Association between epicardial adipose tissue and myocardial work by non-invasive left ventricular pressure-strain loop in people with suspected metabolic syndrome – Scientific Reports

This is the first study to manifest the correlation between EAT thickness and LV myocardial work in subjects with suspected metabolic syndrome. The main findings of the study were: (1) Compared with the thin EAT group, IVSd, LVPWd and LVMI in the thick EAT group were significantly increased, while the absolute values of GLS, E and e’ were significantly decreased; (2) The thick EAT group achieved significantly higher value in GWW in comparison with the thin EAT group. Meanwhile, the GWI, GCW, and GWE were significantly decreased in the thick EAT group; and (3) EAT thickness was inversely correlated with GWI and GCW.

EAT and left ventricular remodeling

In general, the conventional clinical evaluation of left ventricular systolic function is performed through the measurement of myocardial fiber shortening indexes (e.g., left ventricular EF, left ventricular wall thickening, myocardial velocity, and strain)¹⁹. In this study, conventional echocardiographic parameters were compared between the two groups. The results show that IVSd, LVPWd and LVMI in the thick EAT group were significantly increased compared with the thin EAT group, while the absolute values of GLS, E and e’ were significantly decreased. In metabolic syndromes, left ventricular hypertrophy may occur with increased after-load²⁰. It is the most prominent early cardiac manifestation in hypertensive patients, characterized by increased myocardial weight and ventricular remodeling. Diabetic myocardial microangiopathy can lead to chronic myocardial ischemia and hypoxia, cardiomyocyte necrosis, myocardial fibrocyte proliferation, and eventually left ventricular hypertrophy. Moreover, several inflammatory substances released from adipocytes, such as resistin have been suggested to contribute toward the adverse effects of obesity on the heart by promoting myocardial hypertrophy and dysfunction²¹. Extensive research has reported that the myocardial strain obtained by two-dimensional speckle tracking imaging can make left ventricular quantization beyond LVEF a better prognostic marker of cardiac events^22,23,24. In this study, no significant difference in AAO, LAD, LVEDd, LVEF, A and E/e′ was reported between the thin and thick EAT groups. Compared with the traditional index of systolic function, GLS is more sensitive to indicate the degree of myocardial injury, and may decrease prior to the change of LVEF, consistent with previous literature reports. Among the measurements of myocardial function, GLS measured by echocardiography is the most widely studied marker, providing a simple, inexpensive, and quantitative way to assess global long-axis systolic function. However, one of the major limitations of strain imaging is after-load dependence. Moreover, it cannot reflect myocardial work or oxygen demand²⁵. The noninvasive LV pressure-strain loop serves as a novel method of quantifying myocardial work in combination with myocardial strain and LV pressure measurements, and may provide incremental value for assessment of myocardial function²⁶. The work contributed by the respective normal contracting component is positive and is called “constructive work”. In the normal heart, very little work is wasted and thus there is a high work efficiency. Compared with the thin EAT group, GWW was significantly increased in thick EAT group, while GWI, GCW, and GWE notably declined. Prolonged systole and shortened myocardium after aortic valve closure will produce wasted work because it does not result in left ventricular ejection. In early untreated hypertension, diastolic dyssynchrony mainly affected constructive work, whereas post systolic shortening affected wasted work²⁷.

EAT and left ventricular myocardial work

To the best of our knowledge, this study has been the first to evaluate the role of MS on the correlation between EAT and myocardial work. The EAT is located outside the myocardial wall and maintains intimal contact with the epicardial vessels and myocardium, allowing for paracrine or vasocrine effects. Under health conditions, EAT has protective functions (e.g., prevention of hypothermia, secretion of adiponectin by epicardial fat cells, and mechanical protection of coronary circulation) while taking on critical significance in the energy supply of myocardium²⁸. However, excess body fat accumulation is correlated with metabolic abnormalities and myocardial dysfunction^29,30. In this case, the protective properties of EAT may be destroyed and become harmful tissues that promote the development of cardiovascular diseases. Despite the unclear underlying mechanism, EAT has been confirmed as a potential source of inflammatory mediators, comprising interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α. Hirata et al. reported that the infiltration of inflammatory cells was enhanced in the epicardial adipose tissue of patients with coronary artery disease, instead of not in the subcutaneous fat³¹. Moreover, EAT has the potential to secrete adipotropic factors and free fatty acids, which may promote myocardial steatosis and induce cellular oxidative stress, as well as increased nitric oxide synthase activity and production of intracellular nitric oxide, and eventually lead to apoptosis of myofibrillar cells³². Recent research has placed a focus on myocardial fibrosis, a critical histological component of cardiac remodeling. Myocardial fibrosis scarring occurs most commonly after myocardial infarction, but can also occur in a variety of other diseases that promote myocardial fibrosis (e.g., hypertensive heart disease, diabetic hypertrophic cardiomyopathy, and idiopathic dilated cardiomyopathy)³³. As revealed by relevant data, EAT is capable of producing and secreting adipo-fibrokines (e.g., Activin A), which may promote the formation of myocardial fibrosis³⁴.

A significant correlation and agreement existed between the area of the non-invasive LV pressure-strain loop and glucose metabolism examined by positron emission tomography. Glucose metabolism is capable of indicating myocardial work. GCW refers to the work performed by the LV during contraction that contributes to LV ejection and is divided into shortening of cardiomyocytes during contraction and lengthening of cardiomyocytes during isovolumic relaxation. GWI is the total work in the LV pressure-strain loop area calculated from mitral valve closure to mitral valve opening²⁶. The left ventricular mechanics were significantly impaired by speckle tracking echocardiography in patients with metabolic syndrome. Previous studies have shown that epicardial fat volume is negatively correlated with left ventricular systolic dysfunction in patients with heart failure³⁵. In this study, we found that EAT was negatively correlated with GWI and GCW in myocardial work parameters in patients with metabolic syndrome. In middle-aged male subjects with metabolic syndrome, EAT was correlated with inflammation represented by high‑sensitivity C‑reactive protein level, LV mass index, e′ and GLS, suggesting that the inflammatory activity of EAT induced myocardial remodeling and dysfunction²⁹. Besides, this study further confirmed that EAT can have an adverse relationship with LV myocardial work at the early stage of LV remodeling.

LV myocardial work and metabolic syndrome criteria

Furthermore, LV myocardial work were also correlated with SBP, triglyceride, fasting blood glucose in metabolic syndrome. Men and women with impaired fasting glucose and impaired glucose tolerance have more severe alterations in cardiometabolic profiles and inflammatory markers than patients with impaired fasting glucose alone. Even in the absence of high blood pressure, these people were ten times more likely to develop preclinical cardiovascular disease³⁶. Fibroblast growth factor-23 (FGF-23) is a biomarker of cardiovascular disease and may also be an early marker of cardiac injury in obese but otherwise healthy African American adolescents. Obesity may promote FGF-23 production in the absence of chronic kidney disease³⁷. Previous studies have shown that blood pressure, waist circumference, and fasting glucose levels exert the most significant effect on left ventricular deformation of all metabolic syndrome components³⁸. The findings in this study are similar to those of previous studies.

Limitations

Several limitations remained in this study. The correlation between increased EAT thickness and impaired LV myocardial work cannot prove that increased EAT inevitably leads to increased LV injury, and its pathophysiological mechanism needs to be further demonstrated. LV pressure-strain loop technology is based on two-dimensional speckle tracking echocardiography, which requires high-quality ultrasonic images. Brachial systolic pressure examined with a cuff and sphygmomanometer may be inaccurate because systolic pressure varies.