Overview

Similar to non-congenital patients, patients with ACHD are susceptible to HF from valvular disease such as aortic stenosis that results in chronic pressure overload, and aortic or mitral regurgitation that results in chronic volume overload. However, many additional congenital diagnoses can result in heart failure. Although an exhaustive review of CHD is beyond the scope of this article, tables 1 and 2 summarise common congenital lesions and mechanisms resulting in HF.

Conditions of increased ventricular afterload result in ventricular hypertrophy and resultant systolic and diastolic dysfunction. Increased left ventricular afterload may be caused by congenital valvular aortic stenosis due to a unicuspid or bicuspid aortic valve, obstruction proximal to the valve in subaortic stenosis, obstruction distal to the valve in supravalvular aortic stenosis, or obstruction distal and remote from the aortic valve in coarctation of the aorta. Increased right ventricular afterload may be caused by pulmonary valve stenosis, pulmonary artery stenosis or unrepaired tetralogy of Fallot. Surgical pulmonary valvotomy for pulmonary stenosis or during repair of tetralogy of Fallot often converts the condition from one of increased right ventricular afterload to one of increased right ventricular preload due to chronic pulmonary regurgitation.

The physiological impact of a shunt depends on the size and location of the shunt. When the chamber receiving the shunt flow is distal to the tricuspid valve (TV), the resulting physiology is one of left heart volume loading, and right heart pressure loading, and pulmonary hypertension usually develops in patients with uncorrected moderate-large shunts. Examples of such post-tricuspid shunts are VSDs and patent ductus arteriosus (PDA). Isolated left heart volume load from CHD is typically related to mitral regurgitation from congenital abnormalities, such as a cleft mitral valve.

When the chamber receiving the shunt flow is proximal to the TV, the resulting physiology is one of right heart volume loading, with findings of right ventricle (RV) dilation, and eventual systolic and diastolic dysfunction. Examples of pretricuspid shunts are atrial-level shunts, including secundum-type and primum-type atrial septal defects, sinus venous defects and partial anomalous pulmonary venous return. TV abnormalities, most commonly Ebstein’s anomaly, may also result in chronic right heart volume loading from tricuspid regurgitation.

Another unique category of patients with ACHD is those with congenital heart defects or surgical repairs resulting in the anatomic RV functioning as the systemic ventricle. Such patients are prone to combined systolic and diastolic dysfunction of the pressure loaded RV, as the anatomic RV is not optimally suited to decades of work at systemic pressures. Tricuspid regurgitation due to intrinsic TV abnormalities and/or annular dilation often aggravates the physiology by also volume loading the challenged RV.

Patients with defects that are not amenable to two-ventricle repairs typically undergo Fontan palliation, which redirects systemic venous return passively to the pulmonary arteries without an intervening pump. This results in chronic elevations in systemic venous pressure (figure 1), chronic venous congestion and a low cardiac output state. Instead of the usual left HF findings of orthopnoea and pulmonary oedema, Fontan patients with volume overload have symptoms of right HF (ie, lower extremity oedema, abdominal fullness or bloating, early satiety). Varicose veins and chronic congestive hepatopathy are expected findings for Fontan patients, and long-term surveillance should include close monitoring for end-organ damage including hepatic fibrosis and renal dysfunction. Haemodynamic testing and assessment of the liver using biomarkers and liver biopsy can help risk stratify patients with Fontan-associated liver disease. Due to their complex and unique physiology, Fontan patients should be followed at ACHD centres.

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Figure 1

Scheme of the normal cardiovascular circulation (A), and the Fontan circulation early after operation (B), and the Fontan circulation late with increasing pulmonary resistance resulting in increased caval vein pressures and decreased cardiac output (C). Ao, aorta; CV, caval veins; LA, left atrium; LV, left ventricle; P, pulmonary veins; PA, pulmonary artery; S, systemic veins; RA, right atrium; RV, right ventricle; V, single ventricle.43

Cyanotic congenital defects result in shunting of deoxygenated blood from the right heart circulation to the left heart circulation, decreasing the patients’ arterial oxygen saturation. Cyanotic congenital heart defects include tetralogy of Fallot, D-transposition of the great arteries (D-TGA), truncus arteriosus and double outlet RV. In developed countries, most patients with cyanotic congenital heart defects undergo repair early in life with resolution of cyanosis, and the majority will survive to adulthood. If patients with cyanotic congenital heart defects do not undergo repair, most will die in childhood, though the occasional patient may survive into adulthood. Patients with cyanosis due to Eisenmenger syndrome have unrepaired large post-tricuspid shunts (ie, VSD or PDA); after initial left to right shunting in early life, they develop shunt reversal (ie, right to left shunting) due to severely elevated pulmonary vascular resistance. Patients with cyanosis may develop ventricular dysfunction related to chronic pressure overload. Chronic cyanosis results in multiorgan system abnormalities, particularly haematological abnormalities in coagulation.

Diagnosis and testing

Evaluation of patients with ACHD should be undertaken with an understanding of their diagnoses and prior interventions. For stable patients with ACHD, routine visits typically include an examination, EKG and echocardiogram, as well as periodic surveillance for known residual defect or sequelae if not well evaluated by echocardiogram.6 7 Serial evaluation of biomarkers such as natriuretic peptides can also be of value in selecting patients who might benefit from HF referral, evaluation and therapies. New symptoms or arrhythmias should prompt repeat diagnostic testing, with the goal of identifying residual abnormalities and sequelae associated with their disease. For example, patients at risk of coronary stenosis due to prior coronary reimplantation should have guideline-directed surveillance for coronary stenosis7; however, if they present with angina or an angina equivalent, they should undergo repeat assessment of their coronary arteries with a stress test, coronary angiogram, or CT or MRI focused on coronary imaging. Meanwhile, patients with a diagnosis of coarctation of the aorta with refractory hypertension should have CT or MRI imaging focused on the aorta to evaluate for recoarctation.

Serial cardiopulmonary exercise stress testing is a useful tool to assess cardiac work performance and functional capacity, and an unexpected deterioration in results should trigger a more detailed cardiac evaluation. Average values for peak oxygen consumption (peak VO₂) vary by congenital diagnosis (figure 2).8 A decline in peak VO₂ over time using serial cardiopulmonary stress testing predicts hospitalisation and death.9 However, in contrast with patients without ACHD who are typically referred for transplant at a peak VO₂ of ≤14 mL/kg/min, patients with ACHD are referred for transplant evaluation at a broader range of peak VO₂ values, and thus is not as useful as a determinant of optimal timing of transplant referral in the ACHD population.10

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Figure 2

Peak oxygen uptake (peak VO₂) data expressed as a percentage of predicted valve for different congenital heart defects.8 Reprinted from European Heart Journal, 33(11), Kempny A, Dimopoulos K, Uebing A, et al, Reference values for exercise limitations among adults with congenital heart disease. Relation to activities of daily life--single centre experience and review of published data, 1386–96, 2020, with permission from Elsevier. ASD, atrial septal defect; ccTGA, congenitally corrected transposition of the great arteries; CoA, coarctation of the aorta; TGA, transposition of the great arteries; ToF, tetralogy of Fallot; VSD, ventricular septal defect.

Patients with Fontan palliation may remain well compensated for decades after their Fontan surgery, but many will eventually develop ‘failing Fontan’ physiology due to chronic venous congestion and a chronic low cardiac output state. Markers of the ‘failing Fontan’ include ascites and/or lower extremity oedema refractory to diuretic therapy, refractory arrhythmias, cirrhosis, protein-losing enteropathy (PLE) and plastic bronchitis.

Therapies

Management of HF in patients with ACHD should be focused on optimising medication therapy and intervening on any residual haemodynamic lesions or sequelae. Guideline-directed medical therapy (GDMT) is recommended for patients with ACHD with systemic left ventricular dysfunction. Diuretics remain central in management of HF symptoms. Although limited data are available to guide use of GDMT in patients with ACHD with systemic RVs or Fontan physiology,11–13 GDMT may be tried with caution in such patients, particularly if there are additional indications for their use (ie, ACE inhibitors in patients with diabetes).

Pulmonary arterial hypertension occurs in approximately 10% of patients with CHD, and may lead to right HF. Pulmonary vasodilators (phosphodiesterase type 5 inhibitors, endothelin receptor antagonists and prostacyclins) are effective at improving symptoms.14–16 Bosentan has been shown to improve survival in patients with Eisenmenger syndrome.15 These therapies should be prescribed in consultation with pulmonary hypertension and ACHD specialists.

Atrial and ventricular tachyarrhythmias may be addressed with a combination of medication and/or ablation.17 Patients who meet standard indications for cardiac pacing, cardiac resynchronisation therapy (CRT) or implantable cardioverter-defibrillators should be evaluated for device placement.18 19 Patients with systemic RV may benefit from CRT, with mapping to guide optimal lead placement.20–22

Intervention for residual or recurrent lesions or sequelae would be similar to the initial intervention (tables 1 and 2), and may include valve repair or replacement, relief of obstruction and shunt closures when indicated (and in the absence of a contraindication). In addition, electrophysiology study and ablation for arrhythmias, and pacemaker placement for bradyarrhythmias, and defibrillation placement for prevention of sudden cardiac death in the patient with severe systolic dysfunction of the systemic ventricle should be considered.

Decisions about approach and timing of complex interventions should be made by a multidisciplinary team that includes ACHD specialists, imaging specialists, congenital cardiac surgery, congenital electrophysiology and congenital interventionalists. Significant advances in transcatheter devices over the past 20 years have helped decrease the number of operations or reoperations required in patients with CHD, and importantly have decreased morbidity and mortality in patients who otherwise would require high-risk reoperation. For example, patients with Ebstein’s anomaly with right ventricular dysfunction and a failing bioprosthetic TV would previously require reoperation for repeat TV replacement, with associated risk of further deterioration in RV function, ventricular arrhythmias and repeat sternotomy. Such patients would derive significant advantages from transcatheter valve-in-valve implantation compared with surgical reoperation for repeat TV replacement.

Mechanical circulatory support

Patients at end-stage HF may ultimately require heart or multiorgan transplant. Under current organ allocation systems, patients with ACHD spend more time awaiting transplant,23–25 and are more likely to die or deteriorate while awaiting an organ offer than the patients without ACHD.26 27 Because of these circumstances, mechanical circulatory support (MCS) has the potential to benefit the ACHD population without negatively impacting post-transplant outcomes.28

However, patients with ACHD currently account for less than 1% of patients with MCS in the USA.29 Relative to patients without ACHD, MCS options in patients with ACHD are more limited for numerous factors, which may include non-standard anatomy (ie, heterotaxy), multiple prior sternotomies, persistent shunts, malnutrition from PLE or cirrhosis from chronic right-sided congestion. Three-dimensional reconstructions from CT or MRI scans, with virtual placement of different ventricular assist devices (VADs) into the reconstructed images, can be helpful in determining whether the patients’ chest configuration permits placement of VADs.

It is useful to approach MCS in patients with ACHD by categorising the native or palliated anatomy into three categories: (1) systemic left ventricle in a biventricular circulation, (2) systemic RV in a biventricular circulation, and (3) single ventricular physiology.

Use of VADs in patients with systemic left ventricles in a biventricular circulation is familiar, as it fits the paradigm of non-congenital patients. Shunts, mitral valve stenosis or aortic regurgitation should be corrected to allow optimal VAD function after implant. Mitral valve regurgitation does not result in significant problems after VAD implant, and usually does not require attention at the time of VAD implant. Challenges such as dextrocardia and heterotaxy syndrome, and the significance of multiple sternotomies should not be underestimated. The possible need for biventricular support should be assessed during surgical planning and be readily available in the operating room. Patients with ACHD with left ventricular assist devices had similar survival compared with patients without ACHD, but patients with ACHD with biventricular assist devices or total artificial heart had worse survival compared with patients without ACHD.29

For patients with systemic RVs (see table 2) in a biventricular circulation, use of VADs for systemic right ventricular failure is currently limited to case series, but appears to be acceptable.30–32 Efforts should be made to address issues that might impair VAD function as noted above. The anatomic position of the systemic RV can present challenges to VAD placement. For example, early experience showed that VAD placement using conventional implantation techniques can direct the VAD inflow cannula towards the ventricular septum resulting in suction events. Additionally, the hypertrophy and trabeculations of systemic RVs can cause inflow cannula obstruction. In patients with D-TGA who have had an atrial switch, the ventricle is in usual rightward and anterior position; the VAD inflow and outflow cannulas would be confined, and placement of the VAD immediately below the sternum can impair VAD function or compress outflow cannulas on chest closure.

Use of VADs in patients with single ventricle has been described in case reports,33 and has been used as a bridge to transplant in several patients. Similar to use of VADs in patients with a systemic RV, additional research and experience are needed to optimise VAD use in this population. Support of single ventricular systolic dysfunction appears feasible, with several case reports of favourable outcomes using implantable continuous flow devices.34–36 Single ventricular diastolic dysfunction can also lead to HF symptoms, and VAD support appears to help in these settings as well.37 Efforts also continue to investigate the application of a VAD to Fontan pathway failure and is analogous to ‘right heart failure’ by looking at creative ways to place VADs within the Fontan circuit.

Transplant considerations

Similar to patients without congenital heart disease, patients with ACHD are referred for transplant for indications of end-stage HF on maximal tolerated medical therapy, not amenable to further optimisation with surgery or device therapy, or refractory ventricular arrhythmias. In the past two decades, the number of ACHD patients undergoing transplantation has increased significantly (figure 3), and survival has been comparable to those referred for transplant for other indications (figure 4). In addition, Fontan patients with stigmata of a ‘failing Fontan’ may be considered for heart or combined heart-liver transplantation.

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Figure 3

Trends in transplant care for patients with congenital heart disease (CHD) over time.38 Reprinted from J Am Coll Cardiol, 74, Nguyen VP, Dolgner SJ, Dardas TF, et al, Improved Outcomes of Heart Transplantation in Adults With Congenital Heart Disease Receiving Regionalized Care, 2908–18, 2019, with permission from Elsevier

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Figure 4

Kaplan–Meier survival by diagnosis. CHD, congenital heart disease; CM, cardiomyopathy; ICM, ischaemic cardiomyopathy; NICM, non-ischaemic cardiomyopathy; VCM, valvular cardiomyopathy.44 Reprinted from J Heart Lung Transplant, 37, Khush KK, Cherikh WS, Chambers DC, et al, The International thoracic organ transplant Registry of the International Society for heart and lung transplantation: Thirty-fifth adult heart transplantation Report-2018; focus theme: multiorgan transplantation, 1155–68, 20198 with permission from Elsevier

Patients with CHD listed for transplant at centres with expertise in CHD care have better outcomes, and post-transplant survival is more favourable at high-volume regional centres.38 Comprehensive, multidisciplinary evaluation of the patient with ACHD for transplant is summarised in table 3, and notably includes several additional specialties that are not commonly involved in the evaluation of patients without ACHD. The ACHD cardiologist can provide important guidance on the patient’s physiology and comorbidities, consider other therapeutic options to address the patient’s mechanism of HF, or identify out common residual issues such as vessel stenoses that impact transplant.

A congenital interventional cardiologist should perform the required diagnostic catheterisations in patients with moderate-complex ACHD, and address residual stenosis where appropriate (ie, residual coarctation). Identification of important collateral vessels that may cause catastrophic bleeding at time of surgery typically requires a combination of cross-sectional imaging with CT scans and invasive angiography. Patients with ACHD are prone to developing venovenous (VV) collaterals, aortopulmonary (AP) collaterals and pulmonary arteriovenous malformations (AVMs). VV collaterals form between the systemic veins (superior vena cava, inferior vena cava, abdominal veins) and the pulmonary veins in response to elevated systemic venous pressures. While any patient with chronically elevated systemic venous pressures can develop VV collaterals, these are particularly common in patients in Fontan palliation. AP collaterals form between the aorta or its branches (ie, brachiocephalic artery) and the pulmonary arteries, and may be seen in a variety of CHD diagnoses, and are particularly common in those with inadequate forward flow to the pulmonary artery (ie, pulmonary atresia), as the AP collaterals provide an additional source of pulmonary blood flow. Pulmonary AVMs shunt deoxygenated blood from the pulmonary arteries or arterioles to the pulmonary veins, bypassing the capillary bed and alveoli, and may contribute to cyanosis. Although the aetiology of pulmonary AVMs is not well understood, they occur more frequently when the pulmonary circulation does not receive hepatic blood flow, raising the possibility that a ‘hepatic factor’ helps inhibit growth of AVMs.39 Both VV and AP collaterals can cause catastrophic bleeding at the time of surgery. A strategy for targeted transcatheter coil embolisation or device occlusion of VV and AP collaterals prior to transplantation should be considered to mitigate surgical risk. Notably, occlusion of decompressing VV collaterals will increase pressures and decrease in the systemic veins, and should be undertaken with caution, particularly in the Fontan patient.

For patients with ACHD with moderate or complex anatomy, a congenital cardiac surgeon should be involved, either as the primary transplant surgeon or in conjunction with a cardiac transplant surgeon due to the unique technical challenges encountered in the patient with ACHD. First, patients with ACHD may have had multiple prior cardiac surgeries, resulting in high-risk chest re-entry at time of transplant. Second, patients with ACHD may have had anomalies or prior reconstruction of the systemic veins, pulmonary artery and/or veins, and/or aorta requiring additional reconstructive surgery at the time of transplant. Third, patients with dextrocardia or heterotaxy syndrome require special anatomic consideration due to abnormal positioning of the heart, abdominal organs and systemic venous connections.

As patients with right HF or prior Fontan palliation are at risk for liver disease due to chronic venous congestion, such patients should undergo liver biopsy, liver imaging, laboratory evaluation for liver synthetic function and other potential aetiologies of liver disease. Such patients should consult with a hepatologist and liver transplant surgeon who is familiar with CHD to determine whether the liver is sufficiently healthy to undergo the stress of a heart transplantation, or whether a combined heart-liver transplantation is necessary. For patients with dextrocardia or heterotaxy, the liver may be situated midline or in the left upper quadrant of the abdomen, posing an additional technical challenge for the transplant surgeon.

Some patients with ACHD are highly sensitised to foreign antigens due to prior blood transfusions during (often multiple) prior cardiac surgeries. Highly allosensitised patients face longer wait times as their antibodies preclude them from receiving organs from a substantial proportion of the donor pool. In addition, they are at increased risk for rejection, and may require more aggressive immunosuppression post-transplant. For such patients, the heart transplant cardiologist and immunogenetics team often consider a trial of desensitisation therapy; if the antibody profiles improve with desensitisation therapy, they may become acceptable candidates for transplant listing. For patients who are accepted for transplant listing in spite of high allosensitisation, desensitisation therapy can decrease their wait times by expanding their ability to accept organs from a larger proportion of the donor pool, and decrease risk of rejection post-transplant.

Psychiatric evaluation is a central part of any transplant evaluation, and is particularly important in patients with ACHD. Patients with ACHD experience more symptoms of depression and anxiety compared with their peers,40 and diagnosis and treatment of these symptoms are important for post-transplant success. Social worker evaluation of the patients’ compliance and support system is also critical; support from parents or siblings may be particularly important in young adults.

Multiple prior operations in patients with ACHD can result in restrictive lung disease due to impaired diaphragmatic function, which may range from mild decrease in diaphragmatic excursion to complete hemidiaphragm paralysis due to phrenic nerve injury. When undertaken soon after phrenic nerve injury, diaphragmatic plication has been demonstrated to improve respiratory function,41 42 though diaphragmatic plication in the patient with remote injury and a chronically elevated hemidiaphragm is of less clear benefit as the chronically compressed lung may not re-expand after plication. Nonetheless, plication at the time of transplant for patients with borderline restrictive lung disease may be considered for select patients. Compared with patients without ACHD, obstructive lung disease is less commonly seen in the patient with ACHD undergoing transplant evaluation due to generally younger age, and because patients with CHD are strongly discouraged from smoking from a young age due to their cardiac condition.

Nephrology evaluation is indicated for patients with chronic kidney disease (CKD), typically cardiorenal in aetiology due to chronic low cardiac output and renal venous congestion. Post-transplant, renal function often improves in patients with stage I–II CKD due to improvement in cardiac output; however, continuous renal replacement therapy (CRRT) may be needed in the immediate post-transplant period for optimisation of fluid status in patients with stage II–III CKD. Calcineurin inhibitors are potentially nephrotoxic, and require close monitoring of renal function when used for post-transplant immunosuppression. Patients with Fontan palliation often have mild thrombocytopenia due to platelet sequestration, and mild leucopenia. Haematology assessment may be helpful to ensure that the patient does not have a primary bone marrow disorder.

When a patient with complex ACHD is accepted for transplantation, a multidisciplinary surgical planning meeting should be convened, and the medical, surgical, intensive care unit and anaesthesia teams should create a written plan. The plan should ensure adequate time for induction of anaesthesia, safe chest entry, control of bleeding and explant of the recipient heart, and the geographic range of donors should be carefully considered to optimise the donor pool while also minimising donor ischaemic time. Donor height/weight parameters should be adjusted to ensure optimal patient size matching, particularly for patients with heterotaxy. Combined heart-liver transplants should be performed at centres with high-volume heart transplant and liver transplant programmes, and experienced ACHD cardiologists. In addition to the above-mentioned details, the surgical plan for a combined heart-liver transplant should also include the plan for induction of immunosuppression, duration of cardiopulmonary bypass (ie, whether the patient will remain on cardiopulmonary bypass for the liver transplant) and strategies for volume management (ie, CRRT) in the critical perioperative window. While awaiting transplant, patients with ACHD with tenuous haemodynamic status or evidence of progressive end-organ damage may benefit from inpatient admission and listing, as this provides an opportunity for ongoing optimisation prior to transplant. Continuous infusion of inotropes can improve organ perfusion, careful titration of diuretics can maintain the patient in a euvolemic state, thus mitigating risk at the time of transplant.

Summary

Patients with ACHD are a growing heterogeneous population at increased risk of developing HF. Management of HF should be focused on optimal GDMT, addressing residual haemodynamic abnormalities with catheter-based and/or surgical procedures whenever possible. Management of HF, and consideration of MCS and transplant in the patient with ACHD requires a multidisciplinary approach with expertise from multiple surgical and medical specialties. Increasingly, patients with ACHD are undergoing heart and multiorgan transplantation. Early identification, referral and multidisciplinary management have the opportunity to improve outcomes, longevity and quality of life for this patient population.