Cardiac Strain Imaging in Asymptomatic Carriers of Transthyretin Variants

Objective: Explore different echocardiographic parameters, particularly strain imaging, for early pathological changes in asymptomatic ATTR variant carriers. Background: With the rise in genetic testing and availability of multiple echocardiographic parameters, determining which features are most sensitive for detecting early changes in asymptomatic carriers of hereditary transthyretin cardiac amyloidosis (ATTRv-CM) could be helpful for guiding monitoring strategies and implementation. Methods: TTR variant carriers (n=39) were identified after a positive genetic test in individuals without evidence of cardiomyopathy based on routine echocardiography or PYP scan. Baseline echocardiograms were analyzed and compared to matched controls and patients with ATTRv-CM. Structural indices, diastolic parameters, and myocardial and atrial 2D strain analyses were measured and compared for differences in rank and in effect size. Results: TTR variant carriers had a mean age of 51±11 years; 71% were female. Mutations were mainly V30M(29%), T60A(26%), and V122I(24%). Wall thickness measures were significantly higher in carriers compared to controls; however, the largest effect size for differences were observed left atrial(LA), right atrial(RA), and right ventricular(RV) strains (cliff delta >0.33). The proportion of TTR variant carriers meeting abnormal thresholds was different from controls for relative wall thickness>0.42 (16% vs. 0%), p<0.01), |RV strain|<20% (12.8% vs. 1.4%, p=0.02) and |RA reservoir strain|<25% (21.6% vs. 1.3%, p<0.01). After a median follow-up of 3.22 years, 4/26 (15%) TTR carriers developed ATTRv-CM and did not have major baseline dysfunctions. Conclusion: TTR variant carriers show subtle echocardiographic differences from controls, particularly in LA, RA, and RV strains. The implementation of echocardiography for early detection in asymptomatic TTR carriers can be challenging. Future studies should further investigate the usefulness of routinely measuring these features to guide monitoring strategies in this population.