Clinical Importance of Left Atrial Infiltration in Cardiac Transthyretin Amyloidosis

Abstract

Objectives The aim of this study was to characterize left atrial (LA) pathology in explanted hearts with transthyretin amyloid cardiomyopathy (ATTR-CM); LA mechanics using echocardiographic speckle-tracking in a large cohort of patients with ATTR-CM; and to study the association with mortality. Background The clinical significance of LA involvement in ATTR-CM is of great clinical interest. Methods 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 patients with ATTR-CM (551 wild-type (wt)-ATTR-CM; 93 T60A-ATTR-CM; 241 V122I-ATTR-CM; 21 other). Results There was extensive ATTR amyloid infiltration in the 5 atria, with loss of normal architecture, vessels remodeling, capillary disruption, and subendocardial fibrosis. Echo speckle tracking in 906 patients with ATTR-CM 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: 1.23; 95% CI: 1.03-1.49; P = 0.029). There was substantial impairment of the 3 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 22.1% of patients whose electrocardiograms showed sinus rhythm (SR) “atrial electromechanical dissociation” (AEMD). AEMD was associated with poorer prognosis compared with patients with SR and effective mechanical contraction (P = 0.0018). AEMD conferred a similar prognosis to patients in atrial fibrillation. Conclusions 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.

Cardiac Amyloidosis: A Review of Current Imaging Techniques

“…Additionally, there was significant impairment of the 3 phasic functional atrial components (atrial reservoir, conduit and contraction function); indeed 22% of patients in sinus rhythm with atrial electromechanical dissociation had absent atrial contraction. The extensive amyloid infiltration of the left atria on echocardiogram in this study was corroborated with histological analysis of explanted ATTR hearts (33).…”

“…The severity of dysfunction measured by a range of echocardiographic parameters was also shown to differ substantially at the time of diagnosis between patients with three important ATTR-CM genotypes. Those with p.V142I-associated ATTR-CM had the worst echocardiographic parameters, followed by wtATTR-CM and finally p.T80Aassociated ATTR CM, entirely consistent with the prognosis of these three conditions (33).…”

“…Both ventricular and atrial blood stasis have been demonstrated in studies to be substrate for intracardiac thrombi (35). Atrial electromechanical dissociation has been identified as a distinct clinical phenotype in ATTR-CM conferring a poorer prognosis, which merits discussion and consideration of anticoagulant therapy in such patients (33). In addition to the above, pleural and/or pericardial effusion are not uncommon findings in CA, especially in AL-CM (36).…”

Atrial function and geometry differences in transthyretin versus immunoglobulin light chain amyloidosis: a cardiac magnetic resonance study

“…Of interest, a recent study with a large cohort of ATTR cardiomyopathy found atrial electromechanical dissociation in the presence of sinus rhythm within a small proportion of patients. The prognosis for patients with atrial electromechanical dissociation was significantly worse than for patients found with effective booster function and was comparable with patients in atrial fibrillation 16 . In view of new medical therapies recently introduced to block specific stages of amyloidogenesis, there is an opportunity to further investigate LA phasic changes and how these coincide with medical management.…”

“…In our CA cohort we noted that LA booster function was significantly impaired and did not compensate for decreased reservoir function. Although, the loss of LA compliance in CA has been explained as obligatory in response to direct amyloid fibril deposits in atrial walls limiting atrial stretch 15 , 16 an apparent reduced booster strain may also be an integral parameter to consider. Of interest, a recent study with a large cohort of ATTR cardiomyopathy found atrial electromechanical dissociation in the presence of sinus rhythm within a small proportion of patients.…”