 \200 Table 3.4 Differential diagnosis of common foot and leg ulcers Origin Cause Location Pain Appearance Toes, foot Severe Irregular, pink base Main arteries Atherosclerotic lower extremity PAD, Buerger \200\231s disease, acute arterial occlusion Venous Venous disease Malleolar Mild Irregular, pink base Skin infarct Systemic disease, embolism, hypertension Lower third of leg Severe Small after infarction, often multiple Neurotrophic Neuropathy Foot sole None Often deep, infected Adapted from 1) the ACC/AHA Practice Guidelines. Hirsch et al. (2006). Circulation 113:e463 \200\223e465, and 2) Differential Diagnosis of Critical Limb Ischemia. J Vasc Surg 2000; 3 1(1) Supplement 1:S184 \200\223S188. TESTING FOR PERIPHERAL ARTERY DISEASE 141 Testing for peripheral artery disease Ankle \200\223brachial index (ABI) The ABI provides a measure of PAD and is simple and inexpensive to perform (see Fig. 3.2). Calculation is by measuring the systolic blood pres- sure (by Doppler probe) in the brachial, posterior tibia l, and dorsalis pedis arteries. The higher ankle measurement is divided by the higher brach ial measurement. 146 144 142 122 138 100 140 80 1.00 ABI 0.56 Figure 3.2 Ankle \200\223brachial indices (ABI). CHAPTER 3 Peripheral vascular disease 142 ABI 1.0 \200\2231.3 is the normal value. Values >1.3 suggest a noncompressible calci \201 ed vessel. ABI below 0.9 is associated with a >50% stenosis in one or more major vessels an d has a 95% sensitivity for detecting angiogram-positive PAD. ABI 0.4 \200\2230.9 suggests arterial obstruction often associated with claudication. ABI <0.4 represents advanced ische mia. ABIs typically correlate with the clinical measures of lower extremity func- tion such as w alking distances, balance, and overall physical activity. Lower ABIs correlate with a highe r risk of coronary artery disease (CAD), stroke, progressive renal insuf \201 cency, and a ll-cause mortality. Treadmill exercise testing Exercise decreases vascular resistance and enhances blood \202 ow to exer- cising extremities. According to Poiseuille \200\231s law, the pressure gradie nt across the stenosis increases in direct proportion to \202 ow. Exercise in lesions with <70% stenosis may induce a systolic pressure gradient across the s tenosis or increase the systolic pressure gradient. This change can be detected by serial p ost-exercise ABIs at 1-minute intervals for 5 minutes after exercise. This is particularly useful in patients who have normal resting ABIs and typical symptoms of claudication. In addition, treadmill testing allows for an objective measure of the patient \200\231s walking capacity. Duplex ultrasound imaging Ultrasound examination of the lower extremity includes localizati on of stenosis with color Doppler, B-mode imaging, pulse-wave Doppler, and continuous-wave Doppler. Examinations begin with the common femoral artery and proceed dis- tally to the popliteal a rtery. A twofold or greater increase in peak systo- lic velocity at the site of an atherosc lerotic plaque indicates a 50% or greater stenosis. Similarly, a threefold increase in velo city indicates a 75% or greater stenosis. In an occluded artery there is no Doppler signal. When using contrast angiography as a gold standard, duplex ultrasound imaging has a sensitivity of 80% \200\22390% and speci \201 city of 95%. See Figure 3.3. Magnetic resonance angiography Magnetic resonance angiography (MRA) can be used to noninvas ively image the aorta and vascular territories. The resolution of MRA with gado- linium app roaches that of contrast digital subtraction angiography. In patients at risk for complications from conventional angiography, MRA provides an accura te noninvasive tool prior to planning endovascular or surgical intervention. TESTING FOR PERIPHERAL ARTERY DISEASE 143 Normal Progressive disease Early disease Severe disease Figure 3.3 Ultrasonography in peripheral arterial disease. Schematic representation of peri pheral arterial waveforms in duplex Doppler ultrasonography in peripheral vascular disease. The normal peripheral arterial velocity waveform is triphasic and consists of a forward \202 ow systolic peak, reversal of \202 ow in early diastole, and forward \202 ow in la te diastole (top left). With progressive peripheral vascular disease, there is elimination of the reverse \202 ow (top right), a decrease in systolic peak and an increase in \202 ow in diastole (bottom right). Reproduced with permission from Mohler III, ER (2009). Noni nvasive diagnosis of peripheral arterial disease. In Basow DS (Ed.), UpToDate, Waltham, MA. Copyright 2009 UpToDate, Inc. For more information visit www.uptodate.com. Computed tomographic angiography (CTA) Multidetector CT scanners allow for rapid acquisitio n of high-resolution images. The addition of IV contrast allows visualization of the aorta and peripheral arteries. Multidetector technology has improved the spatial resolution of images over a relatively sh ort period of time. In addition, evolving software appli- cations enable three-dimensional display and post-processing techniques that can aid in visualization of stenoses. Contrast angiography This remains the gold standard in evaluation of peripheral vascular di sease. Digital subtraction techniques following contrast administration are typi- cally use d to enhance resolution. While the femoral approach is most common, brachial, axillary, or translumbar approaches can be used to attain aortic access. Summaries of diagnosis of PAD, asymptomatic PAD and leg pain, and clau- dication are given in Figures 3.4, 3.5, and 3.6. CHAPTER 3 Peripheral vascular disease 144 Individuals at Risk for Lower Extremity PAD: Age less than 50 years with diabetes and one other atherosclerosis risk factor (smoking, dy slipidemia, hypertension, or hyperhomocysteinemia) Age 50 to 69 years and history of smokin g or diabetes Age 70 years and older Leg symptoms with exertion (suggestive of claudication ) or ischemic rest pain Abnormal lower extremity pulse examination Know atherosclerotic cor onary, carotid, or renal arterial disease Obtain history of walking impairment and/or limb ischemic symptoms: Obtain a vascular revie w of symptoms: \200 Leg discomfort with exertion \200 Leg pain at rest; nonhealing woun d; gangrene Classic claudication symptoms: Exertional fatigue, discomfort, or frank pain localized to l eg muscle groups that consistently resolves with rest No leg pain \200\234Atypical \200\235 leg pain* Ischemic leg pain at rest \200 Nonhealing wound \200 Gangrene Sudden onset ischemic leg symptoms or signs of acute limb ischemia: The five \200\234Ps \200\235 \200 Perform a resting ankle \200\223brachial index measurement See Figure 3.5, Diagnosis and Treatment of Asymptomatic PAD and Atypical Leg Pain See Figure 3.9 and 3.10, Diagnosis and Treatment of Acute Limp Ischemia See Figures 3.6 and 3.7, Diagnosis and Treatment of Claudication See Figure 3.8, Diagnosis and Treatment of Critical Limp Ischemia See Figure 3.5, Diagnosis and Treatment of Asymptomatic PAD and Atypical Leg Pain Figure 3.4 Steps toward the diagnosis of peripheral arterial disease (PAD). * \200\234Atypi cal \200\235 leg pain is de \201 ned by lower extremity discomfort that is exertional but that does not consistently resolve with rest, consistently limit exercise at a reproducible distance, or meet all \200\234Rose questionnaire \200\235 criteria. \200 The \201 ve \200\234Ps \200\235 are de \201 ned by the clinical symptoms and signs that suggest potent ial limb jeopardy: pain, pulselessness, pallor, parasthesias, and paralysis (with polar bei ng a sixth \200\234P \200\235). Reprinted with permission from the ACC/AHA Practice Guidel ines. Hirsch et al. (2006). Circulation 113:e463 \200\223e465. TESTING FOR PERIPHERAL ARTERY DISEASE 145 Individual at risk of PAD (no leg symptoms or atypical leg symptoms): Consider use of the W alking Impairment Questionnaire Perform a resting ankle \200\223brachial index measurement (see Figure 3.1) ABI less than or equal to 0.90 (abnormal) ABI 0.91 to 1.30 (borderline & normal) ABI greater than 1.30 (abnormal) Measure ankle \200\223brachial index after exercise test Pulse volume recording Toe-brachial index (Duplex ultrasonography*) Normal post-exercise ankle \200\223brachial index: No peripheral arterial disease Decreased post- exercise ankle \200\223 brachial index Normal results: Not peripheral arterial disease Abnormal results Evaluate other causes of leg symptoms \200 Confirmation of PAD diagnosis Risk factor normalization: Immediate smoking cessation Treat hypertension: JNC-7 guidelines Treat lipids: NCEP ATP III guidelines Treat diabetes mellitus: HbAlc less than 7% \200 Pharmacological Risk Reduction: Antiplatelet therapy (ACE inhibition;# Class IIb, LOE C) Figure 3.5 Diagnosis and treatment of asymptomatic peripheral arterial disease (PAD) and at ypical leg pain. *Duplex ultrasonography should generally be reserved for use in symptomati c patients in whom anatomic diagnostic data are required for care. \200 Other causes of l eg pain may include lumbar disk disease, sciatica, radiculopathy, muscle strain, neuropathy , and compartment syndrome. \200 It is not yet proven that treatment of diabetes mellitus will signi \201 cantly reduce PAD-speci \201 c (limb ischemic) end points. Primary treat ment of diabetes mellitus should be continued according to established guidelines. # The be ne \201 t of angiotensin-converting enzyme (ACE) inhibition in individuals without claudic ation has not been speci \201 cally documented in prospective clinical trials but has been extrapolated from other at-risk populations. ABI, ankle \200\223brachial index; HbA1C, hem oglobin A1C; JNC-7, Seventh Report of the Joint National Committee on Prevention, Detection , Evaluation, and Treatment of High Blood Pressure; LOE, level of evidence; NCEP ATP III, N ational Cholesterol Education Program Adult Treatment Panel III. Adapted from 1) Hiatt WR ( 2001). N Engl J Med 344:1608 \200\2231621 and 2) ACC/AHA Practice Guidelines. Hirsch et al. (2006). Circulation 113:e463 \200\223e465. CHAPTER 3 Peripheral vascular disease 146 Classic Claudication Symptoms: Muscle fatigue, cramping, or pain that reproducibly begins d uring exercise and that promptly resolves with rest Chart document the history of walking impairment (pain-free and total walking distance) and specific lifestyle limitations Document pulse examination Exercise ABI (TBI, segmental pressure, or duplex ultrasound examination) ABI ABI greater than 0.90 AbI less than or equal to 0.90 Normal results Abnormal results Confirmed PAD diagnosis No PAD or consider arterial entrapment syndromes Risk factor normalization: Immediate smoking cessation Treat hypertension: JNC-7 guidelines Treat lipids: NCEP ATP III guidelines Treat diabetes mellitus: HBAlc less than 7%* Pharmacological risk reduction: Antiplatelet therapy (ACE inhibition; \200 ClassIIa) Go to Figure 3.7, Treatment of Claudication Figure 3.6 Diagnosis of claudication and systemic risk treatment. * It is not yet proven th at treatment of diabetes mellitus will signi \201 cantly reduce peripheral arterial diseas e (PAD)-speci \201 c (limb ischemic) end points. Primary treatment of diabetes mellitus sh ould be continued according to established guidelines. \200 The bene \201 t of angiotens in-converting enzyme (ACE) inhibition in individuals without claudication has not been spec i \201 cally documented in prospective clinical trials but has been extrapolated from othe r \200\234at-risk \200\235 populations. ABI, ankle \200\223brachial index; HbA1C, hemoglob in A1C; JNC-7, Seventh Report of the Joint National Committee on the Prevention, Detection, Evaluation, and Treatment of High Blood Pressure; LOE, level of evidence; NCEP ATP III, Na tional Cholesterol Education Program Adult Treatment Panel III. Reprinted with permission f rom the ACC/AHA Practice Guidelines. Hirsch et al. (2006). Circulation 113:e463 \200\223e46 5. PROGNOSIS IN PERIPHERAL ARTERY DISEASE 147 Prognosis in peripheral artery disease Many studies have shown an increased cardiovascular risk in patients with PAD, in addition to a risk of limb loss and decreased quality of life . Patients with abnormal ABIs are two to three times more likely to have had a his- tory of MI, angina, heart failure, and/or cerebrovascular accident (CVA). From 60% to 80% of patients with PAD have angiographically signi \201 cant CAD. Nearly 25% of patients with critical limb disease die within a year. In patients who have undergone a mputation, the mortality may be as high as 45% at 1 year, and 25% of patients complaining o f claudication develop worsening symptoms. Mobility loss occurs more frequently in patients with PAD. Critical limb ischemia develops in nearly 8% of patients with claudication in the \201 rst year after diagnosis and at a rate of 2.2% annually thereafter. Both smoking and diabetes independently predict disease p rogression. Treatment The treatment goals for PAD include reduction in cardiovascular morbidity and mor tality with aggressive risk factor modi \201 cation, pharmacological and revascularization therapies, and improvement in quality of life by decreasing the symptoms of claudication ( Figs. 3.7 and 3.8). Confirmed PAD Diagnosis Lifestyle-limiting symptoms No significant functional disability Lifestyle-limiting symptoms with evidence of inflow disease* Pharmacological therapy: Cilostazol (Pentoxifylline) No claudication treatment required. \200 Follow-up visits at least annually to monitor fo r development of leg, coronary, or cerebrovascular ischemic symptoms. Supervised exercise program Further anatomic definition by more extensive noninvasive or angiographic diagnostic techni ques Three-month trial Three-month trial Endovascular therapy or surgical bypass per anatomy Preprogram and postprogram exercise testing for efficacy Clinical improvement: Follow-up visits at least annually Significant disability despite medical therapy and/or inflow endovascular therapy, with doc umentation of outflow \200 PAD, with favorable procedural anatomy and procedural risk-bene fit ratio Evaluation for additional endovascular or surgical revascularization Figure 3.7 Treatment of claudication. *In \202 ow disease should be suspected in individua ls with gluteal or thigh claudication and femoral pulse diminution or bruit and should be c on \201 rmed by noninvasive vascular laboratory diagnostic evidence of aortoiliac stenoses . \200 Out \202 ow disease represents femoropopliteal and infrapopliteal stenoses (the pr esence of occlusive lesions in the lower extremity arterial tree below the inguinal ligamen t from the common femoral artery to the pedal vessels). Reprinted with permission from the ACC/AHA Practice Guidelines. Hirsch et al. (2006). Circulation 113:e463 \200\223e465. CHAPTER 3 Peripheral vascular disease 148 Chronic symptoms: Ischemic rest pain, gangrene, nonhealing wound Ischemic etiology must be established promptly: By examination and objective vascular studies Implication: Impending limb loss History and physical examination Document lower-extremity pulses Document presence of ulcer s or infection Assess factors that may contribute to limb risk: diabetes, neuropathy, chronic renal failur e, infection ABI, TBI, or duplex US No or minimal atherosclerotic arterial occlusive disease Severe lower extremity PAD documented: ABI less than 0.4; flat PVR waveform; absent pedal f low Systemic antibiotics if skin ulceration and limb infection are present Consider atheroembolism, thromboembolism, or phlegmasia cerulea dolens Obtain prompt vascular specialist consultation: Diagnostic testing strategy Creation of the rapeutic intervention plan Patient is not a candidate for revascularization* Patient is a candidate for revascularization Evaluation of source (ECG or Holter monitor; TEE; and/or abdominal US, MRA, or CTA); or ven ous duplex Medical therapy or amputation (when necessary) Define limb arterial anatomy Assess clinical and objectives severity of ischemia Imaging of relevant arterial circulation (noninvasive and angiographic) Revascularization possible (see treatment text, with application of thrombolytic, endovascu lar, and surgical therapies) Revascularization not possible \200 : medical therapy; amputation (when necessary) Ongoing vascular surveillance \200 Written instructions for self-surveillance Figure 3.8 Diagnosis and treatment of critical limb ischemia. *Based on patient comorbiditi es. \200 Based on anatomy or lack of conduit. \200 Risk factor normalization: immediate smoking cessation, treat hypertension per the Seventh Report of the Joint National Committ ee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure guidelines; t reat lipids per National Cholesterol Education Program Adult Treatment Panel III guidelines ; treat diabetes mellitus (HbA1C [hemoglobin A1C] less than 7%; Class IIa). It is not yet p roven that treatment of diabetes mellitus will signi \201 cantly reduce PAD-speci \201 c (limb ischemic) end points. Primary treatment of diabetes mellitus should be continued acco rding to established guidelines. ABI, ankle \200\223brachial index; CTA, computed tomograph ic angiography; ECG, electro- cardiogram; MRA, magnetic resonance angiography; PVR, pulse v olume recording; TBI, toe \200\223brachial index; TEE, transesophageal echocardiography; US , ultrasound. Reprinted with permission from the ACC/AHA Practice Guidelines. Hirsch et al. (2006). Circulation 113:e463 \200\223e465. PROGNOSIS IN PERIPHERAL ARTERY DISEASE 149 Risk factor modi \201 cation Similar to CAD, studies have shown the importance of risk fac tor modi \201 - cation to the reduction of cardiovascular mortality and morbidity associ- ated with PAD. In particular, robust statin data suggest a reduction in cardiovascular even t rates with therapy included in patients with PAD. Similarly, smoking cessation is imperative. Not only do survival rates increase in patients with PAD who do not smoke, but smoking cessation reduces the rate of critical limb ischemi a. While aggressive diabetes control reduces the risk of microvascular events, there are limit ed data to support bene \201 t in regard to macrovas- cular complications. Antihypertensive therapy reduces the risk of cardiovascular events. Blood pressure should t reated according to the current guidelines, which suggest a target of <140/90 for patients with PAD and <130/80 in patients with diabetes. Antiplatelet therapy Antiplatelet therapy has been shown in a large meta-analysis to yield a 22% odds reduction for vascular death, MI, or stroke. In the CHARISMA trial, dual antipla telet therapy with aspirin and clopidogrel was compared to aspirin alone in patients with k nown CAD, CVA, or PAD as well as patients with CAD risk factors. Dual antiplatelet therapy provided no sig- ni \201 cant bene \201 t over aspirin alone on the primary composite end point of MI, stroke, or cardiovascular death. Current guidelines recommend patients with PAD be treated with either acetylsalicylic acid (ASA) or Plavix. Anticoagulation with warfarin is not recommended as it is not more effecti ve than antiplatelet therapy and has more bleeding complications. Pharmacotherapy Vasodilator therapy has not demonstrated ef \201 cacy in the treatment of PAD. Physiologically this may be explained by a relative steal phenomenon that can develop with dilation of proximal vascular beds with vasodila- tor use, which reduces resistance, b lood \202 ow, and perfusion pressure. Distal to the stenosis there would be minimal effec t, as these vascular beds would be endogenously dilated. In addition, in skeletal muscle va sodilators do not reduce oxygen demand. Pentoxyphilline and cilostazol are drugs approved by the U.S. Food and Drug Administration (FDA) for use in patients with claudication. Pentoxyphilline, a xanthine derivative, is tho ught to decrease blood viscos- ity and improve erythrocyte \202 exibility. It may also ha ve anti-in \202 ammatory and antiproliferative effects. In two meta-analyzes, pentoxyphill ine was shown to increase absolute claudication distance by 45 \200\22350 meters com- pared with placebo. Cilostazol is a quinilone derivative and acts as a phosphodiesterase III inhibitor. It ther efore decreases cyclic adenosine monophosphate deg- radation, which increases its concentra tion in platelets and blood vessels. Several trials have reported an increase in absolute c laudication distance by 40% \200\22350% compared with placebo. A comparison study of placeb o, pentoxyphilline, and cilostazol showed that cilostazol had the most CHAPTER 3 Peripheral vascular disease 150 improvement in absolute walking distances while the former two were equivalent. Other drugs have been studied in the treatment of claudication and include statins, angiote nsin-converting enzyme (ACE) inhibitors, serotonin antagonists, calcium channel blockers, L -arginine, vasodilator prostagland- ins, and angiogenic growth factors, to name a few. A re cent study showed ramipril improved maximal claudication time. Preliminary trials of serot- onin antagonists and L-arginine have not been effective in improving walk- ing distances. Similarly, preliminary trials of vasodilator prostaglandins and angiogenic growth factors h ave been disappointing. Exercise rehabilitation A supervised exercise rehabilitation program improves symptoms in p atients with PAD. Meta-analyzes have shown signi \201 cant improvement, with up to 150% in crease in walking distance with regular 30-minute ses- sions at least several times a week for 6 months. It is thought that formation of collateral vessels, improved endothelium- dependent vasodil ation, hemorheology, and muscle metabolism are pos- sible mechanisms for this improvement, Percutaneous transluminal angioplasty and stents In patients with lifestyle-limiting claudi cation, peripheral catheter-based interventions are indicated if a trial of exercise rehabi litation and pharma- cotherapy has failed. Percutaneous intervention should also be conside red when patients have in \202 ow disease with symptoms of thigh or buttock claudication o r diminished femoral artery pulses. Procedural patency rates and durability of the procedure are related to lesion morphology a nd patient characteristics. Shorter vs. longer, larger arteries vs. smaller, and single vs. multiple occlusions have better patency rates. Peripheral arterial surgery Aortobifemoral bypass is the most frequent operation for patien ts with aortoiliac disease. A knitted or woven prothesis made of Dacron or polytetra \202 uoroethylene (PTFE) is anastamosed proximally from the distal aorta to each common femoral artery distally. The surgical operation planned must take into account both in \202 ow and out \202 ow in order to maintain graft patency. Similar to percutaneous procedures, the location of obstru ction along with patient clinical factors contribute to surgical success. In some high-risk patients with critical limb ischemia, extra-anatomic reconstructive proce dures are performed in which the aortoiliac circu- lation is circumvented and instead, axil lobifemoral bypass, iliobifemoral bypass, and femoral femoral bypass are performed. Long-te rm patency rates are lower for these grafts. Five-year patency rates range from 50 to 70% f or the axillobifemoral bypass. The operative mortality for extra- anatomic surgical procedu res is 3% \200\2235%. PROGNOSIS IN PERIPHERAL ARTERY DISEASE 151 Femoral popliteal, femoral tibial, and femoral peroneal artery bypass are potential reconst ructive surgeries for infrainguinal arterial disease. Grafts made of PFTE or in situ or rev ersed saphenous vein are used for the infrainguinal reconstructive surgery. Patency rates a re better for autolo- gous saphenous vein grafts than for synthetic grafts and better for a bove- than for below-knee popliteal anastamosis. In patients with claudication, 5-year patency for femoral popliteal recon- struction is 75% \200\22380%, while in patients with critical limb ischemia the patency is 45% \200\22360% for synthetic vs. autologous vein grafts, respectively. The 5-year patency for synthetic gr afts in the infrapopliteal location is 65% in patients with claudication and 33% in patient s with critical limb ischemia. Graft stenoses can result from technical errors made during surgery, such as retained valve cuffs, intimal \202 ap, or valvotome injury. Fibrous inti mal hyperplasia can result usually within 6 months from surgery. Finally, ath- erosclerosis can develop. This usually results 1 \200\2232 years from surgery. Graft surveillance progr ams in which color duplex ultrasonography is per- formed at regular intervals have enabled the early evaluation of graft sten- osis. This allows for early graft revision and avoids g raft failure. Antiplatelet and Coumarin datives also increase graft patency rates. CHAPTER 3 Peripheral vascular disease 152 Acute limb ischemia Acute limb ischemia develops when there is sudden reduction in arterial blood \202 ow that jeopardizes limb viability. On physical exam, the symp- toms and sign s can be remembered by the \201 ve Ps: pain, pulselessness, pallor, parethesias, and para lysis. The 5-year survival rate after acute limb ischemia caused by thrombosis is close to 45% and less than 20% after embolism. The risk of limb loss depends on the time elapsed before rev ascularization and the severity of ischemia. The causes of limb ischemia include arterial embolism, thrombosis in situ, dissection, and trauma. The history and physical exam typically estab- lish the diagnosis (see Fig. 3.9). Treatment includes analgesic medications for pain, lowering the foot of the bed to increase blood \202 ow by gravitational effects, sheep skin to reduce pressure on the heels, and warm room temperature to reduce cutaneous vasoconstriction (see Fig. 3.10). IV heparin shou ld be adminis- tered as soon as the diagnosis is made. If symptoms persist or viability of the limb is threatened, revascu- larization is indicate d. Intra-arterial thrombolytic therapy, percutaneous mechanical thrombectomy, and surgical revascularization are options for restoring blood \202 ow. ACUTE LIMB ISCHEMIA 153 Rapid or sudden decrease in limb perfusion threatens tissue vaibility History and physical examination; determine time of onset of symptoms Emergent assessment of severity of ischemia: Loss of pulses Loss of motor and sensory funct ion Vascular laboratory assessment ABI, TBI or duplex US Severe PAD documented: \200 ABI less than 0.4 \200 Flat PVR waveform \200 Absent peda l flow No or minimal PAD Consider atheroembolism, thromboembolism, or phlegmasia cerulea dolens Go to Figure 3.10, Treatment of Acute Limb Ischemia Evaluation of source (ECG or Holter monitor; TEE; and/or abdominal ultrasound, MRA, or CTA) ; or venous duplex Figure 3.9 Diagnosis of acute limb ischemia. ABI, ankle \200\223brachial index; CTA, comput ed tomographic angiography; ECG, electrocardiogram; MRA, magnetic resonance angiography; PV R, pulse volume recording; TBI, toe \200\223brachial index; TEE, transesophageal echocardio graphy; US, ultrasound. Adapted from 1) the ACC/ AHA Practice Guidelines. Hirsch et al. (20 06). Circulation 113:e463 \200\223e465 and 2) Rutherford RB, Baker JD, Ernst C, et al. (199 7). J Vasc Surg 26(3):517 \200\223538. 1 5 4 Severe PAD documented: ABI less than 0.4; flat PVR waveform; absent pedal flow C H A P T E R Immediate anticoagulation: Unfractionated heparin or low-molecular-weight heparin Obtain prompt vascular specialist consulation: Diagnostic testing strategy Creation of ther apeutic intervention plan 3 P e r i p h e r a l Assess etiology: \200 Embolic (cardiac, aortic, infrainguinal souces) \200 Progressive PAD and in situ thrombosis (prior claudication history) \200 Leg bypass graft thrombosis \200 Arterial trauma \200 Popliteal cyst or entrapment \200 Phlegmasis cerulea dolens \200 Ergotism \200 Hyperocoagulable state v a s c u l a r Salvageable limb: threatened marginally (reversible ischemia) \200 Salvageble if promptly treated \200 Minimal (toes) or no sensory loss \200 No muscle weakness \200 Inaudiab le (often) arterial Doppler signals \200 Audible venous Doppler signals Nonviable limb (irreversible ischemia) \200 Major tissue loss or permanent nerve damage i nevitable \200 Profound, anesthetic sensory loss \200 Profound paralysis (rigor) \200 Inaudible arterial Doppler signals \200 Inaudible venous Doppler signals Viable limb \200 Not immediately threatened \200 No sensory loss \200 No muscle weakn ess \200 Audible arterial and venous US Salvageable limb: threatened immediately (reversible ischemia) Salvageable with immediate revascularization \200 Sensory loss more than toes, associated with rest pain \200 Mild to moderate muscle weakness \200 Inaudible (usually) arterial Doppler signals \200 Audible venous Doppler signals d i s e a s e Guides to treatment: \200 Site and extent of occlusion \200 Embolus vs. thrombus \200 Native artery vs. bypass graft \200 Duration of ischemia \200 Patient comorbidities \200 Contraindications to thrombolysis or surgery Amputation Revascularization: Thrombolysis, endovascular, surgical Figure 3.10 Treatment of acute limb ischemia. PAD, peripheral arterial disease; PVR, pulse volume recording; US, ultrasonography. Adapted from 1) the ACC/AHA Practice Guidelines. Hir sch et al. (2006). Circulation 113:e463 \200\223e465 and 2) Rutherford RB, Baker JD, Ernst C, et al. (1997). J Vasc Surg 26(3):517 \200\223538. CEREBROVASCULAR DISEASE 155 Cerebrovascular disease Stroke is the leading cause of disability in the United States. Car otid artery disease is common in patients with coronary artery disease. Each year there are approximately 750,000 strokes and 150,000 deaths related to cerebrovascular disease. An asymptomatic carotid bruit is present in 13% of the population and incidence increases w ith age. Transient ischemic attacks are de \201 ned as a focal loss of function related to cerebral ischemia lasting less than 24 hours and localized to a limited area of the brain, whereas stroke is a permanent neurological de \201 cit. Causes of stroke are listed in Ta ble 3.5. Duplex sonography is an important tool in diagnosing carotid artery stenosis and is able to provide both hemodynamic and anatomic informa- tion. MRA can also be used to accurately di agnose extra- and intracranial arterial disease. It is indicated for patients with symptoma tic carotid artery disease to further characterize cerebral anatomy. Standard angiography c an also be performed and is associated with a 1% risk of stroke. Carotid endarterectomy has been shown to be superior to medical therapy in patients with sy mptomatic carotid disease and a high-grade ste- nosis. In patients with mild carotid artery disease, medical therapy is pre- ferred; treatment for those with moderate disease remains controversial. The Asymptomatic Carotid Atherosclerosis Study (ACAS) demon- strated that c arotid endarterectomy is superior to medical therapy in people with asymptomatic carotid st enosis >60%, with a combined peri- operative mortality <3%. In patients with symptomatic ca rotid stenosis <60%, the current medical management includes anticoagulation for 3 months, followed by antiplatelet therapy (ASA or Plavix) inde \201 nitely. Carotid artery stenting has gained acceptance in patients whose opera- tive mortality is el evated. In high-risk patients, surgical mortality may be as high as 18%. Using a standard p ercutaneous approach, the carotid artery can be stented. The SAPPHIRE trial is the only published randomized trial that has com- pared carotid endar terectomy with carotid artery stenting. Patients had at least one high-risk surgical featur e and were included with symptomatic carotid stenosis of >50% or asymptomatic carotid steno sis of >80%. While the primary end point was complex, the carotid-stent arm of the trial ha d signi \201 cantly less composite stroke, MI, and death within 30 days. An ongoing trial of carotid revascularization endarterectomy vs. stent trial (CREST) is rev iewing both treatment strategies in 1400 patients with a goal of 4-year follow-up. CHAPTER 3 Peripheral vascular disease 156 Table 3.5 Causes of stroke Intracardiac thrombus Intracardiac mass lesions Valvular heart disease Infectious endocarditis Paradoxic emboli Large vessel occlusive disease Small-vessel disease (hypertension, DM, arteritis) Carotid atherosclerosis Polycythemia vera Thrombocytosis Antiphospholipid antibody syndrome Cryoglobulinemia Air and fat emboli Cortical vein thrombosis RENOVASCULAR DISEASE 157 Renovascular disease Obstructive renovascular disease can be caused by atherosclerosis or \201 bromuscular dysplasia (FMD). Renal FMD tends to occur in younger patients. There is a female preponderance. FMD typically involves the secondary or distal branches. Renal artery revascularization wit h surgery or percutaneous angioplasty techniques can be curative of hypertension. While the true prevalence of atherosclerotic renal artery disease is not known, in patients identi \201 ed as having atherosclerosis in other vascular beds the prevalence is between 10% and 30%. The true natural history of renal atherosclerotic disease, outcomes after rev ascularization, and appro- priate populations for intervention still require clari \201 ca tion. Clinical signs include known atherosclerosis in alternate vascular beds, onset of hypertens ion (HTN) prior to age 30 (FMD) or after age 55, wors- ening of previously controlled HTN, malignant or resistant hypertension, abdominal or \202 ank bruit, discrepancy in renal si ze, unexplained azotemia or renal function worsened by ACE inhibitors or angiotensin II rec eptor blockers (ARBs), and recurrent heart failure or \202 ash pulmonary edema in a hyper tensive patient with preserved LV function. Diagnostic testing MRA, CTA, and duplex Doppler ultrasonography can be used in the diag- no sis of renal artery stenosis (RAS) (see Fig. 3.11). Captopril renal scintig- raphy, selecti ve renal vein renin measurements, and plasma renin activity are not useful screening tests for RAS. Both MRA and CTA have lower diagnostic accuracy, with sensitivity in 20% \200\22330% range, for lesions caused by FMD. This is likely secondary to their anatomic location. Magnetic resonance angiography Multiple series have shown the high diagnostic accuracy of M RA and increasingly this is becoming the \201 rst-line diagnostic test. Because of links to administration of gadolinium in patients with moderate to severe renal disease to nephro genic systemic \201 brosis, MRA is not recommended in patients with a glomerular \201 l tration rate (GFR) <30. CT angiography Spiral CT with administration of contrast allows for highly accurate non- in vasive imaging of renal arteries. Sensitivity and speci \201 city are roughly in the high 70% and mid 90% range, respectively. Duplex Doppler ultrasonography This allows for both functional and anatomic assessment of R AS. Direct visualization is combined with Doppler measurements for hemodynamic assessment. The sensitivity and speci \201 city are 85% and 92%, respectively. CHAPTER 3 Peripheral vascular disease 158 Clinical Clues to the Diagnosis of Renal Artery Stenosis 1. Onset of hypertension before the age of 30 years of severe hypertension after the age of 55.* (Class I; LOE B) 2. Accelerated, resistant, or malignant ypertension.* (Class I; LOE C) 3. Development of new azotemia or worsening renal function after administration of an AC E inhibitor or ARB agent. (Class I; LOE B) 4. Unexplained atrophic kidney or size discrepan cy between kidneys of greater than 1.5 cm. \200 (Class I; LOE B) 5. Sudden, unexplained pu lmonary edema. (Class I; LOE B) 6. Unexplained renal dysfunction, including individuals sta rting renal replacement therapy. (Class IIa; LOE B) 7. Multi-vessel coronary artery disease . (Class IIb; LOE B) 8. Unexplained congestive heart failure. (Class IIb; LOE C) 9. Refract ory angina. (Class IIb; LOE C) Diagnostic Studies Invasive Imaging Abdominal aortography to assess the renal arteries during coronary and per ipherals angiography Noninvasive Imaging \200 Duplex ultrasound \200 Gadolinium enhanced MRA \200 CT angio graphy Negative noninvasive test result but high clinical index of suspicion Evidence of RAS Evidence of RAS Renal angiography (and hemodynamics) Evidence of RAS See Treatment See Treatment See Treatment Figure 3.11 Clinical clues to the diagnosis of renal artery stenosis (RAS). * For de \201 nition of hypertension, please see Chobanian AV, Bakris GL, Black HR, et al. (2003). The Se venth Report of the Joint National Committee on Prevention, Detection, Evaluation, and Trea tment of High Blood Pressure: the JNC-7 report. JAMA 289:2560 \200\2232572. \200 For exam ple, atrophic kidney due to chronic pyelonephritis is not an indication for RAS evaluation. ACE, angiotensin-converting enzyme; ARB, angiotensin receptor blocking agent; CT, computed tomography; LOE, level of evidence; MRA, magnetic resonance angiography. Reprinted with pe rmission from the ACC/AHA Practice Guidelines. Hirsch et al. (2006). Circulation 113:e463 \200\223e465. RENOVASCULAR DISEASE 159 Revascularization Angiographic lesions >75% in one or both renal arteries suggest reno- vas cular disease. It is important to remember that such \201 ndings may be present in patien ts with or without hypertension who have other vascular disease. The clinical history is particularly important in helping to select patients who are approp riate for percutaneous revascularization (Fig. 3.12). By repeat duplex sonography, while RA S lesion severity may increase over time in most patients, the progression to renal failure is uncommon. The decision to revascularize an RAS is based on the assumption that clinical bene \201 t will be derived from the intervention. The evaluation of resistive index (1-end diastolic v elocity divided by peak systolic velocity) prior to angioplasty may predict which patients will have a successful revascularization procedure. A higher resistive index, >8, may indic ate irreversible intrarenal vascular arteriosclerosis. The procedure is performed from a femoral approach and technical success varies based on the location of the lesion. In general, results are much better with FMD, with <15% procedural failure and infrequent r estenosis rate. In atherosclerotic disease, the failure rate approximates 20% \200\22330% a nd the restenosis rate is between 8% and 30%. The ef \201 cacy of angioplasty improves by insertion of a stent. While clinical trials are limited, anecdotal experience suggests that drug- eluting stents may signi \201 cantly reduce restenosis rates. The current ACC/ AHA guidelines recommend s tenting for ostial atherosclerotic lesions in patients who meet clinical criteria. However, for FMD the guidelines rec- ommend balloon angioplasty with bailout stent placement, if ne cessary. The procedural complication rate is between 5% and 15%. Complications include puncture site hematoma, renal artery dissection, renal artery thrombosis or perforation, and acute renal failure from atheroembolism or contrast-induced nephropathy. Distal embolic protection dev ices have been advocated to help to reduce the complications of atheroembolism.