Predicting adverse cardiac remodeling following ST-elevation myocardial infarction through the assessment of endothelin-1 levels

Abstract

Abstract Adverse cardiac remodeling refers to a complex set of molecular, cellular, and interstitial changes. Cardiac remodeling is linked to an unfavorable prognosis due to its correlation with ventricular dysfunction and the occurrence of malignant arrhythmias. Endothelin-1 is a powerful vasoconstrictor that acts at the level of smooth muscle cells of the vascular wall. In patients with ST-elevation acute myocardial infarction (STEMI), increased circulating endothelin-1 is associated with left ventricular systolic dysfunction and major complication during the in-patient period. The purpose of the study is to evaluate the role of Endothelin-1 as a possible predictor of pathological remodeling six months after STEMI event. Materials and methods 162 patients with STEMI were initially enrolled into the study according to inclusion criteria (percutaneous coronary intervention performed first 12 hours after the event, age of participants 18 years and above). Blood samples for biomarker analysis were collected at admission (endothelin-1, cardiac troponin I). At the end of six months, patients came to the site for a routine check-up including echocardiography with strain. One year after the event, the patients were contacted to collect information about a primary composite endpoint. The primary endpoint was a combination of all-cause death, new incident of myocardial infarction, ischemic stroke or transient ischemic attack, heart failure decompensation with or without hospitalization, hospitalization due to any cardiovascular disease deterioration. All these were defined as a single study outcome. Secondary outcomes, measured as the change from baseline to 6 months in left ventricle (LV) end-diastolic volume >10% and / or LV end-systolic volume >10%. 9% of study subjects reached the primary study outcome. Results the study cohort was stratified into two groups: those with high and low endothelin levels, determined by the median of 2.75 pg/ml. In the group of endothelin above 2.75 pg/ml, a statistically significant increase in end-diastolic volume of the LV (p = 0.002), end-diastolic dimension (p = 0.015), left atrium size (p = 0.008), and indicators of diastolic dysfunction (p =0.024) and LV myocardial mass (p=0.015) 6 months after the event. The ROC analysis revealed that endothelin has prognostic potential for LV remodeling. The cut-off was less than 2,97 pg/ml (sensitivity - 83%, specificity - 62%, area under curve (AUC) 0,70, 95% confident interval (CI) 0,516 – 0,847, p=0,03). Logistic regression analysis was employed to assess the potential of the Endothelin-1 biomarker as a predictor for LV remodeling. Endothelin showed properties of predicting adverse cardiac remodeling (CI 95% 0.696 - 0.956, AUC - 0.861, χ2=9.03 p=0.43). Conclusion measuring the Endothelin-1 level can enable the implementation of appropriate medical interventions in STEMI patients with an unfavorable cardiac remodeling prognosis, helping to prevent the development of heart failure.