- Email: [email protected]
Can Frozen Elephant Trunk Cure Type I Dissection Confined to Thoracic Aorta in Marfan Syndrome?
Journal Pre-proof Can Frozen Elephant Trunk Cure Type I Dissection Confined to Thoracic Aorta in Marfan Syndrome? Yu Chen, MD, Wei-Guo Ma, MD, Jian-Rong Li, MD, Jun Zheng, MD, Qing Li, MD, Yong-Min Liu, MD, Jun-Ming Zhu, MD, Li-Zhong Sun, MD PII:
S0003-4975(19)31276-7
DOI:
https://doi.org/10.1016/j.athoracsur.2019.07.051
Reference:
ATS 32974
To appear in:
The Annals of Thoracic Surgery
Received Date: 30 January 2019 Revised Date:
17 June 2019
Accepted Date: 15 July 2019
Please cite this article as: Chen Y, Ma WG, Li JR, Zheng J, Li Q, Liu YM, Zhu JM, Sun LZ, Can Frozen Elephant Trunk Cure Type I Dissection Confined to Thoracic Aorta in Marfan Syndrome?, The Annals of Thoracic Surgery (2019), doi: https://doi.org/10.1016/j.athoracsur.2019.07.051. 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. © 2019 by The Society of Thoracic Surgeons
Can Frozen Elephant Trunk Cure Type I Dissection Confined to Thoracic Aorta in Marfan Syndrome? Yu Chen, MD,1 Wei-Guo Ma, MD,1,2 Jian-Rong Li, MD,1 Jun Zheng, MD,1,2 Qing Li, MD,1 Yong-Min Liu, MD,1,2 Jun-Ming Zhu, MD,1,2 and Li-Zhong Sun, MD1,2
Running head: Can FET cure type I dissection in MFS? 1
Department of Cardiovascular Surgery, Beijing Anzhen Hospital, Capital Medical
University, and Beijing Institute of Heart Lung and Blood Vessel Diseases; 2Fu Wai Hospital and Cardiovascular Institute, Chinese Academy of Medical Sciences, Beijing, China
Drs. Ma and Chen contributed equally to this work
Presented at the 55th STS Annual Meeting, San Diego, CA, January 27-29, 2019
Corresponding Author: Li-Zhong Sun Department of Cardiovascular Surgery Beijing Anzhen Hospital Beijing 100029, China E-mail: [email protected] Word Count: 4631
1
ABSTRACT Background: To evaluate the long-term impact of frozen elephant trunk (FET) on the distal aorta of patients with Marfan syndrome (MFS) sustaining type I dissection confined to the thoracic aorta (above diaphragmatic hiatus).
Methods: Between 2003 and 2016, 42 MFS (Ghent/revised Ghent criteria) patients (age 33.3±8.9 years; 27 men, 64.3%) with type I dissection above diaphragmatic hiatus involving the arch (22 acute, 52.4%) underwent total arch replacement and FET. Dissection extended distally to mid-descending aorta in 32 (76%) and to above diaphragmatic hiatus in 10 (24%). Operative mortality was 4.8% (2/42). Follow-up was 100% at 6.3±3.0 years.
Results: Maximal aortic sizes (DMaxs) at mid-descending aorta, diaphragmatic hiatus, renal arteries and largest segment of abdominal aorta were 22.8, 21.1, 19.1 and 19.9 mm preoperatively and 23.1, 22.0, 19.8 and 22.4 mm on latest CTA. Dilation and complete remodeling of distal aorta occurred in 10.0% (4/40) and 90% (36/40), respectively. There were 1 late death and 3 distal reoperations. Preoperative abdominal aortic DMax was predictive of distal dilatation (mm) (hazard ratio, HR=1.78, p=0.021) and reoperation (≥ versus <25 mm) (HR=12.88, p=0.037). At 10 years, freedom from dilation, reoperation and
death were 69.8%, 78.1% and 90.0%, respectively. At 8 years, the rates of death, reoperation and reoperation-free survival were 10%, 11% and 79%, respectively.
2
Conclusions: The FET technique has a positive remodeling impact on type I dissection confined to thoracic aorta in MFS patients. This study adds evidence supporting the safety and durability of this extended approach for aortic dissection in Marfan syndrome.
Keywords: Aortic dissection; Marfan syndrome; frozen elephant trunk; Reoperation; Survival; Outcomes
3
Despite the continued improvement in the surgical outcomes of the frozen elephant trunk (FET) technique for type A aortic dissection, the fate of distal aorta after FET remains largely unknown due to the scarcity of imaging data on how the aorta behaves in the long term [1-3]. However, the use of endovascular and open stent grafts for aortic dissection in patients with Marfan syndrome (MFS) sustaining aortic dissection remains controversial because of their inherently weakened aortic wall [4]. Since 2003, we have been using FET for aortic dissection in MFS and achieved favorable early and long-term survival, freedom from reintervention and aortic remodeling [5-7]. Particularly, patients with complete periFET aortic remodeling had higher survival and freedom from reoperation [7]. In this study, we seek to evaluate the long-term clinical and radiological outcomes of the FET technique for type I aortic dissections confined to the thoracic aorta based on our experience over a 15year period.
PATIENTS AND METHODS The Ethics Committees of Beijing Anzhen Hospital of Capital Medical University and Fu Wai Hospital of Chinese Academy of Medical Sciences approved this retrospective study.
Patients Between September 2003 and August 2016, we performed TAR and FET for 42 patients with MFS (27 males, 64.3%) sustaining type I dissection involving the arch but above the diaphragm hiatus (22 acute, 52.4%). Mean age was 33.3±8.9 years (range 17-57). The diagnosis of MFS was based on the Ghent and/or revised Ghent criteria. According to the 14-day cutoff, there were 22 acute and 20 chronic patients (12 presented after 14 days from
4
symptom onset, 6 were diagnosed with an incidental CT finding, and 2 referred for repair of residual dissection left in a prior acute dissection surgery). The mean time from onset to surgery were 4.9 and 242 days (median 3 and 30), respectively (Table 1). The entry tear was located in the ascending aorta in 38 patients (90.5%) and in the arch and proximal descending aorta in 4 (9.5%). The extent of dissection was to mid-descending aorta in 76.2% (32/42) and above diaphragmatic hiatus in 23.8% (10/42). Dissection involved the arch vessels in 41 patients (97.6%), including innominate artery (IA) in 90.5% (38/42), left carotid artery (LCA) in 90.5% (38/42) and left subclavian artery (LSA) in 83.3% (35/42). The sizes of the arch vessels and maximal aortic diameters (DMax, mm) at the levels of the aortic sinus, arch, proximal and mid-descending aorta, diaphragm, renal arteries and abdominal aorta (AbAo) are listed in Table 1. Seven cases of malperfusion syndrome occurred in 5 patients, 3 of whom were with acute dissection (Table 1).
Surgical Indications and Techniques For Marfan patients with type I dissection, TAR + FET is indicated in the following pathologies: 1) an intimal tear located in the arch or descending aorta; 2) aneurysm of the arch or proximal descending aorta (> 40 mm in diameter); 3) dissection, aneurysm, or occlusion of the arch vessels. Our surgical techniques of FET (the Sun operation [8]) have been described in detail previously [5, 9, 10]. In brief, the procedure involves deployment of an FET (Cronus®, MicroPort Medical, Shanghai, China) in the descending aorta, followed by total arch replacement with a 4-branched vascular graft (Maquet Cardiovascular, Wayne, NJ). To minimize the time of cerebral, myocardial, and spinal cord ischemia, distal reperfusion is
5
initiated once the distal anastomosis is completed, and the LCA is reconstructed first (after which rewarming is started and the brain is perfused bilaterally), followed by the ascending aorta (to resume myocardial perfusion), then the LSA, and finally the IA. SACP time refers to the interval from the start of deep hypothermic circulatory arrest to completion of LCA anastomosis. Our neuroprotection strategy includes unilateral selective antegrade cerebral perfusion, distal first strategy to prevent spinal cord ischemia, reconstructing the LCA first, and routine use of neuromonitoring (near-infrared spectroscopy and bispectral index) in high risk patients.
Follow-up and Study Endpoints Clinical and radiological follow-up [7] was complete in 100% (40/40) at mean 6.3±3.0 years (median, 6.1; range, 1.8-12.6). The primary endpoints included late death and distal aortic reoperations. Dilatation of unresected distal aorta was defined as a DMax of > 50 mm (45 mm for a family history of aortic surgery or rupture) or an average growth rate of > 5 mm/year at any segment on CTA.
Statistical Analysis Statistical analysis was performed using Stata 15.1 for Mac (StataCorp, College Station, TX). Data are expressed as the mean ± standard deviation (SD) or number (percentage) and compared using Student t test or Pearson χ2 test for normal distributions, and Mann-Whitney U test for abnormal distributions. Risk factors for distal aortic dilatation (binary), reoperation and late death were identified
6
with Cox regression. Survival and freedom from aortic dilatation and reoperation were estimated using the Kaplan-Meier method. Competing risks of late death and reoperation were analyzed with the Fine and Gray proportional hazards model. A 2-sided p value of < 0.05 was considered statistically significant.
RESULTS Operative Data The times of cardiopulmonary bypass, cross-clamp and selective unilateral antegrade cerebral perfusion were 182.0±36.2, 99.8±30.2, 22.6±6.9 minutes, respectively. Bentall procedure was performed in 39 patients (92.9%) (Table 2).
Operative Mortality and Morbidity Operative mortality was 4.8% (2/42) (Table 2). The causes of death were multiorgan failure and distal aortic rupture in 1 each (2.4%). Complications included stroke in 1 (2.4%), acute renal failure in 1 (2.4%), low cardiac output in 2 (4.8%), and reexploration for bleeding and distal aortic rupture, in 1 each (2.4%). No patients sustained spinal cord ischemia postoperatively. One patient (2.4%) complained of diplopia and became lethargic at 6 postoperative days. CTA detected an occluded IA, which was successfully managed with thrombectomy and LSA-to-IA bypass at 19 days. At discharge, CTA detected a type Ia and type Ib endoleak in 1 patient each.
Changes of Distal Aorta
7
False lumen thrombosis and remodeling of distal aorta Discharge CTA showed that complete coverage of the extent of dissection was achieved in 73.8% of patients (31/42), which did not differ between significantly the acute and chronic groups (72.8% vs 75%, p = 0.862). FL obliteration occurred at the proximal end of FET in 97.5% (39/40). At the levels of FET distal end, unstented descending aorta, diaphragmatic hiatus and AbAo, the FL was obliterated in 95.0%, 100.0%, 100.0% and 100.0%; partially thrombosed in 2.5%, 0%, 0% and 0%; and was patent in 2.5%, 0%, 0% and 0%, respectively. On the latest follow-up CTA, false lumen obliteration was observed at the proximal and distal ends of FET in 100% (40/40) and 97.5% (39/40), down to mid-descending aorta in 97.5% (39/40), diaphragmatic hiatus in 100.0% (40/40) and AbAo in 100.0% (40/40). As shown in Table 3, there was no significant difference in aortic remodeling at all levels between the acute and chronic groups.
Growth rates and distal aortic dilatation The DMaxs at the levels of the FET, unstented descending aorta, diaphragmatic hiatus, renal arteries and AbAo averaged 29.2, 23.1, 22.0, 19.8 and 22.4 mm on the latest CTA, respectively, as compared to 29.2, 22.8, 21.1, 19.1 and 19.9 preoperatively. The respective growth rates were – 0.03, 0.04, 0.22, 0.13 and 0.38 mm/year. The DMax at renal arteries and AbAo grew significantly in patients with a preoperative AbAo DMax of ≥ 25 mm vs < 25 mm (0.68 vs 0.08 mm/year, p = 0.029; 3.22 vs 0.13 mm/year, p = 0.096) (Table 4). Distal aortic dilation occurred in 4 patients, and complete remodeling of the distal aorta was observed in 90.0% (36/40) (Figure 1).
8
The freedom from distal aortic dilatation was 96.4% (95% confidence interval, CI 77.299.5%) and 69.8% (95% CI, 33.5-88.9%) at 5 and 10 years, respectively (Figure 2). At 9 years, freedom from distal dilatation was higher in patients with a preoperative AbAo of < 25 mm (vs ≥ 25 mm) (0% vs 87.5%, p < 0.001).
Fate of Dissected Arch Vessels By the latest follow-up, residual dissection was seen in the IA in 65.0% (26/40), LCA in 30.0% (12/40) and in the LSA in 20.0% (8/40). Of the 36 patients with CT measurements, the IA (distal to the vascular graft) averaged 13.1±3.7 mm in size, measuring 1-2 cm in 72.2% (26/36) and > 2 cm in 5.6% (2/36); the LCA and LSA averaged 8.1±1.0 and 8.2±1.2 mm in size, which were > 1 cm in 8.3% (3/36) and 5.6% (2/36), respectively. Arch vessel stenosis was observed in 12.5% (5/40), including the LSA in 2, and LCA and IA, in 1 each.
Late Aortic Events Five patients developed distal aortic dilation (1 with a distal new entry), 3 of whom were managed with reintervention and 2 were closely monitored. The type Ia endoleak resolved spontaneously at 3 years. The patient with type Ib endoleak was rigorously monitored.
Reoperation Three patients with distal aortic dilation underwent reintervention at mean 7.5±1.4 years (6.0-8.8), including thoracoabdominal aortic replacement, AbAo replacement and endovascular repair (TEVAR) for distal new entry, in one each. Distal aortic DMax was
9
46.0±14.4 mm (range, 30-58 mm) at reintervention. All three patients survived to the latest follow-up. The freedom from distal reoperation was 100.0% (95% CI, 100.0%) and 78.1% (95% CI, 44.2-92.8%) at 5 and 10 years, respectively (Figure 3). At 9 years, freedom from distal aortic reoperation was significantly higher in patients with a preoperative AbAo DMax of < 25 mm (vs ≥25 mm) (87.5% vs 33.3%, p = 0.007).
Late Survival One patient died of non-aortic cause at 6.3 years (Table 2). Survival was 95.2% (95% CI, 82.3-98.8%) and 90.0% (95% CI, 69.5-97.0%) at 5 and 10 years, respectively (Figure 4), which did not differ between the acute and chronic groups (p = 0.702). In competing risks analysis, the incidence was 10% for death, 11% for distal reoperation, and event-free survival was 79% at 8 years (Figure 5).
Risk Factors for Distal Aortic Dilation and Reoperation The preoperative maximal size of the abdominal aorta was predictive of distal aortic dilatation (mm) (hazard ratio, HR = 1.78; 95% Cl, 1.09-2.91; p = 0.021) and distal reoperation (binary, ≥ 25 vs < 25 mm) (HR = 12.88; 95% Cl, 1.16-143.08; p = 0.037).
COMMENT Although there are weak recommendations of using extended arch repair and stent grafting for connective tissue disorders in more recent guidelines [11, 12], there has been continued explorations of using the FET and endografting techniques in patients with MFS [13, 14]. Major concerns over the use of FET in MFS pertain to the inheritably weakened 10
aortic wall, the durability of the stent grafts, and scarcity of long-term data on survival, reintervention and aortic remodeling [15]. This study addresses these concerns by showing that the FET technique had a positive remodeling impact on type I aortic dissection confined to the thoracic aorta. The most important finding of this study is that the FET technique induced complete remodeling of the distal aorta in MFS patients with type I dissection confined to the thoracic aorta. Because residual dissection and persistent patent FL in the descending aorta are risk factors for late aortic dilatation and adversely affect the long-term prognosis in MFS patients [16, 17], ideally complete obliteration of the false lumen in the distal aorta will “cure” such patients of the dreadful dissection. In literature, 30% and 21.6% of patients achieved complete recovery of dissection after total arch replacement without FET [16] and the FET could achieve FL obliteration across the FET in 69-100% [2, 10, 16, 18-20]. In our previous study of 172 MFS patients, complete aortic remodeling was achieved across the FET in 56% and down to the mid-descending aorta in 28.8%. In the present study, the FET technique achieved complete aortic remodeling of the entire thoracic aorta in 90.0% of patients, which shows FL obliteration and normal aortic structure and size. Two recent studies showed that positive remodeling was observed in 44-48% at the diaphragm at 4 years [1, 2]. However, these two studies include only 8 patients with MFS. In contrast, the present cohort of 42 MFS patients has proved that the FET could achieve similar or superior long-term clinical results and aortic remodeling in MFS as compared to non-MFS patients. In addition, the relative short length of dissected aortic segment in this series makes it possible for the FET to exert similar impact on the false lumen and aortic wall, which led to similar remodeling in acute and chronic patients. These results argue that the FET technique may be the most appropriate treatment option for MFS patients with type I dissection confined to the thoracic aorta, given its advantage of the positive remodeling effect and avoidance of problematic issues associated with staged repair [21]. Furthermore, in MFS patients with type I
11
dissection extending beyond the diaphragm, it may be reasonable to use a longer FET or add a bare-metal stent distally to promote remodeling across longer segments of distal aorta [7, 22]. Another important finding of this study is that the untreated aortic segments remained stable after FET, preventing dissection and rupture of the residual thoracic aorta. Schoenhoff and associates reported that the distal aortic diameter was greater in patients with aortic root surgery than those without [23]. An in vitro model suggested that wall tension in the residual aorta increases after ascending aortic replacement [24]. In this study, there was little growth in the distal aorta after FET, as shown by the stable DMaxs and minimal growth rates at all distal segments upon follow-up CTA. These results have proved the durability of the FET technique in promoting complete remodeling of the distal aorta for MFS patients with type I dissection confined to the thoracic aorta. In the Euro Heart Survey database, 31% of reinterventions in patients with MFS have been performed on the distal aorta [23]. However, it remains unclear how and when a new dissection would happen to affect the primarily untreated aortic segments. Nor has the impact of a preoperative dilated abdominal aorta and aortic growth rate on late outcomes been studied, especially for MFS patients. In this cohort, a patient with a preoperative AbAo of > 25 mm was followed up for 6 years after FET until he underwent thoracoabdominal aortic replacement when his AbAo diameter reached 50 mm. This case shows that the FET technique can delay reintervention on the distal aorta and prevent rupture. We also found that preoperative maximal abdominal aorta size was a predictor for distal aortic dilatation and reoperation, and freedom from distal reoperation was significantly lower in patients with a preoperative maximal AbAo diameter of > 25 mm at 10 years. Therefore, for patients with a preoperative abdominal aortic size of ≥ 25 mm, we recommend close monitoring with
12
ultrasound and CT and surgical repair when the abdominal aorta reaches 5 cm in diameter. In addition, due attention should be paid to MFS patients with irregular distal aortic wall, new entry tears, and other risk factors for atherosclerosis, such as hypertension, hyperlipidemia, and smoking, etc.
Study Limitations The study is limited by its retrospective nature, small sample size and lack of a control group. While the patients in the present cohort were all comers, a selection bias did exist in our work pertaining to some moribund patients with irreversible ischemia and secondary end-organ failure and to a natural selection process during patient transfer from other centers. Although this study suggest that the FET may be an optimal approach to type I aortic dissection confined to thoracic aorta in MFS, this is only our single institution experience. Therefore, this technique may not be directly translatable in other centers and warrants further study in large patient population, preferably in a randomized, controlled and multicenter setting. Most importantly, it should be pointed out that those young Marfan patients (mean age 33 years) continue to face persistent and significant risk of distal aortic dilation, reoperation and death despite a more aggressive operation with total arch replacement and frozen elephant trunk. This is corroborative of Dr. Crawford’s wise comment that "No patient should be considered as cured of the disease" [25], which pertains to aortic dissection patients in general. The present cohort is an even more vulnerable subgroup and the importance of rigorous lifelong clinical and radiologic follow-up in such patients cannot be overemphasized.
Conclusions
13
The results of this study show that frozen elephant trunk technique has a positive remodeling impact on type I dissections confined to thoracic aorta in MFS patients, achieving complete remodeling of the distal aorta and favorable survival and freedom from reoperation in the long term. This study adds evidence supporting the safety and durability of this extended approach in setting of type I aortic dissection for patients with Marfan syndrome.
14
References 1.
Dohle DS, Tsagakis K, Janosi RA, et al. Aortic remodelling in aortic dissection after frozen elephant trunk. Eur J Cardiothorac Surg 2016;49:111-7.
2.
Weiss G, Santer D, Dumfarth J, et al. Evaluation of the downstream aorta after frozen elephant trunk repair for aortic dissections in terms of diameter and false lumen status. Eur J Cardiothorac Surg 2016;49:118-24.
3.
Halstead JC, Meier M, Etz C, et al. The fate of the distal aorta after repair of acute type A aortic dissection. J Thorac Cardiovasc Surg 2007;133:127-35.
4.
Waterford SD, Moon MR. Stent grafting in Marfan syndrome? We are not convinced. J Thorac Cardiovasc Surg 2018;156:1773-5.
5.
Ma WG, Zhang W, Zhu JM, et al. Long-term outcomes of frozen elephant trunk for type A aortic dissection in patients with Marfan syndrome. J Thorac Cardiovasc Surg 2017;154:1175-89 e2.
6.
Chen Y, Ma WG, Zheng J, Liu YM, Zhu JM, Sun LZ. Total arch replacement and frozen elephant trunk for type A aortic dissection after Bentall procedure in Marfan syndrome. J Thorac Dis 2018;10:2377-87.
7.
Chen Y, Ma WG, Zhi AH, et al. Fate of distal aorta after frozen elephant trunk and total arch replacement for type A aortic dissection in Marfan syndrome. J Thorac Cardiovasc Surg 2019;157:835-49.
8.
Ma WG, Zheng J, Zhang W, et al. Frozen elephant trunk with total arch replacement for type A aortic dissections: Does acuity affect operative mortality? J Thorac Cardiovasc Surg 2014;148:963-70; discussion 70-2.
9.
Ma WG, Zhu JM, Zheng J, et al. Sun's procedure for complex aortic arch repair: total arch replacement using a tetrafurcate graft with stented elephant trunk implantation. Ann Cardiothorac Surg 2013;2:642-8.
10. Sun LZ, Qi RD, Chang Q, et al. Surgery for Marfan patients with acute type A dissection using a stented elephant trunk procedure. Ann Thorac Surg 2008;86:1821-5. 11. Appoo JJ, Bozinovski J, Chu MW, et al. Canadian Cardiovascular Society/Canadian Society of Cardiac Surgeons/Canadian Society for Vascular Surgery Joint Position Statement on Open and Endovascular Surgery for Thoracic Aortic Disease. Can J Cardiol 2016;32:703-13.
15
12. Czerny M, Schmidli J, Adler S, et al. Current options and recommendations for the treatment of thoracic aortic pathologies involving the aortic arch. Eur J Cardiothorac Surg 2019;55:133-62. 13. Uchida N, Katayama A, Kuraoka M, et al. Extended aortic repair using frozen elephant trunk technique for Marfan syndrome with acute aortic dissection. Ann Thorac Cardiovasc Surg 2013;19:279-82. 14. Yoshitake A, Shimizu H, Kawaguchi S, Itoh T, Kawajiri H, Yozu R. Hybrid repair of subclavian-axillary artery aneurysms and aortic arch aneurysm in a patient with Marfan syndrome. Ann Thorac Surg 2013;95:1441-3. 15. Sundt TM, 3rd. The can-should problem. J Thorac Cardiovasc Surg 2011;142:e91. 16. Park KH, Lim C, Choi JH, et al. Midterm change of descending aortic false lumen after repair of acute type I dissection. Ann Thorac Surg 2009;87:103-8. 17. Geisbuesch S, Schray D, Bischoff MS, Lin HM, Di Luozzo G, Griepp RB. Frequency of reoperations in patients with Marfan syndrome. Ann Thorac Surg 2012;93:1496501. 18. Girdauskas E, Kuntze T, Borger MA, Falk V, Mohr FW. Distal aortic reinterventions after root surgery in Marfan patients. Ann Thorac Surg 2008;86:1815-9. 19. Uchida N, Shibamura H, Katayama A, Shimada N, Sutoh M, Ishihara H. Operative strategy for acute type A aortic dissection: ascending aortic or hemiarch versus total arch replacement with frozen elephant trunk. Ann Thorac Surg 2009;87:773-7. 20. Pacini D, Tsagakis K, Jakob H, et al. The frozen elephant trunk for the treatment of chronic dissection of the thoracic aorta: a multicenter experience. Ann Thorac Surg 2011;92:1663-70; discussion 70. 21. Ikeno Y, Yokawa K, Nakai H, et al. Results of staged repair of aortic disease in patients with Marfan syndrome. J Thorac Cardiovasc Surg 2019;157:2138-47.e2. 22. Ma WG, Zheng J, Sun LZ, Elefteriades JA. Open stented grafts for frozen elephant trunk technique: Technical aspects and current outcomes. Aorta (Stamford) 2015;3:122-35. 23. Schoenhoff FS, Carrel TP. Re-interventions on the thoracic and thoracoabdominal aorta in patients with Marfan syndrome. Ann Cardiothorac Surg 2017;6:662-71. 24. Scharfschwerdt M, Leonhard M, Lehmann J, Richardt D, Goldmann H, Sievers HH. In vitro investigation of a novel elastic vascular prosthesis for valve-sparing aortic root
16
and ascending aorta replacement. Eur J Cardiothorac Surg 2016;49:1370-3. 25. Crawford ES. The diagnosis and management of aortic dissection. JAMA 1990;264:2537-41.
17
TABLE 1. Preoperative clinical profiles Variable
Total (n = 42)
Age, y 33.3±8.9 Male gender, n (%) 27 (64.3%) Time from onset to diagnosis, day 188 ± 596 Median (interquartile range) 3.5 (1-16.5) Time from onset to surgery, day 208 ± 598 Median (interquartile range) 16.5 (4.8-57.3) Hypertension, n (%) 14 (33.3%) Smoking history, n (%) 10 (23.8%) Family history of aortic dissection, n (%) 16 (38.1%) History of proximal aortic surgery, n (%) 5 (11.9%) Composite root replacement 3 (7.1%) Aortic valve replacement 1 (2.4%) Wheat procedure 1 (2.4%) Preoperative aortic size, mm Aortic sinus 66.5±14.4 Aortic arch 31.3±7.6 Proximal descending aorta 29.2±5.4 Mid-descending aorta 22.8±2.9 Diaphragm 21.1±2.2 Renal arteries 19.1±2.3 Abdominal aorta 19.9±2.7 Aortic regurgitation, n (%) Moderate 11 (26.2%) Severe 26 (61.9%) Malperfusion syndrome, n (%) 5 (11.9%) Stroke 1 (2.4%) Acute myocardial infarction 1 (2.4%) Acute cardiac tamponade 3 (7.1%) Acute heart failure 1 (2.4%) Arch vessel involvement, n (%) Innominate artery 38 (90.5%) Left carotid artery 38 (90.5%) Left subclavian artery 35 (83.3%)
Acute (n = 22)
Chronic (n = 20)
P value
33.5±9.0 15 (68.2%) 3.7 ± 3.9 2 (1- 4.8) 7.2 ± 5.8 5 (2.8-12.3) 7 (31.8%) 6 (27.3%) 10 (45.5%) 1 (4.5%) 0 1 (4.5%) 0
33.2±9.1 12 (60.0%) 391 ± 828 18 (3-365) 428 ± 821 63.5 (32.3-371) 7 (35.0%) 4 (20.0%) 6 (30.0%) 4 (20.0%) 3 (15.0%) 0 1 (5.0%)
62.5±12.0 28.8±3.0 27.2±2.5 22.5±1.9 21.5±2.4 19.0±2.0 20.2±2.7
71.6±16.0 34.3±10.3 31.4±6.8 23.2±3.8 20.6±2.1 19.4±2.6 19.7±2.9
5 (22.7%) 16 (72.7%) 3 (13.6%) 1 (4.5%) 0 2 (9.1%) 0
6 (30.0%) 10 (50.0%) 2 (10.0%) 0 1 (5.0%) 1 (5.0%) 1 (5.0%)
0.716 0.335 0.288 0.607 0.288
19 (86.4%) 20 (90.9%) 19 (86.4%)
19 (95.0%) 18 (90.0%) 16 (80.0%)
0.341 0.920 0.580
0.901 0.580 0.050 0.034 0.827 0.580 0.303 0.122 0.059 0.335 0.288 0.047 0.042 0.020 0.454 0.226 0.597 0.571 0.203
18
TABLE 2. Operative and late outcomes Variable Operative Data Cardiopulmonary bypass time, min Cross-clamp time, min Antegrade cerebral perfusion time, min Concomitant procedures Composite root replacement Coronary artery bypass grafting Frozen elephant trunk Diameter, mm Length, cm Postoperative maximal aortic diameter, mm Proximal descending aorta Mid-descending aorta Diaphragm hiatus Renal arteries Abdominal aorta (most dilated segment) Operative Outcomes Operative mortality Complication and reintervention Stroke Low cardiac output Acute renal failure Distal aortic rupture Reexploration for bleeding Innominate artery occlusion Type I endoleak Late Outcomes Late death Distal aortic dilatation Distal new entry Distal reintervention Thoracoabdominal aortic aneurysm repair Thoracic endovascular aortic repair
Total (n = 42)
Acute (n = 22)
Chronic (n = 20)
p value
182.0±36.2 99.8±30.2 22.6±6.9
185.7±35.2 110.8±35.0 23.8±7.8
178.0±37.8 88.3±18.8 21.4±5.8
0.502 0.015 0.281
39 (92.9%) 3 (7.1%)
22 (100%) 1 (4.5%)
17 (85.0%) 2 (10.0%)
0.059 0.493
25.7±1.3 10.2±0.9
25.5±1.3 10.2±0.6
25.9±1.4 10.2±1.1
0.338 0.803
29.2±3.9 23.1±2.9 22.0±2.6 19.8±3.7 22.4±8.7
28.2±2.1 23.3±2.6 22.9±2.9 20.0±3.5 22.8±8.2
30.4±5.0 22.8±3.2 21.1±1.8 19.6±3.9 21.9±9.4
0.111 0.555 0.035 0.741 0.736
2 (4.8%) 4 (9.5%) 1 (2.4%) 2 (4.8%) 1 (2.4%) 1 (2.4%) 1 (2.4%) 1 (4.8%) 2 (4.8%)
1 (4.5%) 2 (9.1%) 1 (4.5%) 1 (4.5%) 1 (4.5%) 0 1 (4.5%) 1 (4.5%) 1 (4.5%)
1 (5.0%) 2 (10.0%) 0 1 (5.0%) 0 1 (5.0%) 0 0 1 (5.0%)
0.945 0.920 0.335 0.945 0.335 0.288 0.335 0.335 0.945
1 (2.5%) 4 (10.0%) 1 (2.5%) 3 (7.5%) 2 (5.0%) 1 (2.5%)
1 (4.8%) 3 (14.3%) 1 (4.8%) 2 (9.5%) 1 (4.8%) 1 (4.8%)
0 1 (5.3%) 0 1 (5.3%) 1 (5.3%) 0
0.335 0.342 0.335 0.609 0.942 0.335
19
TABLE 3. Complete remodeling of distal aorta between acute and chronic patients Aortic segment Frozen elephant trunk
Acute (n = 21, %) Remodeling No 100.0 0
Chronic (n = 19, %) Remodeling No 94.7 5.3
p value 0.287
Unstented descending aorta
95.2
4.8
100.0
0
0.335
Diaphragmatic hiatus
95.2
4.8
100.0
0
0.335
Abdominal aorta
95.2
4.8
94.7
5.3
0.942
20
TABLE 4. Aortic growth rates stratified by preoperative maximal abdominal aortic size Growth rate (mm/year) Frozen elephant trunk
Total Preoperative maximal abdominal aortic size p value (n = 37) < 25 mm (n = 34) ≥ 25 mm (n = 3) 0.24 0.618 –0.03 –0.06
Unstented descending aorta
0.04
0.01
0.35
0.112
Diaphragm hiatus
0.22
0.23
0.15
0.700
Renal arteries
0.13
0.08
0.68
0.029
Abdominal aorta (most dilated part)
0.38
0.13
3.22
0.096
21
Figure Legends Figure 1. In an MFS patient with type I aortic dissection (A), CTA at 8 years after frozen elephant trunk (FET) procedure showed complete aortic remodeling beyond the FET (red arrow), as evidenced by disappeared false lumen and normal distal aortic structure and diameter
Figure 2. Freedom from distal aortic dilatation
Figure 3. Freedom from reoperation
Figure 4. Kaplan-Meier survival
Figure 5. Competing risks of death and reoperation
22
S0003-4975(19)31276-7
DOI:
https://doi.org/10.1016/j.athoracsur.2019.07.051
Reference:
ATS 32974
To appear in:
The Annals of Thoracic Surgery
Received Date: 30 January 2019 Revised Date:
17 June 2019
Accepted Date: 15 July 2019
Please cite this article as: Chen Y, Ma WG, Li JR, Zheng J, Li Q, Liu YM, Zhu JM, Sun LZ, Can Frozen Elephant Trunk Cure Type I Dissection Confined to Thoracic Aorta in Marfan Syndrome?, The Annals of Thoracic Surgery (2019), doi: https://doi.org/10.1016/j.athoracsur.2019.07.051. 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. © 2019 by The Society of Thoracic Surgeons
Can Frozen Elephant Trunk Cure Type I Dissection Confined to Thoracic Aorta in Marfan Syndrome? Yu Chen, MD,1 Wei-Guo Ma, MD,1,2 Jian-Rong Li, MD,1 Jun Zheng, MD,1,2 Qing Li, MD,1 Yong-Min Liu, MD,1,2 Jun-Ming Zhu, MD,1,2 and Li-Zhong Sun, MD1,2
Running head: Can FET cure type I dissection in MFS? 1
Department of Cardiovascular Surgery, Beijing Anzhen Hospital, Capital Medical
University, and Beijing Institute of Heart Lung and Blood Vessel Diseases; 2Fu Wai Hospital and Cardiovascular Institute, Chinese Academy of Medical Sciences, Beijing, China
Drs. Ma and Chen contributed equally to this work
Presented at the 55th STS Annual Meeting, San Diego, CA, January 27-29, 2019
Corresponding Author: Li-Zhong Sun Department of Cardiovascular Surgery Beijing Anzhen Hospital Beijing 100029, China E-mail: [email protected] Word Count: 4631
1
ABSTRACT Background: To evaluate the long-term impact of frozen elephant trunk (FET) on the distal aorta of patients with Marfan syndrome (MFS) sustaining type I dissection confined to the thoracic aorta (above diaphragmatic hiatus).
Methods: Between 2003 and 2016, 42 MFS (Ghent/revised Ghent criteria) patients (age 33.3±8.9 years; 27 men, 64.3%) with type I dissection above diaphragmatic hiatus involving the arch (22 acute, 52.4%) underwent total arch replacement and FET. Dissection extended distally to mid-descending aorta in 32 (76%) and to above diaphragmatic hiatus in 10 (24%). Operative mortality was 4.8% (2/42). Follow-up was 100% at 6.3±3.0 years.
Results: Maximal aortic sizes (DMaxs) at mid-descending aorta, diaphragmatic hiatus, renal arteries and largest segment of abdominal aorta were 22.8, 21.1, 19.1 and 19.9 mm preoperatively and 23.1, 22.0, 19.8 and 22.4 mm on latest CTA. Dilation and complete remodeling of distal aorta occurred in 10.0% (4/40) and 90% (36/40), respectively. There were 1 late death and 3 distal reoperations. Preoperative abdominal aortic DMax was predictive of distal dilatation (mm) (hazard ratio, HR=1.78, p=0.021) and reoperation (≥ versus <25 mm) (HR=12.88, p=0.037). At 10 years, freedom from dilation, reoperation and
death were 69.8%, 78.1% and 90.0%, respectively. At 8 years, the rates of death, reoperation and reoperation-free survival were 10%, 11% and 79%, respectively.
2
Conclusions: The FET technique has a positive remodeling impact on type I dissection confined to thoracic aorta in MFS patients. This study adds evidence supporting the safety and durability of this extended approach for aortic dissection in Marfan syndrome.
Keywords: Aortic dissection; Marfan syndrome; frozen elephant trunk; Reoperation; Survival; Outcomes
3
Despite the continued improvement in the surgical outcomes of the frozen elephant trunk (FET) technique for type A aortic dissection, the fate of distal aorta after FET remains largely unknown due to the scarcity of imaging data on how the aorta behaves in the long term [1-3]. However, the use of endovascular and open stent grafts for aortic dissection in patients with Marfan syndrome (MFS) sustaining aortic dissection remains controversial because of their inherently weakened aortic wall [4]. Since 2003, we have been using FET for aortic dissection in MFS and achieved favorable early and long-term survival, freedom from reintervention and aortic remodeling [5-7]. Particularly, patients with complete periFET aortic remodeling had higher survival and freedom from reoperation [7]. In this study, we seek to evaluate the long-term clinical and radiological outcomes of the FET technique for type I aortic dissections confined to the thoracic aorta based on our experience over a 15year period.
PATIENTS AND METHODS The Ethics Committees of Beijing Anzhen Hospital of Capital Medical University and Fu Wai Hospital of Chinese Academy of Medical Sciences approved this retrospective study.
Patients Between September 2003 and August 2016, we performed TAR and FET for 42 patients with MFS (27 males, 64.3%) sustaining type I dissection involving the arch but above the diaphragm hiatus (22 acute, 52.4%). Mean age was 33.3±8.9 years (range 17-57). The diagnosis of MFS was based on the Ghent and/or revised Ghent criteria. According to the 14-day cutoff, there were 22 acute and 20 chronic patients (12 presented after 14 days from
4
symptom onset, 6 were diagnosed with an incidental CT finding, and 2 referred for repair of residual dissection left in a prior acute dissection surgery). The mean time from onset to surgery were 4.9 and 242 days (median 3 and 30), respectively (Table 1). The entry tear was located in the ascending aorta in 38 patients (90.5%) and in the arch and proximal descending aorta in 4 (9.5%). The extent of dissection was to mid-descending aorta in 76.2% (32/42) and above diaphragmatic hiatus in 23.8% (10/42). Dissection involved the arch vessels in 41 patients (97.6%), including innominate artery (IA) in 90.5% (38/42), left carotid artery (LCA) in 90.5% (38/42) and left subclavian artery (LSA) in 83.3% (35/42). The sizes of the arch vessels and maximal aortic diameters (DMax, mm) at the levels of the aortic sinus, arch, proximal and mid-descending aorta, diaphragm, renal arteries and abdominal aorta (AbAo) are listed in Table 1. Seven cases of malperfusion syndrome occurred in 5 patients, 3 of whom were with acute dissection (Table 1).
Surgical Indications and Techniques For Marfan patients with type I dissection, TAR + FET is indicated in the following pathologies: 1) an intimal tear located in the arch or descending aorta; 2) aneurysm of the arch or proximal descending aorta (> 40 mm in diameter); 3) dissection, aneurysm, or occlusion of the arch vessels. Our surgical techniques of FET (the Sun operation [8]) have been described in detail previously [5, 9, 10]. In brief, the procedure involves deployment of an FET (Cronus®, MicroPort Medical, Shanghai, China) in the descending aorta, followed by total arch replacement with a 4-branched vascular graft (Maquet Cardiovascular, Wayne, NJ). To minimize the time of cerebral, myocardial, and spinal cord ischemia, distal reperfusion is
5
initiated once the distal anastomosis is completed, and the LCA is reconstructed first (after which rewarming is started and the brain is perfused bilaterally), followed by the ascending aorta (to resume myocardial perfusion), then the LSA, and finally the IA. SACP time refers to the interval from the start of deep hypothermic circulatory arrest to completion of LCA anastomosis. Our neuroprotection strategy includes unilateral selective antegrade cerebral perfusion, distal first strategy to prevent spinal cord ischemia, reconstructing the LCA first, and routine use of neuromonitoring (near-infrared spectroscopy and bispectral index) in high risk patients.
Follow-up and Study Endpoints Clinical and radiological follow-up [7] was complete in 100% (40/40) at mean 6.3±3.0 years (median, 6.1; range, 1.8-12.6). The primary endpoints included late death and distal aortic reoperations. Dilatation of unresected distal aorta was defined as a DMax of > 50 mm (45 mm for a family history of aortic surgery or rupture) or an average growth rate of > 5 mm/year at any segment on CTA.
Statistical Analysis Statistical analysis was performed using Stata 15.1 for Mac (StataCorp, College Station, TX). Data are expressed as the mean ± standard deviation (SD) or number (percentage) and compared using Student t test or Pearson χ2 test for normal distributions, and Mann-Whitney U test for abnormal distributions. Risk factors for distal aortic dilatation (binary), reoperation and late death were identified
6
with Cox regression. Survival and freedom from aortic dilatation and reoperation were estimated using the Kaplan-Meier method. Competing risks of late death and reoperation were analyzed with the Fine and Gray proportional hazards model. A 2-sided p value of < 0.05 was considered statistically significant.
RESULTS Operative Data The times of cardiopulmonary bypass, cross-clamp and selective unilateral antegrade cerebral perfusion were 182.0±36.2, 99.8±30.2, 22.6±6.9 minutes, respectively. Bentall procedure was performed in 39 patients (92.9%) (Table 2).
Operative Mortality and Morbidity Operative mortality was 4.8% (2/42) (Table 2). The causes of death were multiorgan failure and distal aortic rupture in 1 each (2.4%). Complications included stroke in 1 (2.4%), acute renal failure in 1 (2.4%), low cardiac output in 2 (4.8%), and reexploration for bleeding and distal aortic rupture, in 1 each (2.4%). No patients sustained spinal cord ischemia postoperatively. One patient (2.4%) complained of diplopia and became lethargic at 6 postoperative days. CTA detected an occluded IA, which was successfully managed with thrombectomy and LSA-to-IA bypass at 19 days. At discharge, CTA detected a type Ia and type Ib endoleak in 1 patient each.
Changes of Distal Aorta
7
False lumen thrombosis and remodeling of distal aorta Discharge CTA showed that complete coverage of the extent of dissection was achieved in 73.8% of patients (31/42), which did not differ between significantly the acute and chronic groups (72.8% vs 75%, p = 0.862). FL obliteration occurred at the proximal end of FET in 97.5% (39/40). At the levels of FET distal end, unstented descending aorta, diaphragmatic hiatus and AbAo, the FL was obliterated in 95.0%, 100.0%, 100.0% and 100.0%; partially thrombosed in 2.5%, 0%, 0% and 0%; and was patent in 2.5%, 0%, 0% and 0%, respectively. On the latest follow-up CTA, false lumen obliteration was observed at the proximal and distal ends of FET in 100% (40/40) and 97.5% (39/40), down to mid-descending aorta in 97.5% (39/40), diaphragmatic hiatus in 100.0% (40/40) and AbAo in 100.0% (40/40). As shown in Table 3, there was no significant difference in aortic remodeling at all levels between the acute and chronic groups.
Growth rates and distal aortic dilatation The DMaxs at the levels of the FET, unstented descending aorta, diaphragmatic hiatus, renal arteries and AbAo averaged 29.2, 23.1, 22.0, 19.8 and 22.4 mm on the latest CTA, respectively, as compared to 29.2, 22.8, 21.1, 19.1 and 19.9 preoperatively. The respective growth rates were – 0.03, 0.04, 0.22, 0.13 and 0.38 mm/year. The DMax at renal arteries and AbAo grew significantly in patients with a preoperative AbAo DMax of ≥ 25 mm vs < 25 mm (0.68 vs 0.08 mm/year, p = 0.029; 3.22 vs 0.13 mm/year, p = 0.096) (Table 4). Distal aortic dilation occurred in 4 patients, and complete remodeling of the distal aorta was observed in 90.0% (36/40) (Figure 1).
8
The freedom from distal aortic dilatation was 96.4% (95% confidence interval, CI 77.299.5%) and 69.8% (95% CI, 33.5-88.9%) at 5 and 10 years, respectively (Figure 2). At 9 years, freedom from distal dilatation was higher in patients with a preoperative AbAo of < 25 mm (vs ≥ 25 mm) (0% vs 87.5%, p < 0.001).
Fate of Dissected Arch Vessels By the latest follow-up, residual dissection was seen in the IA in 65.0% (26/40), LCA in 30.0% (12/40) and in the LSA in 20.0% (8/40). Of the 36 patients with CT measurements, the IA (distal to the vascular graft) averaged 13.1±3.7 mm in size, measuring 1-2 cm in 72.2% (26/36) and > 2 cm in 5.6% (2/36); the LCA and LSA averaged 8.1±1.0 and 8.2±1.2 mm in size, which were > 1 cm in 8.3% (3/36) and 5.6% (2/36), respectively. Arch vessel stenosis was observed in 12.5% (5/40), including the LSA in 2, and LCA and IA, in 1 each.
Late Aortic Events Five patients developed distal aortic dilation (1 with a distal new entry), 3 of whom were managed with reintervention and 2 were closely monitored. The type Ia endoleak resolved spontaneously at 3 years. The patient with type Ib endoleak was rigorously monitored.
Reoperation Three patients with distal aortic dilation underwent reintervention at mean 7.5±1.4 years (6.0-8.8), including thoracoabdominal aortic replacement, AbAo replacement and endovascular repair (TEVAR) for distal new entry, in one each. Distal aortic DMax was
9
46.0±14.4 mm (range, 30-58 mm) at reintervention. All three patients survived to the latest follow-up. The freedom from distal reoperation was 100.0% (95% CI, 100.0%) and 78.1% (95% CI, 44.2-92.8%) at 5 and 10 years, respectively (Figure 3). At 9 years, freedom from distal aortic reoperation was significantly higher in patients with a preoperative AbAo DMax of < 25 mm (vs ≥25 mm) (87.5% vs 33.3%, p = 0.007).
Late Survival One patient died of non-aortic cause at 6.3 years (Table 2). Survival was 95.2% (95% CI, 82.3-98.8%) and 90.0% (95% CI, 69.5-97.0%) at 5 and 10 years, respectively (Figure 4), which did not differ between the acute and chronic groups (p = 0.702). In competing risks analysis, the incidence was 10% for death, 11% for distal reoperation, and event-free survival was 79% at 8 years (Figure 5).
Risk Factors for Distal Aortic Dilation and Reoperation The preoperative maximal size of the abdominal aorta was predictive of distal aortic dilatation (mm) (hazard ratio, HR = 1.78; 95% Cl, 1.09-2.91; p = 0.021) and distal reoperation (binary, ≥ 25 vs < 25 mm) (HR = 12.88; 95% Cl, 1.16-143.08; p = 0.037).
COMMENT Although there are weak recommendations of using extended arch repair and stent grafting for connective tissue disorders in more recent guidelines [11, 12], there has been continued explorations of using the FET and endografting techniques in patients with MFS [13, 14]. Major concerns over the use of FET in MFS pertain to the inheritably weakened 10
aortic wall, the durability of the stent grafts, and scarcity of long-term data on survival, reintervention and aortic remodeling [15]. This study addresses these concerns by showing that the FET technique had a positive remodeling impact on type I aortic dissection confined to the thoracic aorta. The most important finding of this study is that the FET technique induced complete remodeling of the distal aorta in MFS patients with type I dissection confined to the thoracic aorta. Because residual dissection and persistent patent FL in the descending aorta are risk factors for late aortic dilatation and adversely affect the long-term prognosis in MFS patients [16, 17], ideally complete obliteration of the false lumen in the distal aorta will “cure” such patients of the dreadful dissection. In literature, 30% and 21.6% of patients achieved complete recovery of dissection after total arch replacement without FET [16] and the FET could achieve FL obliteration across the FET in 69-100% [2, 10, 16, 18-20]. In our previous study of 172 MFS patients, complete aortic remodeling was achieved across the FET in 56% and down to the mid-descending aorta in 28.8%. In the present study, the FET technique achieved complete aortic remodeling of the entire thoracic aorta in 90.0% of patients, which shows FL obliteration and normal aortic structure and size. Two recent studies showed that positive remodeling was observed in 44-48% at the diaphragm at 4 years [1, 2]. However, these two studies include only 8 patients with MFS. In contrast, the present cohort of 42 MFS patients has proved that the FET could achieve similar or superior long-term clinical results and aortic remodeling in MFS as compared to non-MFS patients. In addition, the relative short length of dissected aortic segment in this series makes it possible for the FET to exert similar impact on the false lumen and aortic wall, which led to similar remodeling in acute and chronic patients. These results argue that the FET technique may be the most appropriate treatment option for MFS patients with type I dissection confined to the thoracic aorta, given its advantage of the positive remodeling effect and avoidance of problematic issues associated with staged repair [21]. Furthermore, in MFS patients with type I
11
dissection extending beyond the diaphragm, it may be reasonable to use a longer FET or add a bare-metal stent distally to promote remodeling across longer segments of distal aorta [7, 22]. Another important finding of this study is that the untreated aortic segments remained stable after FET, preventing dissection and rupture of the residual thoracic aorta. Schoenhoff and associates reported that the distal aortic diameter was greater in patients with aortic root surgery than those without [23]. An in vitro model suggested that wall tension in the residual aorta increases after ascending aortic replacement [24]. In this study, there was little growth in the distal aorta after FET, as shown by the stable DMaxs and minimal growth rates at all distal segments upon follow-up CTA. These results have proved the durability of the FET technique in promoting complete remodeling of the distal aorta for MFS patients with type I dissection confined to the thoracic aorta. In the Euro Heart Survey database, 31% of reinterventions in patients with MFS have been performed on the distal aorta [23]. However, it remains unclear how and when a new dissection would happen to affect the primarily untreated aortic segments. Nor has the impact of a preoperative dilated abdominal aorta and aortic growth rate on late outcomes been studied, especially for MFS patients. In this cohort, a patient with a preoperative AbAo of > 25 mm was followed up for 6 years after FET until he underwent thoracoabdominal aortic replacement when his AbAo diameter reached 50 mm. This case shows that the FET technique can delay reintervention on the distal aorta and prevent rupture. We also found that preoperative maximal abdominal aorta size was a predictor for distal aortic dilatation and reoperation, and freedom from distal reoperation was significantly lower in patients with a preoperative maximal AbAo diameter of > 25 mm at 10 years. Therefore, for patients with a preoperative abdominal aortic size of ≥ 25 mm, we recommend close monitoring with
12
ultrasound and CT and surgical repair when the abdominal aorta reaches 5 cm in diameter. In addition, due attention should be paid to MFS patients with irregular distal aortic wall, new entry tears, and other risk factors for atherosclerosis, such as hypertension, hyperlipidemia, and smoking, etc.
Study Limitations The study is limited by its retrospective nature, small sample size and lack of a control group. While the patients in the present cohort were all comers, a selection bias did exist in our work pertaining to some moribund patients with irreversible ischemia and secondary end-organ failure and to a natural selection process during patient transfer from other centers. Although this study suggest that the FET may be an optimal approach to type I aortic dissection confined to thoracic aorta in MFS, this is only our single institution experience. Therefore, this technique may not be directly translatable in other centers and warrants further study in large patient population, preferably in a randomized, controlled and multicenter setting. Most importantly, it should be pointed out that those young Marfan patients (mean age 33 years) continue to face persistent and significant risk of distal aortic dilation, reoperation and death despite a more aggressive operation with total arch replacement and frozen elephant trunk. This is corroborative of Dr. Crawford’s wise comment that "No patient should be considered as cured of the disease" [25], which pertains to aortic dissection patients in general. The present cohort is an even more vulnerable subgroup and the importance of rigorous lifelong clinical and radiologic follow-up in such patients cannot be overemphasized.
Conclusions
13
The results of this study show that frozen elephant trunk technique has a positive remodeling impact on type I dissections confined to thoracic aorta in MFS patients, achieving complete remodeling of the distal aorta and favorable survival and freedom from reoperation in the long term. This study adds evidence supporting the safety and durability of this extended approach in setting of type I aortic dissection for patients with Marfan syndrome.
14
References 1.
Dohle DS, Tsagakis K, Janosi RA, et al. Aortic remodelling in aortic dissection after frozen elephant trunk. Eur J Cardiothorac Surg 2016;49:111-7.
2.
Weiss G, Santer D, Dumfarth J, et al. Evaluation of the downstream aorta after frozen elephant trunk repair for aortic dissections in terms of diameter and false lumen status. Eur J Cardiothorac Surg 2016;49:118-24.
3.
Halstead JC, Meier M, Etz C, et al. The fate of the distal aorta after repair of acute type A aortic dissection. J Thorac Cardiovasc Surg 2007;133:127-35.
4.
Waterford SD, Moon MR. Stent grafting in Marfan syndrome? We are not convinced. J Thorac Cardiovasc Surg 2018;156:1773-5.
5.
Ma WG, Zhang W, Zhu JM, et al. Long-term outcomes of frozen elephant trunk for type A aortic dissection in patients with Marfan syndrome. J Thorac Cardiovasc Surg 2017;154:1175-89 e2.
6.
Chen Y, Ma WG, Zheng J, Liu YM, Zhu JM, Sun LZ. Total arch replacement and frozen elephant trunk for type A aortic dissection after Bentall procedure in Marfan syndrome. J Thorac Dis 2018;10:2377-87.
7.
Chen Y, Ma WG, Zhi AH, et al. Fate of distal aorta after frozen elephant trunk and total arch replacement for type A aortic dissection in Marfan syndrome. J Thorac Cardiovasc Surg 2019;157:835-49.
8.
Ma WG, Zheng J, Zhang W, et al. Frozen elephant trunk with total arch replacement for type A aortic dissections: Does acuity affect operative mortality? J Thorac Cardiovasc Surg 2014;148:963-70; discussion 70-2.
9.
Ma WG, Zhu JM, Zheng J, et al. Sun's procedure for complex aortic arch repair: total arch replacement using a tetrafurcate graft with stented elephant trunk implantation. Ann Cardiothorac Surg 2013;2:642-8.
10. Sun LZ, Qi RD, Chang Q, et al. Surgery for Marfan patients with acute type A dissection using a stented elephant trunk procedure. Ann Thorac Surg 2008;86:1821-5. 11. Appoo JJ, Bozinovski J, Chu MW, et al. Canadian Cardiovascular Society/Canadian Society of Cardiac Surgeons/Canadian Society for Vascular Surgery Joint Position Statement on Open and Endovascular Surgery for Thoracic Aortic Disease. Can J Cardiol 2016;32:703-13.
15
12. Czerny M, Schmidli J, Adler S, et al. Current options and recommendations for the treatment of thoracic aortic pathologies involving the aortic arch. Eur J Cardiothorac Surg 2019;55:133-62. 13. Uchida N, Katayama A, Kuraoka M, et al. Extended aortic repair using frozen elephant trunk technique for Marfan syndrome with acute aortic dissection. Ann Thorac Cardiovasc Surg 2013;19:279-82. 14. Yoshitake A, Shimizu H, Kawaguchi S, Itoh T, Kawajiri H, Yozu R. Hybrid repair of subclavian-axillary artery aneurysms and aortic arch aneurysm in a patient with Marfan syndrome. Ann Thorac Surg 2013;95:1441-3. 15. Sundt TM, 3rd. The can-should problem. J Thorac Cardiovasc Surg 2011;142:e91. 16. Park KH, Lim C, Choi JH, et al. Midterm change of descending aortic false lumen after repair of acute type I dissection. Ann Thorac Surg 2009;87:103-8. 17. Geisbuesch S, Schray D, Bischoff MS, Lin HM, Di Luozzo G, Griepp RB. Frequency of reoperations in patients with Marfan syndrome. Ann Thorac Surg 2012;93:1496501. 18. Girdauskas E, Kuntze T, Borger MA, Falk V, Mohr FW. Distal aortic reinterventions after root surgery in Marfan patients. Ann Thorac Surg 2008;86:1815-9. 19. Uchida N, Shibamura H, Katayama A, Shimada N, Sutoh M, Ishihara H. Operative strategy for acute type A aortic dissection: ascending aortic or hemiarch versus total arch replacement with frozen elephant trunk. Ann Thorac Surg 2009;87:773-7. 20. Pacini D, Tsagakis K, Jakob H, et al. The frozen elephant trunk for the treatment of chronic dissection of the thoracic aorta: a multicenter experience. Ann Thorac Surg 2011;92:1663-70; discussion 70. 21. Ikeno Y, Yokawa K, Nakai H, et al. Results of staged repair of aortic disease in patients with Marfan syndrome. J Thorac Cardiovasc Surg 2019;157:2138-47.e2. 22. Ma WG, Zheng J, Sun LZ, Elefteriades JA. Open stented grafts for frozen elephant trunk technique: Technical aspects and current outcomes. Aorta (Stamford) 2015;3:122-35. 23. Schoenhoff FS, Carrel TP. Re-interventions on the thoracic and thoracoabdominal aorta in patients with Marfan syndrome. Ann Cardiothorac Surg 2017;6:662-71. 24. Scharfschwerdt M, Leonhard M, Lehmann J, Richardt D, Goldmann H, Sievers HH. In vitro investigation of a novel elastic vascular prosthesis for valve-sparing aortic root
16
and ascending aorta replacement. Eur J Cardiothorac Surg 2016;49:1370-3. 25. Crawford ES. The diagnosis and management of aortic dissection. JAMA 1990;264:2537-41.
17
TABLE 1. Preoperative clinical profiles Variable
Total (n = 42)
Age, y 33.3±8.9 Male gender, n (%) 27 (64.3%) Time from onset to diagnosis, day 188 ± 596 Median (interquartile range) 3.5 (1-16.5) Time from onset to surgery, day 208 ± 598 Median (interquartile range) 16.5 (4.8-57.3) Hypertension, n (%) 14 (33.3%) Smoking history, n (%) 10 (23.8%) Family history of aortic dissection, n (%) 16 (38.1%) History of proximal aortic surgery, n (%) 5 (11.9%) Composite root replacement 3 (7.1%) Aortic valve replacement 1 (2.4%) Wheat procedure 1 (2.4%) Preoperative aortic size, mm Aortic sinus 66.5±14.4 Aortic arch 31.3±7.6 Proximal descending aorta 29.2±5.4 Mid-descending aorta 22.8±2.9 Diaphragm 21.1±2.2 Renal arteries 19.1±2.3 Abdominal aorta 19.9±2.7 Aortic regurgitation, n (%) Moderate 11 (26.2%) Severe 26 (61.9%) Malperfusion syndrome, n (%) 5 (11.9%) Stroke 1 (2.4%) Acute myocardial infarction 1 (2.4%) Acute cardiac tamponade 3 (7.1%) Acute heart failure 1 (2.4%) Arch vessel involvement, n (%) Innominate artery 38 (90.5%) Left carotid artery 38 (90.5%) Left subclavian artery 35 (83.3%)
Acute (n = 22)
Chronic (n = 20)
P value
33.5±9.0 15 (68.2%) 3.7 ± 3.9 2 (1- 4.8) 7.2 ± 5.8 5 (2.8-12.3) 7 (31.8%) 6 (27.3%) 10 (45.5%) 1 (4.5%) 0 1 (4.5%) 0
33.2±9.1 12 (60.0%) 391 ± 828 18 (3-365) 428 ± 821 63.5 (32.3-371) 7 (35.0%) 4 (20.0%) 6 (30.0%) 4 (20.0%) 3 (15.0%) 0 1 (5.0%)
62.5±12.0 28.8±3.0 27.2±2.5 22.5±1.9 21.5±2.4 19.0±2.0 20.2±2.7
71.6±16.0 34.3±10.3 31.4±6.8 23.2±3.8 20.6±2.1 19.4±2.6 19.7±2.9
5 (22.7%) 16 (72.7%) 3 (13.6%) 1 (4.5%) 0 2 (9.1%) 0
6 (30.0%) 10 (50.0%) 2 (10.0%) 0 1 (5.0%) 1 (5.0%) 1 (5.0%)
0.716 0.335 0.288 0.607 0.288
19 (86.4%) 20 (90.9%) 19 (86.4%)
19 (95.0%) 18 (90.0%) 16 (80.0%)
0.341 0.920 0.580
0.901 0.580 0.050 0.034 0.827 0.580 0.303 0.122 0.059 0.335 0.288 0.047 0.042 0.020 0.454 0.226 0.597 0.571 0.203
18
TABLE 2. Operative and late outcomes Variable Operative Data Cardiopulmonary bypass time, min Cross-clamp time, min Antegrade cerebral perfusion time, min Concomitant procedures Composite root replacement Coronary artery bypass grafting Frozen elephant trunk Diameter, mm Length, cm Postoperative maximal aortic diameter, mm Proximal descending aorta Mid-descending aorta Diaphragm hiatus Renal arteries Abdominal aorta (most dilated segment) Operative Outcomes Operative mortality Complication and reintervention Stroke Low cardiac output Acute renal failure Distal aortic rupture Reexploration for bleeding Innominate artery occlusion Type I endoleak Late Outcomes Late death Distal aortic dilatation Distal new entry Distal reintervention Thoracoabdominal aortic aneurysm repair Thoracic endovascular aortic repair
Total (n = 42)
Acute (n = 22)
Chronic (n = 20)
p value
182.0±36.2 99.8±30.2 22.6±6.9
185.7±35.2 110.8±35.0 23.8±7.8
178.0±37.8 88.3±18.8 21.4±5.8
0.502 0.015 0.281
39 (92.9%) 3 (7.1%)
22 (100%) 1 (4.5%)
17 (85.0%) 2 (10.0%)
0.059 0.493
25.7±1.3 10.2±0.9
25.5±1.3 10.2±0.6
25.9±1.4 10.2±1.1
0.338 0.803
29.2±3.9 23.1±2.9 22.0±2.6 19.8±3.7 22.4±8.7
28.2±2.1 23.3±2.6 22.9±2.9 20.0±3.5 22.8±8.2
30.4±5.0 22.8±3.2 21.1±1.8 19.6±3.9 21.9±9.4
0.111 0.555 0.035 0.741 0.736
2 (4.8%) 4 (9.5%) 1 (2.4%) 2 (4.8%) 1 (2.4%) 1 (2.4%) 1 (2.4%) 1 (4.8%) 2 (4.8%)
1 (4.5%) 2 (9.1%) 1 (4.5%) 1 (4.5%) 1 (4.5%) 0 1 (4.5%) 1 (4.5%) 1 (4.5%)
1 (5.0%) 2 (10.0%) 0 1 (5.0%) 0 1 (5.0%) 0 0 1 (5.0%)
0.945 0.920 0.335 0.945 0.335 0.288 0.335 0.335 0.945
1 (2.5%) 4 (10.0%) 1 (2.5%) 3 (7.5%) 2 (5.0%) 1 (2.5%)
1 (4.8%) 3 (14.3%) 1 (4.8%) 2 (9.5%) 1 (4.8%) 1 (4.8%)
0 1 (5.3%) 0 1 (5.3%) 1 (5.3%) 0
0.335 0.342 0.335 0.609 0.942 0.335
19
TABLE 3. Complete remodeling of distal aorta between acute and chronic patients Aortic segment Frozen elephant trunk
Acute (n = 21, %) Remodeling No 100.0 0
Chronic (n = 19, %) Remodeling No 94.7 5.3
p value 0.287
Unstented descending aorta
95.2
4.8
100.0
0
0.335
Diaphragmatic hiatus
95.2
4.8
100.0
0
0.335
Abdominal aorta
95.2
4.8
94.7
5.3
0.942
20
TABLE 4. Aortic growth rates stratified by preoperative maximal abdominal aortic size Growth rate (mm/year) Frozen elephant trunk
Total Preoperative maximal abdominal aortic size p value (n = 37) < 25 mm (n = 34) ≥ 25 mm (n = 3) 0.24 0.618 –0.03 –0.06
Unstented descending aorta
0.04
0.01
0.35
0.112
Diaphragm hiatus
0.22
0.23
0.15
0.700
Renal arteries
0.13
0.08
0.68
0.029
Abdominal aorta (most dilated part)
0.38
0.13
3.22
0.096
21
Figure Legends Figure 1. In an MFS patient with type I aortic dissection (A), CTA at 8 years after frozen elephant trunk (FET) procedure showed complete aortic remodeling beyond the FET (red arrow), as evidenced by disappeared false lumen and normal distal aortic structure and diameter
Figure 2. Freedom from distal aortic dilatation
Figure 3. Freedom from reoperation
Figure 4. Kaplan-Meier survival
Figure 5. Competing risks of death and reoperation
22