Relationship Between Focal and Diffuse Fibrosis Assessed by CMR and Clinical Outcomes in Heart Failure with Preserved Ejection Fraction
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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/m 2 versus 10.9 ± 2.8 ml/m 2; 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).
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CMR imaging revealed more prevalent fibrosis in HFpEF subjects than in control subjects, and the HFpEF group was associated with adverse outcomes.
“Cardiac magnetic resonance (CMR) imaging revealed more prevalent fibrosis in HFpEF subjects than in control subjects, and the first group was associated with adverse outcomes [105,106].”
From Dysregulated epicardial adipose tissue as a risk factor and potential therapeutic target of heart failure with preserved ejection fraction in diabetes (2022) · cites this paper as [105]
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- Authors
- Kanagala, P., Cheng, A. S. H., Singh, A., Khan, J. N., Gulsin, G. S., Patel, P., Gupta, P., Arnold, J. R., Squire, I. B., Ng, L. L., & McCann, G. P.
- Affiliations
- University of Leicester (GB)
- National Health Service (GB)
- Corresponding author
- Kanagala, Prathap
- ORCID
- Venue
- JACC. Cardiovascular imaging
- Publisher
- Elsevier BV
- Published
- 2019-11
- Volume
- 12
- Issue
- 11
- Pages
- 2291-2301
- ISSN
- 1876-7591 (ISSN-L)
- 1936-878X
- OpenAlex
- W2912610266
- Cited by
- 126
- References
- 35
- Citations by year
- 2026: 9 · 2025: 18 · 2024: 16 · 2023: 20 · 2022: 17 · 2021: 15 · 2020: 23 · 2019: 8
- FWCI
- 10.40
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- JACC. Cardiovascular imaging (publishedVersion)
- PubMed (publishedVersion)
- Figshare (submittedVersion, cc-by-nc-nd)
- Funders
- National Institute for Health and Care Research (CL-2016-11-001, RP-2017-08-ST2-007, 2014‐07‐045)
- British Heart Foundation
- Medical Research Council
- Topics
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Cardiac Imaging and Diagnostics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiomyopathy and Myosin Studies
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac Fibrosis and Remodeling
- Keywords
- heart failure with preserved ejection fraction, myocardial fibrosis, focal fibrosis, diffuse fibrosis, extracellular volume, late gadolinium enhancement, T1 mapping, clinical outcomes, heart failure hospitalization, mortality, E/e' ratio, left atrial remodeling, ventricular remodeling, renal dysfunction, myocardial infarction, prognosis, left ventricular mass
- MeSH terms
- Progression-Free Survival, Aged, Aged, 80 and over, Contrast Media, England, Extracellular Space, Female, Fibrosis, Heart Failure, Humans, Male, Middle Aged, Myocardium, Organometallic Compounds, Predictive Value of Tests, Prospective Studies, Stroke Volume, Prevalence, Case-Control Studies, Ventricular Function, Left, Magnetic Resonance Imaging, Cine, Ventricular Remodeling, Asymptomatic Diseases
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