Survival outcomes correlate with the level of cell-free circulating DNA in ST-elevation myocardial infarction

Abstract

Background: Myocardial infarction (MI) can lead to higher cellular damage, making cell-free DNA (cfDNA) a potential biomarker for assessing disease severity. The aim of this study is to evaluate survival predictions using cfDNA measurements and assess its correlation with MI.

Materials and methods: A direct fluorescence assay was employed to measure cfDNA content in the blood samples of participants. The inclusion criteria included patients who gave informed consent, suffering from ST-elevation myocardial infraction (STEMI) based on established diagnostic criteria (joint ESC/ACC guidelines), between the age of 18 and 80 years old, and had elevated troponin biomarker levels. The study included 150 patients diagnosed with STEMI and 50 healthy volunteers as controls. Serial monitoring of patients was conducted to track their postdisease status. The rate of change of cfDNA was calculated and daily measurements for 7 days were recorded.

Results: Mean levels of cfDNA were found to be 5.93 times higher in patients with STEMI compared to healthy controls, providing clear evidence of a clinical correlation between cfDNA and STEMI. Patients were further categorized based on their survival status within a 90-day period. The study observed a strong predictive relationship between the rate of change of cfDNA during daily measurements and survival outcomes. To assess its predictive capability, a receiver operating characteristics (ROC) curve analysis was performed. The ROC analysis identified an optimal cutoff value of 2.50 for cfDNA, with a sensitivity of 81.5% and specificity of 74.0% in predicting disease outcomes.

Conclusion: This study demonstrates a robust association between cfDNA and STEMI, indicating that cfDNA levels can be a valuable early prognostic factor for patients. Serial measurements of cfDNA during early disease onset hold promise as an effective approach for predicting survival outcomes in MI patients.

Keywords: Biomarkers; cardiovascular diseases; cell-free nucleic acids; prognosis.

Figure 1

Distinction of cell-free DNA (cfDNA) within acute myocardial infarction (AMI) patients and healthy volunteers. Baseline reference measurements were taken from February 2016 to March 2017. (a) Study design comparing different groups of participants. (b) cfDNA concentration extracted from plasma showed higher content in AMI patients. (c) Correlation of cardiac troponin I with cfDNA for each patient using the Spearman’s correlation coefficient, rho. AMI = Acute myocardial infarction, cfDNA = Cell-free DNA, CV = Coefficient of variation. **denotes p value < 0.0001

Figure 2

Serial measurements and trend analysis for acute myocardial infarction patients and healthy volunteers. (a) Monitoring of cell-free DNA (cfDNA) variations daily showed an initial increasing trend upon manifestation of the disease. (b) Coefficient of variation measurements of the study cohort that addressed variability during the 7-day measurements. (c) The maximum rate of change in cfDNA measurements for each individual showing good separation with healthy volunteers. AMI = Acute myocardial infarction, cfDNA = Cell-free DNA, CV = Coefficient of variation

Figure 3

Analysis of the variations in cell-free DNA (cfDNA) and its implication for 90-day survival in acute myocardial infarction patients. (a) Measurements of maximum cfDNA concentration, coefficient of variation (CV), and rate of change in cfDNA in the survival vs nonsurvival group. (b) Receiver operating characteristics analysis for the parameters maximum cfDNA concentration, CV, and rate of change in cfDNA to determine the optimal cutoff value for each test. cfDNA = Cell-free DNA, CV = Coefficient of variation, AUC = Area under the curve, CI = Confidence interval. **denotes p value < 0.0001

Figure 4

Survival analysis to gauge the prognostic utility to use cell-free DNA (cfDNA) to stratify acute myocardial infarction (AMI) patients. (a) Separation of patient cohort using maximum cfDNA concentrations. (b) Coefficient of variation measurements within AMI patients showed good prognostic utility to predict mortality with a hazard ratio of 1.99. (c) The maximum rate of change in cfDNA in each patient showed good prognostic value to identify high-risk patients. cfDNA = Cell-free DNA, CI = Confidence interval, CV = Coefficient of variation