Pathophysiology and Risk of Atrial Fibrillation Detected After Ischemic Stroke (PARADISE)

The PAthophysiology and Risk of Atrial Fibrillation Detected After Ischemic StrokE (PARADISE): Prospective Non-interventional Cohort Study

This prospective non-interventional cohort study investigates the pathophysiology of Atrial Fibrillation Detected After Stroke or transient ischemic attack (AFDAS) by comparing the autonomic function and inflammation between patients with AFDAS, patients with atrial fibrillation (AF) diagnosed before the ischemic event or known AF (KAF), and patients with normal sinus rhythm (NSR) after 14 day of cardiac monitoring following the event onset.

Study Overview

• Status: Active, not recruiting
• Conditions: Atrial Fibrillation; Transient Ischemic Attack; Stroke, Ischemic

Detailed Description

This study enrolls patients with acute ischemic stroke at the London Health Sciences Center in London, Ontario, Canada. The heart rhythm of the patients is monitored with a CardioSTAT® Holter device (Icentia) for 14 days after the ischemic event onset. Based on this cardiac monitoring and previous medical history, patients are stratified into three groups: (a) atrial fibrillation detected after stroke or transient ischemic attack (AFDAS), (b) atrial fibrillation diagnosed before the ischemic event or known AF (KAF), and (c) normal sinus rhythm (NSR).

Autonomic function is assessed by the levels of plasma catecholamines, a battery of validated autonomic tests [autonomic reflex screening (ARS)], heart rate variability (HRV) through data obtained by Holter monitoring by standard quantitative analysis methods according to the guidelines of the European Society of Cardiology and the North American Society of Pacing and Electrophysiology and by the analysis of diurnal variation of heart rate. Blood samples are collected for the analysis of inflammatory markers (e.g. CRP, TNF-α, IL-1β, and IL-6), and potential AFDAS predictors such as brain natriuretic peptide (BNP- AFDAS biomarker), endothelin-1 (endothelial dysfunction marker), Lipoprotein(a) [Lp(a)] and thrombin-activatable fibrinolysis inhibitor (TAFI) plasma levels, TAFI activity, TAFI single nucleotide polymorphisms (SNPs), apo(a) isoform size and plasma catecholamines levels. Furthermore, specific neuroimaging findings (e.g., specific regions of the insula or its connections) and clinical features (e.g., impaired interoceptive processing, cognitive impairment, etc) are also analyzed. Interoception is assessed using a heartbeat detection task without feedback condition and gait, balance, frailty, and cognitive status in patients are evaluated by the administration of a battery of tests. Stroke recurrence will be assessed by a structured phone interview at 6 and 12 months after the initial stroke.

• Study Type: Observational
• Enrollment (Estimated): 100

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • London, Ontario, Canada, N6A 5A5
      • University Hospital, London Helath Sciences Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Probability Sample

Study Population

Ischemic stroke and transient ischemic attack patients presenting at the University Hospital of the London Health Science Center, London, Ontario, Canada.

Description

Inclusion Criteria:

1. MCA territory-transient ischemic attack or -acute ischemic stroke patients seen in the Emergency Department or admitted to University Hospital, London, Ontario, Canada
2. Age ≥ 18 years old
3. Patient or Substitute Decision Maker must give written informed consent

Exclusion Criteria:

1. Patients with autonomic dysfunction such as Parkinson's disease that can be interfering with outcome assessment based on qualified investigator's judgment.
2. Patients taking tricyclic antidepressant (TCAs)
3. Patients in whom the acute stroke is primarily hemorrhagic
4. Patients with both TIA and atrial fibrillation
5. Patients with both TIA and large vessel disease
6. Patients with inflammatory diseases

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort
AFDAS; patients without history of atrial fibrillation before the qualifying stroke or transient ischemic attack who are diagnosed with atrial fibrillation during the 14 days of monitoring
KAF; atrial fibrillation known before the stroke or transient ischemic attack
NSR; patients without a history of atrial fibrillation who do not develop atrial fibrillation during the 14 days of cardiac monitoring

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes and Differences in Autonomic Function	Differences in Composite Autonomic Severity Score (CASS) on an 11-point scale between patients with (a) AFDAS, (b) KAF , and (c) NSR	Within 48 hours of stroke onset and at 12, 30 and 90 days.
Changes and Differences in Inflammatory Responses	Differences in levels of plasma markers or temporal responses (CRP,TNFα, IL-6, IL-1β, etc) between patients with (a) AFDAS, (b)KAF and (c) NSR.	Within 48 hours of stroke onset and at 12, 30 and 90 days.
Changes and Differences in Heart Rate Variability (HRV)	Differences in HRV parameters between patients with (a) AFDAS, and (b) NSR	At 14 days.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Biomarkers	Differences in levels of plasma markers (BNP,endothelin-1, Lp(a), and TAFI) or neuroimaging/clinical predictors between patients with (a) AFDAS , (b) KAF and (c) NSR	Within 48 hours of stroke onset, at 12, 30 and 90 days and at 6 months.
Atrial Fibrillation Burden	Difference in atrial fibrillation burden (sum of atrial fibrillation episodes for a period of time) of AFDAS subjects with mild stroke/TIA compared to AFDAS subjects with moderate/severe stroke.	At 14 days
Gait Impairments	Differences in gait parameters in patients with a) AFDAS , (b) KAF and (c) NSR.	At 6 months
Frailty	Differences in frailty in patients with (a) AFDAS , (b) KAF and (c) NSR	At 6 months
Cognitive Impairment	Differences in cognition in patients with (a) AFDAS , (b) KAF and (c) NSR	At 6 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Stroke Recurrence	Number of stroke recurrences in patients with (a) AFDAS , (b) KAF and (c) NSR	At 90, 180, and 360 days
Death	Number of deaths in (a) AFDAS , (b) KAF and (c) NSR groups	At 90, 180, and 360 days

Collaborators and Investigators

• Sponsor: Lawson Health Research Institute
• Collaborators: Western University, Canada; London Health Sciences Centre; Parkwood Hospital, London, Ontario; El Instituto de Neurociencia Cognitiva y Traslacional (INCYT); Instituto de Neurologia Cognitiva (INECO)
• Investigators: Principal Investigator: Luciano A Sposato, MD, Lawson Health Research Institute, London Health Sciences Center, Western University

Study record dates

Study Major Dates

• Study Start (Actual): April 18, 2017
• Primary Completion (Estimated): May 7, 2024
• Study Completion (Estimated): May 7, 2025

Study Registration Dates

• First Submitted: August 24, 2017
• First Submitted That Met QC Criteria: September 5, 2017
• First Posted (Actual): September 7, 2017

Study Record Updates

• Last Update Posted (Actual): October 5, 2023
• Last Update Submitted That Met QC Criteria: October 4, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Keywords: Inflammation; Cognitive impairment; Autonomic Dysfunction; Interoception; Gait impairment
• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Arrhythmias, Cardiac; Brain Ischemia; Stroke; Ischemic Stroke; Ischemia; Ischemic Attack, Transient; Atrial Fibrillation
• Other Study ID Numbers: R-17-032

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No