The U-CLEAR study: Uncovering hemodynamic and vascular contributors to chronic refractory lower extremity edema

Objectives Chronic refractory lower-extremity edema often remains undiagnosed despite standard evaluations that focus primarily on excluding deep vein thrombosis. We aimed to elucidate the underlying etiologies and assess the utility of a comprehensive, structured diagnostic protocol. Methods We retrospectively analyzed a prospectively enrolled, referral-based cohort of 58 patients with chronic refractory lower- extremity edema who underwent a structured multimodal diagnostic protocol after failure of standard noninvasive evaluation. Etiologies were classified as non-thrombotic iliac vein lesions, pulmonary hypertension, superficial venous insufficiency, or multifactorial. Results Non-thrombotic iliac vein lesions, pulmonary hypertension, and superficial venous insufficiency were identified in 55.2%, 48.3%, and 43.1% of patients, respectively. Single etiologies accounted for 51.7% of cases, 41.4% were multifactorial, and 6.9% remained unclassified. Among pulmonary hypertension cases, isolated postcapillary pulmonary hypertension associated with heart failure with preserved ejection fraction was the most common (13.8%). Superficial venous insufficiency was the sole cause in 12.1% of cases, while in others, it coexisted with non-thrombotic iliac vein lesions or pulmonary hypertension. Interventions included iliocaval endovascular therapy (n = 23) and saphenous vein ablation ( n = 10), with the remainder receiving conservative therapy. Over a median follow-up of 2.98 years, 86.2% of patients achieved objective clinical improvement. Conclusions This protocol reduced the number of repeated low-yield ultrasound examinations and facilitated targeted treatment. A structured diagnostic protocol integrating duplex ultrasonography, invasive hemodynamic testing, and intravascular imaging enables accurate etiologic classification of chronic refractory lower extremity edema. This approach identifies treatable contributors, supports tailored interventions, and may improve outcomes while reducing unnecessary testing.