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7.5.2 Therapy

Outcomes in adult CHD-associated PAH have improved with the availability of new PAH therapies, advances in surgical and perioperative management, and a team-based, multidisciplinary approach in PH centres. These patients should be managed by specialized health professionals. Patient education, behavioural modifications, and social and psychological support are all important aspects of management. Shunt closure (surgical or interventional) may only be considered in patients with prevalent systemic-to-pulmonary shunting without significantly increased PVR. Criteria for defect closure based on Qp/Qs ratio and (baseline and/or after targeted PAH treatment) PVR have been proposed by the 2020 ESC Guidelines for the management of adult congenital heart disease.101 Decisions on shunt closure should not be made on haemodynamic numbers alone, and a multiparametric strategy should be followed. For instance, shunt closure is not indicated in the case of desaturation during exercise in the 6MWT or CPET, or when there is secondary erythrocytosis suggesting dynamic reversal of shunt. There is no evidence for a long-term benefit of a treat-and-repair approach in patients with adult CHD-associated PAH with prevalent systemic-to-pulmonary shunts; therefore, there is a need for future prospective studies.564 Defect closure is contraindicated in all patients with Eisenmenger syndrome, and may also adversely affect patients with small/coincidental defects that behave similarly to IPAH.565 There are no prospective data available on the usefulness of vasoreactivity testing, balloon closure testing, or lung biopsy for assessing operability and normalization of PVR after closure.566 Patients with adult CHD-associated PAH may present with clinical deterioration in different circumstances, such as arrhythmia, during non-cardiac surgery requiring general anaesthesia, dehydration or bleeding, thrombo-embolism, and lung infections. Surgeries should be limited to those deemed essential, and performed in specialized centres with anaesthetists experienced in adult CHD and PAH. Endocarditis should be suspected in patients with sepsis, whereas a cerebral abscess should be excluded in those with neurological symptoms or new headache, especially in those with low oxygen saturations and complex anatomies. It is recommended to avoid strenuous exercise, but mild and moderate activities seem to be beneficial.567 Patients should receive all recommended vaccinations and endocarditis prophylaxis in the presence of cyanosis. Although pregnant patients with left-to-right shunts and stable, well-controlled PAH have tolerated pregnancy well under specialized care, pregnancy is still associated with both high maternal mortality and foetal complications in Eisenmenger syndrome and should be discouraged in this setting;568,569 hence, effective contraception is highly recommended. Levonorgestrel-based, long-acting, reversible contraception implants or intrauterine devices have been recommended for these patients.570 Secondary erythrocytosis is beneficial for adequate oxygen transport and delivery, and routine phlebotomy should be avoided whenever possible. Symptoms of hyperviscosity in the presence of haematocrit .65% should be approached with appropriate hydration. Iron deficiency should be corrected. When i.v. iron supplementation is administered, special care should be taken to avoid air emboli during administration.571 Supplemental oxygen therapy has not been shown to impact survival.

Oral anticoagulant treatment with VKAs may be considered in patients with large PA aneurysms with thrombus, atrial arrhythmias, and previous thrombo-embolic events, but with low bleeding risk. In patients with very high Hb levels (.20 mg/dL), standard international normalized ratio measures are less accurate, and citrate-adjusted blood bottles must be used. Regarding using novel oral anticoagulants (NOACs), a large, nationwide, German, adult CHD database (including 106 NOAC-treated patients with Eisenmenger syndrome) showed that NOAC users had higher longterm risk of bleeding, major adverse cardiovascular events, and mortality compared with those on VKAs, suggesting that initiating NOACs should be reserved for experienced adult CHD centres, carefully weighing potential benefits and risks.572,573 Compared with other group 1 subgroups, limited data exist on the use of drugs approved for PAH in patients with adult CHD-associated PAH. Bosentan improved 6MWD and decreased PVR in patients with Eisenmenger syndrome in WHO-FC III.574 Patients with more complex lesions were less likely to respond to PAH therapies compared with patients with simple lesions. An RCT investigating the efficacy of macitentan found no effect on 6MWD in a mixed cohort of patients with Eisenmenger syndrome (6MWD improved in both treatment and placebo arms), although decreases in NT-proBNP and PVR were noted in the macitentan arm.575 Experiences with other ERAs and PDE5is have shown favourable functional and haemodynamic results in Eisenmenger syndrome.576 In a small, single-centre, pilot study, adding nebulized iloprost to a background of oral PAH therapy failed to improve 6MWD in Eisenmenger syndrome.577 In case symptoms persist or in clinical deterioration, a sequential and symptom-orientated treatment strategy is recommended in Eisenmenger syndrome, starting with an oral ERA (or PDE5i) and escalating therapy. Should symptoms not adequately improve with oral therapies, i.v./s.c. options should be proactively considered.578 There is a theoretical risk of paradoxical embolism in right-to-left shunt lesions with the presence of a central venous catheter for i.v. therapy; therefore, s.c. prostacyclin analogue infusion may be considered. The effect of PAH therapies in patients with prevalent systemic-to-pulmonary shunts is less well established. Patients with small/coincidental defects should be treated with PAH medication.557 This is also the case for patients with PAH after defect correction who have increased mortality compared with those with Eisenmenger syndrome.579 These patients were included in major RCTs with PAH therapies and should be evaluated based on comprehensive risk assessment (Table 16).580 The effect of PAH therapies in patients with segmental PH remains a matter of debate.101,581 While some series have reported promising results, there have been cases where therapies were not tolerated.581 Similarly, using PAH therapies in Fontan circulation has yielded conflicting results, and results of further studies are awaited.582–584 Heart–lung transplantation or LTx with heart surgery is an option in highly selected cases not responsive to medical treatment; however, it is limited by organ availability and lesion complexity. Mortality is high during the first year after surgery, especially after heart–lung transplantation, but remains relatively low thereafter.585 Downloaded from academic.oup.com/eurheartj/article/43/38/3618/6673929 by guest on 07 October 2026