HEart and BRain Interfaces in Acute Ischemic Stroke

Completed

• Conditions: Stroke; Atrial Fibrillation

• Registration Number: NCT02142413
• Lead Sponsor: Charite University, Berlin, Germany

Brief Summary

The primary aim of this prospective observational study is to investigate whether an enhanced diagnostic MRI work-up (including cardiac MRI, angiography of the aortic arch and the brain-supplying arteries) combined with an in-hospital Holter-ECG of up to 5 days duration leads to a significant increase in relevant pathologic findings with respect to stroke aetiology as compared to the findings obtained by a routine diagnostic work-up (including stroke unit monitoring, 24h-Holter-ECG, echocardiography, Doppler-ultrasound of the brain-supplying arteries) in patients with acute ischemic stroke and no atrial fibrillation according to past medical history or baseline ECG. A better understanding of the stroke aetiology may improve secondary stroke prevention and long term outcome.

Detailed Description

Variations and delays in the diagnostic procedures during hospitalization after acute ischemic stroke are still common, and at the same time, stroke aetiology remains cryptogenic in about 20-25% of stroke unit patients. Recent studies have shown that (a) cardiac MRI is now able to detect cardiac sources of embolism (thrombi and aortic plaques) with equal sensitivity as compared to echocardiography, and (b) prolonged ECG monitoring up to several days/weeks/years can significantly increase the detection rate of atrial fibrillation. These developments might allow a faster and more effective diagnostic work-up in patients with acute ischemic stroke compared to standard diagnostic procedures including doppler-ultrasound of the extracranial brain-supplying arteries, echocardiography, 24-h-Holter ECG and stroke unit monitoring. This prospective observational trial therefore aims to assess the detection rate of pathologic findings relevant to stroke aetiology as obtained by an enhanced MRI set-up (including cardiac MRI, MR-angiography of the brain-supplying arteries) and a prolonged Holter-ECG (of up to 5 days after the stroke) in comparison to findings obtained by routine diagnostic procedures after acute stroke.

Moreover, cumulating evidence implies that acute ischemic stroke can lead to cardiac damage. Since the underlying pathophysiological mechanisms are still poorly understood, the HEBRAS study attempts to tackle the relationship between stroke localization (e.g. insular involvement), observed cardiac damage (as indicated by troponin elevation) and activation of autonomic nervous system (as indicated by impairment of heart rate variability and elevated urinary norepinephrine levels), respectively.

Finally, to clarify the prognostic impact of stroke-induced autonomic dysfunction, heart rate variability will be analysed with respect to functional outcome, mortality, recurrent stroke and myocardial injury.

Study Timeline

• Study Start: 2014-05
• Study First Submitted: 2014-05-14
• Study First Submitted QC: 2014-05-16
• Study First Posted: 2014-05-20
• Primary Completion: 2017-02
• Study Completion: 2018-03
• Status Verified: 2018-07
• Last Update Submitted: 2018-07-17
• Last Update Posted: 2018-07-18

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 368

Inclusion Criteria

• Age ≥18 years
• Written informed consent by the patient
• Acute ischemic stroke, as confirmed by cerebral MRI or CT
• Admission to the stroke unit of the Department of Neurology, Charité, Campus Benjamin Franklin

Exclusion Criteria

• Atrial fibrillation known by past medical history or documented by routine electrocardiogram (ECG) on hospital admission
• Participation in an interventional clinical trial
• Pre-stroke life expectancy <1 year
• Mechanic heart valve, cardiac pacemaker or other contraindications to undergo MRI
• History of adverse response to MRI contrast agents
• Known Liver disease prior to stroke
• Mild to severe renal dysfunction (creatinine > 1.3 mg/dl (females); creatinine > 1,7 mg/dl (males))
• Severe congestive heart failure (NYHA III or IV).

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Stroke aetiology	From admission to the stroke unit to hospital discharge, or up to 5 days during hospital stay	Detection rate of pathologic findings relevant to stroke aetiology (i.e. atrial fibrillation, cardiac thrombi, severe carotid stenosis, aortic plaque \> 4mm) in patients with acute ischemic stroke obtained by enhanced diagnostic MRI work-up (cardiac MRI, MR-angiography combined with prolonged Holter-ECG of up to 5 days during the in-hospital stay) in comparison to findings obtained by the routine diagnostic work-up at the Department of Neurology; Charité, Campus Benjamin Franklin (consisting of stroke unit monitoring, echocardiography, ultrasound of the brain-supplying arteries, and 24-hour Holter-ECG).

Secondary Outcome Measures

Name	Time	Method
Stroke localization and cardiac dysfunction	From admission to the stroke unit to hospital discharge, or up to 5 days during hospital stay	Association of stroke localization (e.g. insular cortex involvement) to autonomic changes (as indicated by elevated urinary norepinephrine levels and heart rate variability) or cardiac dysfunction (as indicated by troponin T serum levels), respectively.
Outcome	day 90 and day 365 after stroke onset	Association of heart rate variability to poor functional outcome (mRS\>2) and mortality at day 90, as well as to the combined endpoint of recurrent ischemic stroke and myocardial infarction or death at day 365.
Atrial fibrillation	up to 5 days after hospital discharge	Rate of first detected paroxysmal atrial fibrillation by prolonged Holter-ECG monitoring (up to 5 days) after hospital discharge.

Trial Locations

Locations (1)

Charité, University Medicine Berlin; 🇩🇪 Berlin, Germany