Medical therapy versus TEVAR for uncomplicated type B aortic dissection

Abstract

The standard of care in uncomplicated acute type B aortic dissection (uTBAD) has been optimal medical management. Surgical repair and endovascular interventions are adjuncts in managing complicated type B dissection. Increasing safety and confidence in the thoracic endovascular aortic repair (TEVAR) and recent data indicating long-term complications in medical management of uTBAD has brought a shift in treatment approach. TEVAR at best remains controversial, yet there is a subset, which will definitely benefit from intervention.

Introduction

In 1760, following the sudden demise of King George I, the Royal physician Frank Nichols reported cardiac tamponade as the cause of death. He documented presence of blood in the pericardium and transverse fissure in the trunk of aorta separating it from its external wall causing empty chambers of heart. This is probably the first ever death attributed to aortic dissection. In 1802, Maunoir proposed the term “aortic dissection”, while in 1819, René Laennec was apparently the first to use the term “dissecting aneurysm.” The extensive works of DeBakey in the field of aortic dissection brought this disease to the forefront. The creation of the International Registry of Acute Aortic Dissection (IRAD) in 1996 further added to the knowledge and understanding of aortic dissection and has influenced its treatment options [1]. Early successes of TEVAR for treatment of aortic dissections have significantly altered the in-hospital mortality and morbidity of thoracic aortic dissections.

It is postulated that 38% of aortic dissections are diagnosed at autopsy [2]. Given the nature of its presentation, acute aortic dissection is the most frequent and catastrophic manifestation of the so-called acute aortic syndrome (which also includes intramural hematoma, penetrating aortic ulcer, and ruptured thoracic aortic aneurysm [1]. Stanford further classified it as type A and type B aortic dissection. There is no ambiguity about primary surgical management of type A dissection as it is associated with much higher mortality rates compared with type B.

According to IRAD registry, type B aortic dissection (TBAD) is a life-threatening condition that is associated with around 13% in-hospital mortality and is further classified into complicated and uncomplicated dissections [3]. Complicated type B dissection is associated with rupture, mal-perfusion syndrome, refractory pain, or rapid aortic expansion at onset or during the hospital stay. Uncomplicated type B dissection occurs without the aforementioned complications at presentation [3] [4]. As per European society of cardiology guidelines 2014, the management of complicated TBAD is either emergent TEVAR or a surgical intervention in adjunct to the medical therapy, whereas medical therapy has been the mainstay of treatment in uncomplicated TBAD [5]. For uTBAD on medical management, reported in-hospital 30-day mortality is between 6 and 10%. The 1-year, 4-year, and 5-year survival rates were 81.6%, 72.3%, and 60% respectively. Dilation of false lumen in up to 50% is seen in 5 years [3, 6]. TEVAR since the time it was introduced by Dake et al. has increasingly been accepted as a safe alternative to surgery [3, 4].

TEVAR has been successfully deployed for complicated TBAD and is the standard choice of treatment unless there are clear indications for open surgery (lower extremities artery disease, severe tortuosity of the iliac arteries, a sharp angulation of the aortic arch, and the absence of a proximal landing zone for the stent graft). Records of a European clinical registry has shown a 30-day mortality of 8%, with 8% risk of stroke and 2% risk of spinal cord ischemia in 50 acute TBAD patients [5]. Hence, the pertinent question here is whether early TEVAR as a procedure is a safe option and if it is, then, is there any criteria or protocol that can be followed.

Pathogenesis and natural history of uncomplicated type B aortic dissection

An intimo-medial tear acts as the entry point and creates a secondary channel known as the false lumen. The false lumen then may progress in a spiraled (common), straight, or retrograde (rare) manner. Increased pressure within false lumen compresses true lumen, which might lead to ischemic and mal-perfusion complications. Location of entry tear is generally in proximal part of the aorta with secondary entry tears or fenestration in the distal thoracic aorta, the abdominal aorta, or iliac arteries. Presence of intramural hematoma and penetrating aortic ulcer and connective tissue disorders weaken the aorta. This group of patients is more predisposed to aortic dissection. Male sex, advanced age, hypertension, and prior cardiac surgery especially in a younger age group are also known risk factors [1].

Diagnosis of dissection within 14 days is termed as acute, whereas duration of more than 14 days is termed as chronic. A sub-acute phase also has recently been suggested between 2 and 6 weeks following symptoms, which may show rapid expansion of the aorta rendering the patient unstable. Also, a mobile and flexible dissected septum as seen in the acute setting is more easily fixed by intervention compared with chronic condition where it is likely to be fibrotic and stiff. Information regarding septal mobility is essential for TEVAR to be effective as a modality of treatment and indicator of future aortic remodeling.

Intravascular ultrasound (IVUS), transesophageal echocardiography (TEE), dynamic CT, or magnetic resonance angiogram aid in assessing septal mobility [1, 7].

Intense, severe inter-scapular pain, often propagating downwards toward the lower abdomen with progression of dissection, is classical symptoms of TBAD. A number of patients have atypical presentation mimicking a heart attack, stroke, or acute limb ischemia as the longitudinal extent of dissection increases. The pain follows the longitudinal progress of the dissection. The presentation follows circadian and diurnal patterns, with a preponderance of instances in the winter months and in the early morning hours [1, 8].

According to proponents of medical management, the future course of uTBAD is fairly benign. They respond well to medical management with over 90% of survival rates within first 30 days. Aortic dilatation is more likely to be proximal than distal and has very low rate of rupture [8]. However, there is evidence of 30% mortality rate at 5 years due to aneurysm expansion in chronic stable dissections treated with medical management alone. Data from the IRAD registry shows that a partially thrombosed false lumen is associated with complications like aortic dilatations and late onset of mal-perfusion syndrome and therefore requires more intensive follow-up. Prophylactic aortic intervention in these cases has better outcomes compared with medical management [9, 10].

Medical management in acute dissection

Initial management goal of all uTBAD is to reduce hemodynamic forces and reduce extension of dissection and rupture. This is achieved with anti-impulse therapy, which uses a combination of drugs to achieve negative inotropy (leading to reduction in rate of rise of blood pressure), negative chronotropy (leading to lower peak systolic pressure), and alpha blockade (to prevent compensatory vasoconstriction). Medical therapy includes intravenous β-blockers as primary mode of control of blood pressure. In patients not responding to β-blockers or with poor tolerance of the drug, calcium channel blockers and or renin-angiotensin inhibitors can be used as alternatives. β-blockers and calcium channel blockers are associated with improved long-term survival in acute TBAD patients. In addition, calcium channel blockers reduce aortic expansion. Pain should be relieved with intravenous opiates since emotional stress may increase blood pressure considerably, potentially further propagating the dissection [11].

Medical treatment for chronic aortic dissection

For prevention of aortic expansion and promotion of aortic remodeling, medical therapy is instituted in chronic uTBAD. The aim is to achieve strict heart rate and blood pressure control with help of calcium channel blockers, angiotensin receptor blockers, and statins. These medications have a positive effect and aid in achieving reduced aortic growth and complications. β-blockers and angiotensin receptor blockers further aid in reducing aortic growth in TBAD patients with Marfan’s syndrome. α1-adrenergic and non-specific β-blockers can be used as alternate medication. Patient should be on strict surveillance and control of hypertension is of prime importance in these patients [11].

Medical management of uTBAD stabilizes the disease. However, aortic degeneration and aneurysm formation of dissected aorta continues. As reported by DeBakey et al. in 1982 and Juvonen et al. in 1999, aneurysm is seen in over 40% of patient with uTBAD within 5 years from the index event, aortic repair is needed in 20–50% of patients, and 30% rupture rate is seen once aortic diameter reaches 6 cm [12].

Thoracic endovascular aortic repair

Introduction of TEVAR has revolutionized the treatment approach in TBAD. TEVAR has become an attractive alternative to surgery in recent years, with major in-hospital complication rates ranging from 3.4 to 11.1% compared with a complication rate of 40% with surgery. The stent graft covers the primary entry tear, discontinues blood flow into the false lumen, expands true lumen and depressurizes the false lumen preventing extension of dissection, and ideally leading to false lumen thrombosis with subsequent aortic remodeling. TEVAR for TBAD stabilizes the patient hemodynamically and reverses end-organ ischemia. The procedure can be done safely in surgically unfit patients and is associated with minimal procedural morbidity. Though the cost of intervention is significantly higher when compared with surgery, the hospital admission period is shortened [11].

Number of TEVAR cases done at our (SGRH) center are approximately 25 cases per year, indications for which vary from aneurysms, trauma to complicated dissections. Retrospective analysis of the last 3 years, data shows that 14 cases of TEVAR were most likely sequelae of uncomplicated dissections. Figures 1, 2, and 3 are a few images which demonstrate type B aortic dissections. The timing for TEVAR following index event varied from 55 days to 7 years. One case could be considered as sub-acute as he presented to us with history of trauma about 6 weeks ago and underwent TEVAR due to recurrence of pain. Patients with uTBAD are being followed-up at 1 month, 3 months, 6 months, and 1 year with NCCT. TEVAR is reserved for symptomatic patients, false lumen diameter exceeding 22 mm, and persistent false lumen.

Fig. 1.

Reconstructed image of type B acute aortic dissection distal to the subclavian artery with adequate landing zone

Fig. 2.

Axial images showing entry tear at the origin of the left subclavian artery

Fig. 3.

Axial images showing true and false lumen in type B aortic dissection

Adequate preoperative sizing of the stent graft is a key aspect to achieve adequate fixation, without damaging the aortic wall. Device size is based on the diameter of the aorta proximal to dissection, and a neck length of 2 cm is a necessary for adequate fixation. Greater than 10% oversizing is potentially catastrophic as this is associated with new tears, retrograde dissection, and stent graft migration.

Cannulating a narrowed true lumen is a challenge, which is overcome by use of transesophageal echocardiography and intravascular ultrasound. Alternatively, antegrade approach via brachial artery and snaring of guide wire can be undertaken. Iliac conduits have also been used. For deployment of the stent graft in a curved thoracic aorta, a tip capture system allows selective release of the proximal spring, so as to permit adjustment in positioning of endograft. Fully expanded stent graft is not necessary as it is dependent on aortic remodeling. Coverage of the left subclavian artery may be needed in most cases, and if need be, carotid-subclavian bypass may also be considered. Rarely, TEVAR device requires coverage of the left carotid artery, wherein a carotid-to-carotid bypass is performed prior to TEVAR. Technical success rates of TEVAR are high for both acute TBAD (ranging from 93.3 to 100%) as well as for chronic TBAD (ranging from 77.6 to 100%) [11]. Our technical success for chronic TBAD has been similar.

INSTEAD trial

The investigation of stent grafts in aortic dissection (INSTEAD) trial published in 2009 was the first randomized controlled trial, which compared optimal medical management with TEVAR for patients with type B aortic dissection. uTBAD patients were analyzed with 72 in operative group and 68 in medical therapy group. The primary end point of the study was all-cause mortality at 2 years. Aortic-related mortality, aortic remodeling, and disease progression (need for conversion or additional procedures) were secondary end points. No survival benefit was seen with TEVAR group. However, the TEVAR group showed significantly higher rates of aortic remodeling with true lumen expansion and false lumen thrombosis and regression. The limitations of the INSTEAD trial included its lack of power (the initial power analysis was based on a mortality calculation of at least 20%, which was not reached), and its relatively short follow-up of 2 years.

Despite its small sample size, it did show a positive aortic remodeling benefit after operative intervention in uTBAD. INSTEAD-XL (investigation of stent grafts in aortic dissection trial with extended length) was published in 2013. The analysis of long-term results in the intervention group showed reduced all-cause mortality (11.1% in TEVAR vs. 19.3% in optimal medical management (OMT) group), aortic specific mortality (6.9% in TEVAR vs. 19.3% in OMT group), and increased freedom from disease progression and aorta-specific events (95.9% in TEVAR and 71.9% in OMT group). Both improved survival and freedom from progression after 5 years were associated with false lumen thrombosis induced by stent graft in over 90% of cases. Morphological evidence of aortic remodeling was present in almost 80% of patients in TEVAR group at 5 years, compared with only 10% of patients in best medical management group [13].

Acute dissection stent grafting or best medical treatment trial

Acute dissection stent grafting or best medical treatment (ADSORB) trial is the prospective randomized clinical trial of acute uncomplicated type B dissection. The primary endpoints were false lumen thrombosis, aortic dilatation, and aortic rupture at 1 year. The study compared best medical treatment (BMT) alone or BMT with endo-luminal repair using a Gore thoracic aortic graft device (TAG+BMT). At the 1-year follow-up, the decrease in maximum false lumen diameter was seen in BMT+TAG group by − 7.0 mm compared with an increase of 4.3 mm in the BMT group (p < .001). The overall transverse diameter was the same at the beginning, but after 1 year, the BMT group remained same while the BMT+TAG group decreased in size. Incomplete false lumen thrombosis was found in 43% of the TAG+BMT group and 97% of the BMT group (p < .001). Aortic dilatation was found in 37% of the TAG+BMT patients and 45% of the BMT patients. There was no dissection-related mortality in either group [6].

There was significantly more remodeling in the 1st year among the patients in the TAG+BMT group than in the BMT-only group. This trial also brought out clinical indicators where intervention is likely to be a better choice [6].

Clinical predictors of progression of uTBAD

The selection of patients who may benefit from intervention with uTBAD remains the key in reducing complications and maximizing the benefits in aortic repair. Trimarchi et al. in 2014 summarized demographic, clinical, pharmacological, and radiological risk factors predicting aortic enlargement and potentially influencing the decision to intervene in a selected group of patients. Important predictors of poor outcome with only best medical management as observed in ADSORB and INSTEAD trials are enumerated below:

1. Partial thrombosis of the false lumen

2. Aortic diameter ≥ 40 mm during acute phase

3. An elliptical configuration of the true lumen/round configuration of the false lumen

4. Patent false lumen

5. Proximal descending thoracic aorta false lumen diameter ≥ 22 mm on initial imaging, sac formation in partially thrombosed false lumen

6. Single entry tear

7. False lumen/intimal tear located in the inner aortic curvature

8. Large entry tear (≥ 10 mm) located in the proximal part of the dissection.

Limitations in both these trials have been the protocols for false lumen thrombosis. For better accuracy, magnetic resonance imaging with blood-pooled agent should be used for determining false lumen thrombosis. Also, there is unlikely to be any false lumen thrombosis distal to stent graft, especially in visceral arteries with type III B dissection. There is no clarity regarding length of stent graft. A 15-cm stent graft was considered safe, but paraplegia rate may increase if the whole descending thoracic aorta is to be covered. [6, 12, 13]

Conclusion

The European Society of Cardiology guidelines 2014 for uncomplicated type B aortic dissection recommends medical therapy as the primary modality of treatment (class IC) [5]. Recommendation of TEVAR is class II B, as the efficacy of this modality is yet to be established. Therefore, decision to offer a prophylactic TEVAR for an asymptomatic patient with uncomplicated acute TBAD must be made judiciously. There is need for procedure to be done with minimal morbidity and no mortality, by a very experienced team in high-volume institution, sound protocols to establish efficacy and cost-benefit analysis.

★Class of recommendation: I, evidence and/or general agreement; IIa, weight of evidence/opinion is in favour of usefulness; IIb, usefulness/efficacy is less well established by evidence/opinion; Level of evidence: A, data derived from multiple randomized clinical trials or meta-analyses; B, data derived from a single randomized clinical trial or large non-randomized studies; C, consensus of opinion of the experts and/or small studies, retrospective studies, registries.

Compliance with ethical standards

Ethical statement, informed consent, human and animal rights statement not applicable being a review article.

Conflict of interest

The authors declare that they have no conflict of interest.