Myocardial Recovery in Patients With Systolic Heart Failure and Autoantibodies Against β1-Adrenergic Receptors

Yuji Nagatomo; Dennis M. McNamara; Jeffrey D. Alexis; Leslie T. Cooper; G. William Dec; Daniel F. Pauly; Richard Sheppard; Randall C. Starling; W. H.Wilson Tang; Karen Janosko; Charles McTiernan; Barry London; Karen Hanley-Yanez; John Gorcsan; Hidekazu Tanaka; Mathew Suffoletto; Cynthia Oblak; Annette McNallan; Lu Anne Koenig; Paul Mather; Natalie Pierson; Sharon Rubin; Yanique Bell; Alicia Ervin; John Boehmer; Patricia Frey; Jeffrey Alexis; Janice Schrack; Pam LaDuke; Guillermo Torre-Amione; Jeannie Arredondo; Pamela C. Smith; Stephanie Fuoco; Ilan S. Wittstein; Elayne Breton; Vinay Thohan; Deborah Wesley; Diane Cocca-Spofford; David W. Markham; Lynn Fernandez; Colleen Debes; Mark J. Zucker; Laura Adams; Peter Liu; Judith Renton; Jagat Narula; Byron Allen; Elizabeth Westberg

doi:10.1016/j.jacc.2016.11.067

Myocardial Recovery in Patients With Systolic Heart Failure and Autoantibodies Against β₁-Adrenergic Receptors

Yuji Nagatomo, Dennis M. McNamara, Jeffrey D. Alexis, Leslie T. Cooper, G. William Dec, Daniel F. Pauly, Richard Sheppard, Randall C. Starling, W. H.Wilson Tang, Karen Janosko, Charles McTiernan, Barry London, Karen Hanley-Yanez, John Gorcsan, Hidekazu Tanaka, Mathew Suffoletto, Cynthia Oblak, Annette McNallan, Lu Anne Koenig, Paul MatherNatalie Pierson, Sharon Rubin, Yanique Bell, Alicia Ervin, John Boehmer, Patricia Frey, Jeffrey Alexis, Janice Schrack, Pam LaDuke, Guillermo Torre-Amione, Jeannie Arredondo, Pamela C. Smith, Stephanie Fuoco, Ilan S. Wittstein, Elayne Breton, Vinay Thohan, Deborah Wesley, Diane Cocca-Spofford, David W. Markham, Lynn Fernandez, Colleen Debes, Mark J. Zucker, Laura Adams, Peter Liu, Judith Renton, Jagat Narula, Byron Allen, Elizabeth Westberg

Research output: Contribution to journal › Article › peer-review

25 Scopus citations

Abstract

Background Among various cardiac autoantibodies (AAbs), those recognizing the β₁-adrenergic receptor (β₁AR) demonstrate agonist-like effects and induce myocardial damage that can be reversed by β-blockers and immunoglobulin G3 (IgG3) immunoadsorption. Objectives The goal of this study was to investigate the role of β₁AR-AAbs belonging to the IgG3 subclass in patients with recent-onset cardiomyopathy. Methods Peripheral blood samples were drawn at enrollment in patients with recent-onset cardiomyopathy (left ventricular ejection fraction [LVEF] ≤0.40; <6 months). The presence of IgG and IgG3-β₁AR-AAb was determined, and echocardiograms were assessed, at baseline and 6 months. Patients were followed up for ≤48 months. Results Among the 353 patients who had blood samples adequate for the analysis, 62 (18%) were positive for IgG3-β₁AR-AAbs (IgG3 group), 58 (16%) were positive for IgG but not IgG3 (non-IgG3 group), and the remaining were negative. There were no significant differences in baseline systolic blood pressure, heart rate, or LVEF among the groups at baseline. Left ventricular end-diastolic and end-systolic diameters were significantly larger in the non-IgG3 group compared with the other groups (left ventricular end-diastolic diameter, p < 0.01; left ventricular end-systolic diameter, p = 0.03). At 6 months, LVEF was significantly higher in the IgG3 group (p = 0.007). Multiple regression analysis showed that IgG3-β₁AR-AAb was an independent predictor of LVEF at 6 months and change in LVEF over 6 months, even after multivariable adjustment (LVEF at 6 months, β = 0.20, p = 0.01; change in LVEF, β = 0.20, p = 0.008). In patients with high New York Heart Association functional class (III or IV) at baseline, the IgG3 group had a lower incidence of the composite endpoint of all-cause death, cardiac transplantation, and hospitalization due to heart failure, whereas the non-IgG3 group had the highest incidence of the composite endpoint. Conclusions IgG3-β₁AR-AAbs were associated with more favorable myocardial recovery in patients with recent-onset cardiomyopathy.

Original language	English (US)
Pages (from-to)	968-977
Number of pages	10
Journal	Journal of the American College of Cardiology
Volume	69
Issue number	8
DOIs	https://doi.org/10.1016/j.jacc.2016.11.067
State	Published - Feb 28 2017

Keywords

IgG3
autoantibody
recent-onset cardiomyopathy
β-blocker

ASJC Scopus subject areas

Cardiology and Cardiovascular Medicine

Access to Document

10.1016/j.jacc.2016.11.067

Cite this

Nagatomo, Y., McNamara, D. M., Alexis, J. D., Cooper, L. T., Dec, G. W., Pauly, D. F., Sheppard, R., Starling, R. C., Tang, W. H. W., Janosko, K., McTiernan, C., London, B., Hanley-Yanez, K., Gorcsan, J., Tanaka, H., Suffoletto, M., Oblak, C., McNallan, A., Koenig, L. A., ... Westberg, E. (2017). Myocardial Recovery in Patients With Systolic Heart Failure and Autoantibodies Against β₁-Adrenergic Receptors. Journal of the American College of Cardiology, 69(8), 968-977. https://doi.org/10.1016/j.jacc.2016.11.067

Nagatomo, Y, McNamara, DM, Alexis, JD, Cooper, LT, Dec, GW, Pauly, DF, Sheppard, R, Starling, RC, Tang, WHW, Janosko, K, McTiernan, C, London, B, Hanley-Yanez, K, Gorcsan, J, Tanaka, H, Suffoletto, M, Oblak, C, McNallan, A, Koenig, LA, Mather, P, Pierson, N, Rubin, S, Bell, Y, Ervin, A, Boehmer, J, Frey, P, Alexis, J, Schrack, J, LaDuke, P, Torre-Amione, G, Arredondo, J, Smith, PC, Fuoco, S, Wittstein, IS, Breton, E, Thohan, V, Wesley, D, Cocca-Spofford, D, Markham, DW, Fernandez, L, Debes, C, Zucker, MJ, Adams, L, Liu, P, Renton, J, Narula, J, Allen, B & Westberg, E 2017, 'Myocardial Recovery in Patients With Systolic Heart Failure and Autoantibodies Against β₁-Adrenergic Receptors', Journal of the American College of Cardiology, vol. 69, no. 8, pp. 968-977. https://doi.org/10.1016/j.jacc.2016.11.067

@article{d62fe56552314fba8f07773b7c8c9d0f,

title = "Myocardial Recovery in Patients With Systolic Heart Failure and Autoantibodies Against β1-Adrenergic Receptors",

abstract = "Background Among various cardiac autoantibodies (AAbs), those recognizing the β1-adrenergic receptor (β1AR) demonstrate agonist-like effects and induce myocardial damage that can be reversed by β-blockers and immunoglobulin G3 (IgG3) immunoadsorption. Objectives The goal of this study was to investigate the role of β1AR-AAbs belonging to the IgG3 subclass in patients with recent-onset cardiomyopathy. Methods Peripheral blood samples were drawn at enrollment in patients with recent-onset cardiomyopathy (left ventricular ejection fraction [LVEF] ≤0.40; <6 months). The presence of IgG and IgG3-β1AR-AAb was determined, and echocardiograms were assessed, at baseline and 6 months. Patients were followed up for ≤48 months. Results Among the 353 patients who had blood samples adequate for the analysis, 62 (18%) were positive for IgG3-β1AR-AAbs (IgG3 group), 58 (16%) were positive for IgG but not IgG3 (non-IgG3 group), and the remaining were negative. There were no significant differences in baseline systolic blood pressure, heart rate, or LVEF among the groups at baseline. Left ventricular end-diastolic and end-systolic diameters were significantly larger in the non-IgG3 group compared with the other groups (left ventricular end-diastolic diameter, p < 0.01; left ventricular end-systolic diameter, p = 0.03). At 6 months, LVEF was significantly higher in the IgG3 group (p = 0.007). Multiple regression analysis showed that IgG3-β1AR-AAb was an independent predictor of LVEF at 6 months and change in LVEF over 6 months, even after multivariable adjustment (LVEF at 6 months, β = 0.20, p = 0.01; change in LVEF, β = 0.20, p = 0.008). In patients with high New York Heart Association functional class (III or IV) at baseline, the IgG3 group had a lower incidence of the composite endpoint of all-cause death, cardiac transplantation, and hospitalization due to heart failure, whereas the non-IgG3 group had the highest incidence of the composite endpoint. Conclusions IgG3-β1AR-AAbs were associated with more favorable myocardial recovery in patients with recent-onset cardiomyopathy.",

keywords = "IgG3, autoantibody, recent-onset cardiomyopathy, β-blocker",

author = "Yuji Nagatomo and McNamara, {Dennis M.} and Alexis, {Jeffrey D.} and Cooper, {Leslie T.} and Dec, {G. William} and Pauly, {Daniel F.} and Richard Sheppard and Starling, {Randall C.} and Tang, {W. H.Wilson} and Karen Janosko and Charles McTiernan and Barry London and Karen Hanley-Yanez and John Gorcsan and Hidekazu Tanaka and Mathew Suffoletto and Cynthia Oblak and Annette McNallan and Koenig, {Lu Anne} and Paul Mather and Natalie Pierson and Sharon Rubin and Yanique Bell and Alicia Ervin and John Boehmer and Patricia Frey and Jeffrey Alexis and Janice Schrack and Pam LaDuke and Guillermo Torre-Amione and Jeannie Arredondo and Smith, {Pamela C.} and Stephanie Fuoco and Wittstein, {Ilan S.} and Elayne Breton and Vinay Thohan and Deborah Wesley and Diane Cocca-Spofford and Markham, {David W.} and Lynn Fernandez and Colleen Debes and Zucker, {Mark J.} and Laura Adams and Peter Liu and Judith Renton and Jagat Narula and Byron Allen and Elizabeth Westberg",

note = "Publisher Copyright: {\textcopyright} 2017 American College of Cardiology Foundation",

year = "2017",

month = feb,

day = "28",

doi = "10.1016/j.jacc.2016.11.067",

language = "English (US)",

volume = "69",

pages = "968--977",

journal = "Journal of the American College of Cardiology",

issn = "0735-1097",

publisher = "Elsevier",

number = "8",

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TY - JOUR

T1 - Myocardial Recovery in Patients With Systolic Heart Failure and Autoantibodies Against β1-Adrenergic Receptors

AU - Nagatomo, Yuji

AU - McNamara, Dennis M.

AU - Alexis, Jeffrey D.

AU - Cooper, Leslie T.

AU - Dec, G. William

AU - Pauly, Daniel F.

AU - Sheppard, Richard

AU - Starling, Randall C.

AU - Tang, W. H.Wilson

AU - Janosko, Karen

AU - McTiernan, Charles

AU - London, Barry

AU - Hanley-Yanez, Karen

AU - Gorcsan, John

AU - Tanaka, Hidekazu

AU - Suffoletto, Mathew

AU - Oblak, Cynthia

AU - McNallan, Annette

AU - Koenig, Lu Anne

AU - Mather, Paul

AU - Pierson, Natalie

AU - Rubin, Sharon

AU - Bell, Yanique

AU - Ervin, Alicia

AU - Boehmer, John

AU - Frey, Patricia

AU - Alexis, Jeffrey

AU - Schrack, Janice

AU - LaDuke, Pam

AU - Torre-Amione, Guillermo

AU - Arredondo, Jeannie

AU - Smith, Pamela C.

AU - Fuoco, Stephanie

AU - Wittstein, Ilan S.

AU - Breton, Elayne

AU - Thohan, Vinay

AU - Wesley, Deborah

AU - Cocca-Spofford, Diane

AU - Markham, David W.

AU - Fernandez, Lynn

AU - Debes, Colleen

AU - Zucker, Mark J.

AU - Adams, Laura

AU - Liu, Peter

AU - Renton, Judith

AU - Narula, Jagat

AU - Allen, Byron

AU - Westberg, Elizabeth

PY - 2017/2/28

Y1 - 2017/2/28

N2 - Background Among various cardiac autoantibodies (AAbs), those recognizing the β1-adrenergic receptor (β1AR) demonstrate agonist-like effects and induce myocardial damage that can be reversed by β-blockers and immunoglobulin G3 (IgG3) immunoadsorption. Objectives The goal of this study was to investigate the role of β1AR-AAbs belonging to the IgG3 subclass in patients with recent-onset cardiomyopathy. Methods Peripheral blood samples were drawn at enrollment in patients with recent-onset cardiomyopathy (left ventricular ejection fraction [LVEF] ≤0.40; <6 months). The presence of IgG and IgG3-β1AR-AAb was determined, and echocardiograms were assessed, at baseline and 6 months. Patients were followed up for ≤48 months. Results Among the 353 patients who had blood samples adequate for the analysis, 62 (18%) were positive for IgG3-β1AR-AAbs (IgG3 group), 58 (16%) were positive for IgG but not IgG3 (non-IgG3 group), and the remaining were negative. There were no significant differences in baseline systolic blood pressure, heart rate, or LVEF among the groups at baseline. Left ventricular end-diastolic and end-systolic diameters were significantly larger in the non-IgG3 group compared with the other groups (left ventricular end-diastolic diameter, p < 0.01; left ventricular end-systolic diameter, p = 0.03). At 6 months, LVEF was significantly higher in the IgG3 group (p = 0.007). Multiple regression analysis showed that IgG3-β1AR-AAb was an independent predictor of LVEF at 6 months and change in LVEF over 6 months, even after multivariable adjustment (LVEF at 6 months, β = 0.20, p = 0.01; change in LVEF, β = 0.20, p = 0.008). In patients with high New York Heart Association functional class (III or IV) at baseline, the IgG3 group had a lower incidence of the composite endpoint of all-cause death, cardiac transplantation, and hospitalization due to heart failure, whereas the non-IgG3 group had the highest incidence of the composite endpoint. Conclusions IgG3-β1AR-AAbs were associated with more favorable myocardial recovery in patients with recent-onset cardiomyopathy.

AB - Background Among various cardiac autoantibodies (AAbs), those recognizing the β1-adrenergic receptor (β1AR) demonstrate agonist-like effects and induce myocardial damage that can be reversed by β-blockers and immunoglobulin G3 (IgG3) immunoadsorption. Objectives The goal of this study was to investigate the role of β1AR-AAbs belonging to the IgG3 subclass in patients with recent-onset cardiomyopathy. Methods Peripheral blood samples were drawn at enrollment in patients with recent-onset cardiomyopathy (left ventricular ejection fraction [LVEF] ≤0.40; <6 months). The presence of IgG and IgG3-β1AR-AAb was determined, and echocardiograms were assessed, at baseline and 6 months. Patients were followed up for ≤48 months. Results Among the 353 patients who had blood samples adequate for the analysis, 62 (18%) were positive for IgG3-β1AR-AAbs (IgG3 group), 58 (16%) were positive for IgG but not IgG3 (non-IgG3 group), and the remaining were negative. There were no significant differences in baseline systolic blood pressure, heart rate, or LVEF among the groups at baseline. Left ventricular end-diastolic and end-systolic diameters were significantly larger in the non-IgG3 group compared with the other groups (left ventricular end-diastolic diameter, p < 0.01; left ventricular end-systolic diameter, p = 0.03). At 6 months, LVEF was significantly higher in the IgG3 group (p = 0.007). Multiple regression analysis showed that IgG3-β1AR-AAb was an independent predictor of LVEF at 6 months and change in LVEF over 6 months, even after multivariable adjustment (LVEF at 6 months, β = 0.20, p = 0.01; change in LVEF, β = 0.20, p = 0.008). In patients with high New York Heart Association functional class (III or IV) at baseline, the IgG3 group had a lower incidence of the composite endpoint of all-cause death, cardiac transplantation, and hospitalization due to heart failure, whereas the non-IgG3 group had the highest incidence of the composite endpoint. Conclusions IgG3-β1AR-AAbs were associated with more favorable myocardial recovery in patients with recent-onset cardiomyopathy.

KW - IgG3

KW - autoantibody

KW - recent-onset cardiomyopathy

KW - β-blocker

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