Combining Circulating MicroRNA and NT-proBNP to Detect and Categorize Heart Failure Subtypes

Area of Science:

• Biomarker discovery and validation
• Cardiovascular diagnostics
• Molecular signatures for heart failure

Background:

• Clinicians require enhanced diagnostic tools for nonacute heart failure with preserved ejection fraction (HFpEF).
• Current diagnostic methods including NT-proBNP may not be definitive for HFpEF.

Purpose of the Study:

• To derive and validate circulating microRNA (miRNA) signatures for nonacute heart failure (HF).
• To assess the diagnostic performance of miRNA panels, alone and in combination with NT-proBNP.

Main Methods:

• Discovery and validation cohorts (N=1,710) from Singapore and New Zealand.
• MicroRNA biomarker panel discovery and independent validation in multiple cohorts.
• Performance evaluation using area under the curve (AUC), specificity, and accuracy.

Main Results:

• An 8-miRNA panel achieved high accuracy (AUC 0.96) in discovery, validated at 0.87-0.88.
• Combining miRNA panels with NT-proBNP significantly improved diagnostic metrics (AUC up to 0.99).
• The panel distinguished HFpEF from HF with reduced ejection fraction (AUC 0.81) and reclassified false negatives.

Conclusions:

• Multi-miRNA panels combined with NT-proBNP demonstrate high discriminatory power for nonacute HF.
• This approach enhances specificity and accuracy, particularly valuable when clinical assessment and NT-proBNP are insufficient.
• Potential utility for improved diagnosis of nonacute HF, especially in HFpEF cases.