Limb Ischemia (Peripheral Vascular Disease) Case File

Limb Ischemia (Peripheral Vascular Disease) Case File

Eugene C. Toy, MD, Gabriel M. Aisenberg, MD

Case 13

A 58-year-old man presents to the emergency center (EC) complaining of severe pain in his left calf and foot that woke him from his sleep. He has a history of chronic stable angina, hypercholesterolemia, and hypertension, for which he takes aspirin, atenolol, and simvastatin. For several years, he has experienced pain in both calves and feet with walking. The pain has gradually progressed so that he can now walk only 100 ft before he has to stop. He occasionally has experienced mild pain in his feet at night, but the pain usually gets better when he sits up and hangs his feet off the bed. This time, the pain was more severe and did not improve, and he now feels like the foot is numb, and he cannot move his toes.

On physical examination, he is afebrile, with a heart rate of 72 beats per minute (bpm) and a blood pressure of 125/74 mm Hg. Head and neck examination is significant for a right carotid bruit. His chest is clear to auscultation; his heart rhythm is regular with a nondisplaced apical impulse, an S4 gallop, and no murmurs. His abdomen is benign, with no tenderness or masses. He has bilateral femoral bruits, and his femoral and popliteal pulses are palpable bilaterally. His pedal pulses are diminished; they are present on the right but absent on the left. The left distal leg and foot are pale and cold to touch, with very slow capillary refill.

▶ What is the most likely diagnosis?

▶ What is your next step?

ANSWERS TO CASE 13:

Limb Ischemia (Peripheral Vascular Disease)

Summary: A 58-year-old man presents with

• Severe pain and numbness of his left foot
• Angina and a carotid bruit suggesting systemic atherosclerotic disease
• Femoral bruits bilaterally and bilateral calf claudication
• Sudden onset of pain, pallor, and pulselessness in the left foot

Most likely diagnosis: Acute limb ischemia, either thrombotic arterial occlusion or embolism from a more proximal source.

Next step: Angiogram of the lower extremity.

ANALYSIS

Objectives

1. Understand the clinical presentation of a patient with atherosclerotic peripheral vascular disease, including acute limb ischemia. (EPA 1)
2. Describe the evaluation and medical management of peripheral vascular disease. (EPA 3, 4)
3. Understand the indications for extremity revascularization. (EPA 4, 10, 12)

Considerations

This patient has diffuse atherosclerotic vascular disease, including coronary artery disease, carotid disease, and peripheral vascular disease. His history of calf pain with ambulation and resolution with rest is classic for claudication. Recently, the perfusion of his left leg likely was worsening, requiring his waking up and dangling his leg to enable blood flow and to help the pain. Rest pain is a warning sign of possible critical limb vascular insufficiency. The patient complains of the sudden onset of pain, pallor, and pulselessness, indicative of acute arterial occlusion. His limb ischemia may result from acute arterial occlusion caused by an embolus possibly originating from a thrombus in the heart, the aorta, or a large proximal artery such as the iliac. Magnetic resonance (MR) or computed tomography (CT) angiography, or possibly a conventional arteriogram, would be needed to first determine the arterial anatomy and define the best mode of revascularization. Then, depending on the level of occlusion, the patient may require urgent arterial thromboembolectomy.

APPROACH TO:

Peripheral Vascular Disease

DEFINITIONS

ANKLE-BRACHIAL INDEX (ABI): Ratio of ankle to brachial systolic blood pressure, determined clinically or by using Doppler ultrasound flow. Normal ratio is 0.9–1.4.

CLAUDICATION: Pain, ache, or cramp in muscles that increases with walking or leg exertion in a predictable manner and resolves with rest.

“6 P’s” OF PERIPHERAL VASCULAR DISEASE: Pain, pallor, paresthesia, poikilothermia (coolness), pulselessness, and paralysis.

CLINICAL APPROACH

Pathophysiology

Although atherosclerosis is a systemic disease, clinicians often focus on the coronary circulation and pay less attention to the extremities. Yet, atherosclerotic peripheral arterial disease (PAD) is estimated to affect up to 16% of Americans who are 55 years and older and may exist without clinically recognized coronary or cerebrovascular disease. Furthermore, PAD confers the same risk of cardiovascular death as in persons with a prior myocardial infarction or stroke. The most important risk factors for PAD are cigarette smoking and diabetes mellitus. Hypertension, dyslipidemia, and elevated homocysteine levels also play significant roles.

Less common causes of chronic peripheral arterial insufficiency include thromboangiitis obliterans, or Buerger disease, an inflammatory condition of small- and medium-sized arteries that may affect the upper or lower extremities. It is found almost exclusively in smokers, especially men younger than 40 years. Fibromuscular dysplasia is a hyperplastic disorder affecting medium and small arteries that usually occurs in women. Generally, the renal or carotid arteries are involved, but when the arteries to the limbs are affected, the clinical symptoms are identical to those of atherosclerotic PAD. Takayasu arteritis is an inflammatory condition, seen primarily in younger women, that usually affects branches of the aorta, most commonly the subclavian arteries, and causes arm claudication and Raynaud phenomenon, along with constitutional symptoms such as fever and weight loss.

Patients with chronic peripheral arterial insufficiency who present with sudden unremitting pain may have an acute arterial occlusion, most commonly the result of embolism or in situ thrombosis. The heart is the most common source of emboli; conditions that may cause cardiogenic emboli include atrial fibrillation, dilated cardiomyopathy, and endocarditis. Artery-to-artery embolization of atherosclerotic debris from the aorta or large vessels may occur spontaneously or, more often, after an intravascular procedure, such as arterial catheterization. Emboli tend to lodge at the bifurcation of two vessels, most often in the femoral, iliac, popliteal, or tibioperoneal arteries. Arterial thrombosis may occur in atherosclerotic vessels at the site of stenosis or in an area of aneurysmal dilation, which may also complicate atherosclerotic disease.

Clinical Presentation

Patients with acute arterial occlusion may present with a number of signs, which can be remembered as six P’s: pain, pallor, pulselessness, paresthesias, poikilothermia (coolness), and paralysis. The first five signs occur fairly quickly with acute ischemia; paralysis will develop if the arterial occlusion is severe and persistent.

The most common symptom associated with chronic arterial insufficiency caused by PAD is intermittent claudication (pain, achiness, fatigue, or other discomfort that occurs in one or both legs during exercise and is relieved with rest). It is ischemic pain and occurs distal to the site of the arterial stenosis, most commonly in the calves. The symptoms often are progressive and may severely limit a patient’s activities and reduce the patient’s functional status. An individual with proximal stenosis, such as aortoiliac disease, may complain of exertional pain in the buttocks and thighs. Severe occlusion may produce rest pain, which often occurs at night and may be relieved by sitting up and dangling the legs, using gravity to assist blood flow to the feet.

On physical examination, palpation of the peripheral pulses may be diminished or absent below the level of occlusion; bruits may indicate accelerated blood flow velocity and turbulence at the sites of stenosis. Bruits may be heard in the abdomen with aortoiliac stenosis and in the groin with femoral artery stenosis. Elevation of the feet above the level of the heart in the supine patient (known as the Buerger test) often induces pallor in the soles. If the legs are then placed in the dependent position, they frequently develop rubor as a result of reactive hyperemia. Chronic arterial insufficiency may cause hair loss on the legs and feet, thickened and brittle toenails, and shiny atrophic skin. Severe ischemia may produce ulcers or gangrene, typically at the distal extremities.

When PAD is suspected, the test most commonly used to evaluate for arterial insufficiency is the ABI. Systolic blood pressures are measured by Doppler ultrasonography in each arm and in the dorsalis pedis and posterior tibial arteries in each ankle. Normally, blood pressures in the large arteries of the legs and arms are similar. In fact, blood pressures in the legs often are higher than in the arms because of an artifact of measurement, so the normal ratio of ankle-to-brachial pressures is 0.9–1.4. Patients with claudication typically have ABI values ranging from 0.41 to 0.90, and those with critical leg ischemia have ABI values less than or equal to 0.40. Further evaluation with exercise treadmill testing can clarify the diagnosis when symptoms are equivocal, allow for assessment of functional limitations (eg, maximal walking distance), and evaluate for concomitant coronary artery disease. Additional imaging, such as magnetic resonance angiography (MRA) or computed tomography angiography (CTA), is not used in routine diagnostic evaluation but can help determine arterial anatomy before a revascularization procedure.

Treatment

The goals of therapy include reductions in cardiovascular morbidity, improvement in quality of life by alleviating symptoms, and preservation of limb viability.

Risk Factor Modification. The first step in managing patients with PAD is risk factor modification. Because of the likelihood of coexisting atherosclerotic vascular disease such as coronary artery disease, patients with symptomatic PAD have an

estimated mortality rate of 50% in 10 years, most often as a consequence of cardiovascular events. Smoking is, by far, the single most important risk factor impacting both claudication symptoms and overall cardiovascular mortality. Besides slowing the progression to critical leg ischemia, tobacco cessation reduces the risk of fatal or nonfatal myocardial infarction by as much as 50%, more than any other medical or surgical intervention. In addition, treatment of hypercholesterolemia, control of hypertension and diabetes, and use of antiplatelet agents such as aspirin or clopidogrel all have been shown to improve cardiovascular health and may have an effect on peripheral arterial circulation. Carefully supervised exercise programs can improve muscle strength and prolong walking distance by promoting the development of collateral blood flow.

Medications for Claudication. Specific medications for improving claudication symptoms have been used with some benefit. Pentoxifylline, a substituted xanthine derivative that increases erythrocyte elasticity, has been reported to decrease blood viscosity, thus allowing improved blood flow to the microcirculation; however, results from clinical trials are conflicting, and the benefit of pentoxifylline, if present, appears small. Cilostazol, a phosphodiesterase inhibitor with vasodilatory and antiplatelet properties, has been approved by the Food and Drug Administration for treatment of claudication. It has been shown in randomized controlled trials to improve maximal walking distance and quality of life. Figure 13–1 shows an algorithm for management of PAD.

Revascularization. Patients with critical leg ischemia, defined as ABI less than 0.40, severe or disabling claudication, unremitting rest pain, or nonhealing ulcers, should be evaluated for a revascularization procedure. This can be accomplished by percutaneous angioplasty, with or without placement of intra-arterial stents, or surgical bypass grafting. Angiography (either conventional arteriogram or MRA) should be performed to define the flow-limiting lesions prior to any vascular procedure. Ideal candidates for arterial revascularization are those with discrete stenosis of large vessels; diffuse atherosclerotic and small-vessel disease responds poorly.

Managing acute arterial occlusions. Rapid restoration of arterial supply is mandatory in patients with an acute arterial occlusion that threatens limb viability. Initial management includes anticoagulation with heparin to prevent propagation of the thrombus. The affected limb should be placed below the horizontal plane without any pressure applied to it. Conventional arteriography is used to identify the location of the occlusion and to plan for the method of revascularization. Surgical removal of an embolus or arterial bypass may be performed, particularly if a large proximal artery is occluded. A balloon catheter may also be used to remove the clot. Alternatively, a catheter can be used to deliver intra-arterial thrombolytic therapy directly into the thrombus, sometimes in conjunction with stent placement. In comparison to systemic fibrinolytic therapy, localized infusion is associated with fewer bleeding complications.

CASE CORRELATION

• See also Case 2 (Metabolic Syndrome), Case 3 (Acute Coronary Syndrome), and Case 6 (Hypertension, Outpatient).

Figure 13–1. Algorithm for management of peripheral arterial disease. ABI, ankle-brachial index; ACE, angiotensin-converting enzyme; ASA, aspirin; BP, blood pressure; LDL, low-density lipoprotein; MRA, magnetic resonance angiography; PAD, peripheral arterial disease. (Data from Hiatt W. Medical treatment of peripheral arterial disease and claudication. N Engl J Med. 2001;344:1608-1621.)

COMPREHENSION QUESTIONS

13.1 A 49-year-old smoker with hypertension, diabetes, and hypercholesterolemia comes to the clinic complaining of pain in his calves when he walks two to three blocks. Which of the following therapies might offer him the greatest benefit in symptom reduction and in overall mortality?

A. Aspirin

B. Limb revascularization procedure

C. Cilostazol

D. Smoking cessation

E. Pravastatin

13.2 A 31-year-old male smoker presents with resting pain in his legs and a nonhealing foot ulcer. Which of the following is the most likely cause of arterial insufficiency in this patient?

A. Cholesterol embolism

B. Fibromuscular dysplasia

C. Thromboangiitis obliterans (Buerger disease)

D. Takayasu arteritis

E. Psychogenic pain

13.3 A 21-year-old woman presents with fever, fatigue, and unequal pulses and blood pressures in her arms. Which of the following is the most likely cause of arterial insufficiency in this patient?

A. Cholesterol embolism

B. Fibromuscular dysplasia

C. Thromboangiitis obliterans (Buerger disease)

D. Takayasu arteritis

E. Psychogenic pain

13.4 A 62-year-old man presents with livedo reticularis and three blue toes, including one with gangrene following cardiac catheterization. Which of the following is the most likely cause of this patient’s findings?

A. Cholesterol embolism

B. Fibromuscular dysplasia

C. Thromboangiitis obliterans (Buerger disease)

D. Takayasu aortitis

E. Psychogenic pain

13.5 A 67-year-old woman is noted to have significant peripheral vascular disease. She is evaluated by the cardiovascular surgeon but not felt to be a surgical candidate. Which of the following conditions is likely to be present in this patient?

A. Diffuse atherosclerotic disease

B. Leg pain at rest

C. Symptoms that do not improve with pharmacologic management

D. Nonhealing ulcers of the ankle

ANSWERS

13.1 D. Tobacco cessation is the most important intervention to improve cardiovascular morbidity and mortality in high-risk patients, such as those with PAD, and to improve claudication symptoms. Cilostazol (answer C) may help with claudication symptoms but will not affect cardiovascular mortality. Aspirin (answer A), angiotensin-converting enzyme inhibitors, and beta-hydroxy-beta-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors are important adjuncts for risk factor modification and for relief of symptoms, but their benefits pale in comparison to smoking cessation.

13.2 C. Thromboangiitis obliterans, or Buerger disease, is a disease of young male smokers and may cause symptoms of chronic arterial insufficiency in either legs or arms. Cholesterol embolisms (answer A) are most likely to occur after a vascular procedure, including cardiac catheterization. Location of arterial insufficiency is also important for differentiation of the cause. For example, fibromuscular dysplasia (answer B) is more likely to involve the renal arteries and extracranial cerebrovascular arteries rather than peripheral arteries of the extremities. Takayasu arteritis (answer D) is a large-vessel vasculitis that primarily affects the aorta and the primary branches.

13.3 D. Takayasu arteritis is associated with symptoms of inflammation such as fever, and it most often affects the subclavian arteries, producing stenotic lesions that may cause unequal blood pressures, diminished pulses, and ischemic pain in the affected limbs. The other answer choices typically do not cause fever.

13.4 A. Embolism of cholesterol and other atherosclerotic debris from the aorta or other large vessels to small vessels of skin or digits may complicate any intra-arterial procedure. Signs may include livedo reticularis, ulcers, gangrene, renal involvement, and ocular involvement. Eosinophilia may be found on laboratory work. The other answer choices may be associated with pain, but not sudden onset of ischemia.

13.5 A. Surgical therapy is reserved for those with severe symptoms after exercise despite pharmacologic agents or in cases where quality of life is impaired. Pain at rest (answer B), refractoriness to medical therapy (answer C), and the presence of nonhealing ulcers and/or gangrene (answer D) are some indications for surgical intervention. Duplex ultrasound can help discern whether the patient is a potential surgical candidate. Arteriography may also be performed. Diffuse atherosclerotic disease is a contraindication for surgery since bypass would not help in the face of significant and widespread disease.

CLINICAL PEARLS

▶ Smoking cessation is the single most important intervention for athero-sclerotic peripheral vascular disease. Other treatments include pentoxi-fylline or cilostazol, structured regular exercise, and cardiovascular risk factor modification.

▶ Revascularization by angioplasty or bypass grafting may be indicated for patients with debilitating claudication, ischemic rest pain, or tissue necrosis.

▶ Acute arterial occlusion that threatens limb viability is a medical emer-gency and requires immediate anticoagulation and investigation with conventional arteriography.

▶ Acute severe ischemia of an extremity causes the “six P’s”: pain, pallor, pulselessness, paresthesias, poikilothermia, and paralysis.

▶ Chronic incomplete arterial occlusion may result only in exertional pain or fatigue, pallor on elevation of the extremity, and rubor on dependency.

REFERENCES

Creager M, Loscalzo J. Arterial diseases of the extremities. In: Jameson J, Fauci AS, Kasper DL, et al, eds. Harrison’s Principles of Internal Medicine. 20th ed. New York, NY: McGraw Hill; 2018. 

Gerhard-Herman MD, Gornik HL, Barrett C, et al. 2016 AHA/ACC guideline on the management of patients with lower extremity peripheral artery disease: executive summary: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Circulation. 2017;135(12):686-725. 

Hankey GJ, Normal PE, Eikelboom JW, et al. Medical treatment of peripheral arterial disease. JAMA. 2006;295:547. 

Hirsch AT, Haskal ZJ, Hertzer NR, et al. ACC/AHA 2005 practice guidelines for the management of patients with peripheral arterial disease. Circulation. 2006;113:e463. Katzen BT. Clinical diagnosis and prognosis of acute limb ischemia. Rev Cardiovasc Med. 2002; 3(suppl 2):S2-S6.

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