With half of all patients with late Fontan failure having preserved systolic ventricular function,271,272 the utility of this type of routine surveillance may be limited More sensitive markers of cardiac function would be useful In particular, an increased end-diastolic volume (EDV) index, most reliably measured with cardiac MRI, may be a better marker for cardiac status and appears to have better prognostic value in the Fontan population.264,273,274 EDV reflects the preload of the systemic ventricle and is influenced by a combination of factors including venous capacitance and degree of ventricular dilatation It is elevated immediately after Fontan completion but reduces to normal levels after the first year.275 The etiology behind the progressive increase in EDV in the later years is not understood It may be the result of chronic volume overload, secondary to fluid retention, aortopulmonary collaterals, atrioventricular valve regurgitation, and ventricular dyssynchrony secondary to arrhythmia.274 The electrocardiogram provides insight into loss of sinus node function, heart block, and other arrhythmias, which are particularly prevalent in those with original atriopulmonary type Fontan connections.276,277 Holter monitoring and event and implantable loop recorder monitoring add layers of additional surveillance where arrhythmia is suspected Symptoms may be underreported in the Fontan population due to a lifetime adjustment to a different functional normality, and self-assessment of functional status is poorly correlated with quantitative assessment.278 Hence serial assessment with cardiopulmonary exercise testing is useful for ongoing surveillance Exercise capacity declines over time, and the rate of decline may better predict future adverse events than the absolute exercise capacity at a particular point in time.37,38,45,278–280 The frequency and age at which to start is not clearly established, especially in those in New York Heart Association class 1 or 2 The liver and kidney are detrimentally impacted by elevated systemic venous pressure and restricted cardiac output Consequently, abnormalities of these organs are often apparent in the Fontan population and can be found even in those with little in the way of functional limitation.153,161,163,166,281 Current recommendations are for intermittent screening with liver and renal function serum testing and ultrasound scans without clearly specified intervals.248,251,253 The sensitivity and specificity of these tests as early screening tools in this population are not conclusive.11,153,166,168,282,283 New biomarkers and imaging modalities are emerging,281,283,284 but, as with existing renal and liver function testing, their predictive value needs to be established prior to their being incorporated into surveillance programs Recent reports of hepatocellular carcinoma in older Fontan patients with cirrhosis highlight the importance of screening for both of these conditions.181 Routine surveillance and testing in the Fontan population are an evolving process As information from larger population-based studies emerges, more robust guidelines can be developed for the lifetime care of the Fontan patient Medical Treatment Anticoagulation Given the propensity for thrombosis in the Fontan circulation,139,140,143,285–289 the need for antithrombotic prophylaxis is generally accepted, with the highest rates of thrombosis described in retrospective studies where prophylaxis was not universal.129,287,290,291 The two most widely used prophylactic medications are aspirin and warfarin Even with these agents, there remains a substantial rate of thrombosis (7% to 19% of cases).129,131,287,290–294 The mortality risk associated with clinically evident thrombosis is significant, ranging from 12% to 28%.287,290,291,294,295 Moreover, the recurrence risk is substantial, with further thromboses occurring in more than a quarter of patients.131,290 Two time periods of greatest risk for thrombosis have been identified, within the first year of Fontan operation and late (≥10 years post Fontan).129,290,291,296 There is a diversity of opinion as to whether warfarin or aspirin should be used as primary antithrombotic prophylaxis in Fontan patients This is reflected in marked practice variation as detailed in recent surveys.248,249 Dosage regimes and INR targets are poorly defined, and current guidelines are unable to provide conclusive evidence for their recommendations.297 The only prospective randomized control trial to date comparing aspirin and warfarin131 did not demonstrate a clear difference in thrombotic events between the two regimes over a 2-year period, despite intensive thrombosis surveillance Nevertheless, subanalysis suggests that those receiving warfarin who have consistently subtherapeutic INR measurements are at higher risk of thrombotic events.296 This finding is supported by several retrospective analyses.291–294 Anticoagulation with warfarin carries a significant risk of serious hemorrhagic events Of interest in the aforementioned study, this type of complication occurred in 1.75% in the warfarin group over 2 years compared with none in the aspirin group.131 Others have reported significant bleeding events on prophylactic anticoagulation with events primarily occurring in patients anticoagulated with warfarin, especially when taken for many years.290–292 In the adult Fontan population, the ideal antithrombotic regime is a conundrum because there may be an increased risk of hemorrhage related to gastric varices and other comorbidities, in addition to the risk of thrombosis To further complicate matters, there is a high risk of a second thrombotic event if a patient commenced on warfarin following a thrombotic event has his or her warfarin discontinued because of a bleeding event.290 In addition to the elevated risk profile, long-term warfarin therapy carries a higher financial cost and has greater impact on QOL compared with aspirin The need for regular blood tests, the difficulty in maintaining a consistent therapeutic window, and the need to avoid at-risk activities has significant economic social and psychological cost.298 Given the aforementioned, many centers limit warfarin prophylaxis to the high-risk early postoperative Fontan period, using aspirin after the first postoperative year in all but those at higher than normal risk of thrombotic episodes There is little experience with the use of newer antithrombotic agents in the Fontan circulation, but this may change Perhaps of greater interest is the potential role pharmacogenetics may have in individualizing the prophylaxis regimen Genetic variants are known to influence warfarin dose requirements and the risk of bleeding events early after starting treatment.298,299 In addition, aspirin resistance is well recognized.300–302 Routine testing for genetic susceptibility to thrombosis, propensity for bleeding, and resistance to antithrombotic medication may form part of the assessment and treatment individualization in the future However, with the possible exception of aspirin resistance, there is currently insufficient evidence to support a recommendation in this area.303 Role of Angiotensin-Converting Enzyme Inhibition, Aldosterone Antagonists, and βBlockade In the well Fontan patient, the use of angiotensin-converting enzyme (ACE) inhibitors, known to be efficacious in adult patients with structurally normal