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European Journal of Cardio-Thoracic Surgery 45 (2014) 967–975 doi:10.1093/ejcts/ezt493 Advance Access publication 24 October 2013

Marco Di Eusanioa,b,*, Sebastiano Castrovincia, David H. Tianb, Gianluca Folesania, Mariano Cefarellia, Antonio Pantaleoa, Giacomo Muranaa, Paolo Berrettaa, Tristan D. Yanb,c and Roberto Di Bartolomeoa a b c

Department of Cardiac Surgery, Sant’Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy The Collaborative Research (CORE) Group, Sydney, Australia Department of Cardiothoracic Surgery, Royal Prince Alfred Hospital, University of Sydney, Sydney, Australia

* Corresponding author. Department of Cardiac Surgery, Sant’Orsola-Malpighi Hospital, University of Bologna, Via Massarenti 9, 40128 Bologna, Italy. Tel: +39-051-6364505; fax: +39-051-6364509; e-mail: [email protected] (M. Di Eusanio). Received 16 May 2013; received in revised form 29 August 2013; accepted 5 September 2013

Summary Several studies have shown that after DeBakey type 1 acute aortic dissection (DB1-AAD) surgery, 70% of the surviving patients still present with a dissected distal aorta that can eventually dilate, rupture, lead to distal malperfusion or require secondary extensive interventions. In order to minimize these complications, different surgeons have advocated total thoracic aorta remodelling procedures during primary aortic repair to promote false-lumen obliteration and distal thrombosis. Such management, which includes arch replacement and antegrade stenting of the dissected descending thoracic aorta (DTA), remains controversial due to its perceived increased operative mortality. Furthermore, the desired long-term benefits remain to be confirmed. The present article aimed to evaluate results of antegrade stenting of DTA during surgery for DB1-AAD, focusing on in-hospital mortality and morbidity, and long-term survival, occurrence of distal aortic remodelling and freedom from aortic reinterventions. Early results from the identified studies suggested that hybrid repair of DB1-AAD with antegrade DTA stenting was associated with satisfactory in-hospital mortality (10.0%) and stroke (4.8%) rates, while the risk of spinal cord injury appeared to be higher (4.3%) than that reported from historical controls. Furthermore, antegrade stenting of DTA was associated with promising rates of partial/complete thrombosis of the peristent DTA false lumen (88.9%), suggesting that aortic remodelling is highly probable with this approach. Evidence on long-term results after proximal acute dissection repair is still sparse, and mostly jeopardized by limited data beyond 5 years. Further investigations with longer term follow-up and with specifically designed protocols to assess longterm clinical outcomes (late aortic mortality and freedom from distal aortic reinterventions) of total thoracic aortic remodelling procedures vs more conservative management are warranted to reach more definitive conclusions. Keywords: Great vessels • Aorta • Acute dissection • Hybrid repair • Outcomes

INTRODUCTION DeBakey type 1 acute aortic dissection (DB1-AAD) is a disease of poor prognosis if untreated, with death mostly occurring due to aortic rupture, tamponade and organ malperfusion. For DB1-AAD patients, surgery represents the mainstay of therapy and is centred on excision of the proximal intimal tear, replacement of the supracoronary ascending aorta (or hemiarch) and re-establishment of a dominant flow in the distal true lumen. Yet, despite substantial improvement of surgical care, hospital mortality after surgery remains substantial, in the range of 15–30%, and is mostly determined by clinical conditions at presentation [1, 2]. For this reason, during the primary surgical repair, a conservative approach aiming to minimize the operative risk has been for long the most common approach in patients with DB1-AAD, and ascending aorta or hemiarch replacement with resuspension of the aortic valve undoubtedly remains the most common procedure in this setting [3].

Nevertheless, a large amount of data have shown that 70% of the surviving patients present a dissected distal aorta that can eventually dilate, rupture, lead to distal malperfusion or require secondary extensive interventions [4–8]. Thus, many surgeons, especially those with more experience in aortic surgery, have advocated more extensive primary operations involving arch replacement and antegrade stenting of the dissected descending thoracic aorta (DTA) hoping to minimize the need for reinterventions at follow-up by promoting false-lumen obliteration and distal thrombosis [9–14]. Such management, however, remains controversial due to its increased technical complexity and perceived higher operative mortality. Furthermore, the desired longterm benefits remain to be confirmed. The present article aims to review results of antegrade stenting of DTA during surgery for DB1-AAD, focusing on in-hospital mortality and morbidity as well as on long-term survival, occurrence of distal aortic remodelling and freedom from aortic reinterventions.

© The Author 2013. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

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Antegrade stenting of the descending thoracic aorta during DeBakey type 1 acute aortic dissection repair

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Literature search criteria To achieve maximum sensitivity of the search strategy and to identify all studies, PubMed databases were searched from inception to April 2013, using ‘frozen elephant trunk’ OR ‘stented elephant trunk’ OR ‘antegrade stenting descending thoracic aorta’ as either keywords or MeSH terms. All retrieved articles were reviewed and assessed according to the inclusion/exclusion criteria. The reference lists of all included articles were reviewed for further identification of potentially relevant studies. Eligible studies for the present review included studies that focused on hybrid DB1-AAD repair with antegrade stenting of DTA. Case reports, editorial, expert opinion and comment types of publication were excluded from this review as well as review articles because of potential doubling of results. Studies involving 50% of studies. Statistical analysis was conducted using the Comprehensive Meta-analysis Package (Biostat, Englewood, NJ, USA) statistical software.

RESULTS A total of 345 studies were identified. After detailed evaluation of these articles, 13 studies remained for assessment. All of the included studies were observational retrospective trials (Table 1). In these studies, 598 patients underwent arch repair with antegrade DTA stenting for a DB1-AAD.

Patients’ characteristics and operative data Overall, 75.5% of patients were male, with a pooled mean age of 54.2 years. Patient demographics reported by more than half of the studies included hypertension (72.2%), coronary artery disease (10.0%), tamponade (14.3%) and Marfan’s syndrome (12.2%) (Tables 2 and 3). Intraoperatively, as a method of brain protection, ASCP with moderate hypothermia was used in nine studies [12–17, 19–22], ASCP with deep hypothermia in one study [25], deep hypothermic circulatory arrest (DHCA) in one study [9], DHCA or ASCP in one study [10] and a combination of antegrade and retrograde cerebral perfusion in another study [18]. Nine studies provided data on temperature at circulatory arrest [9, 10, 12–15, 17, 19–22], which ranged between 18 and 28°C. Pooled average ASCP time, CPB time and

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Author

Year

Study period

Institution

Study type

Number of patients

Mean follow-up (months)

Jakob et al. Shimamura et al. Pochettino et al. Chen et al. Jakob et al. Sun et al. Uchida et al. Shi et al. Shen et al. Hoffman et al. Xiao et al. Shrestha et al. Roselli et al.

2008 2008 2009 2010 2011 2011 2011 2011 2012 2013 2013 2013 2013

2001–2007 1994–2004 2005–2008 2004–2009 2005–2010 2003–2008 1997–2010 2007–2010 2010–2010 2009–2011 2008–2011 2010–2011 2009–2012

University Hospital Essen (Essen, Germany) Osaka Prefectural Hospital (Osaka, Japan) Hospital of the University of Pennsylvania (Philadelphia, USA) Nanjing First Hospital (Nanjing China) International E-vita Open Registry Fuwai Hospital (Beijing, China) Hiroshima-city Asa General Hospital (Hiroshima, Japan) First Affiliated Hospital (Shenyang, China) The Second Xiangya Hospital (Hunan, China) University Hospital RWTH (Aachen, Germany) West China Hospital (Sichuan, China) Hannover Medical School, (Hannover, Germany) Cleveland Clinic (Cleveland, OH, USA)

OS OS OS OS OS OS OS OS OS OS OS OS OS Total number of patients

22 29 36 27 88 148 80 46 22 32 33 18 17 598

23 60 16 30 – 42 74.3 14 12 17 27 – 5

OS: observational study.

Table 2: Summary of preoperative characteristics Author

Age

Male

Hypertension

Redo

Coronary artery disease

Chronic renal failure

History of stroke

Marfan

Tamponade

Jakob et al. Shimamura et al. Pochettino et al. Chen et al. Jakob et al. Sun et al.

57 ± 12 N/A

17 (77.0) N/A

21 (95.0) N/A

1 (5.0) N/A

5 (23.0) N/A

6(27.0) N/A

3 (14.0) N/A

5 (23.0) N/A

8 (36.0) N/A

59 ± 13

–

26 (72.0)

–

3 (8.0)

1 (3.0)

3(8.0)

–

–

51.2 ± 9.8 59 ± 13 45 ± 11

– – 107 (72.3)

– 4 (5.0) –

4 (14.3) 12 (14.0) 5 (3.4)

1 (3.6) 13 (15.0) –

1 (3.6) 5 (6.0) –

66.8 ± 10.8 52.7 ± 12.3 45.4 ± 10.4 58 ± 9 48 ± 11.6 N/A 61.4 ± 17.5 54.2 ± 14.0 45.0 66.8

– 39 (84.8) 13 (59.1) – 18 (54.5) N/A – 72.2% 54.5% 95.0%

– – –

– 3 (6.5) – 3 (9.3) – N/A – 10.0% 3.4% 23.0%

– 3 (6.5) – 1 (3.1) – N/A – NA NA NA

22 (27.5) – – 4 (12.5) – N/A – NA NA NA

3(10.7) 5 (6.0) 19 (12.8) 3 (3.7) 9 (19.6) 3 (13.6) 2 (6.2) 7 (21.2) N/A – 12.2% 3.7% 23.0%

1 (3.6) 20 (23.0) 3 (2.0)

Uchida et al. Shi et al. Shen et al. Hoffman et al. Xiao et al. Shrestha et al. Roselli et al. Pooled average Minimum Maximum

22 (79.0) 68 (77.0) 126 (85.1) 36 (45.0) 35 (76.1) 16 (72.7) 26 (81.2) 24 (73.0) N/A 14 (82.0) 75.5% 45.0% 85.1%

– N/A – NA NA NA

28 (35) – 2 (9.1) 4 (3.1) – N/A – 14.3% 2.0% 36%

All values expressed as number and percentage. N/A: not applicable.

myocardial ischaemia time were 49.3 min (range, 24–78), 205.9 min (range, 107.9–17.7) and 120 min (range, 79.7–174), respectively.

Short-term outcomes: mortality, PND and SCI Mortality was reported either as in hospital [9, 10, 12, 13, 15–19, 21, 22, 25] or at 30-days [20] (Table 4). Overall, average weighted mortality was 10.0% (range 0–27.7%).

Data on PND (stroke or coma) were available in 10 studies [9, 10, 13, 15–18, 21, 22, 25], while SCI was reported in all studies. Postoperative stroke occurred in 4.8% of patients (range, 0– 12.0%), while SCI occurred in 4.3% of patients (range, 0–13.8%). Nine studies reported data on renal failure [9, 10, 13, 15–19, 21, 22, 25], with a prevalence of 10.2% (range, 0–54.5%), while respiratory failure occurred in 16.7% (range, 3.7–45.5%) of patients. Hospital stay ranged between 18.7 and 26.3 days (pooled average, 22).

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Table 1: Summary of study characteristics

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Table 3: Summary of operative characteristics Author

Prosthesis

Circulatory arrest temperature (°C)

Method of brain protection

Cerebral perfusion time (min)

CPB time (min)

Myocardial ischaemia (min)

Jakob et al.

Talent Medtronic or E-vita open hybrid stent-graft ( JOTEC GmbH, Hechingen) Noncoated polyester graft with Gianturco stent (William Cook Europe A/S, Bjaeverskov, Denmark) Dacron graft (Vascutec Ltd, Renfrewshire, Scotland) with Gore TAG stent (W.L. Gore & Associates, Flagstaff, AZ, USA) Woven Dacron graft with Gianturco-type self-expandable metallic stent (Microport Medical Corp., Shanghai, China) E-vita open hybrid stent-graft ( JOTEC GmbH, Hechingen, Germany Four-branch prosthetic graft (Boston Scientific, Inc., Boston, MA) with stent-graft (Microport Medical Corp., Shanghai, China) Polyester fabric prosthesis (UBE, Tokyo, Japan) with self-expanding Z-shaped stent Self-expandable stent vessel prosthesis (Microport Medical Corp., Shanghai, China) Four-branch graft with self-expanding stent (Yuhengjia Sci-Tech Co. Ltd, Beijing, China) E-vita open hybrid stent-graft ( JOTEC GmbH, Hechingen, Germany 4-branch prosthetic graft with stent-graft (Shanghai Micro Port Medical Co, Ltd, Shanghai, China) Thoraflex (Vascutek, Terumo, Inchinnan, Scotland, UK) Dacron graft with GORE TAG stent-grafts (Gore Medical, Flagstaff, AZ, USA) N/A

25

ASCP

59 ± 18

245 ± 64

139 ± 32

24

ASCP

N/A

N/A

N/A

–

ASCP/ RCP

60 ± 13

245 ± 39

–

22–25

ASCP

38.8 ± 9.7

213.2 ± 47.2

141.9 ± 32.5

–

ASCP

68 ± 22

243 ± 65

139 ± 48

18–22

ASCP

24 ± 9

197 ± 47

107 ± 27

28

ASCP

78 ± 18

178 ± 48

101 ± 22

24

ASCP

35.5 ± 7.1

107.9 ± 17.7

79.7 ± 15.8

22

ASCP

50.9 ± 26.1

179 ± 67.6

134 ± 46.5

20

DHCA/ASCP

43 ± 4

204 ± 40

136 ± 39

22–24

ASCP

52.2 ± 33.2

296.9 ± 54.3

174.2 ± 39.3

20–24

ASCP

N/A

N/A

N/A

18

DHCA

–

–

–

N/A

N/A

49.3 ± 26.8

205.9 ± 66.6

120.0 ± 41.3

N/A N/A

N/A N/A

24 ± 19 78 ± 18

107.9 ± 17.7 296.9 ± 54.3

79.7 ± 15.8 174 ± 39.3

Shimamura et al. Pochettino et al. Chen et al. Jakob et al. Sun et al. Uchida et al. Shi et al. Shen et al. Hoffman et al. Xiao et al.

Shrestha et al. Roselli et al. Pooled average Minimum Maximum

N/A N/A

CPB: cardiopulmonary bypass; ASCP: antegrade selective cerebral perfusion; RCP: retrograde cerebral perfusion; DHCA: deep hypotermic circulatory arrest; N/A: not applicable.

Long-term outcomes: aortic remodelling, survival and freedom from re-intervention Long-term data were sparse and limited beyond 1 year. Six studies reported 1-year survival [10, 16, 18, 21, 22, 25], which ranged between 79 and 100%. 5-year survival ranged between 68 and 96% [16, 22, 25] (Figs 1–3). Pooled average of 1-year freedom from reintervention was 92.3% (range, 71.8–100%). Pooled average aortic remodelling, as indicated by a partial/complete thrombosis of the peristent DTA false lumen, was 88.9% (range, 48.4–100%), and was >90% in more than half of the studies with DTA imaging follow-up data available [10, 13, 16, 17, 19, 22, 25].

DISCUSSION Open arch repair and antegrade stenting of DTA is emerging as an attractive option in the management of type 1 DeBakey dissections. By repairing the dissected DTA, this approach is intended to substantially reduce late aortic events and improve long-term outcomes of surviving individuals with chronic residual dissection.

This comprehensive approach, however, is in strict opposition to one of the most entrenched principles of aortic dissection surgery ( perform the simplest and shortest operation that will have the least adverse impact on the patient) and remains controversial due to its complexity and perceived higher risk of early mortality and morbidity. In the present article, we sought to review available early and long-term outcomes data for total thoracic aorta remodelling procedures in patients with DB1-AAD undergoing arch repair and antegrade stenting of DTA. We used these data both to assess safety of this approach and to discuss short and long-term arguments for its application in DB1-AAD patients (Table 5).

Is arch repair and antegrade stenting of DTA a safe procedure? One of the main arguments against the practice of these radical procedures in patients with DB1-AAD is the perceived increased early risk they pose. Undoubtedly, extensive aortic arch surgery is technically more demanding, which is a concern when less experienced

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Author

In-hospital mortality

PND

SCI

Renal failure

Respiratory failure

Reoperation for bleeding

In-hospital stay (days)

Jakob et al. Shimamura et al. Pochettino et al. Chen et al. Jakob et al. Sun et al. Uchida et al. Shi et al. Shen et al. Hoffman et al. Xiao et al. Shrestha et al. Roselli et al. Pooled average Minimum Maximum

2 (9.0) 2 (6.8)a 5 (14.0) 4 (14.8) 16 (18.0) 7 (4.7) 4 (5.0) 1 (2.2) 2 (9.1) 1 (3.1) 6 (18.2) 5 (27.7) 0 10.0% 0% 27.7%

2 (9.0) (N/A) 1 (3.0) 3 (11.1) 5 (6.0) 4 (2.7) 2 (2.5) 0 – 0 0 N/A 2 (12.0) 4.8% 0% 12%

0 4 (13.8) 3 (9.0) 0 5 (6.0) 3 (2.0) 0 0 1 (4.5) 0 0 0 0 4.3% 0% 13.8%

12 (54.5) N/A 6 (17.0) 2 (7.4) 32 (36.4) 1 (0.7) 3 (3.8) – – 0 1 (3.0) – 3 (19.0) 10.2% 0% 54.5%

10 (45.5) N/A – 1 (3.7) 33 (38.0) 14 (9.5) 6 (7.5) – 2 (9.1) 8 (25.0) 6 (18.2) – 2 (12.0) 16.7% 3.7% 45.5%

– N/A – 3 (11.1) 16 (18.0) 5 (3.4) 4 (5.0) 2 (4.3) – 4 (12.5) – 6 (33.3) – 10.1% 3.4% 33.3%

25 ± 15 N/A – 23 – – 18.7 ± 5.9 21.2 ± 12.7 19 ± 8 26.3 ± 10.5 – 20 ± 12 22.0 ± 10.7 18.7 26.3

All values expressed as number and percentage. 30-day mortality PND: permanent neurological dysfunction; Respiratory failure: assisted ventilation >72 h, or >5 days or requiring tracheostomy, pneumonia, pulmonary embolism; SCI: spinal cord injury; Renal failure: transient or permanent haemodialysis; N/A: not applicable.

a

Figure 1: Peristent false-lumen thrombosis for studies utilizing antegrade stenting of the descending thoracic aorta (DTA) during DB1-AAD repair.

Figure 2: Freedom from reoperation for studies utilizing antegrade stenting of the descending thoracic aorta during DB1-AAD repair. The size of the circles corresponds to the size of the study cohort.

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Table 4: Summary of early outcomes

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Figure 3: Long-term survival for studies utilizing antegrade stenting of the descending thoracic aorta during DB1-AAD repair. The size of the circles corresponds to the size of the study cohort.

Table 5: Potential indications and requisites for arch replacement and antegrade descending thoracic aorta stenting (total aortic remodelling) during DB1-AAD surgery Disease-related Complex primary and re-entry intimal tears, involving distal arch and/or proximal DTA Distal arch/DTA false-lumen impending rupture Distal aortic malperfusion due to DTA true lumen compression or collapse Aneurysmal arch and proximal DTA Severely damaged aortic arch or poor aortic tissue quality (whereby distal aortic arch anastomosis could not be safely performed) Patient-related Patient with adequate performance status, able to withstand TAR (as deemed by the operating surgeon) Institution- or surgeon-related Adequate equipment and surgical/endovascular expertise DTA: descending thoracic aorta; DB1-AAD: DeBakey type 1 acute aortic dissection; TAR: total-arch replacement.

personnel are required to operate in an emergent setting. Moreover, hybrid arch reconstructions are associated with longer periods of CPB and circulatory arrest, which are well known risk factors for mortality and major morbidity during aortic surgery. Kim et al. [26], in a recent study, compared outcomes of TAR vs hemiarch replacement in 188 consecutive patients with DB1-AAD, and found that TAR was associated with significantly higher hazard ratios (HR) for mortality (HR: 2.4) and neurological complications (HR: 3.2), compared with the control operation, with no benefits in terms of late redo surgery. Such data, supporting a conservative management of DB1-AAD, confirmed conclusions already reached by other authors [3, 27]. In contrast to this position, data are available in the literature indicating that the extent of the aortic replacement does not represent a risk factor for early adverse outcomes, even during type A or DB1-AAD operations, especially when advanced methods of brain protection (ASCP) are employed [28–31]. The controversy regarding different early risks associated with hemiarch or TAR can be extended to arch repair with DTA stenting. Moreover, the latter procedures certainly add technical complexity, require experience and skills with the endovascular forms of therapy and likely pose higher risk of SCI [32] for the patient.

Results from our literature search indicated in hospital (or 30-days mortality), PND and SCI rates of 10.0, 4.8 and 4.3%, respectively. We believe that, despite all limitations inherent to raw data from review types of studies such as ours, the abovementioned figures at least suggest that, in selected patients operated on in selected institutions, hybrid radical repair of DB1-AAD is a safe procedure associated with satisfactory in-hospital mortality and stroke rates, while the risk of SCI appeared to be higher than that reported in more conservatively managed series.

Acute arguments for DTA stenting during DB1-AAD repair: distal malperfusion, complex arch tears and distal arch rupture In contemporary series, distal malperfusion syndromes occur in up to 30% of patients, and represent one of the strongest determinants of early death in patients with acute dissection. An analysis of 276 patients from the Leipzig Heart Center operated on for type A acute dissections found in-hospital mortality to be twice as

high in patients with malperfusion when compared with that observed in patients without malperfusion (29.0 vs 13.6%; P = 0.002) [33]. Geirsson et al. [34] similarly highlighted the negative prognostic weight of preoperative malperfusion in 221 patients at the University of Pennsylvania: hospital mortality was 30.5% in the malperfusion group vs only a 6.5% in the uncomplicated counterpart. In both studies, malperfusion processes involved arterial beds beyond the left subclavian artery in
70% of cases, with multiple and mesenteric malperfusion unquestionably representing the worst-case scenario in terms of early risk [33–35]. Originated from the endovascular experience in the treatment of type B AADs complicated by distal malperfusion [36, 37], acute arguments for DTA stenting during primary operations for DB1AAD lie in its potential to fully open the compressed true lumen and to cover additional entry tears located in the proximal DTA, which endure pressurization of the false lumen. Roselli et al. [9] from Cleveland clinic and Tsagakis et al. [38] from Essen recently showed excellent results in patients with malperfusion managed with a stented/frozen elephant trunk approach. They both brought up the importance of angiography after surgical repair to control for residual malperfusion and pointed out the frequent need for secondary endovascular procedures with branch vessel stenting to optimize final results. The excellent outcomes with this approach deserve to be considered and emphasize the importance of a multidisciplinary approach with adequate hybrid operative rooms in this modern management of AAD. TAR during primary DB1-AAD surgery can be indicated in primary intimal tears extensively involving the aortic arch, distal false-lumen rupture at the aortic arch and other conditions such as aneurysmal dilatation of the aortic arch (Table 5). Although elective TAR can be performed with a reasonably low risk in experienced centres, outcomes after TAR in acute dissection patients can be less predictable. In particular, bleeding and rupture, often very difficult to control, can complicate deep distal anastomosis when dealing with an extremely fragile dissected aortic wall. In such a difficult setting, a hybrid approach, by stenting the distal aortic arch and DTA, may facilitate surgery allowing an easier and more controllable distal anastomosis that can be performed proximal to the offspring of the left subclavian or common carotid arteries [39]. Furthermore, stent-grafting the DTA, by avoiding persistent DTA false-lumen perfusion, enhances haemostasis at the distal anastomotic site. The use of stent-grafts in elective patients with Marfan or other connective diseases is controversial mostly due to the limited longterm data available for the endovascular procedures, the young age of these patients, the increased risk of stent-related degeneration of the weakened Marfan aortic wall and the relatively good results of open surgery in experienced centres. Stent-graft therapy is more liberally performed in the acutely dissecting patients, and, in this setting, often indicated as a ‘rescue’ or ‘bridge’ therapy to subsequent more durable open procedures. This notion seems to be confirmed by our data showing that Marfan patients represented 12.2% of our study population.

Long-term arguments for DTA stenting during DB1-AAD repair Despite successful surgical resection of the primary entry tear during the initial surgery, due to the presence of secondary distal intimal tears, continuous blood flow in the DTA false lumen often persists. Consequently, patency of the false lumen in DTA is

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reported in the range 64–90% after type A AAD repair, and is likely to be higher after DB1-AAD repair [4, 8, 40–42]. Aneurysmal degeneration of the patent DTA false lumen is a key-factor for the long-term prognosis of the surviving DB1-AAD patients [4, 8, 41–45]. Thus, antegrade stenting of DTA at initial surgery, by inducing coverage of secondary entry tears located in the proximal DTA and obliteration of the false lumen at the proximal DTA, is expected to mitigate DTA dilatation, and therefore, to improve long-term survival by reducing aortic-related deaths and need for complex distal aortic reinterventions. However, the literature on long-term results after proximal acute dissection repair is scarce, and existing results are jeopardized by inconsistencies in measurement techniques and limited data beyond 5 years. Some studies, ultimately rejecting extensive primary interventions with stenting of DTA for DB1-AAD, have shown stable dissection evolutions with very low growth rates independent of the status of false lumen at DTA ( patent vs thrombosed vs partially thrombosed), and with low rates of distal reinterventions at 10 years ( < 16%) [4, 46–48]. On the other hand, there are a number of studies representing an accelerated growth rate of the residual dissected DTA, which, especially among subjects with a patent DTA false lumen, appears to be associated with significantly poorer 10-year survival and freedom from reoperation [5, 8, 41–45]. The latter studies suggest room for improvement, likely achievable with prophylactic stenting of DTA at primary repair. Recent investigations have identified additional anatomical variables that, in the acute or sub-acute phase, may predict poor longterm outcomes and that might support, in appropriate conditions, a prophylactic stenting of DTA. These variables, which have to be taken with great caution and thoughtfully integrated with the overall patient’ risk profile, include (i) a DTA diameter at initial presentation of >35 mm, indicated as a risk factor for a patent false lumen postoperatively [48], (ii) an initial false lumen maximal diameter of >22 mm, associated with accelerated aortic dilatation and occurrence of adverse aortic events [49] and (iii) a proximal intimal tear of >10 mm, associated with increased dissection related events and mortality at the follow-up [45]. In addition, younger age and Marfan or other connective diseases pose a higher risk of distal aortic reintervention [5, 45] that, crucially, may have less than ideal outcomes. Estrera et al. [50] reported a hospital mortality of 11% after aortic reinterventions in 63 patients surviving an acute type A dissection, and Geirsson et al. [5] reported a 10-year freedom for reintervention of 50% among patients younger than 45 years: hospital mortality was 31% after secondary operations.

What have we learnt from type B AAD trials? The INSTEAD (Investigation of Stent Grafts in Patients with type B Aortic Dissection) multicentre prospective randomized controlled trial was designed to examine the difference in survival in elective survivors of uncomplicated type B aortic dissection patients receiving best medical therapy vs those receiving best medical therapy plus aortic stent-grafting [51]. In this study, thoracic endovascular aortic repair (TEVAR) failed to improve 2-year survival and adverse event rates despite favourable aortic remodelling, which occurred in 91.3% of patients with TEVAR vs 19.4% of those who received medical treatment (P < 0.001). Thus, although data from INSTEAD supported the concept of a complication-specific approach instead of TEVAR for all type B dissections, it confirmed that stent-graft scaffolding enhances falselumen thrombosis and aortic remodelling in type B dissection that

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may translate into prognostic benefits that could potentially be seen at longer follow-up. The need for longer follow-up to fully assess the effects of TEVAR in this setting is confirmed by a study by Evangelista et al. [45], which denoted an increased mortality and need for surgical/endovascular treatment starting only from the third year of follow-up after acute aortic syndromes (type A and B) in patients with persistent false lumen. Fattori et al. [52] recently examined 1129 consecutive patients with type B AAD enrolled in International Registry of Acute Dissection (IRAD) who received medical (n = 853, 75.6%) or TEVAR (n = 276, 24.4%) therapy. The 5-year Kaplan–Meier mortality estimates were significantly lower for patients managed with interventional techniques (15.5% TEVAR vs 29.0% medical), despite the initially higher risk profile due to the complicated nature of the dissection patients subjected to TEVAR. The IRAD database analysis supports the premise of long-term advantages in survival with selected endovascular treatment when compared with medical management alone.

Long-term outcomes: aortic remodelling, reinterventions and survival Long-term data, from the literature on aortic remodelling, reinterventions and survival after DB1-AAD repair, should be taken with great caution. This is due to: the absolute lack of randomized controlled trials, the limited size of the study populations, the shortness of follow-up, the implementation of different techniques and materials from different institutions, the difficulties to distinguish distal aortic reinterventions among all reinterventions, the tendency to report competitive results for the newer techniques, and, not the least of which, due to the intrinsic demographic differences existing between eastern patients, who mostly receive antegrade DTA stenting, and western patients, most of whom undergo classic conservative management. Nevertheless, from our review, it emerges that aortic remodelling is highly expected after antegrade DTA stenting, as indicated by 88.9% averaged rate of partial/ complete thrombosis of the peristent DTA false lumen (Fig. 1) [9, 10, 13, 15–22, 25]. These data, consistent with the INSTEAD trial, compare favourably with those reported for conservative management, for which the rate of DTA partial or complete thrombosis is in the range 33.3–77.8% [8, 40, 53–58]. It should be noted, however, that aortic remodelling is only an imaging condition that, until proven otherwise, does not necessarily imply improved survival and freedom from reoperation, which, as previously remarked, remain of more difficult interpretation. Freedom from reoperation at 1 year was 92.3% on average [10, 12, 16, 18–21] (Fig. 2). Long-term survival (Fig. 3) varied between 79 and 100% at 1 year [10, 16, 18, 19, 21, 25], 68–96% at 5 years [16, 22, 25] and 75–97.2% at 10 years [13, 25]. Thus, it emerges that further investigations with longer follow-up and with specifically designed protocols to assess long-term clinical outcomes of total thoracic aorta remodelling procedures vs more conservative ones are strongly warranted to reach definitive conclusions on this intriguing subject.

CONCLUSIONS Antegrade stenting of DTA during DB1-AAD surgical repair is increasingly performed. Despite the added complexity, some institutions have shown excellent early outcomes and very promising distal aortic remodelling rates with this approach.

The present data deserve to be seriously considered and represent, in our opinion, a valid base for future studies designed to more conclusively confirm the hypothesized late benefits of antegrade DTA stenting during DB1-AAD repair, namely improved late survival and freedom from distal aortic reoperation. In contrast to the enthusiasm shown by institutions advocating a liberal use of extensive aortic repairs with antegrade DTA stenting in DB1-AAD, and despite our positive results with the frozen elephant trunk surgery [59], we still believe that patient’ selection is crucial to obtaining favourable outcomes (Table 5). In particular, we opt for a more conservative repair in the elderly patients as well as in those critically presenting with shock and advanced end organ dysfunction. Conversely, we support a more aggressive approach with prophylactic stenting of DTA in the younger subjects or in those who present with distal malperfusion due to severe compression of the DTA true lumen. Furthermore, the implementation of endovascular techniques with distal arch and/or DTA stentgrafting can enable simplified arch surgical reconstructions in patients presenting with complex arch tears or distal arch rupture.

Funding Conflict of interest: none declared.

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