Background: While myocardial fibrosis has been proposed as the hallmark of pathologic remodeling, its role in myocardial dysfunction is not always recognized in paradigms of cardiac dysfunction. We hypothesized that myocardial fibrosis: 1) would correlate strongly to BNP, a nonspecific and quantitative metric of cardiac dysfunction and potent predictor of outcomes, even after adjustment for key metrics of cardiac changes; and 2) would be prevalent in the setting of cardiac dysfunction. Methods and Results: In 135 patients without myocardial infarction, amyloidosis or hypertrophic cardiomyopathy who were referred for contrast enhanced cardiac magnetic resonance, we quantified the extracellular volume fraction (Ve--a validated and quantitative metric of myocardial fibrosis):Ve = [λ · ρ · (1-hematocrit)] - Vpwhere ρ= specific density of myocardium (1.05), Vp is the myocardial plasma volume fraction (assumed to be a constant 4.5% reflecting capillary density), and λ=[ΔR1 myocardium ] / [ΔR1 bloodpool ] pre and post Gadolinium contrast (where R1=1/T1). T1 was measured with a modified ECG-gated Look-Locker IR-SSFP sequence validated against CuSO4 phantoms. BNP levels were log transformed given their skewed distribution. Elevated Ve was defined as >25%, (above the 99 th percentile in healthy volunteers). In linear regression models, Ve strongly related to ln BNP (unadjusted t value 8.4, p<0.0001, R2=0.35) even after adjusting for ejection fraction (EF), age, sex, diuretic use, myocardial mass index, and body mass index (adjusted t value 4.4, p<0.0001, R2=0.65). Similar data were obtained when circumferential or meridional wall stress was substituted for EF (not shown). In the 40% of patients with EF<50%, 71% had elevated Ve (chi square 24, p<0.0001). In the 45% of patients with BNP>100 pg/mL, 75% had elevated Ve (chi square 24, p<0.0001). Conclusions: Myocardial fibrosis is strongly and independently associated with cardiac dysfunction quantified by BNP levels. Myocardial fibrosis is highly prevalent in those with cardiac dysfunction defined by EF<50% or BNP>100 pg/mL. These data suggest an important role of myocardial fibrosis in human myocardial dysfunction. Paradigms of cardiac dysfunction should include the role of myocardial fibrosis.
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