FIG 73.33 Change in lean mass and peak VO2 with resistance training versus nontraining controls Error bars shown are standard error of the mean VO2 oxygen uptake (From Cordina R, O'Meagher S, Karmali A, et al Resistance training improves cardiac output, exercise capacity and tolerance to positive airway pressure in Fontan physiology Int J Cardiol 2013;168[2]:780–788.) Do exercise programs have the capacity to improve QOL and longevity of the Fontan circulation? Lower function class and lower exercise capacity are known to be predictors with Fontan failure The hypothesis that improving exercise capacity through training will reduce the risk of failure is attractive but has yet to be proven and will likely be the focus of much attention over the coming years Other Medical Therapies Although widely used, there is little evidence to support routine treatment with ACE inhibition, β-blockade, or aldosterone inhibitors.412 Indeed—as detailed earlier—randomized studies have demonstrated no benefit, and long-term studies of safety have not been reported.249 Likewise, modification of the prothrombotic state and reduction of the risk of thrombosis with antiplatelet or anticoagulant medication remain unproven.392 Given the heterogeneous nature of morphologic and functional abnormalities in those with a Fontan circulation, and the long time-course over which failure of the Fontan circulation occurs, it is doubtful that new trials will shed light on the efficacy of these medications in the foreseeable future Nevertheless, there may be subsets of patients who will benefit from certain treatments For example, one-half of adult Fontan patients have aspirin resistance and may benefit from other forms of antithrombotic prophylaxis.393 Furthermore, variable expression of genetic polymorphisms in the RAA system and kallikrein-bradykinin pathways influences the outcome in adults with coronary artery disease treated with ACE inhibitors.413 Further investigation in the Fontan population may well identify subsets of patients more likely to benefit from this type of treatment Practice Variation, Networks, and Registries Because there is little information to support a common lifetime surveillance plan for patients with a Fontan circulation, there is significant practice variation between, and often within, institutions.248,249 The recent emergence of regional and multiinstitutional registries and networks provides the basis for the uniform surveillance and audit of relatively large groups of patients.35,414 Iterative assessment of surveillance protocols, with attention to the detection of early signs of failure, has the capacity to improve outcome and provide an increasingly rational and cost-effective lifetime care pathway.415 Surgical Design and Computational Fluid Dynamics The functional status of patients late after Fontan is intimately associated with the optimization of flow of the Fontan circuit There is converging evidence that the smaller the loss of kinetic energy to the blood flow is in the Fontan circuit, the better the exercise capacity One could expect that the operations with the best design may also result in the best long-term outcomes Yet this population is characterized by a wide variation of pulmonary artery size, position, and orientation so that one operation that fits all is not possible Progress in this direction is twofold First, it is likely that improving minor distortion and obstruction in the Fontan pathway by interventional catheterization or with reoperation could benefit some patients Secondly, computational flow dynamic technology has the capacity to assist patient-specific design, so that models can be constructed before the Fontan operation and the Fontan circuit can be tailored for an individual patient in a way that optimizes flow and minimizes energy loss There has been significant progress in this area Indeed the rationale for the total cavopulmonary connection version of the Fontan operation was designed using early computational fluid dynamics techniques with the principle of optimizing circuit flow energetics and minimizing energy lost through collision and recirculation.4 Nevertheless, despite promising results, progress in the area of individualizing Fontan design has not yet been translated into widespread use Implanted Ventricular Assist Devices The population of patients with a Fontan circulation is expected to double in the next 2 decades, and it is likely that there will not be enough donor organs for the growing number of those with a failing Fontan circulation.32,416 Hence there would be tremendous benefit if a mechanical device were able to provide safe long-term circulatory support as an alternative to transplantation To date, attempts to support the Fontan circulation with conventional assist devices designed for the failure of the systemic left ventricle have been disappointing.417,418 These devices involve the implantation of a pneumatic paracorporeal device between the systemic ventricle and the aorta Unfortunately, this mode of support is not able to adequately decrease the systemic venous pressure in the failing Fontan circulation, and the use of these types of devices is associated with mortality of greater than 40% It is likely that patients surviving this mode of support are those whose main mode of failure is primary ventricular dysfunction.417–420 Two alternative strategies have been initiated Some have suspected that mechanical support of the failing systemic ventricle with a continuous flow device may be preferable, and the first successes of this strategy are currently emerging.421 It is possible that continuous flow devices are more apt at maintaining a low pressure in the pulmonary