- Email: [email protected]
A Single-Institution Experience with the AneuRx Stent Graft for Endovascular Repair of Abdominal Aortic Aneurysm
A Single-Institution Experience with the AneuRx Stent Graft for Endovascular Repair of Abdominal Aortic Aneurysm Sumona Smith, Sally Mountcastle, Andrea Burridge, Thomas F. Dodson, Atef A. Salam, Karthik Kasirajan, Ross Milner, Ravi Veeraswamy, and Elliot L. Chaikof, Atlanta, Georgia
We report our experience of endovascular repair of infrarenal abdominal aortic aneurysms (EVAR) using the modular AneuRx Stent Graft System. We retrospectively reviewed the outcomes of 113 patients who underwent EVAR with the AneuRx system performed at our institution between October 1999 and August 2003. The mean age of this group was 72.5 years, with 71% (n ¼ 80) over the age of 70 years and 95% (n ¼ 107) males. Aneurysm diameter ranged 4.0-9.0 cm, with 33% (n ¼ 37) >6.0 cm. The average duration of late follow-up was 32.6 ± 24.8 months (median ¼ 37). Successful deployment of the modular AneuRx system was noted in all patients. There were no immediate operative conversions, deaths within 24 hr of operation, or type I or III endoleaks observed at the completion of the procedure. Thirty-day mortality was 3.5% (n ¼ 4). Acute deployment-related complications occurred in 10% (n ¼ 13) of patients and included misdeployment, operative bleeding, arterial perforation/dissection, and access site complications. Acute systemic complications were present in nine patients, predominantly renal and cardiac complications. An endoleak noted at any time occurred in 25% of patients, with 40% of those requiring a secondary intervention. Two patients suffered late aneurysm rupture due to a type I endoleak and graft infection. Kaplan-Meier analysis revealed 5-year freedom from secondary intervention of 72.4%; freedom from aneurysm-related death of 93.9%; and probability of survival based on all-cause mortality of 60.1%. Endovascular treatment with the modular AneuRx Stent Graft System is safe and effective, producing acceptable rates of disease-free survival and mid-term clinical outcome.
INTRODUCTION The less invasive nature of endovascular aortic aneurysm repair (EVAR) has made it an attractive option for the treatment of abdominal aortic aneurysms (AAAs), yet questions remain regarding the long-term clinical efficacy of this approach.1,2 Since the approval of commercial endovascular grafts for the treatment of aortic aneurysms in 1998, the
Supported by a research grant from Medtronic, Inc. Division of Vascular Surgery and Endovascular Therapy, Joseph B. Whitehead Department of Surgery, Emory University School of Medicine, and Veterans Affairs Hospital, Atlanta, GA. Correspondence to: Elliot L. Chaikof, MD, PhD, Division of Vascular Surgery and Endovascular Therapy, 101 Woodruff Circle, Room 5105, Atlanta, GA 30322, USA, E-mail: [email protected] Ann Vasc Surg 2008; 22: 221-226 DOI: 10.1016/j.avsg.2008.01.001 Ó Annals of Vascular Surgery Inc. Published online: March 17, 2008
number aneurysms treated by EVAR in the United States has increased substantially. Several singlecenter reports have noted that 65-70% of infrarenal AAAx are currently managed by EVAR,3 and in New York State in 2002 the number of AAAs repaired by endovascular procedures outnumbered those repaired by open surgical techniques.4 Significantly, level I evidence recently generated through the Endovascular Aneurysm Repair versus Open Repair in Patients with Abdominal Aortic Aneurysm (EVAR) and the Dutch Randomized Endovascular Aneurysm Management (DREAM) clinical trials using a wide variety of devices has now confirmed that endovascular therapy is associated with a reduction in aneurysm-related deaths compared to open surgery. This mortality benefit, in addition to reduced perioperative morbidity, decreased lengths of stay in both hospital and intensive care unit settings, and reduced blood loss and transfusion requirements, has provided further support to the advantages of 221
222 Smith et al.
EVAR over open repair.5-7 Thus, while problems remain, including increased cost and the need for reintervention, EVAR appears to provide both an effective and a durable option for treatment of AAA both in clinical trials and in ‘‘real-world’’ settings. Of the currently available endovascular grafts, the AneuRx Stent Graft System (Medtronic, Santa Rosa, CA) was the first to be commercially approved by the U.S. Food and Drug Administration (FDA). In January 2005, Medtronic reported data from pivotal clinical trials that included a 5-year freedom from aneurysm rupture of 96.7% and a freedom from aneurysm-related death of 91.3%. While commendable, clinical trial data may not necessarily reflect outcomes for those patients treated outside of the relatively restrictive inclusion and exclusion criteria and the requisite scrutiny of an industry-sponsored investigation. In this regard, several centers have highlighted concerns regarding the AneuRx system, including an increased incidence of clinically significant device migration. Notably, in December 2003 the FDA issued a public health notification, which stated that ‘‘the risk of late AAA-related mortality associated with AneuRx may exceed that associated with open surgery [and] the overall AAA-associated mortality from the AneuRx Stent Graft is likely to cross-over and exceed the AAA-associated mortality from open surgery at some point in time.’’8 Given the uncertainties in clinical performance raised by these reports, use of the AneuRx device decreased significantly at our institution after an initial experience with over 100 implants. In this study, we reviewed our experience with patients initially treated with the AneuRx device in order to assess the effectiveness and durability of this endograft with a particular emphasis on aneurysm-related death, need for reintervention, and all-cause mortality.
PATIENTS AND METHODS Patient Population We retrospectively reviewed all patients who underwent endovascular treatment of aortoiliac aneurysms with an AneuRx device between October 1999 and August 2003 at Emory University Hospital and the Atlanta Veterans Affairs Medical Center. The Emory University Institutional Review Board approved this study. Information pertaining to preoperative imaging, operative procedure, perioperative and postoperative complications, and follow-up data was gathered from hospital medical records, radiology imaging databases, and telephone interviews.
Annals of Vascular Surgery
Operative Procedures All patients were evaluated preoperatively with contrast-enhanced computed tomography (CT) of the abdomen and pelvis. In select instances, preoperative angiography and intravascular ultrasound were performed. Based on morphology and size of the abdominal aorta and iliac arteries, attending surgeons determined which patients would be appropriate for endovascular repair. All procedures were performed in the operating room with open exposure of the femoral arteries. Using the Seldinger technique and under fluoroscopic guidance, the main device along with a variable number of components were deployed to exclude the aneurysm. Postprocedure angiograms were performed to assess device placement and the presence as well as type of endoleaks. Adjunctive surgical or endovascular procedures were performed at the time of the original operation, as deemed necessary by the attending surgeon. Reporting of technical and clinical outcomes, including description of early and late complications, followed Society of Vascular Surgery reporting standard guidelines.9 Statistical Analysis Continuous data are presented as mean ± standard deviation and range. Life-table analysis was performed to determine the probability of freedom from death, aneurysm rupture, and secondary intervention.
RESULTS From October 1999 to August 2003, 113 patients were treated for aortoiliac aneurysms with the AneuRx stent graft. Mean patient age was 73.8 ± 7.5 years, with 71% (n ¼ 80) over the age of 70 years. The study population consisted largely of male patients (n ¼ 107, 95%). Preoperative aneurysm diameter ranged 4.0-9.0 cm (5.7 ± 0.9), with 33% (n ¼ 37) of aneurysms >6.0 cm. The technical success rate was 100%, without perioperative mortality within 24 hr of device implantation or a type I/ III endoleak noted by angiography at the termination of the procedure. Perioperative complications are listed (Table I) and discussed in detail below. Thirty-day mortality was 3.5% (n ¼ 4) due to two fatal cardiac events and complications related to acute hypogastric ischemia and known lung cancer. Both cardiac events were precipitated by significant intraoperative blood loss at the time of device deployment. In one patient with a large AAA and bilateral iliac aneurysms, severe pelvic ischemia
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Outcomes with the AneuRx stent graft
Table I. Perioperative complications Category
Total (endoleaks not included) Deployment-related Failed deployment ± conversion Operative bleeding Arterial perforation/rupture Access artery dissection/ thrombosis Access site hematoma Access site lymphocele/ lymphorrhea Access site infection Implant-related Ruptured aneurysm Endograft infection (led to rupture) Endograft migration Postoperative endograft limb obstruction Buttock/leg claudication/ ischemia Systemic Cardiovascular Renal Fever of unknown origin Other
223
Table II. Causes of death >30 days postoperation
Complications % Total (n) complications
36
2
6
3 1 2
8 3 6
1 1
3 3
3
8
1 1
3 3
6 1
17 3
1
3
4 4 2 3
11 11 6 8
occurred after bilateral internal iliac artery embolizations. In addition, the patient’s hospital course was further complicated by a right retroperitoneal hematoma, which followed endograft placement. Mortality after 30 days was due to various causes (Table II).
Causes
Patients (n)
Complications of myocardial infarction Cardiac arrhythmia Complications of congestive heart failure Complications of renal failure Respiratory failure Cerebrovascular accident Cancer Sepsis Complications of aneurysmal disease Indeterminate Total
2 1 5 2 1 1 5 1 1 12 31
in another case, due to angioplasty-induced iliac artery rupture. Arterial perforation or dissection. Iliac rupture occurred in one patient (0.9%) after an attempted angioplasty to facilitate device delivery. The rupture was treated by exclusion and ileofemoral bypass grafting. An additional two patients (1.8%) were diagnosed with iliac artery dissection. In one instance, a dissection was noted intraoperatively and stenting was performed. In the second patient, follow-up CT imaging revealed a dissection, which was not treated by further intervention. Access site complications. Local groin complications were observed in five patients (4.5%). One patient was readmitted with lymphorrhea, which resolved spontaneously. An additional patient underwent evacuation of a groin hematoma 1 week after the initial operation. Three patients required local wound care and antibiotics. One patient was receiving steroid therapy for chronic pulmonary disease, while another had unrecognized adrenal insufficiency. Acute Systemic Complications
Acute Deployment-Related Complications Failed deployment. Misdeployment led to additional procedures in two patients (1.8%). One patient required a femoralefemoral bypass graft after a misplaced aortic cuff inadvertently converted a bifurcated endograft into an aorto-uni-iliac device. In another patient, a malpositioned graft led to occlusion of the left renal artery and partial obstruction of the orifice of the right renal artery, which necessitated the deployment of a stent. Operative bleeding. Three patients required blood transfusion (2.7%). Transfusion was required, in one instance, for significant blood loss during placement of a polytetrafluoroethylene iliac conduit and,
Cardiac. Perioperative myocardial infarction occurred in three (2.6%) patients. One patient died within 30 days of surgery. Another patient initially recovered but died 6 months later from congestive heart failure. A third patient was discharged 3 weeks after endovascular repair. A patient with a prior history of atrial fibrillation (AF) developed refractory AF that required a prolonged stay in the intensive care unit. Renal. An acute rise in serum creatinine was observed in four (3.5%) patients. In three patients, hemodialysis was not required nor was hospital stay prolonged. Transient dialysis was necessary in one patient with a preoperative creatinine of 2.0 mg/ dL that increased postoperatively with development of pulmonary edema. This patient died 3 months
224 Smith et al.
later from worsening renal failure and congestive heart failure. Miscellaneous systemic complications. Two patients (1.8%) had postoperative fevers that were unrelated to an infectious source. An additional two patients (1.8%) experienced postoperative lower extremity edema that was not attributed to deep venous thrombosis. In these four cases, further diagnostic testing led to an additional day of hospitalization. One patient was diagnosed with adrenal insufficiency. Late Outcomes Follow-up data were obtained from radiographic imaging and office visits as well as telephone interviews over an average interval of 32.6 ± 24.8 months (median ¼ 37). Endoleak. During the follow-up period, endoleaks occurred in 25% (n ¼ 28) of patients. Nearly 40% (n ¼ 10) of endoleaks resolved spontaneously, all of which were type II endoleaks, while an additional 40% (n ¼ 12, 10.6% of the total population) required further intervention, with one patient undergoing surgical conversion to open repair. Of the remaining six patients, one continues to be followed by serial imaging, three have died due to non-aneurysm-related disease, and two have been lost to follow-up. Sixty percent of endoleaks were type II (n ¼ 17), 20% (n ¼ 6) were type I, and 20% (n ¼ 6) were undefined. Type I endoleaks were attributed to proximal endograft migration, as a consequence of an inadequate infrarenal aortic neck. Endograft migration. Six patients (5%) were affected by clinically significant endograft migration leading to type I endoleak. Five of the six were successfully treated by placement of a second endovascular cuff. Treatment was declined in one patient with metastatic liver cancer. In one case of successful cuff placement, the endoleak recurred 2 years after intervention with associated aneurysm expansion. Further treatment was deferred due to poor patient health. Postoperative endograft limb obstruction. One patient (0.9%) was readmitted 2 years after treatment with lower extremity ischemia secondary to limb thrombosis. Treatment with thrombolysis and balloon angioplasty was successful. Ruptured aneurysm. There were two patients who presented with late aneurysm rupture (1.8%): one was treated by endovascular intervention, and the second underwent open repair. In one case, a proximal type I endoleak that was attributed to endograft migration led to a contained rupture. The patient was successfully treated by placement of a proximal
Annals of Vascular Surgery
extension cuff. In a second patient, aneurysm rupture was related to late device infection. There was no known antecedent event. The infected endograft was explanted, and revascularization was performed with an axillobifemoral bypass. This patient developed acute renal failure and died several months after repair. Kaplan-Meier analysis revealed that the probability of freedom from aneurysm-related death was 94.0 ± 2.9% at 5 years, which includes four perioperative deaths and one late death due to aneurysm rupture (Fig. 1). In contrast, the probability of survival from all-cause mortality was 60.1 ± 5.7% at 5 years (Fig. 2). The probability of freedom from any secondary intervention, whether endovascular or open surgery, was 90.8 ± 3.1% at 2 years and 72.4 ± 6.5% at 5 years (Fig. 3).
DISCUSSION After EVAR, patients are subjected to rigorous radiographic and clinical follow-up to detect potential mid-term and late complications, which may include aneurysm rupture or expansion, endoleak, device infection, limb thrombosis, or device migration. Positional stability of the device is essential for durability and freedom from secondary procedures. Short proximal10 and distal11 fixation lengths, aortic neck dilation, and endograft oversizing12 have been implicated as risk factors for endograft migration. In this study, device migration, which was associated with a clinical event or reintervention, was identified in six patients (5%). Indeed, review of initial postoperative scans revealed that 50% (3/6) of this group had an aortic landing zone <1.5 cm or iliac landing zones <2.0 cm. Two patients had short proximal landing zones, while one patient had both an inadequate proximal landing zone and a short left iliac landing zone. Admittedly, other reports have described a significantly higher incidence of late migration than that observed in our review.12-15 For example, in a retrospective review of 77 patients treated with an AneuRx endograft, Tonnessen et al.13 reported that the probability of migration (>10 mm or a clinical event) was 10.5% and 28% at 2 and 4 years, respectively. Of the 14 patients identified over a 39-month period, migration was an incidental finding in six and association with type I endoleak, aneurysm growth, or component separation was observed in the remaining eight. These investigators noted that the initial neck length was shorter (mean 22 mm) and a significant subset (22%) displayed neck dilation >3 mm among those
Vol. 22, No. 2, 2008
Fig. 1. Kaplan-Meier analysis of aneurysm-related death.
Fig. 2. Kaplan-Meier analysis of overall patient survival.
presenting with device migration. We acknowledge that the incidence of late device migration in our report may have been underestimated due to the absence of a more rigorous review of threedimensional imaging data and to the inability to unambiguously determine the cause of death for all patients. Nonetheless, the importance of adequate device fixation was emphasized early during our experience with this device, which was first utilized at our center after its commercial approval. Several recent reports have now noted lower incidences of AneuRx device migration, presumably due to adherence to modified recommendations related to the selection of patients with optimal proximal and distal landing zones.16,17 The 30-day mortality in our review was 3.5%, which is greater than that reported in the EVAR
Outcomes with the AneuRx stent graft
225
Fig. 3. Kaplan-Meier analysis of secondary intervention.
1 (1.7%) and DREAM (1.2%) randomized clinical trials or among the 1,193 patients treated during the AneuRx clinical trial (2%).5,6,18 However, similar mortality rates (approximately 3%) have been noted in reports that include a lumped analysis of both patients suitable for open repair as well as those at prohibitive surgical risk. 19-23 Indeed, among patients considered at substantially increased risk for surgery, the EVAR 2 trial reported an overall 30-day mortality rate of 9%.24 The 5-year freedom from aneurysm-related death in our review was 93.9%, which reflects an additional late death due to an infected device. The probability of all-cause mortality was 18%, 34%, and 40% at 2, 4, and 5 years. These data are similar to those reported by the DREAM (2year mortality 20.4%) and EVAR 1 (4-year mortality 26%) trials as well as those in an analysis of the AneuRx clinical trial patients (5-year mortality 37%).5,6,18 The reintervention rates in our review were 10% and 18% at 2 and 4 years, respectively, which are similar to the reported probabilities of reintervention of 13% for patients enrolled in the DREAM trial at 2 years and 20% for those in the EVAR 1 trial at 4 years.5,6 Moreover, these data are consistent with a recent systematic review that noted a reintervention rate of 16.2% during follow-up of 7-35 months among 11,010 patients treated by EVAR in 34 studies.25 It is noteworthy, however, that a leveling off of the probability of reintervention was not observed during our study period. Thus, despite the high rate of disease-free survival and mid-term clinical success, lifelong surveillance continues to be essential for all patients treated with the AneuRx Stent Graft System.
226 Smith et al.
Annals of Vascular Surgery
REFERENCES
aortic aneurysm repair: a comparison of AneuRx and Zenith endografts. J Vasc Surg 2005;42:392-401. Sampaio SM, Panneton JM, Mozes G, et al. Aortic neck dilation after endovascular abdominal aortic aneurysm repair: should oversizing be blamed? Ann Vasc Surg 2006;20: 338-345. Sampaio SM, Panneton JM, Mozes G, et al. AneuRx device migration: incidence, risk factors, and consequences. Ann Vasc Surg 2005;19:178-185. Biebl M, Hakaim AG, Oldenburg WA, et al. Midterm results of a single-center experience with commercially available devices for endovascular aneurysm repair. Mt Sinai J Med 2005;72:127-135. Azizzadeh A, Sanchez L, Rubin BG, et al. Aortic neck attachment failure and the AneuRx graft: incidence, treatment options, and early results. Ann Vasc Surg 2005;19:516-521. Zarins CK, White RA, Moll FL, et al. The AneuRx stent graft: four-year results and worldwide experience 2000. J Vasc Surg 2001;33(2 Suppl):S135-S145. Seriki DM, Ashleigh RJ, Welch C, et al. Midterm follow-up of a single-center experience of endovascular repair of abdominal aortic aneurysms with use of the Talent stent-graft. J Vasc Interv Radiol 2006;17:973-977. Thomas SM, Gaines PA, Beard JD. Short-term (30-day) outcome of endovascular treatment of abdominal aortic aneurysm: results from the prospective Registry of Endovascular Treatment of Abdominal Aortic Aneurysm (RETA). Eur J Vasc Endovasc Surg 2001;21:57-64. Sicard GA, Zwolak RM, Siami FS, et al. Endovascular abdominal aortic aneurysm repair: long-term outcome measures in patients at high-risk for open surgery. J Vasc Surg 2006;44:229-236. Carpenter JP. The Powerlink bifurcated system for endovascular aortic aneurysm repair: four-year results of the US multicenter trial. J Cardiovasc Surg 2006;47:239-243. Bush RL, Johnson ML, Collins T, et al. Open versus endovascular abdominal aortic aneurysm repair in VA hospitals. J Am Coll Surg 2006;202:577-587. EVAR Trial Participants. Endovascular aneurysm repair and outcome in patients unfit for open repair of abdominal aortic aneurysm (EVAR trial 2): randomised controlled trial. Lancet 2005;365:2187-2192. Drury D, Michaels JA, Jones L, Ayiku L. Systematic review of recent evidence for the safety and efficacy of elective endovascular repair in the management of infrarenal abdominal aortic aneurysm. Br J Surg 2005;92:937-946.
1. Lederle FA. Abdominal aortic aneurysm: open versus endovascular repair. N Engl J Med 2004;351:1677-1679. 2. Lederle FA. Endovascular repair of abdominal aortic aneurysmdround two. N Engl J Med 2005;352:2443-2445. 3. Brewster DC, Jones JE, Chung TK, et al. Long-term outcomes after endovascular abdominal aortic aneurysm repair: the first decade. Ann Surg 2006;244:426-438. 4. Anderson PL, Arons RR, Moskowitz AJ, et al. A statewide experience with endovascular abdominal aortic aneurysm repair: rapid diffusion with excellent early results. J Vasc Surg 2004;39:10-19. 5. Blankensteijn JD, de Jong SE, Prinssen M, et al. Dutch Randomized Endovascular Aneurysm Management (DREAM) Trial Group. Two-year outcomes after conventional or endovascular repair of abdominal aortic aneurysms. N Engl J Med 2005;352:2398-2405. 6. EVAR Trial Participants. Endovascular Aneurysm Repair versus Open Repair in Patients with Abdominal Aortic Aneurysm (EVAR trial 1): randomized controlled trial. Lancet 2005;365:2179-2186. 7. Rutherford RB. Randomized EVAR trials and the advent of level I evidence: a paradigm shift in the management of large abdominal aortic aneurysms? Semin Vasc Surg 2006;19:69-74. 8. Feigal Jr, DW. FDA Public Health Notification; Updated Data on Mortality Associated with Medtronic AVE AneuRxÒ Stent Graft System. www.fda.gov/cdrh/safety/aneurx.html. Accessed December 17, 2003. 9. Chaikof EL, Blankensteijn JD, Harris PL, et al. Reporting standard for endovascular aortic aneurysm repair. J Vasc Surg 2002;35:1048-1060. 10. Zarins CK, Bloch DA, Fogarty TJ, et al. Stent graft migration after endovascular aneurysm repair: importance of proximal fixation. J Vasc Surg 2003;38:1264-1272. 11. Heikkinen MA, Alsac JM, Arko FR, Metsa¨noja R, Zvaigzne A, Zarins CK. The importance of iliac fixation in prevention of stent graft migration. J Vasc Surg 2006;43: 1130-1137. 12. Conners MS, III, Sternbergh WC, III, Money SR, et al. Endograft migration one to four years after endovascular abdominal aortic aneurysm repair with the AneuRx device: a cautionary note. J Vasc Surg 2002;36:476-484. 13. Tonnessen BH, Sternbergh WC, III, Money SR. Mid- and long-term device migration after endovascular abdominal
14.
15.
16.
17.
18.
19.
20.
21.
22.
23.
24.
25.
We report our experience of endovascular repair of infrarenal abdominal aortic aneurysms (EVAR) using the modular AneuRx Stent Graft System. We retrospectively reviewed the outcomes of 113 patients who underwent EVAR with the AneuRx system performed at our institution between October 1999 and August 2003. The mean age of this group was 72.5 years, with 71% (n ¼ 80) over the age of 70 years and 95% (n ¼ 107) males. Aneurysm diameter ranged 4.0-9.0 cm, with 33% (n ¼ 37) >6.0 cm. The average duration of late follow-up was 32.6 ± 24.8 months (median ¼ 37). Successful deployment of the modular AneuRx system was noted in all patients. There were no immediate operative conversions, deaths within 24 hr of operation, or type I or III endoleaks observed at the completion of the procedure. Thirty-day mortality was 3.5% (n ¼ 4). Acute deployment-related complications occurred in 10% (n ¼ 13) of patients and included misdeployment, operative bleeding, arterial perforation/dissection, and access site complications. Acute systemic complications were present in nine patients, predominantly renal and cardiac complications. An endoleak noted at any time occurred in 25% of patients, with 40% of those requiring a secondary intervention. Two patients suffered late aneurysm rupture due to a type I endoleak and graft infection. Kaplan-Meier analysis revealed 5-year freedom from secondary intervention of 72.4%; freedom from aneurysm-related death of 93.9%; and probability of survival based on all-cause mortality of 60.1%. Endovascular treatment with the modular AneuRx Stent Graft System is safe and effective, producing acceptable rates of disease-free survival and mid-term clinical outcome.
INTRODUCTION The less invasive nature of endovascular aortic aneurysm repair (EVAR) has made it an attractive option for the treatment of abdominal aortic aneurysms (AAAs), yet questions remain regarding the long-term clinical efficacy of this approach.1,2 Since the approval of commercial endovascular grafts for the treatment of aortic aneurysms in 1998, the
Supported by a research grant from Medtronic, Inc. Division of Vascular Surgery and Endovascular Therapy, Joseph B. Whitehead Department of Surgery, Emory University School of Medicine, and Veterans Affairs Hospital, Atlanta, GA. Correspondence to: Elliot L. Chaikof, MD, PhD, Division of Vascular Surgery and Endovascular Therapy, 101 Woodruff Circle, Room 5105, Atlanta, GA 30322, USA, E-mail: [email protected] Ann Vasc Surg 2008; 22: 221-226 DOI: 10.1016/j.avsg.2008.01.001 Ó Annals of Vascular Surgery Inc. Published online: March 17, 2008
number aneurysms treated by EVAR in the United States has increased substantially. Several singlecenter reports have noted that 65-70% of infrarenal AAAx are currently managed by EVAR,3 and in New York State in 2002 the number of AAAs repaired by endovascular procedures outnumbered those repaired by open surgical techniques.4 Significantly, level I evidence recently generated through the Endovascular Aneurysm Repair versus Open Repair in Patients with Abdominal Aortic Aneurysm (EVAR) and the Dutch Randomized Endovascular Aneurysm Management (DREAM) clinical trials using a wide variety of devices has now confirmed that endovascular therapy is associated with a reduction in aneurysm-related deaths compared to open surgery. This mortality benefit, in addition to reduced perioperative morbidity, decreased lengths of stay in both hospital and intensive care unit settings, and reduced blood loss and transfusion requirements, has provided further support to the advantages of 221
222 Smith et al.
EVAR over open repair.5-7 Thus, while problems remain, including increased cost and the need for reintervention, EVAR appears to provide both an effective and a durable option for treatment of AAA both in clinical trials and in ‘‘real-world’’ settings. Of the currently available endovascular grafts, the AneuRx Stent Graft System (Medtronic, Santa Rosa, CA) was the first to be commercially approved by the U.S. Food and Drug Administration (FDA). In January 2005, Medtronic reported data from pivotal clinical trials that included a 5-year freedom from aneurysm rupture of 96.7% and a freedom from aneurysm-related death of 91.3%. While commendable, clinical trial data may not necessarily reflect outcomes for those patients treated outside of the relatively restrictive inclusion and exclusion criteria and the requisite scrutiny of an industry-sponsored investigation. In this regard, several centers have highlighted concerns regarding the AneuRx system, including an increased incidence of clinically significant device migration. Notably, in December 2003 the FDA issued a public health notification, which stated that ‘‘the risk of late AAA-related mortality associated with AneuRx may exceed that associated with open surgery [and] the overall AAA-associated mortality from the AneuRx Stent Graft is likely to cross-over and exceed the AAA-associated mortality from open surgery at some point in time.’’8 Given the uncertainties in clinical performance raised by these reports, use of the AneuRx device decreased significantly at our institution after an initial experience with over 100 implants. In this study, we reviewed our experience with patients initially treated with the AneuRx device in order to assess the effectiveness and durability of this endograft with a particular emphasis on aneurysm-related death, need for reintervention, and all-cause mortality.
PATIENTS AND METHODS Patient Population We retrospectively reviewed all patients who underwent endovascular treatment of aortoiliac aneurysms with an AneuRx device between October 1999 and August 2003 at Emory University Hospital and the Atlanta Veterans Affairs Medical Center. The Emory University Institutional Review Board approved this study. Information pertaining to preoperative imaging, operative procedure, perioperative and postoperative complications, and follow-up data was gathered from hospital medical records, radiology imaging databases, and telephone interviews.
Annals of Vascular Surgery
Operative Procedures All patients were evaluated preoperatively with contrast-enhanced computed tomography (CT) of the abdomen and pelvis. In select instances, preoperative angiography and intravascular ultrasound were performed. Based on morphology and size of the abdominal aorta and iliac arteries, attending surgeons determined which patients would be appropriate for endovascular repair. All procedures were performed in the operating room with open exposure of the femoral arteries. Using the Seldinger technique and under fluoroscopic guidance, the main device along with a variable number of components were deployed to exclude the aneurysm. Postprocedure angiograms were performed to assess device placement and the presence as well as type of endoleaks. Adjunctive surgical or endovascular procedures were performed at the time of the original operation, as deemed necessary by the attending surgeon. Reporting of technical and clinical outcomes, including description of early and late complications, followed Society of Vascular Surgery reporting standard guidelines.9 Statistical Analysis Continuous data are presented as mean ± standard deviation and range. Life-table analysis was performed to determine the probability of freedom from death, aneurysm rupture, and secondary intervention.
RESULTS From October 1999 to August 2003, 113 patients were treated for aortoiliac aneurysms with the AneuRx stent graft. Mean patient age was 73.8 ± 7.5 years, with 71% (n ¼ 80) over the age of 70 years. The study population consisted largely of male patients (n ¼ 107, 95%). Preoperative aneurysm diameter ranged 4.0-9.0 cm (5.7 ± 0.9), with 33% (n ¼ 37) of aneurysms >6.0 cm. The technical success rate was 100%, without perioperative mortality within 24 hr of device implantation or a type I/ III endoleak noted by angiography at the termination of the procedure. Perioperative complications are listed (Table I) and discussed in detail below. Thirty-day mortality was 3.5% (n ¼ 4) due to two fatal cardiac events and complications related to acute hypogastric ischemia and known lung cancer. Both cardiac events were precipitated by significant intraoperative blood loss at the time of device deployment. In one patient with a large AAA and bilateral iliac aneurysms, severe pelvic ischemia
Vol. 22, No. 2, 2008
Outcomes with the AneuRx stent graft
Table I. Perioperative complications Category
Total (endoleaks not included) Deployment-related Failed deployment ± conversion Operative bleeding Arterial perforation/rupture Access artery dissection/ thrombosis Access site hematoma Access site lymphocele/ lymphorrhea Access site infection Implant-related Ruptured aneurysm Endograft infection (led to rupture) Endograft migration Postoperative endograft limb obstruction Buttock/leg claudication/ ischemia Systemic Cardiovascular Renal Fever of unknown origin Other
223
Table II. Causes of death >30 days postoperation
Complications % Total (n) complications
36
2
6
3 1 2
8 3 6
1 1
3 3
3
8
1 1
3 3
6 1
17 3
1
3
4 4 2 3
11 11 6 8
occurred after bilateral internal iliac artery embolizations. In addition, the patient’s hospital course was further complicated by a right retroperitoneal hematoma, which followed endograft placement. Mortality after 30 days was due to various causes (Table II).
Causes
Patients (n)
Complications of myocardial infarction Cardiac arrhythmia Complications of congestive heart failure Complications of renal failure Respiratory failure Cerebrovascular accident Cancer Sepsis Complications of aneurysmal disease Indeterminate Total
2 1 5 2 1 1 5 1 1 12 31
in another case, due to angioplasty-induced iliac artery rupture. Arterial perforation or dissection. Iliac rupture occurred in one patient (0.9%) after an attempted angioplasty to facilitate device delivery. The rupture was treated by exclusion and ileofemoral bypass grafting. An additional two patients (1.8%) were diagnosed with iliac artery dissection. In one instance, a dissection was noted intraoperatively and stenting was performed. In the second patient, follow-up CT imaging revealed a dissection, which was not treated by further intervention. Access site complications. Local groin complications were observed in five patients (4.5%). One patient was readmitted with lymphorrhea, which resolved spontaneously. An additional patient underwent evacuation of a groin hematoma 1 week after the initial operation. Three patients required local wound care and antibiotics. One patient was receiving steroid therapy for chronic pulmonary disease, while another had unrecognized adrenal insufficiency. Acute Systemic Complications
Acute Deployment-Related Complications Failed deployment. Misdeployment led to additional procedures in two patients (1.8%). One patient required a femoralefemoral bypass graft after a misplaced aortic cuff inadvertently converted a bifurcated endograft into an aorto-uni-iliac device. In another patient, a malpositioned graft led to occlusion of the left renal artery and partial obstruction of the orifice of the right renal artery, which necessitated the deployment of a stent. Operative bleeding. Three patients required blood transfusion (2.7%). Transfusion was required, in one instance, for significant blood loss during placement of a polytetrafluoroethylene iliac conduit and,
Cardiac. Perioperative myocardial infarction occurred in three (2.6%) patients. One patient died within 30 days of surgery. Another patient initially recovered but died 6 months later from congestive heart failure. A third patient was discharged 3 weeks after endovascular repair. A patient with a prior history of atrial fibrillation (AF) developed refractory AF that required a prolonged stay in the intensive care unit. Renal. An acute rise in serum creatinine was observed in four (3.5%) patients. In three patients, hemodialysis was not required nor was hospital stay prolonged. Transient dialysis was necessary in one patient with a preoperative creatinine of 2.0 mg/ dL that increased postoperatively with development of pulmonary edema. This patient died 3 months
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later from worsening renal failure and congestive heart failure. Miscellaneous systemic complications. Two patients (1.8%) had postoperative fevers that were unrelated to an infectious source. An additional two patients (1.8%) experienced postoperative lower extremity edema that was not attributed to deep venous thrombosis. In these four cases, further diagnostic testing led to an additional day of hospitalization. One patient was diagnosed with adrenal insufficiency. Late Outcomes Follow-up data were obtained from radiographic imaging and office visits as well as telephone interviews over an average interval of 32.6 ± 24.8 months (median ¼ 37). Endoleak. During the follow-up period, endoleaks occurred in 25% (n ¼ 28) of patients. Nearly 40% (n ¼ 10) of endoleaks resolved spontaneously, all of which were type II endoleaks, while an additional 40% (n ¼ 12, 10.6% of the total population) required further intervention, with one patient undergoing surgical conversion to open repair. Of the remaining six patients, one continues to be followed by serial imaging, three have died due to non-aneurysm-related disease, and two have been lost to follow-up. Sixty percent of endoleaks were type II (n ¼ 17), 20% (n ¼ 6) were type I, and 20% (n ¼ 6) were undefined. Type I endoleaks were attributed to proximal endograft migration, as a consequence of an inadequate infrarenal aortic neck. Endograft migration. Six patients (5%) were affected by clinically significant endograft migration leading to type I endoleak. Five of the six were successfully treated by placement of a second endovascular cuff. Treatment was declined in one patient with metastatic liver cancer. In one case of successful cuff placement, the endoleak recurred 2 years after intervention with associated aneurysm expansion. Further treatment was deferred due to poor patient health. Postoperative endograft limb obstruction. One patient (0.9%) was readmitted 2 years after treatment with lower extremity ischemia secondary to limb thrombosis. Treatment with thrombolysis and balloon angioplasty was successful. Ruptured aneurysm. There were two patients who presented with late aneurysm rupture (1.8%): one was treated by endovascular intervention, and the second underwent open repair. In one case, a proximal type I endoleak that was attributed to endograft migration led to a contained rupture. The patient was successfully treated by placement of a proximal
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extension cuff. In a second patient, aneurysm rupture was related to late device infection. There was no known antecedent event. The infected endograft was explanted, and revascularization was performed with an axillobifemoral bypass. This patient developed acute renal failure and died several months after repair. Kaplan-Meier analysis revealed that the probability of freedom from aneurysm-related death was 94.0 ± 2.9% at 5 years, which includes four perioperative deaths and one late death due to aneurysm rupture (Fig. 1). In contrast, the probability of survival from all-cause mortality was 60.1 ± 5.7% at 5 years (Fig. 2). The probability of freedom from any secondary intervention, whether endovascular or open surgery, was 90.8 ± 3.1% at 2 years and 72.4 ± 6.5% at 5 years (Fig. 3).
DISCUSSION After EVAR, patients are subjected to rigorous radiographic and clinical follow-up to detect potential mid-term and late complications, which may include aneurysm rupture or expansion, endoleak, device infection, limb thrombosis, or device migration. Positional stability of the device is essential for durability and freedom from secondary procedures. Short proximal10 and distal11 fixation lengths, aortic neck dilation, and endograft oversizing12 have been implicated as risk factors for endograft migration. In this study, device migration, which was associated with a clinical event or reintervention, was identified in six patients (5%). Indeed, review of initial postoperative scans revealed that 50% (3/6) of this group had an aortic landing zone <1.5 cm or iliac landing zones <2.0 cm. Two patients had short proximal landing zones, while one patient had both an inadequate proximal landing zone and a short left iliac landing zone. Admittedly, other reports have described a significantly higher incidence of late migration than that observed in our review.12-15 For example, in a retrospective review of 77 patients treated with an AneuRx endograft, Tonnessen et al.13 reported that the probability of migration (>10 mm or a clinical event) was 10.5% and 28% at 2 and 4 years, respectively. Of the 14 patients identified over a 39-month period, migration was an incidental finding in six and association with type I endoleak, aneurysm growth, or component separation was observed in the remaining eight. These investigators noted that the initial neck length was shorter (mean 22 mm) and a significant subset (22%) displayed neck dilation >3 mm among those
Vol. 22, No. 2, 2008
Fig. 1. Kaplan-Meier analysis of aneurysm-related death.
Fig. 2. Kaplan-Meier analysis of overall patient survival.
presenting with device migration. We acknowledge that the incidence of late device migration in our report may have been underestimated due to the absence of a more rigorous review of threedimensional imaging data and to the inability to unambiguously determine the cause of death for all patients. Nonetheless, the importance of adequate device fixation was emphasized early during our experience with this device, which was first utilized at our center after its commercial approval. Several recent reports have now noted lower incidences of AneuRx device migration, presumably due to adherence to modified recommendations related to the selection of patients with optimal proximal and distal landing zones.16,17 The 30-day mortality in our review was 3.5%, which is greater than that reported in the EVAR
Outcomes with the AneuRx stent graft
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Fig. 3. Kaplan-Meier analysis of secondary intervention.
1 (1.7%) and DREAM (1.2%) randomized clinical trials or among the 1,193 patients treated during the AneuRx clinical trial (2%).5,6,18 However, similar mortality rates (approximately 3%) have been noted in reports that include a lumped analysis of both patients suitable for open repair as well as those at prohibitive surgical risk. 19-23 Indeed, among patients considered at substantially increased risk for surgery, the EVAR 2 trial reported an overall 30-day mortality rate of 9%.24 The 5-year freedom from aneurysm-related death in our review was 93.9%, which reflects an additional late death due to an infected device. The probability of all-cause mortality was 18%, 34%, and 40% at 2, 4, and 5 years. These data are similar to those reported by the DREAM (2year mortality 20.4%) and EVAR 1 (4-year mortality 26%) trials as well as those in an analysis of the AneuRx clinical trial patients (5-year mortality 37%).5,6,18 The reintervention rates in our review were 10% and 18% at 2 and 4 years, respectively, which are similar to the reported probabilities of reintervention of 13% for patients enrolled in the DREAM trial at 2 years and 20% for those in the EVAR 1 trial at 4 years.5,6 Moreover, these data are consistent with a recent systematic review that noted a reintervention rate of 16.2% during follow-up of 7-35 months among 11,010 patients treated by EVAR in 34 studies.25 It is noteworthy, however, that a leveling off of the probability of reintervention was not observed during our study period. Thus, despite the high rate of disease-free survival and mid-term clinical success, lifelong surveillance continues to be essential for all patients treated with the AneuRx Stent Graft System.
226 Smith et al.
Annals of Vascular Surgery
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