Outcomes of Hypoplastic Left Heart Syndrome by Subtype and Presence of Ventriculocoronary Connections: A Fetal Heart Society Multicenter Retrospective Study

BACKGROUND: Hypoplastic left heart syndrome (HLHS) is classified by anatomic subtype: mitral atresia and aortic atresia (MA/AA), mitral stenosis and aortic atresia (MS/AA), and mitral stenosis and aortic stenosis (MS/AS). The MS/AA subtype is associated with ventriculocoronary connections (VCCs). We assessed whether specific HLHS subtypes are associated with an increased risk of mortality and whether this risk is stratified by VCCs identified during fetal or postnatal echocardiography. We also assessed whether the type of neonatal intervention performed modified the risk. METHODS: We performed a multicenter retrospective cohort study of fetuses and infants <2 months old with HLHS who were admitted between January 2012 and December 2016 to participating Fetal Heart Society institutions. Clinical and demographic data were collected. Fetal and transthoracic echocardiograms from a subset of patients with MS/AA and those with suspected VCCs were reviewed. Cox proportional hazards analysis was performed, controlling for cardiac center (random effect), birth weight, genetic diagnosis, extracardiac malformation, and restricted/intact atrial septum. RESULTS: Among 16 centers, 591 patients were born alive with intention to treat. MA/AA was the most common subtype (261, 44%), followed by MS/AA (200, 34%) and MS/AS (130, 22%). Of those with MS/AA, 115 (58%) had suspected VCCs. Median follow-up was 9.0 (interquartile range: 7.0, 10.8) years. Overall transplant-free survival (TFS) was 55.6% at 5 years and 49.4% at 10 years. When comparing MA/AA, MS/AS, and MS/AA with and without VCCs (reference group: MS/AA without VCCs), MS/AA with VCCs had the lowest TFS (hazard ratio [HR], 1.69 [1.12, 2.57]; 5-year TFS, 44.7%; 10-year TFS, 40.3%). This was followed by MA/AA (HR, 1.40 [0.95, 2.05]; 5-year TFS, 54.1%; 10-year TFS, 46.6%). Survival of MS/AA without VCCs (5-year TFS, 60.4%; 10-year TFS, 56.9%) was similar to MS/AS (HR, 0.91 [0.59, 1.41]; 5-year TFS, 65.0%; 10-year TFS, 58.3%). Among those with a prenatal diagnosis of HLHS (n=532), patients with MS/AA and VCCs suspected on fetal echocardiogram had a lower TFS compared with those with MS/AA without fetal suspicion for VCCs (HR, 1.79 [1.12, 2.85]). Fetal echocardiography was used to diagnose VCCs in 33 of 103 (32%) cases with MS/AA and VCCs suspected postnatally. Of patients with MS/AA and VCCs, type of stage I palliation was not associated with TFS ( P =0.784). CONCLUSIONS: In a large, multicenter cohort of HLHS patients, the MS/AA subtype with VCCs had the lowest TFS. Prenatal diagnosis of VCCs was associated with a lower TFS. This study underscores the prognostic value of assessing for VCCs in patients with HLHS both before and after birth.