Inflammation, Endoleaks, and Aortic Remodeling—The Chicken or the Egg

Shalaby and colleagues1have taken a fresh look at inflammationandaortic aneurysmsbyexamining thecontinued remodeling of the residual aneurysmal sac after endovascular repair of infrarenal aortic aneurysms (endovascular aneurysm repair [EVAR]). Two long-term pitfalls for EVAR areendoleaksandcontinuedexpansionof the residual sac.The rate of type II endoleaks may be as low as 15%2 or as high as 27%.3Type II endoleaksusually involve continued flowwithin the aneurysm sac. Approximately 60% resolve within 6 months, but persistence of a type II endoleak after the first 6 months is associatedwith higher rates (55%) of aneurysm sac enlargement.2 The search for risk factors for type II endoleaks and sac expansion have primarily focused on anatomical factors (after all, it is a plumbingproblem): thenumber of patent lumbars, the sizeof the inferiormesenteric artery, theburden of laminated thrombus in the aneurysm, or the technical complexities of the endovascular procedure. Inflammation in the arterialwall has long been suspected as a causative factor for thedevelopment and expansionof an infrarenal aortic aneurysm, which is the most common type of sporadic, nonsyndromic aneurysm. An abundance of inflammatory cells can be found in the aneurysm wall, as well as increases in proteolytic activity and matrix protein degradation.4 This article1 suggests that increased systemic inflammationmay play a role in the failure of sac shrinkage and the development of endoleaks. In a retrospective group of 79 patients undergoingEVAR, 65%had some type of inflammatory condition (eg, allergic rhinitis, osteoarthritis, gout, or rheumatoid arthritis). The “inflammatory” group showed comparable long-termsurvival, experiencedmorepostoperativecomplications (no surprise), and had a significantly higher rate of type II endoleaks, as well as less sac shrinkage in the longterm. Their observations support the intuitive idea that excessive systemic inflammation leads to a failure of aorticwall fibrosis and contraction, resulting in retarded sac shrinkage. Why should this cause more endoleaks, primarily an anatomic problem? Instead of the conventional wisdom that endoleaks cause a failure of sac shrinkage, perhaps the reverse is true: does failure of sac shrinkage foster endoleaks? Themain caveat to their conclusions is that their classification of systemic inflammatory diseasewas based on a diagnosis proffered by others and lacked independent confirmation or, even better, some objective measurements of inflammation.Without confirmatorydata, itwouldbehard to understandhowallergic rhinitisandrheumatoidarthritismight confer a similar derangement of the systemic inflammatory state. This points to a key therapeutic question: what aspect(s) of systemic inflammationmightbeassociatedwith failure of aortic remodeling and which pathways are involved? Some directions for further study may be found in disorders in transforminggrowth factor–βsignalingandtheSMADgenes, bothofwhich share clinical associationswith aneurysmal diseases and osteoarthritis.4,5