Ralota KK, Layland J. Vasospastic angina: Pathophysiology, diagnosis, and emerging therapeutic approaches. World J Cardiol 2025; 17(10): 108594 [DOI: 10.4330/wjc.v17.i10.108594]
Corresponding Author of This Article
Jamie Layland, MD, PhD, Consultant, FRACP, MRCP, Professor, Senior Researcher, Department of Cardiology, Monash University, 2 Hastings Road, Frankston 3199, Victoria, Australia. jlayland@phcn.vic.gov.au
Research Domain of This Article
Cardiac & Cardiovascular Systems
Article-Type of This Article
Review
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
World J Cardiol. Oct 26, 2025; 17(10): 108594 Published online Oct 26, 2025. doi: 10.4330/wjc.v17.i10.108594
Vasospastic angina: Pathophysiology, diagnosis, and emerging therapeutic approaches
Kristoffer Ken Ralota, Jamie Layland
Kristoffer Ken Ralota, Department of Cardiology, Peninsula Health, Frankston 3199, Victoria, Australia
Jamie Layland, Department of Cardiology, Peninsula Health and Department of Medicine, Peninsula Clinical School, Monash University, Frankston 3199, Victoria, Australia
Co-corresponding authors: Kristoffer Ken Ralota and Jamie Layland.
Author contributions: Ralota K drafted and prepared the manuscript; Layland J supervised the writing of the manuscript, including its conceptualization and review. Both authors have read and approved the final manuscript. Ralota K drafted the manuscript, its content, flow, and narrative, helped in vetting of related literature for inclusion of their contents into this manuscript, enacted necessary revisions of the manuscript, preparation and submission of the current version of the manuscript. Layland J is the senior researcher who conceptualized the manuscript, was responsible for reviewing revisions of the manuscript, helped in vetting of related literature for inclusion of their contents into this manuscript, and supervised the entire process. This collaboration between Ralota K and Layland J is crucial for the publication of this manuscript.
Conflict-of-interest statement: All authors declare no conflicts of interest.
Open Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Jamie Layland, MD, PhD, Consultant, FRACP, MRCP, Professor, Senior Researcher, Department of Cardiology, Monash University, 2 Hastings Road, Frankston 3199, Victoria, Australia. jlayland@phcn.vic.gov.au
Received: April 18, 2025 Revised: May 31, 2025 Accepted: September 19, 2025 Published online: October 26, 2025 Processing time: 189 Days and 19.4 Hours
Abstract
Vasospastic angina (VSA) is a distinct endotype of ischemia with non-obstructive coronary arteries characterized by transient coronary artery spasm and myocardial ischemia in the absence of significant fixed stenosis. It is an underdiagnosed and often challenging condition that can lead to recurrent angina, myocardial infarction, and sudden cardiac death. VSA arises from a multifactorial interplay of endothelial dysfunction, vascular smooth muscle hyperreactivity, inflammation, and autonomic dysregulation. While calcium channel blockers and nitrates remain the mainstay of therapy, there is a growing body of evidence in the use of novel and emerging treatments including Rho-kinase inhibitors, endothelin receptor antagonists, and anti-inflammatory agents for refractory cases. Diagnostic evaluation relies on clinical features and, when necessary, invasive coronary pharmacological provocation testing. This narrative review examines the current understanding of VSA, discusses current international guideline-based diagnostic and therapeutic strategies, and highlights novel and investigational approaches that may broaden the treatment armamentarium against it.
Core Tip: Vasospastic angina (VSA) is an under-recognized but clinically significant cause of myocardial ischemia, arrhythmia, and sudden cardiac death in patients without obstructive coronary artery disease. This narrative review provides an up-to-date revision of VSA pathophysiology, diagnostic strategies including provocation testing, and current guideline-recommended management. It also highlights promising emerging therapies—such as Rho-kinase inhibitors, endothelin receptor antagonists, and immunomodulatory agents—offering new hope for patients with refractory symptoms. Recognizing and treating VSA proactively can reduce adverse events and improve quality of life in this high-risk yet often overlooked condition.
