Author + information
- Received March 21, 2016
- Accepted March 29, 2016
- Published online June 21, 2016.
- Yong-Lin Qin, MDa,
- Feng Wang, MDb,
- Tian-Xiao Li, MDc,
- Wei Ding, MDa,
- Gang Deng, MDa,
- Bo Xie, MDa and
- Gao-Jun Teng, MDa,∗ ()
- aCenter of Interventional Radiology and Vascular Surgery, Department of Radiology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, China
- bDepartment of Interventional Radiology, the First Affiliated Hospital of Dalian Medical University, Dalian, China
- cDepartment of Interventional Radiology, Henan Provincial People’s Hospital, Zhengzhou University, Zhengzhou, China
- ↵∗Reprint requests and correspondence:
Dr. Gao-Jun Teng, Department of Radiology, Zhongda Hospital, School of Medicine, Southeast University, 87 Dingjiaqiao Road, Nanjing 210009, China.
Background Thoracic endovascular aortic repair (TEVAR) has been used in patients with uncomplicated type B acute aortic dissection (B-AAD) to reduce late morbidity and mortality. The outcomes of comparisons between TEVAR and best medical treatment (BMT) on patients with uncomplicated type B-AAD are inconsistent in the published reports.
Objectives This study sought to further clarify the early and long-term (11-year) outcomes of TEVAR in patients with uncomplicated type B-AAD compared with those with BMT treatment.
Methods Between February 2003 and August 2014, 338 patients with uncomplicated type B-AAD were retrospectively identified in 3 tertiary medical centers. Information about baseline characteristics was collected from medical records. Images were retrieved from the imaging archiving system, and the thrombosis status of the false lumen and extent of the dissection were evaluated via computed tomography angiography. Early and late outcomes were recorded and analyzed.
Results TEVAR procedures were performed on 184 patients (TEVAR group) and BMT for 154 patients (BMT group). Early events and 30-day mortality were not significantly different between the 2 groups. Patients receiving BMT had significantly higher aortic-related adverse events compared with those in the TEVAR group (p = 0.025). All-cause mortality with TEVAR was significantly lower than that of BMT (p = 0.01).
Conclusions This study confirmed the feasibility of TEVAR for uncomplicated type B aortic dissection in the acute setting with fewer aortic-related adverse events and a lower mortality rate compared with BMT.
The morbidity and mortality rate in type B acute aortic dissections (B-AAD) is highest within 10 to 14 days after acute onset (1,2). Current consensus holds that patients with complicated type B-AAD could be treated with thoracic endovascular aortic repair (TEVAR) (3), leading to better in-hospital survival than open surgery (4). Patients with uncomplicated type B-AAD are commonly treated with conservative therapy (best medical treatment [BMT]) although the long-term outcome of medical therapy alone is suboptimal (5), with a reported 30% to 50% mortality rate at 5 years and a delayed expansion of the false lumen in 20% to 50% of patients at 4 years (6).
Given that a thrombosed false lumen predicts lower event rates with type B-AAD (7) and favorable false lumen remolding after TEVAR for type B aortic dissection (8–10), TEVAR has also been used in patients with uncomplicated type B-AAD to reduce late morbidity and mortality (8,11,12). Recently, several studies have compared early and late outcomes of TEVAR and BMT in patients with type B-AAD (8,11–16). However, the findings of these studies of patients with uncomplicated type B-AAD have been inconsistent, likely due to different patient enrollment criteria (8,11,12,15) and/or short follow-up duration (11,14–16).
For patients treated with BMT, mortality rates at 3, 5, and 6 years have previously been reported as 22.4% (17), 27.9% (18), and 42% (5), respectively. With improved operator skills and better technology, TEVAR might emerge as the first-line therapy for uncomplicated type B-AAD (13). However, the results following preemptive TEVAR for uncomplicated type B-AAD in the acute setting require long-term observation to determine the benefits.
The aim of this retrospective study was to further clarify the early and long-term outcomes of TEVAR in patients with uncomplicated type B-AAD compared with those receiving BMT.
Between February 2003 and August 2014, all patients with uncomplicated type B-AAD were identified retrospectively through a review of hospital admitting notes and radiology department procedural logs in 3 medical centers in China. Uncomplicated type B-AAD is defined as dissection without rupture, malperfusion syndromes, refractory pain, or rapid aortic expansion at onset or during presentation at the hospital (13). Final survival state was determined via the review of hospital admitting notes or telephone follow-up. The clinical ethics committees of all hospitals approved the protocol.
For all eligible patients, we retrospectively reviewed all of their computed tomography angiography (CTA) scans. The anatomic characteristics, thrombosis status of the false lumen, and extent of the dissection (using the orifice of the celiac trunk as a threshold marker) were evaluated and documented in the chart at the time of assessment.
Inclusion criteria of this study were: 1) age 18 to 80 years; 2) onset of symptoms to treatment ≤14 days; 3) primary entry tear confined to the descending thoracic aorta, with no involvement of the aortic arch; and 4) maximum transverse diameter of the thoracic aorta ≤55 mm.
Patients were excluded if an aortic dissection was secondary to trauma, iatrogenic injury, or intramural hematoma; if the patient was inappropriate for TEVAR due to unfavorable anatomic characteristics; or if the patient had Marfan syndrome or Ehlers-Danlos syndrome.
Study patients were categorized into 2 groups based on their treatment. The TEVAR group consisted of patients with uncomplicated type B-AAD treated with TEVAR and antihypertensive medications. The BMT group consisted of patients with uncomplicated type B-AAD treated exclusively with medical management.
The decision making for TEVAR was usually done by the consensus of the patient and their family with fully informed consent. Spinal cord protective measures were not routinely used in these patients. When the primary tear was close to the left subclavian artery (LSA) and/or the left common carotid artery (LCCA), the origins of the LSA and/or the LCCA were covered by the stent graft. Debranching of the LCCA and LSA was performed pre-procedurally via a right common carotid artery (RCCA)-LCCA bypass or during the procedure using the chimney technique. Chimney stenting was performed in the LSA based on radiographic assessments of vertebrobasilar circulation. A distal bare stent in the aorta was deployed to prevent further expansion of the distal end of the stent graft, when it was deemed necessary based on an angiographic evaluation of the diameter of the true and false lumens.
Antihypertensive medications (calcium-channel blockers, nitroglycerine, β-blockers, or a combination) were administered to all patients (TEVAR and BMT) with systolic blood pressure (SBP) >120 mm Hg at presentation. The initial goals for BMT were to reduce SBP to 100 to 120 mm Hg and relieve pain. If chest pain was persistent, a non-narcotic analgesic (buprenorphine hydrochloride) or narcotic analgesic (morphine hydrochloride) was administered intravenously, again for all patients (TEVAR and BMT).
After discharge, all patients (TEVAR and BMT) with hypertension were treated with calcium antagonists, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, or β-blockers (either alone or in combination) to maintain the morning SBP (≤140 mm Hg).
In this study, an early event was defined as occurring within 30 days following the diagnosis. A late event was defined as one associated with the dissection that occurred >30 days following the diagnosis. Aortic-related adverse events included rupture, aortic enlargement (>60 mm), retrograde type A aortic dissection (A-AD), ulcer-like projection (defined as a localized blood-filled pouch protruding from the true lumen into the thrombosed false lumen of the aorta), endoleak, or stent graft-induced new entry (SINE).
Significant differences between groups were determined with the Fisher exact test for categorical variables and Student t tests for continuous variables. A Kaplan-Meier analysis was used to estimate the overall survival and freedom from aortic-related adverse events, and log-rank tests were used to discriminate between the Kaplan-Meier curves. All of the these statistical tests were 2-sided, and the significance level was <0.05. Statistical analyses were performed using SPSS version 13.0 (SPSS, Chicago, Illinois).
A total of 338 patients were enrolled in this study, with TEVAR procedures performed on 184 patients (TEVAR group). The baseline characteristics, comorbidity profiles, extension of dissection, and patency of false lumen were evenly distributed between the TEVAR and BMT groups (Table 1).
A total of 193 stent grafts were implanted in 184 patients (Talent [Medtronic, Minneapolis, Minnesota] in 42 patients; Zenith [Cook Medical, Bloomington, Indiana] in 34 patients; GORE TAG [W.L. Gore & Associates, Flagstaff, Arizona] in 18 patients; Aegis [Microport, Shanghai, China] in 57 patients; and Ankura [Lifetech Scientific, Shenzhen, China] in 33 patients) with a mean coverage length 159.2 ± 24.5 mm. Among patients in the TEVAR group, 2 (1.1%) underwent an RCCA-LCCA bypass, 1 (0.5%) had an RCCA-LCCA-LSA bypass, 9 (4.9%) received chimney stenting in the LSA, and 2 (1.1%) had chimney stenting in the LCCA. The LSA orifice was covered directly with a stent graft without a debranching procedure in 3 (1.6%) patients.
Among the 338 qualified patients, 159 (47.0%) patients (TEVAR group, n = 89; BMT group, n = 70) presented with elevated SBP. In all of these patients, the SBP was lowered to <120 mm Hg with medication during hospitalization. After discharge, all patients (TEVAR and BMT groups) with hypertension were followed by a group of cardiovascular physicians and treated with calcium antagonists, angiotensin-converting enzyme inhibitors, angiotensin-receptor blockers, or β-blockers, either alone or in combination, and blood pressure was controlled to approximately 120/80 mm Hg for the first month and ≤140/90 mm Hg thereafter.
Detail of early events are listed in Table 2. In the TEVAR group, 16 type Ia endoleaks and 1 type Ib endoleak were observed immediately following stent graft angiography. These patients were left untreated and followed. One patient treated with chimney stenting in the LCCA experienced a transient stroke but completely recovered before discharge. On day 7 post-TEVAR, 1 patient died of multiorgan failure. No paraplegia or paraparesis was found in these patients. Among the patients in the BMT group, 2 complained of chest pain and subsequently underwent TEVAR; 1 patient experienced a retrograde dissection with increased hemomediastinum also underwent TEVAR for complicated aortic dissection; and 1 patient experienced multiorgan failure and died on day 10. Among the patients in the BMT group, 3 patients experienced sudden death due to aortic rupture before discharge.
Follow-up CTA imaging was available for all patients; the final survival state was determined via telephone follow-up in 25 patients. The mean follow-up time was not significantly different between the 2 groups (Table 2).
Late event rate was significantly higher in the BMT group compared with the TEVAR group (p = 0.005) (Table 2). A total of 50 late deaths were reported, including 27 aortic-related late deaths, 24 of which were due to a ruptured false lumen in the descending aorta and the remaining 3 to retrograde type A-AD. A total of 18 deaths were classified as unrelated to the dissection (cardiac-related deaths n = 4; cancer-related deaths n = 10; pulmonary infection-related deaths n = 3; death caused by traffic accident n = 1). The etiology in the other 5 deaths could not be determined.
The cumulative freedom from aortic-related adverse events at 5-year follow-up was 71.8% in the TEVAR group and 62.2% in the BMT group. The patients treated with BMT experienced significantly more aortic-related adverse events compared with patients treated with TEVAR (p = 0.025) (Figure 1).
The cumulative survival rates from all causes of death at the fifth year was 89.2% in the TEVAR group and 85.7% in the BMT group. Log-rank tests revealed a significantly higher mortality rate in the BMT group versus the TEVAR group (p = 0.01) (Figure 2A).
The long-term prognosis of uncomplicated type B-AAD treated with BMT is poor. The present study compared TEVAR with BMT regarding outcomes in patients with uncomplicated type B-AAD (Central Illustration).
The early event rate in patients with uncomplicated type B-AAD who are treated with TEVAR was largely unknown. In our study, the early event rate in the TEVAR group was 10.3%, which was higher than that of the BMT group (4.5%), although the difference was not statistically significant. The early event rate in the BMT group was consistent with findings from previous studies (19,20). In the TEVAR group, most of the early events (17 of 19) seemed minor or transient, but regular surveillance was warranted if type I endoleak presented. However, in the BMT group, 4 major complications (1 organ failure and 3 ruptures) occurred, plus 3 uncomplicated dissections became complicated despite aggressive antihypertensive management. Therefore, the TEVAR-related early events may have been more frequent, but they were not the major complications associated with BMT.
In previous studies, the early mortality rates in patients with type B aortic dissection treated with TEVAR range between 2.4% and 10.9% (8,14) and, in patients treated with BMT, the range has been between 0% and 10.6% (5,11,21,22). In a different approach from previous studies, the ADSORB (Acute Dissection Stent Grafting or Best Medical Treatment) trial was the first randomized trial to compared BMT with TEVAR for patients with uncomplicated type B-AAD (13). In the ADSORB trial (16), no deaths occurred in either the TEVAR or BMT group during the first 30 days. In our study, the early mortality rate was 0.5% with TEVAR and 2.6% with BMT. However, compared with other studies, 30-day mortality rates were lower in patients treated with TEVAR in both the ADSORB trial and our research. This discrepancy can be explained by the remarkable difference in pre-treatment patient selection. The patients who were selected for TEVAR in the early reports presented with complicated type B aortic dissection or combined series including both acute and chronic type B aortic dissection. By contrast, the patients assigned to TEVAR in the ADSORB trial (16) and our study had only uncomplicated type B-AAD.
In the present study, the main causes of late events in patients treated with BMT were aortic enlargement (28 of 59; 47.5%) and aortic rupture (19 of 59; 32.2%). Consistent with early reports, aortic enlargement was associated with aortic rupture in patients with uncomplicated type B-AAD treated with medical therapy only (19) and was therefore an important late event. Type I endoleak (11 of 35; 31.4%) and SINE (9 of 35; 25.7%) were the main late events in patients treated with TEVAR. Type I endoleak was not a perpetual complication of TEVAR, and 5 type Ia endoleaks and 1 type Ib endoleak after TEVAR disappeared by final CTA imaging in this study. Consistent with an earlier report (23), SINE was a severe complication in the TEVAR group and was associated with substantial mortality The patients in the BMT group experienced more aortic-related adverse events than those treated with TEVAR (Figure 1), and this result was partially consistent with our earlier report (11).
Previous studies in patients with complicated and uncomplicated type B-AAD treated with TEVAR have reported 1- and 5-year overall survival rates of 83% and 79%, respectively (24). In the longest follow-up to date for overall survival in patients with type B-AAD treated with BMT, the overall survival rates are 35% and 17% at 10 and 15 years, respectively (25). Although the ADSORB trial was the first randomized trial of uncomplicated type B-AAD (13), some questions have been raised regarding the ADSORB trial’s design (small sample size, the primary endpoint selected, and short duration of follow-up). Thus, the ADSORB trial did not have adequate statistical power to detect differences in aortic-related and all-cause mortality (26). The INSTEAD-XL (Investigation of Stent Grafts in Aortic Dissection With Extended Follow-Up) trial is the only prospective randomized trial to investigate the efficacy of TEVAR for uncomplicated aortic dissections, although the patients treated with TEVAR had a wide range of times from symptom onset to treatment (2 to 52 weeks after symptom onset). The INSTEAD-XL trial showed TEVAR in addition to optimal medical treatment is associated with improved 5-year aorta-specific survival and delayed disease progression (27). In our earlier report, patients with type B-AAD treated with TEVAR did not have a significantly lower mortality rate compared with those in the BMT group during 5-year follow-up (11). In the present study, only patients with uncomplicated type B-AAD were included with a longer follow-up duration, and the mortality rate from all causes was significantly lower in patients treated with TEVAR compared with the BMT group (Figure 2A).
Aortic-related risk factors for death include false lumen patency, arch involvement, and rupture (28). Aortic rupture is the primary cause of aortic-related death following TEVAR and comprises 50% to 100% of all causes of death (12,29,30). The aortic-related deaths in our series were also mostly due to aortic rupture (24 of 27; 88.9%). There were an additional 3 deaths due to retrograde type A-AD that occurred during follow-up. We cannot exclude the possibility that the deaths of unknown etiology might also be due to aortic-related events, such as retrograde type A-AD or rupture. Therefore, both aortic-related and unknown deaths were composited and analyzed, and the patients in the BMT group had more deaths compared with the TEVAR group (Figure 2B). In the present study, both aortic-related adverse events and all-cause deaths were also combined and analyzed; the patients in the BMT group had significantly more events compared with the TEVAR group (Figure 3).
This study had several limitations, including its retrospective nature, different procedural protocols in 3 hospitals (such as various TEVAR procedure manipulations and medical regimens in different hospitals), and various coverage length of stent grafts selected based on individual preference and local availability.
This study confirmed the feasibility of TEVAR for uncomplicated type B-AAD in the acute setting with lower aortic-related adverse events and a lower mortality rate compared with BMT after 5 years of follow-up. Given that the TEVAR procedure did not significantly lower morbidity and mortality compared with BMT during the early years of follow-up, TEVAR should be considered as a therapy to improve late outcomes in young adults or patients with longer life expectancy.
COMPETENCY IN PATIENT CARE AND PROCEDURAL SKILLS: In a retrospective study of patients with uncomplicated type B acute dissection of the thoracic aorta, TEVAR was associated with a lower rate of adverse aortic events and mortality than medical treatment.
TRANSLATIONAL OUTLOOK: Randomized trials are needed to compare the long-term outcomes of TEVAR with medical treatment in patients with uncomplicated type B-AAD.
The authors thank Wenlin Fan in Hahnemann University Hospital/Drexel University College of Medicine, Philadelphia, Pennsylvania, for kindly providing writing assistance, and Jie Min in Public Health School, Southeast University, Nanjing, China, for assistance with the statistical analysis.
This study is sponsored by the National Key Basic Research Program of China (973 Program; 2013CB733800, 2013CB733803), and Jiangsu provincial special program of medical Science (BL2013029). The National Key Basic Research Program of China and Jiangsu provincial special program of medical Science had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; or decision to submit the manuscript for publication. The authors have reported that they have no relationships relevant to the contents of this paper to disclose.
- Abbreviations and Acronyms
- type A aortic dissection
- type B acute aortic dissection
- best medical treatment
- computed tomography angiography
- left common carotid artery
- left subclavian artery
- right common carotid artery
- systolic blood pressure
- stent graft-induced new entry
- thoracic endovascular aortic repair
- Received March 21, 2016.
- Accepted March 29, 2016.
- American College of Cardiology Foundation
- Erbel R.,
- Oelert H.,
- Meyer J.,
- et al.
- Fattori R.,
- Montgomery D.,
- Lovato L.,
- et al.
- Qin Y.L.,
- Deng G.,
- Li T.X.,
- Wang W.,
- Teng G.J.
- Nienaber C.A.,
- Rousseau H.,
- Eggebrecht H.,
- et al.
- Shah T.R.,
- Rockman C.B.,
- Adelman M.A.,
- et al.
- Tsai T.T.,
- Fattori R.,
- Trimarchi S.,
- et al.
- Garbade J.,
- Jenniches M.,
- Borger M.A.,
- et al.
- Fattori R.,
- Cao P.,
- De Rango P.,
- et al.
- Tolenaar J.L.,
- Froehlich W.,
- Jonker F.H.,
- et al.
- Eggebrecht H.,
- Thompson M.,
- Rousseau H.,
- et al.
- Nienaber C.A.,
- Kische S.,
- Rousseau H.,
- et al.
- Kitai T.,
- Kaji S.,
- Yamamuro A.,
- et al.