727279
research-article2017
JETXXX10.1177/1526602817727279Journal of Endovascular TherapyKouvelos et al
A SAGE Publication
Commentary
Postimplantation Syndrome: An Underrecognized EVAR Complication
Journal of Endovascular Therapy 1–2 © The Author(s) 2017 Reprints and permissions: sagepub.com/journalsPermissions.nav https://doi.org/10.1177/1526602817727279 DOI: 10.1177/1526602817727279 www.jevt.org
George N. Kouvelos, MD, MSc, PhD1, Eleni Arnaoutoglou, MD, PhD2, Athanasios D. Giannoukas, MD, MSc, PhD, FEBVS1, and Miltiadis Matsagkas, MD, PhD, FEBVS1 Keywords abdominal aortic aneurysm, endovascular aneurysm repair, endovascular aneurysm sealing, inflammation, Nellix, postimplantation syndrome Know your enemy and know yourself and you can fight a hundred battles without disaster. —Sun Tzu (The Art of War)
Inflammation seems to play an important role both in the pathogenesis of an abdominal aortic aneurysm (AAA) and following endovascular aneurysm repair (EVAR). The systemic inflammatory response immediately following EVAR, known as the postimplantation syndrome (PIS), has not been studied adequately despite its presence in approximately a third of EVAR patients.1 Endovascular aneurysm sealing (EVAS) has introduced a totally novel technology in AAA treatment that completely seals the aneurysm sac from the systemic circulation with the use of polymer-filled endobags surrounding the endograft lumen.2 In the October 2017 issue of the JEVT, Berg et al3 compared the risk of PIS after EVAR and EVAS, finding a trend toward a lower incidence of PIS in the EVAS group. The 30-day clinical outcome was worse in patients who received a polyester stent-graft, while there was also a trend toward fewer adverse events and endoleaks in patients without PIS. The exact effect of the EVAS endobags on thrombus remodeling and their relation to thrombotic and inflammatory properties remains unknown. It has been proposed that aneurysm thrombus has a role in the inflammatory response. In the early days of EVAR, it was shown that AAA mural thrombus contains high amounts of interleukin (IL)-6, which might be released during manipulations with endovascular instruments.4 A recent report found no differences in either total preoperative AAA volume or in the amount of newly formed thrombus between PIS and non-PIS groups.5 These results have also been confirmed by Voûte et al6 in 136 patients, weakening the theory that AAA mural thrombus was the cause of PIS. In the present study, the EVAS approach showed a diminished inflammatory response compared to EVAR overall (5.1% vs 20.5%) and especially to polyester endografts (5.1% vs 31%). However, no data
are provided to elucidate potential pathophysiological factors that may contribute to these results. The relation of PIS to patient outcomes has not been adequately established. In most studies PIS is considered a benign condition, although it may lead to more intense postoperative care, resulting in prolonged hospitalization.7 In a prospective study of 214 EVAR patients, those with PIS were more likely to suffer from an adverse event during the 30 days after the procedure.5 Adverse events occurred in 25.9% of the PIS group compared with 2.9% of the non-PIS group and included any major cardiovascular event, acute renal failure, readmission, or death from any cause. In the present study, Berg et al3 also found a higher incidence of serious adverse events (20% vs 4%, p=0.12) and endoleak (20% vs 3%, p=0.08) in patients with PIS, though these did not reach statistical significance probably because of the small sample size and the retrospective study design. Considering the effect of PIS on patient outcomes, the main question remains whether we should alter our approach and treat patients with PIS focusing on the elimination of the inflammatory response. Literature data are scarce, and no therapeutic algorithm has ever been established. Preoperative high-dose glucocorticoid administration in a randomized trial reduced systematic inflammatory response after EVAR but had no effect on 30-day surgical or medical morbidity.8 Interestingly, Bischoff et al9 reported that 71% of the German 1
Department of Vascular Surgery, Faculty of Medicine, School of Health Sciences, University of Thessaly, Larissa, Greece 2 Department of Anesthesiology, Faculty of Medicine, School of Health Sciences, University of Thessaly, Larissa, Greece Invited commentaries published in the Journal of Endovascular Therapy reflect the opinions of the author(s) and do not necessarily represent the views of the Journal, the International Society of Endovascular Specialists, or SAGE Publications Inc. Corresponding Author: George N. Kouvelos, Department of Vascular Surgery, Larissa University Hospital, Mezurlo 41110, Larissa, Greece. Email: [email protected]
2 vascular centers they surveyed had treated PIS with nonsteroidal anti-inflammatory drugs (NSAIDs). It is reasonable that some patients with an intense inflammatory response might benefit from an anti-inflammatory therapeutic treatment, although this is still unproven. In our practice, we have seen favorable outcomes after giving oral NSAIDs to patients with intense inflammatory response.10 Future studies should focus on the identification of those patients who may benefit from any treatment by investigating the effect of routine or symptom-based anti-inflammatory therapy on 30-day and long-term outcome. Furthermore, the role of preventive preoperative anti-inflammatory strategy remains another interesting target of future research. Differences between the type of the stent-graft deployed and the development of PIS might indicate that the inflammatory response varies with different materials. In the study by Berg et al,3 patients treated with polyester stent-grafts experienced higher temperature, leukocyte count, and highsensitivity C-reactive protein (hs-CRP) levels relative to EVAS and polytetrafluoroethylene (PTFE) stent-grafts. The stent-grafts used in EVAS are made of PTFE, and perhaps this might contribute to the lower PIS rate. Other studies have also confirmed the association of polyester endografts with a higher risk for an inflammatory response.5,6 Based on these findings, the type of endograft material, and especially polyester, seems to play an important role in PIS development. It may also have a predictive role in identifying a significant number of EVAR patients who may require closer surveillance after the procedure. Another interesting point of the study by Berg et al3 is the association of endoleak and the post-EVAR inflammatory process. The endoleak rate was proportionally higher in patients with PIS compared to the non-PIS group, although the difference reached only marginal statistical significance. We have observed similar results (unpublished data). It is difficult, however, to tell whether the inflammatory process eases endoleak formation or the endoleak may sustain the inflammatory response. A type II endoleak originating from multiple channels that may have inward and outward flow can provide a pathway for inflammatory mediators to reach and remain in contact with the systemic circulation. While the interplay between thrombosis and inflammation has been recognized, it is not known yet the association of PIS and its effect on sac thrombosis. In a recent study, platelet activation represented by CD36 expression was significantly higher in polyester grafts compared with PTFE grafts without, however, any correlation with the occurrence of PIS or postoperative levels of hs-CRP.11 EVAS is associated with fewer type II endoleaks; moreover, the possibility of inward and outward channels in the aneurysm sac is almost nil, minimizing the interplay between the inflammatory and thrombotic mediators. Perhaps these features may partially explain the low PIS rates. Despite the 25 years of EVAR evolution, PIS remains an underrecognized complication. The number of studies reporting on the association of PIS and a worse postoperative outcome is increasing. As new technologies for
Journal of Endovascular Therapy 00(0) endovascular treatment of AAAs emerge, more data on their behavior regarding the inflammatory response are needed. Future studies on PIS should emphasize a better understanding of the underlying pathophysiology, predictors, and risk factors, as well as determining whether preventive strategies are necessary. Declaration of Conflicting Interests The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
Funding The author(s) received no financial support for the research, authorship, and/or publication of this article.
References 1. Arnaoutoglou E, Kouvelos G, Papa N, et al. Prospective evaluation of postimplantation syndrome evolution on patient outcomes after endovascular aneurysm repair for abdominal aortic aneurysm. J Vasc Surg. 2016;63:1248–1255. 2. Thompson MM, Heyligers JM, Hayes PD, et al, for the EVAS FORWARD Global Registry Investigators. Endovascular aneurysm sealing: early and midterm results from the EVAS FORWARD Global Registry. J Endovasc Ther. 2016;23: 685–692. 3. Berg P, Stroetges R, Miller LE, et al. A propensity score–matched analysis of inflammatory response with endovascular aneurysm sealing vs endovascular aneurysm repair. J Endovasc Ther. 2017;24:xx–xx. 4. Swartbol P, Norgren L, Pärsson H, et al. Endovascular abdominal aortic aneurysm repair induces significant alterations in surface adhesion molecule expression on donor white blood cells exposed to patient plasma. Eur J Vasc Endovasc Surg. 1997;14:48–59. 5. Arnaoutoglou E, Kouvelos G, Papa N, et al. Prospective evaluation of post-implantation inflammatory response after EVAR for AAA: influence on patients’ 30 day outcome. Eur J Vasc Endovasc Surg. 2015;49:175–183. 6. Voûte MT, Bastos Gonçalves FM, van de Luijtgaarden KM, et al. Stent graft composition plays a material role in the postimplantation syndrome. J Vasc Surg. 2012;56:1503–1509. 7. Arnaoutoglou E, Kouvelos G, Milionis H, et al. Post implantation syndrome following endovascular abdominal aortic aneurysm repair: preliminary data. Interact Cardiovasc Thorac Surg. 2011;12:609–614. 8. de la Motte L, Kehlet H, Vogt K, et al. Preoperative methylprednisolone enhances recovery after endovascular aortic repair: a randomized, double-blind, placebo-controlled clinical trial. Ann Surg. 2014;260:540–548. 9. Bischoff M, Hafner S, Able T, et al. Incidence and treatment of postimplantation syndrome after endovascular repair of infrarenal aortic aneurysms. Gefasschirurgie. 2013;18:381–387. 10. Arnaoutoglou E, Papas N, Milionis H, et al. Post-implantation syndrome after endovascular repair of aortic aneurysms: need for postdischarge surveillance. Interact Cardiovasc Thorac Surg. 2010;11:449–454. 11. Arnaoutoglou E, Kouvelos G, Papa N, et al. Platelet activation after endovascular repair of abdominal aortic aneurysm. Vascular. 2016;24:287–294.
research-article2017
JETXXX10.1177/1526602817727279Journal of Endovascular TherapyKouvelos et al
A SAGE Publication
Commentary
Postimplantation Syndrome: An Underrecognized EVAR Complication
Journal of Endovascular Therapy 1–2 © The Author(s) 2017 Reprints and permissions: sagepub.com/journalsPermissions.nav https://doi.org/10.1177/1526602817727279 DOI: 10.1177/1526602817727279 www.jevt.org
George N. Kouvelos, MD, MSc, PhD1, Eleni Arnaoutoglou, MD, PhD2, Athanasios D. Giannoukas, MD, MSc, PhD, FEBVS1, and Miltiadis Matsagkas, MD, PhD, FEBVS1 Keywords abdominal aortic aneurysm, endovascular aneurysm repair, endovascular aneurysm sealing, inflammation, Nellix, postimplantation syndrome Know your enemy and know yourself and you can fight a hundred battles without disaster. —Sun Tzu (The Art of War)
Inflammation seems to play an important role both in the pathogenesis of an abdominal aortic aneurysm (AAA) and following endovascular aneurysm repair (EVAR). The systemic inflammatory response immediately following EVAR, known as the postimplantation syndrome (PIS), has not been studied adequately despite its presence in approximately a third of EVAR patients.1 Endovascular aneurysm sealing (EVAS) has introduced a totally novel technology in AAA treatment that completely seals the aneurysm sac from the systemic circulation with the use of polymer-filled endobags surrounding the endograft lumen.2 In the October 2017 issue of the JEVT, Berg et al3 compared the risk of PIS after EVAR and EVAS, finding a trend toward a lower incidence of PIS in the EVAS group. The 30-day clinical outcome was worse in patients who received a polyester stent-graft, while there was also a trend toward fewer adverse events and endoleaks in patients without PIS. The exact effect of the EVAS endobags on thrombus remodeling and their relation to thrombotic and inflammatory properties remains unknown. It has been proposed that aneurysm thrombus has a role in the inflammatory response. In the early days of EVAR, it was shown that AAA mural thrombus contains high amounts of interleukin (IL)-6, which might be released during manipulations with endovascular instruments.4 A recent report found no differences in either total preoperative AAA volume or in the amount of newly formed thrombus between PIS and non-PIS groups.5 These results have also been confirmed by Voûte et al6 in 136 patients, weakening the theory that AAA mural thrombus was the cause of PIS. In the present study, the EVAS approach showed a diminished inflammatory response compared to EVAR overall (5.1% vs 20.5%) and especially to polyester endografts (5.1% vs 31%). However, no data
are provided to elucidate potential pathophysiological factors that may contribute to these results. The relation of PIS to patient outcomes has not been adequately established. In most studies PIS is considered a benign condition, although it may lead to more intense postoperative care, resulting in prolonged hospitalization.7 In a prospective study of 214 EVAR patients, those with PIS were more likely to suffer from an adverse event during the 30 days after the procedure.5 Adverse events occurred in 25.9% of the PIS group compared with 2.9% of the non-PIS group and included any major cardiovascular event, acute renal failure, readmission, or death from any cause. In the present study, Berg et al3 also found a higher incidence of serious adverse events (20% vs 4%, p=0.12) and endoleak (20% vs 3%, p=0.08) in patients with PIS, though these did not reach statistical significance probably because of the small sample size and the retrospective study design. Considering the effect of PIS on patient outcomes, the main question remains whether we should alter our approach and treat patients with PIS focusing on the elimination of the inflammatory response. Literature data are scarce, and no therapeutic algorithm has ever been established. Preoperative high-dose glucocorticoid administration in a randomized trial reduced systematic inflammatory response after EVAR but had no effect on 30-day surgical or medical morbidity.8 Interestingly, Bischoff et al9 reported that 71% of the German 1
Department of Vascular Surgery, Faculty of Medicine, School of Health Sciences, University of Thessaly, Larissa, Greece 2 Department of Anesthesiology, Faculty of Medicine, School of Health Sciences, University of Thessaly, Larissa, Greece Invited commentaries published in the Journal of Endovascular Therapy reflect the opinions of the author(s) and do not necessarily represent the views of the Journal, the International Society of Endovascular Specialists, or SAGE Publications Inc. Corresponding Author: George N. Kouvelos, Department of Vascular Surgery, Larissa University Hospital, Mezurlo 41110, Larissa, Greece. Email: [email protected]
2 vascular centers they surveyed had treated PIS with nonsteroidal anti-inflammatory drugs (NSAIDs). It is reasonable that some patients with an intense inflammatory response might benefit from an anti-inflammatory therapeutic treatment, although this is still unproven. In our practice, we have seen favorable outcomes after giving oral NSAIDs to patients with intense inflammatory response.10 Future studies should focus on the identification of those patients who may benefit from any treatment by investigating the effect of routine or symptom-based anti-inflammatory therapy on 30-day and long-term outcome. Furthermore, the role of preventive preoperative anti-inflammatory strategy remains another interesting target of future research. Differences between the type of the stent-graft deployed and the development of PIS might indicate that the inflammatory response varies with different materials. In the study by Berg et al,3 patients treated with polyester stent-grafts experienced higher temperature, leukocyte count, and highsensitivity C-reactive protein (hs-CRP) levels relative to EVAS and polytetrafluoroethylene (PTFE) stent-grafts. The stent-grafts used in EVAS are made of PTFE, and perhaps this might contribute to the lower PIS rate. Other studies have also confirmed the association of polyester endografts with a higher risk for an inflammatory response.5,6 Based on these findings, the type of endograft material, and especially polyester, seems to play an important role in PIS development. It may also have a predictive role in identifying a significant number of EVAR patients who may require closer surveillance after the procedure. Another interesting point of the study by Berg et al3 is the association of endoleak and the post-EVAR inflammatory process. The endoleak rate was proportionally higher in patients with PIS compared to the non-PIS group, although the difference reached only marginal statistical significance. We have observed similar results (unpublished data). It is difficult, however, to tell whether the inflammatory process eases endoleak formation or the endoleak may sustain the inflammatory response. A type II endoleak originating from multiple channels that may have inward and outward flow can provide a pathway for inflammatory mediators to reach and remain in contact with the systemic circulation. While the interplay between thrombosis and inflammation has been recognized, it is not known yet the association of PIS and its effect on sac thrombosis. In a recent study, platelet activation represented by CD36 expression was significantly higher in polyester grafts compared with PTFE grafts without, however, any correlation with the occurrence of PIS or postoperative levels of hs-CRP.11 EVAS is associated with fewer type II endoleaks; moreover, the possibility of inward and outward channels in the aneurysm sac is almost nil, minimizing the interplay between the inflammatory and thrombotic mediators. Perhaps these features may partially explain the low PIS rates. Despite the 25 years of EVAR evolution, PIS remains an underrecognized complication. The number of studies reporting on the association of PIS and a worse postoperative outcome is increasing. As new technologies for
Journal of Endovascular Therapy 00(0) endovascular treatment of AAAs emerge, more data on their behavior regarding the inflammatory response are needed. Future studies on PIS should emphasize a better understanding of the underlying pathophysiology, predictors, and risk factors, as well as determining whether preventive strategies are necessary. Declaration of Conflicting Interests The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
Funding The author(s) received no financial support for the research, authorship, and/or publication of this article.
References 1. Arnaoutoglou E, Kouvelos G, Papa N, et al. Prospective evaluation of postimplantation syndrome evolution on patient outcomes after endovascular aneurysm repair for abdominal aortic aneurysm. J Vasc Surg. 2016;63:1248–1255. 2. Thompson MM, Heyligers JM, Hayes PD, et al, for the EVAS FORWARD Global Registry Investigators. Endovascular aneurysm sealing: early and midterm results from the EVAS FORWARD Global Registry. J Endovasc Ther. 2016;23: 685–692. 3. Berg P, Stroetges R, Miller LE, et al. A propensity score–matched analysis of inflammatory response with endovascular aneurysm sealing vs endovascular aneurysm repair. J Endovasc Ther. 2017;24:xx–xx. 4. Swartbol P, Norgren L, Pärsson H, et al. Endovascular abdominal aortic aneurysm repair induces significant alterations in surface adhesion molecule expression on donor white blood cells exposed to patient plasma. Eur J Vasc Endovasc Surg. 1997;14:48–59. 5. Arnaoutoglou E, Kouvelos G, Papa N, et al. Prospective evaluation of post-implantation inflammatory response after EVAR for AAA: influence on patients’ 30 day outcome. Eur J Vasc Endovasc Surg. 2015;49:175–183. 6. Voûte MT, Bastos Gonçalves FM, van de Luijtgaarden KM, et al. Stent graft composition plays a material role in the postimplantation syndrome. J Vasc Surg. 2012;56:1503–1509. 7. Arnaoutoglou E, Kouvelos G, Milionis H, et al. Post implantation syndrome following endovascular abdominal aortic aneurysm repair: preliminary data. Interact Cardiovasc Thorac Surg. 2011;12:609–614. 8. de la Motte L, Kehlet H, Vogt K, et al. Preoperative methylprednisolone enhances recovery after endovascular aortic repair: a randomized, double-blind, placebo-controlled clinical trial. Ann Surg. 2014;260:540–548. 9. Bischoff M, Hafner S, Able T, et al. Incidence and treatment of postimplantation syndrome after endovascular repair of infrarenal aortic aneurysms. Gefasschirurgie. 2013;18:381–387. 10. Arnaoutoglou E, Papas N, Milionis H, et al. Post-implantation syndrome after endovascular repair of aortic aneurysms: need for postdischarge surveillance. Interact Cardiovasc Thorac Surg. 2010;11:449–454. 11. Arnaoutoglou E, Kouvelos G, Papa N, et al. Platelet activation after endovascular repair of abdominal aortic aneurysm. Vascular. 2016;24:287–294.
