Kounis Syndrome in the Modern Era: A Comprehensive Review of Allergic Acute Coronary Syndromes

Figures

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  Figure 1. Contemporary pathophysiological and clinical classification of KS. The figure summarizes the four currently recognized subtypes of KS according to their underlying mechanisms, coronary substrates, angiographic characteristics, and clinical equivalents. Type I KS is characterized by allergic coronary vasomotor dysfunction involving epicardial and/or microvascular spasm in patients without significant obstructive coronary artery disease and corresponds to an allergic vasospastic ACS phenotype within the contemporary MINOCA spectrum. Type II KS occurs when an allergic reaction triggers destabilization of a pre-existing atherosclerotic plaque, leading to plaque rupture or erosion with thrombosis and type 1 myocardial infarction. Type III KS includes hypersensitivity-mediated stent failure and is subdivided into IIIa (allergic stent thrombosis) and IIIb (allergic stent restenosis). Type IV KS represents the bypass-graft counterpart and encompasses allergic thrombosis and/or vasospasm involving coronary artery bypass grafts. The lower panel illustrates a biochemical qualifier applicable to all KS subtypes, distinguishing allergic unstable angina from allergic myocardial infarction…

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  Figure 2. Angiographic patterns of epicardial coronary vasospasm and mechanisms underlying the absence of angiographically visible spasm. Epicardial vasospasm may present as focal, multifocal, diffuse monovessel, or multivessel constriction. A normal coronary angiogram does not exclude a vasospastic mechanism, as spasm may be confined to the coronary microcirculation, may have resolved spontaneously before imaging, may regress after administration of anti-allergic or vasodilator therapy, or may reflect the simultaneous contribution of multiple mechanisms. These concepts are particularly relevant in patients with suspected Kounis syndrome type I.

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  Figure 3. Comprehensive diagnostic algorithm for Kounis syndrome (KS). Starting from the identification of an allergic or hypersensitivity trigger associated with ACS, the algorithm guides the diagnostic work-up toward the appropriate KS subtype. Coronary angiography, or CCTA in low-risk patients, represents the cornerstone of anatomical assessment, with additional non-invasive imaging modalities, including CMR or SPECT, and, in selected cases, invasive coronary functional testing, potentially being required for a definitive diagnosis of type I KS, by identifying epicardial coronary vasospasm and/or CMD. Abbreviations: ACS, acute coronary syndrome; CABG, coronary artery bypass graft; CAD, coronary artery disease; CCTA, coronary computed tomography angiography; CFR, coronary flow reserve; CMD, coronary microvascular dysfunction; CMR, cardiac magnetic resonance; ECG, electrocardiographic; FFR, fractional flow reserve; IgE, immunoglobulin E; IMR, index of microvascular resistance; IVUS, intravascular ultrasound; OCT, optical coherence tomography; SPECT, single-photon emission computed tomography.

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  Figure 4. Integrated therapeutic approach to KS. The algorithm summarizes the contemporary management of KS, highlighting the simultaneous treatment of the allergic reaction and the acute coronary syndrome according to the underlying subtype. Initial management includes prompt stabilization and anti-allergic therapy, whereas coronary treatment differs between vasospastic (type I) and thrombosis-related forms (type II to IV). The figure also emphasizes therapeutic precautions, individualized treatment decisions, and strict allergen avoidance to reduce the risk of recurrence. Note: thrombus aspiration and histological examination are recommended for type III. Abbreviations: ACS, acute coronary syndrome; DAPT, dual antiplatelet therapy; KS, Kounis syndrome; PCI, percutaneous coronary intervention.