A new study suggests that people with a rare heart condition called transthyretin amyloid cardiomyopathy (ATTR-CM) may be at higher risk of stroke—even if their heart rhythm looks normal.
The research, which will be presented at the American Heart Association’s Scientific Sessions 2025, also points to a new tool that may help doctors identify which patients are most at risk.
ATTR-CM is a progressive disease where a protein called transthyretin becomes misshapen and builds up in the heart. This makes the heart muscle stiff and less able to relax and fill with blood. Over time, this can lead to heart failure and raise the risk of stroke or a transient ischemic attack (TIA), which is sometimes called a “mini-stroke.”
This condition has long been considered rare, but it’s often underdiagnosed, so the true number of cases is unknown. Until now, there has been no clear way to know which patients with ATTR-CM are most likely to have a stroke.
In the new study, researchers reviewed the health records of more than 2,300 people with ATTR-CM in the United Kingdom between 2003 and 2023.
They found that about 1 in 8 people with a normal heart rhythm actually had a hidden problem called atrial electromechanical dissociation (AEMD). This is when the upper part of the heart (the atrium) looks normal on a heart test, but it doesn’t contract properly to pump blood.
During an average follow-up of three years, the researchers found that people with AEMD were more than three times as likely to have a stroke or TIA than those whose atrium worked normally. These patients were also more likely to develop an irregular heart rhythm called atrial fibrillation, which is a known stroke risk factor.
To help spot this hidden risk, the researchers developed a tool that uses two common measures taken during an echocardiogram, a heart ultrasound test. They discovered that the weaker the atrium’s squeeze, the higher the stroke risk. In the highest-risk group, 9 out of 100 people had a stroke each year.
This risk was the same for people with different genetic types of ATTR-CM and across different stages of the disease, showing that atrial dysfunction may be a common reason why these patients have strokes.
The researchers say this finding shifts the focus from just looking at heart rhythm to paying attention to how well the atrium pumps. Even if a person has a normal rhythm, poor atrial function may still put them at risk.
The study was observational, so it cannot prove that AEMD directly causes strokes. The next step is to test this tool in more people and see if treating high-risk patients with blood thinners can reduce their stroke risk.
Experts not involved in the study say the findings are important but caution that the test used—called speckle-tracking strain echocardiography—is not widely available yet. They also note that the study only looked at one national center, so more research is needed.
In total, the study included 2,310 adults with an average age of 76. Most participants were men and had a form of the disease that occurs with aging (wild-type ATTR). Over the three years, 5% of participants had a stroke or TIA, and 31% developed atrial fibrillation.
This new research offers hope that better tools can help doctors spot people at higher risk for stroke, even before symptoms appear. In the future, this could lead to more personalized care and fewer life-threatening strokes in people with ATTR-CM.
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