Author + information
- Received September 18, 2018
- Revision received November 12, 2018
- Accepted November 15, 2018
- Published online February 13, 2019.
- Prathap Kanagala, MBBS, PhDa,b,∗ (, )
- Adrian S.H. Cheng, MBBS, MDa,c,
- Anvesha Singh, MBChBa,
- Jamal N. Khan, MBChB, PhDa,
- Gaurav S. Gulsina,
- Prashanth Patel, MBBSa,
- Pankaj Gupta, DPBa,
- Jayanth R. Arnold, BMBChB, DPhila,
- Iain B. Squire, MBChB, MDa,
- Leong L. Ng, MBBChir, MDa and
- Gerry P. McCann, MBChB, MDa
- aDepartment of Cardiovascular Sciences, University of Leicester, National Institute for Health Research, Leicester Biomedical Research Centre, Leicester, United Kingdom
- bDepartment of Cardiology, Aintree University Hospital, Liverpool, United Kingdom
- cDepartment of Cardiology, Kettering General Hospital National Health Service Foundation Trust, Kettering, United Kingdom
- ↵∗Address for correspondence:
Dr. Prathap Kanagala, Department of Cardiovascular Sciences, Glenfield Hospital, Groby Road, Leicester LE3 9QP, United Kingdom.
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)
- cardiac magnetic resonance imaging
- diffuse fibrosis
- focal fibrosis
- heart failure with preserved ejection fraction
- left ventricular diastolic dysfunction
Supported by the National Institute for Health Research (NIHR) Leicester Cardiovascular Biomedical Research Centre and NIHR Comprehensive Local Research Network. Dr. McCann is supported by British Heart Foundation, Medical Research Council, and NIHR Career Development fellowship 2014-07-045. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
- Received September 18, 2018.
- Revision received November 12, 2018.
- Accepted November 15, 2018.
- 2019 American College of Cardiology Foundation
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