CARDIOVASCULAR JOURNAL OF AFRICA • Vol 22, No 2, March/April 2011
AFRICA
59
Editorial
Left ventricular dysfunction in sickle cell disease: the
value of an electrocardiographic marker of increased
risk of arrhythmia
Sickle cell disease is one of the most prevalent genetic diseases
worldwide; affecting 1/400 individuals of African descent as well
as people of Arab, Indian and Hispanic descents.
1-3
Abnormalities
of cardiovascular function have increasingly been documented in
sickle cell disease patients. Reports from several clinical studies
in recent times have drawn attention to some ‘emerging’ cardiac
pathologies in sickle cell disease and their potentially negative
impact on cardiovascular function in these patients. Among these
include myocardial infarction without coronary artery disease,
pulmonary hypertension and cor pulmonale.
4-7
Moreover, sudden
unexpected death has become increasingly recognised as an
important clinical feature of both the homozygous and heterozy-
gous sickling syndromes; although the exact nature and its cause
has remained unexplained.
8-10
The emergence of cardiac complications in sickle cell disease
patients could be attributed to the increasing life expectancy
observed in these patients. Recent data indicates that 86 to 90%
of patients survive to beyond 20 years of age.
11
With the contin-
ued development of improved management and supportive care
for patients with sickle cell anaemia and the resultant increase in
life span, the spectrum of cardiac dysfunction is likely to enlarge
in the future.
The mechanism underlying cardiac dysfunction in sickle cell
anaemia has been extensively studied and multiple mechanisms
have been proposed. In addition to the impaired microvascular
circulation from intravascular plugs of sickled erythrocytes,
other contributory factors include: extensive fibromuscular
dysplastic narrowing of small cardiac arteries, non-inflammatory
focal degeneration and apoptosis, platelet abnormalities or simi-
lar stimuli for endothelial and smooth muscle proliferation.
12-14
The hyperkinetic circulation as a result of chronic anaemia
contributes to eccentric ventricular hypertrophy and cardio-
megaly, and the severity of cardiac chamber dilatation progresses
with increasing anaemia.
5,15
Despite myocardial remodelling/
hypertrophy, the patients have increased myocardial wall stress
as well as impaired ventricular relaxation.
16
Data from clinical studies evaluating left ventricular systolic
function using load-independent measures of myocardial contrac-
tility have revealed significant systolic dysfunction in sickle cell
anaemia patients.
17,18
The development of left ventricular systolic
and/or diastolic dysfunction in sickle cell anaemia is associated
with increased morbidity and mortality.
19
There is a large body
of evidence showing that diastolic dysfunction in sickle cell
disease contributes to pulmonary hypertension and represents an
independent predictor of mortality in these patients.
19
It has been recognised that ischaemic phenomena associated
with sickle cell anaemia could elicit morphological and function-
al abnormalities in the cardiac conducting system, resulting in
paroxysmal arrhythmia and could further worsen the ventricular
dysfunction.
5
Such electrical instability induced by myocardial
ischaemia has been postulated to be the cause of sudden cardiac
death in patients with sickle cell disease.
5,10
In the presence of left ventricular diastolic dysfunction, atrial
fibrillation and indeed any form of arrhythmia causes significant
cardiac decompensation. Atrial fibrillation in sickle cell disease
is believed to be due to increase in atrial size with accompanying
advanced atrial remodelling and profound global electrophys-
iological changes in refractoriness. Additional factors affecting
atrial refractoriness include autonomic impairment, scars, and
changes in the cellular membrane function.
20
Several non-invasive
electrocardiographic indicators have been investigated to predict
the occurrence of arrhythmia in left ventricular diastolic dysfunc-
tion. On a 12-lead surface electrocardiogram, P-wave dispersion,
because of its relationship to the non-homogenous and interrupt-
ed conduction of sinus impulses both intra- and interatrially, is
recognised as a non-invasive marker of risk of atrial fibrillation.
21
In the light of this, one pertinent question needs to be
addressed: what is the clinical utility of P-wave dispersion in
sickle cell anaemia? A step towards unravelling this puzzle
would involve the examination of the relationship between
P-wave dispersion and measures of left ventricular function in
sickle cell anaemia patients, and the comparison of the indices
with those of appropriately matched controls. In this connection,
the article in this issue, ‘P-wave dispersion: relationship to left
ventricular function in sickle cell anaemia’ is of relevance. The
authors showed that P-wave duration and P-wave dispersion were
significantly increased in sickle cell anaemia and that P-wave
dispersion had a negative correlation with indices of left ventric-
ular diastolic function. This novel study provides an interesting
insight into the potential value of this simple electrocardiographic
tool in the evaluation of ventricular function in sickle cell anae-
mia. This is especially useful in resource-limited areas of devel-
oping countries where access to modern investigative modalities
is lacking. Major challenges in the use of this tool are the diffi-
culty in standardisation of methods and the lack of acceptable
normal limits of P-wave dispersion in the general population.
It is expected that this pilot study will stimulate further
research efforts to determine the diagnostic/normal cut-off
values, and specificity and sensitivity, as well as the long-term
prognostic significance of increased P-wave dispersion in sickle
cell disease.
I OGUANOBI, MB, BS, MSc, FWACP, FMCP,
Department of Medicine, Federal Medical Centre, Asaba,
Delta State, Nigeria
