Myh6 Variants Result In Significant Reduction In Systolic And Diastolic Atrial Function In Neonates With Hypoplastic Left Heart Syndrome
Melissa Anfinson, PhD, Sara Creighton, Pippa Simpson, Jeanne James, Megan Schoessling, Peter Frommelt, Aoy Tomita-Mitchell, Michael E. Mitchell.
Children's Hospital of Wisconsin, Medical College of Wisconsin, Milwaukee, WI, USA.
Objective(s): MYH6 variants are the most common genetic risk factor for hypoplastic left heart syndrome (HLHS). MYH6 is expressed in the neonatal atria; variants are associated with decreased cardiac transplant-free survival. Our aim was to identify measure of atrial function that can direct therapeutic intervention in this high-risk group.
Methods: This was a retrospective, blinded assessment of pre-stage I atrial function in HLHS using two-dimensional speckle tracking echocardiography. Variant carriers were control-matched based. Studies were obtained shortly after birth, prior to surgical intervention. Results: 19 HLHS patients with MYH6 variants had echocardiograms available; 18 were matched to two controls each, one had a single appropriate control. Active RA strain was decreased in MYH6 variant carriers (-1.41%, IQR -2.13, -0.25) vs controls (-3.53%, IQR -5.53, -1.28), indicating impaired atrial contractility (p=0.008). Reservoir RA SR trended lower in MYH6 variant carriers (1.06%/sec, IQR 0.78, 1.43) vs controls (1.23%/sec, IQR 1.06, 1.55), suggesting decreased RA compliance (p=0.096). Conduit and reservoir RA strain correlated with heart rate in MYH6 variant carriers (conduit R2=0.469, p=0.043; reservoir R2=0.499, p=0.029) but not controls, showing variant carriers continue to depend on passive ventricular filling at high heart rates.
Conclusions: We identified functional consequences associated with MYH6 variants, a known risk factor for poor outcomes in HLHS. Specifically, HLHS patients carrying MYH6 variants exhibit impaired RA contractility. This demonstrates how knowledge of MYH6 variants can inform decisions regarding targeted intervention and provide justification for early genetic screening in HLHS.
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