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Peripheral Artery Disease l(EY POltlTS (ondnued) early recognition of PAD provides a unique opportunity to identiff persons at increased cardiovascular risk and to mod . CT angiography is the imaging modality of choice in ify risk factors. According to guidelines from the American patients in whom acute thoracic aortic disease is suspected. Heart Association (AHA) and the American College of o Intravenous p-blockers are first-line treatment to Cardiology (ACC). <-rbtaining a screening ankle brachial index reduce heart rate and blood pressure in patients with (ABI) to identify PAD is reasonable in asymptomatic persons acute aortic dissection without cardiogenic shock. with one of the following characteristics that signify increased . Emergency surgery should be considered for acute aor risk: (l) age 65 years or older. (Z) age so to 64 years rt'ith risk tic dissection complicated by cardiogenic shock, type A tactors for atherosclerosis (e.g., smoking. diabetes. hyperten aortic dissection, and type A intramural hematoma. sion, dyslipidemia) or family history t-rf PAD, (3) age younger than 50 years with diabetes and one additional risk factrtr for atherosclerosis. or (4) known atherosclerotic disease in Role of Genetic Testing and another vascular bed (coronary carotid, subclavian. renal. or Family Screening mesenteric artery stenosis or abdominal aortic aneurysm). The U.S. Preventive Services Task Force concluded that there is Genetic conditions that predispose patients to TAA syndromes insufficient evidence to support screening for lower extremity include Marfan syndrome. Ehlers Danlos syndrome, and PAD with an ABI. Loeys Dietz. syndrome (see 'fable 35). Clinical findings and family history olconnective tissue disease olten trigger genetic t(EY P0t1{IS testing for either diagnostic confirmation or screening of fam o The primary risk factors for peripheral artery disease ily members. Noninvasive in.raging of the aorta should be include smoking, diabetes mellitus, hypertension, performed if a pathogenic genetic mutation is found. Routine hyperlipidemia, and advanced age. surveillance (initially at 6 months ar.rd then annually if find- o Screening for peripheral artery disease (PAD) with ings are stable) should be perfbrmed to ensure that the aorta is ankle brachial index testing may be considered in not enlarging rapidly. patients at increased risk for PAD. In first degree relatives of patients with TAA and/or dis section, noninvasive aortic imaging should be perfornted to identify those with asymptomatic disease. Screening echocar diography might be considered in first degree relatives of Clinical Presentation patients with a bicuspid valve. l'irst degree relatives of patients Lower extremity PAD, by virtue of being defined by an abnor with a mutant gene (e.g., F8,ry1, TGFBRl, TGFBR2, COL3A1, mal ABI value rather than by symptoms. has a lvide spectrum MYHLL) associated with aortic aneurysm andior dissection ol clinical manifestations. Patients may present with exer should undergo genetic counseling and testing. Relatives with tional leg pain relieved by rest (intermittent claudication), the identified genetic mutation should then undergo noninva atypical exertional leg pain. ischemic rest pain. nonhealing sive aortic imaging. wounds, ischemic ulcers. or gangrene. Approximately 25'X, to 30'7, of patients with lower extremity PAD present with intermittent claudication. Peripheral Artery Disease Patients with intermittent claudication often have reduced exercise capacity and functional status compared with Epidemiology and Screening age- and sex-matched controls, and their annual risk lor Peripheral artery disease (PAD) is typically characterized by myocardial infarction, stroke. or cardiovascular death is narrowing of the aortic bilurcation and arleries of the lower approximately 5'){, to 77,. Most patients with intermittent extremities, including the iliac, femoral, popliteal, and tibial claudication have stable symptoms; however. symptoms arteries. Atherosclerosis is the most common cause. Risk fac worsen in approximately 25'7, of patients. and 10'2, to 20'l,, of tors for PAD include smoking (current or past), diabetes mel- patients will undergo lower extremity revascularization litus, hypertension. hyperlipidemia, increasing age, and family procedures over a 5-year period. history of atherosclerosis. PAD occurs at a later age in women Fewer than 5'X, of patients with PAD present u,ith chronic than in men, and because women have a longer life span, the limb threatening ischemia (CLTI; also termed critical limb overall prevalence is higher in women. The incidence of PAD ischemia), the most severe fbrm of PAD. CLTI n-ranifests as begins to increase at around age 40 years and rises to approxi- ischemic rest pain, tissue ulceration, and gangrene. Arterial leg mately 10'1, at age 70 years. ulcers commonly occur on the distal toes, plantar aspect of the PAD is considered a coronary heart disease risk equiva- foot, anterior portion of the lower leg where minimal collateral lent, and both asymptomatic and symptomatic patients with arterial circulation is present, and sites of trauma. Arterial PAD are at increased risk fbr ischernic events, including ulcers usually are painful and have sharply demarcated myocardial infarction, stroke. and cardiovascular death. Thus. borders with a dry. pale gray or yellow wound base witl.rout

l(EY POltlTS (ondnued) early recognition of PAD provides a unique opportunity to identiff persons at increased cardiovascular risk and to mod . CT angiography is the imaging modality of choice in ify risk factors. According to guidelines from the American patients in whom acute thoracic aortic disease is suspected. Heart Association (AHA) and the American College of o Intravenous p-blockers are first-line treatment to Cardiology (ACC). <-rbtaining a screening ankle brachial index reduce heart rate and blood pressure in patients with (ABI) to identify PAD is reasonable in asymptomatic persons acute aortic dissection without cardiogenic shock. with one of the following characteristics that signify increased . Emergency surgery should be considered for acute aor risk: (l) age 65 years or older. (Z) age so to 64 years rt'ith risk tic dissection complicated by cardiogenic shock, type A tactors for atherosclerosis (e.g., smoking. diabetes. hyperten aortic dissection, and type A intramural hematoma. sion, dyslipidemia) or family history t-rf PAD, (3) age younger than 50 years with diabetes and one additional risk factrtr for atherosclerosis. or (4) known atherosclerotic disease in Role of Genetic Testing and another vascular bed (coronary carotid, subclavian. renal. or Family Screening mesenteric artery stenosis or abdominal aortic aneurysm). The U.S. Preventive Services Task Force concluded that there is Genetic conditions that predispose patients to TAA syndromes insufficient evidence to support screening for lower extremity include Marfan syndrome. Ehlers Danlos syndrome, and PAD with an ABI. Loeys Dietz. syndrome (see 'fable 35). Clinical findings and family history olconnective tissue disease olten trigger genetic t(EY P0t1{IS testing for either diagnostic confirmation or screening of fam o The primary risk factors for peripheral artery disease ily members. Noninvasive in.raging of the aorta should be include smoking, diabetes mellitus, hypertension, performed if a pathogenic genetic mutation is found. Routine hyperlipidemia, and advanced age. surveillance (initially at 6 months ar.rd then annually if find- o Screening for peripheral artery disease (PAD) with ings are stable) should be perfbrmed to ensure that the aorta is ankle brachial index testing may be considered in not enlarging rapidly. patients at increased risk for PAD. In first degree relatives of patients with TAA and/or dis section, noninvasive aortic imaging should be perfornted to identify those with asymptomatic disease. Screening echocar diography might be considered in first degree relatives of Clinical Presentation patients with a bicuspid valve. l'irst degree relatives of patients Lower extremity PAD, by virtue of being defined by an abnor with a mutant gene (e.g., F8,ry1, TGFBRl, TGFBR2, COL3A1, mal ABI value rather than by symptoms. has a lvide spectrum MYHLL) associated with aortic aneurysm andior dissection ol clinical manifestations. Patients may present with exer should undergo genetic counseling and testing. Relatives with tional leg pain relieved by rest (intermittent claudication), the identified genetic mutation should then undergo noninva atypical exertional leg pain. ischemic rest pain. nonhealing sive aortic imaging. wounds, ischemic ulcers. or gangrene. Approximately 25'X, to 30'7, of patients with lower extremity PAD present with intermittent claudication. Peripheral Artery Disease Patients with intermittent claudication often have reduced exercise capacity and functional status compared with Epidemiology and Screening age- and sex-matched controls, and their annual risk lor Peripheral artery disease (PAD) is typically characterized by myocardial infarction, stroke. or cardiovascular death is narrowing of the aortic bilurcation and arleries of the lower approximately 5'){, to 77,. Most patients with intermittent extremities, including the iliac, femoral, popliteal, and tibial claudication have stable symptoms; however. symptoms arteries. Atherosclerosis is the most common cause. Risk fac worsen in approximately 25'7, of patients. and 10'2, to 20'l,, of tors for PAD include smoking (current or past), diabetes mel- patients will undergo lower extremity revascularization litus, hypertension. hyperlipidemia, increasing age, and family procedures over a 5-year period. history of atherosclerosis. PAD occurs at a later age in women Fewer than 5'X, of patients with PAD present u,ith chronic than in men, and because women have a longer life span, the limb threatening ischemia (CLTI; also termed critical limb overall prevalence is higher in women. The incidence of PAD ischemia), the most severe fbrm of PAD. CLTI n-ranifests as begins to increase at around age 40 years and rises to approxi- ischemic rest pain, tissue ulceration, and gangrene. Arterial leg mately 10'1, at age 70 years. ulcers commonly occur on the distal toes, plantar aspect of the PAD is considered a coronary heart disease risk equiva- foot, anterior portion of the lower leg where minimal collateral lent, and both asymptomatic and symptomatic patients with arterial circulation is present, and sites of trauma. Arterial PAD are at increased risk fbr ischernic events, including ulcers usually are painful and have sharply demarcated myocardial infarction, stroke. and cardiovascular death. Thus. borders with a dry. pale gray or yellow wound base witl.rout 106

Peripheral Artery Disease Evaluation History and Physical Examination A detailed history review of symptoms, and physical examina- tion are essential in the evaluation for vascular disease. Patients should be asked about walking impairment, a[zpical limb symptoms (leg weakness, paresthesia), intermittent clau dication, and ischemic rest pain. In patients with ex.ertional leg symptoms, intermittent claudication should be differenti- ated from pseudoclaudication (symptoms that arise from spi- nal stenosis) (Table 38). Patients also should be questioned about skin breakdown and loot ulcers and educated on the importance of foot protection and wearing shoes (specifically, hard soled shoes) when walking outside the home. Components of the physical examination in patients with suspected PAD are listed in Table 39. Vascular examination of patients suspected of having lower extremify PAD should include comprehensive pulse examination, auscultation for bruits, and inspection of the feet for skin and toenail changes. Patients with PAD may exhibit diminished, absent, or asym metric pulses, and bruits may be heard at or near sites of arte- rial stenosis. Patients with CLTI may have coolness in the

Evaluation History and Physical Examination A detailed history review of symptoms, and physical examina- tion are essential in the evaluation for vascular disease. Patients should be asked about walking impairment, a[zpical limb symptoms (leg weakness, paresthesia), intermittent clau dication, and ischemic rest pain. In patients with ex.ertional leg symptoms, intermittent claudication should be differenti- ated from pseudoclaudication (symptoms that arise from spi- nal stenosis) (Table 38). Patients also should be questioned about skin breakdown and loot ulcers and educated on the importance of foot protection and wearing shoes (specifically, hard soled shoes) when walking outside the home. Components of the physical examination in patients with suspected PAD are listed in Table 39. Vascular examination of patients suspected of having lower extremify PAD should include comprehensive pulse examination, auscultation for bruits, and inspection of the feet for skin and toenail changes. Patients with PAD may exhibit diminished, absent, or asym metric pulses, and bruits may be heard at or near sites of arte- rial stenosis. Patients with CLTI may have coolness in the TABLE 38. Discriminating Claudication from Pseu d ocla u d icatio n

Evaluation History and Physical Examination A detailed history review of symptoms, and physical examina- tion are essential in the evaluation for vascular disease. Patients should be asked about walking impairment, a[zpical limb symptoms (leg weakness, paresthesia), intermittent clau dication, and ischemic rest pain. In patients with ex.ertional leg symptoms, intermittent claudication should be differenti- ated from pseudoclaudication (symptoms that arise from spi- nal stenosis) (Table 38). Patients also should be questioned about skin breakdown and loot ulcers and educated on the importance of foot protection and wearing shoes (specifically, hard soled shoes) when walking outside the home. Components of the physical examination in patients with suspected PAD are listed in Table 39. Vascular examination of patients suspected of having lower extremify PAD should include comprehensive pulse examination, auscultation for bruits, and inspection of the feet for skin and toenail changes. Patients with PAD may exhibit diminished, absent, or asym metric pulses, and bruits may be heard at or near sites of arte- rial stenosis. Patients with CLTI may have coolness in the TABLE 38. Discriminating Claudication from Pseu d ocla u d icatio n Characteristic Claudication Pseudoclaudication t Nature of Cramping, Same as for f I G U R E 5 9, Arterial insufliciency ukers (top panel) appear sharply demarcated discomfort tightness, claudication plus or "punched out" with a dry pale, gray, or yellow base, and the surrounding skin is aching, fatigue tingling, burning, red, taut, and tender. Arterial ulcers are more likely to occur on the toes, plantar numbness, weakness surfaces of the foot, and the heel. Venous stasis ulcers(boftom panel) are typically Location of Buttock, hi p, Same as for less painful and ocrur on the medial side of the lower leg (between the cal{ and discomfort thigh, calf, foot claudication; most the ankle) in areas of hyperpigmentation. Venous ulcers are typically irregularly often bilateral shaped and shallow with yellow granulation tissue. They often weep serous fluid; Exercise-ind uced Yes Variable the ulcers are rarely necrotic. Walking distance Consistent Variable at onset of symptoms evidence of granulation tissue (Figure 59). Patients with CLII often have reduced exercise capacity and functional status, Discomfort No Yes occurs with and these patients have a 30'/. rate of major amputation and a standing still 20% mortality rate within l year of diagnosis. Surgical or endo Action for relief Stand or sit Sit, flexion at the vascular revascularization is usually necessary to salvage the waist foot or limb. <30 min Time to relief <5 min IEY POIf,TS o Peripheral artery disease may be asymptomatic or pre- TABLE 39. Physical Examination of Patients for Peripheral sent as intermittent claudication, atypical exertional leg Artery Disease pain, or, rarely, chronic limb-threatening ischemia. Measure blood pressure in both arms (systolic blood pressure . Patients with peripheral artery disease have reduced difference >1 5 mm Hg suggests subclavian stenosis) exercise capacity and an elevated risk for cardiovascular Auscultate for presence of arterial bruits (e.9., femoral artery) morbidity and mortality. Palpate for presence of abdominal aortic aneurysm . Ulcers due to peripheral artery disease often cause sig- Palpate and record pulses (radial, brachial, carotid, femoral, nificant pain; ulcers are usually sharply demarcated and popliteal, posterior tibial, dorsalis pedis) located on the distal extremities, such as the distal toes Evaluate for elevation pallor and dependent rubor of foot and anterior portion of the lower leg, where minimal lnspect feet for ulcers, fissures, calluses, tinea, and tendinous collateral arterial circulation is present. xanthoma; evaluate overall skin care

Characteristic Claudication Pseudoclaudication t Nature of Cramping, Same as for f I G U R E 5 9, Arterial insufliciency ukers (top panel) appear sharply demarcated discomfort tightness, claudication plus or "punched out" with a dry pale, gray, or yellow base, and the surrounding skin is aching, fatigue tingling, burning, red, taut, and tender. Arterial ulcers are more likely to occur on the toes, plantar numbness, weakness surfaces of the foot, and the heel. Venous stasis ulcers(boftom panel) are typically Location of Buttock, hi p, Same as for less painful and ocrur on the medial side of the lower leg (between the cal{ and discomfort thigh, calf, foot claudication; most the ankle) in areas of hyperpigmentation. Venous ulcers are typically irregularly often bilateral shaped and shallow with yellow granulation tissue. They often weep serous fluid; Exercise-ind uced Yes Variable the ulcers are rarely necrotic. Walking distance Consistent Variable at onset of symptoms evidence of granulation tissue (Figure 59). Patients with CLII often have reduced exercise capacity and functional status, Discomfort No Yes occurs with and these patients have a 30'/. rate of major amputation and a standing still 20% mortality rate within l year of diagnosis. Surgical or endo Action for relief Stand or sit Sit, flexion at the vascular revascularization is usually necessary to salvage the waist foot or limb. <30 min Time to relief <5 min IEY POIf,TS o Peripheral artery disease may be asymptomatic or pre- TABLE 39. Physical Examination of Patients for Peripheral sent as intermittent claudication, atypical exertional leg Artery Disease pain, or, rarely, chronic limb-threatening ischemia. Measure blood pressure in both arms (systolic blood pressure . Patients with peripheral artery disease have reduced difference >1 5 mm Hg suggests subclavian stenosis) exercise capacity and an elevated risk for cardiovascular Auscultate for presence of arterial bruits (e.9., femoral artery) morbidity and mortality. Palpate for presence of abdominal aortic aneurysm . Ulcers due to peripheral artery disease often cause sig- Palpate and record pulses (radial, brachial, carotid, femoral, nificant pain; ulcers are usually sharply demarcated and popliteal, posterior tibial, dorsalis pedis) located on the distal extremities, such as the distal toes Evaluate for elevation pallor and dependent rubor of foot and anterior portion of the lower leg, where minimal lnspect feet for ulcers, fissures, calluses, tinea, and tendinous collateral arterial circulation is present. xanthoma; evaluate overall skin care 107

Peripheral Artery Disease affected extremity as well as evidence of poor wound healing TABLE 41 . lmaging Modalities for the Diagnosis of PAD or active ulceration. Clinicians should distinguish CLTI from lmaging Advantages Limitafions chronic venous disease (leg edema; pigmented, brawny indu : fUodality ration of the gaiter zone; ulceration of the shin or ankle) Arterial duplex Widely available Limited abilityto because these conditions are treated differently (see MKSAP l9 ultrasonography detect stenosis in Does not require General Internal Medicine 1). the pelvis and in administration of patients with severe contrast dye calcifications Diagnostic Testing lnexpensive Poor utility for The most commonly used diagnostic modality for identiffing infrapopliteal stenosis lower extremity PAD is measurement of the ABI, the ratio of CT angiography Widely available Risk for contrast- lower extremity to upper extremity systolic blood pressures. induced Useful in defining Guidelines recommend ABI testing in all patients with history nephropathy the severity of PAD or physical examination findings suggestive of PAD. ABI meas Very expensive urement is simple, inexpensive, and noninvasive, with a sen Magnetic Useful in defining Contraindicated in sitivity and specificity approaching 90'7,. ABI values also have resonance the severity of patients with prognostic importance; low values are associated with higher angiography PAD implanted pacemak- ers or defibrillators rates ofmyocardial infarction, stroke, and death. Risk for nephrogenic When undergoing ABI testing, patients should rest for systemic fibrosis in 10 minutes in a supine position before the physician measures patients with severe the ankle pressures and brachial pressures with a Doppler kidney disease" machine. Blood pressures should be measured in both arms Very expensive and in both legs at the dorsalis pedis and posterior tibial ankle PAD = penpheral aftery disease. locations. To calculate the ABI for each leg, the higher ankle "Group I gadolinium based contrast agents are contraindicated in patients with an pressure in that leg is divided by the higher brachial artery estlmated glomerular filt.ation rate less than 30 mUmin/1.73 m2 or acute kidney injury; pressure (regardless ofside). The ankle pressure is the same as safety or slightly higher than the brachial pressure in healthy per sonsi therefore, a normal resting ABI is between 1.00 and 1.40 Segmental pressure measurements in a vascular laboratory (Table 4O). In the presence of atherosclerotic narrowing of the may be used to localize diseased vessels. The procedure involves limb arteries, the downstream blood pressure, and thus the pulse volume recordings (measurement of the magnitude and ABI value, is lower. A resting ABI of 0.90 or less is diagnostic contour of blood pulse volume in the lower extremities) and for PAD and correlates with abnormalities seen on imaging of blood pressure measurements at several locations in the lower the arterial tree. Generally. patients with claudication have an extremities (high thigh, low thigh, calf. posterior tibial artery. ABI of 0.4 to 0.9, whereas patients with ischemic rest pain, and dorsalis pedis artery) (Figure 60). ulceration, organgrene have an ABI ofless than 0.4. A resting Other imaging studies used to delineate the anatomic ABI greater than 1.40 indicates the presence ofnoncompress- location and severity of lower extremity PAD include arterial ible, calcified arteries in the lower extremities and is consid duplex ultrasonography, CT angiography, and magnetic reso ered uninterpretable. A toe-brachial index is used for diagnosis nance angiography (Table 4l). These imaging modalities are in these patients, with a value of less than 0.70 indicating PAD. most often used to plan for endovascular or surgical revascu- Exercise ABI testing is useful in patients with ABI values Iarization procedures. Invasive angiography is often preferred between 0.91 and 1.40 and high pretest probability. It requires because endovascular revascularization procedures can be ABI measurements at rest and after treadmill walking or plan- performed concurrently. tar flexion exercises. A postexercise ankle pressure drop of fEY POITIS 30 mm Hg or more or significant decline in the ABI suggests PAD. r An ankle-brachial index of 0.90 or less is diagnostic of peripheral artery disease. TABLE 40. Interpretation of the Ankle-Brachial lndex Ankle-Brachiallndex lnterpretation . An ankle-brachial index greater than 1.40 indicates the presence of noncompressible arteries in the lower .40 Noncompressible (calcified) vessel (uninterpretable result) extremities and is considered uninterpretable; a toe brachial index is used for diagnosis ofperipheral artery : 1.00-1.40 Normal disease in these patients. 0.91-0.99 Borderline o In patients with peripheral artery disease, imaging with CT 0.4 -0.90 Mild to moderate PAD angiography or magnetic resonanc€ angio,gaphy is usefuJ 0.00-0.40 Severe PAD in identiSing the location and severity of stenosis and PAD = peripheral anery disease. planning for endo scular or surgical revascularization.

affected extremity as well as evidence of poor wound healing TABLE 41 . lmaging Modalities for the Diagnosis of PAD or active ulceration. Clinicians should distinguish CLTI from lmaging Advantages Limitafions chronic venous disease (leg edema; pigmented, brawny indu : fUodality ration of the gaiter zone; ulceration of the shin or ankle) Arterial duplex Widely available Limited abilityto because these conditions are treated differently (see MKSAP l9 ultrasonography detect stenosis in Does not require General Internal Medicine 1). the pelvis and in administration of patients with severe contrast dye calcifications Diagnostic Testing lnexpensive Poor utility for The most commonly used diagnostic modality for identiffing infrapopliteal stenosis lower extremity PAD is measurement of the ABI, the ratio of CT angiography Widely available Risk for contrast- lower extremity to upper extremity systolic blood pressures. induced Useful in defining Guidelines recommend ABI testing in all patients with history nephropathy the severity of PAD or physical examination findings suggestive of PAD. ABI meas Very expensive urement is simple, inexpensive, and noninvasive, with a sen Magnetic Useful in defining Contraindicated in sitivity and specificity approaching 90'7,. ABI values also have resonance the severity of patients with prognostic importance; low values are associated with higher angiography PAD implanted pacemak- ers or defibrillators rates ofmyocardial infarction, stroke, and death. Risk for nephrogenic When undergoing ABI testing, patients should rest for systemic fibrosis in 10 minutes in a supine position before the physician measures patients with severe the ankle pressures and brachial pressures with a Doppler kidney disease" machine. Blood pressures should be measured in both arms Very expensive and in both legs at the dorsalis pedis and posterior tibial ankle PAD = penpheral aftery disease. locations. To calculate the ABI for each leg, the higher ankle "Group I gadolinium based contrast agents are contraindicated in patients with an pressure in that leg is divided by the higher brachial artery estlmated glomerular filt.ation rate less than 30 mUmin/1.73 m2 or acute kidney injury; pressure (regardless ofside). The ankle pressure is the same as safety or slightly higher than the brachial pressure in healthy per sonsi therefore, a normal resting ABI is between 1.00 and 1.40 Segmental pressure measurements in a vascular laboratory (Table 4O). In the presence of atherosclerotic narrowing of the may be used to localize diseased vessels. The procedure involves limb arteries, the downstream blood pressure, and thus the pulse volume recordings (measurement of the magnitude and ABI value, is lower. A resting ABI of 0.90 or less is diagnostic contour of blood pulse volume in the lower extremities) and for PAD and correlates with abnormalities seen on imaging of blood pressure measurements at several locations in the lower the arterial tree. Generally. patients with claudication have an extremities (high thigh, low thigh, calf. posterior tibial artery. ABI of 0.4 to 0.9, whereas patients with ischemic rest pain, and dorsalis pedis artery) (Figure 60). ulceration, organgrene have an ABI ofless than 0.4. A resting Other imaging studies used to delineate the anatomic ABI greater than 1.40 indicates the presence ofnoncompress- location and severity of lower extremity PAD include arterial ible, calcified arteries in the lower extremities and is consid duplex ultrasonography, CT angiography, and magnetic reso ered uninterpretable. A toe-brachial index is used for diagnosis nance angiography (Table 4l). These imaging modalities are in these patients, with a value of less than 0.70 indicating PAD. most often used to plan for endovascular or surgical revascu- Exercise ABI testing is useful in patients with ABI values Iarization procedures. Invasive angiography is often preferred between 0.91 and 1.40 and high pretest probability. It requires because endovascular revascularization procedures can be ABI measurements at rest and after treadmill walking or plan- performed concurrently. tar flexion exercises. A postexercise ankle pressure drop of fEY POITIS 30 mm Hg or more or significant decline in the ABI suggests PAD. r An ankle-brachial index of 0.90 or less is diagnostic of peripheral artery disease. TABLE 40. Interpretation of the Ankle-Brachial lndex Ankle-Brachiallndex lnterpretation . An ankle-brachial index greater than 1.40 indicates the presence of noncompressible arteries in the lower .40 Noncompressible (calcified) vessel (uninterpretable result) extremities and is considered uninterpretable; a toe brachial index is used for diagnosis ofperipheral artery : 1.00-1.40 Normal disease in these patients. 0.91-0.99 Borderline o In patients with peripheral artery disease, imaging with CT 0.4 -0.90 Mild to moderate PAD angiography or magnetic resonanc€ angio,gaphy is usefuJ 0.00-0.40 Severe PAD in identiSing the location and severity of stenosis and PAD = peripheral anery disease. planning for endo scular or surgical revascularization. 108

Peripheral Artery Disease Segmented BP I S"g..nt-Brachial lnd ex 119 Brachial 121 t 145 175 1.20 1.45 129 170 1.07 1.40 96 153 0.79 1.26 8s (PT) 1 6s (PT) Gain:100% 0.70 1.36 Gain R) Dorsalis Pedis 80 (DP) 1s1 (DP) L) Dorsalis 0.66 1.25 Gain:100% Gain: 95% 0.70 Ankle-Brachial lndex 1.36 FIGURE 60.Apulsevolumerecordingdemonstratingdecreasedperfusioninthepatienttrightside.Anankle-brachial indexvalueof0.T0ontherightsideisconsistent upstroke and downstroke (the width of the waveform is much narrower compared with the width of the waveform on the right side). When the amplitude of the waveform is significantly blunted and the width is broader, it suggests moderate to severe disease. BP = blood pressure; DP = dorsalis pedis; PT= posteriortibial.

upstroke and downstroke (the width of the waveform is much narrower compared with the width of the waveform on the right side). When the amplitude of the waveform is significantly blunted and the width is broader, it suggests moderate to severe disease. BP = blood pressure; DP = dorsalis pedis; PT= posteriortibial. Medical Therapy Association recommendations on diabetes management, with particular attention to foot care (see MKSAP l9 Endocrinologz Treatment of PAD focuses on reducing cardiovascular risk, and Metabolism). improving functional status and quality of life, decreasing Dyslipidemia has a mild effect on the development of claudication symptoms, and preventing tissue injury and PAD. According to AHA/ACC guidelines, patients with PAD amputation. should be treated with high intensity statin therapy, and patients with PAD who are older than 75 years or intolerant of Cardiovascular Risk Reduction high intensity statins should be treated with moderate inten Cigarette smoking is the most important modifiable risk factor sity statin therapy (see MKSAP 19 General Internal Medicine 1). for PAD. Smoking cessation is imperative to lowering the risk Blood pressure control has been associated with a reduc for myocardial infarction and stroke and improving overall tion in cardiovascular events in patients with PAD. The survival in patients with PAD. Smoking cessation is also asso AHA/ACC recommends a blood pressure target of less than ciated with decreased risk for major amputation, improved 130/80 mm Hg in patients with PAD. Adults with hypertension patency rates following revascularization, and less disease and PAD are treated similarly to patients without PAD (see progression. MKSAP 19 Nephrologi). Diabetes is also a strong risk factor for PAD; however, Although older studies linked nonselective p blockers intensive glucose control has not been demonstrated to reduce (such as propranolol) with increased complications in patients macrovascular complications, including myocardial infarc with severe PAD, fi selective B blockers appear to be better tion, stroke, or amputation. Regardless, patients with PAD and tolerated and can be used with caution if otherwise indicated concomitant diabetes should adhere to American Diabetes for cardiovascular risk reduction. A meta-analysis showed no

Medical Therapy Association recommendations on diabetes management, with particular attention to foot care (see MKSAP l9 Endocrinologz Treatment of PAD focuses on reducing cardiovascular risk, and Metabolism). improving functional status and quality of life, decreasing Dyslipidemia has a mild effect on the development of claudication symptoms, and preventing tissue injury and PAD. According to AHA/ACC guidelines, patients with PAD amputation. should be treated with high intensity statin therapy, and patients with PAD who are older than 75 years or intolerant of Cardiovascular Risk Reduction high intensity statins should be treated with moderate inten Cigarette smoking is the most important modifiable risk factor sity statin therapy (see MKSAP 19 General Internal Medicine 1). for PAD. Smoking cessation is imperative to lowering the risk Blood pressure control has been associated with a reduc for myocardial infarction and stroke and improving overall tion in cardiovascular events in patients with PAD. The survival in patients with PAD. Smoking cessation is also asso AHA/ACC recommends a blood pressure target of less than ciated with decreased risk for major amputation, improved 130/80 mm Hg in patients with PAD. Adults with hypertension patency rates following revascularization, and less disease and PAD are treated similarly to patients without PAD (see progression. MKSAP 19 Nephrologi). Diabetes is also a strong risk factor for PAD; however, Although older studies linked nonselective p blockers intensive glucose control has not been demonstrated to reduce (such as propranolol) with increased complications in patients macrovascular complications, including myocardial infarc with severe PAD, fi selective B blockers appear to be better tion, stroke, or amputation. Regardless, patients with PAD and tolerated and can be used with caution if otherwise indicated concomitant diabetes should adhere to American Diabetes for cardiovascular risk reduction. A meta-analysis showed no 109

Peripheral Artery Disease increased risk for symptom exacerbation in patients with mild Cilostazol. a phosphodiesterase inhibitor $'ith antiplatelet to moderate PAD treated with selective B-blockers. and vasodilator activiry increases pain free walking distance and overall walking distance in patients with claudication. and Antithrombotic Therapy clinical practice guidelines recomrnend that a therapeutic trial Current guidelines recommend antiplatelet monotherapy in of cilostazol be considered in patients with claudication. As patients with PAD to reduce risk for myocardial infarction, with other oral phosphodiesterase inhibitors (e.g.. inotropes stroke, and peripheral arterial events, including CLTI. Despite such as milrinone). the FDA has placed a black box warning on little supporting evidence, aspirin has been recommended by use of cilostazol in patients with heart failure. There is no experts as the primary antiplatelet agent in patients with PAD. approved pharmacotherapy lor patients with CLTI. In patients who are aspirin intolerant, clopidogrel is recom TtY POITII mended as an acceptable alternative. There is no compelling evidence lor the use of dual antiplatelet therapy with aspirin . Smoking cessation is essential to reducing cardiovascular plus clopidogrel in patients with PAD alone. ln the CHARISMA risk in patients with peripheral artery disease. trial, patients with PAD who were treated with aspirin plus . Antiplatelet monotherapy, typically low-dose aspirin. clopidogrel had a reduced rate of hospitalization lor myocar reduces risk for myocardial infarction, stroke, and dial infarction and ischemic events, which was mitigated by a peripheral arterial events, including chronic limb higher rate of bleeding. threatening ischemia, in patients with peripheral artery Evidence from the COMPASS trial demonstrated that disease. aspirin (100 mg/d) plus rivaroxaban (2.s mg twice daily). a o Supervised exercise training is the most effective treat direct factor Xa inhibitor, was associated with improved major ment for improving functional status in patients with adverse cardiovascular and limb end points when compared peripheral artery disease. with aspirin plus placebo in patients with coronary artery o Cilostazol is recommended for patients with intermit- disease and PAD. Major bleeding, primarily gastrointestinal tent claudication but is contraindicated in patients with bleeding, was increased in patients assigned to receive aspirin heart failure. plus rivaroxaban; however, fatal or critical organ bleeding was not significantly different between the groups. In the VOYAGER trial, patients undergoing endovascular or surgical revascu larization for PAD had a significantly lower incidence of the I nterventional Therapy primary efficacy outcome (a composite of acute limb ischemia, Endovascular or surgical revascularization is eflective in major amputation for vascular causes, myocardial infarction. relieving symptoms and improving functional capacity and ischemic stroke, or death from cardiovascular causes) when wound healing in patients with intermittent claudication or assigned to rivaroxaban (2.5 mg twice daily) plus aspirin com CLTL Referral for revascularization is indicated in patients pared with aspirin alone. with life limiting claudication, rest pain, ulceration, or gan There is no evidence that oral anticoagulation with a grene, especially if there has been an inadequate response to vitamin K antagonist (warfarin) is more effective than anti exercise training, antiplatelet medication. cilostazol, and/or platelet monotherapy in patients with PAD. and warfarin wound treatment. Patients with CLTI (ABI <0.40, a flat wave antico:rgulation is associated rn,ith an increased risk for form on pulse volume recording, and low or absent pedal flow major bleeding, including intracerebral bleeding. There is on duplex ultrasonography) should be considered for urgent also no evidence that direct acting oral anticoagulant ther revascularization. Revascularization should also be considered apy alone is superior to antiplatelet monotherapy in patients in patients with a favorable risk benefit ratio. as determined with PAD. by patient factors (age, f railty, comorbid conditions). anatomic factors (severity and burden of atherosclerotic disease. loca Symptom Relief tion of disease in the lower extremities), operator expertise. Improving functional status and quality of life is ol high and type olprocedure. Revascularization is not recommended importance for patients with PAD. In patients who can exer in asymptomatic patients. cise, supervised exercise training has been associated with Endovascular revascularization use has dramatically improved functional performance and is recommended fbr increased in recent years because it is minimally invasive and patients with intermittent claudication. Systematic reviews confers a lower risk for perioperative adverse events compared comparing supervised exercise with home exercise have with surgical revascularization. Endovascular techniques reported improvements in maximal walking distance and ini- include balloon angioplasty, stenting (bare metal or drug elut tial claudication distance that favor supervised exercise; how- ing), and atherectomy (laser or various cutting options). In ever, no statistically significant differences in quality of life patients with isolated iliac disease. endovascular revasculari were observed. The Centers for Medicare & Medicaid Services zation is favored over surgery because of lower morbidity and approved coverage of supervised exercise training for patients mortality, high procedural success, and high patency rates over with claudication in 2017. time. Most patients undergo balloon angioplasty with stenting

increased risk for symptom exacerbation in patients with mild Cilostazol. a phosphodiesterase inhibitor $'ith antiplatelet to moderate PAD treated with selective B-blockers. and vasodilator activiry increases pain free walking distance and overall walking distance in patients with claudication. and Antithrombotic Therapy clinical practice guidelines recomrnend that a therapeutic trial Current guidelines recommend antiplatelet monotherapy in of cilostazol be considered in patients with claudication. As patients with PAD to reduce risk for myocardial infarction, with other oral phosphodiesterase inhibitors (e.g.. inotropes stroke, and peripheral arterial events, including CLTI. Despite such as milrinone). the FDA has placed a black box warning on little supporting evidence, aspirin has been recommended by use of cilostazol in patients with heart failure. There is no experts as the primary antiplatelet agent in patients with PAD. approved pharmacotherapy lor patients with CLTI. In patients who are aspirin intolerant, clopidogrel is recom TtY POITII mended as an acceptable alternative. There is no compelling evidence lor the use of dual antiplatelet therapy with aspirin . Smoking cessation is essential to reducing cardiovascular plus clopidogrel in patients with PAD alone. ln the CHARISMA risk in patients with peripheral artery disease. trial, patients with PAD who were treated with aspirin plus . Antiplatelet monotherapy, typically low-dose aspirin. clopidogrel had a reduced rate of hospitalization lor myocar reduces risk for myocardial infarction, stroke, and dial infarction and ischemic events, which was mitigated by a peripheral arterial events, including chronic limb higher rate of bleeding. threatening ischemia, in patients with peripheral artery Evidence from the COMPASS trial demonstrated that disease. aspirin (100 mg/d) plus rivaroxaban (2.s mg twice daily). a o Supervised exercise training is the most effective treat direct factor Xa inhibitor, was associated with improved major ment for improving functional status in patients with adverse cardiovascular and limb end points when compared peripheral artery disease. with aspirin plus placebo in patients with coronary artery o Cilostazol is recommended for patients with intermit- disease and PAD. Major bleeding, primarily gastrointestinal tent claudication but is contraindicated in patients with bleeding, was increased in patients assigned to receive aspirin heart failure. plus rivaroxaban; however, fatal or critical organ bleeding was not significantly different between the groups. In the VOYAGER trial, patients undergoing endovascular or surgical revascu larization for PAD had a significantly lower incidence of the I nterventional Therapy primary efficacy outcome (a composite of acute limb ischemia, Endovascular or surgical revascularization is eflective in major amputation for vascular causes, myocardial infarction. relieving symptoms and improving functional capacity and ischemic stroke, or death from cardiovascular causes) when wound healing in patients with intermittent claudication or assigned to rivaroxaban (2.5 mg twice daily) plus aspirin com CLTL Referral for revascularization is indicated in patients pared with aspirin alone. with life limiting claudication, rest pain, ulceration, or gan There is no evidence that oral anticoagulation with a grene, especially if there has been an inadequate response to vitamin K antagonist (warfarin) is more effective than anti exercise training, antiplatelet medication. cilostazol, and/or platelet monotherapy in patients with PAD. and warfarin wound treatment. Patients with CLTI (ABI <0.40, a flat wave antico:rgulation is associated rn,ith an increased risk for form on pulse volume recording, and low or absent pedal flow major bleeding, including intracerebral bleeding. There is on duplex ultrasonography) should be considered for urgent also no evidence that direct acting oral anticoagulant ther revascularization. Revascularization should also be considered apy alone is superior to antiplatelet monotherapy in patients in patients with a favorable risk benefit ratio. as determined with PAD. by patient factors (age, f railty, comorbid conditions). anatomic factors (severity and burden of atherosclerotic disease. loca Symptom Relief tion of disease in the lower extremities), operator expertise. Improving functional status and quality of life is ol high and type olprocedure. Revascularization is not recommended importance for patients with PAD. In patients who can exer in asymptomatic patients. cise, supervised exercise training has been associated with Endovascular revascularization use has dramatically improved functional performance and is recommended fbr increased in recent years because it is minimally invasive and patients with intermittent claudication. Systematic reviews confers a lower risk for perioperative adverse events compared comparing supervised exercise with home exercise have with surgical revascularization. Endovascular techniques reported improvements in maximal walking distance and ini- include balloon angioplasty, stenting (bare metal or drug elut tial claudication distance that favor supervised exercise; how- ing), and atherectomy (laser or various cutting options). In ever, no statistically significant differences in quality of life patients with isolated iliac disease. endovascular revasculari were observed. The Centers for Medicare & Medicaid Services zation is favored over surgery because of lower morbidity and approved coverage of supervised exercise training for patients mortality, high procedural success, and high patency rates over with claudication in 2017. time. Most patients undergo balloon angioplasty with stenting 110

Cardiovascular Disease in Cancer Survivors of the iliac arteries, which lras a sigr.rificantly higher long term weakness. lf compartment syndrome occurs, surgical fasciot success rate than angioplasty al<tne. omy is indicated to prevent irreversible neurologic and soft In patients with f'emoral, popliteal, or tibial artery tissue damage. (infrainguinal) disease, the patency rates for endovascular r(EY P0r{TS revascularization are not as high as for iliac disease. Although infrainguinal disease was traditionally treated with angio- o Acute limb ischemia is characterized by at Ieast one of plasty alone, the advent ot atherectomy devices, nitinol the "6 P's": paresthesia, pain, pallor, pulselessness, (nickel titanium) stents, and paclitaxel coated devices has poikilothermia (coolness), and paralysis. L changed management. However, despite early efficacy data in . Patients with acute limb ischemia should receive emergent randomized controlled triirls. paclitaxel coated devices have anticoagulation therapy and diagnostic angiography in been associated with higher all cause death rates after 2 years preparation for endovascu lar or surgical revascularization. compared with standard treatments. . Careful monitoring after limb reperfusion is required Surgical revasculariz:rtion is still recommended for because of frequent reocclusion, limb edema, and the patients with complex anatomy that may limit percutaneous possibility of compartment syndrome. procedural success and long term patency (e.g., long chronic total occlusions, multisegment disease). The traro most com mon surgical techniques are endarterectomy and surgical bypass. Cardiovascu la r Disease Hybrid revascularization, whicl'r combines surgical and endovascular approaches in a single setting or finite time in Cancer Survivors frirme. has been used more fiequently in conjunction with the Cardiotoxicity of Radiation rise in endovascular revascularization; however, it is not cur rently recommended by clinical practice guidelines. Therapy to the Thorax Radiation therapy improves survival in patients with Hodgkin KEY POIl{IS lymphoma, early stage breast cancel and other thoracic . In patients with life limiting claudication and inadequate malignancies. With higher survival rates, cardiovascular dis response to exercise or pharmacologic therapy, endo ease has emerged as the most common nonmalignant cause of vascular or surgical revascularization is indicated. death in patients treated with chest radiation therapy, account . Patients with chronic limb threatening ischemia should ing fbr 25'){, of deaths in survivors of Hodgkin lymphon.ra. be considered for urgent revascularization. Radiation therapy causes a wide spectrum of cardiovas cular diseases (Table 42). 'lhoracic irradiation damages all cells, including those of the pericardium, myocardium, valves, Acute Limb lschemia coronary and peripheral vasculature, and conduction systenl. Acute limb ischemia is an infic.quent but life threatening with clinical disease usually presenting two to three decades manifestation of PAD. Patients classically present with at least after treatment. The risk fbr radiation induced cardiac injury one of the "6 P's": paresthesia, pain, pallor, pulselessness, is increased further in patients taking concomitant anthracy poikilothermia (coolness), and paralysis. The most common clines or trastuzumab. Contemporary techniques that limit cause is acute thrombosis of a lower extremity artery stent, or total dosage and field size have decreased the risk for cardiac bypass graft. Other causes include thromboembolism, vessel conlplications following radiation therapy. dissection (usually occurring periprocedurally), or trauma. Acute pericarditis is the most common early manifesta Acute limb ischemia represents a trne medical emergency; tion of radiotoxicify, affecting 2.5')(, of patients. The presenta l0'7, to 157, olpatients undergo amputation during initial hos tion, diagnosis, and treatment are similar to those of idiopathic pitalization, and 207, of patients die within 1 year. acute pericarditis. Chronic or constrictive pericarditis develops Anticoagulation, typically with unfractionated heparin, should be initiated as soon as the diagnosis is suspected. TABLE 42, Cardiovascular Diseases Related to Radiation Therapy Specialists with expertise in revascularization should be con sulted, and diagnostic angiography should be performed Cardiomyopathy immediately to define the anatomic level of occlusion. In addi Conduction defects (atrioventricular block, bundle branch block) tion to surgical and endovascular revascularization options, Coronary artery disease catheter directed thrombolysis improves outcomes in patients Coronary microvascular injury with acute limb ischemiu. Pericardial disease (acute pericarditis, chronic constrictive Careful monitoring is required after limb reperflsion pericarditis, pericardial effusion) because of frequent reocclusion, limb edema, and the possi Peripheral artery disease bility of compartment syndrome. Signs and symptoms of com Valvular disease partment syndrome include severe pain, hypoesthesia, and leg

of the iliac arteries, which lras a sigr.rificantly higher long term weakness. lf compartment syndrome occurs, surgical fasciot success rate than angioplasty al<tne. omy is indicated to prevent irreversible neurologic and soft In patients with f'emoral, popliteal, or tibial artery tissue damage. (infrainguinal) disease, the patency rates for endovascular r(EY P0r{TS revascularization are not as high as for iliac disease. Although infrainguinal disease was traditionally treated with angio- o Acute limb ischemia is characterized by at Ieast one of plasty alone, the advent ot atherectomy devices, nitinol the "6 P's": paresthesia, pain, pallor, pulselessness, (nickel titanium) stents, and paclitaxel coated devices has poikilothermia (coolness), and paralysis. L changed management. However, despite early efficacy data in . Patients with acute limb ischemia should receive emergent randomized controlled triirls. paclitaxel coated devices have anticoagulation therapy and diagnostic angiography in been associated with higher all cause death rates after 2 years preparation for endovascu lar or surgical revascularization. compared with standard treatments. . Careful monitoring after limb reperfusion is required Surgical revasculariz:rtion is still recommended for because of frequent reocclusion, limb edema, and the patients with complex anatomy that may limit percutaneous possibility of compartment syndrome. procedural success and long term patency (e.g., long chronic total occlusions, multisegment disease). The traro most com mon surgical techniques are endarterectomy and surgical bypass. Cardiovascu la r Disease Hybrid revascularization, whicl'r combines surgical and endovascular approaches in a single setting or finite time in Cancer Survivors frirme. has been used more fiequently in conjunction with the Cardiotoxicity of Radiation rise in endovascular revascularization; however, it is not cur rently recommended by clinical practice guidelines. Therapy to the Thorax Radiation therapy improves survival in patients with Hodgkin KEY POIl{IS lymphoma, early stage breast cancel and other thoracic . In patients with life limiting claudication and inadequate malignancies. With higher survival rates, cardiovascular dis response to exercise or pharmacologic therapy, endo ease has emerged as the most common nonmalignant cause of vascular or surgical revascularization is indicated. death in patients treated with chest radiation therapy, account . Patients with chronic limb threatening ischemia should ing fbr 25'){, of deaths in survivors of Hodgkin lymphon.ra. be considered for urgent revascularization. Radiation therapy causes a wide spectrum of cardiovas cular diseases (Table 42). 'lhoracic irradiation damages all cells, including those of the pericardium, myocardium, valves, Acute Limb lschemia coronary and peripheral vasculature, and conduction systenl. Acute limb ischemia is an infic.quent but life threatening with clinical disease usually presenting two to three decades manifestation of PAD. Patients classically present with at least after treatment. The risk fbr radiation induced cardiac injury one of the "6 P's": paresthesia, pain, pallor, pulselessness, is increased further in patients taking concomitant anthracy poikilothermia (coolness), and paralysis. The most common clines or trastuzumab. Contemporary techniques that limit cause is acute thrombosis of a lower extremity artery stent, or total dosage and field size have decreased the risk for cardiac bypass graft. Other causes include thromboembolism, vessel conlplications following radiation therapy. dissection (usually occurring periprocedurally), or trauma. Acute pericarditis is the most common early manifesta Acute limb ischemia represents a trne medical emergency; tion of radiotoxicify, affecting 2.5')(, of patients. The presenta l0'7, to 157, olpatients undergo amputation during initial hos tion, diagnosis, and treatment are similar to those of idiopathic pitalization, and 207, of patients die within 1 year. acute pericarditis. Chronic or constrictive pericarditis develops Anticoagulation, typically with unfractionated heparin, should be initiated as soon as the diagnosis is suspected. TABLE 42, Cardiovascular Diseases Related to Radiation Therapy Specialists with expertise in revascularization should be con sulted, and diagnostic angiography should be performed Cardiomyopathy immediately to define the anatomic level of occlusion. In addi Conduction defects (atrioventricular block, bundle branch block) tion to surgical and endovascular revascularization options, Coronary artery disease catheter directed thrombolysis improves outcomes in patients Coronary microvascular injury with acute limb ischemiu. Pericardial disease (acute pericarditis, chronic constrictive Careful monitoring is required after limb reperflsion pericarditis, pericardial effusion) because of frequent reocclusion, limb edema, and the possi Peripheral artery disease bility of compartment syndrome. Signs and symptoms of com Valvular disease partment syndrome include severe pain, hypoesthesia, and leg 111