Left ventricular strain does not differentiate amyloidogenic profiles in at-risk individuals withTTRVal142Ile

AbstractObjectivesTo identify echocardiographic signatures featuring left ventricular longitudinal strain (LS) associated with genetic risk for cardiac amyloidosis (CA) due to theTTRVal142Ile (V142I) variant in African American (AA) and Hispanic/Latinx (H/L) individuals.BackgroundHereditary transthyretin amyloidosis (hATTR) can cause CA in ∼60-70% of older V142I carriers, but amyloid deposition progresses over many years. Disease-modifying therapy for CA is now available and early initiation is a priority for improving outcomes. Genomic screening programs and familial cascade genetic testing uncover pre-symptomatic V142I carriers, yet no guidelines exist for early CA detection.MethodsExome sequencing data linked to electronic health records (EHRs) of BioMebiobank participants were queried for AA or H/LTTR- andTTR+ (V142I) subjects without hATTR diagnoses and with prior echocardiograms suitable for retrospective LS analysis. Systemic “red flag” features of ATTR were extracted from EHRs ofTTR+ subjects. Speckle tracking echocardiography was retrospectively applied to determine global (GLS) and segmental LS. Relative apical sparing (RAS) was calculated.Results57TTR+ and 46TTR-age- and ancestry-matched subjects were included. GLS declined with age in females but not males, and was abnormal (<16%) in 18 (31.6%)TTR+ and 7 (15.2%)TTR-subjects (p = 0.066). Apical sparing was observed in 13 (22.8%)TTR+ and 11 (23.9%)TTR-subjects (p = 1.0). After adjusting for relevant demographic and echocardiographic covariates, neither GLS nor RAS was associated withTTR+ V142I status. Red flag features were not associated with GLS or RAS inTTR+ subjects.ConclusionsNeither GLS nor RAS were significantly different betweenTTR+ andTTR-subjects. Since >50% ofTTR+ subjects were ≥ 60 years old, penetrance of CA by echocardiography among unselected V142I carriers may be lower than previously estimated. These findings indicate that surveillance for CA in individuals at increased genetic risk due to V142I should not rely solely on echocardiography, even with LS.