Please use this identifier to cite or link to this item: https://doi.org/10.1016/j.jacc.2018.11.060
Title: Combining Circulating MicroRNA and NT-proBNP to Detect and Categorize Heart Failure Subtypes
Authors: Wong, Lee Lee 
Zou, Ruiyang 
Zhou, Lihan 
Lim, Jia Yuen 
Phua, Dominic CY
Liu, Chengcheng
Chong, Jenny PC
Ng, Jessica YX 
Liew, Oi Wah 
Chan, Siew Pang 
Chen, Yei-Tsung 
Chan, Michelle MY
Yeo, Poh Shuan D
Ng, Tze Pin 
Ling, Lieng H 
Sim, David 
Leong, Kui Toh G
Ong, Hean Y 
Jaufeerally, Fazlur 
Wong, Raymond 
Chai, Ping 
Low, Adrian F 
Lund, Mayanna
Devlin, Gerry
Troughton, Richard
Cameron, Vicky A
Doughty, Robert N
Lam, Carolyn SP 
Too, Heng Phon 
Richards, Arthur Mark 
Keywords: Science & Technology
Life Sciences & Biomedicine
Cardiac & Cardiovascular Systems
Cardiovascular System & Cardiology
biomarker
diagnosis
heart failure
microRNA
BRAIN NATRIURETIC PEPTIDE
REDUCED EJECTION FRACTION
DIAGNOSIS
ASSOCIATION
PREVALENCE
EXPRESSION
BIOMARKER
ACCURACY
MARKERS
TRENDS
Issue Date: 26-Mar-2019
Publisher: ELSEVIER SCIENCE INC
Citation: Wong, Lee Lee, Zou, Ruiyang, Zhou, Lihan, Lim, Jia Yuen, Phua, Dominic CY, Liu, Chengcheng, Chong, Jenny PC, Ng, Jessica YX, Liew, Oi Wah, Chan, Siew Pang, Chen, Yei-Tsung, Chan, Michelle MY, Yeo, Poh Shuan D, Ng, Tze Pin, Ling, Lieng H, Sim, David, Leong, Kui Toh G, Ong, Hean Y, Jaufeerally, Fazlur, Wong, Raymond, Chai, Ping, Low, Adrian F, Lund, Mayanna, Devlin, Gerry, Troughton, Richard, Cameron, Vicky A, Doughty, Robert N, Lam, Carolyn SP, Too, Heng Phon, Richards, Arthur Mark (2019-03-26). Combining Circulating MicroRNA and NT-proBNP to Detect and Categorize Heart Failure Subtypes. JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY 73 (11) : 1300-1313. ScholarBank@NUS Repository. https://doi.org/10.1016/j.jacc.2018.11.060
Abstract: Background: Clinicians need improved tools to better identify nonacute heart failure with preserved ejection fraction (HFpEF). Objectives: The purpose of this study was to derive and validate circulating microRNA signatures for nonacute heart failure (HF). Methods: Discovery and validation cohorts (N = 1,710), comprised 903 HF and 807 non-HF patients from Singapore and New Zealand (NZ). MicroRNA biomarker panel discovery in a Singapore cohort (n = 546) was independently validated in a second Singapore cohort (Validation 1; n = 448) and a NZ cohort (Validation 2; n = 716). Results: In discovery, an 8-microRNA panel identified HF with an area under the curve (AUC) 0.96, specificity 0.88, and accuracy 0.89. Corresponding metrics were 0.88, 0.66, and 0.77 in Validation 1, and 0.87, 0.58, and 0.74 in Validation 2. Combining microRNA panels with N-terminal pro–B-type natriuretic peptide (NT-proBNP) clearly improved specificity and accuracy from AUC 0.96, specificity 0.91, and accuracy 0.90 for NT-proBNP alone to corresponding metrics of 0.99, 0.99, and 0.93 in the discovery and 0.97, 0.96, and 0.93 in Validation 1. The 8-microRNA discovery panel distinguished HFpEF from HF with reduced ejection fraction with AUC 0.81, specificity 0.66, and accuracy 0.72. Corresponding metrics were 0.65, 0.41, and 0.56 in Validation 1 and 0.65, 0.41, and 0.62 in Validation 2. For phenotype categorization, combined markers achieved AUC 0.87, specificity 0.75, and accuracy 0.77 in the discovery with corresponding metrics of 0.74, 0.59, and 0.67 in Validation 1 and 0.72, 0.52, and 0.68 in Validation 2, as compared with NT-proBNP alone of AUC 0.71, specificity 0.46, and accuracy 0.62 in the discovery; with corresponding metrics of 0.72, 0.44, and 0.57 in Validation 1 and 0.69, 0.48, and 0.66 in Validation 2. Accordingly, false negative (FN) (81% Singapore and all NZ FN cases were HFpEF) as classified by a guideline-endorsed NT-proBNP ruleout threshold, were correctly reclassified by the 8-microRNA panel in the majority (72% and 88% of FN in Singapore and NZ, respectively) of cases. Conclusions: Multi-microRNA panels in combination with NT-proBNP are highly discriminatory and improved specificity and accuracy in identifying nonacute HF. These findings suggest potential utility in the identification of nonacute HF, where clinical assessment, imaging, and NT-proBNP may not be definitive, especially in HFpEF.
Source Title: JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
URI: https://scholarbank.nus.edu.sg/handle/10635/234578
ISSN: 0735-1097
1558-3597
DOI: 10.1016/j.jacc.2018.11.060
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