Novel methods of cardiac risk assessment in patients with chronic kidney disease and renal transplant recipients

Author: Ranjit Shah

Shah, Ranjit, 2020 Novel methods of cardiac risk assessment in patients with chronic kidney disease and renal transplant recipients, Flinders University, College of Medicine and Public Health

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Cardiovascular disease is the major cause of death in the chronic kidney disease (CKD) population. Coronary artery disease (CAD) in CKD is often asymptomatic, with multi-vessel ischaemia, and carries a poor prognosis. Although the risk of death is reduced with renal transplantation, cardiovascular disease is still one of the major causes of death post-transplant with mechanisms not well defined.

Despite the high prevalence of CAD, current functional cardiac investigations to assess inducible myocardial ischaemia in CKD population are suboptimal and may lead to significant adverse effects. Multi-modality cardiovascular magnetic resonance (CMR) imaging has emerged as a non-invasive clinical tool to assess cardiomyopathy, infarction and viability and myocardial perfusion, without risk of radiation. Stress CMR potentially detects inducible myocardial ischaemia from both epicardial and microvascular CAD. The use of gadolinium contrast is, however, contraindicated in the CKD population. Using Oxygen-sensitive CMR (OS-CMR) it has previously been shown that CKD patients have reduced myocardial oxygenation response to stress. Furthermore, the reduced OS-CMR signal intensity in the CKD population could be related to the declining renal function.

The aims of this thesis are to 1) to investigate the prognostic utility of OS-CMR imaging and feature tracking CMR (FT-CMR) derived myocardial deformation in asymptomatic CKD patients with and without diabetes mellitus and 2) utilise other novel Gadolinium-free CMR techniques and serum biochemical markers to assess coronary artery disease in the CKD population as a measure of ischaemia.

Chapter 3 shows that the blunted myocardial oxygenation response to stress and abnormal myocardial deformation in patients with CKD without known coronary artery disease is an independent predictor of adverse events.

Chapter 4 examines the diagnostic ability of CMR stress T1 mapping technique to detect coronary artery disease in CKD patients with and without CAD. In this chapter, it is demonstrated that in patients with CKD, stress T1 response is impaired and may be able to differentiate between remote, ischaemic and infarcted segments.

Chapter 5 compares the ability of OS-CMR imaging and Stress CMR T1 mapping in the diagnosis of myocardial ischaemia in patients with CKD. This study shows that in patients with CKD, stress T1 response may be a more accurate method of diagnosing myocardial ischaemia than stress OS-CMR response.

The study in chapter 6 investigates the association between Paraventricular Adipose Tissue (PVAT) and CKD. In this chapter, there was a trend seen for the PVAT volume to be increased in patients with CKD when compared to participants without CKD. However, this increased PVAT volume did not seem to be an independent predictor of adverse events in the small population that was studied.

Chapter 7 demonstrates that there is a significant association between plasma Asymmetric Dimethylarginine (ADMA) and Stress T1 response in CKD patients. However,  OS-CMR SI was not significantly associated with circulating ADMA or HMA levels.

The studies in this thesis were done in relatively small number of patients and need to be confirmed with larger, multi-centre studies. Nonetheless these studies do achieve in demonstrating the utility of novel methods of cardiac risk assessment in the very high-risk group of CKD patients. These studies will also help in further understand the complex pathogenetic mechanisms that lead to the higher CVD risk in CKD patients.

Keywords: Chronic Kidney Disease, Coronary Artery disease, OS-CMR, BOLD, T1 mapping

Subject: Medicine thesis

Thesis type: Doctor of Philosophy
Completed: 2020
School: College of Medicine and Public Health
Supervisor: Prof Joseph Selvanayagam