Injury and Healing Response of Healthy Peripheral Arterial Tissue to Intravascular Lithotripsy: A Prospective Animal Study

Abstract

ObjectivesIntravascular lithotripsy (IVL) is a novel clinical technique for the management of severely calcified lesions. However, the biological effects of shock wave on the healthy arterial tissue have not been demonstrated. The preclinical safety study aimed to investigate the vascular response to IVL shock wave compared to plain old balloon angioplasty (POBA) in porcine peripheral arteries.MethodsThe left and right iliofemoral arterial segments of 16 mini-pigs were subjected to IVL and POBA, respectively. The vascular response was evaluated using quantitative vascular angiography (QVA), light microscopy, and scanning electron microscopy (SEM) at 0, 5, and 28 days.ResultsWith the emission of shock wave, adjacent muscle contraction was observed. QVA showed there was no statistically significant difference in percent diameter stenosis and late lumen loss between the two groups. SEM examination showed the endothelial cell layer was intact in both groups at all timepoints. Under light microscopy, no area stenosis was observed. However, IVL shock wave resulted in significantly higher percent area stenosis and intimal area at 28 days. Neointima score showed a trend toward a higher rate in the IVL group, although there was no statistically significant difference at 28 days. There were no statistically significant differences in the scored parameters between groups at all timepoints. However, the parameters of inflammation and neointima showed a trend toward higher scores in the IVL group. After disruption of the internal elastic lamina, the arteries demonstrated significantly neointimal thickening.ConclusionsThe safety and operability of IVL are comparable to POBA. The histological response of healthy arteries to IVL shock wave is mild and sustained. IVL shock wave do not cause serious vascular tissue damage, especially endothelial denudation.

In vivo evaluation of intravascular lithotripsy in a healthy porcine coronary model

“…17,18 This study confirmed for the first time that IVL does not cause arrhythmia, acute arterial occlusion, vasospasm, or perforation in healthy coronary arteries. This result is consistent with that of a preclinical study of the shock wave balloon in peripheral arteries, 12 which further verified the safety of this technique.…”

“…14,19 In addition, the epicardial coronary artery is mainly surrounded by loose adipose tissue, whereas the peripheral artery is wrapped by a large amount of skeletal muscle. Previous studies have shown that shock waves can be transmitted to nearby skeletal muscles through peripheral arteries, 12 which may alleviate damage to the vascular wall of peripheral arteries. Further study and optimization of the energy emitted by the coronary IVL balloon are needed to reduce damage of coronary media and adventitia.…”

“…In theory, the effect of shock waves passing through soft tissues with acoustic impedance, such as water, muscle, and fat, is very mild. In preclinical studies, IVL has been shown to cause minimal damage to the normal porcine iliac artery and adjacent structures 12,13 . However, the effects of shock waves on the coronary artery remain unclear.…”

“…In preclinical studies, IVL has been shown to cause minimal damage to the normal porcine iliac artery and adjacent structures. 12,13 However, the effects of shock waves on the coronary artery remain unclear. Considering the structural differences between the coronary and peripheral arteries and the rapid increase in the use of IVL in coronary artery diseases, it is essential to clarify the effect of shock waves on the coronary artery for the safe application of IVL.…”

Review of intravascular lithotripsy for treating coronary, peripheral artery, and valve calcifications

“…Since circumferential sonic pressure waves also can affect noncalcium plaque, post‐IVL procedural inflammation may occur. Recent studies have demonstrated inflammation of the media and adventitia layers in response to IVL, 31 which may lead to negative remodeling. Future studies investigating the long‐term impact of IVL, and other calcium modification techniques, are also needed.…”