Low-intensity pulsed ultrasound decreases major amputation in patients with critical limb ischemia: 5-year follow-up study.

Farina Mohamad Yusoff,Masato Kajikawa,Takayuki Yamaji,Shinji Kishimoto,Ayumu Nakashima,Aya Mizobuchi,Yuji Takaeko,Yu Hashimoto,Tatsuya Maruhashi,Yukihito Higashi,Yiming Han,Yoshiaki Taniyama

doi:10.1371/journal.pone.0256504

Farina Mohamad Yusoff, Masato Kajikawa + Show 10 more

Open Access

https://doi.org/10.1371/journal.pone.0256504

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Journal: PloS one	Publication Date: Aug 19, 2021
Citations: 2	License type: CC BY 4.0

Affiliation: Hiroshima University Hospital, Hiroshima University

Abstract

Various therapeutic strategies for angiogenesis are performed to improve symptoms in patients with critical limb ischemia (CLI). Pre-clinical studies have shown that low-intensity pulsed ultrasound (LIPUS) exposure induces angiogenesis. LIPUS may be a new stratergy for treatment of CLI. The purpose of this pilot trial was to evaluate outcomes in patients with CLI who were treated with LIPUS. Fourteen patients with CLI, who were not candidates for angioplasty or surgical revascularization, were enrolled in this study. Historical control data were obtained from the Hiroshima University PAD database. The primary endpoints were major amputation and death. The outcomes were compared in 16 lower limbs of the 14 patients with CLI who were treated with LIPUS and in 14 lower limbs of 14 patients with CLI as historical controls. All patients were followed for after 5 years after treatment with LIPUS. The mean duration of LIPUS exposure in the LIPUS group was 381± 283 days. During the 5-year follow-up periods, there were 3 major amputations and 7 deaths in the LIPUS group and there were 14 major amputations and 7 deaths in the historical control group. The overall amputation-free survival rate was significantly higher in patients who were treated with LIPUS than in historical controls. There was no significant difference between overall mortality-free survival rates in the LIPUS group and historical control group. LIPUS is a noninvasive option for therapeutic angiogenesis with the potential to reduce the incidence of major amputations in patients with CLI.

Highlights

Critical limb ischemia (CLI) has been considered as the end-spectrum of peripheral artery disease (PAD) and manifests as chronic (>14 days) inadequate tissue perfusion with or without tissue loss
Amputation-free survival rates and overall survival rates for patients with CLI who were treated with low-intensity pulsed ultrasound (LIPUS) were compared to those of historical controls
Kaplan-Meier analysis revealed the overall amputation-free survival rate was significantly higher in patients who were treated with LIPUS than in historical controls (Fig 2)

Summary

Introduction

Critical limb ischemia (CLI) has been considered as the end-spectrum of peripheral artery disease (PAD) and manifests as chronic (>14 days) inadequate tissue perfusion with or without tissue loss. The cost of care, re-hospitalization, re-interventions and rehabilitation after limb amputation has been a global economic burden. All of these factors significantly impair the quality of life for patients with CLI by imposing a substantial burden on a patient’s emotional, social, and physical well-being [6]. Through stimulation of angiogenic factors such as interleukin-8, basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF), via the extracellular signal-regulated kinase (ERK)/Akt/endothelial nitric oxide synthase/VEGF pathway, LIPUS exposure has the potential to provide beneficial cellular therapeutic effects on limb ischemia by inducing microvascular regeneration and to improve clinical symptoms in patients with CLI and reduce the risk of amputation [14]. The present study was performed to evaluate 5-year outcomes in atherosclerotic PAD patients with CLI who were treated with LIPUS

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