This activity has been planned and implemented in accordance with the accreditation requirements and policies of the Accreditation Council for Continuing Medical Education (ACCME) through the joint providership of Indiana University School of Medicine (IUSM) and IU Health Physicians. IUSM is accredited by the ACCME to provide continuing medical education for physicians.
IUSM designates this enduring material for a maximum of 1.00 AMA PRA Category 1 CreditsTM. Physicians should claim only the credit commensurate with the extent of their participation in the activity.
FACULTY DISCLOSURE STATEMENT
In accordance with the ACCME Standards for Commercial Support, educational programs sponsored by IUSM must demonstrate balance, independence, objectivity, and scientific rigor. All faculty, authors, editors, and planning committee members participating in an IUSM-sponsored activity are required to disclose any relevant financial interest or other relationship with the manufacturer(s) of any commercial product(s) and/or provider(s) of commercial services that are discussed in an educational activity.
Dr. Andres Fajardo has disclosed that he received reimbursement for travel expenses related to proctoring for Cook Medical. Any potential conflict of interest has been resolved.
After reading this article, the reader should be able to:
• Discuss the pathophysiology of abdominal aortic aneurysm (AAA).
• Identify the major risk factors for AAA development.
• Describe AAA screening and goal management.
• Summarize the nonsurgical treatment of asymptomatic AAA.
• Compare and contrast the interventional strategies used for aneurysm repair.
Expiration Date: June 2017
This CME activity does not have any commercial support.
A 72-year-old man who is a long-term smoker (80 pack-years) and currently taking medications for hypertension and hypercholesterolemia undergoes ultrasound screening for abdominal aortic aneurysm (AAA). An aneurysm is detected (Figure 1 see page 2), and he is referred to Indiana University Health for possible surgical intervention. Computed tomography angiography (CTA) is performed and demonstrates a 5.5 cm juxtarenal AAA (Figure 2 see page 3).*
Overview of Abdominal Aortic Aneurysm
AAA is a degenerative process occurring between the diaphragm and the aortic bifurcation that results in a segmental, full-thickness dilatation of the abdominal aorta exceeding the normal vessel diameter by 50 percent (i.e., ≥3.0 cm). AAAs, approximately 85 percent of which are infrarenal,1 are usually asymptomatic until they rupture, an often fatal event with a mortality of 85 to 90 percent.2 Of those patients who reach the hospital, only 50 to 70 percent survive. Thus, the goal of management is to identify and treat AAAs in advance of rupture.
Nonmodifiable risk factors for AAA include older age (≥50 years for men, ≥60-70 years for women); male gender and/or a family history of the disorder, either of which quadruples risk; connective tissue disease (e.g., Mar fan syndrome, Ehlers-Danlos syndome); and white race.3 Conversely, female gender,* African heritage, and the presence of diabetes mellitus are negatively associated with AAA.
Smoking is the strongest modifiable risk factor for AAA, associated with a seven-fold increase in risk.5 One study estimated that continued smoking increases the rate of aneurysm growth by 20 to 25 percent.6 Other modifiable risk factors for AAA include hypertension, elevated cholesterol levels, obesity, and pre-existing atherosclerotic disease.
Recommendations of the US Preventive Services Task Force call for one-time AAA screening in men aged 65 to 75 years who have ever smoked (grade B recommendation), selective screening in men aged 65 to 75 years who have never smoked (grade C recommendation), and no screening for women.7 Medicare covers screening for individuals with a family history of AAA.
AAAs are occasionally detected when a pulsatile abdominal mass is palpated on routine physical examination. Because of the retroperitoneal location of the aorta, however, the accuracy of physical exam as a screening tool is low, particularly in obese individuals and/or for small aneurysms.
“Ultrasonography is highly sensitive (95 percent) and specific (100 percent) and is the primary method used for aneurysm screening in asymptomatic patients,” reports Andres Fajardo, MD, assistant professor of surgery at Indiana University School of Medicine. “CT scanning and magnetic resonance imaging (MRI) are more expensive, incur risks, and are reserved for pre-interventional planning.”
When a small, asymptomatic AAA (3.0-5.4 cm in diameter) is detected, it should be monitored for expansion. The recommended frequency of surveillance is determined by aneurysm size: 3.0 to 3.4 cm diameter, every three years; 3.5 to 4.4 cm, yearly; and 4.5 to 5.4, every six months.8
Risk factor modification is the first step in aneurysm prevention and the management of small, asymptomatic AAAs. Aneurysm prevalence and size are strongly correlated with the amount and duration of smoking, and smoking cessation can reverse this risk.3 Lifestyle changes linked to a reduction in AAA risk include regular exercise and a diet adequate in fruits, vegetables, and nuts.
The link between hypertension or hypercholesterolemia and the occurrence of AAA suggests that controlling these coexisting conditions with medication may decrease risk—or at least, reduce the incidence of other cardiovascular events. Drugs such as beta-blockers, anti-inflammatory agents, and antibiotics have been evaluated for their ability to limit AAA expansion, but to date, none has been shown beneficial. Clinical trials are ongoing of several pharmacotherapy regimens, including higher-dose doxycycline and drugs that inhibit the renninangiotensin pathway.
“The objective of elective intervention in patients with AAA is to prevent rupture,” explains Dr. Fajardo. “Although the diameter of an abdominal aortic aneurysm is the best predictor of outcome, small aneurysms occasionally rupture. Consequently, any symptomatic aneurysm (typically evidenced by pain in the abdomen, back, or flank) should be immediately repaired, as the time from symptom onset to rupture and death can be brief.”
Open Surgical and Endovascular AAA Repair
Two approaches are used to repair AAAs: open surgical repair, introduced in the 1950s, and endovascular repair, first reported in 1991.
Open surgical repair involves making an abdominal or flank incision, controlling the vessels above and below the aneurysm, and opening the aneurysm sac with interposition of a synthetic graft. The hospital stay averages seven to nine days, full recovery generally takes months, and 30-day mortality rates range from two to five percent.
The less invasive endovascular aneurysm repair (EVAR), which now accounts for more than 75 percent of all AAA repairs, involves the intraluminal introduction of a covered stent through the femoral and iliac arteries (Figure 3). The stent functions as a sleeve that anchors the normal aorta above the aneurysm and the iliac arteries below it.
“EVAR can be performed percutaneously under general or local anesthesia,” Dr. Fajardo describes. “The hospital stay is one to three days, full recovery occurs over days to a few weeks, and 30-day mortality is approximately one percent.”
Three major randomized trials comparing long-term (seven to 10 years) outcomes for open repair versus EVAR yielded similar results. The UK Endovascular Aneurysm Repair (EVAR 1) trial,9 the Dutch Randomized Endovascular Aneurysm Management (DREAM) trial,10 and the Open versus Endovascular Repair (OVER) Veterans Affairs Cooperative Study11 all found an initial survival benefit for EVAR that disappeared over a period of one to three years, culminating in comparable long-term total and aneurysm-related mortality.
Complications related to open surgical repair of an AAA, such as ventral hernia or adhesions, occasionally require additional surgical interventions. After an open repair, ultrasound or CT monitoring for new or recurrent aneurysmal disease is recommended at five-year intervals.8
“The most common complication of EVAR is the development of endoleaks that reperfuse the aneurysm and lead to its continued expansion,” explains Dr. Fajardo. “Because of the potential for reperfusion and the risk—albeit very low—for aneurysm rupture, patients who have undergone endovascular repair require long-term monitoring. At IU Health, this entails ultrasonography or CT performed at one month, six months, and 12 months post-intervention and yearly thereafter.”
Technologic Advances in Endovascular Repair
Juxtarenal AAAs, which account for approximately 15 percent of all AAAs, have particularly complex anatomic morphology that may preclude the use of conventional EVAR.
“Because a juxtarenal aortic aneurysm has a short proximal neck, open repair remains the gold standard of treatment,” Dr. Fajardo reports. “Fenestrated endovascular aneurysm repair (F-EVAR) has emerged as a promising endovascular alternative to open repair, particularly for high-risk patients deemed unsuitable for open surgery with suprarenal cross-clamping.”
The Zenith® fenestrated endograft (Cook Medical Inc, Bloomington, IN) is a custom-manufactured device with scallops and fenestrations to accommodate branch vessels, as delineated by preoperative high-resolution CT imaging. Excellent two-year outcomes reported for the pivotal US fenestrated trial12 led to approval of the endograft by the US Food and Drug Administration in 2012. Postapproval studies have continued to demonstrate a high degree of safety and efficacy with its use.13,14 However, Dr. Fajardo cautions that additional studies with longer-term follow-up are needed to assess the durability of this treatment modality.
Owing to the size of the patient’s AAA, repair is recommended. The location of the aneurysm limits repair options to open surgery or F-EVAR. The patient elects to undergo F-EVAR, and an endograft tailored to the anatomy of his abdominal vasculature is manufactured. Three weeks later, surgery is performed at IU Health Methodist Hospital. A percutaneous approach is used to place the stent (Figure 4). Total time in the operating room is approximately three hours. The patient is discharged to home after a two-day hospital stay and experiences an uneventful recovery.
At his latest follow-up visit 18 months after surgery, he continues to remain stable, with CT showing complete exclusion of the AAA. The patient reports he has successfully stopped smoking.
“Abdominal aortic aneurysm is linked to approximately 15,000 US deaths per year, but this is probably an underestimate, given that unexplained sudden death can be related to aneurysm rupture,” Dr. Fajardo emphasizes. “Ultrasound screening of high-risk individuals is essential, and when an aneurysm is diagnosed, the patient should be referred to a high-volume center staffed by a multidisciplinary team of surgeons, physicians, and nurses and that offers both open surgical and endovascular repair as treatment options.”
A current limitation of the Zenith fenestrated endograft is that it is tailored to an individual’s anatomy. Consequently, the device requires about three weeks to manufacture, precluding its use in symptomatic patients and those with ruptured AAAs, in whom definitive repair cannot be delayed. A trial evaluating the Zenith p-Branch Pararenal Endovascular Graft®, an “off-the-shelf” version of the customized Zenith endograft, is underway at 20 US centers, including IU Health.
“The p-Branch has two different designs, with varying locations for pivoting the renal ‘windows,’” explains Dr. Fajardo, who is one of the trial investigators. “The unique design of this device may ultimately allow more patients with complex abdominal aneurysms—perhaps up to 60 to 70 percent of this population—to undergo a minimally invasive repair.”
For additional information about this study, please contact Janet Klein at 317-962-0287.
In the future, stem cell therapy may provide a new approach to the management of AAA, avoiding the need for surgery in some patients. Scientists in the IU Division of Vascular Surgery were the first to demonstrate that adult stem cells, specifically mesenchymal stem cells derived from bone marrow, decreased aor tic aneurysm expansion in experimental models.15 On the basis of these exciting results, the investigators have obtained US Food and Drug Administration approval and National Institutes of Health funding for a first-inhuman phase I clinical trial, under the direction of Dr. Michael Murphy, to assess the safety and efficacy of administering mesenchymal stem cells to patients with small AAAs (3.5 to 4.5 cm in diameter). The rate of aneurysm enlargement, changes in levels of inflammatory cells, and aortic inflammation will be followed for up to two years post-treatment.
Dr. Fajardo received his medical degree from the Universidad del Valle in Cali, Colombia, did his residency in general surgery at IU School of Medicine, and completed a fellowship in vascular surgery at Washington University in St. Louis, MO. His research focuses on aneurysms, carotid artery disease, and peripheral artery disease, and he is a co-investigator for clinical studies funded by the National Institutes of Health, the National Heart, Lung, and Blood Institute, and companies developing new devices for the treatment of vascular disease.
A member of the Society for Vascular Surgery and a fellow of the American College of Surgeons, Dr. Fajardo is the author of several peer-reviewed publications and has lectured extensively in the United States and internationally.
1. Jongkind V, Yeung KK, Akkersdijk GJ, et al. Juxtarenal aortic aneurysm repair. J Vasc Surg. 2010;52(3):760-767.
2. Kent KC. Clinical practice. Abdominal aortic aneurysms. N Engl J Med. 2014;371(22):2101-2108.
3. Kent KC, Zwolak RM, Egorova NN, et al. Analysis of risk factors for abdominal aortic aneurysm in a cohort of more than 3 million individuals. J Vasc Surg. 2010;52(3):539-548.
4. Dillavou ED, Muluk SC, Makaroun MS. A decade of change in abdominal aortic aneurysm repair in the United States: Have we improved outcomes equally between men and women? J Vasc Surg. 2006;43(2):230-238; discussion 238.
5. Chaikof EL, Brewster DC, Dalman RL, et al. The care of patients with an abdominal aortic aneurysm: the Society for Vascular Surgery practice guidelines. J Vasc Surg. 2009;50(4 Suppl):S2-49.
6. Powell JT, Greenhalgh RM. Clinical practice. Small abdominal aortic aneurysms. N Engl J Med. 2003;348(19):1895-1901.
7. US Preventive Services Task Force. Rockville, MD: Screening for abdominal aortic aneurysm, June 2014; available at http://www.uspreventiveservicestaskforce.org/Page/Document/UpdateSummaryFinal/abdominal-aortic-aneurysm-screening
8. Chaikof EL, Brewster DC, Dalman RL, et al. SVS practice guidelines for the care of patients with an abdominal aortic aneurysm: executive summary. J Vasc Surg. 2009;50(4):880-896.
9. United Kingdom EVAR Trial Investigators. Endovascular versus open repair of abdominal aortic aneurysm. N Engl J Med. 2010;362(20):1863-1871.
10. De Bruin JL, Baas AF, Buth J, et al. Long-term outcome of open or endovascular repair of abdominal aortic aneurysm. N Engl J Med. 2010;362(20):1881-1889.
11. Lederle FA, Freischlag JA, Kyriakides TC, et al. Long-term comparison of endovascular and open repair of abdominal aortic aneurysm. N Engl J Med. 2012;367(21):1988-1997.
12. Greenberg RK, Sternbergh WC, 3rd, Makaroun M, et al. Intermediate results of a United States multicenter trial of fenestrated endograft repair for juxtarenal abdominal aortic aneurysms. J Vasc Surg. 2009;50(4):730-737 e731.
13. Vemuri C, Oderich GS, Lee JT, et al. Postapproval outcomes of juxtarenal aortic aneurysms treated with the Zenith fenestrated endovascular graft. J Vasc Surg. 2014;60(2):295-300.
14. Tran K, Fajardo A, Ullery B, Goltz C, Lee JT. Renal function changes following fenestrated endovascular aneurysm repair. J Vasc Surg. 2016 (epublished May 27);63(6).
15. Sharma AK, Lu G, Jester A, et al. Experimental abdominal aortic aneurysm formation is mediated by IL-17 and attenuated by mesenchymal stem cell treatment. Circulation. 2012;126(11 Suppl 1):S38-45.