Cell-Free DNA Profiles End-Organ Injury and Predicts Outcomes in Advanced Heart Failure With Left Ventricular Assist...

Area of Science:

• Cardiovascular Medicine
• Biomarker Discovery
• Genomics

Background:

• Adverse events following durable left ventricular assist device (LVAD) implantation present significant challenges to patient survival.
• Current risk stratification methods for LVAD recipients are limited.
• Cell-free DNA (cfDNA) is emerging as a promising biomarker for assessing end-organ injury and improving risk stratification.

Purpose of the Study:

• To investigate the potential of plasma cell-free DNA (cfDNA) as a biomarker for risk stratification in patients undergoing left ventricular assist device (LVAD) implantation.
• To compare cfDNA levels in patients with and without LVADs, and to assess changes in cfDNA following LVAD implantation.
• To determine the association between pre-implantation cfDNA levels and post-LVAD adverse events.

Main Methods:

• A multicenter prospective cohort study involving patients with heart failure with and without LVADs, and a control group of healthy individuals.
• Quantification of nuclear cfDNA (ncfDNA) and mitochondrial cfDNA using digital droplet polymerase chain reaction.
• Identification of tissue-specific cfDNA using whole-genome bisulfite sequencing.
• Statistical analysis including Wilcoxon rank-sum test, paired t-test, and log-rank tests to compare cfDNA levels and outcomes.

Main Results:

• Patients with LVADs exhibited significantly higher ncfDNA and mtDNA levels compared to healthy controls.
• Patients without LVADs had higher ncfDNA levels than those with LVADs.
• LVAD implantation led to a significant reduction in ncfDNA levels, including those specific to the innate immune system, vascular endothelium, gastrointestinal tract, and liver.
• Elevated pre-LVAD ncfDNA levels were associated with a higher risk of infection and hemocompatibility-related adverse events.

Conclusions:

• LVAD implantation is associated with decreased systemic and tissue-specific cfDNA levels.
• cfDNA measurements show potential as a valuable tool for enhancing the risk stratification of patients considered for LVAD implantation, predicting post-operative outcomes.