Outcome of patients suffering from acute type B aortic dissection: a retrospective single-centre analysis of 135 consecutive patients

European Journal of Cardio-thoracic Surgery 38 (2010) 285 292 www.elsevier.com/locate/ejcts Outcome of patients suffering from acute type B aortic dissection: a retrospective single-centre analysis of 135 consecutive patients Jens Garbade a, *, Moritz Jenniches a,1, Michael A. Borger a, Markus J. Barten a, Dierk Scheinert b, Matthias Gutberlet c, Thomas Walther a, Friedrich-Wilhelm Mohr a a Department of Cardiac Surgery, Heart Center, Leipzig University, Struempellstrasse 39, 04289 Leipzig, Germany b Department of Angiology, Heart Center, Leipzig University, Struempellstrasse 41, 04289 Leipzig, Germany c Department of Radiology, Heart Center, Leipzig University, Struempellstrasse 39, 04289 Leipzig, Germany Received 12 October 2009; received in revised form 5 February 2010; accepted 11 February 2010; Available online 8 April 2010 Abstract Objectives: Acute uncomplicated Stanford type B aortic dissection (TBAD) is optimally managed with medical treatment. However, surgery and thoracic endovascular aortic repair (TEVAR) are occasionally indicated, particularly when end-organ ischaemia develops. This study assesses the perioperative and long-term outcomes of medical, interventional and surgical management of acute TBAD. Methods: A total of 135 consecutive patients with acute TBAD treated at our institution between 2000 and 2008 were analysed. Of these patients, 84 were treated medically (group A, median age: 65 years, interquartile range (IQR): 34 90), 46 patients received TEVAR (group B, median age: 65, IQR: 23 83) and five patients underwent open surgical management (group C, median age: 60 years, IQR: 44 69). Clinical data and information on complications, reintervention and acute and long-term mortality were retrospectively collected and examined. Follow-up was made on 98% of patients with a median time span of 1107 days (IQR: 870 1343). Results: There were no significant differences in age, gender, body mass index or co-morbidities among the three treatment groups. Group B patients had the highest rate of ruptures (n = 7) and impending ruptures (n = 19). Indications for surgery in group C were impending rupture with malperfusion (n = 1), rupture (n = 2) and refractory pain (n = 2). The maximal diameter of dissection was significantly higher in group C (mean: 52.6 mm, IQR: 36 82, p < 0.05) than in group B (mean: 42.0 mm, IQR: 20 74) and group A (mean: 40.6, IQR: 23 66). The 30-day and 5-year mortality rates, respectively, were 8.5% and 27.9% for group A, 20.0% and 43.7% for group B ( p = 0.018 for group A) and 20.0% for both time points for group C patients. The rate of re-intervention was significantly higher in group A (A: 22/ 84, 26.2% vs B: 8/46, 17.4%; p = 0.049, and group C: 1/5, 20%). The rate of major complications (e.g., stroke, paraplegia and/or vascular problems) did not differ among groups. Conclusions: Medical, interventional and surgical management for acute TBAD result in acceptable survival rates. Although stent implantation and surgery were reserved for patients with complications of TBAD in the current study, results were good for both treatment modalities. Randomised prospective trials should be performed to determine whether conservative, TEVAR or surgical management is most advantageous for complicated acute TBAD patients. # 2010 European Association for Cardio-Thoracic Surgery. Published by Elsevier B.V. All rights reserved. Keywords: Acute type B dissection; Open surgical repair; Endovascular repair; Mortality 1. Introduction In the era of growing minimally invasive strategies, acute pathologies of thoracic aorta are an area of increasing interest. For patients presenting with acute type B aortic dissection (TBAD), several different treatment strategies exist, including minimally invasive thoracic endovascular aortic repair (TEVAR). Management recommendations for acute pathologies of the descending aorta are mostly derived from registry data and expert opinion, as opposed to randomised clinical trials [1 9]. Nonetheless, there is Presented at the 23rd Annual Meeting of the European Association for Cardio-thoracic Surgery, Vienna, Austria, October 18 21, 2009. * Corresponding author. Tel.: +49 341 8651421; fax: +49 341 8651452. E-mail address: garbade@med.uni-leipzig.de (J. Garbade). 1 The author contributed equally to the study. general consensus that patients with stable, acute, uncomplicated TBAD should be treated conservatively with antihypertensives and heart rate control, followed by regular ambulatory visits and imaging [10,11]. The 3-year survival in patients suffering from acute TBAD has been estimated to be 77% for conservative therapy, 82% for open surgical repair and 76% for the endovascular approach [12]. However, patients treated with medical management are thought to have an elevated rate of up to 20% of late complications including rupture, impending rupture and malperfusion [4]. Interventional therapy is normally recommended for acute complicated TBAD, since the expected mortality without therapy may be as high as 50 85% in such patients [2]. As opposed to uncomplicated TBAD, open surgical repair has been the historical standard therapy in patients 1010-7940/$ see front matter # 2010 European Association for Cardio-Thoracic Surgery. Published by Elsevier B.V. All rights reserved. doi:10.1016/j.ejcts.2010.02.038

286 J. Garbade et al. / European Journal of Cardio-thoracic Surgery 38 (2010) 285 292 presenting with complicated TBAD. Bozinovski and Coselli found a perioperative mortality rate of 22.4% and a paraplegia rate of 6.6% in complicated TBAD patients, with a further 19.7% of patients requiring postoperative haemodialysis [13]. In view of these suboptimal rates of morbidity and mortality for these high-risk patients, less-invasive endovascular approaches (i.e., TEVAR) have gained increasing interest as a primary treatment strategy. Recently published results of TEVAR for uncomplicated and complicated TBAD demonstrated low perioperative and mid-term mortality and morbidity rates, particularly in emergency situations [3,14]. Nevertheless, paraplegia rates of up to 20% and late failure rates of 37% have been demonstrated in some centres [15]. Management of this devastating disease process therefore remains a clinical challenge. In order to shed more light on this issue, we retrospectively examined the results of a large TBAD patient cohort treated over a contemporary time period that included TEVAR therapy. The purpose of our study was to assess the perioperative and long-term outcomes of medical, interventional and surgical management of patients presenting with acute TBAD. 2. Patients and methods 2.1. Study population and data collection We retrospectively examined all patients who presented with TBAD between 2000 and 2008 at our centre, as identified through our institutional databank. Of the 187 identified patients with TBAD who were treated over this time period, 135 had an acute presentation and form the focus of the current study. Aortic dissection was classified as type B according to the Stanford classification, that is, a dissection of the thoracic aorta that did not involve the ascending aorta. In some cases (n = 5), the aortic arch was retrogradely involved. Patients who presented with traumatic transsection of the aorta, type A aortic dissection or chronic TBAD were excluded from our study. TBAD and extent of dissection were diagnosed by computerised tomography in 100% of patients. The aortic pathology was considered acute if patients presented to our hospital within 14 days of initial symptom onset. Complicated TBAD was defined as the presence of one or more of the following conditions: resistant hypertension despite adequate medical therapy, persistent pain, endorgan malperfusion, impending rupture, rupture or central/ peripheral neurological complications [2]. Patients were divided into three groups according to the predominant management strategy that was administered during their index hospital admission: group A isolated conservative management with aggressive antihypertensive therapy; group B TEVAR; and group C open thoracoabdominal surgery. All patients received aggressive antihypertensive therapy, regardless of the group assignment. Groups B and C patients were classified according to their respective group if TEVAR or surgery was performed at any time during their index hospital admission. Choice of treatment strategy was determined by the clinical team and followed conventional expert opinion or recommended published guidelines at that time. The indications for TEVAR or surgery were impending aortic rupture (n = 20), rupture with end-organ malperfusion (n = 9), recurrent pain (n = 8), refractory hypertension (n = 10) and extension of dissection (n = 2). In two patients no clear indication for interventional therapy could be found in the chart. 2.2. Medical therapy The primary strategy for TBAD was medical therapy to reduce the contractile force and blood pressure management to maintain systolic blood pressure less than 120 mm Hg, according to published guideline and recommendations [2,10]. Administration of morphine (75%) and beta-blockers (88%), in combination with vasodilatators (e.g., nitroderivate (45%) and diuretics (72%)) or angiotensin-converting enzyme inhibitors (66%), was used in our cohort to achieve stable blood pressure conditions. In patients with refractory hypertension, a combination of several antihypertensives was administered. 2.3. Endovascular procedure Endovascular techniques used for TEVAR have been described previously in detail [20]. Briefly, all interventions were performed by interventional cardiologists/radiologists, as well as a cardiothoracic surgeon, in a hybrid operating room with C-arm fluoroscopy. All procedures were performed under general anaesthesia. Using a left brachial approach, a 5-French angiographic pigtail catheter was placed into the ascending aorta. This catheter allows contrast injection during the intervention and helps to identify the origin of the left subclavian artery, an important landmark for stent positioning. The common femoral artery, or in some cases the common iliac artery, was exposed. Heparin 5000 U was administered and the artery was cannulated. To facilitate the delivery of stent graft to the thoracic aorta, an ultra-stiff guidewire was used. The proximal landing zone was the distal aortic arch (i.e., proximal to the left subclavian artery) and descending thoracic aorta. Three different stent grafts were used in the current series: (1) Talent prosthesis (Medtronic Vascular, Santa Rosa, CA, USA), n = 56; (2) Gore/TAG (W.L. Gore & Associates, Flagstaff, AZ, USA), n = 23 patients; (3) Valiant (Medtronic Vascular), n = 12. The Talent device is a self-expanding endoprosthesis consisting of circumferential nitinol stent springs arranged as a tube to conform to the aortic lumen, covered on the outside with a Dacron graft. For implantation, this prosthesis is compressed in a polytetrafluoroethylene (PTFE) sheath with an outer diameter of 22 27 French. For deployment, the graft is held in a position with a pusher while the sheath is withdrawn. The Gore/TAG device is made up of an ultra-thin expandable PTFE (eptfe) graft with an outer self-expanding nitinol support structure. The prosthesis is mounted on a catheter-based delivery system and is deployed by pulling back a string attached to the graft, once the system is placed in the desired location. In all cases, post-dilatation with a compliant aortic balloon catheter was performed in the section covered by endoprosthesis to achieve optimal alignment of the graft

J. Garbade et al. / European Journal of Cardio-thoracic Surgery 38 (2010) 285 292 287 with the surrounding aortic wall. Each patient received an average of 1.4 0.7 endovascular prostheses. 2.4. Open surgical technique The indications for open repair were progressive enlargement of dissection (n = 1), rupture (n = 2), impending rupture with malperfusion (n = 1) and prolonged neurological dysfunction (paraplegia, n = 1). Replacement of the aorta was limited to the descending aorta in two patients; the distal aortic arch and descending aorta in one patient; and the descending and abdominal aorta in two cases. Operative details have been previously published [20]. Briefly, four patients underwent posterolateral thoracotomy and one patient received a full sternotomy due to proximal extension of dissection into the distal aortic arch. Cardiopulmonary bypass (CPB) or isolated left heart bypass was used in three patients, and in two patients the procedure was performed without CPB using the clamp-and-sew technique. Hypothermic circulatory arrest (22 8C) was necessary in one case while the descending aorta was cross clamped. In this case a Dacron graft with a side arm was used to ensure perfusion of the upper body, after the hemiarch was reconstructed. Left heart bypass was performed with mild hypothermia (32 8C). The descending aorta was replaced by a Dacron vascular graft in all patients. In two patients, the abdominal aorta was replaced by a Dacron graft during selective perfusion of the abdominal organs. Clinical data, including demographics, risk factors, history of previous cardiovascular surgery, symptoms, management details and postoperative mortality and morbidity, were prospectively collected in our in-house database and then retrospectively analysed. Follow-up was made by telephone and/or mail interview with the patient and/or a family member, as well as the family physician, in 98% of patients. The median follow-up time was 1107 days (interquartile range (IQR): 870 1343) for all patients and did not differ significantly among treatment groups: group A, 1102 days (IQR: 834 1369); group B, 1399 days (IQR: 640 2157); and group C, 1107 days (IQR: 0 2774). 2.5. Statistical methods Standard definitions were used for patient variables and outcomes. Categorical variables are expressed as percentages and continuous variables are expressed as mean standard deviation (SD) throughout the article. Statistical comparisons among treatment groups were made with the chi-square or Fisher s exact test for categorical variables and with the Student s unpaired t-test for continuous variables. Actuarial survival was computed according to the Kaplan Meier method and comparisons between treatment groups were performed with the log rank test. Cox regression analysis was used to determine independent predictors of long-term survival. Statistical analyses were performed using the SPSS 14.0 for Windows statistical software package (SPSS, Inc., Chicago, IL, USA). A p-value of less than 0.05 was considered to indicate statistical significance. Statistical support was supplied by the Department of Biostatistics of the University of Leipzig. All authors have read and agree to the entire article as written. 3. Results 3.1. Study population Preoperative characteristics for patients presenting with acute TBAD aresummarised in Table 1. A majority of patients were male and the median age for the entire cohort was 63 years. There was no significant difference with regard to age, gender, body mass index (BMI) or co-morbidities among the three treatment groups. Nearly all patients had a Table 1 Baseline clinical patient characteristics. Group A conservative N =84 Group B TEVAR N =46 Group C surgery N =5 Age Median 65 IQR 34 90 Median 65 IQR 23 83 Median 60 IQR 44 69 Male sex 78.6% 69.6% 60.0% BMI Median 26.9 IQR 20 45 Median 27.6 IQR 21 39 Median 29.9 IQR 21 39 Diabetes 19.0% 19.6% 20.0% Adipositas 36.9% 30.4% 60.0% HLP 17.9% 17.4% 20.0% Hypertension 100% 87.0% 100% COPD 11.9% 19.5% 20.0% Previous surgery 7.2% 13.0% 40.0% Aneurysm 70.3% 75.0% 100% Max. diameter of dissection [mm] Median 40.6 IQR 23 66 42.0 IQR 20 74 Median 52.6 * IQR 36 82 Rupture 0% 15.2% 40.0% Impending rupture 4.8% 41.3% 20.0% Time to therapy 1 day IQR 0.5 1.5 3.0 days # IQR 0.6 5.4 Immediately TEVAR: thoracic endovascular aortic repair, N: patient number; BMI: body mass index; HLP: hyperlipoproteinemia; COPD: chronic obstructive pulmonary disease; IQR: interquartile range. * p < 0.05 versus group A and C. # p = 0.009 versus group A.

288 J. Garbade et al. / European Journal of Cardio-thoracic Surgery 38 (2010) 285 292 pre-existing history of hypertension. Surgically treated patients were more likely to have undergone previous cardiac surgery. In group A, 63 patients had uncomplicated and 21 complicated type B dissections. In group B, 27 patients presented with complicated lesions, whereas 19 were uncomplicated. All five patients treated by open surgical repair had complicated TBAD. The proportion of complicated acute TBAD was higher in the TEVAR (58%) and surgical groups (100%) than the conservative-treated patients (25%, p = 0.04). In particular, patients who received interventional therapy had a higher incidence of impending rupture or rupture (group B: 56%; group C: 60%) than the conservatively treated patients (group A: 5%, p = 0.02). Table 2 displays the extent of aortic involvement in patients with acute TBAD. Retrograde arch involvement occurred more often in patients treated by open surgical repair and TEVAR than in conservatively treated patients. The maximal diameter of dissected aorta was significantly larger in group C (mean: 52.6 mm, IQR: 36 82, p < 0.05) than in group B (mean: 42.0 mm, IQR: 20 74) and group A patients (mean: 40.6, IQR: 23 66). The mean duration from the time of diagnosis to treatment group-specific therapy was 1.0 day (IQR: 0.4 1.5) for group A, 3.0 days (IQR: 0.6 5.4) for group B ( p = 0.009 for group A) and immediately for group C patients (Table 1). 3.2. Perioperative management and long-term outcomes Of the isolated 135 patients (101 men) suffering from acute TBAD, 84 were treated medically (group A, median age: 65 years, IQR: 34 90), 46 patients received TEVAR (group B, median age: 65 years, IQR: 23 83) and five patients underwent open surgical repair (group C, median age: 60 years, IQR: 44 69). Fig. 1 shows the survival curves estimated by the Kaplan Meier method stratified by in-hospital management strategy. The 30-day, 1-year, 3-year and 5-year mortality rates were 8.5%, 13.8%, 19.1% and 27.9% for group A patients; 20.0%, 26.7% and 43.7% (3-year and 5-year mortality rates) for group B patients; and 20.0% for all time points for group C patients, respectively. Patients in the TEVAR group had a significantly higher mortality rate than those in the conservative treatment group ( p = 0.018). Fig. 2 displays the relationship between long-term survival and complicated or uncomplicated presentation of acute TBAD. Patients who presented with acute complicated aortic pathologies had a markedly decreased survival rate than Fig. 1. Kaplan Meier survival curve stratified by the three in-hospital treatment strategies. Patients treated with endostent therapy as the initial management strategy had a significantly worse survival than patients who underwent conservative medical therapy ( p = 0.018 by log rank test). those who presented with uncomplicated TBAD ( p = 0.001). Table 3 presents the multivariate Cox regression predictors of long-term mortality. Chronic obstructive pulmonary disease (COPD; hazard ratio (HR), 2.56; 95% confidence interval (CI), 1.26 5.21; p = 0.007), renal failure (HR, 2.02; 95% CI, 1.05 3.90; p = 0.032) and complicated TBAD (HR, Table 2 Extent of aortic dissection involvement. Region Group A conservative Group B TEVAR Group C surgery Zone 1 Arch involvement Zone 2 Isolated descending thoracic aorta Zone 3 Thoraco-abdominal aorta Zone 4 Extension to iliac vessels TEVAR: thoracic endovascular aortic repair. 1.2% 6.5% 20.0% 95.8% 100.0% 100.0% 95.9% 70.9% 80.0% 58.7% 32.6% 40.0% Fig. 2. Kaplan Meier survival of uncomplicated and complicated acute TBAD patients. Patients presenting with acute complicated TBAD had a significantly worse long-term survival ( p = 0.001, log rank).

J. Garbade et al. / European Journal of Cardio-thoracic Surgery 38 (2010) 285 292 289 Table 3 Cox regression analysis of independent predictors of death during follow-up. HR (95% CI) p Diabetes 1.34 (0.67 3.04) 0.35 Smoking 0.83 (0.38 1.83) 0.64 HLP 0.83 (0.34 2.00) 0.68 Hypertension 1.07 (0.15 7.98) 0.95 Previous surgery 1.17 (0.45 3.02) 0.75 Adipositas 0.55 (0.26 1.17) 0.12 Aneurysm 2.25 (0.87 5.85) 0.08 COPD 2.56 (1.26 5.21) 0.007 Renal failure 2.02 (1.05 3.90) 0.032 Complicated TBAD 5.0 (2.8 9.0) 0.001 HR: hazard ratio; CI: confidence interval; HLP: hyperlipoproteinemia; COPD: chronic, obstructive pulmonary disease; TBAD: type B aortic dissection. 5.0; 95% CI, 2.8 9.0; p = 0.001) were identified as independent predictors of mortality during follow-up. Re-intervention (i.e., surgery or TEVAR) was required in 26.2% of medically treated patients (n = 22), 17.4% of stentgraft repair patients (n = 8) and 20% of surgically managed patients (n = 1). Fig. 3 shows that re-interventions occurred most frequently within the first year after acute TBAD presentation. The rate of major complications (e.g., stroke, paraplegia and/or vascular complications) did not differ significantly among the treatment groups. Compared with patients receiving endovascular repair, patients undergoing conservative management were more likely to develop renal failure. In five TEVAR patients (10.9%) severe device-related complications occurred including perforation of the oesophagus in two patients and severe infection of the endograft in three patients (Table 4). 4. Discussion Our results show that, despite several advances in the management of TBAD, early and late morbidity and mortality rates continue to be substantial for patients who present acutely with this disease process. In particular, the long-term mortality of acute TBAD hospital survivors seems to exceed Fig. 3. Actuarial freedom from re-intervention (surgery or stenting) according to initial in-hospital management strategy. Re-intervention occurred mostly within the first year of follow-up. the follow-up mortality observed after acute type A dissection [12,16]. Five years after admission to the hospital, only 60% of stent-graft treated patients were alive in the current series. Patients who were treated with open surgical repair, although small in number, had a 5-year survival rate of approximately 80%, whereas two-thirds of conservatively treated patients were alive at this time period. The present single-centre survival analysis began at patient admission to the hospital and included in-hospital mortality as well as mortality after discharge. We attempted to focus on the association of treatment modality and early and follow-up morbidity and mortality. Although our study is limited by its retrospective nature and subsequent inevitable selection bias, it is important to note that it is one of the largest studies to date of acute TBAD patients managed in the contemporary TEVAR era. We therefore believe that useful observations and insights can be gleaned from our results. Table 4 Follow-up complications and re-interventions according to management strategy. Group A conservative N =84 Group B TEVAR N =46 Group C surgery N =5 Neurological complications 30-day 14.3% 23.0% 20.0% 5-years 19.1% 36.2% 20.0% Renal failure 42.9% 29.5% 40.0% Vascular problems 36.9% 35.6% 40.0% Cardiac arrhythmia 8.6% 12.9% 0% Re-intervention (TEVAR or surgery) N =22 26.2% N =8 17.4% N =1 20.0% First re-intervention 1 surgery 4 surgery 1 TEVAR 21 TEVAR 4 re-tevar Second re-intervention 2 re-tevar 4 surgery 1 re-re-tevar 1 re-surgery Device-related complications Penetration into the oesophagus 2 Infection 3 TEVAR: thoracic endovascular aortic repair; N: number of patients.

290 J. Garbade et al. / European Journal of Cardio-thoracic Surgery 38 (2010) 285 292 Previous studies have demonstrated significant differences in terms of in-hospital mortality stratified by type of treatment modality for patients presenting with acute TBAD [5,17]. The International Registry of Acute Aortic Dissection (IRAD) investigators have previously reported a hospital mortality of 32% for patients treated by open surgical repair, 7% for patients managed by TEVAR and 10% for those who underwent conservative medical therapy alone [18]. Recently published data in 76 patients with acute TBAD revealed an in-hospital mortality of 22.4% in patients treated by open surgical repair, with a neurological complication rate of 6.6% and an incidence of renal failure of 19.7% [13]. In our single-centre cohort, we observed an in-hospital mortality of 8.5% for medical therapy alone, compared with 20% for both TEVAR and surgery. However, TEVAR and surgical patients had a higher prevalence of complicated TBAD. Despite our observed differences in early mortality rates, treatment strategy did not have a significant impact on longterm survival. Cox regression analysis revealed that complicated TBAD, COPD, renal failure and the presence of an aneurysm were independent predictors of mortality (Table 3). These predictors of mortality were similar to those identified by other investigators [12,18,19]. Fig. 2 shows the impact of clinical status of TBAD on follow-up survival. It is not surprising that the observed early and late mortality in the TEVAR group is higher than the medically treated arm, since a larger proportion of TEVAR patients had complicated TBAD (58%) with impending rupture and rupture. A recently published paper focussing on surgically managed patients found no difference in postoperative complications or operative mortality in acute TBAD patients with or without rupture [13]. The IRAD investigators reported that post-dissection variables such as pleural effusion on chest radiography, inhospital renal failure, hypotension and shock had a stronger impact on late survival than pre-existing variables [14]. The delay from symptom onset and diagnosis to effective therapy may influence the outcomes of TBAD patients, even in catastrophic scenarios. In the current study, all patients received aggressive antihypertensive therapy immediately upon hospital admission. It may be speculated that our observed time period of 3 days between symptom onset and stent therapy may have contributed to the reduced survival in this patient group. Such a delay may lead to further clinical deterioration secondary to prolonged false lumen perfusion and expansion, with a resultant increased risk of end-organ failure and late rupture. The primary goal of acute TBAD patients should be the depressurisation and minimisation of the false lumen to achieve a complete thrombosis. Any delay of definitive treatment could potentially result in poorer outcomes. In patients who were treated conservatively and in those receiving TEVAR therapy, we observed a relatively high rate of re-intervention during follow-up. The risk was highest in the first 12 months after the index hospital admission. In a recently published analysis of acute TBAD from the IRAD investigators, 73% of patients were managed medically with an in-hospital mortality of 10%. Even in patients who did not develop acute complications, however, the long-term prognosis was suboptimal with an observed mortality of 20 40%, despite optimal medical and interventional therapy [12]. Such observations stress the fact that TBAD is a chronic disease that requires aggressive medical therapy and regular surveillance and imaging. Factors that can influence the need for re-intervention include poor aortic wall tissue quality, aortic lesion complexity, challenging anatomical characteristics of chronically dissected aorta and rapid expansion of the true or false lumen. Further studies should focus on identification of those patients who are at high risk for future re-intervention, and whether or not the initial treatment strategy affects this risk. Although our results may suggest that the risk of reintervention is the lowest for surgically treated patients, at least in the initial 5 years after diagnosis (Fig. 3), it should be noted that there were a small number of surgically treated patients. Minimally invasive approaches such as TEVAR are an attractive option for acute TBAD patients, but severe devicerelated complications can nonetheless occur. In our cohort we observed three patients with fatal infection of the stent and two with stent perforation of the oesophagus during follow-up. Furthermore, we recently reported a series of 14 patients who underwent surgical management after previous TEVAR therapy [20]. Of these, 10 patients received endostenting due to acute or chronic TBAD. The overall inhospital mortality was 7% for the post-stent implantation operation; no postoperative strokes or paraparesis were observed; and 79% of patients were alive after a mean followup of 13.5 months. Thus, secondary surgical repair after TEVAR can be performed with very good results, despite the challenging clinical scenario [20]. Although select centres have demonstrated good results, surgical management of acute TBAD is still associated with considerable mortality rates, reported between 0% up to 27% and exceeding 50% in patients operated on under emergency conditions [13,17,19]. General consensus therefore exists that surgery may be reserved for acute TBAD in those patients who are unsuitable for or refractory to conventional medical or TEVAR management [2,14]. The current indications for TEVAR therapy are similar to the previously accepted indications for open surgical repair, that is, intractable pain, rapidly expanding false lumen, diameter over 55 mm and signs of imminent rupture or malperfusion [13]. Recently published data suggest that TEVAR may be superior to open repair in complicated aortic pathology, including TBAD, cases with regard to in-hospital morbidity and early mortality [2]. Paraplegia, in particular, appears to be a rare phenomenon in TEVAR patients [5,21,25]. However, complications such as retrograde type A aortic dissection, endoleaks, late reperfusion of the false lumen, perforation and severe infection have been occasionally observed. Since these complications can occur early or late after TEVAR therapy, stringent follow-up imaging is recommended in all patients with additional re-intervention as required [20,22].In addition, TEVAR therapy may be contraindicated in patients with Marfan s syndrome and other connective tissue disorders. Although TEVAR may be occasionally used in Marfan s syndrome patients under emergency conditions as a bridge to definitive open repair, its use has failed to impact on early outcomes for such patients [24]. TEVAR is an established approach in treating acute TBAD, with particular benefits in emergency scenarios. Whether

J. Garbade et al. / European Journal of Cardio-thoracic Surgery 38 (2010) 285 292 291 endografting is beneficial in patients with uncomplicated TBAD is currently controversial and under clinical investigation. The pathology of acute TBAD differs from chronic TBAD, and the primary goal of therapy is therefore also different. The goal of TEVAR for acute TBAD is to close the proximal entry site and to depressurise the false lumen, leading to its thrombosis, better perfusion of the true lumen and end organs and subsequent aortic remodelling. By contrast, most TEVAR therapy for chronic TBAD is performed because of large or rapidly expanding aneurysms. In order to clarify the benefit of prophylactic endovascular repair in patients with chronic TBAD versus best medical treatment, final results from the INSTEAD (INvestigation of STEnt Grafts in Aortic Dissection) trial are eagerly awaited. However, interim analyses did not demonstrate a survival benefit for stent-graft therapy in the first year postintervention [23]. 4.1. Limitations The main limitation of our study is its retrospective nature and the subsequent treatment bias that is inherent to such studies. Determination of the optimal treatment strategy for acute TBAD is therefore challenging. In addition, our study had a small number of patients who underwent open surgical repair, despite the large number of conservatively and stent-treated patients. This is a reflection of the fact that the current series is contemporary and performed in the era of widely available TEVAR therapy. Despite these limitations, we believe our acute TBAD study adds some important information to our understanding of this uncommon, but devastating, disease process. In conclusion, early and long-term mortality for acute TBAD remains a challenge, even in the era of TEVAR therapy. However, acceptable outcomes can be achieved even in complicated clinical scenarios. Conservative medical therapy for uncomplicated acute TBAD is associated with a relatively low risk of early mortality and morbidity, but regular followup is required because of the high rate of re-interventions. Further studies should focus more on the long-term results of medical, endovascular and surgical therapy to more precisely determine which patients are more likely benefit from which primary strategy. References [1] Akin I, Kische S, Ince H, Nienaber CA. Indication, timing and results of endovascular treatment of type B dissection. Eur J Vasc Endovasc Surg 2009;37:289 96. [2] Svensson LG, Kouchoukos NT, Miller DC, Bavaria JE, Coselli JS, Curi MA, Eggebrecht H, Elefteriades JA, Erbel R, Gleason TG, Lytle BW, Mitchell RS, Nienaber CA, Roselli EE, Safi HJ, Shemin RJ, Sicard GA, Sundt 3rd TM, Szeto WY, Wheatley 3rd GH. Society of Thoracic Surgeons Endovascular Surgery Task F. Expert consensus document on the treatment of descending thoracic aortic disease using endovascular stent-grafts. Ann Thorac Surg 2008;85:S1 41. [3] Dick F, Hinder D, Immer FF, Savolainen H, Do DD, Carrel TP, Schmidli J. Thoracic endovascular aortic repair: impact of urgency on outcome and quality of life. Eur J Cardiothorac Surg 2009;35:96 103. [4] Hagan PG, Nienaber CA, Isselbacher EM, Bruckman D, Karavite DJ, Russman PL, Evangelista A, Fattori R, Suzuki T, Oh JK, Moore AG, Malouf JF, Pape LA, Gaca C, Sechtem U, Lenferink S, Deutsch HJ, Diedrichs H, Marcos y Robles J, Llovet A, Gilon D, Das SK, Armstrong WF, Deeb GM, Eagle KA. The International Registry of Acute Aortic Dissection (IRAD): new insights into an old disease. JAMA 2000;283:897 903. [5] Fattori R, Tsai TT, Myrmel T, Evangelista A, Cooper JV, Trimarchi S, Li J, Lovato L, Kische S, Eagle KA, Isselbacher EM, Nienaber CA. 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;1:395 402. [6] Kaya A, Heijmen RH, Rousseau H, Nienaber CA, Ehrlich M, Amabile P, Beregi JP, Fattori R. Emergency treatment of the thoracic aorta: results in 113 consecutive acute patients (the Talent Thoracic Retrospective Registry). Eur J Cardiothorac Surg 2009;35:276 81. [7] Lin PH, Huynh TT, Kougias P, Huh J, LeMaire SA, Coselli JS. Descending thoracic aortic dissection: evaluation and management in the era of endovascular technology. Vasc Endovascular Surg 2009;43:5 24. [8] Fujita W, Daitoku K, Taniguchi S, Fukuda I. Endovascular stent placement for acute type-b aortic dissection with malperfusion an intentional surgical delay and a possible bridging therapy. Interact Cardiovasc Thorac Surg 2009;8:266 8. [9] Xenos ES, Minion DJ, Davenport DL, Hamdallah O, Abedi NN, Sorial EE, Endean ED. Endovascular versus open repair for descending thoracic aortic rupture: institutional experience and meta-analysis. Eur J Cardiothorac Surg 2009;35:282 6. [10] Khoynezhad A, Plestis KA. Managing emergency hypertension in aortic dissection and aortic aneurysm surgery. J Card Surg 2006;21(Suppl. 1):S3 7. [11] Kodama K, Nishigami K, Sakamoto T, Sawamura T, Hirayama T, Misumi H, Nakao K. Tight heart rate control reduces secondary adverse events in patients with type B acute aortic dissection. Circulation 2008;118:S167 70. [12] Tsai TT, Fattori R, Trimarchi S, Isselbacher E, Myrmel T, Evangelista A, Hutchison S, Sechtem U, Cooper JV, Smith DE, Pape L, Froehlich J, Raghupathy A, Januzzi JL, Eagle KA, Nienaber CA. International Registry of Acute Aortic Dissection. 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 31. [13] Bozinovski J, Coselli JS. Outcomes and survival in surgical treatment of descending thoracic aorta with acute dissection. Ann Thorac Surg 2008;85:965 70 [discussion 970 961]. [14] Tsai TT, Trimarchi S, Nienaber CA. Acute aortic dissection: perspectives from the International Registry of Acute Aortic Dissection (IRAD). Eur J Vasc Endovasc Surg 2009;37:149 59. [15] Feezor RJ, Martin TD, Hess Jr PJ, Beaver TM, Klodell CT, Lee WA. Early outcomes after endovascular management of acute, complicated type B aortic dissection. J Vasc Surg 2009;49:561 6 [discussion 566 567]. [16] Chiappini B, Schepens M, Tan E, Dell Amore A, Morshuis W, Dossche K, Bergonzini M, Camurri N, Reggiani LB, Marinelli G, Di Bartolomeo R. Early and late outcomes of acute type A aortic dissection: analysis of risk factors in 487 consecutive patients. Eur Heart J 2005;26:180 6. [17] Trimarchi S, Nienaber CA, Rampoldi V, Myrmel T, Suzuki T, Bossone E, Tolva V, Deeb MG, Upchurch Jr GR, Cooper JV, Fang J, Isselbacher EM, Sundt TM, 3rd, Eagle KA, Investigators I. Role and results of surgery in acute type B aortic dissection: insights from the International Registry of Acute Aortic Dissection (IRAD). Circulation 2006;114:I357 64. [18] Suzuki T, Mehta RH, Ince H, Nagai R, Sakomura Y, Weber F, Sumiyoshi T, Bossone E, Trimarchi S, Cooper JV, Smith DE, Isselbacher EM, Eagle KA, Nienaber CA. International Registry of Aortic D. Clinical profiles and outcomes of acute type B aortic dissection in the current era: lessons from the International Registry of Aortic Dissection (IRAD). Circulation 2003;108(Suppl. 1):II312 7. [19] Umana JP, Miller DC, Mitchell RS. What is the best treatment for patients with acute type B aortic dissections medical, surgical, or endovascular stent-grafting? Ann Thorac Surg 2002;74:S1840 3 [discussion S1857 1863]. [20] Girdauskas E, Falk V, Kuntze T, Borger MA, Schmidt A, Scheinert D, Mohr FW. Secondary surgical procedures after endovascular stent grafting of the thoracic aorta: successful approaches to a challenging clinical problem. J Thorac Cardiovasc Surg 2008;136:1289 94. [21] Huptas S, Mehta RH, Kuhl H, Tsagakis K, Reinsch N, Kahlert P, Jakob HG, Erbel R, Eggebrecht H. Aortic remodeling in type B aortic dissection: effects of endovascular stent-graft repair and medical treatment on true and false lumen volumes. J Endovasc Ther 2009;16:28 38. [22] Dong ZH, Fu WG, Wang YQ, Guo da Q, Xu X, Ji Y, Chen B, Jiang JH, Yang J, Shi ZY, Zhu T, Shi Y. Retrograde type A aortic dissection after endovascular stent graft placement for treatment of type B dissection. Circulation 2009;119:735 41.

292 J. Garbade et al. / European Journal of Cardio-thoracic Surgery 38 (2010) 285 292 [23] Nienaber CA, Zannetti S, Barbieri B, Kische S, Schareck W, Rehders TC; INSTEAD study collaborators. Investigation of stent grafts in patients with type B aortic dissection: design of the INSTEAD trial a prospective, multicenter, European randomized trial. Am Heart J 2005;149:592 9. [24] Ehrlich MP, Nienaber CA, Rousseau H, Beregi JP, Piquet P, Schepens M, Bartoli JM, Schillinger M, Fattori R. Short-term conversion to open surgery after endovascular stent-grafting of the thoracic aorta: the Talent thoracic registry. J Thorac Cardiovasc Surg 2008;135:1322 6. [25] Sullivian TM, Sundt 3rd TM. Complications of thoracic aortic endografts: spinal cord ischemia and stroke. J Vasc Surg 2006;43:85A 8A. Appendix A. Conference discussion Dr T. Sundt (Rochester, Minnesota, USA): I think that these are very important studies. I agree with Thierry Carrel s comment that the IRAD database (and we are participants in the IRAD database) is not perfect. And I don t want to offend anyone, but among the challenges in interpreting the data from IRAD is that the data are not audited. Frankly, the database was created principally by medical cardiologists and vascular medicine physicians rather than surgeons, so they re looked at in a nonsurgical way. And so these kinds of single-centre experiences can give us a lot of the detailed information that we need, particularly as we move forward in trying to define the place of stent-graft therapies in the treatments of these diseases. This is particularly true in the group of patients with uncomplicated dissections. It s a little confusing for me when we divide up the series in so many different directions. I understand the logic behind your interest in comparing medical TEVAR and surgical therapy, but I don t believe we can make much comparing those groups to one another in this study because they re so different inherently. I am most interested in focusing on the medically treated group who have uncomplicated dissection, because that s really where the controversy will be in TEVAR. If I understood correctly, in your medically treated group, the mortality rate was 10% early, and that about a quarter of those patients in the medical group, if I read the manuscript right, actually had complicated dissections. Is that true? Dr Garbade: In the medically treated group, 4 patients had severe complications, impending ruptures, and another 17 patients had also complicated pathologies; they suffered from persistent pain and refractory hypertension despite adequate medication. In principle, I think these symptoms are very, very soft characteristics and investigator-dependent compared to rupture or impending rupture. So that s why we focused only on rupture and impending rupture as clear signs of worse clinical scenarios. Dr Sundt: So if you look only at your medical group and remove those complicated ones, what s the early mortality rate there? Is that the 6.4% for uncomplicated? Dr Garbade: Yes. The mortality is somewhat higher than uncomplicated TBAD, but not significantly. Dr Sundt: So those were all treated medically. So that s what we can expect for a medical baseline for uncomplicated dissections is a mortality rate of 6%, about? Dr Garbade: Approximately 6%, yes. Dr Sundt: The other thing that s obvious in looking at your data is that the late survival is disappointing. You re not the first to see that. I think Craig Miller has pointed that out for years. And it s an interesting challenge for us as surgeons because we are episodic caregivers, we don t give longitudinal care. And yet, once a patient has had a dissection, they have a chronic disease. One of the reasons why TEVAR may be effective in many individual series is that it then ties the patient back to the physician, so we re looking at their blood pressure. Do you have any sense of what the blood pressure control was in the long run for your medical group? Because that s a critical parameter in determining long-term survival. Dr Garbade: I completely agree that imaging the blood pressure is very important, but we have no data about it, particularly in the long-term followup. Dr Sundt: That s common. You re not to be criticized for that. It s one of the challenges we have in dealing with this condition and creates a strange sort of circumstance where we are pressed to be more aggressive at an operation when the best treatment actually may be adequate medical follow-up. Your survival dropped off, as you noted, within the first year or so. What do you think about the role of semi-elective intervention at 6 weeks to 6 months for the patient with type B dissection as a strategy? The late survival of the surgical group is quite good. The highest risk associated with operation is at the acute event. So can we split the baby and do the operation electively at 6 weeks to 6 months? Dr Garbade: That could be an elegant opportunity or strategy to wait, to see, and to operate later on. Also another opportunity could be in patients suffering from connective tissue disorders, for instance Marfan patients, to stent in worst scenarios as a bridge, and 2 or 3 months to decide about possible open repair; this could be a good decision-making process. Dr Sundt: And that was actually my last question. I find that for patients with a defined connective tissue disease, I m much more aggressive about getting early imaging and oftentimes anticipate doing an elective operation earlier. So my question was going to be stratifying the acute patient for who needs more aggressive follow-up. Dr L. von Segesser (Lausanne, Switzerland): Can you tell us how you allocated the patients? Because I have seen in your conservative group, which means medical treatment at the base, you had diameters up to 6.6 cm. Is that wrong? Dr Garbade: No, in the medically treated patients the median diameter was 42 mm. Dr von Segesser: That was the mean. But maximum diameter was 6.6 cm. In our practice we would maybe even, if the patient is stable, not operate him immediately or stent him immediately, but we would do it at 3 weeks. We would not leave it as a permanent medical group. Dr Garbade: These patients with a great diameter after dissection had worse co-morbidities and that s why they were only treated by medication. They were not eligible for stent. Dr von Segesser: Does that exist? It can be done using local anaesthesia? Dr Garbade: That s true. But there was a kinking and the route of the abdominal aorta was not eligible for stent implantation. In our Department, the primary decision was always made by our cardiologists and the angiologists. Dr von Segesser: It s always the cardiologist s fault. We know that. Dr Garbade: And if they had problems, they called us. That s everywhere. Dr B. Zipfel (Berlin, Germany): I have a problem with this comparison of TEVAR and conservative treatment, because there were obviously decisions made between these two, so one should not go home with the message that TEVAR has a mortality of 20% and conservative has 6%. I think that s wrong. I have two questions. First, you have to define what is impending rupture. You had 4 patients in the conservative group with impending rupture. Why didn t you decide to do anything on these? Second, I missed malperfusion as a complication in this study. Didn t you see any? Dr Garbade: Yes, to your first question concerning impending ruptures, the small number of impending ruptures in our conservative arm. The CT scan revealed only a small leakage of solution and therefore we decided to treat this patient conservatively only. And with respect to malperfusion, in our patient cohort I ve mentioned that in the TEVAR group we had a re-intervention rate of about 17.6%. And the reason for that was mostly endoleaks, and in 2 patients due to malperfusion. That s right. We analysed retrospectively whether the patient had malperfusion in the follow-up, but I have not shown this data here. Dr Zipfel: But to come back, you didn t have malperfusion as the primary indication for TEVAR? This is for us one of the most serious complications. Dr Garbade: You know the Stanford classification of complicated/ uncomplicated TBAD. And malperfusion is defined as a complicated type B aortic dissection if malperfusion occurred. Dr Zipfel: But you don t have the figures, how many malperfusion patients were in that group? Dr Garbade: That s correct, this analysis is currently in progress.