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