Cardiac biomarkers in chronic kidney disease are independently associated with myocardial edema and diffuse fibrosis by cardiovascular magnetic resonance

Background: High sensitivity cardiac troponin T (hs-cTnT) and NT-pro-brain natriuretic peptide (NT-pro BNP) are often elevated in chronic kidney disease (CKD) and associated with both cardiovascular remodeling and outcome. Relationship between these biomarkers and quantitative imaging measures of myocardial fibrosis and edema by T1 and T2 mapping remains unknown. Methods: Consecutive patients with established CKD and estimated glomerular filtration rate (eGFR)<59 ml/min/1.73 m(2) (n=276) were compared to age/sex matched patients with eGFR >= 60 ml/min/1.73 m(2) (n=242) and healthy controls (n=38). Comprehensive cardiovascular magnetic resonance (CMR) with native T1 and T2 mapping, myocardial ischemia and scar imaging was performed with venous sampling immediately prior to CMR. Results: Patients with CKD showed significant cardiac remodeling in comparison with both healthy individuals and non-CKD patients, including a stepwise increase of native T1 and T2 (p<0.001 between all CKD stages). Native T1 and T2 were the sole imaging markers independently associated with worsening CKD in patients [B=0.125 (95% CI 0.022-0.235) and B=0.272 (95% CI 0.164-0.374) with p=0.019 and <0.001 respectively]. At univariable analysis, both hs-cTnT and NT-pro BNP significantly correlated with native T1 and T2 in groups with eGFR 30-59 ml/min/1.73 m(2) and eGFR<29 ml/min/1.73 m(2) groups, with associations being stronger at lower eGFR (NT-pro BNP (log transformed, lg10): native T1 r=0.43 and r=0.57, native T2 r=0.39 and r=0.48 respectively; log-transformed hs-cTnT(lg10): native T1 r=0.23 and r=0.43, native T2 r=0.38 and r=0.58 respectively, p<0.001 for all, p<0.05 for interaction). On multivariable analyses, we found independent associations of native T1 with NT-pro BNP [(B=0.308 (95% CI 0.129-0.407), p<0.001 and B=0.334 (95% CI 0.154-0.660), p=0.002 for eGFR 30-59 ml/min/1.73 m(2) and eGFR <29 ml/min/1.73 m(2), respectively] and of T2 with hs-cTnT [B=0.417 (95% CI 0.219-0.650), p<0.001 for eGFR<29 ml/min/1.73 m(2)]. Conclusions: We demonstrate independent associations between cardiac biomarkers with imaging markers of interstitial expansion, which are CKD-group specific. Our findings indicate the role of diffuse non-ischemic tissue processes, including excess of myocardial fluid in addition to diffuse fibrosis in CKD-related adverse remodeling.

Automated summary

The study demonstrates close associations between cardiac biomarkers including high sensitivity cardiac troponin T (hs-cTnT) and NT-pro-brain natriuretic peptide (NT-pro BNP) with quantitative imaging measures of myocardial fibrosis and edema by T1 and T2 mapping in patients with chronic kidney disease. Native T1 and T2 were significantly associated with worsening CKD in patients, and hs-cTnT and NT-pro BNP correlated with T1 and T2 mapping in patients with lower estimated glomerular filtration rate, suggesting the role of diffuse non-ischemic tissue processes in CKD-related cardiac remodeling.