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a Department of Surgery, University of Michigan Cardiovascular Center, Ann Arbor, Michigan
b Department of Radiology, University of Michigan Cardiovascular Center, Ann Arbor, Michigan
Accepted for publication February 9, 2009.
* Address correspondence to Dr Patel, Department of Surgery, Section of Cardiac Surgery, 5144 Cardiovascular Center, 1500 E Medical Center Dr SPC 5864, Ann Arbor, MI 48109-5864 (Email: hjpatel{at}med.umich.edu).
Presented at the Fifty-fifth Annual Meeting of the Southern Thoracic Surgical Association, Austin, TX, Nov 5–8, 2008.
| Dr Patel discloses a financial relationship with W. L. Gore and Medtronic.
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Abstract |
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Methods: Of 170 patients undergoing thoracic endovascular repair (1993 to 2008), 20 presenting with ITAP were identified. Indications for intervention included aortobronchial (n = 10), aortoesophageal (n = 2), or aortocutaneous fistulae (n = 1), or mycotic aneurysms (n = 7). Underlying disease included fusiform aneurysm (n = 1), saccular aneurysm or pseudoaneurysm (n = 18), or dissection (n = 1). Four patients had ITAP from infected grafts. Follow-up was 100% complete (mean, 28.6 months).
Results: Median age was 73 years. A history of immunosuppression was present in 4; concurrent malignancy was present in 5. Arch repair was needed in 8; total descending, in 6. Three patients underwent hybrid thoracic endovascular repair or debranching procedures. Causes of in-hospital mortality (n = 3; 15.0%) included refractory hypoxemia (n = 1) and sepsis from tracheoesophageal fistula (n = 1) or pneumonia (n = 1). Dialysis was needed in 2; none sustained postoperative stroke or paraplegia. Mean Kaplan-Meier survival was 39.0 months. Late mortality was seen in 13 patients, with 3 attributed to recurrent ITAP. There was a trend for recurrence of ITAP when thoracic endovascular repair was originally performed in an infected graft (p = 0.08). At last imaging follow-up, 14 patients had a healed aorta.
Conclusions: Treatment with thoracic endovascular repair for ITAP can be accomplished with acceptable results. Late mortality is frequently related to underlying comorbidities, rather than complications from the aortic disease itself, suggesting that thoracic endovascular repair is an appropriate palliative therapeutic option in this high-risk cohort.
Infectious thoracic aortic pathology (ITAP), including aortobronchial, aortoesophageal, and aortocutaneous fistulae as well as mycotic aneurysms, constitutes a formidable clinical pathologic disorder. In the absence of intervention, the natural history of this disease is poor, with mortality rates exceeding 55% [1]. Although open repair is considered the gold standard approach for this entity, recent reports with this approach have suggested high rates of morbidity and mortality [1–4]. The successful application of thoracic endovascular repair (TEVAR) as a therapeutic option for degenerative noninfected thoracic aneurysms has prompted attempts to treat ITAP with TEVAR to improve early outcomes [5–7]. The current analysis was undertaken to determine whether TEVAR provided satisfactory early and late outcomes when applied in the setting of ITAP in a cohort primarily considered to be at high risk for undergoing open repair.
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Material and Methods |
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Data from all patients undergoing TEVAR at the University of Michigan Hospitals between 1993 and 2008 were retrospectively analyzed. The diagnosis of ITAP was made by the combination of clinical factors, including presenting clinical history and physical examination, and blood culture data, as well as the use of dynamic computed tomography. Of the 170 patients undergoing TEVAR during this era, 20 patients were identified with ITAP and constituted the study group.
All patients were evaluated initially by a thoracic surgeon with specific expertise in thoracic aortic reconstruction. Nineteen patients were deemed at high risk for open surgery, and TEVAR was offered in lieu of medical therapy. The remaining patient refused open surgery and was offered TEVAR as an alternative. A collaborative multidisciplinary team consisting of thoracic or vascular surgeons and interventional radiologists then assessed suitability for TEVAR. Endograft sizing was performed using spiral computed tomography with or without three-dimensional reconstruction, intravascular ultrasound, and calibrated angiography. Three patients required adjunctive debranching procedures (visceral or renal in 2 and total arch in 1) to achieve satisfactory landing zones to permit endovascular repair. In all 3 patients, TEVAR was done after the debranching procedure as part of the overall operative procedure under the same anesthetic. Percutaneous access was used to obtain necessary angiograms; the access vessel for endograft delivery was isolated through an open exposure. Device positioning and deployment were guided by angiographic landmarks or intravascular ultrasound. Completion aortography was performed, and all type I or type III endoleaks were treated when identified either by repeat balloon dilatation to profile or with additional coverage of the treated or adjacent aortic segments.
Postoperative management for prevention of spinal cord ischemia was conducted according to standardized protocols as previously described [5]. Lumbar drains were used at the discretion of the operating surgeon in 4 patients, and no immediate complications were identified.
The primary outcome of this study was all-cause mortality. Data were collected from clinic visit notes, hospital charts, and imaging studies, and mortality was verified by interrogation of the National Death Index. Follow-up was 100% complete as of October 2008 (mean follow-up time of 28.6 ± 32.4 months).
Data were analyzed using SPSS (SPSS Inc, Chicago, IL). Dichotomous variables were evaluated using 
2 analysis; continuous variables using an independent samples Student's t test. Survival was analyzed by Kaplan-Meier methods. All results with probability values less than 0.05 were considered statistically significant.
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Results |
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Isolated mycotic aneurysms were seen in 7 patients, all presenting with underlying rapidly growing saccular aneurysms. Three additional patients presented with identified mycotic aneurysms, as well as hemoptysis (n = 2) or aortocutaneous fistula (n = 1). An additional 10 patients presented with isolated aortobronchial (n = 8) or aortoesophageal (n = 2) fistulae. Underlying disease included saccular aneurysms (n = 18), fusiform aneurysm (n = 1), and chronic dissection with a new acute dissection (n = 1). Four patients had ITAP at the site of a previous aortic repair. Pathogens were identified in 11 patients and included Staphylococcus aureus (n = 6), Enterococcus (n = 2), Streptococcus (n = 1), Salmonella (n = 1), and Aspergillus (n = 1). Antibiotic therapy was individualized in all, and included protracted courses (greater than 24 hours) in all patients. Details are listed in Table 1.
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Early Results
Technical success was achieved in all patients. Both patients with preoperative creatinine greater than 2 mg/dL required temporary hemodialysis. No patients sustained postoperative stroke or spinal cord ischemia. Four patients exhibited postoperative pneumonia. The median postoperative length of stay was 11 days. In-hospital mortality was seen in 3 patients (15.0%). One patient was hypoxic (oxygen saturations at 80% to 85%) secondary to significant hemoptysis from a pseudoaneurysm at the site of previous coarctation repair. He underwent emergent TEVAR and temporary left pulmonary artery balloon occlusion in an attempt to improve the ventilation–perfusion mismatch. He subsequently expired as a result of progressive hypoxia and end-organ dysfunction on the first postoperative day. The second patient had a mediastinal abscess and aortoesophageal fistula after Botox injection for achalasia. She underwent TEVAR, but expired after a protracted course complicated by development of a tracheoesophageal fistula. She was found both on postoperative imaging and at autopsy to have an excluded and healed aortoesophageal fistula. The final patient had a recent history of transhiatal esophagectomy with subsequent conduit necrosis requiring gastrectomy. He presented with fevers and development of a mycotic aneurysm, and later with hemoptysis. After undergoing TEVAR, he had a protracted course and subsequently expired as a result of sepsis secondary to the presence of multidrug-resistant pneumonia. Multiple computed tomographic scans had demonstrated satisfactory exclusion of his aneurysm. No preoperative or intraoperative variables were identified that correlated with early mortality on univariate analysis. However, a trend toward significance was demonstrated for those patients having postoperative pneumonia (p = 0.088).
Late Results
Endoleak was seen in 3 patients (15%). In 1 patient, the predischarge computed tomographic scan identified an endoleak of indeterminant type. No further imaging was obtained in this patient who expired of unknown causes 5 months after TEVAR. The second patient had either a type 2 or 3 endoleak at 30 days. Subsequent imaging studies 2 months later revealed a stable sac size with endoleak, but the development of new gas bubbles in the aneurysm sac. This elderly patient (95 years old) did not wish to undergo another procedure, and expired in hospice secondary to failure to thrive at 4 months after TEVAR. Finally, the last patient treated for an acute or chronic dissection with aneurysm with a visceral or renal debranching and TEVAR procedure has a stable endoleak with a decreasing sac size at 6 months after TEVAR.
The overall crude mortality rate for this group was 65% (n = 13). A Kaplan-Meier survival analysis is shown in Figure 1 and demonstrates a mean survival of 39.0 ± 8.9 months. No variables were identified that correlated with late mortality on univariate analysis.
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Comment |
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Recent studies suggesting reduced morbidity and mortality achieved with TEVAR when compared with open surgery have prompted its use in high-risk pathologic settings including blunt aortic injury, aortic rupture, and acute dissection. Several modest series have reported outcomes with TEVAR for ITAP [6–8]. Gonzalez-Fajardo and colleagues [7] described the endovascular approach in two patients with aortoesophageal fistulae and suggested a high risk for reinfection. They attributed the risk of reinfection to the placement of prosthetic material in an infected field without debridement. Wheatley and associates [8] have reported favorable results with the use of TEVAR for aortobronchial fistulae in 7 patients. No recurrent endograft infection was reported at a mean follow-up of 42 months. The report from Ting and coworkers [6] for 7 patients undergoing TEVAR for mycotic aneurysms described no in-hospital mortality and no recurrent endograft infection at a median of 34 months. Interestingly, despite the late success of TEVAR for both groups, antibiotic regimens were completely different, with the latter group emphasizing the need for lifelong antibiotic therapy.
The current analysis was conducted specifically to focus on the results of endoluminal therapy in this high-risk cohort. Based on the results seen in our study, the following salient points can serve as conclusions. First, thoracic aortic infections frequently arise in debilitated individuals who have a significant number of comorbidities. Second, endoluminal therapy can be performed with acceptable early results. Early mortality was not attributed to the aneurysm itself, but rather to other causes (nonaortic-related sepsis or hypoxia from the initial hemoptysis). Rates of morbidity were low, with no neurologic sequelae seen, and the need for temporary dialysis was identified only in those with severe preexisting renal dysfunction. Third, late mortality is frequently seen in this cohort, and is often not related to the aorta. Fourth, despite the insertion of a prosthesis in an infected nondebrided field, rates of reinfection were lower than expected. Indeed, the only documented reinfections identified in the study group were an early infection in an elderly woman without complete aneurysm exclusion (early type 2 or 3 endoleak) and late infections (at 36 and 54 months) in 2 patients who had TEVAR for infected prosthetic grafts. Finally, this finding of late recurrent ITAP despite negative interval imaging underscores our assumption that one is likely never completely treated of the infection, and that TEVAR is considered a palliative option in this high-risk group.
The association with documented recurrent ITAP when the original TEVAR was performed for an infected graft deserves mention. Recurrent ITAP was identified in 2 of 4 patients (50%) treated for a graft infection, in comparison to recurrence in 1 of 16 (6.3%; p = 0.08) treated in native aorta. It may be in this setting in which adequate debridement of infected material may play a significant role in decreasing recurrent ITAP, because antibiotic therapy may be able to sterilize the native aorta, but not the graft. This is supported by the demonstrated limited success of medical therapy alone in mycotic aneurysms [1]. In contrast, the results were encouraging for those patients presenting with ITAP occurring in native aorta, and support the emergence of TEVAR as a viable therapeutic option for patients in this group. However, future studies are warranted to validate this, and should likely include a comparison group consisting of similar patients undergoing open repair.
At the University of Michigan, our current approach for patients presenting with ITAP is to assess whether they are appropriate candidates for open aortic resection, wide debridement of infected tissue, and extraanatomic bypass. If patients are not considered suitable for open repair, we then will evaluate them for TEVAR as either a definitive repair or as a bridge to open repair if their clinical status improves sufficiently for them to be considered operable. Prolonged antibiotic therapy (at least 6 weeks and possibly even lifelong) is considered an important adjunct, as this approach is an in situ grafting procedure without debridement in an infected field.
There are important limitations of this study. First, this is a retrospective analysis, and the sample size is small. In addition, no comparison group is present in this analysis. However, given the infrequency with which ITAP is observed, randomized trials or even direct comparisons between treatment modalities may be exceedingly difficult. Also, no standardized antibiotic regimen was observed, although all patients received protracted courses of antibiotics. Although similar results have been reported in ours as well as other series in which duration of antibiotic therapy differs, our current practice recommends intravenous antibiotics for 3 to 6 weeks and then maintenance therapy indefinitely if tolerated. Finally, causes of death were not available in all patients. Although a negative computed tomographic scan may have been obtained within several months of death, it is possible that a sudden death episode may have been secondary to an indolent reinfection presenting with aortic rupture.
In summary, TEVAR is a suitable therapy for ITAP. Because of the presence of significant comorbidities in this group of patients, TEVAR in this setting may be viewed as a suitable palliative option. However, late infection can recur even years after the initial operation, and long-term suppressive antibiotics may be an appropriate additional therapy.
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Discussion |
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The first is, in our own experience in over 200 TEVAR patients at the University of Florida in recent years, we have tried this approach in 4 patients with infected aortas, but only 1 of these was a long-term survivor. This particular patient had a penetrating thoracic ulcer with lung parenchyma erosion and hemoptysis, but an actual fistula per se was never demonstrated. I note that you had 10 patients with aortobronchial fistulas. Were these true fistulas or more similar to our patient with a simple kind of erosion into the parenchyma?
I also noted in your manuscript several patients who died in the first year suddenly or with no specific etiology, and your Kaplan-Meier 1-year survival was 50%. Do you think some of those patients with sudden death had recurrent infection as the etiology of their demise?
Your approach is reasonable for frail elderly patients, but do you advocate this approach for all patients? And specifically, if you are faced with a younger patient with no comorbidities, would your group favor a primary TEVAR approach?
Also, you treated 4 patients with infected aortic grafts and 2 of these had recurrent infection. Do you now avoid these patients, and are there any other groups of patients that you specifically avoid?
And then finally, do all of these patients, in your opinion, need lifelong suppressive antibiotic therapy?
Thank you for sending me the manuscript in advance and the privilege of discussing your paper.
DR PATEL: Thank you, Dr Beaver, for some very pointed and salient questions. I am just going to take them in perhaps a different order.
Lifelong antibiotics, we believe, are really a very important adjunctive aspect of it, particularly since the classic surgical dictum of wide debridement and extraanatomic bypass is not followed with this protocol. Most patients in this group received a protracted course of antibiotics, but lack of this adjunct was not identified as an associated variable for late reinfection on univariate analysis.
Most of these patients who present are debilitated. In our experience, we have not seen mycotic aneurysms or fistulous connections in patients who are young and otherwise relatively healthy. So to answer your question about performing these in everybody who comes in, I am not sure that we would necessarily support that at present. We do believe that the gold standard therapy for infected thoracic aortic pathology remains open repair. However, we feel that in those patients who are considered high risk for surgery, TEVAR is a very suitable palliative approach, understanding that a lot of these patients will succumb from comorbid conditions.
A significant portion of these patients that did go on to expire within the first year had actual negative imaging studies within several months of death. However, it is possible that the mortality that was observed was due to a ruptured aorta from an indolent reinfection.
To answer your question of whether we would avoid patients with infected grafts, we believe that the gold standard again in that setting is excision of the infected graft and extraanatomic bypass. We have approximately 20 patients that we have done this to with an open standpoint, and we do believe that this is a good option for the appropriate patient. The patients that were reported here really were not necessarily considered suitable for either a redo sternotomy or a redo thoracotomy, excision of graft, and extraanatomic bypass, and they received stent grafting as an alternative to medical therapy in that setting.
Finally, I would like to answer to your last question regarding whether these fistulous connections were truly infected and whether they involved the mainstem bronchus. These patients presented in urgent settings, and were toxic appearing and ill from both their hemoptysis as well from their presumed infection. One elderly patient who had sudden growth was felt to have eroded into the lung parenchyma and was treated with TEVAR and a short course of antibiotics. Unfortunately, she then went on to develop gas bubbles at her 3-month CT (computed tomographic) scan. I therefore presume that her presentation was likely infectious in etiology and not just a simple parenchymal erosion. In addition, in our experience, aortobronchial fistulae typically do not present with mainstem bronchi involvement, but often with parenchymal and small bronchiolar involvement.
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