PARADISE: Pathophysiology and Risk of Atrial Fibrillation Detected After Ischemic Stroke

Sponsor

Lawson Health Research Institute (Other)

Overall Status

Active, not recruiting

CT.gov ID

NCT03275155

Collaborator

Western University, Canada (Other), University of Western Ontario, Canada (Other), London Health Sciences Centre (Other), Parkwood Hospital, London, Ontario (Other), El Instituto de Neurociencia Cognitiva y Traslacional (INCYT) (Other), Instituto de Neurologia Cognitiva (INECO) (Other)

100

Enrollment

Location

72.6

Anticipated Duration (Months)

1.4

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Stroke, Ischemic Transient Ischemic Attack Atrial Fibrillation

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 Design

Study Type:

Observational

Anticipated Enrollment :

100 participants

Observational Model:

Cohort

Time Perspective:

Prospective

Official Title:

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

Actual Study Start Date :

Apr 18, 2017

Anticipated Primary Completion Date :

May 7, 2023

Anticipated Study Completion Date :

May 7, 2023

Arms and Interventions

Arm	Intervention/Treatment
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

Outcome Measures

Primary Outcome Measures

Changes and Differences in Autonomic Function [Within 48 hours of stroke onset and at 12, 30 and 90 days.]
Differences in Composite Autonomic Severity Score (CASS) on an 11-point scale between patients with (a) AFDAS, (b) KAF , and (c) NSR
Changes and Differences in Inflammatory Responses [Within 48 hours of stroke onset and at 12, 30 and 90 days.]
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.
Changes and Differences in Heart Rate Variability (HRV) [At 14 days.]
Differences in HRV parameters between patients with (a) AFDAS, and (b) NSR

Secondary Outcome Measures

Biomarkers [Within 48 hours of stroke onset, at 12, 30 and 90 days and at 6 months.]
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
Atrial Fibrillation Burden [At 14 days]
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.
Gait Impairments [At 6 months]
Differences in gait parameters in patients with a) AFDAS , (b) KAF and (c) NSR.
Frailty [At 6 months]
Differences in frailty in patients with (a) AFDAS , (b) KAF and (c) NSR
Cognitive Impairment [At 6 months]
Differences in cognition in patients with (a) AFDAS , (b) KAF and (c) NSR

Other Outcome Measures

Stroke Recurrence [At 90, 180, and 360 days]
Number of stroke recurrences in patients with (a) AFDAS , (b) KAF and (c) NSR
Death [At 90, 180, and 360 days]
Number of deaths in (a) AFDAS , (b) KAF and (c) NSR groups

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

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

Exclusion Criteria:

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