Abstract 11276: Differentiating Cardiac Fibrosis From Hypertrophy in Chronic Kidney Disease Hemodialysis Patients Using Gadolinium-Free Imaging and Biomarkers of Extracellular Matrix Turnover

Abstract

Purpose: Cardiac stress blood biomarkers are typically correlated to hypertrophy or diastolic dysfunction but not fibrosis in chronic kidney disease (CKD). Cardiac fibrosis can be measured without gadolinium as elevated normalized signal difference (ΔS/S o ) between pairs of magnetization transfer (MT) weighted magnetic resonance (MRI) images. We used MT-MRI to compare blood biomarkers to fibrosis, hypertrophy and diastolic strain rate in CKD patients on hemodialysis (CKD5). Hypothesis: Biomarkers of cardiac stress correlate with left ventricular (LV) hypertrophy, not fibrosis, in CKD5 patients. Methods: MT-MRI generated maps of ΔS/S o in 23 CKD5 patients and 21 controls (Fig 1A, B). Fibrotic burden was defined as divergence in ΔS/S o compared to a standard distribution (Fig 1C). In a subset of 12-15 per group, serum troponin T (TnT), fibroblast growth factor 23 (FGF23), matrix metalloproteases (MMP) 2 and 9 and tissue inhibitor of MMP (TIMP) 1 and 2 were measured by ELISA and analyzed with Spearman correlations. Feature tracking measured strain. Results: CKD5 patients had higher ΔS/S o (146.2 ± 18.7%), divergence (10.0 ± 9.2%) and LV mass index (81.6 ± 28.9 g/m 2 ) than controls (133.5 ± 11.5%, 5.4 ± 3.7%, 57.9 ± 15.5 g/m 2 , all p <0.05). Ejection fraction, diastolic strain rate and longitudinal strain were similar. While TnT, FGF23 and TIMP1/2 correlated with mass, only TIMP1 correlated with fibrotic burden (Table 1). Conclusions: Most stress biomarkers correlate with hypertrophy but not fibrosis in CKD5 patients. Activation of cardiac fibroblasts by TIMP1 and correlation of TIMP1 with degree of fibrosis suggest TIMP1 as an alternative target to attenuate cardiac fibrosis in CKD5 patients.