Differentiating the Prognostic Determinants of Myocardial Steatosis for Heart Failure With Preserved Ejection Fraction by Cardiac Magnetic Resonance Imaging

Abstract

Background Myocardial steatosis and fibrosis may play a role in the pathophysiology of heart failure with preserved ejection fraction. We therefore investigated the prognostic significance of epicardial fat (epicardial adipose tissue [EAT]) and myocardial diffuse fibrosis. Methods and Results Myocardial fibrosis, estimated as extracellular volume (ECV), and EAT were measured using cardiac magnetic resonance imaging in 163 subjects with heart failure with preserved ejection fraction. We also evaluated cardiac structure and diastolic and systolic function by echocardiography and cardiac magnetic resonance imaging. After 24 months' follow-up, 39 (24%) subjects had experienced cardiovascular events, including hospitalization for heart failure, acute coronary syndrome, and cardiovascular death. Median EAT and mean ECV were significantly higher in subjects with cardiovascular events than survivors (EAT, 35 [25-45] versus 31 [21-38], P=0.006 and ECV, 28.9±3.16% versus 27.2±3.56%, P=0.04). Subjects with high EAT (≥42 g) had increased risk of cardiovascular events (hazard ratio [HR], 2.528 [95% CI, 1.704-4.981]; P=0.032). High ECV (>29%) was also significantly associated with poorer outcomes (HR, 1.647 [95% CI, 1.263-2.548]; P=0.013). With respect to secondary end points, high EAT and high ECV were associated with increased risk of the incident acute coronary syndrome (HR, 1.982 [95% CI, 1.008-4.123]; P=0.049) and hospitalization for heart failure (HR, 1.789 [95% CI, 1.102-6.987]; P=0.033), respectively. Conclusions Our study suggested that increased epicardial fat and ECV detected by cardiac magnetic resonance imaging have an impact on cardiovascular prognosis, in particular acute coronary syndrome and hospitalization for heart failure, respectively.

Keywords: cardiac magnetic resonance imaging; epicardial fat; extracellular volume; heart failure with preserved ejection fraction; myocardial steatosis; prognosis.

Figure 1. Patient enrollment diagram.

*Significant valvular heart disease indicated for percutaneous or surgical intervention. **Ten patients were excluded due to septal scar (5 patients with acute myocardial infarction and 5 patients with hypertrophic cardiomyopathy). Thirteen patients were excluded due to indeterminate diastolic function. ACS indicates acute coronary syndrome; CMRI, cardiac magnetic resonance imaging; COPD, chronic obstructive pulmonary disease; CV, cardiovascular; e', early diastolic mitral annular velocity; E, mitral peak velocity of early filling; eGFR, estimated glomerular filtration rate; HCM, hypertrophic cardiomyopathy; HFmrEF, heart failure with midrange ejection fraction; HFpEF, heart failure with preserved ejection fraction; HFrEF, heart failure with reduced ejection fraction; HHF, hospitalization for heart failure; LAVI, left atrial volume index; LVMI, left ventricular mass index; NT‐proBNP, N‐terminal pro‐B‐type natriuretic peptide; TR, tricuspid regurgitation; and VHD, valvular heart disease.

Figure 2. Associations of high vs low epicardial adipose tissue (EAT) and extracellular volume (ECV), and the risk of the overall cardiovascular composite end points.

Kaplan‐Meier plot for the risk of the composite end points for patients stratified by (A) EAT levels above (green) and below (blue) 42 g (log rank, 0.031) and (B) ECV levels above (green) and below (blue) 29% (log rank, 0.011). Clinical outcomes for EAT and ECV. Restricted cubic spine analyses of overall cardiovascular composite end points. Epicardial fat (C) and ECV (D). Solid line indicates hazard ratio and dashed line indicates 95% CI.

Figure 3. Associations of high vs low epicardial adipose tissue (EAT) and extracellular volume (ECV), and the risk of the hospitalization for heart failure (HHF).

Kaplan‐Meier plot for the risk of the composite end points for patients stratified by (A) EAT levels above (green) and below (blue) 42 g (log rank, 0.677) and (B) ECV levels above (green) and below (blue) 29% (log rank, 0.025). Clinical outcomes for EAT and ECV. Restricted cubic spine analyses of HHF. Epicardial fat (C) and ECV (D). Solid line indicates hazard ratio and dashed line indicated 95% CI.

Figure 4. Associations of high vs low epicardial adipose tissue (EAT) and extracellular volume (ECV), and the risk of the acute coronary syndrome (ACS).

Kaplan‐Meier plot for the risk of the composite end points for patients stratified by EAT levels above (green) and below (blue) 42 g (log rank, 0.013) (A) and ECV levels above (green) and below (blue) 29% (log rank, 0.584) (B). Clinical outcomes for EAT and ECV. Restricted cubic spine analyses of ACS. Epicardial fat (C) and ECV (D). Solid line indicates hazard ratio, and dashed line indicates 95% CI.