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Title: Left ventricular remodelling in chronic kidney disease : correlation with aortic stiffness
Author: Sulemane, Samir
ISNI:       0000 0004 6495 7813
Awarding Body: Imperial College London
Current Institution: Imperial College London
Date of Award: 2017
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Chronic kidney disease (CKD) is associated with increased cardiovascular (CV) morbidity and mortality. Early detection of CV disease (CVD) can enable therapeutic interventions in earlier stages and potentially slow disease progression, reduce complications related to CV risk, and improve quality of life and survival rates. This prospective, observational study was designed to assess the use of novel speckle tracking echocardiography (STE) and arterial tonometry in a clinical setting. It focuses primarily on the assessment of CKD patients who have no clinical evidence of CVD and have normal left ventricular (LV) ejection fraction (LVEF) as assessed by conventional echocardiography. Our cohort comprised 106 CKD patients of all stages, 38 healthy controls and 38 risk factor matched controls that were hypertensive and/or diabetic with normal renal function The first aim of this study was to investigate the association between STE markers with worsening glomerular filtration rate (eGFR). Our data showed that worsening eGFR is associated with early and asymptomatic impairment of systolic (reduced global longitudinal strain (GLS), global longitudinal strain rate (GLSRs) and increased LV twist) and diastolic (segmental diastolic dysfunction) myocardial function. In addition, we found that both LV twist and GLS can be useful to differentiate CV involvement in patients with CKD in the presence of risk factors such as hypertension (HT) and/or diabetes mellitus (DM). The second aim was to explore a possible association between aortic pulse wave velocity (aPWV), a marker of arterial stiffness, and STE markers. The results showed that arterial stiffness was inversely and independently associated with eGFR in our cohort. Moreover, among the STE parameters, only LV twist was significantly associated with the presence of arterial stiffness. These findings suggest a close interaction between arterial and LV twist mechanics early in the CV disease continuum. Finally, we aimed to investigate the prognostic value of STE and aPWV in our cohort. Our primary endpoint was a composite of major adverse CV events (MACE). Over a median follow-up period of 49 months, 26 patients (24.5%) reached the primary endpoint. A multivariate Cox proportional hazards model showed that GLS and aPWV were significant independent predictors of outcomes. Moreover, patients with increased (more impaired) GLS and higher aPWV had reduced MACE-free rates. In summary, this study shows that, in CKD patients who have no previous history of CVD and who have normal LVEF as assessed by conventional echocardiography, early subclinical abnormalities in cardiac structure and function are associated with kidney function decline. Moreover, we demonstrated, for the first time, an association between aPWV and LV twist in CKD patients. In addition, we found that GLS and aPWV improves the characterisation of the risk in this cohort, as they are associated with the occurrence of adverse cardiac events.
Supervisor: Nihoyannopoulos, Petros Sponsor: Fundacao para a Ciencia e a Tecnologia
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral