Long-Term Outcomes of Endovascular Repair of Thoracic Aortic Aneurysms

Abstract

The thoracic aorta is a dynamic structure composed of the aortic root, ascending aorta, aortic arch, and descending aorta. It is subject to the pressure and volume of the cardiac cycle and susceptible to atherosclerotic and aneurysmal changes. With these changes, the risk for acute aortic syndromes increases, thus creating the impetus for earlier interventions. The previous standard of open surgical repair has undergone a transition in recent years toward endovascular repair being favored in the descending and abdominal aortas with ongoing investigation into approaches for the ascending and aortic arch. These therapies have been shown to improve early mortality and morbidity outcomes with the caveat of more interventions compared with open surgery. We undertook this review to analyze the current data available regarding long-term outcomes in patients undergoing endovascular repair for thoracic aortic disease. The data support long-term benefit of endovascular repair for thoracic aortic disease. The primary indications identified for reintervention are endoleak and further aneurysmal degeneration. As the devices available for endovascular repair evolve, ongoing review of these outcomes will be necessary. It will also be important to trend the results as further techniques become available for endovascular repair of the ascending aorta and aortic arch.

The aorta supplies oxygenated blood from the left heart to the body's systemic circulation. It is composed of three histologic layers: inner tunica intima, middle tunica media, and outer tunica adventitia. The diaphragm is used to divide the thoracic aorta originating from the aortic valve and the abdominal aorta which terminates by branching into the iliac arteries in the pelvis. The thoracic aorta may be further divided into four segments: the aortic root, ascending aorta, aortic arch, and descending aorta. ¹ The aorta is generally considered to be dilated or aneurysmal once the diameter is above 4.0 cm. ²

By definition thoracic aortic aneurysms (TAAs) are true aneurysms that include all three layers of the vessel wall. The aortic root and ascending aorta are most commonly involved in TAAs at around 60%. This is followed by the descending aorta at 40%, aortic arch at 10%, and thoracoabdominal aneurysms at 10%. ³ Morphologically, TAAs are primarily fusiform with a small proportion of saccular aneurysms. ⁴

The natural history of TAAs has been well-studied. Complications from aortic aneurysms are related to their size and include aortic dissection, intramural hematoma (IMH), and penetrating ulceration. The most devastating complication is aortic rupture and is more common with acute aortic syndromes (AASs). The two classic systems for categorizing aortic dissections are the DeBakey and Stanford systems ( Fig. 1 ). The DeBakey system uses three categories: Type I dissections begin in the ascending aorta and include the aortic arch and descending aorta, Type II dissections only involve the ascending aorta, while Type III dissections include the descending aorta (IIIa) and may extend to the abdominal aorta (IIIb). The Stanford system uses two categories: Type A aortic dissection (TAAD) is any dissection involving the ascending aorta while Type B aortic dissections (TBADs) are those that do not involve the ascending aorta. ¹ A newer classification system proposed by the Society of Thoracic Surgeons (STS) and the Society of Vascular Surgery (SVS) divides the aorta into 12 zones with dissections classified by the site of initial tear and further categorized by the proximal and distal extent of the dissection flap ( Fig. 2 ). ⁵

Fig. 1.

DeBakey and Stanford classifications of aortic dissection (reproduced with permission from Carrel T, Sundt TM 3rd, von Kodolitsch Y, Czerny M. Acute aortic dissection. Lancet 2023;401(10378):773–788).

Fig. 2.

STS/SVS aortic zones for dissection definition (reproduced with permission from Blakeslee-Carter J, Pearce BJ, Sutzko DC, Spangler E, Passman M, Beck AW. Progressive aortic enlargement in medically managed acute type B aortic dissections with visceral aortic involvement. J Vasc Surg 2022;76(6):1466–1476.e1). STS, Society of Thoracic Surgeons; SVS, Society for Vascular Surgery.

The risk of AASs has been shown to increase with increasing aortic diameter. This is due to the increased wall tension as defined by the Law of Laplace wherein wall tension is directly proportional to the radius of the vessel. In their seminal study Coady et al ⁶ found the median size of the ascending aorta to be 6.0 cm and the median of the descending aorta to be 7.2 cm at the time of aortic dissection or rupture. This has defined the current standards for intervention at 5.5 cm diameter of the ascending aorta and 6.5 cm diameter of the descending aorta in otherwise healthy low-risk patients. This study also found that the average annual growth rate of aneurysms increased with size with the mean overall growth rate of 0.12 cm/year. The increasing incidence of aortic dissection with increasing aortic diameter was strengthened by the recent KP-TAA study that again showed an inflection point at 6.0 cm in the ascending aortic diameter. ⁷ These criteria do not account for differences in patient body habitus, however. Recent data have shown that consideration of patient height to aortic diameter may be used to further risk stratify. ⁸

It is this understanding of aortic histology and pathophysiology that guides the current approaches to intervention, classically with open surgery and more contemporarily with increasing use of endovascular devices.

History of Thoracic Aortic Aneurysm Repair

Open Surgery

Drs. DeBakey and Cooley are credited with the first successful repair of a descending TAA (DTAA) by resection and replacement with a homograft in January 1953. ⁹ This case and subsequent series in thoracoabdominal aortic aneurysm (AAA) repairs led to increased surgical volume and the need for artificial aortic tissue replacement options. Again Dr. DeBakey is credited with introducing Dacron as a suitable material for vascular grafts with capability for expansion that mimicked the native aorta. ¹⁰ Following the introduction of Dacron grafts, an extra-anatomy approach with complete resection of aneurysmal tissue was favored for repair in an effort to limit ischemic complications. In the 1960s, Dr. Crawford began to introduce the inclusion technique and button anastomosis for visceral vessels. These techniques saw a significant improvement in survival. Many protective adjuncts were also developed during this time period, including left heart bypass, cerebrospinal fluid (CSF) drainage, and cold renal perfusion. The techniques developed by Drs. DeBakey, Cooley, and Crawford continue to guide the current approach to open repair of thoracic and thoracoabdominal aortic aneurysms ( Fig. 3 ). ¹¹

Fig. 3.

Crawford classification of thoracoabdominal aortic aneurysms (reproduced with permission from Estrera AL, Sandhu HK, Charlton-Ouw KM, Afifi RO, Azizzadeh A, Miller CC 3rd, Safi HJ. A quarter century of organ protection in open thoracoabdominal repair. Ann Surg 2015;262(4):660–668).

Endovascular Repair

Endovascular aneurysm repair (EVAR) has largely supplanted open surgery as the preferred approach to aneurysms of the thoracic and abdominal aorta. The efficacy of EVAR was initially demonstrated in AAAs in multiple randomized controlled trials (RCTs) and has since been extrapolated to thoracic EVAR (TEVAR) on a device-by-device basis with prospective studies. ¹²

The United Kingdom (UK) EVAR trial 1 compared elective repair of AAAs via EVAR or open surgery in patients aged 60 years or more with aneurysms of 5.5 cm or greater that were considered candidates for either approach. Mid-term and long-term outcomes found similar mortality between the groups but higher reintervention rates in the EVAR group. ^{13 14 15} The EVAR trial 2 evaluated patients deemed unfit for surgery and compared EVAR to medical management with similar overall mortality between the groups at 4 years. ¹⁶ The Dutch Randomized Endovascular Aneurysm Management (DREAM) trial comparing open repair and EVAR in patients with 5 cm or greater diameter AAA found decreased early mortality (1.2 vs. 4.6%) and complication rates (4.7 vs. 9.8%) in the EVAR group compared with open surgery but similar long-term survival rates (38.5 vs. 42.2%) with increased reintervention (37.8 vs. 21.1%) in the EVAR group. ^{17 18} The French Aneurysme de l'aorte abdominale, Chirurgie versus Endoprothese (ACE) trial found similar survival free of death or major events between EVAR and open surgery (82.4 vs. 85.1%) but an increased rate of reintervention in the EVAR group (16 vs. 2.4%). ¹⁹ The United States Veterans Affairs Open Versus Endovascular Repair (OVER) trial found lower 30-day mortality in the EVAR group (0.5 vs. 3.0%) compared with open surgery but no difference in mortality (32.0 vs. 33.4%) or reintervention rate (22.1 vs. 18.8%) at 5.2 years of mean follow-up. ^{20 21}

Subsequent meta-analysis of the EVAR trial 1, DREAM trial, ACE trial, and OVER trial outcomes was performed to assess the loss of early mortality benefit of EVAR. Early mortality was confirmed in the EVAR group with convergence of survival curves between the two groups after 3 years. After the 3-year mark, aneurysm-related mortality was increased in the EVAR group. Subgroup analysis identified patients with peripheral artery disease as benefitting from open repair compared with EVAR in the mid-term. ²² Overall, these results showed early benefits to EVAR but called into question the durability of the stents available at the time and identified the need for long-term postoperative surveillance after EVAR.

Hybrid Approaches

Aneurysms of the thoracic aorta with involved ascending aorta, aortic arch, or arch vessels pose a unique problem as they do not fall into the simple categories of open surgical repair versus endovascular repair. An increasing area of interest has been the hybrid approach with open surgical treatment of the ascending aorta and aortic arch combined with TEVAR. Depending on the extent of the aneurysm, surgical alterations to normal vascular anatomy may allow for placement of stent grafts more proximally in the aorta. ²³ This approach allows for treatment of a greater cohort of patients than TEVAR alone and may avoid otherwise significantly larger operations for the same group. ²⁴

Approach and Outcomes by Type

Descending Thoracic Aorta

Guidelines

Descending Thoracic Aortic Aneurysm

The SVS has released clinical practice guidelines for the management of DTAA. ²⁵ All of the following recommendations are Grade I with A or B level of evidence. In patients with DTAA undergoing consideration for TEVAR, preoperative computed tomography (CT) angiography with fine cuts should be performed of the entire aorta, iliac and femoral vessels, and the head and neck to assess the anatomy. Three-dimensional reconstruction should be routinely used for case planning. Postoperative contrast-enhanced CT should be performed at 1 month, 12 months, and then yearly after TEVAR. More frequent imaging can be considered based on findings of concern at the 1-month scan. For the treatment of elective DTAA in patients who are candidates for either TEVAR or open surgery, TEVAR is the preferred approach due to decreased morbidity, length of stay, and short-term mortality.

The indications for TEVAR in DTAA are asymptomatic patients with DTAA maximum diameter that exceeds 5.5 cm in low-risk patients with appropriate anatomy (Grade IB) and higher diameter thresholds for high-risk patients where treatment benefit is lower than risk of DTAA itself (Grade 2C).

Type B Aortic Dissection

Aortic dissection, IMH, and penetrating aortic ulcers (PAUs) are pathologies within a spectrum of AASs. Treatment is often on a nonelective basis and guidelines differ from elective DTAA repair. TBADs may be considered complicated, high risk, or uncomplicated on presentation with the potential for progression during care. Complicated TBAD is characterized by rupture or end-organ malperfusion. Uncomplicated TBADs do not demonstrate rupture, malperfusion, or high-risk features. The high-risk features are refractory pain or hypertension, bloody pleural effusion, aortic diameter larger than 40 mm, false lumen diameter greater than 22 mm, and an entry tear on the lesser curve of the aorta.

The STS and American Association for Thoracic Surgery have released joint clinical practice guidelines for the management of TBAD. ²⁶ Within those guidelines, the following relevant recommendations were made. In patients with acute complicated TBAD, TEVAR is indicated for patients with favorable anatomy (Class IB). In patients with unsuitable anatomy, open surgical repair should be considered (Class IIA). The recommended treatment for patients with uncomplicated TBAD is optimal medical therapy (OMT; Class IB). Prophylactic TEVAR may be considered in uncomplicated TBAD to reduce long-term aortic-related death and adverse events (Class IIB). In patients with chronic TBAD, open surgical repair should be considered when indications for intervention are met, comorbidities are not prohibitive, and anatomy is unsuitable for TEVAR (Class IIA). TEVAR is reasonable in these patients when anatomy is suitable for TEVAR and they are high risk for open repair (Class IIA).

Outcomes

Unlike with the trials presented above regarding EVAR for AAA, most of the outcome data regarding TEVAR are from single-center observational studies and retrospective database reviews. We will discuss some of these studies that provide the current understanding of the expected results with TEVAR for various thoracic aortic pathologies.

DTAA

Harky et al published a systematic review and meta-analysis comparing open surgical repair and TEVAR for DTAA in 2018. ²⁷ This review included 13 studies and 14,580 patients, of which 73% underwent open surgery and 27% had TEVAR. The TEVAR cohort was notable for being older and more often undergoing urgent or emergent procedures. Duration of intensive care unit and overall hospital stay were significantly shorter in the TEVAR group. The major morbidity with TEVAR was vascular complications (5.29%). Operative mortality was also higher than in open surgery (4.4 vs. 3.2%), but 1- and 5-year mortality were similar in both groups. This meta-analysis was limited by the varying follow-up periods of the respective studies, the mostly retrospective studies being included, and often single-center studies, all of which could limit the generalizability and reliability of the results. This study included operations performed from 1992 to 2013 and technological advances in TEVAR have been made.

One such single-center experience of TEVAR for DTAA was published by Fossaceca et al in 2013. ²⁸ Over the period from January 2005 to December 2011, they treated 53 patients with DTAA with TEVAR. In total, 37.7% of the cases were performed emergently, 18.8% underwent concomitant carotid-subclavian bypass surgery, and 35.8% required CSF drainage. Postoperative mortality with a mean follow-up of 25.6 months was 7.5% and major complications were found in 9.4% of cases.

The first endograft approved for DTAA was the TAG endograft by W.L. Gore & Associates, which received Food and Drug Administration (FDA) approval in 2005. When compared with open surgery, the TAG endograft showed lower rates of aneurysm-related death at 5 years (2.8 vs. 11.7%). ²⁹ Another early device was the TX2 endograft by Cook Medical which showed similar long-term survival and lower postoperative complications compared with open surgery at 5 years. ³⁰ The Talent Thoracic Stent Graft by Medtronic Vascular showed 5-year freedom from aneurysm-related mortality of 96.1% and freedom from secondary endovascular procedures of 81.5%. ³¹ The Valiant Thoracic Stent Graft by Medtronic Vascular was found to be noninferior to the Talent system at 12 months for all-cause mortality and showed lower incidence of aneurysm growth >5 mm and secondary procedures for endoleak. ³² Overall, the thoracic endografts may be categorized by the presence or absence of a proximal bare stent. The Medtronic Valiant, Bolton Relay, Cook Zenith, Jotec E-vita, and Gore C-TAG all have a proximal bare stent which is thought to improve sealing of the proximal neck. The Gore TAG, Cook TX2, and Bolton Relay plus do not have a proximal bare stent. ³³

The results above and widening array of devices have led to the adoption of TEVAR as first-line treatment for DTAA in patients with appropriate anatomy. More recent study has gone into the effects of stent graft material on outcomes. The Gore TAG is composed of expanded polytetrafluoroethylene and was compared with the Relay Plus a Dacron graft. When comparing the rates of mortality, spinal cord ischemia (SCI), endoleak, and reinterventions, the outcomes were similar at 3 years regardless of graft composition. ³⁴ As we see longer survival in patients with aortic endografts, consideration will need to be made regarding the alteration in flow hemodynamics compared with the native aorta. It is known that the aortic endografts are stiffer than the native aortic tissue and could theoretically lead to left ventricular strain and congestive heart failure. ³⁵ While the data to support these outcomes are limited in practice, they may be expected to arise as the population of patients with endografts grows and ages. Further study of TEVAR should include considerations of graft composition and flow hemodynamics to address these concerns.

Complicated TBAD

TEVAR has become the standard of care for acute complicated TBAD due to improved morbidity and mortality compared with open surgery. ^{36 37 38 39} These early results have been confirmed in many subsequent single-center and retrospective studies with increasing evidence for long-term efficacy. Stelzmueller et al reported on 55 patients presenting with acute complicated TBAD between March 2001 and December 2016. ⁴⁰ Overall in-hospital mortality for the cohort was 9% with a statistically significant increase in the patients presenting with malperfusion, pending rupture, or rupture compared with those with persistent pain, rapid enlargement of the aorta, or changes to the true to false lumen ratio. The most common complication was early endoleaks in 34% with five patients requiring reintervention within 30 days. Freedom from aorta-related death at 5 years was 77%.

As the TEVAR approach has become the preferred option for complicated TBAD, focus has shifted to improvements in technology and technical aspects of endograft placement. A recent RCT evaluated the outcomes with standard TEVAR versus TEVAR with bare metal stent (BMS). ⁴¹ This prospective study performed at two centers in China between 2010 and 2013 randomized 84 patients with acute complicated TBAD to receive TEVAR or TEVAR with BMS. During 5 years of follow-up, there was a single death (2.4%) in the TEVAR-BMS group versus 5 deaths (11.9%) in the TEVAR group. Of those death, 4 in the TEVAR group were considered aorta-related mortality. They also noted significant increases in the true lumen diameter and complete false lumen thrombosis in the TEVAR-BMS group.

These results were similar to the multinational Study of Thoracic Aortic Type B Dissection Using Endoluminal Repair (STABLE I) study which enrolled 86 patients in the United States, Europe, and Australia from 2007 to 2012. ⁴² This study examined both acute (55 patients) and nonacute (31 patients) TBAD undergoing TEVAR with a distal BMS with follow-up to 5 years. Five-year freedom from aorta-related mortality was 83.9% in the acute TBAD group and 70.1% in the nonacute TBAD group, but the difference was not statistically significant. They also noted progressive increase in true lumen diameter and complete false lumen thrombosis throughout the follow-up period. The studies point to TEVAR with the addition of a BMS leading to improved aortic remodeling thus decreasing aortic-related death in patients with TBAD.

One of the most challenging sequelae of DTAA and TBAD is a rupture of the descending thoracic aorta (rDTAA) with high associated mortality. Open repair is known to have high rates of perioperative morbidity and mortality. ⁴³ This condition has also seen a trend toward improved outcomes with TEVAR. ^{44 45} A recent nationwide multicenter retrospective review from Sweden identified 140 patients between January 2000 and December 2015 who underwent TEVAR for rDTAA. ⁴⁶ The overall complication rate was 45% with stroke (14.7%), paraplegia (9.6%), and major bleeding (9.6%) as the most common contributing conditions. The most common TEVAR-related complication was endoleak in 22.1% of patients. Reintervention was performed in 19.7% of patients. Survival was 80% at 30 days, 71.7% at 3 months, 65.3% at 1 year, and 31.9% at 5 years. They found history of stroke, age, and previous aortic intervention as preoperative risk factors for mortality and major bleeding, stroke, and renal failure as postoperative risk factors. Even with timely repair, rDTAA carries poor long-term survival, but TEVAR has led to improvements in short-term survival.

Uncomplicated TBAD

The current paradigm for uncomplicated TBAD remains conservative management with OMT. The physiologic goals of OMT are to regulate the patient's heart rate and blood pressure to minimize further propagation of the dissection and growth of the false lumen. One concern with conservative management is the loss of patients to follow-up when they require lifelong surveillance. Multiple trials have since examined the role of TEVAR in uncomplicated TBAD. The Investigation of Stent Grafts in Aortic Dissection (INSTEAD) trial was an RCT comparing TEVAR plus OMT or OMT alone for stable uncomplicated TBAD. ⁴⁷ They enrolled 140 patients with follow-up to 5 years after the procedure. Patients were between 14 days and 1 year from diagnosis. All-cause mortality (11.1 vs. 19.3%), aorta-related mortality (6.9 vs. 19.3%), and dissection progression (27 vs. 46.1%) were all lower in the TEVAR plus OMT group compared with the OMT alone group at 5 years. In patients who underwent TEVAR, false lumen thrombosis was identified in 90.6% of cases at 5 years. The Acute Dissection Stentgraft or Best Medical Treatment (ADSROB) trial was a prospective multicenter RCT comparing TEVAR or OMT in 61 patients with uncomplicated TBAD within 14 days of diagnosis. ⁴⁸ They examined false lumen thrombosis, aortic dilation, and aortic rupture as endpoints with significantly more patients in the OMT alone group (100 vs. 50%) reaching one of the endpoints. While this study did not examine mortality, it showed the positive aortic remodeling that occurs early in patients with uncomplicated TBAD undergoing TEVAR.

These results have started to shift the question of whether TEVAR is appropriate for uncomplicated TBAD to what the optimal timing of TEVAR is in patients. One such review by Jubouri et al helps elucidate this issue. ⁴⁹ Patient presentation was previously broken into the hyperacute (within 24 hours of symptoms), acute (within 24 hours to 14 days), subacute (14 days to 6 weeks), and chronic (longer than 6 weeks) phases when considering outcomes. Further reviews in 2016 ⁵⁰ and 2017 ⁵¹ supported TEVAR intervention in the subacute phase for uncomplicated TBAD as the optimal window. During this window, the patients should be undergoing appropriate medical treatment and surveillance to ensure no progression to complicated TBAD or AASs.

Closer analysis of TEVAR outcomes between the acute phase and the subacute phase have been performed in a single-center retrospective review by Xie et al. ⁵² They identified 267 patients who underwent TEVAR for uncomplicated TBAD with 130 performed in the acute phase and 137 performed in the subacute phase. The subacute phase for their study was defined as 15 to 90 days after diagnosis. While not statistically significant, there was a trend toward increased 30-day mortality with intervention in the acute phase (3.8 vs. 0.7%). Long-term outcomes were otherwise similar between the two groups, suggesting that delaying intervention with TEVAR in uncomplicated TBAD until the subacute phase may result in better overall outcomes.

The SVS and STS updated the classification system for chronicity of uncomplicated TBAD in 2020 such that hyperacute was less than 24 hours, acute was 1 to 14 days, subacute was 15 to 90 days, and chronic was greater than 90 days from diagnosis. ⁵³ A review of the Vascular Quality Initiative registry utilizing this new classification was performed and identified 1,476 operations performed from August 2014 to November 2020. By chronicity, they were performed 8.2% in the hyperacute, 56.4% in the acute, 21.4% in the subacute, and 14.0% in the chronic phase. Hyperacute and acute repairs were associated with increased rates of in-hospital stroke. Hyperacute and subacute repairs were associated with increased rates of SCI. There was no difference in 30-day mortality between the groups. These data point to increased risks of TEVAR in the hyperacute phase of uncomplicated TBAD but leave questions about appropriate timing of repair in the newly defined subacute and chronic phases. Further study will be required to fully define the optimal timeframe for TEVAR in uncomplicated TBAD, but the newly forming consensus appears to be shifting toward the appropriateness of TEVAR in acceptable patients with uncomplicated TBAD rather than solely medical treatment.

Type A Aortic Dissection and Ascending Aortic Aneurysm

Guidelines

AASs are life-threatening complications of aortic pathology that carry increasing mortality without early identification and intervention with a described increased in mortality of 1 to 2% every hour of nonintervention. ⁵⁴ Patients with suspected AAS should undergo CT imaging (Class IC). Various pretest probability scores exist including the plain chest X-ray findings, ⁵⁵ Aortic Dissection Detection Risk Score (ADD-RS), ⁵⁶ and Aorta Simplified Score (AORTAs) ⁵⁷ to assist with clinical evaluation. Early medical management with anti-impulse therapy is recommended to decrease aortic wall stress (Class IB) and long-term β blocker therapy should be prescribed to reduce late aortic-related events (Class IB). At this time, open surgical management of TAAD, Type A IMH, and penetrating aortic ulcer remains the standard of care due to the risk of life-threatening complications (all Class IB). ¹

Outcomes

Treatment of TAAD, AASs, and ascending aortic aneurysms using TEVAR is limited by the valuable anatomy of the ascending aorta, including the aortic valve, coronary ostia, and sinotubular junction proximally and the aortic arch vessels distally, leaving little room for endograft landing zones. However, there have been increasing attempts to develop techniques to address these pathologies endovascularly. Most of the results related to endovascular intervention for the ascending aorta have been reported in small series or case reports of high-risk patients and tend to involve IMH or retrograde dissection. ^{54 55 58 59}

One large systematic review identified 118 patients reported in the literature as having undergone primary TEVAR of the ascending aorta between January 1995 and January 2017. ^{56 60} In total, 50% of patients presented with TAAD, 29.7% with ascending aortic pseudoaneurysms, 5.1% with ascending aortic aneurysm, 4.2% with PAU, and 2.5% with aortic rupture. Mortality was 15.2% with aorta-related mortality reported at 5% with a follow-up of 17.2 months. Complications were reported as 18.6% with Type I endoleak, 9.3% requiring reintervention, 3.4% conversion to open surgical repair, and 3.4% stroke rate. The outcomes were encouraging for a very select group of high-risk patients with the utilization of off-label placement of TEVAR, EVAR, and custom-made grafts. However, the small sample sizes, lack of devices specific to the ascending aorta, and limited follow-up make it impossible to reliably comment on the long-term outcomes of TEVAR for the ascending aorta at this time.

Unique Situations and Special Populations

Connective Tissue Disorders

Patients with heritable connective tissue disorders (HCTDs) remain at high risk for development of aortic pathology throughout their lifetimes and represent a clinical challenge in determination of timing and extent of intervention when indicated. Within this group the most common diagnoses are Marfan syndrome (MFS), Ehlers–Danlos syndrome, and Loeys–Dietz syndrome with MFS having the highest overall incidence. Due to their increased risk of aortic complications, the guidelines for intervention are more aggressive than in the general population. The 2022 American College of Cardiology/American Heart Association (ACC/AHA) guidelines recommend replacement of the aortic root and ascending aorta once the diameter reaches 5 cm in MFS with no other indications for surgery or 4.5 cm if they have high-risk history or features. ¹ While TEVAR has become standard of care for DTAA in the general population, studies have demonstrated higher rate of endoleaks, reintervention, and mortality in patients with HCTD. ⁶¹ The utilization of TEVAR in this population has been growing but remains secondary to open surgery in those patients deemed appropriate risk for open repair.

Trauma

Blunt thoracic aortic injury (BTAI) is a rare but life-threatening surgical emergency in the trauma setting. It is often associated with rapid acceleration–deceleration events and affects the aorta at its “fixed” points, most commonly the aortic isthmus distal to the left subclavian artery. There is significant prehospital mortality and in-hospital management ranges from conservative nonoperative care to emergent surgical intervention. ^{62 63 64} In the modern era, endovascular repair is the preferred approach to BTAI for patients who meet indications for repair and have appropriate anatomy (Grade IB from ACC/AHA). ¹ There have been no RCTs comparing open surgical repair to TEVAR in BTAI; however, meta-analysis has shown improvement in procedure-related mortality and overall 30-day mortality with TEVAR even in the setting of higher injury severity score for the patients undergoing TEVAR. ^{65 66} Durability of TEVAR in these patients is an important consideration as they tend to be younger and can be expected to live longer with a prosthesis. A recent study evaluated long-term outcomes in their experience following 38 patients with a median follow-up of 80 months. ⁶⁷ They noted no TEVAR-related mortality and 10.5% overall procedure-related complications with 7.9% distal infoldings and 2.6% Type I endoleak. All complications were identified within the first year of placement and no morphologic changes to the aorta during follow-up.

Octogenarians

In general, octogenarians are a high-risk group for aortic surgery due to accumulation of medical comorbidities, increased frailty, and decreased expected life-year benefit from the surgery itself. This has made TEVAR an attractive option for patients in this age group requiring aortic intervention from the onset. A review of the Vascular Quality Initiative database evaluated patients with DTAA or TBAD undergoing TEVAR. ⁶⁸ They identified a total of 2,042 patients, of which 19.1% (390 total) were octogenarians. These patients tended to be more likely female, white, with larger aortic diameter, less proximal disease, and underwent intervention under local or regional anesthesia. Compared with nonoctogenarians, there was no difference in in-hospital mortality. One-year mortality hazard was increased compared with nonoctogenarians, but the driver of this increase was not identified. One other notable finding was that octogenarians had a higher risk of in-hospital complications specifically with repair of DTAA compared with nonoctogenarians.

A separate review of the National Inpatient Sample database from 2012 to 2017 identified 676 (16.5%) patients over the age of 80 from a total of 4,108 patients who underwent TEVAR during the study period. ⁶⁹ These patients also trended slightly more female and were majority white. DTAA was the pathology in 61.4% of octogenarians. In-hospital complications were similar between octogenarians and nonoctogenarians. Age was not associated with increased risk of in-hospital mortality; however, in the subgroup analysis of rDTAA, the mortality rate was higher in octogenarians. These data are limited to in-hospital and 1-year outcomes, but results suggest the appropriateness of TEVAR for elective treatment of octogenarians with thoracic aortic disease. Long-term outcomes are likely to be limited by the patient population and expected survival at baseline.

Patient Ethnicity and Race

As with all aspects of health care, there are concerns about equitable distribution of TEVAR access across racial, ethnic, and socioeconomic lines. Previous studies have suggested that TEVAR utilization actually reversed disparate trends in outcomes with regard to the black community. ^{70 71} A recent review of the National Inpatient Sample database between 2010 and 2017 for all TEVARs performed for TBAD and DTAA identified 25,260 admissions. ⁷² Of this group, 19.6% were black, 5.7% were Hispanic, and 6.5% classified as other. In black patients, TEVAR was more often performed urgently or emergently for TBAD compared with white patients (65.6 vs. 41.1%). Over the study period, the utilization of TEVAR in the black population did increase. There was no association between race or ethnicity with in-hospital mortality following multivariable analysis. These data support TEVAR as a driver of equitable care for thoracic aortic disease in a diverse patient population.

Frozen Elephant Trunk

The frozen elephant trunk (FET) procedure is a combination operation utilizing both open surgical repair and stent grafting for complex aortic pathologies. It classically includes standard surgical resection and replacement of the ascending aorta and aortic arch with direct reimplantation of the branch vessels and placement of a stent graft into the open descending thoracic aorta. The most common indication is acute aortic dissections. Published data support acceptable long-term outcomes in patients undergoing FET. A systematic review in 2020 found survival of 89.6% at 1 year, 85.2% at 3 years, and 82.0% at 5 years after surgery. The reintervention-free interval was also promising with rates of 93.9% at 1 year, 89.3% at 3 years, and 86.8% at 5 years. Overall mortality was 10.2%. ⁷³ As with other stent graft interventions, these patients require long-term surveillance imaging and follow-up ( Fig. 4 ).

Fig. 4.

Hybrid repair with ascending aortic replacement and debranching on right versus standard open surgical aortic arch debranching and replacement (reproduced with permission from Shi F, Wang Z. Acute aortic dissection surgery: hybrid debranching versus total arch replacement. J Cardiothorac Vasc Anesth 2020;34(6):1487–1493).

Chimney/Snorkel

An area of complexity in endovascular aortic repair involves the management of direct arterial branches from the aorta, specifically the renal and mesenteric arteries. One approach first described by Greenberg et al ⁷⁴ and since used more widely is the snorkel/chimney (chEVAR) technique. In the renal position, this involves placement of parallel stent grafts into the renal arteries to maintain perfusion followed by EVAR placement. A study of the performance of the chimney technique for the treatment of complex aortic pathologies (PERICLES) registry was conducted in 2021 to assess the long-term outcomes of chEVAR. ⁷⁵ Mean follow-up was 28.2 months with an all-cause mortality rate of 25.5%. This chimney graft occlusion rate was 6.2% with the absence of an infrarenal neck and sealing zone diameter over 30 mm associated with technical failure.

Kommerell's Diverticulum

Kommerell's diverticulum (KD) is the aneurysmal degeneration of an aberrant right subclavian artery. Intervention is generally indicated in KD due to the potential for further dilation, dissection, or rupture. The classic repair includes a left thoracotomy, ligation of the aberrant vessel, and appropriate revascularization. Recently the hybrid approach of partial or total aortic arch debranching followed by TEVAR has been utilized in KD. Recent data indicate favorable outcomes, although with the caveat of small sample sizes. An Italian multicenter study identified 16 KD patients who underwent hybrid repair. ⁷⁶ They had one mortality and one early reintervention due to bypass occlusion. At 4 years of follow-up, they had no further aortic-related mortality and a single case of asymptomatic bypass graft occlusion.

Long-Term Complications and Considerations

Open Surgery

The widespread adoption of TEVAR for an array of pathologies in the thoracic aorta has led to an increased patient population with thoracic endografts being followed and presenting with unique complications. Due to the patient complexity, much of these data arise from high-volume aortic centers of excellence. One such study from Roselli et al at Cleveland Clinic described the results of open aortic repair after TEVAR in 50 patients. ⁷³ The period of study was from July 2001 to January 2012 with 25 patients undergoing open arch operations, 17 patients undergoing thoracoabdominal operations, 6 patients undergoing descending aortic operations, and 2 patients requiring extra-anatomic bypass. The median interval from TEVAR to reintervention was 13.9 months. The indications for open repair were Type I endoleaks in 19 patients, chronic aortic dissection with persistent false lumen in 16 patients, retrograde aortic dissection in 9 patients, and graft infection in 6 patients. In-hospital mortality was 6 and 67% survival at a median follow-up of 2.9 years.

Another study by Ikeno et al evaluated the long-term outcomes of patients that required open surgery after TEVAR. ⁷⁴ They performed a retrospective review identifying 41 patients between October 1999 and July 2017 requiring open surgery for complications of TEVAR. The indications for surgery included 14 patients with endoleak, 10 patients with endograft infection, 9 patients with persistent false lumen expansion, and 5 patients with retrograde aortic dissection. They performed descending aortic replacement in 15 patients, thoracoabdominal aortic replacement in 14 patients, and aortic arch replacement in 12 patients. In-hospital mortality was 14.6%, 5-year survival was 73.7%, and freedom from reintervention was 88.5%.

These studies show that even with experience the need for open surgical intervention following TEVAR carries high upfront risk, but the long-term results are consistent with those expected from initial open surgical repair. The rate of need for open surgical repair after TEVAR is not well defined but may be expected to range from 0.4 to 7.9% based on prior studies. ^{75 76} The most common indications are endoleaks, retrograde aortic dissections, persistent false lumen dilation, and endograft infection. A variety of surgical approaches exist depending on the specific pathology as well as a range of options for management of the existing endograft. ⁷⁷

Endoleak

Endoleak is a complication unique to endovascular graft placement that has been well described in the literature relating to EVAR and TEVAR. ⁷⁸ Continued flow into the aneurysm sac may be classified into five broad categories with Type 1 endoleak involving flow at the proximal or distal landing zones, Type 2 as retrograde flow from patent aortic side branches, Type 3 as a failure of the graft itself, Type 4 as porosity of the graft, and Type 5 as ongoing aneurysm enlargement without clear endoleak source ( Table 1 ). Type 1 and Type 3 require early intervention. The Type 1 endoleak has an overall incidence rate of around 9% and accounts for over 50% of the need for reintervention following TEVAR. ^{79 80} It may be further categorized as Type 1a if the endoleak is at the proximal end of the stent or Type 1b if it is the distal end. Due to the nature of a Type 1 endoleak making rupture risk high, it requires early intervention. There are a variety of reintervention options available beyond this review's scope. ⁸¹ However, it is an important complication that may present late after the initial TEVAR procedure and requires ongoing surveillance with CT imaging.

Table 1. Types of endoleak.

Endoleak	Cause of sac perfusion	Management
1	Flow from the proximal or distal graft attachment site	Prompt
a	Proximal graft attachment site	Angioplasty, Palmaz or cuff extension, chimney extension and embolization
b	Distal graft attachment site	Angioplasty and extension of distal limb
c	Endoleak at the site of an iliac occluder plug	Insertion of an additional iliac occluder plug or embolization
2	Retrograde flow through patent aortic side branch vessels	Conservative if sac size stable/embolization if sac size increases
3	Mechanical graft failure	Prompt
a	Modular disconnection	Placement of additional endograft components
	Leak at a fenestration, branch, or visceral stent
b	Fabric tear
4	Graft porosity	Conservative. Transient phenomenon.
5	Sac size increase with no visible endoleak.	May consider catheter angiography with cone beam CT.

Abbreviation: CT, computed tomography.

Source: Reproduced with permission from Ameli-Renani S, Pavlidis V, Morgan RA. Secondary endoleak management following TEVAR and EVAR. Cardiovasc Intervent Radiol 2020;43(12):1839–1854. ⁸²

Retrograde Dissection

Retrograde Type A aortic dissection (RTAD) following TEVAR is a rare complication that carries a significant mortality rate. The most common theory is that the stent graft interaction with an already dissected aorta creates a new entry tear that propagates proximally in the aorta. ⁸² This may be referred to as proximal stent-graft-induced new entry (SINE) which has also been described distal to the endograft. ⁸³ A recent systematic review and meta-analysis found the incidence of RTAD to be 2.3% with higher rates early after TEVAR. ⁸⁴ Other risk factors associated with development of RTAT were acute TBAD and use of a proximal BMS. The mortality rate in the study from RTAD was 42.2%, which was consistent with previously reported outcomes. While RTAD was identified more often in the early postoperative phase, it is an important consideration during long-term follow-up. The data suggest a correlation between institutional and proceduralist volume and decreased incidence of RTAD that may be interpreted as RTAD often occurring due to technical complications.

Aneurysmal Degeneration

TEVAR for TBAD as discussed prior has become the standard of care in complicated cases and with increasing utilization in uncomplicated cases. One of the important metrics for successful TEVAR is the progression of the false lumen following the stent placement. If the false lumen remains perfused, it may continue to grow and lead to aneurysmal degeneration and risk of rupture. Somewhat counterintuitive is the data that support better outcomes with a patent false lumen compared with a partially thrombosed false lumen. This may be due to the patent false lumen allowing an entry and exit point for blood while the partially thrombosed false lumen may only allow blood to enter the false lumen, thus increasing intraluminal pressure. ^{85 86} Of course, a completely thrombosed false lumen is the best result and a marker for success following TEVAR. A variety of techniques exist for management of nonthrombosed false lumen following TEVAR ⁸⁷ that are again outside the scope of this review, but it remains an important long-term complication that limits the benefits of TEVAR in certain patients.

Spinal Cord Ischemia

SCI is a serious complication of both open and endovascular repair of the thoracic and thoracoabdominal aorta. In open repair, rates of SCI have been reported at around 7% even at large volume centers. ⁸⁸ In endovascular repair, the rates of SCI have been shown to range from 2.5 to 8% with an associated decrease in survival. ⁸⁹ One of the strategies utilized in open repair to minimize SCI has been CSF drainage and monitoring in the perioperative phase. A recent systematic review found prophylactic use of CSF drainage in patients undergoing TEVAR for DTAA or thoracoabdominal aortic aneurysms did not benefit from SCI rates and the added complication of CSF drainage itself. ⁹⁰ They identified 28 retrospective studies with a total of 4,814 patients, of which 2,599 underwent CSF drainage. The rate of SCI was 5% in both groups with the CSF drainage group also having a 10% rate of procedural complications. Overall mortality between the groups was not able to be compared due to lack of data. SCI remains a serious complication of both open and endovascular aortic repairs and further study on options for mitigating the risk is needed.

Infection and Fistula

Infection of the endograft following TEVAR is quite rare but treatment is complicated and carries high morbidity and mortality as the entire graft often requires removal and there may be associated fistulas. In multiple series from high-volume centers, endograft infection was cited as a cause of open surgical repair following TEVAR. ^{73 91 92} Many patients required further reintervention and faced significantly higher mortality than those undergoing open surgery following TEVAR for other indications. The fistulas that develop following TEVAR are most commonly to the airway (aortobronchial or aortopulmonary) or to the esophagus (aortoesophageal) with rates around 0.6% for airway fistulas and 1.5% for esophageal fistulas. ^{93 94} In both infections and fistulas, the endograft is often fully removed and the graft being placed is soaked in antibiotic solution to minimize risk of further infection.

Current and Future Devices

Since the introduction of TEVAR in the United States in 1994 and the first FDA-approved device in 2005, TEVAR endografts have undergone several changes. The first generation of TEVAR grafts had large delivery systems requiring larger access vessels, excluding many patients, and leading to more vascular injuries. They also tended to require rapid pacing during deployment for precise placement. Additionally, the rates of endoleak and stent graft migration were higher in early generation devices. Modern generations of endografts have been designed to address these initial shortcomings. These current devices tend to have lower profile delivery systems and improved proximal stent graft fixation. ⁹⁵

Outside of ongoing device optimization, the next arena for endovascular therapy in the thoracic aorta is expected to be the ascending aorta and aortic arch. Certain unique aspects of the anatomy of the ascending aorta contribute to the difficulty in endovascular therapy in this territory. The ascending aorta elongates as patients age, which has been shown to contribute to stent graft migration. It also typically has a longer outer curvature than inner curvature and has a dynamic diameter throughout the cardiac cycle, all of which can make stent deployment difficult. Two notable devices are the Relay Custom Medical Device by Terumo Aortic that can be built to specific anatomic dimensions of the patient but is not available in the United States and the Gore Ascending Stent Graft, which is being studied in the United States with encouraging early results. ⁹⁶

With the introduction of newer devices and extending the range of aortic pathologies being treated endovascularly it is worth understanding the change in complication rates with these changes. One such study evaluated the rate of Type I and Type III endoleak in the various generations of stent grafts. ⁹⁷ When divided into four generations, the 5-year freedom from endoleak was 65.6% for the first generation, 61.4% for the second generation, 76.2% for the third generation, and 69.1% for the fourth generation. When comparing the first two generations with the newer two generations, the endoleak rate was significantly lower in the new generations. It will be important to continue to reexamine these results as newer devices are introduced to the endovascular therapy arena.

Discussion

Endovascular repair has become the preferred approach for most aortic pathology distal to the left subclavian artery. Advances in endograft technology and techniques have led to decreased incidence of complications and improvements in survival. While the evidence for TEVAR does not come in the form of RCTs, many single-center series and database reviews have demonstrated a trend toward less complications, mortality rates, and shorter hospital stays compared with open surgery. ⁹⁸ TEVAR is no longer a “new technology” and data are being collected from a growing number of patients with endografts over longer periods of time. Some of these data suggest reasons for patient readmissions and reinterventions following TEVAR and help to illuminate the ideal timeframes for intervention in different pathologies. Aortic-related events following TEVAR may require further reintervention with aneurysmal degeneration, endoleaks, and distal SINEs commonly cited as causes. ^{99 100 101 102 103 104} Much of the outcome data currently available are limited to follow-up of 5 years or less. One recent single-center study has released results out to 12 years, showing aorta-specific survival of 96% with a 7% reintervention rate for endoleak in patients with DTAA. ¹⁰³ Further results with similar findings will help reinforce the role of TEVAR with the known early benefits and provide evidence for long-term durability.

Conclusion

Definitive data on the long-term outcomes of TEVAR are limited, but promising. Early benefits of TEVAR over open repair for descending aortic pathology in most populations are known. Durability of repair and freedom from reoperation beyond 5 years remain to be proven.