Functional Autoantibodies Against Angiotensin II Receptor Type 1 and Endothelin-1 Receptor Type A Predict Adverse Remodeling and Cardiovascular Events After Acute Myocardial Infarction

Introduction: Myocardial infarction is a leading cause of death worldwide. Although advances have been made in acute treatment, an incomplete understanding of left ventricular (LV) remodeling (LVR) processes has limited the effectiveness of therapies to reduce late-stage mortality. Hypothesis: We hypothesized that autoantibodies (AAs) activating angiotensin II receptor type 1 (AT1R-AAs) and endothelin-1 receptor type A (ETAR-AAs) are associated with LVR after ST-elevation myocardial infarction (STEMI) and with recurrent major adverse cardiac events (MACE). Methods: We studied 131 STEMI patients (age 61±11 years, 112 males) treated with primary percutaneous coronary intervention between February 2021 and January 2022 at Padua University Medical Center. Within 48 hours of admission standard 2D echocardiography was performed and blood samples were obtained for AAs level measurement. Echocardiography was performed at 6 months repeatedly in all patients. The endpoint was LVR, defined as an increase of 20% or more of LV end-diastolic volume index. Results: Overall, 41 (32%) patients experienced LVR. The titer for the autoantibodies was significantly higher in patients with LVR (p=0.009 for AT1R-AAs; p=0.01 for ETAR-AAs). The prevalence of AT1R-AAs and ETAR-AAs seropositivity was higher in patients with LVR (39% vs. 11%, p<0.001 and 37% vs. 12%, p=0.001, respectively). At multivariable analysis, AT1R-AAs seropositivity was the strongest predictor of LVR (OR=4.25, p=0.002). Similarly, AT1R-AAs seropositivity was a strong predictor of recurrent MACE, both before (OR, 4.09; p = 0.006) and after (OR 19.6; p=0.002) adjusting for the confounding factors. Conclusions: Our results support the hypothesis that AT1R-AAs and ETAR-AAs concentration are a risk factor for LVR in STEMI patients. AT1R-AAs is also a predictor of recurrent MACE. These initial observations may set the stage for a better pathophysiological understanding of the mechanisms contributing to LVR.