Advanced Endovascular TherapyofAortic Disease€¦ · Michael E. DeBakey Department of Surgery, Baylor College of Medicine Houston, TX, USA Changyi Chen, MD, PhD Professor of Surgery

AdvancedEndovascularTherapy of AorticDiseaseEDITED BY

Alan B. Lumsden, MD, ChBProfessor of Surgery, Division of Vascular Surgery and Endovascular Therapy

Michael E. DeBakey Department of Surgery, Baylor College of Medicine

Houston, TX, USA

Peter H. Lin, MDChief of Vascular Surgery, Michael E. DeBakey Veterans Affairs Medical Center

Chief of Interventional Radiology, Michael E. DeBakey Veterans Affairs Medical Center

Associate Professor of Surgery, Division of Vascular Surgery and Endovascular Therapy


Houston, TX, USA

Changyi Chen, MD, PhDProfessor of Surgery & Molecular and Cellular Biology, Director, Molecular Surgeon Research Center

Vice Chairman, Surgical Research, Division of Vascular Surgery and Endovascular Therapy


Houston, TX, USA

Juan C. Parodi, MDProfessor of Surgery

Chief of Endovascular Surgery

Division of Vascular & Endovascular Surgery Department of Surgery

University of Miami Medical School

Miami, FL, USA

AdvancedEndovascularTherapy of AorticDisease

AdvancedEndovascularTherapy of AorticDiseaseEDITED BY

Alan B. Lumsden, MD, ChBProfessor of Surgery, Division of Vascular Surgery and Endovascular Therapy


Houston, TX, USA

Peter H. Lin, MDChief of Vascular Surgery, Michael E. DeBakey Veterans Affairs Medical Center

Chief of Interventional Radiology, Michael E. DeBakey Veterans Affairs Medical Center

Associate Professor of Surgery, Division of Vascular Surgery and Endovascular Therapy


Houston, TX, USA

Changyi Chen, MD, PhDProfessor of Surgery & Molecular and Cellular Biology, Director, Molecular Surgeon Research Center

Vice Chairman, Surgical Research, Division of Vascular Surgery and Endovascular Therapy


Houston, TX, USA

Juan C. Parodi, MDProfessor of Surgery

Chief of Endovascular Surgery

Division of Vascular & Endovascular Surgery Department of Surgery

University of Miami Medical School

Miami, FL, USA

C© 2007 by Blackwell Publishing

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1 2007

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Advanced endovascular therapy of aortic disease / edited by Alan B. Lumsden . . . [et al.].

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ISBN-13: 978-1-4051-5570-0 (alk. paper)

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1. Blood-vessels – Endoscopic surgery. 2. Aorta–Diseases. 3. Aorta–Surgery.

I. Lumsden, Alan B.

[DNLM: 1. Aortic Diseases – surgery. 2. Angiography. 3. Angioplasty. WG 410

A244 2007]

RD598.5.A384 2007

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Contents

Acknowledgments, vii

Contributors, ix

Preface, xiii

Part I Natural history and preoperativeplanning

1 Etiology and pathogenesis of aortic disease, 3Bo Risberg & Lars Lonn

2 Clinical consideration of aortic disease:atherosclerosis, aneurysm, dissection,and traumatic injury, 11Lars Lonn, & Bo Risberg

3 Thoracic aortic aneurysms: classification,incidence, etiology, natural history, andresults, 25Hazim J. Safi

4 Angiographic aortic anatomy and variants, 31Louis G. Martin

5 Patient selection for thoracic endografts:today and tomorrow, 41Mark A. Farber

6 Noninvasive aortic imaging modalities: CT,MRI, intravascular ultrasound (IVUS),and transesophagealechocardiography (TEE), 45Tae K. Song, & Rodney A. White

7 Preoperative imaging and device sizing inendovascular management of thoracic aorticaneurysms, 53Panagiotis Kougias, Hosam El Sayed, & Wei Zhou

8 Intramural hematoma and penetratingulcer, 61Michael D. Dake

9 Patient follow-up and evaluation ofabdominal and thoracic stent grafts, 65Jan D. Blankensteijn

Part II Thoracic aortic aneurysm

10 Endovascular therapy of thoracic aneurysms:Gore TAG trial results, 75Jae-Sung Cho, Shan-e-ali Haider, & MichelS. Makaroun

11 Medtronic TALENT and VALIANT devices:moving toward the next generation of thoracicaortic stent grafts, 85Ron Fairman

12 Early clinical experience with the Bolton Relaythoracic stent graft, 91Frank J. Criado

13 Clinical results of the EUROSTAR thoracicregistry, 95Peter Harris, Lina Leurs, Randolph Statius vanEps, & Jacob Buth

14 Management of aortic aneurysms anddissections with the Zenith TX2 stentgraft, 105W. Anthony Lee

Part III Aortic dissection and traumaticaortic injury

15 Aortic dissection: evaluation andmanagement—choosing the rightintervention, 117David M. Williams

16 Aortic dissection: role of fenestration andstents in the endograft era, 123David M. Williams

v

vi Contents

17 Blunt trauma to the thoracic aorta: currentchallenges, 127Kenneth L. Mattox, Cliff Whigham, Richard G.Fisher, & Matthew J. Wall, Jr.

18 Traumatic disruption of the aorta, 135Ross Milner, Karthik Kasirajan, &Elliot Chaikof

19 Should endovascular repair be considered thestandard treatment in traumatic thoracicaortic injury? 141Peter H. Lin, Tam T. Huynh, & Eric K. Peden

Part IV Techniques, new devices, andsurveillance

20 Site-specific aortic endografting: caseexamples and discussion—the ascendingaorta, 155Edward B. Diethrich

21 Improved endograft fixation—a role for aorticendostapling? 169Brian R. Hopkinson

22 Treating smaller aneurysms: is there arationale? 175Kenneth Ouriel

23 Management strategies, adjuncts, andtechnical tips to facilitate endovasculartreatment of ruptured abdominal aorticaneurysms, 181Frank J. Veith, Nicholas J. Gargiulo III, &Evan C. Lipsitz

24 Postoperative imaging surveillance andendoleak management after endovascularrepair of thoracic aortic aneurysms, 187S. William Stavropoulos, & JeffreyP. Carpenter

25 Percutaneous repair of abdominal aorticaneurysms with local anesthesia andconscious sedation, 193Zvonimir Krajcer, Neil E. Strickman,Ali Mortazavi, & Kathryn Dougherty

26 Endoleak management in the abdominalaorta, 199Jennifer L. Ash, Syed M. Hussain, & KimJ. Hodgson

27 Aneurysm sac pressure measurement with apressure sensor in endovascular aorticaneurysm repair, 209Lisandro Carnero & Ross Milner

Index, 217

Acknowledgments

We would like to thank all the faculty contributorsfor their tireless efforts in the preparation of thechapters. We are indebted to Yvette Whittier, ouradministrative coordinator, for her countless hoursof hard work in bringing this project together. Last,

but not least, we are grateful to our families, Cathy,Aaron, Amber, Donal, Sarah, Terry, Mark, Pete, andCynthia, for their patience and support in makingthis book a reality.

vii

Contributors

Jennifer L. Ash, MDDepartment of SurgeryUniversity of Illinois College of MedicinePeoria, ILUSA

Jan D. Blankensteijn, MDDepartment of Vascular SurgeryRadboud University Nijmegen Medical CentreNijmegenThe Netherlands

Jacob Buth, MDCatharina HospitalEindhovenThe Netherlands

Lisandro Carnero, MDDivision of Vascular SurgeryDepartment of SurgeryEmory University School of MedicineAtlanta, GAUSA

Jeffrey P. Carpenter, MDDepartment of SurgeryHospital of the University of PennsylvaniaPhiladelphia, PAUSA

Elliot Chaikof, MD, PhDDivision of Vascular SurgeryDepartment of SurgeryEmory University School of MedicineAtlanta, GAUSA

Jae-Sung Cho, MDDivision of Vascular SurgeryDepartment of SurgeryUniversity of Pittsburgh School of MedicinePittsburgh, PAUSA

Frank J. Criado, MDDivision of Vascular SurgeryDepartment of SurgeryUnion Memorial Hospital-MedStar HealthBaltimore, MDUSA

Michael D. Dake, MDProfessor of Radiology, Internal Medicine (PulmonaryDisease), Surgery;Chairman of the UVA Department of Radiology and theHarrison Medical Teaching Professor of RadiologyCharlottesville, VAUSA

Edward B. Diethrich, MDArizona Heart Institute and Arizona Heart HospitalPhoenix, AZUSA

Kathryn Dougherty, RNDepartment of CardiologySt. Luke’s Episcopal HospitalThe Texas Heart InstituteHouston, TXUSA

Hosam El Sayed, MDDivision of Vascular Surgery and Endovascular TherapyMichael E. DeBakey Department of SurgeryBaylor College of MedicineHouston, TXUSA

Ron Fairman, MDDivision of Vascular SurgeryDepartment of SurgeryUniversity of PennsylvaniaPhiladelphia, PAUSA

Mark A. Farber, MDDivision of Vascular SurgeryDepartment of SurgeryUniversity of North CarolinaChapel Hill, NCUSA

ix

x Contributors

Richard G. Fisher, MDDepartment of RadiologyBaylor College of MedicineHouston, TXUSA

Nicholas J. Gargiulo III, MDDivision of Vascular SurgeryDepartment of SurgeryMontefiore Medical CenterNew York, NYUSA

Shan-e-ali Haider, MDDivision of Vascular SurgeryDepartment of SurgeryUniversity of Pittsburgh School of MedicinePittsburgh, PAUSA

Peter Harris, MD, FRCSRegional Vascular UnitRoyal Liverpool University HospitalLiverpoolUK

Kim J. Hodgson, MDDivision of Vascular SurgeryDepartment of SurgerySouthern Illinois UniversitySpringfield, ILUSA

Brian R. Hopkinson, MDDivision of Vascular SurgeryDepartment of SurgeryUniversity of NottinghamQueen’s Medical CentreNottinghamUK

Syed M. Hussain, MDVascular and Endovascular SurgeryHeartCare MidwestAssistant Clinical Professor of SurgeryUniversity of Illinois College of Medicine at PeoriaPeoria, IL, USA

Tam T. Huynh, MDDivision of Vascular Surgery and Endovascular TherapyMichael E. DeBakey Department of SurgeryBaylor College of MedicineHouston, TXUSA

Karthik Kasirajan, MDDivision of Vascular SurgeryDepartment of SurgeryEmory University School of MedicineAtlanta, GAUSA

Panagiotis Kougias, MDDivision of Vascular Surgery and Endovascular TherapyMichael E. DeBakey Department of SurgeryBaylor College of MedicineHouston, TXUSA

Zvonimir Krajcer, MDDepartment of CardiologySt. Luke’s Episcopal HospitalThe Texas Heart InstituteHouston, TXUSA

W. Anthony Lee, MDDivision of Vascular Surgery and Endovascular TherapyUniversity of Florida College of MedicineGainesville, FLUSA

Lina Leurs, MDCatharina HospitalEindhovenThe Netherlands

Peter H. Lin, MDDivision of Vascular Surgery and Endovascular TherapyMichael E. DeBakey Department of SurgeryBaylor College of MedicineHouston, TXUSA

Evan C. Lipsitz, MDDivision of Vascular SurgeryDepartment of SurgeryMontefiore Medical CenterNew York, NYUSA

Lars Lonn, MD, PhDDepartments of RadiologySahlgrenska University HospitalGoteborg UniversityGoteborgSweden

Contributors xi

Michel S. Makaroun, MDDivision of Vascular SurgeryDepartment of SurgeryUniversity of Pittsburgh School of MedicinePittsburgh, PAUSA

Louis G. Martin, MDVascular and Interventional RadiologyDepartment of RadiologyEmory University School of MedicineAtlanta, GAUSA

Kenneth L. Mattox, MDMichael E. DeBakey Department of SurgeryBaylor College of MedicineHouston, TXUSA

Ross Milner, MDDivision of Vascular SurgeryDepartment of SurgeryEmory University School of MedicineAtlanta, GAUSA

Ali Mortazavi, MDDepartment of CardiologySt. Luke’s Episcopal HospitalThe Texas Heart InstituteHouston, TXUSA

Kenneth Ouriel, MDDivision of SurgeryThe Cleveland ClinicCleveland, OHUSA

Eric K. Peden, MDDivision of Vascular Surgery and Endovascular TherapyMichael E. DeBakey Department of SurgeryBaylor College of MedicineHouston, TXUSA

Bo Risberg, MD, PhDDepartments of SurgerySahlgrenska University HospitalGoteborg UniversityGoteborgSweden

Hazim J. Safi, MD, FACSDepartment of Cardiothoracic and Vascular SurgeryThe University of Texas Medical School at HoustonMemorial Hermann Heart and Vascular InstituteHouston, TXUSA

Tae K. Song, MDDivision of Vascular SurgeryDepartment of SurgeryHarbor-UCLA Medical CenterTorrance, CAUSA

Randolph Statius-van Eps, MDCatharina HospitalEindhovenThe Netherlands

S. William Stavropoulos, MDDepartments of RadiologyHospital of the University of PennsylvaniaPhiladelphia, PAUSA

Neil E. Strickman, MDDepartment of CardiologySt. Luke’s Episcopal HospitalThe Texas Heart InstituteHouston, TXUSA

Frank J. Veith, MDDepartment of Vascular SurgeryThe Cleveland ClinicCleveland, OHUSA

Matthew J. Wall, Jr., MDMichael E. DeBakey Department of SurgeryBaylor College of MedicineHouston, TXUSA

Cliff Whigham, DODepartment of RadiologyBaylor College of MedicineHouston, TXUSA

Rodney A. White, MDDivision of Vascular SurgeryDepartment of SurgeryHarbor-UCLA Medical CenterTorrance, CAUSA

xii Contributors

David M. Williams, MDDivision of Interventional RadiologyDepartment of RadiologyUniversity of MichiganAnn Arbor, MIUSA

Wei Zhou, MDDivision of Vascular Surgery and Endovascular TherapyMichael E. DeBakey Department of SurgeryBaylor College of MedicineHouston, TXUSA

Preface

Since the concept of using an endovascular stent-graft to repair an abdominal aortic aneurysm wasinitially described by Dr. Parodi and Dr. Palmaz,this treatment strategy has undergone a dramatictechnological evolution. This evolution is furtherfueled by the increased public acceptance of thisminimally-invasive therapy, miniaturization of en-dovascular stent-grafts, and availability of mul-tiple devices approved by the Food and DrugAdministration (FDA). Growing evidence clearlysupports the early treatment success of this treat-ment strategy, in terms of morbidity and mor-tality reduction, when compared to the conven-tional open repair in well-selected patient cohorts.Advances in this endovascular technology have alsobroadened the treatment armamentarium of tho-racic aortic pathologies. Since the FDA has approvedthe use of endovascular repair of descending tho-racic aneurysms, many researchers have found abeneficial role of using this technology in the treat-ment of other thoracic aortic pathologies, includingdissection and traumatic transection.

Treatment outcome of endovascular repair ofaortic diseases is highly dependent on the ap-propriate patient selection, physician’s experience,and post-procedural device surveillance. Dissemi-nating the clinical experiences from physician ex-perts in this field will undoubtedly educate other

endovascular interventionalists and potentially im-prove treatment outcome for all physicians whoperform endovascular aortic procedures. The basisof this book “Advanced Endovascular Therapy ofAortic Disease” represents the collection of clinicalexperiences from a group of well-known endovas-cular interventionalists who participated in the 2006Total Endovascular Aorta Symposium, sponsoredby the Division of Vascular Surgery and Endovas-cular Therapy of the Baylor College of Medicine. Atotal of 26 chapters are included which cover foursections, including natural history and preoperativeplanning, thoracic aortic aneurysm, aortic dissec-tion and traumatic aortic injury, and techniques,new devices, and surveillance.

It is our hope that the collection of these chaptersprovided by faculty experts in the field of endovas-cular aortic therapy as assembled in this symposiumwill help to enhance the practice of endovascularinterventionalists. It is our sincere privilege to putforth this compendium book as a token of theircontributions to the field of endovascular aortictherapy.

Alan B. Lumsden, MB, ChB

Peter H. Lin, MD

Changyi Chen, MD, PhD

Juan C. Parodi, MD

xiii

I PART I

Natural history andpreoperative planning

1 CHAPTER 1

Etiology and pathogenesisof aortic disease

Bo Risberg & Lars Lonn

The aorta can be affected by a variety of pathologicalconditions. Some of them have a clear genetic com-ponent and affect young patients or patients in theearly adolescence. Most pathology is however en-countered in the grown-up population and is causedby degenerative diseases. This chapter will focuson the following pathological conditions that affectthe aorta: atherosclerosis, aneurysms, dissections,Marfan’s syndrome, Ehlers–Danlos syndrome, andTakayasu’s disease.

Atherosclerosis

Atherosclerosis is a systemic and generalized dis-ease that is the main cause for premature death inthe adult population in the Western world. Severalvascular beds are affected simultaneously, the heart,brain, viscera, and extremities. The pathophysiol-ogy of atherosclerosis in large arteries, such as aorta,is not different from that in small vessels. The etiol-ogy of atherosclerosis is extremely complex. Despiteintense research there is still a long way to go beforewe have a good understanding of the disease that isreflected in new preventive and therapeutic strate-gies. The atherosclerotic process involves predomi-nantly the intimal and medial layers of the wall.

The response to injury hypothesis proposed byRoss has had a heavy input on atherosclerotic re-search [1, 2]. It has stimulated research on endothe-lial interaction with blood cells and signaling tosmooth muscle cells. An initial event is some sortof injury to the endothelium leading to permeabil-ity alterations allowing passage of large moleculessuch as lipids. The injury may not be mechanical.Low-density lipoproteins in hypercholesteroemicpatients can in itself cause endothelial injury.

The thromboresistance is lost with increased riskfor thrombosis. Platelets adhere to the site of injury.They release growth factors, e.g. PDGF (platelet-derived growth factor) which is a strong mitogen forsmooth muscle cell proliferation. This local stimu-lus leads to accumulation of smooth muscle cellswithin the intima and deposition of extracellularmatrix proteins. Furthermore, there is depositionof lipids and infiltration of lipid-loaded cells. A pro-liferative lesion has been formed.

Fatty streak and fibrous plaqueThe intimal layer with the endothelial cells is thefirst line of defense against atherosclerosis. The veryfirst event is the fatty streak which consists of lipidaccumulation in macrophages located in and be-neath the endothelium [3]. Depending on geneticsand life style, the fatty streak may either regress orprogress into atheroma. Progression of lipid accu-mulation leads to focal intimal thickenings. Forma-tion of fibrous plaques is usually not seen until inthe fourth decade. Fibrotic tissue and smooth mus-cle cells form a fibrous cap surrounding the lipidcore. There is a necrotic center of amorphous ma-terial, extracellular proteins, matrix fibers, lipid-containing cells, cholesterol crystals, and calciumsalts. The plaques are infiltrated with vasa vasorum.The lipid-rich core is extremely thrombogenic dueits high content of tissue factor. An intact fibrouscap prevents release of procoagulative activity.

The lesions can be characterized as soft or hard.The soft plaques are dominated by lipid depo-sition in the necrotic core. They are particularlyprone to rupture leading to thrombotic complica-tions. The hard sclerotic lesions are characterized by

3

4 PART I Natural history and preoperative planning

calcification. They cause stenosis and, depending onthe degree of flow impairment, ischemia.

Inflammation and plaqueThe involvement of inflammatory cells as well astheir activation has put forward the hypothesis ofinflammation as an initial event in atherosclerosis.The atheromatous plaque consists of a core of foamcells and lipids. The border regions, shoulders, of theplaque are made up of inflammatory cells such asT-cells, macrophages, and mast cells [4]. These cellsproduce cytokines as signs of activation [5]. Theplaques are predominantly located in areas of flowdisturbances such as branches. The macrophagesproduce PDGF as a mitogen, cytokines and growthfactors. Interleukin 1 (IL-1), tumor necrosis factorα

(TNF-α), transforming growth factor β (TGF-β),and several others factors are produced. Throughthese mediators, the macrophages can affect andregulate cellular organization in the plaque. Themacrophages may be antigen presenting cells toT-lymphocytes that participate in the inflammatoryprocess. Oxidized LDL is such an antigen that cantrigger the inflammation [6].

Role of the endotheliumThe integrity of the endothelium is essential inpreventing the initial developments of the plaque.Perturbation of the endothelium causes expressionof growth factors that stimulate proliferation ofsmooth muscle cells. Likewise adhesion moleculesare expressed on the endothelial surface causing cel-lular interactions. Platelets adhere to the endothe-lium through expression of their surface glycopro-teins Ib and IIb/IIIa. Specific adhesion moleculessuch as selectins are involved in leukocyte rollingon the surface followed by sticking and extravasa-tion of the cells. VCAM-1, vascular cell adhesionmolecule, adheres monocytes and lymphocytes andis upregulated by high cholesterol levels. Activatedadhering cells and cells in the vessel wall release in-flammatory mediators, e.g., cytokines. Proteolyticenzymes, metalloproteinases (MMPs), and their in-hibitors are activated and contribute to the devel-opment of the plaque by facilitating migration andproliferation of cells.

Recent research has demonstrated the impor-tance of a variety of immune cells in the atheroscle-rotic process. T-cells activated from antigens release

cytokines, which trigger activation of macrophagesand other vascular cells. The process is balanced byregulatory T-cells, which produce IL-10 and TGF-β,both anti-inflammatory mediators. Release of in-flammatory cytokines especially IL-6 will stimu-late production of CRP in the liver. An excellentand comprehensive review of inflammation andatherosclerosis was recently published [7].

Plaque ruptureThere is an overwhelming body of knowledge onthe role of plaque rupture to initiate thrombosis andischemia [8]. Most of the data stems from coronaryarteries but the process does not differ in other partsof the vascular system.

The lipid core of the plaque is highly thrombo-genic due to its content of tissue factor. When thelipid is sealed in its fibrous cap, it is harmless butwhen released it initiates an immediate and verystrong coagulation. Activated macrophages in theplaque express tissue factor, which further enhancesthe thrombotic state.

The shoulders of the plaque are at risk for rup-ture. Cytokine-mediated cell activation leads toproteolytic degradation of the matrix particularly inthe shoulder region. MMPs are key players in theseevents. Functional polymorphism in several MMPgenes is associated with atherosclerotic manifesta-tions and complications such as coronary thrombo-sis, myocardial infarction, stenosis, arterial stiffness,and blood pressure [9]. MMP genotyping can prob-ably be of importance in the clinical managementof cardiovascular patients in the future.

In small arteries such as the coronaries, plaquerupture can lead to thrombotic occlusion. In largerarteries including the aorta, this can occur aswell only if there is a pronounced stenosis. Moreoften plaque rupture will cause ulceration withthrombotic depositions and subsequent risk forembolization.

Degeneration of the plaqueDegeneration of the plaques can occur fromnecrotic changes in the plaque. Insufficient circu-lation through the vasa vasorum causes ischemia.Activated MMPs degrade the extracellular matrixthereby contributing to the plaque destabilization.The plaque degeneration can lead to ulceration or

CHAPTER 1 Etiology and pathogenesis of aortic disease 5

other complications such as thrombosis or em-bolization of thrombotic or atheromatous material.

Plaque and flowThe likelihood of developing atherosclerotic lesionsdiffers between arteries at various locations. Plaquesdevelop in relation to branches, twists, and bends.Typically they are found in the proximal, upstreampart of the orifice. One common feature is flow dis-turbances with turbulence, flow separation, and lowshear stress. Shear stress influences directly the en-dothelium, which leads to increased permeabilityand altered cellular functions such as expression ofnitric oxide and adhesion molecules. Plaques lo-calize predominantly in areas with low shear stresswhile areas of high shear stress are relatively sparedfrom atherosclerosis [10].

Formation of a stenotic plaque does not initiallyencroach on the luminal transverse area and vol-ume. There is a compensatory enlargement of theartery to accommodate the plaque without affect-ing flow. Usually the plaque is eccentric in the vesselleaving a rounded lumen but an oval vessel. This hasbeen demonstrated in different parts of the vasculartree. Large plaques may however encircle the wholecircumference and cause a stenosis [11].

Constriction and dilatation, mediated throughthe endothelium, are means of keeping wall shearstress constant [12].

Infection and atherosclerosisThe strong inflammatory components of the diseasehave put forward the intriguing question of an infec-tious etiology to atherosclerosis. Virus and bacteriahave been found in diseased vessel wall. Until now acausative role has not been established. Chlamydiapneumoniae is found in a large number of patientswith atherosclerosis. About 60% of these patientsare seropositive. No relations have been found be-tween symptoms, degree of atherosclerosis, and ex-tent of C. pneumoniae involvement [13]. Similarly,no correlation was found between plaque desta-bilization and herpes simplex or cytomegalovirusseroreactivity.

A few studies have been published on effects ofantibiotics against C. pneumoniae for prevention ofcoronary events and with negative results [14, 15].Chlamydia may not be the cause of atherosclerosisbut can speed up the development and progression

of the disease [16], perhaps by enhancing the in-flammatory reaction. Much of this basic researchwill of course have implications on the future ther-apeutic strategy.

Atherosclerosis in different partsof the aortaThe manifestations of atherosclerosis differ not onlyin different vascular regions such as carotid, coro-nary, and femoral arteries but also in various partsof the aorta.

The infrarenal abdominal aorta is a frequent siteof plaques with or without ulcerations. Ulceratedareas are covered by thrombotic material. Emboliza-tion from these areas can cause focal ischemia inthe lower extremities. Often there is a heavy calci-fication. The stenotic lesions can develop into totalocclusions. The atherosclerotic process causes me-dial degeneration with risk for dilatation while thethoracic aorta is relatively spared these severe man-ifestations.

These findings could be due to different architec-ture in the thoracic and the abdominal aorta. Thevascular nutrition differs in these two regions of theaorta. In the thoracic aorta, the main part of the ves-sel wall is supplied by vasa vasorum. The abdominalaorta lacks vasa vasorum and relies on diffusion ofoxygen and nutrients from the lumen. The likeli-hood of ischemia in this part of the aorta is thusgreater and this can contribute to the degenerationof the wall.

Risk factors for atherosclerosisSeveral risk factors for atherosclerosis have beenidentified. Most are associated with the metabolicsyndrome and they are all life-style associated. Themetabolic syndrome is already a widespread condi-tion affecting 10–25% of western populations andits prevalence is increasing. Adipositas, hyperten-sion, hyperlipidemia, and type-2 diabetes are dom-inating components of this syndrome. The attrac-tiveness of the metabolic syndrome as an entity liesin the assumption that the syndrome has greaterpower to predict morbidity and mortality than in-dividual components themselves.

Smoking initiates the atherosclerotic process atan earlier stage and accelerates its progression. Smo-king is probably the most important factor in thedevelopment of atherosclerosis. The mechanistic


details are still unknown but it is likely that oxygen-free radicals play a role. Cessation of smokingdecreases the risk for clinical manifestations ofatherosclerosis probably by arresting the progres-sion of the lesions.

The role of lipidsDisturbances in lipid metabolism have since longbeen associated with atherosclerosis. High choles-terol levels lead to accumulation of cholesterol estersin macrophages, which are turned into foam cells.High levels of LDL can change the endothelial bar-rier, particularly oxidized LDL can be noxious tothe endothelium. Modified LDL can via scavengerreceptors be taken up by macrophages leading toformation of foam cells.

The hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductas inhibitors (statins) are effective inLDL lowering. The enzyme is the rate-limiting stepin the cholesterol synthesis. Another action, proba-bly of equal importance, is its anti-inflammatory ef-fect. Through this mechanism, the very early eventsin atherogenesis can probably be prevented.

Another exciting approach to treat atherosclero-sis is by using recombinant Apo-AI Milano thatin animal experiments can cause regression ofatherosclerosis. It is a variant of apolipoprotein A-Iidentified in an Italian subpopulation characterizedby low HDL and low incidence of atherosclerosis.The drug was recently found to reduce the atheromavolume in coronary arteries in a controlled random-ized trial in humans [17].

Aneurysms

Aneurysms develop in the degenerated aorta.Atherosclerosis is the most common cause for de-generation of the wall. Genetic components havebeen identified in Marfan’s syndrome and Ehlers–Danlos disease. Even in the most common, degen-erative, form of aortic aneurysms there is a geneticcomponent. There is a clear familiar occurrencewith a risk of about 25% for first-degree probands[18].

Degradation of elastin has been associated withdilatation while rupture of the wall is related to col-lagen degradation [19]. MMP-9 (gelatinase B) thatdegrades elastin, collagen type IV, fibronectin, andother matrix proteins has been linked to aneurys-mal disease. High levels of MMP-9 and MMP-3

have been found in abdominal aortic aneurysmaltissue [20, 21]. Levels of MMP-9 are associated withaneurysmal size [22].

Of particular interest is the importance of mu-tations in the genes coding for MMPs. Single nu-cleotide polymorphism in the MMP-9 gene atlocation-1562 (1562 bases from the start of thegene) has been associated with atherosclerosis andintracranial aneurysms. The latter is however con-troversial [23]. This mutation has been linked toaortic aneurysms in one study [24] while this wasnot confirmed in another investigation [25]. Thelatter study furthermore indicated that genetic vari-ations in inhibitors of MMPs, TIMPs, were involvedin aneurysm formation. More research is clearlyneeded to establish details of the genetic interplayin aortic aneurysms.

The aneurysmal pathology is characterized bya chronic inflammation with destruction of theextracellular matrix, remodeling of the wall lay-ers, and reduction in number of smooth musclecells. The smooth muscle cells are essential for pro-duction of extracellular matrix proteins. Less sup-portive scaffold enhances the degradation. The bal-ance between MMPs and their inhibitors, TIMPs,is pivotal in the degradation of the wall. As theprocess progresses, dilatation occurs. This leads toflow disturbances, changes in wall tension with re-duced tensile strength, and finally rupture. Thera-peutic trials with doxycycline, a MMP inhibitor, areongoing and preliminary results are encouragingwith less progression of aneurysmal size in treatedpatients [26].

Dissections

Acute dissection can occur following degenerationwith weakening of the wall. The most common formis the atherosclerotic variety typically seen in hyper-tensive patients. Lipid deposition, intimal thicken-ing, fibrosis, and calcification are seen. The extracel-lular matrix is degraded with lysis of elastin, collagenbreakdown, and cellular apoptosis. Through the ac-tion of MMPs the intima and vessel wall becomefragile. The elastin synthesis may be inefficient.Macrophages, which express the elastin gene andproduce tropoelastin, may play an important roleby producing a defective elastin [27]. The histol-ogy is characterized by media necrosis, scarcity ofsmooth muscle cells, and loss of elastin [28].

CHAPTER 1 Etiology and pathogenesis of aortic disease 7

The polymerization of elastin is a very compli-cated process. Fibulin-5 is an extracellular proteinexpressed in the basement membrane in blood ves-sels. It is a key player in the synthesis of elastin.Patients with dissection in the thoracic aorta wererecently found to have reduced levels of fibulin-5[29]. This means that a low content of elastin inpatients with dissection could be due to reducedsynthesis, increased degradation or both.

Familial dissection in the ascending aorta (typeA) was recently linked to a genetic mutation involv-ing dysregulation TGF-β signaling. This suggeststhat TGF-β may have a critical role in this condi-tion [30].

Obstruction of the vasa vasorum can cause lo-cal ischemia in the wall. The burden of mechanicalstress in the hypertensive patient facilitates disrup-tion.

The intramural hematoma is regarded as a specialvariety of a localized dissection even if this concepthas been disputed recently [31]. The etiology maybe disruption of a medial vasa vasorum causing alocalized bleeding with hematoma. The intramu-ral hematomas are particularly hazardous since ap-proximately half of these patients go on to dissectionor rupture [32].

Localized ulcers can occur in all parts of the aorta.They develop from plaque rupture and constituteweak points in the wall where a dissection can start.

There has been an interesting discussion on sea-sonal variation and the influence of atmosphericconditions on thoracic dissections. There seems tobe a peak in wintertime [33, 34]. Atmospheric pres-sure and temperature seemed to be unrelated toaortic dissection in another recent study [35].

Marfan’s syndrome

Marfan’s syndrome is an autosomal dominant traitwith main manifestations from the connective tis-sue with degeneration of the elastic fibers. The in-cidence is about 1/5000 inhabitants. Typically themain abnormalities are found in the cardiovascu-lar, skeletal, and ocular systems.

Apart from mitral valve prolapse, dilatation of theaorta is typical for the cardiovascular involvement.The aortic dilatation is progressive and starts withenlargement of the sinuses of Valsalva. All parts ofthe aorta can be affected as the disease progressesdistally. The most serious complications are dis-

section of the aorta or aneurysm formation withrupture. The patients are typically long and slen-der with arachnodactily (long fingers). They havepectus excavatus, flat feet, and scoliosis. The ocularabnormalities are mainly lens luxation and myopia.

The aortic wall is thin with fragmentation of theelastic fibers in the medial layer. There is also defec-tive synthesis and crosslinking of elastin. Collagenmetabolism is affected as well with signs of increasedcollagen turnover (elevated hydroxyproline secre-tion in the urine and low proline/hydroxyprolineratio) [36].

The genetic defect responsible for Marfan’s syn-drome has been localized to the fibrillin gene(FBN1) on chromosome 15. Fibrillin is a glycopro-tein about 350 kD. A large number of mutations(>500) in the gene are found in Marfan patients. Inthe connective tissue there is a reduced fibrillin-1deposition. This leads to defect fibrillin aggregationand crosslinking of elastin. Extracellular microfib-rils are mainly made up of fibrillin. The defective mi-crofibrils impair anchoring and structural mainte-nance in various tissues. The elastin formed is moreeasily degraded by MMPs. The weakness in the wallleads to aneurysmal dilatation and/or dissection.

Ehlers–Danlos syndrome

The Ehlers–Danlos syndrome is a genetically deter-mined disease of the connective tissue. The main ab-normalities are found in the described skin, joints,and arteries. Of all the 11 types of Ehlers–Danlossyndrome described, number IV is of particular in-terest from a cardiovascular point of view. This formis an autosomal dominant or recessive trait. The ar-terial manifestations make type IV particularly seri-ous. The major cutaneous symptom is echymoses.Collagen type III synthesis is reduced in the arterialsystem. This renders the vessels thin and fragile. Es-pecially the medial layer is thin with fragmentationof the internal elastic membrane.

Takayasu’s disease

Takayasu described this disease in 1908 [37]. It ischaracterized by a chronic inflammation that ispredominantly localized to the arch. Synonymousnames are “pulseless disease” or “aortic archsyndrome,” names that are quite descriptive of thenature of the disease. However, the disease is not


limited to the aortic arch but is found in most otherlarge vessels. Women are much more frequentlyaffected than men with a ratio of 4:1. The diseasealways starts before 40 years of age with a meanonset around 30. The incidence is 2–3 per millioninhabitants in the USA.

Macroscopic findingsStenotic processes that can involve all parts of theaorta and its main branches characterize the dis-ease. The walls are thickened with perivascular scle-rosis. The external diameter of the vessel is notaffected. The stenotic process intrudes into the lu-men and reduces the luminal surface area. In ad-vanced cases, there may be complete occlusion. Typ-ically there is a poststenotic dilation in Takayasu’sdisease. Aortic aneurysms or dissection are not fea-tures of the disease. The supra-aortic branches areinvolved in 50% of the cases. The clinical symptomsdepend on the extent and location of the lesions.

The typical lesions are usually seen in the archand its branches but changes can occur in all otherbranches such as the visceral and the iliac vessels.

Microscopic findingsThe most characteristic finding is that of a chronicinflammation. The most pronounced changesare seen in the adventitial and medial layers. Theadventitia is site for a sclerotic collagenous densetissue and with thickening of the vasa vasora.The media show breakage of the elastic fibers andwith signs of neovascularization. The vessel wall isinfiltrated with inflammatory cells, lymphocytes,histiocytes, and sometimes giant cells. The intimais grossly thickened with a loose connective tissue.The intimal changes are secondary to the patholog-ical processes in the outer layers. Sometimes frankdeposition of atherosclerotic material can be seen inthe stenotic lesions. The histopathological changescan be related to the clinical stage. In the activephase, the findings of granulomas and infiltrationwith inflammatory cells are common. Later duringthe occlusive stage, the chronic inflammation withscarring is predominant.

The granulomatous appearance in the chronicstage has initiated speculations on tuberculosis be-ing of etiological importance. Antigens from mu-cobacteria can cause granuloma. In recent clini-cal surveys, tuberculosis was found in 20% of the

patients [38] and tuberculin test was positive in 47%[39]. The inflammatory component of the disease isfurther stressed by a correlation between IL-8 levelsin plasma and degree of disease activity [40].

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Advanced Endovascular TherapyofAortic Disease€¦ · Michael E. DeBakey Department of Surgery, Baylor College of Medicine Houston, TX, USA Changyi Chen, MD, PhD Professor of Surgery