Contralateral Carotid Intraplaque Hemorrhage May Reduce the Predictive Value of Fat-Suppressed T1-Weighted MRI in Symptomatic Carotid Disease
To the Editor:
We read with interest the article by Altaf et al,1 which examines prospectively whether the identification of intraplaque hemorrhage (IPH) by MRI predicts recurrent clinical cerebrovascular events in patients with high-grade symptomatic carotid stenosis. However, we have several concerns.
First, 44/66 (67%) patients had MR-defined IPH in their symptomatic carotid vessel of which 15 experienced ipsilateral recurrent ischemic events. We assume multispectral imaging of both the left and right internal carotid artery was acquired simultaneously but there is no reference either to the incidence of IPH in the contralateral (asymptomatic) vessel or subsequent cerebral event rate in that carotid territory. We would have thought that studying features such as IPH of asymptomatic and symptomatic plaques in the same patient at the same time-point is an ideal way to control for all known and unknown risk factors of atherosclerosis and would eliminate the environmental, genetic and temporal variability inherent in most histological comparisons of lesions in symptomatic and asymptomatic patients. If the positive rate for IPH in the asymptomatic carotid artery is also as high, this might imply that MR-defined IPH is in fact not a risk factor for an event and that other components such as lipid core size, inflammation and fibrous cap thickness may be more relevant. Were this to be the case, it would create a substantially different interpretation of the data presented. Furthermore, the association of IPH and symptoms remains controversial. Previous studies found no hemorrhagic differences between symptomatic and asymptomatic plaques2–5; therefore, data pertaining to contralateral IPH incidence would be essential when attempting to make this link between plaque morphology and symptomatology.
In their Figure 1, the authors show IPH bilaterally in 1 patient. Did this individual go on to develop symptoms in both left and right carotid territories? If not, we fail to see how bilateral signal change can be associated with lateralizing symptoms in this case. Indeed IPH may be a reflection of the complexity of atheroma burden as a systemic process, which would naturally be associated with a higher event rate.
In their discussion, the authors claim that “the high negative predictive value for recurrent ischemic events in the absence of IPH will reduce the benefit from carotid endarterectomy (CEA).” We maintain that this is a rather bold statement in light of a small, single-center, noncontrolled observational cohort study. Certainly contralateral carotid artery data would be essential to evaluate this further and only appropriately powered, large epidemiological studies with lengthy follow-up would be adequate to truly answer this question. Furthermore, of those patients that did not have IPH in their ipsilateral vessel, what proportion of these displayed IPH in their asymptomatic contralateral vessel?
With regards to the MR methodology, how did the authors avoid misinterpretation of IPH for lipid, which may also be bright on T1-weighted imaging and could be a problem if there is incomplete fat suppression? Was histological correlation performed? The presence of IPH was based on consensus of 2 experienced readers, which implies that there was some inconsistency in interpreting the images. Intra- and interobserver agreement data would have been useful to confirm that the analysis was reproducible and reliable. Was the technique reproducible at different time-points?
Finally, if this imaging technique is to help in the selection of patients for CEA, would the authors not have been better served by using it to identify patients with mild to moderate carotid stenosis who are at higher risk of ipsilateral stroke/transient ischemic attack? Randomized clinical trials have already shown a clear benefit from CEA in patients with high-grade symptomatic carotid stenosis.6,7
J.H.G. is a GSK paid consultant.
Altaf N, MacSweeney ST, Gladman J, Auer DP. Carotid intraplaque hemorrhage predicts recurrent symptoms in patients with high-grade carotid stenosis. Stroke. 2007; 38: 1633–1635.
Golledge J, Greenhalgh RM, Davies AH. The symptomatic carotid plaque. Stroke. 2000; 31: 774–781.
Hatsukami TS, Ferguson MS, Beach KW, Gordon D, Detmer P, Burns D, Alpers C, Strandness DE Jr. Carotid plaque morphology and clinical events. Stroke. 1997; 28: 95–100.
Carr S, Farb A, Pearce WH, Virmani R, Yao JS. Atherosclerotic plaque rupture in symptomatic carotid artery stenosis. J Vasc Surg. 1996; 23: 755–765,discussion 765–756.
Barnett HJ, Taylor DW, Eliasziw M, Fox AJ, Ferguson GG, Haynes RB, Rankin RN, Clagett GP, Hachinski VC, Sackett DL, Thorpe KE, Meldrum HE, Spence JD; North American Symptomatic Carotid Endarterectomy Trial Collaborators. Benefit of carotid endarterectomy in patients with symptomatic moderate or severe stenosis. N Engl J Med. 1998; 339: 1415–1425.