{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T04:54:52Z","timestamp":1781758492546,"version":"3.54.5"},"reference-count":35,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T00:00:00Z","timestamp":1781740800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cardiovasc. Med."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Coronary microvascular disease (CMVD) is a major cause of angina in patients with ischemia and nonobstructive coronary arteries (INOCA) syndrome. It is characterized by an imbalance between myocardial oxygen supply and demand, leading to reduced exercise tolerance and impaired quality of life. Because of heterogeneous diagnostic approaches and the lack of disease-modifying therapies, CMVD remains underdiagnosed and undertreated. Shexiang Tongxin Dropping Pill (STDP), a traditional Chinese medicine formulation, has shown protective effects on the coronary microvasculature in preclinical and preliminary clinical studies. However, high-quality randomized evidence and objective functional validation are still lacking. This study therefore aims to evaluate the efficacy and safety of STDP in patients with CMVD using cardiopulmonary exercise testing (CPET) as the primary functional outcome and to develop an artificial intelligence (AI)-assisted myocardial contrast echocardiography (MCE) tool to improve CMVD detection and subgroup classification.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Design<\/jats:title>\n                    <jats:p>This is a prospective, multicenter, randomized, double-blind, placebo-controlled clinical trial with a nested diagnostic design. CMVD will be diagnosed by stress MCE, and eligibility will require evidence of reduced myocardial perfusion or perfusion defects. Eligible patients with CMVD will be randomized at a 1:1 ratio to receive STDP or a matched placebo for 12 weeks. The primary endpoint is the change in peak oxygen uptake (peak VO\u2082) measured by cardiopulmonary exercise testing (CPET). The secondary outcomes include other CPET indices, angina severity, quality of life, and circulating biomarkers. The nested diagnostic study uses retrospectively and prospectively collected MCE datasets to develop AI-based models for automated myocardial segmentation, perfusion curve analysis, and CMVD classification, with performance assessed against established reference standards.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>By combining quantitative microvascular imaging, functional exercise assessment, and AI-assisted diagnostics in a single protocol, this study proposes a therapeutic-diagnostic framework for CMVD. This study is expected to provide high-quality randomized evidence for the use of STDP in CMVD and to offer a scalable and objective approach to improve diagnosis, risk stratification, and individualized management in patients with functional coronary ischemia.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Clinical Trial registration<\/jats:title>\n                    <jats:p>\n                      <jats:ext-link>http:\/\/itmctr.ccebtcm.org.cn\/<\/jats:ext-link>\n                      , International Traditional Medicine Clinical Trial Registry (ITMCTR), TMCTR2025000414.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fcvm.2026.1875936","type":"journal-article","created":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T04:36:06Z","timestamp":1781757366000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Shexiang Tongxin dropping pill for coronary microvascular disease: rationale and design of a multicenter randomized trial with a cardiopulmonary exercise testing primary endpoint and AI-enhanced myocardial contrast echocardiograph"],"prefix":"10.3389","volume":"13","author":[{"given":"Meiyi","family":"Su","sequence":"first","affiliation":[{"name":"The Second Clinical College, Guangzhou University of Chinese Medicine","place":["Guangzhou, China"]},{"name":"The Second Affiliated Hospital of Guangzhou University of Chinese Medicine","place":["Guangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuqing","family":"Tang","sequence":"additional","affiliation":[{"name":"Dongguan Hospital of Traditional Chinese Medicine, Guangzhou University of Chinese Medicine","place":["Dongguan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pengtao","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Ultrasonography, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine","place":["Guangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huan","family":"Cen","sequence":"additional","affiliation":[{"name":"Department of Ultrasonography, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine","place":["Guangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shaonan","family":"Liu","sequence":"additional","affiliation":[{"name":"The Second Clinical College, Guangzhou University of Chinese Medicine","place":["Guangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xianlun","family":"Li","sequence":"additional","affiliation":[{"name":"China-Japan Friendship Hospital (Institute of Clinical Medical Sciences), Chinese Academy of Medical Sciences & Peking Union Medical College","place":["Beijing, China"]},{"name":"Department of Integrative Medicine Cardiology, China-Japan Friendship Hospital","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Wang","sequence":"additional","affiliation":[{"name":"The Second Clinical College, Guangzhou University of Chinese Medicine","place":["Guangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Wang","sequence":"additional","affiliation":[{"name":"The Second Clinical College, Guangzhou University of Chinese Medicine","place":["Guangzhou, China"]},{"name":"Dongguan Hospital of Traditional Chinese Medicine, Guangzhou University of Chinese Medicine","place":["Dongguan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,6,18]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"3415","DOI":"10.1093\/eurheartj\/ehae177","article-title":"2024 ESC guidelines for the management of chronic coronary syndromes","volume":"45","author":"Vrints","year":"2024","journal-title":"Eur Heart 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