Patterns of Arterial Obstruction in Chronic Limb-Threatening Ischemia: A Comprehensive Histopathological Analysis of Amputated Limbs

Introduction: Chronic limb-threatening ischemia (CLTI) represents the most severe manifestation of peripheral artery disease (PAD). The obstructive arterial pattern leading to CLTI is a mix of big artery disease (BAD) and small artery disease (SAD), however we lack data regarding their prevalence and distribution. This study investigates the pathological patterns of vascular obstruction in patients with CLTI who underwent major amputation for unreconstructable vascular disease and/or unsalvageable foot. Methods: This is a prospective, observational study. Arterial segments were systematically collected throughout the entire vascular tree of amputated limbs from CLTI patients and analysed for atherosclerotic lesions, medial artery calcification (MAC), and intimal thickening (IT). Results: The study included 26 patients (53.8% male, mean age 77.9 ± 8.9 years). Most of the patients presented with extensive tissue loss (96.1%) and severe ischemia (100%), high rates of infection (92.3%), and advanced Global Limb Anatomic Staging System stages (84.7%). Of 310 arterial segments, 73.2% showed MAC, 81.9% exhibited IT, and 18.7% had atherosclerotic lesions. Atherosclerotic lesions were confined to femoro-popliteal (86.7%) and proximal below-the-knee (BTK) arteries (27.5%), disappearing in distal BTK and foot arteries. MAC and IT were ubiquitous and associated in the femoro-popliteal arteries (P. 0.04), proximal BTK arteries (0.003), distal BTK arteries (0.077) and foot arteries (P 0.046). Obstructing (>50% lumen diameter) atherosclerotic lesions were the primary cause of obstruction in femoro-popliteal arteries, while obstructive IT was more common in BTK and foot arteries. Conclusion: Arterial obstruction in CLTI results from both, atherosclerosis and MAC-IT, with MAC-IT predominating in distal arteries.