Heart failure is the terminal stage of the progression of various cardiovascular diseases. The patient's own heart develops systolic or diastolic dysfunction, and it has a high mortality rate. Approximately 40 million heart failure patients are reported worldwide every year, and the mortality rate exceeds 10% (1, 2). Heart failure patients can be divided into three categories according to left ventricular ejection fraction (LVEF): heart failure with reduced ejection fraction, heart failure with preserved ejection fraction (HFpEF), and mildly reduced ejection fraction heart failure (3). HFpEF is a heterogeneous syndrome with multiple comorbidities, multiple cardiac and extracardiac pathophysiological abnormalities, and multiple phenotypic manifestations (4). There is currently no effective treatment for HFpEF, and few treatments can effectively improve patient survival rates. The focus of treatment is only on optimizing risk factors for HFpEF.

HFpEF continues to present challenges for treatment because of its heterogeneity of pathogenesis and lack of effective treatments, making prognostication an important area of research (5).

Epicardial adipose tissue (EAT) is a metabolically active depot of visceral fat located between the myocardium and the visceral pericardium that is in contact with coronary vessels and myocardial tissue, ultimately leading to both local inflammation and cardiac remodeling. EAT enlarges abnormally in patients with HFpEF and may mediate this process by secreting proinflammatory and fibrotic cytokines, leading to impaired relaxation of the myocardial wall and diastolic dysfunction (6, 7).

That said, the prognostic significance and potential to use EAT thickness as a prognostic marker among patients with HFpEF is not well evaluated, particularly among East Asian population groups in which there is a greater prevalence of non-obesity phenotypes ,with overall body composition differing from that of Western profile groups. Thus, existing findings are not transferable in East Asian cohorts, highlighting the need to investigate these region-specific data (8, 9).

For this reason, this study investigated the association of EAT thickness and clinical outcomes in HFpEF patients from an East Asian, non-obese population. Using transthoracic echocardiography to evaluate EAT, we were also able to show that EAT could be examined as a non-invasive biomarker for risk stratification and prognostication (10).

Heart failure is a clinical syndrome in which the typical signs and symptoms are caused by structural and/or functional cardiac abnormalities, resulting in reduced cardiac output or increased intracardiac pressure at rest or during stress, thereby reducing the return of blood to the cardiac veins. It cannot flow out sufficiently, resulting in venous blood stasis and insufficient blood supply in the blood vessels, which causes a syndrome of cardiac circulatory dysfunction (12–14). Heart failure is the most prominent cause of hospitalization worldwide, affecting 3.6 million new patients annually and causing a socioeconomic burden of billions of dollars annually. Heart failure is the leading cause of hospitalization for people aged 65 and above in China, and the mortality rate is high (15). Although patients with HFpEF have higher ejection fractions, echocardiography shows that patients with HFpEF are similar to patients with heart failure with reduced ejection fraction, and the pathogenesis of HFpEF is more heterogeneous and complex, which is mainly related to ventricular diastolic dysfunction (16, 17). Compared with heart failure patients with reduced ejection fraction, the clinical treatment effect of HFpEF is poor, and the mortality rate is even higher than the former. Therefore, the prognosis of HFpEF patients is a current research hotspot.

Clinically, HFpEF is mainly characterized by diastolic dysfunction, accompanied by left ventricular hypertrophy, left atrium enlargement, decreased diastolic function, impaired cardiac function, inflammatory infiltration of cardiac tissue, and collagen deposition, leading to ventricular remodeling. Left ventricular end-diastolic diameter (LVEDD), left atrial diameter (LAD), LVMI, and LVEF are indicators reflecting ventricular remodeling. The results of this study showed that EAT thickness, LVMI, LAVI, and E/e′ were higher in the observation group than in the control group (P < 0.05), and LVEF was lower than in the control group (P < 0.05). It is suggested that echocardiographic parameters can reflect changes in ventricular morphology and configuration in patients with heart failure occurrence and development, which are closely related to changes in the above parameter values. LVEF is routinely used to evaluate the overall systolic function of the left ventricle.

EAT is visceral fat deposited between the visceral pericardium and the myocardium and in direct contact with the myocardium and coronary arteries. From a physiological perspective, EAT acts as a temperature regulator and provides energy to the myocardium. Furthermore, EAT behaves as a metabolically active endocrine organ and secretes bioactive molecules that affect the heart and coronary arteries through paracrine or angiocrimin effects. It can produce proinflammatory adipokines (such as leptin, TNF-α, IL-6, and resistin) and downregulate anti-inflammatory adipokines (such as adiponectin and omentin-1) (18). The thickness of EAT is directly proportional to its proinflammatory effect (19). The increase in EAT thickness indicates that chronic inflammation is more intense, and the cardiac load gradually increases. Inflammatory cytokines regulate the phenotype and function of all cardiomyocytes and inhibit the contractile function of cardiomyocytes. They induce inflammatory activation of macrophages, stimulate microvascular inflammation and dysfunction, and promote a matrix-degrading phenotype of fibroblasts, leading to ventricular remodeling. The addition of proinflammatory factors makes myocardial damage more serious and can mediate the apoptosis of myocardial tissue cells. Direct mechanical compression of the myocardium may also be exerted when the EAT thickness increases, leading to a constrictive pericarditis-like condition. Because of the limited flexibility of the pericardium, increased EAT thickness will lead to a reduction in the expansion ability of the wrapped myocardium, leading to diastolic dysfunction and increased cardiac filling pressure (20–22).

In this study, EAT thickness was negatively correlated with LVEF, while it was positively correlated with LVMI, LAVI, and E/e′ (all P < 0.05), highlighting the link to adverse cardiac remodeling. Notably, these results are in keeping with previous findings. Okuno et al. found increased EAT volume correlated with the diastolic strain rate and adverse remodeling in HFpEF (23). Albani et al. confirmed that the inflammatory signaling process facilitated by EAT influences ventricular stiffness and fibrosis, which is a hallmark of HFpEF (24). Parisi et al. confirmed that echocardiographic EAT thickness was able to independently predict arrhythmia, HF progression, and mortality (25).

EAT is also the heart's visceral fat depot. In a healthy state, EAT represents approximately 20% of the heart's weight, with the main visceral fat depots located around the right coronary artery and left anterior descending coronary artery, with some distribution around the atrium, right ventricular free wall, and apical wall (26). A microscopic evaluation of EAT shows a predominance of white adipocytes, which are responsible for energy storage. The cellularity of EAT is greater than that of subcutaneous or other visceral fat depots, associated with less mature adipocytes and more preadipocytes. The visceral fat of EAT not only provides mechanical protection to the heart and peripheral blood vessels but also acts as a unique endocrine organ. Under pathological conditions, it can facilitate the accumulation of EAT and promote the conversion of EAT into a proinflammatory and profibrotic phenotype (27).

The univariate analysis in this study showed that hemoglobin and eGFR values were lower in the poor prognosis group compared with the good prognosis group (P < 0.05), and EAT thickness, blood lactate level, and Scr level were all higher in the poor prognosis group (P < 0.05). The Kaplan–Meier survival curves revealed that patients with an EAT thickness >7.59 mm had significantly less event-free survival compared with patients with an EAT thickness ≤7.59 mm. Through the multivariate Cox analysis, we found that increased EAT thickness, lower hemoglobin level, and increased lactate level were independent variables predictive of poor prognosis (all P < 0.05). We are in agreement with Maimaituxun et al. (28), who found that EAT volume negatively correlated with global longitudinal strain in HF patients, thus supporting the association between EAT and decrements in systolic function.

In addition, prior studies have shown that HFpEF patients have significantly greater total and total ventricular EAT volumes compared with HFrEF patients, even with BMI matching (29). Another study with a cohort of 155 HFpEF patients showed that greater EAT predicted worse outcomes over 24 months of follow-up (30). In a meta-analysis of 1,983 patients from 12 studies of heart failure, it was shown that increased EAT thickness was significantly correlated to increased BNP levels and HF severity (31–34).

This study demonstrated that there could be a strong predictive power of EAT and, in this case, the ROC curve analysis yielded an AUC of 0.892, a sensitivity rate of 89.13%, and a specificity rate of 88.39%. This suggests that echocardiographic EAT thickness could be a valid non-invasive parameter of prognosis in patients with HFpEF.

This study has several limitations. First, it is a single-center study with a small sample size, which can limit external generalizability. Second, there was limited biomarker data (for instance, BNP or NT-proBNP), which were not available for all patients, and many other prognostic biomarkers were not evaluated or collected during the study period. Thirdly, EAT was assessed using echocardiography rather than CT or MRI, which will minimize spatial accuracy and dimensional accuracy. Fourth, we did not consider the factor of interobserver variability in measuring EAT. Finally, the observational nature of this study limits the potential for drawing causal conclusions.

Despite these stated limitations, our findings support the clinical value of EAT thickness as a prognostic marker for HFpEF and suggest a further exploration of how EAT luminosity could be of value for risk refinement and risk stratification. There is a need for future multicenter studies using volumetric imaging modalities to confirm our findings.

EAT thickness is independently associated with adverse events in patients with HFpEF. EAT thickness may represent a simple, non-invasive, and readily available measure of cardiac remodeling and risk stratification. Additional multicenter studies are necessary to confirm its prognostic utility.