ORIGINAL ARTICLE

Retrograde Aortic Dissection After Thoracic Endovascular Aortic Repair Ludovic Canaud, MD, PhD, Baris A. Ozdemir, BSc, MRCS, Benjamin O. Patterson, BSc, MRCS, Peter J. E. Holt, PhD, FRCS, Ian M. Loftus, MD, FRCS, and Matt M. Thompson, MD, FRCS

Objective: To provide data regarding the etiology and timing of retrograde type A aortic dissection (RTAD) after thoracic endovascular aortic repair (TEVAR). Methods: Details of patients who had RTAD after TEVAR were obtained from the MOTHER Registry supplemented by data from a systematic review of the literature. Univariate analysis and binary logistic regression analysis of patient or technical factors was performed. Results: In MOTHER, RTAD developed in 16 of the 1010 patients (1.6%). Binary logistic regression demonstrated that an indication of TEVAR for aortic dissection (acute P = 0.000212; chronic P = 0.006) and device oversizing (OR 1.14 per 1% increase in oversizing above 9%, P < 0.0001) were significantly more frequent in patients with RTAD. Data from the systematic review was pooled with MOTHER data and demonstrated that RTAD occurred in 1.7% (168/9894). Most of RTAD occurred in the immediate postoperative (58%) period and was associated with a high mortality rate (33.6%). The odds ratio of RTAD for an acute aortic dissection was 10.0 (CI: 4.7–21.9) and 3.4 (CI: 1.3– 8.8) for chronic aortic dissection. The incidence of RTAD was not significantly different for endografts with proximal bare stent (2.8%) or nonbare stent (1.9%) (P = 0.1298). Conclusions: Although RTAD after TEVAR is an uncommon complication, it has a high mortality rate. RTAD is significantly more frequent in patients treated for acute and chronic type B dissection, and when the endograft is significantly oversized. The proximal endograft configuration was not associated with any difference in the incidence of RTAD. Keywords: complications, retrograde dissection, TEVAR, thoracic aorta (Ann Surg 2014;260:389–395)

T

horacic endovascular aortic repair (TEVAR) is extensively utilized as a treatment modality for pathology affecting the descending thoracic aorta and distal aortic arch. One of the most feared complications of this procedure is retrograde type A aortic dissection (RTAD), which has a low incidence but high mortality. Several reports have considered the etiological factors contributing to this potentially lethal complication, but data so far have been preliminary and interpretation made difficult by heterogenicity of data quality and reporting parameters. In the European Registry on Endovascular Aortic Repair Complications, Eggebrecht et al1 reported 63 cases of RTAD among 4750 TEVAR procedures. In this series, it was suggested that the use of proximal bare spring endografts might be an important causative factor for RTAD. However,

From the Department of Outcomes Research, St George’s Vascular Institute, London, United Kingdom. Ludovic Canaud and Baris A. Ozdemir hold joint first authorship/contributorship on this work. Disclosure: Ludovic Canaud is financially supported by the French Society for Vascular Surgery. The authors declare no conflicts of interest. Reprints: Ludovic Canaud, MD, PhD, St George’s Vascular Institute, Room 4.007, St George’s Healthcare NHS Trust, Blackshaw Road, London SW17 0QT, UK. E-mail: [email protected]. C 2014 by Lippincott Williams & Wilkins Copyright  ISSN: 0003-4932/14/26002-0389 DOI: 10.1097/SLA.0000000000000585

Annals of Surgery r Volume 260, Number 2, August 2014

the ratio of proximal bare spring to proximal nonbare stent grafts was not reported.2 There is a general consensus that RTAD may be more common in patients with acute type B aortic dissection, but no definite association has been proven to date. Equally, there have been many mechanisms proposed to cause RTAD (extension of disease, wire trauma, and trauma from differing proximal endograft configurations) but little hard evidence to support evolving clinical practice or graft design. The aim of this study was to provide insight into the etiological and procedural factors associated with RTAD following TEVAR. Data were obtained from the MOTHER3 registry and were supplemented by cases from a systematic review of the literature. Data from both sources were aggregated to report the contemporary literature.

METHODS MOTHER Database The MOTHER registry comprises the combined data from 5 prospective trials and institutional data from a single UK center, which has been previously described.3 Briefly, the registry consists of the endovascular arm of a phase II/III trial (VALOR I4 ), the intervention arm of a randomized controlled trial, INSTEAD,5 and 3 phase IV trials (VALOR II,6 Captivia, and VIRTUE7 ). The single institute series included all TEVARs performed over a period of 8 years that used the Talent or Valiant stent graft systems. All of the trials had stringent protocols for data collection and validation. The institutional series was prospectively maintained, and follow-up was done by computed tomography. Morphological data available in the Mother registry were as follows: proximal aortic neck diameter, distal neck aortic diameter, aortic diameter at left subclavian artery, aortic diameter at left common carotid artery, and maximum aneurysm diameter. Device oversizing was calculated according to the diameter from the adventitia to adventitia of the proximal landing zone as compared with the diameter of the proximal endograft implanted.

Systematic Review Search Strategy The systematic review conformed to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. A literature search was undertaken to identify all published English language studies reporting RTAD after TEVAR. The EMBASE, MEDLINE, and COCHRANE databases were searched, for the period of 1993 to January 2013. Key words entered in this search were “TEVAR,” “retrograde dissection,” “thoracic stent-graft,” “endograft,” and “graft” with the Boolean operator OR. The reference lists of the articles obtained were reviewed for pertinent citations. In addition to those identified by the literature search data from the most important trial for the Gore Tag Thoracic Endograft8 and the Zenith TX2 Endovascular Graft9 was included in analysis.

Study Selection Studies were eligible for inclusion if they included patients who developed RTAD after TEVAR and reported clinical outcomes. www.annalsofsurgery.com | 389

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When studies contained duplicate data, the article with the most contemporary, or best documented material was used for analysis.

postoperative day in 8 (50%) (range, 0–611). RTAD caused sudden death in 4 (25%) patients.

Data extraction

Relationship of RTAD to Indication for TEVAR

Data regarding procedural characteristics, management, and outcomes were extracted. Particular attention was given to the ratio of proximal bare stent to proximal nonbare stent endograft usage in patients with and without RTAD.

The incidence of RTAD after TEVAR for acute aortic dissection was 4.3% (5/114) for chronic dissection 3% (6/195) and was 0.7% (5/670) in patients treated for degenerative aneurysm. When entered into a binary logistic regression analysis, the incidence of RTAD was significantly higher in patients with acute aortic dissection (OR 15.0, P = 0.000212) and chronic aortic dissection (OR 9.0, P = 0.006185).

Pooled Analysis of Systematic Review and MOTHER Data from the MOTHER registry were pooled with data from series reporting • the incidence of RTAD within a units total experience of TEVAR and indication for TEVAR. • the incidence of RTAD within a units total experience of TEVAR and proximal stent-graft configuration (proximal bare stent or non bare stent) to define the association of RTAD with proximal endograft configuration. • the incidence of RTAD within a units total experience of TEVAR and proximal landing zone to define the association of RTAD with proximal landing zone. This combined database facilitated comparison of the incidence of RTAD in patients treated with bare and nonbare proximal stent configurations, according to the proximal landing zone or according to the indication for TEVAR. The numbers of patients in each of the 3 analyses were different due to sporadic reporting of all 3 parameters in articles contributing to the systematic review.

Statistical Analysis Statistical analysis was undertaken using R [R Core Team (2013). R: A language and environment for statistical computing. R Foundation for Statistical Computing, Vienna, Austria. ISBN 3900051-07-0, URL http://www.R-project.org/]. Initially univariate analysis was performed to identify variables associated with RTAD in the MOTHER data and the pooled systematic review and MOTHER data. The χ 2 test or Fisher exact test was used for analysis of categorical data. Wilcoxon rank-sum test with continuity correction was used for analysis of numerical data. MOTHER data variables with P < 0.1 on univariate analysis were included in a binary logistic regression analysis. Because of the lack of detail in the aggregate data reported in the review papers, it was not possible to perform a regression analysis for the pooled data. The Holm-Bonferroni method was utilized to account for multiplicity of testing in the analysis of the aggregate data from the MOTHER and systematic review.

Stent Graft Oversizing Comparative Kernal density plots of device oversizing estimated from frequency functions are shown in Figure 1 for all MOTHER patients with and without RTAD. On univariate analysis, patients with RTAD had significantly greater device oversizing (22.0% vs 10.3%; P < 0.0001). When entered into a binary logistic regression analysis, RTAD was associated with device oversizing (each 1% oversizing increase above 9% led to an increase in OR of RTAD by 1.14 P < 0.0001). On univariate analysis in TEVAR patients with type B dissection, the mean oversizing in patients who developed retrograde type A dissection was significantly higher than those who did not develop this complication (24.4% vs 14.1%; P = 0.0006654). This is graphically demonstrated in the kernel density plot in Figure 2. On univariate analysis in TEVAR patients with degenerative aneurysms, the mean oversizing in patients who developed retrograde type A dissection was significantly higher than those who did not develop this complication (18.1% vs 9.6%; P = 0.01624). This is graphically demonstrated in the kernel density plot in Figure 3.

Proximal landing zone The incidence of RTAD after TEVAR was 0% (0/12) in zone 0, 1.5% (1/68) in zone 1, 2.7% (9/330) in zone 2, 1.0% (4/409) in zone 3, and 1% (2/191) in zone 4 (P = 0.2917).

Pooled Analysis of Patients Included in the MOTHER Database and Systematic Review The initial electronic search yielded 472 articles. After screening of titles and abstracts, and additional searches by hand in accordance with the inclusion criteria, data from 538–59 published studies

RESULTS MOTHER Database The MOTHER database contained 1010 patients: 670 patients with thoracic aortic aneurysm, 114 patients with acute type B aortic dissection, 195 patients with chronic type B aortic dissection, and 31 patients with other aortic pathology. Comorbidities, proximal landing zone, aortic diameter distal to the brachiocephalic trunk, maximum aneurysm diameter, and total length of aorta covered were congruent between patients with RTAD and those without.

Incidence of RTAD RTAD occurred in 16 (1.6%) patients. The mean age was 64 years (range, 33–84), and 68.7% were men.

Time to RTAD RTAD occurred intraoperatively in 2 patients (12.5%), before the 30th postoperative day in 6 (37.5%), and after the 30th 390 | www.annalsofsurgery.com

FIGURE 1. Comparative Kernal density plots of device oversizing for all MOTHER patients with (n: 13) (blue dashed line) and without RTAD (n: 513) (black solid line). Kernal density plots are graphical representations of estimates of probability density function.  C 2014 Lippincott Williams & Wilkins

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Retrograde Aortic Dissection After TEVAR

TABLE 1. Incidence, Timing, Indication for TEVAR, Proximal Landing Zone (Ishimaru Classification), Outcomes, Proximal Stent-Graft Configuration Oversizing of Patients Included in the Systematic Review and of the MOTHER Database MOTHER Registry RTAD (n) Incidence, % (n) Time to RTAD (mean days) Indication

16 1.58 (16/1010) 110.1 Aortic Acute 4.3 (5/114) dissection Chronic 3 (6/195) Total 3.5 (11/309) Degenerative aneurysm 0.7 (5/670) Traumatic aortic transection 0 (0/15) Penetrating aortic ulcer 0 (0/16) Proximal landing zone Zone 0 0 (0/12) Zone 1 1.5 (1/68) Zone 2 2.7 (9/330) Zone 3 1.0 (4/409) Zone 4 1 (2/191) Proximal stent-graft configuration Proximal bare stent 1.6 (16/997) Nonproximal bare stent 0 (0/13) Oversizing RTAD: 22% Non RTAD: 10.3%§ 30-day mortality 32.1 (56/174)

Pooled Systematic Review and MOTHER 190 1.7 (168/9894) 257.4 8.4 (26/309)∗ 3 (10/325)∗ 4% (81/2004) 0.9% (12/1315)∗ 0 (0/99)∗ 0 (0/112)∗ 6.8 (8/118)† 2.4 (2/85)† 4.1 (28/691)† 1.3 (17/1346)†

P

∗P

= 0.0000000000591

†P = 0.00002555

‡P = 0.1298

2.8 (48/1724)‡ 1.9 (28/1456)‡ —

§P < 0.0000001217

50 (8/16)

33.6 (64/190)

The incidence of RTAD varied significantly with the indication for TEVAR (∗ ), proximal landing zone (†) and percentage of proximal oversizing (‡) but not proximal stent-graft configuration (§).

were included (Fig. 4, Table 1). The data from the systematic review were combined with the 1010 patients in the MOTHER registry to describe the largest cohort of patients with RTAD reported to date.

Incidence of RTAD Thirty-nine series1,8,9,11,12,13,15,17–20,24–29,31–36,40,44–52,54–59 reporting the incidence of RTAD in their total TEVAR experience were pooled with data from the MOTHER registry. RTAD occurred in 1.7% of the patients (168/9894). The incidence of RTAD has dramatically increased after 2010: 1.49% (95/6374) until 2010 and 2.27% (73/3211) after 2010 (P = 0.008105).

Timing of RTAD Time to RTAD was reported in 90.5% of the patients (172/190). RTAD occurred intraoperatively in 20.9% of the patients (36/172), before the 30th postoperative day in 50% of the patients (86/172), and after the 30th postoperative day in 29.1% of the patients (50/172) (range, 0–1825) (Fig. 5).

Outcomes Emergent surgical aortic repair was performed in 135 (71.1%) patients. The overall 30-day mortality was 33.6% (n: 64): Table 2.

Proximal Stent-Graft Configuration

Density

Density

The results of 268,9,11,12,14,15,18–20,23,25,26,28,33,34,36,44,45,48–52,54–57,59 series reporting both the incidence of RTAD and proximal stent-graft configuration were pooled with data from the MOTHER registry (Tables 1 and 3).

Oversizing percentage

FIGURE 2. Comparative Kernal density plots of device oversizing for MOTHER patients with type B dissection (n: 8) (blue dashed line) and without RTAD (n: 47) (black solid line). Kernal density plots are graphical representations of estimates of probability density function.  C 2014 Lippincott Williams & Wilkins

Oversizing percentage

FIGURE 3. Comparative Kernal density plots of device oversizing for MOTHER patients with degenerative aneurysms (n: 5) (blue dashed line) and without RTAD (n: 478) (black solid line). www.annalsofsurgery.com | 391

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FIGURE 5. Histogram of days to RTAD. Pooled systematic review and MOTHER data. The horizontal axis is plotted to log scale but labels indicate days to RTAD (IE, intraoperative).

FIGURE 4. Flow chart of incidence of series reporting the incidence of RTAD alongside total experience of TEVAR and proximal stent-graft configuration (proximal bare stent or non proximal bare stent) pooled with the MOTHER database. The overall incidence of RTAD in these series was 2.4% (76/3180). TEVAR was performed for aortic dissection in 81.5% and for a degenerative aneurysm in 18.5%. In 1724 cases, the endograft had a proximal bare stent [Talent (n: 990) and Valiant (n: 622) (Medtronic Vascular, Santa Rosa, CA) or Vasoflow (n: 14; Weike Medical Apparatus and Instrument, Inc, Suzhou, China) or Aegis (n: 34; Microport, Shanghai, China) or Bolton Relay (n: 1; Bolton Medical, Sunrise, FL) or Griking (n: 35; Grikin, Beijing, China) Ankura (n: 1; Lifetech, Shenzhen, China) or E-vita thoracic stent graft (n: 1; Jotec Company, Hechingen, Germany) or homemade stentgraft (n: 26)], and in 1456 cases nonbare stent proximal configuration was utilized [TAG (n: 931; W. L. Gore & Associates, Flagstaff, AZ) or Zenith TX (n: 239; Cook Medical, Bloomington, IN) or Zenith TX2 (n: 160; Cook Medical, Bloomington, IN) or AneuRyx (n: 31; Medtronic Vascular, Santa Rosa, CA) or Valiant nonbare stent (n: 1; Medtronic Vascular, Santa Rosa, CA) or homemade stent-graft (n: 94)]. The incidence of RTAD was not significantly different in patients with proximal bare stent and nonbare stent endografts (2.8 vs 1.9%, P = 0.1298).

Indication for TEVAR The results of the 29 series8,9,11,12,14,15,17–20,25–29,31,34,40,44,45,48, reporting the indication for TEVAR in their total experience were pooled with data from the MOTHER registry. The incidence of RTAD varied significantly according to the initial indication for TEVAR (P < 0.0001). The incidence of RTAD after TEVAR was 4% (81/2004) for type B aortic dissec-

50–52,54–56,57,59

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tion, 0.9% (12/1315) for degenerative aneurysm, and 0% for either traumatic aortic transection or penetrating aortic ulcer. Fourteen series11,14,15,17,24,25,28,29,31,32,36,44,48,50,51,56,57,59 reported the temporal classification of the dissection, and these were pooled with data from the MOTHER registry. The incidence of RTAD after TEVAR for acute type B aortic dissection was 8.4% (26/309) and 3% (10/325) for chronic dissection. The OR of RTAD (relative to a degenerative aneurysm) was 10.0 (CI: 4.7–21.9) for an acute aortic dissection and 3.4 (CI: 1.3–8.8) for a chronic aortic dissection.

Proximal Landing Zone and RTAD The results of the 20 series8,9,11,13,1517,24,25,28,29,31,32,36,44,48, reporting the proximal landing zone in their total experience were pooled with data from the MOTHER registry. The rate of RTAD after TEVAR varied significantly according to the proximal Ishimaru landing zone; 6.8% (8/118) in zone 0, 2.4% (2/85) in zone 1, 4.1% (28/691) in zone 2, and 1.3% (17/1346) in zones 3 and 4, P < 0.0001). The OR of RTAD relative to zone 3 or 4 was 5.7 in zone 0 (CI: 2.1–14.4), 1.9 in zone 1 (CI: 0.2–8.2), and 3.3 in zone 2 (CI: 1.8–6.6). The differences in indication for TEVAR and proximal landing zone between patients with and without RTAD remained significant after accounting for multiplicity of testing with the Holm-Bonferroni method with a preselected significance level of 0.05. 50–52,56,58,59

DISCUSSION Endovascular repair of the thoracic aorta has become a firstline therapy for many diseases of the descending thoracic aorta.60 Despite excellent early outcomes, TEVAR is associated with a specific range of complications that may be attributable to manipulation and deployment of devices within the aortic arch and proximal descending thoracic aorta, particularly RTAD and atheroembolic stroke. RTAD has been extensively described after TEVAR but the precise mechanism has not been elucidated. Suggested etiological factors include damage to the aortic wall by catheters, wires, and endovascular devices and extension of the aortic disease. This study has used high-quality data from the MOTHER registry, aggregated with a systematic review to investigate the timing, etiology, and outcome of RTAD after TEVAR. The combination of the MOTHER database and systematic review was designed to facilitate meaningful analysis by constructing a large enough  C 2014 Lippincott Williams & Wilkins

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TABLE 2. Combined MOTHER and Systematic Review Database: Outcomes

Totaro et al10 Pamler et al 11 Shimono et al12 Pasic et al13 Czermak et al14 Kato et al15 Bethuyne et al16 Fattori et al17 Hansen et al18 Grabenwoger et al19 Lee et al20 Savini et al21 Modine et al22 Dong Xu et al23 Rubin et al24 B¨ockler et al25 Xu et al26 Neuhauser et al27 Dubener et al28 Zipfel et al29 Panos et al30 Flecher et al31 Girdauskas et al32 Kpodonu et al33 Kische et al34 Langer et al35 Kaya et al36 Eggebrecht et al1 Estrera et al37 Piffaretti et al38 Tshomba et al39 Dong et al40 Bellos et al41 Tiwari et al42 She et al43 Oberhuber et al44 Parsa et al45 Geisb¨usch et al46 Chiesa et al47 Kim et al48 Canaud et al49 Williams et al50 Lombardi et al51 Waterman et al52 Lu et al53 Gorlitzer et al54 Qing et al55 Yang et al56 Cochennec et al57 Czerny et al58 Ehrlich et al59 MOTHER3 Total

Nonsurgical Management% (n)

30-Day Mortality,% (n)

0 (0) 0 (0) 0 (0) 0 (0) 0 (0) 0 (0) 0 (0) 0 (0) 66.6 (2) 0 (0) 0 (0) 0 (0) 0 (0) 100 (1) 66.6 (2) 0 (0) 100 (3) 20 (1) 0 (0) 0 (0) 0 (0) 33.3 (1) 0 (0) 57.1 (4) 28.5 (2) 0 (0) 50 (1) 14.3 (9) 0 (0) 0 (0) 0 (0) 31.2 (5) 0 (0) 0 (0) 100 (1) 0 (0) 0 (0) 33.3 (1) 0 (0) 33.3 (1) 0 (0) 16.6 (1) 0 (0) 0 (0) 0 (0) 25 (1) 0 (0) 0 (0) 40 (2) 50 (2) 100 (1) 75 (14) 28.9 (55)

0 (0) 0 0 0 (0) 0 (0) 0 (0) 0 (0) 0 (0) 66.6 (2) 100 (1) 0 (0) 0 (0) 0 (0) 100 (1) 66.6 (2) 100 (1) 33.3 (1) 20 (1) 0 (0) 0 (0) 0 (0) 100 (3) 0 (0) 57.1 (4) 28.5 (2) 0 (0) 50 (1) 42 (20) 0 (0) 100 (1) 0 (0) 25 (4) 0 (0) 0 (0) 0 (0) 0 (0) 0 (0) 66.6 (2) 33.3 (1) 33.3 (1) 0 (0) 33.3 (2) 0 (0) 0 (0) 0 (0) 25 (1) 0 (0) 0 (0) 40 (2) 50 (2) 100 (1) 50 (8) 33.6 (64)

database to allow subgroup analysis. In particular it allowed the assessment of the impact of proximal stent configuration on the incidence of retrograde type A dissection. The study has elucidated 3 key novel findings, which have implications for clinical practice and graft design. It has been demonstrated that RTAD was predominately associated with TEVAR performed for type B aortic dissections as opposed to thoracic aneurysms. In addition, RTAD was strongly associated with the extent of device oversizing. Each percentage increase in endograft oversizing above 9% resulted in a relative  C 2014 Lippincott Williams & Wilkins

Retrograde Aortic Dissection After TEVAR

TABLE 3. Incidence of RTAD: Combined Data From MOTHER, and Published Literature From Units Reporting Incidence of RTAD Alongside Both Their Whole Experience of TEVAR As Well As Proximal Stent Graft Configuration BS

NonBS

Ration BS/No BS

Stent-Graft Involved

Pamler et al11 Shimono et al12

2 0

0 1

3/11 0/37

Czermak et al14 Kato et al15

1 0

0 1

14/4 0/38

Hansen et al16 Grabenwoger et al19 Lee et al20

3 1 1

0 0 0

28/32 32/48 26/20

Dong Xu et al23 B¨ockler et al25 Xu et al26

3 0 4

0 1 0

30/0 6/31 63/0

Dubener et al28 Kpodonu et al33 Kische et al34 Kaya et al1 Oberhuber et al44 Parsa et al45 Kim et al48 Canaud et al49

1 0 1 2 0 0 3 1

0 7 0 0 1 2 0 3

13/0 0/287 180/0 113/0 10/19 1/50 41/0 42/140

Williams et al50

2

4

43/266

Lombardi et al51 Waterman et al52 Gorlitzer et al54 Qing et al55 Yang et al56 Cochennec et al57

0 0 4 0 0 2

3 1 0 1 1 2

0/40 0/16 24/5 0/32 0/61 7/10

Ehrlich et al59 Bavaria et al8 Matsumura et al9 MOTHER3

1 — — 16

0 0 0 0

29/0 0/137 0/160 997/13

Talent (2) Homemade nonbare stent Talent (1) Homemade nonbare stent Talent (3) Talent (3) Homemade bare stent Talent (3) TAG (1) Talent or Vasoflow or Aegis Talent (1) TAG (7) Talent (1) Talent (2) TAG (1) Zenith TX (1) Talent/Valiant (3) Valiant (1) TAG (3) Talent (2) Zenith TX (2) TAG (2) Zenith TX (3) Zenith TX (1) Valiant (4) Zenith TX (1) Zenith TX (1) Valiant (2) Zenith TX (2) Talent (1)

Total

48

28

1724/1159

2.8%

2.4%

2883

RR

Talent (8) Valiant (8) Talent (1) Valiant (18)

BS indicates proximal bare stent.

increased risk of RTAD by 14%. Finally, the effect of the proximal endograft configuration was investigated. There appeared to be no effect of graft configuration on the incidence of RTAD, with proximal bare stent configuration having an equivalent incidence of RTAD to endografts with no proximal bare spring. Clearly, RTAD is associated with damage to the aortic wall during TEVAR. The extent of aortic wall damage and the likelihood of RTAD will be determined by the fragility of the aortic wall and the magnitude of the trauma. The results of this study suggest that the fragility of the aortic wall predisposes to RTAD. A significantly greater proportion of patients who developed RTAD were initially treated for aortic dissection with the majority of these having acute dissection. In this study, the aggregated data revealed that the odds ratio for RTAD in acute dissection was 10.0 when compared with patients with degenerative thoracic aneurysms. Experience from open surgical repair confirms that the aortic wall is fragile in www.annalsofsurgery.com | 393

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acute dissection and this fragility appears to translate into a higher incidence of RTAD after TEVAR. The influence of acute dissection and aortic fragility on RTAD has been illustrated in other reports. Hata et al61 reported a 2.2% incidence of RTAD in a cohort of 180 patients treated with best medical therapy for acute type B dissection, a similar incidence to that described after TEVAR. Dong et al62 revealed the outcome of TEVAR in patients with Marfan syndrome and aortic dissection. In this report describing 4 patients without previous ascending replacement, 3 developed RTAD. This study also demonstrated that the extent of graft oversizing was associated with an increased risk of RTAD. Increased graft oversizing (>9%) appeared to translate to an increased relative risk of RTAD by 14% for each percent oversize. This is an important point for clinical practice and suggests that in patients with aortic fragility (acute aortic dissection and patients with connective tissue disease), endograft sizing should consider the increased risk of RTAD. Many clinicians now consider a 10% oversize to be appropriate in patients with acute aortic dissection. There has been a debate for the last few years about whether thoracic endografts should be specific for the pathology treated, with differing graft designs and configurations for thoracic dissections and aneurysms. This debate has been stimulated, in part, by reports that have suggested that a proximal bare stent configuration is associated with an increased risk of RTAD.1,23,27,50 The evidence base for the culpability of bare proximal stents is largely circumstantial due to the lack of comparative groups in previous reports and the small sample size of institutional case series. This study demonstrated that stent grafts with proximal bare stent configuration (61.5%) are the most frequently utilized devices for TEVAR. However, this study also observed that there was no difference in the incidence of RTAD in patients treated with endografts with bare stent or nonbare stent configuration. It remains likely that there are other endograft specific factors, in addition to the proximal configuration, that impact on the development of RTAD. In particular, the extent of graft oversizing should be stressed. This study also observed that deployment of the stent-graft in the aortic arch (zone 0–2) is also a significant risk factor of RTAD, with a high odds ratio in zone 0. The association of RTAD in proximal aortic arch procedures has been previously observed. In a transcontinental registry,58 the incidence of RTAD has been reported in up to 7.5% during zone 0 total debranching. Several attempts have been made to clarify this association. This increased risk may result from aortic side-clamping under pulsatile flow. In one study,63 acute ascending aortic dissection was reported in 0.97% after off-pump coronary artery bypass surgery. Van Prehn et al64 have reported the significant compliance of the ascending aorta. This compliance mismatch between the still rigid stent-graft and the compliant ascending aorta might further be evaluated as a concurrent mechanism for the increased incidence of RTAD that is seen with the zone 0 proximal landing zone. The incidence of RTAD has dramatically increased after 2010. This higher rate could be explained by the fact that the complexity of the reconstructions has become greater as the technology has evolved. In this study, the majority of RTAD occurred intraoperatively (20.9%) or in the immediate postoperative (50%) period. The occurrence of the RTAD during the perioperative course underlines the likely trigger effect of the endovascular repair. Nevertheless, 29.1% of the patients suffered a RTAD 30 days after the procedure. This lapse of time between the procedure and RTAD supports that this complication can also be related to the natural progression of the disease itself or to a chronic interaction between the endograft and the aortic wall.

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This study has several limitations including the lack of uniform reporting standards in the reports utilized in the systematic review. Unfortunately, procedural data that might predispose to retrograde dissection such as the use of proximal stent graft extensions, intraoperative ballooning, and intraoperative type I endoleak were not consistently reported in most of the articles included in the review and so cannot be commented on in this article. The MOTHER data set was a well validated, prospectively collected registry but did not have extensive core laboratory data, which limited the amount of aortic morphological variables in the study.

CONCLUSIONS Although RTAD after TEVAR is an uncommon complication, it has a high mortality rate, and the future evolution of TEVAR will need to address this complication. This study adds considerably to the understanding of RTAD after TEVAR. The importance of considering the fragility of the aortic wall is emphasized by the fact that RTAD is significantly more frequent in patients treated for acute and chronic type B dissection. The technical aspects of TEVAR have been shown to influence RTAD with oversizing of the endograft being implicated. Inappropriate endograft oversizing, particularly in patients with aortic wall fragility, should be avoided. Iteration of endograft design will be important in reducing the incidence of RTAD, but this study suggests that the presence of a bare proximal stent does not lead to an increased rate of RTAD.

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Annals of Surgery r Volume 260, Number 2, August 2014

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Retrograde aortic dissection after thoracic endovascular aortic repair.

To provide data regarding the etiology and timing of retrograde type A aortic dissection (RTAD) after thoracic endovascular aortic repair (TEVAR)...
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