Risk of Adverse Cardiovascular Outcomes: Clinical Significance of Epicardial Adipose Tissue Quantity (Volume) and Quality (T1)

Background: Epicardial adipose tissue (EAT) is an active metabolic depot implicated in arrhythmogenesis, adverse myocardial remodeling, and heart failure progression. While EAT volume has been implicated in atrial fibrillation, ventricular arrhythmias, coronary artery disease and heart failure, the prognostic relevance of EAT quality quantified with T1 mapping (a metric in which low T1 values have been associated with a pro-inflammatory phenotype of EAT) remains uncertain. We aimed to evaluate whether EAT volume and EAT T1 values measured by cardiac magnetic resonance (CMR) are associated with major clinical outcomes.

Methods: We retrospectively reviewed 200 patients who underwent clinically indicated CMR with both short and long axis T1 mapping, along with cine imaging, T2-mapping and LGE imaging performed in accordance with SCMR guidelines. EAT volume was segmented manually over both ventricles at end systole on SSFP cine short-axis images. Native EAT T1 was measured using standard MOLLI 5(3)3 sequences by averaging the three largest possible ROIs (basal and mid SA, 4C LA) that could be placed in the EAT while avoiding areas of artifact, myocardium, and coronary vessels. Outcomes were ascertained through longitudinal follow-up and included major adverse cardiac events (MACE), ventricular tachycardia/ventricular fibrillation (VT/VF), atrial fibrillation (AF), heart failure hospitalization, myocardial infarction (MI), cardiac death (CV death), and all-cause mortality. Associations between EAT parameters and baseline demographic data were assessed by LASSO regression analysis. Associations between EAT parameters and outcomes were assessed using Wilcoxon signed-rank test.

Results: A total of 200 patients (mean age 56.5 ± 15.6 years, 55% male) were included, with a median follow-up of 7.4 years. LASSO identified age, BMI, LV mass, hypertension and diabetes as correlates of high EAT volume but none correlated with EAT T1. There was a statistically significant increase in EAT volume in those who developed the outcomes of VT/VF (HR p=0.01), AF (p=0.006), heart failure hospitalization (p=0.02), cardiac death (p=0.01), and all-cause mortality (p=0.01), but not MI. When using the composite outcome of MACE (VT/VF, hospital admission, and CV Death) there was again a statistically significant elevation in EAT volume (p=0.0005). Native EAT T1 values showed no significant association with any of the outcomes assessed (all p >0.05).

Conclusion: EAT volume, but not EAT T1 values, was associated with a higher risk of arrhythmias, heart failure hospitalization, cardiac death, and all-cause mortality. These findings suggest that the burden of EAT may be more prognostically relevant than its tissue characteristics as assessed by T1 mapping. Quantification of EAT volume by CMR may provide incremental value for risk stratification in patients at risk for adverse cardiovascular outcomes.

Table 1

TABLE 1
Category		Number	%
Gender	Male	110	55.0%
	Female	90	45.0%
Race	White	156	78.0%
	AA	30	15.0%
	Asian	3	1.5%
	Hispanic	5	2.5%
	Other	6	3.0%
BMI		31.2 ± 7.5
BSA		2.05 ± 0.30
Scanner Strength	1.5	146	73.0%
	3.0	54	27.0%
Former Smoker	Yes	76	38.0%
Current Smoker	Yes	29	14.5%
HTN	Yes	152	76.0%
HLD	Yes	140	70.0%
DM	Yes	73	36.5%
CKD	Yes	50	25.0%
COPD	Yes	35	17.5%
Metabolic Syndrome	Yes	14	7.0%
VT/VF	Yes	17	8.5%
MI	Yes	47	23.5%
HF Admission	Yes	48	24.0%
CV Death	Yes	9	4.5%
Death	Yes	38	19.0%
A-fib	Yes	37	18.5%

Figure1: Top row shows SSFP Cine SA image at end systole (top right) with EAT segmentation for EAT volume (top left). The red contour identifies the exetrnal surface of myocardium and green contour identifies the visceral pericardium. Bottom row shows T1 mapping with ROI for EAT T1 value in SA (bottom left) and 4C LA (bottom right).
Figure 2: Mean EAT volume analysis across six outcomes including A) VT/VF, B) HF Admission, C) Atrial Fibrillation, D) MACE (composite outcome of VT/VF, HF Admission, and CV Death), E) CV Death, and F) All Cause Death.