Author + information
- Received October 1, 2019
- Revision received November 4, 2019
- Accepted November 4, 2019
- Published online February 24, 2020.
- Brittany Butts, PhDa,
- Mustafa I. Ahmed, MDa,
- Navkaranbir S. Bajaj, MD, MPHa,
- Pamela Cox Powell, MSa,
- Betty Pat, PhDa,
- Silvio Litovsky, MDb,
- Himanshu Gupta, MDa,c,d,
- Steven G. Lloyd, MDa,c,
- Thomas S. Denney, PhDe,
- Xiaoxia Zhang, PhDe,
- Inmaculada Aban, PhDf,
- Sakthivel Sadayappan, PhD, MBAg,
- James W. McNamara, PhDg,
- Michael J. Watson, PhDh,
- Carlos M. Ferrario, MDi,
- James F. Collawn, PhDj,
- Clifton Lewis, MDk,
- James E. Davies, MDk and
- Louis J. Dell’Italia, MDa,c,∗ ()
- aDepartment of Medicine, Division of Cardiovascular Disease, University of Alabama at Birmingham, Birmingham, Alabama
- bDepartment of Pathology, University of Alabama at Birmingham, Birmingham, Alabama
- cDepartment of Veterans Affairs Medical Center, Birmingham, Alabama
- dDepartment of Cardiology, Valley Health System, Paramus, New Jersey
- eDepartment of Electrical and Computer Engineering, Auburn University School of Engineering, Auburn, Alabama
- fDepartment of Biostatistics, University of Alabama at Birmingham, Birmingham, Alabama
- gDivision of Cardiovascular Disease, University of Cincinnati College of Medicine, Cincinnati, Ohio
- hDivision of Cardiothoracic Surgery, Department of Surgery, Duke University, Durham, North Carolina
- iDepartment of Surgery, Wake Forest University Health Science Center, Winston-Salem, North Carolina
- jDepartment of Cell, Developmental, and Integrative Biology, University of Alabama at Birmingham, Birmingham, Alabama
- kDepartment of Surgery, Division of Thoracic and Cardiovascular Surgery, University of Alabama at Birmingham, Birmingham, Alabama
- ↵∗Address for correspondence:
Dr. Louis J. Dell’Italia, Birmingham VA Medical Center, 700 South 19th Street, Birmingham, Alabama 35233.
• Extensive LA fibrosis is related to an increase in LA size and decrease in total LA EF. This supports the contention that the LA is not merely a bystander of MR but rather is actively involved in the pathophysiology of MR.
• Chymase is plentiful in the human heart, especially in the LA, and correlates with extracellular matrix accumulation in primary MR.
• Because of the unreliability of the LV ejection fraction in primary MR, future studies may consider LA size and total LA EF for timing of surgical intervention of asymptomatic moderate to severe MR.
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.
Drs. Ferrario and Dell’Italia were supported by the National Heart, Lung, and Blood Institute (NHLBI) (P01 HL051952). Dr. Dell’Italia was supported by the NHLBI and the Specialized Centers of Clinically Oriented Research (P50HL077100), by the National Institutes of Health National Center for Medical Rehabilitation Research (4T32HD071866), and by the Department of Veteran Affairs for Merit Review (1CX000993-01). Dr. Bajaj was supported by an American College of Cardiology Presidential Career Development award, Walter B. Frommeyer, Junior Fellowship in Investigative Medicine and National Center for Advancing Translational Research of the National Institutes of Health (UL1TR001417). Dr. Sadayappan is a consultant with Amgen, Merck, MyoKardia, Red Saree Inc., Leducq Foundation, and AstraZeneca. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
The authors attest they are in compliance with human studies committees and animal welfare regulations of the authors’ institutions and Food and Drug Administration guidelines, including patient consent where appropriate. For more information, visit the JACC: Basic to Translational Science author instructions page.
- Received October 1, 2019.
- Revision received November 4, 2019.
- Accepted November 4, 2019.