Coronary vasomotor disorders (CVD) are characterized by transient hypercontraction of coronary vascular smooth muscle cells, leading to hypercontraction of epicardial and/or microvascular coronary circulation. CVDs play a relevant role in the pathogenesis of ischemia, angina and myocardial infarction with non-obstructive coronary arteries. Invasive provocative testing with intracoronary Acetylcholine (ACh) administration is the gold standard tool for addressing CVD, providing relevant therapeutic and prognostic implications. However, safety concerns preclude the widespread incorporation of the ACh test into clinical practice. The purpose of this review is to shed light on the pathophysiology underlying CVD and on the clinical role of the ACh test, focusing on safety profile and prognostic implications. We will also discuss contemporary evidence on the management of CVD and the role of the ACh test in driving a personalized approach of patients with CVD.

Despite significant advances in understanding and management, cardiovascular diseases remain the leading cause of mortality worldwide. Historically, diagnostic and therapeutic strategies have typically targeted obstructive coronary arteries. However, growing evidence supports the pivotal role of non-obstructive mechanisms in myocardial ischemia, prompting a new classification that distinguishes Acute Myocardial Ischemic Syndromes from Non-Acute Myocardial Ischemic Syndromes. In this evolving context, Optical Coherence Tomography (OCT) plays an important diagnostic role in the assessment of both obstructive and non-obstructive ischemic mechanisms. In Acute Myocardial Ischemic Syndromes, OCT enables the identification of major plaque destabilization mechanisms and contributes to the diagnosis of Myocardial Infarction with Non-Obstructive Coronary Arteries, helping to differentiate between atherosclerotic and non-atherosclerotic causes. In Non-Acute Myocardial Ischemic Syndromes, OCT assists in evaluating stenosis severity, plaque morphology, vulnerability, and healing, and may contribute to the diagnosis of Ischemia with Non-Obstructive Coronary Arteries, identifying myocardial bridge and epicardial spasm alongside conventional functional assessment of intermediate stenoses. This narrative review outlines the expanding clinical applications of OCT across the full spectrum of ischemic syndromes, emphasizing its role in bridging obstructive and non-obstructive pathophysiology and supporting a more comprehensive diagnostic approach to ischemic heart disease.

BACKGROUND: The pullback pressure gradient (PPG) is a novel physiological metric that quantifies coronary artery disease patterns as focal or diffuse on a scale from 0 to 1. This study assessed the relationship between PPG and residual angina at 1 year. METHODS: PPG Global is a prospective, investigator-initiated, single-arm, multicenter study that enrolled patients with at least 1 lesion with a fractional flow reserve ≤0.80 intended to be treated with percutaneous coronary intervention. After the PPG calculation, physicians could revise treatment assignment to medical therapy or coronary artery bypass graft surgery instead of percutaneous coronary intervention. Focal and diffuse disease were defined based on the median PPG value of 0.62. Patient-reported outcomes were assessed using the Seattle Angina Questionnaire at baseline and 1-year follow-up. RESULTS: The study included 947 patients with PPG and the Seattle Angina Questionnaire at 1 year. The mean age was 67.6±10.2 years, 24% were female, and 29% had diabetes. At 1 year, patients with focal coronary artery disease reported less angina than those with diffuse disease (Seattle Angina Questionnaire angina frequency score, 95.3±9.9 versus 92.5±15.0; P =0.006). PPG was independently associated with improvement in angina ( P =0.017). CONCLUSIONS: In patients with flow-limiting coronary artery disease, a focal disease pattern defined by high PPG was associated with greater symptomatic relief at 1 year compared with diffuse disease (low PPG). By capturing the underlying pathophysiologic distribution of epicardial disease and its relation to post-treatment symptom relief, PPG may support a more tailored revascularization decision-making and percutaneous coronary intervention strategy.

Background: Sex differences in coronary artery disease (CAD) have been increasingly recognized, as women present with distinct clinical characteristics and outcomes compared with men. This study investigated the impact of sex on pathophysiological CAD patterns (focal versus diffuse) in stable patients undergoing percutaneous coronary interventions (PCI). Methods: We conducted a subanalysis of the PPG Global (Pullback Pressure Gradient Global Registry) study, a multicenter, prospective trial including 993 patients (236 [23.8%] women and 757 [76.2%] men) with hemodynamically significant CAD, defined as fractional flow reserve ≤0.80. The pullback pressure gradient metric categorized CAD patterns as focal or diffuse. Patient‐reported outcomes were collected using the 7‐item Seattle Angina Questionnaire. Optimal revascularization was defined as post‐PCI fractional flow reserve ≥0.88. Results: Women were significantly older than men, with a mean age of 69.8±10.3 years compared with 67.0±10.1 years ( P <0.001). Despite similar baseline fractional flow reserve (0.69±0.12 versus 0.67±0.11, P =0.093), women reported more severe symptoms compared with men, as reflected in the Seattle Angina Questionnaire‐7 angina frequency score (mean 76.7±22.9 versus 81.5±20.3, P =0.002). Women exhibited a more focal CAD pattern (pullback pressure gradient 0.65±0.16 versus 0.61±0.16, P =0.001) and achieved higher post‐PCI fractional flow reserve values (0.88±0.07 versus 0.87±0.07, P =0.02). Women undergoing PCI had a higher rate of optimal revascularization (54% versus 44%, P =0.01). Conclusions: This study reveals clinically significant differences in CAD patterns between sexes, with women demonstrating a higher burden of angina, more focal disease distribution, and better physiological results after PCI.

Acute and Chronic Coronary Syndromes represent two major medical challenges and are the leading cause of cardiovascular mortality and morbidity. While Chronic Coronary Syndrome (CCS) can be defined as the whole group of structural and/or functional abnormalities involving coronary arteries before and after an acute event, Acute Coronary Syndrome (ACS) encompasses the condition of acute myocardial ischemia (with or without consequent myocardial injury and troponin release) due to dynamic mechanisms such as athero-thrombosis or vasospasm. Because of this complex interplay between structural and functional mechanisms arising from both the epicardial and microvascular compartments, a comprehensive approach to fully investigate the whole spectrum of coronary disease is therefore essential. To address this issue, the invasive functional assessment has evolved through the years, from a way to guide revascularization to a meticulous protocol for characterizing ischemia-leading mechanisms and stratifying prognosis both in ACS and CCS. However, coronary physiology remains underused in clinical practice, and multiple gaps in knowledge still exist; on top of this, there is increasing heterogeneity regarding how to perform functional assessment, with different protocols proposed by various centers. The aim of this review is to summarize the evidence in the field of coronary physiology, and to discuss how and when to use it at its best.