Epicardial adipose tissue, myocardial remodelling and adverse outcomes in asymptomatic aortic stenosis: a post hoc analysis of a randomised controlled trial

Abstract

Background: Epicardial adipose tissue represents a metabolically active visceral fat depot that is in direct contact with the left ventricular myocardium. While it is associated with coronary artery disease, little is known regarding its role in aortic stenosis. We sought to investigate the association of epicardial adipose tissue with aortic stenosis severity and progression, myocardial remodelling and function, and mortality in asymptomatic patients with aortic stenosis.

Methods: In a post hoc analysis of 124 patients with asymptomatic mild-to-severe aortic stenosis participating in a prospective clinical trial, baseline epicardial adipose tissue was quantified on CT angiography using fully automated deep learning-enabled software. Aortic stenosis disease severity was assessed at baseline and 1 year. The primary endpoint was all-cause mortality.

Results: Neither epicardial adipose tissue volume nor attenuation correlated with aortic stenosis severity or subsequent disease progression as assessed by echocardiography or CT (p>0.05 for all). Epicardial adipose tissue volume correlated with plasma cardiac troponin concentration (r=0.23, p=0.009), left ventricular mass (r=0.46, p<0.001), ejection fraction (r=-0.28, p=0.002), global longitudinal strain (r=0.28, p=0.017), and left atrial volume (r=0.39, p<0.001). During the median follow-up of 48 (IQR 26-73) months, a total of 23 (18%) patients died. In multivariable analysis, both epicardial adipose tissue volume (HR 1.82, 95% CI 1.10 to 3.03; p=0.021) and plasma cardiac troponin concentration (HR 1.47, 95% CI 1.13 to 1.90; p=0.004) were associated with all-cause mortality, after adjustment for age, body mass index and left ventricular ejection fraction. Patients with epicardial adipose tissue volume >90 mm³ had 3-4 times higher risk of death (adjusted HR 3.74, 95% CI 1.08 to 12.96; p=0.037).

Conclusions: Epicardial adipose tissue volume does not associate with aortic stenosis severity or its progression but does correlate with blood and imaging biomarkers of impaired myocardial health. The latter may explain the association of epicardial adipose tissue volume with an increased risk of all-cause mortality in patients with asymptomatic aortic stenosis.

Clinicaltrials: gov (NCT02132026).

Keywords: Aortic stenosis; Computed Tomography Angiography; Risk Assessment.

Figure 1

Deep learning based epicardial adipose tissue quantification Example of fully automated deep learning enabled epicardial adipose tissue segmentation (red overlay) from computed tomography angiography (A-C), with 3-dimensional volume rendering image of epicardial adipose tissue shown in red (D).

Figure 2

Epicardial adipose tissue volume across aortic stenosis severity levels There were no significant differences in epicardial adipose tissue volume between patients with mild, moderate and severe aortic stenosis (97 [80–130] mm ³ vs 99 [72–148] mm³ vs 110 [76–147] mm³, respectively; overall p=0.987).

Figure 3

Relation between epicardial adipose tissue volume and markers of myocardial remodelling Epicardial adipose tissue volume correlated with left ventricular mass (rho=0.46, p<0.001) (A). Patients with mildly reduced ejection fraction had higher epicardial adipose tissue volume compared to patients with preserved ejection fraction (164 [97–202] mm³ vs 96 [74–128] mm³; p=0.009) (B).

Figure 4

Study characteristics of patients who died during follow-up Patients who died were more likely to be male (96% versus 74%, p=0.025) (A), to have an ejection fraction below 55% (22% versus 6%, p=0.016) (B), a higher baseline cardiac troponin concentration (7.3 versus 5.0 ng/mL, p=0.035) (C), and higher epicardial adipose tissue volume (128 versus 94 mL, p=0.014) (D).

Figure 5

The epicardial adipose tissue volume threshold of 90 mm³ predicted all-cause mortality during follow-up (A) Forrest plot for multivariable Cox regression analysis. Epicardial adipose tissue threshold of 90 mm³ was an independent predictor of all-cause mortality, and patients with high epicardial adipose tissue volume had 3- to 4-fold increase in risk of death. (B) Kaplan-Meier Curves demonstrating event-free survival using the 90 mm³ epicardial adipose tissue volume threshold. High epicardial adipose tissue volume was associated with adverse prognosis (logrank p=0.026). Epicardial adipose tissue volume quantified from CT angiography in (C) a patient in their 70s with moderate aortic stenosis and epicardial fat volume of 73 mm³ who did not experience death during follow-up, and in (D) a patient in their 70s with moderate aortic stenosis and epicardial adipose tissue volume of 192 mm³ who died during follow-up. * Per 1 standard deviation increment. HR = hazard ratio, CI = confidence interval.