Cur- rent evidence confirms that adults with repaired TOF are at risk of severe PR, RV dilation and dysfunction, LV dysfunction and electromechanical dyssynchrony, all of which contribute to adverse clinical outcomes late after TOF repair.S4.3.5-1,S4.3.5-20 S4.3.5-24 Despite intense in- terest and numerous publications on pulmonary valve replacement in adults with repaired TOF, optimal tim- ing for this intervention remains uncertain, and most studies have focused on preoperative RV volumes that would result in normalization of postoperative RV In adults with repaired Recommendations for TOF (Continued) COR LOE Recommendations CLINICAL STATEMENTS AND GUIDELINES TOF, prevalence rates for atrial and ventricular arrhyth- mias have been estimated to be 20% and 15%, respec- tively, with steep increases after 45 years of age.S4.3.5-28 The incidence of SCD after surgical repair of TOF is Currently, factors associated with SCD in patients with TOF have largely been identified from observa- tional, predominantly retrospective studies. Despite nu- merous studies that identified factors associated with malignant ventricular arrhythmias and SCD, risk stratifi- cation remains imperfect. Primary prevention ICDs should generally be consid- ered in patients who otherwise meet standard qualify- ing criteria (ie, LV ejection fraction 35% with NYHA class II or III symptoms).S4.3.5-31 S4.3.5-33 There may be a role for primary prevention ICDs in selected adults with TOF who have additional risk factors for SCD but would not meet standard criteria otherwise. See Section 3.3 for recommendations on who should perform surgeries, cardiac catheterization, and other procedures in these patients; Section 3.4 for rec- ommendations on diagnostic evaluation; Figure 4 for Figure 4. Pulmonary valve replacement in patients with TOF repair and PR. *Symptoms may include dyspnea, chest pain, and/or exercise intolerance referable to PR or otherwise unexplained. See recommendation 6 supporting text.


*Symptoms may include dyspnea, chest pain, and/or exercise intolerance referable to PR or otherwise unexplained. See recommendation 6 supporting text. ACHD indicates adult congenital heart disease; HF, heart failure; LV, left ventricular; LVEDV, left ventricular end diastolic volume; PR, pulmonary regurgitation; RV, right ventricular; RVEDV, right ventricular end diastolic volume; RVEDVI, right ventricular end diastolic volume index; RVESVI, right ventricular end systolic volume index; RVOT, right ventricular outflow tract; RVSP, right ventricular systolic pressure; and TOF, tetralogy of Fallot. CLINICAL STATEMENTS AND GUIDELINES a diagnostic and treatment algorithm for repaired TOF with residual PR; and Table 27 for routine testing and follow-up intervals. Recommendation-Specific Supportive Text 1. Cardiac magnetic resonance imaging is the gold standard imaging modality for quantification of right ventricular size and function in patients with repaired TOF. It also allows for quantification of valve regurgitation and pulmonary and sys- temic flows as well as delineating pulmonary ar- tery anatomy and detection of scar tissue in the ventricular myocardium. Serial cardiac magnetic resonance imaging examinations allows for longi- tudinal follow-up of patients with repaired TOF and provides useful information that aids in the timing of pulmonary valve replacement.S4.3.5-1,S4.3.5-34 S4.3.5-37 2. Before any surgical or percutaneous intervention in patients with TOF, the origins and proximal courses of the coronary arteries should be delin- eated. Patients with repaired TOF and abnormal coronary artery anatomy have a substantial risk of coronary artery compression during percuta- neous pulmonary valve replacement or direct in- jury to the coronary during surgical pulmonary valve replacement. During cardiac catheteriza- tion, the coronary pattern may be demonstrated by performing simultaneous RVOT angiography and coronary angiography.S4.3.5-2 Coronary com- pression testing generally involves simultaneous coronary angiography or aortography and bal- loon dilation of the RVOT to ascertain whether a balloon expanded stent will compress the cor- onary artery. 3.


During cardiac catheteriza- tion, the coronary pattern may be demonstrated by performing simultaneous RVOT angiography and coronary angiography.S4.3.5-2 Coronary com- pression testing generally involves simultaneous coronary angiography or aortography and bal- loon dilation of the RVOT to ascertain whether a balloon expanded stent will compress the cor- onary artery. 3. Additional risk factors for SCD include:S4.3.5-24,S4.3.5-38, a. LV systolic or diastolic dysfunction b. Nonsustained VT, QRS duration 180 ms c. Extensive RV fibrosis by CMR In adults with TOF, inducible sustained VT has been associated with an increased risk of clinical VT or SCD, beyond standard ECG, hemodynamic, and clinical factors.S4.3.5-5 Programmed ventricular stimulation is most useful in risk stratifying pa- tients at moderate risk of SCD rather than as a rou- tine surveillance tool in low-risk populations.S4.3.5-7 4. Cardiac catheterization is the only method that can accurately and reliably determine PA pressure and pulmonary vascular resistance. 5. Symptomatic patients (with dyspnea, chest pain, and/or exercise intolerance otherwise unex- plained) with repaired TOF and severe PR who undergo pulmonary valve replacement often re- port improved functional class after intervention. Improvement in symptoms often correlates with a reduction in RV size and relief of PR.S4.3.5-9 S4.3.5-11 Symptom improvement is more likely in patients with underlying PS and PR than in patients with PR alone. For patients with significant LV or RV dysfunction, pulmonary valve replacement may not be tolerated or sufficient; therefore, evalua- tion by ACHD cardiologists and HF cardiologists is appropriate to decide appropriate course of action, particularly in deciding if a patient may be appropriate for mechanical circulatory support or heart transplant. Table 27.


For patients with significant LV or RV dysfunction, pulmonary valve replacement may not be tolerated or sufficient; therefore, evalua- tion by ACHD cardiologists and HF cardiologists is appropriate to decide appropriate course of action, particularly in deciding if a patient may be appropriate for mechanical circulatory support or heart transplant. Table 27. TOF: Routine Follow-Up and Testing Intervals Frequency of Routine Follow-Up and Testing Physiological Stage A* (mo) Physiological Stage B* (mo) Physiological Stage C* (mo) Physiological Stage D* (mo) Pulse oximetry As needed As needed Each visit Each visit Holter monitor As needed As needed 12 24 12 24 *See Tables 3 and 4 for details on the ACHD AP classification system. Routine TTE may be unnecessary in a year when CMR imaging is performed unless clinical indications warrant otherwise. CMR may be indicated for assessment of right ventricular size and function, pulmonary valve function, pulmonary artery anatomy and left heart abnormalities. Baseline study is recommended with periodic follow-up CMR, with frequency of repeat imaging determined by anatomic and physiological findings. CCT may be used if CMR is not feasible and to evaluate origin and course of the coronary arteries, and cross-sectional imaging status post-stent therapy. If cardiac CCT is used instead of CMR imaging, the frequency should be weighed against radiation exposure. 6-minute walk test or CPET, depending on clinical indication. ACHD indicates adult congenital heart disease; CCT, cardiac computed tomography; CMR, cardiovascular magnetic resonance imaging; CPET, cardiopulmonary exercise test; ECG, electrocardiogram; TOF, tetralogy of Fallot; and TTE, transthoracic echocardiogram. CLINICAL STATEMENTS AND GUIDELINES 6. There are data that indicate that pulmonary valve replacement performed prior to specific ventric- ular size is associated with normalization of RV volumes. However, it is not yet evident that this correlates with an improvement in mortality.


However, it is not yet evident that this correlates with an improvement in mortality. Clinically, it therefore is most compelling to per- form pulmonary valve replacement if 2 of the fol- lowing are met:S4.3.5-1,S4.3.5-9,S4.3.5-12 S4.3.5-14 a. Mild or moderate RV or LV systolic dysfunction b. Severe RV dilation (RV end-diastolic volume , or RV end-systolic volume , or RV end-diastolic volume 2x LV end-diastolic volume). c. RV systolic pressure due to RVOT obstruction 2/3 systemic pressure d. Progressive reduction in objective exercise tolerance The increasing use of CMR in the long- term follow-up for patients with repaired TOF has provided quantification of ventricular size, function, and PR. However, there is lack of con- sensus regarding optimal indications and timing of pulmonary valve replacement in this popula- tion. Pulmonary valve replacement results in re- duction of RV volume and relief of PR; however, these are only surrogates for outcomes. Many patients with repaired TOF may deny symptoms yet demonstrate reduced exercise tolerance. Pulmonary valve replacement in such patients has been associated with improved functional 7. Risk factors for SCD include: a. LV systolic or diastolic dysfunction b. Nonsustained VT c. QRS duration 180 ms d. Extensive RV scarring e. Inducible sustained VT at electrophysiological study The largest study of patients with repaired TOF and ICDs included 121 patients from 11 North American and European sites followed for a median of 3.7 years after ICD implantation.


Risk factors for SCD include: a. LV systolic or diastolic dysfunction b. Nonsustained VT c. QRS duration 180 ms d. Extensive RV scarring e. Inducible sustained VT at electrophysiological study The largest study of patients with repaired TOF and ICDs included 121 patients from 11 North American and European sites followed for a median of 3.7 years after ICD implantation. Overall, 30% of patients received at least 1 ap- propriate ICD discharge, corresponding to annual appropriate shock rates of 7.7% and 9.8% for primary and secondary prevention indications, Unlike patients with acquired HF, evidence suggests that patients with TOF who have inducible sustained polymorphic VT (hazard ratio: 12.9) fare as poorly as or worse than those with inducible sustained monomorphic VT.S4.3.5-5 Negative consequences associated with ICDs in adults with TOF must be carefully considered in selecting appropriate candidates. These include high rates of inappropriate shocks (5% to 6% per year), lead-related complications, and unfa- vorable patient-reported outcomes, including im- paired QoL, anxiety, depression, and psychosexual 8. In patients with repaired TOF and moderate or greater PR who are undergoing cardiac surgery for a separate lesion (eg, RVOT aneurysm, TR, branch PA stenosis, residual VS D, arrhythmia ablation, coronary artery revascularization, aortic root re- placement), it may be reasonable to concurrently perform pulmonary valve replacement.S4.3.5-41 9. Although correction of the hemodynamic lesion (ie, PR), may be clinically beneficial, pulmonary valve replacement alone has not consistently been demonstrated to reduce risk of subsequent VT or SCD.S4.3.5-42 Thus, in addition to pulmonary valve replacement, VT surgery and/or ICD implan- tation may be considered.S4.3.5-43 4.3.6. Right Ventricle to-Pulmonary Artery Conduit Recommendations for Right Ventricle to-PA Conduit Referenced studies that support recommendations are summarized in Online Data Supplement 44.


Right Ventricle to-Pulmonary Artery Conduit Recommendations for Right Ventricle to-PA Conduit Referenced studies that support recommendations are summarized in Online Data Supplement 44. COR LOE Recommendations Diagnostic I B-NR Coronary artery compression testing with simultaneous coronary angiography and high-pressure balloon dilation in the conduit is indicated before right ventricle to-PA conduit stenting or transcatheter valve I B-NR In patients with stented right ventricle to-PA conduits and worsening PS or PR, evaluation for conduit complications should be performed, including fluoroscopy to evaluate for stent fracture and blood cultures to assess for IE.S4.3.6-3,S4.3.6-4 IIa C-LD In adults with right ventricle to-PA conduit and arrhythmia, congestive HF, unexplained ventricular dysfunction or cyanosis cardiac catheterization is reasonable to assess the Therapeutic IIa B-NR Right ventricle to-PA conduit intervention is reasonable for adults with right ventricle to-PA conduit and moderate or greater PR or moderate or greater stenosis (Table 22) with reduced functional capacity or IIb B-NR Right ventricle to-PA conduit intervention may be reasonable for asymptomatic adults with right ventricle to-PA conduit and severe stenosis or severe regurgitation with reduced RV ejection fraction or RV Synopsis Right ventricle to-PA conduits are widely used in the treatment of severe RVOT obstructive lesions including CLINICAL STATEMENTS AND GUIDELINES pulmonary atresia. These conduits may be homografts or prosthetic conduits with bioprosthetic valves used within the conduit. A minority of conduits may show early dysfunction because of kinking or aneurysmal di- lation.


A minority of conduits may show early dysfunction because of kinking or aneurysmal di- lation. The remainder will become dysfunctional over time and usually require replacement or intervention because of progressive stenosis within the conduit or at the valve, and/or valvular regurgitation, at a mean inter- val of 10 to 15 years from placement, although some conduits may last much longer than that.S4.3.6-15,S4.3.6-16 See Section 3.3 for recommendations on who should perform surgeries, cardiac catheterization, and other procedures in these patients; Section 3.4 for rec- ommendations on diagnostic evaluation; and Table 28 for routine testing and follow-up intervals. Recommendation-Specific Supportive Text 1. Coronary compression testing generally involves simultaneous selective coronary angiography or aortography and balloon dilation in the RVOT, to ascertain whether a balloon expanded stent will compress the coronary artery. Coronary artery compression with conduit balloon angioplasty or stenting occurs in approximately 5% to 6% of patients with right ventricle to-PA conduits and usually involves the left main/left anterior descending in those with conventional coronary anatomy. Patients with anomalous right or left coronary arteries are at risk of coronary com- pression as are those with reimplanted coronary arteries. 2. Right ventricle to-PA conduit stent fracture is common and occurred in approximately 26% of patients in the Melody Valve Investigational Device Exemption trial,S4.3.6-7 especially in patients who did not undergo conduit prestenting. Stent fracture typically presents with progressive ste- nosis and in those with transcatheter valves may also present with worsening PR. Patients with an increase in PR or PS should have fluoroscopic or x-ray assessment to rule out stent fracture.


Patients with an increase in PR or PS should have fluoroscopic or x-ray assessment to rule out stent fracture. Annualized rate of IE is up to 2.4% of patients treated with Melody valve implantation, but in- fection in most cases involves valves other than the Melody valve, including left-sided valves.S4.3.6-3, Patients typically present with fever and malaise as well as worsening PS or PR. Cases may respond well to medical management with intravenous antibiotics if IE is identified and treatment initiated early in the disease course, although sometimes surgical removal of the valve may be necessary. 3. Although noninvasive imaging with echocardiog- raphy, CMR, or CTA provides a reasonably com- prehensive assessment of ventricular function, conduit function, and patency as well as pulmo- nary arterial anatomy, cardiac catheterization is reasonable to directly assess hemodynamics in the setting of clinical decompensation. Direct assessment of intracardiac and pulmonary arterial pressures and cardiac output provides useful infor- mation regarding volume status, pulmonary arte- rial resistance, and degree of conduit stenosis or regurgitation. Because of anatomic and technical factors, noninvasive imaging may provide equiv- ocal information and may underestimate the de- gree of conduit stenosis or regurgitation; invasive assessment is especially important in such cases. 4. Right ventricle to-PA conduit intervention includes surgical replacement or percutaneous stenting and/or transcatheter valve placement. Patients with moderate or greater conduit stenosis (Table 22) and/or regurgitation who have reduced exercise capacity or arrhythmias can benefit from surgical Table 28. Right Ventricle to-PA Conduit: Routine Follow-Up and Testing Intervals Frequency of Routine Follow-Up and Testing Physiological Stage A* (mo) Physiological Stage B* (mo) Physiological Stage C* (mo) Physiological Stage D* (mo) Exercise test As needed As needed 12 24 12 24 *See Tables 3 and 4 for details on the ACHD AP classification system.


Right Ventricle to-PA Conduit: Routine Follow-Up and Testing Intervals Frequency of Routine Follow-Up and Testing Physiological Stage A* (mo) Physiological Stage B* (mo) Physiological Stage C* (mo) Physiological Stage D* (mo) Exercise test As needed As needed 12 24 12 24 *See Tables 3 and 4 for details on the ACHD AP classification system. Routine TTE may be unnecessary in a year when CMR imaging is performed unless clinical indications warrant otherwise. CMR may be indicated for assessment of right ventricular size and function and valvular function, conduit anatomy and pulmonary artery anatomy. Baseline study is recommended with periodic follow-up CMR, with frequency of repeat imaging determined by anatomic and physiological findings. CCT may be used if CMR is not feasible and to evaluate cross-sectional imaging status post-stent therapy. If CCT is used instead of CMR imaging, the frequency should be weighed against radiation exposure. 6-minute walk test or CPET, depending on clinical indication. ACHD indicates adult congenital heart disease; CCT, cardiac computed tomography; CMR, cardiovascular magnetic resonance; CPET, cardiopulmonary exercise test; ECG, electrocardiogram; PA, pulmonary artery; and TTE, transthoracic echocardiogram. CLINICAL STATEMENTS AND GUIDELINES or transcatheter conduit intervention to relieve ste- nosis and/or regurgitation. Transcatheter stenting and pulmonary valve replacement may be per- formed with high procedural success and low mor- tality rates, and result in improved hemodynamics and improved exercise capacity. Surgical conduit replacement carries a higher risk of periprocedural complications with good long-term outcomes. Predictors of conduit dysfunction and reopera- tion include placement of small diameter conduits; therefore, insertion of conduits with the largest possible diameter should be attempted,S4.3.6-8 antic- ipating that subsequent valve replacement may be via a transcatheter approach. 5.


Predictors of conduit dysfunction and reopera- tion include placement of small diameter conduits; therefore, insertion of conduits with the largest possible diameter should be attempted,S4.3.6-8 antic- ipating that subsequent valve replacement may be via a transcatheter approach. 5. Right ventricle to-PA conduit intervention, which includes surgical replacement or percutaneous stenting and/or transcatheter valve placement, may be reasonable in asymptomatic patients with severe right ventricle to-PA conduit stenosis or regurgitation in the presence of reduced RV systolic function or dilation in the expectation of improvement in hemodynamics, decreased RV size, improved RV stroke volume, and improved RV ejection fraction. Moreover, peak oxygen con- sumption and anaerobic threshold may also im- prove with conduit intervention. 4.4. Complex Lesions 4.4.1. Transposition of the Great Arteries 4.4.1.1. Transposition of the Great Arteries With Atrial Switch Recommendations for d-TGA With Atrial Switch Referenced studies that support recommendations are summarized in Online Data Supplement 45. COR LOE Recommendations Diagnostic I C-EO Ambulatory monitoring for bradycardia or sinus node dysfunction is recommended for adults with d-TGA with atrial switch, especially if treated with beta blockers or other rate-slowing agents. I C-EO Adults with d-TGA with atrial switch repair should undergo annual imaging with either echocardiography or CMR to evaluate for common long-term complications of the atrial switch.


I C-EO Adults with d-TGA with atrial switch repair should undergo annual imaging with either echocardiography or CMR to evaluate for common long-term complications of the atrial switch. IIa C-LD Assessment for a communication through the interatrial baffle or venous stenosis is reasonable for adults with d-TGA with atrial switch, particularly if transvenous pacemaker/ICD implantation is considered or leads are already present.S4.4.1.1-1 Therapeutic I B-NR GDMT with appropriate attention to the need for anticoagulation is recommended to promptly restore sinus rhythm for adults with d-TGA with atrial switch repair presenting with atrial arrhythmia.S4.4.1.1-2 Synopsis Common problems for patients with d-TGA with atrial switch (Mustard or Senning procedure) include leak across or obstruction of the venous pathways, arrhyth- mias, need for pacemakers/defibrillators, and systolic dysfunction of the systemic ventricle. Although re- ports describing these sequelae abound, data that in- form management decisions are sparse, and many of the most common clinical issues cannot be addressed by data-supported recommendations. Two such issues are medical therapy for RV dysfunction and prevention of SCD. The systematic review report, Medical Therapy for Systemic Right Ventricles: A Systematic Review (Part 1) for the 2018 AHA/ACC Guideline for the Management of Adults With Congenital Heart Disease, has the complete systematic evidence reviewS4.4.1.1-3 for addi- tional data and analyses. The results from the question Are outcomes improved with angiotensin-converting enzyme inhibitors, angiotensin-receptor blockers, beta blockers, or aldosterone antagonists alone or in combi- nation in patients with a systemic right ventricle? and the writing committee s review of the totality of the literature demonstrated that medical therapy for sys- tolic ventricular dysfunction remains largely uncertain. Consequently, no recommendations regarding specific medical therapy for systolic dysfunction of the systemic right ventricle can be made.


Consequently, no recommendations regarding specific medical therapy for systolic dysfunction of the systemic right ventricle can be made. In addition to the report provided by the ERC regard- ing angiotensin-converting enzyme inhibitor, angioten- sin-receptor blocker, and aldosterone antagonist use for patients with systemic right ventricles, beta block- ers and other commonly used HF medications lack data to support recommendations in the treatment of atrial Concerns regarding rou- tine use of beta blockers for asymptomatic RV dysfunc- tion include potentially greater predisposition to brady- cardia and limited distensibility of the interatrial baffle, which creates a preload limited physiology.S4.4.1.1-8 Al- though no clear benefit has been demonstrated for HF medical therapy overall, there is speculation of benefit in more symptomatic patients or those with larger and/ or more dysfunctional right ventricles. Patients with dysfunction of the systemic right ven- tricle are at risk of developing ventricular arrhythmias. The role of ICD implantation for primary prevention of arrhythmia in patients with a low systemic ventric- ular ejection fraction is uncertain. This practice is un- supported by any research and cannot be universally recommended. Many such patients do not progress to receive therapies from their device.S4.4.1.1-2 Decisions re- garding primary prevention ICD implantation is based on the patients' full clinical presentation and in con- sultation with cardiac electrophysiologists with ACHD expertise. CLINICAL STATEMENTS AND GUIDELINES See Section 3.3 for recommendations on who should perform surgeries, cardiac catheterization, and other procedures in these patients; Section 3.4 for rec- ommendations on diagnostic evaluation; Table 29 for routine testing and follow-up intervals; and Online Data Supplement 25 for referenced studies. Recommendation-Specific Supportive Text 1.


CLINICAL STATEMENTS AND GUIDELINES See Section 3.3 for recommendations on who should perform surgeries, cardiac catheterization, and other procedures in these patients; Section 3.4 for rec- ommendations on diagnostic evaluation; Table 29 for routine testing and follow-up intervals; and Online Data Supplement 25 for referenced studies. Recommendation-Specific Supportive Text 1. There is a progressive loss of sinus rhythm in patients who have undergone the Senning or Mustard procedure for d-TGA, and the develop- ment of significant sinus bradycardia, while often asymptomatic, is important to identify, because it will influence and limit treatment with antiar- rhythmic medications. 2. Patients with d-TGA with atrial switch have ab- normal cardiac anatomy, with common long-term complications including systemic RV dysfunc- tion, TR, subpulmonic obstruction, obstruction of systemic or pulmonary venous return, and baffle leaks. Imaging should be goal-directed with an understanding of potential long-term sequelae, and nuanced for the patient s particular CMR offers quantification of systemic RV function and should be used rou- tinely unless there are contraindications. Late gad- olinium enhancement is an important tool that can identify areas of myocardial scar that are associ- ated with adverse clinical markers including atrial The importance of change in late gadolinium enhancement over time in direct- ing care is less clear, so repetitive use of gadolinium contrast for this purpose is of less value. 3. Recognizing both the abnormal venous path- ways after atrial switch palliation and the risk of thromboembolic complications from transvenous pacing leads in those with intracardiac shunts, thorough assessment of the venous pathways for either obstruction or baffle leak is a prudent step before lead placement or revision. Baffle leaks should be sought because they are common and may alter treatment considerations such as thromboembolic concerns or options for closure.


Baffle leaks should be sought because they are common and may alter treatment considerations such as thromboembolic concerns or options for closure. Echocardiography using agitated saline con- trast is a sensitive method for this assessment. It is unnecessary on every study, but interval assess- ment of baffle leak is appropriate, especially in circumstances where therapy may be altered by the result. In some patients, injection in upper and lower extremities may be necessary to eval- uate superior and/or inferior systemic venous baffle leak, respectively, because a negative study from an injection in upper extremity may not exclude an inferior systemic venous baffle leak. Assessment for baffle leak may involve use of TTE with agitated saline contrast, TEE, intracardiac echocardiography, or angiography.S4.4.1.1-1 4. Sustained intra-atrial reentrant tachycardia is a po- tential cause of SCD in adults who have undergone atrial switch and puts patients at risk for throm- boembolism. Treatment to maintain sinus rhythm may involve antiarrhythmic medication or catheter ablation. Although there are not data demonstrat- ing that maintenance of sinus rhythm prevents SCD, there is evidence that atrial arrhythmias preceded or coexisted with VT in 50% of cases, suggesting that atrial arrhythmias are a common trigger for ventricular arrhythmias.S4.4.1.1-2,S4.4.1.1-11 Table 29. d-TGA With Atrial Switch: Routine Follow-Up and Testing Intervals Frequency of Routine Follow-Up and Testing Physiological Stage A* (mo) Physiological Stage B* (mo) Physiological Stage C* (mo) Physiological Stage D* (mo) Pulse oximetry 12 12 Each visit Each visit *See Tables 3 and 4 for details on the ACHD AP classification system. Routine TTE may be unnecessary in a year when CMR imaging is performed unless clinical indications warrant otherwise. CMR may be indicated for assessment of ventricular size and function, systemic and venous baffle obstruction and leaks, and valvular function.


CMR may be indicated for assessment of ventricular size and function, systemic and venous baffle obstruction and leaks, and valvular function. Baseline study is recommended with periodic follow-up CMR, with frequency of repeat imaging determined anatomic and physiological findings. CCT may be used if CMR is not feasible and to evaluate cross-sectional imaging status post-stent therapy. If CCT is used instead of CMR imaging, the frequency should be weighed against radiation exposure. 6-minute exercise test or CPET, depending on clinical indication. ACHD indicates adult congenital heart disease; CCT cardiac computed tomography; CMR, cardiovascular magnetic resonance imaging; CPET, cardiopulmonary exercise test; d-TGA, dextro-transposition of the great arteries; ECG, electrocardiogram; and TTE, transthoracic echocardiogram. CLINICAL STATEMENTS AND GUIDELINES There is a biologically plausible explanation that may include longer atrial tachycardia cycle lengths in the context of extensive atrial sutures/scar that could favor rapid (eg, 1:1) ventricular conduction, a reduction in stroke volume with faster heart rates attributable to poor atrial transport, and myocardial ischemia despite the absence of CAD attributable to an inefficient coronary circulation supplying the systemic ventricle.S4.4.1.1-12 Efforts to maintain sinus rhythm or atrial pacing (and not simply rate control) should be the initial strategy of management, acknowledging that patients may rarely tolerate permanent atrial tachycardia when attempts to maintain sinus rhythm have failed. Atrial arrhythmias predominantly involve tissue of right atrial origin which, because of the surgi- cal anatomy, is found primarily in the pulmonary venous atrium, making access for catheter abla- tion challenging. 4.4.1.2. Transposition of the Great Arteries With Arterial Switch Recommendations for d-TGA With Arterial Switch Referenced studies that support recommendations are summarized in Online Data Supplement 46.


Transposition of the Great Arteries With Arterial Switch Recommendations for d-TGA With Arterial Switch Referenced studies that support recommendations are summarized in Online Data Supplement 46. COR LOE Recommendations Diagnostic I C-LD Baseline and serial imaging with either echocardiography or CMR should be performed in adults with d-TGA with arterial switch who have neoaortic dilation, valve dysfunction or PA or branch PA stenosis or I C-EO Coronary revascularization for adults with d-TGA with arterial switch should be planned by surgeons or interventional cardiologists with expertise in revascularization in collaboration with ACHD providers to ensure coronary and pulmonary artery anatomy are understood IIa B-NR It is reasonable to perform anatomic evaluation of coronary artery patency (catheter angiography, or CT or MR angiography) in asymptomatic adults with d-TGA with arterial switch.S4.4.1.2-4,S4.4.1.2-5 IIa C-EO Physiological tests of myocardial perfusion for adults with d-TGA after arterial switch can be beneficial for assessing symptoms suggestive of myocardial ischemia. IIa C-EO GDMT is reasonable to determine the need for coronary revascularization for adults with d-TGA after arterial switch.S4.4.1.2-6 S4.4.1.2-8 Therapeutic IIa C-EO GDMT is reasonable to determine indications for aortic valve replacement in adults with d-TGA after arterial switch with severe neoaortic valve regurgitation.S4.4.1.2-6 IIa C-EO Catheter or surgical intervention for PS is reasonable in adults with d-TGA after arterial switch with symptoms of HF or decreased exercise capacity attributable to PS. Synopsis Complications after the arterial switch include: 1) ste- nosis at the arterial anastomotic sites, most commonly supravalvular PS; 2) neoaortic root dilation; 3) neoaor- tic valve regurgitation (native pulmonary valve); and 4) coronary obstruction. Evaluation for the first 3 com- plications listed is accomplished by usual imaging, in- cluding echocardiography, CCT, and/or CMR. Coronary complications are inadequately evaluated by resting echocardiography, and stress imaging in asymptomatic patients is not sensitive.


Coronary complications are inadequately evaluated by resting echocardiography, and stress imaging in asymptomatic patients is not sensitive. It is unclear that coronary ab- normalities will present de novo or that those present in childhood will progress. However, because patients did not receive an arterial switch before the late 1980s, the long-term natural history of the coronary arteries after arterial switch is still unknown. This is particularly true regarding the impact of risks for concomitant ac- quired coronary artery disease in patients whose coro- nary substrate is not normal. At this time, investigation and management of suspected coronary abnormalities in adults with the arterial switch for TGA should largely be symptom-driven and in accordance with existing guidelines for acquired coronary artery diseases. Several residua and sequelae in adults after arte- rial switch merit consideration of reoperation. Severe RVOT obstruction (Table 22) not amenable or respon- sive to percutaneous treatment is an indication for re- operation; lesser degrees of obstruction can be consid- ered an indication for intervention if greater degrees of exercise are desired. Pulmonary valve replacement or repair is often considered when severe PR is present and there is significant RV dilation or RV dysfunction. Coronary ostial stenosis late after arterial switch may be repaired by coronary artery bypass graft surgery or ostial arterioplasty techniques. The threshold aortic di- ameter at which dissection/rupture risk exceeds the risk of operation is not known, and consequently the threshold for prophylactic operation for neoaortic root dilation is undefined. See Section 3.3 for recommendations on who should perform surgeries, cardiac catheterization, and other procedures in these patients; Section 3.4 for rec- ommendations on diagnostic evaluation; and Table 30 for routine testing and follow-up intervals. Recommendation-Specific Supportive Text 1.


See Section 3.3 for recommendations on who should perform surgeries, cardiac catheterization, and other procedures in these patients; Section 3.4 for rec- ommendations on diagnostic evaluation; and Table 30 for routine testing and follow-up intervals. Recommendation-Specific Supportive Text 1. Imaging in patients after arterial switch should be performed with specific sequelae in mind, including PS (recognizing the Lecompte maneuver has been used during surgery in most), and neoaortic root and valve problems. Some patients with early ar- terial switch repairs had right ventricle to-PA con- duits placed and may have related complications. CLINICAL STATEMENTS AND GUIDELINES 2. Because of nuances of the arterial switch, deci- sions regarding coronary intervention should be considered jointly by ACHD providers and those with expertise in coronary revascularization tech- niques. Abnormalities commonly occur proximally and close to the anteriorly positioned coronary buttons. Coronary buttons are usually located posterior to the main PA after the Lecompte ma- neuver. Revascularization techniques may include revision of the coronary buttons, ostioplasty, in- terposition grafts, or coronary bypass grafting. 3. There is evidence that coronary abnormalities are common after arterial switch (6% to 10%), es- pecially in the setting of coronary anomalies at birth, or extensive manipulation of the coronaries at the time of the operation. However, most cor- onary problems and events described so far tend to occur in childhood in the first few years after surgery, with limited experience in adults,S4.4.1.2-1, although the prevalence of coronary issues may increase as the popula- tion ages. Physiological testing lacks sensitivity. Therefore, a benchmark assessment of the ana- tomic course and patency of the coronary arter- ies (ie, catheter angiography or CT angiography) is prudent in adults in whom this information has not already been obtained.


Therefore, a benchmark assessment of the ana- tomic course and patency of the coronary arter- ies (ie, catheter angiography or CT angiography) is prudent in adults in whom this information has not already been obtained. MR coronary angiography may also be an option for evaluat- ing coronary patency.S4.4.1.2-9 Thereafter, coro- nary investigations will be prompted largely by symptoms. 4. Once the coronary anatomy in an arterial switch recipient is documented, there is little justifica- tion for serial anatomic imaging in an asympto- matic individual. Symptomatic patients should be offered stress physiological imaging and repeat anatomic imaging considered if symptoms are suggestive of coronary ischemia.S4.4.1.2-8 5. Decisions about the indications and approach for coronary intervention after an arterial switch can be guided according to management rec- ommendations for care of atherosclerotic cor- onary disease, emphasizing prudent medical therapy and a symptom-guided approach to The unique aspects of the anatomic abnormalities and unusual course of the proximal coronary arteries must be kept in mind, mandating collaboration between ACHD providers and those with the necessary surgical or interventional expertise. 6. Although some degree of neoaortic valve regurgi- tation is common, surgery to replace the neoaor- tic valve has only rarely been reported. Indications for valve replacement should be based on LV size and/or symptoms according to the 2014 VHD The more common concern is dilation of the neoaortic root with preserved aortic valve competence. Valve-sparing root re- placement is often considered in such cases, but surgical options should be individualized based upon anatomy and changes over time. There are not data to support a specific aortic diam- eter beyond which the risk of dissection or rup- ture increases sufficiently to warrant prophylactic aortic replacement. 7.


There are not data to support a specific aortic diam- eter beyond which the risk of dissection or rup- ture increases sufficiently to warrant prophylactic aortic replacement. 7. PS affects 5% to 15% of patients after arterial and may occur anywhere in the pulmonary tree including the pulmonary valve, main PA, and branch pulmo- nary arteries. Interventional decisions should be guided by a combination of symptoms and se- verity of stenosis. Table 30. d-TGA With Arterial Switch: Routine Follow-Up and Testing Intervals Frequency of Routine Follow-Up and Testing Physiological Stage A* (mo) Physiological Stage B* (mo) Physiological Stage C* (mo) Physiological Stage D* (mo) *See ACHD AP classification Table 4. Routine TTE may be unnecessary in a year when CMR imaging is performed unless clinical indications warrant otherwise. CMR may be indicated for assessment of neoaortic size, the origin and proximal course of the coronary arteries, branch pulmonary arteries, ventricular function and valvular function. Baseline study is recommended with periodic follow-up CMR, with frequency of repeat imaging determined by anatomic and physiological findings. CCT or catheterization once to establish knowledge of coronary artery anatomy and then as warranted by clinical condition. CCT may be used if CMR is not feasible and to evaluate coronary artery anatomy and cross-sectional imaging status-post stent therapy. If CCT is used instead of CMR imaging, the frequency should be weighed against radiation exposure. 6-minute exercise test or CPET, depending on clinical indication. ACHD indicates adult congenital heart disease; CCT, cardiac computed tomography; CMR, cardiovascular magnetic resonance imaging; CPET, cardiopulmonary exercise test; d-TGA, dextro-transposition of the great arteries; ECG, electrocardiogram; and TTE, transthoracic echocardiogram. CLINICAL STATEMENTS AND GUIDELINES 4.4.1.3.


ACHD indicates adult congenital heart disease; CCT, cardiac computed tomography; CMR, cardiovascular magnetic resonance imaging; CPET, cardiopulmonary exercise test; d-TGA, dextro-transposition of the great arteries; ECG, electrocardiogram; and TTE, transthoracic echocardiogram. CLINICAL STATEMENTS AND GUIDELINES 4.4.1.3. Transposition of the Great Arteries With Rastelli Type Repair See Section 3.3 for recommendations on who should perform surgeries, cardiac catheterization, and other procedures in these patients; and Section 3.4 for rec- ommendations on diagnostic evaluation. The Rastelli operation is performed in patients with d-TGA with VSD and PS and for variations of double outlet right ventricle with PS. The operation consists of 2 main components: 1. An intracardiac baffle that directs oxygenated blood from the left ventricle via a nonrestrictive VSD to the aorta. 2. A right ventricle to-PA conduit, which is usually valved. The operation is designed to use the morphologic left ventricle as the systemic ventricle and the morpho- logic right ventricle as the subpulmonic ventricle. Long- term considerations after the Rastelli operation include: 1. Right ventricle to-PA conduit dysfunction (Section 2. VSD patch leaks/dehiscence (Section 4.1.3) 3. LV-to-aorta internal baffle stenosis (Section 4.2.3) 4. Scar-based VT Medical treatment, catheter interventions, and sur- gical interventions for each of these conditions, which may occur in isolation or in combination, may be con- sidered in accordance with the recommended treat- ments for each of the individual conditions as outlined in this guideline document. 4.4.1.4. Congenitally Corrected Transposition of the Great Arteries Recommendations for Congenitally Corrected Transposition of the Great Arteries Referenced studies that support recommendations are summarized in Online Data Supplement 47.


Congenitally Corrected Transposition of the Great Arteries Recommendations for Congenitally Corrected Transposition of the Great Arteries Referenced studies that support recommendations are summarized in Online Data Supplement 47. COR LOE Recommendations Diagnostic IIa C-LD CMR is reasonable in adults with CCTGA to determine systemic RV dimensions and Therapeutic I B-NR Tricuspid valve replacement is recommended for symptomatic adults with CCTGA and severe TR, and preserved or mildly depressed systemic ventricular function.S4.4.1.4-3,S4.4.1.4-4 IIa C-LD Tricuspid valve replacement is reasonable for asymptomatic adults with CCTGA and severe TR with dilation or mild dysfunction of the systemic ventricle.S4.4.1.4-3 IIb B-NR Conduit intervention/replacement may be considered for adults with CCTGA and symptomatic subpulmonary left ventricle to- PA conduit dysfunction, recognizing that unloading the subpulmonary ventricle may have a detrimental impact on systemic atrioventricular valve function.S4.4.1.4-5 Synopsis The clinical course of adults with CCTGA often de- pends on the presence and severity of associated car- which will often have required pediatric intervention. Rarely, CCTGA may be first diag- nosed in adulthood, particularly if patients do not have associated cardiac lesions. Conduction abnormalities are common, and the prevalence of spontaneous com- plete heart block increases with age.S4.4.1.4-7,S4.4.1.4-8 PS, ASD, and VSD are common. Seventy percent to 90% of patients with CCTGA have a dysplastic or Ebstein- like malformation of the tricuspid valve. This anatomi- cally abnormal systemic atrioventricular valve is at risk of progressive TR, which is an independent predictor of death in CCTGA.S4.4.1.4-4,S4.4.1.4-9 The systematic review report, Medical Therapy for Systemic Right Ventricles: A Systematic Review (Part 1) for the 2018 AHA/ACC Guideline for the Manage- ment of Adults With Congenital Heart Disease. S4.4.1.4-10 addressed the role of medical therapies for manage- ment of functional deterioration in systemic RVsS4.4.1.4- (see additional details in Section 3.17).


S4.4.1.4-10 addressed the role of medical therapies for manage- ment of functional deterioration in systemic RVsS4.4.1.4- (see additional details in Section 3.17). See Section 3.3 for recommendations on who should perform surgeries, cardiac catheterization, and other procedures in these patients; Section 3.4 for rec- ommendations on diagnostic evaluation; and Table 31 for routine testing and follow-up intervals. Recommendation-Specific Supportive Text 1. CMR is useful for quantification of systemic RV size and function.S4.4.1.4-1,S4.4.1.4-2 Administration of gadolinium contrast is useful in identifying fi- brotic myocardium demonstrated by late gado- 2. Symptomatic adults with CCTGA and severe TR with no more than mildly depressed systemic ven- tricular function should be evaluated for tricuspid valve replacement. In general, tricuspid valve re- placement is preferred to tricuspid repair in the adult CCTGA population. TR is often because of a dysplastic tricuspid valve and has been shown to be an independent predictor of death in CCTGA Systemic RV dysfunction is often attributable to longstanding TR, and efforts should be made to relieve the TR before worsen- Tricuspid valve repair has been attempted; however, recurrent clinically significant TR is observed frequently after tricuspid valve repair in patients with CCTGA; hence, valve replacement is preferred.S4.4.1.4-15 3. Many adult CCTGA patients are referred for tri- cuspid valve replacement late, when symptomatic and already suffering from moderate-to-severe CLINICAL STATEMENTS AND GUIDELINES TR and ventricular dysfunction.S4.4.1.4-16 In CCTGA patients referred for TVR, 10-year postopera- tive survival is <20% when the preoperative sys- temic ventricular ejection fraction is <40%S4.4.1.4-9 In a retrospective review of 46 CCTGA patients referred for TR surgery, preoper- ative systemic ventricular ejection fraction was the only independent predictor of postoperative sys- temic ventricular ejection fraction at 1 year.S4.4.1.4-3 4.


Many adult CCTGA patients are referred for tri- cuspid valve replacement late, when symptomatic and already suffering from moderate-to-severe CLINICAL STATEMENTS AND GUIDELINES TR and ventricular dysfunction.S4.4.1.4-16 In CCTGA patients referred for TVR, 10-year postopera- tive survival is <20% when the preoperative sys- temic ventricular ejection fraction is <40%S4.4.1.4-9 In a retrospective review of 46 CCTGA patients referred for TR surgery, preoper- ative systemic ventricular ejection fraction was the only independent predictor of postoperative sys- temic ventricular ejection fraction at 1 year.S4.4.1.4-3 4. Adults with CCTGA and pulmonary atresia or ste- nosis were often managed in childhood by plac- ing a conduit from the morphologic LV to the PA, and progressive conduit dysfunction is common. Conduit intervention or replacement will diminish the pressure in the subpulmonic ventricle and may result in ventricular septal shift toward the subpulmonic left ventricle, including the septal leaflet of the systemic tricuspid valve and thus can result in worsening of TR and a detrimental impact on systemic RV function.S4.4.1.4-5 4.4.2. Fontan Palliation of Single Ventricle Physiology (Including Tricuspid Atresia and Double Inlet Left Ventricle) Recommendations for Fontan Palliation of Single Ventricle Physiology Referenced studies that support recommendations are summarized in Online Data Supplement 48. COR LOE Recommendations Diagnostic I C-LD New presentation of an atrial tachyarrhythmia in adults with Fontan palliation should be managed promptly and include prevention of thromboembolic events and consultation with an electrophysiologist with CHD Diagnostic (Continued) I C-EO Adults after Fontan palliation should be evaluated annually with either echocardiography or CMR. I C-EO Cardiac catheterization should be performed in adults before initial Fontan surgery or revision of a prior Fontan connection to assess suitability of preintervention hemodynamics for Fontan physiology or revision of a prior Fontan connection.


I C-EO Cardiac catheterization should be performed in adults before initial Fontan surgery or revision of a prior Fontan connection to assess suitability of preintervention hemodynamics for Fontan physiology or revision of a prior Fontan connection. I C-EO New onset or worsening atrial tachyarrhythmias in adults with single ventricle after Fontan palliation should prompt a search for potential hemodynamic abnormalities, which may necessitate imaging and/or cardiac catheterization. IIa B-R In adults with Fontan palliation, it is reasonable to encourage a regular exercise program appropriate to their IIa C-LD Imaging of the liver (ultrasonography, CMR, CT) and laboratory evaluation of liver function for fibrosis, cirrhosis, and/or hepatocellular carcinoma are reasonable in adults after Fontan IIa C-EO In adults after Fontan palliation, it is reasonable to perform biochemical and hematological testing on an annual basis especially for liver and renal function. IIa C-LD Cardiac catheterization can be useful to evaluate a symptomatic adult after Fontan palliation when noninvasive testing is insufficient to guide therapy.S4.4.2-7,S4.4.2-8 IIa C-LD Evaluation for cardiac transplantation is reasonable in adults with Fontan palliation and signs and symptoms of protein-losing Recommendations for Fontan Palliation of Single Ventricle Physiology (Continued) COR LOE Recommendations Table 31. CCTGA: Routine Follow-Up and Testing Intervals Frequency of Routine Follow-Up and Testing Physiological Stage A* (mo) Physiological Stage B* (mo) Physiological Stage C* (mo) Physiological Stage D* (mo) Pulse oximetry As needed As needed Each visit Each visit *See Tables 3 and 4 for details on the ACHD AP classification system. Routine TTE may be unnecessary in a year when CMR imaging is performed unless clinical indications warrant otherwise. CMR may be indicated for assessment of ventricular size and function and valvular function. Baseline study is recommended with periodic follow-up CMR, with frequency of repeat imaging determined by anatomic and physiological findings.


Baseline study is recommended with periodic follow-up CMR, with frequency of repeat imaging determined by anatomic and physiological findings. CCT may be used if CMR is not feasible. If CCT is used instead of CMR imaging, the frequency should be weighed against radiation exposure. 6-minute walk test or CPET, depending on clinical indication. ACHD indicates adult congenital heart disease; CCT, cardiac computed tomography; CCTGA, congenitally corrected transposition of the great arteries; CMR, cardiovascular magnetic resonance imaging; CPET, cardiopulmonary exercise test; ECG, electrocardiogram; and TTE, transthoracic echocardiogram. CLINICAL STATEMENTS AND GUIDELINES Diagnostic (Continued) IIb C-EO It may be reasonable to perform catheterization in asymptomatic adults after Fontan palliation to evaluate hemodynamics, oxygenation and cardiac function to guide optimal medical, interventional and/or surgical therapy. Therapeutic I C-EO Anticoagulation with a vitamin K antagonist is recommended for adults with Fontan palliation with known or suspected thrombus, thromboembolic events, or prior atrial arrhythmia, and no contraindications to anticoagulation. IIa C-LD Catheter ablation can be useful in adults after Fontan palliation with intra-atrial reentrant tachycardia or focal atrial IIa C-LD Fontan revision surgery, including arrhythmia surgery as indicated, is reasonable for adults with atriopulmonary Fontan connections with recurrent atrial tachyarrhythmias refractory to pharmacological therapy and catheter ablation who have preserved systolic ventricular function and severe atrial IIa B-R Pulmonary vasoactive medications can be beneficial to improve exercise capacity in adults with Fontan repair.S4.4.2-19 S4.4.2-25 IIb B-NR Antiplatelet therapy or anticoagulation with a vitamin K antagonist may be considered in adults after Fontan palliation without known or suspected thrombus, thromboembolic events, or prior IIb C-LD Reoperation or intervention for structural/ anatomic abnormalities in a Fontan palliated patient with symptoms or with failure of the Fontan circulation may be Synopsis Fontan repairs are the most common palliation of sin- gle ventricle physiology seen in adults.


IIa C-LD Catheter ablation can be useful in adults after Fontan palliation with intra-atrial reentrant tachycardia or focal atrial IIa C-LD Fontan revision surgery, including arrhythmia surgery as indicated, is reasonable for adults with atriopulmonary Fontan connections with recurrent atrial tachyarrhythmias refractory to pharmacological therapy and catheter ablation who have preserved systolic ventricular function and severe atrial IIa B-R Pulmonary vasoactive medications can be beneficial to improve exercise capacity in adults with Fontan repair.S4.4.2-19 S4.4.2-25 IIb B-NR Antiplatelet therapy or anticoagulation with a vitamin K antagonist may be considered in adults after Fontan palliation without known or suspected thrombus, thromboembolic events, or prior IIb C-LD Reoperation or intervention for structural/ anatomic abnormalities in a Fontan palliated patient with symptoms or with failure of the Fontan circulation may be Synopsis Fontan repairs are the most common palliation of sin- gle ventricle physiology seen in adults. The physiology is complex, with long-term consequences related to the obligatory elevation in central venous pressure and reduced cardiac output. Proposed medical therapy for the failing Fontan, which may manifest as protein- losing enteropathy, hepatic dysfunction, lower extrem- ity venous congestion, and/or exercise limitation, has included many different modalities, although there is limited proven benefit in published research. Options for medical therapy include aldosterone antagonists or subcutaneous unfractionated heparin, which may sta- bilize the proteoglycan layer of the gut. PAH therapies are of increasing interest. Endothelin antagonists have been studied in a single RCT, which showed improved exercise capacity in 75 subjects randomized to bosen- tan compared with placebo.S4.4.2-19 Two other small non- randomized studies demonstrated minimal response to Corticosteroids, specifically budesonide, may be helpful for Fontan patients with hypoalbuminemia in the setting of protein-losing enteropathy poorly re- sponsive to other therapies.


Endothelin antagonists have been studied in a single RCT, which showed improved exercise capacity in 75 subjects randomized to bosen- tan compared with placebo.S4.4.2-19 Two other small non- randomized studies demonstrated minimal response to Corticosteroids, specifically budesonide, may be helpful for Fontan patients with hypoalbuminemia in the setting of protein-losing enteropathy poorly re- sponsive to other therapies. Budesonide seems to have fewer systemic effects than other oral steroids; how- ever, close monitoring for signs of hypercortisolism Octreotide may be con- sidered; it is a therapy with favorable but very limited anecdotal experience reported, with further research A combination of these therapies may be applied in an affected patient, as such strat- egies collectively appear to have produced improved outcome compared with historic controls.S4.4.2-31 Fontan surgery has been associated with prolonga- tion of atrial refractory periods, extensive atrial scar- ring, and intra-atrial conduction delay.S4.4.2-32 S4.4.2-38 Si- nus node dysfunction occurs in up to 45% of adults during long-term follow-up after Fontan surgery and has been associated with a reduction in preload to the single ventricle, increased pulmonary venous pres- sure, reduced cardiac output, plastic bronchitis, and Transvenous atrial pacing may be feasible in most adults with atrio- pulmonary Fontan connections and in some with intra- cardiac lateral tunnels,S4.4.2-44 although the potential for thrombotic complications must be addressed. Ventric- ular pacing may be performed via the coronary sinus in selected patients, but most require an epicardial Management of atrial arrhyth- mias is discussed in the associated recommendations. See Section 3.3 for recommendations on who should perform surgeries, cardiac catheterization and other procedures in these patients; Section 3.4 for rec- ommendations on diagnostic evaluation; and Table 32 for routine testing and follow-up intervals. Recommendation-Specific Supportive Text 1.


See Section 3.3 for recommendations on who should perform surgeries, cardiac catheterization and other procedures in these patients; Section 3.4 for rec- ommendations on diagnostic evaluation; and Table 32 for routine testing and follow-up intervals. Recommendation-Specific Supportive Text 1. Atrial tachyarrhythmias occur in up to 60% of adults with Fontan palliation and are associated These arrhythmias may be difficult to manage, are usually poorly tolerated, and cause serious hemodynamic compromise often with dire consequences.S4.4.2-1 Therefore, they should be addressed promptly, including urgent consultation with ACHD provid- ers who can help guide immediate management strategies, even if remotely. Consideration for anti- thrombotic therapy in Fontan patients should take into account the high prevalence of thrombus for- mation and potentially catastrophic impact of pul- monary or systemic thromboembolus. Standard Recommendations for Fontan Palliation of Single Ventricle Physiology (Continued) COR LOE Recommendations CLINICAL STATEMENTS AND GUIDELINES decision-making strategies about rhythm versus rate control or thromboembolic prophylaxis de- rived from and recommended for patients with acquired heart disease and AF do not apply to patients with Fontan physiology, for whom rhythm control and anticoagulation are of greater impor- tance than would be concluded from application of the standard algorithms. Sinus node dysfunction may predispose Fontan patients to atrial tachyarrhythmias, the most common being macro-reentrant circuits or intra-atrial reentrant tachycardia.S4.4.2-13,S4.4.2-47 Nearly 90% of Fontan patients who die from HF have coexisting atrial tachyarrhythmias.S4.4.2-48 Fontan patients are at increased risk of complica- tions from antiarrhythmic therapy, such as tors- ades de pointes with dofetilideS4.4.2-49 and amio- Such agents should be used cautiously and in consultation with ACHD cardiologists and electrophysiology specialists with expertise in ACHD. 2.


Sinus node dysfunction may predispose Fontan patients to atrial tachyarrhythmias, the most common being macro-reentrant circuits or intra-atrial reentrant tachycardia.S4.4.2-13,S4.4.2-47 Nearly 90% of Fontan patients who die from HF have coexisting atrial tachyarrhythmias.S4.4.2-48 Fontan patients are at increased risk of complica- tions from antiarrhythmic therapy, such as tors- ades de pointes with dofetilideS4.4.2-49 and amio- Such agents should be used cautiously and in consultation with ACHD cardiologists and electrophysiology specialists with expertise in ACHD. 2. Serial imaging can be valuable for assessing many of the long-term sequelae of Fontan palliation such as thrombosis, right-to-left shunts (eg, fen- estration, intrapulmonary AV malformation), ob- structive lesions, systemic AV valve dysfunction, diastolic or systolic ventricular function, collat- eral burden, and branch PA obstruction. Imaging can be challenging and requires informed un- derstanding about the patient's particular situa- tion. Although CCT is possible in patients with Fontan physiology, it is challenging to ensure contrast dispersal through the pulmonary vas- culature because of streaming of venous return to the PA from multiple separate sources (eg, superior vena cava, inferior vena cava right atrium 3. Hemodynamic assessment, particularly of the pul- monary circulation, is crucial to making informed decisions about the type and timing of surgical intervention. 4. Hemodynamic problems may first manifest through arrhythmia. Thus, first presentation of arrhythmia should warrant thorough review of the patient s Fontan circulation and ventricular function. 5. Aerobic exercise may help maintain respiratory mechanics, which can improve transpulmonary flow in the Fontan circulation. Stroke volume dur- ing exercise and exercise capacity are directly re- lated to skeletal muscle function. Consequently, strength training may improve exercise capacity in patients with Fontan palliation. 6.


Consequently, strength training may improve exercise capacity in patients with Fontan palliation. 6. There is increasing recognition of hepatic vul- nerability after Fontan palliation, including but uncertainty about which patients are at highest risk, or how to address problems when identified. Routine assessment of liver function and structure may help inform broader decisions such as timing and risk of sur- gery or transplantation, as well as provide insights into the emerging natural history of this unique condition. Consultation with a hepatologist may be of value in interpreting and following the liver abnormalities encountered in patients with Fontan physiology. 7. Recognizing the multiorgan vulnerability of the Fontan circulation, annual routine blood tests Table 32. Fontan Palliation: Routine Follow-Up and Testing Intervals Frequency of Routine Follow-Up and Testing Physiological Stage A* (mo) Physiologic al Stage B* (mo) Physiological Stage C* (mo) Physiological Stage D* (mo) Pulse oximetry 12 12 Each visit Each visit *See Tables 3 and 4 for details on the ACHD AP classification system. Routine TTE may be unnecessary in a year when CMR imaging is performed unless clinical indications warrant otherwise. CMR may be indicated for assessment of the long-term sequelae of Fontan palliation: thrombosis, right-to-left shunts (eg, fenestration. intrapulmonary atrioventricular malformation), obstructive lesion, systemic atrioventricular valve dysfunction, ventricular size and function, collateral burden, and branch pulmonary artery obstruction. Baseline study is recommended with periodic follow- up CMR, with frequency of repeat imaging determined by anatomic and physiological findings. CCT may be used if CMR is not feasible and to evaluate cross-sectional imaging status-post stent therapy. CCT with contrast injection in Fontan patients can be misleading; therefore, it should be done only when clinically indicated and when it can be appropriately protocoled and interpreted.


CCT with contrast injection in Fontan patients can be misleading; therefore, it should be done only when clinically indicated and when it can be appropriately protocoled and interpreted. If CCT is used instead of CMR imaging, the frequency should be weighed against radiation exposure. 6-minute walk test or CPET, depending on clinical indication. ACHD indicates adult congenital heart disease; CCT, cardiac computed tomography; CMR, cardiovascular magnetic resonance imaging; CPET, cardiopulmonary exercise test; ECG, electrocardiogram; and TTE, transthoracic echocardiogram. CLINICAL STATEMENTS AND GUIDELINES may have a role in identifying and addressing problems early. 8. Because of both the anatomic and physiological complexities of these patients, and the potential for concurrent intervention, hemodynamic and interventional cardiac catheterization of the adult with single ventricle/Fontan palliation should be performed only by persons with expertise in CHD in coordination with an ACHD cardiologist. Recognizing that it is difficult to accurately assess Fontan hemodynamics by clinical examination or noninvasive imaging, cardiac catheterization may be needed in these scenarios and others: a. Interval hemodynamic assessment, as filling pressures, mean PA pressure, and pulmonary vascular resistance may change over timeS4.4.2-8 b. Creation or closure of a fenestration or veno- veno collaterals, although with uncertain ben- efit of either interventionS4.4.2-54 S4.4.2-56 c. Treatment of baffle obstruction, even in the setting of low or no pressure gradientS4.4.2-57 d. Assessment of protein-losing enteropathy or ascites, because elevated Fontan pressure cor- relates with such complications, and lowering pressures may offer the potential for clinical e. Facilitation of transvenous liver biopsy for monitoring liver function including as part of a pretransplantation assessment f. Preoperative assessment before Fontan 9. Protein-losing enteropathy and plastic bronchitis contribute substantially to perioperative mortality, yet transplantation may be curative.S4.4.2-9,S4.4.2-11 Medical therapy options are often ineffective. Therefore, consideration of transplantation early in the course of PLE may be warranted.


Therefore, consideration of transplantation early in the course of PLE may be warranted. Evaluation of additional organs is necessary, particularly the liver, as these patients are susceptible to cirrhosis as a consequence of the Fontan circulation. Although symptoms may improve, there are no published data regarding impact on survival for transplanted Fontan patients with PLE compared with those who do not undergo transplantation. 10. Although catheterization plays an important role in management of single ventricle/Fontan patients, it is often driven by symptoms. The role of routine hemodynamic assessment is less certain. 11. Fontan circulation imparts risk of thrombosis, and anticoagulation with vitamin K antagonists should be offered as preventive therapy in clin- ical situations including prior arrhythmia.S4.4.2-60 Patients may also benefit from anticoagulation if they have significant residual intracardiac right- to-left shunt or veno-veno collaterals. 12. Catheter ablation has been associated with improved clinical status despite the frequent co- existence of multiple arrhythmia substrates.S4.4.2-61 Given the progressive nature of the atrial myop- athy, successful ablation is less frequent than in acquired heart disease or other congenital heart diseases, and recurrence is common. The devel- opment of new arrhythmias over time remains problematic, but multiple ablation procedures may be justified in selected patients.S4.4.2-13,S4.4.2-14 13. Conversion to a total cavopulmonary connec- tion Fontan combined with a modified right atrial Maze procedure may be considered in patients with symptomatic refractory recurrent intra-atrial In the pres- ence of documented AF, a left atrial Cox Maze procedure may also be indicated.S4.4.2-16,S4.4.2-62 Some patients may not be appropriate surgical candidates for reasons of elevated PA or Fontan pressures, elevated ventricular end-diastolic pres- sures, or renal or hepatic dysfunction, and the de- cision to perform Fontan revision surgery is rarely straightforward. 14.


Conversion to a total cavopulmonary connec- tion Fontan combined with a modified right atrial Maze procedure may be considered in patients with symptomatic refractory recurrent intra-atrial In the pres- ence of documented AF, a left atrial Cox Maze procedure may also be indicated.S4.4.2-16,S4.4.2-62 Some patients may not be appropriate surgical candidates for reasons of elevated PA or Fontan pressures, elevated ventricular end-diastolic pres- sures, or renal or hepatic dysfunction, and the de- cision to perform Fontan revision surgery is rarely straightforward. 14. Pulmonary vasoactive medications, specifically endothelin receptor antagonists and PDE-5 inhibitors, are of increasing interest as a means of reducing pulmonary vascular resistance and improving cardiac output. In limited studies, use of PDE-5 inhibitors appears favorable for Fontan patients with improvement noted in pulmonary blood flow and exercise capacity.S4.4.2-21,S4.4.2-63 Use of endothelin antagonists has been investigated in a randomized trial.S4.4.2-19 After 14 weeks of ran- domization in 69 subjects successfully completing the study, there was a modest but significant in- crease in peak oxygen consumption and exercise duration in those taking bosentan compared with those on placebo. 15. Although anticoagulation is prudent in those with prior arrhythmia or known thromboem- bolic events, routine use of anticoagulation with vitamin K antagonist cannot as yet be strongly recommended. An RCT in Fontan children/ado- lescents did not show benefit,S4.4.2-64 although adults later after Fontan may be more at risk. However, a secondary analysis of that RCT as an found the risk of throm- boembolism was lower in those patients on war- farin who consistently achieved minimum target international normalized ratio levels, as well as in those on acetylsalicylic acid compared with patients who often failed to meet target interna- tional normalized ratio level.


However, a secondary analysis of that RCT as an found the risk of throm- boembolism was lower in those patients on war- farin who consistently achieved minimum target international normalized ratio levels, as well as in those on acetylsalicylic acid compared with patients who often failed to meet target interna- tional normalized ratio level. Rates of thrombosis were considerably higher in patients on warfarin who did not consistently achieve target inter- national normalized ratio. A study of modes of CLINICAL STATEMENTS AND GUIDELINES death in atriopulmonary Fontan patients dem- onstrated lower rates of death in patients on some antiplatelet agent or anticoagulation compared with those on none.S4.4.2-1 Direct oral anticoagulants are unstudied and thus cannot be recommended at the present time. There are con- cerns about liver function vulnerability in Fontan patients, which theoretically may increase the risk of complications with some of those agents. 16. There are occasions where surgery or catheter intervention may be alternatives to transplanta- tion for a failing Fontan after weighing risks and benefits of the intended procedure (ie, alle- viation of atrioventricular valve regurgitation, sys- temic or pulmonary venous pathway obstruction). Reoperation for atrioventricular valve regurgita- tion may be high-risk, particularly when systemic ventricular function is impaired. Although valve repair is preferred and operative risk is usually lower, it is not always possible. Risk of valve re- placement in this setting is high. 4.4.3.


Risk of valve re- placement in this setting is high. 4.4.3. Hypoplastic Left Heart Syndrome/Norwood Repair The Norwood repair is the first of 3 steps in palliation for hypoplastic left heart syndrome and consists of a- trial septectomy, transection, and ligation of the distal main PA with construction of a systemic-to-PA shunt, and anastomosis of the proximal stump of the main PA to the hypoplastic ascending aorta with augmentation of the entire aortic arch from the sinotubular junction to beyond the ductus arteriosus. Hypoplastic left heart syndrome is fatal unless surgical palliation is performed in the neonatal period. Subsequent surgeries include a bidirectional cavopulmonary anastomosis (often per- formed around 6 months of age), followed finally by a Fontan procedure (often at approximately 2 to 4 years of age). Sequelae of hypoplastic left heart syndrome are largely those of the Fontan palliation, but additional concerns related to the underlying anatomy and the Norwood repair is important in patients with hypoplas- tic left heart syndrome. These include aortic obstruction related to anastomosis of the PA and aorta, and neo- aortic dilation. Additionally, native anatomy wherein coronary arteries arise from a small aortic root make coronary ischemia a greater concern than in other un- derlying disorders managed with Fontan repair. The fre- quency and spectrum of long-term sequelae specific to the Norwood repair are not yet known. 4.4.4. Truncus Arteriosus Truncus arteriosus in the adult has almost invariably been repaired in childhood, and in the rare circum- stances when an adult has unrepaired truncus arte- riosus, Eisenmenger physiology is typical. Pulmonary hypertension may be present in repaired patients. The types of operative repairs may involve VSD clo- sure, right ventricle to-PA conduit placement, recon- struction of the pulmonary arteries, and replacement of the truncal (neoaortic) valve.


The types of operative repairs may involve VSD clo- sure, right ventricle to-PA conduit placement, recon- struction of the pulmonary arteries, and replacement of the truncal (neoaortic) valve. Unifocalization of the pulmonary arteries may be necessary in very complex cases. The aorta may be dilated. Recommendations regarding assessment and management of truncus arteriosus can generally be inferred in the recommen- dations for the specific components, including right ventricle to-PA conduit, VSD, aortic valve disease, and aortopathies. 4.4.5. Double Outlet Right Ventricle Double outlet right ventricle is an anatomic descrip- tor that includes abnormalities similar to TOF in some patients (when the aorta is closely related to the VSD) and similar to d-TGA with a VSD in others (when the PA is more closely related to the VSD than the aorta). Repairs are predicated on the underlying anatomy and may involve VSD closure with relief of PS, right ventricle to-PA conduit, or Rastelli-type repair. In se- vere cases, single-ventricle physiology may be present. Consequently, recommendations for the management of a patient with double outlet right ventricle can gen- erally be inferred in the recommendations for the le- sion with the most similar anatomy and physiology (eg, TOF can reasonably be based on the recommen- dations in Section 4.4.1, recognizing that a patient with double outlet right ventricle is more likely to have residual LVOT obstruction). 4.4.6. Severe PAH and Eisenmenger Syndrome 4.4.6.1. Severe PAH Recommendations for Severe PAH Referenced studies that support recommendations are summarized in Online Data Supplement 49.


Severe PAH Recommendations for Severe PAH Referenced studies that support recommendations are summarized in Online Data Supplement 49. COR LOE Recommendations Diagnostic I B-NR Patients with ACHD with pulmonary vascular resistance 2.5 Wood units or greater ) should be assessed collaboratively by an ACHD cardiologist and an expert in pulmonary hypertension to develop a management plan.S4.4.6.1-1 S4.4.6.1-17 I B-NR Adults with septal or great artery shunts should undergo periodic screening for pulmonary hypertension with I B-NR Cardiac catheterization to assess pulmonary vascular hemodynamics is recommended for adults with septal or great artery shunts and clinical symptoms, signs, or echocardiographic findings suggestive of I B-NR In adults with septal or great artery shunts, cardiac catheterization with hemodynamics (performed before or at time of closure) is beneficial to assess suitability for CLINICAL STATEMENTS AND GUIDELINES Diagnostic (Continued) I C-EO BNP, chest x-ray, 6-minute walk test, and cardiac catheterization are useful for initial and follow-up evaluation of patients with ACHD with PAH. Synopsis Pulmonary hypertension is defined as elevation of mean pulmonary arterial pressure to 25 mm Hg at rest and does not imply a specific underlying pathophysiology. Pulmonary hypertension is further classified on the ba- sis of the presumed mechanism (including elevation of pulmonary venous pressure [denoted as postcapillary pulmonary hypertension ], parenchymal or restrictive lung disease, rheumatologic disease, portal hyperten- sion, toxin exposure, and thromboembolism). It is also classified by developmental or acquired anatomic ab- normalities of decreased pulmonary arterial capacitance, impedance, or stenosis throughout the pulmonary arte- rial vascular bed. PAH as initially described required pul- monary venous pressure 15 mm Hg with concomitant elevation of pulmonary vascular resistance. Although left-to-right shunting was the initial research model of triggered PAH, pulmonary hypertension in patients with ACHD can be caused by, or associated with, any of the factors described above.


Although left-to-right shunting was the initial research model of triggered PAH, pulmonary hypertension in patients with ACHD can be caused by, or associated with, any of the factors described above. Effective therapies may be spe- cific to the primary mechanism of pulmonary hyperten- sion in a given patient, so patients with CHD should have thorough investigation for all potential contributing eti- ologies to pulmonary hypertension that may require spe- cific therapy if best clinical outcomes are to be achieved. Adverse effects of pulmonary hypertension therapies in patients with ACHD with pulmonary hypertension may differ from those noted in other patients, because of concomitant multiorgan and vascular effects from long- standing congenital heart and vascular disease. Shunt-related PAH in patients with ACHD can de- velop in the pre- or perioperative period but also may develop years to decades after closure of defects. Mechanisms for development of PAH may include ge- netic factors and environmental exposures. Severity of PAH may range from incidentally noted mild pressure and resistance elevation to profound systemic or supra- systemic levels of PA pressure and pulmonary vascular resistance. If an anatomic defect that allows shunting is present, shunt reversal and cyanosis may develop as pulmonary resistance rises above systemic resistance (ie, Eisenmenger syndrome). See Section 3.3 for recommendations on who should perform surgeries, cardiac catheterization, and other procedures in these patients; Section 3.4 for rec- ommendations on diagnostic evaluation; and Table 33 for routine testing and follow-up intervals. Recommendation-Specific Supportive Text 1. Patients with ACHD with pulmonary hyperten- sion, particularly PAH, have a poorer prognosis than do patients with ACHD with similar histo- ries and anatomic abnormalities who do not have pulmonary hypertension.


Patients with ACHD with pulmonary hyperten- sion, particularly PAH, have a poorer prognosis than do patients with ACHD with similar histo- ries and anatomic abnormalities who do not have pulmonary hypertension. The fields of ACHD and pulmonary vascular disease care have increasingly disparate but complementary bodies of know- ledge, and both are necessary to achieve op- timal outcomes for patients with PAH. Clinicians cross-trained in both subspecialties or partnering experts from each subspecialty appear necessary to fully counsel patients with ACHD with PAH re- garding: diagnostic evaluation, prognosis, lifestyle choices, suitability for operative or catheter-based repair of existing shunts or vascular obstructions contributing to PAH, nature and effectiveness of additional medical therapies, mechanical circula- tory and pulmonary vascular support, and goals of care. 2. PAH may develop years after shunt closure in patients with ACHD. Predictors for the develop- ment or presence of PAH include: a. Anatomic defects: complete AVSD, sinus ve- nosus defect, large nonrestrictive defect (ASD >2 cm, VSD >1 cm, PDA >0.6 cm), and concomitant ACHD AP classification II or III abnormalities. b. Preintervention Qp:Qs 3 and/or PASP >40 mm Hg. c. Presence of associated syndrome (eg, Down syndrome). Recommendations for Severe PAH (Continued) COR LOE Recommendations Table 33. Pulmonary Hypertension and Eisenmenger Syndrome: Routine Follow-Up and Testing Intervals Frequency of Routine Follow-Up and Testing Physiological Stage C* (mo) Physiological Stage D* (mo) Outpatient ACHD cardiologist 6 12 3 6 Pulse oximetry Each visit Each visit CMR As needed As needed Cardiac catheterization As needed As needed *See Tables 3 and 4 for details on the ACHD AP classification system. Routine TTE may be unnecessary in a year when CMR imaging is performed unless clinical indications warrant otherwise. CMR may be indicated for assessment of right ventricular function and CHD anatomy not clarified with TTE.


CMR may be indicated for assessment of right ventricular function and CHD anatomy not clarified with TTE. Baseline study is recommended with periodic follow-up CMR, with frequency of repeat imaging determined by anatomic and physiological findings. 6-minute walk test or CPET, depending on clinical indication. Cardiac catheterization should be performed at baseline and as needed. ACHD indicates adult congenital heart disease; CMR, cardiovascular magnetic resonance; CPET, cardiopulmonary exercise test; ECG, electrocardiogram; and TTE, transthoracic echocardiogram. CLINICAL STATEMENTS AND GUIDELINES d. Older age at repair. e. Female sex. f. Otherwise unexplained symptoms potentially attributable to PAH (decreased exercise ca- pacity, syncope, chest pain, hemoptysis). g. Findings on clinical examination: systemic ar- terial desaturation, elevated systemic venous pressures, other evidence of fluid retention, loud P2, new TR or PR, new arrhythmia, decreased exercise capacity, electrocardi- ographic findings consistent with subpul- monary ventricular hypertrophy or dilation. Echocardiography may demonstrate subpul- monic ventricular dysfunction and/or enlarge- ment and estimate central venous and PA pressures. However, echocardiography alone is insufficient to accurately determine PA pressure or pulmonary vascular resistance, so echocardiography is best used in conjunction with data obtained at cardiac catheterization when making decisions about instituting or changing therapy for PAH.S4.4.6.1-19 S4.4.6.1-21 3. Cardiac catheterization remains the standard for accurate diagnosis of pulmonary hypertension syndromes and for selection of optimal thera- pies for patients with ACHD with pulmonary hypertension. 4. Mechanical interventions targeting relief of ana- tomic contributors to PAH (eg, closure of septal or great arterial defects to eliminate shunting) may be considered as part of short-term plans of care for patients with ACHD with PAH. However, even modest residual levels of PAH substantially determine intermediate and longer-term out- comes. Patients should be followed for pulmo- nary hypertension. 5.


However, even modest residual levels of PAH substantially determine intermediate and longer-term out- comes. Patients should be followed for pulmo- nary hypertension. 5. Although history, noninvasive testing, and labo- ratory analysis (biochemistry and hematology) are all part of the workup of pulmonary hyperten- sion associated with CHD, cardiac catheterization with careful hemodynamic measurements, with or without provocative maneuvers and/or angiog- raphy, remains fundamental to accurate diagnosis and design of therapeutic plans. 4.4.6.2. Eisenmenger Syndrome Recommendations for Eisenmenger Syndrome Referenced studies that support recommendations are summarized in Online Data Supplement 50. COR LOE Recommendations Diagnostic I C-EO When evaluating adults with presumed Eisenmenger syndrome, clinicians should confirm diagnostic imaging and cardiac catheterization data accuracy and exclude other potential contributors to right-to-left shunting or pulmonary hypertension. Therapeutic I A Bosentan is beneficial in symptomatic adults with Eisenmenger syndrome with ASD or IIa B-R In symptomatic adults with Eisenmenger syndrome, bosentan and PDE-5 inhibitors are reasonable in combination if symptomatic improvement does not occur with either IIa C-EO Bosentan is a reasonable therapy to treat symptomatic adults with Eisenmenger syndrome with 1 of the following: shunts other than ASD/VSD (eg, PDA, aortopulmonary window) (Level of Evidence C-EO), or complex congenital or Down (Level of Evidence B-NR). B-NR IIa B-NR It is reasonable to use PDE-5 inhibitors (eg, sildenafil, tadalafil) to treat symptomatic adults with Eisenmenger syndrome with ASD, VSD, or great artery Synopsis Historically Eisenmenger syndrome has been under- stood as the most advanced form of PAH associated with congenital intracardiac and great arterial shunting. The natural course and outcomes of PAH in patients with ACHD with Eisenmenger syndrome, as contrasted to other adults with PAH, remain incompletely defined.


The natural course and outcomes of PAH in patients with ACHD with Eisenmenger syndrome, as contrasted to other adults with PAH, remain incompletely defined. However, it is believed that better survival and func- tional ability of untreated adults with Eisenmenger syn- drome might be explained by sharing of loading condi- tions between right- and left-sided cardiac chambers, as well as multiorgan system adaptations that develop over time. The fundamental cause of Eisenmenger syndrome is elevated pulmonary vascular resistance driving right- to-left intracardiac or great arterial shunting leading to systemic arterial desaturation. The risk of development of Eisenmenger syndrome is influenced by concomitant congenital syndromes, anatomic location of congenital defects, size of anatomic defects, genetic factors, and environmental exposures. Pathophysiological mechanisms contributing to de- velopment of Eisenmenger syndrome are not fully un- derstood. Suggested triggers and pathways include blood flow-induced shear and circumferential stress, vasoconstriction, and vascular cell proliferation associ- ated with fibrosis and thrombosis. Cyanosis, erythrocytosis, abnormalities of loading conditions, and abnormalities of systemic and pulmo- nary perfusion all contribute to functional incapacity and potential for multiorgan system dysfunction and other sequelae, including stroke, brain abscess, osteo- Recommendations for Eisenmenger Syndrome (Continued) COR LOE Recommendations CLINICAL STATEMENTS AND GUIDELINES arthropathy, iron deficiency, reduced glomerular clear- ance and susceptibility to acute renal insufficiency, ne- phrosis, pulmonary arterial thrombosis and dissection, hemoptysis, pulmonary parenchymal infections, dias- tolic and systolic cardiac dysfunction, arrhythmia, HF, and SCD. Palliative therapies that may be helpful include sup- plemental oxygen if systemic arterial oxygen saturation is empirically noted to rise in response, systemic antico- agulation, and avoidance of circumstances recognized to contribute to risk (eg, high altitude, pregnancy, ex- posure to high heat or humidity leading to vasodilation, nephrotoxin exposure, extreme exertion, large shifts in intravascular volume). However, supportive data for these strategies are limited or nonexistent.


However, supportive data for these strategies are limited or nonexistent. Systemic an- ticoagulation has the potential for adverse as well as possible helpful effects. Mechanical circulatory and pulmonary support, lung transplantation with concomitant repair of anatomic cardiovascular defects, and heart lung transplantation have all been applied in patients with ACHD with Eisen- menger syndrome with deteriorating functional ability. Indications for such therapies for adults with Eisen- menger syndrome are not standardized; comparative outcomes have not been tested, and to date successes have been limited. However, pharmacological treat- ment of PAH is helpful in the management of certain patients with Eisenmenger syndrome. See Section 3.3 for recommendations on who should perform surgeries, cardiac catheterization, and other procedures in these patients; Section 3.4 for rec- ommendations on diagnostic evaluation; and Table 33 for routine testing and follow-up intervals. Recommendation-Specific Supportive Text 1. Right-to-left shunting through septal defects or connections between the great arteries associ- ated with subpulmonary ventricular hypertension may be diagnosed as Eisenmenger syndrome. PAH medications may be beneficial for patients with Eisenmenger syndrome; however, other conditions may cause right-to-left shunting for reasons other than shunt-related PAH and thus may require different treatment options. These other conditions include: a) severe pulmonary hy- pertension of other cause (eg, thromboembolic disease, rheumatic disease), b) subpulmonary chamber outflow obstruction, c) abnormalities of subpulmonary chamber compliance, and d) vas- cular streaming. Accurate diagnosis is necessary to guide therapy. For example, PAH therapies will not be beneficial if the source of right-to- left shunting is RVOT obstruction; rather, allevi- ation of the RVOT obstruction is the necessary treatment. Accurate diagnosis of Eisenmenger syndrome and exclusion of other potential con- tributors to right-to-left shunting or pulmonary hypertension by means of advanced imaging and cardiac catheterization are crucial prerequisites to optimize therapy for adults with Eisenmenger syndrome. 2.


Accurate diagnosis of Eisenmenger syndrome and exclusion of other potential con- tributors to right-to-left shunting or pulmonary hypertension by means of advanced imaging and cardiac catheterization are crucial prerequisites to optimize therapy for adults with Eisenmenger syndrome. 2. In adults with Eisenmenger syndrome associated with ASD or VSD in World Health Organization functional class III or IV, RCTs demonstrate improved 6-minute walk distance, hemody- namics, and subjective functional ability after 4 months of oral bosentan.S4.4.6.2-17 Longer-term benefit has been demonstrated through open- label extension of this initial RCTS4.4.6.2-1 and in single-center registry cohorts.S4.4.6.2-1,S4.4.6.2-17 There may be a class effect for endothelin receptor antagonists, but others have not been studied in this population. 3. A randomized crossover trial of combination PAH therapy (PDE-5 inhibitor therapy and endothelin receptor antagonist therapy) enrolled adults with Eisenmenger syndrome or with idiopathic PAH and demonstrated improvement in systemic ar- terial saturation but not in functional ability or Use of combination PAH therapy for adults with Eisenmenger syndrome was further supported by a single-center co- hort series suggesting improvement in 6-minute walk testing and hemodynamics in adults with Eisenmenger syndrome using combined PDE-5 in- hibitory therapy and endothelin receptor antago- 4. Open-label single-center registries and cohort studies of adults with Eisenmenger syndrome, attributable to shunts other than ASD/VSD or with complex congenital heart lesions, suggest benefit in functional capacity or hemodynamics after months of endothelin receptor antagonist Patients with ACHD and Down syndrome have greater likelihood to de- velop pulmonary hypertension, and they have unique comorbidities that influence the nature of their pulmonary hypertension, the metrics used in follow-up, and the potential for benefit from as well as adverse response to therapy.


Open-label single-center registries and cohort studies of adults with Eisenmenger syndrome, attributable to shunts other than ASD/VSD or with complex congenital heart lesions, suggest benefit in functional capacity or hemodynamics after months of endothelin receptor antagonist Patients with ACHD and Down syndrome have greater likelihood to de- velop pulmonary hypertension, and they have unique comorbidities that influence the nature of their pulmonary hypertension, the metrics used in follow-up, and the potential for benefit from as well as adverse response to therapy. Open-label single-center registries and cohorts of adults with Down syndrome and Eisenmenger syndrome suggest benefit in subjective and/or objective functional capacity after months of endothelin re- ceptor antagonist therapy, generally as contrasted to performance before institution of endothe- lin receptor antagonist therapy.S4.4.6.2-8 S4.4.6.2-10 Accurate diagnosis of PAH and Eisenmenger syn- drome remains essential before initiating such therapy. CLINICAL STATEMENTS AND GUIDELINES regarding PDE-5 inhibitor therapy for adults with Eisenmenger syndrome have limita- tions, but are supported by multiple open-label prospective studies and information from a large single-center retrospective registry.S4.4.6.2-1,S4.4.6.2-11 These studies suggest benefit in functional capacity and hemodynamics after use of either sildenafil or tadalafil at varying doses and for varying periods of follow-up. Benefit was ei- ther in comparison to subjects performance before institution of therapy or to other adults with similar Eisenmenger syndrome anatomy and physiology who were not prescribed PDE-5 inhibitors. 4.4.7. Coronary Anomalies Coronary abnormalities are among the most com- mon congenital cardiovascular anomalies, surpassing in prevalence nearly all others combined. Coronary anomalies include anomalous aortic origin of a coro- nary artery (AAOCA), coronary fistula, and myocardial bridge. Many congenital coronary abnormalities have a benign outcome.


Coronary anomalies include anomalous aortic origin of a coro- nary artery (AAOCA), coronary fistula, and myocardial bridge. Many congenital coronary abnormalities have a benign outcome. In contrast, natural history studies of anomalous coronary artery from the PA (particularly anomalous left coronary artery from the PA) suggest poor outcome in untreated patients; similar natural history studies are lacking regarding untreated patients with AAOCA, but other evidence raises concern. See Table 34 and Figure 5 for a diagnostic and treatment algorithm for AAOCA. Assessment of the risk of SCD in patients with AAOCA and of the role of AAOCA in causing ische- mia or symptoms is difficult because available data do not adequately capture the clinical spectrum of these anomalies. Autopsy series are available that help de- scribe the anomalies found in patients who suffered SCD contrasted to other causes of death.S4.4.7-1 S4.4.7-5 There are surgical case series that describe findings before operation, operative anatomy and postopera- There are imaging studies describing the anatomy and potential pathophysio- logical abnormalities associated with AAOCA.S4.4.7-6, There are surgical series describing im- provement in symptoms after operation.S4.4.7-6 S4.4.7-8 There are surveys and registries that describe the heterogeneous management strategies applied to What is lacking are data prov- ing that any particular management strategy prevents SCD. As a consequence, decisions regarding whether surgery is necessary or exercise restriction or medi- cal therapy might be beneficial are all based on syn- thesizing limited data and applying to an individual patient. Clinicians commonly extrapolate to assist in medical decision-making, but the consequences of Table 34.


Clinicians commonly extrapolate to assist in medical decision-making, but the consequences of Table 34. Factors That May Relate to the Clinical Importance of AAOCA and Risk of SCD Age AAOCA is more commonly invoked as the cause of SCD in patients <35 y of age than in patients >35 y of age, in whom atherosclerotic coronary disease becomes a more prevalent cause. However, death has been attributed to AAOCA in patients of all ages; there does not seem to be an age beyond which the AAOCA may not be relevant, even in the setting of atherosclerotic coronary disease and other concomitant conditions.S4.4.7-1,S4.4.7-2 Anatomy of coronary ostium and proximal coronary course Slit-like/fish-mouth-shaped orifice, acute angle takeoff, intramural course, interarterial course and hypoplasia of the proximal coronary artery have all been proposed as reasons for symptoms, ischemia and SCD in patients with AAOCA. The slit- like orifice is more commonly seen in anomalous right coronary artery arising from the left sinus. Each of these anatomic findings offers a pathophysiological mechanism for intermittent ischemia, particularly at times of high cardiac output and/or increased aortic wall tension, such as during exercise.S4.4.7-6,S4.4.7-9 S4.4.7-11 Anomalous origin Left coronary artery arising from the right cusp is less common than the right coronary artery arising from the left cusp but is more often found in autopsy series of SCD.S4.4.7-1,S4.4.7-3,S4.4.7-15 This suggests that anomalous origin of the left coronary artery from the right cusp is more likely to cause SCD than anomalous origin of the right coronary artery from the left cusp. This may be due either to anatomic features that make anomalous aortic origin of the left coronary artery prone to coronary compromise or because a larger proportion of myocardium is supplied by the left coronary artery, or both.


This may be due either to anatomic features that make anomalous aortic origin of the left coronary artery prone to coronary compromise or because a larger proportion of myocardium is supplied by the left coronary artery, or both. Exercise Autopsy series suggest a most patients die during, or in close temporal association with, exercise.S4.4.7-3 S4.4.7-5 Ischemia Autopsy series demonstrate myocardial fibrosis in a significant number of patients whose deaths were attributed to AAOCA, particularly in patients with anomalous left coronary artery arising from the right cusp.S4.4.7-5 Surgical series describe patients with ischemia or MI before surgical repair in the absence of other CAD, suggesting a relation of the coronary anomaly to the ischemia.S4.4.7-16 This suggests that had perfusion imaging been obtained before SCD, ischemia would have been found in such patients.S4.4.7-17,S4.4.7-18 However, other data indicate that a normal stress test does not preclude a SCD event, with the proviso that most of those studies used only stress ECG, rather than the more sensitive and specific modalities of nuclear perfusion imaging or stress echocardiography. In addition, postoperative studies have shown that ischemia may be found after surgical repair in the distribution not supplied by the abnormal coronary artery and may not persist on repeat Symptoms In autopsy and surgical series, a significant number of patients reported cardiovascular symptoms, including before SCD events.S4.4.7-4,S4.4.7-7,S4.4.7-8,S4.4.7-20,S4.4.7-21 Symptoms are more commonly reported in patients in whom the left coronary artery arises from the right sinus. Surgical series have described improvement in symptoms after surgical AAOCA indicates anomalous aortic origin of the coronary artery; CAD, coronary artery disease; ECG, electrocardiogram; MI, myocardial infarction; and SCD, sudden cardiac death. CLINICAL STATEMENTS AND GUIDELINES being wrong for a young patient with AAOCA may be perceived to be greater than for many other con- ditions.