Association of Female Menopause With Atrioventricular Mechanics and Outcomes

Kuo-Tzu Sung; Chanchal Chandramouli; Chi-In Lo; Jui-Peng Tsai; Yau-Huei Lai; Chih-Chung Hsiao; Shin-Yi Tsai; Chun-Ho Yun; Ta-Chuan Hung; Jen-Yuan Kuo; Jiun-Lu Lin; Charles Jia-Yin Hou; Ying-Ju Chen; Cheng-Huang Su; Chung-Lieh Hung; Bernard E Bulwer; Hung-I Yeh; Carolyn S P Lam

doi:10.3389/fcvm.2022.804336

Association of Female Menopause With Atrioventricular Mechanics and Outcomes

Front Cardiovasc Med. 2022 Apr 21:9:804336. doi: 10.3389/fcvm.2022.804336. eCollection 2022.

Authors

Kuo-Tzu Sung^{1

2

3}, Chanchal Chandramouli^{4

5}, Chi-In Lo¹, Jui-Peng Tsai^{1

2}, Yau-Huei Lai¹, Chih-Chung Hsiao^{1

2}, Shin-Yi Tsai^{2

6

7}, Chun-Ho Yun², Ta-Chuan Hung^{1

2}, Jen-Yuan Kuo^{1

2}, Jiun-Lu Lin², Charles Jia-Yin Hou^{1

2}, Ying-Ju Chen⁸, Cheng-Huang Su^{1

2}, Chung-Lieh Hung^{1

2

3

9}, Bernard E Bulwer^{10

11}, Hung-I Yeh^{5

12}, Carolyn S P Lam^{4

5

12}

Affiliations

¹ Division of Cardiology, Department of Internal Medicine, MacKay Memorial Hospital, Taipei, Taiwan.
² Department of Medicine, Mackay Medical College, New Taipei City, Taiwan.
³ Institute of Clinical Medicine, National Yang Ming University, Taipei, Taiwan.
⁴ National Heart Research Institute, National Heart Centre Singapore, Singapore, Singapore.
⁵ Academic Clinical Programme, Duke-National University of Singapore, Singapore, Singapore.
⁶ Department of Biomedical Imaging and Radiological Science, National Yang Ming University, Taipei, Taiwan.
⁷ School of Public Health, Johns Hopkins University Bloomberg, Baltimore, MD, United States.
⁸ Department of Telehealth, MacKay Memorial Hospital, Taipei, Taiwan.
⁹ Institute of Biomedical Sciences, Mackay Medical College, New Taipei City, Taiwan.
¹⁰ Brigham and Women's Hospital, Boston, MA, United States.
¹¹ Massachusetts College of Pharmacy and Health Sciences, Boston, MA, United States.
¹² Department of Medicine, University Medical Centre Groningen, Groningen, Netherlands.

Abstract

Background: Despite known sex differences in cardiac structure and function, little is known about how menopause and estrogen associate with atrioventricular mechanics and outcomes.

Objective: To study how, sex differences, loss of estrogen in menopause and duration of menopause, relate to atrioventricular mechanics and outcomes.

Methods: Among 4051 asymptomatic adults (49.8 ± 10.8 years, 35%women), left ventricular (LV) and left atrial (LA) mechanics were assessed using speckle-tracking.

Results: Post-menopausal (vs. pre-menopausal) women had similar LV ejection fraction but reduced GLS, reduced PALS, increased LA stiffness, higher LV sphericity and LV torsion (all p < 0.001). Multivariable analysis showed menopause to be associated with greater LV sphericity (0.02, 95%CI 0.01, 0.03), higher indexed LV mass (LVMi), lower mitral e', lower LV GLS (0.37, 95%CI 0.04-0.70), higher LV torsion, larger LA volume, worse PALS (∼2.4-fold) and greater LA stiffness (0.028, 95%CI 0.01-0.05). Increasing years of menopause was associated with further reduction in GLS, markedly worse LA mechanics despite greater LV sphericity and higher torsion. Lower estradiol levels correlated with more impaired LV diastolic function, impaired LV GLS, greater LA stiffness, and increased LV sphericity and LV torsion (all p < 0.05). Approximately 5.5% (37/669) of post-menopausal women incident HF over 2.9 years of follow-up. Greater LV sphericity [adjusted hazard ratio (aHR) 1.04, 95%CI 1.00-1.07], impaired GLS (aHR 0.87, 95%CI 0.78-0.97), reduced peak left atrial longitudinal strain (PALS, aHR 0.94, 95%CI 0.90-0.99) and higher LA stiffness (aHR 10.5, 95%CI 1.69-64.6) were independently associated with the primary outcome of HF hospitalizations in post-menopause. Both PALS < 23% (aHR:1.32, 95%CI 1.01-3.49) and GLS < 16% (aHR:5.80, 95%CI 1.79-18.8) remained prognostic for the incidence of HF in post-menopausal women in dichotomous analyses, even after adjusting for confounders. Results were consistent with composite outcomes of HF hospitalizations and 1-year all-cause mortality as well.

Conclusion: Menopause was associated with greater LV/LA remodeling and reduced LV longitudinal and LA function in women. The cardiac functional deficit with menopause and lower estradiol levels, along with their independent prognostic value post-menopause, may elucidate sex differences in heart failure further.

Keywords: echocardiography; estrogen; heart failure; left atrial strain; menopause; remodeling; women.