Time to reconsider thromboembolic risk and anticoagulation in transthyretin cardiac amyloidosis?

Abstract

Transthyretin cardiac amyloidosis (ATTR-CA) is considered an exemplar of 'restrictive cardiomyopathy' caused by extracellular deposition of amyloid fibrils derived from plasma transthyretin. 1 Whilst increased ventricular wall thickness is the hallmark of ATTR-CA, the atria are a frequently overlooked but common site of amyloid deposit. 2,3 Atrial fibrillation (AF) is the most common arrhythmia in ATTR-CA and exposes patients to the risk of thrombus formation and embolic events. 4,5 A remarkable incidence of atrial thrombi has been found in patients with ATTR-CA, either in the atrial appendage or attached to the atrial walls, also in a substantial number of those in sinus rhythm (SR). 4,5 Major advances in imaging such as bone tracer scintigraphy and cardiac magnetic resonance have transformed the non-invasive approach to diagnosis of ATTR-CA, 6,7 which has emerged as a much under-recognized cause of heart failure (HF) and mortality 8 in different clinical settings. 9-11 Nevertheless, solid evidence on the management of AF, estimation of thromboembolic risk and recommendations on initiation of oral anticoagulant therapy (OAT) in patients with ATTR-CA is lacking.In the last issue of the Journal, we read with interest the study by Vilches et al. 12 that tries to shed light upon the current knowledge gap on systemic embolism in ATTR-CA. The authors conducted a multicentre, retrospective analysis among four international amyloid centres exploring the incidence, prevalence and factors associated with systemic embolism in a population of ≈1200 patients with ATTR-CA. They collected information on the development of AF, thromboembolic events -including stroke, transient ischaemic attack or peripheral embolism -and OAT at first clinical evaluation and during follow-up.

Early diagnosis and management of cardiac amyloidosis: A clinical perspective

“…73,74 This has opened a debate on whether anticoagulation should always be prescribed in CA, particularly when atrial fibrillation is present. 74 Given the concomitant bleeding risk associated with systemic amyloidosis, deciding whether to initiate anticoagulants is difficult. Furthermore, the scores routinely used to support or discourage anticoagulation may appear less useful, as they do not take into account all the relevant factors.…”

“…Thromboembolic events have been observed in patients with sinus rhythm and may also result from noncardiac causes 72 . Reasons for this greater risk include renal loss of endogenous anticoagulants in nephrotic syndrome associated with AL, increased immobility, or the procoagulant activity of certain chemotherapies 73,74 . This has opened a debate on whether anticoagulation should always be prescribed in CA, particularly when atrial fibrillation is present 74 .…”

“…72 Reasons for this greater risk include renal loss of endogenous anticoagulants in nephrotic syndrome associated with AL, increased immobility, or the procoagulant activity of certain chemotherapies. 73,74 This has opened a debate on whether anticoagulation should always be prescribed in CA, particularly when atrial fibrillation is present. 74 Given the concomitant bleeding risk associated with systemic amyloidosis, deciding whether to initiate anticoagulants is difficult.…”