Association of Angiotensin II Receptor Type 1 and Endothelin‐1 Receptor Type A Agonistic Autoantibodies With Adverse Remodeling and Cardiovascular Events After Acute Myocardial Infarction

Abstract

Background The left ventricular remodeling (LVR) process has limited the effectiveness of therapies after myocardial infarction. The relationship between autoantibodies activating AT1R‐AAs (angiotensin II receptor type 1‐AAs) and ETAR‐AAs (autoantibodies activating endothelin‐1 receptor type A) with myocardial infarction has been described. Among patients with ST‐segment–elevation myocardial infarction, we investigated the relationship between these autoantibodies with LVR and subsequent major adverse cardiac events. Methods and Results In this prospective observational study, we included 131 patients with ST‐segment–elevation myocardial infarction (61±11 years of age, 112 men) treated with primary percutaneous coronary intervention. Within 48 hours of admission, 2‐dimensional transthoracic echocardiography was performed, and blood samples were obtained. The seropositive threshold for AT1R‐AAs and ETAR‐AAs was >10 U/mL. Patients were followed up at 6 months, when repeat transthoracic echocardiography was performed. The primary end points were LVR, defined as a 20% increase in left ventricular end‐diastolic volume index, and major adverse cardiac event occurrence at follow‐up, defined as cardiac death, nonfatal re‐myocardial infarction, and hospitalization for heart failure. Forty‐one (31%) patients experienced LVR. The prevalence of AT1R‐AAs and ETAR‐AAs seropositivity was higher in patients with versus without LVR (39% versus 11%, P<0.001 and 37% versus 12%, P=0.001, respectively). In multivariable analysis, AT1R‐AAs seropositivity was significantly associated with LVR (odds ratio [OR], 4.66; P=0.002) and represented a risk factor for subsequent major adverse cardiac events (OR, 19.6; P=0.002). Conclusions AT1R‐AAs and ETAR‐AAs are associated with LVR in patients with ST‐segment–elevation myocardial infarction. AT1R‐AAs are also significantly associated with recurrent major adverse cardiac events. These initial observations may set the stage for a better pathophysiological understanding of the mechanisms contributing to LVR and ST‐segment–elevation myocardial infarction prognosis.

Keywords

• antibodies
• immunology
• prognosis
• remodeling
• STEMI