Abstract 4369739: Refining Prediction of Cerebrovascular Events in ATTR-CM with Sinus Rhythm to Guide Preventive Anticoagulation

Abstract

Background: Patients with transthyretin amyloid cardiomyopathy (ATTR-CM) face a significant risk of cerebrovascular events, even when in sinus rhythm (SR). However, no validated tool exists to identify those at highest risk. Hypothesis: Atrial amyloid infiltration may cause loss of effective left atrial (LA) contraction despite SR, a phenomenon termed atrial electromechanical dissociation (AEMD). We postulate that LA dysfunction, particularly AEMD, increases the risk of cerebrovascular events and could guide preventive anticoagulation at individual level. Aims: To (i) characterize the LA phenotype using speckle-tracking strain analysis, (ii) assess the potential association of LA function with stroke or TIA, and (iii) develop an algorithm to predict 1-year risk of cerebrovascular events in patients with SR. Methods: Retrospective analysis of patients diagnosed with ATTR-CM (Jan 2003–Dec 2023) at the UK National Amyloidosis Centre. LA function was assessed by speckle-tracking analysis. AEMD was defined as SR with absent LA strain contraction. The primary outcome was time to either stroke or TIA. The secondary outcome was AF development. Results: Among 2310 ATTR-CM patients (74.5% wild-type),116(5.0%) had AEMD,757(32.8%) had SR with LA contraction and 1437(62.2%) had AF on anticoagulation. Over 34[IQR18–54] months,5.0%(n=114) patients experienced the composite outcome of stroke/TIA and 30.9%(n=270/874 in SR) developed AF. AEMD was associated with an increased risk of stroke/TIA compared to SR with LA contraction (HR:3.10,95%CI1.95-4.96;p<0.001) and to AF on anticoagulation (HR:10.62,95%CI6.21-18.16;p<0.001)(Fig 1). AEMD also conferred greater risk of AF development(HR:2.40,95%CI1.80–3.19,p<0.001)(Fig 1). These finding were consistent across the 3 main genotypes (wild-type, T60A and V122I), the 3 NAC disease stages and disease-modifying treatment/enrolment in clinical trials. A flowchart for predicting 1-year risk of stroke/TIA was developed combining transmitral A wave and LA contraction. A-wave ≥90 cm/s ruled out stroke/TIA with sensitivity 96.6% and NPV 98.7%. In patients with A-wave <90 cm/s, worse LA contraction was associatied to a higher risk of stroke/TIA(HR1.28,95%CI1.10–1.50,p=0.001). Risk increased stepwise, peaking in AEMD (9.5 events/100 pt-years)(Tab 1). Conclusion: LA dysfunction, especially AEMD, confers greater risk of stroke/TIA and AF risk in ATTR-CM patients. AEMD may identify high-risk patients who could benefit from preventive anticoagulation.