Optimal Timing of Pharmacological Spasm Provocation During Interventional Diagnostic Procedures

Coronary microvascular dysfunction (CMD) is increasingly recognized as a clinically significant cause of angina in patients with ischemia and nonobstructive coronary artery disease (INOCA). Therefore, CMD has gained considerable attention in contemporary cardiovascular medicine. A comprehensive assessment of INOCA includes both the spasm provocation test (SPT), which can diagnose vasospastic angina (VSA), and coronary microvascular function test (CMVFT), which is used to evaluate CMD. However, the optimal sequence of these tests during interventional diagnostic procedures remains under debate. Several institutions perform SPT followed by CMVFT after nitrate administration. However, this approach raises concerns regarding the potential confounding effects of vasospasm severity, use of pharmacological agents, development of procedure-related complications on CMVFT measurements, and the frequency of CMD. Conversely, performing CMVFT prior to SPT might reduce the subsequent spasm inducibility attributed to the vasodilatory or endothelial-modulating effects of diagnostic agents, potentially leading to the underdiagnosis of VSA. This review comprehensively examined the advantages and disadvantages of each sequencing strategy, thereby emphasizing existing gaps in standardization and proposing future directions for optimizing the diagnostic algorithm in patients undergoing interventional diagnostic procedures for suspected INOCA. Establishing evidence-based protocols is essential for accurate phenotyping and for guiding individualized therapeutic strategies in this complex patient population.