PROFILING CARDIAC BIOMARKERS PREDICTS CARDIAC PATHOPHYSIOLOGY IN URAEMIC CARDIOMYOPATHY.

A CROSTHWAITE1,2,  R LIM3, R MASTERSON4, E VELCOSKA2, A HEDLEY1, L BURRELL2,  M ROBERTS6, O FAROUQUE1,2, F IERINO7,2
1Department of Nephrology, Austin Health, Heidelberg, Australia, 2Department of Medicine, University of Melbourne, , Australia, 3Department of Radiology, Austin Health, Heidelberg, Australia, 4Department of Nephrology, Melbourne Health, Parkville, Australia, 5Department of Cardiology, Austin Health, Heidelberg, Australia, 6Department of Renal Medicine, Eastern Health Clinical School, Monash University, Box Hill, Australia, 7Department of Nephrology, St. Vincent’s Hospital Melbourne, Fitzroy, Australia

Aim: Define cardiac structural and functional changes and serum cardiac biomarker profile in end-stage kidney disease (ESKD).
Background: “Uraemic Cardiomyopathy” describes various cardiac structural and functional abnormalities in chronic and ESKD. Cardiac biomarkers predict clinical outcomes and represent surrogate markers of pathophysiological processes defined by cardiac magnetic resonance imaging (cMRI).
Method: Baseline data from two prospective observational cohort studies in adults with ESKD. All patients underwent transthoracic echocardiography (TTE), cMRI, stress nuclear cardiac perfusion imaging (rNPI) and measurement of cardiac biomarkers (angiotensin converting enzyme 2 (ACE2) activity, high-sensitivity cardiac troponin T (hscTnT) and N-terminal proBNP (NT-proBNP).
Results: Patient characteristics (n=65) were: mean age 52.6±14.0 years, 74% male, 83% requiring dialysis with median cumulative dialysis vintage 1.92 (0.59,4.79) years and previous renal transplant recipients (22%). Cardiovascular risk factors were prevalent: Hypertension (92%), Dyslipidaemia (72%), Diabetes (22%), Smoking (46%) and known cardiovascular disease (34%).26(44%) and 30(47%) had LV hypertrophy and 14(23%) and 7(11%) had LV systolic dysfunction by cMRI and TTE criteria respectively. 30(48%) had diastolic dysfunction. Baseline mean cMRI LVMI (80g/m2, 95%CI 74-85) and median LVEF 64%(57,67) were normal. 11(18%) demonstrated perfusion defects (rNPI).Geometric mean hs-cTnT (41.7ng/L 95%CI 33.8-51.9), NT-proBNP (608ng/L 95%CI 407-898) and median ACE2 activity (19.5pmol/mL/min IQR 10.4,25.3) were elevated.Hs-cTnT (r=0.71 p<0.001)  and ACE2 (r=0.61 p<0.001) correlated with LVMI(cMRI). Hs-cTnT predicted LVH(cMRI) (ROC AUC 0.84 95%CI 0.73-0.94) and diastolic dysfunction (TTE) (ROC AUC 0.75 95%CI 0.62–0.87). NT-proBNP predicted systolic dysfunction (cMRI) (ROC AUC 0.75 95%CI 0.62-0.88). ACE2 predicted diastolic dysfunction (TTE) (ROC AUC 0.67 95%CI 0.54-0.82).
Conclusion: Elevated cardiac biomarkers are common in ESKD and highly predictive of cardiac structural/functional changes. Further work defining profiles for clinical application are in progress.


Biography:
Amy Crosthwaite is a Nephrologist, General and Obstetric Physician and PhD candidate at the University of Melbourne. Her research examines the cardiac structural and functional changes associated with chronic and end-stage kidney disease and the impact of renal transplantation and extended hours haemodialysis.

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