SHORT AND INTERMEDIATE TERM FOLLOW UP OF ALL INFANTS DIAGNOSED WITH PULMONARY ATRESIA AND VENTRICULAR SEPTAL DEFECT - A FIVE YEAR FOLLOW UP STUDY PROJECT REPORT Submitted during the course of DM Cardiology by DR. PRIYADARSHINI. A Trainee DEPARTMENT OF CARDIOLOGY Jan 2014 – Dec 2016 SREE CHITRA TIRUNAL INSTITUTE FOR MEDICAL SCIENCES AND TECHNOLOGY, TRIVANDRUM, KERALA,
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SHORT AND INTERMEDIATE TERM FOLLOW UP OF ALL
INFANTS DIAGNOSED WITH PULMONARY ATRESIA AND
VENTRICULAR SEPTAL DEFECT - A FIVE YEAR FOLLOW UP
STUDY
PROJECT REPORT
Submitted during the course of DM Cardiology by
DR. PRIYADARSHINI. A
Trainee
DEPARTMENT OF CARDIOLOGY
Jan 2014 – Dec 2016
SREE CHITRA TIRUNAL INSTITUTE FOR MEDICAL
SCIENCES AND TECHNOLOGY, TRIVANDRUM, KERALA,
DECLARATION
I, Dr. Priyadarshini A, hereby declare that the project in this book, titled
“Short and intermediate term follow up of all infants diagnosed with pulmonary
atresia and ventricular septal defect - A five year follow up study” was
undertaken by me under the supervision of the faculty, Department of
Cardiology, Sree Chitra Tirunal Institute for Medical Sciences and Technology.
Trivandrum Dr Priyadarshini A
3/10/16 DM Cardiology trainee
FORWARDED
The candidate, Priyadarshini A, has carried out the minimum required
project.
Thiruvananthapuram Prof. (Dr )Ajit Kumar VK
3/10/16 Head of Department of Cardiology
CERTIFICATE
This is to certify that this thesis titled “Short and intermediate term follow up of
all infants diagnosed with pulmonary atresia and ventricular septal defect - a
five year follow up study” has been prepared by Dr. Priyadarshini. A, DM
Cardiology Resident, Department of Cardiology at Sree Chitra Tirunal Institute
for Medical Sciences & Technology, Thiruvananthapuram. She has shown keen
interest in preparing this project.
GUIDE
Dr. Krishnamoorthy.K.M
Professor, Department of Cardiology
SCTIMST, Thiruvananthapuram
CO GUIDE
Dr. Deepa S. Kumar
Assistant Professor, Department of Cardiology
SCTIMST, Thiruvananthapuram
Dedicated to my
teachers, family and
friends
TABLE OF CONTENTS
Abstract i
Introduction 1
Aims and Objectives 6
Review of literature 8
Materials and methods 17
Statistical analysis 19
Results 20
Discussion 42
Conclusion 48
Limitation 49
References 50
Annexure 54
ABBREVIATIONS
VSD – Ventricular septal defect
PA – Pulmonary atresia
MAPCA – Major Aorto-pulmonary collaterals
PDA - Patent ductus arteriosus
RVOT – Right ventricular outflow tract
CT – Computed tomography
MRI – Magnetic resonance imaging
TOF – Tetralogy of Fallot
DRPA – Diameter of right pulmonary artery at the hilum
DLPA – Diameter of left pulmonary artery at the hilum
DDTAO- Diameter of descending thoracic Aorta at the diaphragm
PDA 6 18.2 0 0 6 14 Intervention vs No intervention
Complete repair 9 11.8 4 12.5 13 12 1.027 2 0.598
Palliation 29 38.2 9 28.1 38 35.2 No intervention 38 50 19 59.4 57 52.8 Mc Goon ratio
<1.2 19 25 9 28.1 28 25.9 0.115 1 0.735
=>1.2 57 75 23 71.9 80 74.1 Age at surgery
<=10 32 84.2 11 84.6 43 84.3 0.001 1 0.972
>10 6 15.8 2 15.4 8 15.7 Associated Syndrome
4 5.3 5 15.6 9 8.3 3.165 1 0.075
In multi variate analysis only long segment pulmonary atresia remained a
significant predictor of death (p = 0.023).
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Table 7:
Binary logistic regression model for outcome of death as dependent variable
B S.E. Wald df p
Long / short segment
atresia -1.515 .665 5.191 1 .023
Prematurity 1.102 .649 2.888 1 .089
Prostaglandin usage .689 .482 2.044 1 .153
Associated syndrome 1.127 .793 2.018 1 .155
Survival analysis:
Kaplan Meier curves were plotted for the entire cohort and also for various
subgroups like and are shown below. One year survival for the entire cohort was
70.3%, at 2 years it was 68.2% and was 65% at 4 years.
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Fig 6:
Kaplan Meier curve for survival for the entire population
One year survival for children with duct dependent pulmonary circulation
was 70.9%, in MAPCA dependent circulation was 68.1% and was 67.8% in the
group having both duct and MAPCAs.
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Fig 7:
Kaplan Meier curve for survival based on source of pulmonary blood flow
Figure showing years of follow up in the x axis and and cumulative survival in the y axis
One year survival in children who underwent Aorto-pulmonary shunt as the
initial palliation was 72.5%, 75.9% in those undergoing any form of palliation
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(surgical or interventional),76.9 % in those undergoing ICR and 64.6 % in those
not undergoing any form of intervention.
Fig 8:
Survival curves depending on intervention performed
41
0 10 20 30 40 50 60 70 80
Entire cohort
Non MAPCA group
MAPCA group
Complete repair
Palliation group
No intervention group
70
71
68
79
77
65
Key findings - 1 Year survival
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DISCUSSION:
Both old ((33) (34)) and contemporary (21) series show at MAPCA
dependent circulation occurs in about 25 – 31%. This is in line with our series
where the MAPCA dependent group constituted 25.9 % (n=28)
Data from our study suggests that about three fourths (3/4) of the duct
dependent population required some form of intervention and once intervened,
survival was good, around 80%. On the contrary, in the MAPCA dependent group,
majority of them survived without any intervention. In the mixed group, survival
with intervention was around 50% and without any intervention was 71%. Duct
dependent cohort is the subgroup which needed intervention in infancy to alleviate
worsening cyanosis and the other two subgroups were less vulnerable, though
MAPCA group was better in terms of survival without any intervention, re-
iterating the fact that MAPCA s were a more stable source of pulmonary blood
flow in an infant. The fact that many in the MAPCA group (n= 9) were planned for
an unifocalisation and still had not undergone the same during the period in which,
they were followed up in this study should be borne in mind. In our study,
mortality rate after ICR is 15.38% whereas 2 of the 3 children who underwent
unifocalisation with ICR is 66.67%.
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As early as 1978, survival data were published for VSD-PA, with necropsy
data and it was published that survival without surgery was 50% at 1 year and 8%
at 10 years ((35)).
One year survival in our series is 70.3 %. This conforms with other studies,
which also show a similar high rate of attrition in the first year of life. 47.2%
children underwent some form of intervention, whereas 39.8% underwent initial
palliation with ductal stenting or Aorto-pulmonary shunt. Primary ICR rate was 6.4
% (7 among 108 patients). Only 13.6 % of patients, who underwent initial
palliation underwent corrective surgery on follow up of 18 months. Children who
underwent initial palliation (ductal stenting/ Aorto-pulmonary shunt), on an
average underwent corrective surgery in mean period of 15.29 months. On the
other hand, children without any palliation underwent corrective surgery in 16.02
months after their initial diagnosis. The average time to initial palliation was 2.71
months.
In a landmark paper by Amark et al, evaluating the factors associated with
mortality and predicting complete repair, 220 children with ventricular septal
defect and pulmonary atresia, diagnosed over a period of 30 years were followed
up. In their series, definitive repair was attained in 75%. Systemic pulmonary
artery shunt was done in 57%, complete primary repair was done in 31% and RV
ventricular outflow reconstruction in 12 %. After initial palliative shunt, 68.5% of
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patients underwent complete repair. Risk factors for death after initial operation
included younger age at repair, earlier birth cohort, fewer broncho-pulmonary
segments supplied by native pulmonary arteries, and placement of an Aorto-
pulmonary shunt. 10 - year survival rate in this series after initial surgery was 71%.
Only 15.9% of children in their series did not undergo any form of intervention.
Nearly half of them (n=105) underwent an initial Aorto-pulmonary shunt. They
also found that higher rates of initial complete repair occurred in later birth cohorts
as opposed to earlier ones. 38 children underwent 47 re-operations and 56 patients
underwent 104 catheter based interventions. Catheter based interventions were
more common in the MAPCA group and were done sooner after complete repair at
a median gap of 1.1 years after surgery.
Mortality in the MAPCA group in this series was 39.6%, 55.56 % without
intervention, 33.33 % after unifocalisation and 30.43% in the initially palliated
group.
The above data suggests that though rates of initial palliation with Aorto-
pulmonary shunts in our series is similar to the western data, rates of primary
repair and corrective surgery after initial palliation were much lesser in our cohort,
though our follow up was relatively short term and many children were awaiting
surgical procedures. In our study, we could not find strong predictors of mortality
other than length of pulmonary atresia and prematurity. Since our complete repair
45
rates were low, no meaningful survival analysis of this subgroup was done. No
child in our study, underwent a repeat surgical procedure or catheter based
intervention primarily because of low ICR rates and secondarily due to shorter
follow up compared to historical cohorts. Whereas the population in the series by
Amark et al, represents the modified natural history of VSD-PA; Our study was a
combination of both unmodified and modified natural history in view of lower
rates of complete repair.
In a French study (36), 52 patients with VSD-PA were followed up over a
period of 8.6 years, 26 (50%) were duct dependent and the rest were MAPCA
dependent. Corrective surgery was performed in 14 (53.8%) in the former group
and 9 (34.6%) in the latter group. After a mean follow up of 8.6 years, 71% were
alive, 39 % were corrected and 11.5% were deemed inoperable.
When MAPCA dependent and MAPCA + PDA group are pooled together in
our study, they constitute about 44.5% of the study population, which is similar to
the above population. 18.7% of children the mixed group as described above were
deemed unsuitable for any form of repair in view of poor pulmonary anatomy.
Rates of cardiac catheterization are very low in our study – only 2 patients had
undergone cardiac catheterisation for delineation of MAPCAs. This may be due to
improvement in echo techniques and deployment of additional modalities of
imaging, when clarity was not achieved with echocardiography alone.
46
Though there is debate regarding the approach to managing children with
VSD-PA and MAPCAs, with some groups advocating single stage repair with
unifocalisation and some advocating staged repair with initial Aorto-pulmonary or
RV-PA conduit to promote the growth of PAs, we have only attempted 3 cases of
unifocalisation with intracardiac repair in a single stage procedure. Two of the 3
children aged 7 and 37 months, where unifocalisation with ICR was done died due
to suprasystemic RV pressures despite fenestration.
Among the patients, who died in the T1 period, 10 had sudden death. In 4
children, there is history cyanosis/ spell. Two died of lower respiratory tract
infections and 2 died due to issues related to prematurity. In the T2 period, one
died of lower respiratory tract infection and the other death was sudden.
In another surgical series from India, Murthy et al ((37)) have reported
outcomes of single stage unifocalisation in 124 patients over 13 years. Of these
patients during the initial procedure, 60% underwent complete repair, 21%
underwent only RV-PA conduit and the VSD was left behind whereas in the
remaining 19% only Aorto-pulmonary shunt was accomplished. There were 16
early deaths and 3 late deaths in this series amounting to a total mortality of 15.3%.
The authors concluded that single-stage unifocalization performed at an early age
achieves normalization of physiology with correction of cyanosis or pulmonary
hypertension and attendant complications. Early single-stage unifocalization
47
decreases the number of subsequent surgeries and hospitalizations, and thereby, is
cost effective also compared to a multi staged procedure.
The deaths post single staged unifocalisation with intra cardiac repair in our
series was due to RV hypertension and mandated fenestration of the VSD patch. It
is difficult to conclude at this point in time if a staged unifocalisation would have
been a better option versus an earlier rehabilitation of pulmonary arteries.
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CONCLUSION:
Survival in a child with VSD-pulmonary atresia in our setting can be
estimated to be around 70% at 12 months
Duct dependent infants are more vulnerable to worsening hypoxemia and
warrant palliative intervention in early infancy
Death most commonly occurs in the ‘T1’ period, prior to any palliation
Only 12% of patients in our study proceeded to complete repair
Only length of pulmonary atresia was a predictor of mortality
Meticulous monitoring of saturation at nearby points of health care may lead
to prompt referral and improve mortality data as majority of deaths happen
before any palliation
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LIMITATIONS:
The current study is a retrospective analysis of data, some patients were lost
to follow up and hence follow up data are limited to the last hospital visit or
telephonic enquiry.
The average duration of follow up was 18.9 months, which only indicates
the intermediate term follow up of these patients. Long term data remain elusive.
Since it is a medium term follow up, true data of intervention on branch pulmonary
arteries is not represented. Many patients were awaiting unifocalisation or ICR at
the end of study, hence percentage of children undergoing procedure may be an
under-estimate. Longer follow up would give us the true numerator of percentage
of children proceeding to complete repair.
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