Diffuse Interstitial Fibrosis and Myocardial Dysfunction in Early Chronic Kidney Disease

Abstract

Early-stage chronic kidney disease (CKD) is an under-recognized highly prevalent cardiovascular (CV) risk factor. Despite a clustering of conventional atherosclerotic risk factors, it is hypothesized that nonatherosclerotic processes, including left ventricular (LV) hypertrophy and fibrosis, account for a significant excess of CV risk. This cross-sectional observational study of 129 age- (mean age 57±10 years) and gender-matched subjects examined: nondiabetic CKD stages 2 to 4 (mean glomerular filtration rate 50±22 ml/min/1.73 m2) with no history of CV disease, subjects who are hypertensive with normal renal function, and healthy controls. Cardiac magnetic resonance imaging was performed for assessment of LV volumes and systolic function (myocardial deformation). Diffuse myocardial fibrosis was assessed using T1 mapping for native myocardial T1 times before contrast and myocardial extracellular volume (ECV) after gadolinium administration in combination with standard late gadolinium enhancement techniques for detection of coarse fibrosis. Patients with CKD had increased native T1 times (986±37 ms) and ECV (0.28±0.04) compared with controls (955±30 ms, 0.25±0.03) and subjects who are hypertensive (956±31 ms, 0.25±0.02, p<0.05). Both T1 times and ECV were correlated with impaired systolic function as assessed by global longitudinal systolic strain (r=-0.22, p<0.05, and r=-0.43, p<0.01, respectively). There were no differences in LV volumes, ejection fraction, or LV mass. T1 times and ECV did not correlate with conventional CV risk factors. In conclusion, diffuse myocardial fibrosis is increased in early CKD and is associated with abnormal global longitudinal strain, an early feature of uremic cardiomyopathy and a key indicator of adverse CV prognosis.

Novel cardiac nuclear magnetic resonance method for noninvasive assessment of myocardial fibrosis in hemodialysis patients

“…The control values we found are similar to those previously published (34). One further study of patients with CKD (not on dialysis) by Edwards et al has looked at native T1 signal using the MOLLI sequence imaged at 1.5T (14). They measured native T1 values of the inter-ventricular septum at basal and mid-myocardial level, finding native T1 times significantly higher than matched controls and patients with hypertension.…”

“…Subtle, subclinical impairment of cardiac systolic function may be detected by assessing myocardial systolic strain, which measures myocardial deformation (13). CMR studies have shown that global myocardial strain is reduced in patients with CKD (14,15) and ESRD (16).…”

Implantable loop recorders in patients with unexplained syncope: Clinical predictors of pacemaker implantation

“…Accordingly, cMRI studies revealed myocardial fibrotic alterations in patients with chronic kidney disease [22]. Based on these alterations in myocardial interstitial structure chronic changes in sinus node function and cardiac conduction system are reasonable [23,24].…”

Letter by Edwards et al Regarding Article, “Coronary Microvascular Rarefaction and Myocardial Fibrosis in Heart Failure With Preserved Ejection Fraction”

“…2,5 We have recently used T1-mapping cardiac MRI in patients with CKD stages 2 to 4 to detect diffuse interstitial myocardial fibrosis. In comparison with healthy controls and hypertensive subjects with normal renal function, diffuse fibrosis measured by extracellular volume was increased in CKD and was correlated with reductions in global LV longitudinal strain and strain rate, but not with LV ejection fraction, LV mass, or conventional cardiovascular risk factors.…”

“…Interestingly, the role of chronic kidney disease (CKD) in the pathogenesis of HFpEF is not discussed, despite a mean estimated glomerular filtration rate of 38 mL•min The phenotype of uremic cardiomyopathy or, perhaps more correctly, renal heart disease (because most patients are not uremic until stage 5 CKD) is present from the earliest stages of CKD 4 and closely resembles that of HFpEF with progressive left ventricular (LV) hypertrophy, increased arterial-ventricular systolic and diastolic stiffness, and myocardial fibrosis. 2,5 We have recently used T1-mapping cardiac MRI in patients with CKD stages 2 to 4 to detect diffuse interstitial myocardial fibrosis. In comparison with healthy controls and hypertensive subjects with normal renal function, diffuse fibrosis measured by extracellular volume was increased in CKD and was correlated with reductions in global LV longitudinal strain and strain rate, but not with LV ejection fraction, LV mass, or conventional cardiovascular risk factors.…”