Expedite and facilitate diagnostic work up of transient ischemic attack and minor ischemic stroke: dynamic 320-detector row CT angiography of cardiac and carotid sources of emboli compared to currrently used diagnostic procedures

Patients who suffer from a TIA or IS are at high risk of early (recurrent)
stroke, the majority occurring within the first weeks after the initial event.
The main goal of the diagnostic evaluation is to identify patients with
symptomatic carotid disease who will benefit from carotid endarterectomy and to
identify patients with TIA/IS caused by a cardiac embolus. Early diagnostic
evaluation and rapid initiation of treatment reduces the risk of early
(recurrent) IS substantially. Carotid ultrasound and TTE/TEE are used to screen
for large artery atherosclerosis and cardiac sources of emboli, but have
well-known limitations (e.g. interobserver variability and major patient
discomfort). TEE identifies a cardiac embolic source with an absolute
indication for oral anticoagulation in appr. 20% of patients with TIA/IS
without pre-existent indication for anticoagulation. Despite this, TEE is
usually replaced by the non-invasive TTE and both are only performed in
selected patients and usually not at first presentation of the patient.
Further, changes in intracranial vessels and hemodynamic factors may account
for 10-15% of causes of (recurrent) TIA/IS, but are usually not screened for.
CT angiography provides an alternative: accurate diagnosis of severe carotid
stenosis, diagnosis of cardiogenic thrombus, and intracranial stenosis > 50%
has been shown in earlier studies. With the introduction of the 320-detector
row CT scanner (16 cm coverage) a comprehensive imaging protocol has become
possible, permitting screening for causes of TIA/IS in the heart, aorta and
carotid arteries together with dynamic evaluation of intracranial vessels and
whole brain perfusion, all in one examintaion.

Main study objective of this study is:
To evaluate whether the 320-detector volumetric CT technology can replace
carotid duplex scanning and TEE in the diagnostic workup in TIA/IS patients.
Specific aims of this main study objective are:
1. To assess the yield of cardiac CT for detecting minor and major
cardioembolic sources in the acute stage of patients presenting with TIA/IS.
2. To determine whether accuracy of CT angiography of carotid arteries for
degree of carotid stenosis (>50A% and > 70%) is comparable with that of carotid
ultrasound scanning.
3. To determine false positive, false negative, positive and negative
predictive value of the 320-detector row volume CT scanner for detection of
cardiac and aortic sources of emboli compared to TTE/TEE.

This is a prospective crossectional study. 200 patients, age > 50 years, will
be included in this study. Approximately 43 to 54 patients visit our TIA/IS
out-patient clinic per week; therefore, we expect to require an inclusion
period of approximately one to 1.5-2 years. Patients who have experienced a
TIA or IS usually visit our TIA/IS out-patient clinic within 72 hours after
the event. Within 24 hours of admission, patients are seen by a vascular
neurologist. As part of the routine work-up, blood analysis and carotid
ultrasound will be performed in the morning; in the afternoon, unenhanced CT
and * if carotid ultrasound shows a carotid stenosis or is inconclusive * CT
angiography of the carotid arteries will be is performed. All patients will be
informed about this study by their treating vascular neurologist. When the
inclusion criteria are met and patients are willing to participate, a written
informed consent will be obtained. In patients who have given informed consent
unenhanced CT, whole brain CTP/CTA, CTA of thoracic aorta and carotid CTA will
be performed in the afternoon. TTE or TEE will be performed within 72 hours
after the visit to our TIA/IS-outpatient clinic. In patients who already use
oral anticoagulation or in patients with proven atrial fibrillation or a
significant carotid stenosis TTE/TEE will not be performed, since these
patients already have an indication for oral anticoagulation, and findings of
TTE/TEE will not change therapeutic management.

Identification of etiology of TIA/IS is important, since the cause of TIA/IS
affects prognosis, outcome and management. Identification of major cardiac risk
factors, e.g. thrombi in left atrium, is imperative since these findings will
have implications in terms of choice of (anticoagulant) treatment that reduces
the risk of stroke. TEE is the standard reference to identify cardiac sources
of emboli, showin abnormalities even in TIA/IS patients without pre-existent
indication for anticoagulation. However, TEE is often replaced by non-invasive
TTE since major patient discomfort is inherent to the TEE procedure. Moreover,
both TTE and TEE are only performed in selected patients and often not
performed at first presentation of the patient resulting in a delay in the
start of oral anticoagulation in case of a cardiac embolus. Rapid an accurate
classification of degree of carotid stenosis is important as the benefit of
surgery depends on this. Carotid ultrasound is widely used to screen for
stenosis, but this procedure provides limited information, is investigator
dependent and requires skilled operators. Further, intracranial vessel
pathology and hemodynamic disturbances account for 10-15% of causes of TIA/IS,
but are usually not screened for. With the 320-detector row volume CT scanner
it has become possible to provide a *one-stop-shop* diagnostic work up of the
cardiac, carotid and intracranial region implying a major improvement for large
number of TIA/IS patients in terms of patient comfort, logistics and (probably)
reproducibility.
Estimated radiation dose for the entire scan protocol will be approximately 13
mSv. We will only include patients > 50 yrs. Radiation risks for the patients
will be in the order of one in the hundred thousand (category IIa) or in the
order of one in ten thousand (category IIb).
With the intravenous application of iodinated contrast media, there is a
minimal chance of developing an adverse reaction to iodine contrast media.
Patients who have a history of anaphylactic reactions to iodine based contrast
media will not be included in this study. Experienced, well-trained
radiographers and radiologists are present during the CT investigation; this
personnel will act immediately if an allergic reaction occurs.
Further, there is a small risk of developing contrast-induced nephropathy.
Therefore, the GFR will be determined prior to contrast injection. Patients
showing a GFR < 50 ml/min will be excluded from the study due to the increased
risk of developing contrast induced nephropathy.