significant cyanosis The lack of pulsatility within the pulmonary arteries further compromises pulmonary vascular resistance calculations.60,376 Embolization of venovenous collaterals has been the traditional mainstay of treatment to improve oxygen saturations and symptoms However, recent data, albeit retrospective, suggest worsened survival in patients who have embolization compared with those who are treated medically.355 In addition to pulmonary vascular remodeling, patients with type III Fontan failure typically have multiorgan system involvement, including cirrhosis and/or portal hypertension, and the interrelationship of the heart and liver is of particular importance in this subtype of Fontan failure Elevated CVP causes liver congestion and alterations in liver perfusion, which lead to fibrosis and cirrhosis over time More recently recognized is the phenomenon of liver disease causing heart disease and the constellation of abnormalities that have been described as the cirrhotic cardiomyopathy Approximately 50% or more of cirrhotic patients may have features of cardiac dysfunction that are the result of liver disease These include diastolic dysfunction, chamber dilation, systolic dysfunction, QT prolongation, arrhythmias, conduction abnormalities, and blunted heart rate response with chronotropic incompetence The pathophysiology is complex and multifactorial but appears to be related to the neurohormonal changes of cirrhosis In addition, increased plasma volume and fluid retention, as well as the systemic vasodilation and reduced systemic vascular resistance, necessitate an increase in cardiac output and place an increased burden on the heart This is especially an issue for the Fontan circulation Pulmonary arteriovenous malformations due to the lack of hepatic effluent can also occur,377 resulting in cyanosis and further volume load Additional factors attributable to liver disease include abnormalities in cardiac cell membrane composition that include alterations in cholesterol and phospholipid metabolism β-Receptor downregulation, changes in potassium channels, muscarinic receptor alterations, and abnormal calcium handling may all play a role.378 Treatment of this phenotype can be particularly difficult In addition to relief of congestion with loop diuretics and aldosterone inhibitors, it is often necessary to discontinue medications that lower the systemic vascular resistance, such as ACE inhibitors and ARBs These medications should be generally avoided in this subgroup because of the risk of hypotension and kidney injury, including hepatorenal syndrome.379 Vasoconstrictors, such as midodrine, can sometimes be useful to increase systemic vascular resistance and preserve organ perfusion.380,381 If pulmonary vascular resistance is elevated or if there are significant venovenous collaterals, some have advocated the use of pulmonary vasodilator therapy, although currently data are insufficient to make a broad recommendation These medications are expensive and not without risks For example, the effects of sildenafil may not be limited to pulmonary vascular dilation but can also cause peripheral vasodilation Bosentan should be used with caution in patients with liver disease There is a subset of Fontan failure patients who benefit from pulmonary vasodilator therapy, but additional studies are needed to better identify this subset Type IV: Fontan Failure With Abnormal Lymphatics Lymphatic abnormalities are not infrequent in patients with a Fontan circulation and can present as PLE or plastic bronchitis, with the latter occurring more frequently in the pediatric population The prolonged loss of serum proteins that include albumin and immunoglobulins can lead to anasarca, malnutrition, and recurrent bacterial infections A thorough hemodynamic evaluation to ensure there is no anatomic obstruction within the Fontan circuit or pulmonary arteries is critical in all patients with Fontan failure but even more so in this phenotype Lymphangiography or magnetic resonance lymphatic imaging can be particularly helpful in the evaluation of plastic bronchitis382 and can guide thoracic duct ligation or percutaneous lymphatic interventions.383 Inhaled tissue plasminogen activator and vest therapy have also been used.384,385 There is experience treating PLE with oral budesonide, and there may be a role for pulmonary vasodilator therapy, although data are limited.203,386 Cardiac transplantation is the definitive treatment.387 As in plastic bronchitis, there is growing interest in percutaneous embolization of abnormal lymphatic channels that form between liver and small bowel and spill albumin-rich lymph into the intestinal lumen Indeed, a recent report demonstrated improved symptoms and albumin levels after percutaneous embolization of hepatoduodenal channels identified by hepatic lymphangiography and contrast-guided duodenoscopy.188 Further studies are needed to determine the long-term effects of this strategy Exercise Pulmonary blood flow is dependent on adequate systemic venous return, which is augmented during exertion by the ventilatory pump and by the muscle pump The ventilatory pump increases venous return to the chest with inspiration and the negative pressure generated by the diaphragm and respiratory muscles The ventilatory pump may contribute less to augmentation of venous return when compared with the muscle pump, where exercising muscles pump blood and improve pulmonary blood flow and cardiac output.334 Resistance training has been traditionally discouraged in patients with severe heart disease However, a small Australian study demonstrated improved exercise capacity and objective measures of cardiac output with moderate to high intensity resistance training The subjects in this study underwent supervised high-intensity total body resistance training 3 days for 20 weeks with a focus on calf muscles Resistance training machines were used, and the subjects were instructed to avoid Valsalva maneuver by exhaling during the strain portion of the exercise Valsalva maneuver can lead to a drop in venous return and cardiac output Participants performed three sets of eight repetitions on each machine, which included chest press, lateral pulldown, seated row, leg press, knee extension, knee flexion, and calf raises that were both seated and standing The participants of the study were relatively healthy without significant hypoxia, heart failure, or cardiac arrhythmia.336 Aerobic exercise was not added to resistance training in this study Resistance training likely provides more benefit than aerobic training for the purposes of improving exercise capacity in the Fontan population.388 Although exercise in general and resistance training in particular appear to have therapeutic merit in healthier Fontan patients, additional studies are needed to determine the therapeutic role of resistance training in those with Fontan failure Anticoagulation Although practices vary, our experience is that most Fontan failure patients require anticoagulation Thromboembolic events are common in patients with Fontan circulation and are in need of thromboembolic prophylaxis However, there is no clear consensus about when to use aspirin, vitamin K antagonists, or other anticoagulants Practice guidelines from the American College of Cardiology and the American Heart Association recommend vitamin K antagonists for Fontan patients with atrial shunt, atrial thrombus, atrial arrhythmias, or thromboembolic event Most experts would also anticoagulate patients with classic atriopulmonary Fontan, particularly with a dilated right ... and can present as PLE or plastic bronchitis, with the latter occurring more frequently in the pediatric population The prolonged loss of serum proteins that include albumin and immunoglobulins can lead to anasarca, malnutrition, and... there is no clear consensus about when to use aspirin, vitamin K antagonists, or other anticoagulants Practice guidelines from the American College of Cardiology and the American Heart Association recommend vitamin K antagonists for Fontan patients with atrial shunt, atrial thrombus, atrial