Part One: For the Motion. Level 1 Evidence is Necessary Comparing TEVAR and Medical Management of Uncomplicated Type B Aortic Dissection

Abstract

Before we get stuck into the debate, some basic information needs to be provided. Dissection of the aorta is a life-threatening disease and is considered as “acute” when the diagnosis is made within 2 weeks of the initial symptoms. The definition of an acute dissection is even not uniform in that several pathologies, such as intramural hematoma and penetrating aortic ulcer that may evolve to a dissection, are included.1Eggebrecht H. Plicht B. Kahlert P. Erbel R. Intramural hematoma and penetrating ulcers: indications to endovascular treatment.Eur J Vasc Endovasc Surg. 2009; 38: 659-665Abstract Full Text Full Text PDF PubMed Scopus (130) Google Scholar Acute dissection of the ascending aorta (DeBakey I or II, or Stanford A), with an assumed mortality rate of 1–2% per hour in the first 24 hours of symptom onset requires a prompt surgical therapy.2Hirst Jr., A.E. Johns Jr., V.J. Kime Jr., S.W. Dissecting aneurysm of the aorta: a review of 505 cases.Medicine (Baltimore). 1958; 37: 217-279Crossref PubMed Scopus (1128) Google Scholar, 3DeBakey M.E. Beall Jr., A.C. Cooley D.A. Crawford E.S. Morris Jr., G.C. Garrett H.E. et al.Dissecting aneurysms of the aorta.Surg Clin North Am. 1966; 46: 1045-1055PubMed Google Scholar, 4Tsai T.T. Trimarchi S. Nienaber C.A. Acute aortic dissection: perspectives from the International Registry of Acute Aortic Dissection (IRAD).Eur J Vasc Endovasc Surg. 2009; 37: 149-159Abstract Full Text Full Text PDF PubMed Scopus (332) Google Scholar Medical therapy alone in this setting is associated with 50% mortality at 30 days in older series,2Hirst Jr., A.E. Johns Jr., V.J. Kime Jr., S.W. Dissecting aneurysm of the aorta: a review of 505 cases.Medicine (Baltimore). 1958; 37: 217-279Crossref PubMed Scopus (1128) Google Scholar and has been reported to be lower with surgery.5Bekkers J.A. Bol Raap G. Takkenberg J.J. Bogers A.J. Acute type A aortic dissection: long-term results and reoperations.Eur J Cardiothorac Surg. 2013; 43: 389-396Crossref PubMed Scopus (74) Google Scholar However, there is no evidence based on randomized controlled trials (RCT) or comparative studies to answer this question. According to the International Registry of acute Aortic Dissection (IRAD) dissection of the aorta occurs in the descending aorta (DeBakey III or Stanford B) in about 37% of patients.4Tsai T.T. Trimarchi S. Nienaber C.A. Acute aortic dissection: perspectives from the International Registry of Acute Aortic Dissection (IRAD).Eur J Vasc Endovasc Surg. 2009; 37: 149-159Abstract Full Text Full Text PDF PubMed Scopus (332) Google Scholar Data from the IRAD registry are currently setting a trend on the views of acute dissection, for both type A and type B. This important register is multicentered and has gathered details of numerous patients, adding very useful information, such as predictors for mortality and complications. However, several questions cannot be answered by this register, like how many of the uncomplicated dissections will become complicated and how standardized the different therapy options are. No information is provided regarding hypertension control. These are extremely important questions for initial decision-making. Although acute type B dissection carries a lower initial overall mortality than type A dissections, with about 10% deaths within 30 days, the diagnosis can be difficult—and sometimes even delayed—owing to multiple possible symptoms. The outcome of type B dissections is related to the clinical presentation and can be worsened by severe life-threatening complications. The most common ones are death, rupture, malperfusion, retrograde dissection into the ascending aorta, refractory pain, and, in the long run, aortic dilatation and aneurysm formation.6Fattori R. Tsai T.T. Myrmel T. Evangelista A. Cooper J.V. Trimarchi S. et al.Complicated acute type B dissection: is surgery still the best option?: a report from the International Registry of Acute Aortic Dissection.JACC Cardiovasc Interv. 2008; 1: 395-402Abstract Full Text Full Text PDF PubMed Scopus (336) Google Scholar, 7Elefteriades J.A. Lovoulos C.J. Coady M.A. Tellides G. Kopf G.S. Rizzo J.A. Management of descending aortic dissection.Ann Thorac Surg. 1999; 67: 2002-2005Abstract Full Text Full Text PDF PubMed Scopus (197) Google Scholar Occurrence of at least one of those conditions thus makes a dissection “complicated.” About 30% of acute type B aortic dissections (BAD) are complicated by peripheral vascular ischemia or hemodynamic instability, with a subsequent high risk of death,8Trimarchi S. Eagle K.A. Nienaber C.A. Pyeritz R.E. Jonker F.H. Suzuki T. et al.Importance of refractory pain and hypertension in acute type B aortic dissection: insights from the International Registry of Acute Aortic Dissection (IRAD).Circulation. 2010; 122: 1283-1289Crossref PubMed Scopus (155) Google Scholar, 9Glower D.D. Fann J.I. Speier R.H. Morrison L. White W.D. Smith L.R. et al.Comparison of medical and surgical therapy for uncomplicated descending aortic dissection.Circulation. 1990; 82: IV39-46PubMed Google Scholar, 10Marui A. Mochizuki T. Mitsui N. Koyama T. Kimura F. Horibe M. Toward the best treatment for uncomplicated patients with type B acute aortic dissection: a consideration for sound surgical indication.Circulation. 1999; 100: II275-II280PubMed Google Scholar, 11Doroghazi R.M. Slater E.E. DeSanctis R.W. Buckley M.J. Austen W.G. Rosenthal S. Long-term survival of patients with treated aortic dissection.J Am Coll Cardiol. 1984; 3: 1026-1034Abstract Full Text PDF PubMed Scopus (191) Google Scholar but we do not know which patient will get these complications. In addition to these early complications, aneurysmal evolution occurred within 5 years in 20–50% of the patients who had survived the acute phase,11Doroghazi R.M. Slater E.E. DeSanctis R.W. Buckley M.J. Austen W.G. Rosenthal S. Long-term survival of patients with treated aortic dissection.J Am Coll Cardiol. 1984; 3: 1026-1034Abstract Full Text PDF PubMed Scopus (191) Google Scholar, 12Shu C. He H. Li Q.M. Li M. Jiang X.H. Luo M.Y. Endovascular repair of complicated acute type-B aortic dissection with stentgraft: early and mid-term results.Eur J Vasc Endovasc Surg. 2011; 42: 448-453Abstract Full Text Full Text PDF PubMed Scopus (45) Google Scholar and these are the complications that we aim to prevent. IRAD data have shown that the most common cause of death is rupture (40%) followed by intestinal ischemia (17–39%).5Bekkers J.A. Bol Raap G. Takkenberg J.J. Bogers A.J. Acute type A aortic dissection: long-term results and reoperations.Eur J Cardiothorac Surg. 2013; 43: 389-396Crossref PubMed Scopus (74) Google Scholar Although not scientifically proven, but based on good clinical practice, there is a general agreement that patients with an initially uncomplicated BAD should receive medical therapy with close monitoring of blood pressure to decrease the shear forces on the aortic wall. Basic medical treatment comprises β-blockers, diuretics, calcium-blockers, and angiotensin converting enzyme-inhibitors with—in the acute phase—additional α-blockers, as well as nitroglycerine. The primary aim of this approach is to obtain a systolic blood pressure between 100 and 120 mmHg, with the maintenance of a urinary output and prevention of malperfusion of the visceral organs. In a series of 171 cases of acute BAD with a median follow-up of 2.3 years, Kodama et al.13Kodama K. Nishigami K. Sakamoto T. Sawamura T. Hirayama T. Misumi K. et al.Tight heart rate control reduces secondary adverse events in patients with type B acute aortic dissection.Circulation. 2008; 118: S167-S170Crossref PubMed Scopus (106) Google Scholar found that, although use of β-blockers did not itself affect outcomes, heart rate control was associated with a significant reduction in overall aortic complications (12.5% vs. 36% in controls). Meanwhile, current data revealed a mortality rate of medically-treated BAD of around 10% within the first month. From the IRAD data it could be concluded that calcium channel-blockers were correlated with a better survival during follow-up in BAD, whereas β-blockers improved the outcome after surgery for type A aortic dissections.14Hagan P.G. Nienaber C.A. Isselbacher E.M. Bruckman D. Karavite D.J. Russmann P.L. et al.The International Registry of Acute Aortic Dissection (IRAD): new insights into an old disease.J Am Med Assoc. 2000; 283: 897-903Crossref PubMed Scopus (2680) Google Scholar, 15Suzuki T. Isselbacher E.M. Nienaber C.A. Pyeritz R.E. Eagle K.A. Tsai T.T. et al.Type-selective benefits of medications in treatment of acute aortic dissection (from the International Registry of Acute Aortic Dissection [IRAD]).Am J Cardiol. 2012; 109: 122-127Abstract Full Text Full Text PDF PubMed Scopus (142) Google Scholar These conflicting data need to be clarified in future RCTs using β-blockers and calcium channel-blockers in patients with only type B dissections leaving type A dissection patients for a separate study. The same confusion exists when addressing the long-term survival of patients with BAD. In this context, only one publication from Sweden has shown that after surviving the first month, the long-term survival was not different from that of the general population,16Winnerkvist A. Lockowandt U. Rasmussen E. Rådegran K. A prospective study of medically treated acute type B aortic dissection.Eur J Vasc Endovasc Surg. 2006; 32: 349-355Abstract Full Text Full Text PDF PubMed Scopus (146) Google Scholar whereas other authors have reported a significant number of complications with 48–82% survival at 5 years. IRAD data have confirmed this trend by showing that 189 consecutive patients with acute BAD, who were successfully discharged alive following medical therapy, had a 3-year survival of 78%.17Tsai T.T. Fattori R. Trimarchi S. Isselbacher E. Myrmel T. Evangelista A. et al.Long-term survival in patients presenting with type B acute aortic dissection: insights from the International Registry of Acute Aortic Dissection.Circulation. 2006; 114: 2226-2231Crossref PubMed Scopus (423) Google Scholar In this setting, 25–50% of patients treated medically will develop late aortic-related complications with the need for an endovascular or open repair. Thus, we are lacking reliable information on the survival of patients with type B dissections. Endovascular repair is a well-known alternative to open repair for the treatment of abdominal aortic aneurysm, supported by two initial European prospective, randomized trials (Dutch Randomised Endovascular Aneurysm Management [DREAM], Endovascular Aneurysm Repair [EVAR]).18Greenhalgh R.M. Brown L.C. Kwong G.P. Powell J.T. Thompson S.G. EVAR Trial ParticipantsComparison of endovascular aneurysm repair with open repair in patients with abdominal aortic aneurysm (EVAR trial 1), 30-day operative mortality results: randomised controlled trial.Lancet. 2004; 364: 843-848Abstract Full Text Full Text PDF PubMed Scopus (1636) Google Scholar, 19Prinssen M. Verhoeven E.L. Buth J. Cuypers P.W. van Sambeek M.R. Balm R. et al.A randomized trial comparing conventional and endovascular repair of abdominal aortic aneurysms.N Engl J Med. 2004; 351: 1607-1618Crossref PubMed Scopus (1670) Google Scholar, 20Rutherford R.B. Randomized EVAR trials and advent of level i evidence: a paradigm shift in management of large abdominal aortic aneurysms?.Semin Vasc Surg. 2006; 19: 69-74Abstract Full Text Full Text PDF PubMed Scopus (32) Google Scholar Accordingly, but despite the lack of RCTs, the use of stent grafts has been introduced, and have been reported to be favorable in thoracic aortic aneurysms and in traumatic thoracic aortic ruptures.21Hoffer E.K. Forauer A.R. Silas A.M. Gemery J.M. Endovascular stent-graft or open surgical repair for blunt thoracic aortic trauma: systematic review.J Vasc Interv Radiol. 2008; 19: 1153-1164Abstract Full Text Full Text PDF PubMed Scopus (79) Google Scholar, 22Verdant A. Endovascular management of traumatic aortic injuries.Can J Surg. 2006; 49: 217PubMed Google Scholar, 23Patel H.J. Williams D.M. Upchurch Jr., G.R. Dasika N.L. Passow M.C. Prager R.L. et al.A comparison of open and endovascular descending thoracic aortic repair in patients older than 75 years of age.Ann Thorac Surg. 2008; 85: 1597-1603Abstract Full Text Full Text PDF PubMed Scopus (48) Google Scholar Since the first report of thoracic endovascular aortic repair (TEVAR) in aortic dissections by Dake et al. in 1999,24Dake M.D. Kato N. Mitchell R.S. Semba C.P. Razavi M.K. Shimono T. et al.Endovascular stent-graft placement for the treatment of acute aortic dissection.N Engl J Med. 1999; 340: 1546-1552Crossref PubMed Scopus (1108) Google Scholar several cohort studies have demonstrated feasibility and efficacy, but so far there is no RCT of TEVAR for the treatment of acute complicated type B dissection, although non-randomized studies suggested lower mortality rates when compared with open surgery.24Dake M.D. Kato N. Mitchell R.S. Semba C.P. Razavi M.K. Shimono T. et al.Endovascular stent-graft placement for the treatment of acute aortic dissection.N Engl J Med. 1999; 340: 1546-1552Crossref PubMed Scopus (1108) Google Scholar, 25Khoynezhad A. Donayre C.E. Omari B.O. Kopchok G.E. Walot I. White R.A. Midterm results of endovascular treatment of complicated acute type B aortic dissection.J Thorac Cardiovasc Surg. 2009; 138: 625-631Abstract Full Text Full Text PDF PubMed Scopus (76) Google Scholar, 26Zeeshan A. Woo E.Y. Bavaria J.E. Fairman R.M. Desai N.D. Pochettino A. et al.Thoracic endovascular aortic repair for acute complicated type B aortic dissection: superiority relative to conventional open surgical and medical therapy.J Thorac Cardiovasc Surg. 2010; 140: S109-S115Abstract Full Text Full Text PDF PubMed Scopus (114) Google Scholar It is true that the results of stents or fenestration procedures for treating vascular malperfusion caused by BAD are encouraging with respect to vessel patency, but not to mortality.27Patel H.J. Williams D.M. Meerkov M. Dasika N.L. Upchurch Jr., G.R. Deeb G.M. Long-term results of percutaneous management of malperfusion in acute type B aortic dissection: implications for thoracic aortic endovascular repair.J Thorac Cardiovasc Surg. 2009; 138: 300-308Abstract Full Text Full Text PDF PubMed Scopus (77) Google Scholar, 28Slonim S. Miller D.C. Mitchell R.S. Semba C.P. Razavi M.K. Dake M.D. Aortic dissection: percutaneous management of ischemic complications with endovascular stents and balloon fenestration.J Vasc Surg. 1996; 23: 241-251Abstract Full Text Full Text PDF PubMed Scopus (206) Google Scholar, 29Park K.B. Do Y.S. Kim S.S. Kim D.K. Choe Y.H. Endovascular treatment of acute complicated aortic dissection: long-term follow-up of clinical outcomes and CT findings.J Vasc Interv Radiol. 2009; 20: 334-341Abstract Full Text Full Text PDF PubMed Scopus (19) Google Scholar, 30Midulla M. Renaud A. Martinelli T. Koussa M. Mounier-Vehier C. Prat A. et al.Endovascular fenestration in aortic dissection with acute malperfusion syndrome: immediate and late follow-up.J Thorac Cardiovasc Surg. 2011; 142: 66-72Abstract Full Text Full Text PDF PubMed Scopus (64) Google Scholar However, all these series are retrospective and without a control group of patients, and, subsequently, their scientific evidence is low. We have shown in our updated meta-analysis of TEVAR for predominantly acute uncomplicated BAD an average weighted 30-day mortality of 10.0% (68 studies, 1,685 patients), and a late mortality with a weighted average event rate of 11% (63 studies, 1,609 patients), suggesting that TEVAR may also be beneficial in these cases. Our meta-analysis of four single-arm studies with a total of 501 patients regarding best medical treatment (BMT) for uncomplicated BAD showed an average weighted rate for late mortality or late complications of 13.8% and a 30-day mortality of 11% (seven studies, 962 patients). However, these data cannot be used as evidence as the numbers were small and a control group was lacking. Another meta-analysis of four non-randomized studies each comparing TEVAR with BMT for complicated BAD (292 patients with medical treatment and 141 patients with TEVAR) showed no significant difference between the two therapeutic options. Again, these data are of limited value owing to the limited number of patients and the non-randomized study design. Regarding uncomplicated chronic BAD, the results of a randomized trial comparing TEVAR with BMT after 2 weeks were recently published (Investigation of STEnt Grafts in Aortic Dissection [INSTEAD] trial).31Nienaber C.A. Rousseau H. Eggebrecht H. Kische S. Fattori R. Rehders T. et al.Randomized comparison of strategies for type B aortic dissection: the INvestigation of STEnt Grafts in Aortic Dissection (INSTEAD) trial.Circulation. 2009; 120: 2519-2528Crossref PubMed Scopus (575) Google Scholar This trial showed that when the stent graft was placed between 2 weeks and 1 year after the onset of the acute dissection, TEVAR did not do better than BMT on 2-year all-cause or aortic related mortality. Even if underpowered for mortality, the INSTEAD trial has shown that there was a remodeling of the aorta leading to an enlarged true lumen with regression of the false lumen. Aortic remodeling with thrombosis of the thoracic false lumen occurred in 91.3% of patients with TEVAR versus 19.4% of patients with BMT. There are arguments against the use of stent grafts in the vulnerable dissected aorta, but the INSTEAD trial clearly showed that TEVAR was not associated with a higher mortality than BMT in chronic uncomplicated BAD. We are awaiting the publication of the long-term follow-up results, which, when orally presented, has shown a better survival of the TEVAR group than the BMT group. Accordingly, TEVAR might be a better therapeutic option than BMT alone for 20–30% of patients with uncomplicated BAD that will develop an aneurysmal dilatation of the false lumen, requiring late surgical intervention. The reason might be found in the hazard of having a patent false lumen, which was described by Akutsu et al.,32Akutsu K. Nejima J. Kiuchi K. Sasaki K. Ochi M. Tanaka K. Effects of the patent false lumen on the long-term outcome of type B acute aortic dissection.Eur J Cardiothorac Surg. 2004; 26: 359-366Crossref PubMed Scopus (171) Google Scholar who found a higher mortality rate in patients with a patent false lumen than in those with a thrombosed one. In this setting, a multivariate analysis has shown that baseline maximum descending aortic diameter, proximal location, and size of the entry tear were predictors of related adverse events, whereas mortality was predicted by the maximum diameter of the descending thoracic aorta, entry tear size, and Marfan syndrome.33Evangelista A. Salas A. Ribera A. Ferreira-González I. Cuellar H. Pineda V. et al.Long-term outcome of aortic dissection with patent false lumen: predictive role of entry tear size and location.Circulation. 2012; 125: 3133-3141Crossref PubMed Scopus (269) Google Scholar These results again underline the need for a prospective RCT to study the long-term result of TEVAR + BMT versus BMT alone in patients with BAD. Following the review of the available data, what evidence-based concept do we have for the treatment of acute uncomplicated type B dissection? Absolutely none! All our knowledge is based on a large, but heterogeneous, registry of type A and type B dissections—the results of which demonstrate the risk of false lumen enlargement—and one RCT on chronic uncomplicated type B dissections, which demonstrates the safety of TEVAR for treating the dissected aorta, leading to thrombosis of the false lumen. What advantage is there in treating a dissection in the first 2 weeks after the initial event where no remodeling processes or stabilization of the aortic wall layers have occurred? Covering the entry tear of acute type B dissections and thereby causing a thrombosis of the false lumen in an early phase of the disease could be the solution to avoiding late lumen enlargement, as well as treating some malperfusion complications, as observed in our own clinical practice. Currently, there is no level I evidence to support the routine use of TEVAR for DeBakey III dissections, and there is no level I evidence for medical treatment either. The need for interventions in uncomplicated BAD is characterized by a paucity of relevant data, most of them being derived from TEVAR in complicated aortic dissections, where mortality for TEVAR is in the same range as BMT for uncomplicated dissections. But are we comparing the same patients? It is likely that the two cohorts are very different. Furthermore, the treatment paradigm still under use, which advocates intervention only in the complicated cases, is derived from those times when open surgery had a worse risk-to-benefit ratio than medical therapy. Today, with the evolution of TEVAR and improved stent grafts, standardization of TEVAR might shift the risk-to-benefit ratio in favor of early intervention. For obvious reasons, though, this needs to be scientifically proven. The European “Acute Dissection Stent-graft Or Best medical treatment” (ADSORB) study, which is evaluating TEVAR + BMT versus BMT alone in patients with acute uncomplicated BAD, has completed its enrolment, and the results of the study are urgently needed to determine the best way to treat this potentially lethal disease.34Brunkwall J. Lammer J. Verhoeven E. Taylor P. ADSORB: a study on the efficacy of endovascular grafting in uncomplicated acute dissection of the descending aorta.Eur J Vasc Endovasc Surg. 2012; 44: 31-36Abstract Full Text Full Text PDF PubMed Scopus (97) Google Scholar