hearts and congestive heart failure,304,305 has little evidence base There have been two randomized controlled trials in children with a functionally univentricular heart: one prior to the Fontan306 and one smaller study after.307 Neither demonstrated benefit in terms of improved growth parameters, ventricular function,306 or exercise performance.307 ACE inhibitors are frequently used in Fontan patients with and without systolic dysfunction,248,308 on the assumption that the development and/or progression of ventricular dysfunction will be delayed, particularly in the setting of a systemic right ventricle Despite their wide spread use, the efficacy of ACE inhibition in the Fontan circulation remains unproven,308 and the extrapolation of treatment effect from populations with different forms of heart failure should be made with caution Aldosterone antagonists reduce mortality when used in conjunction with ACE inhibition in adults with congestive heart failure and a structurally normal heart.309,310 The potential mechanisms for this effect include modification of adverse remodeling by reducing interstitial fibrosis, and a reduction in the risk of ventricular arrhythmia and sudden death due to an increase in serum potassium levels The Fontan circulation is associated with increased activation of the renin-angiotensin-aldosterone (RAA) system.311 There is evidence in children with congenital heart disease and adults with Fontan failure that diastolic ventricular dysfunction is associated with increased RAA system activation and with high-risk RAA system genotypes.312,313 There is a high prevalence of diastolic dysfunction in Fontan patients, and a therapeutic role for these medications has been postulated However, there is little evidence of therapeutic efficacy in the Fontan population to date.314 As with ACE inhibition, β-blockade carries a mortality and morbidity benefit for adult patients with congestive heart failure and systolic dysfunction.315 The same effect has not been demonstrated in children, although studies have been underpowered.316–319 A single study in a small group of children and adults with Fontan failure and ventricular dysfunction showed an improvement in ejection fraction following treatment with carvedilol.320 β-Blockade can be useful for the treatment of atrial and ventricular arrhythmia in the Fontan circulation, but careful monitoring is required in the presence of heart block and sinus node dysfunction There is no other indication for its use in the Fontan patient with normal ventricular function In summary, there are few studies assessing the efficacy of these medications and those that do exist are generally small and often statistically underpowered Although there is no strong evidence in the Fontan setting to support the use of medications that have become the mainstay of heart failure treatment strategies in the adults with acquired heart disease, there is little to suggest harm when used in the setting of heart failure accompanied by systolic dysfunction in the Fontan population Pediatric and congenital heart failure guidelines support their use,321–323 and they remain potential options to ameliorate the Fontan circulation where evidence of overt systolic dysfunction is found.324–326 There is currently no evidence to suggest these medications provide a protective effect in patients with normal ventricular function despite their not infrequent use in this context Exercise Reduced exercise participation and physical deconditioning are common in the Fontan population The etiology is complex, in part related to the decreased exercise capacity but also to perceptions of physical ability and the psychosocial reaction to living with chronic disease Inactivity is thought largely responsible for the reduced bone density and muscle mass reported in Fontan patients,11,89,156,327 although medication use, especially diuretics and antithrombotic treatment, may also contribute These factors are increasingly recognized as having a detrimental impact on exercise capacity.89,328–332 Recent studies have demonstrated that not only is exercise safe for Fontan patients, especially at submaximal levels, but exercise may be even more important as a therapeutic entity because it compensates for the lack of a pulmonary pump and may improve chronotropic incompetence and respiratory reserve.66,78,333–335 Although exercise as a therapy is still in its infancy, it is generally acknowledged that encouraging regular exercise to promote cardiorespiratory fitness and muscle conditioning should be recommended as part of long-term Fontan care, with the aim of preserving or enhancing functional capacity.78,333,335–337 Birth Control Despite a high incidence of infertility in women with a Fontan circulation, there are an increasing number of reports of successful pregnancies.338–342 If pregnancy is considered, prepregnancy counseling and careful planning ensure that risks are understood and mitigated as far as is possible.250,253,343–345 Unintended pregnancy in women with a Fontan circulation carries a significant risk to the fetus and mother.340 For the fetus, the risk includes exposure to medications that are potential teratogens and placental dysfunction as a consequence of the Fontan circulation The latter is manifest in high rates of miscarriage and intrauterine growth retardation Risks to the mother include a limited ability to increase cardiac output, an increased risk of arrhythmia, progression of ventricular impairment, and a hypercoagulable state.339–342 Sexual health and discussion related to pregnancy risk should be undertaken at an early stage—ideally before sexual maturity is reached.345 There are multiple potential contraception methods for women with a Fontan circulation (Table 73.3) Preparations containing estrogen are not recommended, due to their prothrombotic risk.341,342,344,345 There are multiple progesterone-only options for women, including tablet, implantation, and long-acting intramuscular injection; however, side effects and a limited window for missed doses with some oral forms, make these medications less appealing for some women.342,345 Intrauterine devices are not contraindicated, but recognition of the potential for severe vagal response during insertion needs to be taken into account, as does the risk of infection The latter is highest at the time of insertion and then falls to the background rate of sexually transmissible infection.341,342,345,346 Simple barrier protection methods can also be used, but reliance on these as the only contraception method carries a higher risk of contraception failure even with reliable use.345 Table 73.3 Contraception Methods and Recommendations in Women With a Fontan Circulation Type of Contraception Abstinence Combined estrogen/progesterone pill Progesterone-only pill Benefits Risks No interactions Relies on absolute compliance Thrombogenic Interacts with warfarin Dependent on daily compliance Side effects, especially menstrual irregularity Some only 3 h window of cover for missed dose Formulation variation in overall efficacy Dependent on daily High intrinsic efficacy Long window of cover for missed dose (12 h) Not thrombogenic Recommendation in Fontan Patients Recommended Avoid Recommended ... used in the setting of heart failure accompanied by systolic dysfunction in the Fontan population Pediatric and congenital heart failure guidelines support their use,321–323 and they remain potential options to ameliorate the Fontan circulation