Clinical importance of left atrial infiltration in cardiac transthyretin amyloidosis
Francesco Bandera, Raffaele Martone, Liza Chacko, Sashiananthan Ganesananthan, JA Gilbertson, Markella Ponticos, Aviva Petrie, Francesco Cappelli, Marco Guazzi, Luciano Potena, Claudio Rapezzi, Ornella Leone, Philip N. Hawkins, JD Gillmore, Marianna Fontana
Abstract
Abstract Funding Acknowledgements Type of funding sources: None. INTRODUCTION The clinical significance of left atrial (LA) involvement in ATTR amyloidosis cardiomyopathy (ATTR-CM) has not been characterized. The aims of this study were to characterize: (1)LA pathology in explanted ATTR-CM hearts; (2)LA mechanics using echocardiographic speckle-tracking in a large cohort of ATTR-CM patients; (3)to study the association with mortality. METHODS AND RESULTS Congo red staining and immunohistochemistry was performed to assess the presence, type and extent of amyloid and associated changes in 5 explanted ATTR-CM atria. Echo speckle-tracking was used to assess LA reservoir, conduit, contractile function and stiffness in 906 ATTR-CM patients (551 wt-ATTR-CM;93 T60A-ATTR-CM;241 V122I-ATTR-CM;21 other). There was extensive ATTR amyloid infiltration in the 5 atria with loss of normal architecture, vessels remodelling, capillary disruption and subendocardial fibrosis. Echo speckle-tracking in 906 ATTR-CM patients demonstrated increased atrial stiffness [median(25th-75th quartile) 1.83(1.15-2.92)] that remained independently associated with prognosis, after adjusting for known predictors (lnLA stiff:HR = 1.26,CI 1.07-1.57;p = 0.009). 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)%; contraction function 4.0(2.29-6.56)%]. Atrial contraction was absent in 21.6% of patients whose ECG showed sinus rhythm (SR)-"atrial electro-mechanical dissociation"(AEMD). AEMD was associated with poorer prognosis compared to SR patients with effective mechanical contraction (p < 0.0001). AEMD conferred a similar prognosis to patients in AF. CONCLUSION The phenotype of ATTR-CM includes significant infiltration of the atrial walls with progressive loss of atrial function and increased stiffness, which is a strong independent predictor of mortality. AEMD emerged as a distinctive phenotype identifying patients in SR with poor prognosis. Abstract Figure.