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

• Published in: JACC. Cardiovascular imaging Vol. 12; no. 11; pp. 2291 - 2301
• Main Authors: Kanagala, Prathap, Cheng, Adrian S.H., Singh, Anvesha, Khan, Jamal N., Gulsin, Gaurav S., Patel, Prashanth, Gupta, Pankaj, Arnold, Jayanth R., Squire, Iain B., Ng, Leong L., McCann, Gerry P.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.11.2019
• Subjects: Aged; Aged, 80 and over; Asymptomatic Diseases; cardiac magnetic resonance imaging; Case-Control Studies; Contrast Media - administration & dosage; diffuse fibrosis; England - epidemiology; Extracellular Space; Female; Fibrosis; focal fibrosis; Heart Failure - diagnostic imaging; Heart Failure - epidemiology; Heart Failure - pathology; Heart Failure - physiopathology; heart failure with preserved ejection fraction; Humans; left ventricular diastolic dysfunction; Magnetic Resonance Imaging, Cine; Male; Middle Aged; Myocardium - pathology; Organometallic Compounds - administration & dosage; Predictive Value of Tests; Prevalence; prognosis; Progression-Free Survival; Prospective Studies; Stroke Volume; Ventricular Function, Left; Ventricular Remodeling; England; diffuse fibrosis; RV; cardiac magnetic resonance imaging; BNP; CMR; LV; HFpEF; LGE; prognosis; focal fibrosis; left ventricular diastolic dysfunction; heart failure with preserved ejection fraction; ECV; MI; iECV; LAVImax
• ISSN: 1936-878X; 1876-7591; 1876-7591
• DOI: 10.1016/j.jcmg.2018.11.031

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. Myocardial fibrosis has been implicated in the pathophysiology of HFpEF. 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. 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). 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) [Display omitted]