Adult congenital heart disease-related heart failure: challenges and opportunities in pharmacological therapies and device interventions

Neijenhuis, R.M.L. (2026)

Doctoral Thesis

Adults with congenital heart disease frequently develop heart failure. While it is the principal cause of morbidity and mortality, few evidence-based treatments exist for heart failure in this patient group. This thesis investigates novel pharmacological and device-based treatment options specifically for this population.
A substantial part of the research focuses on sodium-glucose cotransporter 2 inhibitors (SGLT2i), one of the four central pharmacotherapy classes in the treatment of conventional heart failure. Through the international ACHIEVE-SGLT2i registry, this thesis demonstrates that SGLT2i are safe and well-tolerated in adults with congenital heart disease. Moreover, there are indications of improved ventricular function and reduced heart failure hospitalisation rates, both in patients with a systemic right ventricle and in those with a single ventricle circulation. The thesis also shows that angiotensin receptor-neprilysin inhibitors (ARNI), another key pharmacotherapy class, improve quality of life in patients with systemic right ventricular failure. Furthermore, two device-based interventions are evaluated: percutaneous closure of baffle leaks in patients with transposition of the great arteries who have undergone the atrial switch procedure, and cardiac resynchronisation therapy (CRT). The thesis concludes with a chapter, co-authored with a patient, that highlights the importance of patient involvement.

• Adult Congenital Heart Disease
• ACHD
• Congenital Heart Disease
• Heart Failure
• Systemic Right Ventricle
• sRV
• Transposition of the Great Arteries
• Fontan Circulation
• Single ventricle
• Univentricular

• All authors: Neijenhuis, R.M.L.
• Supervisor: Jukema, J.W.; Jongbloed, M.R.M.
• Co-supervisor: Egorova, A.D.
• Committee: Rotmans, J.I.; Blom, N.A.; Roos-Hesselink, J.W.; Veldtman, G.R.
• Qualification: Doctor (dr.)
• Awarding Institution: Faculty of Medicine, Leiden University Medical Center (LUMC), Leiden University
• Date: 2026-09-11
• ISBN (print): 9789083723815
• Sponsorship: Publication of this thesis was kindly supported by: ChipSoft, Leopold Meijler fonds, Boehringer Ingelheim B.V., and BIOTRONIK Nederland B.V. The financial support provided by the KNAW Ter Meulen Grant (The Royal Netherlands Academy of Arts & Sciences), Foundation “De Drie Lichten”, and AstraZeneca for the studies presented in this thesis is gratefully acknowledged.