Clinical importance of left atrial infiltration in cardiac transthyretin amyloidosis

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.

Systemic embolism in amyloid transthyretin cardiomyopathy

“…More work is needed in this area to identify ATTR‐CM patients without AF who are at higher risk of embolic events and who could benefit from close atrial thrombus/AF screening or early treatment with OAC. In this regard, identification of atrial dysfunction by strain echocardiography that has been found to be present in cardiac amyloidosis irrespectively of atrial cavity size, diastolic dysfunction and electrical atrial activity should be explored 21–23 . Unfortunately, atrial strain echocardiography data were not available in our cohort.…”

“…In this regard, identification of atrial dysfunction by strain echocardiography that has been found to be present in cardiac amyloidosis irrespectively of atrial cavity size, diastolic dysfunction and electrical atrial activity should be explored. [21][22][23] Unfortunately, atrial strain echocardiography data were not available in our cohort.…”

Association Between Atrial Uptake on Cardiac Scintigraphy With Technetium-99m-Pyrophosphate Labeled Bone-Seeking Tracers and Atrial Fibrillation

“…(3) How does AU relate to abnormal atrial strain and increased atrial stiffness reported in patients with ATTR-CA? 27 (4) Does AU represent a modifiable substrate with ablation therapy? (5) Can medical therapy such as tafamadis known to stabilize ATTR-CA progression modify subsequent risk of incident AF?…”

Red flags for the diagnosis of cardiac amyloidosis: simple suggestions to raise suspicion and achieve earlier diagnosis

“…99 Extensive atrial amyloid infiltration and consequently blunted atrial function have been recently described by Bandera et al with ATTR-CM revealed augmented atrial stiffness and all the three components of the atrial functioning (reservoir, conduit and contraction) were significantly impaired. 100 Furthermore, peak left atrial longitudinal strain was independently associated with the diagnosis of CA and, among patients with unexplained LVH, those with blunted peak left atrial longitudinal strain showed a eight-fold higher risk for CA beyond standard echocardiographic variables and cardiac biomarkers. 101 In a recent study performed in 13 tertiary Italian centers, the echocardiograms of patients aged 55 years performed during 15 days were collected (known CA or other cardiomyopathies with hypertrophic phenotype were excluded).…”