From Natriuretic Peptides to microRNAs: Multi-Analyte Liquid Biopsy Horizons in Heart Failure

Heart failure (HF) is a leading cause of morbidity and mortality worldwide, underscoring the need for improved diagnostic, prognostic, and therapeutic strategies. Circulating microRNAs (c-miRNAs) have emerged as promising non-invasive biomarkers due to their stability, tissue specificity, and regulatory roles in cardiac pathophysiology. This review highlights the potential of c-miRNAs in enhancing HF diagnosis, risk stratification, and therapeutic monitoring, particularly when integrated with conventional biomarkers such as natriuretic peptides, galectin-3, soluble ST2, and high-sensitivity troponins. We explore the roles of key miRNAs in HF pathogenesis—including cardiac hypertrophy, fibrosis, inflammation, apoptosis, and vascular remodeling—and discuss their diagnostic and prognostic significance. The potential of multi-analyte liquid biopsy approaches that combine c-miRNAs with protein biomarkers is also examined within the context of precision medicine. Despite promising data, challenges related to standardization, assay variability, and clinical validation remain. Addressing these gaps through harmonized protocols and large-scale studies will be essential for translating c-miRNAs into routine HF management.