Abstract Body (Do not enter title and authors here): BACKGROUND: Chronic limb threatening ischemia (CLTI) is defined as the presence of peripheral artery disease (PAD) in combination with rest pain or tissue loss and represents advanced arterial occlusive disease. Little is known about associated venous pathology as prior pathologic reports were limited to evaluation of maximally diseased arterial lesions.

OBJECTIVES: To characterize arterial and venous histopathology in patients with CLTI.

METHODS: Tissue containing peripheral arteries and veins from the femoropopliteal to distal tibial arteries was harvested from 10 patients who underwent amputation for CLTI (Fig 1). Vessels were sectioned at 0.5 cm intervals, and histopathologic features were catalogued across 535 arterial and 493 venous sections.

RESULTS: Consistent with PAD, atherosclerotic lesions were more prevalent in proximal than distal arteries; 81.8% (27/33) femoropopliteal sections compared to 26.6% (134/502) of tibial sections. Severe stenosis (>90%) was noted in 21.9% (117) of sections and was associated with atherosclerosis (pathological intimal thickening, fibroatheroma, fibrocalcific or fibro-osseous lesions) in 10.3% (12), luminal thrombi in 68.4% (80), or both in 21.4% (25) of arterial sections.

In all patients and in 99.0% (488/493) of venous sections, irrespective of the degree of arterial luminal stenosis, adjacent large (≥1000µm) and small diameter veins revealed marked thickening of the vessel wall comprised of fibrosis and smooth muscle hyperplasia (Fig 2). While large veins retained luminal patency, small veins exhibited severe luminal stenosis or obliteration. Venous thrombosis was uncommon, occurring in 3.0% (15/493) of sections.

CONCLUSIONS: Venous remodeling with stenosis and occlusion is highly prevalent and coincides with arterial disease pathology in patients with CLTI. This novel finding of previously underappreciated and severely altered venous pathology suggests a possible additional mechanism for limb ischemia in CLTI.