AbstractCardiovascular morbidity and mortality following anthracycline therapy poses a significant clinical challenge. Cardiovascular magnetic resonance (CMR) is a non-invasive imaging modality that offers unique insight into both the pathophysiology and evaluation of anthracycline cardiotoxicity. This thesis comprises a series of investigations in patients treated with anthracycline chemotherapy using CMR.
In Chapter 3, the phenotype of late stage anthracycline cardiomyopathy is described. Surrogate CMR markers of both focal (late gadolinium enhancement; LGE) and diffuse (elevated native myocardial T1 mapping measurements) fibrosis are associated with adverse left ventricular remodelling and impaired left ventricular ejection fraction (LVEF). In addition a higher rate of hospitalisation for heart failure was identified in patients with elevated native myocardial T1 mapping measurements. In Chapter 4, anthracycline treated patients with normal range LVEF are shown to have significant perturbations of CMR derived 2D and 3D global longitudinal strain (GLS), native myocardial T1, ECV, indexed left ventricular mass and indexed myocardial cell volume, compared with a control population of similar age, sex and LVEF. It is also demonstrated that these parameters have good to excellent levels of inter- and intra-observer reproducibility. In Chapter 5, cardiotoxicity is prospectively characterised using multiparametric CMR, echocardiography and blood biomarkers, including microRNA (miRNA). It is reported that baseline CMR derived mitral annular plane systolic excursion (MAPSE) and baseline circulating miRNA-181-5p and miRNA-221-3p are associated with poor recovery of LVEF 6 months after completion of anthracycline chemotherapy.
In conclusion, multiparametric CMR provides unique, valuable insights into the pathophysiology and cardiovascular effects of anthracycline chemotherapy, which could potentially inform risk stratification, monitoring and treatment strategies in patients receiving cardiotoxic cancer therapy.
|Date of Award||26 Nov 2020|
|Supervisor||David Marks (Supervisor) & Chiara Bucciarelli-Ducci (Supervisor)|