Atrial Mechanical Contraction Predicts Cerebrovascular Risk in Patients With Transthyretin Amyloid Cardiomyopathy and Sinus Rhythm

Patients with transthyretin amyloid cardiomyopathy (ATTR-CM) remain at risk of cerebrovascular events even when in sinus rhythm (SR), yet the majority of these patients are unrecognized. This study sought to identify patients in SR at high risk of cerebrovascular events. We analyzed patients diagnosed with ATTR-CM between January 2003 and December 2023 at the UK National Amyloidosis Centre. Left atrial (LA) function was assessed using speckle-tracking strain echocardiography. Atrial electromechanical dissociation (AEMD) was defined as SR on electrocardiogram with absent left atrial strain contraction (LASc). Patients in SR were stratified according to LASc tertiles. The primary outcome was a cerebrovascular event defined as stroke or transient ischemic attack (TIA), whichever occurred first. The secondary outcome was development of atrial fibrillation (AF). Death was treated as a competing event. The study comprised 2,310 patients with ATTR-CM, of which 873 patients were in SR and not receiving anticoagulation (age 77 years, 82% male, 61% wild type, CHA 2 DS 2 -VASc 4). AEMD was present in 115 patients (13.2%). Of the patients in SR, over a median of 34 months (Q1-Q3: 18-54 months), 269 patients (30.8%) developed incident AF and 85 (9.7%) experienced stroke/TIA. Patients with baseline AF receiving anticoagulation had a rate of stroke or TIA of 0.7 per 100 person-years. AEMD was associated with a 2.4-fold higher incident AF and 3-fold higher risk of stroke or TIA compared with SR with LA mechanical contraction (8.7 vs 2.5 per 100 person-years, respectively, for stroke or TIA), independent of CHA 2 DS 2 -based scores and markers of disease severity. Among 758 patients in SR without AEMD, LASc tertiles (<4%, 4%-7%, >7%) exhibited an independent association with 1-year risk of stroke or TIA, with LASc <4% being associated with 10-fold increased risk compared to LASc >7%. This association was consistent after adjustment for NAC stage and prior cerebrovascular events. Adding LASc tertiles to CHA 2 DS 2 -VASc or CHA 2 DS 2 -VA significantly improved model fit and risk reclassification at 1 year. LA dysfunction, particularly AEMD and severely impaired LASc, is associated with increased cerebrovascular events in ATTR-CM. Using LAS analysis may refine risk stratification and help identify patients with ATTR-CM in SR who might potentially benefit from intensified extended rhythm monitoring or prophylactic anticoagulation.