Effects of Hypertrophic and Dilated Cardiac Geometric Remodeling on Ejection Fraction

Yu Zheng; Wei Xuan Chan; Christopher J Charles; A Mark Richards; Smita Sampath; Asad Abu Bakar Ali; Hwa Liang Leo; Choon Hwai Yap

doi:10.3389/fphys.2022.898775

Effects of Hypertrophic and Dilated Cardiac Geometric Remodeling on Ejection Fraction

Front Physiol. 2022 May 31:13:898775. doi: 10.3389/fphys.2022.898775. eCollection 2022.

Authors

Yu Zheng¹, Wei Xuan Chan¹, Christopher J Charles^{2

3

4}, A Mark Richards^{3

4}, Smita Sampath⁵, Asad Abu Bakar Ali⁵, Hwa Liang Leo¹, Choon Hwai Yap⁶

Affiliations

¹ Department of Biomedical Engineering, National University of Singapore, Singapore, Singapore.
² Department of Surgery, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
³ Cardiovascular Research Institute, National University of Singapore, Singapore, Singapore.
⁴ Christchurch Heart Institute, Department of Medicine, University of Otago, Christchurch, New Zealand.
⁵ Translational Biomarkers, Merck Sharp & Dohme, Singapore, Singapore.
⁶ Department of Bioengineering, Imperial College London, London, United Kingdom.

Abstract

Background: Both heart failure (HF) with preserved ejection fraction (HFpEF) and heart failure with reduced ejection fraction (HFrEF) can present a wide variety of cardiac morphologies consequent to cardiac remodeling. We sought to study if geometric changes to the heart during such remodeling will adversely affect the ejection fraction (EF) parameter's ability to serve as an indicator of heart function, and to identify the mechanism for it. Methods and Results: A numerical model that simulated the conversion of myocardial strain to stroke volume was developed from two porcine animal models of heart failure. Hypertrophic wall thickening was found to elevate EF, while left ventricle (LV) dilation was found to depress EF when myocardial strain was kept constant, causing EF to inaccurately represent the overall strain function. This was caused by EF being calculated using the endocardial boundary rather than the mid-wall layer. Radial displacement of the endocardial boundary resulted in endocardial strain deviating from the overall LV strain, and this deviation varied with LV geometric changes. This suggested that using the epi- or endo-boundaries to calculate functional parameters was not effective, and explained why EF could be adversely affected by geometric changes. Further, when EF was modified by calculating it at the mid-wall layer instead of at the endocardium, this shortcoming was resolved, and the mid-wall EF could differentiate between healthy and HFpEF subjects in our animal models, while the traditional EF could not. Conclusion: We presented the mechanism to explain why EF can no longer effectively indicate cardiac function during cardiac geometric changes relevant to HF remodeling, losing the ability to distinguish between hypertrophic diseased hearts from healthy hearts. Measuring EF at the mid-wall location rather than endocardium can avoid the shortcoming and better represent the cardiac strain function.

Keywords: HFPEF; cardiac function; cardiac geometry remodelling; ejection fraction; mid-wall ejection fraction; myocardial strain.