Immunosuppressive Agents and Thoracic Aortic Aneurysm: Real Correlation or Mere Coincidence?

Abstract

Background Atherosclerosis, hypertension, age, and fibrillopathies are well-known risk factors for the development of aortic aneurysm. We discovered that a significant proportion of our patients were previously on chemotherapy treatment or long-term treatment with cytostatic agents or immunosuppressive drugs. Thus, we examined this phenomenon.

Methods A total of 224 patients with thoracic aorta aneurysm were retrospectively analyzed after aortic surgery from 2006 to 2016. Seventy-three patients received aortic wrapping and 151 patients underwent aortic replacement of which 89 had a valve-carrying conduit and 62 a supracoronary ascending replacement. Aortic morphology was assessed by means of compute tomography scan before and after surgery. Demographic data, risk profile, and postoperative complications were collected. Short- and long-term survival analysis was performed. Statistical analysis was performed with SPSS 19.0.

Results Eighty-eight of 224 patients undergoing aortic surgery because of aortic aneurysm had previously or currently been treated with immunosuppressive agents. Dilatation of the ascending aorta was more pronounced in patients without such therapy. Demographic profile, intraoperative, as well as short- and long-term postoperative results did not differ significantly between both groups.

Conclusion The potential effect of immunosuppressant and cytostatic therapies on the development of an aortic aneurysm needs further study. Because of the astoundingly high proportion of these patients being found in an unselected aortic aneurysm cohort with immunosuppressive therapy in the past should be monitored for potential development of aortic aneurysm. If it occurs and requires treatment these patients can fortunately be operated upon with the same short- and long-term outcome than patients without such previous therapy.

Keywords

aortic aneurysm - immunosuppressant - aortic surgery - aortic wall - risk factor

Note

Presented at the 48th Annual Meeting of the German Society for Thoracic and Cardiovascular Surgery, Congress Center Wiesbaden, February 2019.

Publikationsverlauf

Eingereicht: 20. Juli 2020

Angenommen: 15. Oktober 2020

Artikel online veröffentlicht:
18. Januar 2021

• References

• 1 Nolasco P, Fernandes CG, Ribeiro-Silva JC. et al. Impaired vascular smooth muscle cell force-generating capacity and phenotypic deregulation in Marfan Syndrome mice. Biochim Biophys Acta Mol Basis Dis 2020; 1866 (01) 165587
• 2 Disabella E, Grasso M, Gambarin FI. et al. Risk of dissection in thoracic aneurysms associated with mutations of smooth muscle alpha-actin 2 (ACTA2). Heart 2011; 97 (04) 321-326
• 3 Yuan SM. Syphilitic aortic aneurysm. Z Rheumatol 2018; 77 (08) 741-748
• 4 Shalhub S, Byers PH, Hicks KL. et al. A multi-institutional experience in the aortic and arterial pathology in individuals with genetically confirmed vascular Ehlers-Danlos syndrome. J Vasc Surg 2019; 70 (05) 1543-1554
• 5 Renard M, Callewaert B, Baetens M. et al. Novel MYH11 and ACTA2 mutations reveal a role for enhanced TGFβ signaling in FTAAD. Int J Cardiol 2013; 165 (02) 314-321
• 6 Mizushima I, Inoue D, Yamamoto M. et al. Clinical course after corticosteroid therapy in IgG4-related aortitis/periaortitis and periarteritis: a retrospective multicenter study. Arthritis Res Ther 2014; 16 (04) R156
• 7 Kasashima S, Zen Y. IgG4-related inflammatory abdominal aortic aneurysm. Curr Opin Rheumatol 2011; 23 (01) 18-23
• 8 Inoue D, Zen Y, Abo H. et al. Immunoglobulin G4-related periaortitis and periarteritis: CT findings in 17 patients. Radiology 2011; 261 (02) 625-633
• 9 Zen Y, Kasashima S, Inoue D. Retroperitoneal and aortic manifestations of immunoglobulin G4-related disease. Semin Diagn Pathol 2012; 29 (04) 212-218
• 10 Englesbe MJ, Wu AH, Clowes AW, Zierler RE. The prevalence and natural history of aortic aneurysms in heart and abdominal organ transplant patients. J Vasc Surg 2003; 37 (01) 27-31
• 11 Miller JD, Clabaugh SE, Smith DR, Stevens RB, Wrenshall LE. Interleukin-2 is present in human blood vessels and released in biologically active form by heparanase. Immunol Cell Biol 2012; 90 (02) 159-167
• 12 Lindeman JH, Rabelink TJ, van Bockel JH. Immunosuppression and the abdominal aortic aneurysm: Doctor Jekyll or Mister Hyde?. Circulation 2011; 124 (18) e463-e465
• 13 Rizas KD, Ippagunta N, Tilson III MD. Immune cells and molecular mediators in the pathogenesis of the abdominal aortic aneurysm. Cardiol Rev 2009; 17 (05) 201-210
• 14 RKI and DESTATIS, Gesundheitsberichterstattung des Bundes, Gesundheitsberichterstattung des Bundes, Diagnosedaten der Krankenhäuser ab, 2000 (Eckdaten der vollstationären Patienten und Patientinnen), Gliederungsmerkmale: Jahre, Behandlungs-/Wohnort, ICD10. . Accessed August 26, 2020 at: http://www.gbe-bund.de/oowa921-install/servlet/oowa/aw92/dboowasys921.xwdevkit/xwd_init?gbe.isgbetol/xs_start_neu/&p_aid=i&p_aid=16876777&nummer=550&p_sprache=D&p_indsp=-&p_aid=88723285.
• 15 R Core Team, R: A Language and Environment for Statistical Computing, Vienna, Austria: R Foundation for Statistical Computing. 2018
• 16 Leopardi M, Di Marco E, Musilli A, Ricevuto E, Bruera G, Ventura M. Effects of chemotherapy in patients with concomitant aortic aneurysm and malignant disease. Ann Vasc Surg 2017; 45: 268.e13-268.e20
• 17 Yajima K, Koga A, Okumura T. et al. A patient with lung cancer experiencing abdominal aortic aneurysm rupture during bevacizumab treatment-case report [in Japanese]. Gan To Kagaku Ryoho 2019; 46 (09) 1449-1451
• 18 Golden MA, Vaughn DJ, Crooks GW, Holland GA, Bavaria JE. Aortic dissection in a patient receiving chemotherapy for Hodgkin's disease--a case report. Angiology 1997; 48 (12) 1063-1065
• 19 Zanow J, Leistner Y, Ludewig S, Rauchfuss F, Settmacher U. Unusual course of an abdominal aortic aneurysm in a patient treated with chemotherapy for gastric cancer. J Vasc Surg 2012; 55 (03) 841-843
• 20 Zamorano JL, Lancellotti P, Rodriguez Muñoz D. et al; ESC Scientific Document Group. 2016 ESC Position Paper on cancer treatments and cardiovascular toxicity developed under the auspices of the ESC Committee for Practice Guidelines: the Task Force for cancer treatments and cardiovascular toxicity of the European Society of Cardiology (ESC). Eur Heart J 2016; 37 (36) 2768-2801
• 21 Goodwin R, Ding K, Seymour L. et al; from the NCIC Clinical Trials Group, Kingston, Ontario, Canada. Treatment-emergent hypertension and outcomes in patients with advanced non-small-cell lung cancer receiving chemotherapy with or without the vascular endothelial growth factor receptor inhibitor cediranib: NCIC Clinical Trials Group Study BR24. Ann Oncol 2010; 21 (11) 2220-2226
• 22 Içli F, Karaoğuz H, Dinçol D. et al. Severe vascular toxicity associated with cisplatin-based chemotherapy. Cancer 1993; 72 (02) 587-593
• 23 Harrell RM, Sibley R, Vogelzang NJ. Renal vascular lesions after chemotherapy with vinblastine, bleomycin, and cisplatin. Am J Med 1982; 73 (03) 429-433
• 24 Shimizu K, Mitchell RN, Libby P. Inflammation and cellular immune responses in abdominal aortic aneurysms. Arterioscler Thromb Vasc Biol 2006; 26 (05) 987-994
• 25 He R, Guo DC, Estrera AL. et al. Characterization of the inflammatory and apoptotic cells in the aortas of patients with ascending thoracic aortic aneurysms and dissections. J Thorac Cardiovasc Surg 2006; 131 (03) 671-678
• 26 Koch AE, Kunkel SL, Pearce WH. et al. Enhanced production of the chemotactic cytokines interleukin-8 and monocyte chemoattractant protein-1 in human abdominal aortic aneurysms. Am J Pathol 1993; 142 (05) 1423-1431
• 27 Wallinder J, Bergqvist D, Henriksson AE. Proinflammatory and anti-inflammatory cytokine balance in patients with abdominal aortic aneurysm and the impact of aneurysm size. Vasc Endovascular Surg 2009; 43 (03) 258-261
• 28 Lindholt JS, Shi GP. Chronic inflammation, immune response, and infection in abdominal aortic aneurysms. Eur J Vasc Endovasc Surg 2006; 31 (05) 453-463
• 29 Middleton RK, Lloyd GM, Bown MJ, Cooper NJ, London NJ, Sayers RD. The pro-inflammatory and chemotactic cytokine microenvironment of the abdominal aortic aneurysm wall: a protein array study. J Vasc Surg 2007; 45 (03) 574-580