To our knowledge, this is the first study investigating the role of EAT and PCAT, calculated from CCTA, in HFpEF. We found that these CCTA parameters were significantly associated with all-cause mortality and rehospitalization. Multivariate stepwise analysis revealed that EAT and PCAT-RCA were predictive of outcome in HFpEF patients. ROC curves demonstrated that EAT > 56.29 cm3 and RCA attenuation < -69.31HU were significantly associated with shorter survival. Our findings offer a novel and promising noninvasive method for clinical assessment and risk stratification of patients with HFpEF.
Epicardial adipose tissue (EAT) is a distinct adipose tissue located between the myocardium and visceral pericardium, and has been shown to produce pro-inflammatory cytokines and adipokines that may contribute to myocardial inflammation and fibrosis[23, 24]. Several studies have demonstrated a significant association between increased EAT volume and the development and progression of HFpEF[9, 25]. Previous studies primarily measured EAT using echocardiography and found it to be a predictor of adverse outcomes in HFpEF[25]. In one such study by Monti CB, increased EAT thickness measured by echocardiography was associated with worse clinical outcomes in patients with HFpEF[26]. Thickening of EAT is associated with adverse outcomes, possibly due to the secretion of pro-inflammatory and pro-atherogenic adipokines, and increased mechanical restraint[27, 28]. These outcomes include left ventricular diastolic dysfunction, higher levels of NT-proBNP, as well as mortality and hospitalization. Recently, Liu J used non-contrast CT to find that EAT density was an independent impact factor of cardiometabolic risk in HFpEF[19]. In this study, we more accurately measured the volume of EAT using CCTA, which can reduce the interference of atrial and ventricular blood on the measurement of EAT.
PCAT is a type of perivascular adipose tissue that has been shown to produce several bioactive substances, such as inflammatory mediators and hormones, which can influence the growth and pathophysiology of blood vessel walls[29, 30]. Two large cohort studies, the SCOT-HEART[31] and CRISP-CT study[32], found that PCAT attenuation coefficient, especially in the right coronary artery (RCA), was associated with an adverse cerebrovascular prognosis in patients with coronary heart disease[33]. In our study, we confirmed that the RCA attenuation coefficient was specifically expressed in HFpEF and adverse prognosis, particularly when compared with the other two branches (LCX and LAD). We speculate that this is because the RCA follows a more regular course, and is less affected by collateral vessels during measurement, particularly in the right-dominant Chinese population.
In HFpEF patients, PCAT is involved in regulating vascular function, inflammation, and fibrosis[34]. Through its derived adipokines, PCAT can affect cardiac metabolism, including insulin resistance, oxidative stress, and diastolic dysfunction, which play a role in the pathophysiology of HFpEF[18]. However, the exact mechanisms by which PCAT contributes to HFpEF are not yet fully understood, and further research is needed.
Despite the promising findings regarding the role of EAT and PCAT in HFpEF[35], further studies are needed to fully understand the underlying mechanisms and to develop effective therapies targeting these adipose tissue depots. Future studies may also explore the potential of other imaging modalities, such as positron emission tomography (PET), to better assess cardiac metabolism and inflammation in HFpEF.
Our study has several limitations. First, the relatively low number of fatal events reported in our study may reduce the statistical power of some subgroup analyses. To minimize this effect, we incorporated common readmissions in HFpEF patients as a composite endpoint to increase the credibility of our findings. Second, we mainly analyzed the relationship between EAT and PCAT in healthy individuals and HFpEF patients, and extensive research is still needed to confirm and discover their roles in other types of heart failure. Thirdly, we used 0.75mm thickness images to measure and calculate EAT and PCAT, and did not conduct experiments on CT models from other manufacturers to ensure data consistency. Although there are many measurement methods for PCAT, we used Laing et al.'s widely used methods, but we will compare different methods in the future.