Variants Are Associated with Atrial Dysfunction in Neonates with Hypoplastic Left Heart Syndrome.

: variants are the most well-known genetic risk factor (10%) for hypoplastic left heart syndrome (HLHS) and are associated with decreased cardiac transplant-free survival. encodes for α-myosin heavy chain (α-MHC), a contractile protein expressed in the neonatal atria. We therefore assessed atrial function in HLHS patients with variants. : We performed a retrospective, blinded assessment of pre-stage I atrial function using 2D speckle-tracking echocardiography (2D-STE). Variant carriers were control-matched based on AV valve anatomy, sex, and birth year. Studies were obtained postnatally from awake patients prior to surgical intervention. Right atrial (RA) and right ventricular (RV) strain and strain rate (SR) were measured from the apical four-chamber view. : A total of 19 HLHS patients with variants had echocardiograms available; 18 were matched to two controls each, and one had a single control. RA active strain (ASct) was decreased in variant carriers (-1.41%, IQR -2.13, -0.25) vs. controls (-3.53%, IQR -5.53, -1.28; = 0.008). No significant differences were identified in RV strain between the groups. RA reservoir strain (ASr) and conduit strain (AScd) positively correlated with heart rate (HR) in variant carriers only (ASr R = 0.499, = 0.029; AScd R = 0.469, = 0.043). RV global longitudinal strain (GLS) as well as RV systolic strain (VSs) and strain rate (VSRs) correlated with HR in controls only (GLS R = 0.325, = 0.050; VSs R = 0.419, = 0.010; VSRs R = 0.410, = 0.012). : We identified functional consequences associated with variants, a known risk factor for poor outcomes in HLHS. variant carriers exhibit impaired RA contractility despite there being no differences in RV function between variant carriers and controls. variants are also associated with an ineffective RA reservoir and conduit function at high heart rates, despite preserved RV diastolic function. RA dysfunction and reduced atrial "kick" may therefore be a significant contributor to RV failure and worse clinical outcomes in HLHS patients with variants.