Title

Factors associated with cardiac dysfunction following anthracyline-based chemotherapy in adults in a tertiary hospital in Nairobi

Date of Award

2019

Document Type

Dissertation

Degree Name

Master of Medicine (MMed)

First Supervisor/Advisor

Dr. Anders Barasa

Second Supervisor/Advisor

Dr. Asim Jamal Shaikh

Third Supervisor/Advisor

Dr. Jeilan Mohamed

Department

Internal Medicine (East Africa)

Abstract

Introduction: Anthracyclines are known to improve survival in some malignancies, but may also be associated with irreversible cardiotoxicity, which is partly dose dependent. Early detection of cardiotoxicity provides an opportunity for treatment adjustment. Several parameters predict development of clinically manifest cardiac dysfunction. The study aimed to evaluate clinical and echocardiographic parameters which predict development of cardiac dysfunction in a sub-Saharan African population.

Methods: Patients with a diagnosis of cancer and receiving anthracyclines at AKUH,N were evaluated if they met eligibility criteria (≥18years at first anthracycline administration, archived baseline echocardiogram, no prior history of heart disease or use of anthracyclines). Patients underwent echocardiographic, baseline clinical , drug therapy, radio-therapy and cardiovascular risk factor assessments. Echocardiographic global longitudinal strain (GLS), left ventricular (LV) ejection fraction and LV volumes were assessed. A relative decline from baseline in GLS of >15%, an absolute decline in LVEF >10 percentage points to <53%, or symptomatic absolute decline in LVEF of 6-10 percentage points to <53% defined LV dysfunction (cases). Factors associated with development ofLV dysfunction were compared between cases and controls (no LV dysfunction).

Results: From 14-Oct-2013 to 11-Apr-2019, 504 patients who received anthracyclines were screened. 141 fullfilled inclusion criteria and were analysed (mean age, 47.7 years ± 11.2, Africans 95%, females 85.1%). Breast cancer patients were 82%, lymphoma 12%, sarcoma 5%, and leukaemia 1%. 39 (27.7%) had cardiac dysfunction, 30 of whom fulfilled the GLS criterion. Mean time interval between echocardiograms was 14.3 months (cases 16.4 ± 16.9; controls 14.4 ± 13.2), mean anthracycline dose was 244.7mg/m2 ± 72.2 (cases 254.5 ± 78.7; controls 241 ± 69.6), and mean symptom scores (DASI) were 50.0 ± 13.3 (cases 48.5 ± 13.4; controls 50.5 ± 13.2). Mean cardiotoxic doxorubicin equivalence dose was 236.7 mg/m2 ± 57.4 for cases and 217.3 ± 61.9 for controls [p = 0.033, OR = 1.00 (95% CI: 0.99 - 1.01)]. Cycle intervals, body surface area, body mass index, blood pressure, age, concomitant medication, radiation use and cardiovascular factors were similar. Echocardiographic parameters – E/a ratio and e’ were significantly reduced in cases (E/a 1.02 ± 0.33 for cases vs 1.16 ± 0.36 for controls, p =0.02: e’ 0.10 ± 0.05 for cases vs 0.11 ± 0.05 for controls, p =0.011).

Conclusion: This is the first study evaluating early cardiotoxicity in an adult Sub-Saharan population receiving standard dose anthracyclines. The incidence of early cardiotoxicity was 27.7%, which was higher than in previously studied populations and had no relation to functional activity. Routine pre- and post-exposure cardiac assessment should be considered in an African population receiving anthracyclines to pre-empt the development of cardiac disease.

This document is available in the relevant AKU library

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