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Multivessel coronary artery disease (CAD), defined as ≥50% stenosis in 2 or more epicardial arteries, is associated with a high burden of morbidity and mortality in acute coronary syndrome (ACS) patients. A salient challenge for managing this cohort is selecting the optimal revascularisation strategy, for which the use of coronary physiology has been increasingly recognised. Fractional flow reserve (FFR) is an invasive, pressure wire-based, physiological index measuring the functional significance of coronary lesions. Understanding this can help practitioners evaluate which lesions could induce myocardial ischaemia and, thus, decide which vessels require urgent revascularisation. Non-hyperaemic physiology-based indices, such as instantaneous wave-free ratio (iFR), provide valid alternatives to FFR. While FFR and iFR are recommended by international guidelines in stable CAD, there is ongoing discussion regarding the role of physiology in patients with ACS and multivessel disease (MVD); growing evidence supports FFR use in the latter. Compelling findings show FFR-guided complete percutaneous coronary intervention (PCI) can reduce adverse cardiovascular events, mortality, and repeat revascularisations in ACS and MVD patients compared to angiography-based PCI. However, FFR is limited in identifying non-flow-limiting vulnerable plaques, which can disadvantage high-risk patients. Here, integrating coronary physiology assessment with intracoronary imaging in decision-making can improve outcomes and quality of life. Further research into novel physiology-based tools in ACS and MVD is needed. This review aims to highlight the key evidence surrounding the role of FFR and other functional indices in guiding PCI strategy in ACS and MVD patients., Competing Interests: The authors have no conflicts of interest to declare.

The mechanism underlying ischaemic heart disease (IHD) has been primarily attributed to obstructive coronary artery disease (CAD). However, non-obstructive coronary arteries are identified in >50% of patients undergoing elective coronary angiography, recently leading to growing interest in the investigation and management of angina/ischaemia with non-obstructive coronary arteries (ANOCA/INOCA). INOCA is an umbrella term encompassing a multiple spectrum of possible pathogenetic entities, including coronary vasomotor disorders which consist of two major endotypes: coronary microvascular dysfunction (CMD) and vasospastic angina. Both conditions can coexist and be associated with concomitant obstructive CAD. Particularly, CMD refers to myocardial ischaemia due to reduced vasodilatory capacity of coronary microcirculation secondary to structural remodelling or impaired resting microvascular tone (functional) or a combination of both. CMD is not a benign condition and is more prevalent in women presenting with chronic coronary syndrome compared to men. In this setting, an impaired coronary flow reserve has been associated with increased risk of major adverse cardiovascular events. ANOCA/INOCA patients also experience impaired quality of life and associated increased healthcare costs. Therefore, research in this scenario has led to better definition, classification, and prognostic stratification based on the underlying pathophysiological mechanisms. The development and validation of non-invasive imaging modalities, invasive coronary vasomotor function testing and angiography-derived indices provide a comprehensive characterisation of CMD. The present narrative review aims to summarise current data relating to the diagnostic approach to CMD and provides details on the sequence that therapeutic management should follow., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Vasospastic angina (VSA) refers to chest pain experienced as a consequence of myocardial ischaemia caused by epicardial coronary spasm, a sudden narrowing of the vessels responsible for an inadequate supply of blood and oxygen. Coronary artery spasm is a heterogeneous phenomenon that can occur in patients with non-obstructive coronary arteries and obstructive coronary artery disease, with transient spasm causing chest pain and persistent spasm potentially leading to acute myocardial infarction (MI). VSA was originally described as Prinzmetal angina or variant angina, classically presenting at rest, unlike most cases of angina (though in some patients, vasospasm may be triggered by exertion, emotional, mental or physical stress), and associated with transient electrocardiographic changes (transient ST-segment elevation, depression and/or T-wave changes). Ischaemia with non-obstructive coronary arteries (INOCA) is not a benign condition, as patients are at elevated risk of cardiovascular events including acute coronary syndrome, hospitalization due to heart failure, stroke and repeat cardiovascular procedures. INOCA patients also experience impaired quality of life and associated increased healthcare costs. VSA, an endotype of INOCA, is associated with major adverse events, including sudden cardiac death, acute MI and syncope, necessitating the study of the most effective treatment options currently available. The present literature review aims to summarize current data relating to the diagnosis and management of VSA and provide details on the sequence that treatment should follow.