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Clinical Characteristics and Long-Term Outcomes of Midaortic Syndrome
Journal Pre-proof Clinical Characteristics and Long-Term Outcomes of Mid-Aortic Syndrome Ritesh S. Patel, MD, Stephanie Nguyen, MD, Michelle T. Lee, MD, Matt D. Price, MS, Heidi Krause, BS, Van Thi Thanh Truong, MS, Harleen K. Sandhu, MD, MPH, Kristofer M. Charlton-Ouw, MD, Scott A. LeMaire, MD, Joseph S. Coselli, MD, Siddharth K. Prakash, MD, PhD PII:
S0890-5096(20)30016-9
DOI:
https://doi.org/10.1016/j.avsg.2019.12.039
Reference:
AVSG 4851
To appear in:
Annals of Vascular Surgery
Received Date: 29 September 2019 Revised Date:
8 December 2019
Accepted Date: 17 December 2019
Please cite this article as: Patel RS, Nguyen S, Lee MT, Price MD, Krause H, Thanh Truong VT, Sandhu HK, Charlton-Ouw KM, LeMaire SA, Coselli JS, Prakash SK, Clinical Characteristics and Long-Term Outcomes of Mid-Aortic Syndrome, Annals of Vascular Surgery (2020), doi: https://doi.org/10.1016/ j.avsg.2019.12.039. This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. © 2020 Published by Elsevier Inc.
Clinical Characteristics and Long-Term Outcomes of Mid-Aortic Syndrome
1 2 3
Ritesh S. Patel, MD1, Stephanie Nguyen, MD2, Michelle T. Lee, MD1, Matt D. Price, MS3, Heidi
4
Krause, BS3, Van Thi Thanh Truong, MS4, Harleen K. Sandhu, MD, MPH5, Kristofer M.
5
Charlton-Ouw, MD4, Scott A. LeMaire, MD3, Joseph S. Coselli, MD3, and Siddharth K. Prakash
6
MD, PhD6
7 8
1
9
McGovern Medical School, Houston, Texas, USA
Department of Internal Medicine, University of Texas Health Science Center Houston,
10
2
University of Texas Health Science Center, McGovern Medical School, Houston, Texas, USA
11
3
Division of Cardiothoracic Surgery, Michael E. DeBakey Department of Surgery, Baylor
12
College of Medicine, and Department of Cardiovascular Surgery, The Texas Heart Institute,
13
Houston, Texas, USA
14
4
Center for Clinical Research and Evidence-Based Medicine, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, Texas, USA
15 16
5
17
Center Houston, McGovern Medical School at the Memorial Hermann Hospital – Heart and
18
Vascular Institute, Houston, Texas, USA
19
6
Department of Cardiothoracic and Vascular Surgery, University of Texas Health Science
Department of Internal Medicine, Division of Cardiovascular Medicine, University of Texas
20
Health Science Center Houston, McGovern Medical School, Memorial Hermann Hospital –
21
Heart and Vascular Institute, Houston, Texas, USA
22 23
Conflicts of Interest: None
24 25
Disclosure: Dr. Coselli participates in clinical trials with and/or consults for Terumo Aortic,
26
Medtronic, W.L. Gore, Edward Lifesciences and Abbott Laboratories, and receives royalties and
27
grant support from Terumo Aortic. Dr. LeMaire participates in clinical trials with and/or consults
28
for Terumo Aortic, Baxter Healthcare, Medtronic, W.L. Gore, and CytoSorbents.
29 30
This study was presented at The Texas Society for Vascular and Endovascular Surgery Annual
31
Meeting, Houston, Texas November 2-3, 2018
32 33
Corresponding Author:
34
Siddharth K. Prakash, MD, PhD
35
University of Texas Health Science Center at Houston
36
McGovern Medical School
37
Department of Internal Medicine
38
6431 Fannin Street, MSB 6.100
39
Houston, TX 77030
40
Phone: (713) 500-7003
41
Fax: (713) 500-0693
42
Email: [email protected]
43 44 45
Key words: Mid-aortic syndrome; Middle aortic syndrome; Abdominal aorta coarctation;
46
Renovascular hypertension; Aorto-aortic bypass
47
OBJECTIVE:
48
Mid-aortic syndrome (MAS) is a rare congenital or acquired condition marked by segmental or
49
diffuse stenosis of the distal thoracic and/or abdominal aorta and its branches. The optimal
50
approach to medical or interventional management of MAS and long-term outcomes in adults are
51
not well defined. We reviewed MAS cases to characterize the natural history of aortic disease,
52
identify prognostic factors and evaluate the durability of invasive interventions.
53
METHODS:
54
We conducted a retrospective review of MAS patients who presented to Memorial Hermann
55
Hospital and Baylor College of Medicine between 1997 and 2018. We categorized cases
56
according to demographic and clinical manifestations, etiologies, the extent of aortic
57
involvement, interventions and vascular outcomes.
58
RESULTS:
59
We identified a cohort of 13 MAS patients. The etiology of MAS was identified in 6 cases,
60
including genetic syndromes (Neurofibromatosis Type 1 (2/13), Williams syndrome (1/13),
61
fibromuscular dysplasia (2/13), and Takayasu arteritis (1/13)). Mean age at first documented
62
clinical event was 25.2 (2-67) years but cases with genetic etiologies presented significantly
63
younger (18.2 years). The most common primary anatomic site was the suprarenal and infrarenal
64
aorta (zones 5-8). Extra-aortic locations involved the renal (4/13), celiac (3/13), and superior
65
mesenteric (3/13) arteries. Clinical manifestations included hypertension (13/13), claudication
66
(9/13) and postprandial abdominal pain (5/13). All patients with available follow-up data
67
underwent at least one surgical or endovascular intervention (range: 1-8). Postoperative
68
complications included renal failure requiring post-discharge hemodialysis and respiratory
69
failure. There were no deaths in long-term follow-up.
70
CONCLUSIONS:
71
MAS is a complex vasculopathy with substantial variability in clinical presentation and anatomic
72
distribution. Extensive disease frequently requires multiple invasive interventions and results in
73
refractory hypertension, which may predict subsequent clinical events. A multidisciplinary
74
approach with long-term monitoring is essential for preservation of end-organ function and
75
quality of life in this debilitating disease.
76 77
1. INTRODUCTION Mid-aortic syndrome (MAS) is a rare condition marked by segmental or diffuse stenosis
78
of the distal thoracic and/or abdominal aorta and its branches. Both congenital and acquired
79
causes have been described. Congenital MAS has been attributed to developmental defects in the
80
fusion of the dorsal aorta, while acquired cases are associated with autoimmune diseases such as
81
Takayasu and giant cell arteritis, and heritable vasculopathies such as fibromuscular dysplasia,
82
neurofibromatosis, Williams syndrome, Alagille syndrome and retroperitoneal fibrosis.1,2,3
83
Most MAS cases are diagnosed in children or adolescents who present with visceral or
84
limb ischemia and severe hypertension. Symptoms may be associated with hypertensive end-
85
organ damage, visceral malperfusion or lower limb ischemia. Other complications may include
86
renal insufficiency, mesenteric ischemia, heart failure and subarachnoid hemorrhage.4,5,6 Without
87
prompt interventions, patients uniformly succumb to progressive vascular complications and
88
severe hypertension, and fewer than 20% survive past age 407,8. Treatment of recurrent vascular
89
events requires a multidisciplinary approach that integrates medical management with
90
endovascular and open surgical interventions. Refractory hypertension due to renovascular
91
disease may exacerbate the clinical course of MAS patients. Vascular occlusions and aneurysms
92
often recur despite initially effective interventions7 and optimal long-term treatment strategies
93
are unclear.
94
The primary objective of our case series is to determine the associations between clinical
95
features, interventions, and vascular outcomes in MAS patients. Early recognition and prompt
96
collaborative therapy is essential for effective management of this debilitating disease.
97 98
2. MATERIAL AND METHODS
99
Our retrospective review included eligible MAS patients who presented to Memorial
100
Hermann Hospital and Baylor College of Medicine between 1997 and 2018. The diagnosis of
101
MAS was verified by imaging that confirmed suprarenal, intrarenal (between the renal arteries
102
and superior mesenteric artery), or infrarenal narrowing or occlusion of the abdominal aorta. To
103
minimize variance, one of us (SAL) adjudicated zone involvement in all cases using aortic zone
104
criteria defined in the literature9 (Figure 1a) by direct review of available computed tomographic
105
angiogram images (Figure 1b). The extent of disease was also characterized by ostial or distal
106
involvement, and segmental or diffuse morphology.
107
The etiology of MAS was classified as genetic, autoimmune/inflammatory, or unsolved.
108
We categorized cases with onset in infancy or childhood as congenital. Etiology was defined as
109
genetic if any of the following disorders were present: Williams syndrome, Neurofibromatosis
110
type 1 (NF-1), Alagille syndrome, or Fibromuscular Dysplasia (FMD). FMD was categorized as
111
genetic due to its autosomal dominant inheritance in families and the recent identification of one
112
causal gene, PHACTR1.22 The autoimmune category included Takayasu arteritis, giant cell
113
arteritis, retroperitoneal fibrosis, or other vasculitis.
114
Medical therapies consisted of anti-hypertensive medications such as beta-blockers (BB),
115
calcium channel blockers (CCB), angiotensin converting enzyme inhibitors (ACEi) or
116
angiotensin receptor blockers (ARB). Endovascular interventions included percutaneous
117
transluminal angioplasty (PTA) or Thoracic Endovascular Aortic Repair (TEVAR) with self-
118
expanding, covered stents. Open surgical interventions included aorto-aortic bypass grafting with
119
prosthetic conduits, graft vascular replacement, patch angioplasty, renal artery bypass or
120
reimplantation, renal autotransplantation and nephrectomy. Post-operative complications were
121
documented if they met pre-specified criteria.
122
Clinical data, including the mean age at initial presentation, sex, race, cardiovascular risk
123
factors, the type and extent of subsequent aortic interventions and medical therapies, were
124
abstracted from medical records. A questionnaire was developed to determine sequelae and time
125
to recurrence and patients were contacted to complete them.
126
This study was approved by the institutional review boards of The University of Texas
127
Health Science Center at Houston and Baylor College of Medicine. For patients who underwent
128
operations after protocol approval, informed consent was obtained whenever possible. A waiver
129
of consent was approved for patients who could not provide consent because of their illness and
130
who had no family members available to provide consent for them. For patients who underwent
131
surgery before the protocol was approved, waiver of consent was approved.
132 133
3. RESULTS
134
3.1 Patient characteristics
135
Table 1 displays the demographic information, clinical features and anatomic
136
distributions of 13 MAS cases. The cohort consists of four males and nine females. Follow-up
137
data were available for 11 cases (84%) with a median follow-up interval of 11 years (IQR 3-20).
138
Six patients who were diagnosed with genetic causes of MAS (Williams Syndrome, FMD, and
139
NF-1) presented primarily as children. One adult patient was diagnosed with Takayasu arteritis.
140
In the other seven cases, a probable cause of MAS could not be determined from review of
141
clinical records.
142 143
3.2 Clinical manifestations
144
All patients initially presented with hypertensive urgencies or emergencies requiring
145
parenteral and long-term oral antihypertensive medications. Other common presenting features
146
included claudication (8) and anginal chest pain (6). Three patients presented with signs and
147
symptoms suggestive of visceral ischemia. Two patients were diagnosed with heart failure, and
148
two developed renal infarctions after renal artery occlusions. In summary, patients in our series
149
developed frequent evidence of ischemic end-organ damage most prominently affecting the
150
lower extremities, heart, and visceral organs.
151 152 153
3.3 Vessel involvement Although the extent of thoracoabdominal stenosis was comparable across our cohort,
154
individuals with earlier presentations tended to develop more extensive extra-aortic disease
155
involving branch vessels, leading to more pronounced end-organ damage4. The combination of
156
suprarenal aortic stenosis and bilateral renal artery stenosis or occlusion was described in three
157
cases (1, 2, 4). The descending thoracic aorta was affected in three cases (1, 7, 9). Case 3
158
presented with near total occlusion of the left subclavian artery, leading to subclavian steal
159
syndrome with a systolic BP difference of 62 mmHg between the left and right upper
160
extremities. In the subset of 6 cases with available images, the minimum luminal diameter varied
161
between 0 and 11.6 mm (Figure 1). Stenoses or occlusions of the celiac, renal and inferior
162
mesenteric ostia were common: most subjects presented due to involvement of the supra-renal
163
aorta in zone 5 (n=9), zone 6 (n=10) or zone 7 (n=8), or the inter-renal aorta in zone 8 (n= 7,
164
Figure 2).
165 166
3.4 Interventions
167
Ten of 13 patients required open surgical aorto-aortic bypasses from the ascending
168
thoracic aorta (ATA, Figure 3a) or descending thoracic aorta (DTA, Figure 3b) to the abdominal
169
aorta. Three patients received endovascular interventions (Table 2). Four patients required re-
170
intervention. Case 1 had a total of 7 re-interventions: multiple interventions to the superior
171
mesenteric artery (SMA) and left renal artery, balloon angioplasty of the DTA, bilateral aorto-
172
renal bypass with right and left renal artery reimplantation, as well as bypasses from the celiac
173
artery to SMA, DTA to infrarenal aorta, and ATA to infrarenal aorta. In other cases, re-
174
interventions involved additional aortic segments or branch vessels: ATA to infrarenal aorta
175
(case 4), DTA to infrarenal aorta (case 2), and left carotid to left axillary artery (case 6). Case 11,
176
one of the three patients who underwent endovascular interventions, required a second
177
endovascular intervention to the DTA. No re-interventions were reported for 6 subjects, but two
178
of these subjects were lost to follow up.
179 180 181
3.5 Operative outcomes There were no significant intraoperative complications or immediate postoperative
182
deaths, but perioperative and long-term complications did affect 6 of 13 cases (45%). Case 3
183
developed renal failure requiring long-term hemodialysis. Case 1 developed aneurysmal
184
dilatation of the renal and visceral homograft bypasses and in the DTA at the site of balloon
185
angioplasty. Case 4 developed mural graft thrombus on a previous endograft requiring re-
186
intervention. Case 12 presented with stenosis of zones 6 and 7 that involved visceral vessels,
187
requiring splenectomy. Case 11 required open repair of the right common femoral access site
188
after endovascular intervention. One of the three TEVAR cases (5, 9, and 11) required a single
189
re-intervention after 6 years.
190 191 192
3.6 Clinical outcomes The probability of being free from vascular reintervention was 0.88 (standard error =
193
0.12) at 10 years (Figure 4). We confirmed that 11 of 13 subjects were alive at the latest follow
194
up. We detected a modest improvement in hypertension control in 5 patients based on
195
comparisons of antihypertensive medications that were required before and after intervention.
196
Overall, the mean number of antihypertensive prescriptions remained similar (1.9±0.9 to 1.5±1,
197
p=0.27). Two patients (Cases 9 and 13) were able to discontinue all antihypertensive therapies at
198
discharge.
199 200 201
4. DISCUSSION Stenosis of the abdominal aorta was first described in 184810, but the term “middle aortic
202
syndrome” was coined by Sen in 1963.11 MAS is a rare disease characterized by localized or
203
diffuse stenosis of the thoracoabdominal aorta. Patients often present in childhood with severe
204
hypertension that remains difficult to control, even after successful interventions. Most cases
205
require a multidisciplinary approach for blood pressure management and preservation of end-
206
organ function, with frequent recurrences and significant residual hypertension.
207
The anatomic extent of MAS is extremely variable. Focal stenosis is more frequent in the
208
suprarenal (60-70%), than inter-renal (20-25%), or infrarenal (10-15%) aorta. Involvement of
209
visceral vessels, particularly renal artery stenosis (66-80%), SMA stenosis (30-60%), or celiac
210
artery stenosis (22-60%)4,12, is also common. The IMA is rarely occluded and may in fact
211
develop compensatory dilation due to collateralization to maintain mesenteric perfusion.4 In
212
contrast, a significant proportion of our cohort developed inter-renal aortic stenosis (7/13, 54%),
213
rather than celiac (23%) or renal artery stenosis (31%). Therefore, surveillance of MAS should
214
include careful longitudinal analysis of branch vessels and multiple aortic segments.
215
Evidence of malperfusion is frequent in MAS and is a clear indication for invasive
216
management. 4,13 As our series demonstrates, a multidisciplinary team of cardiologists, surgeons
217
and endovascular specialists can facilitate the evaluation and triage of symptomatic patients. In
218
complex cases with extensive disease, an open surgical approach generally provides more
219
durable outcomes than endovascular interventions.14,15,16 Half of all patients who undergo aortic
220
TEVAR require reintervention within 5 years.17,18 In our series, Dacron grafts proved to be
221
resilient and rarely required re-intervention when used to bypass affected segments, with one
222
exception in our cohort: a single patient who developed a mural graft thrombus that required
223
intervention. Most re-interventions were required for new stenoses of distal aortic segments or
224
visceral vessels rather than for previously bypassed aortic zones. Lifelong surveillance with
225
regular follow up is essential to reduce morbidity and mortality from progressive disease.
226
Several new surgical approaches may expand the range of durable and effective treatment
227
options to more MAS patients. Renal auto-transplantation is a promising adjunctive technique to
228
address MAS-associated renovascular hypertension due to symptomatic renal artery stenosis. For
229
patients with dual renal arteries, cold perfusion with ex vivo vascular reconstruction may help to
230
preserve renal function by reducing ischemic time. In one case series, this approach led to
231
acceptable outcomes in adolescent MAS patients.19 In patients with bilateral renovascular
232
disease, aortic bypass combined with orthotopic renal transplantation remains the standard of
233
care.20 For some pediatric MAS patients, tissue expanders can effectively lengthen normal aortic
234
tissues proximal or distal to stenosed segments.21 Retro-aortic expansion can allow for excision
235
and repair of stenotic segments by primary anastomosis without bypass grafting to mitigate end-
236
organ ischemia at younger ages and may also reduce late operative complications.
237
Genetic mutations play an important but under-recognized role in MAS. Whole exome
238
sequencing recently identified mutations of vascular disease genes such as NF1, causing
239
neurofibromatosis, and JAG1, causing Alagille Syndome,13 in 43% of MAS patients. Patients
240
who had an identifiable genetic etiology in this cohort presented at an earlier age (18.2±17 vs
241
31.3±18 years). The identification of a causal genetic mutation may direct clinicians to screen
242
for other associated clinical features, or to identify affected relatives before they develop
243
significant disease. Thus, clinical evaluation and follow-up genetic testing for a suspected
244
genetic etiology should be included in the routine workup of all MAS patients.
245 246
5. CONCLUSIONS
247
MAS is a complex disorder with devastating consequences caused by visceral and aortic
248
malperfusion. The long-term outcomes of MAS, particularly after complex aortic interventions,
249
are not well characterized. In this case series, we identified genetic and clinical factors that may
250
be associated with adverse outcomes. These data highlight the recurrent vascular events that
251
necessitate lifelong follow up of MAS patients. Open surgical and endovascular approaches are
252
durable and lead to an improvement in symptoms if patients are intervened on at an early stage.
253
Significant delays in diagnosis or intervention frequently lead to severe end-organ damage from
254
intractable hypertension. Analysis of larger multi-institutional cohorts with more extensive
255
longitudinal imaging will be necessary to identify factors influencing recurrence risk and
256
mortality.
257
258
6. ACKNOWLEDGEMENTS
259
This work was supported in part by the Cheves and Isabella Smythe Distinguished Professorship
260
in Internal Medicine at the University of Texas Health Science Center at Houston (SKP), the
261
Jimmy and Roberta Howell Professorship in Cardiovascular Surgery at Baylor College of
262
Medicine (SAL), and the Cullen Foundation (JSC). The authors wish to thank Matt Price, MS,
263
RHIA and Hiruni Amarasekara, MS, for providing access to images and clinical data, and Chris
264
Akers, MA, for creating the medical illustrations in Figures 1a and 3.
265
7. FIGURE CAPTIONS
266
Figure 1a: Aortic Zones used to determine zone involvement on CT imaging (adapted from
267
Society for Vascular Surgery Ad Hoc Committee on TRS. Reporting Standards for TEVAR9). A:
268
Distal boundary of Zone 3 (2 cm distal to subclavian artery); B: Distal boundary of Zone 4 (mid-
269
descending aorta at T6); C: Celiac artery; D: Superior mesenteric artery; E: Inferior mesenteric
270
artery.
271
Figure 1b: Abdominal CT angiogram of MAS case 6. The minimum diameter of the abdominal
272
aorta (circled) was 2.1 mm.
273
Figure 2: Frequency graph of aortic zone involvement, as defined by Society for Vascular
274
Surgery Ad Hoc Committee on TRS. Reporting Standards for TEVAR.9 Images were directly
275
reviewed by one of the authors (SAL) to minimize interrater variability.
276
Figure 3a: Representative before and after illustrations of an open aortic bypass operation
277
between the ascending and abdominal aorta (Cases 6 and 8).
278
Figure 3b: Representative before and after illustrations of an open aortic bypass operation
279
between the descending and abdominal aorta (Cases 3, 4, 10 and 12).
280
Figure 4: Kaplan-Meier curve of freedom from reintervention illustrates the durability of
281
interventions. Numbers above the plot line enumerate the total number of individuals who were
282
censored between each time point. The median length of follow up was 11 years.
283
284
8. REFERENCES [1] Delis KT & Gloviczki P. Middle aortic syndrome: from presentation to contemporary
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open surgical and endovascular treatment. Perspect Vasc Surg Endovasc Ther
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2005;17:187-203.
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[2] Connolly JE, Wilson SE, Lawrence PL et al. Middle aortic syndrome: distal thoracic and
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abdominal coarctation, a disorder with multiple etiologies. J Am Coll Surg
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2002;194:774-81.
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[3] Kim SM, Jung IM, Han A et al. Surgical treatment of middle aortic syndrome with
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Takayasu arteritis or midaortic dysplastic syndrome. Eur J Vasc Endovasc Surg
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2015;50:206-12.
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[4] Porras D, Stein DR, Ferguson MA et al. Midaortic syndrome: 30 years of experience with medical, endovascular and surgical management. Pediatr Nephrol 2013;28:2023-33. [5] Kuzeyli K, Cakir E, Dinc H et al. Midaortic syndrome and subarachnoid hemorrhage
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associated with ruptured middle cerebral artery aneurysm: case report and review of the
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literature. Neurosurgery 2003;52:1460-4.
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[6] Ishii K, Isono M, Kasai N et al. Midaortic Syndrome in childhood associated with a ruptured cerebral aneurysm: a case report. Surg Neurol 2001;55:209-212. [7] Graham LM, Zelenock GB, Erlandson EE, et al. Abdominal aortic coarctation and segmental hypoplasia. Surgery 1979;86:519-29. [8] Senning, A & Johansson L. Coarctation of the abdominal aorta. J Thorac Cardiovasc Surg 1960;40:517-23. [9] Fillinger MF, Greenberg RK, McKinsey JF et al. Reporting standards for thoracic endovascular aortic repair (TEVAR). Journal of Vascular Surgery 2010;52:1022-33.
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[10] Quain R. Partial Coarctation of the Abdominal Aorta. Trans Path Soc London 1847;1:244– 246. [11] Sen PK, Kinare SG, Engineer SD et al. The Middle Aortic Syndrome. Br Heart J 1963;25:610–618. [12] Rumman RK, Nickel C, Matsuda-Abedini M et al. Disease Beyond the Arch: A Systematic
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Review of Middle Aortic Syndrome in Childhood. Am J of Hypertens 2015;28:833-46
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[13] Warejko JK, Schueler M, Vivante A et al . Whole exome sequencing reveals a monogenic
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cause of disease in ≈43% of 35 Families With Midaortic Syndrome. Hypertension
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2018;71:691-99.
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[14] Panayiotopoulos YP, Tyrrell MR, Koffman G et al. Mid-aortic syndrome presenting in childhood. Br J Surg 1996;83:235-40. [15] Poupalou A, Salomon R, Boudjemline Y et al. Aortic bypass and bilateral renal autotransplantation for mid-aortic syndrome. Pediatr Nephrol. 2013;28:1871-4.
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[16] Matsumoto M, Suehiro K, & Kubo H. Ascending aorta-abdominal aorta bypass with the
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reconstruction of superior mesenteric and bilateral renal arteries for mid-aortic syndrome.
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Jpn J Thorac Cardiovasc Surg 2006;54:535-8.
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[17] Spadaccio C, Nappi F, Al-Attar N et al. Old Myths, New Concerns: the Long-Term Effects
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of Ascending Aorta Replacement with Dacron Grafts. Not All That Glitters is Gold. J of
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Cardiovasc Trans Res 2016;9:334-342.
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[18] Son SA, Lee DH, Oh TH et al. Risk Factors Associated with Reintervention After Thoracic
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Endovascular Aortic Repair for Descending Aortic Pathologies. Vascular and Endovascular
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Surgery 2019;53:181-88.
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[19] Bleacher J, Turner ME, Quivers E et al. Renal autotransplantation for renovascular hypertension caused by midaortic syndrome. J Pediatr Surg 1997;32:248-50. [20] Zhang H, Li F, Ren H et al. Aortic bypass and orthotopic right renal autotransplantation for midaortic syndrome: a case report. BMC Surg 2014;14:86. [21] Kim, HB, Vakili K, Ramos-Gonzalez GJ et al. Tissue expander-stimulated lengthening of
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1664-1672.
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[22] Di Monaco S, Georges A, Lengelé JP et al. Genomics of Fibromuscular Dysplasia. Int J Mol Sci. 2018;19(5):1526.
Table 1: Clinical Features of MAS Cohort Case
Age at presentation
Presenting Symptoms
End organ damage
Etiology
Aortic Zone involvement
1
2
CVA*, HTN†
None
FMD‡
4, 5, 6, 7, 8, 9
2
6
CVA, claudication, HTN
CKD §, LVH[], CVA
NF-1||
8
3
67
HTN
CKD, LVH
Undetermined
5,6,7
4
25
HTN
CKD
Undetermined
5, 6, 7, 8, 9
Total occlusion
5
37
HTN, abdominal pain
Mesenteric ischemia
Undetermined
4, 5
11.6
6
37
HTN, claudication
None
Undetermined
5, 6, 7, 8, 9, 10
2.1
7
49
HTN
LVH
FMD
5, 6
8
17
Abdominal pain
None
Williams syndrome
5, 6, 7
8.64
9
11
Chest pain, HTN
CVA
NF-1
4, 5
9.98
10
14
HTN, abdominal pain
None
Undetermined
5, 6, 7, 8, 9
11
24
Hypertensive urgency
None
Takayasu's arteritis
5
12
20
HTN, acute pulmonary edema
None
Undetermined
6, 7
13
19
HTN, chest pain
LVH, CHF¶
Undetermined
3, 4, 5, 6, 7, 8, 9, 10
Table 1 Legend *Cerebrovascular accident †Hypertension ‡fibromuscular §Chronic
dysplasia
kidney disease
Narrowest luminal diameter (mm)
8.97
[]Left
ventricular hypertrophy
||
Neurofibromatosis type 1
¶
Congestive heart failure
Table 2: Clinical Course of MAS Patients Case
Intervention
Initial Intervention
1
Surgery
Celiac-SMA* anastomosis, Left renal artery reimplantation
Reinterventions
Post-op Complications
1) Patch angioplasty of SMA
Pneumothorax
2) DTA†-SMA bypass, Left aortorenal bypass
Acute blood loss anemia
3) Repeat Left aorto-renal bypass
Lactic acidosis
4) Repair of Left aorto-renal conduit aneurysm
Left hydronephrosis
# BP meds pre-op
# BP meds post-op
1
1
5) Supraceliac-infrarenal aortic bypass 6) Balloon angioplasty of DTA 7) DTA-infrarenal aortic bypass 2
Surgery
BL‡ aorto-renal bypass
DTA-infrarenal aortic bypass
BLE§ paresthesia
2
3
3
Surgery
DTA-infrarenal aortic bypass
None
ACRF[]
4
2
4
Surgery
DTA-infrarenal aortic bypass
Ascending to infrarenal aortic bypass
Mural thrombus of prior graft
2
2
5
Endovascular
TEVAR|| (covered stent x1)
None
-
2
1
6
Surgery
Ascending-infrarenal aortic bypass
Left carotid-axillary artery bypass
-
1
1
7
Surgery
Proximal-distal DTA bypass
None
-
2
2
8
Surgery
Ascending-infrarenal
None
-
2
2
aortic bypass 9
Endovascular
TEVAR (covered stent x2)
None
-
1
0
10
Surgery
DTA-infrarenal aortic bypass
None
-
2
1
11
Endovascular
Balloon angioplasty of DTA
TEVAR (distal DTA)
Femoral artery repair
1
2
TEVAR (covered stent x1)
12
Surgery
DTA-infrarenal aortic bypass
Unknown
Splenectomy
2
3
13
Surgery
Transverse aortic arch repair
Unknown
-
3
0
Table 2 Legend * Superior mesenteric artery †Descending thoracic
aorta
‡
Bilateral
§
bilateral lower extremity
[]
Acute on chronic renal failure
||
thoracic endovascular aortic repair
¶
Congestive heart failure
S0890-5096(20)30016-9
DOI:
https://doi.org/10.1016/j.avsg.2019.12.039
Reference:
AVSG 4851
To appear in:
Annals of Vascular Surgery
Received Date: 29 September 2019 Revised Date:
8 December 2019
Accepted Date: 17 December 2019
Please cite this article as: Patel RS, Nguyen S, Lee MT, Price MD, Krause H, Thanh Truong VT, Sandhu HK, Charlton-Ouw KM, LeMaire SA, Coselli JS, Prakash SK, Clinical Characteristics and Long-Term Outcomes of Mid-Aortic Syndrome, Annals of Vascular Surgery (2020), doi: https://doi.org/10.1016/ j.avsg.2019.12.039. This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. © 2020 Published by Elsevier Inc.
Clinical Characteristics and Long-Term Outcomes of Mid-Aortic Syndrome
1 2 3
Ritesh S. Patel, MD1, Stephanie Nguyen, MD2, Michelle T. Lee, MD1, Matt D. Price, MS3, Heidi
4
Krause, BS3, Van Thi Thanh Truong, MS4, Harleen K. Sandhu, MD, MPH5, Kristofer M.
5
Charlton-Ouw, MD4, Scott A. LeMaire, MD3, Joseph S. Coselli, MD3, and Siddharth K. Prakash
6
MD, PhD6
7 8
1
9
McGovern Medical School, Houston, Texas, USA
Department of Internal Medicine, University of Texas Health Science Center Houston,
10
2
University of Texas Health Science Center, McGovern Medical School, Houston, Texas, USA
11
3
Division of Cardiothoracic Surgery, Michael E. DeBakey Department of Surgery, Baylor
12
College of Medicine, and Department of Cardiovascular Surgery, The Texas Heart Institute,
13
Houston, Texas, USA
14
4
Center for Clinical Research and Evidence-Based Medicine, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, Texas, USA
15 16
5
17
Center Houston, McGovern Medical School at the Memorial Hermann Hospital – Heart and
18
Vascular Institute, Houston, Texas, USA
19
6
Department of Cardiothoracic and Vascular Surgery, University of Texas Health Science
Department of Internal Medicine, Division of Cardiovascular Medicine, University of Texas
20
Health Science Center Houston, McGovern Medical School, Memorial Hermann Hospital –
21
Heart and Vascular Institute, Houston, Texas, USA
22 23
Conflicts of Interest: None
24 25
Disclosure: Dr. Coselli participates in clinical trials with and/or consults for Terumo Aortic,
26
Medtronic, W.L. Gore, Edward Lifesciences and Abbott Laboratories, and receives royalties and
27
grant support from Terumo Aortic. Dr. LeMaire participates in clinical trials with and/or consults
28
for Terumo Aortic, Baxter Healthcare, Medtronic, W.L. Gore, and CytoSorbents.
29 30
This study was presented at The Texas Society for Vascular and Endovascular Surgery Annual
31
Meeting, Houston, Texas November 2-3, 2018
32 33
Corresponding Author:
34
Siddharth K. Prakash, MD, PhD
35
University of Texas Health Science Center at Houston
36
McGovern Medical School
37
Department of Internal Medicine
38
6431 Fannin Street, MSB 6.100
39
Houston, TX 77030
40
Phone: (713) 500-7003
41
Fax: (713) 500-0693
42
Email: [email protected]
43 44 45
Key words: Mid-aortic syndrome; Middle aortic syndrome; Abdominal aorta coarctation;
46
Renovascular hypertension; Aorto-aortic bypass
47
OBJECTIVE:
48
Mid-aortic syndrome (MAS) is a rare congenital or acquired condition marked by segmental or
49
diffuse stenosis of the distal thoracic and/or abdominal aorta and its branches. The optimal
50
approach to medical or interventional management of MAS and long-term outcomes in adults are
51
not well defined. We reviewed MAS cases to characterize the natural history of aortic disease,
52
identify prognostic factors and evaluate the durability of invasive interventions.
53
METHODS:
54
We conducted a retrospective review of MAS patients who presented to Memorial Hermann
55
Hospital and Baylor College of Medicine between 1997 and 2018. We categorized cases
56
according to demographic and clinical manifestations, etiologies, the extent of aortic
57
involvement, interventions and vascular outcomes.
58
RESULTS:
59
We identified a cohort of 13 MAS patients. The etiology of MAS was identified in 6 cases,
60
including genetic syndromes (Neurofibromatosis Type 1 (2/13), Williams syndrome (1/13),
61
fibromuscular dysplasia (2/13), and Takayasu arteritis (1/13)). Mean age at first documented
62
clinical event was 25.2 (2-67) years but cases with genetic etiologies presented significantly
63
younger (18.2 years). The most common primary anatomic site was the suprarenal and infrarenal
64
aorta (zones 5-8). Extra-aortic locations involved the renal (4/13), celiac (3/13), and superior
65
mesenteric (3/13) arteries. Clinical manifestations included hypertension (13/13), claudication
66
(9/13) and postprandial abdominal pain (5/13). All patients with available follow-up data
67
underwent at least one surgical or endovascular intervention (range: 1-8). Postoperative
68
complications included renal failure requiring post-discharge hemodialysis and respiratory
69
failure. There were no deaths in long-term follow-up.
70
CONCLUSIONS:
71
MAS is a complex vasculopathy with substantial variability in clinical presentation and anatomic
72
distribution. Extensive disease frequently requires multiple invasive interventions and results in
73
refractory hypertension, which may predict subsequent clinical events. A multidisciplinary
74
approach with long-term monitoring is essential for preservation of end-organ function and
75
quality of life in this debilitating disease.
76 77
1. INTRODUCTION Mid-aortic syndrome (MAS) is a rare condition marked by segmental or diffuse stenosis
78
of the distal thoracic and/or abdominal aorta and its branches. Both congenital and acquired
79
causes have been described. Congenital MAS has been attributed to developmental defects in the
80
fusion of the dorsal aorta, while acquired cases are associated with autoimmune diseases such as
81
Takayasu and giant cell arteritis, and heritable vasculopathies such as fibromuscular dysplasia,
82
neurofibromatosis, Williams syndrome, Alagille syndrome and retroperitoneal fibrosis.1,2,3
83
Most MAS cases are diagnosed in children or adolescents who present with visceral or
84
limb ischemia and severe hypertension. Symptoms may be associated with hypertensive end-
85
organ damage, visceral malperfusion or lower limb ischemia. Other complications may include
86
renal insufficiency, mesenteric ischemia, heart failure and subarachnoid hemorrhage.4,5,6 Without
87
prompt interventions, patients uniformly succumb to progressive vascular complications and
88
severe hypertension, and fewer than 20% survive past age 407,8. Treatment of recurrent vascular
89
events requires a multidisciplinary approach that integrates medical management with
90
endovascular and open surgical interventions. Refractory hypertension due to renovascular
91
disease may exacerbate the clinical course of MAS patients. Vascular occlusions and aneurysms
92
often recur despite initially effective interventions7 and optimal long-term treatment strategies
93
are unclear.
94
The primary objective of our case series is to determine the associations between clinical
95
features, interventions, and vascular outcomes in MAS patients. Early recognition and prompt
96
collaborative therapy is essential for effective management of this debilitating disease.
97 98
2. MATERIAL AND METHODS
99
Our retrospective review included eligible MAS patients who presented to Memorial
100
Hermann Hospital and Baylor College of Medicine between 1997 and 2018. The diagnosis of
101
MAS was verified by imaging that confirmed suprarenal, intrarenal (between the renal arteries
102
and superior mesenteric artery), or infrarenal narrowing or occlusion of the abdominal aorta. To
103
minimize variance, one of us (SAL) adjudicated zone involvement in all cases using aortic zone
104
criteria defined in the literature9 (Figure 1a) by direct review of available computed tomographic
105
angiogram images (Figure 1b). The extent of disease was also characterized by ostial or distal
106
involvement, and segmental or diffuse morphology.
107
The etiology of MAS was classified as genetic, autoimmune/inflammatory, or unsolved.
108
We categorized cases with onset in infancy or childhood as congenital. Etiology was defined as
109
genetic if any of the following disorders were present: Williams syndrome, Neurofibromatosis
110
type 1 (NF-1), Alagille syndrome, or Fibromuscular Dysplasia (FMD). FMD was categorized as
111
genetic due to its autosomal dominant inheritance in families and the recent identification of one
112
causal gene, PHACTR1.22 The autoimmune category included Takayasu arteritis, giant cell
113
arteritis, retroperitoneal fibrosis, or other vasculitis.
114
Medical therapies consisted of anti-hypertensive medications such as beta-blockers (BB),
115
calcium channel blockers (CCB), angiotensin converting enzyme inhibitors (ACEi) or
116
angiotensin receptor blockers (ARB). Endovascular interventions included percutaneous
117
transluminal angioplasty (PTA) or Thoracic Endovascular Aortic Repair (TEVAR) with self-
118
expanding, covered stents. Open surgical interventions included aorto-aortic bypass grafting with
119
prosthetic conduits, graft vascular replacement, patch angioplasty, renal artery bypass or
120
reimplantation, renal autotransplantation and nephrectomy. Post-operative complications were
121
documented if they met pre-specified criteria.
122
Clinical data, including the mean age at initial presentation, sex, race, cardiovascular risk
123
factors, the type and extent of subsequent aortic interventions and medical therapies, were
124
abstracted from medical records. A questionnaire was developed to determine sequelae and time
125
to recurrence and patients were contacted to complete them.
126
This study was approved by the institutional review boards of The University of Texas
127
Health Science Center at Houston and Baylor College of Medicine. For patients who underwent
128
operations after protocol approval, informed consent was obtained whenever possible. A waiver
129
of consent was approved for patients who could not provide consent because of their illness and
130
who had no family members available to provide consent for them. For patients who underwent
131
surgery before the protocol was approved, waiver of consent was approved.
132 133
3. RESULTS
134
3.1 Patient characteristics
135
Table 1 displays the demographic information, clinical features and anatomic
136
distributions of 13 MAS cases. The cohort consists of four males and nine females. Follow-up
137
data were available for 11 cases (84%) with a median follow-up interval of 11 years (IQR 3-20).
138
Six patients who were diagnosed with genetic causes of MAS (Williams Syndrome, FMD, and
139
NF-1) presented primarily as children. One adult patient was diagnosed with Takayasu arteritis.
140
In the other seven cases, a probable cause of MAS could not be determined from review of
141
clinical records.
142 143
3.2 Clinical manifestations
144
All patients initially presented with hypertensive urgencies or emergencies requiring
145
parenteral and long-term oral antihypertensive medications. Other common presenting features
146
included claudication (8) and anginal chest pain (6). Three patients presented with signs and
147
symptoms suggestive of visceral ischemia. Two patients were diagnosed with heart failure, and
148
two developed renal infarctions after renal artery occlusions. In summary, patients in our series
149
developed frequent evidence of ischemic end-organ damage most prominently affecting the
150
lower extremities, heart, and visceral organs.
151 152 153
3.3 Vessel involvement Although the extent of thoracoabdominal stenosis was comparable across our cohort,
154
individuals with earlier presentations tended to develop more extensive extra-aortic disease
155
involving branch vessels, leading to more pronounced end-organ damage4. The combination of
156
suprarenal aortic stenosis and bilateral renal artery stenosis or occlusion was described in three
157
cases (1, 2, 4). The descending thoracic aorta was affected in three cases (1, 7, 9). Case 3
158
presented with near total occlusion of the left subclavian artery, leading to subclavian steal
159
syndrome with a systolic BP difference of 62 mmHg between the left and right upper
160
extremities. In the subset of 6 cases with available images, the minimum luminal diameter varied
161
between 0 and 11.6 mm (Figure 1). Stenoses or occlusions of the celiac, renal and inferior
162
mesenteric ostia were common: most subjects presented due to involvement of the supra-renal
163
aorta in zone 5 (n=9), zone 6 (n=10) or zone 7 (n=8), or the inter-renal aorta in zone 8 (n= 7,
164
Figure 2).
165 166
3.4 Interventions
167
Ten of 13 patients required open surgical aorto-aortic bypasses from the ascending
168
thoracic aorta (ATA, Figure 3a) or descending thoracic aorta (DTA, Figure 3b) to the abdominal
169
aorta. Three patients received endovascular interventions (Table 2). Four patients required re-
170
intervention. Case 1 had a total of 7 re-interventions: multiple interventions to the superior
171
mesenteric artery (SMA) and left renal artery, balloon angioplasty of the DTA, bilateral aorto-
172
renal bypass with right and left renal artery reimplantation, as well as bypasses from the celiac
173
artery to SMA, DTA to infrarenal aorta, and ATA to infrarenal aorta. In other cases, re-
174
interventions involved additional aortic segments or branch vessels: ATA to infrarenal aorta
175
(case 4), DTA to infrarenal aorta (case 2), and left carotid to left axillary artery (case 6). Case 11,
176
one of the three patients who underwent endovascular interventions, required a second
177
endovascular intervention to the DTA. No re-interventions were reported for 6 subjects, but two
178
of these subjects were lost to follow up.
179 180 181
3.5 Operative outcomes There were no significant intraoperative complications or immediate postoperative
182
deaths, but perioperative and long-term complications did affect 6 of 13 cases (45%). Case 3
183
developed renal failure requiring long-term hemodialysis. Case 1 developed aneurysmal
184
dilatation of the renal and visceral homograft bypasses and in the DTA at the site of balloon
185
angioplasty. Case 4 developed mural graft thrombus on a previous endograft requiring re-
186
intervention. Case 12 presented with stenosis of zones 6 and 7 that involved visceral vessels,
187
requiring splenectomy. Case 11 required open repair of the right common femoral access site
188
after endovascular intervention. One of the three TEVAR cases (5, 9, and 11) required a single
189
re-intervention after 6 years.
190 191 192
3.6 Clinical outcomes The probability of being free from vascular reintervention was 0.88 (standard error =
193
0.12) at 10 years (Figure 4). We confirmed that 11 of 13 subjects were alive at the latest follow
194
up. We detected a modest improvement in hypertension control in 5 patients based on
195
comparisons of antihypertensive medications that were required before and after intervention.
196
Overall, the mean number of antihypertensive prescriptions remained similar (1.9±0.9 to 1.5±1,
197
p=0.27). Two patients (Cases 9 and 13) were able to discontinue all antihypertensive therapies at
198
discharge.
199 200 201
4. DISCUSSION Stenosis of the abdominal aorta was first described in 184810, but the term “middle aortic
202
syndrome” was coined by Sen in 1963.11 MAS is a rare disease characterized by localized or
203
diffuse stenosis of the thoracoabdominal aorta. Patients often present in childhood with severe
204
hypertension that remains difficult to control, even after successful interventions. Most cases
205
require a multidisciplinary approach for blood pressure management and preservation of end-
206
organ function, with frequent recurrences and significant residual hypertension.
207
The anatomic extent of MAS is extremely variable. Focal stenosis is more frequent in the
208
suprarenal (60-70%), than inter-renal (20-25%), or infrarenal (10-15%) aorta. Involvement of
209
visceral vessels, particularly renal artery stenosis (66-80%), SMA stenosis (30-60%), or celiac
210
artery stenosis (22-60%)4,12, is also common. The IMA is rarely occluded and may in fact
211
develop compensatory dilation due to collateralization to maintain mesenteric perfusion.4 In
212
contrast, a significant proportion of our cohort developed inter-renal aortic stenosis (7/13, 54%),
213
rather than celiac (23%) or renal artery stenosis (31%). Therefore, surveillance of MAS should
214
include careful longitudinal analysis of branch vessels and multiple aortic segments.
215
Evidence of malperfusion is frequent in MAS and is a clear indication for invasive
216
management. 4,13 As our series demonstrates, a multidisciplinary team of cardiologists, surgeons
217
and endovascular specialists can facilitate the evaluation and triage of symptomatic patients. In
218
complex cases with extensive disease, an open surgical approach generally provides more
219
durable outcomes than endovascular interventions.14,15,16 Half of all patients who undergo aortic
220
TEVAR require reintervention within 5 years.17,18 In our series, Dacron grafts proved to be
221
resilient and rarely required re-intervention when used to bypass affected segments, with one
222
exception in our cohort: a single patient who developed a mural graft thrombus that required
223
intervention. Most re-interventions were required for new stenoses of distal aortic segments or
224
visceral vessels rather than for previously bypassed aortic zones. Lifelong surveillance with
225
regular follow up is essential to reduce morbidity and mortality from progressive disease.
226
Several new surgical approaches may expand the range of durable and effective treatment
227
options to more MAS patients. Renal auto-transplantation is a promising adjunctive technique to
228
address MAS-associated renovascular hypertension due to symptomatic renal artery stenosis. For
229
patients with dual renal arteries, cold perfusion with ex vivo vascular reconstruction may help to
230
preserve renal function by reducing ischemic time. In one case series, this approach led to
231
acceptable outcomes in adolescent MAS patients.19 In patients with bilateral renovascular
232
disease, aortic bypass combined with orthotopic renal transplantation remains the standard of
233
care.20 For some pediatric MAS patients, tissue expanders can effectively lengthen normal aortic
234
tissues proximal or distal to stenosed segments.21 Retro-aortic expansion can allow for excision
235
and repair of stenotic segments by primary anastomosis without bypass grafting to mitigate end-
236
organ ischemia at younger ages and may also reduce late operative complications.
237
Genetic mutations play an important but under-recognized role in MAS. Whole exome
238
sequencing recently identified mutations of vascular disease genes such as NF1, causing
239
neurofibromatosis, and JAG1, causing Alagille Syndome,13 in 43% of MAS patients. Patients
240
who had an identifiable genetic etiology in this cohort presented at an earlier age (18.2±17 vs
241
31.3±18 years). The identification of a causal genetic mutation may direct clinicians to screen
242
for other associated clinical features, or to identify affected relatives before they develop
243
significant disease. Thus, clinical evaluation and follow-up genetic testing for a suspected
244
genetic etiology should be included in the routine workup of all MAS patients.
245 246
5. CONCLUSIONS
247
MAS is a complex disorder with devastating consequences caused by visceral and aortic
248
malperfusion. The long-term outcomes of MAS, particularly after complex aortic interventions,
249
are not well characterized. In this case series, we identified genetic and clinical factors that may
250
be associated with adverse outcomes. These data highlight the recurrent vascular events that
251
necessitate lifelong follow up of MAS patients. Open surgical and endovascular approaches are
252
durable and lead to an improvement in symptoms if patients are intervened on at an early stage.
253
Significant delays in diagnosis or intervention frequently lead to severe end-organ damage from
254
intractable hypertension. Analysis of larger multi-institutional cohorts with more extensive
255
longitudinal imaging will be necessary to identify factors influencing recurrence risk and
256
mortality.
257
258
6. ACKNOWLEDGEMENTS
259
This work was supported in part by the Cheves and Isabella Smythe Distinguished Professorship
260
in Internal Medicine at the University of Texas Health Science Center at Houston (SKP), the
261
Jimmy and Roberta Howell Professorship in Cardiovascular Surgery at Baylor College of
262
Medicine (SAL), and the Cullen Foundation (JSC). The authors wish to thank Matt Price, MS,
263
RHIA and Hiruni Amarasekara, MS, for providing access to images and clinical data, and Chris
264
Akers, MA, for creating the medical illustrations in Figures 1a and 3.
265
7. FIGURE CAPTIONS
266
Figure 1a: Aortic Zones used to determine zone involvement on CT imaging (adapted from
267
Society for Vascular Surgery Ad Hoc Committee on TRS. Reporting Standards for TEVAR9). A:
268
Distal boundary of Zone 3 (2 cm distal to subclavian artery); B: Distal boundary of Zone 4 (mid-
269
descending aorta at T6); C: Celiac artery; D: Superior mesenteric artery; E: Inferior mesenteric
270
artery.
271
Figure 1b: Abdominal CT angiogram of MAS case 6. The minimum diameter of the abdominal
272
aorta (circled) was 2.1 mm.
273
Figure 2: Frequency graph of aortic zone involvement, as defined by Society for Vascular
274
Surgery Ad Hoc Committee on TRS. Reporting Standards for TEVAR.9 Images were directly
275
reviewed by one of the authors (SAL) to minimize interrater variability.
276
Figure 3a: Representative before and after illustrations of an open aortic bypass operation
277
between the ascending and abdominal aorta (Cases 6 and 8).
278
Figure 3b: Representative before and after illustrations of an open aortic bypass operation
279
between the descending and abdominal aorta (Cases 3, 4, 10 and 12).
280
Figure 4: Kaplan-Meier curve of freedom from reintervention illustrates the durability of
281
interventions. Numbers above the plot line enumerate the total number of individuals who were
282
censored between each time point. The median length of follow up was 11 years.
283
284
8. REFERENCES [1] Delis KT & Gloviczki P. Middle aortic syndrome: from presentation to contemporary
285
open surgical and endovascular treatment. Perspect Vasc Surg Endovasc Ther
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2005;17:187-203.
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[2] Connolly JE, Wilson SE, Lawrence PL et al. Middle aortic syndrome: distal thoracic and
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abdominal coarctation, a disorder with multiple etiologies. J Am Coll Surg
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2002;194:774-81.
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[3] Kim SM, Jung IM, Han A et al. Surgical treatment of middle aortic syndrome with
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Takayasu arteritis or midaortic dysplastic syndrome. Eur J Vasc Endovasc Surg
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2015;50:206-12.
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[4] Porras D, Stein DR, Ferguson MA et al. Midaortic syndrome: 30 years of experience with medical, endovascular and surgical management. Pediatr Nephrol 2013;28:2023-33. [5] Kuzeyli K, Cakir E, Dinc H et al. Midaortic syndrome and subarachnoid hemorrhage
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associated with ruptured middle cerebral artery aneurysm: case report and review of the
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literature. Neurosurgery 2003;52:1460-4.
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[6] Ishii K, Isono M, Kasai N et al. Midaortic Syndrome in childhood associated with a ruptured cerebral aneurysm: a case report. Surg Neurol 2001;55:209-212. [7] Graham LM, Zelenock GB, Erlandson EE, et al. Abdominal aortic coarctation and segmental hypoplasia. Surgery 1979;86:519-29. [8] Senning, A & Johansson L. Coarctation of the abdominal aorta. J Thorac Cardiovasc Surg 1960;40:517-23. [9] Fillinger MF, Greenberg RK, McKinsey JF et al. Reporting standards for thoracic endovascular aortic repair (TEVAR). Journal of Vascular Surgery 2010;52:1022-33.
306 307 308 309 310
[10] Quain R. Partial Coarctation of the Abdominal Aorta. Trans Path Soc London 1847;1:244– 246. [11] Sen PK, Kinare SG, Engineer SD et al. The Middle Aortic Syndrome. Br Heart J 1963;25:610–618. [12] Rumman RK, Nickel C, Matsuda-Abedini M et al. Disease Beyond the Arch: A Systematic
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Review of Middle Aortic Syndrome in Childhood. Am J of Hypertens 2015;28:833-46
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[13] Warejko JK, Schueler M, Vivante A et al . Whole exome sequencing reveals a monogenic
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cause of disease in ≈43% of 35 Families With Midaortic Syndrome. Hypertension
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2018;71:691-99.
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[14] Panayiotopoulos YP, Tyrrell MR, Koffman G et al. Mid-aortic syndrome presenting in childhood. Br J Surg 1996;83:235-40. [15] Poupalou A, Salomon R, Boudjemline Y et al. Aortic bypass and bilateral renal autotransplantation for mid-aortic syndrome. Pediatr Nephrol. 2013;28:1871-4.
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[16] Matsumoto M, Suehiro K, & Kubo H. Ascending aorta-abdominal aorta bypass with the
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reconstruction of superior mesenteric and bilateral renal arteries for mid-aortic syndrome.
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Jpn J Thorac Cardiovasc Surg 2006;54:535-8.
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[17] Spadaccio C, Nappi F, Al-Attar N et al. Old Myths, New Concerns: the Long-Term Effects
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of Ascending Aorta Replacement with Dacron Grafts. Not All That Glitters is Gold. J of
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Cardiovasc Trans Res 2016;9:334-342.
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[18] Son SA, Lee DH, Oh TH et al. Risk Factors Associated with Reintervention After Thoracic
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Endovascular Aortic Repair for Descending Aortic Pathologies. Vascular and Endovascular
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Surgery 2019;53:181-88.
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[19] Bleacher J, Turner ME, Quivers E et al. Renal autotransplantation for renovascular hypertension caused by midaortic syndrome. J Pediatr Surg 1997;32:248-50. [20] Zhang H, Li F, Ren H et al. Aortic bypass and orthotopic right renal autotransplantation for midaortic syndrome: a case report. BMC Surg 2014;14:86. [21] Kim, HB, Vakili K, Ramos-Gonzalez GJ et al. Tissue expander-stimulated lengthening of
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1664-1672.
335 336
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Table 1: Clinical Features of MAS Cohort Case
Age at presentation
Presenting Symptoms
End organ damage
Etiology
Aortic Zone involvement
1
2
CVA*, HTN†
None
FMD‡
4, 5, 6, 7, 8, 9
2
6
CVA, claudication, HTN
CKD §, LVH[], CVA
NF-1||
8
3
67
HTN
CKD, LVH
Undetermined
5,6,7
4
25
HTN
CKD
Undetermined
5, 6, 7, 8, 9
Total occlusion
5
37
HTN, abdominal pain
Mesenteric ischemia
Undetermined
4, 5
11.6
6
37
HTN, claudication
None
Undetermined
5, 6, 7, 8, 9, 10
2.1
7
49
HTN
LVH
FMD
5, 6
8
17
Abdominal pain
None
Williams syndrome
5, 6, 7
8.64
9
11
Chest pain, HTN
CVA
NF-1
4, 5
9.98
10
14
HTN, abdominal pain
None
Undetermined
5, 6, 7, 8, 9
11
24
Hypertensive urgency
None
Takayasu's arteritis
5
12
20
HTN, acute pulmonary edema
None
Undetermined
6, 7
13
19
HTN, chest pain
LVH, CHF¶
Undetermined
3, 4, 5, 6, 7, 8, 9, 10
Table 1 Legend *Cerebrovascular accident †Hypertension ‡fibromuscular §Chronic
dysplasia
kidney disease
Narrowest luminal diameter (mm)
8.97
[]Left
ventricular hypertrophy
||
Neurofibromatosis type 1
¶
Congestive heart failure
Table 2: Clinical Course of MAS Patients Case
Intervention
Initial Intervention
1
Surgery
Celiac-SMA* anastomosis, Left renal artery reimplantation
Reinterventions
Post-op Complications
1) Patch angioplasty of SMA
Pneumothorax
2) DTA†-SMA bypass, Left aortorenal bypass
Acute blood loss anemia
3) Repeat Left aorto-renal bypass
Lactic acidosis
4) Repair of Left aorto-renal conduit aneurysm
Left hydronephrosis
# BP meds pre-op
# BP meds post-op
1
1
5) Supraceliac-infrarenal aortic bypass 6) Balloon angioplasty of DTA 7) DTA-infrarenal aortic bypass 2
Surgery
BL‡ aorto-renal bypass
DTA-infrarenal aortic bypass
BLE§ paresthesia
2
3
3
Surgery
DTA-infrarenal aortic bypass
None
ACRF[]
4
2
4
Surgery
DTA-infrarenal aortic bypass
Ascending to infrarenal aortic bypass
Mural thrombus of prior graft
2
2
5
Endovascular
TEVAR|| (covered stent x1)
None
-
2
1
6
Surgery
Ascending-infrarenal aortic bypass
Left carotid-axillary artery bypass
-
1
1
7
Surgery
Proximal-distal DTA bypass
None
-
2
2
8
Surgery
Ascending-infrarenal
None
-
2
2
aortic bypass 9
Endovascular
TEVAR (covered stent x2)
None
-
1
0
10
Surgery
DTA-infrarenal aortic bypass
None
-
2
1
11
Endovascular
Balloon angioplasty of DTA
TEVAR (distal DTA)
Femoral artery repair
1
2
TEVAR (covered stent x1)
12
Surgery
DTA-infrarenal aortic bypass
Unknown
Splenectomy
2
3
13
Surgery
Transverse aortic arch repair
Unknown
-
3
0
Table 2 Legend * Superior mesenteric artery †Descending thoracic
aorta
‡
Bilateral
§
bilateral lower extremity
[]
Acute on chronic renal failure
||
thoracic endovascular aortic repair
¶
Congestive heart failure