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

• Published in: PloS one 2023-06, Vol.18 (6), p.e0287714-e0287714
• Main Authors: Shindo, Tomohiko, Ito, Kenta, Ogata, Tsuyoshi, Kurosawa, Ryo, Eguchi, Kumiko, Kagaya, Yuta, Hanawa, Kenichiro, Hasebe, Yuhi, Nishimiya, Kensuke, Shiroto, Takashi, Takahashi, Jun, Okumura, Yasuo, Noguchi, Teruo, Ozaki, Yukio, Daida, Hiroyuki, Hagiwara, Nobuhisa, Masuyama, Tohru, Chikamori, Taishiro, Fukumoto, Yoshihiro, Tsujita, Kenichi, Kanai, Hiroshi, Yasuda, Satoshi, Shimokawa, Hiroaki
• Format: Article
• Language: English
• Subjects: Acute coronary syndrome; Angina; Angina pectoris; Angina Pectoris - drug therapy; Angina Pectoris - therapy; Angiogenesis; Cardiac patients; Cardiovascular diseases; Care and treatment; Clinical trials; Complications and side effects; Coronary artery bypass; Coronary vessels; Double-Blind Method; Double-blind studies; Ejection fraction; Endothelium; Enrollments; Health services; Heart; Heart surgery; Humans; Ischemia; Medical prognosis; Medical research; Medicine and Health Sciences; Medicine, Experimental; Nitrates; Nitric oxide; Nitric-oxide synthase; Nitroglycerin; Nitroglycerin - therapeutic use; Patient outcomes; Patients; Percutaneous Coronary Intervention; Physicians; Pilot Projects; Placebos; Prognosis; Quality of Life; Registration; Research and Analysis Methods; Review boards; Therapy; Treatment Outcome; Ultrasonic imaging; Ultrasonic Waves; Ultrasound
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0287714

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). 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