P6025Myocardial ultrastructural changes in progressive CKD: the key intermediaries of “uraemic” cardiomyopathy?

Abstract

Background: Cardiovascular (CV) mortality is elevated from the earliest stages (eGFR <75 ml/min/1.73m2) of chronic kidney disease (CKD) and is associated with high rates of death from heart failure. Diffuse interstitial fibrosis (DIF) is present early in CKD and associated with abnormal myocardial contractility, but it is not known whether there is a graded relationship with declining renal function. Purpose: To characterise the relationship between T1 as a marker of DIF, myocardial structure and function across the stages of CKD. Methods: 119 patients with CKD; stage 2 to 5 (eGFR <90ml/min/1.73m2), without diabetes mellitus or known CV disease underwent CMR (1.5T). T1 mapping and extracellular volume (ECV) were used as markers of interstitial fibrosis, and T2 mapping to assess myocardial free water content. Gadolinium was given if eGFR >30ml/min/1.73m2. Patients with evidence of ischaemic heart disease on exercise stress echocardiography were excluded. Results: Native septal myocardial T1, T2, LV volumes, LV mass and NT-proBNP increased with worsening renal function (Table 1). Systolic function was normal by ejection fraction. Myocardial T1 time was inversely associated with: eGFR r=-0.344, p<0.001 (figure 1), and haematocrit r=-0.374, p<0.001, and directly with indexed LV mass r=0.345, p<0.001, T2 time r=0.673, p<0.001 and NTproBNP r=0.375, p<0.001. Myocardial T2 times were higher in the CKD cohort (normal range 50±2 ms) and were similarly associated with eGFR r=-0.340, p=0.003, haematocrit r=-0.295, p=0.013, LV mass r=0.445, p<0.001 and NTproBNP r=0.312, p=0.013. LV mass and T2 times did not differ between CKD stages 2-4, but T1 times did (r=-0.274, p=0.017). 47 patients with early CKD received gadolinium, with mean ECV 0.27±0.04, higher than for controls (ECV 0.24±0.02, p=0.017). Conclusions: The inverse graded relationship between myocardial T1 time and eGFR supports the concept of increasing DIF with deteriorating renal function. This was paralleled by increases in myocardial water (T2) and myocyte hypertrophy (LV mass). This relationship suggests a direct causative link between DIF and renal failure. (Figure Presented).