Cardiovascular Journal of Africa: Vol 31 No 5 (September/October 2020)

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CARDIOVASCULAR JOURNAL OF AFRICA • Volume 31, No 5, September/October 2020 262 AFRICA
Review Article
Subclinical anthracycline therapy-related cardiac
dysfunction: an ignored stage B heart failure in an
African population
Wan Zhu Zhang, Feriel Azibani, Karen Sliwa
Abstract
Anthracyclines are potent antineoplastic agents with a proven
efficacy in the treatment of many paediatric and adult
haematological and solid-organ cancers. Anthracycline ther-
apy-related cardiac dysfunction (ATRCD) is the commonest
and most well-studied chemotherapy-induced cardiovascu-
lar toxicity. Therefore patients who received anthracycline
therapy are considered in stage A heart failure. Recent study
findings suggest that anthracycline cardiotoxicity represents a
continuum that begins with subclinical myocardial cell injury,
followed by an early asymptomatic decline in left ventricular
ejection fraction that can progress to symptomatic heart fail-
ure if left untreated. In Western countries, ATRCD has been
reported in 57% of anthracyclines-treated patients. However,
data on incidence and spectrum of ATRCD in Africa are not
available. This literature review aimed to highlight the concept
of subclinical ATRCD as a stage B heart failure in the spec-
trum of ATRCD, and the importance of early detection.
We emphasise the potential burden and risk of subclinical
ATRCD in the African population, with the ultimate aim of
drawing the attention of health workers in Africa to improve
care of the relevant population.
Keywords: subclinical anthracycline therapy-related cardiac
dysfunction, stage B heart failure, African population
Submitted 20/9/19, accepted 28/5/20
Published online 24/6/20
Cardiovasc J Afr 2020; 31: 262–266
DOI: 10.5830/CVJA-2020-013
Anthracyclines are potent antineoplastic agents with proven
efficacy in the treatment of many paediatric and adult
haematological and solid-organ cancers. Anthracycline therapy-
related cardiac dysfunction (ATRCD) is the most notorious
and well-studied chemotherapy-induced cardiovascular toxicity.
This dose-dependent ATCRD was first described in 1971
in a cohort of 67 patients treated with Adriamycin for a
variety of tumours. 1 The clinical significance of anthracycline
cardiotoxicity is growing with the increasing number of cancer
survivors worldwide. ATRCD is defined as a decrease in left
ventricular ejection fraction (LVEF) of > 10%, to a value < 53%.2
Anthracycline toxicity may be acute, early or late. Acute
toxicity, which develops in 1% of patients immediately after
infusion, is uncommon and generally reversible.3 Early effects
occur within the first year of treatment, while late effects manifest
after several years (median of seven years after treatment).4,5
Early- and late-onset cardiac dysfunction are more likely to be
irreversible.5
In the literature there is wide variation in the reported
frequency of clinical cardiotoxicity. Differences in study
population, treatment protocols and duration of follow up
could account for this wide variability. The prevalence of late
asymptomatic ATRCD has been reported to be more than 57%
at a median of 6.4 years after treatment among survivors of
childhood cancers,6 and the incidence of symptomatic heart
failure as high as 16%, 0.9 to 4.8 years after treatment.7
According to the American College of Cardiology and
American Heart Association guidelines,8 patients who received
cardiotoxic agents are considered in stage A heart failure. This
identifies patients who are at a high risk for developing heart
failure with no evidence of cardiac structural disorder. Stage
B refers to patients with cardiac structural disorder but who
have never developed symptoms of heart failure. Stage C denotes
patients with symptoms of heart failure associated with
underlying structural heart disease, and stage D designates the
patient with end-stage disease who requires specialised treatment
strategies such as mechanical circulatory support, continuous
inotropic infusions, cardiac transplantation or hospice care. This
Table 1. Classification of heart failure (HF)
Stage of HF Definition
A High risk for developing HF with no evidence of cardiac
structural disorder
B Cardiac structural disorder but has never developed symptoms
of HF
C Symptoms of HF associated with underlying structural heart
disease
D End-stage disease requiring specialised treatment strategies
Hatter Institute For Cardiovascular Research In Africa,
University of Cape Town, Cape Town, South Africa
Wan Zhu Zhang, MMed,
Feriel Azibani, PhD
Karen Sliwa, PhD
Uganda Heart Institute, Kampala, Uganda
Wan Zhu Zhang, MMed,