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Clinical Outcomes of 3343 Children and Adults with Rheumatic Heart Disease from 14 Developing
Countries: 2-Year Follow-up of the Global Rheumatic Heart Disease Registry (REMEDY)
Liesl Zühlke, PhD Ganesan Karthikeyan, DM Mark E. Engel, PhD Koon Teo, PhD Salim Yusuf, D Phil Bongani Mayosi, D Phil
for the REMEDY investigators
Lowincomecountries
(n1110,33.2%)
Lowermiddleincomecountries
(n1370,41%)
Uppermiddleincomecountries
(n863,25.8%)
Ethiopia(n400) Egypt (n286) Namibia(n266)
Kenya(n316) India(n293) SouthAfrica(n654)
Malawi(n37) Mozambique(n41)
Rwanda(n5) Nigeria (n199)
Uganda(n311) Sudan(n175)
Zambia(n116) Yemen(n301)
MethodsIo Prospectiveregistryover24monthso Baselineandfollow-upassessments
o Baseline:clinicalcharacteristics,pharmacologicaltreatments,anduseofpercutaneousandsurgicalinterventions
o Follow-upcompletedinNovember2014o Adversecardiovasculareventso Death,Atrialfibrillation(AF),Bleeding,CongestiveHeartFailure,Hospitalisation,Pregnancy,Thrombosis,Stroke,SystemicEmbolism,InfectiveEndocarditis,Surgery/valvuloplasty
Participants 3343
Age, median[IQR] 28[18-40]
Females,n(%) 2211(66.2)
Womeninchildbearingage(12-51), n(%) 1825(54.6)
Unemployedadults, n(%) 1815(75.3)
ConclusionsI• TherearegapsintheimplementationofmedicalandsurgicalinterventionsofproveneffectivenessforRHDinlowandmiddleincomecountries.
• Theseinclude:• Suboptimaluseofpenicillinforsecondaryprophylaxis.• Inadequatemonitoringandcontroloforalanticoagulanttherapy.• ExtremelylimiteduseofcontraceptioninwomenwithRHD.• Disparitiesintheuseofpercutaneousandsurgicalinterventionsbetweencountriesofdifferentincomegroups.
• Ourdatareflectsthataccesstoevidence-basedinterventionsforRHDareinadequateamongthepoorest.
MethodsII
• Incidencerate• Univariable comparisons• MultivariableCoxregressionmodels
• Apriorimodelsfordeath,CCFandStroke/thromboembolism
• Totalfollow-uptime:• 5232.09person-years
• Totallosttofollow-up:• 383(11.4%)
• Follow-upmethods:• Clinicalvisit:52%• Telephonic,thirdpartyorviahospitalrecords:19.7%
• Died:16.9%
Mortality
Deaths
n 500(16.9%)
Medianageatdeath(IQR)
28.6(17.4-46.6)
Rateper1000patient-years(95%CI)
First year 116.3(104.3-129.8)
Subsequentperiod
65.4(56.4-75.8)
Upper middle income countries
Lower middle income countries
Low income countries
Hazard ratio
0.5 2.01.0
0.001
<0.001
Baselinevariable Hazardratio 95%Confidence
interval
pvalue
Age 1.02 1.01- 1.02 <0.0001
Femalesex 0.65 0.52- 0.80 <0.0001
Educationbeyondprimaryschool 0.67 0.54- 0.85 0.001
Atrialfibrillation 1.40 1.10- 1.78 0.008
Severedisease 2.36 1.80- 3.11 0.01
Congestiveheartfailureatenrolment 2.16 1.70- 2.72 0.001
NewYorkHeartAssociationfunctionalclassIII/IV 1.67 1.32- 2.1 0.001
Onsecondaryantibioticprophylaxisatenrolment 0.86 0.70- 1.07 0.165
Adverseevents
Lowincome
countries
(N=956)
Lower-middle
income
countries
(N=1158)
Upper-middle
income
countries
(N=838)
p
Death,n(%) 200(20.8) 195(16.8) 105(12.5) <0.001
Congestiveheartfailure,n(%) 87(9.0) 66(5.7) 51(6.1) 0.006
Atrialfibrillation, n(%) 28(2.9) 14(1.2) 14(1.7) 0.013
Strokeortransientischaemic attack,n(%) 14(1.5) 12(1.0) 20(2.4) 0.053
CHF MultivariateHazard ratios- compositeofCHFandDeath
n 204
EnrolledinCHF
2.11 (1.67-2.75)P<0.001
NYHAIII&IV
1.76 (1.42-2.17)P<0.001
SevereValvedisease
2.15(1.68-2.75)P<0.001
Secondaryprophylaxis
0.81(0.65-0.99)P=0.04
Higherthanprimaryeducation
0.70(0.57-0.87)P=0.001
Surgeryandvalvuloplasty
3,13,9
7,3
10,8
13,113,8
0
2
4
6
8
10
12
14
16
Surgery* Surgery&valvuloplasties**
%
Crudeincidenceratesofinterventions
Low-income Low-middleincome Uppermiddleincomecountries
*p<0.0001**p<0.0001
Comparisonofbaselinecharacteristicsofpatientslosttofollow-upcomparedtothosewhosevitalstatuswasknownattheendofthestudy
Vitalstatusknown
2960 (88.5)
Losttofollow-up
383(11.5)
p
Age( med,IQR) 28(18-41) 26(17-36) 0.0016
Low-incomecountries 964(32.6) 146(38.1)
<0.0001Upper-middleincomecountries 838(28.3) 25(6.5)
Severe involvement 1470(49.6) 239(62.4) <0.0001
Previousinterventionorsurgery 2212(74.9) 339(34.6)<0.0001
NYHAIII&IV 679(23.3) 130(34.6)<0.0001
Higher education 1328(44.6) 96(24.6) <0.0001
Conclusions• Thiscontemporaryregistryindicatesuneqivocablythattheratesofdeath,CHFandstrokearehighamongstsymptomaticpatientslivinginRHDinLMICsdespitetheirrelativelylowage.
• Nearly20%developedoneofthesecomplicationsovertwoyears.• Mortalitywassignificantlyhigherinpatientslivinginlow-incomecountriesandamongstthelesseducated.
• Betteraccesstohigh-qualitytertiarycareservicesandoptimisingtheuseofproveninterventionsarelikelytoimproveoutcomes.
• MoreresearchisneededtodeviseeffectivewaysofimprovingaccesstoessentialcareamongstpatientswithRHDinLMICs.
Global Rheumatic Heart Disease RegistryAcknowledgements and thanks
PrincipalinvestigatorsanddatamanagersPatientsandstaffSteeringcommitteeProfBongani Mayosi
ProfGanesan KarthikeyanProfMarkEngel
FundersCannectinNovartis
WorldHeartFederationPASCAR
MedicalResearchCouncil
PopulationHealthResearchInstituteProfSYusuf,DrKoonTeo,PamMackie,
Sumathy RangarajanShofique Islam,KatyaMauff
andKathrynManningParticipatinghospitals,centresandclinics
Localfunders
EgyptProf. AzzaAbul-FadlProf. SaharShakerSheta
EthiopiaProf. AbrahamHaileamlakDr.DejumaYadetaWandimu DanielDrArayaGidey DestaDrBekele Alemayehu ShashoDrDufera Mekonnen Begna
IndiaProf. Ganesan KarthikeyanDrJitender SharmaDrGauravPurohit
KenyaProf. StephenOgendoDrBernardGituraDrChristineYukoJowi
MalawiDr.NeilKennedy
MozambiqueProf. AlbertinoDamascenoDr.AnaOlgaMocumbiNeusa Jessen
NigeriaDr.Moshood AdeoyeProf.FideliaBode-ThomasDr.Okechukwu OgahDrTaiwo OlunugaDr.DikeOjjiProf.MahmoudSaniGaniyu AmusaLudu AuduCharityDurojaiye-AmoduNgozi ElekwaOlukemi IgeOgechi MadukaOludolapo MarcaulayShamsudeen MohammedHalim OdiachiBasilOkeahialamChristopherYilgwan
RwandaDr.JosephMucumbitsi
SouthAfricaProfBongani MayosiDrMarkEngelAlexiaJoachimDr.BlancheCupidoRezeen DanielsProf.Phindile MntlaDr.ChrisSuttonDrRajeevMisraPriscillaAdolfJabulani MbokaziSusanPerkinsDr.LieslZühlke
CTandCoordinationOfficeVeronicaFrancisDylanBarthProfPatrickCommerfordFeliciaGiliDrJohnLawrensonCaroliseLemmerNonkululeko KoyanaDrWendyMatthiassenAlet MeiringPeggyMgwayiLwaziMhlantiAliceNgcolombaSimpiwe NkepuProfMpiko NtsekheJanineSaaimanUnitaSeptemberDrKathieWalkerMarnievandeWall
DepartmentofStatisticsKatyaMauff
DepartmentofMedicineKathrynManning
UgandaDr.CharlesMondoDrEmmy OkelloDrPeterLwabi
SudanProf.AhmedEl-SayedHudaH.M.ElhassanTagwa EltahirHudaHamidAhmedS.Ibrahim
YemenProf.MohammedAl-Kebsi
ZambiaDrJohnMusuku
PHRISumathyRangarajanPamMackieShofiquelIslamDrKoonTeoDrSalimYusuf
NamibiaDrChristopherHugo-HammanDrHenningduToitDrMasomi KaayaDrLiina SikwayaDrAndreasWilberg