Kate Best1, Judith Rankin1

LONG-TERM SURVIVAL OF CHILDREN BORN WITH CONGENITAL HEART DISEASE: A

SYSTEMATIC REVIEW

1 Institute of Health & Society, Newcastle University, UK

BACKGROUND Objectives of PhD

• Describe the prevalence of CHD, trends and risk factors using BINOCAR data.

• Conduct a systematic review on the long-term survival of children born with CHD.

• Analyse survival and predictors of survival of children born with CHD using BINOCAR data linked to death registrations.

• Predict the future prevalence/survival of CHDs.

BACKGROUND

Prevalence of CHD: 80 per 10,000 total births

05

10

15

20

Pre

vale

nce

pe

r 1

0,00

0 to

tal b

irth

s

1990 1995 2000 2005 2010Year of delivery

Mild CHD Moderate CHDSevere CHD

Infant survival has been frequently reported

But after infancy, mortality remains higher than that of the general population

BACKGROUND

0.0

00

.25

0.5

00

.75

1.0

0

0 5 10 15 20 25analysis time

AVSD CoA

Ebstein's HLHTAPVR ToFTricuspid atresia VSD

Kaplan-Meier survival estimates

Individuals with CHD require highly specialised healthcare

Long-term follow-up of children born with CHD is important in predicting life time healthcare requirements

BACKGROUND

PREVIOUS RESEARCH

In 2008, a systematic review on the long-term prognosis of CHD was published BUT it included hospital-based studies Survival %

97.299.6

98.195.4

96.995.793.5

98.587.4

97.590.2

96.892.9

AIM

To conduct a systematic review of all population-based studies that report the long-term survival of individuals born with CHD.

• Compare survival estimates

• Examine predictors of survival

METHODS

MEDLINE, EMBASE and Scopus from their inception to October 2013

Inclusion criteria:

• Population-based studies

• Cases ascertained at birth

• Survival estimates reported at age ≥5

• Survival estimates correspond to all CHD combined or by subtype

METHODS

Exclusion criteria

• Studies not available from the British Library

• Studies not written in English

METHODS

Search strategy:

• MeSH-terms (e.g. “exp Heart Defects, Congenital/ep, mo”) and key words (e.g. “congenital” and “heart” or “cardiac”)

• Core journals & reference lists were searched

• Titles and abstracts were screened according to the inclusion criteria and irrelevant citations were excluded. Full articles were then retrieved.

METHODS

Data extraction

• Two data extractors

• Study descriptions extracted

• Kaplan-Meier survival estimates and 95% confidence intervals (CIs) were extracted from each included study

• Authors contacted for clarification

METHODS

Data summary/ Analysis

• Studies that included and excluded cases with extra-cardiac anomalies grouped separately

• Summary estimates were estimated using meta-analyses.

RESULTS

6,269 citation identified from electronic database searching

1,178 duplicates

5,091 titles reviewed

88 abstracts reviewed

35 full papers reviewed

25 studies excluded10 were not population-based studies5 reported infant survival only3 reported mortality rates by year of death2 reported survival of all congenital anomalies only2 did not report survival estimates at the specified ages2 reported survival categorised by another variable only1 excluded cases of certain ethnicities

10 studies included

RESULTS

Dastgiri, Gilmour et al. 2003

Fixler, Nembhard et al. 2010

Frid, Bjorkhem et al. 2004

Garne 2004

Miller, Siffel et al. 2010

Moons, Sluysmans et al. 2009

Olsen, Christensen et al. 2010

Samanek and Voriskova 1999

Tennant, Pearce et al. 2010

Wang, Hu et al. 2011

1970 1980 1990 2000 2010

Study periods

RESULTS

Dastgiri, Gilmour et al. 2003

Fixler, Nembhard et al. 2010

Frid, Bjorkhem et al. 2004

Garne 2004

Miller, Siffel et al. 2010

Moons, Sluysmans et al. 2009

Olsen, Christensen et al. 2010

Samanek and Voriskova 1999

Tennant, Pearce et al. 2010

Wang, Hu et al. 2011

1970 1980 1990 2000 2010

Follow-up periods

RESULTS

Dastgiri, Gilmour et al. 2003

Fixler, Nembhard et al. 2010

Frid, Bjorkhem et al. 2004

Garne 2004

Miller, Siffel et al. 2010

Moons, Sluysmans et al. 2009

Olsen, Christensen et al. 2010

Samanek and Voriskova 1999

Tennant, Pearce et al. 2010

Wang, Hu et al. 2011

1970 1980 1990 2000 2010

Follow-up periods25

20

15

25

5

10

5

15

5

5

Max age

RESULTS

Fixler

Dastgiri Frid

Garne

Miller

Moons

Olsen

Samanek

Tennant

Wang

RESULTSStudy CHD subtypes

Dastgiri et al. 2003 All subtypes combinedFixler et al. 2010 Single Ventricle, Hypoplastic left heart,

Pulmonary atresia, Tricuspid atresiaFrid, et al. 2004 AVSDGarne et al 2004 All subtypes combined and individuallyMiller et al. 2010 AVSDMoons et al. 2009 All subtypes combined and individually

Olsen et al. 2010 All subtypes combined and individually

Samanek et al 1999 All subtypes combined and individually

Tennant et al. 2010 All subtypes combined and individually

Wang et al. 2011 Hypoplastic left heart, TGV, ToF, Common Trunkus, CoA, AVSD, Aortic atresia/stenosis

RESULTSStudy CHD subtypes

Dastgiri et al. 2003 All subtypes combinedFixler et al. 2010 Single Ventricle, Hypoplastic left heart,

Pulmonary atresia, Tricuspid atresiaFrid, et al. 2004 AVSDGarne et al 2004 All subtypes combined and individuallyMiller et al. 2010 AVSDMoons et al. 2009 All subtypes combined and individually,

including VSDOlsen et al. 2010 All subtypes combined and individually

Samanek et al 1999 All subtypes combined and individually

Tennant et al. 2010 All subtypes combined and individually

Wang et al. 2011 Hypoplastic left heart, TGV, ToF, Common Trunkus, CoA, AVSD, Aortic atresia/stenosis

RESULTS: VSD

Tennant Tennant Tennant Tennant

Garne

Moons

Olsen Samanek

Olsen

8590

9510

0

5 10 15 20 25 5 10 15 20 25

Excluding extra-cardiac anomalies Including extra-cardiac anomalies

95% CI Survival estimate

Perc

enta

ge S

urvi

ved

Age

RESULTS: AVSD

FridMiller

Tennant

FridMiller

Tennant

Frid

Tennant Tennant

Frid

Garne

Moons

Samanek

Wang FridOlsen

Samanek

Frid

Samanek

Wang OlsenWang

2040

6080

100

5 10 15 20 25 5 10 15 20 25

Excluding extra-cardiac anomalies Including extra-cardiac anomalies

95% CI Survival estimate

Perc

enta

ge S

urvi

ved

Age

RESULTS AVSD

2040

6080

100

5 10 15 20 25 5 10 15 20 25

Excluding extra-cardiac anomalies Including extra-cardiac anomalies

95% CI Survival estimate

Perc

enta

ge S

urvi

ved

Age

69 (55-81) 64

(48-79) 68(41-89)

65 (58-71)

61(56-67)

60(56-64)

51(41-61)

RESULTS: HLH

Fixler

Tennant

Fixler

Garne

Moons

Samanek

Wang

Samanek Samanek

WangWang

020

4060

80

5 10 15 20 25 5 10 15 20 25

Excluding extra-cardiac anomalies Including extra-cardiac anomalies

95% CI Survival estimate

Perc

enta

ge S

urvi

ved

Age

RESULTS: HLH

020

4060

80

5 10 15 20 25 5 10 15 20 25

Excluding extra-cardiac anomalies Including extra-cardiac anomalies

95% CI Survival estimate

Perc

enta

ge S

urvi

ved

Age

18(1-66) 18

(3.5-39) 9(8-59)

RESULTS: ALL CHD SUBTYPES

Dastgiri

Garne

Tennant

Olsen

Tennant Tennant Tennant

Olsen

Garne

Moons

Samanek

Olsen

Samanek Samanek

Olsen

7080

9010

0

5 10 15 20 25 5 10 15 20 25

Excluding extra-cardiac anomalies Including extra-cardiac anomalies

95% CI Survival estimate

Perc

enta

ge S

urvi

ved

Age

RESULTS: ALL CHD SUBTYPES70

8090

100

5 10 15 20 25 5 10 15 20 25

Excluding extra-cardiac anomalies Including extra-cardiac anomalies

95% CI Survival estimate

Perc

enta

ge S

urvi

ved

Age

87 (86-88)

84 (67-96)

86 (72-96)

76(74-79)

RESULTS

Sources of heterogeneity

• Study period

• Ascertainment of milder forms

• Ascertainment of cases with extra-cardiac anomalies

• Coding of cases with multiple CHD

RESULTS

Predictors of survival

• Year of birth (5 studies)

◦ All 5 studies reported improved survival over time

• Sex (2 studies)

◦ No association (AVSD only) (Frid)

◦ Females increased risk of death (All CHD) (Wang)

RESULTS• Maternal age at delivery (2 studies)

◦ No association (SV physiology)

◦ Increased survival with increasing maternal age (All CHD).8

11.

21.

4RR

<20 20-24 25-29 30-34 35+ Maternal age

95% CI RR

STRENGTHS & LIMITATIONS Strengths:

• Restricted to population-based studies

• Separated studies including/excluding extra-cardiac anomalies

• Systematic search strategy

◦ Authors contacted

◦ 2 data extractors

STRENGTHS & LIMITATIONS Limitations:

• Survival up to age 25 only

• 4 studies up to age 5 only

• Most studies included cases with extra-cardiac anomalies

• No studies from low income populations

• Small sample sizes for individual subtypes

• Doesn’t account for morbidity

• Little information on surgeries

FURTHER RESEARCH Further research is required into the long-term survival:

• Subtypes separately

• Of isolated cases of CHD in particular

• Predictors of survival (in particular socioeconomic position)

• Survival in low income populations

• Survival associated with surgeries

CONCLUSION

Survival varies substantially by CHD subtype

Further research into long-term survival and predictors is required

This information would inform health service planning and for informing parents when a CHD is detected antenatally or in early childhood

ACKNOWLEDGEMENTS

Thank-you to the British Heart Foundation for funding this study

Thank-you for listening!