Mind the Heart: diagnostic yield of cardiac CT-angiography in the acute phase of ischemic stroke

Stroke is the second leading cause of mortality and disability worldwide. About
one third of ischemic strokes are caused by cardioembolism. Early determination
of stroke etiology is essential for three reasons:
1. Detection of etiology is more likely to succeed directly after the stroke
(*smoking gun*). For instance, an intracardiac thrombus may vanish after
intravenous thrombolysis.
2. The choice of secondary prevention depends on the etiology. Cardioembolic
stroke generally requires treatment with oral anticoagulation.
3. The risk of recurrence is highest early after the initial stroke. Early
detection of the cause can prevent recurrent strokes.

The current acute ischemic stroke work-up includes a combination of brain
imaging (CT or MRI), imaging of the intra- and extracranial arteries (CTA, MRA
or ultrasound), cardiac rhythm monitoring (ECG, Holter) and imaging of the
heart (ultrasound).

In the acute phase (currently defined as 24 hours after symptom onset) patients
undergo a CTA of the brain and cervical arteries. In most hospitals, the heart
and aortic arch are not generally included in this CTA. Recently, the AMC
started including the heart and aortic arch as part of standard care.
Echocardiography is performed days to weeks after the initial stroke, on an
elective basis. Stroke patients receive ECG and/or rhythm monitor, but these
auxillary investigations can't identify all cardiac causes. All these
investigations are time-consuming, sometimes invasive, expensive, and may delay
adequate treatment.

In addition, ideally these often very ill stroke patients should undergo as few
burdensome investigations as possible. Therefore, a *one-stop-shop* for
diagnosis and determination of the underlying etiology in the acute phase in
patients with acute ischemic stroke would be an important innovation of stroke
care.

Hypothesis
We hypothesize that a CTA of the heart and entire aortic arch, performed in the
acute phase (defined as within window for reperfusion therapy through
thrombolysis or thrombectomy) in patients with acute ischemic stroke, is
superior to echography for detecting cardio-aortic sources of acute ischemic
stroke.

Research questions
1. Does a CTA of the heart and aortic arch in the acute phase in patients with
acute ischemic stroke have a higher diagnostic yield than transthoracic
echocardiography for diagnosis of high-risk cardio-aortic causes of acute
ischemic stroke?
2. What is the inter-observer variability of interpretation of cardio-aortic
CTA images in patients with acute ischemic stroke?
3. Does implementation of a CTA of the heart and aortic arch in the acute phase
result in treatment of cardio-aortic abnormalities?
4. Are there differences between males and females in terms of occurrence and
subtype of cardio-aortic causes of acute ischemic stroke, treatment choice and
outcome?
5. What is the proportion of cardiac thrombi, identified on CTA of the heart,
which dissolve on sequential imaging at 24 hours and 7 days after initial CTA
imaging?

Prospective observational single center cohort study. Site: AMC.
Patients will undergo a standard care ECG triggered CTA in the acute setting,
including the heart, aortic arch, cervical and intracranial arteries - prior to
the start of reperfusion therapy. Patients will also receive standard care ECG,
Holter, transthoracic echocardiography. In the study the yield of CTA will be
systematically compared to transthoracic echocardiography for detection of
cardio-aortic causes of ischemic stroke.

In a proportion of patients (circa 25%) in whom transthoracic echocardiography
is not performed as part of standard care, transthoracic echocardiography will
be performed as part of research, after informed consent has been obtained.
In a small proportion of patients (circa 8%), those who have a cardiac thrombus
as identified on CTA of the heart, sequential CTA of the heart will be
performed at 24 hours and, for patients with a persisting thrombus, at 7 days
after initial imaging, after informed consent has been obtained.

Please also see C1 onderzoeksprotocol 4.2 Study procedures.

Burden and risks associated with participation are minimal.

Clinical and imaging patient data which are obtained as part of standard care
will be used, after written informed consent. As part of standard care,
patients will be contacted for a follow-up evaluation by a trained stroke nurse
at 90 days. For this study, patients will be contacted once by phone after 2
years for a conversation of maximum 15 minutes. There are no psychologically
intrusive questions.

In a proportion of patients (circa 25%) in whom transthoracic echocardiography
is not performed as part of standard care, transthoracic echocardiography will
be performed as part of research, after informed consent has been obtained.
In a small proportion of patients (circa 8%), those who have a cardiac thrombus
as identified on CTA of the heart, sequential CTA of the heart will be
performed at 24 hours and, for patients with a persisting thrombus, at 7 days
after initial imaging, after informed consent has been obtained.

Please also see C1 onderzoeksprotocol 7.4 Benefits and risks assessment, group
relatedness.