Detecting subclinical anthracycline therapy related cardiac dysfunction in low income country (SATRACD study)

Doctoral Thesis


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Introduction: Anthracycline therapy-related cardiac dysfunction (ATRCD) is the most common chemotherapy-induced cardiovascular toxicity. It begins with subclinical myocardial cell injury that can be detected using speckle tracking echocardiography (STE), together with Troponin-I. Limited availability of STE in Uganda posts challenges in detecting subclinical ATRCD. Anthracycline can also affect cancer survivors' cardiovascular health through altering patients' lipid homoeostasis. This PhD project aims to describe the incidence and predictors of subclinical ATRCD, assess the accuracy of simple echocardiographic parameters on detecting subclinical ATRCD and investigate the lipoprotein subfractions change after anthracycline therapy. Methods and results: Two hundred seven cancer patients who were scheduled for anthracycline based chemotherapy were recruited and followed up to 6 months after ending chemotherapy. Patients' clinical characteristics, laboratory tests, electrocardiogram and echocardiographic data were collected at the baseline and at each follow up visits. Among the 207 patients, 178 (86.0%) were female, with a median age of 42 years. The cumulative incidence of subclinical and clinical ATRCD were 35.0% and 8.8% respectively at the 6 months after ending the therapy. No factor was found to predict subclinical ATRCD in multivariable model. The development of clinical ATRCD associated with HIV infection and development of subclinical ATRCD at the end of anthracycline therapy. The reduction of mitral annular plane systolic excursion (ΔMAPSE) ≥ 2mm or reduction of mitral annular peak systolic velocity (Δ S') ≥ 0.5cm/s from the baseline defined subclinical ATRCD with fairly good accuracy. Very low density lipoprotein subfraction increased and mean low density lipoprotein particle size decreased following anthracycline therapy. Conclusion: There is high incidence of subclinical ATRCD in Uganda cancer patients. Cardiac surveillance at baseline and ending of anthracycline therapy is essential to identify subclinical ATRCD patients who are at high risk of developing clinical ATRCD, particular in HIV positive patients. The conventional echocardiographic parameters ΔMAPSE and ΔS' may be used to screen subclinical ATRCD in resource limited settings. Anthracycline changes lipoprotein subfraction to more atherogenic pattern. Further studies are needed to explore more on its role on lipid metabolism.