Association of a Novel Diagnostic Biomarker, the Plasma Cardiac Bridging Integrator 1 Score, With Heart Failure With Preserved Ejection Fraction and Cardiovascular Hospitalization

Abstract

IMPORTANCE Transverse tubule remodeling is a hallmark of heart failure. Cardiac bridging integrator 1 (cBIN1) is a circulating membrane scaffolding protein that is essential for transverse tubule health, and its plasma level declines with disease. OBJECTIVE To determine if a cBIN1-derived score can serve as a diagnostic biomarker of heart failure with preserved ejection fraction (HFpEF). DESIGN, SETTING, AND PARTICIPANTS In this cohort study, the cBIN1 score (CS) was determined from enzyme-linked immunoabsorbent assay-measured plasma cBIN1 concentrations from study participants in an ambulatory heart failure clinic at Cedars-Sinai Medical Center. Consecutive patients with a confirmed diagnosis of heart failure with preserved ejection fraction (HFpEF; defined by a left ventricular ejection fraction Ն50%) were recruited from July 2014 to November 2015 and compared with age-matched and sex-matched healthy volunteers with no known cardiovascular diagnoses and participants with risk factors for heart failure but no known HFpEF. Baseline characteristics and 1-year longitudinal clinical information were obtained through electronic medical records. Data analysis occurred from November 2016 to November 2017. MAIN OUTCOMES AND MEASURES The analysis examined the ability of the CS and N-terminal pro-B-type natriuretic peptide (NT-proBNP) results to differentiate among patients with HFpEF, healthy control participants, and control participants with risk factors for heart failure. We further explored the association of the CS with future cardiovascular hospitalizations. RESULTS A total of 52 consecutive patients with a confirmed diagnosis of HFpEF were enrolled (mean [SD] age, 57 [15] years; 33 [63%] male). The CS values are significantly higher in the patients with HFpEF (median [interquartile range (IQR)], 1.85 [1.51-2.28]) than in the 2 control cohorts (healthy control participants: median [IQR], −0.03 [−0.48 to 0.

Natriuretic peptides for the detection of diastolic dysfunction and heart failure with preserved ejection fraction—a systematic review and meta-analysis

“…Twenty-eight were performed in Europe [ 20 , 32 – 36 , 38 , 40 , 41 , 43 – 45 , 50 , 52 , 53 , 55 – 57 , 59 , 63 , 64 , 66 , 69 , 73 , 76 – 78 ], 11 in North America [ 22 , 37 , 39 , 46 , 49 , 54 , 65 , 70 , 72 , 74 , 75 ], 11 in Asia [ 31 , 42 , 47 , 51 , 58 , 60 – 62 , 67 , 68 , 71 ] and one was a multi-country study [ 48 ]. The control populations were either healthy controls ( N = 14) [ 31 , 35 , 59 , 60 , 62 , 65 , 67 – 69 , 71 , 72 , 75 – 77 ] or were recruited at the same department as the patient population, but without DD or HFpEF ( N = 37) [ 32 – 34 , 36 – 42 , 58 , 61 , 63 , 64 , 66 , 70 ]. The mean age of the DD and HFpEF populations ranged from 51 to 74 years and...…”

Effect of BIN1 on cardiac dysfunction and malignant arrhythmias

“…cBIN1 in plasma is present in microparticles of ventricular cardiomyocyte origin and decrease significantly in BIN1 HT mice . In a recent study, the cBIN1 store, a biomarker based on the normalized reciprocal of plasma cBIN1 concentration, was much higher in stable patients with HF compared with healthy volunteers . Therefore, its availability in the blood makes it an attractive biomarker for cardiomyocyte remodelling.…”

Exogenous Cardiac Bridging Integrator 1 Benefits Mouse Hearts With Pre-existing Pressure Overload-Induced Heart Failure

“…Reduced myocardial cBIN1 can be detected in human blood, a result of cBIN1-membrane turnover and microparticle release (Xu et al, 2017). In humans, plasma CS (cBIN1 score) is an index of myocyte cBIN1 level, which identifies myocardial structural remodeling, facilitating HF diagnosis and prognosis (Nikolova et al, 2018). In mouse hearts subjected to chronic stress, pretreatment with exogenous cBIN1 preserves the microdomain-organized distribution of Cav1.2 and SERCA2a, maintaining normal inotropy and lusitropy (Liu et al, 2020).…”