Non-coding RNAs as potential clinical biomarkers of heart failure: analytical validation, laboratory methodology, and clinical implementation pathways.
Abstract
Heart failure (HF) is a heterogeneous clinical syndrome that has pathophysiologic manifestations of hemodynamic abnormalities, downstream neurohumoral activation and inflammation, myocardial fibrosis, metabolic dysfunction, and cardiomyocyte injury. Relevant to the issue of B-type natriuretic peptide (BNP) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) as clinically established biomarkers, their interpretation may be influenced by confounding factors such as obesity, renal dysfunction, atrial fibrillation, and HF phenotype. Recent data highlight a broad spectrum of non-coding RNA (ncRNA) types, including microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs), which can be detected in circulating samples and participate in regulatory networks associated with myocardial remodeling, supporting their investigation as potential complementary biomarkers. A structured literature search of PubMed/MEDLINE, Web of Science Core Collection, and Scopus from database inception to August 6, 2026, was conducted according to predefined eligibility, study-selection, and evidence-appraisal criteria. Here, HF-associated ncRNAs are assessed from perspectives including biological relevance, pre-analytical variables, detection platforms, quality control (QC), analytical and clinical validation, clinical-use scenarios, and implementation pathways. The available evidence so far rather supports a role in which ncRNAs serve as adjunctive rather than stand-alone biomarkers. The field is highlighted by the fact that presently no ncRNA-based assay is ready for routine clinical use in HF. Harmonized pre-analytical and analytical workflows, independent multicenter validation, predefined clinical-use scenarios, as well as demonstration of incremental clinical value and cost-effectiveness beyond established biomarkers, imaging, and clinical variables will be needed for future progress.