Circulation Research

RES

Prognostic Value of Lymphocyte G Protein-Coupled Receptor Kinase-2 Protein Levels in Patients With Heart Failure

GRK2 and Prognosis in Heart Failure

CIRCRES/2015/308207D

10.1161/CIRCRESAHA.115.308207 118

04/01/16

Bridges-Lyman Gemma

410-3275005

410-3279322

Prabhu, Sumanth University of Alabama at Birmingham

Dr.

Walter

Koch

walter.koch@temple.edu

Dr.

Temple University School of Medicine

3500 N. Broad St.

Philadelphia

Pennsylvania

19140

UNITED STATES

215-707-9820

215-707-9890

16929

Giuseppe

Rengo

Salvatore Maugeri Foundation

giuseppe.rengo@unina.it

111624

Gennaro

Pagano

King's College London

gennaro.pagano@kcl.ac.uk

122025

Pasquale

Perrone-Filardi

Federico II University of Naples

fpperron@unina.it

22126

Grazia Daniela

Femminella

Federico II University of Naples

danielaf@virgilio.it

122030

Valentina

Parisi

Federico II University of Naples

valentina.parisi@unina.it

243097

Alessandro

Cannavo

Temple University School of Medicine

alessandro.cannavo@temple.edu

191712

Daniela

Liccardo

Federico II University of Naples

liccardo.daniela@gmail.com

122016

Klara

Komici

Federico II University of Naples

alb.munera@hotmail.com

122026

Giuseppina

Gambino

Federico II University of Naples

pina.gambino@gmail.com

304517

Maria Loreta

D'Amico

Federico II University of Naples

loreta.damico@hotmail.it

317398

Claudio

de Lucia

Federico II University of Naples

drclaudiodelucia@gmail.com

325614

Stefania

Paolillo

Federico II University of Naples

paolilloste@gmail.com

121083

Bruno

Trimarco

Federico II University of Naples

trimarco@unina.it

1708

Dino

Franco

Vitale

Salvatore Maugeri Foundation

dvitale@fsm.it

71881

Nicola

Ferrara

Federico II University of Naples

nicferra@unina.it

122029

Walter

Koch

Temple University School of Medicine

walter.koch@temple.edu

16929

Dario

Leosco

Federico II University of Naples

dleosco@unina.it

30943

12/18/2015

02/11/2016

02/16/2016

02/17/2016

04/01/2016

Clinical Track

Clinical/Translational Research

Rationale: Sympathetic nervous system (SNS) hyperactivity is associated with poor prognosis in patients with HF, yet routine assessment of SNS activation is not recommended for clinical practice. Myocardial G protein-coupled receptor kinase 2 (GRK2) is up-regulated in heart failure (HF) patients, causing dysfunctional β-adrenergic receptor signaling. Importantly, myocardial GRK2 levels correlate with levels found in peripheral lymphocytes of HF patients. Objective: The independent prognostic value of blood GRK2 measurements in HF patients has never been investigated, thus, the purpose of the present study was to evaluate whether lymphocyte GRK2 levels predict clinical outcome in HF patients. Methods and Results: We prospectively studied 257 HF patients with mean left ventricular ejection fraction (LVEF) of 31.4±8.5%. At the time of enrollment, plasma norepinephrine, serum NT-proBNP and lymphocyte GRK2 levels, as well as clinical and instrumental variables were measured. The prognostic value of GRK2 to predict cardiovascular (CV) death and all-cause mortality was assessed using the Cox proportional hazard model including demographic, clinical, instrumental and laboratory data. Over a mean follow-up period of 37.5±20.2 months (range: 3-60 months) there were 102 CV deaths. Age, LVEF, NYHA class, Chronic Obstructive Pulmonary Disease, Chronic Kidney Disease, N-terminal-pro Brain Natriuretic Peptide, and lymphocyte GRK2 protein levels were independent predictors of CV mortality in HF patients. GRK2 levels showed an additional prognostic and clinical value over demographic and clinical variables. The independent prognostic value of lymphocyte GRK2 levels was also confirmed for all-cause mortality. Conclusions: Lymphocyte GRK2 protein levels can independently predict prognosis in patients with HF.

yes

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CircRes_CIRCRES-2015-308207D_Trimarco_1708_disclosure.pdf

CircRes_CIRCRES-2015-308207D_Trimarco_1708_copyright.pdf

PAP: 02/16/15 Funding: Howard Hughes Medical Institute (HHMI): No National Institutes of Health (NIH): Yes Not applicable for this manuscript: No Other: Yes Wellcome Trust: No Subject Codes: [10015] Biomarkers [10094] Heart Failure gbridgeslyman