Emile R. Mohler, MD, MSVM, FACC, FAHA is Director of Vascular Medicine for the University of Pennsylvania Health System, and Professor of Medicine for the Perelman School of Medicine at the University of Pennsylvania, Philadelphia Pennsylvania, USA Michael R. Jaff, DO, FACP, FACC, FAHA, MSVM is Professor of Medicine, Harvard Medical School and President of Newton-Wellesley Hospital in Newton, Massachusetts, USA.

• Contributors xiPreface xiii1 Epidemiology of Peripheral Artery Disease 1Wobo Bekwelem and Alan T. HirschDefinitions 1PADClinical Syndromes 2Prevalence and Incidence 3Asymptomatic PAD 8Claudication 10Atypical Leg Pain 12Critical Limb Ischemia 12Acute Limb Ischemia 13Risk Factors for Development of PAD 13Tobacco Use 14Diabetes Mellitus 15Dyslipidemia 15Hypertension 16Homocysteinemia 16C]Reactive Protein and Fibrinogen 17Obesity 17Other Risk Factors 18Awareness of PAD in the Community 20Progression, Natural History, and Outcomes of PAD 20Progression 20Natural History and Outcomes 22Summary 24References 262 Office Evaluation of Peripheral Artery Disease – History and Physical Examination Strategies 37Maen Nusair and Robert S. DieterIntroduction 37Identifying At-Risk Individuals 37Regional Symptom Analysis 38Neurologic Symptoms 38Thoracic Symptoms 40Abdominal Pain 41Extremity Pain 42Skin Manifestations 44Physical Examination 46General Appearance 46Head and Neck Examination 46Chest 48Abdominal Examination 48Lower Extremity Examination 49Palpating for Pulses 50Auscultation 52References 533 Vascular Laboratory Evaluation of Peripheral Artery Disease 57Thomas RookeIntroduction 57Anatomic 57Hemodynamic 57Functional 58Physiological Testing 58Background/History 58Physiological Invasive Testing 58Physiological Non]Invasive Testing 58Vascular Laboratory 59Doppler 59Motion Detection 59Waveform Analysis 60Plethysmography 60PVR Amplitude 61PVR Contour 62Ankle–Brachial Index (ABI) and Segmental Pressures 63Tissue Perfusion 65Transcutaneous Oximetry (TcPO2) 66Duplex Scanning 67Background/History 67Imaging (Anatomy) 67Doppler (Hemodynamic) 68Vascular Laboratory Accreditation 69References 694 Magnetic Resonance, Computed Tomographic, and Angiographic Imaging of Peripheral Artery Disease 73Thomas Le, Masahiro Horikawa and John A. KaufmanIntroduction 73Computed Tomography Angiography 73Basics 73Image Acquisition and Interpretation 74Protocol 74Advantages 76Pitfalls 76Calcification 76Artifacts 76Radiation Exposure 76Contrast]Induced Nephropathy 76Anaphylaxis 77Magnetic Resonance Angiography 77Basics 77Image Acquisition and Interpretation 77Protocol 77Non]Contrast]Enhanced MRA 77Contrast]Enhanced MRA (CE]MRA) 78Post]Processing and Interpretation 78Advantages 78Pitfalls 80Time 80Nephrogenic Systemic Fibrosis 80Bolus Timing 80Artifacts 80Other Pitfalls 80Conventional Angiography 81Basics 81Image Acquisition and Interpretation 81Pre]Procedure Patient Care 81Protocol 81Advantages 82Pitfalls 82Contrast]Induced Nephropathy and Anaphylaxis 82Artifacts 84Other Disadvantages 84Intravascular Ultrasonography 84Basics 84Advantages 85Pitfalls 85Results 85Aortoiliac 85CTA 85MRA 86Runoff 86CTA 86MRA 86Pedal 87CTA 87MRA 87Conclusion 87References 875 Non-atherosclerotic Peripheral Artery Disease 91Mitchell D. Weinberg and Ido WeinbergIntroduction – Presentation of Peripheral Artery Disease 91When Should Non-atherosclerotic Causes of PAD Be Suspected? 92Entities that Make up Non-atherosclerotic PAD 94Popliteal Artery Entrapment Syndrome 94External Iliac Artery Endofibrosis 98Fibromuscular Dysplasia 99Cystic Adventitial Disease 100Vasculitis 101Idiopathic Mid]aortic Syndrome 102Arterial Manifestations of Pseudoxanthoma Elasticum 102Chronic Exertional Compartment Syndrome 103Musculoskeletal Pathology 103Diagnostic Evaluation of Patients with Leg Pain with Exertion 104Treatment Considerations 105Conclusions 105References 1056 Medical Therapy of Peripheral Artery Disease 111Lee Joseph and Esther S. H. KimIntroduction 111Atherosclerotic Risk Factor Management 111Hypertension 112Diabetes Mellitus 113Hyperlipidemia 114Tobacco Cessation 114Antiplatelet Agents 116Management of Claudication 117Claudication Pharmacotherapy 118Cilostazol 118Exercise Therapy 118Claudication Management Strategies: A Comparison 119Lower Extremity Wound Care 120Summary 121References 1217 Endovascular Treatment of Peripheral Artery Disease 129Vikram Prasanna, Jay Giri and R. Kevin RogersIntroduction 129Clinical Background 129Intermittent Claudication 129Critical Limb Ischemia 131Limb Prognosis/Overall Survival 131Typical Anatomy in Patients with CLI 131Patency Issues 131Indications for Endovascular Therapy for CLI 131Background for Endovascular Therapy 132Anatomy 132Technical Background 136Preprocedural Imaging 136Access 138Anticoagulation 139Antiplatelet Management 141Radiation 143Chronic Total Occlusions 143Clinical Evidence for Peripheral Intervention 145Aorto]Iliac Interventions 145Angioplasty vs. Stent 146Polytetrafluoroethylene (PTFE)]Covered versus Bare Metal Balloon]Expandable Stents 147Femoropopliteal Interventions 147Angioplasty versus Stenting 149Drug]Eluting Stents in Femoropopliteal Arteries 149Drug]Coated Balloon (DCB) Therapy in Femoropopliteal Disease 150Covered Stents in Femoropopliteal Disease 151Atherectomy 152Specialty Balloons 153Tibioperoneal and Pedal Interventions 153Post-procedural Care 155Conclusion 155References 1568 Surgical Management of Peripheral Artery Disease 163Julia Glaser and Scott M. DamrauerWhen to Refer Patients with Claudication 163When to Refer Patients with CLI 164Revascularization Options and Results 166Iliac Revascularizations 166Femoropopliteal Disease 169Tibioperoneal Disease 171Complications of Revascularization 173Preoperative Evaluation and Management 175Conclusion 175References 176Index 179

Emile R. Mohler, MD, MSVM, FACC, FAHA is Director of Vascular Medicine for the University of Pennsylvania Health System, and Professor of Medicine for the Perelman School of Medicine at the University of Pennsylvania, Philadelphia Pennsylvania, USA Michael R. Jaff, DO, FACP, FACC, FAHA, MSVM is Professor of Medicine, Harvard Medical School and President of Newton-Wellesley Hospital in Newton, Massachusetts, USA.

• Contributors xiPreface xiii1 Epidemiology of Peripheral Artery Disease 1Wobo Bekwelem and Alan T. HirschDefinitions 1PADClinical Syndromes 2Prevalence and Incidence 3Asymptomatic PAD 8Claudication 10Atypical Leg Pain 12Critical Limb Ischemia 12Acute Limb Ischemia 13Risk Factors for Development of PAD 13Tobacco Use 14Diabetes Mellitus 15Dyslipidemia 15Hypertension 16Homocysteinemia 16C]Reactive Protein and Fibrinogen 17Obesity 17Other Risk Factors 18Awareness of PAD in the Community 20Progression, Natural History, and Outcomes of PAD 20Progression 20Natural History and Outcomes 22Summary 24References 262 Office Evaluation of Peripheral Artery Disease – History and Physical Examination Strategies 37Maen Nusair and Robert S. DieterIntroduction 37Identifying At-Risk Individuals 37Regional Symptom Analysis 38Neurologic Symptoms 38Thoracic Symptoms 40Abdominal Pain 41Extremity Pain 42Skin Manifestations 44Physical Examination 46General Appearance 46Head and Neck Examination 46Chest 48Abdominal Examination 48Lower Extremity Examination 49Palpating for Pulses 50Auscultation 52References 533 Vascular Laboratory Evaluation of Peripheral Artery Disease 57Thomas RookeIntroduction 57Anatomic 57Hemodynamic 57Functional 58Physiological Testing 58Background/History 58Physiological Invasive Testing 58Physiological Non]Invasive Testing 58Vascular Laboratory 59Doppler 59Motion Detection 59Waveform Analysis 60Plethysmography 60PVR Amplitude 61PVR Contour 62Ankle–Brachial Index (ABI) and Segmental Pressures 63Tissue Perfusion 65Transcutaneous Oximetry (TcPO2) 66Duplex Scanning 67Background/History 67Imaging (Anatomy) 67Doppler (Hemodynamic) 68Vascular Laboratory Accreditation 69References 694 Magnetic Resonance, Computed Tomographic, and Angiographic Imaging of Peripheral Artery Disease 73Thomas Le, Masahiro Horikawa and John A. KaufmanIntroduction 73Computed Tomography Angiography 73Basics 73Image Acquisition and Interpretation 74Protocol 74Advantages 76Pitfalls 76Calcification 76Artifacts 76Radiation Exposure 76Contrast]Induced Nephropathy 76Anaphylaxis 77Magnetic Resonance Angiography 77Basics 77Image Acquisition and Interpretation 77Protocol 77Non]Contrast]Enhanced MRA 77Contrast]Enhanced MRA (CE]MRA) 78Post]Processing and Interpretation 78Advantages 78Pitfalls 80Time 80Nephrogenic Systemic Fibrosis 80Bolus Timing 80Artifacts 80Other Pitfalls 80Conventional Angiography 81Basics 81Image Acquisition and Interpretation 81Pre]Procedure Patient Care 81Protocol 81Advantages 82Pitfalls 82Contrast]Induced Nephropathy and Anaphylaxis 82Artifacts 84Other Disadvantages 84Intravascular Ultrasonography 84Basics 84Advantages 85Pitfalls 85Results 85Aortoiliac 85CTA 85MRA 86Runoff 86CTA 86MRA 86Pedal 87CTA 87MRA 87Conclusion 87References 875 Non-atherosclerotic Peripheral Artery Disease 91Mitchell D. Weinberg and Ido WeinbergIntroduction – Presentation of Peripheral Artery Disease 91When Should Non-atherosclerotic Causes of PAD Be Suspected? 92Entities that Make up Non-atherosclerotic PAD 94Popliteal Artery Entrapment Syndrome 94External Iliac Artery Endofibrosis 98Fibromuscular Dysplasia 99Cystic Adventitial Disease 100Vasculitis 101Idiopathic Mid]aortic Syndrome 102Arterial Manifestations of Pseudoxanthoma Elasticum 102Chronic Exertional Compartment Syndrome 103Musculoskeletal Pathology 103Diagnostic Evaluation of Patients with Leg Pain with Exertion 104Treatment Considerations 105Conclusions 105References 1056 Medical Therapy of Peripheral Artery Disease 111Lee Joseph and Esther S. H. KimIntroduction 111Atherosclerotic Risk Factor Management 111Hypertension 112Diabetes Mellitus 113Hyperlipidemia 114Tobacco Cessation 114Antiplatelet Agents 116Management of Claudication 117Claudication Pharmacotherapy 118Cilostazol 118Exercise Therapy 118Claudication Management Strategies: A Comparison 119Lower Extremity Wound Care 120Summary 121References 1217 Endovascular Treatment of Peripheral Artery Disease 129Vikram Prasanna, Jay Giri and R. Kevin RogersIntroduction 129Clinical Background 129Intermittent Claudication 129Critical Limb Ischemia 131Limb Prognosis/Overall Survival 131Typical Anatomy in Patients with CLI 131Patency Issues 131Indications for Endovascular Therapy for CLI 131Background for Endovascular Therapy 132Anatomy 132Technical Background 136Preprocedural Imaging 136Access 138Anticoagulation 139Antiplatelet Management 141Radiation 143Chronic Total Occlusions 143Clinical Evidence for Peripheral Intervention 145Aorto]Iliac Interventions 145Angioplasty vs. Stent 146Polytetrafluoroethylene (PTFE)]Covered versus Bare Metal Balloon]Expandable Stents 147Femoropopliteal Interventions 147Angioplasty versus Stenting 149Drug]Eluting Stents in Femoropopliteal Arteries 149Drug]Coated Balloon (DCB) Therapy in Femoropopliteal Disease 150Covered Stents in Femoropopliteal Disease 151Atherectomy 152Specialty Balloons 153Tibioperoneal and Pedal Interventions 153Post-procedural Care 155Conclusion 155References 1568 Surgical Management of Peripheral Artery Disease 163Julia Glaser and Scott M. DamrauerWhen to Refer Patients with Claudication 163When to Refer Patients with CLI 164Revascularization Options and Results 166Iliac Revascularizations 166Femoropopliteal Disease 169Tibioperoneal Disease 171Complications of Revascularization 173Preoperative Evaluation and Management 175Conclusion 175References 176Index 179

Emile R. Mohler, MD, MSVM, FACC, FAHA is Director of Vascular Medicine for the University of Pennsylvania Health System, and Professor of Medicine for the Perelman School of Medicine at the University of Pennsylvania, Philadelphia Pennsylvania, USA Michael R. Jaff, DO, FACP, FACC, FAHA, MSVM is Professor of Medicine, Harvard Medical School and President of Newton-Wellesley Hospital in Newton, Massachusetts, USA.

• Contributors xiPreface xiii1 Epidemiology of Peripheral Artery Disease 1Wobo Bekwelem and Alan T. HirschDefinitions 1PADClinical Syndromes 2Prevalence and Incidence 3Asymptomatic PAD 8Claudication 10Atypical Leg Pain 12Critical Limb Ischemia 12Acute Limb Ischemia 13Risk Factors for Development of PAD 13Tobacco Use 14Diabetes Mellitus 15Dyslipidemia 15Hypertension 16Homocysteinemia 16C]Reactive Protein and Fibrinogen 17Obesity 17Other Risk Factors 18Awareness of PAD in the Community 20Progression, Natural History, and Outcomes of PAD 20Progression 20Natural History and Outcomes 22Summary 24References 262 Office Evaluation of Peripheral Artery Disease – History and Physical Examination Strategies 37Maen Nusair and Robert S. DieterIntroduction 37Identifying At-Risk Individuals 37Regional Symptom Analysis 38Neurologic Symptoms 38Thoracic Symptoms 40Abdominal Pain 41Extremity Pain 42Skin Manifestations 44Physical Examination 46General Appearance 46Head and Neck Examination 46Chest 48Abdominal Examination 48Lower Extremity Examination 49Palpating for Pulses 50Auscultation 52References 533 Vascular Laboratory Evaluation of Peripheral Artery Disease 57Thomas RookeIntroduction 57Anatomic 57Hemodynamic 57Functional 58Physiological Testing 58Background/History 58Physiological Invasive Testing 58Physiological Non]Invasive Testing 58Vascular Laboratory 59Doppler 59Motion Detection 59Waveform Analysis 60Plethysmography 60PVR Amplitude 61PVR Contour 62Ankle–Brachial Index (ABI) and Segmental Pressures 63Tissue Perfusion 65Transcutaneous Oximetry (TcPO2) 66Duplex Scanning 67Background/History 67Imaging (Anatomy) 67Doppler (Hemodynamic) 68Vascular Laboratory Accreditation 69References 694 Magnetic Resonance, Computed Tomographic, and Angiographic Imaging of Peripheral Artery Disease 73Thomas Le, Masahiro Horikawa and John A. KaufmanIntroduction 73Computed Tomography Angiography 73Basics 73Image Acquisition and Interpretation 74Protocol 74Advantages 76Pitfalls 76Calcification 76Artifacts 76Radiation Exposure 76Contrast]Induced Nephropathy 76Anaphylaxis 77Magnetic Resonance Angiography 77Basics 77Image Acquisition and Interpretation 77Protocol 77Non]Contrast]Enhanced MRA 77Contrast]Enhanced MRA (CE]MRA) 78Post]Processing and Interpretation 78Advantages 78Pitfalls 80Time 80Nephrogenic Systemic Fibrosis 80Bolus Timing 80Artifacts 80Other Pitfalls 80Conventional Angiography 81Basics 81Image Acquisition and Interpretation 81Pre]Procedure Patient Care 81Protocol 81Advantages 82Pitfalls 82Contrast]Induced Nephropathy and Anaphylaxis 82Artifacts 84Other Disadvantages 84Intravascular Ultrasonography 84Basics 84Advantages 85Pitfalls 85Results 85Aortoiliac 85CTA 85MRA 86Runoff 86CTA 86MRA 86Pedal 87CTA 87MRA 87Conclusion 87References 875 Non-atherosclerotic Peripheral Artery Disease 91Mitchell D. Weinberg and Ido WeinbergIntroduction – Presentation of Peripheral Artery Disease 91When Should Non-atherosclerotic Causes of PAD Be Suspected? 92Entities that Make up Non-atherosclerotic PAD 94Popliteal Artery Entrapment Syndrome 94External Iliac Artery Endofibrosis 98Fibromuscular Dysplasia 99Cystic Adventitial Disease 100Vasculitis 101Idiopathic Mid]aortic Syndrome 102Arterial Manifestations of Pseudoxanthoma Elasticum 102Chronic Exertional Compartment Syndrome 103Musculoskeletal Pathology 103Diagnostic Evaluation of Patients with Leg Pain with Exertion 104Treatment Considerations 105Conclusions 105References 1056 Medical Therapy of Peripheral Artery Disease 111Lee Joseph and Esther S. H. KimIntroduction 111Atherosclerotic Risk Factor Management 111Hypertension 112Diabetes Mellitus 113Hyperlipidemia 114Tobacco Cessation 114Antiplatelet Agents 116Management of Claudication 117Claudication Pharmacotherapy 118Cilostazol 118Exercise Therapy 118Claudication Management Strategies: A Comparison 119Lower Extremity Wound Care 120Summary 121References 1217 Endovascular Treatment of Peripheral Artery Disease 129Vikram Prasanna, Jay Giri and R. Kevin RogersIntroduction 129Clinical Background 129Intermittent Claudication 129Critical Limb Ischemia 131Limb Prognosis/Overall Survival 131Typical Anatomy in Patients with CLI 131Patency Issues 131Indications for Endovascular Therapy for CLI 131Background for Endovascular Therapy 132Anatomy 132Technical Background 136Preprocedural Imaging 136Access 138Anticoagulation 139Antiplatelet Management 141Radiation 143Chronic Total Occlusions 143Clinical Evidence for Peripheral Intervention 145Aorto]Iliac Interventions 145Angioplasty vs. Stent 146Polytetrafluoroethylene (PTFE)]Covered versus Bare Metal Balloon]Expandable Stents 147Femoropopliteal Interventions 147Angioplasty versus Stenting 149Drug]Eluting Stents in Femoropopliteal Arteries 149Drug]Coated Balloon (DCB) Therapy in Femoropopliteal Disease 150Covered Stents in Femoropopliteal Disease 151Atherectomy 152Specialty Balloons 153Tibioperoneal and Pedal Interventions 153Post-procedural Care 155Conclusion 155References 1568 Surgical Management of Peripheral Artery Disease 163Julia Glaser and Scott M. DamrauerWhen to Refer Patients with Claudication 163When to Refer Patients with CLI 164Revascularization Options and Results 166Iliac Revascularizations 166Femoropopliteal Disease 169Tibioperoneal Disease 171Complications of Revascularization 173Preoperative Evaluation and Management 175Conclusion 175References 176Index 179