Left Atrial Strain and Cryptogenic Stroke (LAS-ESUS)

January 6, 2026 updated by: Leyla Sade, University of Pittsburgh

Left Atrial Strain: A Biomarker for Cryptogenic Stroke Prevention

Cryptogenic stroke is a type of stroke in which the cause of the blood clot cannot be identified, leaving many patients without a clear treatment plan and at high risk for another stroke. Current medical guidelines recommend blood-thinning medication (anticoagulation) only when atrial fibrillation (AF) -an irregular heart rhythm- can be documented. However, AF may occur silently and remain undetected. Long term implantable (placed invasively under the skin) devices may be needed to capture these episodes.

AF is known to develop from disease of the left atrium, the upper chamber of the heart that receives blood from the lungs. When the left atrium does not contract normally, blood flow may slow down, increasing the risk of clot formation. Nowadays, the left atrial (LA) function can be quantified precisely using a noninvasive ultrasound technique called strain imaging.

This study aims to determine whether reduced LA function is associated with cryptogenic stroke and its recurrence even when AF is not observed. If such an association is confirmed, LA strain could serve as a new biomarker to identify patients at risk, earlier than the development of overt AF, enhance preventive measures to reduce recurrent strokes. Because echocardiographic strain imaging is safe, cost-effective, and widely available, it may become an important tool for improving care in this high-risk population.

Study Overview

Status

Recruiting

Conditions

Detailed Description

Cryptogenic stroke accounts for nearly one-third of ischemic strokes, yet its underlying mechanism often remains unidentified, leaving patients without targeted therapy. Atrial fibrillation (AF) is detected up to one third of cryptogenic strokes, but its detection frequently requires prolonged monitoring due to subclinical paroxysmal episodes. Increasing evidence suggests that structural and functional abnormalities of the left atrium (LA) precede AF and contribute to thromboembolic risk independently of rhythm disturbances.

This multicenter retrospective study aims to determine whether impaired LA strain, a sensitive echocardiographic measure of atrial function, is associated with cryptogenic stroke and can predict recurrent events. Echocardiographic images of the patients who were referred to the echocardiography laboratory as part of stroke work up will be analyzed offline, using standardized speckle-tracking software. De-identified clinical and imaging data will be collected in the central core laboratory at the University of Pittsburgh for uniform analysis and validation.

By establishing LA strain as a biomarker of atrial cardiopathy and cryptogenic stroke risk, this study seeks to bridge the current gap between stroke classification and management. Demonstrating the independent association between LA dysfunction and cryptogenic stroke and the recurrence of cryptogenic stroke independently of AF could support the use of LA strain as a risk marker to for monitoring patient and developing preventive strategies such as anticoagulation without documented AF. Hence, our findings may improve preventive care and reduce the burden of disabilities due to cryptogenic stroke.

Study Type

Observational

Enrollment (Estimated)

900

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • United States
    • Pennsylvania
      • Pittsburgh, Pennsylvania, United States, 15213
        • Recruiting
        • UPMC Presbyterian
        • Contact:
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Sampling Method

Non-Probability Sample

Study Population

Participants will be selected from adult patients evaluated for stroke at the University of Pittsburgh Medical Center (UPMC) and collaborating university hospitals that serve as tertiary care centers with established cardiovascular imaging programs.

Only subjects who have already undergone transthoracic echocardiography as part of their stroke workup, and who have clinical and imaging data available for retrospective analysis will be included.

The UPMC will provide both the data collection platform -REDCap- and Echocardiography Core Laboratory for centralized image analysis.

Description

Inclusion Criteria:

  • Adult patients (age > 18 years and < 80 years) who had a complete transthoracic echocardiography (TTE) exam at the University of Pittsburgh Medical Center (UPMC) Presbyterian Echocardiography Lab with a referral diagnosis of suspected stroke.

    2- Patients with an established diagnosis of stroke by stroke neurologists.

    3- Patients in sinus rhythm documented at the time of referral.

    4- Availability of adequate echocardiographic images for strain quantification.

    5- Clinical follow-up data available for evaluation of study endpoints, including stroke recurrence, atrial fibrillation development, and mortality.

    6- Patients from collaborating centers will be included with de-identified echocardiographic images and clinical data meeting the above criteria.

Exclusion Criteria:

Incomplete or technically difficult transthoracic echocardiography (TTE) studies and studies from subjects younger than 18 years of age will be excluded. Additional exclusion criteria include:

1- Pre-existing atrial fibrillation (AF): Patients with a documented history AF prior to the index echocardiography study will be excluded because it is well established that AF justifies cryptogenic stroke requiring anticoagulation.

2 -Structural heart disease: Patients with significant structural abnormalities, such as moderate or severe mitral stenosis, moderate or severe mitral regurgitation, prosthetic heart valves, devices in the left atrium, atrial septal defect or patent foramen ovale will be excluded as these conditions are known causes of stroke and abnormal left atrial function.

3- Coagulopathy: Patient having disease leading to hypercoagulable (thrombus formation) state will be excluded (presence of cancer, antiphospholipid antibodies, hematological diseases).

4- Inadequate clinical follow-up: Patients with insufficient follow-up data or missing medical records that preclude evaluation of study endpoints (e.g., stroke recurrence, AF development) will be excluded unless death is documented.

5- Poor image quality for strain analysis: Patients having echo exams with inadequate image quality that prevent reliable strain quantification will be excluded.

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Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Cryptogenic Stroke Cohort
Subjects in sinus rhythm who had a diagnosis of ischemic embolic stroke in whom no clear embolic source was identified after standard diagnostic evaluation (TOAST classification: Embolic Stroke of Undetermined Source) and who had transthoracic echocardiography (TTE) as part of the stroke work up will constitute the first group.
Non-Cryptogenic Stroke Cohort (Comparator Group)

Subjects in sinus rhythm who had a non-cryptogenic stroke (e.g., large artery atherosclerosis, small vessel disease, hemorrhagic) and who underwent transthoracic echocardiography as part of the clinical stroke workup.

This group will serve as a comparator for the primary analysis to determine whether LA strain determines cryptogenic stroke among other stroke subtypes.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Correlation between left atrial strain (percent deformation) and the rate of cryptogenic stroke
Time Frame: Baseline
Quantitative left atrial (LA) strain (% deformation), measured by speckle-tracking echocardiography from transthoracic echocardiograms obtained during stroke workup, will be compared with the rate of cryptogenic stroke.
Baseline

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Prediction of recurrent cryptogenic stroke by left atrial strain (percent deformation)
Time Frame: Up to 1 year from date of index transthoracic echocardiography.
The number of recurrent cryptogenic stroke events during follow-up, as assessed by left atrial (LA) strain (% deformation) quantified at baseline echocardiogram.
Up to 1 year from date of index transthoracic echocardiography.
Incidence of cardiovascular and cerebrovascular mortality among patients with impaired LA strain (percent deformation)
Time Frame: Up to 1 year from date of index transthoracic echocardiography.
The number of cardiovascular and cerebrovascular mortality during follow-up, as assessed by left atrial (LA) strain (% deformation) quantified at baseline echocardiogram.
Up to 1 year from date of index transthoracic echocardiography.
Incidence of newly detected atrial fibrillation among patients with impaired LA strain
Time Frame: Up to 1 year from date of index transthoracic echocardiography.
The number of new-onset atrial fibrillation during follow-up, as assessed by left atrial (LA) strain (% deformation) quantified at baseline echocardiogram.
Up to 1 year from date of index transthoracic echocardiography.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Pittsburgh

Investigators

  • Principal Investigator: Leyla E Sade, MD, University of Pittsburgh Medical Center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

December 17, 2025

Primary Completion (Estimated)

December 31, 2027

Study Completion (Estimated)

December 31, 2027

Study Registration Dates

First Submitted

October 28, 2025

First Submitted That Met QC Criteria

October 31, 2025

First Posted (Estimated)

November 4, 2025

Study Record Updates

Last Update Posted (Actual)

January 7, 2026

Last Update Submitted That Met QC Criteria

January 6, 2026

Last Verified

January 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • STUDY25010088

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

De-identified individual participant data (IPD) collected in this study, including baseline characteristics, clinical outcomes, and left atrial strain measurements, will be shared. Data will be available upon reasonable request for researchers conducting methodologically sound studies that align with the objectives of this research.

IPD Sharing Time Frame

IPD and supporting documents will be available starting 6 months after publication of the primary results and will remain accessible for 5 years thereafter.

IPD Sharing Access Criteria

Access to the dataset will be granted to researchers upon submission of a formal request, outlining the study objectives and analysis plan. Approval will be contingent upon compliance with ethical guidelines, data privacy regulations, and institutional review board (IRB) requirements. Researchers will be required to sign a data-sharing agreement (DSA) before receiving access with the University of Pittsburgh..

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP
  • CSR

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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