Abstract Body (Do not enter title and authors here): Background: Hereditary transthyretin amyloidosis (ATTR) is often missed due to variable presentations, ranging from primarily neurologic to solely cardiac. Nearly 50% of ATTR mutation carriers develop cardiomyopathy; thus, understanding their subclinical echocardiographic abnormalities could inform early disease presentation.

Objective: Define the echocardiographic profiles of ATTR genotype-positive, cardiac phenotype-negative (Gen+/Ph-) individuals compared to matched controls and those with confirmed cardiac disease (Gen+/Ph+).

Methods: ATTR Gen+/Ph- individuals were identified based on positive genetic test and no signs of cardiac infiltration by routine echo or PYP scan. Baseline echocardiograms were analyzed and compared to age-, sex- and comorbidity-matched controls, and to Gen+/Ph+ patients with ejection fraction >50%. Structural indices, diastolic parameters and 2D strain analyses of the left ventricle (LV), left atrium (LA), right ventricle (RV) and right atrium (RA) were measured and compared for differences in rank (Mann-Whitney U test) and in effect size (Cliff’s δ).

Results: In the ATTR Gen+/Ph- group (n=39), mean age was 52±12 years, 69% were female. Mutations were V122I (23%), V30M (30%) and T60A (26%). The distribution of functional echocardiographic indices differed significantly from controls (n=78) (Table 1), with the largest effect size observed for RA reservoir strain, RV free wall longitudinal strain and LA reservoir strain (Figure 1). The proportion of ATTR Gen+/Ph- patients meeting the guidelines abnormal thresholds was different from controls for E/e’>14 (1.3% vs 10.3%), p=0.04),RV strain>-20% (1.3% vs 12.8%, p=0.02) and RA reservoir strain>-25% (1.3% vs 17.9%, p<0.01). Compared to a Gen+/Ph+ group (n=43), the distribution of all measured parameters differed significantly from the Gen+/Ph- group.

Conclusion: ATTR genetic carriers seem to be most different from controls in certain functional, rather than structural, echocardiographic indices. Longitudinal studies are needed to guide screening and early management in this population.