Introduction: Patients with congenital heart disease (CHD) often present with ventricular dysfunction and severe heart failure. Heart failure drug therapy is well established in pts. with acquired heart disease, however, evidence for the effectiveness of novel heart failure drugs across the spectrum of CHD is lacking. We performed a cross-sectional and longitudinal study to evaluate the prevalence of heart failure and use of heart failure medication in Germany based on a large health insurance database, focusing on novel SGLT-2 inhibitors and Angiotensin Receptor-Neprilysin Inhibitor (Sacubitril/Valsartan, ARNI) medication.

Methods: Patients with CHD were identified using administrative data of the BARMER health insurance dataset between 2005 and 2021. Information on patient-demographics, diagnosis of underlying CHD, disease complexity, heart failure medication and associated co-morbidities were assessed.

Results: Overall 92,315 CHD pts. (47.3 % male, median age 22 [IQR 11-54] years) were identified. Of these, 18,487 (20.0%, 47.2 % male, median age 71 [IQR 46-84] years) had a diagnosis of heart failure. In this CHD cohort, the most used heart failure drugs were ACE inhibitors (n=19,086 pts., 20.7%), angiotensin receptor blockers (ARBs, 11,275 pts., 12.2%), betablockers (21,519 pts., 23.3%) and mineralocorticoid receptor antagonists (MRAs, 6,555 pts., 7.1%). 25,937 pts. received diuretic therapy. Cardiac glycosides were used in 2,755 pts. (3.0 %). Between 2005 and 2020 the use of heart failure drugs increased by 25% for ACE inhibitors,21.1% for ARBs, 32.8% for MRAs and 89.4% for betablockers, respectively. Starting from 2015, ARNIs and SGLT-2 inhibitors (after 2016) were introduced into CHD treatment. In total 1,049 CHD pts. were treated with SGLT-2 inhibitors and/or ARNIs (59.2% male, 71.0 % mild complexity, 19.9 % moderate complexity and 9.0 % complex CHD, median age 69.5 [IQR 61-81] years). Of these, 838 pts. received ARNIs and 639 SGLT-2 inhibitors (38.9% dapagliflozin, 57.2% empagliflozin). The majority of SGLT2 inhibitor pts. had a concomitant diagnosis of diabetes, however, 105 pts. with isolated heart failure and without diabetes could be identified. Of pts. on SGLT2/ARNI therapy, 745 had mild complexity, 209 moderate complexity (84 aortic coarctation, 71 atrioventricular septal defects, 31 tetralogy of Fallot) and 95 complex CHD (42 Eisenmenger syndrome, 33 transposition of the great arteries and 19 univentricular physiology). Pts. with SGLT2/ARNI therapy were significantly more likely to be male (59.2% vs. 46.5 %, p<0.001), have simpler forms of CHD (p<0.001), have a higher age at therapy (median 69.5 vs. 62.4 years, p=0.0015) and a higher prevalence of renal dysfunction (15.5 % vs. 9.6 %, p<0.001) or supraventricular cardiac arrhythmias (84.3% vs. 69.4%, p<0.001) compared to heart failure pts. without SGLT2/ARNI therapy. 

Conclusion: Based on a large nationwide cohort of pts. with CHD we found that heart failure is common and increasingly requires therapy. The use of heart failure medication increased over the last 15 years and despite the lack of prospective randomized data novel SGLT-2 inhibitors/ARNIs are being rapidly introduced empirically into clinical treatment of CHD pts. Especially male CHD pts. with simpler defects and associated co-morbidities seem to be subjected to therapy. Further prospective data is required to assess the risks and benefits of SGLT2/ARNI therapy in this vulnerable cohort given the increasing use.