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95th Annual Meeting: American Association for Thoracic
Surgery
Late survival and RV performance in matched children after Norwood:
Norwood-BT vs Norwood-Sano Travis Wilder Brian McCrindle Alistair
Phillips Eugene Blackstone Rajeswaran Jeevanantham William Williams
William DeCampli JefferyJacobs MarshallJacobs TaraKaramlou
PaulKirshbom GaryLofland GerhardZiemer EdwardHickey Good morning,
Dr. Ohye, members and guests 95th Annual Meeting: American
Association for Thoracic Surgery 2015, Seattle, WA No disclosures
Congenital Heart Surgeons Society
N = 692 Neonates Critical Left Ventricular Outflow Tract
Obstruction 2005 2014: 21 Institutions Aortic atresia/critical AS
Ductal-dependent The Congenital heart surgeons society has enrolled
692 neonates with critical Left ventricular outflow tract
obstruction into a research database since 2005 Congenital Heart
Surgeons Society
N = 692 Neonates Critical Left Ventricular Outflow Tract
Obstruction 2005 2014: 21 Institutions Aortic atresia/critical AS
Ductal-dependent Aortic Valvotomy n = 107 Ross-Konno/ Yasui n = 8
Transplant n = 5 Norwood n = 454 Hybrid n = 110 and because this is
an all-inclusive inception cohort, covering a broad spectrum of
disease, neonates were managed with a variety of initial
procedures; however, the majority 454 underwent a stage-1 Norwood
operation Stage-1 Norwood n = 454 BT (51%) n = 232 SANO (49%) n =
222
Ohye RG, et al. NEJM, 362;21 May, 2010 Ohye RG, et al. NEJM, 362;21
May, 2010 which included 232 Norwood-BT shunt operations and 222
Norwood operations with Sano modifications and recently the Sano
operation has been shown to have improved early survival However,
the enthusiasm for the Sano operation has somewhat diminished
because of concerns surrounding long-term ventricular dysfunction
BT vs SANO Difference in survival Difference in RV dysfunction
Difference in tricuspid regurgitation So we set out to determine
the difference is long-term survival, RV dysfunction and TR Overall
survival for all children
SANO 71% 59% % Survival P < 0.001 BT Among all children, the
overall, unadjusted survival was superior after a Sano; however,
comparing survival among all children from each group doesnt
adjusted for potential baseline differences between the groups so
in order to try and compare apples to apples our analysis focused
on a subset of propensity-matched children Years after Norwood
Propensity-Matching 100%
BT vs SANO 100% And to briefly conceptualize this strategy,
consider the red boxes represent all children who had a BT, blue
boxes are children who had a SANO and the shapes are variations in
baseline characteristics Using a propensity-score, generated from
these baseline characteristics we identified, as close as possible
similar children in each group... Matched Children BT (75%) n = 169
SANO (74%) n = 169 n = 338
which subsequently resulted in 169 matched-pairs, or about
three-quarters of all children who underwent a Norwood Age at
operation (days) 6.5 5 6.3 5 .14 Birth weight (kg)
BT (169) SANO (169) Variable Value P Age at operation (days) 6.5 5
6.3 5 .14 Birth weight (kg) 3.2 0.4 3.2 0.5 .92 Birth weight <
2.5 kg 9 (5%) 11 (7%) .61 BSA at operation (m2) 0.21 0.02 .71
Aortic valve annulus (cm) 0.15 0.2 0.14 0.2 .82 Aortic valve
atresia 90 (55%) 89 (57%) .74 TV annulus (cm) 1.3 .2 .77 MV annulus
(cm) .24 .3 .22 .4 .44 Mitral valve atresia 70 (45%) 75 (48%) AI 22
(15%) 19 (13%) Transverse arch coarctation 52 (32%) 50 (30%) .81
Small/restrictive ASD 54 (44%) 49 (41%) .67 Important RV
dysfunction 2 (1%) .97 Important TR 10 (6%) 14 (9%) .42 Renal
insufficiency 1 (1%) 2 ( 1%) .56 Metabolic acidosis 20 (12%) 1 and
this list of baseline characteristics Age at operation (days) 6.5 5
6.3 5 .14 Birth weight (kg)
BT (169) SANO (169) Variable Value P Age at operation (days) 6.5 5
6.3 5 .14 Birth weight (kg) 3.2 0.4 3.2 0.5 .92 Birth weight <
2.5 kg 9 (5%) 11 (7%) .61 BSA at operation (m2) 0.21 0.02 .71
Aortic valve annulus (cm) 0.15 0.2 0.14 0.2 .82 Aortic valve
atresia 90 (55%) 89 (57%) .74 TV annulus (cm) 1.3 .2 .77 MV annulus
(cm) .24 .3 .22 .4 .44 Mitral valve atresia 70 (45%) 75 (48%) AI 22
(15%) 19 (13%) Transverse arch coarctation 52 (32%) 50 (30%) .81
Small/restrictive ASD 54 (44%) 49 (41%) .67 Important RV
dysfunction 2 (1%) .97 Important TR 10 (6%) 14 (9%) .42 Renal
insufficiency 1 (1%) 2 ( 1%) .56 Metabolic acidosis 20 (12%) 1
shows a similar baseline profile between groups Age at operation
(days) 6.5 5 6.3 5 .14 Birth weight (kg)
BT (169) SANO (169) Variable Value P Age at operation (days) 6.5 5
6.3 5 .14 Birth weight (kg) 3.2 0.4 3.2 0.5 .92 Birth weight <
2.5 kg 9 (5%) 11 (7%) .61 BSA at operation (m2) 0.21 0.02 .71
Aortic valve annulus (cm) 0.15 0.2 0.14 0.2 .82 Aortic valve
atresia 90 (55%) 89 (57%) .74 TV annulus (cm) 1.3 .2 .77 MV annulus
(cm) .24 .3 .22 .4 .44 Mitral valve atresia 70 (45%) 75 (48%) AI 22
(15%) 19 (13%) Transverse arch coarctation 52 (32%) 50 (30%) .81
Small/restrictive ASD 54 (44%) 49 (41%) .67 Important RV
dysfunction 2 (1%) .97 Important TR 10 (6%) 14 (9%) .42 Renal
insufficiency 1 (1%) 2 ( 1%) .56 Metabolic acidosis 20 (12%) 1
Including key variables such as birth weight Age at operation
(days) 6.5 5 6.3 5 .14 Birth weight (kg)
BT (169) SANO (169) Variable Value P Age at operation (days) 6.5 5
6.3 5 .14 Birth weight (kg) 3.2 0.4 3.2 0.5 .92 Birth weight <
2.5 kg 9 (5%) 11 (7%) .61 BSA at operation (m2) 0.21 0.02 .71
Aortic valve annulus (cm) 0.15 0.2 0.14 0.2 .82 Aortic valve
atresia 90 (55%) 89 (57%) .74 TV annulus (cm) 1.3 .2 .77 MV annulus
(cm) .24 .3 .22 .4 .44 Mitral valve atresia 70 (45%) 75 (48%) AI 22
(15%) 19 (13%) Transverse arch coarctation 52 (32%) 50 (30%) .81
Small/restrictive ASD 54 (44%) 49 (41%) .67 Important RV
dysfunction 2 (1%) .97 Important TR 10 (6%) 14 (9%) .42 Renal
insufficiency 1 (1%) 2 ( 1%) .56 Metabolic acidosis 20 (12%) 1
Aortic valve atresia Age at operation (days) 6.5 5 6.3 5 .14 Birth
weight (kg)
BT (169) SANO (169) Variable Value P Age at operation (days) 6.5 5
6.3 5 .14 Birth weight (kg) 3.2 0.4 3.2 0.5 .92 Birth weight <
2.5 kg 9 (5%) 11 (7%) .61 BSA at operation (m2) 0.21 0.02 .71
Aortic valve annulus (cm) 0.15 0.2 0.14 0.2 .82 Aortic valve
atresia 90 (55%) 89 (57%) .74 TV annulus (cm) 1.3 .2 .77 MV annulus
(cm) .24 .3 .22 .4 .44 Mitral valve atresia 70 (45%) 75 (48%) AI 22
(15%) 19 (13%) Transverse arch coarctation 52 (32%) 50 (30%) .81
Small/restrictive ASD 54 (44%) 49 (41%) .67 Important RV
dysfunction 2 (1%) .97 Important TR 10 (6%) 14 (9%) .42 Renal
insufficiency 1 (1%) 2 ( 1%) .56 Metabolic acidosis 20 (12%) 1 And
baseline RV dysfunction and TR So we are in fact comparing apples
to apples. 1. Parametric hazard analysis: a. Competing end-states
b
1. Parametric hazard analysis: a. Competing end-states b. Overall
survival c. Transplant-free survival We used parametric hazard
analysis to evaluate transition to various competing end-states,
overall survival and transplant-free survival End-states after
Norwood All Matched Children (n=338)
% Initially end-states were evaluated for 338 propensity matched
children Years after Norwood End-states after Norwood All Matched
Children (n=338)
Alive without definitive palliation % Immediately after Norwood all
children are alive without further intervention represented by
black curve at time-zero, and thereafter transition into various
mutually exclusive end-states. 9% Years after Norwood End-states
after Norwood All Matched Children (n=338)
Alive without definitive palliation % By 6-years a small percentage
of children underwent biventricular repair transplantation
Transplant 2-V 9% 4% 2% Years after Norwood End-states after
Norwood All Matched Children (n=338)
Alive without definitive palliation Fontan 52% % Just over half
reached a Fontan Transplant 2-V 9% 4% 2% Years after Norwood
End-states after Norwood All Matched Children (n=338)
Alive without definitive palliation Fontan 52% % Dead 33% And a
third of children died Transplant 2-V 9% 4% 2% Years after Norwood
End-states after Norwood
Mortality BT (n=169) Death after BT % 42% When end-states were
evaluated independently for each operation type, children who
underwent BT had a 42% mortality before a definitive palliation
Years after Norwood End-states after Norwood
Mortality SANO (n=169) Death after BT % 42% Death after SANO
Compared to children who underwent a SANO who only had a 24%
mortality 24% Years after Norwood End-states after BT (n=169)
Definitive Palliation Fontan % 49% Furthermore, children who
underwent a BT were less likely to transition to definitive
palliation Transplant/2-V 3% Years after Norwood End-states after
SANO (n=169)
Definitive Palliation Fontan Fontan 54% % 49% Transplant/2-V
Compared to children who underwent a SANOand although this wasnt
statistically different, it does imply that these children are more
likely to reach a definitive palliation - irrespective of the final
strategy. Transplant/2-V 10% 3% Years after Norwood Overall
survival n = 338 SANO BT % Survival Years after Norwood 70%
55% % Survival P < 0.001 BT And that is reflected in this
overall, survival cure, now for only propensity matched children,
with this survival curve showing that the overall survival was
significantly better after Sano regardless of where they end up
Years after Norwood Transplant-free survival
SANO 64% 53% % Survival P = 0.004 BT Similarly, when we compared
transplant-free survival although there was a late convergence
between the survival curves, children who underwent a Sano had a
better freedom from death or transplant at all points in time
during the 6-year follow-up. Years after Norwood SANO Systemic RV
Ventriculotomy
Ohye RG, et al. NEJM, 362;21 May, 2010 Systemic RV A primary
objection to the Sano, is that an incision (or ventriculotomy) is
required to the systemic ventricle, which theoretically compromises
late ventricular function and perhaps tricuspid valve performance
Ventriculotomy 2. Prevalence of RV dysfunction and TR: Mixed-model
regression analysisof repeated echos
Therefore we examined the prevalence of RV dysfunction to and
tricuspid valve regurgitation between the 2 surgical options The
next portion of our analysis focused on the prevalence of RV
dysfunction and tricuspid regurgitation. Reports analyzed from
every echo on every patient
2. Prevalence of RV dysfunction and TR: Mixed-model regression
analysisof repeated echos And did so by using mixed-model
regression to analyzing reports from every echo we could acquire
for all children, throughout follow-up. Reports analyzed from every
echo on every patient N = 2,993 echos Grades of RV dysfunction and
TR From institutional echo reports
1=trivial 2=mild 3=mild-to-moderate 4=moderate 5=moderate-to-severe
6=severe Initially, RV dysfunction and TR were graded from trivial
to severe using a 6 point scale, according to the reports Grades of
RV dysfunction and TR From institutional echo reports
1=trivial 2=mild 3=mild-to-moderate 4=moderate 5=moderate-to-severe
6=severe Important RV dysfunction and TR However, we considered
moderate or worse to be clinically important dysfunction and
regurgitation, and this is the threshold we used for our analysis.
RV dysfunction after Norwood
2474 echos for 292 children Moderate RV dysfunction(%) We first
determined prevalence of important RV dysfunction for all
propensity matched children after Norwood which is represented by
the blue curve which demonstrating the change in prevalence of
important RV dysfunction on the vertical axis over time after
Norwood operation on the horizontal axis; and for all survivors,
important RV dysfunction peaks to nearly 12% within the initial 6
months, after which there is a decline to low, stable, late levels
Years after Norwood RV dysfunction after Norwood
BT vs SANO Early ,P = 0.019 BT Moderate RV dysfunction(%) SANO We
then stratified the prevalence of RV dysfunction by the type of
Norwood,and children who underwent BT had a significant increase in
the early prevalence of RV dysfunction, nearly 3 times that of the
Sano operation despite similar preoperative RV dysfunction between
both groups - Thereafter, however, both groups experienced a
declining prevalence, resulting in a non-significant difference in
late RV dysfunction. Late, P = 0.36 Years after Norwood
Transplant-free survival and RV dysfunction
BT vs SANO Transplant-free survival: BT vs SANO 64% 53% % To get a
better idea of the relationship between survival and RV dysfunction
we plotted transplant-free survival over the same time Years after
Norwood Transplant-free survival and RV dysfunction
BT vs SANO Transplant-free survival: BT vs SANO 64% 53% % RV
dysfunction: BT vs SANO as the prevalence of RV dysfunction Years
after Norwood Transplant-free survival and RV dysfunction
BT vs SANO Transplant-free survival: BT vs SANO 64% 53% % Early
hazard RV dysfunction: BT vs SANO And not surprisingly, the early
hazard for death, coincided temporally with the peak prevalence of
RV dysfunction and although this is rather intuitive, is suggestive
of a causal link between RV dysfunction and survival and
furthermore it suggests the morbidity and mortality of a Norwood
occur early Peak prevalence Years after Norwood Transplant-free
survival after stage-2
BT (n=108) vs SANO (n=125) 81% 80% SANO BT P= 0.68 % Survival Which
is emphasized by comparing transplant-free after transition to a
stage-2 cavopulmonary shunt operationand survival conditional on
achieving stage-2 which is now time-zero on this figure was not
different between BT or SANO Years after Stage-2 RV dysfunction
after stage-2
BT vs SANO SANO Moderate RV dysfunction(%) Similarly, there wasnt a
difference in RV dysfunction after stage-2, and this emphasizes
that the cost of Norwood -and specifically a BT - occurs early;
However, after transition to a staged ventricular unloading
operation, survival and RV dysfunction are stable for both groups.
P= 0.675 BT Years after Stage-2 Tricuspid regurgitation after
Norwood
2423 echos for 288 children Moderate TR(%) Finally, switching our
attention to trends in tricuspid regurgitation Notice that
clinically important TR generally affects a higher proportionof
children - about 10-15% - throughout follow-up, and that the
time-related variations are less pronounced than that of RV
dysfunction Years after Norwood Tricuspid regurgitation after
Norwood
BT vs SANO Early ,P = 0.003 BT Moderate TR(%) Late, P = 0.68 SANO
And when TRwas stratified by type of Norwood, BT operations were
associated with a significant early increase in TR, however late TR
was similar between groups. Years after Norwood Summary For
comparable neonates with critical LVOTO undergoing stage-1 Norwood:
Overall and transplant-free survival are better after SANO Summary
For comparable neonates with critical LVOTO undergoing stage-1
Norwood: Overall and transplant-free survival are better after SANO
Early RV dysfunction and TR areworse after BT Summary For
comparable neonates with critical LVOTO undergoing stage-1 Norwood:
Overall and transplant-free survival are better after SANO Early RV
dysfunction and TR areworse after BT Late RV dysfunction and TR
aresimilar between groups Implication Children undergoing SANO are
more likely to be alive at 6 years irrespective of final physiology
Suggesting that SANO is preferable to BT for stage-1 palliation