DOI: 10.1161/CIRCULATIONAHA.112.114199
Rheumatic Heart Disease: The Tip of the Iceberg
Running title: Sliwa et al.; RHD-tip of iceberg
Downloaded from http://circ.ahajournals.org/ by guest on July 31, 2017
Karen Sliwa, MD, PhD1 and Peter Zilla, MD, PhD2
1
Hatter Institute for Cardiovascular Research in Africa, Cape Heart Centre, Dept
Deept
pt of
of Medicine,
Medi
Me
dici
di
cine
ci
ne,,
Faculty of Health Sciences, 2Chris Barnard Dept of Cardiothoracic Surgery; Cape
pe H
Hea
Heart
eart
rt C
Cen
Centre,
entr
tree,
University of Cape Town, Cape Town, South Africa
Add
dress for Correspondence:
Corr
Co
rresspond
rr
nden
en
ncee:
Address
Karen
Kaareen Sliwa,
S iw
Sl
wa, M
MD,
D, PhD
D,
PhD
D
Hatter
Hatt
tter
e Ins
Institute
stiitu
t te ffor
orr C
Cardiovascular
a diov
ar
ovascuular
ar Resea
Research
arc
rchh in
i A
Africa
fricaa
Cape
C pe Heart
Ca
Hea
e rt Centre
Cen
entr
te
tr
University of Cape Town
4th floor Chris Barnard Building, Faculty of Health Sciences
Private Bag X3, Observatory
7935 South Africa
Tel: +27 (21) 406 6457
Fax: +27 (21) 4478789
E-mail: [email protected]
Journal Subject Codes: [19] Valvular heart disease; [100] Health policy and outcome research
Key words: Editorials; race/ethnicity; rheumatic heart disease; valve replacement; valvular
regurgitation; Africa
1
DOI: 10.1161/CIRCULATIONAHA.112.114199
Rheumatic heart disease (RHD) remains one of the largest preventable burdens of disease in the
world. It is perceived as a disease of childhood as it is acquired by streptococcal throat infection
of the tonsillo-pharynx, leading to an inflammatory reaction that involves many organs,
including the heart. However, cases in children of 5-14 years are likely to represent only 15-20%
of all cases within all age groups of vulnerable populations.1
As a disease of poverty and low socio-economic circumstances, RHD is prevalent in the
developing world. This association with the poorest and weakest of society represents a double
tragedy: while the lack of access to education, infrastructure and medical facilities turns a
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preventable and surgically treatable condition into a major cause of suffering, incapacity and
death, global awareness remains depressingly low.
Although RHD has received increasing attention in the past few years, leading to
de
ecl
clar
arat
ar
atio
at
ions
io
ns,2 def
ns
definition
effin
init
i ion of areas of research3 and
ndd nnew
ew diagnosticc cr
ccriteria
iter
erria oon echocardiography, aas
declarations,
well
w
elll as
as suggestions
suggesstiion
onss for
for prevention
preven
prev
enttion
en
tionn programs
ppro
rogr
grramss insight
innsigght
ght into
in
nto incidences,
iinc
nccid
den
encees, disease
dis
i ease
see pprogression
rogr
ro
grresssiion
on aand
nd
d
mortality
data.
mo
ort
r al
alit
i y remains
it
reema
main
in
ns largely
l rg
la
gelly speculative
speecul
ecul
ulaati
tivve
ve due
due to
to a lack
lack
k ooff da
data
ta..
ta
With
h the
the adoption
adop
ad
opti
op
t on
ti
o of
of echocardiography
e ho
ec
hoca
card
ca
r io
rd
ogr
grap
aphy
ap
hy to
to project-funded
proj
pr
o ecctoj
t fu
fund
nded
nd
ed screening
scr
cree
cr
eeni
ee
ning
ni
ng ppro
programs,
ro
ogr
gram
ams,
am
s, it emergedd
that previous estimates may have distinctly under-estimated the prevalence of the disease.4 As
screening programs generally focus on school children, they concentrate on the most accessible
and reliable cohort for the assessment of disease-incidence. Yet, echo-based incidences of RHD
in school children are age-dependent,5 as a 71% increase in children younger than 9 years, to
those older than 12 years,4 was shown. Although the ten times higher sensitivity of echoscreening over clinical assessment4 detects in 90% of cases clinically silent RHD, almost half of
these valve lesions are already functionally moderate to severe.6 Therefore, together with the
effectiveness of secondary penicillin prophylaxis, the case for echo screening programs is strong.
2
DOI: 10.1161/CIRCULATIONAHA.112.114199
However, as important as school-screening programs are for secondary prophylaxis, they
address only the tip of the iceberg, in view of the disease progression in the undiagnosed post
school-age population groups. In contrast to the assessment of early disease incidence in school
children, data on disease progression rely on the screening of adult population cohorts, years
after manifestation of the disease. Historical knowledge largely comes from the developed world,
prior to disease eradication, when the natural history of RHD was already mitigated by high
socio-economic standards. In developing countries, pregnancy screenings provide some insight6
but require a more advanced level of socio-economic development of a society than the
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screening of school children. One of the few follow-up studies to date reports a 16% progression
rate
ate from acute rheumatic fever (RF) to severe, clinically relevant chronic valve lesi
llesions
esiion
ns wi
with
within
thiin
th
in
less
ess than 15 years in Brazil.7 Given an estimated 60% progression rate from RF to RHD,8 the
ac
ctu
ual progression
ppro
ro
ogr
gresssion
on rate
r of echocardiographicallyy diagnosed
ddiaagnosed casess would
wouuld therefore
tthe
h refore be closer to
actual
225%.
5%. The propo
proportion
porrtion of
o tthese
hese
he
see ppatients
atie
iennts
ie
nt th
that
hat eeventually
veentu
ual
allly ddie
iee rremains
emai
em
ainns tthe
he bbiggest
igges
ggesst un
unkn
unknown
knoown
kn
own in
n tth
the
he
natu
na
natural
tura
tu
raal history
hist
hi
sttor
oryy of
of RHD.
RHD
D. Sporadic
Sporrad
Sp
dic reports
rreepor
eporrtss from
ffro
rom
ro
m countries
coun
co
untr
un
t ies
ies like
likke Ethiopia
li
Eth
hio
opi
piaa suggest
sugg
su
g est
gg
est that
t at 70%
th
70%
% of
of
patients die before
bef
efor
o e they
or
they are
aree 26years
26y
6 ea
ears
rs old.
old
d. 9 P
Previous
revi
re
v ou
vi
ouss gl
glob
global
obal
al eestimates
stim
st
im
mate
t s of 5500,000
00,0
00
,000
,0
000 ddeaths/year
eath
ea
ths/
th
s year8 havee
s/
been recently increased to 1.4 million/year.10 Apart from prophylactic prevention, the vast
majority of these deaths might be preventable through surgical valve repairs or replacements.
Thus, as the political will for funding and implementation of both prophylaxis programs
and the roll-out of cardiac surgery will depend on better insight into the impact of RHD on
population health, productivity and premature mortality, the next big challenge in the combat of
RHD will be better insight into the natural history of the disease.11 Yet, early detection by using
the newest screening guidelines (2006 NIH/WHO) does represent a crucial first step.
The study by Beaton et al,12 performed in Kampala, Uganda, addresses the limited data
3
DOI: 10.1161/CIRCULATIONAHA.112.114199
from Sub-Saharan Africa on echocardiography in children. Auscultation and portable
echocardiography was used to screen 4869 randomly selected schoolchildren, aged 5-16 years.
The strengths of the study are the large sample size, the carefully planned prospective design and
the systematic application of criteria for diagnosis. The study design is interesting and novel in
that it provided simple pre-screening and, if any abnormality was detected, very detailed
assessment by a cardiologist at Mulago Hospital, Kampala. Through this novel approach the
researchers were able to screen 200-250 children with one sonographer, in one day, while two
other staff members served as organizers and data tabulators. Each school-based screening took
Downloaded from http://circ.ahajournals.org/ by guest on July 31, 2017
approximately two minutes to complete. Echocardiography detected 3 times as many cases of
RHD,
with
RHD than auscultation. Lower socioeconomic groups had significantly more RH
HD, w
itth al
also
so
more advanced disease presentation. The burden of disease in that cohort was 15 cases per 1000.
The
authors
interestingly
calculation
Ugandan
Th
he au
uth
thor
orss in
or
inte
ere
resstingly
st
expanded their calculat
atio
at
i n to the Ugand
io
dan
a ppopulation
opuulation of an estimated
op
would
1188 million
million children
chiild
drenn in the
he age
age group
gro
roup
up 5-16
5-1
-166 years.
yeearrs. By
By this
thiis calculation,
calc
ca
l ulat
lc
ulatio
ion,
n, 2266,400
66,44000 ccases
ases
as
es w
ou
uld
d bbee
detected,
while
would
examination.
Their
that
dete
de
tect
te
cted
ct
e , wh
ed
whi
ile only
ile
only 888,200
8,20
8,
2 0 wo
20
w
uldd be
ul
be ddetected
etec
et
ecttedd by cclinical
ec
lin
nic
ical
al eexa
ami
mina
naati
tion
on
n. Thei
T
hei
eirr da
ddata
taa ssuggest
uggge
gest
st ttha
hatt
ha
screening
efforts
targeting
10-year-old
children
lower
socioeconomic
cohorts
creening ef
ffo
ort
rtss ta
targ
rget
rg
e in
et
i g 10
10-y
-yea
earea
r-ol
o d ch
ol
chil
i dr
il
dren
en iinn lo
lowe
werr so
oci
cioe
oeco
oe
c no
co
nomi
m c co
mi
coho
h rt
ho
rtss ma
mayy maximize
sub-clinical detection.
Their data are different to another study using echocardiography based screening in subSaharan Africa. The study performed by Marijon et al4 in 2170 otherwise healthy school children
in Mozambique, between 2001-2002, found a substantially higher burden of disease (30.4 cases
per 1000), corresponding with 33/1000 in Tonga,13 24/1000 in New Zealand’s Maoris14 and
51/1000 in India.12 Apart from including children as young as 5 years and, as such, encountering
an expectably lower incidence, the difference might also be explained by difference in region,
socioeconomic circumstances or echocardiographic criteria used.
4
DOI: 10.1161/CIRCULATIONAHA.112.114199
The authors critically discuss various levels of screening by echocardiography via careful
clinical assessment and comment on the use of various guidelines, including the new criteria
from the World Heart Federation, published February 2012.15 The study supports the inclusion of
portable echocardiography in screening protocols, even in resource- and medical staffconstrained settings.
A recent study from the Heart of Soweto cohort, reporting on the incidence and clinical
characteristics of newly diagnosed rheumatic heart disease in adulthood from an urban African
community, found an estimated incidence of new cases of RHD for those aged > 14 years to be
Downloaded from http://circ.ahajournals.org/ by guest on July 31, 2017
in the region of 23.5 cases/100 000 per annum.6 Many of those patients presented late, with an
echocardiographic ejection fraction of less than 45% in 17% of the cases and an
n eelevated
leeva
v teed ri
righ
rightghttgh
sided
ided pressure in 18% of the cases. Therefore 22% of this cohort of 344 cases had valve
replacement
epl
plac
aceemen
ac
emen
entt oorr rrepair
epai
ep
a r within one year, with a fu
further
urt
rthe
her 26% being ad
he
admi
admitted
ittted for initial diagnosis of
suspected
bacterial
usppec
e ted bact
cter
eria
iall endocarditis
en
ndoocaardi
diti
tiss within
ti
with
with
thin
n 30
30 months.
monthss.
mon
A further
fur
urtther
therr burden
bur
urdden
den of late
lat
a e diagnosis
diaagno
di
gnosis
osis of
of RHD
RHD is
is the
the
h fact
ffac
act that
ac
thatt women
wom
omen
en often
oft
ften
en only
onl
nlyy present
prres
esen
entt with
wiith
symptomatic
audit
ymptomaticc RH
RHD
D wh
when
en
n ppregnant.
regn
re
g an
gn
ant.
t A 44-year
t.
-yea
-y
earr au
ea
audi
diit off cardiac
ccar
ardi
ar
diac
di
ac disease
dis
isea
e se in
in pregnancy
preg
pr
egna
eg
naanc
ncyy in a South
African hospital found an etiology of 63.5% of RHD and 20.1% of prosthetic VHD, probably of
RHD origin, which contributes to the unacceptably high maternal mortality in South Africa.16
While a predominant lesion in RHD patients presenting in pregnancy is mitral stenosis which is
amenable to balloon- or surgically-closed mitral valvotomy, 60%17 to 84%9 of cases presenting
outside of pregnancy involve mitral regurgitation and 1517 to 4018 aortic regurgitation, eventually
making open heart surgery inevitable.
Even extrapolating the authors’ relatively low incidence of 15/1000 to an African
population of one billion would result in 15 million RHD patients with almost 400,000 new cases
5
DOI: 10.1161/CIRCULATIONAHA.112.114199
per year of which 100,000/year may need heart valve surgery at some stage in their lives. Taking
the higher incidences reported from Mozambique, this number would be as high as
200,000/year.4 At present, only South Africa, Egypt, Sudan, Kenya and, most recently, Namibia
have established independent cardiac surgical programs that do not rely on sporadic ‘fly-in’
missions. Yet, even there, a majority of hospitals cater for the few private patients, while the
largely indigent RHD patients rely on a small number of public hospitals. Therefore, the already
dismal access to 18 open heart surgeries/million population as opposed to 1222/million in the
USA19 is in reality distinctly lower. In South Africa – which boast two-thirds of all hospitals that
Downloaded from http://circ.ahajournals.org/ by guest on July 31, 2017
provide cardiac surgery on the African continent - only 15% of these cater to the indigent
patients with RHD. Thus, over 50 million patients compete for limited access to
o 7 ppublic
ubbli
licc ce
cent
centres
n re
nt
r s
inn the one African country that has the best established cardiac surgical facilities. The situation is
ev
even
ven more
mor
oree dramatic
dram
dr
amat
atiic
at
ic in countries like Uganda, wh
wher
where
eree the incidenc
incidence
ce high
highlighted
ghhli
ligh
g ted by the authors
co
contrasts
ontra
ntr sts withh the
the almost
alm
mosst complete
comp
co
mple
mp
lete
tee inability
inaabiility off routine
rouutine referral
refer
eferrraal to
o ccardiac
arrdi
diac
ac ssurgery.
urge
ur
gery
ry.
This
weaknesses.
were
T
hiis study,
stud
st
uddy,, as
as with
wiith all
ll studies,
sstu
tudi
tu
diees,
di
es, also
also has
h s we
weak
ak
kneessses
es.. On
Only
ly
y lleft-sided
eftef
t-ssidded va
vvalves
l ess w
lv
erre
examined for
or ffeatures
e tu
ea
ure
ress of
o R
RHD.
HD. Th
HD
This
iss iis by ffar
a th
ar
thee mo
most
st ccommon
ommo
om
monn ar
mo
aarea
ea ffor
or RH
RHD,
D,, bbut
u a number
ut
number of
cases involving the right side may have been missed. Spending only approximately 2 minutes per
child and doing screening on more than 200 cases a day, by one sonographer, might have led to
missing a number of cases. The number of views recorded for secondary evaluation must have
been limited by this approach.
The authors did not include a cost calculation. This would have been of particular
interest, as this study was carried out in a developing world set-up with limited funding. In the
cost calculation the salaries of the three staff members, as well as the equipment needed for
cardiac ultrasound, would need to be included.
6
DOI: 10.1161/CIRCULATIONAHA.112.114199
Furthermore, the use of the much cheaper hand-held portable echocardiography to detect
rheumatic heart disease in children and adults with symptoms should be explored, as the image
quality might be sufficient for screening purposes (Figure 1). Interestingly the World Health
Organization supported the development of a simple, affordable, solar-powered blood-pressure
device.20 Support for other cheaper devices, as for cardiac ultrasound, would be laudable.
In conclusion, the authors have provided a significant contribution to the knowledge of
childhood incidence of RHD in a hitherto unreported part of Sub-Saharan Africa. Well
conducted studies like this will continue to be important for creating awareness for the fact that
Downloaded from http://circ.ahajournals.org/ by guest on July 31, 2017
we only begin to see the tip of an iceberg which developed countries have long erased from their
adar screen. Without deeper understanding of the disease progression and the ac
ctuaal im
impa
pact
pa
ct ooff
radar
actual
impact
RHD on the respective countries, however, the necessary political pressure for the roll-out of
eco
ond
ndaary
ary prophylaxis
p ophy
pr
hyylaxi
lax s and surgical therapy willl be
be insufficient.
secondary
Co
onf
nfli
l ct
c of Interest
Inteere
In
restt Disclosures:
Dissclossurres
es: No
N
nee
Conflict
None
References
s:
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Figure Legend:
Figure 1. A. Patient with rheumatic mitral valve disease imaged with a top-of-the
top-of-th
he range
rannge
ra
nge cardiac
card
ca
rdia
dia
iacc
ultrasound machine. B. Patient with rheumatic mitral valve disease imag
imaged
aged with a hand held
cardiac
ultrasound
machine.
ca
ard
dia
iac ultr
t assou
ound
nd m
mac
acchi
h ne
ne..
9
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Rheumatic Heart Disease: The Tip of the Iceberg
Karen Sliwa and Peter Zilla
Circulation. published online May 24, 2012;
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