Associations and prognostic significance of diffuse myocardial fibrosis by cardiovascular magnetic resonance in heart failure with preserved ejection fraction

Clotilde Roy, Alisson Slimani, Christophe de Meester, Mihaela Amzulescu, Agnes Pasquet, David Vancraeynest, Christophe Beauloye, Jean-Louis Vanoverschelde, Bernhard L Gerber, Anne-Catherine Pouleur, Clotilde Roy, Alisson Slimani, Christophe de Meester, Mihaela Amzulescu, Agnes Pasquet, David Vancraeynest, Christophe Beauloye, Jean-Louis Vanoverschelde, Bernhard L Gerber, Anne-Catherine Pouleur

Abstract

Background: Increased myocardial fibrosis may play a key role in heart failure with preserved ejection fraction (HFpEF) pathophysiology. The study aim was to evaluate the presence, associations, and prognostic significance of diffuse fibrosis in HFpEF patients compared to age- and sex-matched controls.

Methods: We prospectively included 118 consecutive HFpEF patients. Diffuse myocardial fibrosis was estimated by extracellular volume (ECV) quantified by cardiovascular magnetic resonance with the modified Look-Locker inversion recovery sequence. We determined an ECV age- and sex-adjusted cutoff value (33%) in 26 controls.

Results: Mean ECV was significantly higher in HFpEF patients versus healthy controls (32.9 ± 4.8% vs 28.2 ± 2.4%, P < 0.001). Multivariate logistic regression showed that body mass index (BMI) (odds ratio (OR) =0.92 [0.86-0.98], P = 0.011), diabetes (OR = 2.62 [1.11-6.18], P = 0.028), and transmitral peak E wave velocity (OR = 1.02 [1.00-1.03], P = 0.022) were significantly associated with abnormal ECV value. During a median follow-up of 11 ± 6 months, the primary outcome (all-cause mortality or first heart failure hospitalization) occurred in 38 patients. In multivariate Cox regression analysis, diabetes (hazard ratio (HR) =1.98 [1.04; 3.76], P = 0.038) and hemoglobin level (HR = 0.81 [0.67; 0.98], P = 0.028) were significant predictors of composite outcome. The ECV ability to improve this model added significant prognostic information. We then developed a risk score including diabetes, hemoglobin and ECV > 33% demonstrating significant prediction of risk and validated this score in a validation cohort of 53 patients. Kaplan-Meier curves showed a significant difference according to tertiles of the probability score (P < 0.001).

Conclusion: Among HFpEF patients, high ECV, likely reflecting abnormal diffuse myocardial fibrosis, was associated with a higher rate of all-cause death and first HF hospitalization in short term follow up.

Trial registration: Characterization of Heart Failure With Preserved Ejection Fraction.

Trial registration number: NCT03197350 . Date of registration: 20/06/2017. This trial was retrospectively registered.

Keywords: Cardiac magnetic resonance; Diffuse myocardial fibrosis; Prognosis.

Conflict of interest statement

Ethics approval and consent to participate

The study was approved by the IRB of the Cliniques St. Luc, Université Catholique de Louvain and all participants gave written permission to participating in the study.

Consent for publication

NA

Competing interests

The Cliniques St. Luc UCL has a master clinical research agreement with Philips Medical Instruments, and the MOLLI patch was supplied by Philips Healthcare under the terms of this agreement. The authors declare that they have no competing interests.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Fig. 1
Fig. 1
Extracellular volume fraction (ECV) values between age- and sex-matched healthy controls and heart failure with preserved ejection fraction (HFpEF) patients
Fig. 2
Fig. 2
(a) Mortality and HF hospitalization Kaplan Meier Curves (b) Event-free survival in HFpEF patients according to ECV cutoff

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