Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Plasma cBIN1 Score (CS) Identifies HFpEF and Can Predict Cardiac Hospitalization in Stable Ambulatory Patients

Andriana P. Nikolova
,
Tara C. Hitzeman
,
Rachel Baum
,
Bing Xu
,
Sosse Agvanian
,
Yu Xie
,
Dael R. Geft
,
David H. Chang
,
Jaime D. Moriguchi
,
Antoine Hage
,
Babak Azarbal
,
Lawrence S. Czer
,
Michelle M. Kittleson
,
Jignesh K. Patel
,
Alan H. B. Wu
,
Jon A. Kobashigawa
,
Michele Hamilton
,
TingTing Hong
* ,
Robin Shaw
*
Version 1 : Received: 5 January 2018 / Approved: 7 January 2018 / Online: 7 January 2018 (13:49:49 CET)

How to cite: Nikolova, A.P.; Hitzeman, T.C.; Baum, R.; Xu, B.; Agvanian, S.; Xie, Y.; Geft, D.R.; Chang, D.H.; Moriguchi, J.D.; Hage, A.; Azarbal, B.; Czer, L.S.; Kittleson, M.M.; Patel, J.K.; Wu, A.H.B.; Kobashigawa, J.A.; Hamilton, M.; Hong, T.; Shaw, R. Plasma cBIN1 Score (CS) Identifies HFpEF and Can Predict Cardiac Hospitalization in Stable Ambulatory Patients. Preprints 2018, 2018010041. https://doi.org/10.20944/preprints201801.0041.v1 Nikolova, A.P.; Hitzeman, T.C.; Baum, R.; Xu, B.; Agvanian, S.; Xie, Y.; Geft, D.R.; Chang, D.H.; Moriguchi, J.D.; Hage, A.; Azarbal, B.; Czer, L.S.; Kittleson, M.M.; Patel, J.K.; Wu, A.H.B.; Kobashigawa, J.A.; Hamilton, M.; Hong, T.; Shaw, R. Plasma cBIN1 Score (CS) Identifies HFpEF and Can Predict Cardiac Hospitalization in Stable Ambulatory Patients. Preprints 2018, 2018010041. https://doi.org/10.20944/preprints201801.0041.v1

Abstract

Objective: We determined, in stable ambulatory heart failure with preserved ejection fraction (HFpEF) subjects and matched controls, the capability of a novel blood based cardiac-specific cBIN1 Score (CS) to diagnose heart failure and prognosticate future hospitalization. Background: Heart failure (HF) poses a costly health care burden worldwide with rising prevalence. Abnormal calcium signaling is intrinsic to HF pathophysiology and correlates with reduced expression of a cardiac membrane scaffolding protein, cardiac bridging integrator 1 (cBIN1). We hypothesize that CS, a numerical score derived from plasma cBIN1 concentration, is a diagnostic and prognostic biomarker of HF. Methods: Plasma cBIN1 is quantified by an ELISA test, and CS is calculated as the natural log of the normalized reciprocal of plasma cBIN1 concentration. We determined CS among 52 clinically stable individuals with HFpEF (LVEF ≥ 50%) (mean age 57 ± 15 years old, 63% men) and 104 age and sex matched volunteers with no known history of HF. We obtained plasma concentrations of NT-proBNP, a marker of volume status, as comparison. Baseline co-morbidities and one year longitudinal clinical information were obtained through electronic medical records. Results: Median CS is 0 (IQR -0.4 – 0.6) in the control cohort and is increased to 1.8 in the HFpEF cohort (IQR 1.5 – 2.3, p < 0.0001). For HFpEF diagnosis, CS has a receiver operating characteristic (ROC) area under the curve (AUC) of 0.94 (95% CI 0.95 – 0.99) and NT-proBNP of 0.89 (95% CI 0.83 – 0.95). Kaplan-Meier analysis of one year cardiovascular hospitalizations reveals that HFpEF patients with CS ≥ 1.8 have a hazard ratio (HR) of 4.0 (95% CI 1.4 – 11.2, p=0.009). Combining CS ≥ 1.8 with NT-proBNP ≥ 300 pg/mL, increases HR to 21.4 (95% CI 2.7 – 171.6, p=0.004). Conclusions: In a cohort of stable ambulatory HF patients with cardiomyopathies of multiple etiologies and preserved ejection fraction, a positive CS correlates with worsening myocardial health and predicts future hospitalization. CS, a marker of cardiac muscle health, provides a novel index to informing the management of stable ambulatory HF patients.

Keywords

biomarkers; heart failure with preserved ejection fraction (HFpEF); cBIN1; cBIN1 Score (CS)

Subject

Medicine and Pharmacology, Cardiac and Cardiovascular Systems

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Download PDF

Comments (0)

We encourage comments and feedback from a broad range of readers. See criteria for comments and our Diversity statement.

Leave a public comment
Send a private comment to the author(s)
* All users must log in before leaving a comment
Views 0
Downloads 0
Comments 0
Metrics 0
Get PDF Cite Share 0
Bookmark BibSonomy Mendeley Reddit Delicious
×
Alerts
Notify me about updates to this article or when a peer-reviewed version is published.
We use cookies on our website to ensure you get the best experience.
Read more about our cookies here.