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Neuregulin as a heart failure therapy and mediator of reverse remodeling.

ABSTRACT: The beta isoform of Neuregulin-1 (NRG-1?), along with its receptors (ErbB2-4), is required for cardiac development. NRG-1?, as well as the ErbB2 and ErbB4 receptors, is also essential for maintenance of adult heart function. These observations have led to its evaluation as a therapeutic for heart failure. Animal studies and ongoing clinical trials have demonstrated beneficial effects of two forms of recombinant NRG-1? on cardiac function. In addition to the possible role for recombinant NRG-1?s as heart failure therapies, endogenous NRG-1?/ErbB signaling appears to play a role in restoring cardiac function after injury. The potential mechanisms by which NRG-1? may act as both a therapy and a mediator of reverse remodeling remain incompletely understood. In addition to direct effects on cardiac myocytes NRG-1? acts on the vasculature, interstitium, cardiac fibroblasts, and hematopoietic and immune cells, which, collectively, may contribute to NRG-1?'s role in maintaining cardiac structure and function, as well as mediating reverse remodeling.

SUBMITTER: Galindo CL

PROVIDER: S-EPMC3975684 | biostudies-literature | 2014 Mar

REPOSITORIES: biostudies-literature

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Neuregulin as a heart failure therapy and mediator of reverse remodeling.

Galindo Cristi L CL Ryzhov Sergey S Sawyer Douglas B DB

Current heart failure reports 20140301 1

The beta isoform of Neuregulin-1 (NRG-1β), along with its receptors (ErbB2-4), is required for cardiac development. NRG-1β, as well as the ErbB2 and ErbB4 receptors, is also essential for maintenance of adult heart function. These observations have led to its evaluation as a therapeutic for heart failure. Animal studies and ongoing clinical trials have demonstrated beneficial effects of two forms of recombinant NRG-1β on cardiac function. In addition to the possible role for recombinant NRG-1βs ...[more]

PMID: 24234399

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Project description:BackgroundTranscatheter mitral valve repair (TMVR) has been shown to have acute effects on mitral valve geometry in patients with functional mitral regurgitation (FMR). This study investigates the impact of MitraClip® therapy-induced annular remodeling on clinical outcome and mitral regurgitation in heart failure patients.MethodsTMVR was performed successfully in 45 patients with FMR. In this study, mitral valve datasets were obtained before and directly after MitraClip® implantation using three-dimensional (3D) transesophageal echocardiography, and were analyzed offline retrospectively using dedicated 3D reconstruction software. Patients underwent clinical and echocardiographic evaluation at baseline and after 6 months. At follow-up, the patients were allocated into two groups according to their improvement in New York Heart Association (NYHA) functional class: a Low Responder group with ΔNYHA <1.5 (n = 25); and a High Responder group with ΔNYHA ≥1.5 (n = 20).ResultsAt 6-month follow-up, data analysis revealed that while mitral regurgitation was reduced significantly in both groups, only the High Responder group had experienced significant downsizing of the 3D circumference (137 ± 14 mm to 126 ± 13 mm; p < 0.01) and the anterior-to-posterior diameter (33 ± 5 mm to 29 ± 4 mm; p < 0.01) of the mitral annulus during the intervention. Furthermore, only the High Responder group with reverse annular remodeling as shown had substantial advances in quality of life (Minnesota living with heart failure questionnaire: 55 ± 10 to 34 ± 14 points; p < 0.01) and functional status (6-min walk distance: 290 ± 104 m to 462 ± 111 m; p = 0.07).ConclusionOur study demonstrates that instantaneous left ventricular annular remodeling during MitraClip® implantation is associated with improved clinical outcome of heart failure patients with functional mitral regurgitation. Trial registration The study was approved by the local ethics committee (Study Number 4497R, Registration ID: 2013121585).Trial registrationNCT02033811 Retrospectively registered January 9, 2014.

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Neuregulin as a heart failure therapy and mediator of reverse remodeling.

Publications

Neuregulin as a heart failure therapy and mediator of reverse remodeling.

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