Textbook of Interventional Cardiovascular Pharmacology - part 10 pps

Combination therapy Combination therapy with a thrombolytic agent and GPIIb/IIIa inhibitor has been studied in acute MI. Various randomized trials (TAMI-8, IMPACT, INTRO AMI, TIMI-14, SPEED, GUSTO V) in the coronary literature have shown that combination therapy reduced thrombolysis time and permitted a reduction of thrombolytic doses by 25% to 50% of the normal dose. This is explained by the fact that thrombus is composed of both fibrin and platelets. Thrombolytics only address the fibrin component of acute thrombus. Furthermore, thrombolytics may actually activate platelets directly resulting in additional thrombus formation. Therefore, the addition of GPIIb/ IIIa inhibition facilitates the efficiency of the thrombolytic agent. It is also known that GPIIb/IIIa inhibition alone can actually dissolve platelet rich clot (41,42,43). There are several small studies examining this concept of thrombolytic infusion with GPIIb/IIIa inhibition to reduce lytic infusion time and improve efficacy as summarized below. This concept is not universally proven in these studies. A larger randomized trail is needed to examine this concept before a clinical practice recommendation can be made. Tepes et al. reported the first clinical experience with abcix- imab and urokinase combination therapy in the peripheral circulation (44). Schweizer et al. used abciximab and rt-PA versus rt-PA with ASA in an 84 patient trial and found a significantly shorter duration of thrombolytic infusion was required to achieve lytic success in the combination group as well as improved clinical endpoints of less re-hospitalization, re-intervention, and amputation compared to ASA and heparin (45). Duda et al. prospectively studied 70 patients in the PROMPT trial of UK and abciximab versus UK alone. The trial showed the combination therapy resulted in a decreased infusion time, improved amputation free survival, and improved open surgery free survival at 90 days (46). Interestingly, a post hoc economic analysis of the PROMPT trial found an economic benefit to combination therapy at 90 days based on endpoints of amputation free survival, survival without open surgery, lack of major amputation and lack of major complications. The extra cost of abciximab was more than offset by the decreased costs through improved patient outcomes (47). Yoon et al. retrospectively compared the clinical outcomes of 17 patients who received eptifibatide and rt-PA to an age- matched group of patients who received only rt-PA. The study demonstrated a significantly decreased thrombolytic dose in the combination group (9.0 ϩ/– 4.4 mg vs. 38.9 ϩ/– 30.7 mg) (48). Syed et al. reported that intra-arterial eptifi- batide infusion with reteplase can be successful in restoring blood flow in the presence of chronic arterial thrombus (49). With combination therapy using reteplase and abciximab, a prospective double center study of 50 patients was reported by Drescher et al (50). Recently, however, the 74 patient RELAX trial comparing reteplase and abciximab combination therapy to reteplase monotherapy found no significant differ- ence in safety and efficacy in all major clinical end points (death, amputation, PTA/stent, surgical revascularization). The trial did demonstrate a decreased rate of distal embolic event in the combination group (51). Very limited clinical data is available for tenecteplase and eptifibatide combination therapy. A small 16 patient study did show feasibility of combining these agents with positive efficacy and safety (52). However, there was a negative safety correlation with the use of abciximab with tenecteplase in a recent 37 patient study (53). A 60 patient study comparing treatment with abciximab and rt-PA to treatment with tirofiban with rt-PA found no difference in bleeding complications, re-hospitalization, re- intervention, or amputation rate. The duration of lysis was only slightly shorter in the abciximab group but this was not clinically relevant (149.7 ϩ 18 vs. 139.3 ϩ31.3 min) (54). The 50 patient APART trial recently compared reteplase plus abciximab or urokinase plus abciximab and found overall no significant differences except a decreased thrombolysis time in the urokinase and abciximab group (120 min vs. 200 min, p ϭ 0.001) (55). References 1 McLean J. The thromboplastic action of cephalin. Am J Physiol 1916; 41:250–257. 2 Johnson EA, Mulloy B. The molecular weight range of mucosal heparin preparations. Carbohydr Res 1976; 51:119–127. 3 Rosenberg RD, Lam L. Correlation between structure and function of heparin. Proc Natl Acad Sci USA 1979; 76:1218–1222. 4 Hirsh J, Warkentin TE, Shaughnessy SG, et al. Heparin and low-molecular-weight heparin: mechanisms of action, phar- macokinetics, dosing, monitoring, efficacy, and safety. Chest 2001; 119(1 suppl):64S–94S. 5 Weitz JI, Crowther M: Direct thrombin inhibitors. Thromb Res 2002; 106:V275–V284. 6 Hirsh j, Anand SS, Halperin JL, Fuster V. Guide to Anticoagulant therapy: heparin. Circulation 2001; 103:2994–3018. 7 Levine MN, Raskob G, Landefeld S, Kearon C. Hemorrhagic complications of anticoagulant treatment. Chest 2001; 119(1 suppl):108S–121S. 8 Wester JP, de Valk HW, Nieuwenhuis HK, et al. Risk factors for bleeding during treatment of acute venous thromboembolism. Thromb Haemost 1996; 76:682–688. 9 Gupta AK, Kovacs MJ, Sauder DN. Heparin-induced throm- bocytopenia. Ann Pharmacotherapy 1998; 32:55–59. 10 Weitz JI, Crowther M: Direct thrombin inhibitors. Thromb Res 2002; 106:V275–284. 11 Wiggins BS, Spinler S, Wittkowsky AK, Stringer KA. Bivalirudin. a direct thrombin inhibitor for percutaneous transluminal coronary angioplasty. Pharmacotherapy 2002; 22:1007–1018. 580 Anticoagulants in peripheral vascular interventions 1180 Chap49 3/14/07 5:00 PM Page 580 12 Bates SM, Weitz JI. Direct thrombin inhibitors for treatment of arterial thrombosis: Potential differences between bivalirudin and hirudin. Am J Cardiol 1998; 82:12–18. 13 Direct thrombin inhibitors in acute coronary syndromes: Principal results of a meta-analysis based on individual patients’ data. Lancet 2002; 359:294–302. 14 Bittl JA, Strony J, Brinker JA, et al. Treatment with bivalirudin (Hirulog) as compared with heparin during coronary angio- plasty for unstable or postinfarction angina. Hirulog Angioplasty Study Investigators. N Engl J Med 1995; 333:764–769. 15 Lincoff AM, Bittl JA, Harrington RA, et al. and for the REPLACE-2 Investigators. bivalirudin and provisional glycopro- tein IIb/IIIa blockade compared with heparin and planned glycoprotein IIb/IIIa blockade during percutaneous coronary intervention: REPLACE-2 randomized trial. JAMA 2003; 289:853–863. 16 Alle D, Hall P, Shammas N, et al. The Angiomax peripheral procedure registry of vascular events trial (APPROVE): In hospital and 30-day results. J Invas Cardiol 2004; 16:651–656. 17 Eres A. Use of bivalirudin as the foundation anticoagulant during percutaneous peripheral interventions. J Invas Cardiol 2006; 18:125–128. 18 Allie D, Lirtzman M, Watt DH, et al. Bivalirudin as a foundation anticoagulant in peripheral vascular disease: a safe and feasible alternative for renal and iliac interventions. J Invasive Cardiol 2003; 15:334–342. 19 Shammas N, Lemke J, Dippel E et al. Bivalirudin in peripheral vascular interventions: A single center experience. J Invas Cardiol 2003; 15:401–404. 20 Comerota AJ, Rao AK, Throm RC, et al. A prospective, randomized, blinded, and placebo-controlled trial of intraoper- ative intraarterial urokinase infusion during lower extremity revascularization: Regional and systemic effects. Ann Surg 1993; 218:534. 21 Varadi A, Patthy L. Location of plasminogen-binding sites in human fibrin(ogen). Biochemistry 1983; 22:2240–2246. 22 Ouriel K, Shortell C, DeWeese J, et al. A comparison of throm- bolytic therapy with operative revascularization in the initial treatment of acute peripheral arterial ischemia. J Vasc Surg 1994; 19:1021. 23 Ouriel K, Veith FJ, Sasahara AA, et al. Thrombolysis or periph- eral artery surgery: phase 1 results. J Vasc Surg 1996; 23:64–75. 24 Ouriel K, Veith FJ, Sasahara AA. A comparison of recombinant urokinase with vascular surgery as initial treatment for acute arterial occlusion of the legs. N Engl J Med 1998; 338:1105–1111. 25 Goldhaber SZ, Kessler CM, Heit J, et al. Randomized controlled trial of recombinant tissue plasminogen activator versus urokinase in the treatment of acute pulmonary embolism. Lancet 1988; 2:293–298. 26 The Stile Investigators. Results of a prospective randomized trial evaluating surgery versus thrombolysis for ischemia of the lower extremity. Ann Surg 1994; 220:251–268. 27 Ouriel K, Katzen B, Mewissen M, et al. Reteplase in the treat- ment of peripheral arterial and venous occlusions: a pilot study. J Vasc Interv Radiol 2000; 11(7):849–854. 28 Castaneda F, Swischuk JL, Li R, Young K, Smouse B, Brady T. Declining-dose study of reteplase treatment for lower extremity arterial occlusions. J Vasc Interv Radiol 2002; 13(11):1093–1098. References 581 29 Kiproff PM, Yammine K, Potts JM, et al. Reteplase infusion in the treatment of acute lower extremity occlusions. J Thromb Thrombolysis 13:75–79, 2002. 30 McCluskey ER, Refino CJ, Zioncheck TF, et al. Tenecteplase: Biochemistry, pharmacology, and clinical experience. In Sasahara AA, Loscalzo J (eds): New Therapeutic Agents in Thrombosis and Thrombolysis, 2nd ed. New York: Marcel Dekker, 2003:501–511. 31 Razavi MK, Wong H, Kee ST, Sze DY, Semba CP, Dake MD. Initial clinical results of tenecteplase (TNK) in catheter-directed thrombolytic therapy. J Endovasc Ther 2002; 9(5):593–598. 32 Burkart DJ, Borsa JJ, Anthony JP, Thurlo SR. Thrombolysis of occluded peripheral arteries and veins with tenecteplase: a pilot study. J Vasc Interv Radiol 2002; 13(11):1099–1102. 33 Dasgupta H, Blankenship JC, Wood GC, Frey CM, Demko SL, Menapace FJ. Thrombocytopenia complicating treatment with intravenous glycoprotein IIb/IIIa receptor inhibitors: a pooled analysis. Am Heart J 2000; 140(2):206–211. 34 Scarborough RM, Kleiman NS, Phillips DR. Platelet glycopro- tein IIb/IIIa antagonists. What are the relevant issues concerning their pharmacology and clinical use? Circulation 1999; 100(4):437–444. 35 Ansel GM, Silver MJ, Botti CF Jr, et al. Functional and clinical outcomes of nitinol stenting with and without abciximab for complex superficial femoral artery disease: a randomized trial. Catheter Cardiovasc Interv 2006; 67(2):288–297. 36 Dorffler-Melly J, Mahler F, Do DD, Triller J, Baumgartner I. Adjunctive abciximab improves patency and functional outcome in endovascular treatment of femoropopliteal occlu- sions: initial experience. Radiology 2005; 237(3):1103–1119. 37 Rocha-Singh KJ, Rutherford J. Glycoprotein IIb-IIIa receptor inhibition with eptifibatide in percutaneous intervention for symptomatic peripheral vascular disease: the circulate pilot trial. Catheter Cardiovasc Interv 2005; 66(4):470–473. 38 Shammas NW, Dippel EJ, Lemke JH, et al. Eptifibatide in peripheral vascular interventions: results of the Integrilin Reduces Inflammation in Peripheral Vascular Interventions (INFLAME) trial. J Invasive Cardiol 2006 18(1):6–12. 39 Merlini PA, Rossi M, Menozzi A, et al. Thrombocytopenia caused by abciximab or tirofiban and its association with clini- cal outcome in patients undergoing coronary stenting. Circulation 2004; 109(18):2203–2206. Epub 2004 Apr 26. 40 Allie DE, Hebert CJ, Lirtzman MD, et al. A safety and feasibility report of combined direct thrombin and GP IIb/IIIa inhibition with bivalirudin and tirofiban in peripheral vascular disease intervention: treating critical limb ischemia like acute coronary syndrome. J Invasive Cardiol 2005; 17(8):427–432. 41 Gold HK, Garabedian HD, Dinsmore RE, et al. Restoration of coronary flow in myocardial infarction by intravenous chimeric 7E3 antibody without exogenous plasminogen activators. Observations in animals and humans. Circulation 1997; 95(7):1755–1759. 42 Rerkpattanapipat P, Kotler MN, Yazdanfar S. Images in cardiovascular medicine. Rapid dissolution of massive intracoronary thrombosis with platelet glycoprotein IIb/IIIa receptor inhibitor. Circulation 1999; 99(22):2965. No abstract available. 43 Berkompas DC. Abciximab combined with angioplasty in a patient with renal artery stent subacute thrombosis. Cathet Cardiovasc Diagn 1998; 45(3):272–274. 1180 Chap49 3/14/07 5:00 PM Page 581 44 Tepe G, Duda SH, Erley CM, Schott U, Huppert PE, Claussen CD. [The adjuvant use of the monoclonal antibody c7E3 Fab in peripheral arterial thrombolysis] Rofo 1997; 166(3):254–257. German. 45 Schweizer J, Kirch W, Koch R, Muller A, Hellner G, Forkmann L. Short- and long-term results of abciximab versus aspirin in conjunction with thrombolysis for patients with peripheral occlusive arterial disease and arterial thrombosis. Angiology 2000; 51(11):913–923. 46 Duda SH, Tepe G, Luz O, et al. Peripheral artery occlusion: treatment with abciximab plus urokinase versus with urokinase alone—a randomized pilot trial (the PROMPT Study). Platelet receptor antibodies in order to manage peripheral artery thrombosis. radiology 2001; 221(3):689–696. 47 Duda SH, Tepe G, Luz O, et al. Peripheral artery occlusion: treatment with abciximab plus urokinase versus with urokinase alone–a randomized pilot trial (the PROMPT Study). platelet receptor antibodies in order to manage peripheral artery thrombosis. Radiology 2001; 221(3):689–696. 48 Yoon HC, Miller FJ Jr. Using a peptide inhibitor of the glyco- protein IIb/IIIa platelet receptor: initial experience in patients with acute peripheral arterial occlusions. AJR Am J Roentgenol 2002; 178(3):617–622. 49 Syed, MI, Shaikh, A. Combination thrombolysis/GPIIbIIIa inhibition in chronic peripheral thrombosis- A case report. New Deve- lopments in Vascular Disease. Vol 1, (4) Spring 2003: 12–17. 50 Drescher P, McGuckin J, Rilling WS, Crain MR. Catheter- directed thrombolytic therapy in peripheral artery occlusions: combining reteplase and abciximab. AJR Am J Roentgenol 2003; 180(5):1385–1391. 51 Ouriel K, Castaneda F, McNamara T, et al. Reteplase monotherapy and reteplase/abciximab combination therapy in peripheral arterial occlusive disease: results from the RELAX trial. J Vasc Interv Radiol 2004; 15(3):229–238. 52 Burkart DJ, Borsa JJ, Anthony JP, Thurlo SR. Thrombolysis of acute peripheral arterial and venous occlusions with tenecteplase and eptifibatide: a pilot study. 582 Anticoagulants in peripheral vascular interventions 1180 Chap49 3/14/07 5:00 PM Page 582 Introduction Fifteen years ago, the only option for patients with large abdominal aortic aneurysms (AAA) that required either elec- tive or emergent repair was an open surgical approach using a transperitoneal or retroperitoneal incision. Now with the advent of endovascular approaches to aortic diseases, many patients, especially those in the high-risk groups, have a mini- mally invasive option to permit repair of aortic aneurysms, dissections, pseudoaneurysms, and ruptures. The endovascular procedure is most frequently used to treat infrarenal AAAs that are a leading cause of death in the older population. As our population ages, we will encounter AAAs more frequently than ever before. An aneurysm is defined by a size greater than 5 cm or 2.5 times the normal diameter of the native artery. Most aneurysms begin below the renal arteries and end close to the iliac bifurcation. More complicated AAAs exist involving the suprarenal aorta and visceral vessels and extending into the iliac arteries. The preva- lence of AAAs is 3% to 10% for patients older than 50 years (1). They occur more frequently in men and reach a peak inci- dence close to the age of 80 years. AAA rupture is associated with an 80% to 90% mortality rate and therefore the focus of AAA treatment is on intervening before the aneurysm ruptures; elective repair has mortality rate of less than 5%. The first endovascular repair of an AAA in a human was performed by Parodi in 1991. He made an endograft by combining a prosthetic vascular graft with expandable Palmaz stents (2). Since this milestone, the field has undergone immense growth and has benefited from many technologic advances that have permitted a wider application of this treat- ment modality. The patient population that has benefited most has been the population at high risk for open surgical repair. These patients have severe comorbidities including and not limited to old age, renal, heart, and pulmonary diseases. Endovascular aneurysm repair (EVAR) of AAAs, results in a quick recovery, can be done under local anesthesia and has fewer systemic complications than open surgical repair. The goal of this chapter is to describe patient and aneurysm selection factors, the procedure and endografts, review clini- cal trials, outcomes and complications and address some of the controversial and challenging areas of EVAR with a view to the future. Patient selection factors Abdominal aortic aneurysms can present as an incidental asymp- tomatic finding on imaging or with symptoms, most prominently, back and abdominal pain. The asymptomatic aneurysms can be detected during routine physical examination but are more likely found during workup for other complaints or as part of a screen- ing program for patients who are at high risk for developing AAAs (positive family or personal history of aneurysms). Intervention is indicated for symptomatic aneurysms regardless of size, and asymptomatic aneurysms with a size greater than 5 cm in diam- eter or with an increase in size greater than 10% per year as these groups have the greatest chance of rupture. Controversy exists as to when to intervene in females with aneurysms less than 5 cm diameter. Given smaller native aorta in this group, the aneurysmal dilatation can be greater than 2.5 times the diameter of the native aorta and less than 5 cm in diameter. Given the smaller native aorta in this group, the aneurysmat dilatation can be greater than 2.5 times the diameter of the native aorta and less than 5 cm in diameter. This smaller size of aneurysm may put the patient at equivalent risk of rupture. There are patient selection factors for EVAR of AAAs that set this procedure apart from open repair. The durability of the open repair is well known and has been demonstrated in multiple clinical studies. EVAR on the other hand requires routine and frequent follow-up with ultrasound examination and or CT scans to evaluate the repair for the development of complications that require secondary interventions. The patient must be able to commit to this follow-up routine in order to be eligible for the procedure. In general, patients who are young with few comorbidites are still advised to undergo open surgical repair because of the demonstrated 50 Repair of AAAs Alexandra A. MacLean and Barry T. Katzen 1180 Chap50 3/14/07 11:49 AM Page 583 longevity of the repair and ease of follow-up. EVAR has become the procedure of choice for patients at high risk for open repair given an older age and other morbidities (3). Aneurysm assessment The aneurysm and aorta are assessed with a 3D reconstruc- tion CT scan or aortography with a calibrated catheter (Table 1, Fig. 1). The fitness of the femoral arteries is evalu- ated as the access route. They should be greater than 7 mm in diameter and free from extensive atherosclerotic or stenotic disease. The anatomy of the proximal neck is important; the length of aneurysm free aorta from the most caudal renal artery to the beginning of aneurysmal dilatation must be at least 15 mm to permit adequate seal of the device to a segment of normal aorta. In addition, the angulation of the neck is ideally less than 60°. The placement of an endovascular device is not possible when the neck is too large. The size limitation comes from the need to have device sizes that can be packaged into sheaths deliverable through the femoral artery. The shape of the neck is described as tapered, reverse tapered, or straight, with the latter being ideal. The distal landing zone is evaluated for the location of the hypogastric artery and presence of iliac aneurysms. Once again, an area adequate for seal of the device to the iliac artery is located, usually 20 mm in length. If a common iliac aneurysm precludes landing the device proximal to the takeoff of the hypogastric artery, then the patient’s circulation is evaluated for preoperative embolization of the hypogastric artery. This will permit the device to land distal to the hypogastric artery and backflow from this artery is eliminated by the embolization. The visceral vessels are evaluated for patency because the required coverage of the inferior mesenteric artery mandates that blood supply to the viscera be adequate from other sources (celiac and superior mesenteric arteries). With expe- rience, some of these contraindications can be overcome with suprarenal attachment devices, additional cuffs, and limbs, but for the nascent EVAR physician the contraindica- tions should be acknowledged and adherence to the fundamental principles of endovascular device implantation will permit good outcomes. EVAR technology Endograft design is derived directly from the traditional grafts used in open aortic surgery. The endograft body comes in one piece (unibody) or as a bifurcated graft (Fig. 2). The unibody endograft is designed to land into one of the iliac arteries, thereby necessitating contralateral iliac occlusion and a femoro-femoral bypass graft. Most of the procedures carried out today use a bifurcated graft that comes with extensions into the limbs and additional cuffs. This design provides greater flexibility for matching the device to the particular aneurysm features. The early endografts were unsupported throughout the body with stents at the proximal and distal ends. Today, the endografts have a metal skeleton throughout the graft providing a supported structure. The metal skeleton is covered with a fabric [polyester or polyte- trafluoroethylene (PTFE)]. To prevent slippage of the endograft, it is secured either by radial force or additional hooks and barbs. The majority of the endografts are designed to fixate and seal to a 15 mm segment of normal infrarenal native aorta. The device is deployed with either a self- expanding or balloon-expanding mechanism. 584 Repair of AAAs CT scan assessment for EVAR eligibility Proximal neck: diameter, length, angle, Presence or absence of thrombus Distal landing zone: diameter and length Iliac arteries: presence of aneurysms and occlusive disease Access arteries (common, external and femoral arteries): Diameter, presence of occlusive disease Contraindications for EVAR Short proximal neck Thrombus presence in proximal landing zone Conical proximal neck Greater than 120° angulation of the proximal neck Critical inferior mesenteric artery Significant iliac occlusive disease Tortuosity of iliac vessels Abbreviation : EVAR, endovascular aneurysm repair. Table 1 Assessment and contraindications Figure 1 ( Left ) Angiogram of infrarenal abdominal aortic aneurysms (AAA) with marker catheter in place; ( Right ) 3D CT reconstruction of an infrarenal AAA. 1180 Chap50 3/14/07 11:49 AM Page 584 The many permutations of these features have led to the generation of multiple devices employing a variety of concepts and approaches ( Table 2). Two devices are no longer available (Ancure and Vanguard/Stentor) but are mentioned because some patients had these implanted and these may be encoun- tered in the clinical setting. Four devices are currently FDA approved for commercial use in the United States (AneuRx, Excluder, Zenith, and PowerLink); the other devices are in clinical trials or in use in Europe. With multiple devices available and increased clinical and technical experiences, it is apparent that each device has its own advantages and disadvantages. The best results can come from optimizing the type of endograft to specific anatomy of a given patient. This is less important in patients with ‘ideal’ anatomic features, but when features such as neck angulation, calcification, access tortuosity are encountered, one device may to superior to another for dealing with the challenging anatomy. On some occasions supraprenal attachment may be necessary and desir- able, in others infrarenal fixation may be sufficient. The procedure: start to finish Once the patient is selected and the appropriate device is in hand to deal with the particular aneurysm morphology, the patient is brought into the interventional or operating room suite for the procedure. The procedure is now performed by interventional radiologists, cardiologists, and vascular surgeons with the patient under general, regional, or local anesthesia (4). The femoral arteries are accessed by either open surgical incisions or percutaneously. An aortogram is performed to locate the renal and hypogastric arteries. The main body is then inserted through either femoral arteriotomy but the largest and most disease free femoral artery is preferred. The patient is anticoagulated as at this point in the procedure blood flow to the legs is interrupted by the size of the sheath; heparin or a direct thrombin inhibitor (e.g., bivalirudin) may be used (5). The location of the renal arteries with respect to the top of the endograft is reassessed. The endograft is then deployed. Next the limbs are inserted through each groin into the respective leg of the endograft. Once again the location of the hypogastric arteries is verified before the limbs are landed just proximal to their orifices or distally if the hypogastric was embolized preoperatively. A completion angiogram is performed and examined for the development of complica- tions, especially Type I endoleaks. If further intervention is required, it is done at this point. Finally, the groins are closed either with sutures or with the aid of one of many percuta- neous closure devices. The distal pulses are examined and documented for further vascular monitoring. Endograft challenges Ruptured aneurysm A ruptured AAA is a devastating event with an overall mortality rate of greater than 90% and 40% to 70% of those patients who make it to the hospital alive die (1). An endovascular approach to ruptured aneurysms has been developed and involves the rapid deployment of a proximal occlusion balloon through the brachial artery to sit in the descending thoracic aorta. Some of the key maneuvers include permissive hypoten- sion, placement of the brachial wire under local anesthesia, performance of a diagnostic angiogram, and of course, readi- ness for conversion to an open procedure if necessary (6,7). The patients who undergo endovascular repair have to be stable enough to have a CT scan performed preoperatively. In one study, the thirty day mortality rate was 10.8% for this approach and the late conversion rate was 9% and was attrib- uted to mainly infection issues and device migration (8). Survival was 89.1% at one year and 69.9% at four years. This was compared with a thirty-day mortality rate of 35% for patients undergoing open repair of ruptures. Difficult neck The difficult neck comes in a variety of types: angulated, coni- cal, stenotic (Fig. 3). The angulated neck makes wire passage challenging, but this can be overcome with the use of flexible sheaths and if necessary brachial artery insertion of the initial wire for retrieval from the femoral artery. In addition, the angulation often straightens during endograft placement and Endograft challenges 585 Available or in trials/development AneuRx (Medtronic, Santa Rosa, CA, U.S.A.) Excluder (W.L. Gore, Flagstaff, AZ, U.S.A.) Zenith (Cook Inc., Bloomington, IN, U.S.A.) PowerLink (Endologix, Irvine, CA, U.S.A.) Talent (Medtronic, Santa Rosa, CA, U.S.A.) Fortron (Cordis Corp., Johnson and Johnson, Miami, FL, U.S.A.) Lifepath (Edwards Lifesciences, Irvine, CA, U.S.A.) Quantum (Cordis Corp., Johnson and Johnson, Miami, FL) Enovus (Trivascular, Santa Rosa, CA, U.S.A.) No longer available Ancure (Guidant Corp., Indianapolis, IN, U.S.A.) Vanguard/Stentor (Boston Scientific Corp., Natick, MA, U.S.A.) Table 2 Endo devices 1180 Chap50 3/14/07 11:49 AM Page 585 therefore the ability to judge the exact postprocedure location of the graft is difficult, especially with respect to the renal arteries. The conical neck can be viewed as a cone with an increas- ing diameter from the renals to the aneurysm sac. This neck is a challenge for endograft sizing and achievement of graft seal to nonaneurysmal aorta. The first issue is often dealt with by decreasing the amount of the usual graft oversizing from the normal 20% to 10% to 15%; this reduces stretching the narrower portion of the conical neck. Endografts that require balloon expansion, as opposed to radial force, may facilitate graft seal when dealing with the conical neck. The third type of challenging neck is the stenotic neck. Once again, the issue centers on the importance of sizing the graft correctly. If the graft is oversized for the stenotic portion, graft infolding may occur. On the other hand, if the graft is undersized, then the neck may seal but the remainder of the repair does not fit properly, leading to endoleak and possible graft migration. Difficult iliac arteries Access to the aorta is usually obtained through the femoral arteries, either by percutaneous methods or by surgical exposure. The presence of tortuous or atherosclerotic iliac arteries makes the insertion of wires and sheaths through the arteriotomy difficult and potentially risky (Fig. 3). CT scan imaging techniques often do not adequately show iliac artery anatomy. Even arteriography cannot reliably measure areas of stenosis. 3D CT scan reconstructions with the ability to insert a virtual sheath help tackle the challenge of preoperative imaging and measuring of iliac arteries. Sometimes it is necessary to access the brachial artery to pass the initial wire into the femoral artery (9) or access the iliac artery or aorta through a retroperitoneal incision with the addition of a conduit to facilitate endograft insertion (10). Small iliac arteries are encountered in 8% of the popula- tion and most are found in women (II). Some arteries can be dilated but not without risk of dissection and rupture. Therefore, a patient with an external iliac artery smaller than 7 mm should undergo either open repair or have the endo- graft inserted through the larger common iliac artery or aorta. Stenotic iliac arteries can also be dilated but with the same risks of dissection and rupture. Aneurysmal iliac disease is a challenging anatomical feature especially for adequate endo- graft distal landing and sealing and may require coverage of the hypogastric artery. EVAR complications One of the distinguishing differences between EVAR and open repair is the higher rate of graft related complications with EVAR (12). Some occur during or soon after the proce- dure whereas others are only noticed during the graft surveillance period (Table 3). Reporting standards have been established to permit comparison of complications (13). The analysis of the Lifeline Registry (2664 EVAR cases and 334 open surgical cases) showed that the thirty-day operative mortality rates for the two groups were similar at 1.7% for EVAR and 1.4% for open surgical. The freedom from rupture was also similar for the two groups at one year: 99.8% and 100% and there was no difference in AAA-related death rates (14). Greenhalgh in the report from the EVAR 1 trial noted that complication rate was 41% for EVAR patients and 9% for open surgical patients within four years of the procedure (15). The aneurysm-related death rate was 4% for EVAR patients and 7% for open surgical patients. The all-cause mortality rates were similar for the two groups (28%). 586 Repair of AAAs Figure 2 Abdominal aortic aneurysms bifurcated supported stent graft (Excluder, Gore). Figure 3 ( Left ) Angulated proximal aortic neck; ( Right ) tortuous iliac arteries. 1180 Chap50 3/14/07 11:49 AM Page 586 EVAR complications 587 Early Type I proximal and distal endoleaks Type IV endoleak Device related complications Inability to deploy stent Arterial complications Systemic complications Cardiac Cerebral Pulmonary Renal Access site and lower limb complications Bleeding, hematoma, false aneurysm Arterial thrombosis Death Conversion Rupture Late Endoleaks: I (a, b), II, III Aneurysm growth greater than or equal to 8 mm Late AAA-related death Death Conversion Rupture Classification of endoleaks Attachment site leaks Proximal end of endograft Distal end of endograft Iliac occluder (plug) Branch leaks (without attachment site connection Simple or to-and-fro (from only one patent branch) Complex or flow-through (with two or more patent branches) Graft defect Junctional leak or modular disconnect Fabric disruption (midgraft hole) Minor (Ͻ2 mm; e.g., suture holes) Major (Ն2 mm) Graft wall (fabric) porosity (Ͻ30 days after graft placement) Table 3 Complications Access complications Access problems occur with either the percutaneous approach or open surgical approach to the vessels for endo- graft insertion. The femoral artery may be injured and require immediate repair with a patch or replacement of a segment. In addition, distal thrombosis may occur from the blockage of the flow into the lower extremities by the sheath and inadequate anticoagulation. This highlights the importance of noting the preoperative pulse examination, so that the post- operative findings can be correctly interpreted. As with any groin procedure, lymph leaks, wound infections and hematomas can occur and vary from the benign that resolves to the serious that requires further intervention (re-exploration, evacuation, muscle flaps, etc.). Device problems Device design evolves to remedy problems associated with structural integrity. There have been reports of fabric erosion (16), hook fractures (17), and component separation (18). Surgical conversion Primary surgical conversion occurs within the first postopera- tive 30 days and secondary surgical conversion occurs any time after that. In an examination of the EUROSTAR (European Collaborators on Stent/graft Techniques for aortic Aneurysm Repair) registry, 2.6% of the 1871 patients required conversion and in 38 patients this occurred in the first postoperative month (primary conversion) (19). Eleven patients underwent open surgical repair during a mean follow-up period of eight months (secondary conversion) and rupture was the most frequent reason for this. Kong et al. examined secondary conversion for the 594 patients in the Excluder clinical trials and noted that 2.7% of the patients underwent late open conversion; no conversions occurred in the first year after the procedure. Freedom from conversion was 96.7% at forty-eight months postoperative. The major indication noted was the development of endotension in the absence of a demonstrable endoleak. Endoleaks Endoleaks are a major concern for those engaged in EVAR (Table 3, Fig. 4). This phenomenon describes the continua- tion of blood flow into the extragraft portion of the aneurysm (20). Endoleaks are related to the graft itself or other factors such as the presence of large patent lumbar arteries (21). The presence of an endoleak increases the chance of rupture. Diagnostic imaging plays an important role in the detection of endoleaks: intraprocedural angiograms, surveillance CT scans, or duplex ultrasounds. The management of endoleaks varies according to the type: type I and III endoleaks should be addressed expediently, and type IV endoleaks usually resolve. The treatment algorithm for 1180 Chap50 3/14/07 11:49 AM Page 587 type II endoleaks is not straightforward as these endoleaks may resolve on their own over time. If a type I endoleak is noted on the completion angiogram, a stent-graft cuff or extension is immediately placed to facilitate better seal. A similar treatment plan is undertaken if the type I endoleak is noted in the post- operative period. Type II endoleaks can be followed and intervention planned if the endoleak does not resolve; some physicians suggest a follow-up CT scan at six months and if the endoleak is present, then the patent artery is either embolized or surgically ligated. Other physicians will only treat type II endoleaks if it is accompanied with sac enlargement. Gelfand et al. examined the clinical significance of type II endoleaks by analyzing data from 10 EVAR trials (22). The authors found that approximately half of the endoleaks disappeared within 12 months. This paper delineated situations when type II endoleak intervention is warranted: AAA sac enlargement after six months, increased sac pressure (Ͼ20% of systolic BP), presence of leak greater than 12 months after procedure. Endograft limb occlusion This is an infrequently encountered problem, occurring in less than 5% of patients, but its morbidity is serious leading to extremity loss (23). Small limb diameter and graft extension to the external iliac artery, as opposed to the common iliac, is a risk factor for the development of limb occlusion. Fifty percent of the thromboses occurred within 30 days of the procedure and almost 70% required intervention: surgical (femorofemoral, axillary-femoral, axillary-bifemoral bypasses) and/or endoluminal techniques (rheolytic and pharmacologic thrombolysis). Graft kinks Stent-graft kinks are more often seen when unsupported endografts are used (24). This complication occurred in 3.7% of the patients in the EUROSTAR registry and was associated with type I and III endoleaks, graft stenosis, graft limb throm- bosis, graft migration, and conversion to open repair (25). In addition, women with angulated AAA necks were atmost risk for stent-graft kink. This problem is usually managed with stenting of the kink. Sac enlargement The AneuRx clinical trial was analyzed by Zarins to describe the phenomenon of aneurysm sac enlargement (26). Twelve percent of the patients experienced aneurysm sac enlarge- ment and these patients were older and usually had an endoleak. When patients with endoleaks were analyzed, 17% had sac enlargement whereas only 2% of patients with- out endoleaks had the same finding. Elevated pressure within the aneurysm sac, also known as endotension, has been reported as one mechanism that is responsible for sac enlargement (27). This finding is documented when the intra- aneurysm pressure is measured during follow-up angiography. Endotension can exist without an endoleak. Device migration The AneuRx trial has also been analyzed to determine the frequency of stent migration and identify risk factors (21,28). Ninety-four of 1119 patients had evidence of stent migration that occurred a mean of 30 months after EVAR. Low initial deployment, below the renals, and short proximal fixation length are the identifiable risk factors. In this study, 68% of the patients required no treatment whereas 23 patients had extender modules placed and seven patients underwent surgical conversion. Surgical conversion was examined in a single center study of 640 patients by Verzini (29). This group found that early conversion (within 30 days) was performed in nine patients and late conversion was carried out in 29. At 588 Repair of AAAs Figure 4 Type IA endoleak noted on completion angiogram. 1180 Chap50 3/14/07 11:49 AM Page 588 six years after EVAR the risk of undergoing a conversion was 9%. A study by Tonnessen et al. examined device migration at mid- and long-term timepoints with the AneuRx and Zentih endografts (30). The AneuRx device had a significantly higher incidence of migration than the Zenith device. At three and four years out from the procedure, the migration rate was 22% and 28%, respectively, for AneuRx and only 2.4% for Zenith. In addition, a greater proportion of the migrated AneuRx endografts had dilated necks compared with the nonmigrated AneuRx endografts. One of the conclusions was that devices with active fixation design (e.g., Zenith) may be protective against migration. Also, a significant proportion of patients with endograft migration required intervention and so this one again highlights the importance of long-term surveillance. Extremity and visceral ischemia Ischemia to the viscera and extremities can also occur and the signs can be subtle (decreased pulses, mild abdominal pain, buttock claudication) or alarmingly obvious (lower extremity mottling, severe abdominal pain, elevated creatinine phos- phokinase levels, or gastrointestinal bleeding) (31). Lower extremity ischemia can result from problems at the femoral access site (dissection, atheroembolization) or from issues with the endograft (limb occlusion, kinking). The former often requires surgical intervention whereas the latter can be managed by interventional techniques like placing additional stents. The endograft covers the inferior mesenteric artery and if the remainder of the visceral and hypogastric circulation is poor or compromised can lead to colonic ischemia. In addi- tion, spinal cord ischemia can manifest in paresis or paralyis due to the coverage of intercostals arteries; this complication is rare but serious. Surveillance The recommended surveillance routine is for a CT scan at 1, 6, and 12 months and annually thereafter. If an endoleak is detected, the frequency of the scans increases to every six months until resolution of the endoleak is detected. Investigators have compared duplex ultrasound with CT scan for surveillance and found that CT scan is superior for endoleak detection (32). Since endoleaks are an important complication with therapeutic implications, CT scans should be used rather than duplex examination for repair surveillance. MRI has been investigated as a useful way to follow these patients. It has advantages over CT scan surveillance because it does not put renal function at risk in this older population. It should especially be entertained in patients with preexisting renal insufficiency (33). Endograft surveillance methods now include the use of an implanted sensor to measure sac pressure to assess for the development of endotension (34,35). The advances in EVAR technology have been accom- panied by a greater understanding of the basic science of aneurysmal disease and cross-fertilization has occurred. For example, Curci has been studying the relationship between the secretion of matrix metalloproteinases (MMPs) and AAAs (36). He has measured increased levels in the aneurysmal rather than the normal arterial wall. This finding led physicians to develop a new method for endograft surveillance: the lack of a decrease in MMP-3 and MMP-9 levels should alert the physician to possibility of a failing endograft repair (37). Advances in the basic science of aneurysm disease are helping us better manage this disease. EVAR outcomes and trial results Examination of outcomes of endovascular AAA repair comes from mainly two sources: databases and clinical trials. Eurostar registry The EUROSTAR Registry was started in 1996 and has contin- ued to provide a substantial amount of data especially for outcome analyses. Data come from 135 vascular centers in Europe (38–40). Outcomes in patients greater than or equal to eighty years old have been analyzed and compared to those less than 80 years (41). The octogenarians more frequently had heart, kidney, and lung disease preoperatively and a greater propor- tion was deemed not fit for surgery compared with the younger group of patients. The thirty-day and in-house mortality rate for octogenarians was significantly higher than the younger group: 5% versus 2%. In addition, this group of patients had higher device-related and systemic complication rates. Finally, aneurysm related and all cause mortality rates were significantly higher for this older group of patients. Dream trial The Dream trial examined outcomes two years following open or endovascular repair of AAAs (42). The cumulative survival rates for the two groups were similar: 89.6% (open), 89.7% (endovascular). There was no significant difference in aneurysm related mortality. The study concluded that the early advantage of EVAR is no longer present after one year following intervention. EVAR outcomes and trial results 589 1180 Chap50 3/14/07 11:49 AM Page 589 [...]... being addressed with point -of- care systems Thus, major clinical breakthroughs are expected with the use of these inhibitors in the management of cerebrovascular and cardiovascular disorders The introduction of novel antiplatelet drugs has added a new dimension to the management of arterial thrombotis—in particular, thrombotic stroke The availability of specific antagonist of adenosine diphosphate (ADP)... results with the use of polyethylene glycol-coupled (PEG) hirudin for treatment of coronary syndromes In addition to the development of LMWHs, understanding the mechanisms of their antithrombotic actions and the relevance of their structural components has led to the development of synthetic analogs of heparin fragments One remarkable approach based on the elucidation of the structure of heparin has led... increments with B verification of absence of back-flow before any repeat injection (B) Hemodynamic documentation of the pre- and post-procedure pressure tracings in this case On the left side, the pressure scale is up to 400 mmHg and a gradient Ͼ60 mmHg is documented; the spike-and-dome configuration of the left ventricular pressure tracing is observed, as well as a steep upstroke of the arterial pressure... intravenous, weight-adjusted heparin is given to maintain an activated clotting time of 200 to 250 seconds 607 benefits from two-year follow-up studies (17,18) and more recently up to five-year follow-up (Table 2) (19) Patients with increased outflow gradients prior to discharge after initial success of septal ablation that improves at threemonth follow-up and that remains less than 50% at one-year follow... decreases the incidence of paradoxical embolism (47), but can also reduce the incidence of migraine in susceptible patients Fifty-five percent of patients with aura and 62% of those without aura experienced a reduction of 1180 Chap51 3/14/07 11:49 AM Page 601 References 4 5 6 Figure 10 PFX electrode 7 headache frequency after PFO closure (49) The MIST study (http://www.migraine-mist.org) found out that... 90% of treated patients (Tables 2 and 3) (10, 11) The immediate post-ablation gradient reduction is probably due to alcohol-mediated septal necrosis and stunning Progressive decrease in the gradient across the outflow on long-term follow-up is secondary to septal thinning and ventricular remodeling Long-term results Successful septal ablation leads to significant improvement in objective tests of exercise... medical therapy of patent foramen ovale and presumed paradoxical thromboemboli: a systematic review Ann Intern Med 2003; 139(9):753–760 Skowasch M, Hein R, Buescheck F, et al Non-Implant Closure of Patent Foramen Ovale: First-in-Man Results Am J Cardiol 2005; 96(suppl 7A) :101 H Schwerzmann M, Wiher S, Nedeltchev K, et al Percutaneous closure of patent foramen ovale reduces the frequency of migraine attacks... or growth factors This device is currently in clinical trials 6 The PFX Closure system (Fig 10) does not involve the implantation of a device The method of action involves the sealing of the flap valve of the foramen ovale to the atrial septum The distal end of the catheter consists of an electrode composed of a metallic wire framework and covered by an elastomeric vacuum housing A retractable outer... after endovascular and open surgical repair of abdominal aortic aneurysms J Vasc Surg 2004; 39(3):497–505 Chaikof EL, Blankensteijn JD, Harris PL, et al Reporting standards for endovascular aortic aneurysm repair J Vasc Surg 2002; 35(5) :104 8 106 0 Lifeline registry of endovascular aneurysm repair: long-term primary outcome measures J Vasc Surg 2005; 42(1):1 10 Greenhalgh RM, Brown LC, Kwong GP et al... Mid- and long-term device migration after endovascular abdominal aortic aneurysm repair: a comparison of AneuRx and Zenith endografts J Vasc Surg 2005; 42(3):392–400; discussion-1 Maldonado TS, Rockman CB, Riles E, et al Ischemic complications after endovascular abdominal aortic aneurysm repair J Vasc Surg 2004; 40(4):703–709; discussion 9 10 Raman KG, Missig-Carroll N, Richardson T, et al Color-flow . current era of thrombolysis about 0.2% of patients develop a VSD as a result of septal necrosis. Medical manage- ment of these patients is limited and carries a 30-day mortality of 94% compared. development of limb occlusion. Fifty percent of the thromboses occurred within 30 days of the procedure and almost 70% required intervention: surgical (femorofemoral, axillary-femoral, axillary-bifemoral. et al. Plasma levels of metalloproteinases-3 and -9 as markers of successful abdomi- nal aortic aneurysm exclusion after endovascular graft treatment. Circulation 2001; 104 (12 suppl 1):I288–1295. 38