Clinical presentation, genetic etiologies and outcomes associated with fetal cardiomyopathies
Introduction: Cardiomyopathy refers to a broad range of heart muscle pathologies and prenatally-detected cardiomyopathy is associated with poor survival. There have been major advances in genetic testing in recent years and fetal surveillance for high risk pregnancies has become the standard of care. We hypothesized that in the recent era, outcomes will have improved and that a higher proportion will have a genetic diagnosis.
Methods: Retrospective, descriptive cohort study over a 17-year period (2003-2019). Cases were identified from our institutional database and echo reports and charts were reviewed.
Results: Twenty-one cases were diagnosed at a mean gestational age (GA) of 23 weeks (13-35 weeks). Sub-types were: 33% (7/21) non-compaction, 14% (3/21) hypertrophic, 29% (6/21) mixed, 14% (3/21) dilated, 10% (2/21) restrictive. At diagnosis 29% (6/21) had hydrops and another 38% (8/21) developed hydrops. Twenty-nine percent (6/21) resulted in termination, 24% (5/21) in intra-uterine deaths and 48% (10/21) in livebirths at a mean GA of 35 weeks (28-39 weeks). Of livebirths, 40% (4/10) remain alive. Of the whole cohort, 29% (6/21) had congenital heart defects (CHD) and 29% (6/21) had arrhythmias. Sixty-two percent (13/21) had a likely/known genetic cause: 1 NONO gene mutation; 1 unbalanced translocation 3;18; 1 Costello syndrome; 1 Noonan syndrome; 2 cousins had an MYH7 mutation; 1 mosaic 13q deletion; 2 suspected mitochondrial disease ; 2 fetuses of the same couple had restrictive cardiomyopathy with an SCN5A mutation and an additional channelopathy gene variant under investigation; 1 with two affected siblings was from a Hutterite family and 1 from a Mennonite family (still under investigation).
Conclusion: In our experience, outcomes remain poor and associated CHD and genetic etiologies are more common than previously reported. Further exploration of fetal cardiomyopathies in the context of advanced genetic testing is critical to improve counselling and develop strategies to improve outcomes.