Plasma BIN1 correlates with heart failure and predicts arrhythmia in patients with arrhythmogenic right ventricular cardiomyopathy.
BACKGROUND
Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a disorder involving diseased cardiac muscle. Bridging integrator 1 (BIN1) is a membrane-associated protein important to cardiomyocyte homeostasis and is downregulated in cardiomyopathy. We hypothesized that BIN1 could be released into the circulation and that blood-available BIN1 can provide useful data on the cardiac status of patients whose hearts are failing secondary to ARVC.


OBJECTIVE
To determine whether plasma BIN1 levels can be used to measure disease severity in patients with ARVC.


METHODS
We performed a retrospective cohort study of 24 patients with ARVC. Plasma BIN1 levels were assessed for their ability to correlate with cardiac functional status and predict ventricular arrhythmias.


RESULTS
Mean plasma BIN1 levels were decreased in patients with ARVC with heart failure (15 ± 7 vs 60 ± 17 in patients without heart failure, P <.05; the plasma BIN1 level was 60 ± 10 in non-ARVC normal controls). BIN1 levels correlated inversely with number of previous ventricular arrhythmia (R = -.47; P <.05), and low BIN1 levels correctly classified patients with advanced heart failure or ventricular arrhythmia (receiver operator curve area under the curve of 0.88 ± 0.07). Low BIN1 levels also predicted future ventricular arrhythmias (receiver operator curve area under the curve of 0.89 ± 0.09). In a stratified analysis, BIN1 levels could predict future arrhythmias in patients without severe heart failure (n = 20) with an accuracy of 82%. In the 7 patients with ARVC with serial blood samples, all of whom had evidence of disease progression during follow-up, plasma BIN1 levels decreased significantly (a decrease of 63%; P <.05).


CONCLUSIONS
Plasma BIN1 level seems to correlate with cardiac functional status and the presence or absence of sustained ventricular arrhythmias in a small cohort of patients with ARVC and can predict future ventricular arrhythmias.
Cardiovascular Research Institute, University of California San Francisco, San Francisco, CA 94158, USA.
Ting-Ting
TT
Hong
Rebecca
R
Cogswell
Cynthia A
CA
James
Guson
G
Kang
Clive R
CR
Pullinger
Mary J
MJ
Malloy
John P
JP
Kane
Julianne
J
Wojciak
Hugh
H
Calkins
Melvin M
MM
Scheinman
Zian H
ZH
Tseng
Peter
P
Ganz
Teresa
T
De Marco
Daniel P
DP
Judge
Robin M
RM
Shaw
D048868:Adaptor Proteins, Signal Transducing / Q000097:blood*; D000328:Adult; D001145:Arrhythmias, Cardiac / Q000097:blood* / Q000175:diagnosis / Q000209:etiology; D019571:Arrhythmogenic Right Ventricular Dysplasia / Q000097:blood / Q000150:complications* / Q000503:physiopathology; D015415:Biomarkers / Q000097:blood; D004452:Echocardiography; D004562:Electrocardiography; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005500:Follow-Up Studies; D016147:Genes, Tumor Suppressor; D006333:Heart Failure / Q000097:blood* / Q000175:diagnosis / Q000209:etiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009687:Nuclear Proteins / Q000097:blood*; D011237:Predictive Value of Tests; D011379:Prognosis; D012189:Retrospective Studies; D012720:Severity of Illness Index; D025521:Tumor Suppressor Proteins / Q000097:blood*
D048868:Adaptor Proteins, Signal Transducing; C101410:BIN1 protein, human; D015415:Biomarkers; D009687:Nuclear Proteins; D025521:Tumor Suppressor Proteins