Abstract Body (Do not enter title and authors here): Background: Heart failure (HF) in adults have benefitted significantly from addition of angiotensin receptor-neprilysin inhibitor (ARNI). However, limited data exist on the efficacy and safety of ARNI in adults with congenital heart disease (ACHD) related HF.
Methods: We conducted a comprehensive search of 3 major databases- PubMed, Scopus, and Embase, and collected articles published the use of ARNI for HF in ACHD patients who were already receiving angiotensin-converting enzyme inhibitors (ACEi)/angiotensin receptor blockers (ARB), beta-blockers, and mineralocorticoid antagonists. We excluded articles on acute decompensated HF and HF with preserved ejection fraction. The primary outcome was the change in NYHA functional class (FC). Additionally, we evaluated the safety and tolerability of ARNI by studying adverse effects such as hypotension, elevated serum creatinine (Cr), and potassium (K⁺). A pooled effect size was calculated based on mean differences (MD) or log odds ratio (LogOR).
Results: Our meta-analysis included 14 studies with a total of 305 patients, aged 25 to 84 (median 42 years) (Table). Among 305 ACHD patients, 70% had systemic RV, 27% had systemic LV, and 3% were Fontan patients with unknown ventricular morphology. When ARNI replaced ACEIs/ARBs and was added to remaining therapies, the pooled analysis indicated that ARNI significantly improved NYHA FC (LogOR: 0.67, 95% confidence interval (CI) 0.15-1.19, p=0.01) (Figure 1A). However, there was no significant change in ventricular function (logOR: 0.37, 95% CI 0.45-0.42, p=0.38). Notably, ARNI use led to a significant decrease in systolic blood pressure (MD=0.49, 95% CI -0.70 to -0.29, p=0.00) (Figure 1B), and elevated Cr levels (MD = 0.30, 95% CI 0.10-0.45, p=0.00) (Figure 1C). No significant change in K⁺ level (MD=0.0, 95% CI -0.61 to 0.61; p=0.99) (Figure 1D). Eighteen patients (6%) discontinued ARNI due to side effects.
Conclusion: Our meta-analysis found that ARNI replacement for ACEIs/ARBs improved NYHA FC in most ACHD HF patients across a heterogeneous group of ACHD HF patients consisting of single ventricle, systemic- RV and LV. However, there was no significant change in ventricular function or natriuretic peptide levels. Hypotension and increased serum Cr are more frequent with ARNI use, warranting close monitoring. Future research is needed to assess composite outcomes, including hospitalizations and mortality in ACHD HF patients after adding ARNI to conventional therapy.