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, Dennis M. McNamara, Karen Janosko, Charles McTiernan, Barry London, Karen Hanley-Yanez, John Gorcsan, Hidekazu Tanaka, Mathew Suffoletto, Randall C. Starling, Cynthia Oblak, Leslie T. Cooper & 34 others 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, Daniel F. Pauly, Pamela C. Smith, Richard Sheppard, Stephanie Fuoco, Ilan S. Wittstein, Elayne Breton, Vinay Thohan, Deborah Wesley, G. William Dec, 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 journalArticle

8 Citations (Scopus)

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 languageEnglish (US)
Pages (from-to)968-977
Number of pages10
JournalJournal of the American College of Cardiology
Volume69
Issue number8
DOIs
StatePublished - Feb 28 2017

Fingerprint

Systolic Heart Failure
Autoantibodies
Adrenergic Receptors
Immunoglobulins
Stroke Volume
Cardiomyopathies
Immunoglobulin G
Blood Pressure
Adrenergic Agonists
Incidence
Heart Transplantation
Cause of Death
Hospitalization
Heart Failure
Heart Rate
Regression Analysis

Keywords

  • autoantibody
  • IgG3
  • recent-onset cardiomyopathy
  • β-blocker

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Nagatomo, Y., McNamara, D. M., Alexis, J. D., Cooper, L. T., Dec, G. W., Pauly, D. F., ... 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

Myocardial Recovery in Patients With Systolic Heart Failure and Autoantibodies Against β1-Adrenergic Receptors. / Nagatomo, Yuji; McNamara, Dennis M.; Alexis, Jeffrey D.; Cooper, Leslie T.; Dec, G. William; Pauly, Daniel F.; Sheppard, Richard; Starling, Randall C.; Tang, W. H Wilson; McNamara, Dennis M.; Janosko, Karen; McTiernan, Charles; London, Barry; Hanley-Yanez, Karen; Gorcsan, John; Tanaka, Hidekazu; Suffoletto, Mathew; Starling, Randall C.; Oblak, Cynthia; Cooper, Leslie T.; McNallan, Annette; Koenig, Lu Anne; Mather, Paul; Pierson, Natalie; Rubin, Sharon; Bell, Yanique; Ervin, Alicia; Boehmer, John; Frey, Patricia; Alexis, Jeffrey; Schrack, Janice; LaDuke, Pam; Torre-Amione, Guillermo; Arredondo, Jeannie; Pauly, Daniel F.; Smith, Pamela C.; Sheppard, Richard; Fuoco, Stephanie; Wittstein, Ilan S.; Breton, Elayne; Thohan, Vinay; Wesley, Deborah; Dec, G. William; Cocca-Spofford, Diane; Markham, David W.; Fernandez, Lynn; Debes, Colleen; Zucker, Mark J.; Adams, Laura; Liu, Peter; Renton, Judith; Narula, Jagat; Allen, Byron; Westberg, Elizabeth.

In: Journal of the American College of Cardiology, Vol. 69, No. 8, 28.02.2017, p. 968-977.

Research output: Contribution to journalArticle

Nagatomo, Y, McNamara, DM, Alexis, JD, Cooper, LT, Dec, GW, Pauly, DF, Sheppard, R, Starling, RC, Tang, WHW, McNamara, DM, Janosko, K, McTiernan, C, London, B, Hanley-Yanez, K, Gorcsan, J, Tanaka, H, Suffoletto, M, Starling, RC, Oblak, C, Cooper, LT, 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, Pauly, DF, Smith, PC, Sheppard, R, Fuoco, S, Wittstein, IS, Breton, E, Thohan, V, Wesley, D, Dec, GW, 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
Nagatomo, Yuji ; McNamara, Dennis M. ; Alexis, Jeffrey D. ; Cooper, Leslie T. ; Dec, G. William ; Pauly, Daniel F. ; Sheppard, Richard ; Starling, Randall C. ; Tang, W. H Wilson ; McNamara, Dennis M. ; Janosko, Karen ; McTiernan, Charles ; London, Barry ; Hanley-Yanez, Karen ; Gorcsan, John ; Tanaka, Hidekazu ; Suffoletto, Mathew ; Starling, Randall C. ; Oblak, Cynthia ; Cooper, Leslie T. ; McNallan, Annette ; Koenig, Lu Anne ; Mather, Paul ; Pierson, Natalie ; Rubin, Sharon ; Bell, Yanique ; Ervin, Alicia ; Boehmer, John ; Frey, Patricia ; Alexis, Jeffrey ; Schrack, Janice ; LaDuke, Pam ; Torre-Amione, Guillermo ; Arredondo, Jeannie ; Pauly, Daniel F. ; Smith, Pamela C. ; Sheppard, Richard ; Fuoco, Stephanie ; Wittstein, Ilan S. ; Breton, Elayne ; Thohan, Vinay ; Wesley, Deborah ; Dec, G. William ; Cocca-Spofford, Diane ; Markham, David W. ; Fernandez, Lynn ; Debes, Colleen ; Zucker, Mark J. ; Adams, Laura ; Liu, Peter ; Renton, Judith ; Narula, Jagat ; Allen, Byron ; Westberg, Elizabeth. / Myocardial Recovery in Patients With Systolic Heart Failure and Autoantibodies Against β1-Adrenergic Receptors. In: Journal of the American College of Cardiology. 2017 ; Vol. 69, No. 8. pp. 968-977.
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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 = "autoantibody, IgG3, 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 McNamara, {Dennis M.} and Karen Janosko and Charles McTiernan and Barry London and Karen Hanley-Yanez and John Gorcsan and Hidekazu Tanaka and Mathew Suffoletto and Starling, {Randall C.} and Cynthia Oblak and Cooper, {Leslie T.} 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 Pauly, {Daniel F.} and Smith, {Pamela C.} and Richard Sheppard and Stephanie Fuoco and Wittstein, {Ilan S.} and Elayne Breton and Vinay Thohan and Deborah Wesley and Dec, {G. William} 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",
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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 - McNamara, Dennis M.

AU - Janosko, Karen

AU - McTiernan, Charles

AU - London, Barry

AU - Hanley-Yanez, Karen

AU - Gorcsan, John

AU - Tanaka, Hidekazu

AU - Suffoletto, Mathew

AU - Starling, Randall C.

AU - Oblak, Cynthia

AU - Cooper, Leslie T.

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 - Pauly, Daniel F.

AU - Smith, Pamela C.

AU - Sheppard, Richard

AU - Fuoco, Stephanie

AU - Wittstein, Ilan S.

AU - Breton, Elayne

AU - Thohan, Vinay

AU - Wesley, Deborah

AU - Dec, G. William

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 - autoantibody

KW - IgG3

KW - recent-onset cardiomyopathy

KW - β-blocker

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