Emilie Bollache1, Paul W.M. Fedak2,3, Pim van Ooij4, Ozair Rahman1, Alex Hong1, Eric J. Keller1, S Chris Malaisrie3, Patrick M. McCarthy3, James C. Carr1, Jeremy D. Collins1, Michael Markl1,5, and Alex J. Barker1
1Department of Radiology, Northwestern University, Chicago, IL, United States, 2Department of Cardiac Sciences, University of Calgary, Calgary, AB, Canada, 3Division of Surgery-Cardiac Surgery, Northwestern University, Chicago, IL, United States, 4Department of Radiology, Academic Medical Center, Amsterdam, Netherlands, 5Department of Biomedical Engineering, Northwestern University, Chicago, IL, United States
Synopsis
Our purpose was to follow up post-surgical changes in peak wall shear
stress (WSS) and extent of at-risk tissue using 4D flow MRI in 34 aortopathy
patients. Highly variable changes between pre- and post-surgery were found
according to the intervention or replaced aortic valve type, while WSS patterns
were unchanged in 20 other patients who did not undergo surgery. The
reproducible 4D flow MRI WSS indices should be studied in larger cohorts and compared
with patient outcome to potentially detect risk of future events in aortopathy
patients, while optimizing the extent of resected aortic tissue.
INTRODUCTION
Arterial wall shear stress (WSS) plays a major role in the regulation of
cellular function and remodeling via endothelial mechanotransduction1
and can be altered in patients with a bicuspid aortic valve (BAV)2.
A recent 4D flow MRI study demonstrated that aortic regions with an abnormally
increased WSS exhibited significant alterations of elastin fibers and extracellular
matrix implicated in aortic wall degeneration3. On the other hand, surgical
management of patients with aortopathy, which is currently based on aortic size
and growth measurements4, has been shown to be inconsistent5.
Better identification of patients who are at high risk for progressive
aortopathy, while limiting overly aggressive aortic resection, is needed. The
purpose of this follow-up 4D flow MRI study was to investigate post-surgical
changes in WSS patterns in patients with aortopathy.METHODS
We included 34 patients with aortopathy scheduled for aortic valve
replacement (AVR) and/or aortic repair who underwent two 4D flow MRI exams (before
and after intervention). Five had AVR alone with no resection of the aorta.
Seventeen had aortic root replacement (ARR) and 12 had hemiarch repair (HA),
among which 23 had concomitant AVR (Table 1). In addition, 20 “control”
aortopathy patients who underwent baseline and follow-up routine surveillance MRI
but no surgery were included. Thus, a total of 108 4D flow MRI studies were
obtained, on 1.5T and 3T scanners (Siemens, Germany), using the following
parameters: prospective ECG and respiratory gating, TE/TR/FA=2.2–2.8ms/4.5–5.4ms/7–15°, spatial resolution=2.2–3.8x1.7–2.7x2.2–3.0mm3,
temporal resolution=36-43ms and encoding velocity=150-400cm/s. After
conventional analysis of 4D flow MRI data6, systolic WSS, which was
averaged over 5 systolic phases, was calculated throughout the entire 3D aortic
surface7 (Figure 1). Furthermore, an aortic ‘heatmap’ was created, providing
tissue regions with a WSS outside of the 95% confidence interval of normal
values previously established in 56 healthy volunteers8. Finally,
WSS patterns in the proximal aorta, comprising the ascending aorta and the
arch, were evaluated based on (Figure 1): 1) peak WSS magnitude, defined as the
averaged 2% highest values calculated from WSS maximal intensity projections
using custom software; 2) ‘at-risk’ tissue area exposed to abnormally high WSS,
calculated from the heatmap, expressed in percentage of the total area. Of
note, in surgery patients, both indices were estimated while excluding the area
to be resected (pre-surgery)/the graft (post-surgery). In order to assess reproducibility,
baseline and follow-up aortic volume was segmented in 10 surgery patients and 10
controls (40 studies) by two blinded operators.RESULTS
Inter-observer variability of the aortic at-risk tissue was low (mean
biases [limits of agreement]: 0.4[-5.4;6.3]%/0.0[-6.3;6.3]% in surgery
patients; 0.6[-2.9;4.1]%/0.1[-2.2;2.5]% in controls, for baseline/follow-up 4D
flow MRI exams, respectively). Table 2 summarizes baseline and follow-up aortic
peak WSS as well as at-risk tissue area, indicating overall small changes in
peak WSS between baseline and follow-up in both groups, except in AVR patients
who received biovalves. However, at-risk tissue area was more variable between
baseline and follow-up in surgery patients, while it remained more stable in controls,
despite longer follow-up durations (Figure 2). All biovalve AVR patients had
lower aortic peak WSS (as reflected by ratio<1) and less extended at-risk
area (as reflected by difference <0) after surgery than before, while in the
remaining surgery ARR and HA groups, results were more heterogeneous with
biovalves. Conversely, most of patients who received a mechanical valve or underwent
valve-sparing procedures, had higher peak WSS and larger at-risk area at
follow-up than at baseline.DISCUSSION
Our main finding is that highly heterogeneous responses to surgery were
observed, while WSS patterns were overall unchanged in patients who did not
undergo surgery (mean follow-up duration >2 years). Previous studies
reported good reproducibility for WSS calculation from 4D flow MRI data9.
Our study confirms these findings (low inter-observer variability of at-risk
tissue area measurement). These inter-observer differences were lower compared
to differences observed between follow-up and baseline, indicating the potential
of 4D flow-derived WSS to reliably detect regions with altered wall shear
forces. Future studies including associations with patient outcome should be
performed to help identifying robust indices to refine the risk of future
events, such as dilatation or rupture, while optimizing the extent of aortic tissue
to be resected. The main limitation of our work is the low number of patients
in each surgery sub-group as well as the variability in follow-up durations.CONCLUSION
This follow-up 4D flow MRI study revealed changes after surgery in
at-risk tissue area, which remained stable in control patients who did not have
surgery. Larger studies including outcomes are warranted to further explore the
effect of surgery on WSS patterns.Acknowledgements
Grant support by the American
Heart Association [16POST27250158] and National Institutes of Health
[R01HL115828 and K25HL119608].References
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