Baseline characteristics and outcome of rheumatic heart disease in REMEDY:

clinical and policy implications

Dr Liesl ZhlkeRed Cross War Memorial Childrens Hospital

University of Cape Town

Clinical and policy indicators

Gaps in implementation

Seckeler et al 2011

Carapetis et al 2005

Global Rheumatic Heart Disease Registry: REMEDY

Country Number of SitesEgypt 2Ethiopia 2India 2Kenya 1Malawi 1Mozambique 2Namibia 1Nigeria 5

South Africa 3Sudan 2Rwanda 1Uganda 1Yemen 1Zambia 1

Karthikeyan, Zuhlke, Engel et al 2012 AHJ

Low income countries

(n 1110, 33.2%)

Lower middle income countries

(n 1370, 41%)

Upper middle income countries

(n 863, 25.8%)

Ethiopia (n 400) Egypt (n 286) Namibia (n 266)

Kenya (n 316) India (n 293) South Africa (n 654)

Malawi (n 37) Mozambique (n 41)

Rwanda (n 5) Nigeria (n 199)

Uganda (n 311) Sudan (n 175)

Zambia (n 116) Yemen (n 301)

Zuhlke, Engel et al Eur Heart Journal

Results

Participants 3 433

Age, median [IQR] 28 [18-40]

Females, n (%) 2 211 (66.2)

Women in childbearing age (12-51) , n (%) 1 825 (54.6)

Children (up to 18 years), n (%) 921 (27.6)

Adults with no formal education, n (%) 458 (19.1)

Unemployed adults, n (%) 1 815 (75.3)

Age and Gender Distribution

54%

46%

Children < 18 years n=941

66%

34%

Total group n=3343

0

50

100

150

200

250

300

350<

56-

1011

-15

16-2

021

-25

26-3

031

-35

36-4

041

-45

46-5

051

-55

56-6

061

-65

66-7

071

-75

76-8

081

-85

>85

Coun

t

Age categories

Male

Female

Low income countriesN=1110(33.2%)

Lower middle income countriesN=1370(41.0%)

Upper middle income countriesN=863(25.8%)

P

Median age[IQR]

24[15-34] 28[18-38] 39[22-52] 0.4

Women in childbearing age

630(86.5%) 783(90.3%) 412(66.9%) 0.01

Womenn=2 211 (66.2%)

Women in childbearing age 1 825(82.5%)

Severe mitral stenosis 416(45.8%)

Prosthetic valves 280(15.3%)

Contraception 65(3.6%)

Pregnant 73(4.0%)

On Warfarin 15(20.5%)

Low income countriesN=1110(33.2%)

Lower middle income countriesN=1370(41.0%)

Upper middle income countriesN=863(25.8%)

P

Stroke 58(5.2%) 52(3.8%) 125(14.5%) 0.0068

CVS * 96 (8.7) 137 (10.1) 191 (22.2) 0.0281

*Cardiovascular complications include any of the following events:

stroke, infective endocarditis, major bleeding, or peripheral embolism;

Findings on history and clinical examination

33%

25%

7%4% 3% 1%

33%

29%

22%

0%

5%

10%

15%

20%

25%

30%

35%

40%

Perc

enta

ge

Participantsn=3343

Decreased LV Ejection Fraction (children) 168(5.3%)

Decreased LV Ejection Fraction (adults) 661(26.5%)

Increased LV End-Diastolic Diameter (children) 454(14.1%)

Increased LV End-Diastolic Diameter

(adults)

742(23%)

35%

44%

19%2%

Percentage Valve involvement

Single Valve

Two Valves

Three Valves

Quadrivalvar disease

Nishimura RA, Otto CM, Bonow RO, et al. 2014

AHA/ACC Guidelines Circulation 2014; 129(23):

Gaps in implementation

Young, female, severe disease

Our patients are young, largely female and generally severely affected.

Women should have pre-pregnancy counseling and referred to reproductive services/combined cardio-obstetric clinics when available.

65%

35%

Warfarin

No Yes

11%

40%34%

15%

INR tests in past 6 months

None

1-3

4-6

Morethan 6

45.20%35.20%

43.60%

38.40%

33%

30.80%

16.40%

31.80%25.60%

0%

20%

40%

60%

80%

100%

Mechanical Valves Atrial Fibrillation High-risk MitralStenosis

Perc

enta

ge

Enrolment INR

Sub-therapeutic Therapeutic Above therapeutic level

69.79

99.1

0.9

59.74

97.2

2.82

29.25

45.6

54.4

0

20

40

60

80

100

120

On prophylaxis Intramuscular penicillin Oral penicillin

Perc

enta

ge

Low income countries Lower middle income countries Upper middle income countries

p=0.0012

p=0.04

p=0.0002

Gaps in implementation

Young, female, severe disease

Poor INR control

Inadequate secondary

prophylaxis

Severely affected /post-surgical patients should be on lifelong penicillin.

We should discuss warfarin management /INR awareness and regular monitoring for patients on OACs.

We need to consider RHD patients for novel research in new medications , innovations and interventions.

2 2 67 6 5 5

14

57

3419 14 13 15 14

21

11

11

1619 22 22

12

14

2

3 2 2 3

8

1 11

3

7

30

5156 58 57 54 58

43

0

10

20

30

40

50

60

70

80

90

100

< 10 years 10-20 years 21-30 years 31-40 years 41-50 years 51-60 years 61-70 years 71-80 years

Perc

enta

ge o

f cas

esPattern of native valve involvement n=2475

Pure MS Pure MR MMVD Isolated AVD MAVD MMAVD

MR MS AR AS TR TS PR PSMild 777 284 704 123 27 9Moderate 609 337 388 72 499 20 83 12Severe 744 625 264 78 321 20 16 6

777

284

704

123

27 9

609

337

388

72

499

2083

12

744

625

264

78

321

20 16 60

100

200

300

400

500

600

700

800

900

1000

Coun

t

Severity of valve lesions

1%

11%

4%

28%

8%

61%

0%

10%

20%

30%

40%

50%

60%

70%

*Valvuloplasty **Surgery

Perc

enta

ge

Low income countries Low middle income countries

p=0.0042

p=0.0306

*n=1109, 1351, 862** n=1110, 1360, 863

Utilisation of surgical and percutaneous interventions

21%

79%

Yes No 72.8 78.985.5

27.221.2

14.5

0

10

20

30

40

50

60

70

80

90

100

Low income Low middleincome

Middle income

Perc

enta

ge

Income categories

Repair

Replacement

Patients awaiting surgery

33%

67%

LVEDD > 55

LVEDD> 55LVEDD< 55

33%

44%

20%3%

Single Valve

Two Valves

Three Valves

Quadrivalvar disease

Patients should be referred for intervention, particularly surgery timeously.

This should include evidenced-based surgical procedures such as repair vs. replacement.

Zhlke et al Heart 2013

Costs

RHD exacts the highest number of disability-adjusted life-years of all cardiovascular diseases

1014-year-olds (5166 per 100 000 people, 95% CI 42536470)

59 years (3620 per 100 000 people, 29464620)

Quality of life, schooling, potential economic and emotional impact.

US$ 791 Million-2.37 Billion in 2010

We should consider decentralised services, consider task-sharing and involve all cadres of health care workers.

All findings reflect health system inadequacies that perpetuate the poor access to health care experience by patients in LIMCs.

Gaps in implementation

Young, female, severe disease

Poor INR control

Inadequate secondary

prophylaxis

Inadequate reproductive

services

Low use of surgical and medical intervention

African Union Directive to Health Ministries:

Prospective registers at sentinel sites Universal access to reproductive health

services for women Decentralise technical expertise Adequate supplies of high-quality BPG Establish Centres of Excellence for cardiac

surgery Multi-sectoral national RHD control

programmes Cultivate strong collaborative frameworks

Conclusions:

REMEDY has significant clinical and policy implications.

It is imperative that we act on these clear directives.

Key is empowering and including the patient while exercising evidence-based principles in management.

RHD-care should be patient-centred and health system strengthening focused.

The patient at the heart of the matter.

I would like to acknowledge all those at the 2006, 2014 and 2015 All-Africa meetings, for their vision, dedication and commitment, in particular Prof

Bongani Mayosi, Dr Mark Engel and the Cape Town ASAP team.

Special thanks to all the REMEDY Pis and the patients involved in the study.

Thank you for your attention

Global Rheumatic Heart Disease RegistryAcknowledgements and thanks

Principal investigators and data managersPatients and staff

Steering committeeProf Bongani Mayosi

Prof Ganesan KarthikeyanDr Mark Engel

FundersCannectinNovartis

World Heart FederationPASCAR

Medical Research Council

Population Health Research InstituteProf S Yusuf, Dr Koon Teo, Pam Mackie, Sumathy Rangarajan

Katya Mauff

Participating hospitals, centres and clinicsLocal funders

EgyptProf. Azza Abul-FadlProf. Sahar Shaker Sheta

EthiopiaProf. Abraham HaileamlakDr. DejumaYadetaWandimu DanielDr Araya Gidey DestaDr Bekele Alemayehu ShashoDr Dufera Mekonnen Begna

IndiaProf. Ganesan KarthikeyanDr Jitender SharmaDr Gaurav Purohit

KenyaProf. Stephen OgendoDr Bernard GituraDr Christine Yuko Jowi

MalawiDr. Neil Kennedy

MozambiqueProf. Albertino DamascenoDr. Ana Olga MocumbiNeusa Jessen

NamibiaDr Christopher Hugo-HammanDr Henning du ToitDr Masomi KaayaDr Liina SikwayaDr Andreas Wilberg

NigeriaDr. Moshood AdeoyeProf. Fidelia Bode-ThomasDr. Okechukwu OgahDr Taiwo OlunugaDr. Dike OjjiProf. Mahmoud SaniGaniyu AmusaLudu AuduCharity Durojaiye-AmoduNgozi ElekwaOlukemi IgeOgechi MadukaOludolapo MarcaulayShamsudeen MohammedHalim OdiachiBasil OkeahialamChristopher Yilgwan

RwandaDr. Joseph Mucumbitsi

South AfricaProf Bongani MayosiDr Mark EngelAlexia JoachimDr. Blanche CupidoRezeen DanielsProf. Phindile MntlaDr. Chris SuttonDr Rajeev MisraPriscilla AdolfJabulani MbokaziSusan Perkins Dr. Liesl Zhlke

SudanProf. Ahmed El-SayedHuda H. M. ElhassanTagwa EltahirHuda HamidAhmed S. Ibrahim

UgandaDr. Charles MondoDr Emmy OkelloDr Peter Lwabi

YemenProf. Mohammed Al-Kebsi

ZambiaDr John Musuku

PHRISumathy RangarajanPam Mackie Shofiquel IslamDr Koon TeoDr Salim Yusuf

CT Coordination OfficeVeronica FrancisDylan BarthProf Patrick CommerfordFelicia GiliDr John LawrensonCarolise LemmerNonkululeko KoyanaDr Wendy MatthiassenAlet MeiringPeggy MgwayiLwazi MhlantiSimpiwe NkepuProf Mpiko NtsekheJanine SaaimanUnita SeptemberDr Kathie WalkerMarnie van de Wall

Department of StatisticsKatya Mauff

Slide Number 1Slide Number 2Slide Number 3Slide Number 4Global Rheumatic Heart Disease Registry: REMEDYSlide Number 6ResultsAge and Gender DistributionSlide Number 9Findings on history and clinical examinationSlide Number 11Slide Number 12Slide Number 13Slide Number 14Slide Number 15Slide Number 16Slide Number 17Slide Number 18Slide Number 19Slide Number 20REMEDYSurgery: too little, too late.Slide Number 22Slide Number 23Slide Number 24CostsSlide Number 26Slide Number 27Slide Number 28Slide Number 29Slide Number 30Global Rheumatic Heart Disease RegistryAcknowledgements and thanksPrincipal investigators and data managersPatients and staffSteering committeeProf Bongani MayosiProf Ganesan KarthikeyanDr Mark EngelFundersCannectin Novartis World Heart FederationPASCARMedical Research CouncilPopulation Health Research InstituteProf S Yusuf, Dr Koon Teo, Pam Mackie, Sumathy RangarajanKatya MauffParticipating hospitals, centres and clinicsLocal funders Slide Number 32