Patients with heart failure with preserved ejection fraction (HFpEF) and increased epicardial adipose tissue have higher body mass index (BMI) and signs of cardiac structural alterations and proteomic markers associated with general adiposity, systemic inflammation, insulin resistance, endothelial dysfunction, and dyslipidemia. These findings were published in the European Journal of Heart Failure.
Researchers evaluated associations between epicardial adipose tissue and obesity, proteomics, measures of coronary microvascular dysfunction, cardiac structure and function, and quality of life in a cohort of patients from the PROMIS-HFpEF (Prevalence of Microvascular Dysfunction in HFpEF) study.
Eligible participants had symptomatic HF with New York Heart Association class II-IV and ejection fraction (EF) of 40% or more. They received a comprehensive medical history and physical examination and were assessed for fasting blood and urine tests, 6-minute walk test, peripheral arterial tonometry, Kansas City Cardiomyopathy Questionnaire Overall Summary Score (KCCQ OSS), and comprehensive transthoracic echocardiography. Comprehensive 2-dimensional, Doppler and tissue Doppler echocardiography were conducted.
Epicardial adipose tissue was measured around patients’ right ventricular free wall in the parasternal long-axis view and averaged across 3 cycles during end-systole. Increased epicardial adipose tissue was defined as epicardial adipose tissue of 9 mm or thicker.
Epicardial adipose tissue was measured with echocardiography in 90% of 202 patients who had successful coronary flow reserve (CFR) testing. Of these patients, 128 had epicardial adipose tissue that was thinner than 9 mm (median age, 76 years; 46% women), and 54 had epicardial adipose tissue that was 9 mm or thicker (median age, 73 years; 43% women).
The overall median (IQR) epicardial adipose tissue was 7 (6-9) mm, and epicardial adipose tissue was moderately and significantly correlated with BMI (r=0.49, P <.001). The patients with epicardial adipose tissue that was 9 mm or thicker had higher triglyceride concentrations (1.3 vs 1.0 mmol/L) and lower N-terminal pro-brain natriuretic peptide (NT-proBNP) levels (466 vs 1120 pg/mL) compared with those who had epicardial adipose tissue that was thinner than 9 mm, respectively.
The participants with increased epicardial adipose tissue had smaller indexed LV volumes on echocardiography with higher EF vs patients with epicardial adipose tissue that was less than 9 mm, although the absolute values were similar in the 2 groups. Patients with increased epicardial adipose tissue had lower early diastolic myocardial velocities and higher right ventricular E/e′. No significant differences in CFR were found between the 2 groups in the full cohort or subgroup analysis (P >.05 for all). KCCQ OSS was nonsignificantly lower in patients who had epicardial adipose tissue that was 9 mm or thicker (P =.07).
In the Orthogonal partial least squares discriminant analysis, the most discriminant variables associated with epicardial adipose tissue that was 9 mm or thicker were BMI, weight, waist circumference, and leptin levels, and the most discriminant variables associated with epicardial adipose tissue that was thinner than 9 mm were insulin-like growth factor binding protein 1, BNP, insulin-like growth factor binding protein 2, and NT-proBNP.
In univariable regression analysis, increased epicardial adipose tissue was positively associated with EF, stroke volume, systolic myocardial velocity, mitral A-wave velocity, E/A ratio, and deceleration time. After adjustment for BMI, only LV septal wall thickness (P =.018) and mitral E wave deceleration time (P =.005) remained significantly and positively associated with epicardial adipose tissue.
The proteomic profile of patients who had increased epicardial adipose tissue demonstrated adiposity, inflammation, oxidative stress, and endothelial dysfunction paired with dysglycemia and dyslipidemia.
The study authors noted that the smaller sample of very obese patients in the cohort needs to be considered when interpreting the findings. Also, a relatively small number of participants are in the subgroup analysis of patients with lower BMI.
“EAT [epicardial adipose tissue] may contribute to HFpEF but it remains unclear whether this is simply mediated by obesity, or if EAT also exerts direct effects independent of its association with obesity,” the investigators wrote.
Disclosure: PROMIS-HFpEF is sponsored by AstraZeneca. Some of the study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.
Venkateshvaran A, Faxen UL, Hage C, et al. Association of epicardial adipose tissue with proteomics, coronary flow reserve, cardiac structure and function, and quality of life in heart failure with preserved ejection fraction: insights from the PROMIS-HFpEF study. Eur J Heart Fail. Published online October 4, 2022. doi: 10.1002/ejhf.2709