Abstract
INTRODUCTION: Balloon angioplasty is one of the most common treatments for Peripheral Artery Disease (PAD), but its clinical outcomes continue to disappoint, particularly when managing calcified lesions. We characterized luminal gains and damage after balloon angioplasty using high-resolution imaging, histology, and mechanical testing. METHODS: Fresh diseased human femoropopliteal arteries (FPA) from n=15 subjects (average age 69 ± 9, range 53-90 years) with different calcium burdens were imaged before, during, and after angioplasty using micro-computed tomography, and luminal gains, calcium fractures, and resulting dissections were quantified. Histology was used to assess structural damage, and biaxial mechanical testing determined damage initiation stretches and stresses. RESULTS: In severely calcified FPAs, calcification often manifested as rings or large plate-like deposits. When calcium spanned the entire circumference, angioplasty produced longitudinal cracks but ~8% luminal area gain. In less calcified arteries, damage manifested primarily as tears along the internal elastic lamina and within the tunica media. Dissections were present in 53% of all FPAs after angioplasty, with a higher prevalence in more calcified vessels and vessels with stenosis (75% each). Damage initiated at lower biaxial stretches (1.11 ± 0.02 vs 1.14-1.15) and lower longitudinal stresses (44 ± 22 kPa vs 57 ± 31 kPa) in severely calcified specimens compared with lightly calcified arteries, but larger calcium burdens generally required more circumferential stress to initiate damage (66 ± 27 kPa). Diabetes mellitus was associated with a higher calcium burden. CONCLUSIONS: Severe calcification limits luminal gains after angioplasty. Less calcified arteries accumulate damage to the healthier wall while calcium remains mostly intact. These results may inform clinical strategies and the development of better devices to treat PAD.