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

Alessandro Ucci1, Claudio Bianchini Massoni1, Paolo Perini1

  • 1Department of Medicine and Surgery, Vascular Surgery, Parma University, Parma, Italy.

Annals of Vascular Surgery
|October 19, 2025
PubMed

Insights

Chronic limb-threatening ischemia (CLTI) involves both atherosclerosis and medial artery calcification with intimal thickening (MAC-IT). MAC-IT is the main cause of obstruction in the small arteries of the foot and below-the-knee in CLTI patients.

Area of Science:

  • Vascular Surgery
  • Cardiovascular Research
  • Pathology

Background:

  • Chronic limb-threatening ischemia (CLTI) is the most severe form of peripheral artery disease.
  • The arterial obstruction patterns in CLTI, involving both large and small vessel disease, are not fully understood.
  • Understanding these patterns is crucial for effective treatment strategies.

Purpose of the Study:

  • To investigate the pathological patterns of vascular obstruction in patients with CLTI undergoing major amputation.
  • To determine the prevalence and distribution of atherosclerotic lesions, medial artery calcification (MAC), and intimal thickening (IT) in the entire vascular tree of CLTI limbs.
  • To differentiate the causes of arterial obstruction in femoropopliteal versus below-the-knee (BTK) and foot arteries.

Main Methods:

  • Prospective observational study design.
  • Systematic collection and analysis of arterial segments from amputated limbs of CLTI patients.
  • Assessment of atherosclerotic lesions, MAC, and IT in all analyzed arterial segments.

Main Results:

  • Atherosclerotic lesions were primarily found in femoropopliteal and proximal BTK arteries, absent in distal BTK and foot arteries.
  • Medial artery calcification (MAC) and intimal thickening (IT) were ubiquitous throughout the vascular tree, particularly in distal segments.
  • Obstructive atherosclerotic lesions dominated in femoropopliteal arteries, while obstructive MAC-IT was more prevalent in BTK and foot arteries.

Conclusions:

  • Arterial obstruction in CLTI is multifactorial, caused by both atherosclerosis and MAC-IT.
  • Medial artery calcification and intimal thickening (MAC-IT) are the predominant pathological patterns causing obstruction in the distal arteries (BTK and foot) in CLTI.
  • These findings highlight the importance of considering small vessel disease in CLTI management.
Abstract

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