Łukasz Wi Niowski, Maciej Biskupski, Robert Błaszczyk, Bartosz Kondracki, Jan Siwiec, Radosław Mlak, Andrzej Głowniak
Overall, noncoding RNAs show promise as adjunctive post-MI biomarkers, but clinical translation requires phase-aligned sampling, assay standardization, external validation, and direct testing of incremental value beyond established clinical, imaging, and protein-biomarker models.
BACKGROUND: Prognosis after myocardial infarction (MI) remains heterogeneous despite contemporary reperfusion and secondary prevention, and biomarkers that capture post-MI recovery, treatment response, and long-term risk are still limited. Noncoding RNAs have therefore attracted interest as biomarkers of post-MI risk and recovery.
METHODS: We conducted a scoping review of human studies evaluating circulating or blood-derived noncoding RNAs, including microRNAs, long noncoding RNAs, circular RNAs, and tRNA-derived small RNAs/tRNA-derived fragments, measured after MI in relation to prognostic phenotypes, clinical outcomes, or treatment-response end points.
RESULTS: Forty-six studies were included. Most were observational, focused on plasma or serum microRNAs, and used quantitative reverse transcription-polymerase chain reaction, but sample size, sampling phase, normalization strategy, end point definition, follow-up duration, and validation approaches varied substantially. Reported associations clustered around reperfusion-related injury/no reflow or microvascular obstruction, left ventricular remodeling or dysfunction, clinical events, including major adverse cardiovascular events and mortality, and a smaller group of treatment-response phenotypes. Directional signals included miR-30e, miR-660-5p, TUG1, and MALAT1 for no reflow; LIPCAR, MICRA, miR-320a, miR-1254, and miR-22-3p for remodeling or ventricular recovery; miR-145, miR-223-3p, miR-126-3p/miR-223-3p, HCG11/miR-532-3p, and exosomal miR-186-5p dynamics for clinical events; and BANCR or selected tRNA-derived small RNAs/tRNA-derived fragments for treatment-response heterogeneity. The most plausible candidates were phenotype specific rather than universal, with event-related microRNA models, imaging-linked remodeling markers, and no-reflow/microvascular obstruction-associated candidates appearing more mature than isolated injury-linked diagnostic microRNAs or single-study treatment-response signals.
CONCLUSIONS: Overall, noncoding RNAs show promise as adjunctive post-MI biomarkers, but clinical translation requires phase-aligned sampling, assay standardization, external validation, and direct testing of incremental value beyond established clinical, imaging, and protein-biomarker models.