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CLINICAL STATEMENTS AND GUIDELINES

Circulation. 2024;149:e1313–e1410. DOI: 10.1161/CIR.0000000000001251 June 11, 2024 e1373

Synopsis ALI is a vascular emergency that requires rapid diagnosis and management, including timely revascularization to reperfuse the ischemic limb (see Section 11.1, “Initial Clinical Evaluation and Diagnostic Approach to ALI,” and Section 11.2.1, “Revascularization for ALI”). Causes of ALI include acute thrombosis of native vessel or bypass grafts in the setting of known diagnosis of PAD, arterial embolism, dissection, and trauma.5 Determination of the potential underlying cause of ALI is crucial to implementing therapies to prevent recurrent events, but such an evaluation should not delay revascularization and other potentially limb-saving therapies. Potential underlying causes of ALI are listed in Table 20.

Recommendation-Specific Supportive Text

1 Underlying PAD is a common cause of ALI. Among

patients with PAD, the rate of ALI is 0.8% to 1.7%.6–8 Most patients with ALI attributable to underlying PAD have a history of lower extremity revascularization, amputation, or lower baseline ABI values (≤0.60).8 Thus, for all patients presenting with ALI, a targeted history regarding known PAD, including previous revascularization procedures, should be obtained. Beyond PAD, other key causes of ALI include native vessel thrombosis and systemic embolization.6 Thus, the history and review of systems should focus on uncovering clinical evidence of these other conditions that can result in ALI, including atrial fibrillation, MI or cardiomyopathy with left ventricular thrombus, valvular heart disease, aortic disease, and hypercoagulable states. A recent history of vascular access (eg, femoral access for catheterization) should be obtained. The history should also capture current medications, including anticoagulants (and when last taken) and family history of thrombosis. The review of systems is performed to capture those that can be clues to these underlying conditions (eg, heart palpations, tachycardia, recent chest pain, symptoms of heart failure, asymmetric leg swelling). Recently, the association of ALI with COVID-19 infection has been established, thus querying for known recent COVID-19 infection as well as fever, cough, and other signs of viral infection should be included.9,10 Although the physical examination initially focuses on rapid targeted evaluation of the ischemic limb(s) to plan revascularization (see Section 11.2.1, “Revascularization for ALI”), further comprehensive examination includes assessment of the heart (eg, for irregular rhythm, presence of murmur) and lungs (eg, for signs of congestive heart failure or infection), limb swelling (eg, suggesting deep vein thrombosis with paradoxical embolization), and examination for other signs of systemic illness. Potential underlying causes of ALI are presented in Table 20. 2.	 With rare exceptions, treatment of ALI should not

be delayed for testing for the underlying cause. For patients in whom underlying PAD is the unclear cause of the ALI event, additional evaluation can be useful to identify a potential underlying cause and implement therapy to prevent recurrence. The association between atrial fibrillation and lower extremity embolic events has been well described, and long-term oral anticoagulation in such patients is important to prevent recurrence.1 Beyond the history and physical examination, testing for an underlying cardiac cause can include electrocardiography or additional heart rhythm monitoring to detect atrial fibrillation, electrocardiography to detect evidence of MI, and echocardiography to further determine whether a cardiac cause for thromboembolism exists, such as valvular vegetation, left atrial or left ventricular thrombus, or intracardiac shunt.1 Landry et al4 reported a series of patients with lower extremity ALI unattributable to underlying PAD or aortic pathology and found a significant prevalence

Table 20.  Underlying Causes of ALI1,4–6,9–18 Underlying PAD with acute thrombosis Thrombosis at sites of arterial stenosis Artery to artery embolization Thrombosis of previous bypass grafts Arterial stent thrombosis Cardiac embolization Atrial fibrillation (ie, left atrial/appendage thrombus) Other intracardiac thrombus (eg, left ventricular thrombus due to

cardiomyopathy) Infective endocarditis Valvular heart disease (eg, mitral stenosis) Intracardiac shunt including paradoxical embolization across a patent

foramen ovale Iatrogenic/access site-related thrombosis (eg, postfemoral access for catheterization) Aortic or arterial dissection Arterial trauma Arterial aneurysm-related thromboembolism (eg, popliteal artery) Hypercoagulable states Antiphospholipid antibody syndrome Heparin-induced thrombocytopenia Cancer-associated arterial thrombosis Others Cancer therapy-associated thrombosis Platinum-based chemotherapy Tyrosine kinase inhibitors Others Other systemic proinflammatory states Vasculitis Sepsis Viral illness, including COVID-19 Other infectious processes Popliteal artery entrapment syndrome ALI indicates acute limb ischemia; COVID-19, coronavirus disease-2019; and PAD, peripheral artery disease.

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