Neurological Complication of Infective Endocarditis: A Prospective Multi-site Cohort Study

Sponsor

the Jeunes en Neuroradiologie Interventionnelle (JENI) research group (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05152225

Collaborator

University Hospital, Limoges (Other), Sainte Anne Hospital (Paris) (Other)

200

Enrollment

5.9

Anticipated Duration (Months)

Study Details

Study Description

Brief Summary

The main objective of this study is to better estimate the rate of infectious intracranial aneurysms (IIA) in proved infective endocarditis (IE). It also aims to identify MRI markers capable of accurately predicting (or excluding) IIA; to assess the impact of the different MRI abnormalities on the outcome; to capture the real-world management of EI with neurological complications in comprehensive IE centers in France

Condition or Disease	Intervention/Treatment	Phase
Endocarditis, Bacterial Aneurysm, Intracranial Mycotic	Diagnostic Test: Brain MRI Diagnostic Test: digital subtraction angiography (DSA)

Detailed Description

Rationale:

The incidence of Infective endocarditis (IE) in developed countries is approximately 3-15 per 100,000 pers-years. Discharge mortality remains 15-30% and therapeutic management suffers in many ways from the paucity of randomized studies.(1) Symptomatic neurological complications, which occur in 15 to 30% of patients, are the most frequent extra-cardiac complication of IE and are deemed to worsen the outcome of EI.(2,3) Among this overall neurological complications, Infectious Intracranial Aneurysms (IIA) are a relatively rare, yet probably underestimate, vessel wall injury caused by septic emboli, with potentially intracranial bleeding for the patients.

Neuroimaging in the context of IE has gained wide acceptance and is encouraged in the current guidelines.(4,5) Nevertheless the benefit of early neuroimaging to optimize the initial therapeutic management remains debated.(6,7) While the appearance and the frequency of the various neurologic complications of EI are well known thanks to prospective cohort studies with systematic pre-therapeutic MRI(8-10), several clinically relevant questions are still unknow or approximate, including: 1/ What is the rate of IIA in proved EI. The current gold standard for the detection of these small and distally located aneurysms remains Digital Subtraction Angiography (DSA) and to our knowledge, there is no prospective unbiased cohort of IE with systematic DSA available in the literature. 2/ Are there MRI signs correlated with the presence of IIA on DSA? Several MRI markers such as sulcal SWI lesion or cerebral microbleeds (CMBs) with contrast enhancement look promising (10), but validation in unbiased prospective studies with systematic MRI and DSA is needed. 3/ What is the impact on the outcome of the different MRI abnormalities and of unruptured and ruptured IIA? As previously mentioned, the value of both MRI and DSA remain unclear to guide the acute therapeutic management of EI. A recent French survey highlighted differences between university Hospital in France in the management of IIA. Thus, the analysis of the current management of EI with neurological complications could also help at informing the design of future randomized trials.

Questions:

Better estimate the rate of IIA in proved EI.
Identify MRI markers able to accurately predict (or exclude) IIA.
What is the impact of different MRI abnormalities on the outcome?
Capture the real-world management of EI with neurological complications in comprehensive EI centers in France

Design and setting:

Multi-site, prospective cohort study, with standardized imaging protocol, in academic centers where MRI and DSA are performed routinely in patients with EI.

Ethics:

As for all non-interventional studies of de-identified data, written informed consent will be waived and a commitment to compliance (Reference Methodology CPMR-4) will be filed to the French data protection authority (CNIL) prior to data centralization, in respect to the General Data Protection Regulation. Patients and proxies will be informed they could oppose the use of their data for research purposes.

Study Design

Study Type:

Observational [Patient Registry]

Anticipated Enrollment :

200 participants

Observational Model:

Cohort

Time Perspective:

Prospective

Official Title:

Neurological Complication of Infective Endocarditis: A Prospective Multi-site Cohort Study With Systematic MRI and Digital Subtraction Angiography

Anticipated Study Start Date :

Jan 1, 2022

Anticipated Primary Completion Date :

Mar 31, 2022

Anticipated Study Completion Date :

Jun 30, 2022

Arms and Interventions

Arm	Intervention/Treatment
Infective endocarditis Infective endocarditis with systematic brain MRI and digital subtraction angiography (DSA) performed routinely.	Diagnostic Test: Brain MRI Brain MRI performed routinely in patients with EI Diagnostic Test: digital subtraction angiography (DSA) Digital Subtraction Angiography (DSA) performed routinely in patients with EI

Arm

Intervention/Treatment

Infective endocarditis

Infective endocarditis with systematic brain MRI and digital subtraction angiography (DSA) performed routinely.

Diagnostic Test: Brain MRI

Brain MRI performed routinely in patients with EI

Diagnostic Test: digital subtraction angiography (DSA)

Digital Subtraction Angiography (DSA) performed routinely in patients with EI

Outcome Measures

Primary Outcome Measures

The assess the occurrence of infectious intracranial aneurysms in proven infective endocarditis [3 months]
In all included cases, infectious intracranial aneurysms will be detected using cerebral Digital Subtraction Angiography (DSA), which remains the current gold standard for the detection of these small and distally located aneurysms. DSA protocol will include 2D and 3D rotational acquisitions on both carotid arteries and one vertebral artery. The number of infective endocarditis with infectious intracranial aneurysms will be referred to the total number of endocarditis to estimate the incidence of these cerebral anomalies.

Secondary Outcome Measures

To assess the diagnostic performance of MRI markers to detect infectious intracranial aneurysms [3 months]
Logistic regression and Linear Discriminant Analysis (LDA) methods will be used to identify the most relevant MRI signs to predict or exclude IIA (on DSA).
To assess the predictive performance of imaging markers on clinical outcome [2 years]
Logistic regression will be used to identify MRI and DSA sign associated with neurological worsening at follow-up.
To assess the rate of symptomatic intracranial haemorrhage following heart surgery [6 months]
In case of neurological deterioration after cardiac surgery, brain imaging (MRI or NCCT) will be performed to detect the occurrence or progression of cerebral haemorrhage. Logistic regression will be used to identify the MRI and DSA signs associated with this neurological complication.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 100 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

patients with left-sided active infective endocarditis (IE) satisfying modified Duke Criteria,
patients who underwent both digital subtraction angiography (DSA) and brainMRI (as part of routine care)
DSA protocol with 3D rotational for both carotids and one vertebral artery
MRI/MRA standardized protocol including at least: Diffusion, FLAIR, 3D SWI, 3DT1SE and post gadolinium 3DT1SE and 3D TOF (large field: from the vertex to the magnum foramen).

Exclusion Criteria:

uncertain diagnosis of IE by infectious disease consultants
patients with chronic IE
MRI performed after the completion of Infectious intracranial aneurysms (IIA) treatment
MRI performed without contrast injection or complete protocol
More than 48-hours delay between performing MRI and DSA