Abstract 13148: Clinical Importance of Left Atrial Infiltration in Cardiac Transthyretin Amyloidosis

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Introduction: The clinical significance of left atrial (LA) involvement and dysfunction in ATTR amyloidosis cardiomyopathy (ATTR-CM) has not been characterized. We sought to study: 1) LA pathology in heart specimens from ATTR-CM patients 2) LA stiffness and mechanics using echocardiographic speckle tracking (EST) in cardiac ATTR-CM 3) the association between parameters of atrial function and mortality. Methods: Congo red staining and immunohistochemistry was performed to assess amyloid in the atria from 5 ATTR-CM heart specimens. 2D EST was used to assess LA reservoir, conduit, contractile function and stiffness in 906 ATTR-CM patients (551 wt ATTR; 93 T60A ATTR; 241 V122I ATTR; and 21 other gene variants). Results: There was extensive ATTR amyloid infiltration in the 5 atria, with loss of normal architecture, infiltration and remodelling of vessels, capillary disruption and subendocardial fibrosis. EST demonstrated increased atrial stiffness [median (25th-75th quartile) 1.83 (1.15-2.92)] that remained independently associated with reduced survival, after adjusting for known prognostic variables (lnLA stiff: HR= 1.26, CI 1.07-1.57; p=.009). There was substantial impairment of the three phasic functional atrial components [reservoir 8.86(5.94-12.97)%; conduit 6.5(4.53-9.28)%; and contraction 4.0(2.29-6.56)%]. Atrial contractile function was absent in 21.6% of patients whose ECG showed sinus rhythm (SR)-atrial electro-mechanical dissociation (AEMD). AEMD was associated with a poorer prognosis compared to SR patients who had effective mechanical contraction (p <.0001). AEMD conferred a similar prognosis to patients in AF. Conclusions: The phenotype of ATTR-CM includes clinically significant infiltration of the atrial walls characterized by progressive loss of function and increased stiffness, a strong independent predictor of mortality. AEMD emerged as a distinctive functional phenotype identifying patients in SR with poor prognosis.