Supplementary Material for: Prevalence of Potential Retrograde Embolization Pathways in the Proximal Descending Aorta in Stroke Patients and Controls

Background: Retrograde diastolic blood flow in the
proximal descending aorta (DAo) connecting complex plaques (≥4 mm thick)
with brain-supplying supra-aortic arteries may constitute a source of
stroke. Yet, data only from high-risk populations (cryptogenic stroke
patients with aortic atheroma ≥3 mm) regarding the prevalence of this
potential stroke mechanism are available. We aimed to quantify the
frequency of this mechanism in unselected patients with cryptogenic
stroke after routine diagnostics and controls without a history of
stroke. Methods: 88 patients (67 stroke patients, 21
cardiac controls) were prospectively included. 3D T1-weighted bright
blood MRI of the aorta was applied for the detection of complex DAo
atheroma. ECG-triggered and navigator-gated 4D flow MRI allowed
measuring time-resolved 3D blood flow in vivo. Potential retrograde
embolization pathways were defined as the co-occurrence of complex
plaques and retrograde blood flow in the DAo reaching the outlet of (a)
the left subclavian artery, (b) the left common carotid artery, or/and
(c) the brachiocephalic trunk. The frequency of these pathways was
analyzed by importing 2D plaque images into 3D blood flow visualization
software. Results: Complex DAo plaques were more frequent
in stroke patients (44 in 31/67 patients (46.3%) vs. 5 in 4/21 controls
(19.1%); p = 0.039), especially in older patients (29/46 (63.04%)
patients ≥60 years of age with 41 plaques vs. 2/21 (9.14%) patients
<60 years of age with 3 plaques; p < 0.001). Contrary to our
assumption, retrograde diastolic blood flow at the DAo occurred in every
patient irrespective of the existence of plaques with a similar extent
in both groups (26 ± 14 vs. 32 ± 18 mm; p = 0.114). Therefore, only the
higher prevalence of complex DAo plaques in stroke patients resulted in a
three times higher frequency of potential retrograde embolization
pathways compared to controls (22/67 (32.8%) vs. 2/21 (9.5%) controls; p
= 0.048). Conclusions: This study revealed that
retrograde flow in the descending aorta is a common phenomenon not only
in stroke patients. The existence of potential retrograde embolization
pathways depends mainly on the occurrence of complex plaques in the area
0 to ∼30 mm behind the outlet of the left subclavian artery, which is
exposed to flow reversal. In conclusion, we have shown that the
frequency of potential retrograde embolization pathways was
significantly higher in stroke patients suggesting that this mechanism
may play a role in retrograde brain embolism.

研究背景：近端胸降主动脉（descending aorta, DAo）内的舒张期逆行血流，若将厚度≥4mm的复杂粥样硬化斑块与脑供血的主动脉弓上动脉相连，则可能成为脑卒中的致病源头。然而目前仅针对高危人群——即主动脉粥样硬化斑块厚度≥3mm的隐源性脑卒中（cryptogenic stroke）患者——开展了此类潜在脑卒中致病机制的患病率相关研究。本研究旨在量化经常规诊断后的非选择性隐源性脑卒中患者，以及无脑卒中病史的对照人群中，该致病机制的发生频率。

研究方法：本研究前瞻性纳入88名受试者，其中脑卒中患者67例，心脏病对照受试者21例。采用主动脉3D T1加权亮血磁共振成像（magnetic resonance imaging, MRI）检测DAo的复杂粥样硬化斑块。通过心电图门控（ECG-triggered）及导航门控（navigator-gated）的4D血流MRI（4D flow MRI），实现体内时间分辨的三维血流测量。将同时满足以下两个条件的情况定义为潜在逆行栓塞通路：DAo内存在复杂粥样硬化斑块，且其腔内逆行血流可抵达（a）左锁骨下动脉（left subclavian artery）开口、（b）左颈总动脉（left common carotid artery）开口，或（c）头臂干（brachiocephalic trunk）开口。通过将二维斑块图像导入三维血流可视化软件（3D blood flow visualization software），对上述通路的发生频率进行分析。

研究结果：脑卒中患者的DAo复杂粥样硬化斑块检出率显著高于对照受试者（67例患者中31例检出44处斑块，占比46.3%；21例对照受试者中4例检出5处斑块，占比19.1%；p=0.039），且该差异在老年人群中尤为显著：≥60岁的46例患者中29例检出41处斑块，占比63.04%；而<60岁的21例患者中仅2例检出3处斑块，占比9.14%（p<0.001）。与本研究预设假设相反，所有受试者的DAo内均存在舒张期逆行血流，且两组间的血流累及范围无显著差异（26±14 vs. 32±18 mm；p=0.114）。因此，仅因脑卒中患者的DAo复杂粥样硬化斑块患病率更高，使其潜在逆行栓塞通路的发生频率较对照受试者提升了两倍（脑卒中患者22/67，占比32.8%；对照受试者2/21，占比9.5%；p=0.048）。

研究结论：本研究表明，胸降主动脉内的逆行血流并非仅见于脑卒中患者，而是一种普遍现象。潜在逆行栓塞通路的存在与否，主要取决于左锁骨下动脉开口后方0~约30mm的血流逆转区域内是否存在复杂粥样硬化斑块。综上，本研究证实脑卒中患者的潜在逆行栓塞通路发生频率显著更高，提示该机制可能在逆行性脑栓塞中发挥一定作用。