This prospective study enrolled 200 consecutive adult patients who presented with type I hypersensitivity reactions—including allergic, hypersensitivity, or anaphylactic reactions—at the ED of the University Hospital of Patras, Greece, between June 2018 and August 2021. A control group comprising healthy volunteer blood donors was concurrently recruited. Written informed consent was obtained from all participants. Clinical, ultrasonographic, and angiographic data were prospectively collected for each patient. As the study was designed and initiated prior to the emergence of Coronavirus disease–19 (COVID-19), data on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection or vaccination were not included. Although 47 patients were enrolled after availability of COVID-19 vaccines (January 2021), information regarding vaccination status was not systematically collected. The study received a priori approval from the Scientific Council of the University of Patras and conforms to the ethical guidelines of the 1975 Declaration of Helsinki.

Eligible participants were adults exhibiting symptoms of acute IgE-mediated type I allergic reactions that manifested within 12 hours before presentation to the ED. These reactions were categorized based on clinical features into acute urticaria (with or without angioedema), acute angioedema, and anaphylaxis. Dermatologists in the ED confirmed allergic reactions through clinical evaluation. Assessed symptoms included cutaneous manifestations (wheals, erythema, and edema), respiratory distress, persistent gastrointestinal symptoms (e.g., abdominal pain and diarrhea), hypotension, shock, and syncope.

Patients were excluded if they had conditions potentially elevating hs-cTnI levels. Exclusion criteria encompassed use of corticosteroids or antihistamines before ED arrival, clinical suspicion of other acute conditions (e.g., pulmonary embolism, acute aortic syndrome, intracranial hemorrhage, acute ischemic stroke, transient ischemic attack, myocarditis, and sepsis), severe anemia (hemoglobin <8 mg/dL), severe hypertension (systolic blood pressure >180 mmHg and/or diastolic blood pressure >110 mmHg), severe respiratory insufficiency, known hypertrophic cardiomyopathy or aortic stenosis, heart failure, severe pulmonary hypertension, chronic kidney disease with an estimated glomerular filtration rate <60 mL/min/1.73 m ², rhabdomyolysis or intense physical exertion, recent (<6 weeks) cardiac intervention or chest trauma, chemotherapy with cardiotoxic agents or monoclonal antibodies, infiltrative diseases (e.g., amyloidosis) or rheumatic diseases, hypothyroidism or hyperthyroidism.

Upon diagnosis, emergency physicians conducted a comprehensive laboratory assessment, including hs-cTnI measurement and electrocardiography (ECG) at baseline (Time 0), followed by repeat assessments at 1 and 3 hours. A cardiologist evaluated the initial ECG for ischemic changes, performed a clinical examination, and determined the presence of angina pectoris. The involvement of a specialist cardiologist did not delay or interfere with the administration of necessary treatments.

Ischemic ECG changes were defined as ST-segment elevation >1 mm, ST-segment depression >0.5 mm, or T-wave inversion >2 mm in 2 or more contiguous leads. Myocardial injury was identified by hs-cTnI levels exceeding the 99th percentile upper reference limit (URL; Abbott Architect). The European Society of Cardiology (ESC) 2015 algorithms, utilizing 0/1-h and 0/3-h hs-cTn protocols, guided the diagnosis of myocardial infarction (MI), irrespective of other ischemic findings. ^,

Patients with elevated cardiac biomarkers or those meeting rule-in criteria for MI underwent transthoracic echocardiography. Those with myocardial injury or rule-in MI (without fulfilling MI criteria, i.e., absence of angina symptoms or ECG changes) underwent dobutamine stress echocardiography upon normalization of hs-cTnI levels. Patients meeting MI criteria (presence of angina symptoms or ECG changes alongside myocardial injury and/or rule-in MI per ESC algorithms) underwent coronary angiography.

For study purposes, patients identified with myocardial injury and/or rule-in MI (excluding those with acute coronary syndrome) were categorized as having myocardial injury. All cardiological assessments were performed at the Cardiology Department of the University Hospital of Patras. A specialist cardiologist interpreted the dobutamine stress echocardiography, while an interventional cardiologist conducted the coronary angiography within 24 h of presentation, guided by high-risk features.

In the control group of voluntary blood donors, data on sex, age, and cardiovascular risk factors were collected, and hs-cTnI levels were measured at the time of blood donation.

Statistical analyses were performed using IBM SPSS Statistics version 29. The normality of the continuous variables was assessed using the Kolmogorov-Smirnov test. Data conforming to a normal distribution are presented as mean ± standard deviation ( SD ), while non-normally distributed data are presented as the median [interquartile range (IQR)]. Incidence rates are expressed as n (%). Comparisons between groups for nominal variables were conducted using the chi-squared test or the chi-squared test for trend where applicable. For continuous variables, comparisons were made using the Student’s t -test for normally distributed data and the Wilcoxon rank-sum test for nonnormally distributed data. For comparisons involving more than 2 groups, Analysis of variance (ANOVA) was used for normally distributed data, followed by the Bonferroni test for pairwise comparisons, and the Kruskal-Wallis test was employed for non-normally distributed data, followed by Dunn’s posthoc test with Bonferroni correction. Unadjusted and multi-adjusted logistic regression was employed to identify predictors of myocardial injury. All variables with a p – value <0.10 in the unadjusted model, after excluding collinearity, were fitted in a multi-adjusted model with backward elimination. Statistical significance for all analyses was defined as a p – value <0.05.

A total of 625 subjects aged >18 years were screened for inclusion in the study. Of these, 425 patients were excluded. Specifically, 222 presented to the ED with symptom onset >12 h prior, 195 had received corticosteroids or antihistamines before arrival, 3 had severe anemia (hemoglobin <8 g/dL), 2 had severe hypertension (systolic blood pressure >180 mmHg), 2 had recently undergone coronary intervention, one had a recent defibrillator implantation, and one had recently received cardiotoxic chemotherapy. Ultimately, 200 patients were included. The baseline patient characteristics are presented in Table 1 .

Of these 200 patients, 105 (52.5%) were male, and 95 (47.5%) were female. 58 (29%) patients had a history of allergy. A total of 138 (69%) were nonsmokers, and 26 (13%) were ex-smokers. Regarding cardiovascular risk factors, 48 (24%) had hypertension, 38 (19%) had dyslipidemia, 10 (5%) had diabetes mellitus, and 23 (11.5%) had a family history of coronary artery disease. Only 8 (4%) patients had a known history of coronary artery disease, treated either with percutaneous coronary intervention or with conservative management. In terms of clinical manifestations, 160 patients (80%) presented with pruritus, 108 (54%) had skin wheals, 105 (52.5%) experienced flushing, and 40 (20%) presented with angioedema. Based on clinical classification, 29 (14.5%) were diagnosed with angioedema (type I hypersensitivity), 147 (73.5%) with urticaria, 12 (6%) with urticaria and angioedema, and 12 (6%) with anaphylaxis. Anaphylactic shock occurred in 11 patients (5.5%), 9 (4.5%) experienced syncope, 5(2.5%) had laryngeal edema, and 12 (6%) reported anginal symptoms or symptoms of thoracic pain. The cardiologist on charge evaluated these symptoms as true angina or in the context of the allergy. No other cardiac symptoms were noted. Electrocardiographic abnormalities were noted in 10 patients (5%). Specifically, ST elevation was noted in 4 patients (2%), ST depression was noted also in 4 patients (2%) and T wave inversion was noted in 2 patients (1%).

Nearly all patients received corticosteroids, and 186 (93%) were treated with antihistamines. Fifteen patients (7.5%) required epinephrine. A total of 149 patients were discharged the same day, while 51 (25.5%) required hospitalization. The allergen could not be identified in 81 patients (40.5%). Identified triggers included food (8 [4%] patients), pharmaceutical agents (61 [30.5%] patients), viral infections (6 [3%] patients), and insect bites (42 [21%] patients).