Combined circulating microRNA and peptide biomarkers for prognostication in heart failure

Q: What is the clinical evidence from this study?

Study design: Cohort. Population: Heart Failure (n=798). Intervention: Multi-marker prognostic model (5 clinical variables, 7 circulating miRNAs, and 3 peptides: NT-proBNP, hs-TnT, GDF15) vs. NT-proBNP alone, MAGGIC score, or clinical model alone. Primary outcome: All-cause mortality (AUC 0.85 (discovery), 0.75 (validation I), 0.74 (validation II), p=<0.001).

Q: What does this research mean for the field?

A combined panel of five clinical variables, seven circulating microRNAs, and three peptides predicts all-cause mortality in heart failure with AUCs of 0.74 to 0.85, significantly outperforming NT-proBNP and the MAGGIC risk score. Novelty: ClaimNovelty.NOVEL_FINDING. Consensus alignment: ConsensusAlignment.NEUTRAL.

Lee Lee Wong; Hiromi Wai Ling Koh; Hyungwon Choi; Ruiyang Zou; Lihan Zhou; Jia Yuen Lim; Dominic C.Y. Phua; Oi Wah Liew; Jenny Pek Ching Chong; Jessica Yan Xia Ng; Siew Pang Chan; Yei‐Tsung Chen; Poh Shuan Daniel Yeo; Lieng Hsi Ling; David Sim; Kui Toh Gerard Leong; Hean Yee Ong; Fazlur Jaufeerally; Raymond Wong; Ping Chai; Adrian F. Low; Mayanna Lund; Gerry Devlin; Richard W. Troughton; Robert N. Doughty; Carolyn S.P. Lam; Heng Phon Too; Mark Richards

doi:10.1093/cvr/cvaf065

Key result

A combined panel of 5 clinical variables, 7 miRNAs, and 3 peptides predicted all-cause mortality in heart failure with AUCs of 0.74-0.85, outperforming NT-proBNP and MAGGIC scores.

Figures

Why the study?

Existing heart failure risk tools often lack accuracy for individualized management, and prior circulating microRNA biomarker studies examined only selected published microRNAs.

Does a combined prognostic panel of circulating microRNAs, peptide biomarkers (NT-proBNP, hs-TnT, GDF15), and clinical variables improve the prediction of all-cause mortality compared to NT-proBNP alone, clinical models, or the MAGGIC score in patients with compensated heart failure?

Key Points

To evaluate whether combining circulating microRNAs, peptide biomarkers, and clinical variables improves prediction of all-cause mortality in patients with chronic heart failure.
Used a regularized Cox proportional-hazards model combining clinical variables, circulating microRNAs, and peptide biomarkers (NT-proBNP, hs-TnT, and GDF15) to predict all-cause mortality.
A panel of five clinical variables, seven microRNAs, and three peptides predicted all-cause mortality with AUCs of 0.85 in discovery, 0.75 in validation I, and 0.74 in validation II, outperforming NT-proBNP and the MAGGIC score.
Adding three peptides and seven microRNAs to the clinical model significantly improved risk classification, yielding continuous net reclassification improvements of 0.63 (P < 0.001) in discovery, 0.53 (P = 0.009) in validation I, and 0.35 (P = 0.004) in validation II.
Kaplan-Meier analysis demonstrated significant differences in survival between high- and low-risk subgroups stratified by the multi-marker model across all cohorts (log-rank test, P < 0.001).

Study Design

Type

Cohort (n=798)

Multicenter

Yes

Structured PICO

Does a combined prognostic panel of circulating microRNAs, peptide biomarkers (NT-proBNP, hs-TnT, GDF15), and clinical variables improve the prediction of all-cause mortality compared to NT-proBNP alone, clinical models, or the MAGGIC score in patients with compensated heart failure?

P

Population

798 patients with compensated heart failure meeting ESC criteria across Singapore and New Zealand cohorts, followed for 2 years.

E

Exposure

Multi-variable prognostic panel combining 5 clinical variables (age, BMI, hypertension, NYHA class, history of myocardial infarction), 7 circulating microRNAs (miR-150-5p, miR-181a-2-3p, miR-186-5p, miR-200c-3p, miR-337-3p, miR-421, miR-503-5p), and 3 peptide biomarkers (NT-proBNP, hs-TnT, GDF15).

C

Comparator

NT-proBNP alone, MAGGIC risk score, or a base clinical model (age, BMI, hypertension, NYHA class, history of myocardial infarction) with or without peptides/miRNAs.

O

Outcome

All-cause mortality over 2 years of follow-up (with 18-month mortality rates reported).hard clinical

Main Result

Effect estimate: AUC 0.85 (discovery), 0.75 (validation I), 0.74 (validation II)

p-value: p=<0.001

Limitations

Other circulating miRNAs not included in the study may have better prognostic value.
The mechanisms underpinning the prognostic associations of the identified miRNAs have not yet been fully explored.
Prospective evaluation is needed to fully assess clinical impact and prognostic utility.
Other circulating miRNAs not included in the 100-miRNA assay may have better prognostic value.
The biological mechanisms underpinning the prognostic associations of the identified miRNAs have not yet been fully explored.
Prospective evaluation is needed to fully assess the clinical impact and prognostic utility of the model.

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Implication

Combining seven circulating microRNAs and three peptide biomarkers (NT-proBNP, hs-TnT, GDF15) with clinical variables outperforms both NT-proBNP alone and the MAGGIC score in predicting all-cause mortality in compensated heart failure patients, improving risk reclassification for approximately 40% of patients.

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Cite This Study

Wong et al. (2025) conducted a cohort in Heart Failure (n=798). Multi-marker prognostic model (5 clinical variables, 7 circulating miRNAs, and 3 peptides: NT-proBNP, hs-TnT, GDF15) vs. NT-proBNP alone, MAGGIC score, or clinical model alone was evaluated on All-cause mortality (AUC 0.85 (discovery), 0.75 (validation I), 0.74 (validation II), p=<0.001). A combined panel of 5 clinical variables, 7 miRNAs, and 3 peptides predicted all-cause mortality in heart failure with AUCs of 0.74-0.85, outperforming NT-proBNP and MAGGIC scores.

synapsesocial.com/papers/6a7a105a1b9920df6d892dbf https://doi.org/10.1093/cvr/cvaf065

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Combined circulating microRNA and peptide biomarkers for prognostication in heart failure

Figures

Key Points

Study Design

Structured PICO

Main Result

Limitations

Ask about this paper

Implication

Abstract

Discussion

Cite This Study

Combined circulating microRNA and peptide biomarkers for prognostication in heart failure

Figures

Key Points

Study Design

Structured PICO

Main Result

Limitations

Ask about this paper

Implication

Abstract

Discussion

Cite This Study

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