The potential value of long non-coding RNA in molecular diagnosis and forensic identification of heart failure

Heart failure (HF), a major cause of cardiovascular mortality worldwide, develops through a multifaceted process involving cardiomyocyte apoptosis and necrosis, metabolic dysregulation, fibrosis, and sustained inflammatory activation. Although B-type natriuretic peptide (BNP) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) are routinely used in clinical assessment, their susceptibility to external influences limits their capacity to fully capture the molecular progression of HF. Emerging evidence has identified long non-coding RNAs (lncRNAs) as important epigenetic regulators that contribute to reduced myocardial contractility and ventricular remodeling. Clinical studies further indicate that circulating lncRNAs - particularly those packaged within exosomes - possess notable stability and strong disease specificity, making them promising candidates for improving diagnostic and prognostic evaluation. With ongoing advances in transcriptomic profiling and exosome-based technologies, the potential use of lncRNAs is also extending into forensic identification. This review synthesizes current insights into lncRNA-mediated regulation in HF progression, evaluates recent developments in circulating lncRNA detection, and explores their emerging forensic applications. It also outlines key limitations in existing research and discusses future directions to support deeper investigation into the molecular mechanisms underlying cardiac death and their relevance to forensic practice.