Letter by Markl and Harloff Regarding Article, “Aortic Arch Plaques and Risk of Recurrent Stroke and Death”
To the Editor:
We read with great interest the recent article by Di Tullio et al1 regarding the incidence of recurrent stroke in a large multicenter trial of stroke patients with aortic plaques treated by either aspirin or warfarin. The reported findings constitute new and valuable information with respect to secondary prevention particularly because randomized trials for the optimal treatment of this major source of cerebral embolism are still absent from the literature.
In the present study, transesophageal echocardiography was used to detect plaques of the aortic arch, ie, between the distal ascending aorta and the branching point of the left subclavian artery. However, accuracy of transesophageal echocardiography for the detection of atheroma in this region is limited because visualization of the aorta is hampered due to restricted insonation angles and air artifacts induced by the trachea and right bronchus.2,3 Accordingly, a recent study showed that magnetic resonance imaging permitting full 3D coverage of the entire aortic arch provided more reliable visualization of the aortic wall and proved to be superior to transesophageal echocardiography for the detection of aortic plaques.4
Furthermore, retrograde embolization from complex plaques in the proximal descending aorta (DAo) was not considered a high-risk source of stroke. The increase of the frequency and thickness of aortic atheroma, including aortic thrombi from the ascending to the descending aorta, was documented in several previous studies.2,3 Accordingly, the highest thromboembolic risk originates from plaques in the DAo. In this context, a recent study using flow-sensitive magnetic resonance imaging with 3D velocity encoding5 in stroke patients proved that flow reversal in the proximal DAo was frequent. Furthermore, individual retrograde embolization pathways originating from complex plaques in the proximal DAo were directly visualized and constituted the only explanation of ischemia in the posterior circulation in individual patients with cryptogenic stroke. The significance of this mechanism is further supported by an odds ratio of 5.5 for the proximal DAo compared with an odds ratio of only 1.5 in the distal DAo for plaques ≥4 mm in a previous large stroke cohort.2
For these reasons, we hypothesize that the true number of relevant large complex and noncomplex plaques associated with the highest risk of stroke2 was underestimated. Overlooked complex plaques may lead to incorrect classification of patients into the different groups in the reported Kaplan–Meier curves of cumulative risk of recurrent stroke event and thus introduce an overestimation of the event probability for patients classified as small or noncomplex plaques. This is a likely reason for the high event rate of 15.2% in patients with small plaques and cryptogenic stroke. Next to the additional assessment of coagulation parameters, optimal imaging of large complex plaques and consideration of retrograde embolization seems to be of particular importance to identify patients who benefit most from warfarin. Therefore, prospective randomized trials based on optimal imaging strategies, ie, transesophageal echocardiography and 3D magnetic resonance imaging, are needed to establish the best therapy of aortic atherosclerosis.
Di Tullio MR, Russo C, Jin Z, Sacco RL, Mohr JP, Homma S, the Patent Foramen Ovale in Cryptogenic Stroke Study Investigators. Aortic arch plaques and risk of recurrent stroke and death. Circulation. 2009; 119: 2376–2382.
Kronzon I, Tunick PA. Aortic atherosclerotic disease and stroke. Circulation. 2006; 114: 63–75.
Harloff A, Dudler P, Frydrychowicz A, Strecker C, Stroh AL, Geibel A, Weiller C, Hetzel A, Hennig J, Markl M. Reliability of aortic MRI at 3 Tesla in patients with acute cryptogenic stroke. J Neurol Neurosurg Psychiatry. 2008; 79: 540–546.
Harloff A, Strecker C, Dudler P, Nussbaumer A, Frydrychowicz A, Olschewski M, Bock J, Stalder AF, Stroh AL, Weiller C, Hennig J, Markl M. Retrograde embolism from the descending aorta: visualization by multidirectional 3D velocity mapping in cryptogenic stroke. Stroke. 2009; 40: 1505–1508.