Initial Experience with Guideline-Directed Heart Failure Therapy in Adult Patients with Univentricular Hearts and Failing Fontan Circulation

All articles of this category (opens in new window) Background: Despite significant advances in the treatment of chronic heart failure (HF) with reduced ejection fraction in patients with normal cardiac anatomy in recent years, the management of HF in adult patients with congenital heart disease—especially those with univentricular hearts and completed Fontan palliation—remains unsupported by strong evidence-based recommendations. This study aims to assess the effectiveness and tolerability of the ESC-recommended therapy for “normal hearts”, including a four-drug combination (angiotensin-converting enzyme inhibitors [ACEi] or angiotensin receptor-neprilysin inhibitors [ARNi], β-blockers [BB], mineralocorticoid receptor antagonists [MRA], and sodium-glucose co-transporter 2 inhibitors [SGLT2i]) in adults with congenital heart disease (ACHD) patients with univentricular heart failure. Methods: The study included 15 adult patients with single-ventricle anatomy of various morphologies who had undergone Fontan palliation and presented with clinical and laboratory signs of HF. We retrospectively analyzed changes in NYHA functional class, renal function, serum potassium, systemic ventricular ejection fraction, and NT-proBNP levels during treatment with a combination of ESC-guideline-directed medical therapies (ARNi or ACEi, β-blockers, MRAs, and SGLT2 inhibitors). The median follow-up duration was 18 months. Results: Age at therapy initiation was significantly lower in patients with a systemic right ventricle compared with those with a systemic left ventricle (median: 28 vs. 47 years, p = 0.005). Likewise, mean systolic blood pressure was significantly lower in the systemic right ventricle group (114 vs. 139 mm Hg, p = 0.044). Among the 15 patients, 10 (67%) received the full regimen of guideline-directed HF-therapy, including sacubitril/valsartan and SGLT2 inhibitors, while 5, with preserved ejection fraction, received treatment without ARNi. A significant reduction in NT-proBNP levels was observed under the exposure to therapy, with the median decreasing from 583 ng/L (range: 274–1,039) to 311 ng/L (range: 121–406) and NYHA class improvement in 40% of patients. The significant drop of systolic pressure from 120 to 111 mm Hg ( p = 0.047) was observed during this study, but it did not require the discontinuation of therapy. No significant changes in renal function or hyperkalemia were observed. Conclusion: Our initial results demonstrate good tolerability and effectiveness of heart failure therapy using a combination of four guideline-directed medications in ACHD patients with Fontan circulation. Publication History Article published online: 17 February 2026 © 2026. Thieme. All rights reserved. Georg Thieme Verlag KG Oswald-Hesse-Straße 50, 70469 Stuttgart, Germany