Cardiac Abnormalities in Stroke Prevention and Risk of Recurrence

Conditions

Cryptogenic Stroke

Keywords

carotid atherosclerosis, heart failure, cardiomyopathy, embolic stroke

Brief summary

This is a multi-center retrospective analysis of consecutive adult patients with cryptogenic stroke patients following a comprehensive workup for the underlying stroke etiology. Patients will be eligible for inclusion if the index stroke event occurred between 1/1/2016 and 06/30/2022.

Detailed description

This is an exploratory observational cohort study of existing registry-based clinical, laboratory, and radiographic data. There are multiple pre-specified hypotheses that will be tested using this data set, which include the entire cohort as well as planned subgroup analyses. The analyses center around patients with cryptogenic stroke (no clear stroke mechanism) but who are characterized by potential embolic sources. These include but are not limited to: left atrial enlargement or dysfunction, left ventricular dysfunction /heart failure with reduced ejection fraction (HFrEF), patent foramen ovale (PFO), paroxysmal atrial fibrillation (pAF), lambl's excrescence, valvular lesions, carotid web, and nonstenotic cervical arterial plaque. A brief summary of several planned hypothesis is itemized below: 1. To evaluate treatment practices in patients with potential embolic sources. 2. To estimate the risk of recurrent stroke, major bleeding, and/or death following an incident stroke event across various potential embolic sources. 3. To compare rates of recurrent stroke, major bleeding, and/or death across various potential embolic sources, when stratified by antithrombotic treatment type. 4. To evaluate type, frequency, and findings of long-term outpatient cardiac event monitoring (for paroxysmal atrial fibrillation). And furthermore, to determine antithrombotic treatment changes following abnormalities detected with such monitoring. 5. To develop and validate a risk prediction model for later atrial fibrillation in cryptogenic stroke by integrating a machine-learning algorithm or convolutional neural network analysis of 12-lead electrocardiographic data with clinical, laboratory, and radiographic parameters. 6. To develop and validate a risk prediction model for later atrial fibrillation, atrial fibrillation burden, and recurrent stroke and/or death using a machine-learning and/or convolutional neural network and/or validated electrophysiologic biomarkers (e.g., p-wave morphology) abstracted from outpatient telemetry, when added to clinical and radiological patient profiles. 7. To compare the sensitivity of various outpatient cardiac telemetry devices for identifying atrial fibrillation. 8. To evaluate real-world treatment practices of patent foramen ovale closure, antithrombotic therapy in patent foramen ovale, and risk of stroke recurrence. 9. To evaluate real-world secondary stroke prevention strategies in patients with heart failure, with and without left ventricular dysfunction.

Khan F, Stretz C, Lewis S, Chahien D, Goldstein E, Siegler JE, Lineback CM, Eklund K, Khasiyev F, Al Kasab S, Culbertson CJ, D'Souza M, Stamm B, Ro J, Kerrigan D, Sharma R, Aboul-Nour H, Nahab F, Omran SS, Linares G, Sehgal S, Melkumova E, Singh E, Zha AM, Thottempudi N, Mannion S, Van Coevering R, Chen L, Thompson SL, Thon JM, Penckofer M, Yu W, Qdais AA, Jillella D, Sloane KL, Dumitrascu OM, Conyers FG, Talat F, Glover PA, Kang J, Patel V, Aziz Y, Zubair A, de Havenon A, Porto CV, Bowman A, Shahrivari M, Brorson JR, Liebeskind DS, Nedelcu S, Ali H, Abdalwahab A, Kam W, Nguyen TN, Herpich F, Farroqui M, Rojas-Soto D, Yaghi S.

2026-09-09

10.1161/jaha.126.050182

Recurrent Stroke in Patients With Cryptogenic Stroke and Left Ventricular Injury: The Cardiac Abnormalities in Stroke Prevention and Recurrence (CASPR) Study.

Sharma R, McNamara KF, Badillo Goicoechea E, Bowman A, Van Coevering R, Chen L, Penckofer M, Singh E, Kerrigan D, Aboul-Nour H, Nahab F, Glover P, Krishnaiah B, Yaghi S, Khasiyev F, Lineback C, Melkumova E, Culbertson C, Nguyen TN, Thompson SL, Jillella D, Daniel JA, Aziz Y, Alvi M, Herpich F, Shahrivari M, Chionatos RA, Elangovan C, Kang J, Zha A, Farooqui M, Rothstein A, Khan F, Smith M, Brown S, Abu Qdais A, Liebeskind DS, Abburi N, Rozental S, Nedelcu S, Thon JM, Stretz C, Thottempudi N, Yu W, Eklund K, Linares G, de Havenon A, Siegler JE.

2026-03-02

10.1161/strokeaha.125.053755

Outcomes of Patients With Embolic Stroke of Undetermined Source Treated With Antiplatelet Agents or Anticoagulation: A Multicenter Cohort Study.

Siegler JE, Goicoechea EB, Penckofer M, Eklund K, Yaghi S, Stretz C, Lineback CM, Stamm B, Peter S, D'Souza M, Conyers FG, Khasiyev F, Kerrigan D, Lewis S, Ali H, Aboul-Nour H, Sharma R, Nahab FB, Glover P, Thompson SL, Alshaer QN, Thottempudi N, de Havenon A, Culbertson CJ, Melkumova E, Chionatos RA, Jillella DV, Daniel JA, Ro J, Frankel MR, Dumitrascu OM, Brown S, Parikh P, Doolittle C, Yahnke I, Sathya A, Kang J, Kirchhoffer K, Bowman A, Smith MM, Brorson JR, Asabere A, Shahrivari M, Elangovan C, Sheibani N, Krishnaiah B, Gaudio E, Sloane KL, Rothstein A, Alvi MM, Annam S, Amankwah C, Kam W, Abburi N, Farooqui M, Rojas-Soto D, Molaie A, Khezri N, Zubair AS, Abbasi M, Van Coevering RJ, Chen L, Nedelcu S, Herpich F, Chahien D, Sehgal S, Liebeskind DS, Linares G, Zha A, Sarkar M, Xi R, Nelson A, Abu Qdais A, Al Kasab S, Singh E, Patel V, Aziz YN, Mehndiratta P, DeMarco A, Sharrief A, Cucchiara B, Salehi Omran S, Nguyen TN, Dubinski M, Ackerman J, Thon J.

2025-07-031 citations

10.1212/wnl.0000000000213876

Interventions

None listed

Study design

Observational model

COHORT

Time perspective

RETROSPECTIVE

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

No

Inclusion criteria

1. Consecutive adult patients (18 yrs of age or older) diagnosed with cryptogenic stroke despite complete neurodiagnostic workup, including the following: A. Transthoracic echocardiogram B. EKG and 24h minimum cardiac telemetry C. Cervical and intracranial vessel imaging D. No known and established source of cerebral embolism after completion of the aforementioned testing E. CT or MRI evidence of acute cerebral infarction F. Onset of stroke or last known well within 2 weeks of hospitalization or study inclusion start date (unless time last known well is unknown) 2. Left ventricular ejection fraction greater than or equal to 20%

Exclusion criteria

1. Patients with an established stroke mechanism that is diagnosed prior to or at the time of the index stroke event. Examples include but are not limited to: A. New diagnosis of atrial fibrillation during index stroke admission, or history of prior atrial fibrillation B. Cervical or intracranial atherosclerosis in a vessel supplying the infarcted brain region, with 50% luminal stenosis by NASCET criteria C. Cervical or intracranial arterial dissection D. Inflammatory vasculopathy (e.g., giant cell arteritis, primary central nervous system angiitis) E. Acute myocardial infarction or cardiac arrest at the time of stroke F. Intracardiac thrombus (e.g., left ventricular, left atrial, left atrial appendage thrombus), irrespective of cardiac function G. Small vessel disease (defined by the presence of a single, subcortical infarction less than 1.5cm in diameter on computed tomography, less than 2.0cm in diameter on diffusion-weighted imaging, or without radiographic evidence of infarction BUT with symptoms consistent with a subcortical syndrome-e.g., pure motor hemiparesis, pure hemisensory impairment, mixed motor-sensory syndrome, ataxic hemiparesis, or dysarthria-clumsy hand syndrome) 2. Patients without follow-up information at 30 days (although patients who expired within 90 days of stroke are still eligible for inclusion) 3. Patients enrolled in a randomized clinical trial in which antithrombotic group is blinded to the investigator 4. Transient ischemic attack 5. Primary intracerebral hemorrhage

Design outcomes

Primary

Measure	Time frame	Description
Prevalence of potential embolic sources	through study completion, an average of 2 years	Epidemiological estimates of prevalence of various potential embolic sources in the cryptogenic stroke population will be calculated across the cohort
The odds of recurrent stroke, major bleeding (according to the International Society of Thrombosis and Hemostasis), and/or death will be estimated across the cohort, with annualized event rates also calculated	At any point during follow-up over a minimum of 90 days after stroke (average of 2 years)	. This outcome will be evaluated across each subgroup of potential embolic source (e.g., valvular lesions present vs. absent, nonstenotic carotid plaque present or absent). Adjusted estimates of event probability will be calculated between patients treated with various antithrombotic types (or class, e.g. anticoagulant vs. antiplatelet) using propensity score matching according to propensity of antithrombotic use
Number of patients treated with antiplatelet, anticoagulant, or combination antithrombotic therapy	through study completion, an average of 2 years	Following the index cryptogenic stroke, the outcome of specific antithrombotic treatment will be compared between patient groups (antiplatelet, anticoagulant, combination antithrombotic)

Countries

United States

Outcome results