the degree of cyanosis, ventricular dysfunction, and pulmonary pressures (117).

1.12.1. Hospitalization and Operation

Cyanotic patients are at high risk during any hospitalization or operation. When hospitalized for medical or surgical problems, these patients should be seen and followed up by an ACHD specialist. Management strategies that should be applied include those likely to reduce the risk of paradoxical emboli related to air in the intravenous lines. Medication adjustment may be needed, with cyanosis taken into account. Early ambulation may prevent venous stasis and thrombophlebitis.

1.12.2. Cardiac Reoperation and Preoperative Evaluation

Although some ACHD patients present without prior intervention, the majority will have undergone 1 or more prior repairs. Review of prior operative notes can provide important insight when a cardiac repair is planned. Repeat sternotomy may be associated with cardiac injury. The heart and great arteries may be closely adherent to the sternum because of the loss of pericardial integrity or presence of conduit material in the anterior mediastinum. In addition, right-sided heart structures may be enlarged or hypertensive, which also increases the potential for injury during sternotomy. Morphological abnormalities of the aorta, pulmonary artery, or ventricle–to–pulmonary artery conduit may also be at increased risk of injury. Peripheral vascular abnormalities may be present secondary to previous cardiac catheterization or operative procedures. For example, the radial pulse may be absent in patients with a prior classic Blalock-Taussig shunt. Femoral artery or vein occlusion may have occurred secondary to prior catheterization procedures or indwelling monitoring lines. Knowledge of the status of femoral or auxiliary vessels before reoperation may be particularly important if cannulation for establishment of cardiopulmonary bypass via these vessels is being planned.

To minimize the potential problems that may arise at the time of rerepair, additional preoperative studies may be necessary. The choice of the various supplemental imaging studies should be individualized on the basis of the surgeon's preference and institutional availability. Imaging studies that are frequently used include ultrasound, cine angiography, or MRI to document patency of cardiac anatomy (or occlusion) and status of femoral or axillary vessels. Coronary angiography or CT angiography is used to identify coronary anomalies or obstructive lesions. CT imaging of the chest may be helpful in identifying the relationship and proximity of the right ventricle, right atrium, aorta, pulmonary artery, or extracardiac conduit to the sternum or anterior chest wall. The importance of reviewing prior surgical notes when a repeat operation is planned cannot be overemphasized.

Men aged 35 years or older, premenopausal women 35 years or older with risk factors for atherosclerosis, and postmenopausal women should be evaluated by cardiac catheterization and coronary angiography to rule out associated coronary artery disease before they undergo reoperative cardiac surgery (112).

Class I

• 1. Patients with CHD and heart failure who may require heart transplantation should be evaluated and managed in tertiary care centers with medical and surgical personnel with experience and expertise in the management of both CHD and heart transplantation. (Level of Evidence: C)

• 2. Patients with CHD and heart or respiratory failure who may require lung or heart/lung transplantation should be evaluated and managed in tertiary care centers with medical and surgical personnel with experience and expertise in the management of CHD and lung or heart/lung transplantation. (Level of Evidence: C)

In ACHD patients, postoperative ventricular failure may occur early after operation but more commonly develops late after operation, often in adulthood. Late systemic ventricular failure can be associated with many congenital diagnoses.

The pretransplantation evaluation involves a multidisciplinary approach that addresses assessment of cardiopulmonary, renal, neurological, hepatic, infectious disease, socioeconomic, and psychological issues. In addition to history and physical examination, diagnostic studies include ECG, echocardiography, chest x-ray, and Holter monitoring. Cardiac catheterization is required to assess pulmonary vascular resistance (PVR) and transpulmonary gradient (231). In addition to cardiac catheterization, MRI or CT angiography is often performed to delineate the anatomy in patients with complex CHD (eg, patients with malposition of the great arteries and/or substernal position of an extracardiac conduit, abnormalities of systemic venous return, and situs abnormalities).

Many patients with long-standing heart failure may have elevated PVR. Consequently, donor right-sided heart failure may result when the heart is abruptly placed proximal to such a high-resistance pulmonary vascular bed. Pharmacological modulation of pulmonary hemodynamics with pulmonary vasodilators during cardiac catheterization helps predict outcome after heart transplantation (232,233). In most centers, a fixed PVR index of 6 units or more or a transpulmonary gradient greater than 15 mm Hg that does not respond to vasodilator therapy (oxygen, nitric oxide, milrinone, or dobutamine) is a contraindication to cardiac transplantation alone, although transplantation from a rare donor with PAH in a Domino procedure with heart/lung transplantation in 1 recipient followed by transplantation of the recipient's heart into another recipient may still be successful.

Contraindications to cardiac transplantation include the following:

• • Active infection

• • Positive serology for human immunodeficiency virus or hepatitis C infections

• • Severe metabolic disease

• • Multiple other severe congenital anomalies

• • Multisystem organ failure

• • Active malignancy

• • Cognitive or behavioral disability that interferes with compliance.

Heart/lung transplantation is usually reserved for patients with uncorrectable or previously repaired or palliated CHD associated with significant pulmonary vascular obstructive disease, such as single-ventricle physiology with pulmonary vascular disease or LV dysfunction with associated pulmonary vascular disease. When a simple cardiac defect is present, such as ASD, VSD, or PDA, the cardiac defect can often be repaired at lung transplantation (234). In the presence of more complex intracardiac abnormalities, combined heart/lung transplantation is usually most appropriate.

Previous thoracotomies are not an absolute contraindication to transplantation, but in the presence of chronic cyanosis, vascular collaterals may lead to fatal hemorrhagic complications. The absence of detectable recurrence of malignancy for 5 years may permit successful transplantation. Obesity is a relative contraindication to transplantation.

Survival rates after heart transplantation have improved over the years, and the current predicted posttransplantation half-life (the time at which 50% of those with transplanted organs remain alive, or median survival) for the entire cohort of pediatric and adult heart recipients is 10 years, with a half-life of 13 years for those who survive the first year; however, having ACHD as an indication for transplant increases that risk during the first year by 2-fold (235).

Advances in selection, technique, and management of patients undergoing lung or heart/lung transplant have resulted in significant improvement in survival. Overall, survival after pediatric lung transplantation as reported by the International Society of Heart and Lung Transplant registry is approximately 75% at 1 year and 60% at 2 years (236). The most common cause of mortality in the first month after lung transplantation is acute graft failure; from 1 month to 1 year after transplantation, infection is the leading cause of death. From 1 to 3 years after lung transplantation, chronic rejection or bronchiolitis obliterans is the leading cause of death. Beyond this time frame, main causes of death include chronic rejection and infection. The outcome for heart/lung transplantation is similar to that for lung transplantation.

Actuarial survival at 10 years after heart/lung transplantation is 20%. Results of lung and heart/lung transplantation for PAH and ACHD are comparable to those reported for children, with an increased risk of early mortality related to perioperative complications and complexity compared with transplantation for obstructive pulmonary disease or cystic fibrosis. Outcomes for lung transplantation and cardiac repair are comparable to those for heart/lung transplantation in the treatment of PAH and CHD (237).

2.1.1. Associated Lesions

ASD can be associated with additional malformations in nearly 30% of cases (Table 9) (239). As a form of AVSD, the primum ASD is nearly always accompanied by a cleft in the anterior mitral valve leaflet. Discrete SubAS may develop postoperatively. Sinus venosus defects frequently have partial anomalous venous drainage of the right pulmonary veins. This association is present in a small number of patients with secundum ASDs as well. Mitral valve prolapse is frequently seen in patients with ASD. Valvular pulmonic stenosis is frequently described in association with ASD, but in some cases, there is a mild RV outflow gradient that is caused by increased flow but not a structural valve abnormality (240,241).

Coronary sinus septal defect, a defect in the roof of the coronary sinus and not technically an ASD, may be accompanied by partial or total anomalous pulmonary venous connection and/or a persistent left superior vena cava draining to the coronary sinus.

2.2.1. Unrepaired Atrial Septal Defect

The consequence of left-to-right shunt across an ASD is RV volume overload and pulmonary overcirculation. Large atrial shunts lead to symptoms from excess pulmonary blood flow and right-sided heart failure, including frequent pulmonary infections, fatigue, exercise intolerance, and palpitations. Atrial arrhythmias—atrial flutter, atrial fibrillation, and sick sinus syndrome—are a common result of long-standing right-sided heart volume and pressure overload. Flow-related PAH accompanies large left-to-right shunts, and pulmonary vascular obstructive disease may develop in adult years but occurs much later with ASD than with high-pressure left-to-right shunts such as VSD or PDA. Paradoxical embolism from peripheral venous or pelvic vein thromboses, atrial arrhythmias, unfiltered intravenous infusions, or indwelling venous catheters is a risk for all defects regardless of size (242–244).

The initial presentation in adulthood most commonly includes symptoms of dyspnea and palpitations (245,246). Other modes of presentation in the previously undiagnosed adult with an ASD include cardiomegaly on routine chest x-ray, a more audible murmur during pregnancy, new onset of atrial flutter/fibrillation, or a paradoxical embolic event. Patients with small defects (less than 10 mm) may remain asymptomatic well into the fourth and fifth decade of life (236,246); however, symptoms may develop with increasing age even with small defects owing to an increase in shunting caused by a decrease in LV compliance secondary to coronary artery disease, acquired valvular disease, or hypertension.

Class I

• 1. ASD should be diagnosed by imaging techniques with demonstration of shunting across the defect and evidence of RV volume overload and any associated anomalies. (Level of Evidence: C)

• 2. Patients with unexplained RV volume overload should be referred to an ACHD center for further diagnostic studies to rule out obscure ASD, partial anomalous venous connection, or coronary sinoseptal defect. (Level of Evidence: C)

Class IIa

• 1. Maximal exercise testing can be useful to document exercise capacity in patients with symptoms that are discrepant with clinical findings or to document changes in oxygen saturation in patients with mild or moderate PAH. (Level of Evidence: C)

• 2. Cardiac catheterization can be useful to rule out concomitant coronary artery disease in patients at risk because of age or other factors. (Level of Evidence: B)

Class III

• 1. In younger patients with uncomplicated ASD for whom imaging results are adequate, diagnostic cardiac catheterization is not indicated. (Level of Evidence: B)

• 2. Maximal exercise testing is not recommended in ASD with severe PAH. (Level of Evidence: B)

The diagnostic workup for a patient with a suspected ASD is directed at defining the presence, size, and location of the ASD; the functional effect of the shunt on the right and left ventricles and the pulmonary circulation; and any associated lesions.

2.3.1. Clinical Examination

Clinical findings include a precordial lift, systolic pulmonary flow murmur, and fixed splitting of the second heart sound (although fixed splitting is not invariable). With large shunts, a diastolic flow rumble across the tricuspid valve is present.

2.3.2. Electrocardiogram

The ECG often shows right-axis deviation, right atrial enlargement, incomplete right bundle-branch block (secundum ASD), superior left-axis deviation (primum ASD), or an abnormal P-wave axis (superiorly located sinus venosus ASD). Complete heart block may be present in association with familial ASD (247). The superior left axis with RV conduction delay seen in primum ASD is due to the anatomic position of the conduction bundles and should not be confused with bifascicular block.

2.3.3. Chest X-Ray

The chest x-ray may show RV and right atrial enlargement, a prominent pulmonary artery segment, and increased pulmonary vascularity.

2.3.4. Echocardiography

A TTE is the primary diagnostic imaging modality for ASD. The study should include 2-dimensional imaging of the atrial septum from the parasternal, apical, and subcostal views with color Doppler demonstration of shunting. Subcostal views with deep inspiration and high right parasternal views can be particularly helpful for imaging ASD in adults. The entire atrial septum from the orifice of the superior vena cava to the orifice of the inferior vena cava should be visualized to detect sinus venosus defects or the extension of large secundum defects in these regions. A TEE may be necessary to identify the connection of all pulmonary veins in patients with ASD. In adults with poor-quality transthoracic images, TEE may be necessary to adequately image the atrial septum (248–251), because it provides exact localization and sizing of the ASD, as well as measurement of septal rims, each of which is important for decision making.

A large coronary sinus orifice with evidence of atrial shunting may indicate a defect in the roof of the coronary sinus (eg, sinoseptal defects). Thus, the entire coronary sinus roof should be imaged when this is suspected. When a coronary sinoseptal defect is associated with lesions that cause right-to-left shunting, the orifice of the coronary sinus may not be enlarged and the defect not recognized until after definitive surgery, at which time a left-to-right shunt may occur. With PAH, the low velocity of the shunt flow across the coronary sinoseptal defect may be difficult to distinguish from other low-velocity flow within the atria.

Right atrial and RV enlargement with diastolic flattening and paradoxical motion of the interventricular septum are evidence of RV volume overload and a significant left-to-right shunt. The RV systolic pressure should be estimated from the peak velocity of the tricuspid regurgitant jet if present. Two-dimensional imaging should assess associated lesions such as mitral valve prolapse, cleft mitral valve, anomalous pulmonary veins, and PS, and their functional significance should be determined by color and spectral Doppler.

Contrast echocardiography with intravenous agitated saline injection is used to confirm the presence of a right-to-left atrial shunt if imaging and color Doppler are not conclusive (252). Additionally, the presence of negative contrast in the right atrium may be helpful in identifying a left-to-right shunt. If a left-to-right shunt or RV volume overload is recognized but unexplained, the patient should be referred to an ACHD center for further imaging studies.

2.3.5. Magnetic Resonance Imaging

MRI provides an additional noninvasive imaging modality if findings by echocardiography are uncertain. Direct visualization of the defect and pulmonary veins is possible, RV volume and function can be quantified, and estimates of shunt size can also be obtained (253–255). Contrast-enhanced ultrafast cine CT can also provide diagnostic information, although the radiation exposure limits its utility in most cases (256).

Diagnostic cardiac catheterization is not required for uncomplicated ASDs in younger patients with adequate noninvasive imaging (257,258). It is generally reserved for investigation of coronary artery disease in those patients at risk by virtue of age or family history and for whom surgical intervention is planned and to assess PVR and reactivity in patients with significant PAH. Catheterization may also be required to evaluate ASD size, pulmonary venous return, and associated valvular disease if noninvasive methods have been unable to provide this information. In most instances, catheterization is now performed in conjunction with device closure of the defect.

2.3.6. Exercise Testing

Exercise testing can be useful to document exercise capacity in patients with symptoms that are discrepant with clinical findings or to document changes in oxygen saturation in patients with PAH. Maximal exercise testing is not recommended in ASD with severe PAH, however.

2.5.1. Recommendations for Medical Therapy

2.5.2. Recommendations for Interventional and Surgical Therapy

2.5.3. Indications for Closure of Atrial Septal Defect

Small ASDs with a diameter of less than 5 mm and no evidence of RV volume overload do not impact the natural history of the individual and thus may not require closure unless associated with paradoxical embolism. Larger defects with evidence of RV volume overload on echocardiography usually only cause symptoms in the third decade of life, and closure is usually indicated to prevent long-term complications such as atrial arrhythmias, reduced exercise tolerance, hemodynamically significant TR, right-to-left shunting and embolism during pregnancy, overt congestive cardiac failure, or pulmonary vascular disease that may develop in up to 5% to 10% of affected (mainly female) individuals.

2.5.4. Catheter Intervention

The development of percutaneous transcatheter closure techniques has provided an alternative method of closure for uncomplicated secundum ASDs with appropriate morphology (260–262). Currently, the majority of secundum ASDs can be closed with a percutaneous catheter technique. When this is not feasible or is not appropriate, surgical closure is recommended.

Sinus venosus, coronary sinus, and primum defects are not amenable to device closure. An ASD with a large septal aneurysm or a multifenestrated atrial septum requires careful evaluation by and consultation with interventional cardiologists before device closure is selected as the method of repair.

2.5.5. Key Issues to Evaluate and Follow-Up

Key issues to evaluate and monitor in adults with ASD are listed in Table 10.

Class I

• 1. Early postoperative symptoms of undue fever, fatigue, vomiting, chest pain, or abdominal pain may represent postpericardiotomy syndrome with tamponade and should prompt immediate evaluation with echocardiography. (Level of Evidence: C)

• 2. Annual clinical follow-up is recommended for patients postoperatively if their ASD was repaired as an adult and the following conditions persist or develop:

  • a. PAH. (Level of Evidence: C)

  • b. Atrial arrhythmias. (Level of Evidence: C)

  • c. RV or LV dysfunction. (Level of Evidence: C)

  • d. Coexisting valvular or other cardiac lesions. (Level of Evidence: C)

• 3. Evaluation for possible device migration, erosion, or other complications is recommended for patients 3 months to 1 year after device closure and periodically thereafter. (Level of Evidence: C)

• 4. Device erosion, which may present with chest pain or syncope, should warrant urgent evaluation. (Level of Evidence: C)

Follow-up for patients after device closure requires clinical assessment of symptoms of arrhythmia, chest pain, or embolic events and echocardiographic surveillance for device position, residual shunting, and complications such as thrombus formation or pericardial effusion. The frequency of echocardiographic follow-up is usually at 24 hours, 1 month, 6 months, and 1 year and at regular intervals thereafter.

Pericardial effusions and cardiac tamponade may occur up to several weeks after surgical repair of ASDs and should be evaluated by clinical examination and echocardiography before hospital discharge and at the early postoperative visits. Patients and their primary care physicians should be instructed to report fever or unusual symptoms of chest or abdominal pain and vomiting or undue fatigue in the first weeks after surgery, because they might represent early signs of cardiac tamponade. Assessment of pulmonary pressure, RV function, and residual atrial shunting should also be made during follow-up echocardiography. Clinical and ECG surveillance for recurrent or new-onset arrhythmia is an important feature of postoperative evaluation. Periodic long-term clinical follow-up is required for patients postoperatively if their ASD was repaired as an adult, if PAH was present preoperatively, if there were atrial arrhythmias either preoperatively or postoperatively, if there was RV or LV dysfunction preoperatively or postoperatively, or if there are coexisting valvular or other cardiac lesions. Patients with ASD who have undergone surgical closure in childhood are generally free of late complications.

2.6.1. Endocarditis Prophylaxis

Endocarditis does not occur in patients with isolated ASDs and is usually associated with concomitant valvular lesions, such as a cleft mitral valve (94). Endocarditis prophylaxis is therefore not indicated for isolated ASDs before or after surgery except for the first 6 months after closure (refer to Section 1.6, Recommendations for Infective Endocarditis, for additional information).

2.6.2. Recommendation for Reproduction

2.6.3. Activity

Patients with small ASDs and without PAH have normal exercise capacity and do not need any limitation of physical activity. In those patients with large left-to-right shunts, exercise is often self-limited owing to decreased cardiopulmonary function (273). Symptomatic supraventricular or ventricular arrhythmias may also compromise exercise capacity and impose limitations on engagement in competitive sports. Patients with significant PAH (peak systolic pulmonary artery pressure greater than 40 mm Hg) should limit their activity to low-intensity sports. Severe PAH with right-to-left shunting is usually self-limiting, but participation in athletics or active physical effort should be avoided (274).

3.1.1. Associated Lesions

Although VSD is most often an isolated lesion, it is a common component of complex abnormalities such as conotruncal defects (eg, tetralogy of Fallot, TGA). VSD can also be associated with left-sided obstructive lesions such as SubAS and coarctation of the aorta. A subpulmonary (supracristal) VSD is often associated with progressive aortic valve regurgitation caused by prolapse of the aortic cusp (usually right) through the defect.

3.3.1. Clinical Examination

VSD is characterized clinically by a systolic murmur that is usually maximal at the left lower sternal border. When RV pressure is low, the VSD murmur is blowing and pansystolic. With incremental increases in RV pressure, the murmur is shorter, softer, and lower pitched. Small, muscular VSDs are usually very high-pitched and occupy early systole only because muscular contraction closes the defect.

3.3.2. Electrocardiogram

In patients with large VSD and significant PAH, the ECG will show biventricular hypertrophy or isolated RV hypertrophy, depending on the extent to which the LVOT has diminished in response to the reduction in left-to-right shunt.

3.3.3. Chest X-Ray

Patients with a small VSD will have a normal chest x-ray. The presence of a significant left-to-right shunt will create the appearance of left atrial and LV enlargement and increased pulmonary vascular markings. Patients with significant PAH will not demonstrate LV enlargement but will have a prominent pulmonary artery segment and diminished pulmonary vascular markings at the periphery of the lung.

3.3.4. Echocardiography

Echocardiography-Doppler is the mainstay of modern diagnosis. Transthoracic echocardiographic studies are almost always diagnostic in children and adolescents and in most adults with good echocardiographic windows. Data to be obtained include the number of defects, location of defect(s), chamber sizes, ventricular function, presence or absence of aortic valve prolapse and/or regurgitation, presence or absence of RV or LV outflow obstruction, and presence or absence of TR. Estimation of RV systolic pressure from TR jet, VSD jet, and/or septal configuration should be a part of the study. In adults with poor echocardiographic windows, TEE may be necessary.

Echocardiography-Doppler of postoperative patients should focus on the presence or absence and location of residual shunting and the evaluation of pulmonary artery pressure by TR or pulmonary regurgitation jet velocity. In addition, patients should be evaluated for AR, ventricular function, and RV or LV outflow obstruction.

3.3.5. Magnetic Resonance Imaging/Computed Tomography

MRI or CT may be useful, if local expertise in cardiac studies is available, for the following:

• • Assessment of pulmonary artery, pulmonary venous, and aortic anatomy if there are coexisting lesions

• • To confirm the anatomy of unusual VSDs such as inlet or apical defects not well seen by echocardiography.

3.3.6. Recommendations for Cardiac Catheterization

3.5.1. Recommendation for Medical Therapy

3.5.2. Recommendations for Surgical Ventricular Septal Defect Closure

3.5.3. Recommendation for Interventional Catheterization

3.6.1. Recommendations for Surgical and Catheter Intervention Follow-Up

3.6.2. Recommendation for Reproduction

3.6.3. Activity

No activity restrictions are indicated for patients with small VSDs, no associated lesions, and normal ventricular function. If pulmonary vascular disease is present, activity is usually self-restricted, but patients should be advised against strenuous exercise or travel to altitudes above 5000 feet. Long-distance air travel should be approached with caution to avoid dehydration, with specific recommendation by an ACHD specialist concerning the need for supplemental oxygen (refer to Section 9, Pulmonary Hypertension/Eisenmenger Physiology).

4.3.1. Clinical Examination

Physical examination of the unoperated patient may show findings of an ASD, a VSD, AV valve regurgitation, LVOT obstruction, or PAH with cyanosis. A patient with severe PAH may have no murmur, a single loud second heart sound, and cyanosis/clubbing.

The typical repaired patient will have a normal examination apart from an apical systolic murmur if there is residual mitral regurgitation or subaortic obstruction. Subaortic obstruction may occur naturally in association with abnormal AV valve attachments or may be the consequence of surgery. In addition, the surgical repair may have created AV valve stenosis. Cyanosis should not be present in the absence of Eisenmenger syndrome or RV outflow obstruction.

4.3.2. Electrocardiogram

The typical ECG shows superior left-axis deviation with a counterclockwise loop in the frontal plane. First-degree AV block may be present. Atrial flutter or fibrillation may develop in the older patient. Left atrial enlargement and LV hypertrophy may be present if there is significant left AV valve regurgitation. RV hypertrophy may predominate if there is PAH or associated RVOT obstruction.

4.3.3. Chest X-Ray

Cardiomegaly may be present due to dilation of the right or left AV heart chambers, depending on the degree and direction of AV valve regurgitation and the degree and level of left-to-right shunting. Increased pulmonary vascular markings are present when there is a significant left-to-right shunt. Pulmonary venous congestion may be seen when there is long-standing mitral regurgitation. In patients with PAH, a prominent main pulmonary artery segment and pruning of distal pulmonary vessels may be present.

4.3.4. Echocardiography

In the patient with a partial and unrepaired AVSD, TTE is the primary imaging modality and should include demonstration of the borders of the primum ASD, a VSD (if present), the morphology and function of the AV valve, ventricular size and shunting, and SubAS (if present). In the patient with a complete and unrepaired AVSD, this will include the presence and size of the septal defect, the morphology and function of the common AV valve, and ventricular size and function. When the ventricular portion of the septal defect is large, the ventricular septum may be deficient apically and inferiorly. Pulmonary artery pressures (expected to be very high in complete AVSD) should be evaluated by measuring TR and pulmonary regurgitation jet velocity with simultaneous systemic blood pressure measurement. Evidence of subaortic obstruction, caused by AV valve attachments to the crest of the interventricular septum, should be sought by imaging and Doppler. In the postrepair patient, residua may include left AV valve dysfunction, SubAS, VSD patch leak, and PAH. It may be difficult to distinguish residual LV to right atrial shunt from TR with RV hypertension. The failure to distinguish these may result in erroneous diagnosis of PAH.

4.3.5. Magnetic Resonance Imaging

MRI may be useful to evaluate venous and arterial anatomy when associated lesions are suspected. Three-dimensional MRI is sometimes helpful in delineating leaflet morphology and outflow anatomy.

4.3.6. Recommendation for Heart Catheterization

4.3.7. Exercise Testing

Exercise testing may be used to objectively assess functional capacity.

4.4.1. Medical Therapy

Most patients need no regular medication in the absence of specific problems. ACE inhibitors and/or diuretics may be used in patients with AV valve regurgitation and symptoms of chronic heart failure. Pulmonary vasodilation therapy may be indicated in patients with PAH and no significant left-to-right shunt who are deemed to be at high risk for surgical repair, but this should be approached with caution because of the potential for producing a significant right-to-left shunt.

4.4.2. Recommendations for Surgical Therapy

4.5.1. Key Postoperative Issues

Late complications may include left AV valve regurgitation and/or stenosis, LVOT obstruction with or without AR, and the development of heart block. Left AV valve regurgitation or stenosis requiring reoperation may occur in approximately 5% to 10% of patients. LVOT obstruction may occur in 5% of patients.

In the patient with prior repair, the onset of atrial arrhythmias should prompt a search for an underlying hemodynamic abnormality. Subaortic obstruction should be ruled out when there is a loud or harsh systolic murmur. Progressive left AV valve regurgitation may occur. The presence of an apical diastolic rumble without evidence of left-sided heart volume overload should prompt evaluation for left AV valve stenosis, particularly when there is evidence of PAH.

4.5.2. Evaluation and Follow-Up of the Repaired Patient

All patients should be assessed by and have periodic or regular follow-up with a cardiologist who has expertise in ACHD. The frequency, although typically annual, may be determined by the extent and degree of residual abnormalities. Appropriate imaging (2-dimensional and Doppler echocardiography in most patients) should be undertaken by staff trained in imaging of complex congenital heart defects and should include serial observation of AV valve function and evaluation of the LVOT. Periodic 24-hour ambulatory monitoring should be performed to assess rhythm abnormalities. Periodic cardiopulmonary testing may be helpful. Other testing should be arranged in response to clinical problems.

4.5.3. Electrophysiology Testing/Pacing Issues in Atrioventricular Septal Defects

In AVSD, the AV node and bundle of His are displaced inferiorly along the AV ring (182). This position puts the conduction system at risk for injury during surgical repair (169). Functional properties of these displaced conduction tissues can be suboptimal early in life (including the possibility of congenital complete heart block) and may worsen with age. For these reasons, the status of AV conduction must be monitored regularly with ECG and periodic Holter monitoring in adults with repaired or palliated AVSD.

4.5.4. Recommendations for Endocarditis Prophylaxis

4.6.1. Genetic Aspects

Trisomy 21, or Down syndrome, is commonly seen in association with AVSD. Such patients have a 50% risk of transmitting trisomy 21 and other genetic defects to their offspring. Reproductive counseling and discussion with the patient and those with medical power of attorney is warranted.

4.6.2. Recommendations for Pregnancy

Class I

• 1. Definitive diagnosis of PDA should be based on visualization by imaging techniques and demonstrations of the shunting across the defect (with or without evidence of clinically significant LV volume overload). (Level of Evidence: C)

Class III

• 1. Diagnostic cardiac catheterization is not indicated for uncomplicated PDA with adequate noninvasive imaging. (Level of Evidence: B)

• 2. Maximal exercise testing is not recommended in PDA with significant PAH. (Level of Evidence: B)

The diagnostic workup for a patient with a suspected PDA is directed at defining the presence and size of the PDA, the functional effect of the shunt on the left atrium and left ventricle, the pulmonary circulation, and any associated lesions.

5.3.1. Clinical Examination

If the PDA is moderate or large, the presence of a continuous machinery-type murmur, heard best at the left infraclavicular area, and increased pulses are almost diagnostic. If PAH is present, only a systolic murmur may be heard. A wide pulse pressure is present when the PDA is large and there is a large left-to-right shunt. This must be distinguished from other causes of wide pulse pressure, such as aortic insufficiency and hyperthyroidism. In a patient with a large ductus and PAH, the oxygen saturation in the upper and lower extremities may be helpful in diagnosis of a large PDA with right-to-left shunt at the ductal level, because unoxygenated blood from the ductus enters the aorta distal to the left subclavian artery, causing cyanosis and often clubbing in the lower extremities.

5.3.2. Electrocardiogram

The ECG may be normal if the ductus is small or may show left atrial enlargement and LV hypertrophy if there is a moderate left-to-right shunt. RV hypertrophy may be present if there is PAH.

5.3.3. Echocardiography

Echocardiography with color Doppler in the parasternal short-axis view is diagnostic of a PDA. Measurement of the transpulmonary gradient across the ductus with continuous-wave Doppler can estimate the pulmonary artery pressure; however, in cases of significant elevation of PVR, echocardiography may not be diagnostic, and cardiac catheterization and angiography may be indicated.

5.3.4. Chest X-Ray

The chest x-ray may or may not show cardiomegaly and increased pulmonary vascular markings, depending on the size of the left-to-right shunt. There may be a prominent proximal pulmonary artery segment indicating elevated pulmonary artery pressure. An enlarged left atrium and left ventricle due to the left-to-right shunt may point to the presence of a significant PDA. One should look for calcification in the region of the ductus, because a calcified ductus is at an increased risk of rupture during surgical repair (284–286).

5.3.5. Cardiac Catheterization

During cardiac catheterization, it is important to evaluate the degree of shunt (in either direction), the PVR, and the reactivity of the vascular bed. Angiography can determine the size and shape of the ductus. If size and shape are suitable, the PDA can be treated in the catheterization laboratory.

5.3.6. Magnetic Resonance Imaging/Computed Tomography

Other diagnostic tests including CT scan or MRI of the chest usually are not necessary to diagnose a PDA.

5.5.1. Recommendations for Medical Therapy

5.5.2. Recommendations for Closure of Patent Ductus Arteriosus

5.5.3. Surgical/Interventional Therapy

Currently, the 2 approaches for PDA closure are surgical closure (285,286) and percutaneous catheter closure.(287–316) Surgical closure of PDA in the adult may pose some problems due to the friability and/or calcification of the ductus, atherosclerosis, and aneurysm formation, as well as the presence of other unrelated comorbid conditions, such as coronary atherosclerosis or renal disease, that may adversely affect the perioperative risk. Adults with PDA are better suited for percutaneous closure with either the occlusion device or coils because of its high success and few complications (317). If the PDA is associated with other conditions that require surgical correction, the ductus may be closed during the same operation, although percutaneous closure of the PDA before other cardiac surgery may decrease the risk of cardiopulmonary bypass.

Class I

• 1. Primary imaging and hemodynamic assessment of AS and aortic valve disease are recommended by echocardiography-Doppler to evaluate the presence and severity of AS or AR; LV size, function, and mass; and dimensions and anatomy of the ascending aorta and associated lesions. (Level of Evidence: B)

• 2. Echocardiography is recommended for reevaluation of patients with AS who experience a change in signs or symptoms and for assessment of changes in AS hemodynamics during pregnancy. (Level of Evidence: B)

• 3. In asymptomatic adolescents and young adults, echocardiography-Doppler is recommended yearly for AS with a mean Doppler gradient greater than 30 mm Hg or peak instantaneous gradient greater than 50 mm Hg and every 2 years for patients with lesser gradients. (Level of Evidence: C)

• 4. Cardiac catheterization is recommended when noninvasive measurements are inconclusive or discordant with clinical signs. (Level of Evidence: C)

• 5. Coronary angiography is recommended before aortic valve surgery for coronary angiography in adults at risk for coronary artery disease. (Level of Evidence: B)

• 6. Coronary angiography is recommended before a Ross procedure if noninvasive imaging of the coronary arteries is inadequate. (Level of Evidence: C)

• 7. A yearly ECG is recommended in young adults less than 30 years of age with mean Doppler gradients greater than 30 mm Hg or peak Doppler gradients greater than 50 mm Hg. (Level of Evidence: C)

• 8. An ECG is recommended every other year in young adults less than 30 years of age with mean Doppler gradients less than 30 mm Hg or peak Doppler gradients less than 50 mm Hg. (Level of Evidence: C)

Class IIa

• 1. In asymptomatic young adults less than 30 years of age, exercise stress testing is reasonable to determine exercise capability, symptoms, and blood pressure response. (Level of Evidence: C)

• 2. Exercise stress testing is reasonable for patients with a mean Doppler gradient greater than 30 mm Hg or peak Doppler gradient greater than 50 mm Hg if the patient is interested in athletic participation or if clinical findings differ from noninvasive measurements. (Level of Evidence: C)

• 3. Exercise stress testing is reasonable for the evaluation of an asymptomatic young adult with a mean Doppler gradient greater than 40 mm Hg or a peak Doppler gradient greater than 64 mm Hg or when the patient anticipates athletic participation or pregnancy. (Level of Evidence: C)

• 4. Dobutamine stress testing can be beneficial in the evaluation of a mild aortic valve gradient in the face of low LV ejection fraction and reduced cardiac output. (Level of Evidence: C)

• 5. MRI/CT can be beneficial to add important information about the anatomy of the thoracic aorta. (Level of Evidence: C)

• 6. Exercise stress testing can be useful to evaluate blood pressure response or elicit exercise-induced symptoms in asymptomatic older adults with AS. (Level of Evidence: B)

Class IIb

• 1. Magnetic resonance angiography may be beneficial in quantifying AR when other data are ambiguous or borderline. (Level of Evidence: C)

Class III

• 1. Exercise stress testing should not be performed in symptomatic patients with AS or those with repolarization abnormality on ECG or systolic dysfunction on echocardiography. (Level of Evidence: C)

6.4.1. Clinical Examination

A delayed carotid upstroke with decreased volume is usual with severe AS. A systolic thrill may be present in the suprasternal notch or at the upper right sternal border. Palpation of the LV impulse may reveal a prominent and sustained apical impulse. A systolic ejection sound is usually present (until the fourth decade, after which calcification may restrict mobility of the cusps), usually loudest at the apex but also radiating to the base. An apical crescendo-decrescendo systolic murmur of AS radiating to the upper right sternal border and over the carotids is characteristic.

In patients with moderate to severe AR and LV enlargement, the apical impulse is displaced laterally and is hyperdynamic. An early diastolic high-pitched murmur of AR is usually loudest along the mid-left sternal border. An AR murmur that is louder at the right sternal border indicates aortic root dilatation.

6.4.2. Electrocardiogram

An ECG may reveal QRS voltage of LV hypertrophy, a left atrial abnormality pattern, and/or ST-T repolarization changes.

6.4.3. Chest X-Ray

The chest x-ray may reveal a prominent right-sided heart–border silhouette of the ascending aorta (if dilated), calcification in the aortic valve (if calcification is present), and a left-sided heart–border silhouette of LV hypertrophy/enlargement.

6.4.4. Echocardiography

The echocardiographic assessment should include valve anatomy and motion; aortic root anatomy and dimensions; LV mass, size/volumes, and function (both systolic and diastolic); and the presence or absence of AR. For AS, the continuity equation should be used in adults to calculate aortic valve area (cm²), preferably indexed to body surface area (cm² per m²).

The peak instantaneous aortic valve gradient alone may overestimate the severity of AS. The mean Doppler gradient may be more reflective of the peak-to-peak gradient as measured at catheterization that is classically used for clinical decision making. Several different methods for quantification of AR should be used, including pressure half-time, jet width, and degree of proximal descending aortic diastolic flow reversal (337).

6.4.5. Magnetic Resonance Imaging/Computed Tomography

MRI/magnetic resonance angiography or CT is valuable in evaluating anatomy of the entire aorta to quantify AR in borderline cases.

6.4.6. Stress Testing

Selective use of exercise stress testing to assess blood pressure and heart rate response, rhythm disorders, and ST-T segment changes may be warranted. The prognostic value of exercise-induced ST depression and T-wave inversion is age dependent, because 80% of adults with AS will have ST depression without prognostic significance. On the other hand, ST-T changes in an adolescent or young adult with exercise may be indications for intervention. The use of stress echocardiography to assess aortic valve area and gradient, LV ejection fraction, and LV volume response may be helpful. The selective use of dobutamine stress echocardiographic studies has been valuable in low-gradient AS with low LV ejection fractions, a situation that is uncommon in adolescents with AS or AR but may be present in older adults with concomitant myocardial or coronary artery disease.

6.4.7. Cardiac Catheterization

Diagnostic catheterization is used selectively when the clinical and echocardiography-Doppler data are incongruent or as a prelude to catheter or surgical intervention. In many laboratories, it is used primarily for the assessment of preoperative coronary anatomy in males greater than 35 years of age or those with other risk factors for atherosclerosis.

6.6.1. Recommendations for Medical Therapy

6.6.2. Catheter and Surgical Intervention

In adults with AS, intervention for significant disease usually involves AVR or Ross repair; however, selected adolescents and young adults may benefit from percutaneous balloon valvuloplasty. This technique should be performed at centers with appropriate experience and expertise (112).

Class I

• 1. Lifelong cardiology follow-up is recommended for all patients with aortic valve disease (AS or AR) (operated or unoperated; refer to Section 6.4, Recommendations for Evaluation of the Unoperated Patient). (Level of Evidence: A)

• 2. Serial imaging assessment of aortic root anatomy is recommended for all patients with BAV, regardless of severity. The frequency of imaging would depend on the size of the aorta at initial assessment: if less than 40 mm, it should be reimaged approximately every 2 years; if greater than or equal to 40 mm, it should be reimaged yearly or more often as progression of root dilation warrants or whenever there is a change in clinical symptoms or findings. (Level of Evidence: B)

• 3. Prepregnancy counseling is recommended for women with AS who are contemplating pregnancy. (Level of Evidence: B)

• 4. Patient referral to a pediatric cardiologist experienced in fetal echocardiography is indicated in the second trimester of pregnancy to search for cardiac defects in the fetus. (Level of Evidence: C)

• 5. Women with BAV and ascending aorta diameter greater than 4.5 cm should be counseled about the high risks of pregnancy. (Level of Evidence: C)

• 6. Patients with moderate to severe AS should be counseled against participation in competitive athletics and strenuous isometric exercise. (Level of Evidence: B)

• 7. Echocardiographic screening for the presence of BAV is recommended for first-degree relatives of patients with BAV. (Level of Evidence: B)

Progressive or recurrent AS, AR, or aortic enlargement may occur in the presence of a BAV. Patients with or without intervention should be followed up at least yearly for symptoms and findings of progressive AS/AR ventricular dysfunction and arrhythmia. This includes resting and stress ECGs to look for ischemic changes or arrhythmia; echocardiography-Doppler to monitor LV size/volume and systolic and diastolic function, aortic valve function, and aortic root size and anatomy; and 24-hour ambulatory ECG monitoring.

With or without intervention, both AS and AR are progressive lesions that may ultimately require surgical intervention. Prosthetic valve complications include endocarditis, thrombosis, periprosthetic regurgitation with or without hemolysis, and obstruction related to pannus in growth. Patients who undergo the Ross procedure (placement of the native pulmonary valve in the aortic position and pulmonary or aortic homograft replacement of the pulmonary valve) are at risk of developing autograft dilatation with progressive neo-AR, right-sided pulmonary homograft obstruction and/or regurgitation, and occasionally myocardial ischemia and/or infarct related to proximal coronary artery obstruction or kinking. Patients who undergo the Bentall procedure (aortic root replacement with a composite valve and graft with coronary reimplantation) are also at risk for proximal coronary obstruction.

Congenital AS with a long-standing significant gradient can be associated with ventricular arrhythmias in adulthood, including the small possibility of sudden cardiac death (346). Patients should be monitored carefully for symptoms and should have regular ECGs, plus periodic ambulatory rhythm monitoring, to assist in early detection of arrhythmias (104,347).

6.7.1. Reproduction

Most pregnancies with congenital AS are uncomplicated, but in those with severe AS, morbidity is higher, although deaths are still rare (348,349). Prepregnancy counseling is recommended. Referral to a fetal cardiologist is indicated in the second trimester because there is an increased risk of transmitting CHD to offspring. Delivery in all but the mildest of cases may be best accomplished at centers experienced with high-risk heart disease. Vaginal delivery is generally preferable to cesarean delivery except in the presence of obstetric contraindications or severe cardiac situations, such as aortic aneurysm, dissection, or critical AS, or in women who are undergoing anticoagulation (because of the risks of intracranial bleeding in the newborn). Delivery may be performed under controlled circumstances at approximately 38 weeks (provided fetal lung maturity is deemed sufficient) with appropriate monitoring of maternal heart rate, blood pressure, and fetal monitoring. Even though the 2007 AHA Scientific Statement on Prevention of Infective Endocarditis does not recommend routine prophylaxis for vaginal delivery or cesarean section, many obstetricians administer antibiotics at the time of rupture of membranes for women with aortic valve disease (74) (refer to Section 1.6, Recommendations for Infective Endocarditis, for additional information). Prepregnancy or prenatal evaluation and counseling in women with congenital aortic valve disease is essential to explore options and manage risks. The role of balloon valvuloplasty in the palliation of symptomatic pregnant women with AS requires further study, but it may be applied successfully if symptoms are refractory to medical therapy (348,350). There is no evidence that pregnancy accelerates progression of congenital AS or AR. In some cases, the drop in systemic vascular resistance that accompanies pregnancy may reduce the regurgitant fraction in AR (351).

6.7.2. Activity/Exercise

Patients with moderate to severe AS who participate in competitive athletics risk sudden cardiac death, likely from arrhythmias; therefore, they should be strongly counseled against competitive athletics and strenuous isometric exercise. Patients with aortopathy should be similarly counseled about the risks of chest injury. Exercise and athletics have been addressed in the report of Task Force 2 on CHD of the 36th Bethesda Conference (49).

6.8.1. Definition

SubAS refers to a discrete fibrous ring or fibromuscular narrowing and is distinct from genetic hypertrophic cardiomyopathy with dynamic LVOT obstruction. Often, the subaortic fibrous ring may extend onto the anterior mitral leaflet. On occasion, accessory mitral tissue or anomalous chords may cause SubAS. SubAS is usually a solitary congenital defect but may be superimposed on other congenital heart defects (eg, VSD) or acquired under certain circumstances (eg, after VSD patching). Although the obstruction is usually fixed, a secondary dynamic component may develop due to myocardial hypertrophy and dynamic LV ejection.

The prevalence of discrete SubAS among ACHD patients has been reported to be 6.5% (352), with a male preponderance of 2:1. In some cases, such as Shones syndrome, SubAS may be familial.

6.8.2. Associated Lesions

SubAS may occur as an associated defect with VSDs, AVSD, or conotruncal anomalies and may develop after patch closure of a perimembranous or malaligned VSD or AVSD (353).

6.8.3. Clinical Course With/Without Previous Intervention

The course of SubAS is often progressive. The unrepaired history includes progressive aortic valve damage, ventricular dysfunction, IE, and sudden cardiac death. The dominant feature may be obstruction or AR (352,354,355). AR occurs in more than 50% of those with SubAS. Once the peak Doppler gradient across the SubAS is more than 30 mm Hg, and if the membrane is immediately adjacent to the aortic valve or there is extension of the membrane onto the mitral valve, LVOT obstruction is likely to be progressive (354). Once the peak instantaneous Doppler LVOT gradient reaches 50 mm Hg or more, there is increased risk for moderate or severe AR (354). Patients are at risk for endocarditis, which will contribute to worsening AR (356).

6.8.4. Clinical Features and Evaluation

6.8.5. Diagnostic Cardiac Catheterization

Noninvasive imaging is usually sufficient for evaluation and monitoring of patients with SubAS. Cardiac catheterization may be indicated when SubAS is associated with other lesions. Accurate measurement of the subvalvular gradient necessitates the use of end-hole or micromanometer-tipped catheters. LV angiography is often unreliable for diagnosis of a discrete subaortic membrane, although carefully angulated views may reveal the membrane.

6.8.6. Problems and Pitfalls

The findings of a discrete fibrous subaortic ring may be subtle on TTE, unless there are good acoustical windows that allow transducer positions perpendicular to the membrane and the LVOT obstruction is examined carefully with color flow Doppler. The degree of SubAS may be underestimated or overestimated in the presence of a VSD, depending on whether the VSD is proximal or distal to the subaortic obstruction.

6.8.7. Management Strategies

6.8.8. Recommendations for Key Issues to Evaluate and Follow-Up

6.8.9. Special Issues

6.9.1. Definition

SupraAS is a fixed obstruction that arises from just above the sinus of Valsalva and extends a variable distance along the aorta. The origin of the coronary arteries is usually proximal to the obstruction, which subjects them to high systolic pressure and limited diastolic flow. There may be partial or complete ostial obstruction of the coronary arteries, ectasia, or aneurysm of the coronary arteries (360). Pathological specimens with diffuse or focal intimal and medial fibrosis, hyperplasia, dysplasia, adventitial fibroelastosis, and occasional intramedial dissection have been reported in children and more commonly in adults (361–363). This may produce significant coronary insufficiency and early onset of coronary artery disease in adult life.

6.9.2. Associated Lesions

SupraAS is commonly seen in Williams syndrome and can be associated with hypoplasia of the entire aorta, renal artery stenosis, stenoses of other major aortic branches, and long-segment peripheral pulmonary artery stenosis. Williams syndrome, an autosomal dominant disorder due to an elastin gene mutation, is associated with abnormal (elfin) facies, cognitive and behavioral disorders, and joint abnormalities. Familial non-Williams SubAS is also associated with branch pulmonary artery stenosis and hypoplasia, as well as hypoplastic descending aorta and renal artery stenosis.

6.9.3. Clinical Course (Unrepaired)

Most patients with SupraAS will be followed up from childhood and may present in adult life with symptoms due to significant outflow obstruction, systemic hypertension, or ischemia. Clinical presentation with ischemic symptomatology referable to insufficient coronary artery flow has been reported due to either anatomic obstruction or myocardial hypertrophy that limits nonepicardial coronary flow (364).

Class I

• 1. TTE and/or TEE with Doppler and either MRI or CT should be performed to assess the anatomy of the LVOT, the ascending aorta, coronary artery anatomy and flow, and main and branch pulmonary artery anatomy and flow. (Level of Evidence: C)

• 2. Assessment of anatomy and flow in the proximal renal arteries is recommended in ACHD patients with SupraAS. (Level of Evidence: C)

• 3. Assessment of systolic and diastolic ventricular function is recommended in ACHD patients with SupraAS. (Level of Evidence: C)

• 4. Assessment of aortic and mitral valve anatomy and function is recommended in ACHD patients with SupraAS. (Level of Evidence: C)

• 5. Adults with a history or presence of SupraAS should be screened periodically for myocardial ischemia. (Level of Evidence: C)

Class IIa

• 1. Exercise testing, dobutamine stress testing, positron emission tomography, or stress sestamibi with adenosine studies can be useful to evaluate the adequacy of myocardial perfusion. (Level of Evidence: C)

6.10.1. Clinical Examination

Preferential flow (Coanda effect) up the rightward portion of the ascending aorta into the right brachiocephalic artery may produce discordant amplitude of arterial pulsations in the carotids and upper extremities. There may also be a differential blood pressure between the right and left arm. A systolic thrill in the suprasternal notch is common. There may be a dynamic LV apical impulse. The second heart sound may be narrowly or paradoxically split. A fourth heart sound may be present over the LV apical thrust. An ejection click is absent. There is a crescendo-decrescendo murmur at the cardiac base, with radiation to the right side of the neck. Careful auscultation over the back and flank may reveal murmurs of peripheral pulmonary artery stenosis or renal artery stenosis. Hypertension and an abdominal bruit may signify renal artery stenosis.

6.10.2. Electrocardiogram

The ECG may reveal LV hypertrophy and secondary ST-T–wave abnormalities versus ischemic changes, depending on the severity of LVOT obstruction and the degree of coronary involvement. ST-T–wave changes may not regress after surgery, even if the gradient has been relieved; therefore, it is important to determine whether these postoperative abnormalities are recent versus chronic.

6.10.3. Chest X-Ray

The chest x-ray is often normal but may reveal LV hypertrophy or asymmetry of the aortic knob.

6.10.4. Imaging

TTE and TEE demonstrate the diameter and anatomy of the aortic sinus, sinotubular ridge, and proximal ascending aorta, the origins of the coronary arteries, the systolic gradient across the SupraAS obstruction, and the degree of LV hypertrophy. MRI/CT is required to more precisely define the anatomy of the aorta and branches, as well as the pulmonary arteries. As with any long-segment obstruction, assessment of the gradient can be challenging and may require cardiac catheterization for complete assessment of hemodynamic severity of the stenosis. Patients with Williams syndrome should have imaging of the entire aorta, including the renal arteries, because of the association with arterial stenosis at any level.

6.10.5. Stress Testing

Stress testing may be helpful to assess coronary involvement and LV compensation.

6.10.6. Myocardial Perfusion Imaging

Noninvasive screening for coronary insufficiency may be helpful if there are symptoms or ECG findings of ischemia or if there is significant coronary involvement on imaging studies. Patients with limited cognitive function may be unable to perform maximal stress testing but pharmacological stress (adenosine or dobutamine) nuclear imaging with positron emission tomography, single photon emission computed tomography, or MRI may be performed.

6.10.7. Cardiac Catheterization

Diagnostic catheterization may help to delineate anatomy and accurately measure gradients. Selective coronary angiography should be approached with caution after thorough noninvasive and angiographic examination of the aortic root, because coronary ostial stenosis is a frequent occurrence in this population. Intravascular ultrasonography may provide definition of coronary artery anatomy and define the nature and extent of the diseased vessel before consideration of repair.

6.11.1. Recommendations for Interventional and Surgical Therapy

6.11.2. Recommendations for Key Issues to Evaluate and Follow-Up

6.11.3. Special Issues

In SupraAS, abnormal systolic forces on the proximal coronary arteries and ostia may accelerate coronary artery disease, and impaired diastolic coronary filling due to ostial obstruction may cause or augment myocardial ischemia. Care must be taken to avoid circumstances that decrease diastolic pressure so that critical coronary perfusion is maintained.

6.11.4. Exercise and Athletics

Refer to Section 6.7.2, Activity/Exercise.

6.11.5. Recommendations for Reproduction

6.12.1. Definition

Discrete coarctation of the aorta consists of short-segment narrowing in the region of the ligamentum arteriosum adjacent to the origin of the left subclavian artery. In some cases, there is also narrowing of the aortic arch or isthmus. Extensive collateral vessels may arise proximal to the obstruction. The presence of abundant collaterals may reduce the gradient across the coarctation and mask the severity of the obstruction. An associated intrinsic abnormality in the aortic wall predisposes to dissection or rupture in the ascending aorta or the area of the coarctation. The adult who had surgical repair of coarctation of the aorta as an infant is more likely to have associated cardiac lesions with BAV, SubAS, VSD, and varying degrees of arch hypoplasia. Residual hemodynamic problems from any of these defects may complicate the clinical course and may require more detailed evaluation and follow-up.

6.12.2. Associated Lesions

Associated lesions include BAV, SubAS, mitral valve abnormalities such as parachute mitral stenosis, VSD, and circle of Willis cerebral artery aneurysm.

6.12.3. Recommendations for Clinical Evaluation and Follow-Up

6.13.1. Electrocardiogram

The ECG may demonstrate LV hypertrophy and secondary ST-T–wave abnormalities but occasionally will show RV conduction delay.

6.13.2. Chest X-Ray

An anterior-posterior projection of the chest x-ray may show a prominent curvilinear shadow along the mid-right sternal border that represents a dilated ascending aorta. An indentation at the coarctation site may produce a “3 sign” adjacent to the area beneath the transverse arch and above the main pulmonary artery silhouette. Notching on the underside of the ribs (usually 3 to 9) from collateral vessels may be apparent.

6.13.3. Echocardiography and Doppler

The coarctation may be demonstrated on a suprasternal notch view of the aortic arch and proximal descending aorta, which, when combined with color flow imaging and continuous-wave spectral Doppler interrogation, may demonstrate turbulence in the proximal descending aorta and show the characteristic flow profile of forward diastolic flow. An abnormal Doppler flow pattern may also be noted in the abdominal aorta, ie, decreased pulsatility and absence of early diastolic flow reversal. Abnormal flow in collateral vessels can be detected by color flow and pulse Doppler. It is also important to measure the dimensions of the aortic annulus, aortic sinuses, sinotubular ridge, and ascending aorta. The anatomy of the aortic valve should be determined, as well as LV size, mass, and function. Careful investigation should rule out associated lesions such as VSD, SubAS, and mitral valve deformity.

6.13.4. Stress Testing

In addition to the usual evaluation of exercise capacity and symptoms, rhythm, and ECG response, stress testing goals include assessment of the systemic arterial blood pressure response at rest and with exercise, which is a surrogate evaluation of the coarctation gradient. Stress-echocardiography–Doppler is valuable and is targeted at obtaining the rest and exercise suprasternal notch continuous-wave Doppler coarctation gradient, including the diastolic profile. Arm-leg blood pressure and echocardiography-Doppler gradient assessment during exercise may be problematic and better assessed with supine ergometer stress testing or dobutamine stress testing.

6.13.5. Magnetic Resonance Imaging/Magnetic Resonance Angiography or Computed Tomography With 3-Dimensional Reconstruction

MRI or CT angiography with 3-dimensional reconstruction identifies the precise location and anatomy of the coarctation and entire aorta, as well as collateral vessels (366). Magnetic resonance angiography to search for aneurysms of the intracranial arteries is appropriate. Magnetic resonance angiography may also be useful to quantify collateral flow.

6.13.6. Catheterization Hemodynamics/Angiography

Diagnostic cardiac catheterization is mainly justified when associated coronary artery disease is suspected and surgery is planned; however, MRI/magnetic resonance angiography or CT remains the preferred means of imaging the area of coarctation. Cardiac catheterization is also indicated if catheter-based intervention (angioplasty or stent) is to be performed, and generally, this should be performed only in centers with interventional capability.

6.13.7. Problems and Pitfalls

In the presence of sizable collaterals, femoral pulses may be less diminished, and catheter-based and Doppler systolic gradients may not capture the degree of obstruction of aortic coarctation and hence may be misleading. Repair of coarctation late in childhood or in adult life often does not prevent persistence or late recurrence of systemic hypertension. Hypertension can also reappear several years after coarctation repair.

6.14.1. Medical Therapy

Hypertension should be controlled by beta blockers, ACE inhibitors, or angiotensin-receptor blockers as first-line medications. The choice of beta blockers or vasodilators may be influenced in part by the aortic root size, the presence of AR, or both.

6.14.2. Recommendations for Interventional and Surgical Treatment of Coarctation of the Aorta in Adults

6.14.3. Recommendations for Key Issues to Evaluate and Follow-Up

6.14.4. Exercise and Athletics

Exercise and athletics have been addressed recently by the 36th Bethesda Conference (49). Significant residual or unrepaired coarctation, associated BAV with AS, or a dilated aortic root warrants prohibition of contact sports, isometric or heavy weight lifting, and sudden stop-start sports. It would be prudent to have a cardiology consultation, stress testing, and an echocardiogram before permitting low- to moderate-level dynamic sports or light weight lifting.

6.14.5. Reproduction

Pregnancy in coarctation of the aorta continues to be a source of concern, but major cardiovascular complications are infrequent (368). An assessment of the hemodynamic status, severity of coarctation, and associated lesions, particularly BAV, AS, or a significantly dilated root, should be undertaken before pregnancy for proper planning and advice. The potential for aortic dissection remains, although it is quite small unless the aorta is dilated significantly.

6.14.6. Endocarditis Prophylaxis

Patients with uncomplicated native coarctation or uncomplicated, recurrent coarctation that is successfully repaired do not require endocarditis prophylaxis unless there is a prior history of endocarditis or a conduit has been inserted or if surgical repair or stenting has been performed less than 6 months previously (refer to Section 1.6, Recommendations for Infective Endocarditis, for additional information).

7.3.1. Definition

Valvular PS is usually an isolated lesion, occurs in approximately 7% to 12% of all CHD, and accounts for 80% to 90% of all lesions that cause RVOT obstruction (379). Its inheritance rate is low, ranging from 1.7% to 3.6% (380,381). Approximately 20% of patients with valvular PS have a dysplastic valve (382,383), and if part of Noonan syndrome, these patients have an autosomal dominant trait with variable penetrance that has been mapped to chromosome 12 (384,385).

There are 3 morphological types of clinical significance.

• 1. The typical dome-shaped pulmonary valve is characterized by a narrow central opening but a preserved, mobile valve mechanism. Three rudimentary raphes are usually present, but clear-cut commissures are not identifiable. The pulmonary trunk is dilated, mostly owing to an inherent medial abnormality. The jet from the stenotic valve tends to favor flow to the left pulmonary arterial branch. Calcification of the valve is occasionally seen in older adult patients.

• 2. The dysplastic pulmonary valve is less common. The leaflets are poorly mobile, and there is marked myxomatous thickening with no commissural fusion. The pulmonary annulus and the outflow tract may also be narrowed. The lesion is a frequent component of the Noonan syndrome.

• 3. The unicuspid or bicuspid pulmonary valve is generally a feature of tetralogy of Fallot. It may or may not create significant obstruction itself.

PS is considered mild when the peak gradient across the valve is less than 30 mm Hg, moderate when the gradient is 30 to 50 mm Hg, and severe when the gradient is greater than 50 mm Hg.

7.4.1. Unrepaired Patients

Valvular PS usually presents with an asymptomatic systolic murmur, but occasionally, a patient will present with exercise intolerance. Stenosis is rarely progressive when the initial gradient is mild, but moderate PS can progress owing to progressive valve stenosis or reactive hypertrophy of the infundibulum.

The outcome of medically managed patients with PS was discussed in the Second Natural History Study (104). Patients with peak-to-peak catheterization-derived gradients greater than 80 mm Hg underwent pulmonary valvotomy. Patients with gradients greater than 50 mm Hg clearly did worse than those with gradients less than 50 mm Hg (104).

7.4.2. Noonan Syndrome Patients With Prior Repair

For the most part, the clinical issues regarding when to intervene in the postoperative patient are similar to those for patients before surgery. The main difference is in the presence of valvular regurgitation. In low-pressure pulmonary regurgitation (mean pulmonary artery pressure less than 20 mm Hg), the diastolic gradient between the RV and pulmonary artery may be quite small, and significant pulmonary regurgitation may be difficult to detect. Restenosis after percutaneous valvuloplasty is more common if a residual gradient greater than 30 mm Hg remains immediately after the procedure. A dilated pulmonary artery may not decrease in size after pulmonary valve intervention.

Class I

• 1. Two-dimensional echocardiography-Doppler, chest x-ray, and ECG are recommended for the initial evaluation of patients with valvular PS. (Level of Evidence: C)

• 2. A follow-up physical examination, echocardiography-Doppler, and ECG are recommended at 5-year intervals in the asymptomatic patient with a peak instantaneous valvular gradient by Doppler less than 30 mm Hg. (Level of Evidence: C)

• 3. A follow-up echocardiography-Doppler is recommended every 2 to 5 years in the asymptomatic patient with a peak instantaneous valvular gradient by Doppler greater than 30 mm Hg. (Level of Evidence: C)

Class III

• 1. Cardiac catheterization is unnecessary for diagnosis of valvular PS and should be used only when percutaneous catheter intervention is contemplated. (Level of Evidence: C)

7.5.1. Clinical Examination

Most adult patients with PS are normal in appearance. In the Noonan syndrome, there is characteristically short stature, webbed neck, hypertelorism, lymphedema, low-set ears and hairlines, hyperelastic skin, chest deformities (eg, flat, pectus excavatum or pectus carinatum), and micrognathia (383). Approximately one third of Noonan patients are mentally disabled, and cryptorchidism is common.

The cardiac examination of a patient with PS is dependent on the severity of stenosis, the pathology of the valve, and any associated cardiac lesions. The physical examination in mild PS is characterized by a normal jugular venous pulse, no RV lift, and a pulmonary ejection sound that tends to decrease with inspiration. It is the only right-sided auscultatory event that decreases with inspiration (owing to premature opening of the pulmonary valve by the atrial kick into the stiff RV). A pulmonary ejection murmur that increases with inspiration is usually heard ending in mid systole. In severe PS, there is usually an elevated jugular venous pressure with a prominent “A” wave. An RV lift is common, and there is a much louder and longer pulmonary ejection murmur with loss of the ejection sound. Wide splitting of S₂ may be present, and P₂ may be reduced or absent. A right-sided S₄ may also be heard. Evidence for right-sided heart failure is uncommon until late in the disease process.

7.5.2. Electrocardiogram

The ECG is usually normal when the RV systolic pressure is less than 60 mm Hg, but more severe obstruction leads to right atrial enlargement, right-axis deviation, and RV hypertrophy (386).

7.5.3. Chest X-Ray

The heart size on chest x-ray is normal unless there is an associated cardiac lesion. Vascular fullness in the left lung base greater than the right base (Chen's sign) is due to the preferential pulmonary flow to the left lung in patients with PS (387). Dilatation of the main pulmonary artery is common in doming PS but not in dysplastic PS. Calcification of the valve may rarely be seen in older patients. The right atrium may be enlarged.

7.5.4. Echocardiography

TTE is generally definitive, but in some patients, TEE may better define the anatomy of the RVOT. A Doppler gradient is readily determined and is used to define when to intervene. Pulmonary valve mobility can also be assessed, along with the presence of other cardiac lesions, and RV function can be semiquantified. Saline microcavitations can help define any right-to-left shunt due to a PFO. When the PS is severe, systolic interventricular septal flattening may be present. In patients with a dysplastic pulmonary valve, the valve can be seen to be thickened and immobile, with the absence of poststenotic dilation of the main pulmonary artery. Evidence of pulmonary regurgitation should be sought by Doppler examination.

7.5.5. Magnetic Resonance Imaging/Computed Tomography

In uncomplicated valvular PS, the use of MRI or CT is simply confirmatory. These studies do provide excellent imaging of the main, branch, and peripheral pulmonary arteries and are useful when these associated lesions are of concern or to assess the degree of pulmonary regurgitation or TR.

7.5.6. Cardiac Catheterization

Cardiac catheterization is rarely necessary for diagnosis. Gradients above, at, and below the pulmonic valve should be obtained. A peak RV systolic pressure of less than 35 mm Hg and a systolic pulmonary valve gradient of less than 10 mm Hg are considered the upper limits of normal. RV angiography helps define contractile function, the presence of infundibular obstruction, and mobility of the pulmonary valve. Angiography of the pulmonary artery can assess the degree of pulmonary regurgitation and any stenotic lesions in the main, branch, or peripheral pulmonary arteries.

There is little progression in PS severity when the gradient is less than 30 mm Hg; such patients can be followed up at least every 5 years with a clinical examination and Doppler echocardiogram. Those with more significant stenosis should be followed up on a yearly basis. Most patients with PS who reach adulthood are asymptomatic and require no specific therapy. If a dynamic outflow tract obstruction exists, therapy with drugs that slow the heart rate and improve diastolic filling time (ie, beta blockers) (388) and those that might potentially reduce the systolic gradient and improve lusitropy (ie, calcium channel blockers and disopyramide) may also be used clinically, in a manner similar to that in patients with hypertrophic cardiomyopathy and other diseases of LV diastolic dysfunction. Elevated right-sided heart pressures, edema, and ascites can be treated with thiazides, loop diuretics, and aldosterone antagonists as appropriate.

7.5.7. Relationship Between Peak Instantaneous Doppler Echocardiographic Pressure Gradients and Peak-to-Peak Cardiac Catheterization Gradients

The 2006 ACC/AHA valvular heart disease guidelines and much of the older literature used the catheter-derived peak-to-peak gradient across the pulmonary valve to determine when to intervene in valvular PS (112). Patients with valvular PS do not require cardiac catheterization for diagnosis, however, and the relationship between the peak-to-peak invasive hemodynamic gradient and the Doppler peak instantaneous gradient becomes relevant in deciding appropriateness for invasive evaluation and intervention. There are recent data that suggest the peak-to-peak gradient by cardiac catheterization correlates best with the mean Doppler (and not peak instantaneous Doppler) gradient in this situation (389) and that the peak instantaneous gradient systematically overestimates the peak-to-peak cardiac catheterization gradient by slightly more than 20 mm Hg. Correlation of the echocardiography-Doppler gradient with other clinical findings is important.

7.6.1. Dyspnea

Dyspnea occurs in patients with severe PS. Whenever symptoms do not match the severity of the anatomy (ie, symptoms with a PS gradient less than 50 mm Hg or no symptoms and a severe PS gradient), exercise studies are often helpful in assessment of functional capacity. A determination of maximal oxygen consumption along with exercise duration is also useful.

7.6.2. Chest Pain

In the older patient or one with multiple risk factors for coronary artery disease, if angina-type symptoms are present, a stress imaging study should be done to help screen for functional coronary artery disease. Markedly enlarged pulmonary artery aneurysms may rarely cause chest pain by compression of the left main coronary artery.

7.6.3. Enlarging Right Ventricle

Progressive RV dilation in patients with PS suggests an associated lesion such as ASD. In the postoperative patient, this may imply restenosis or pulmonary regurgitation. The severity of low-pressure pulmonary regurgitation may be difficult to diagnose clinically or by echocardiography, because the RV end-diastolic pressure may be only a few millimeters of mercury below the pulmonary arterial end-diastolic pressure. This results in a minor diastolic gradient that is difficult to detect by auscultation and color Doppler because the flow is laminar. Occasionally, imaging with MRI or pulmonary angiography may be required.

7.6.4. Pulmonary Arterial Hypertension

Patients with isolated valvular PS are not expected to have PAH. If evidence of PAH is present, then other causes must be considered, such as associated peripheral pulmonary artery stenosis. Patients who had a systemic–to–pulmonary artery shunt as a child may have branch pulmonary artery stenosis at the site of the anastomosis. In some postoperative patients, repair of the PS may have been only part of a larger surgical procedure that included a late VSD closure or patent ductus repair, and pulmonary vascular disease may now complicate the clinical picture.

7.6.5. Cyanosis

Cyanosis is usually not part of RVOT lesions, unless there is an associated ASD or a substantial increase in right atrial pressure and right-to-left shunting through a PFO. Otherwise, one should seek an alternative source of the cyanosis.

7.6.6. Systemic Venous Congestion

The presence of systemic venous congestion suggests significant RV dysfunction and is an uncommon finding in isolated PS. Exceptions occasionally seen in adults are those patients with cor pulmonale due to intrinsic lung disease or to left-sided heart disease, those with constrictive pericarditis or a restrictive cardiomyopathy, and those with severe TR due to other causes (eg, endocarditis, percutaneous pacemaker, or Ebstein's anomaly). These diagnoses must be excluded before the right-sided heart failure is attributed to PS.

7.7.1. Recommendations for Intervention in Patients With Valvular Pulmonary Stenosis

7.7.2. Percutaneous Balloon Pulmonary Valvotomy

Since the initial successful report of percutaneous balloon valvotomy for pulmonary valve stenosis in 1982 (391), the procedure has evolved to become the treatment of choice for patients with classic domed valvular PS. Balloon valvotomy produces relief of the gradient by commissural splitting. As might be expected from the morphology, results in patients with a dysplastic pulmonary valve are less impressive. In the Valvuloplasty and Angioplasty of Congenital Anomalies (VACA) registry, in 784 cases, the mean transvalvular gradient declined from 71 to 28 mm Hg in patients with typical PS and from 79 to 49 mm Hg in patients with a dysplastic valve (392).

The procedure is usually performed from the right femoral vein. Because of the elasticity of the pulmonary annulus, it has been found that oversizing the balloons up to 1.4 times the measured pulmonary annulus is more effective in achieving a successful result (usually defined by a final valvular gradient of less than 20 mm Hg). To accomplish this oversizing in adults, a double-balloon procedure is frequently used. In general, acute complications from the procedure have been minimal. During the acute performance of the valvotomy, vagal symptoms predominate, along with catheter-induced ventricular ectopy and occasionally right bundle-branch block. Other complications include pulmonary valve regurgitation, pulmonary edema (presumably from increasing pulmonary blood flow to previously underperfused lungs), cardiac perforation and tamponade, high-grade AV nodal block, and transient RVOT obstruction. The latter is sometimes referred to as a “suicidal right ventricle” and is due to abrupt infundibular obstruction once the pulmonary valve obstruction has been relieved (393). This may be alleviated by volume expansion and beta blockade. This postprocedural infundibular obstruction tends to regress over time.

7.7.3. Surgical Pulmonary Valvotomy or Valve Replacement

In 1948, the first pulmonary valve commissurotomies were reported by Sellors (394). Varco introduced the technique of “blind” pulmonary valvotomy in 1951 (395), although better results were found with direct visualization and open techniques quickly became the norm. In patients with a dysplastic valve, partial or total valvectomy was required, and often, a transannular patch was needed owing to annular or pulmonary trunk hypoplasia. Residual pulmonary valve regurgitation is commonplace with all these procedures (396), and late pulmonary valve replacement is often necessary decades later.

In patients with PS and significant valvular regurgitation, valve replacement may be required. Mechanical valve replacement (397) is rarely used because of concerns regarding thrombosis and the potential need for measurement of pulmonary pressures; mechanical PVR can be considered in selected patients who have had multiple previous operations and are undergoing warfarin therapy because of another mechanical valve prosthesis. Owing to low pulmonary artery pressure and slow flow despite anticoagulation, there is a high risk of valve thrombosis with mechanical prosthetic valves in the pulmonary position. Bioprosthetic valves (398) can be effectively implanted with good durability in patients of all ages, although valvular degeneration eventually ensues in all. The bovine jugular vein valved xenograft has also been used with good early but mixed late results (399). Although pulmonary homograft replacement (398) is a popular means of surgical reconstruction in children, it has limited durability in the adult patient, especially in the setting of elevated pulmonary artery pressures. Stenosis of the pulmonary homograft has been a particular issue in patients undergoing the Ross procedure (400).

In patients with a markedly dilated main pulmonary artery associated with PS, there are no guidelines to suggest a particular size that requires operative intervention. Because these are low-pressure aneurysms that rarely, if ever, rupture, the decision to intervene surgically is usually a function of whether they are symptomatic, are compressing contiguous structures, or are associated with pulmonary regurgitation and subsequent right ventricle enlargement (378). In these patients, reduction pulmonary arterioplasty or main pulmonary artery replacement with a tube graft or valved tube graft can be accomplished.

Early mortality for isolated pulmonary valve operation is approximately 1% in children. There are no comparable adult data. Freedom from reoperation for bioprosthetic valve deterioration is approximately 90% at 10 years. Residual obstruction may progress. Pulmonary regurgitation may occur; progression of pulmonary regurgitation may eventually necessitate pulmonary valve replacement. Late survival is similar to that of an age-matched population when valvular RVOT obstruction occurs as an isolated lesion.

Class I

• 1. Periodic clinical follow-up is recommended for all patients after surgical or balloon pulmonary valvotomy, with specific attention given to the degree of pulmonary regurgitation; RV pressure, size, and function; and TR. The frequency of follow-up should be determined by the severity of hemodynamic abnormalities but should be at least every 5 years. (Level of Evidence: C)

The murmur of pulmonary regurgitation is easily missed on clinical examination, because it is soft and often short owing to the rapid equilibration of pulmonary artery diastolic pressure with the diastolic pressure in the right ventricle. It may be missed on echocardiography because of minimal turbulence and only small pressure differences between the right ventricle and the pulmonary artery. After pulmonary valvuloplasty the heart size should be normal on chest x-ray. A progressively increasing heart size should prompt the search for pulmonary regurgitation or another lesion. The development of atrial arrhythmias should also prompt a search for residual hemodynamic lesions such as pulmonary regurgitation.

Long-term follow-up data for percutaneous balloon pulmonary valvotomy are now available for up to 10 years. In one representative study (401), mean follow-up of 6.4 plus or minus 3.4 years was available in 62 patients. Some persistent pulmonary regurgitation was present in 39%, and the restenosis (greater than 35 mm Hg at follow-up) rate was only 4.8%. In a smaller study in adults (402) followed up for 4.5 to 9 years, no restenosis was reported in 24 patients after the gradient was reduced from 82 plus or minus 29 mm Hg to 37 plus or minus 14 mm Hg by the acute procedure. In another report of 127 adult patients without valve dysplasia, excellent results were also observed, with a residual gradient primarily found only in those patients who had an inadequate initial result (403). In the VACA registry (404), follow-up data were available on 533 patients a mean of 8.7 years after valvotomy. A suboptimal result (defined as gradient greater than 35 mm Hg at the end of the procedure) was present in 23%. Valve morphology and annulus size were the most significant predictors of long-term results. Pulmonary regurgitation was more commonly seen when the balloon-to-annulus ratio exceeded 1.4, which suggests an optimal ratio of 1.2 to 1.4. Subjective grades of pulmonary regurgitation reported included the following: none (26%), trivial (22%), mild (45%), moderate (7%), and severe (0%). Failure of the original procedure to reduce the gradient significantly also predicted poor long-term success. When restenosis does occur after percutaneous balloon pulmonary valvotomy, it appears that a repeat procedure is effective in patients without dysplastic pulmonary valves (405). Several studies have been reported that compared balloon valvotomy with matched surgical control patients (392,406,407).

In 1 study (406), gradients were slightly but statistically higher in the post–balloon valvotomy group than in the surgical cohort (24 plus or minus 2.7 versus 16 plus or minus 1.5 mm Hg). Pulmonary regurgitation, however, was absent (55%) or mild (45%) in the valvuloplasty group yet at least mild (45%) or moderate (45%) in the surgical cohort. Ventricular ectopy was also much more common in the surgical group (70% versus 5%). Thus, overall results were more favorable in the balloon valvotomy group.

Percutaneous balloon valvotomy thus appears to be an excellent alternative to surgical valvuloplasty or valve replacement in most patients with classic, doming, valvular PS. Its use in patients with a dysplastic valve is much less established, although several authors have suggested situations wherein it may be feasible (408,409). Postoperative valvular, conduit, or homograft stenosis contributes to the causes of clinical RVOT obstruction, with valvular degeneration expected after approximately 10 to 12 years (410). There are some data showing that porcine valves may outlast homografts in children (411). After surgical valvotomy, pulmonary regurgitation is common, and after 3 to 4 decades, RV dysfunction and secondary TR may ensue, necessitating pulmonary valve replacement in some patients. This should be undertaken before there is severe RV enlargement and any more than mild RV dysfunction. Deteriorating exercise capacity or the onset of atrial or ventricular arrhythmias is also a sign of the need for pulmonary valve replacement. This emphasizes the need for lifelong follow-up in such patients (412).

7.8.1. Reproduction

Pregnancy is well tolerated unless the lesion is extremely severe. Percutaneous valvotomy can be performed during pregnancy if necessary, although the need is unusual.

7.8.2. Endocarditis Prophylaxis

Pulmonary valve endocarditis is very rare, and endocarditis prophylaxis is not recommended (413) (refer to Section 1.6, Recommendations for Infective Endocarditis, for additional information).

7.8.3. Exercise and Athletics

The 1986 AHA committee report (414) recommends no restriction of activity with mild PS and nonstrenuous exercise with moderate PS; it restricts only those with severe PS. For the competitive athlete, the special ACC Task Force report (415) recommends that PS patients with peak gradients less than 50 mm Hg may participate in all competitive sports, although those with more severe PS should participate only in low-intensity sports.

7.9.1. Definition and Associated Lesions

Abnormal narrowing of the main pulmonary artery, the major pulmonary arterial branches, and the peripheral pulmonary arteries can all lead to obstruction of RV outflow. Supravalvular PS or pulmonary arterial stenosis is caused by narrowing of the main pulmonary trunk, the pulmonary arterial bifurcation, or the primary and/or intrapulmonary branches. One variant, the hourglass pattern, is similar to SupraAS and is technically a form of valvular PS, because it is due to stenosis at the commissural ridge of the valve (416). The other pulmonary supravalvular lesions are in the main branches or more peripheral and range from single focal lesions to diffuse hypoplastic ones to frank occlusion; they may be secondary to previous placement of a pulmonary artery band. The pulmonary arterial segments distal to patent stenotic lesions often exhibit poststenotic dilation. Membranous forms of obstruction both above and below the pulmonary valve have also been described. Central and peripheral pulmonary artery stenosis may be a major cardiovascular feature in the Alagille and Keutel syndromes (417–421). Pulmonary artery stenoses are also sequelae of the congenital Rubella syndrome, Williams syndrome, or scarring at the site of a previous pulmonary artery band or aorticopulmonary shunt. These lesions appear pathologically as areas of fibrous intimal proliferation with varying degrees of medial hyperplasia and loss of elastic fibers in the affected areas. The lesions can be single or multiple, and their severity can range from mild valvular stenosis to complete occlusion. Similar lesions have been reported in patients with systemic vasculitis, such as Behcet or Takayasu arteritis, and in patients with Ehlers-Danlos and Silver syndrome. Owing to the normally low vascular resistance present in the pulmonary circuit, a great deal of vascular obstruction is required to result in PAH. Despite the fact that it is unclear what severity of stenosis is truly flow-limiting in the pulmonary arteries, most clinicians define an angiographically significant lesion to be greater than 50% diameter narrowing. These significant lesions would be expected to have a pressure gradient across them and to result in hypertension in the more proximal pulmonary artery.

7.9.2. Clinical Course

Peripheral pulmonary artery stenoses tend to occur in multiple tertiary branches of the pulmonary tree and are progressive; by the time patients are seen as adults, there may be considerable loss of lung parenchyma due to totally occluded segmental pulmonary arteries. With PAH, pulmonary valve regurgitation may be expected.

7.10.1. Electrocardiogram

ECG criteria for RV hypertrophy with strain and right-axis deviation are commonplace in the adult and are related to the severity of the lesion and the RV systolic pressure.

7.10.2. Chest X-Ray

The lung fields on chest x-ray may reveal varying shadows of poststenotic peripheral arterial dilatations in patients with peripheral PS.

7.10.3. Echocardiography

TTE-Doppler helps confirm the presence of RV systolic hypertension and any pulmonary valve regurgitation. Echocardiography may also be able to define proximal pulmonary branch stenosis. It is of much less value in the identification of peripheral PS. TEE is likewise useful only when there are proximal pulmonary artery lesions. Radionuclide studies reveal the severity of peripheral PS in different lung segments.

7.10.4. Magnetic Resonance Imaging/Computed Tomography

Cardiac MRI with pulmonary angiography and CT are much superior to echocardiography-Doppler for imaging these lesions, and both can help confirm the diagnosis.

7.10.5. Cardiac Catheterization

Cardiac catheterization with contrast angiography is definitive and provides additional information regarding the extent of these lesions, the angiographic severity, the pressure drop across the lesions, and the degree of any associated PAH.

Class I

• 1. Patients with suspected supravalvular, branch, or peripheral PS should have baseline imaging with echocardiography-Doppler plus 1 of the following: MRI angiography, CT angiography, or contrast angiography. (Level of Evidence: C)

• 2. Once the diagnosis is established, follow-up echocardiography-Doppler to assess RV systolic pressure should be performed periodically, depending on severity. (Level of Evidence: C)

7.11.1. Problems and Pitfalls

Patients with peripheral PS lesions may present with what appears to be a functional precordial murmur. Auscultation over the lung fields should reveal the characteristic vascular bruits. Many patients are asymptomatic. More often in adults, the patient presents with dyspnea of unknown origin. Elevated RV systolic pressure identified by echocardiography should prompt a search for causes of PAH that include collagen vascular disease, portal hypertension, human immunodeficiency virus, use of anorexigens, veno-occlusive disease, sleep apnea, chronic obstructive pulmonary disease, and sarcoidosis (424).

7.11.2. Management Strategies

Class I

• 1. Percutaneous interventional therapy is recommended as the treatment of choice in the management of appropriate focal branch and/or peripheral pulmonary artery stenosis with greater than 50% diameter narrowing, an elevated RV systolic pressure greater than 50 mm Hg, and/or symptoms. (Level of Evidence: B)

• 2. In patients with the above indications for intervention, surgeons with training and expertise in CHD should perform operations for management of branch pulmonary artery stenosis not anatomically amenable to percutaneous interventional therapy. (Level of Evidence: B)

Branch pulmonary artery stenosis and/or hypoplasia may be associated with a variety of cardiac malformations or may be a residual from prior surgical intervention, such as an anastomotic lesion at the distal site of a prior Blalock-Taussig or Potts shunt procedure. Surgical exposure to these areas is often difficult, which favors attempts at percutaneous approaches. In some series, the acute success rate—defined as an increase of greater than 50% of predilation vessel diameter or a 20% decrease in systolic RV–to–aortic systolic pressure ratio (425)—has been as high as 60% initially. Complications have included arterial rupture, unilateral or segmental edema, thrombosis, and hemoptysis. In some instances, higher-pressure balloon inflations have improved results.

The highly elastic pulmonary arteries have proved resilient to balloon procedures, and angioplasty methods have generally given way to stent procedures in which there appears to be a higher initial success rate and a lower intermediate-term incidence of restenosis (426). When restenosis does occur, it may respond to redilation. Stents have proved effective compared with either percutaneous angioplasty or surgical intervention in this situation. Stenting of branch PS has also been used in the operating room as adjunctive therapy.

The use of balloon angioplasty and stenting may also be applied to more distal peripheral PS, although the results have generally been less impressive than with branch stenosis (427). Although initial angiographic results from stenting in this situation often appear encouraging, there are currently inadequate data to recommend the routine use of percutaneous intervention for patients with distal peripheral PS. Surgical intervention with patch enlargement is feasible for supravalvular PS when an oval patch is used (428), and more proximal branch stenosis may also be approached surgically if the vessel is of adequate size. More peripheral stenotic segments cannot usually be corrected with surgery. At times, the only alternative for patients with severe peripheral PS associated with major loss of lung parenchyma is lung transplantation.

7.12.1. Recommendations for Evaluation and Follow-Up

7.13.1. Definition and Associated Lesions

Some gradient is to be expected across any RV–pulmonary artery conduit or any bioprosthetic valve placed in the RVOT. A variety of conduit types have been used in the RVOT, some with valvular tissue and some without. Pulmonary homografts have now come into widespread use, although bioprosthetic (porcine or pericardial) pulmonary valve replacements are still performed. Several groups have also reported experience with use of the valved bovine jugular venous conduit (Contegra), although some issues regarding stenosis at the distal pulmonary site have been noted (429). The normal gradient anticipated across the various prosthetic valves is dependent on the valve size and the flow across the valve. Associated pulmonary regurgitation increases the gradient. A recent review from the American Society of Echocardiography outlines the normally expected Doppler gradients for all prosthetic valves (430) and takes into account the type of valve and the size. Stenosis of the RV–pulmonary artery conduit or any bioprosthetic valve in this position may be graded with the peak Doppler gradient, with a 50-mm Hg gradient considered severe stenosis. This would be expected to result in an RV systolic pressure equal to or greater than 75 mm Hg. In children and young adults, a ratio of RV systolic to LV systolic pressure greater than 0.67 is another parameter for defining a severe lesion. In older adults, the systemic resistance is much higher than in children, and the use of this ratio has been less helpful.

7.13.2 Recommendation for Evaluation and Follow-Up After Right Ventricular–Pulmonary Artery Conduit or Prosthetic Valve

7.13.3. Clinical Examination

A precordial systolic murmur that transmits to the back is an important sign of conduit obstruction. The pulmonary closure sound is usually inaudible. In patients with significant RV obstruction, jugular venous distension with a prominent A wave may be appreciated.

7.13.4. Electrocardiogram

Because all bioprosthetic valves and conduit valves eventually degenerate, both pulmonary regurgitation and stenosis will ensue. As with many lesions that result in RV pressure or volume overload, the ECG may reflect RV hypertrophy or any associated arrhythmias.

7.13.5. Chest X-Ray

The chest x-ray may reveal an enlarging right side of the heart or calcification within the valve or conduit.

7.13.6. Echocardiography

TTE and Doppler are particularly helpful in delineating hemodynamics and facilitate measurement of RV pressure, RV size and function, and gradient across the conduit and prosthetic valve; however, tubular narrowing in a conduit is often associated with underestimation of the gradient.

7.13.7. Magnetic Resonance Imaging/Computed Tomography

CT and MRI can be used to help define lesion severity and may demonstrate conduit adherence to the sternum, something of interest to the surgeon if a reoperation is contemplated.

7.13.8. Cardiac Catheterization

Because distal conduit stenosis is frequent, cardiac catheterization and angiography in addition to CT and MRI can define the level and severity of stenosis.

Class I

• 1. Surgeons with training and expertise in CHD should perform operations for patients with severe pulmonary prosthetic valve stenosis (peak gradient greater than 50 mm Hg) or conduit regurgitation and any of the following:

  • a. Decreased exercise capacity. (Level of Evidence: C)

  • b. Depressed RV function. (Level of Evidence: C)

  • c. At least moderately enlarged RV end-diastolic size. (Level of Evidence: C)

  • d. At least moderate TR. (Level of Evidence: C)

Class IIa

• 1. Either surgical or percutaneous therapy can be useful in symptomatic patients with discrete RV–pulmonary artery conduit obstructive lesions with greater than 50% diameter narrowing or when a bioprosthetic pulmonary valve has a peak gradient by Doppler greater than 50 mm Hg or a mean gradient greater than 30 mm Hg. (Level of Evidence: C)

• 2. Either surgical or percutaneous therapy can be useful in asymptomatic patients when a pulmonary bioprosthetic valve has a peak Doppler gradient greater than 50 mm Hg. (Level of Evidence: C)

Class IIb

• 1. Surgical intervention may be considered preferable to percutaneous catheter intervention when an associated Maze procedure is being considered for the treatment of atrial arrhythmia. (Level of Evidence: C)

7.14.1. Medical Therapy

Medical management of symptomatic patients with residual or recurrent RVOT obstruction is limited to diuresis and is generally ineffective. There are no effective preventative treatments.

7.14.2. Interventional Catheterization

Both angioplasty and stenting have been applied to obstruction in an RV–to–pulmonary artery conduit. Such cases can present difficult issues, and the decision to proceed with a percutaneous intervention should be made in association with an ACHD surgeon or an ACHD interventionalist. Several investigators have reported success in reducing gradients in RV–to–pulmonary artery conduits or bioprostheses using balloon dilation (431,432), stenting, or percutaneous valve replacement (431–433). The value of these options often depends on whether a discrete obstruction occurs at the stenotic conduit valve or is the result of conduit compression between the sternum and heart, intimal peel formation, or obstruction at the ventricular anastomosis. Obstruction of the distal end of the conduit may be amenable to percutaneous balloon intervention in which the procedure may be useful as a temporary palliation that allows postponement of surgical intervention (434).

A potential alternative to either balloon dilation or stenting in conduit obstruction has been presented recently by Bonhoeffer et al (435), wherein pulmonary valves have been implanted percutaneously within the stenotic conduit. The authors used a bovine jugular venous valve mounted onto a balloon-expandable stent for percutaneous placement. Although the procedure is investigational, it appears quite possible that this approach will evolve to provide an excellent option for the therapy of conduit stenosis and regurgitation. The procedural concept has yet to be proven in larger clinical trials and has yet to be shown to be effective in patients with native valvular PS or regurgitation.

7.14.3. Surgical Intervention

Surgical intervention is generally required once there is evidence of important RV enlargement or the development of significant TR. Because of the complexity of these procedures at times, surgical intervention should be done by a team with specific expertise in ACHD issues.

7.14.4. Key Issues to Evaluate and Follow-Up

Most patients are not limited physically unless the gradient across the conduits or prosthetic valves is greater than 50 mm Hg. Pregnancy is well tolerated unless RV failure is a major issue. Much as with postprocedural valvular PS, the degree of obstruction and the severity of the pulmonary regurgitation determine the frequency of follow-up and the necessary studies. For asymptomatic patients with RV pulmonary artery conduits (with or without a valve) and for those with prosthetic pulmonary valves, regular follow-up with echocardiography-Doppler is usually sufficient. Endocarditis prophylaxis is recommended for patients with a prosthetic pulmonary valve or conduit (refer to Section 1.6, Recommendations for Infective Endocarditis).

7.15.1. Definition and Associated Lesions

In patients with a double-chambered right ventricle, the right ventricle is divided into a higher-pressure proximal chamber and lower-pressure distal chamber by anomalous myocardial muscle bundles. The morphological features may be very diverse and may involve an anomalous septoparietal band, an anomalous apical shelf, or an abnormal moderator band (376). The distance between the moderator band and the pulmonary artery may be abnormally short (436).

Although the anatomic substrate is congenital, the degree of RVOT obstruction is progressive over time. In approximately three fourths of cases, the VSD is below (proximal to) the level of the midventricular obstruction. Complete or partial spontaneous closure of the VSD can produce worsening RV outflow obstruction and dysfunction. Other associations include valvular PS, tetralogy of Fallot, and double-outlet right ventricle. Unlike tetralogy of Fallot, there is also subaortic obstruction in a number of these patients. The anomaly is uncommon and occurs in approximately 1% of patients with CHD (437). No genetic pattern has been identified, although it has been reported to develop in approximately 3% of patients with repaired tetralogy of Fallot and 3% to 10% of patients with an isolated VSD (438,439).

7.15.2. Clinical Features and Evaluation of the Unoperated Patient

Although most patients undergo repair before adulthood, some present much later. Symptoms in the adult may mimic coronary disease (angina) or LV dysfunction (dyspnea). Occasionally, dizziness and syncope may occur. Some patients are recognized because of the increasing intensity of a systolic murmur, previously ascribed to a small VSD or functional murmur.

7.15.3. Clinical Examination

If midventricular obstruction is marked, the resulting hypertrophy results in an RV heave, and the murmur across the obstruction is harsh, increases with inspiration, and may be accompanied by a palpable thrill. The murmur of an associated VSD may be evident if present. If there is an associated interatrial connection, or the VSD is proximal to the obstruction, cyanosis may occur. Rarely, RV failure and TR develop as the obstruction progresses. In 1 study of patients without repair, the midventricular gradients increased an average of 6.2 plus or minus 3 mm Hg each year (440).

7.15.4. Electrocardiogram

The ECG usually suggests RV hypertrophy. Right-sided leads may help confirm the diagnosis, with upright T waves in V₃R in 40% of the patients tested (441).

7.15.5. Echocardiography-Doppler Imaging

The TTE is diagnostic, with demonstration of the hypertrophy and Doppler/color flow evidence of midventricular gradient. The VSD may be noted. TEE is not usually necessary for the diagnosis.

7.15.6. Magnetic Resonance Imaging

In addition to TTE, MRI is the most useful imaging modality for defining the anatomy (442).

7.15.7. Cardiac Catheterization

Cardiac catheterization and angiography are confirmatory and provide relevant imaging and hemodynamic and shunt information but are rarely necessary to establish the diagnosis.

7.16.1. Multiple Levels of Right Ventricular Outflow Tract Obstruction

As noted previously, RVOT obstruction can occur at multiple levels that can exist simultaneously. The peak RV systolic pressure, as estimated by echocardiography-Doppler via the TR jet, may be the result of more than 1 level of obstruction; therefore, it is important to investigate this possibility thoroughly before surgical intervention is considered. This is particularly important in the adult, in whom prior surgical procedures and other causes of PAH may complicate the clinical picture.

7.17.1. Recommendations for Intervention in Patients With Double-Chambered Right Ventricle

8.1.1. General Recommendations for Evaluation and Surgical Intervention

Class I

• 1. Adults with a history or presence of SupraAS should be screened every 1 or 2 years for myocardial ischemia. (Level of Evidence: C)

• 2. Interventions for coronary artery obstruction in patients with SupraAS should be performed in ACHD centers with demonstrated expertise in the interventional management of these patients. (Level of Evidence: C)

Although SupraAS may be the least common of the lesions of the LV outflow, lesions may be associated with coronary obstruction from partial to complete ostial obliteration, and patients with these lesions are also at risk for ectasia and aneurysm of the coronary arteries (360). Pathological specimens with diffuse or focal intimal and medial fibrosis, hyperplasia, dysplasia, adventitial fibroelastosis, and occasional intramedial dissection have been reported in children and more commonly in adults (361–363).

8.2.1. Clinical Course (Unrepaired)

Clinical presentation with ischemic symptomatology referable to insufficient coronary artery flow has been reported due to either anatomic obstruction or myocardial hypertrophy that limits nonepicardial coronary flow (364).

8.2.2. Clinical Features

There are no current data describing the incidence of coronary artery symptomatology or outcomes in adults with SupraAS. Nonetheless, given the similarity of pathology to other diffuse coronary arteriopathies, the present writing committee would recommend noninvasive screening for myocardial ischemia in all adults with SupraAS, regardless of repair status. If further definition of coronary artery anatomy were suggested, other imaging modalities such as cardiac catheterization, CT angiography, or intravascular ultrasonography might better define the nature and extent of diseased vessel before consideration of repair.

Class I

• 1. Coronary artery anatomy should be determined before any intervention for RV outflow. (Level of Evidence: C)

Abnormalities seen in CHD include single coronary artery, coronary arteriovenous fistula, intramural coronary artery, supravalvular ridge, accessory left anterior descending coronary artery, and anomalous coronary artery from the pulmonary artery. The most common and important abnormality is the left anterior descending coronary artery arising from the right coronary artery and crossing the RV outflow, which occurs in approximately 3% to 7% of persons with tetralogy of Fallot. The occurrence is more common when the aortic root is more anterior, rightward, or lateral (450).

Given the remarkable survival of adults with tetralogy, it is not of surprise that occurrence of atherosclerotic coronary artery disease has been described (451).

8.3.1. Preintervention Evaluation

Coronary artery origin and course should be delineated before any surgical or interventional procedure, because the potential exists for damage to anomalous coronary arteries to occur during cardiac exposure, surgery on the RVOT, and stenting of RV outflow.

8.3.2. Surgical and Catheterization-Based Interventions

Coronary artery bypass and percutaneous coronary interventions for occurrence of atherosclerotic disease in adults with tetralogy of Fallot have been described (451).

Class I

• 1. Adult survivors with dextro-TGA (d-TGA) after ASO should have noninvasive ischemia testing every 3 to 5 years. (Level of Evidence: C)

8.4.1. Definition and Associated Lesions

The coronary artery course plays an important role in the surgical repair of d-TGA. The most common anatomic arrangement occurs in nearly two thirds of patients, with the left coronary artery arising from the anterior facing sinus and the right coronary artery from the posterior facing sinus. Sixteen percent of patients with d-TGA have a circumflex that arises from the right coronary artery, and the remaining patients have inverted coronary artery variants, single coronary arteries, or intramural coronary arteries (452). Damage to the sinus node coronary artery, whether during surgery or during balloon septostomy, has been implicated in the occurrence of atrial arrhythmias and sinus node dysfunction after repair.

8.4.2. Clinical Course

After great artery translocation and transfer of coronary arteries, early and late postoperative loss of coronary perfusion may occur due to causes such as anatomic torsion, extrinsic compression, focal or diffuse fibrocellular intimal thickening, and small-caliber distal coronary arteries with functional decrease in coronary flow reserve (453–455). Survival free of coronary events has been reported as 93% and 88% at 1 and 15 years, respectively, with many reports associating coronary events with increased mortality (455).

8.4.3. Clinical Features and Evaluation After Arterial Switch Operation

No single ischemia provocation test has been shown to be both sufficiently sensitive and specific to screen for coronary flow abnormalities after a switch repair of d-TGA, and combinations of testing, including echocardiography, nuclear scintigraphy, and exercise testing, have been suggested to improve sensitivity and specificity (455). Given the emergence of an adult population of survivors with d-TGA after ASO, with undefined future course and morbidity, the present writing committee recommends episodic noninvasive ischemia provocation testing every 3 to 5 years. Positive results should be pursued by invasive catheterization with measurement of coronary flow reserve and intravascular ultrasound when appropriate.

8.4.4. Surgical and Catheterization-Based Intervention

Successful surgical, balloon angioplasty, and catheter-based stent revascularizations have been reported after ASO repair for d-TGA (456–458). We recommend that obstructive lesions with associated ischemia or flow abnormalities undergo revascularization appropriate to the lesion.

Class I

• 1. The evaluation of individuals who have survived unexplained aborted sudden cardiac death or with unexplained life-threatening arrhythmia, coronary ischemic symptoms, or LV dysfunction should include assessment of coronary artery origins and course. (Level of Evidence: B)

• 2. CT or magnetic resonance angiography is useful as the initial screening method in centers with expertise in such imaging. (Level of Evidence: B)

• 3. Surgical coronary revascularization should be performed in patients with any of the following indications:

  • a. Anomalous left main coronary artery coursing between the aorta and pulmonary artery. (Level of Evidence: B)

  • b. Documented coronary ischemia due to coronary compression (when coursing between the great arteries or in intramural fashion). (Level of Evidence: B)

  • c. Anomalous origin of the right coronary artery between aorta and pulmonary artery with evidence of ischemia. (Level of Evidence: B)

Class IIa

• 1. Surgical coronary revascularization can be beneficial in the setting of documented vascular wall hypoplasia, coronary compression, or documented obstruction to coronary flow, regardless of inability to document coronary ischemia. (Level of Evidence: C)

• 2. Delineation of potential mechanisms of flow restriction via intravascular ultrasound can be beneficial in patients with documented anomalous coronary artery origin from the opposite sinus. (Level of Evidence: C)

Class IIb

• 1. Surgical coronary revascularization may be reasonable in patients with anomalous left anterior descending coronary artery coursing between the aorta and pulmonary artery. (Level of Evidence: C)

8.5.1. Definition, Associated Lesions, and Clinical Course

Congenital anomalous origin of the coronary arteries may occur in 1% to 1.2% of all coronary angiograms performed, with 0.5% of them having the highest-risk lesions of the left main or left anterior descending branch artery arising from the opposite sinus of Valsalva (459). Coronary anomalies account for approximately 15% of sudden cardiac deaths in athletes (potentially due to torsion or slitlike compression of the proximal coronary artery, exercise-induced compression, vasospasm, or ischemic or scar-induced ventricular arrhythmia) (460,461). In 80% of autopsies in athletes with sudden cardiac death and anomalous coronary artery origins, the affected coronary artery coursed between the aorta and the pulmonary artery (461,462).

8.5.2. Clinical Features and Evaluation of the Unoperated Patient

8.5.3. Management Strategies

Class I

• 1. In patients with an anomalous left coronary artery from the pulmonary artery (ALCAPA), reconstruction of a dual coronary artery supply should be performed. The surgery should be performed by surgeons with training and expertise in CHD at centers with expertise in the management of anomalous coronary artery origins. (Level of Evidence: C)

• 2. For adult survivors of ALCAPA repair, clinical evaluation with echocardiography and noninvasive stress testing is indicated every 3 to 5 years. (Level of Evidence: C)

8.6.1. Definition and Associated Lesions and Clinical Course

ALCAPA is relatively rare, occurring in 1 in 300 000 live births. Improved operative revascularization, ensuing myocardial remodeling, and improved medical management of heart failure have increased survival after ALCAPA repair. Similarly, these improvements in care and the recognition of hibernating myocardium have increased the survival of adults with ALCAPA (471). Most adults survive because of collaterals from the right coronary artery, but they may have myocardial ischemia, LV dysfunction, mitral regurgitation, or ventricular arrhythmia. The transition from single to dual coronary surgical repair was performed first by a Takeuchi intrapulmonary arterial baffle; since then, coronary artery reimplantation or coronary bypass grafting has been used for repair (472).

Suprapulmonary arterial stenosis, baffle leaks, and baffle stenosis have all been reported after Takeuchi baffle repair. Late postrepair AR and residual significant mitral valve disease have both been reported. Chest pain, nuclear and positron emission tomography myocardial perfusion abnormalities, and decreased exercise performance have been noted after dual coronary artery repair and may correlate with residual patchy myocardial fibrosis from preoperative ischemia, as well as from residual proximal graft obstruction (473–476). Proximal, midvessel, and even distal coronary artery obstructions, with coronary flow reserve abnormalities, have been noted and treated with intracoronary balloon dilations, stenting, radiotherapy, and reoperation (477–480). There has been no consistent correlation between long-term outcome and late symptoms, noninvasive ischemia and blood flow abnormality testing, residual coronary anatomic or flow abnormalities, or late interventions.

8.7.1. Surgical Intervention

If patients present in adulthood with decreased systolic function and previously unrecognized ALCAPA, the present writing committee suggests surgical myocardial revascularization to achieve a dual coronary supply, regardless of myocardial viability testing, given the lack of current data to correlate such testing with outcomes. Given the increasing awareness of residual coronary artery, myocardial, and valvular abnormalities, the present writing committee suggests surveillance with echocardiography and noninvasive ischemia provocation testing every 3 to 5 years for patients after repair of ALCAPA.

8.7.2. Surgical and Catheterization-Based Intervention

Surgical repair by either arterial bypass or, more commonly, reimplantation of the anomalous coronary into the aorta is indicated because of the risk of sudden cardiac death (481,482). If ischemia is demonstrated in patients after repair of ALCAPA with either concomitant symptomatology or echocardiographic changes, the present writing committee recommends invasive catheterization with planned intervention determined by clinical findings.

Class I

• 1. If a continuous murmur is present, its origin should be defined either by echocardiography, MRI, CT angiography, or cardiac catheterization. (Level of Evidence: C)

• 2. A large CAVF, regardless of symptomatology, should be closed via either a transcatheter or surgical route after delineation of its course and its potential to fully obliterate the fistula. (Level of Evidence: C)

• 3. A small to moderate CAVF in the presence of documented myocardial ischemia, arrhythmia, otherwise unexplained ventricular systolic or diastolic dysfunction or enlargement, or endarteritis should be closed via either a transcatheter or surgical approach after delineation of its course and its potential to fully obliterate the fistula. (Level of Evidence: C)

Class IIa

• 1. Clinical follow-up with echocardiography every 3 to 5 years can be useful for patients with small, asymptomatic CAVF to exclude development of symptoms or arrhythmias or progression of size or chamber enlargement that might alter management. (Level of Evidence: C)

Class III

• 1. Patients with small, asymptomatic CAVF should not undergo closure of CAVF. (Level of Evidence: C)

8.8.1. Definition

The development of epicardial and intramural coronary arteries has recently become better understood, with increasing awareness of the vasculogenesis involved in regulation of cell fate, cell migration, transition, and patterning (483). Nonetheless, the present writing committee still has a very primitive understanding of CAVF occurrence and long-term outcomes. The incidence is 0.1% to 0.2% of all catheterized patients, second in frequency of all coronary artery congenital abnormalities to anomalous origin of the coronary arteries (484). Fistulas arise from either or both coronary arteries, with drainage more typically to the right atrium, right ventricle, or right atrial–superior vena cava junction, and occasionally to the coronary sinus or left side of the heart.

8.8.2. Clinical Course

Although the potential for associated myocardial ischemia and infarction, endarteritis, dissection, and rupture has been documented, there are few data associating occurrence, shunt properties, anatomic features, and outcomes. Increasing fistula and shunt size may be associated with increased abnormalities of coronary flow and complications that include chest pain, decreased life expectancy, and risk of rupture (485). Small fistulas may slowly increase in size with advancing age and changes in systemic blood pressure and aortic compliance. Periodic clinical evaluation with imaging such as echocardiography to assess both the size of the fistula and ventricular function is reasonable. Sometimes, small fistulas are detected as an incidental finding on echocardiography.

8.8.3. Preintervention Evaluation

Transcatheter delineation of the CAVF course and access to distal drainage should be performed in all patients with audible continuous murmur and recognition of CAVF.

Class I

• 1. Surgeons with training and expertise in CHD should perform operations for management of patients with CAVF. (Level of Evidence: C)

• 2. Transcatheter closure of CAVF should be performed only in centers with expertise in such procedures. (Level of Evidence: C)

• 3. Transcatheter delineation of CAVF course and access to distal drainage should be performed in all patients with audible continuous murmur and recognition of CAVF. (Level of Evidence: C)

8.9.1. Surgical Intervention

Surgical fistula closure can be successful if CAVF is well defined and clear surgical access is believed to be technically achievable. Recurrence may be a problem if anatomic definition is suboptimal, and surgery may be difficult to perform owing to poorly visualized, typically distal fistulous connections. Surgical closure of audible CAVF with appropriate anatomy is recommended in all large CAVFs and in small to moderate CAVFs in the presence of symptoms of myocardial ischemia, threatening arrhythmia, unexplained ventricular dysfunction, or left atrial hypertension.

8.9.2. Catheterization-Based Intervention

Numerous reports of transcatheter closure with coils or detachable devices describe near or complete CAVF occlusion in attempted closure procedures (486). Criteria for transcatheter closure of CAVF are similar to those used for surgical closure of CAVF. Transcatheter closure of CAVF should be performed only in centers with particular expertise in such intervention.

8.9.3. Preintervention Evaluation After Surgical or Catheterization-Based Repair

Patients with CAVF, even after repair, may still have large, patulous epicardial conduits. Intermediate- and longer-term follow-up of these thin-walled, ectatic coronary arteries after either surgical or transcatheter repair appears mandated.

9.2.1. Dynamic Congenital Heart Disease–Pulmonary Arterial Hypertension

The development of CHD-PAH associated with systemic–to–pulmonary artery shunts is dependent on both the type and size of the underlying anatomic defect, as well as the magnitude of shunt flow (shear stress and structural changes lead to intravascular and matrix-dependent inflammatory mediator release and changes). Pulmonary vascular histology resembles that described in idiopathic PAH, with medial thickening and plexiform lesions in severe cases (489). In fact, the hypertensive pulmonary arteriopathy, vasoconstriction, and marked increase in pulmonary ventricular afterload of CHDs was the first model used to assist in the understanding of the vascular and cardiac changes associated with idiopathic PAH (490).

Individuals with an unrepaired truncus arteriosus are at very high risk of developing PAH, whereas those with VSDs and ASDs are at moderate and relatively low risk, respectively. Whether the variation in these risks is related to shunt flow or to an underlying genetic predisposition is unknown. The nature of the anatomic abnormality also determines the age at presentation. Patients with AVSD, truncus arteriosus, transposition of the great vessels, large PDA, and VSD present earliest. Most patients with CHD-PAH have a better prognosis than those with idiopathic PAH.

9.2.2. Immediate Postoperative Congenital Heart Disease–Pulmonary Arterial Hypertension

More commonly reported in children than in ACHD patients, pulmonary vascular reactivity due to perioperative endothelial cell injury may be heightened in the immediate postoperative phase of cardiopulmonary surgery. This can precipitate marked increases in PVR, leading to acute right-sided heart failure with the attendant decrease in cardiac output, systemic hypotension, metabolic acidemia, and right-sided heart ischemia. In addition, airway resistance increases in relation to peribronchial edema and bronchoconstriction, gas exchange suffers, and alveolar edema and cardiovascular collapse may occur in the final stages. Immediate perioperative acute increases in pulmonary resistance that precipitate a “crisis” tend to occur in individuals with more “dynamic” and less “fixed” resistance.

9.2.3. Late Postoperative Congenital Heart Disease–Pulmonary Arterial Hypertension

Typically, late postoperative CHD-PAH is attributed to the timing of anatomic shunt repair that is too late, miscalculation of the likelihood of surgical repair, or the long-standing effects of stable but elevated RV afterload that leads to recalcitrant vascular remodeling. However, when one diagnoses late postoperative CHD-PAH, the multiple additional non–shunt-mediated risk factors (including LV hypertrophy and diastolic dysfunction, valvular abnormalities, pulmonary venous hypertension or obstruction, restrictive or hypoventilatory lung disease, chronic liver disease, and toxin use) that contribute to PAH must be ruled out to target appropriate therapy.

9.2.4. Normal to Mildly Abnormal Pulmonary Vascular Resistance States

Individuals with tricuspid atresia or similar single-ventricle physiologies who undergo surgical creation of cavopulmonary anastomoses (Glenn shunt and its variants or Fontan palliation and its variants) have pulmonary circulation that connects directly to the systemic venous circulation, lacks normal pulsatile flow, and hence depends on low PVR for survival. Because the subpulmonary ventricle has been bypassed, and circulation of blood relies solely on systemic ventricular function, any increase in pulmonary vascular impedance can interfere with LV filling. Thus, maintenance of a low PVR is critically important. Clinical course and further management strategies are discussed elsewhere in these guidelines.

9.2.5. Eisenmenger Physiology

Similar to patients with idiopathic PAH, dyspnea on exertion is the most common presenting symptom of patients with Eisenmenger physiology, followed by palpitation, edema, volume retention, hemoptysis, syncope, and progressive cyanosis (488). Increasingly through the third decade of life, morbidity becomes substantial in this patient population. Eisenmenger patients have additional complications compared with patients with idiopathic or other forms of secondary PAH. Hypoxemia-related secondary erythrocytosis leads to increased blood viscosity and intravascular sludging worsened by associated iron deficiency. Organ damage may result, predominantly noted in cerebrovascular changes from sludging, stroke, and alterations in renal function. Hyperpnea may also occur. Right-sided volume overload and elevated systemic venous pressure may lead to changes in hepatic function. Hyperuricemia may result in gout. Hemoptysis remains a potential threat to life when severe; the occurrence of other clinical bleeding disorders is a matter of debate. Concomitant congenital skeletal abnormalities and restrictive lung disease may worsen hypoxemia. True cardiac ischemic chest pain due to RV ischemia, coronary artery compression by a dilated pulmonary artery, or atherosclerosis may occur with exertion or at rest. Progressive subpulmonary ventricular failure and premature death are the rule in adults with Eisenmenger syndrome, with immediate causes of death including pulmonary ventricular failure, severe hemoptysis from bronchial artery rupture or pulmonary infarction, complications during pregnancy, and cerebral vascular events, including occlusive strokes, systemic paradoxical embolization, and brain abscesses (264,491,492). Death during noncardiac surgery also occurs. Poor functional class is a significant predictor of mortality for Eisenmenger patients, as are serological evidence of low systemic organ perfusion, worsened hypoxemia, and LV systemic dysfunction (493).

Class I

• 1. Care of adult patients with CHD-related PAH should be performed in centers that have shared expertise and training in both ACHD and PAH. (Level of Evidence: C)

• 2. The evaluation of all ACHD patients with suspected PAH should include noninvasive assessment of cardiovascular anatomy and potential shunting, as detailed below:

  • a. Pulse oximetry, with and without administration of supplemental oxygen, as appropriate. (Level of Evidence: C)

  • b. Chest x-ray. (Level of Evidence: C)

  • c. ECG. (Level of Evidence: C)

  • d. Diagnostic cardiovascular imaging via TTE, TEE, MRI, or CT as appropriate. (Level of Evidence: C)

  • e. Complete blood count and nuclear lung scintigraphy. (Level of Evidence: C)

• 3. If PAH is identified but its causes are not fully recognized, additional testing should include the following:

  • a. Pulmonary function tests with volumes and diffusion capacity (diffusing capacity of the lung for carbon monoxide). (Level of Evidence: C)

  • b. Pulmonary embolism–protocol CT with parenchymal lung windows. (Level of Evidence: C)

  • c. Additional testing as appropriate to rule out contributing causes of PAH. (Level of Evidence: C)

  • d. Cardiac catheterization at least once, with potential for vasodilator testing or anatomic intervention, at a center with expertise in catheterization, PAH, and management of CHD-PAH. (Level of Evidence: C)

Class IIa

• 1. It is reasonable to include a 6-minute walk test or similar nonmaximal cardiopulmonary exercise test as part of the functional assessment of patients with CAD-PAH. (Level of Evidence: C)

9.4.1. Dynamic Congenital Heart Disease–Pulmonary Arterial Hypertension

Surgical experience has suggested that the changes that occur with shunt-mediated PAH are reversible, provided the surgery is performed before pulmonary vascular changes are “fixed.” Catheterization-based calculations of pulmonary blood flow (Qp) with isolation of all sources of Qp, individualized measurements of resistance in isolated lung segments, and direct measurement of pulmonary venous pressure are typically used to assess PAH reversibility and the likelihood of surgical success. Acute administration of inhaled (nitric oxide) or intravenously administered (prostacyclin) pulmonary vascular agents is frequently used in such investigations to assess for acute reactivity and potential to subsequently (with surgical or pharmacological intervention) mimic achieved lowering of PVR and, when appropriate to anatomy and physiology, similar lowering of pulmonary artery pressures. However, studies have not been performed that firmly establish the pressures, flows, and resistances that define such reactivity. Many centers use a preoperative PVR less than 10 to 14 Wood units and a pulmonary/systemic resistance ratio less than or equal to two thirds as thresholds associated with better surgical outcomes (494,495), but individual institutions vary with regard to these thresholds, often modifying them according to the specific anatomic lesion and responses to acute vasodilator testing. All additional potential causes of PAH in this population must be excluded, because therapeutic strategies may differ significantly.

An important concept with regard to predicting the outcome of surgery, especially in borderline cases, is that PVR is flow dependent. Thus, it should not be assumed that PVR will necessarily fall in proportion to the reduction in shunt and pulmonary blood flow. High shunt flows can recruit pulmonary vasculature (thereby reducing PVR). With the elimination of shunt, these additionally recruited vascular beds may “de-recruit,” no longer accommodating the increased blood flow, and PVR (and hence pulmonary artery pressure) may fall less than would be predicted on the basis of the reduction of blood flow alone.

9.4.2. Eisenmenger Physiology

Diagnosis and evaluation of Eisenmenger physiology require a detailed history to look for all possible PAH triggers and a thorough understanding of current and past anatomy, as well as knowledge of all past surgical and medical interventions. Documentation of the size and direction of intracardiac or intravascular shunts present at the atrial, ventricular, or great arterial level is required, as is a precise documentation of the extent of the severity of pulmonary arteriolar hypertension. A suggested basic evaluation of adults with presumed Eisenmenger physiology includes assessment of anatomy, degree of PAH, ventricular function, and both the presence and magnitude of secondary complications. Evaluation includes finger and toe oximetry, chest x-ray, ECG, pulmonary function tests with volumes and CO₂ diffusion, anatomic lesion definition (by use of noninvasive or invasive modalities, as necessary), pulmonary embolism–protocol CT with “chest windows,” complete blood count with indices, ferritin and iron studies, and renal and hepatic function tests, along with 6-minute walk testing (with or without oximetry or cardiopulmonary testing). Other tests may be performed as indicated if the diagnosis is less certain: hepatitis B and C panels; cryoglobulins; human immunodeficiency virus serologies; procoagulant evaluation; and rheumatologic serologies (including scleroderma, mixed connective tissue disorder, and systemic lupus erythematosus). A complete cardiac catheterization, with potential for vasodilator testing or anatomic interventions, should be performed, but only at a center with expertise in the diagnosis and management of ACHD and adult patients with PAH. Open lung biopsy presently has a very limited role in patient diagnosis or management.

9.5.1. Recommendations for Medical Therapy of Eisenmenger Physiology

9.6.1. Recommendations for Reproduction

9.6.2. Pregnancy

Pregnancy carries particular risk for individuals with CHD-PAH, especially those with Eisenmenger physiology, with mostly older case series suggesting maternal mortality in the latter group of up to 50% and similarly high levels of fetal loss. Even after a successful pregnancy, maternal mortality may be particularly increased in the first several days after delivery (511). Termination of pregnancy, particularly in its mid and later phases, with its concomitant volume and hormonal fluctuations also carries a high maternal risk. Termination in the first trimester is the safer option. Recent case series have reported individual ability of the adult with Eisenmenger physiology to survive pregnancy with concomitant use of modern vasomodulatory agents. It remains unclear whether the potential for pregnancy survival is any different in persons with Eisenmenger syndrome than in adults with PAH without intravascular shunting, and because of the lack of predictability of outcome, pregnancy remains absolutely contraindicated for these patients. Counseled contraception is strongly advised, although the particular method of such is a matter of debate. Maternal sterilization carries a defined operative risk of mortality, and endoscopic sterilization may be the safer option. Hormonal therapies increase the preexisting potential for thrombosis, although progesterone-only preparations may be considered. Barrier methods have an increased rate of failure, and intrauterine device implantation carries anecdotally increased infection risk, although the highest risk is for local infection in multipartner couples. There is no consensus on comparative contraceptive risks; therefore, the patient should discuss options with a high-risk obstetrician (maternal fetal medicine specialist).

9.6.3. Other Interventions

There are limited case data on surgical or transcatheter attempts to limit pulmonary blood flow so as to potentially remodel the pulmonary vascular bed and alter PVR (509).

9.6.4. Recommendations for Follow-Up

9.6.5. Endocarditis Prophylaxis

Refer to Section 1.6, Recommendations for Infective Endocarditis, for additional information.

10.2.1. Presentation as an Unoperated Patient

Presentation as an unoperated patient is now rare in countries with access to modern cardiac surgery, but it can be seen in immigrants living in the United States and in patients who live in countries without access to surgical repair. An occasional patient is seen with relatively mild pulmonary obstruction and mild cyanosis (the so-called pink tetralogy), in which case the diagnosis may not be made until adult life. It is usually mistaken for a small VSD because of the loud precordial murmur. Other patients who have not had previous access to health care and who have severe RV outflow obstruction but abundant aorticopulmonary collaterals may present late with cyanosis and loud continuous murmurs over the thorax. TTE and cardiac catheterization may confirm the diagnosis. The course and anatomy of the epicardial coronary arteries should be defined before definitive repair.

10.2.2. Postsurgical Presentation

Almost all patients with repairable forms of tetralogy of Fallot in the United States will have had reparative surgery. They are usually asymptomatic. Exercise limitation or atrial and/or ventricular arrhythmias imply hemodynamic difficulties.

10.3.1. Clinical Examination

The typical postrepair patient has a soft ejection systolic murmur from the RVOT. The presence of a low-pitched, delayed diastolic murmur in the pulmonary area is consistent with pulmonary regurgitation. Such patients usually have an absent P₂ component of the second sound. The patient may have a pansystolic murmur of a VSD patch leak. A diastolic murmur of AR may also be heard. The occasional adult patient may present having had a palliative shunt only. Such patients usually have cyanosis and clubbing. If the shunt is patent, a continuous murmur may be heard. In the presence of a prior classic Blalock-Taussig shunt, the brachial and radial pulses may be diminished or absent on that side.

10.3.2. Electrocardiogram

In patients with transventricular repairs (the norm until the 1990s), complete right bundle-branch block is almost always present, in which case QRS duration may reflect the degree of RV dilation. A QRS duration of 180 ms or more has been identified as a risk factor for sustained VT and sudden cardiac death (167). The presence of atrial flutter or fibrillation or of sustained VT reflects severe hemodynamic difficulties (513,514).

10.3.3. Chest X-Ray

In patients with a good hemodynamic result, the heart size is usually normal. Cardiomegaly usually reflects important pulmonary regurgitation and/or TR. The aortic arch is right-sided in 25% of cases.

10.3.4. Initial Surgical Repair

Complete repair is considered 1) in palliated patients without irreversible PAH or unfavorable pulmonary artery anatomy and 2) as a primary operation, usually performed in the first year of life. An adult who has undergone palliation earlier in life can be considered for surgery for complete repair after thorough evaluation indicates favorable anatomy and hemodynamics.

Complete repair consists of VSD closure and relief of RVOT obstruction. Relief of RVOT obstruction may include simple resection of infundibular stenosis (muscle), but if the pulmonary annulus is small, more extensive surgery may be necessary. This may include RV outflow patch augmentation or placement of a transannular patch that disrupts the integrity of the pulmonary valve. Occasionally, an extracardiac conduit must be placed from the right ventricle to the pulmonary artery when an anomalous coronary artery crosses the RVOT. If the pulmonary valve itself is abnormal, a pulmonary valvotomy or pulmonary valve resection may be necessary. Effort should be made to preserve the pulmonary valve during the primary operation when performed in infancy. A PFO or small ASD is usually closed. When complete repair is performed in adulthood, pulmonary valve replacement may be required if the native pulmonary valve integrity is disrupted (Table 14).

Key postoperative issues are summarized below:

• • Residual pulmonary regurgitation

• • RV dilation and dysfunction from pulmonary regurgitation, possibly with associated TR

• • Residual RVOT obstruction

• • Branch pulmonary artery stenosis or hypoplasia

• • Sustained VT

• • Sudden cardiac death

• • AV block, atrial flutter, and/or atrial fibrillation

• • Progressive AR

• • Syndromal associations.

The most common problem encountered in the adult patient after repair is that of pulmonary regurgitation. This is frequently missed on clinical examination because the murmur is short and quiet and the pulmonary regurgitation is often overlooked on echocardiography. Patients who present with arrhythmias or cardiomegaly should undergo a thorough evaluation to rule out underlying hemodynamic abnormalities. AR may also occur, often accompanied by aortic root dilatation.

Class I

• 1. Patients with repaired tetralogy of Fallot should have at least annual follow-up with a cardiologist who has expertise in ACHD. (Level of Evidence: C)

• 2. Patients with tetralogy of Fallot should have echocardiographic examinations and/or MRIs performed by staff with expertise in ACHD. (Level of Evidence: C)

• 3. Screening for heritable causes of their condition (eg, 22q11 deletion) should be offered to all patients with tetralogy of Fallot. (Level of Evidence: C)

• 4. Before pregnancy or if a genetic syndrome is identified, consultation with a geneticist should be arranged for patients with tetralogy of Fallot. (Level of Evidence: B)

• 5. Patients with unrepaired or palliated forms of tetralogy should have a formal evaluation at an ACHD center regarding suitability for repair. (Level of Evidence: B)

All patients should have regular follow-up with a cardiologist who has expertise in ACHD (3,4,10,43,82,515,516). The frequency, although typically annual, may be determined by the extent and degree of residual abnormalities. Appropriate imaging (2-dimensional echocardiography annually in most cases and/or MRI every 2 to 3 years) should be undertaken by staff trained in imaging of complex congenital heart defects. An ECG should be performed annually to assess cardiac rhythm and to evaluate QRS duration. Periodic cardiopulmonary testing may be helpful to facilitate serial follow-up of exercise capacity and to evaluate the potential for exercise-induced arrhythmias. Other testing should be arranged in response to clinical problems, particularly a Holter monitor if there is concern about arrhythmias.

10.4.1. Recommendation for Imaging

Class I

• 1. Catheterization of adults with tetralogy of Fallot should be performed in regional centers with expertise in ACHD. (Level of Evidence: C)

• 2. Coronary artery delineation should be performed before any intervention for the RVOT. (Level of Evidence: C)

Class IIb

• 1. In adults with repaired tetralogy of Fallot, catheterization may be considered to better define potentially treatable causes of otherwise unexplained LV or RV dysfunction, fluid retention, chest pain, or cyanosis. In these circumstances, transcatheter interventions may include:

  • a. Elimination of residual shunts or aortopulmonary collateral vessels. (Level of Evidence: C)

  • b. Dilation (with or without stent implantation) of RVOT obstruction. (Level of Evidence: B)

  • c. Elimination of additional muscular or patch margin VSD. (Level of Evidence: C)

  • d. Elimination of residual ASD. (Level of Evidence: B)

For the unusual case of a patient with tetralogy of Fallot who has undergone palliation with a surgical shunt, catheterization should be performed to assess the potential for repair. The presence or absence of additional muscular VSDs may be determined, as well as the course and anatomy of the epicardial coronary arteries. The pulmonary architecture and vascular pressure and resistance should be delineated, because pulmonary artery distortion and PAH are frequent sequelae of palliative surgical shunts. Potential catheter interventions include elimination of collateral vessels or systemic–pulmonary artery shunts, dilation/stent implantation of obstructed pulmonary arteries, and, more recently, the possibility of percutaneous pulmonary valve implantation. Heart catheterization is not used routinely in the assessment of patients who have undergone repair, except when surgery or other therapy is being considered or for the evaluation of the pulmonary and coronary arteries.

10.5.1. Branch Pulmonary Artery Angioplasty

Balloon angioplasty of a branch pulmonary artery results in intimal and medial dissection and subsequent inflammatory repair and increase in vessel size. Dilation may be considered when RV pressure is more than 50% of the systemic level or at lower pressure when there is RV dysfunction. Balloon pulmonary artery angioplasty may also be considered when there is unbalanced pulmonary blood flow greater than 75%, 25%, or otherwise unexplained dyspnea with severe vascular stenosis (522,523). Pulmonary artery balloon angioplasty may be an effective way to reduce obstruction to pulmonary blood flow, thereby increasing pulmonary vascular capacitance and decreasing PVR (524). Balloon angioplasty is usually effective for intermediate-branch pulmonary artery stenoses/occlusions, although it may require coimplantation of large stents (up to 24 to 26 mm diameter in width, up to 5.8 cm in length) in more proximal main and early branch pulmonary arteries or right ventricle–to–pulmonary artery conduits. Intravascular stents are of potential benefit as well in the presence of intimal flaps, vessel kinks, and stenoses, especially in the early perioperative period. Postdeployment antiinflammatory or antiproliferative/anticoagulant strategies remain undefined. Stent redilation has been shown to be effective in selected patients as late as 10 years after implantation (525). The applicability of these techniques has recently been extended to adults with very distal segmental pulmonary artery stenoses and appears promising (427,526). The transcatheter approach to the management of residual muscular or patch margin VSDs (indications typically include a Qp/Qs greater than 1.5 to 2.0, or less in the setting of PAH, left atrial hypertension, or LV failure) remains an effective alternative to reoperative surgical closure (527,528).

10.5.2. Exercise Testing

Exercise testing may be used to assess functional capacity objectively and to evaluate possible exertional arrhythmias. Serial evaluations may be helpful (55,529).

10.5.3. Diagnostic Catheterization

Catheter assessments and interventions for adults with previously repaired tetralogy of Fallot are indicated for the following when adequate data cannot be obtained noninvasively:

• • Assessment of hemodynamics

• • Assessment of pulmonary blood flow and resistance

• • Assessment of the nature of RV outflow or pulmonary artery obstruction

• • Delineation of coronary artery origin and course before any interventional procedure

• • Assessment of ventricular function and presence of residual septal defects, as well as assessment of the degree of mitral regurgitation or AR. The potential for placement of transcatheter implants to reduce or eliminate residual VSDs should be discussed in advance with the patient and medical-surgical team

• • Assessment of the significance of flow across a PFO or ASD and its potential elimination

• • Performance of coronary angiography, with potential to eliminate symptomatic obstructive lesions

• • Assessment of pulmonary regurgitation and right-sided heart failure.

10.7.1. Medical Therapy

Most patients need no regular medication in the absence of significant residual hemodynamic abnormality. Heart failure medications may be necessary in the setting of RV and LV dysfunction.

Class I

• 1. Surgeons with training and expertise in CHD should perform operations in adults with previous repair of tetralogy of Fallot. (Level of Evidence: C)

• 2. Pulmonary valve replacement is indicated for severe pulmonary regurgitation and symptoms or decreased exercise tolerance. (Level of Evidence: B)

• 3. Coronary artery anatomy, specifically the possibility of an anomalous anterior descending coronary artery across the RVOT, should be ascertained before operative intervention. (Level of Evidence: C)

Class IIa

• 1. Pulmonary valve replacement is reasonable in adults with previous tetralogy of Fallot, severe pulmonary regurgitation, and any of the following:

  • a. Moderate to severe RV dysfunction. (Level of Evidence: B)

  • b. Moderate to severe RV enlargement. (Level of Evidence: B)

  • c. Development of symptomatic or sustained atrial and/or ventricular arrhythmias. (Level of Evidence: C)

  • d. Moderate to severe TR. (Level of Evidence: C)

• 2. Collaboration between ACHD surgeons and ACHD interventional cardiologists, which may include preoperative stenting, intraoperative stenting, or intraoperative patch angioplasty, is reasonable to determine the most feasible treatment for pulmonary artery stenosis. (Level of Evidence: C)

• 3. Surgery is reasonable in adults with prior repair of tetralogy of Fallot and residual RVOT obstruction (valvular or subvalvular) and any of the following indications:

  • a. Residual RVOT obstruction (valvular or subvalvular) with peak instantaneous echocardiography gradient greater than 50 mm Hg. (Level of Evidence: C)

  • b. Residual RVOT obstruction (valvular or subvalvular) with RV/LV pressure ratio greater than 0.7. (Level of Evidence: C)

  • c. Residual RVOT obstruction (valvular or subvalvular) with progressive and/or severe dilatation of the right ventricle with dysfunction. (Level of Evidence: C)

  • d. Residual VSD with a left-to-right shunt greater than 1.5:1. (Level of Evidence: B)

  • e. Severe AR with associated symptoms or more than mild LV dysfunction. (Level of Evidence: C)

  • f. A combination of multiple residual lesions (eg, VSD and RVOT obstruction) leading to RV enlargement or reduced RV function. (Level of Evidence: C)

Late survival after tetralogy repair is excellent; 35-year survival is approximately 85%. The need for reintervention, usually for pulmonary valve insertion, increases after the second decade of life. Surgical intervention is indicated for symptomatic patients with severe pulmonary regurgitation or asymptomatic patients with severe PS or pulmonary regurgitation in association with signs of progressive or severe RV enlargement or dysfunction. Patients with RV–to–pulmonary artery conduit repairs often require further intervention for conduit stenosis or regurgitation. Any intervention that involves the RVOT requires careful preoperative assessment of the coronary anatomy to avoid interruption of an important coronary vessel. Some patients experience increasing AR, which requires surgical intervention.

10.8.1. Recommendations for Interventional Catheterization

10.9.1. Recommendations for Arrhythmias: Pacemaker/Electrophysiology Testing

10.9.2. Reproduction

Pregnancy is not advised in patients with unrepaired tetralogy of Fallot. After repair of tetralogy of Fallot, the prognosis for a successful pregnancy is good provided there are no important hemodynamic residua and functional capacity is good. A comprehensive, informed cardiovascular evaluation is recommended before each pregnancy. Pregnancy is usually well tolerated even in the setting of severe pulmonary regurgitation, as long as RV function is no more than mildly depressed and sinus rhythm is maintained (550).

Patients with tetralogy of Fallot have an increased risk of fetal loss, and their offspring are more likely to have congenital anomalies than offspring in the general population, especially in the setting of a 22q11.2 microdeletion. Screening for 22q11.2 microdeletion should be considered in patients with conotruncal abnormalities before pregnancy to provide appropriate genetic counseling (69). In the absence of a 22q11 deletion, the risk of a fetus having CHD is approximately 4% to 6%. Fetal echocardiography should be offered to the mother in the second trimester.

10.9.3. Exercise

Recommendations are summarized by Task Force 1 of the 36th Bethesda Conference on CHD (3).

10.9.4. Endocarditis Prophylaxis

Refer to the AHA guidelines on endocarditis prophylaxis (72). Also, refer to Section 1.6, Recommendations for Infective Endocarditis, for additional information.

Class I

• 1. Patients with repaired d-TGA should have annual follow-up with a cardiologist who has expertise in the management of ACHD patients. (Level of Evidence: C)

Most adults born with d-TGA will have had 1 or more operations in childhood. All patients should have regular follow-up with a cardiologist who has expertise in ACHD. The frequency may be determined by the degree of residual hemodynamic abnormalities, and these become more common, along with the occurrence of arrhythmias, with advancing age.

All operated d-TGA patients should be seen at least annually by a specialist in an ACHD regional center, with attention given to rhythm disorders, as well as ventricular and valvular function. Stress testing, including cardiopulmonary stress testing, should be applied selectively. If specialized testing is performed, it is best done at a regional center. If significant abnormalities are uncovered by these examinations, or if the patient is symptomatic, more frequent follow-up visits are indicated.

11.4.1. Clinical Features and Evaluation of Dextro-Transposition of the Great Arteries After Atrial Baffle Procedure

Because the ASO only gained acceptance in the 1980s, many adults with d-TGA will have had a Mustard or Senning procedure. These procedures involve an atrial baffle that redirects the systemic venous blood to the mitral valve and left ventricle, which remains committed to the pulmonary artery. The pulmonary venous blood is redirected to the tricuspid valve and right ventricle, which remains committed to the aorta.

The atrial baffle (Mustard or Senning) procedure for d-TGA has characteristic late long-term problems. The most common early structural complications include baffle obstruction, which most commonly affects the superior limb rather than the inferior vena cava. Facial suffusion and “superior vena cava syndrome” may result. Inferior vena cava obstruction may cause hepatic congestion or even cirrhosis. Baffle leaks occur in up to 25% of patients. Most are small but may pose a risk of paradoxical embolus, particularly in the setting of atrial arrhythmias and an endocardial pacemaker. Pulmonary venous obstruction may also occur but is less common. Subpulmonary stenosis and PS may occur, in part related to the abnormal geometry of the left ventricle, which becomes distorted and compressed by the enlarged systemic right ventricle. Long term, the most important complication after atrial baffle is failure of the systemic right ventricle and systemic TR. These complications have a major impact on morbidity and mortality. Important but less common complications include PAH, residual VSD, dynamic subpulmonic stenosis, and a host of conduction and arrhythmia disturbances with the potential for implantation of permanent pacemakers or sudden death (37,108,111,551–558).

11.4.2. Clinical Examination

The adult with a prior atrial baffle procedure may have a relatively normal examination. More commonly, features of RV enlargement and TR are present. A loud A₂ is usually present owing to the anterior position of the aorta and should not be confused with the loud P₂ of PAH. A harsh systolic murmur may be a feature of a residual VSD or subpulmonary stenosis. Heart failure with features of systemic TR occurs with increasing frequency with longer duration of follow-up. Sudden cardiac death also occurs in a small percentage of patients.

11.4.3. Electrocardiogram

The ECG demonstrates right-axis deviation and RV hypertrophy in patients with prior atrial baffle because the right ventricle is the SV. Bradycardia may represent a slow junctional rhythm or complete heart block. Rhythm abnormalities may be further elucidated by ambulatory rhythm monitoring (Holter or event recorder). Bradycardia and/or syncope may be presenting features related to sinus node dysfunction. Exercise testing to determine functional capacity and the potential for arrhythmias may be helpful.

11.4.4. Imaging for Dextro-Transposition of the Great Arteries After Atrial Baffle Procedure

A narrow mediastinal shadow is common on chest x-ray in patients with d-TGA because of the parallel relationship of the great arteries. Ventricular size and pulmonary markings depend on patient status but are normal in patients with preserved ventricular function.

11.4.5. Cardiac Catheterization

Cardiac catheterization is used to assess hemodynamics, baffle leak, superior vena cava or inferior vena cava pathway obstruction, pulmonary venous pathway obstruction, myocardial ischemia, unexplained systemic RV dysfunction, or significant LV stenosis (subpulmonary stenosis or LVOT obstruction) or to assess the PAH, with potential for vasodilator testing. Cardiac catheterization in patients after the atrial baffle procedure also provides the opportunity for intervention. For adults after palliative atrial baffle repair for d-TGA, VSD, and pulmonary vascular disease, catheterization may be indicated to assess the potential for pulmonary artery vasomodulator therapy.

11.5.1. Clinical Examination

Patients with prior ASO are now being seen in adult clinics. They may present with no specific findings on physical examination or with a systolic murmur related to arterial obstruction at the arterial anastomosis site. Diastolic murmurs of aortic or pulmonary regurgitation may be noted.

11.5.2. Electrocardiogram

The ECG should be normal in patients after ASO without residua. Ischemic ECG changes are occasionally noted at rest or may occur with exercise, which suggests compromise of the coronary ostia. This should be evaluated further. RV and LV hypertrophy may occur with outflow obstruction.

11.5.3. Chest X-Ray

The chest x-ray after uncomplicated ASO should be unremarkable. A narrow pedicle may be noted.

11.5.4. Recommendations for Imaging for Dextro-Transposition of the Great Arteries After Arterial Switch Operation

11.5.5. Recommendation for Cardiac Catheterization After Arterial Switch Operation

11.6.1. Electrocardiogram

The ECG in post-Rastelli patients often demonstrates right bundle-branch block. RV hypertrophy and progressive conduction disease may occur with time.

11.6.2. Chest X-Ray

The chest x-ray demonstrates a narrow pedicle with associated features of conduit replacement. Cardiac enlargement may occur with progressive valve disease.

11.6.3. Imaging

Echocardiography is the primary imaging modality in patients with prior Rastelli operation. Recurrent RV or LV outflow obstruction can usually be delineated adequately by echocardiography-Doppler examination. Assessment of RV pressure and the occurrence of conduit obstruction can be facilitated by measurement of TR velocity. Additional important features should include assessment of pulmonary regurgitation, residual or baffle-margin VSD, and development of PAH.

Class I

• 1. Diagnostic catheterization of the adult with d-TGA should be performed in centers with expertise in the catheterization and management of ACHD patients. (Level of Evidence: C)

Class IIa

• 1. For adults with d-TGA after atrial baffle procedure (Mustard or Senning), diagnostic catheterization can be beneficial to assist in the following:

  • a. Hemodynamic assessment. (Level of Evidence: C)

  • b. Assessment of baffle leak. (Level of Evidence: B)

  • c. Assessment of superior vena cava or inferior vena cava pathway obstruction. (Level of Evidence: B)

  • d. Assessment of pulmonary venous pathway obstruction. (Level of Evidence: B)

  • e. Suspected myocardial ischemia or unexplained systemic RV dysfunction. (Level of Evidence: B)

  • f. Significant LV outflow obstruction at any level (LV pressure greater than 50% of systemic levels, or less in the setting of RV dysfunction). (Level of Evidence: B)

  • g. Assessment of PAH, with potential for vasodilator testing. (Level of Evidence: C)

• 2. For adults with d-TGA, VSD, and PS, after Rastelli-type repair, diagnostic catheterization can be beneficial to assist in the following:

  • a. Coronary artery delineation before any intervention for RVOT obstruction. (Level of Evidence: C)

  • b. Assessment of residual VSD. (Level of Evidence: C)

  • c. Assessment of PAH, with potential for vasodilator testing. (Level of Evidence: C)

  • d. Assessment of subaortic obstruction across the left ventricle–to–aorta tunnel. (Level of Evidence: C)

11.7.1. Problems and Pitfalls

The following are potential problems and pitfalls related to adults with d-TGA:

• • Antiarrhythmic therapy, which might aggravate sinus node dysfunction in patients after atrial baffle operation, must be used cautiously.

• • A detailed assessment of the atrial baffle for leak and obstruction must be undertaken before endocardial pacemaker implantation.