Cardiac catheterisation

Full haemodynamic cardiac catherisation enables the measurement of various cardiac and respiratory parameters. Data collected through CC includes transpulmonary gradient (TPG); end-diastolic pressure; PVR; mean pulmonary artery pressure (mPAP); and common atrial pressure. This is enabled through a set of direct calculations for blood flow and resistance as well as estimates and direct measurements. ^{Reference Mohammad Nijres, Murphy, Diab, Awad and Abdulla9} However, due to the added risk of cancer from ionising radiation, ^{Reference Kleinerman10} there has been a growing interest for substitution of CC with less invasive methods. ^{Reference Mohammad Nijres, Murphy, Diab, Awad and Abdulla9,Reference Brown, Gauvreau and Powell11}

Despite this, a recent cohort study aiming to compare CC with ECHO found that patients requiring systemic to pulmonary arterial or left SVC embolisation were not detected by ECHO. In a minority of patients, significant new diagnostic information was revealed through CC, which may have resulted in postponement or exclusion of a Fontan procedure. ^{Reference Mohammad Nijres, Murphy, Diab, Awad and Abdulla9}

Cardiac magnetic resonance

Whilst angiographical catherisation allows for a therapeutic approach in selected cases, its invasive nature makes it less ideal for patients without a need for its therapeutic effect. Accordingly, there is mounting interest in the less-invasive CMR. CMR may be limited by intrinsic factors such as spatial resolution, lack of patient cooperation, and contraindications in patients with metallic devices. However, it offers high diagnostic value through assessment of cardiovascular morphology, ventricular function, and blood flow, through phase contrast flow, cine imaging and magnetic resonance angiography. ^{Reference Schicchi, Secinaro and Muscogiuri12} CMR is more commonly used for post-surgical care but it has been adapted to provide valuable insight in pre-surgical planning. ^{Reference Fogel, Khiabani and Yoganathan13} To benefit from the radiation-free environment offered by CMR as well as the therapeutic advantage of CC, an algorithm has been proposed which seeks to eliminate the need for CC in some patients, ^{Reference Ait-Ali, De Marchi and Lombardi8} illustrated in Figure 2.

Figure 2. A summary of algorithm for preoperative assessment of Fontan candidates reprinted from Ait-Ali et al ^{Reference Ait-Ali, De Marchi and Lombardi8}. ECHO=Echocardiogram; CMR=Cardiac magnetic resonance; CC=Cardiac Catherisation. Candidates for Fontan are assessed with a medical history, ECHO, and CMR imaging. If any of the underlying criteria (1–9) is present, the patient should be considered for CC. This minimises the exposure of all Fontan candidates to radiation in CC.

Computed tomography, angiography, and echocardiography

Another similar protocol was based on conducting non-invasive assessments including ECHO, medical history taking, and non-invasive angiography on patients for whom Fontan was previously excluded by CC was able to correctly identify all the patients who were deemed not fit for the Fontan operation by cardiac catheterisation. ^{Reference Prakash, Khan, Hardy, Torres, Chen and Gersony14} Accordingly, a coherent and precise system should be considered before considering phasing out CC based on institutional experience and strength in imaging modalities.

Fontan management protocols

Several protocols (Table 2 ) have been published with the aim of lowering incidence of postoperative and prolonged pleural effusions (PPE) and hospital length of stay (LOS) in post-Fontan patients. These protocols, focusing on standardised diuretic regimens, afterload reduction, anticoagulation, low-fat diets, fluid restriction, and continuous oxygen therapy, have improved outcomes for Fontan patients by reducing hospital LOS and chest tube drainage. ^{Reference Sunstrom, Muralidaran and Gerrah2,Reference Cava, Bevandic, Steltzer and Tweddell16–Reference Lagergren, Jensen, Beaven and Goudar19} Whilst these results are promising, further multicentre randomised controlled trials are needed to provide stronger evidence for the use of a standardised approach and to determine which approach is best to manage Fontan patients in the postoperative period.

Table 2. Summary of Fontan-specific postoperative management protocols

ACEi = Angiotensin-converting enzyme inhibitor; AT3 = Antithrombin 3; ICU = Intensive care unit; IV = Intravenous; LOS = Length of stay; PICC = peripherally inserted central catheter; PO = Per oral; POD = Postoperative day; TPN = Total parenteral nutrition; LOS = Length of stay.

* Duration and discharge regimen not specified.

† Oral medications continued as outpatient for 2 weeks and weaned as per patient’s cardiologist.

‡ Titration based on patient tolerance and echocardiogram findings of systemic atrioventricular valve regurgitation.

Antibiotic prophylaxis

It is difficult to recommend standardised antibiotic prophylaxis protocols for paediatric cardiac surgery patients due to microbial sensitivity variability. Furthermore, antibiotic pharmacokinetics in paediatric patients undergoing cardiopulmonary bypass (CPB) is not fully known. ^{Reference Jaworski, Kansy, Dzierzanowska-Fangrat and Maruszewski20} A suggested schedule has been proposed covering preoperative nasal swab screening and treatment of Staphylococcus aureus with Mupirocin, intraoperative prophylaxis with cefazolin with vancomycin added if MRSA colonisation is present, and continuation of antibiotics for 48 hours postoperatively (prolonged if delayed sternal closure or ECMO or VAD). However, more research is needed to determine and investigate an optimal protocol. ^{Reference Jaworski, Kansy, Dzierzanowska-Fangrat and Maruszewski20}

Risk factors for prolonged ICU stay

Predictors for early Fontan failure include heterotaxia, low preoperative arterial oxygen saturations, and systemic right ventricle. ^{Reference Ovroutski, Sohn and Barikbin21} Lower oxygen saturations, higher haemoglobin, and increased pulmonary arterial pressure (PAP) are all associated with prolonged ICU LOS, ^{Reference Sasaki, Dykes and Sosa22} suggesting that interventions to optimise the pulmonary circulation prior to surgery may improve postoperative outcomes. Postoperative complications such as PPE, chylothorax, ascites and infection, ^{Reference Ono, Burri and Balling23} AKI, ^{Reference Algaze, Koth, Faberowski, Hanley, Krawczeski and Axelrod24} cardiac abnormalities (such as cardiac arrest, tachyarrhythmias) or the need for unplanned intervention (such as cardiac catheterisation or reoperation), ventilatory and circulatory support, prolonged chest tube drainage, renal replacement therapy (RRT), or blood product transfusion are all associated with increased LOS. ^{Reference Sasaki, Dykes and Sosa22} Considering these risk factors, an evidence-based protocol to safely step down Fontan patients from ICU for ward-based management would be useful.

Survival outcomes

Today, short-term survival after the Fontan procedure is reported to be as high as 98%. ^{Reference Downing, Allen and Glatz50} Medium-term outcomes are also promising, with transplant-free survival rates as high as 95% at 5 years. ^{Reference Downing, Allen and Glatz50} The estimated survival for a Fontan patient operated on today is as high as 85% at 30 years. ^{Reference Rychik, Atz, Celermajer and Deal1,Reference Schilling, Dalziel and Nunn51} Complications that significantly increase mortality include arrhythmia, protein-losing enteropathy (PLE), and venous thromboembolism. ^{Reference Rychik, Atz, Celermajer and Deal1} A summary of long-term complications, recommended surveillance measures for early detection, and methods of management are summarised in Table 3.

Table 3. The surveillance and management of late complications of a Fontan circulation

BNP = B-natriuretic peptide; CMR = Cardiac magnetic resonance; ECG = Electrocardiogram; LFT = Liver function tests; NOAC = Novel oral anticoagulants.

Table 4. List of abbreviations

Fontan circulation failure

Symptoms of heart failure are reported in up to 40% of adults with a Fontan circulation. ^{Reference Piran, Veldtman, Siu, Webb and Liu52} There are two forms of heart failure seen; the typical ventricular pump dysfunction and the physiological consequence of a chronically reduced CO paired with persistently elevated systemic venous pressures. Heart failure signs and symptoms are a major cause of admissions in Fontan circulation patients. ^{Reference Rychik, Atz, Celermajer and Deal1} BNP, cardiopulmonary exercise testing and echocardiography may be used to track significant changes indicating Fontan failure. ^{Reference Atz, Zak and Mahony53}

Initial management of Fontan failure involves comprehensive imaging, including the use of transthoracic echocardiography and CMR. This is particularly to rule out the presence of an obstruction, which would be managed by cardiac catheterisation. ^{Reference Ovroutoski, Ewert, Alexi-Meskishvili, Peters, Hetzer and Berger54} Other management options include diuresis to lower filling pressures and alleviate symptoms. Standard heart failure management such as ACE inhibitors are commonly used in Fontan patients: however, their benefit requires further investigation. ^{Reference Anderson, Breitbart and McCrindle55} There is limited evidence supporting cardiac resynchronisation therapy, which is shown to have mixed results. ^{Reference Dubin, Janousek and Rhee56}

As a bridge to transplantation for failing Fontan patients, both fenestration creation and mechanical circulatory support can be utilised. Transplantation is often the last resort for the failing Fontan resistant to other forms of management. ^{Reference Poh, Cochrane and Galati57} Early transplant referral is beneficial for improving survival. Alongside transplant scarcity, there are no clear guidelines on transplant suitability for Fontan patients, particularly regarding the preferred timing, indications, and contraindications. Additionally, Fontan transplant candidates are more likely to be listed at the lowest urgency status compared to non-congenital heart disease candidates and have a higher cardiovascular mortality when waiting for a transplant. ^{Reference Everitt, Donaldson and Stehlik58} Evidence suggests better survival outcomes in paediatric Fontan transplant recipients, with paediatric 1-year survival after transplant as high as 89% compared to 65% in adults. ^{Reference Simpson, Pruitt and Kirklin59,Reference Murtuza, Hermuzi and Crossland60} Other last-resort options include ventricular assist devices, ^{Reference Horne, Conway, Rebeyka and Buchholz61} with Fontan-specific devices being a promising field for future management of Fontan patients.

Fontan-associated liver disease

Patients with a Fontan circulation have increased risk for Fontan-associated liver disease (FALD) due to physiological consequences of a Fontan circulation, such as elevated systemic venous pressures causing hepatic congestion and reduced CO causing hepatic hypoperfusion. Incidence of severe liver fibrosis on liver biopsy is as high as 68% in post-Fontan patients. ^{Reference Munsterman, Duijnhouwer and Kendall62} Surveillance of Fontan patients for FALD should occur around 10 years after surgery; however, the methods of this surveillance are contraversial. Recent evidence suggests that liver enzymes are rarely elevated in stable FALD and that ultrasound may fail to detect smaller lesions due to the heterogenous parenchyma in a Fontan liver. Consequently, cross-sectional imaging is increasingly used for liver lesion screening with liver biopsy and elastography included in assessment. ^{Reference Emamaullee, Zaidi and Schiano63}

Recommendations to prevent liver complications include avoidance of hepatotoxins including alcohol, amiodarone, and obesity. There is limited evidence suggesting heart transplant alone may stabilise FALD. ^{Reference Emamaullee, Zaidi and Schiano63} Combined heart and liver transplantation (CHLT) is a rare procedure with promising supporting evidence. Both Mayo Clinic and the University of Pennsylvania have recently compared their experiences of heart transplantation and CHLT in Fontan patients; both groups found similar survival rates, but increased rates of acute rejection in the heart transplantation alone cohort. ^{Reference Wong, Gandhi and Daly64,Reference Zhao, Wang and Kamoun65} Thus, Fontan patients with a failing Fontan circulation and evidence of FALD should be considered for CHLT, which may be more beneficial than heart transplantation alone. ^{Reference Emamaullee, Zaidi and Schiano63}

Protein-losing enteropathy

Protein-losing enteropathy (PLE) is a significant complication of Fontan palliation, occurring in up to 12% of Fontan patients. PLE is a loss of lymphatic fluid into the gastrointestinal tract as a consequence of chronically increased systemic venous pressures paired with inflammation of the gastrointestinal tract. This causes loss of high-protein lymph rich fluid, resulting in hypoalbuminaemia. ^{Reference Rychik, Atz, Celermajer and Deal1} PLE presents with symptoms of diarrhoea, peripheral oedema, ascites, and growth failure. It usually presents in the first 10 years after the Fontan procedure. The gold standard for diagnosis is 24-hour stool collection with measurement of elevated α1 anti-trypsin levels. Routine surveillance including serum albumin levels can improve early detection of PLE. ^{Reference Zentner, Celermajer and Gentles66} Conservative management for PLE involves dietary changes such as a high-protein and low-fat diet. However, most evidence suggests that dietary manipulation alone does not alleviate symptoms. ^{Reference Johnson, Driscoll and O’Leary67} Medical management involves diuretics to decrease fluid overload and corticosteroid treatment with budesonide, with some centres utilising spironolactone and octreotide. Finally, a surgical intervention used to alleviate PLE symptoms includes atrial level fenestration, ^{Reference John, Johnson, Khan, Driscoll, Warnes and Cetta68} which can be performed transcatheter. A novel catheterisation based technique involving the selective embolisation of gastrointestinal lymphatic vessels appears promising in a small number of cases; further evidence is needed to clarify its use in PLE management. ^{Reference Itkin, Piccoli and Nadolski69}

Plastic bronchitis

Plastic bronchitis (PB) is another presentation of Fontan failure, which usually occurs within the first few years after the operation in up to 5% of Fontan patients. ^{Reference Rychik, Atz, Celermajer and Deal1,Reference Schumacher, Singh, Kuebler, Aprile, O’Brien and Blume70} Both PB and PLE have a similar aetiology, as PB is caused by lymphatic and bronchial communications leaking lymphatic fluid into the pulmonary system. ^{Reference Dori, Keller and Rome71} Patients present with casts in the pulmonary bronchi comprised of inflammatory debris. Presenting symptoms include breathlessness and coughing fits, often associated with hypoxia. ^{Reference Rychik, Atz, Celermajer and Deal1,Reference Avitabile, Goldberg, Dodds, Dori, Ravishankar and Rychik72} Accordingly, routine surveillance of oxygen saturations may promote early detection. ^{Reference Zentner, Celermajer and Gentles66}

Management of PB is aimed to improve symptoms and airway clearance. Oxygen provision, inhaled tissue plasminogen activator, pulmonary vasodilators, diuretics, and bronchodilators can be useful pharmacological agents to alleviate symptoms in Fontan patients. Intensive chest physiotherapy is also beneficial. ^{Reference Avitabile, Goldberg, Dodds, Dori, Ravishankar and Rychik72} Similar to PLE, embolisation of the lymphatic system is a promising management option. ^{Reference Dori, Keller and Rome71}

Medications used in Fontan patients

The majority of Fontan patients take two or more medications long-term. Commonly utilised medications include antithrombotic agents, ACE inhibitors, cardiac glycosides, and diuretics. However, there is significant variation in medication use in Fontan patients across different centres. ^{Reference Anderson, Breitbart and McCrindle55} Furthermore, there is limited evidence on the effectiveness of these medical therapies in Fontan patients.

ACE inhibitors and β-blockers are sometimes used in Fontan patients but lack supporting evidence. ^{Reference Anderson, Breitbart and McCrindle55} Evidence has shown no benefit in Fontan patients using enalapril; a recent review concluded that ACE inhibitors were overprescribed in Fontan patients with limited rationale. ^{Reference Kouatli, Garcia, Zellers, Weinstein and Mahony73,Reference Wilson, Iyengar and Winlaw74} Additionally, a large multicentre study with a small subset of patients with functionally single ventricle circulations found no benefit with carvedilol use. ^{Reference Shaddy, Boucek and Hsu75}

Hepatotoxic agents such as amiodarone, high dose acetaminophen, NSAIDs, and certain antibiotics should be avoided in Fontan patients (see Table 4 for abbreviations). ^{Reference Emamaullee, Zaidi and Schiano63} Risk-benefit assessment before use of nephrotoxic medications such as ACE inhibitors and diuretics is beneficial, due to the association of a Fontan circulation with increased risk of long-term kidney dysfunction. ^{Reference Zafar, Lubert and Katz76} For female patients, the use of oestrogen-based contraceptives should be avoided due to the increased risk of venous thromboembolism. Progesterone only hormonal contraceptives or barrier methods are a safer alternative. ^{Reference Thorne, MacGregor and Nelson-Piercy77}

Quality of life

The quality of life of Fontan patients is complicated by the interplay of physical, psychological, and social challenges. According to a recent meta-analysis, the health-related quality of life of a Fontan patient is lower than the general population. ^{Reference Marshall, D’Udekem and Sholler78} Both the functional limitations of a Fontan circulation and the psychological impact of patients anticipating Fontan failure are contributors. Older age at Fontan procedure may lead to worse psychological outcomes. ^{Reference Marshall, D’Udekem and Sholler78} More evidence assessing health-related quality of life in older Fontan patients and exploring moderating factors and variables is essential.