Abstract 4139922: Differential Impact of Functional Autoantibodies Against Angiotensin II Receptor Type 1 and Endothelin-1 Receptor Type A on Microvascular Obstruction and Adverse Cardiovascular Events According to Infarct Size

Introduction: autoantibodies (AAs) activating angiotensin II receptor type 1 (AT1R-AAs) and endothelin-1 receptor type A (ETAR-AAs) are associated with microvascular obstruction (MVO) and major adverse cardiovascular events (MACE) after ST-elevation myocardial infarction (STEMI). Hypothesis: we hypothesized that the effect of AT1R-AAs and ETAR-AAs on MVO and MACE is stronger in patients with smaller infarct extension. Indeed, while larger infarcts are expected to face more MVO and worse prognosis, AT1R-AAs and ETAR-AAs could explain the quote of STEMI patients with smaller infarct sizes and poor outcomes. Methods: we studied STEMI patients treated with primary PCI between February 2021 and April 2024 at Padua University Hospital ( Fig A) . Blood samples for AAs level measurements were obtained within 12 h of admission. Patients were defined as seronegative, single, or double seropositive according to the AT1R-AA and ETAR-AA seropositivity (>10 U/mL). Cardiac magnetic resonance (CMR) was performed within 30 days after STEMI. Telephonic interviews and medical record revisions were performed to investigate MACE (death, myocardial reinfarction, and hospitalization for HF). Smaller or larger infarct was defined using the median infarct size in the MVO analysis and the median peak troponin level in the MACE analysis. Results: 56 patients (median age 58 yrs, 82% males) underwent CMR. The degree of seropositivity was associated with the prevalence of MVO in patients with a smaller infarct size (p=0.047), but not in those with a larger infarct size (p=0.129) ( Fig B) . A total of 174 patients (median age 61 yrs, 84% males) were investigated for incident MACE. Compared to seronegativity, double seropositivity was associated with a significantly higher risk of MACE in patients with a smaller (p=0.035), but not a larger (p=0.265), infarct extension ( Fig C). The results were confirmed after adjusting for age and infarct-related artery. Conclusions: the degree of autoantibody seropositivity was strongly correlated with MVO and MACE in patients with smaller infarct sizes, suggesting that AT1R-AAs and ETAR-AAs could play a relevant role in patients who, despite relatively small infarcts, face the adverse complications of STEMI.