ARCADIA: Predicting Risk for Atrial Cardiopathy Poststroke

Damian McNamara

February 19, 2020

LOS ANGELES — Older age, female sex, black race, relative anemia, and a history of cardiovascular disease are associated with greater risk for atrial cardiopathy among people who experienced an embolic stroke of undetermined source (ESUS), new evidence suggests.

Atrial cardiopathy is a suspected cause of ESUS independent of atrial fibrillation. However, clinical predictors to help physicians identify which ESUS patients are at increased risk remain unknown.

The risk for atrial cardiopathy was 34% higher for women versus men with ESUS in this analysis. In addition, black participants had a 29% increased risk compared with others, and each 10 years of age increased risk for atrial cardiopathy by 30% in an univariable analysis.

"Modest effects of these associations suggest that all ESUS patients, regardless of underlying demographic and risk factors, may have atrial cardiopathy," principal investigator Mitchell Elkind, MD, from Columbia University in New York City, said when presenting results here at the 2020 International Stroke Conference (ISC).

For this reason, he added, all people with ESUS should be considered for recruitment into the ongoing AtRial Cardiopathy and Antithrombotic Drugs In Prevention After Cryptogenic Stroke (ARCADIA), of which he is one of the principal investigators.

ESUS is a heterogeneous condition, and some patients may be responsive to anticoagulants and some might not, Elkind said. This observation "led us to consider alternative ways for ischemic disease to lead to stroke. We would hypothesize that the underlying atrium can be a risk for stroke by itself."

Not yet available is the primary efficacy outcome of the multicenter, randomized ARCADIA trial comparing apixaban with aspirin in reducing risk for recurrent stroke of any type. However, Elkind and colleagues have recruited 1505 patients to date, enough to analyze factors that predict risk for recurrent stroke among people with evidence of atrial cardiopathy.

All ARCADIA participants are 45 years of age or older and have no history of atrial fibrillation. Atrial cardiopathy was defined by presence of at least one of three biomarkers: N-terminal pro-brain natriuretic peptide (NT-proBNP), P wave terminal force velocity, or evidence of a left atrial diameter of 3cm/m2 or larger on echocardiography.

Of the 1349 ARCADIA participants eligible for the current analysis, approximately one third met one or more of these criteria for atrial cardiopathy.

Those with atrial cardiopathy were "more likely to be black and be women, and tended to have shorter time from stroke to screening," Elkind said. In addition, heart failure, hypertension, and peripheral artery disease were more common in those with atrial cardiopathy. This group also was more likely to have an elevation in creatinine and lower hemoglobin and hematocrit levels.

"Heart disease, ischemic heart disease and non-hypertensive vascular disease were significant risk factors" for recurrent stroke in the study, Elkind added.

Factors Associated With Presence of Atrial Cardiopathy in an ESUS Population

Factor Relative Risk 95% Confidence Interval P value
Age (10-year difference) 1.20 1.13 - 1.28 <.0001
Black race vs white race 1.19 1.02 - 1.38  .0737
Female sex 1.15 1.00 - 1.32  .0484
Hemoglobin 0.94 0.90 - 0.98  .0032
Presence of nonhypertensive vascular disease 1.32 1.13 - 1.54  .0008
Based on a multivariable analysis.


Elkind said that, surprisingly, there was no independent association between the time to measurement of NT-proBNP and risk, suggesting that this biomarker "does not rise simply in response to stroke, but reflects a stable condition."

The multicenter ARCADIA trial is recruiting additional participants at 142 sites now, Elkind said, "and we are still looking for more sites."

Which Comes First?

"He is looking at what the predictors are for cardiopathy in these patients, which is fascinating for all of us," session moderator Michelle Christina Johansen, MD, Assistant Professor of Neurology at Johns Hopkins University School of Medicine in Baltimore, Maryland, told Medscape Medical News when asked to comment.

There is always the conundrum of what came first — the chicken or the egg, Johansen said. Do these patients have stroke that then somehow led to a state that predisposes them to have atrial cardiopathy? Or, rather, was it an atrial cardiopathy state independent of atrial fibrillation that then led to stroke?

"That is why looking at predictors in this population is of such interest," she said. The study could help identify a subgroup of patients at higher risk for atrial cardiopathy and guide clinical decision-making when patients present with ESUS.

"One of the things I found interesting was that he found that atrial cardiopathy patients were older [a mean 69 years]. This was amazing, because ESUS patients in general tend to be younger," Johansen said.

"And there is about a 4% to 5% risk of recurrence with these patients. So. it was interesting that prior stroke or [transient ischemic attack] was not associated."

The National Institute of Neurological Disorders and Stroke, the BMS-Pfizer Alliance, and Roche provide funding for ARCADIA. Elkind and Johansen disclosed no relevant financial relationships.

International Stroke Conference (ISC) 2020. Abstract 26. Presented February 19, 2020.

For more Medscape Neurology news, join us on Facebook and Twitter


Comments on Medscape are moderated and should be professional in tone and on topic. You must declare any conflicts of interest related to your comments and responses. Please see our Commenting Guide for further information. We reserve the right to remove posts at our sole discretion.
Post as: