Rather than priority dictated by the usual accepted risk markers, pa- tients with ACHD are often listed by exception, a pro- cess that requires the clinician to argue that the patient warrants higher priority than would be evident by apply- ing the used risk markers. There is also significant mortal- ity for patients with ACHD while on the waitlist.S3.14.2-10, Surgical alternatives to transplantation exist for some patients with CHD (eg, valve replacement, shunt closure), but these patients are at high risk of periopera- Ideally, providers will consider early referral to a transplant center with expertise in ACHD transplantation when transplantation becomes a relevant clinical consideration. Additionally, it is advisable to con- sider options for transplantation or ventricular assist de- vice as a backup before other high-risk surgery is pursued. See Online Data Supplement 23 for referenced studies. 3.14.3. Multiorgan Transplant Recognizing the vulnerability of many organ systems in patients with CHD, multiorgan transplantation is often considered, although infrequently performed. Multi- organ transplantation requires a multidisciplinary and comprehensive approach with thoughtful planning and communication among practitioners. Multiorgan transplantation may be performed as se- quential operations or as a single operation. Typically, simultaneous multiorgan procedure in patients with CHD will be heart-lung transplantation for conditions that result in irreversible pulmonary hypertension such as Eisenmenger syndrome.S3.14.3-1,S3.14.3-2 Fewer than 100 heart-lung transplants are performed internationally each year, with a median survival of 3.3 years and 10-year survival of 32%.S3.14.3-3 Survival is worse for heart-lung recipients than single-organ heart or lung recipients pos- sibly, in part, because of longer wait times.S3.14.3-4 CLINICAL STATEMENTS AND GUIDELINES The occurrence of simultaneous heart-liver trans- plantation is an option in patients with severe right-sid- ed HF and in single ventricle patients after Fontan palli- ation. Given the recognized vulnerability of the liver to injury in Fontan patients and the fact that heart alone transplantation outcomes have been poor in patients with concomitant liver dysfunction, transplant centers may favor heart-liver transplantation in those with cir- rhosis, but this policy is not universal. Fewer than 15 such procedures are performed annually in the United States, and approximately 20% of patients are referred because of underlying CHD.S3.14.3-5,S3.14.3-6 Consequently, experience with these procedures is limited,S3.14.3-5,S3.14.3-7 and heterogeneity makes generalizability difficult. Data are insufficient to support recommendations. For all patients, survival mimics that for liver transplantation Outcomes in Fontan patients with or without cirrhosis are not necessarily different in those who receive heart transplantation alone.S3.14.3-5, Multicenter data gathering on patients con- sidered for multiorgan transplantation are needed to inform future recommendations for these therapies. 3.15. Palliative Care Recommendation for Palliative Care Referenced studies that support the recommendation are summarized in Online Data Supplement 24. COR LOE Recommendation IIa B-NR Discussion of end-of-life issues and advance directives can be beneficial for patients with ACHD or their surrogates.S3.15-1 S3.15-3 Recommendation-Specific Supportive Text 1. Patients with ACHD sometimes have significant morbidities not amenable to effective medical or surgical treatment and may be best managed using the consultative expertise of palliative care special- ists. Accurate predictions of prognosis in ACHD are difficult, and patients commonly receive aggressive treatments during their terminal admission.S3.15-4 There is a discrepancy between patient-reported in- terest in discussing advance directives and physician- reported discussions, with more patients interested in such discussions than recognized by providers.S3.15-1, Early discussion of advance planning is favored by nearly twice as many patients as physicians.S3.15-3 Early discussion of end-of-life issues is consistent with patient-centered care and patient satisfaction and can facilitate palliative care. Although discuss- ing end-of-life options would seem appropriate for all patients, there are circumstances (eg, cultural or cognitive) when those conversations may not be appropriate. Similarly, although the goal is not to wait to discuss end-of-life until death is imminent, such discussion may not have the same benefit for young patients who are clinically well with low-risk disease. Thus, it is important to always have and en- courage the option to discuss end-of-life issues, but timing of conversation is individualized. The definition of cyanosis is blueish discoloration of the skin and/or mucous membranes resulting from inade- quate oxygenation of the blood. Generally, for cyanosis to be visible, at least 5 g/L of unsaturated hemoglobin in tissue is needed.S3.16-1 Anemia may result in hypoxe- mia that is not manifest as cyanosis. In this guideline, cyanosis is used as a generic term to identify hypox- emia caused by right-to-left shunting of blood, but not all hypoxemic patients will be visibly cyanotic at all times. Cyanotic heart disease encompasses a widely hetero- geneous group; therefore, an individualized approach is needed for each patient according to the clinical details. Secondary erythrocytosis (a physiological increase in red blood cell mass in response to hypoxemia) and polycythe- mia (a neoplastic proliferation of hematopoietic cells in- cluding the red blood cell line) are fundamentally different conditions that require different treatments. In secondary erythrocytosis, the patient s own homeostatic processes generally direct achievement of an optimal level of red cell mass, estimated by hemoglobin and hematocrit.S3.16-2 Iron deficiency is frequently encountered in cyanotic In addition to contributing to symp- toms, iron deficiency causes a reduction of hemoglobin without a proportional change in hematocrit and thus compromises systemic oxygen transport without lower- Symptoms mimic those of hyperviscos- ity. Consequences of iron deficiency may include stroke and myocardial ischemia,S3.16-4 S3.16-6 although published findings are inconsistent. Iron deficiency requires assess- ment of serum iron, ferritin, and transferrin levels, be- cause mean corpuscular volume is not a reliable screen- Limited data suggest that treatment of transferrin saturation <20% with iron supplementation until iron stores are replete can be done safely.S3.16-8 Although there is an exponential relationship be- tween viscosity and hematocrit, available data do not justify a cut point for a safe hematocrit.S3.16-3 There is no clear correlation between viscosity, iron deficiency, and a patient s symptoms or clinical condition.S3.16-3 The nature and cause of hyperviscosity symptoms are not well understood. The severity and frequency of symp- toms of hyperviscosity do not correlate with measured hematocrit. Phlebotomy is, therefore, rarely necessary in patients with secondary erythrocytosis, and routine phlebotomy is not supported by data. Patients with suspected hyperviscosity need to be rehydrated either CLINICAL STATEMENTS AND GUIDELINES with oral fluids or intravenous normal saline solution as a first-line therapy, evaluated for iron deficiency, and treated if appropriate. Phlebotomy (with equal volume fluid replacement) is sometimes performed in special cases wherein, after adequate hydration, hematocrit remains higher than the patient s baseline and symp- toms persist, or there is evidence of end-organ damage attributable to hyperviscosity (eg, myocardial ischemia, transient ischemic attack/stroke).S3.16-9,S3.16-10 Observational studies in cyanotic individuals have shown evidence of altered synthesis and function of clotting factors that may contribute to both hypo- and and thrombosis and bleeding (particularly epistaxis or hemoptysis) have been described in patients with Eisenmenger syndrome, which may be life-threatening.S3.16-13 S3.16-15 These dispa- rate trends preclude developing universally applicable recommendations, including use of antiplatelet or an- ticoagulant therapy in these patients.S3.16-16 Similarly, there is not a clear role for preoperative phlebotomy to improve coagulation properties. Cyanotic heart disease is a multisystem disorder. Manifestations, in addition to those already discussed, include renal dysfunction, gout, infections, and osteoar- thropathy. Alterations can be found of myocardial,S3.16-17, and retinal blood flow,S3.16-20 and Providers should recognize mul- tiorgan susceptibility and avoid treatments that may have adverse noncardiac effects. Additional practices that may contribute to effective management of cya- notic patients are listed in Table 12. See Online Data Supplement 25 for referenced studies. 3.17. Pharmacological Therapy for ACHD Patients with ACHD are commonly excluded from clin- ical trials, and there are few data to guide pharma- cological therapies. Although it may be tempting to extrapolate from management guidelines developed for patients without CHD (eg, HF guidelines),S3.17-1 treatments may not have the same benefit in the het- erogeneous population of patients with ACHD and in some cases may cause harm. The evaluation of new symptoms in a patient with ACHD must be tailored to the patient s anatomy, surgical repair, and physiol- ogy. Before considering pharmacological therapies, e- valuation for residual shunts, baffle stenosis, valvular or conduit dysfunction, and collateral vessels, any of which may be amenable to interventions, is an impor- tant consideration. The literature documenting pharmacological thera- pies for patients with ACHD is limited to small studies with limited duration of drug administration and fol- low-up. Additionally, the endpoints used are often sur- rogate markers that have not been validated for clinical decision-making, and studies are also often underpow- ered. However, studies in patients with ACHD do exist and evaluate conventional pharmacological therapy, es- pecially for HF and for arrhythmia, including beta block- ers, angiotensin-converting enzyme inhibitors, angio- tensin-receptor blockers, and aldosterone antagonists, although results vary.S3.17-2 S3.17-9 Pharmacological therapies in patients with ACHD are often directed to specific conditions (ie, beta block- ers for arrhythmia treatment). However, there are lim- ited data examining the benefits of beta blockers in specific ACHD populations. Results from a small study indicate that beta-blocker therapy may have potential to improve functional class in patients with a systemic right ventricle and a pacemaker.S3.17-2 Angiotensin- converting enzyme inhibitors and angiotensin-recep- tor blockers have also been assessed in small studies in specific ACHD populations in which no significant benefit on ventricular function or exercise capacity has Data from 1 small trial with a short follow-up interval in patients with a systemic right ventricle suggest that eplerenone may be associ- ated with reduced myocardial fibrosis, as assessed by Some pharmacological therapies affecting the pul- monary vasculature (eg, endothelin-receptor antago- nists and phosphodiesterase type-5 [PDE-5] inhibitors) Table 12. Specific Management Practices for Cyanotic CHD Recording clinical oxygen saturation at rest (>5 min) rather than immediately after effort (eg, walking into a clinic examination room). Meticulous intravenous care to avoid air or particulate matter, which may include use of air/particulate filters on all intravenous access lines, when feasible, and careful de-airing of all lines. Cerebral imaging for any new headache or neurologic sign to assess for possible cerebral abscess, hemorrhage, or stroke. Measurement of serum uric acid and treatment with allopurinol in a patient with a history of gout. Supplemental oxygen as needed for symptom relief but not to a target oxygen saturation level and not if there is no demonstrable symptomatic benefit. Avoidance of or cautious use of therapies that may reduce the patient s hypoxia-mediated drive to ventilation, such as narcotics or, in rare circumstances, excess supplemental oxygen.S3.16-22 Anesthesia by providers with expertise in anesthesia for patients with ACHD for any noncardiac surgery. Non-estrogen containing birth control for women of child-bearing potential (intrauterine device may be a preferred option). Avoidance of birth control entirely is not a safe, acceptable option. Patients can travel safely on commercial airlines without undue risk.S3.16-23 Preflight simulation testing or mandated supplemental oxygen are not usually indicated, although adequate hydration and movement during the flight are appropriate. Measurement of coagulation parameters (eg, activated partial thromboplastin time, international normalized ratio, thrombin time) in a patient with an elevated hematocrit >55% requires adjustment of anticoagulant volume in the blood collection vials to account for reduced plasma volume in the draw.S3.16-24 ACHD indicates adult congenital heart disease and CHD, congenital heart disease. CLINICAL STATEMENTS AND GUIDELINES have a beneficial effect on long-term outcomes in pa- tients with Eisenmenger syndrome.S3.17-10 Similarly, there are limited data on the use of pulmonary vasodilator therapy in Fontan patients, in whom the pulmonary vas- cular resistance may be abnormal.S3.17-11 S3.17-13 Because of the lack of data, clinical recommendations regarding pharmacological therapy for patients with ACHD are unsupported. Individualized care is needed, recognizing the potential benefits and risks of the therapy relative to patient-specific anatomic and physiological issues. See Online Data Supplement 22 for referenced studies. 4. SPECIFIC LESIONS 4.1. Shunt Lesions 4.1.1. Atrial Septal Defect Recommendations for Atrial Septal Defect Referenced studies that support recommendations are summarized in Online Data Supplement 26 and the systematic review COR LOE Recommendations Diagnostic I C-EO Pulse oximetry at rest and during exercise is recommended for evaluation of adults with unrepaired or repaired ASD with residual shunt to determine the direction and magnitude of the shunt. I B-NR CMR, CCT, and/or TEE are useful to evaluate pulmonary venous connections in adults I B-NR Echocardiographic imaging is recommended to guide percutaneous Therapeutic I B-NRSR In adults with isolated secundum ASD causing impaired functional capacity, right atrial and/or RV enlargement, and net left- to-right shunt sufficiently large to cause physiological sequelae (eg, pulmonary systemic blood flow ratio [Qp:Qs] 1.5:1) without cyanosis at rest or during exercise, transcatheter or surgical closure to reduce RV volume and improve exercise tolerance is recommended, provided that systolic PA pressure is less than 50% of systolic systemic pressure and pulmonary vascular resistance is less than one third of the systemic vascular I B-NR Adults with primum ASD, sinus venosus defect or coronary sinus defect causing impaired functional capacity, right atrial and/ or RV enlargement and net left-to-right shunt sufficiently large to cause physiological sequelae (eg, Qp:Qs 1.5:1) without cyanosis at rest or during exercise, should be surgically repaired unless precluded by comorbidities, provided that systolic PA pressure is less than 50% of systemic pressure and pulmonary vascular resistance is less than one third of the systemic vascular resistance.S4.1.1-13,S4.1.1-14 Therapeutic (Continued) IIa C-LDSR In asymptomatic adults with isolated secundum ASD, right atrial and RV enlargement, and net left-to-right shunt sufficiently large to cause physiological sequelae (eg, Qp:Qs 1.5:1 or greater), without cyanosis at rest or during exercise, transcatheter or surgical closure is reasonable to reduce RV volume and/or improve functional capacity, provided that systolic PA pressure is less than 50% of systemic pressure and pulmonary vascular resistance is less than one third systemic resistance.S4.1.1-7 S4.1.1-10,S4.1.1-12 IIa C-LD Surgical closure of a secundum ASD in adults is reasonable when a concomitant surgical procedure is being performed and there is a net left-to-right shunt sufficiently large to cause physiological sequelae (eg, Qp:Qs 1.5:1 or greater) and right atrial and RV enlargement without cyanosis at rest or IIb B-NR Percutaneous or surgical closure may be considered for adults with ASD when net left-to-right shunt (Qp:Qs) is 1.5:1 or greater, PA systolic pressure is 50% or more of systemic arterial systolic pressure, and/or pulmonary vascular resistance is greater than one third of the systemic III: Harm C-LD ASD closure should not be performed in adults with PA systolic pressure greater than two thirds systemic, pulmonary vascular resistance greater than two thirds systemic, and/or a net right-to-left shunt.S4.1.1-21,S4.1.1-22 Synopsis ASDs are common and may occur as a consequence of different anatomic defects, including secundum ASD, primum ASD, sinus venosus defect (not properly a de- fect in the atrial septum but considered in this section), and coronary sinus septal defect. Left-to-right shunting may result in right heart enlargement and RV dysfunc- tion and, in a minority of patients, PAH. Some patients may have right-to-left shunting or paradoxical embo- lism, and some may develop arrhythmias. Percutaneous device or surgical closure are the mainstays of therapy in those with hemodynamic or clinical consequences of the defect. Severe PAH is a contraindication to closure, and its presence must be accurately excluded before ASD may occur with other congenital cardiac ab- normalities. In some circumstances, such as in patients with Ebstein anomaly and pulmonary stenosis (PS) or right HF, the physiology related to the ASD is substan- tially more complex, and ASD closure could result in clinical deterioration. Therefore, these recommenda- tions regarding ASD address only isolated ASDs and not ASD associated with complex CHD. Recommendations for Atrial Septal Defect (Continued) COR LOE Recommendations CLINICAL STATEMENTS AND GUIDELINES The Interventional Therapy Versus Medical Therapy for Secundum Atrial Septal Defect: A Systematic Review (Part 2) for the 2018 AHA/ACC Guideline for the Man- agement of Adults With Congenital Heart Disease S4.1.1-1 has additional data and analyses. The results from the question Are outcomes in asymptomatic patients with unoperated secundum ASD and RV dilatation improved after percutaneous or surgical closure? and the writing committee s review of the totality of the literature were used to frame decision-making. Recommendations that are based on a body of evidence that includes the sys- tematic review conducted by the ERC are denoted by the superscript SR (eg, LOE B-RSR ). See Section 3.3 for recommendations on who should perform surgeries, cardiac catheterization, and other procedures in these patients; Section 3.4 for recom- mendations on diagnostic evaluation; Section 4.4.6 for evaluation and management of severe PAH and Eisen- menger syndrome; and Figure 1 for a diagnostic and treatment algorithm for secundum ASD. See Table 13 for routine follow-up and testing intervals. Recommendation-Specific Supportive Text 1. Pulse oximetry is useful in defining shunt direction at rest and with exercise, which will help guide deci- sions regarding therapeutic options. Pulse oximetry at rest and with exercise may identify patients with increased pulmonary arterial resistance and shunt reversal. In a subset of patients with resting sys- temic oxygen saturation >90%, a decrease in ox- ygen saturation with activity to <90% may occur, emphasizing the importance of performing resting and ambulatory pulse oximetry assessment. 2. TTE has limited use in assessment of anomalous pulmonary venous connections in adults with ASD. Moreover, the poor visualization of the su- perior and posterior atrial septum by TTE in adults may require testing with other imaging modalities to clearly define septal anatomy. TEE is excellent for visualization of the entire atrial septum as well as pulmonary venous connections. Anomalous right upper and middle lobe pulmonary venous connections often occur in combination with su- perior sinus venosus defect; TEE is excellent for visualization of this combination but may not vis- ualize other anomalous pulmonary venous con- nections. Cross-sectional imaging with CMR or CCT is ideal for delineating pulmonary venous connections, particularly those that are associated with veins that may be difficult or impossible to image by echocardiography (eg, innominate vein or vertical vein). CMR has the advantages of not involving ionizing radiation and ability to quantify degree of shunting. 3. It is considered standard of care to use echocar- diographic imaging to guide closure of interatrial communications. TEE and intracardiac echocar- diography are the most widely studied and used modalities for guidance of ASD closure. Defect size, defect morphology, atrial rim adequacy, pul- monary venous anomalies, and left atrial append- age thrombus can all be evaluated using TEE. Echocardiography is also used to determine sizing either by balloon diameter producing complete occlusion of the defect ( stop flow diameter) or by direct visualization and measurement using intracardiac echocardiography. Echocardiography can assess for pericardial effusion and for thrombi on wires or devices. TTE has also been studied for guiding percutaneous ASD closure but is not widely used for this purpose. 4. Cardiac catheterization is performed at the time of transcatheter ASD closure. Provided noninvasive imaging is of sufficiently high quality to estimate pulmonary artery pressures and shunt magni- tude, not every patient with an ASD requires a diagnostic catheterization before surgical closure. However, a diagnostic catheterization may be necessary to determine detailed hemodynamics for decision-making or to clarify discrepant or inconclusive noninvasive imaging data. Patients with reduced functional capacity presumed caused by hemodynamically important secun- dum ASD (moderate or large left-to-right shunt and evidence of right heart volume overload in the absence of significant PAH) benefit from sur- gical or transcatheter closure of the secundum Patients who do not undergo ASD closure have worse long-term outcomes, including more atrial arrhythmias, reduced func- tional capacity, and eventually greater degrees of PAH. Older adults should be evaluated for left atrial hypertension resulting from diastolic dysfunction, which may cause similar symptoms but could result in clinical worsening after ASD closure because of further increase in left atrial pressures when blood from the relatively restric- tive and higher pressure left atrium can no longer decompress into the lower pressure right atrium. Cyanosis with exercise typically occurs in associ- ation with poor RV diastolic compliance and he- modynamics with exercise, and the ASD acts as a pop-off to maintain cardiac output. However, exercise-induced cyanosis is not an absolute con- traindication to ASD closure, because there are rare cases of either streaming or directed tricuspid regurgitation (TR) leading to right-to-left shunting with exercise not related to abnormal RV diastolic pressures that may allow for closure after expert evaluation. Data are most compelling that closure CLINICAL STATEMENTS AND GUIDELINES improves functional status, although some de- scriptive studies support improved long-term out- comes after closure as well.S4.1.1-7 S4.1.1-12 5. Available percutaneously deployed ASD closure devices are approved for closure of secundum- type defects. Primum, sinus venosus, and coronary sinus ASDs should be closed surgically because of the absence of appropriate rims for percuta- neous device placement and the proximity of the atrioventricular valves and conduction system to the closure device. Congenital heart surgeons are trained in the nuances of repair of such defects, including common association with anomalous pulmonary venous connection and abnormalities of the atrioventricular valves.S4.1.1-24,S4.1.1-25 6. Patients who do not undergo ASD closure have worse long-term outcomes, including more atrial arrhythmias, reduced functional capacity, and eventually greater degrees of PAH.S4.1.1-7 S4.1.1-10, However, concomitant diseases may in- fluence the anticipated benefit of ASD closure in ameliorating symptoms and improving func- tional capacity, and it has not been clearly dem- onstrated that ASD closure in asymptomatic adults prevents long-term complications. Data suggest that ASD closure improves functional Table 13. ASD: 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 Exercise test As needed As needed 12 24 6 12 *See Tables 3 and 4 for details on the ACHD AP classification system. 6-minute walk test or CPET, depending on the clinical indication. ACHD indicates adult congenital heart disease; CPET, cardiopulmonary exercise test; ECG, electrocardiogram; and TTE, transthoracic echocardiogram. Figure 1. Secundum ASD. *Combination therapy with bosentan and PDE-5 inhibitor if symptomatic improvement does not occur with either alone. ACHD indicates adult congenital heart disease; ASD, atrial septal defect; PAH, pulmonary artery hypertension; PASP, pulmonary artery systolic pressure; PDE-5, phosphodiesterase type-5 inhibitors; PH, pulmonary hypertension; and Qp:Qs, pulmonary systemic blood flow ratio. CLINICAL STATEMENTS AND GUIDELINES capacity but, in patients with normal functional capacity, the long-term benefit of ASD closure is Pending further study, it is reasonable to close an ASD that is hemodynami- cally important in the absence of significant PAH. Older adults should be evaluated for left atrial hypertension resulting from diastolic dysfunction that may cause symptoms simulating those from an ASD alone, in whom ASD closure could result in clinical worsening because of further increase in left atrial pressure because the relatively restric- tive and higher pressure left atrium can no longer decompress into the lower pressure right atrium. Concomitant tricuspid annuloplasty can be of benefit in patients with moderate or more TR, as the additional volume load may adversely affect RV remodeling. 7. If surgical treatment is necessary for other con- genital or acquired cardiac conditions and the patient has a secundum ASD, it is reasonable to perform ASD closure at the time of surgery. When there is moderate or greater TR, tricuspid valve repair may improve RV remodeling. 8. To evaluate the patient with PAH and ASD, ensure the shunt remains left to right despite elevated pulmonary vascular resistance and/or pulmonary pressure and that pulmonary pressure and PVR are accurately measured. In this circumstance, data derived from invasive hemodynamic assess- ment are important in clarifying the appropriate course of action. The exclusion of patients with severe PAH from ASD closure may eventually be obviated by PA vasodilator and remodeling therapy with prostaglandins, endothelin blockers, and PDE-5 inhibitors. Because of the complexity of the hemodynamics in such patients, collabo- ration between ACHD and pulmonary hyperten- sion providers is important. Pretreatment with PAH therapies and pulmonary arterial remodeling agents, with a demonstrated reduction in pulmo- nary arterial resistance of >20%, portends a fa- vorable prognosis after ASD closure.S4.1.1-26 9. Morbidity and mortality are prohibitively high when surgical repair is attempted in patients with open shunts, such as ASD when Eisenmenger syndrome is present.S4.1.1-21,S4.1.1-22 4.1.2. Anomalous Pulmonary Venous Connections Recommendations for Anomalous Pulmonary Venous Connections Referenced studies that support recommendations are summarized in Online Data Supplement 27. COR LOE Recommendations Diagnostic I B-NR CMR or CTA is recommended for evaluation of partial anomalous pulmonary venous Diagnostic (Continued) IIa B-NR Cardiac catheterization can be useful in adults with partial anomalous pulmonary venous connection to further define Therapeutic I B-NR Surgical repair is recommended for patients with partial anomalous pulmonary venous connection when functional capacity is impaired and RV enlargement is present, there is a net left-to-right shunt sufficiently large to cause physiological sequelae (eg, Qp:Qs 1.5:1), PA systolic pressure is less than 50% systemic pressure, and pulmonary vascular resistance is less than one third of I B-NR Repair of partial anomalous pulmonary venous connection is recommended at the time of closure of a sinus venosus defect or I B-NR Repair of a scimitar vein is recommended in adults when functional capacity is impaired, evidence of RV volume overload is present, there is a net left-to-right shunt sufficiently large to cause physiological sequelae (eg, Qp:Qs 1.5:1), PA systolic pressure is less than 50% systemic pressure and pulmonary vascular resistance is less than one third IIa B-NR Surgery can be useful for right- or left- sided partial anomalous pulmonary venous connection in asymptomatic adults with RV volume overload, net left-to-right shunt sufficiently large to cause physiological sequelae (eg, Qp:Qs 1.5:1), pulmonary pressures less than 50% systemic and pulmonary vascular resistance less than one third systemic.S4.1.2-5 IIa B-NR Surgery can be useful for repair of a scimitar vein in adults with evidence of RV volume overload, with Qp:Qs 1.5:1 or Synopsis Abnormal connection between a pulmonary vein and systemic vein will result in volume overload of the right heart, with a physiological effect similar to that of an ASD. However, in the absence of an associated ASD, a- nomalous pulmonary venous connection differs in that there is no potential for right-to-left shunting, and the magnitude of the left-to-right shunt is not exacerbated by the development of acquired left heart disease. The most common anomalous pulmonary venous connec- tion is of the right upper pulmonary vein to the superior which may be associated with a sinus venosus defect. Other abnormal connections include right pulmonary vein(s) to the inferior vena cava (often via a so-called scimitar vein and associated with se- questration of the right lower lobe), left upper pulmo- nary vein(s) to the left innominate vein, and right upper Recommendations for Anomalous Pulmonary Venous Connections (Continued) COR LOE Recommendations CLINICAL STATEMENTS AND GUIDELINES pulmonary vein(s) connecting high on the superior vena cava. Long-term sequelae of anomalous pulmonary ve- nous connections reflect the impact of right heart vol- ume overload and are similar to the sequelae of ASDs. Surgical repair can be challenging as low-velocity ve- nous flow imparts risk of thrombosis of the surgically operated vein. 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 Section 4.4.6 for evaluation and management of severe PAH and Eisenmenger syndrome. Recommendation-Specific Supportive Text 1. Cross-sectional imaging with CMR or CTA is ideal for delineating pulmonary venous connections. CMR has the advantage of not using ionizing radiation and may also quantify the degree of shunting. Echocardiography is an important part of the evaluation and may identify the anomalous particularly in patients with excel- lent acoustic windows; however, CMR and CTA are superior for evaluating extracardiac vascular anatomy. 2. In higher-risk patients, invasive hemodynamic assessment can be useful for direct measurement of pressures, quantification of shunt magnitude, and measurement of pulmonary arterial resist- ance and responsiveness to pulmonary vasodi- lator therapy. Invasive hemodynamic assessment is especially important in adult patients who are being considered for surgical correction. 3. It is unusual for a single anomalous pulmonary venous connection of only 1 pulmonary lobe to result in a sufficient volume load to justify sur- gical repair. However, if a patient has symptoms referable to the shunt, there is >1 anomalous vein, and a moderate or large left-to-right shunt, then surgical repair is associated with a reduc- tion in RV size and PA pressure.S4.1.2-5 Pulmonary hypertension is a risk for adverse outcomes with surgery. 4. Surgery usually involves intracaval baffling into the left atrium, Warden procedure,S4.1.2-12 or direct reimplantation of the anomalous pulmonary vein directly into the left atrium. 5. Surgical repair of a scimitar vein includes direct reimplantation of the scimitar vein into the left atrium, conduit placement to the left atrium, or intracaval baffling. This surgery can be technically challenging with a greater risk of postoperative vein thrombosis than is associated with more common and simpler anomalous pulmonary vein Pulmonary hypertension is associated with poor outcomes. 6. It is unusual for a single anomalous pulmonary venous connection from only one pulmonary lobe to result in a sufficient volume load to justify sur- gical repair. However, if there is >1 anomalous vein and a moderate or large left-to-right shunt, then surgical repair is associated with a reduction in RV size and PA pressure and can be useful.S4.1.2-5 7. Surgical repair of a scimitar vein includes direct reimplantation of the scimitar vein into the left atrium, side-to-side anastomosis of the scimitar vein to the left atrium and closure of its connec- tion to the inferior vena cava or intracaval baff- ling. This surgery can be technically challenging with a greater risk of postoperative vein throm- bosis than is associated with simpler anomalous pulmonary vein abnormalities.S4.1.2-10 4.1.3. Ventricular Septal Defect Recommendations for Ventricular Septal Defect Referenced studies that support recommendations are summarized in Online Data Supplement 28. COR LOE Recommendations Therapeutic I B-NR Adults with a VSD and evidence of left ventricular volume overload and hemodynamically significant shunts (Qp:Qs 1.5:1) should undergo VSD closure, if PA systolic pressure is less than 50% systemic and pulmonary vascular resistance is less than one third systemic.S4.1.3-1 IIa C-LD Surgical closure of perimembranous or supracristal VSD is reasonable in adults when there is worsening aortic regurgitation (AR) caused by VSD.S4.1.3-1,S4.1.3-2 IIb C-LD Surgical closure of a VSD may be reasonable in adults with a history of IE caused by VSD if not otherwise contraindicated.S4.1.3-3 IIb C-LD Closure of a VSD may be considered in the presence of a net left-to-right shunt (Qp:Qs 1.5:1) when PA systolic pressure is 50% or more than systemic and/or pulmonary vascular resistance is greater than one third III: Harm C-LD VSD closure should not be performed in adults with severe PAH with PA systolic pressure greater than two thirds systemic, pulmonary vascular resistance greater than two thirds systemic and/or a net right-to-left Synopsis Ventricular septal defects (VSDs) initially create a vol- ume load to the left heart, and the magnitude of he- modynamic impact is directly related to the size of the shunt and afterload to the ventricles. Isolated VSDs are the most commonly encountered form of CHD in the Most isolated mus- CLINICAL STATEMENTS AND GUIDELINES cular and perimembranous VSDs are small and close spontaneously. The spectrum of isolated residual VSDs encountered in the adult patient includes: 1. Small restrictive defects. The pulmonary vascular resistance is not significantly elevated and the left-to-right shunt is small (Qp:Qs <1.5:1). 2. Large nonrestrictive defects in cyanotic patients who have developed Eisenmenger syndrome, with pulmonary vascular resistance at systemic levels and shunt reversal (right-to-left). 3. Patients with moderately restrictive defects (Qp:Qs 1.5:1 and <2:1) who have not undergone clo- sure for some reason. These patients often have mild-to-moderate PAH. 4. Patients who have had their defects closed in childhood. These patients may have VSD patch leaks.See Section 3.3 for recommendations on who should perform surgeries, cardiac catheter- ization, and other procedures in these patients; Section 3.4 for recommendations on diagnostic evaluation; Section 4.4.6 for evaluation and management of severe PAH and Eisenmenger syndrome; Figure 2 for a diagnostic and treatment algorithm for ventricular level shunt; and Table 14 for routine testing and follow-up intervals. Recommendation-Specific Supportive Text 1. In the absence of aortic valve prolapse and regur- gitation or IE, small restrictive defects of the mus- cular or membranous septum may be watched conservatively without need for operative inter- vention. In a long-term follow-up registry, the overall survival rate was 87% for all patients with unoperated VSD at 25 years.S4.1.3-1 For patients with small defects (Qp:Qs <1.5:1 and low PA pressure), the survival rate was 96%. Patients with moderate and large defects fared worse with 25-year sur- vival of 86% and 61%, respectively. Those with Eisenmenger syndrome (cyanosis/hypoxemia caused by reversal of shunt to right-to-left) had a Figure 2. Hemodynamically significant ventricular level shunt. *Combination therapy with bosentan and PDE-5 inhibitor, if symptomatic improvement does not occur with either alone. ACHD indicates adult congenital heart disease; AR, aortic regurgitation; IE, infective endocarditis; LV, left ventricular; PAH, pulmonary artery hypertension; PASP, pulmonary artery systolic pressure; PDE-5, phosphodiesterase type-5 inhibitors; PH, pulmonary hypertension; Qp:Qs, pulmonary systemic blood flow ratio; and VSD, ventricular septal defect. CLINICAL STATEMENTS AND GUIDELINES much lower 25-year survival (42%). Larger defects may be repaired but only in the absence of severe PAH and severely elevated pulmonary vascular re- sistance, the presence of which incurs a high peri- Life expectancy after VSD closure in an adult is not normal but has improved over the past 50 years. Transcatheter device occlusion of muscular and peri- membranous VSD is feasible, and trials have dem- onstrated a good safety and efficacy profile.S4.1.3-16, VSD in adults is most commonly either small, or large and associated with Eisenmenger syn- drome; therefore, data regarding optimal manage- ment of moderate VSD in adults are lacking because of relative infrequency of a hemodynamically signif- icant VSD for which closure is an option. 2. Small restrictive defects of the muscular or mem- branous septum may be managed by observa- tion without need for operative intervention. However, 6% of patients with small supracristal (subaortic) or perimembranous defects may de- velop aortic valve prolapse and resultant AR that may be progressive.S4.1.3-1,S4.1.3-2,S4.1.3-18 There is a paucity of data supporting the timing of VSD clo- sure in patients with AR. Ideally, the VSD is closed if AR is progressive to avoid the continued wors- ening of AR and the need for aortic valve replace- ment. In the presence of a VSD, an aortic valve cusp (usually the right coronary cusp) may pro- lapse and partially or completely close the VSD, often with associated AR. At the time of VSD closure, aortic valve repair may be performed in an effort to stabilize or improve AR. For patients who meet GDMT criteria for aortic valve replace- ment, this may be performed concomitant with 3. In patients with unrepaired VSD, there is an increased risk of IE, typically involving the tricuspid and pulmonic valves. 4. Early attempts at surgical closure of nonrestric- tive VSD in patients with Eisenmenger syndrome were associated with an unacceptably high risk of mortality, and the practice was quickly abandoned. However, there are adult patients with large VSD and PAH who may benefit from closure of the VSD if the net shunt is left-to-right either at baseline or with PAH therapies. The use of fenestrated devices and fenestrated surgical patches in these patients leaves a small residual shunt to allow decompres- sion of the right heart.S4.1.3-5,S4.1.3-6 In theory, treat- ment of these patients with PAH therapies before closure could improve outcomes. 5. Closure of nonrestrictive VSD in adults with Eisenmenger syndrome who do not demonstrate left-to-right shunting and a decline in pulmo- nary vascular resistance with PAH therapies car- ries a high risk of mortality and should not be 4.1.4. Atrioventricular Septal Defect Recommendations for Atrioventricular Septal Defect Referenced studies that support recommendations are summarized in Online Data Supplement 29. COR LOE Recommendations Diagnostic IIa C-EO Cardiac catheterization can be useful in adults with atrioventricular septal defect when pulmonary hypertension is suspected. Therapeutic I C-LD Surgery for severe left atrioventricular valve regurgitation is recommended per GDMT indications for mitral I C-EO Surgery for primary repair of atrioventricular septal defect or closure of residual shunts in adults with repaired atrioventricular septal defect is recommended when there is a net left-to-right shunt (Qp:Qs 1.5:1), PA systolic pressure less than 50% systemic and pulmonary vascular resistance less than one third systemic. IIa C-EO Operation for discrete LVOT obstruction in adults with atrioventricular septal defect is reasonable with a maximum gradient of 50 mm Hg or greater, a lesser gradient if HF symptoms are present, or if concomitant moderate-to-severe mitral or AR are present. Table 14. VSD: 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 Exercise test As needed As needed 12 24 6 12 *See Tables 3 and 4 for details on the ACHD AP classification system. 6-minute walk test or CPET, depending on the clinical circumstance. ACHD indicates adult congenital heart disease; CPET, cardiopulmonary exercise test; ECG, electrocardiogram; TTE, transthoracic echocardiogram; and VSD, ventricular septal defect. CLINICAL STATEMENTS AND GUIDELINES Therapeutic (Continued) IIb C-EO Surgery for primary repair of atrioventricular septal defect or closure of residual shunts in adults with repaired atrioventricular septal defect may be considered in the presence of a net left-to-right shunt (Qp:Qs 1.5:1), if PA systolic pressure is 50% or more systemic, and/or pulmonary vascular resistance is greater than one third systemic. III: Harm C-LD Surgery for primary repair of atrioventricular septal defect or closure of residual shunts in adults with repaired atrioventricular septal defect should not be performed with PA systolic pressure greater than two thirds systemic, pulmonary vascular resistance greater than two thirds systemic, or a net Synopsis AVSDs represent about 4% to 5% of congenital heart defects and include a primum ASD, inlet VSD, and com- mon atrioventricular valve. They can occur in several anatomic variations including partial AVSD with only a primum ASD component and typically a cleft left atri- oventricular valve, complete AVSD with both ASD and VSD and a common atrioventricular valve, and transi- tional and intermediate AVSD with incomplete atrial and VSDs and/or incomplete abnormalities of the com- mon atrioventricular valve. AVSD anatomy is also com- monly described by the Rastelli classification.S4.1.4-7,S4.1.4-8 The Rastelli classification describes anatomic variations of the superior bridging leaflet of the atrioventricular valve. In addition to the Rastelli classification or other similar descriptors, the relative sizes of the ventricles as balanced or unbalanced guide the type of repair (eg, bi- ventricular or single ventricle repair). This section refers to patients with balanced AVSD and biventricular repair. AVSD also occurs in association with other congenital lesions including TOF, CoA, and heterotaxy. There is also a strong association with syndromes, most com- monly trisomy 21 (Down syndrome). From a management perspective, most adults with AVSD will have had surgical repair as children. If those with complete AVSD (with large ASD and VSD) are not repaired early in life (typically <6 months of age), ir- reversible pulmonary vascular disease usually develops resulting in Eisenmenger physiology, precluding com- plete repair. For those who underwent a surgical repair, long-term follow-up is required to monitor for left atri- oventricular valve regurgitation and stenosis, left ven- tricular outflow tract (LVOT) obstruction attributable to the abnormal shape of the LVOT, and tachyarrhythmias and bradyarrhythmias. Left atrioventricular valve regur- gitation is the most common reason for later surgical reintervention. There are few long-term follow-up stud- ies of patients after AVSD repair in childhood, so the most effective and efficient timing and type of surveil- lance are still being evaluated. The atrioventricular node is typically displaced infe- riorly in AVSD and is associated with relative hypopla- sia of the left anterior fascicle.S4.1.4-9 Late-onset com- plete heart block (as late as 15 years after surgery) has been noted after surgery in patients operated on for AVSD who were discharged from the hospital with normal conduction, although more commonly seen in those patients with transient postoperative heart block. Regular monitoring for symptoms and screening with an ECG are important to evaluate for conduction See Section 3.3 for recommendations on who should perform surgeries, cardiac catheterization, and other procedures in these patients; Section 3.4 for recommendations on diagnostic evaluation; Sec- tion 4.1.1 for recommendations on primum ASD; Section 4.4.6 for evaluation and management of se- vere PAH and Eisenmenger syndrome associated with AVSD; and Table 15 for routine testing and follow-up intervals. Recommendation-Specific Supportive Text 1. Invasive hemodynamic assessment still has an im- portant role as a confirmatory tool and for the evaluation of pulmonary vasoreactivity, which does carry prognostic significance for adults with shunts. 2. Although the left atrioventricular valve in an AVSD malformation is not anatomically the same as a mitral valve, one can extrapolate the criteria for consideration of left atrioventric- ular valve surgery from the VHD guideline for mitral regurgitation and mitral stenosis.S4.1.4-1 In extrapolating these criteria, there are impor- tant potential differences in this patient popula- tion compared with those with acquired mitral valve disease. There are anatomic differences in position of the annulus, papillary muscles and the morphology of the LVOT, which is an anterior, narrow, and potentially obstructed structure, such that congenital surgical exper- tise is needed. Patients with an AVSD have typically had at least 1 prior attempt to repair the AVSD, have different risks of arrhythmia, and may have other anatomic lesions (eg, sub- aortic stenosis [subAS]). In 1 meta-analysis of studies of adult left atrioventricular valve sur- gery in patients with AVSD, the risk of needing a pacemaker was higher in those who under- went valve replacement than in those who un- In another single-center study, one third of repaired patients required Recommendations for Atrioventricular Septal Defect (Continued) COR LOE Recommendations CLINICAL STATEMENTS AND GUIDELINES an additional reoperation.S4.1.4-3 When replace- ment is required, the choice to use mechanical versus bioprosthetic valve is individualized, but a mechanical valve is usually necessary because of the potential for LVOT obstruction from the struts of the bioprosthetic valve. Nevertheless, valve repair is preferred to valve replacement when it is technically feasible. 3. There are no large studies on residual shunts in patients with AVSD, but extrapolating from in- formation on residual isolated ASD or isolated VSD, a moderate or large residual shunt is likely to result in worsening clinical status over time and thus merits consideration of repair.S4.1.4-11 S4.1.4-13 See Sections 4.1.1 and 4.1.3 for related consider- ations regarding ASD and/or VSD. Pulse oximetry at rest and with ambulation may identify patients with increased pulmonary resistance and shunt reversal. There is a subset of patients with rest- ing systemic oxygen saturation >90% who will have a decrease in oxygen saturation with activity to <90%, emphasizing the importance of per- forming resting and ambulatory pulse oximetry assessment. 4. Patients with AVSD are at risk of LVOT obstruc- tion because of the abnormal anatomy of the LVOT. Surgical resection of LVOT obstruction in association with AVSD is reasonable when there is moderate-to-severe obstruction or less obstruc- tion but associated HF or mitral regurgitation or AR. In isolated subAS studies, worse outcomes were revealed in patients with maximum gradi- ents 50 mm Hg or with gradients <50 mm Hg in association with symptoms of HF.S4.1.4-14 S4.1.4-17 Importantly the LVOT obstruction in AVSD may not be discrete and, therefore, surgical repair may be more complex. When evaluating patients with tunnel-like or complex LVOT obstruction, the peak Doppler gradients and Bernoulli equa- tion may inaccurately reflect the severity of ob- struction, and cardiac catheterization may be needed. 5. Patients with AVSD, particularly those with Down syndrome, are at high risk of developing pulmo- nary vascular disease resulting in Eisenmenger For those who continue to have a net left-to-right shunt despite elevated PA pressures, closure of the defect may prevent exacerbation of PAH. This is an unusual circum- stance and decision-making requires collabora- tion with ACHD and pulmonary hypertension providers. 6. Morbidity and mortality are prohibitively high when surgical repair is attempted in patients with open shunts such as AVSD when Eisenmenger syndrome is present.S4.1.4-5,S4.1.4-6 4.1.5. Patent Ductus Arteriosus Recommendations for Patent Ductus Arteriosus Referenced studies that support recommendations are summarized in Online Data Supplement 30. COR LOE Recommendations Diagnostic I C-EO Measurement of oxygen saturation should be performed in feet and both hands in adults with a PDA to assess for the presence of right-to-left shunting. IIa C-EO In addition to the standard diagnostic tools, cardiac catheterization can be useful in patients with PDA and suspected pulmonary hypertension (Section 3.5). Therapeutic I C-LD PDA closure in adults is recommended if left atrial or LV enlargement is present and attributable to PDA with net left-to-right shunt, PA systolic pressure less than 50% systemic and pulmonary vascular resistance less than one third systemic.S4.1.5-1 S4.1.5-3 IIb B-NR PDA closure in adults may be considered in the presence of a net left-to-right shunt if PA systolic pressure is 50% or greater systemic, and/or pulmonary vascular resistance is greater than one third systemic.S4.1.5-3,S4.1.5-4 III: Harm C-LD PDA closure should not be performed in adults with a net right-to-left shunt and PA systolic pressure greater than two thirds systemic or pulmonary vascular resistance greater than two thirds systemic.S4.1.5-5 Table 15. AVSD: 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 Exercise test As needed As needed 12 24 6 12 *See Tables 3 and 4 for details on the ACHD AP classification system. 6-minute walk test or CPET, depending on the clinical indication. ACHD indicates adult congenital heart disease; AVSD, atrioventricular septal defect; CPET, cardiopulmonary exercise testing; ECG, electrocardiogram; and TTE, transthoracic echocardiogram. CLINICAL STATEMENTS AND GUIDELINES Synopsis The ductus arteriosus is a vascular connection be- tween the aorta and PA that is present in fetal life. It typically closes shortly after birth but, in some people, it will remain patent. Patent ductus arteriosus (PDA) is found in about 0.3% to 0.8% of term infants and is twice as common in females as males.S4.1.5-6 S4.1.5-8 The clinical and physiological manifestations of the PDA are dependent on the size of the vessel and the rel- ative systemic and pulmonary vascular resistances. The PDA can range from a small hemodynamically insignificant lesion that is not heard on auscultation to one that without intervention is large enough to cause congestive HF and pulmonary hypertension. Many PDAs are now closed in infancy or childhood with catheter-based or surgical approaches. For those whose ductus remains patent in adulthood, catheter- based or surgical intervention consideration depends on the symptoms and physiological expression of the lesion. Follow-up of these patients as adults is impor- tant for all, although timing and testing will vary a- mong individuals. See Section 3.3 for recommendations on who should perform surgeries, cardiac catheterization, and other procedures in these patients; Section 3.4 for recom- mendations on diagnostic evaluation; Section 4.4.6 for recommendations on severe PAH (4.4.6.1) and Eisen- menger syndrome (4.4.6.2) associated with PDA; and Table 16 for routine testing and follow-up intervals. Recommendation-Specific Supportive Text 1. Because cyanosis caused by right-to-left shunting in PDA may manifest predominantly downstream from the ductal insertion into the aorta, accurate assessment of oxygen saturation by oximetry and assessment of cyanosis should be done in the feet and both hands. As with other types of shunts, pulse oximetry with ambulation as well as at rest may identify patients with increased pulmonary arterial resistance and dynamic shunt reversal in- duced by exercise. A subset of patients with rest- ing systemic oxygen saturation >90% will have a decrease in oxygen saturation with activity to <90%, emphasizing the importance of per- forming resting and ambulatory pulse oximetry assessment. 2. Invasive hemodynamic assessment still has an im- portant role as a confirmatory tool and for the evaluation of pulmonary vasoreactivity, which car- ries prognostic significance.S4.1.5-1,S4.1.5-4 3. When signs of volume overload are indicative of significant left-to-right shunt, closing the PDA is likely to prevent further left atrial or LV enlarge- ment, progression or development of PAH, and pulmonary hypertension secondary to left HF and will possibly provide symptom relief if symp- toms are present. Closure is typically performed percutaneously with good success and minimal Pulmonary blood flow and thus Qp:Qs can be difficult to calculate accurately because of differences in right/left PA blood flow caused by the flow from the PDA. Invasive he- modynamics including pulmonary vascular resist- ance are generally relied on for decision-making. Surgical closure can be performed but is poten- tially hazardous in adults because of calcification and tissue fragility. 4. Even with elevated pulmonary pressure and el- evated pulmonary vascular resistance, closure of a PDA may improve clinical status in some patients with persistent left-to-right shunting and prevent further progression of PAH.S4.1.5-3,S4.1.5-4 Consultation with ACHD and pulmonary hyper- tension providers is important given the low fre- quency of this circumstance and the complexity of decision-making. 5. Morbidity and mortality are high when closure of a shunt is attempted in patients with Eisenmenger physiology with elevated pulmonary pressure and net right-to-left shunting.S4.1.5-5 Table 16. PDA: 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 Exercise test As needed As needed 12 24 6 12 *See Tables 3 and 4 for details on the ACHD AP classification system. Upper and lower extremity. 6-minute walk test or CPET, depending on the clinical indication. ACHD indicates adult congenital heart disease; ECG, electrocardiogram; CPET, cardiopulmonary exercise test; PDA, patent ductus arteriosus; and TTE, transthoracic echocardiogram. CLINICAL STATEMENTS AND GUIDELINES 4.2. Left-Sided Obstructive Lesions 4.2.1. Cor Triatriatum Recommendations for Cor Triatriatum Referenced studies that support recommendations are summarized in Online Data Supplement 31. COR LOE Recommendations Diagnostic I B-NR Adults presenting with cor triatriatum sinister should be evaluated for other congenital abnormalities, particularly ASD, VSD, and anomalous pulmonary venous connection.S4.2.1-1 IIa B-NR In adults with prior repair of cor triatriatum sinister and recurrent symptoms, it is reasonable to evaluate for pulmonary vein Therapeutic I B-NR Surgical repair is indicated for adults with cor triatriatum sinister for symptoms attributable to the obstruction or a substantial gradient across the membraneS4.2.1-3 Synopsis Cor triatriatum occurs when a membrane divides either the left atrium (sinister), or right atrium (dexter). Cor tria- triatum sinister is usually associated with other congen- ital malformations, specifically ASD, VSD, or anomalous pulmonary venous connection (partial or total).S4.2.1-1 The left atrial appendage is invariably in the same chamber as the mitral valve, separated from the pulmo- nary veins by the membrane. Supravalvular mitral steno- sis is typically caused by a fibrous ring on the atrial side of the mitral valve, separating the mitral valve from both the left atrial appendage and the pulmonary veins. The finding will have similar physiology to cor triatriatum and similar indications for intervention. It can be associated with an abnormal mitral valve that may also require in- tervention. Supravalvular mitral stenosis often comprises one part of a more complex sequence of serial left-sided inflow and outflow obstructions (ie, Shone complex). See Section 3.3 for recommendations on who should perform surgeries, cardiac catheterization, and other procedures in these patients; and Section 3.4 for recommendations on diagnostic evaluation. Recommendation-Specific Supportive Text 1. Cor triatriatum sinister is a membrane spanning the left atrium. Surgery has been largely success- ful with relatively few early or late deaths, which are usually attributable to associated congenital The gradient across the de- fect at the time of surgery was at least 8 mm Hg (mean 17 mm Hg; range 8 to 40 mm Hg).S4.2.1-3 After repair, recurrence of stenosis is not ex- pected. Although pulmonary vein stenosis has been demonstrated before and after surgery,S4.2.1-2 it is not usually progressive over time and has not been associated with PAH. 2. Pulmonary venous stenosis has been demon- strated before and after surgery, but it is not usually progressive over time and has not been associated with PAH. 3. Although risks of isolated cor triatriatum sinister surgery is low, it should be performed when there is evidence of a substantial gradient. In 1 series, the mean gradient at the time of surgical repair was at least 8 mm Hg.S4.2.1-3 It is conceivable that on occasion, clinical circumstances (ie, symp- toms, arrhythmia) would warrant intervention in patients with lower gradients. 4.2.2. Congenital Mitral Stenosis Recommendation for Congenital Mitral Stenosis Referenced studies that support the recommendation are summarized in Online Data Supplement 32. COR LOE Recommendation I B-NR Adults with congenital mitral stenosis or a parachute mitral valve should be evaluated for other left-sided obstructive Synopsis Congenital mitral valve disease may be anatomically complex and is often accompanied by other lesions. Indications for intervention in mitral stenosis are de- scribed in the 2014 VHD guidelineS4.2.2-3 and apply to those patients with congenital mitral stenosis. Balloon mitral valvuloplasty is rarely, if ever, indicated or effec- tive in congenital mitral stenosis. 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 17 for routine testing and follow-up intervals. Recommendation-Specific Supportive Text 1. Parachute mitral valve is most commonly found in the presence of other congenital abnormali- ties such as the components of Shone complex. Recurrence and progression of the various asso- ciated lesions are expected, subsequent surger- ies are common, and mortality may be associated with other defects.S4.2.2-2 Therefore, these patients require follow-up at a center where such abnor- malities can be followed and future interventions considered. Choices and techniques for valve re- pair or replacement are based on consideration of coexisting abnormalities including the likelihood of future surgery. CLINICAL STATEMENTS AND GUIDELINES 4.2.3. Subaortic Stenosis Recommendations for Subaortic Stenosis Referenced studies that support recommendations are summarized in Online Data Supplement 33. COR LOE Recommendations Diagnostic IIb C-LD Stress testing for adults with LVOT obstruction to determine exercise capacity, symptoms, electrocardiographic changes, or arrhythmias may be reasonable in the presence of otherwise equivocal indications Therapeutic I C-EO Surgical intervention is recommended for adults with subAS, a maximum gradient 50 mm Hg or more and symptoms attributable to the subAS. I C-LD Surgical intervention is recommended for adults with subAS and less than 50 mm Hg maximum gradient and HF or ischemic symptoms, and/or LV systolic dysfunction attributable to subAS.S4.2.3-3 IIb C-LD To prevent the progression of AR, surgical intervention may be considered for asymptomatic adults with subAS and at least mild AR and a maximum gradient of 50 mm Hg or more.S4.2.3-4 S4.2.3-6 Synopsis SubAS may occur as a discrete membrane below the aortic valve in the LVOT, as a longer tunnel-like obstruc- tion, as a consequence of chordal attachments in pa- tients with abnormalities such as AVSD, or because of surgical repairs involving VSD baffled to a transposed aorta, such as seen in the Rastelli operation. SubAS may occur in isolation or as part of a suite of abnormalities. In adults with Shone complex or its variants, subAS may be one of several LV obstructive lesions, including vari- ants of congenital mitral stenosis, supravalvular mitral stenosis, valvular aortic stenosis, supravalvular aortic stenosis, and CoA.S4.2.3-7 SubAS tends to recur, particularly when initial resec- tion is needed in childhood. Surgical repair for subAS carries a 10% to 15% risk of complete heart block.S4.2.3-6 SubAS may be first diagnosed in adulthood and may be confused with hypertrophic obstructive cardiomyopa- thy when LV hypertrophy of sufficient severity has de- veloped such that the subaortic membrane is less evi- dent on imaging. The recommendations in this guideline apply to subAS caused by a discrete membrane or tunnel-like obstruction. Similar principles may apply to more com- plex causes of subAS, but insufficient data exist to sup- port recommendations for more complex lesions, and extrapolation needs to take the additional anatomic complexity into account. Turbulent flow created distal to the subaortic ob- struction may cause barotrauma to the adjacent aortic valve leaflets and result in progressive AR, which may itself become clinically significant. Resection of the sub- aortic obstruction ideally delays or prevents the even- tual need for aortic valve replacement, and concomi- tant aortic valve repair could also help delay the need for aortic valve replacement in these cases. 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 18 for routine testing and follow-up intervals. Recommendation-Specific Supportive Text 1. Exercise stress testing may be reasonable in the assessment of exercise capacity, stress-induced arrhythmias, and ischemia in patients with subAS and may be considered as an adjunct to echocar- diographic imaging. 2. Patients with symptomatic subAS should attain symptomatic improvement from surgical relief of the obstruction. In some cases, concomitant AVR may be needed, if indicated according to GDMT. 3. Patients with depressed LV systolic function and severe subAS may not manifest a resting gradient of 50 mm Hg. In this population, evaluation and decisions regarding surgical relief of LVOT obstruc- tion can be extrapolated from the existing aortic stenosis data and should be considered as per the Additionally, patients Table 17. Congenital Mitral Stenosis: 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 Tables 3 and 4 for details on the ACHD AP classification system. 6-minute walk test or CPET, depending on the clinical indication. ACHD indicates adult congenital heart disease; CPET, cardiopulmonary exercise test; ECG, electrocardiogram; and TTE, transthoracic echocardiogram. CLINICAL STATEMENTS AND GUIDELINES with preserved LV systolic function but poor LV compliance may present with signs or symptoms of HF and a resting maximum gradient <50 mm Hg. These patients may benefit from surgical re- lief of LVOT obstruction. Patients with evidence of resting or stress-induced ischemia in the absence of obstructive coronary artery disease and in the presence of moderate subAS (maximum gradient >30 mm Hg and <50 mm Hg) may benefit from surgical relief of subAS.S4.2.3-9 4. Discrete subAS tends to be progressive with age, and patients with a resting maximum gradient 50 mm Hg are more likely to have progressive subAS and concomitant moderate or severe aortic Therefore, surgical inter- vention may be considered in the asymptomatic patient with severe subAS. Tunnel-type subAS, which is often associated with a small aortic valve annulus, is associated with worse long-term out- comes and a higher risk of recurrence after sur- gical resection compared with subAS caused by a discrete membrane.S4.2.3-5 Surgical intervention on patients with asymptomatic subAS (maximum gradient 50 mm Hg) with preserved LV ejection fraction may delay progression of, or improve the degree of, aortic valve regurgitation. SubAS in adults may progress more slowly than in children, and although mild AR is common, it may not be progressive in medium-term follow-up.S4.2.3-10 4.2.4. Congenital Valvular Aortic Stenosis Recommendations for Congenital Valvular Aortic Stenosis Referenced studies that support recommendations are summarized in Online Data Supplement 34. COR LOE Recommendations Diagnostic I B-NR Adults with bicuspid aortic valve should be evaluated for coarctation of the aorta by clinical examination and imaging IIa B-NR It is reasonable to screen first-degree relatives of patients with bicuspid aortic valve or unicuspid aortic valve with echocardiography for valve disease and Therapeutic IIb B-NR In adults with bicuspid aortic valve stenosis and a noncalcified valve with no more than mild AR meeting indications for intervention it may be reasonable to treat with balloon valvuloplasty.S4.2.4-6 Synopsis Indications for aortic valve replacement according to generally apply. Recom- mendations above deal with issues specific to congen- ital aortic valve disease, which includes BAV, as well as unicuspid aortic valve and aortic stenosis caused by hy- poplastic aortic annulus. The underlying anatomy must be taken into account in patients with congenital aortic stenosis, as intervention may need to include annular enlarging procedures and other surgical techniques not commonly used in valvular aortic stenosis. 