pulmonary valve replacement ( pvr ) or right ventricular outflow tract reconstruction ( rvotr ) is the most common valve replacement / repair procedure performed in the society of thoracic surgeons ( sts ) congenital database , comprising 16% of procedures performed in the adult congenital population .
there is a growing population of children surviving well into adulthood with repaired congenital heart disease and the number of pvr / rvotr procedures required will grow with this population . since ross performed the first rvotr using an aortic homograft in 1966 , the search for the optimal conduit choice has been the subject of much debate . whilst a cryopreserved homograft is the gold standard ,
calcification and homograft failure remain an issue , with only 40 - 75% of homografts remaining free from structural valve deterioration ( svd ) at 10 years in the congenital population [ 2 , 3 ] .
an alternative is the medtronic freestyle valve , derived from a porcine aortic root , decellularised using glutaraldehyde and treated with alpha - amino oleic acid to minimize xenograft calcification .
potential benefits include its stentless design , the possibility to achieve a greater effective orifice area , the availability in a range of sizes ( 19 - 29 mm ) , and the lack of requirement for lifelong anticoagulation .
the aim of this study , therefore , was to systematically review all of the primary publications describing the outcomes associated with using the freestyle valve for rvotr in both the ross procedure and in congenital heart disease , primarily to determine short - term rates of structural valve dysfunction and reintervention , and functional status .
a review of available literature was undertaken via online searches of the major clinical databases : medline , pubmed , cochrane database and google scholar .
the search terms used were -  freestyle  or  xenograft  or  stentless  , and 
bibliographies , from included papers , were assessed for suitable references in an attempt to avoid missing potentially useful material .
publications were eligible for inclusion if they presented original data on freestyle valves in the pulmonary position .
review articles and opinion pieces , isolated case reports and animal studies were excluded  because they lacked any outcomes of interest .
all publications deemed suitable for inclusion on the above criteria were reviewed separately by two authors ( bd and da ) to ensure suitability and disagreements resolved by consensus .
the primary outcome of interest was rates of structural valve deterioration as defined   by akins et al .   in their joint sts
secondary outcomes of interest included reintervention ( defined as percutaneous balloon valvuloplasty , percutaneous pvr or surgical revision ) and functional status ( defined according to new york heart association class or modified ross score ) .
meta - analysis was undertaken where sufficient data existed to pool studies , using a fixed effects or random effects model depending on study heterogeneity .
we defined a priori two subgroups : one group that underwent rvotr as part of a ross procedure and another group that underwent rvotr as surgical management of congenital heart disease .
two statistical models , namely , fixed effects and random effects models , were used depending on study heterogeneity .
fixed effects models were used if the between study variance was less than 0 , whilst a random effects model was used , where the between study variance was larger than 0 . a search for comparative series of alternative bioprostheses and homografts
was also performed to allow for comparison with the results of our meta - analysis .
a total of 435 papers were initially retrieved with the search strategy described above , of which 13 retrospective case series fulfilled the eligibility criteria and were included in the systematic review .
one study presented their data only as a kaplan meier curve and so could not be analysed with the other 12 studies but was reviewed separately .
the twelve papers included in the meta - analysis yielded data on 311 patients with a mean follow - up of 33.6 months . of the 12 studies , 2 reported on solely paediatric patients , 3 reported solely on adult patients and 7 reported data on both paediatric and adult patients .
seven of the papers solely reviewed cohorts of patients that rvotr were performed on as part of a ross procedure , while the other 5 papers were from series of predominantly congenital cases ( table 1 ) .
twelve studies ( n=311 ) reported echocardiographic data on svd at 34 months follow up ( range 10 - 98 months ) .
the mean rate of svd was 4.8% ( 95% ci 0.8 - 10.6% ) . analyzing ross recipients
separately ( 7 studies , n=137 ) , the pooled rate of svd was 7.1% ( 95% confidence interval ( ci ) 0.2 - 19.3% ) at 45 months follow up . for congenital recipients ( 5 studies , n=174 patients ) the pooled rate of svd was 3.5% ( 95% ci 0.9 - 7.3% ) at 18 months .
heterogeneity between studies was high , so random effects modeling was used for this analysis .
reintervention was reported in twelve studies ( n=311 ) with a mean follow - up of 34 months .
reintervention occurred in nine patients ( mean 1.1% , 95% ci 0.0 - 3.3% ) . analyzing ross recipients separately ( 7 studies , n=137 ) , the rate of reintervention was 2.1% ( 95% ci 0.0 - 6.4% ) at 45 months .
the 5 congenital series ( n=174 ) were also analysed separately and had a mean rate of reintervention of 1.0% ( 95% ci 0.1 - 3.7% ) at 18 months .
heterogeneity between studies was low , so fixed effects modeling was used for this analysis . in the whole cohort , the mean time to reintervention was 28 months .
the indications for reintervention were subvalvar stenosis due to pannus and stricture formation at the proximal suture line ( n=7 ) and true valvular stenosis ( n=2 ) .
five of these reinterventions were percutaneous ( 2 balloon valvuloplasties , 3 percutaneous valve replacements ) , and 4 were open surgical conduit replacements . in comparison ,
lee et al .   reported only 31% freedom from reintervention in their cohort of 23 patients with a mean of 91 months follow up .
they did not state what proportion of reinterventions were due to svd , but did describe that three cases were due to conduit compression by the overlying sternum . functional status .
eight of the twelve studies ( n=214 ) provided data on the functional status of their patients with a mean follow - up of 36 months .
freedom from the symptoms of heart failure was 97.7% ( 95% ci 94.6 - 99.7% ) . in the ross population ( n=53 )
, it was 91.7% ( 95% ci 81.2 - 98.9% ) . in the congenital population ( n=161 )
heterogeneity between studies was low , so fixed effects modeling was used for this analysis ( table 2 ) . pooled outcome data for freestyle valves .
a review of all available prosthetic options was also performed to allow for comparison between the many available alternatives ( see table 3 ) .
there is a shortage of truly long - term data available , however 5-year results are available for most bioprostheses . across all bioprostheses a 5-year failure rate of 10 - 40% exists , with failure rates at 10 years climbing to 25 - 60% ( table 3 ) .
to our knowledge , this is the first systematic review and meta - analysis of the performance of the medtronic freestyle valve in the pulmonary position .
first , our results suggest that the freestyle valve has a low incidence of svd , reintervention and symptoms of heart failure , and compares well with alternative bioprostheses at similar relatively short duration of follow - up .
this is an atypical failure mode for rv - pa conduits and it may relate to the stiffness of the freestyle root wall in comparison to the mobility of the muscular rvot leading to anastomotic site tension .
second , long - term follow up data for the freestyle valve in the pulmonary position is limited .
only 3 studies [ 5 , 7 , 8 ] have truly long - term data on the performance of the freestyle valve and display markedly different results .
dohmen   and hechadi   had no svd or reintervention at 60 and 98 months follow - up respectively , while lee   describes a 69% rate of reintervention at 90 months .
further studies are required to truly determine the long - term outcomes of this valve in the pulmonary position .
third , the promising findings potentially increasing options for rvotr may stimulate competition within the industry and provide the impetus to reduce the cost of these bioprostheses ; a cost - effectiveness analysis may provide further useful data to guide clinicians .
the meta - analysis did not include any randomized controlled trials of the freestyle valve , the patient numbers were low and the duration of follow up relatively short , precluding definitive conclusions in comparing valve outcomes .
the included studies were also heterogeneous in nature with a mixture of pediatric and adult patients , and no data on valve sizes used was available .
we did however identify a priori subgroups for analysis and did not find substantial differences upon analysis according to ross or congenital procedure , although mean length of follow - up differed between these two groups .
pulmonary valve replacement or right ventricular outflow tract reconstruction using the freestyle valve is associated with satisfactory short - term echocardiographic and clinical outcomes , including functional status and freedom from reintervention at over 2 years .
freestyle valves may be a reasonable alternative to homografts or other bioprostheses , particularly when homografts are not readily available .
determination of the optimal valve , however , is currently limited by lack of long - term comparative data and this review has identified a significant need for long - term data on the freestyle valve in the pulmonary position .
 introductionreconstruction of the right ventricular outflow tract is the most commonly performed valve repair / replacement procedure in congenital cardiac surgery . 
 there is an ongoing shortage of homografts , and existing bioprosthetic options suffer from substantial rates of structural valve deterioration over time . 
 the medtronic freestyle valve is used extensively in the aortic position , but little data is available on its performance in the pulmonary position.methodsa systematic review and meta - analysis of primary studies reporting echocardiographic and clinical outcomes , including reintervention and functional status , associated with the freestyle valve in the pulmonary position for both ross and congenital surgery.results13 observational studies including 334 patients with a mean follow - up of 34 months ( range 10 - 98 months ) fulfilled the eligibility criteria and were included in the review . 
 structural valve deterioration occurred in 4.8% ( 95%  confidence interval 0.8 - 10.6% ) of patients . 
 reintervention was required in 1.1% ( 95% confidence interval  0.0 - 3.3% ) . 
 freedom from symptoms of heart failure occurred in 97.7% ( 94.6 - 99.7% ) . 
 the results did not change substantially when analysed according to ross or congenital surgery.conclusionsthe freestyle valve performs well at short - term follow - up and provides a viable alternative when homografts are unavailable . 
 further long - term studies are required to better assess its role in right ventricular outflow tract reconstruction . 
Introduction
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