Interstitial Fibrosis, Functional Status, and Outcomes in Heart Failure With Preserved Ejection Fraction: Insights From a Prospective Cardiac Magnetic Resonance Imaging Study.

BACKGROUND Myocardial extracellular volume (ECV) accumulation is one of the key pathophysiologic features of heart failure with preserved ejection fraction (HFpEF). Our aims were to (1) measure ECV by cardiac magnetic resonance T1 mapping using the modified Look-Locker inversion recovery (MOLLI) sequence, (2) validate MOLLI-ECV against histology, and (3) investigate the relationship between MOLLI-ECV and prognosis in HFpEF. METHODS AND RESULTS One-hundred seventeen consecutive HFpEF patients underwent cardiac magnetic resonance imaging, coronary angiography, and invasive hemodynamic assessments at baseline. Eighteen patients also underwent left ventricular biopsy for histological analysis (Histo-ECV). To assess the prognostic impact of MOLLI-ECV, its association with hospitalization for heart failure/cardiac death was tested by multivariable Cox regression analysis. Histo-ECV was 30.1±4.6% and was significantly correlated with MOLLI-ECV (R=0.494, P=0.037). Patients were followed for 24.0 months (6.0-32.0 months), during which 34 had a cardiac event. By Kaplan-Meier analysis, patients with MOLLI-ECV ≥ the median (28.9%) had shorter event-free survival (log-rank, P=0.028). MOLLI-ECV significantly correlated with N-terminal prohormone of brain natriuretic peptide (P<0.001), 6-minute walk distance (P=0.004), New York Heart Association functional class (P=0.009), right atrial pressure (P=0.037), and stroke volume (P=0.043). By multivariable Cox regression analysis, MOLLI-ECV was associated with outcome among imaging variables (P=0.038) but not after adjustment for clinical and invasive hemodynamic parameters. CONCLUSIONS We demonstrate that MOLLI-ECV in HFpEF accurately reflects histological ECV, correlates with markers of disease severity, and is associated with outcome among cardiac magnetic resonance parameters but not after adjustment for important clinical and invasive hemodynamic parameters. Nevertheless, MOLLI-ECV has the potential of becoming an important biomarker in HFpEF.