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Relationship Between Focal and Diffuse Fibrosis Assessed by CMR and Clinical Outcomes in Heart Failure With Preserved Ejection Fraction

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posted on 2020-07-31, 15:22 authored by Prathap Kanagala, Adrian SH Cheng, Anvesha Singh, Lama N Khan, Gaurav S Gulsin, Prashanth Patel, Pankaj Gupta, Jayanth R Arnold, Iain B Squire, Leong L Ng, Gerry P McCann
Objectives: This study sought to assess the presence and extent of focal and diffuse fibrosis in heart failure in patients with preserved ejection fraction (HFpEF) compared to asymptomatic control subjects, and the relationship of fibrosis to clinical outcome.
Background: Myocardial fibrosis has been implicated in the pathophysiology of HFpEF.
Methods: In this prospective, observational study, 140 subjects of similar age and sex (HFpEF: n = 96; control subjects: n = 44; 73 ± 8 years of age; 49% males) underwent cardiac magnetic resonance imaging. Late gadolinium-enhanced (LGE) imaging and T1 mapping to calculate myocardial extracellular volume indexed to body surface area (iECV) were used to assess fibrosis.
Results: Patients with HFpEF had more concentric remodeling and worse diastolic function. Focal fibrosis was more frequent in HFpEF subjects (overall: n = 49; infarction: n = 17; nonischemic cases: n = 36; mixed patterns: n = 4) than in control subjects (overall: n = 3). Diffuse fibrosis was also greater in HFpEF subjects than control subjects (iECV: 13.7 ± 4.4 ml/m2 versus 10.9 ± 2.8 ml/m2; p < 0.0001). During median follow-up (1,429 days), there were 42 composite events (14 deaths; 28 heart failure hospitalizations) in cases of HFpEF. Myocardial infarction revealed on LGE imaging was a predictor of outcomes on univariate analysis only. With multivariate analysis, iECV (hazard ratio [HR]: 1.689; 95% confidence interval [CI]: 1.141 to 2.501; p = 0.009) was an independent predictor of outcome along with mitral peak velocity of early filling (E)-to-early diastolic mitral annular velocity (E′) (E/E′) ratio (HR: 1.716; 95% CI: 1.191 to 2.472; p = 0.004) and prior HF hospitalization (HR: 2.537; 95% CI: 1.090 to 5.902; p = 0.031). iECV was also significantly associated with ventricular/left atrial remodeling and renal dysfunction: right ventricular end-diastolic volume indexed (r = 0.456; p < 0.0001), left ventricular mass/volume (r = 0.348; p = 0.001), maximal left atrial volume indexed (r = 0. 269; p = 0.009), and creatinine (r = 0.271; p = 0.009).
Conclusions: Both focal and diffuse myocardial fibrosis are more prevalent in HFpEF subjects than in control subjects of similar age and sex. iECV significantly correlates with indices of ventricular/left atrial remodeling and renal dysfunction and is an independent predictor of adverse outcome in HFpEF. (Developing Imaging And plasMa biOmarkers iN Describing Heart Failure With Preserved Ejection Fraction [DIAMONDHFpEF]; NCT03050593)

History

Citation

JACC: Cardiovascular Imaging, Volume 12, Issue 11, Part 2, November 2019, Pages 2291-2301

Author affiliation

Department of Cardiovascular Sciences

Version

  • AM (Accepted Manuscript)

Published in

JACC: Cardiovascular Imaging

Volume

12

Issue

11

Pagination

2291 - 2301

Publisher

Elsevier

issn

1876-7591

eissn

1876-7591

Acceptance date

2018-11-15

Copyright date

2018

Spatial coverage

United States

Language

English

Publisher version

https://www.sciencedirect.com/science/article/abs/pii/S1936878X19300750