Outcomes of Children with Hypoplastic Left Heart Syndrome and Systemic Ventricular Dysfunction on Guideline Directed Medical Therapy

Purpose Right ventricular dysfunction (RV dysfxn) in hypoplastic left heart syndrome (HLHS) is associated with increased mortality. Such patients (pts) are often commenced on heart failure (HF) medications despite a lack of evidence. We hypothesized that guideline directed medical therapy (GDMT) would be associated with improved function (fxn) and reduced mortality. Methods The SickKids HF Database is a retrospective cohort of all paediatric HLHS pts from 2001 to 2017, with at least mild RV dysfxn on echocardiogram lasting >30 days, or death or transplant within 30 days onset of dysfxn. Normalization of fxn was defined as qualitatively normal RV fxn on echocardiogram lasting ≥30 days after dysfxn onset. The primary endpoint was normalization of RV fxn with GDMT at 70% of target dosing (TD). Secondary outcomes included transplant-free survival (TFS) with GDMT. Descriptive statistics and time to event analysis were used. Results Our cohort included 99 pts with median age at onset of dysfxn 2.6(1.0-5.3) months. Overall TFS was 44% at 5 years after dysfxn onset and 51 (52%) pts had normalization of RV fxn. TFS was 14% at 2 years after dysfxn onset in pts with persistent dysfxn versus 78% in pts with normalization of fxn. TD in ≥1 HF medication was reached in 57(58%) pts by study endpoint. In those with normalization of RV fxn; 24(47%) were on 1 medication at TD versus 13 (27%) with persistent dysfxn (p<0.0001), and 14 (27%) were on 2 medications at TD versus 4(8%) with persistent dysfxn (p=0.0004). Of those in whom fxn normalized, 35 (69%) were on TD ACEi versus 14(29%) with persistent dysfxn, 12(14%) were on TD beta blocker, and 21(41%) were on TD spironolactone. TD ACEi correlated with improved 5-year TFS (25% to 60%, p<0.0001, Figure 1A). Figure 1B delineates changes in TFS with GDMT. Conclusion In our cohort of pts with HLHS and RV dysfxn, GDMT was associated with increased rate of normalization of fxn and improved TFS at 5 years after dysfxn onset.