Introduction: Obesity is a risk strong factor for heart failure with preserved ejection fraction (EF), in which diastolic dysfunction plays a critical role_{^{1, 2,3, 4}}. Obesity is often associated with multiple comorbidities. Whether obese subjects with no clinical signs or comorbidities have diastolic dysfunction is unclear. Feature tracking technique derived from cardiac magnetic resonance (CMR) can non-invasively detect early myocardial dysfunction with preserved EF⁵. Recent studies demonstrated that left atrial (LA) longitudinal strain is associated with left ventricular (LV) end-diastolic pressure and filling pressures, which are invasive gold standards for assessing diastolic function ^{6, 7}. In addition to BMI, dual X-ray absorptiometry (DXA) further divides body fat, such as android, gynoid, trunk, and visceral fat⁸. These fat tissue have been linked to cardiovascular risk factors^9-11. However, the effect of these regional fat distribution on left heart function is unclear. Therefore, this study assessed the effect of uncomplicated obesity on diastolic function by measuring LA and LV strain and volume-time curve using CMR and evaluate the association between diastolic function with fat distribution.
Methods: The study complied with the Declaration of Helsinki and was approved by the Institutional Review Board of our Hospital. Written informed consents were obtained from all participants. We prospectively recruited 49 mild-to-moderate obese subjects and 43 healthy volunteers between 18 and 60 years old. BMI was categorized into the three groups according to the Asia criteria: healthy weight (18.5-23.0 kg/m²), overweight (23.0-27.5kg/m²), and obesity (≥27.5kg/m²). Subjects were excluded if they had any of the following conditions: hypertension and diabetes; history of lipid-lowering, hypoglycemic, or antihypertensive drugs; history of cardiovascular diseases or cardiovascular procedures; major systemic diseases that may affect the myocardium, such as connective tissue disease; respiratory diseases that could affect heart, such as obstructive sleep apnea; renal failure; and any contraindication to CMR imaging. CMR examinations were performed with an 18-element surface coil on 3.0 T whole-body scanner (MAGNETOM Skyra, Siemens Medical Solutions, Erlangen, Germany). A balanced steady-state free precession sequence was used to acquire continuous cine images in the short-axis view and two- and four-chamber cine images in the long-axis view. The parameters are as follows: TR/TE=3.3/1.22 ms, flip angle=41°, slice thickness=8 mm, field of view=360×320 mm², matrix size=208×166, and a temporal resolution=39.34 ms. CMR data was imported to commercially available software (CVI 42 version 5.11.3). LA strain [total, passive, and active strains (ε^s, ε^e, and ε^a) and peak positive, early and late negative strain rates (SRs, SRe, and SRa)], LV strain [peak diastolic/systolic strain rates (PDSR and PSSR)] and volume-time curve [peak filling rate/end‑diastolic volume (PFR/EDV) and peak ejection rate/end‑diastolic volume (PER/EDV)] were measured. DXA (Lunar iDXA, GE Medical Systems Lunar) was used to measure body fat distribution. All statistical analyses were performed using the SPSS (version 23). Continuous data between obesity and controls were compared using Student’s t-test and Whitney U-test. Pearson’s correlation and linear regression were used to estimate the correlation.
Results: The obese participants had impaired diastolic function, manifested as lower LV circumferential and longitudinal PDSR (1.3±0.2s^-1 vs. 1.5±0.3s^-1, 0.8±0.2s^-1 vs. 1.1±0.2s^-1, all P<0.05), LV PFR/EDV (3.5±0.6 s^-1 vs. 3.9±0.7 s^-1, P=0.012), and declined LA reservoir function [ε^s and SRs (46.4±8.4% vs. 51±12%, 1.9±0.5s^-1 vs. 2.3±0.5s^-1; all P<0.05)] and conduit function [ε^e and SRe (30.8±8.0% vs. 35.5±9.8%, 3.1±0.8s^-1 vs. 3.5±1.0s^-1; all P<0.05)] compared with controls. The LV systolic function parameters (PSSR and PER/EDV) and LA pumping function was not different between obesity and controls. Multivariable linear regression analysis demonstrated that trunk fat was independently associated with LA ε^e (β=-0.520, P=0.001; R²=0.270) and LV circumferential PDSR (β=−0.417, P=0.003; R²=0.174); visceral fat and peripheral fat were associated with LV longitudinal PDSR (β=−0.342, P=0.038; β=0.376, P=0.024; R²=0.389); gynoid fat was associated with LA ε^s (β=0.384, P=0.014; R²=0.148) and LV PFR/EDV (β=0.285, P=0.047; R²=0.081).
Discussion: In our study, subclinical diastolic dysfunction is found in obese adults with preserved LVEF. Earlier echocardiographic studies have shown both systolic and diastolic dysfunction in severe obesity. These findings may suggest that mild-moderate uncomplicated obesity initially develop diastolic dysfunction rather than systolic dysfunction. Our study also demonstrated that obese subjects had decreased LA reservoir and conduit function and preserved pump function compared with controls. Previous literature indicated that LA reservoir and conduit function were impaired in all grades of diastolic dysfunction, while pump function was increased in mild diastolic dysfunction and reduced as diastolic dysfunction progressed^{12, 13}. The findings of LA function in our study may reveal mild diastolic dysfunction in these obese individuals. Moreover, our results showed that central fat distributions (visceral fat and trunk fat) had negative relationships while peripheral fat distributions (peripheral fat and gynoid fat) had positive relationships on diastolic function. The different effects of these fat distributions on metabolic factors (such as dyslipidemia), inflammatory cytokines, and adipokines may partially explain the discrepant effects of fat distributions on cardiac function.
Conclusion: CMR-derived feature tracking and volume-time curve non-invasively detected subclinical diastolic dysfunction in early adult obesity with preserved LVEF. Central fat has a negative association while peripheral fat has a positive association on diastolic function. This finding suggests that recognizing the role of different areas of fat on the heart may be beneficial for obese patients.

Acknowledgements

This work was supported by grants from the National Natural Science Foundation of China (No. 81601462), the Key Research & Development Project of Science and Technology of Sichuan Province (No. 2021YFS0142), the Science and Technology Department of Sichuan Province (No. 2019YFS0302), and the 1.3.5. Project for Disciplines of Excellence, West China Hospital, Sichuan University (No. ZYGD18017).