Assessing heart-pumping glitch may reduce stroke risk in adults with heart muscle disease: Study

A hidden atrial dysfunction may raise stroke risk in people with transthyretin amyloid cardiomyopathy (ATTR-CM); however, a non-invasive assessment tool may help identify those at increased risk, according to a preliminary study to be presented at the American Heart Association’s Scientific Sessions 2025. The disease is a progressive condition that stiffens the heart muscle and may raise the risk of stroke, even when the heart rhythm appears normal.

The meeting, Nov. 7-10, in New Orleans, is a premier global exchange of the latest scientific advancements, research and evidence-based clinical practice updates in cardiovascular science.

Transthyretin amyloid cardiomyopathy (ATTR-CM) is a potentially fatal disease that has historically been considered rare. However, it is difficult to know the actual number of people with the disorder because it is often underrecognized. In this condition, a protein called transthyretin becomes misshapen and accumulates in the heart, nerves and other organs. This protein buildup can stiffen the heart walls, making it difficult for the left ventricle to relax and fill with a regular heart rhythm. Patients also face a significant risk of stroke or transient ischemic attack (TIA) – a temporary blockage of blood to the brain. However, no tool exists to identify those at highest risk for stroke or TIA from this condition, according to the study.

“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., consultant cardiologist at Cardiovascular Department, University of Trieste, Italy, and researcher at the National Amyloidosis Centre, University College London. “Our study indicates that atrial contraction may matter as much as heart rhythm in predicting risk. This hidden dysfunction could help guide earlier conversations and treatment about preventive strategies including anticoagulation medications.”

Researchers at the U.K. National Amyloidosis Centre analyzed health records between 2003 and 2023 and reviewed those of more than 2,300 adults with transthyretin amyloid cardiomyopathy. About 1 in 8 of the patients with regular heart rhythm had atrial electromechanical dissociation (AEMD), a condition where the upper heart chamber, the atrium, looks normal on an electrocardiogram, yet does not contract and pump blood effectively.

During nearly three years of follow-up, researchers found:

♦ people with poor contraction of the atria were more than 3 times as likely to experience a stroke or TIA – compared to people with normal heart rhythm with normal atrial contraction; and

♦ these adults were also more likely to develop an irregular heart rhythm known as atrial fibrillation – a risk factor for stroke – during follow-up.

With this data, researchers developed a risk-prediction tool that uses two measures widely available on echocardiograms to measure the mechanical function of the atrial chamber. They found that stroke risk rose steadily as the atrium’s ability to squeeze weakened. In the highest-risk group ­– people with poor contraction – the rate was about 9 strokes per 100 people each year. The risk pattern was consistent across people with different genetic subtypes of ATTR amyloidosis and across different disease stages, suggesting atrial dysfunction represents a common driver of stroke risk in this condition.

“These findings shift attention from rhythm function to how well the atrium actually squeezes,” Porcari said.

The study is observational, so it cannot prove cause and effect. The next step is to conduct a prospective, multicenter study to investigate how this tool works and if preventive anticoagulation can lower the risk of stroke in people with atrial electromechanical dissociation. Researchers said the goal is to generate practice-ready evidence that can guide individualized decisions and, ultimately, help prevent disabling or fatal cerebrovascular events.

Fernando D. Testai, M.D., Ph.D., FAHA, vice-chair of the American Heart Association’s Brain Health Committee, who was not involved in the study 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.

“This study offers evidence of a strong predictor of future stroke or TIA,” said Testai, professor of neurology and rehabilitation at the University of Illinois College of Medicine in Chicago. “However, several challenges must be addressed before this approach can be integrated into clinical practice. The diagnosis of atrial electromechanical dissociation relied on speckle-tracking strain echocardiography, a specialized imaging technique which is not widely accessible and the findings require validation in larger, independent groups.”

The study reviewed data from one national center, so the results may not apply to all people with cardiac amyloidosis. Other limitations include that the classification of strokes was sometimes missing, and more research is needed to determine potential treatment options for people with AEMD.

Study details, background and design:

♦ A total of 2,310 adults with transthyretin amyloid cardiomyopathy (average age 76 years, 86% males and 74.5% with wild-type ATTR) were included in this analysis. About 75% of people had what is called the wild-type form, which develops with aging rather than being inherited; 5% had AEMD; about 33% had normal heart rhythm with effective left atrial contraction and 62% had atrial fibrillation on anticoagulation.

♦ Participants were observed from diagnosis to death, which was about three years, on average, Pocari said. Over 34 months, 5% of patients experienced a stroke or TIA and 31% developed atrial fibrillation.

♦ The analysis reviewed data from January 2003 to December 2023 from the U.K. National Amyloidosis Centre.

Reference: Assessing heart-pumping glitch may reduce stroke risk in adults with heart muscle disease, American Heart Association, Meeting: American Heart Association Scientific Sessions 2025.