PERICARDIAL FAT AND CARDIAC FUNCTION • Association of Pericardial Fat with Cardiac Structure, Function, and Mechanics: The Multi-Ethnic Study of Atherosclerosis

INTRODUCTION

Pericardial adipose tissue – fat superficial to the parietal pericardium (pericardial fat) and fat located between the myocardium and the visceral pericardium (epicardial fat) – has been linked to coronary artery disease, atrial fibrillation (AF), and abnormal cardiac structure and function.

Epicardial fat lies in direct contact with cardiomyocytes and secretes numerous bioactive factors, which have been implicated in adiposity-associated inflammation and insulin resistance. This in turn contributes to myocardial fat deposition and fibrosis. Epicardial adipose tissue is also metabolically active, expressing high amounts of proteins associated with lipid metabolism.

In heart failure with preserved ejection fraction (HfpEF), pericardial adipose tissue is associated with increased cardiac filling pressures and more severe pulmonary hypertension.

Previous studies demonstrated that pericardial fat is associated with an increased risk for heart failure in individuals without prior cardiac disease, but these studies did not explore potential mechanisms.

Therefore, the authors utilized data from the Multi-Ethnic Study of Atherosclerosis (MESA) to examine the association between pericardial adipose tissue volume by computed tomography (CT) with cardiac structure and function by echocardiography. The volume of pericardial fat determined by this method has been demonstrated to approximate that of epicardial fat and is independently associated with increased risk for incident heart failure.

The authors hypothesized that increased pericardial fat volume would be independently associated with abnormal cardiac mechanics, greater symptom burden, and reduced exercise capacity.

METHODS

Study Population

MESA is a multicenter prospective cohort study designed to investigate the prevalence, correlates, and progression of subclinical cardiovascular disease in adults without previous clinical cardiovascular disease. It comprises 6,814 men and women ages 45-85 years old recruited from six U.S. field sites and followed over six exams from 2000 to 2018.

Participants were free of clinical cardiovascular disease at the time of recruitment. Standardized definitions were used to determine incident diagnoses of coronary heart disease (CHD), congestive heart failure (CHF), and AF. Since right heart function may be impacted by pulmonary disease, additional covariates included spirometry and quantitated emphysema by CT obtained as part of the MESA Lung Study, which enrolled 3,965 MESA participants in 2004-6.

Exposure Variable: Pericardial Fat Volume Assessment

Pericardial fat volumes (which include both pericardial and epicardial fat) were determined using volumetric assessment of CT imaging obtained during exam 1 (2000-2002). A subset of participants had repeated assessments at exams 2 (2002-4), 3 (2004-5), and 4 (2005-7).

Outcome Variables

Among MESA participants, 3,032 underwent echocardiography at exam 6 as part of the MESA Early Heart Failure Study, an ancillary study to examine the mechanisms and phenotypes of early heart failure.

All 2D, Doppler, and M-mode echocardiographic measurements were performed by two experienced research sonographers blinded to all other data. Measures of cardiac mechanics, chamber quantification, and cardiac function were performed in accordance with the recommendations of the ASE. A still image containing an overlay of the echocardiographic tracing was captured for each measurement performed and archived for review and verification by two cardiologist over-readers with expertise in echocardiography. Speckle tracking analysis was also performed using GE Echo PAC software. For ease of reporting and interpretation, all strain values were reported as absolute values (with lower absolute strain values corresponding to worse cardiac mechanics). Quality control metrics for inter- and interobserver variability were performed on a sample of 100 studies.

RESULTS

Among 6,814 participants initially recruited in MESA, the authors included the 3,032 participants who underwent echocardiography at exam 6. At baseline, this cohort was 53% female, with mean age 57 years, and 40% White, 25% Black or African American, 22% Hispanic, and 13% Asian.

All participants were free of cardiovascular disease at exam 1, but by exam 6, 398 (13.1%) participants had AF, 75 (2.5%) had CHF, and 198 (6.5%) had CHD.

Baseline (exam 1) pericardial fat volume (mean, 73.6 cm3; SD = 39.3 cm3 ) was positively correlated with BMI, although there was substantial variation among those with high BMI. Those in the highest quartile of pericardial fat were predominantly male and older, with a greater proportion of White and Hispanic participants, higher BMI, and greater prevalence of baseline cardiovascular risk factors.

Among the 3,032 participants, there were 6,371 observations of pericardial fat volume between exams 1 and 4 (average 2.1 observations per participant). Over time, mean pericardial fat volume increased by 1.19 cm per year.

In univariate analysis, higher pericardial fat volume at baseline was associated with lower (worse) absolute LV global longitudinal strain and LA reservoir strain, in addition to other indices of LV systolic and diastolic function. The association of pericardial fat volume with LA reservoir strain and greater LV mass persisted but was attenuated by adjustment for age, sex, race, site, BMI, waist-hip ratio, smoking status, pack-years smoked, FEV1/FVC, percent emphysema, hypertension, and AF status.

Pericardial fat volume was associated with greater mitral E/e’ ratio, lower e’ velocity, and lower LA reservoir strain following a preload challenge via passive leg-raise maneuver.

Increased pericardial fat volume was also associated with lower (worse) absolute RV free wall and right atrial (RA) reservoir strain in univariate analysis, which persisted but was somewhat attenuated in multivariable models.

Pericardial fat volume was also associated with lower tricuspid annular plane systolic excursion (TAPSE), fractional area change (FAC), and RV s’ velocity – association that were largely unchanged after further adjusting for pulmonary artery systolic pressure (PASP), LV strain, E/e’ ratio, LA volume, and LA strain.

CONCLUSION

The authors concluded that in this large, diverse cohort of elderly adults free of baseline cardiovascular disease, pericardial fat volume was associated with distinct atrial and ventricular abnormalities by echocardiography after nearly 20 years of follow-up.

pericardial fat volume remained independently associated with cardiac function after adjusting for overall adiposity (i.e., BMI and waist-hip ratio) and other potential confounders.

In addition, the authors commented that these distinct changes in cardiac structure and function are accompanied by decreased 6MWD, suggesting a potential mechanistic role for pericardial fat in early heart failure.