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Canadian Journal of Cardiology

Fontan Circuit Thrombus in Adults: Often Silent, Rarely Innocent

  • Emilie Laflamme
    Affiliations
    Division of Cardiology, Peter Munk Cardiac Centre, University Health Network and University of Toronto, Toronto, Ontario, Canada
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  • S. Lucy Roche
    Correspondence
    Corresponding author: Dr S. Lucy Roche, UHN Toronto General Hospital, Toronto Congenital Cardiac Center, Department of Cardiology, 5N 521-585 University Ave, Toronto, Ontario M5G 2N2, Canada. Tel.: +1-416-340-3266; fax: +1-416-340-5014.
    Affiliations
    Division of Cardiology, Peter Munk Cardiac Centre, University Health Network and University of Toronto, Toronto, Ontario, Canada
    Search for articles by this author
Published:September 21, 2019DOI:https://doi.org/10.1016/j.cjca.2019.09.008
      A Fontan circulation is a surgically modified vasculature with pathways created to separate oxygenated and deoxygenated blood and to permit function with only a single ventricular pump. In effect, systemic venous blood reaches the lungs passively. Achieving a Fontan circulation can require several surgeries or interventional procedures and has become the usual approach for diagnoses such as tricuspid atresia, hypoplastic left heart syndrome, double inlet left ventricle, or an unbalanced atrioventricular septal defect. The ability to pursue a Fontan strategy (in any of its many iterations or refinements) has undoubtedly transformed outcomes for infants born with a single ventricle physiology. Era-related 20-year survival rates might be as high as 90% for children who received surgery in the 2000s.
      • van der Ven J.P.G.
      • van den Bosch E.
      • Bogers A.J.C.C.
      • Helbing W.A.
      State of the art of the Fontan strategy for treatment of univentricular heart disease.
      To uphold the legacy of this success, attention must now turn to promoting health and mitigating complications in the still-growing population of adult survivors. Growth in the number of adults living with congenital heart disease is set to continue until approximately 2050
      • Benziger C.P.
      • Stout K.
      • Zaragoza-Macias E.
      • Bertozzi-Villa A.
      • Flaxman A.D.
      Projected growth of the adult congenital heart disease population in the United States to 2050: an integrative systems modeling approach.
      and estimates from New Zealand have predicted that the adult Fontan population will double in size over the next 20 years.
      • Schilling C.
      • Dalziel K.
      • Nunn R.
      • et al.
      The Fontan epidemic: population projections from the Australia and New Zealand Fontan Registry.
      Although most adult Fontan patients have yet to enter their 40s, their risk of death is among the highest for any form of adult congenital heart disease and many patients experience substantial morbidity.
      • Greutmann M.
      • Tobler D.
      • Kovacs A.H.
      • et al.
      Increasing mortality burden among adults with complex congenital heart disease.
      ,
      • Diller G.P.
      • Kempny A.
      • Alonso-Gonzalez R.
      • et al.
      Survival prospects and circumstances of death in contemporary adult congenital heart disease patients under follow-up at a large tertiary centre.
      Problems relate not only, or even primarily, to cardiac residua, but rather to the chronic effects of the Fontan circulation on all body systems (Fig. 1).
      Figure thumbnail gr1
      Figure 1Schematic representation of the chronic multisystemic effect of a Fontan circulation. The yellow boxes represent underlying mechanistic drivers and the grey boxes, clinical consequences. AV, atrioventricular; eGFR, estimated glomerular filtration rate; LA, left atrium.
      The emerging cohort of adult Fontan patients has much to teach us about life with this extraordinary physiology and there remain far more puzzles than answers. However, over the past decade, like the number of patients, the body of research has begun to grow, and we have learned which questions are the most pressing. The hematologic and hemodynamic abnormalities that result in an increasing risk of thromboembolism in the decades after Fontan creation
      • Seipelt R.G.
      • Franke A.
      • Vazquez-Jimenez J.F.
      • et al.
      Thromboembolic complications after fontan procedures: comparison of different therapeutic approaches.
      certainly demand attention because they contribute to at least 8% of Fontan deaths in adults.
      • Khairy P.
      • Fernandes S.M.
      • Mayer J.E.
      • et al.
      Long-term survival, modes of death, and predictors of mortality in patients with Fontan surgery.
      In this issue of the Canadian Journal of Cardiology, Sathananthan et al. focus on this important complication.
      • Sathananthan G.
      • Johal N.
      • Verma T.
      • et al.
      Clinical importance of Fontan circuit thrombus in the adult population: significant association with increased risk of cardiovascular events.
      They report their sizeable, single-centre, retrospective experience of adult Fontan patients who underwent cross-sectional imaging.
      • Sathananthan G.
      • Johal N.
      • Verma T.
      • et al.
      Clinical importance of Fontan circuit thrombus in the adult population: significant association with increased risk of cardiovascular events.
      Their data adds epidemiologic and phenotypic detail and the authors make the case for better recognition of Fontan thrombus as a manifestation of wider Fontan failure. It is an argument that carries weight.
      Thrombus in Fontan patients can be located in either the venous Fontan circuit and pulmonary arteries, or in the systemic arterial circulation, where it can cause stroke or peripheral embolism.
      • Attard C.
      • Huang J.
      • Monagle P.
      • Ignjatovic V.
      Pathophysiology of thrombosis and anticoagulation post Fontan surgery.
      Although Sathananthan et al. report that systemic arterial thrombus occurred in 10 patients, their study focused on thrombus in the venous Fontan circulation and its relation to clinical outcomes.
      • Sathananthan G.
      • Johal N.
      • Verma T.
      • et al.
      Clinical importance of Fontan circuit thrombus in the adult population: significant association with increased risk of cardiovascular events.
      Of the 67 Fontan patients who underwent cardiac magnetic resonance (CMR) or computed tomography (CT) imaging, 22% (15 patients) were diagnosed with Fontan circuit thrombosis. A significant proportion of patients with thrombus were already prescribed warfarin (40%) or aspirin (27%) at the time of diagnosis. As previously reported,
      • Egbe A.C.
      • Connolly H.M.
      • Niaz T.
      • et al.
      Prevalence and outcome of thrombotic and embolic complications in adults after Fontan operation.
      ,
      • Deshaies C.
      • Hamilton R.M.
      • Shohoudi A.
      • et al.
      Thromboembolic risk after atriopulmonary, lateral tunnel, and extracardiac conduit Fontan surgery.
      thrombosis was more frequent in older-style Fontan circuits than in more contemporary cavopulmonary pathways.
      • Sathananthan G.
      • Johal N.
      • Verma T.
      • et al.
      Clinical importance of Fontan circuit thrombus in the adult population: significant association with increased risk of cardiovascular events.
      In this study, more patients with Fontan thrombus than without experienced the composite outcome of death, heart transplantation, or cardiac surgery (27% vs 8%) and thrombus was also linked, although less closely related to, softer indices of ill health.
      • Sathananthan G.
      • Johal N.
      • Verma T.
      • et al.
      Clinical importance of Fontan circuit thrombus in the adult population: significant association with increased risk of cardiovascular events.
      Previous studies have associated clinically apparent thromboembolic events to an increased risk of heart failure hospitalization and death or shown that a proportion of Fontan deaths are caused by thrombus.
      • Khairy P.
      • Fernandes S.M.
      • Mayer J.E.
      • et al.
      Long-term survival, modes of death, and predictors of mortality in patients with Fontan surgery.
      ,
      • Egbe A.C.
      • Connolly H.M.
      • Niaz T.
      • et al.
      Prevalence and outcome of thrombotic and embolic complications in adults after Fontan operation.
      However, this is the first study, to our knowledge, to attempt to estimate the overall prevalence of Fontan circuit thrombosis (clinically apparent and silent) and then investigate its significance.
      • Sathananthan G.
      • Johal N.
      • Verma T.
      • et al.
      Clinical importance of Fontan circuit thrombus in the adult population: significant association with increased risk of cardiovascular events.

      No Evidence of Thrombus? Until Proven Otherwise…

      The study from Sathananthan et al. contains important and new information about clinically silent Fontan thrombus (ie, thrombus present without clinical symptoms or signs and not seen on echocardiography).
      • Sathananthan G.
      • Johal N.
      • Verma T.
      • et al.
      Clinical importance of Fontan circuit thrombus in the adult population: significant association with increased risk of cardiovascular events.
      In their study, 40% of the thrombus detected on cross-sectional imaging was clinically silent and 14% of patients with no pretest suspicion were nevertheless diagnosed with Fontan thrombus when they underwent CMR or CT imaging.
      • Sathananthan G.
      • Johal N.
      • Verma T.
      • et al.
      Clinical importance of Fontan circuit thrombus in the adult population: significant association with increased risk of cardiovascular events.
      In previous reports, the incidence of silent thrombus has varied from 9% to 33% with differences in study methodology and thrombus definition likely to explain the wide range.
      • Wilson T.G.
      • Shi W.Y.
      • Iyengar A.J.
      • et al.
      Twenty-five year outcomes of the lateral tunnel Fontan procedure.
      • Grewal J.
      • Al Hussein M.
      • Feldstein J.
      • et al.
      Evaluation of silent thrombus after the Fontan operation.
      • Varma C.
      • Warr M.R.
      • Hendler A.L.
      • et al.
      Prevalence of “silent” pulmonary emboli in adults after the Fontan operation.
      • Balling G.
      • Vogt M.
      • Kaemmerer H.
      • et al.
      Intracardiac thrombus formation after the Fontan operation.
      Advantages of the study by Sathananthan et al. are that all patients underwent cross-sectional imaging, that images were acquired using techniques reliable for detection of thrombus in slow flowing circulations, and that images were reviewed by experts in congenital heart disease.
      • Sathananthan G.
      • Johal N.
      • Verma T.
      • et al.
      Clinical importance of Fontan circuit thrombus in the adult population: significant association with increased risk of cardiovascular events.
      In this cohort, only 20% of the patients diagnosed with thrombus had concerning echocardiograms
      • Sathananthan G.
      • Johal N.
      • Verma T.
      • et al.
      Clinical importance of Fontan circuit thrombus in the adult population: significant association with increased risk of cardiovascular events.
      and we agree that definitively establishing the presence or absence of thrombus in Fontan patients using either transthoracic or transesophageal echocardiography is difficult. In clinical practice, we sometimes fail to clear Fontan patients for direct current cardioversion because transesophageal echocardiography returns a high suspicion of thrombus, only to find contemporaneous cross-sectional imaging conclusively excludes it. Because of the challenges of echocardiography and the lack of symptoms is sometimes false reassurance, Sathananthan et al. suggest we need to consider increased use of routine advanced imaging in Fontan patients.
      • Sathananthan G.
      • Johal N.
      • Verma T.
      • et al.
      Clinical importance of Fontan circuit thrombus in the adult population: significant association with increased risk of cardiovascular events.
      Their argument is stronger because they also show associations between thrombus and adverse clinical events.
      • Sathananthan G.
      • Johal N.
      • Verma T.
      • et al.
      Clinical importance of Fontan circuit thrombus in the adult population: significant association with increased risk of cardiovascular events.
      As a separate issue, which would necessitate longer discussion, the substantial risk of silent thrombus should be considered when debating whether Fontan patients benefit from routine anticoagulation.

      Routine Advanced Imaging: Who, When, and How?

      If routine cross-sectional imaging is of interest in the early detection and treatment of Fontan circuit thrombosis, questions about access, imaging modality, and frequency remain. In their practice, and in line with American Heart Association/American College of Cardiology guidelines,
      • Stout K.K.
      • Daniels C.J.
      • Aboulhosn J.A.
      • et al.
      2018 AHA/ACC guideline for the management of adults with congenital heart disease: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines.
      Sathananthan et al. perform cross-sectional imaging in Fontan patients at 3- to 5-year intervals.
      • Sathananthan G.
      • Johal N.
      • Verma T.
      • et al.
      Clinical importance of Fontan circuit thrombus in the adult population: significant association with increased risk of cardiovascular events.
      At the current time, it is unlikely that most Canadian adult Fontan patients attain this standard of care. Advanced imaging in this population requires institutional availability and a high level of training and expertise. In their methods section, Sathananthan et al. rightly emphasize technical aspects such as location of contrast injection and timing of image acquisition.
      • Sathananthan G.
      • Johal N.
      • Verma T.
      • et al.
      Clinical importance of Fontan circuit thrombus in the adult population: significant association with increased risk of cardiovascular events.
      The hazard of over-calling Fontan thrombus or pulmonary embolism due to slow contrast mixing and incomplete opacification is well described.
      • Yeong M.
      • Loughborough W.
      • Hamilton M.
      • Manghat N.
      Role of cardiac MRI and CT in Fontan circulation.
      ,
      • Hauser J.A.
      • Taylor A.M.
      • Pandya B.
      How to image the adult patient with Fontan circulation.
      In their informative article about the role of CMR and CT imaging in Fontan patients, Yeong et al. explain that adequate imaging requires more time in the scanner and more contrast than is usual for general cardiac studies.
      • Yeong M.
      • Loughborough W.
      • Hamilton M.
      • Manghat N.
      Role of cardiac MRI and CT in Fontan circulation.
      Time factors are important for work flow and because the kidney is also affected by chronic exposure to Fontan physiology, additional consideration must be given to the risks of contrast.
      • Opotowsky A.R.
      • Baraona F.R.
      • Mc Causland F.R.
      • et al.
      Estimated glomerular filtration rate and urine biomarkers in patients with single-ventricle Fontan circulation.
      Most patients in the study by Sathananthan et al. underwent CT (78%) imaging instead of CMR (22%),
      • Sathananthan G.
      • Johal N.
      • Verma T.
      • et al.
      Clinical importance of Fontan circuit thrombus in the adult population: significant association with increased risk of cardiovascular events.
      and, although not discussed by the authors, this probably reflects another barrier to routine cross-sectional imaging in this population. Degrading artifacts caused by vascular coils, fenestration closure devices, and epicardial or transvenous pacemaker systems are limiting factors in the use of CMR in Fontan patients.
      • Yeong M.
      • Loughborough W.
      • Hamilton M.
      • Manghat N.
      Role of cardiac MRI and CT in Fontan circulation.
      ,
      • Hauser J.A.
      • Taylor A.M.
      • Pandya B.
      How to image the adult patient with Fontan circulation.
      If regular cross-sectional imaging becomes standard of care, we will certainly expose the adult Fontan population to more ionizing radiation. Taking all of this and cost into account, perhaps the results of Sathananthan et al. would better be considered an argument for an individualized imaging plan for every Fontan patient with attention given to baseline risk factors such as age and type of Fontan circuit, as well as to the risks and benefits of the various imaging techniques at our disposal.

      An Incidental Finding That Opens Pandora’s Box

      Fontan circuit thrombosis presents in many different ways, from an incidental finding to acute major cardiovascular collapse. Sathananthan et al. describe 4 patients who presented with hemodynamic or respiratory instability for whom thrombolysis was the initial management strategy.
      • Sathananthan G.
      • Johal N.
      • Verma T.
      • et al.
      Clinical importance of Fontan circuit thrombus in the adult population: significant association with increased risk of cardiovascular events.
      Decision-making in patients with an acute clinical presentation is certainly challenging, because all options seem high-risk and the literature contains only case reports.
      • Torok R.D.
      • Fleming G.A.
      • Hill K.D.
      Transcatheter pulmonary embolectomy after Fontan.
      • Kudumula V.
      • Mathur S.
      • Bulock F.
      Successful thrombolysis of massive intracardiac thrombus in atriopulmonary Fontan circulation.
      • Mosquera V.X.
      • Marini M.
      • Portela F.
      • Cao I.
      Late complication of classic Fontan operation: giant right atrial thrombus and massive pulmonary thromboembolism.
      • Gaitan B.D.
      • Ramakrishna H.
      • DiNardo J.A.
      • Cannesson M.
      Case 1-2010 pulmonary thrombectomy in an adult with Fontan circulation.
      With its focus on prevalence and late implications, a weakness of the study by Sathananthan et al. is the lack of information about the management of Fontan thrombus or about the success of chosen management strategies.
      • Sathananthan G.
      • Johal N.
      • Verma T.
      • et al.
      Clinical importance of Fontan circuit thrombus in the adult population: significant association with increased risk of cardiovascular events.
      Successful thrombolysis, either with systemic infusion or catheter-directed local thrombolysis and surgical embolectomy,
      • Torok R.D.
      • Fleming G.A.
      • Hill K.D.
      Transcatheter pulmonary embolectomy after Fontan.
      • Kudumula V.
      • Mathur S.
      • Bulock F.
      Successful thrombolysis of massive intracardiac thrombus in atriopulmonary Fontan circulation.
      • Mosquera V.X.
      • Marini M.
      • Portela F.
      • Cao I.
      Late complication of classic Fontan operation: giant right atrial thrombus and massive pulmonary thromboembolism.
      • Gaitan B.D.
      • Ramakrishna H.
      • DiNardo J.A.
      • Cannesson M.
      Case 1-2010 pulmonary thrombectomy in an adult with Fontan circulation.
      • Khan A.
      • Gowda S.
      • Parekh D.
      • Qureshi A.M.
      Use of ultrasound-accelerated, catheter-directed local thrombolysis for venous and arterial occlusions in a pediatric hospital.
      • Hedrick M.
      • Elkins R.C.
      • Knott-Craig C.J.
      • Razook J.D.
      Successful thrombectomy for thrombosis of the right side of the heart after the Fontan operation. Report of two cases and review of the literature.
      • Tsang W.
      • Johansson B.
      • Salehian O.
      • et al.
      Intracardiac thrombus in adults with the Fontan circulation.
      has been reported but at this point it is impossible to know whether similar results can be obtained from supportive management and closely monitored oral anticoagulation. There is no straightforward decision pathway and multidisciplinary team discussion is mandated. Although initial treatment might appear simpler when chronic thrombus is discovered incidentally, this scenario should nevertheless impose a deep-thinking process. The occurrence of thrombus should prompt us to question the state of our patient’s Fontan circulation: could there be asymptomatic, untreated underlying atrial arrhythmia? Should we measure the patient’s Fontan pressures? Can the patient’s hemodynamics be improved? And should that be attempted, if to do so requires surgery? What will be gained? And what could be risked? In the slow, insidious, but frequently relentless progression of Fontan failure (Fig. 1), detection of circuit thrombosis should trigger further investigation and intensify management discussion. In our practice, it triggers referral to the adult congenital heart disease (ACHD) heart failure clinic for consideration of all options including discussion of where the patient might be on the path toward consideration for heart transplantation (Fig. 2).
      Figure thumbnail gr2
      Figure 2A clinical vignette detailing the complex care pathway of an adult Fontan patient after incidental diagnosis of a large right atrial thrombus. ACHD, adult congenital heart disease; CMR, cardiac magnetic resonance; CT, computed tomography; INR, international normalized ratio; iv, intravenous.

      Facing the Emerging Challenges Alongside Our Patients

      The population of adult Fontan patients in Canada continues to increase, and we need collective strategies and planning to face the challenges of late complications. National and provincial discussion about care delivery are necessary to unify and optimize management. The benefits of a structured multidisciplinary team approach with coordinated care pathways for the follow-up of children with a Fontan circulation were evaluated in a recent publication.
      • Di Maria M.V.
      • Barrett C.
      • Rafferty C.
      • et al.
      Initiating a Fontan multidisciplinary clinic: decreasing care variability, improving surveillance, and subsequent treatment of Fontan survivors.
      After implementation of the program, there was an increase in appropriate testing and several undiagnosed pathologies were identified and treated in a timely manner.
      • Di Maria M.V.
      • Barrett C.
      • Rafferty C.
      • et al.
      Initiating a Fontan multidisciplinary clinic: decreasing care variability, improving surveillance, and subsequent treatment of Fontan survivors.
      Dedicated ACHD Fontan clinics are certainly something to consider. In a country such as Canada, patients might live at great distances from institutions with access to the technology and level of expertise required. Perhaps yearly review in a smaller, local ACHD centre with 3- to 5-year review in a central hub multidisciplinary Fontan clinic could be a model to consider. It is even more problematic that many adult Fontan survivors receive no care at all from ACHD specialists. In 2009, Marelli’s group reported that fewer than 80% of Quebec’s complex ACHD patients were seen by specialists after their 18th birthday
      • Mackie A.S.
      • Ionescu-Ittu R.
      • Therrien J.
      • et al.
      Children and adults with congenital heart disease lost to follow-up: who and when?.
      and our own estimates in Toronto suggest loss to follow-up numbers of similar scale. However, most of these adults maintain contact with their primary care physician,
      • Mackie A.S.
      • Ionescu-Ittu R.
      • Therrien J.
      • et al.
      Children and adults with congenital heart disease lost to follow-up: who and when?.
      which affords an opportunity for reconnection with specialist teams, if that physician was aware of the need. Studies like that from Sathananthan et al. enhance our understanding of Fontan failure. As we learn more about the needs of this new population, it becomes increasingly urgent we act to optimize and standardize adult Fontan follow-up, to reconnect with lost to follow-up patients, and to facilitate access to expert care, regardless of postal code.

      Disclosures

      The authors have no conflicts of interest to disclose.

      References

        • van der Ven J.P.G.
        • van den Bosch E.
        • Bogers A.J.C.C.
        • Helbing W.A.
        State of the art of the Fontan strategy for treatment of univentricular heart disease.
        F1000Res. 2018; 7 (Faculty Rev-935): F1000
        • Benziger C.P.
        • Stout K.
        • Zaragoza-Macias E.
        • Bertozzi-Villa A.
        • Flaxman A.D.
        Projected growth of the adult congenital heart disease population in the United States to 2050: an integrative systems modeling approach.
        Popul Health Metr. 2015; 13: 29
        • Schilling C.
        • Dalziel K.
        • Nunn R.
        • et al.
        The Fontan epidemic: population projections from the Australia and New Zealand Fontan Registry.
        Int J Cardiol. 2016; 219: 14-19
        • Greutmann M.
        • Tobler D.
        • Kovacs A.H.
        • et al.
        Increasing mortality burden among adults with complex congenital heart disease.
        Congenit Heart Dis. 2015; 10: 117-127
        • Diller G.P.
        • Kempny A.
        • Alonso-Gonzalez R.
        • et al.
        Survival prospects and circumstances of death in contemporary adult congenital heart disease patients under follow-up at a large tertiary centre.
        Circulation. 2015; 132: 2118-2125
        • Seipelt R.G.
        • Franke A.
        • Vazquez-Jimenez J.F.
        • et al.
        Thromboembolic complications after fontan procedures: comparison of different therapeutic approaches.
        Ann Thorac Surg. 2002; 74: 556-562
        • Khairy P.
        • Fernandes S.M.
        • Mayer J.E.
        • et al.
        Long-term survival, modes of death, and predictors of mortality in patients with Fontan surgery.
        Circulation. 2008; 117: 85-92
        • Sathananthan G.
        • Johal N.
        • Verma T.
        • et al.
        Clinical importance of Fontan circuit thrombus in the adult population: significant association with increased risk of cardiovascular events.
        Can J Cardiol. 2019; 35: 1807-1814
        • Attard C.
        • Huang J.
        • Monagle P.
        • Ignjatovic V.
        Pathophysiology of thrombosis and anticoagulation post Fontan surgery.
        Thromb Res. 2018; 172: 204-213
        • Egbe A.C.
        • Connolly H.M.
        • Niaz T.
        • et al.
        Prevalence and outcome of thrombotic and embolic complications in adults after Fontan operation.
        Am Heart J. 2017; 183: 10-17
        • Deshaies C.
        • Hamilton R.M.
        • Shohoudi A.
        • et al.
        Thromboembolic risk after atriopulmonary, lateral tunnel, and extracardiac conduit Fontan surgery.
        J Am Coll Cardiol. 2019; 74: 1071-1081
        • Wilson T.G.
        • Shi W.Y.
        • Iyengar A.J.
        • et al.
        Twenty-five year outcomes of the lateral tunnel Fontan procedure.
        Semin Thorac Cardiovasc Surg. 2017; 29: 347-353
        • Grewal J.
        • Al Hussein M.
        • Feldstein J.
        • et al.
        Evaluation of silent thrombus after the Fontan operation.
        Congenit Heart Dis. 2013; 8: 40-47
        • Varma C.
        • Warr M.R.
        • Hendler A.L.
        • et al.
        Prevalence of “silent” pulmonary emboli in adults after the Fontan operation.
        J Am Coll Cardiol. 2003; 41: 2252-2258
        • Balling G.
        • Vogt M.
        • Kaemmerer H.
        • et al.
        Intracardiac thrombus formation after the Fontan operation.
        J Thorac Cardiovasc Surg. 2000; 119: 745-752
        • Stout K.K.
        • Daniels C.J.
        • Aboulhosn J.A.
        • et al.
        2018 AHA/ACC guideline for the management of adults with congenital heart disease: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines.
        J Am Coll Cardiol. 2019; 73: e81-e192
        • Yeong M.
        • Loughborough W.
        • Hamilton M.
        • Manghat N.
        Role of cardiac MRI and CT in Fontan circulation.
        J Congenit Cardiol. 2017; 1: 1-12
        • Hauser J.A.
        • Taylor A.M.
        • Pandya B.
        How to image the adult patient with Fontan circulation.
        Circ Cardiovasc Imaging. 2017; 10: 1-7
        • Opotowsky A.R.
        • Baraona F.R.
        • Mc Causland F.R.
        • et al.
        Estimated glomerular filtration rate and urine biomarkers in patients with single-ventricle Fontan circulation.
        Heart. 2017; 103: 434-442
        • Torok R.D.
        • Fleming G.A.
        • Hill K.D.
        Transcatheter pulmonary embolectomy after Fontan.
        Catheter Cardiovasc Interv. 2016; 87: 939-944
        • Kudumula V.
        • Mathur S.
        • Bulock F.
        Successful thrombolysis of massive intracardiac thrombus in atriopulmonary Fontan circulation.
        Cardiol Young. 2010; 20: 443-444
        • Mosquera V.X.
        • Marini M.
        • Portela F.
        • Cao I.
        Late complication of classic Fontan operation: giant right atrial thrombus and massive pulmonary thromboembolism.
        J Card Surg. 2008; 23: 776-778
        • Gaitan B.D.
        • Ramakrishna H.
        • DiNardo J.A.
        • Cannesson M.
        Case 1-2010 pulmonary thrombectomy in an adult with Fontan circulation.
        J Cardiothorac Vasc Anesth. 2010; 24: 173-182
        • Khan A.
        • Gowda S.
        • Parekh D.
        • Qureshi A.M.
        Use of ultrasound-accelerated, catheter-directed local thrombolysis for venous and arterial occlusions in a pediatric hospital.
        J Invasive Cardiol. 2018; 30: 387-392
        • Hedrick M.
        • Elkins R.C.
        • Knott-Craig C.J.
        • Razook J.D.
        Successful thrombectomy for thrombosis of the right side of the heart after the Fontan operation. Report of two cases and review of the literature.
        J Thorac Cardiovasc Surg. 1993; 2: 297-301
        • Tsang W.
        • Johansson B.
        • Salehian O.
        • et al.
        Intracardiac thrombus in adults with the Fontan circulation.
        Cardiol Young. 2007; 17: 646-651
        • Di Maria M.V.
        • Barrett C.
        • Rafferty C.
        • et al.
        Initiating a Fontan multidisciplinary clinic: decreasing care variability, improving surveillance, and subsequent treatment of Fontan survivors.
        Congenit Heart Dis. 2019; 14: 590-599
        • Mackie A.S.
        • Ionescu-Ittu R.
        • Therrien J.
        • et al.
        Children and adults with congenital heart disease lost to follow-up: who and when?.
        Circulation. 2009; 120: 302-309

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