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............................................................................................................................................................................. neurohormones and markers of myocardial injury (high-sensitivity troponins) or inflammation (high-sensitivity C-reactive protein). Among the neurohormones, natriuretic peptides [B-type natriuretic peptide (BNP) and N-terminal-pro-BNP (NT-pro-BNP)] are best studied in ACHD patients. They carry important prognostic information, but are less useful to diagnose heart failure across different cardiac lesions due to a cut-off variability depending on the underlying defect and type of repair.26 They are most useful in patients with biventricular circulation and least useful in patients with a Fontan circulation.27 Serial testing of natriuretic peptides plays a role in identifying patients at risk for adverse events. Of note, natriuretic peptides may be increased in cyanotic heart disease simply due to hypoxiainduced peptide secretion.28

3.4 Therapeutic considerations

3.4.1 Heart failure The development of heart failure is a common problem affecting 2050% of the ACHD population, and is a main cause of death.29 The incidence is increasing and is probably underestimated. Since latent signs and symptoms of heart failure might occur frequently, patients at high risk of developing heart failure require systematic follow-up and diagnostic screening.30 Any haemodynamic abnormalities, including arrhythmias, potentially causing heart failure that can be addressed by intervention or surgery must be excluded and, if possible, treated first. In the absence of specific guidelines, ACHD practitioners follow the current guidelines for medical treatment for both heart failure and common heart failure-related comorbidities, such as diabetes mellitus, AF, central sleep apnoea, iron deficiency, and cachexia.31 However, as the pathophysiology of cardiorespiratory dysfunction is often different from the failing circulation in patients with non-congenital (acquired) heart disease, extrapolation of results from published heart failure studies to ACHD patients are inappropriate, particularly in patients with a systemic right ventricle (RV), a failing subpulmonary ventricle, or in patients with a single ventricle physiology. The pathophysiology of ACHD heart failure with systolic ventricular dysfunction includes a broad spectrum of causes. Both systemic and subpulmonary ventricles, whether morphological left or right, single ventricles included, might be chronically overloaded by pressure and/or volume, which leads to progressive ventricular dysfunction. Altered myocardial architecture (noncompaction) and ventricular interdependence can compromise systolic ventricular function. Myocardial injury (limited myocardial protection during bypass, after ventriculotomy, and after chronic hypoxia) may occur in CHD patients. Finally, ischaemic heart disease  mainly related to ageing or congenital coronary anomalies  and persistent tachyarrhythmia might be responsible for impaired systemic and subpulmonary ventricular function.30 The few available data on heart failure treatments, specifically in ACHD patients, are often not conclusive and derived from small patient cohorts. As a consequence, ACHDspecific recommendations are mostly based on clinical experience or position statements.30 In a biventricular circulation, patients with an impaired systemic LV are generally treated with conventional heart failure therapy; this is also applied in symptomatic patients with a failing systemic RV. Diuretics mainly control symptoms; whether the longterm use of inhibitors of the reninangiotensin aldosterone system or beta blockers influences clinical outcome remains unknown. Also, no long-term clinical benefit of conventional heart failure treatment has been shown in a failing subpulmonary ventricle, although diuretics might alleviate symptoms. Treatment of symptomatic patients with a failing single ventricle in a Fontan circulation, or in the case of a persistent right-to-left (RL) shunt, should always be carefully initiated, taking the labile balance of ventricular preload and systemic afterload into account. In ACHD patients with heart failure, there are currently only a few small studies looking at the new drug sacubitril/valsartan, which was found to decrease morbidity and mortality and implemented in the therapy of chronic heart failure in recent ESC Guidelines31, however, no recommendation can be made at this moment. Heart failure with preserved EF is also not uncommon in ACHD patients. Therapeutic recommendations should follow the general heart failure guidelines. On top of medical treatment, cardiac resynchronization therapy (CRT) has gained increasing interest for use in ACHD patients with congestive heart failure, despite little evidence on indications and outcomes. Efficacy of CRT in CHD may vary with the underlying structural and functional substrate, such as anatomy of the systemic ventricle (left, right, or functionally single), presence and degree of structural systemic atrioventricular (AV) valve regurgitation, primary myocardial disease or scarring, and type of electrical conduction delay.32

It is expected that the incidence of acute heart failure in ACHD patients will also increase over time due to increasing age and more complex diseases. The knowledge of correct use of inotropes, the availability of extra-corporal membrane oxygenation, and advanced bridging techniques are the minimum requirements to adequately support ACHD patients with acute heart failure; transfer to an expert centre is recommended.33 Heart transplantation may also be considered as a therapeutic option for end-stage heart failure. Outcome after transplant surgery is continuously improving, particularly in CHD patients, but perioperative mortality still remains higher than in other underlying diseases. This is mainly related to previous cardiac surgery, complex anatomy and pathophysiology, and comorbidities (multisystem disorder). The increased use of ventricular assist devices can bridge patients to transplantation; in selected patients, it may be an option as destination therapy. Some patients may have extreme complex anatomy or high levels of antibodies against the human leucocyte antigens and are not eligible for transplantation. In some patients, multiorgan transplantation is required. Heartlung transplantation is applied in CHD patients with irreversible PAH such as Eisenmenger syndrome, however, the lack of donor organs is a major limitation. Simultaneous heart-liver transplantation is rarely done in liver failure after Fontan palliation or in patients with long-standing hepatic pressure load due to right heart failure [e.g. unrecognized Ebstein’s malformation of the tricuspid valve (TV)]; experience of this kind of surgery is limited. In all cases, timely evaluation for transplantation by ACHD heart failure specialists in a transplant centre with ACHD expertise is recommended. Advance care planning, eventually including palliative care, should be offered to all advanced heart failure patients.

3.4.2 Arrhythmias and sudden cardiac death 3.4.2.1 Arrhythmia substrates The entire spectrum of arrhythmias may be encountered in ACHD patients. However, some congenital arrhythmia substrates are related to the malformation itself (Table 7 and section 4). Longer life expectancy (in conjunction with exposure to conventional risk factors for arrhythmogenic substrates) increases the prevalence of Downloaded from academic.oup.com/eurheartj/article/42/6/563/5898606 by guest on 07 October 2026