Fetal Cardiomyopathy in the Contemporary Era: A Multicenter Fetal Heart Society Research Collaborative Study

BACKGROUND: – Fetal cardiomyopathy is a rare condition, often with an unknown cause and associated with high perinatal mortality. Recent years have seen improvement in fetal cardiac screening, genetic testing, and management. We sought to investigate genetic associations and clinical outcomes of fetal cardiomyopathy in the contemporary era. METHODS: – A single-arm (descriptive) retrospective cohort study of fetal cardiomyopathy cases diagnosed from January 2017 to December 2021 at 26 North American centers in the Fetal Heart Society Research Collaborative was undertaken. Cases attributable to maternal diabetes, extra-cardiac conditions, structural heart disease, or arrhythmias were excluded. Genetic testing results, extra-cardiac structural anomalies, and outcomes were collected. Logistic regression was performed to determine prenatal risk factors for death or cardiac transplantation by 1-year of age. Descriptive competing-risk analyses (cumulative incidence functions) and Kaplan-Meier survival estimates were used to describe outcomes. Multivariable logistic regression with 5 prespecified covariates was performed to identify prenatal factors associated with death or cardiac transplantation by 1-year of age. RESULTS: – In 148 cases of fetal cardiomyopathy, 6.7% (10/148) opted for pregnancy termination, 8.6% (12/138) of continuing pregnancies experienced fetal death, and 1.4% (2/138) were lost to follow-up. Among continuing pregnancies, overall 1-year survival was 61.5% (85/138) with 1-year transplant-free survival of 50.0% (69/138). Of live births, 8.8% (11/124) received palliative care from the outset, and 21.2% (24/113) of those with intention to treat were listed for cardiac transplant, of whom 75.0% (18/24) received transplantation by age 1-year. Genetic etiologies were found in 34.0% (50/147) of the cohort, with variants of uncertain significance detected in an additional 27.2% (40/147). Fetal hydrops at the time of prenatal diagnosis (P=0.001) and a prenatal diagnosis of extracardiac structural anomalies (P≤0.001) were significantly associated with death or transplant by 1-year of age. CONCLUSIONS: – Fetal cardiomyopathy outcomes have improved in the current era, although only half achieve 1-year cardiac transplant-free survival. Genetic testing identifies a cause in one-third of cases. Hydrops at the time of fetal cardiomyopathy diagnosis and a prenatal diagnosis of extra-cardiac structural anomalies remain important risk factors for mortality.