Reduced Left Atrial Emptying Fraction and Chymase Activation in Pathophysiology of Primary Mitral Regurgitation

Brittany Butts; Mustafa I Ahmed; Navkaranbir S Bajaj; Pamela Cox Powell; Betty Pat; Silvio Litovsky; Himanshu Gupta; Steven G Lloyd; Thomas S Denney; Xiaoxia Zhang; Inmaculada Aban; Sakthivel Sadayappan; James W McNamara; Michael J Watson; Carlos M Ferrario; James F Collawn; Clifton Lewis; James E Davies; Louis J Dell'Italia

doi:10.1016/j.jacbts.2019.11.006

Reduced Left Atrial Emptying Fraction and Chymase Activation in Pathophysiology of Primary Mitral Regurgitation

JACC Basic Transl Sci. 2020 Jan 22;5(2):109-122. doi: 10.1016/j.jacbts.2019.11.006. eCollection 2020 Feb.

Authors

Brittany Butts¹, Mustafa I Ahmed¹, Navkaranbir S Bajaj¹, Pamela Cox Powell¹, Betty Pat¹, Silvio Litovsky², Himanshu Gupta^{1

3

4}, Steven G Lloyd^{1

3}, Thomas S Denney⁵, Xiaoxia Zhang⁵, Inmaculada Aban⁶, Sakthivel Sadayappan⁷, James W McNamara⁷, Michael J Watson⁸, Carlos M Ferrario⁹, James F Collawn¹⁰, Clifton Lewis¹¹, James E Davies¹¹, Louis J Dell'Italia^{1

3}

Affiliations

¹ Department of Medicine, Division of Cardiovascular Disease, University of Alabama at Birmingham, Birmingham, Alabama.
² Department of Pathology, University of Alabama at Birmingham, Birmingham, Alabama.
³ Department of Veterans Affairs Medical Center, Birmingham, Alabama.
⁴ Department of Cardiology, Valley Health System, Paramus, New Jersey.
⁵ Department of Electrical and Computer Engineering, Auburn University School of Engineering, Auburn, Alabama.
⁶ Department of Biostatistics, University of Alabama at Birmingham, Birmingham, Alabama.
⁷ Division of Cardiovascular Disease, University of Cincinnati College of Medicine, Cincinnati, Ohio.
⁸ Division of Cardiothoracic Surgery, Department of Surgery, Duke University, Durham, North Carolina.
⁹ Department of Surgery, Wake Forest University Health Science Center, Winston-Salem, North Carolina.
¹⁰ Department of Cell, Developmental, and Integrative Biology, University of Alabama at Birmingham, Birmingham, Alabama.
¹¹ Department of Surgery, Division of Thoracic and Cardiovascular Surgery, University of Alabama at Birmingham, Birmingham, Alabama.

Abstract

Increasing left atrial (LA) size predicts outcomes in patients with isolated mitral regurgitation (MR). Chymase is plentiful in the human heart and affects extracellular matrix remodeling. Chymase activation correlates to LA fibrosis, LA enlargement, and a decreased total LA emptying fraction in addition to having a potential intracellular role in mediating myofibrillar breakdown in LA myocytes. Because of the unreliability of the left ventricular ejection fraction in predicting outcomes in MR, LA size and the total LA emptying fraction may be more suitable indicators for timing of surgical intervention.

Keywords: EF, ejection fraction; LA EF, left atrial emptying fraction; LA, left atrial; LV, left ventricle; MR, mitral regurgitation; MV, mitral valve; RA, right atrial; TEM, transmission electron microscopy; TGF, transforming growth factor; chymase; fibrosis; left atrium; left ventricle; mitral regurgitation; mitral valve.

Abstract

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