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Randomized Controlled Trial
. 2023 Jun 23;18(6):e0287714.
doi: 10.1371/journal.pone.0287714. eCollection 2023.

A randomized, double-blind, placebo-controlled pilot trial of low-intensity pulsed ultrasound therapy for refractory angina pectoris

Tomohiko Shindo  1 , Kenta Ito  1 , Tsuyoshi Ogata  1 , Ryo Kurosawa  1 , Kumiko Eguchi  1 , Yuta Kagaya  1 , Kenichiro Hanawa  1 , Yuhi Hasebe  1 , Kensuke Nishimiya  1 , Takashi Shiroto  1 , Jun Takahashi  1 , Yasuo Okumura  2 , Teruo Noguchi  3 , Yukio Ozaki  4 , Hiroyuki Daida  5 , Nobuhisa Hagiwara  6 , Tohru Masuyama  7 , Taishiro Chikamori  8 , Yoshihiro Fukumoto  9 , Kenichi Tsujita  10 , Hiroshi Kanai  11 , Satoshi Yasuda  1 , Hiroaki Shimokawa  12
Affiliations
Randomized Controlled Trial

A randomized, double-blind, placebo-controlled pilot trial of low-intensity pulsed ultrasound therapy for refractory angina pectoris

Tomohiko Shindo et al. PLoS One. .

Abstract

Background: Despite the advances in the treatment of cardiovascular diseases, effective treatment remains to be established to improve the quality of life and prognosis of patients with chronic coronary syndromes. This study was aimed to evaluate the effectiveness and safety of the low-intensity pulsed ultrasound (LIPUS) therapy, which we have developed as a novel non-invasive angiogenic therapy through upregulation of endothelial nitric oxide synthase (eNOS).

Methods and findings: We conducted a randomized, double-blind, placebo-controlled (RCT) pilot trial of the LIPUS therapy for patients with refractory angina pectoris. The patients who received optimal medical therapy without indication of PCI or CABG due to the lack of graftability or complexity of coronary lesions were enrolled. They were randomly divided into the LIPUS treatment group (N = 31) and the placebo group (N = 25) in a 1:1 fashion. The LIPUS therapy was performed in a transthoracic manner for 20 min for 3 sections each (mitral, papillary muscle, and apex levels) under the conditions that we identified; frequency 1.875 MHz, intensity 0.25 MPa, and 32 cycles. The primary endpoint was weekly use of nitroglycerin. Secondary endpoints included stress myocardial perfusion imaging and others. The average weekly nitroglycerin use (times/week) was decreased from 5.50 to 2.44 in the LIPUS group and from 5.94 to 2.83 in the placebo group. The changes in the average weekly nitroglycerin use were comparable; -3.06 (95% CI: -4.481 to -1.648) in the LIPUS group (P<0.01) and -3.10 (95% CI: -4.848 to -1.356) in the placebo group (P<0.01). No adverse effects were noted.

Conclusions: In the present study, the LIPUS therapy did not further ameliorate chest pain as compared with optimal medications alone in patients with refractory angina pectoris. The present findings need to be confirmed in another trial with a large number of patients. (Registration ID: UMIN000012369).

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Conflict of interest statement

The authors have declared that no competing interests exist.

Figures

Fig 1
Fig 1. LIPUS therapy for angina pectoris.
(A) Left, LIPUS therapy equipment (LIPUS machine and chest band). Right, 3 cross-sections for the therapy (mitral valve, papillary muscle, and apical levels). (B) Trial protocols. (C) CONSORT flow diagram. LIPUS: low-intensity pulsed ultrasound.
Fig 2
Fig 2. Results of the LIPUS therapy on primary and secondary outcomes.
(A) Weekly use of nitroglycerin. (B) Extent of myocardial ischemia evaluated by stress myocardial perfusion imaging. (C) Kaplan-Meier curve of all-cause death. (D) Kaplan-Meier curve of MACE. LIPUS: low-intensity pulsed ultrasound.
See this image and copyright information in PMC

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