Atrial Dysfunction Triples Stroke Risk in Transthyretin Amyloid Cardiomyopathy Patients

People with transthyretin amyloid cardiomyopathy who experience atrial electromechanical dissociation face significantly elevated stroke risk, according to research to be presented at the American Heart Association's Scientific Sessions 2025. The study found these individuals were more than three times as likely to experience stroke or transient ischemic attack compared to those with normal heart rhythm and effective atrial contraction. Transthyretin amyloid cardiomyopathy involves misshapen protein accumulation in the heart, stiffening heart walls and impairing the left ventricle's ability to relax and fill with blood.

The research analyzed health records of more than 2,300 adults with the condition between 2003 and 2023 from the U.K. National Amyloidosis Centre. Approximately one in eight patients with regular heart rhythm exhibited atrial electromechanical dissociation, where the atrium appears normal on electrocardiogram but doesn't contract effectively. During nearly three years of follow-up, these individuals showed dramatically increased stroke risk and were more likely to develop atrial fibrillation. The highest-risk group experienced about nine strokes per 100 people annually.

"Even with a regular heart rhythm, some people with transthyretin amyloid cardiomyopathy are still at risk of stroke if their atrium doesn't squeeze well," said study author Aldostefano Porcari, M.D., Ph.D. "Our study indicates that atrial contraction may matter as much as heart rhythm in predicting risk." Using this data, researchers developed a risk-prediction tool employing two measures widely available on echocardiograms to assess mechanical function of the atrial chamber. The tool demonstrated that stroke risk increased steadily as the atrium's ability to squeeze weakened.

The risk pattern remained consistent across different genetic subtypes of ATTR amyloidosis and various disease stages, suggesting atrial dysfunction represents a common driver of stroke risk. Fernando D. Testai, M.D., Ph.D., FAHA, vice-chair of the American Heart Association's Brain Health Committee, noted that "patients with amyloid cardiomyopathy who remain in sinus rhythm still exhibit a significantly elevated stroke risk compared to the general population, so there is a need for novel strategies to identify high-risk individuals who may benefit from anticoagulation, even in the absence of atrial fibrillation." However, Testai cautioned that the diagnosis of atrial electromechanical dissociation relied on speckle-tracking strain echocardiography, a specialized imaging technique not widely accessible.

The study's findings could potentially guide earlier conversations about preventive strategies including anticoagulation medications. Researchers plan to conduct prospective, multicenter studies to investigate how the tool works and whether preventive anticoagulation can lower stroke risk in people with atrial electromechanical dissociation. The goal is to generate practice-ready evidence that can guide individualized decisions and help prevent disabling or fatal cerebrovascular events.