Assessing Stroke Risk in ATTR-CM with Atrial Mechanics

A new longitudinal analysis from the UK National Amyloidosis Centre adds to a growing body of evidence demonstrating that impaired left atrial (LA) mechanical contraction—particularly atrial electromechanical dissociation (AEMD)—is strongly associated with cerebrovascular risk, even in patients who remain in sinus rhythm.

Published in the Journal of the American College of Cardiology, this study evaluated 2,310 patients with ATTR-CM diagnosed between 2003 and 2023, including 873 individuals in sinus rhythm who were not receiving anticoagulation. Investigators used speckle-tracking echocardiographic strain imaging to assess LA function through left atrial strain contraction (LASc), reservoir strain, and the presence of AEMD, defined as preserved sinus rhythm on ECG despite the absence of effective atrial contraction on strain analysis.

Over a median follow-up of 34 months, 9.7% of patients in sinus rhythm experienced stroke or transient ischemic attack (TIA), while 30.8% developed incident atrial fibrillation (AF). Among patients with AEMD, cerebrovascular risk increased substantially. Additionally, five-year cumulative incidence of stroke or TIA reached 21% in patients with AEMD compared with 8% in patients with preserved atrial mechanical contraction. AEMD independently conferred nearly a threefold higher risk of stroke or TIA and a 2.4-fold higher risk of incident AF.

Notably, most cerebrovascular events occurred before AF was clinically documented, and in several cases, AF was identified only shortly before the neurologic event. The pattern reinforces a growing concept in amyloid cardiomyopathy: atrial mechanical failure may precede electrical instability and may represent an important contributor to thromboembolic risk.

The investigators also identified a clinically useful gradient of risk based on LASc values. Patients with LASc below 4% demonstrated approximately tenfold higher 1-year risk of stroke or TIA compared with patients whose LASc exceeded 7%. By contrast, patients with preserved LASc demonstrated relatively low annual event rates.

These findings expose an important limitation of conventional stroke prevention models. Current frameworks, like CHA₂DS₂-VASc, were developed in populations with nonvalvular AF and might not fully  capture the biology of amyloid-associated atrial dysfunction. In this cohort, adding LASc and AEMD to traditional risk scores significantly improved statistical risk reclassification and model performance for 1-year cerebrovascular risk prediction.

Patients with ATTR-CM in sinus rhythm could potentially be stratified into three clinically meaningful phenotypes:

• High risk: AEMD or LASc <4%
• Intermediate risk: LASc 4%–7%
• Lower risk: LASc >7%

The implications may extend beyond anticoagulation decisions alone. Patients with severely impaired atrial mechanics may warrant intensified rhythm surveillance or extended rhythm monitoring, because LA strain and AEMD may identify thromboembolic risk before AF is clinically documented. Future work could explore the feasibility of integrating these measures into structured risk pathways for closer cerebrovascular surveillance.

At the same time, the investigators stop short of recommending empiric anticoagulation based solely on atrial strain abnormalities. Patients with ATTR-CM are typically older, medically complex, and vulnerable to bleeding complications. The retrospective design, absence of systematic prolonged rhythm monitoring, and lack of external validation mean the findings remain hypothesis-generating. Prospective trials will determine whether mechanics-guided anticoagulation strategies can improve outcomes.

Reference:
Porcari A, Dal Passo B, Venneri L, et al. Atrial mechanical contraction predicts cerebrovascular risk in patients with transthyretin amyloid cardiomyopathy and sinus rhythm. J Am Coll Cardiol. Published online February 18, 2026. doi:10.1016/j.jacc.2025.12.033