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Focal and Diffuse Fibrosis in HFpEF and Outcomes
Study Questions:
What is the presence and extent of focal and diffuse fibrosis in heart failure with preserved ejection fraction (HFpEF) compared to asymptomatic controls, and their relation to clinical outcome?
Methods:
The investigators conducted a prospective, observational study of 140 subjects of similar age and sex distributions (HFpEF n = 96, controls n = 44, age 73 ± 8 years, males 49%) who underwent cardiovascular magnetic resonance imaging. Late gadolinium-enhanced imaging (LGE) and T1 mapping to calculate myocardial extracellular volume indexed to body surface area (iECV) were used to assess fibrosis. The combined accuracy of the independent variables to predict events was then tested by receiver operator characteristics (ROC) analysis.
Results:
Patients with HFpEF had more concentric remodeling and worse diastolic function. Focal fibrosis was more frequent in HFpEF (overall n = 49; infarction n = 17; nonischemic n = 36; mixed pattern n = 4) compared to controls (overall n = 3). Diffuse fibrosis was also greater in HFpEF than controls (iECV: 13.7 ± 4.4 ml/m2 vs. 10.9 ± 2.8 ml/m2, p < 0.0001). During median follow-up (1,429 days), there were 42 composite events (14 deaths, 28 HF hospitalizations) in HFpEF. Myocardial infarction on LGE was a predictor of outcomes on univariable analysis only. With multivariable analysis, iECV (hazard ratio [HR], 1.689; 95% confidence interval [CI], 1.141-2.501; p = 0.009) was an independent predictor of outcome along with E/E’ (HR, 1.716; 95% CI, 1.191-2.472; p = 0.004) and prior HF hospitalization (HR, 2.537; 95% CI, 1.090-5.902; 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:
The authors concluded that both focal and diffuse myocardial fibrosis are more prevalent in HFpEF compared to controls of similar age and sex.
Perspective:
This study reports that both focal and diffuse fibrosis are elevated in HFpEF compared to asymptomatic controls. Furthermore, diffuse fibrosis, as assessed by iECV, independently predicted prognosis in HFpEF; and iECV was associated with markers of ventricular and left atrial remodeling, as well as renal dysfunction. These data lend further support to a growing body of evidence highlighting ECV and iECV as promising biomarkers across a spectrum of cardiac pathologies. Given the prognostic implications of fibrosis, additional studies of therapies to reduce diffuse fibrosis should be considered to prevent and potentially treat HFpEF.
Clinical Topics: Arrhythmias and Clinical EP, Heart Failure and Cardiomyopathies, Noninvasive Imaging, Prevention, Acute Heart Failure, Heart Failure and Cardiac Biomarkers, Magnetic Resonance Imaging
Keywords: Atrial Remodeling, Biomarkers, Creatinine, Diagnostic Imaging, Fibrosis, Gadolinium, Heart Failure, Magnetic Resonance Imaging, Myocardial Infarction, Myocardium, Renal Insufficiency, Secondary Prevention, Stroke Volume
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