Long-term performance of homografts versus stented bioprosthetic valves in the pulmonary position in patients aged 10–20 years

Long-term performance of homografts versus stented bioprosthetic valves in the pulmonary position... Abstract OBJECTIVES We aimed to compare the long-term performance of pulmonary homografts and stented bioprosthetic valves in the pulmonary position in patients aged 10–20 years. METHODS Between January 1995 and December 2015, 188 patients aged 10–20 years undergoing pulmonary valve replacement were identified retrospectively from hospital databases in both congenital cardiac centres in Brisbane. Valve performance was evaluated using previously described standard criteria. Propensity score matching was used to balance the 2 treatment groups. RESULTS Freedom from structural valve degeneration in homografts (n = 131) was 97%, 92% and 85% at 3, 5 and 10 years, respectively, and 91% and 53% at 3 and 5 years, respectively, in the bioprosthesis group (n = 57). Freedom from reintervention in homografts was 96%, 93% and 88% at 3, 5 and 10 years, respectively, and 93% and 68% at 3 and 5 years, respectively, in the bioprosthesis group. The unadjusted Cox regression analysis demonstrated that a bioprosthesis was at 5.64 times the risk of structural valve degeneration and 3.89 times the risk of reintervention. The Cox regression analysis performed on the propensity matched sample (45 pairs of patients) revealed that a bioprosthesis was at almost 10 times the risk of experiencing structural valve degeneration [hazard ratio (HR) = 9.18] and at more than 8 times the risk of undergoing a reintervention (HR = 8.34). CONCLUSIONS In our patient population, pulmonary homografts outperformed stented bioprosthetic valves within 5 years when implanted in the pulmonary position in patients aged 10–20 years. We recommend the use of a pulmonary homograft for pulmonary valve replacement in this age group in patients undergoing surgery for congenital heart disease. Pulmonary valve replacement, Homograft, Bioprosthetic valve INTRODUCTION In patients born with congenital heart disease, relief of right ventricular outflow tract obstruction often results in the development of pulmonary regurgitation (PR) later in life. Although initially this may be well tolerated, long-standing PR eventually results in dilation of the right ventricle with reduced exercise tolerance and increased risk of arrhythmias and sudden death [1]. Timely replacement of the pulmonary valve can mitigate or even reverse progression of right ventricle dilation [2, 3]. However, the optimal timing and the best prosthesis for pulmonary valve replacement (PVR) remain unclear [4, 5]. Older children and adolescents can often accommodate an adult-sized prosthesis greater than 19 mm in diameter in the pulmonary position. The commonest options include homografts (aortic or pulmonary), stented or stentless xenograft bioprosthesis, mechanical valves or bovine jugular conduits (Contegra®). Although all 4 have a comparable haemodynamic profile, each has unique advantages and disadvantages that influence selection. Historically, homografts have been the preferred choice for PVR. However, their biggest limitation is availability. Mechanical valves require anticoagulation with warfarin. The bovine jugular vein conduit (Contegra) is also available in diameters of 20 mm and 22 mm but is becoming increasingly difficult to obtain in these sizes in Brisbane. Stented xenograft bioprosthetic valves are readily available, have comparable haemodynamics to homografts and do not need anticoagulation. Increased use of the bioprosthesis began in the late 1990s and was first adopted in Brisbane around 2005. Heart donor shortage, lack of availability of the appropriate size, extended indications for surgery, availability of good long-term performance data in the aortic position and introduction of percutaneous valve-in-valve technology contributed to the change in practice. However, data on long-term durability are conflicting, and some evidence is available suggesting an accelerated rate of degeneration in the younger population [6–8]. To date, only limited direct comparative data exist between homografts and stented xenograft bioprosthetic valves in the pulmonary position and even less information on the performance of these valves in adolescents and young adults. As more information becomes available on the deleterious effects of PR on the right ventricle, there is a growing tendency to refer patients for valve implantation at an earlier age even in the absence of symptoms. This trend has been reflected internationally with an increasing number of adolescents being referred for PVR [9]. We aimed to directly compare the long-term performance of pulmonary homografts and stented xenograft bioprosthetic valves in the pulmonary position in patients aged 10–20 years. METHODS Sample All patients aged 10–20 years at the time of PVR between 1 January 1995 and 31 December 2015 were identified retrospectively from hospital databases. Patient data were collected from the only 2 congenital centres for the state of Queensland, both of which are located in Brisbane. Study patients had either a cryopreserved pulmonary homograft or a bovine or porcine pericardial bioprosthesis inserted in the pulmonary position. We have not implanted a mechanical valve in our unit since 2008, and they have been excluded from the study. Four patients received an aortic homograft in the pulmonary position throughout the study period and were also excluded from the analysis. End points Valve performance was evaluated using previously published criteria [10]. The primary end points were freedom from reintervention and structural valve degeneration (SVD; peak transpulmonary gradient ≥50 mmHg or more than moderate PR). Secondary end points are given in Table 1. Table 1: Differences in secondary end points by valve type Clinical outcomes Full sample % (n) Homograft % (n) Bioprosthesis % (n) P-value Non-structural valve degeneration 3.7 (7) 3.7 (5) 3.6 (2) 0.943 Valve thrombosis 0.0 (0) 0.0 (0) 0.0 (0) ** Embolism 2.7 (5) 3.8 (5) 0.0 (0) 0.140 Bleeding event 4.1 (6) 3.1 (4) 4.2 (2) 0.350 Operated valve endocarditis 1.1 (2) 0.8 (1) 1.8 (1) 0.530 Valve-related mortality 0.5 (1) 0.0 (0) 1.8 (1) 0.124 Sudden unexplained death 0.5 (1) 0.8 (1) 0.0 (0) 0.514 Cardiac death 0.5 (1) 0.8 (1) 0.0 (0) 0.514 All-cause mortality 1.1 (2) 0.8 (1) 1.8 (1) 0.530 Permanent valve-related impairment 2.7 (5) 2.3 (3) 3.6 (2) 0.613 Major adverse valve-related event 5.8 (11) 6.1 (8) 5.4 (3) 0.851 Clinical outcomes Full sample % (n) Homograft % (n) Bioprosthesis % (n) P-value Non-structural valve degeneration 3.7 (7) 3.7 (5) 3.6 (2) 0.943 Valve thrombosis 0.0 (0) 0.0 (0) 0.0 (0) ** Embolism 2.7 (5) 3.8 (5) 0.0 (0) 0.140 Bleeding event 4.1 (6) 3.1 (4) 4.2 (2) 0.350 Operated valve endocarditis 1.1 (2) 0.8 (1) 1.8 (1) 0.530 Valve-related mortality 0.5 (1) 0.0 (0) 1.8 (1) 0.124 Sudden unexplained death 0.5 (1) 0.8 (1) 0.0 (0) 0.514 Cardiac death 0.5 (1) 0.8 (1) 0.0 (0) 0.514 All-cause mortality 1.1 (2) 0.8 (1) 1.8 (1) 0.530 Permanent valve-related impairment 2.7 (5) 2.3 (3) 3.6 (2) 0.613 Major adverse valve-related event 5.8 (11) 6.1 (8) 5.4 (3) 0.851 Table 1: Differences in secondary end points by valve type Clinical outcomes Full sample % (n) Homograft % (n) Bioprosthesis % (n) P-value Non-structural valve degeneration 3.7 (7) 3.7 (5) 3.6 (2) 0.943 Valve thrombosis 0.0 (0) 0.0 (0) 0.0 (0) ** Embolism 2.7 (5) 3.8 (5) 0.0 (0) 0.140 Bleeding event 4.1 (6) 3.1 (4) 4.2 (2) 0.350 Operated valve endocarditis 1.1 (2) 0.8 (1) 1.8 (1) 0.530 Valve-related mortality 0.5 (1) 0.0 (0) 1.8 (1) 0.124 Sudden unexplained death 0.5 (1) 0.8 (1) 0.0 (0) 0.514 Cardiac death 0.5 (1) 0.8 (1) 0.0 (0) 0.514 All-cause mortality 1.1 (2) 0.8 (1) 1.8 (1) 0.530 Permanent valve-related impairment 2.7 (5) 2.3 (3) 3.6 (2) 0.613 Major adverse valve-related event 5.8 (11) 6.1 (8) 5.4 (3) 0.851 Clinical outcomes Full sample % (n) Homograft % (n) Bioprosthesis % (n) P-value Non-structural valve degeneration 3.7 (7) 3.7 (5) 3.6 (2) 0.943 Valve thrombosis 0.0 (0) 0.0 (0) 0.0 (0) ** Embolism 2.7 (5) 3.8 (5) 0.0 (0) 0.140 Bleeding event 4.1 (6) 3.1 (4) 4.2 (2) 0.350 Operated valve endocarditis 1.1 (2) 0.8 (1) 1.8 (1) 0.530 Valve-related mortality 0.5 (1) 0.0 (0) 1.8 (1) 0.124 Sudden unexplained death 0.5 (1) 0.8 (1) 0.0 (0) 0.514 Cardiac death 0.5 (1) 0.8 (1) 0.0 (0) 0.514 All-cause mortality 1.1 (2) 0.8 (1) 1.8 (1) 0.530 Permanent valve-related impairment 2.7 (5) 2.3 (3) 3.6 (2) 0.613 Major adverse valve-related event 5.8 (11) 6.1 (8) 5.4 (3) 0.851 Covariates Measured covariates included age, sex, height, weight, body surface area (BSA), valve size, z-score, prosthesis location (orthotopic or non-orthotopic), indication for surgery (PR, pulmonary stenosis and Ross procedure) and diagnosis. Orthotopic placement refers to placement of the valve within the native right ventricular outflow tract. The study was deemed low to negligible risk by the hospital’s ethics committee, and consent was waived. Statistical analysis The homograft and bioprosthesis groups were first examined for differences in covariates, using χ2 statistics for categorical covariates (or the Fisher’s exact tests for analyses with a cell count <10) and t-statistics for continuous covariates. Subsequently, the Kaplan–Meier curves and log-rank tests were used to compare time to SVD and freedom from reintervention separately between groups. The univariable Cox regression analysis was then used to calculate the unadjusted increased risk of SVD and reintervention in groups. Next, propensity scores were used to balance the 2 treatment groups (i.e. homograft and bioprosthesis) according to a number of baseline covariates selected a priori, including age, weight, height, BSA at surgery, sex, prosthesis size (mm), prosthesis location (1 = orthotopic; 2 = non-orthotopic) and diagnosis [1 = tetralogy of Fallot (TOF), 2 = all other diagnoses]. As PR was the indication for all patients receiving a bioprosthesis, we reran the final analysis among only patients indicated for PR as a means of controlling for this variable. The propensity score was estimated using a logistic regression model with 1:1 nearest neighbour matching without replacement based on an acceptable caliper width of 0.2 times the standard deviation of the logit of the propensity score. Balance diagnostics were then assessed by calculating the residual bias with values above 0.1 indicative of balance not having been achieved. Finally, the Cox regression analysis was used to calculate the increased risk of SVD and reintervention over the study period due to receiving a bioprosthesis among the sample of propensity score-matched pairs. The standard errors of these models were calculated with a clustered sandwich estimator to account for the lack of independence among the matched pairs. All analyses were undertaken in Stata version 14.2 (StataCorp LP, College Station, TX, USA). RESULTS Sample Between 1 January 1995 and 31 December 2015, 209 consecutive patients aged 10–20 years who underwent PVR and met the study inclusion criteria were identified from the hospital databases. Twenty-one patients had no recorded height or weight at surgery in the surgical database, and their hospital records at the Prince Charles Hospital were destroyed. We were unable to obtain follow-up data on these 21 patients. Complete demographic and follow-up data were obtained on 188 patients. A bioprosthesis was implanted in 30.3% of patients (n = 57, 38 bovine, 19 porcine), and a pulmonary homograft was implanted in 69.7% of patients (n = 131). The bioprostheses implanted included 13 EPIC (porcine; St Jude Medical, Saint Paul, MN, USA), 5 Magna Ease (bovine; Edwards, Irvine, CA, USA) and 38 Trifecta (bovine, St Jude Medical) valves. Baseline characteristics including sex, age, BSA, weight, height and prosthesis size were similar between the homograft and bioprosthesis groups (mean of 24.3 mm and 24.0 mm, respectively; Table 1); 43.2% (n = 57) of homografts were placed in the non-orthotopic position when compared with 23.2% (n = 13) of bioprostheses (P < 0.05). PR was the indication for surgery in 78.8% (n = 104) of homografts when compared with 100% (n = 57) of bioprostheses (P < 0.05). The original diagnosis was TOF in 45.5% (n = 60) of homografts and in 60.7% (n = 34) of bioprostheses (P < 0.05; Tables 2 and 3). The median follow-up in the homograft group was 9.11 years when compared with 3.02 years in the bioprosthesis group (P < 0.001). Table 2: Distribution of covariates Homograft Bioprosthesis (n = 131) (n = 57) Categorical covariates  Sex, % (n)   Male 61.4 (81) 46.4 (26)   Female 38.6 (51) 53.6 (30)  Prosthesis location, % (n)   Orthotopic 56.8 (75) 76.8 (43)   Non-orthotopic 43.2 (57) 23.2 (13)  Indication for surgery, % (n)   PR 78.8 (104) 100 (56)   PS 12.9 (17) 0 (0)   Non-structural 1.5 (2) 0 (0)   Ross procedure 6.8 (9) 0 (0)  Diagnosis (all), % (n)   TOF 45.5 (60) 60.7 (34)   PS 4.6 (6) 19.6 (11)   Pulmonary atresia 18.9 (25) 7.14 (4)   AS 6.1 (8) 0 (0)   Truncus 6.1 (8) 0 (0)   TGA 9.1 (12) 1.8 (1)   DORV 3.8 (5) 7.1 (4)   Other 6.1 (8) 3.6 (2)  Diagnosis (binary), % (n)   TOF 45.5 (60) 60.7 (34)   All others 54.6 (72) 39.3 (22) Quantitative covariates  Age (days), mean + SD 15.1 + 2.7 15.2 + 2.8  Height (cm), mean + SD 160.7 + 14.1 161.9 + 12.5  Weight (kg), mean + SD 54.5 + 16.4 53.4 + 16.2  Body surface area, mean + SD 1.5 + 0.3 1.5 + 0.3  Prosthesis size (mm), mean + SD 24.3 + 1.8 24.0 + 1.4 Homograft Bioprosthesis (n = 131) (n = 57) Categorical covariates  Sex, % (n)   Male 61.4 (81) 46.4 (26)   Female 38.6 (51) 53.6 (30)  Prosthesis location, % (n)   Orthotopic 56.8 (75) 76.8 (43)   Non-orthotopic 43.2 (57) 23.2 (13)  Indication for surgery, % (n)   PR 78.8 (104) 100 (56)   PS 12.9 (17) 0 (0)   Non-structural 1.5 (2) 0 (0)   Ross procedure 6.8 (9) 0 (0)  Diagnosis (all), % (n)   TOF 45.5 (60) 60.7 (34)   PS 4.6 (6) 19.6 (11)   Pulmonary atresia 18.9 (25) 7.14 (4)   AS 6.1 (8) 0 (0)   Truncus 6.1 (8) 0 (0)   TGA 9.1 (12) 1.8 (1)   DORV 3.8 (5) 7.1 (4)   Other 6.1 (8) 3.6 (2)  Diagnosis (binary), % (n)   TOF 45.5 (60) 60.7 (34)   All others 54.6 (72) 39.3 (22) Quantitative covariates  Age (days), mean + SD 15.1 + 2.7 15.2 + 2.8  Height (cm), mean + SD 160.7 + 14.1 161.9 + 12.5  Weight (kg), mean + SD 54.5 + 16.4 53.4 + 16.2  Body surface area, mean + SD 1.5 + 0.3 1.5 + 0.3  Prosthesis size (mm), mean + SD 24.3 + 1.8 24.0 + 1.4 Bold values indicate statistical significance >0.05. AS: aortic stenosis; DORV: double outlet right ventricle; PR: pulmonary regurgitation; PS: pulmonary stenosis; SD: standard deviation; TGA: transposition of the great arteries; TOF: tetralogy of Fallot. Table 2: Distribution of covariates Homograft Bioprosthesis (n = 131) (n = 57) Categorical covariates  Sex, % (n)   Male 61.4 (81) 46.4 (26)   Female 38.6 (51) 53.6 (30)  Prosthesis location, % (n)   Orthotopic 56.8 (75) 76.8 (43)   Non-orthotopic 43.2 (57) 23.2 (13)  Indication for surgery, % (n)   PR 78.8 (104) 100 (56)   PS 12.9 (17) 0 (0)   Non-structural 1.5 (2) 0 (0)   Ross procedure 6.8 (9) 0 (0)  Diagnosis (all), % (n)   TOF 45.5 (60) 60.7 (34)   PS 4.6 (6) 19.6 (11)   Pulmonary atresia 18.9 (25) 7.14 (4)   AS 6.1 (8) 0 (0)   Truncus 6.1 (8) 0 (0)   TGA 9.1 (12) 1.8 (1)   DORV 3.8 (5) 7.1 (4)   Other 6.1 (8) 3.6 (2)  Diagnosis (binary), % (n)   TOF 45.5 (60) 60.7 (34)   All others 54.6 (72) 39.3 (22) Quantitative covariates  Age (days), mean + SD 15.1 + 2.7 15.2 + 2.8  Height (cm), mean + SD 160.7 + 14.1 161.9 + 12.5  Weight (kg), mean + SD 54.5 + 16.4 53.4 + 16.2  Body surface area, mean + SD 1.5 + 0.3 1.5 + 0.3  Prosthesis size (mm), mean + SD 24.3 + 1.8 24.0 + 1.4 Homograft Bioprosthesis (n = 131) (n = 57) Categorical covariates  Sex, % (n)   Male 61.4 (81) 46.4 (26)   Female 38.6 (51) 53.6 (30)  Prosthesis location, % (n)   Orthotopic 56.8 (75) 76.8 (43)   Non-orthotopic 43.2 (57) 23.2 (13)  Indication for surgery, % (n)   PR 78.8 (104) 100 (56)   PS 12.9 (17) 0 (0)   Non-structural 1.5 (2) 0 (0)   Ross procedure 6.8 (9) 0 (0)  Diagnosis (all), % (n)   TOF 45.5 (60) 60.7 (34)   PS 4.6 (6) 19.6 (11)   Pulmonary atresia 18.9 (25) 7.14 (4)   AS 6.1 (8) 0 (0)   Truncus 6.1 (8) 0 (0)   TGA 9.1 (12) 1.8 (1)   DORV 3.8 (5) 7.1 (4)   Other 6.1 (8) 3.6 (2)  Diagnosis (binary), % (n)   TOF 45.5 (60) 60.7 (34)   All others 54.6 (72) 39.3 (22) Quantitative covariates  Age (days), mean + SD 15.1 + 2.7 15.2 + 2.8  Height (cm), mean + SD 160.7 + 14.1 161.9 + 12.5  Weight (kg), mean + SD 54.5 + 16.4 53.4 + 16.2  Body surface area, mean + SD 1.5 + 0.3 1.5 + 0.3  Prosthesis size (mm), mean + SD 24.3 + 1.8 24.0 + 1.4 Bold values indicate statistical significance >0.05. AS: aortic stenosis; DORV: double outlet right ventricle; PR: pulmonary regurgitation; PS: pulmonary stenosis; SD: standard deviation; TGA: transposition of the great arteries; TOF: tetralogy of Fallot. Table 3: Distribution of the covariates by structural valve degeneration and reintervention Structural valve degeneration Reintervention No Yes No Yes Categorical covariates  Sex, % (n)   Male 56.6 (90) 58.6 (17) 56.6 (94) 59.1 (13)   Female 43.4 (69) 41.4 (12) 43.4 (72) 40.9 (9)  Prosthesis location, % (n)   Orthotopic 66.7 (106) 41.4 (12) 65.1 (108) 45.45 (10)   Non-orthotopic 33.3 (53) 58.6 (17) 34.9 (58) 54.6 (12)  Indication for surgery, % (n)   PR 85.5 (136) 82.8 (24) 86.8 (144) 72.7 (16)   PS 10.1 (16) 3.5 (1) 9.0 (2) 9.1 (17)   Non-structural 1.3 (2) 0 (0) 1.2 (2) 0 (0)   Ross procedure 3.1 (5) 13.8 (4) 3.0 (5) 18.1 (4)  Diagnosis (all), % (n)   TOF 54.1 (86) 27.6 (8) 52.4 (87) 31.8 (7)   PS 8.8 (14) 10.3 (3) 9.0 (15) 9.1 (2)   Pulmonary atresia 13.8 (22) 24.1 (7) 15.1 (25) 18.2 (4)   AS 4.4 (7) 3.5 (1) 4.22 (7) 4.6 (1)   Truncus 3.8 (6) 6.9 (2) 3.61 (6) 9.1 (2)   TGA 5.7 (9) 13.8 (4) 4.8 (8) 22.7 (5)   DORV 5.0 (8) 3.5 (1) 4.8 (8) 4.6 (1)   Other 4.4 (7) 10.3 (3) 6.0 (10) 0 (0)  Diagnosis (binary), % (n)   TOF 54.1 (86) 27.6 (8) 52.4 (87) 31.8 (7)   All others 45.9 (73) 72.4 (21) 47.6 (79) 68.2 (15) Quantitative covariates  Age (years), mean + SD 15.11 + 2.7 14.3 + 2.3 15.3 + 2.7 14.1 + 2.7  Height (cm), mean + SD 161.5 + 13.3 158.6 + 15.4 161.4 + 13.1 158.8 + 17.6  Weight (kg), mean + SD 54.7 + 16.4 51.3 + 15.6 54.6 + 16.3 51.2 + 16.2  Body surface area, mean + SD 1.6 + 0.3 1.5 + 0.3 1.5 + 0.3 1.5 + 0.3  Prosthesis size (mm), mean + SD 24.4 + 1.7 23.3 + 1.7 24.4 + 1.7 23.1 + 1.7 Structural valve degeneration Reintervention No Yes No Yes Categorical covariates  Sex, % (n)   Male 56.6 (90) 58.6 (17) 56.6 (94) 59.1 (13)   Female 43.4 (69) 41.4 (12) 43.4 (72) 40.9 (9)  Prosthesis location, % (n)   Orthotopic 66.7 (106) 41.4 (12) 65.1 (108) 45.45 (10)   Non-orthotopic 33.3 (53) 58.6 (17) 34.9 (58) 54.6 (12)  Indication for surgery, % (n)   PR 85.5 (136) 82.8 (24) 86.8 (144) 72.7 (16)   PS 10.1 (16) 3.5 (1) 9.0 (2) 9.1 (17)   Non-structural 1.3 (2) 0 (0) 1.2 (2) 0 (0)   Ross procedure 3.1 (5) 13.8 (4) 3.0 (5) 18.1 (4)  Diagnosis (all), % (n)   TOF 54.1 (86) 27.6 (8) 52.4 (87) 31.8 (7)   PS 8.8 (14) 10.3 (3) 9.0 (15) 9.1 (2)   Pulmonary atresia 13.8 (22) 24.1 (7) 15.1 (25) 18.2 (4)   AS 4.4 (7) 3.5 (1) 4.22 (7) 4.6 (1)   Truncus 3.8 (6) 6.9 (2) 3.61 (6) 9.1 (2)   TGA 5.7 (9) 13.8 (4) 4.8 (8) 22.7 (5)   DORV 5.0 (8) 3.5 (1) 4.8 (8) 4.6 (1)   Other 4.4 (7) 10.3 (3) 6.0 (10) 0 (0)  Diagnosis (binary), % (n)   TOF 54.1 (86) 27.6 (8) 52.4 (87) 31.8 (7)   All others 45.9 (73) 72.4 (21) 47.6 (79) 68.2 (15) Quantitative covariates  Age (years), mean + SD 15.11 + 2.7 14.3 + 2.3 15.3 + 2.7 14.1 + 2.7  Height (cm), mean + SD 161.5 + 13.3 158.6 + 15.4 161.4 + 13.1 158.8 + 17.6  Weight (kg), mean + SD 54.7 + 16.4 51.3 + 15.6 54.6 + 16.3 51.2 + 16.2  Body surface area, mean + SD 1.6 + 0.3 1.5 + 0.3 1.5 + 0.3 1.5 + 0.3  Prosthesis size (mm), mean + SD 24.4 + 1.7 23.3 + 1.7 24.4 + 1.7 23.1 + 1.7 Bold values indicate significant associations. AS: aortic stenosis; DORV: double outlet right ventricle; PR: pulmonary regurgitation; PS: pulmonary stenosis; SD: standard deviation; TGA: transposition of the great arteries; TOF: tetralogy of Fallot. Table 3: Distribution of the covariates by structural valve degeneration and reintervention Structural valve degeneration Reintervention No Yes No Yes Categorical covariates  Sex, % (n)   Male 56.6 (90) 58.6 (17) 56.6 (94) 59.1 (13)   Female 43.4 (69) 41.4 (12) 43.4 (72) 40.9 (9)  Prosthesis location, % (n)   Orthotopic 66.7 (106) 41.4 (12) 65.1 (108) 45.45 (10)   Non-orthotopic 33.3 (53) 58.6 (17) 34.9 (58) 54.6 (12)  Indication for surgery, % (n)   PR 85.5 (136) 82.8 (24) 86.8 (144) 72.7 (16)   PS 10.1 (16) 3.5 (1) 9.0 (2) 9.1 (17)   Non-structural 1.3 (2) 0 (0) 1.2 (2) 0 (0)   Ross procedure 3.1 (5) 13.8 (4) 3.0 (5) 18.1 (4)  Diagnosis (all), % (n)   TOF 54.1 (86) 27.6 (8) 52.4 (87) 31.8 (7)   PS 8.8 (14) 10.3 (3) 9.0 (15) 9.1 (2)   Pulmonary atresia 13.8 (22) 24.1 (7) 15.1 (25) 18.2 (4)   AS 4.4 (7) 3.5 (1) 4.22 (7) 4.6 (1)   Truncus 3.8 (6) 6.9 (2) 3.61 (6) 9.1 (2)   TGA 5.7 (9) 13.8 (4) 4.8 (8) 22.7 (5)   DORV 5.0 (8) 3.5 (1) 4.8 (8) 4.6 (1)   Other 4.4 (7) 10.3 (3) 6.0 (10) 0 (0)  Diagnosis (binary), % (n)   TOF 54.1 (86) 27.6 (8) 52.4 (87) 31.8 (7)   All others 45.9 (73) 72.4 (21) 47.6 (79) 68.2 (15) Quantitative covariates  Age (years), mean + SD 15.11 + 2.7 14.3 + 2.3 15.3 + 2.7 14.1 + 2.7  Height (cm), mean + SD 161.5 + 13.3 158.6 + 15.4 161.4 + 13.1 158.8 + 17.6  Weight (kg), mean + SD 54.7 + 16.4 51.3 + 15.6 54.6 + 16.3 51.2 + 16.2  Body surface area, mean + SD 1.6 + 0.3 1.5 + 0.3 1.5 + 0.3 1.5 + 0.3  Prosthesis size (mm), mean + SD 24.4 + 1.7 23.3 + 1.7 24.4 + 1.7 23.1 + 1.7 Structural valve degeneration Reintervention No Yes No Yes Categorical covariates  Sex, % (n)   Male 56.6 (90) 58.6 (17) 56.6 (94) 59.1 (13)   Female 43.4 (69) 41.4 (12) 43.4 (72) 40.9 (9)  Prosthesis location, % (n)   Orthotopic 66.7 (106) 41.4 (12) 65.1 (108) 45.45 (10)   Non-orthotopic 33.3 (53) 58.6 (17) 34.9 (58) 54.6 (12)  Indication for surgery, % (n)   PR 85.5 (136) 82.8 (24) 86.8 (144) 72.7 (16)   PS 10.1 (16) 3.5 (1) 9.0 (2) 9.1 (17)   Non-structural 1.3 (2) 0 (0) 1.2 (2) 0 (0)   Ross procedure 3.1 (5) 13.8 (4) 3.0 (5) 18.1 (4)  Diagnosis (all), % (n)   TOF 54.1 (86) 27.6 (8) 52.4 (87) 31.8 (7)   PS 8.8 (14) 10.3 (3) 9.0 (15) 9.1 (2)   Pulmonary atresia 13.8 (22) 24.1 (7) 15.1 (25) 18.2 (4)   AS 4.4 (7) 3.5 (1) 4.22 (7) 4.6 (1)   Truncus 3.8 (6) 6.9 (2) 3.61 (6) 9.1 (2)   TGA 5.7 (9) 13.8 (4) 4.8 (8) 22.7 (5)   DORV 5.0 (8) 3.5 (1) 4.8 (8) 4.6 (1)   Other 4.4 (7) 10.3 (3) 6.0 (10) 0 (0)  Diagnosis (binary), % (n)   TOF 54.1 (86) 27.6 (8) 52.4 (87) 31.8 (7)   All others 45.9 (73) 72.4 (21) 47.6 (79) 68.2 (15) Quantitative covariates  Age (years), mean + SD 15.11 + 2.7 14.3 + 2.3 15.3 + 2.7 14.1 + 2.7  Height (cm), mean + SD 161.5 + 13.3 158.6 + 15.4 161.4 + 13.1 158.8 + 17.6  Weight (kg), mean + SD 54.7 + 16.4 51.3 + 15.6 54.6 + 16.3 51.2 + 16.2  Body surface area, mean + SD 1.6 + 0.3 1.5 + 0.3 1.5 + 0.3 1.5 + 0.3  Prosthesis size (mm), mean + SD 24.4 + 1.7 23.3 + 1.7 24.4 + 1.7 23.1 + 1.7 Bold values indicate significant associations. AS: aortic stenosis; DORV: double outlet right ventricle; PR: pulmonary regurgitation; PS: pulmonary stenosis; SD: standard deviation; TGA: transposition of the great arteries; TOF: tetralogy of Fallot. Primary end points The end points of SVD and reintervention were not associated with the covariates such as sex, age, height, weight or BSA. Non-orthotopic prosthesis location and a diagnosis other than TOF were associated with SVD but not reintervention. Tables 2 and 3 indicate that a larger proportion of bioprosthesis patients received a prosthesis in the orthotopic position than homograft patients. Patients who experienced SVD were less likely to have received a prosthesis in the orthotopic position, whereas no relationship between reintervention and prosthesis location was observed. SVD was associated with a smaller mean prosthesis size of 23.3 mm when compared with a mean of 24.4 mm in those who did not develop SVD (Table 3). In the bioprosthesis group, 16.1% (n = 9) and 12.5% (n = 7) experienced SVD and reintervention within the study period, respectively. In the homograft group, 15.2% (n = 20) and 11.4% (n = 15) experienced SVD and reintervention, respectively. Figure 1A and B show the Kaplan–Meier curves for SVD and reintervention by prosthesis type. Graphical differences evident in the survival curves for SVD and reintervention were found to be statistically significant (P < 0.001 and P = 0.006, respectively). Figure 1: View largeDownload slide (A)Kaplan–Meier curves showing freedom from SVD after surgery compared between homografts (blue) and bioprosthetic valves (red) (log-rank test, P-value <0.001). (B)Kaplan–Meier curves showing freedom from reintervention after surgery compared between homografts (blue) and bioprosthetic valves (red) (log-rank test, P-value = 0.006). SVD: structural valve degeneration. Figure 1: View largeDownload slide (A)Kaplan–Meier curves showing freedom from SVD after surgery compared between homografts (blue) and bioprosthetic valves (red) (log-rank test, P-value <0.001). (B)Kaplan–Meier curves showing freedom from reintervention after surgery compared between homografts (blue) and bioprosthetic valves (red) (log-rank test, P-value = 0.006). SVD: structural valve degeneration. The unadjusted Cox regression analysis among the full sample found that patients who received a bioprosthesis were at 5.64 (95% CI = 2.11, 15.07) times the risk of SVD and 3.89 (95% CI = 1.40, 10.82) times the risk of reintervention over the study period. Subgroup analysis demonstrated no statistical difference in the performance of bovine and porcine bioprosthesis though there appears to be a trend towards better performance of the bovine bioprosthesis (Fig. 2A and B). Figure 2: View largeDownload slide (A)Kaplan–Meier curves showing freedom from SVD after surgery compared between bovine (blue) and porcine (red) bioprosthetic valves (log-rank test, P-value <0.152). (B)Kaplan–Meier curves of days until reintervention after surgery compared between bovine (blue) and porcine (red) bioprosthesis (log-rank test, P-value = 0.063). SVD: structural valve degeneration. Figure 2: View largeDownload slide (A)Kaplan–Meier curves showing freedom from SVD after surgery compared between bovine (blue) and porcine (red) bioprosthetic valves (log-rank test, P-value <0.152). (B)Kaplan–Meier curves of days until reintervention after surgery compared between bovine (blue) and porcine (red) bioprosthesis (log-rank test, P-value = 0.063). SVD: structural valve degeneration. Accounting for confounding covariates using propensity score matching Propensity score matching resulted in a total of 45 pairs of patients (45 with each prosthesis type – total of 90 patients) with adequate balance achieved for all covariates included in the propensity score and a median residual bias of 0.045 (Table 4). The Cox regression analysis performed on the propensity matched sample revealed that patients receiving a bioprosthesis were at almost 10 times the risk of experiencing SVD [hazard ratio (HR) = 9.18; 95% CI = 1.28, 65.64] and at more than 8 times the risk of undergoing a reintervention (HR = 8.34; 95% CI = 1.02, 67.86) during the study period. Table 4: Propensity matching: distribution of covariates by matched sample Homograft (n = 45) Bioprosthesis (n = 45) Residual bias Categorical covariates  Sex, % (n)   Male 53 (24) 49 (22) 0.088  Prosthesis location, % (n)   Orthotopic 73 (33) 71 (32) 0.049  Diagnosis (binary), % (n)   TOF 42 (19) 40 (18) 0.045 Quantitative covariates  Age (days), mean + SD 5584 + 1005 5614 + 1057 0.029  Height (cm), mean + SD 162.2 + 14.4 162.2 + 13.2 0.005  Weight (kg), mean + SD 54.4 + 15.2 55.6 + 15.6 0.075  Body surface area, mean + SD 1.56 + 0.27 1.57 + 0.26 0.062  Prosthesis size (mm), mean + SD 24.3 + 1.9 24.2 + 1.5 0.026 Homograft (n = 45) Bioprosthesis (n = 45) Residual bias Categorical covariates  Sex, % (n)   Male 53 (24) 49 (22) 0.088  Prosthesis location, % (n)   Orthotopic 73 (33) 71 (32) 0.049  Diagnosis (binary), % (n)   TOF 42 (19) 40 (18) 0.045 Quantitative covariates  Age (days), mean + SD 5584 + 1005 5614 + 1057 0.029  Height (cm), mean + SD 162.2 + 14.4 162.2 + 13.2 0.005  Weight (kg), mean + SD 54.4 + 15.2 55.6 + 15.6 0.075  Body surface area, mean + SD 1.56 + 0.27 1.57 + 0.26 0.062  Prosthesis size (mm), mean + SD 24.3 + 1.9 24.2 + 1.5 0.026 Analysis based on 90 matched patients (45 with a homograft and 45 with a bioprosthesis). The median bias for all the covariates was 0.047. SD: standard deviation; TOF: tetralogy of Fallot. Table 4: Propensity matching: distribution of covariates by matched sample Homograft (n = 45) Bioprosthesis (n = 45) Residual bias Categorical covariates  Sex, % (n)   Male 53 (24) 49 (22) 0.088  Prosthesis location, % (n)   Orthotopic 73 (33) 71 (32) 0.049  Diagnosis (binary), % (n)   TOF 42 (19) 40 (18) 0.045 Quantitative covariates  Age (days), mean + SD 5584 + 1005 5614 + 1057 0.029  Height (cm), mean + SD 162.2 + 14.4 162.2 + 13.2 0.005  Weight (kg), mean + SD 54.4 + 15.2 55.6 + 15.6 0.075  Body surface area, mean + SD 1.56 + 0.27 1.57 + 0.26 0.062  Prosthesis size (mm), mean + SD 24.3 + 1.9 24.2 + 1.5 0.026 Homograft (n = 45) Bioprosthesis (n = 45) Residual bias Categorical covariates  Sex, % (n)   Male 53 (24) 49 (22) 0.088  Prosthesis location, % (n)   Orthotopic 73 (33) 71 (32) 0.049  Diagnosis (binary), % (n)   TOF 42 (19) 40 (18) 0.045 Quantitative covariates  Age (days), mean + SD 5584 + 1005 5614 + 1057 0.029  Height (cm), mean + SD 162.2 + 14.4 162.2 + 13.2 0.005  Weight (kg), mean + SD 54.4 + 15.2 55.6 + 15.6 0.075  Body surface area, mean + SD 1.56 + 0.27 1.57 + 0.26 0.062  Prosthesis size (mm), mean + SD 24.3 + 1.9 24.2 + 1.5 0.026 Analysis based on 90 matched patients (45 with a homograft and 45 with a bioprosthesis). The median bias for all the covariates was 0.047. SD: standard deviation; TOF: tetralogy of Fallot. Secondary end points Two deaths were recorded over the study period (homograft n = 1, bioprosthesis n = 1). No statistically significant differences were observed between the homograft and bioprosthesis groups for non-structural valve deterioration, thrombosis, embolism, endocarditis, valve-related mortality, sudden unexplained death, cardiac death, all-cause mortality, permanent valve-related impairment and major adverse valve-related events (Table 1). DISCUSSION Our study aimed to compare the long-term performance of pulmonary homografts and stented xenograft bioprosthetic valves in the pulmonary position in patients aged 10–20 years at the time of implantation. The unadjusted Cox regression analysis revealed that a bioprosthesis was associated with 5.64 times the risk of SVD and 3.89 times the risk of reintervention when compared with pulmonary homografts. This risk increased to 9.18 times for SVD and 8.34 times for reintervention when adjusted for covariates using propensity score matching. Xenograft bioprosthetic valves (bovine pericardial or porcine) in the pulmonary position in adolescents and young adults Kwak et al. [11] in their comparison of 63 Carpentier-Edwards bovine pericardial valves with 40 Hancock 2 porcine valves (mean age 12.8 years) noted a higher rate of failure in the bovine pericardial valve group with freedom from reoperation of 97%, 87% and 50% at 1, 3 and 5 years, respectively. The relatively poor performance of bioprosthetic valves in our series is similar, with freedom from SVD decreasing from 91% at 3 years to 53% at 5 years and freedom from reintervention decreasing from 93% at 3 years to 68% at 5 years. Lee et al. [12] in their series of 181 patients (mean age 14 years) reported freedom from reoperation of 93% and 51% and freedom from valve dysfunction of 92% and 20% at 5 and 10 years, respectively. Valve function was stable up to 5 years, but by 10 years, approximately 80% required reoperation or manifested with valve dysfunction. In the report from Chen et al. [7] involving 170 PVR patients (median follow-up 48 months), freedom from reintervention dropped from 94% at 5 years to 36% at 10 years. After 39 months of follow-up, SVD was significantly worse in patients who had undergone PVR at younger than 15 years with a significantly higher risk for reintervention (HR 19.54). Buchholz et al. [13] identified age <19 years as a risk factor with freedom from valve degeneration of 65% at 5 years and 40% at 10 years when compared with 95% and 80%, respectively, in patients older than 19 years. In the largest published series to date, Nomoto et al. reported their experience with 611 bioprosthetic valves (median age 17.8 years; 50% <18 years). The risk of reintervention was approximately 5 times greater for children than adults. The reintervention rate rose from 8% at 5 years to 46% by 10 years. However, their analysis also included patients younger than 12 years who had significantly worse outcomes than older patients [14]. Homografts in the pulmonary position in adolescents and young adults In our study, pulmonary homografts demonstrated freedom from SVD of 92%, 85% and 82% at 5, 10 and 15 years, respectively. The freedom from reintervention was 93%, 88% and 85% at 5, 10 and 15 years, respectively. Similar findings have been reported by other investigators. Sarikouch et al. [15] reported 84.2% freedom from reintervention for cryopreserved homografts at 10 years (mean age 5.2 years). Boethig et al. [16] in their analysis of 188 homografts reported 83% freedom from reoperation at 10 years in patients over the age of 10 years. Forbess et al. [17] reported 5-year freedom from reintervention of 81% for cryopreserved homografts in children older than 10 years. Their study included a significant number of aortic homografts that were found to have accelerated degeneration in the cohort older than 10 years. Aortic homografts have previously been shown to have accelerated degeneration secondary to calcification in the pulmonary position and were excluded from our study [18]. Comparison of homografts and bioprosthetic valves in the pulmonary position in adolescents and young adults In our study, the performance of bioprosthetic valves and homografts was comparable within the first 3 years following implantation. By 5 years, homografts significantly outperformed bioprosthetic valves. Little published data are available directly comparing the performance of bioprosthetic valves with homografts in the pulmonary position in adolescents and young adults with only 1 study with sufficiently large numbers to permit a meaningful interpretation. Kanter et al. [19] reported the outcome of 100 PVRs (62 homografts and 38 porcine bioprosthetic valves) in 93 children. The mean age and valve size in the homograft group was 9.3 years and 21 mm, respectively, and the mean age and valve size in the porcine group was 11.4 years and 26 mm, respectively. No significant difference was observed between the 2 groups with respect to pulmonary stenosis. Severe PR was more common in the homograft group. At a mean follow-up of 5 years, a small but definite early reoperation rate was observed in the homograft group. In contrast, reoperation was not performed in the porcine group until 8 years after valve replacement. However, on closer examination of the data, the authors noted that all 7 children with a homograft who required replacement had the original pulmonary valve placed at the of age ≤3 years. The freedom from reoperation at 8 years for children older than 3 years at the time of PVR with a homograft was 100%. In their cohort, the overall age was younger, and only 44% (n = 17 of 38) of patients in the bioprosthesis group received a stented bioprosthesis when compared with our own study. Zubairi et al. [20] compared the performance of 56 cryopreserved pulmonary homografts with 113 heterografts. No difference in reoperation was observed among the 4 heterograft valve types and between homografts and heterografts with freedom of reoperation of 93% at 5 years and 71% at 10 years. The multivariate analysis identified younger age as a risk factor for early (<3 years) and late failure. Homografts were an independent risk factor for early failure. However, a higher proportion of children younger than 10 years received a homograft, and in children older than 10 years, no difference in reoperation was observed between homografts and heterografts. We identified only 1 previous study with similar methodology to ours. Batlivala et al. [21] reported a retrospective, single-centre comparison in patients aged 10–21 years who underwent PVR from May 1990 to December 2009 (median follow-up 4.4 years): 84 cryopreserved homografts (aortic n = 50, pulmonary n = 34) and 170 bioprosthetic valves. At 5 years, freedom from moderate or severe pulmonary stenosis was 86% and freedom from moderate or severe PR was 84% with no difference between the 2 cohorts. Freedom from any reintervention was 90%, 67% and 47% at 3, 5 and 15 years, respectively. Freedom from PVR was 96%, 74% and 48% at 5, 10 and 15 years, respectively. The performance of bioprosthetic valves in their study mirrored the findings from our study. However, in contradistinction to our study, the authors found no difference between the homograft and bioprosthetic valve cohorts at all time points. The duration of follow-up was longer in our study (median 7.1 years vs 4.4 years). Additionally, the homograft group in this study contained 50 aortic homografts, which have previously been shown to deteriorate more rapidly in the pulmonary position [22]. Only 4 aortic homografts were available in our study population, and in the interest of consistency, we intentionally excluded them from the final analysis. Bovine versus porcine bioprosthetic valves Our subgroup analysis comparing the durability of bovine and porcine bioprosthesis demonstrated a trend towards higher reintervention rates in porcine valves. However, similar to other published reports, no statistically significant difference was observed in the performance of these 2 valve types [7]. Limitations Our findings must be interpreted in the light of several limitations. First, although we used propensity scores to match the comparison groups by important prognostic factors, this method was limited by the range of data collected, and our hospital records failed to account for factors such as donor homograft and recipient blood group compatibility. Second, patients receiving a bioprosthesis were more likely to have had their operations recently when compared with those receiving homografts resulting in unequal follow-up times and cohort effects by which bioprosthesis patients were likely to benefit from more recent advances in surgical and medical technologies. Importantly, however, both of these potential biases are likely to have attenuated our effect estimates, thus leaving our substantive conclusion unchanged. Third, the sample size among the bioprosthesis group is comparatively small as we approach 5 years. Finally, among the initial 209 participants, 21 were excluded from the analysis due to having no recorded height or weight at surgery. Although those lost to follow-up were more likely to be older, have valves inserted in an extra-anatomical position and were more likely to have a TOF diagnosis, having retained 90% of the sample, we believe it unlikely that this attrition would bias our results. CONCLUSION In our patient population, pulmonary homografts outperformed stented xenograft bioprosthetic valves when implanted in the pulmonary position in patients aged 10–20 years. The difference in performance was evident by 5 years. On the basis of these findings, we recommend the use of a pulmonary homograft for PVR in this age group in patients undergoing surgery for congenital heart disease. Conflict of interest: none declared. REFERENCES 1 Lee C , Kim YM , Lee CH , Kwak JG , Park CS , Song JY et al. Outcomes of pulmonary valve replacement in 170 patients with chronic pulmonary regurgitation after relief of right ventricular outflow tract obstruction: implications for optimal timing of pulmonary valve replacement . 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Younger age and valve oversizing are predictors of structural valve deterioration after pulmonary valve replacement in patients with tetralogy of Fallot . J Thorac Cardiovasc Surg 2012 ; 143 : 352 – 60 . Google Scholar CrossRef Search ADS PubMed 7 Chen XJ , Smith PB , Jaggers J , Lodge AJ. Bioprosthetic pulmonary valve replacement: contemporary analysis of a large, single-center series of 170 cases . J Thorac Cardiovasc Surg 2013 ; 146 : 1461 – 6 . Google Scholar CrossRef Search ADS PubMed 8 Kwak JG , Lee C , Lee M , Lee CH , Jang SI , Lee SY et al. Does implantation of larger bioprosthetic pulmonary valves in young patients guarantee durability in adults? Durability analysis of stented bioprosthetic valves in the pulmonary position in patients with tetralogy of Fallot . Eur J Cardiothorac Surg 2016 ; 49 : 1207 – 12 . Google Scholar CrossRef Search ADS PubMed 9 Warnes CA , Liberthson R , Danielson GK , Dore A , Harris L , Hoffman JI et al. Task force 1: the changing profile of congenital heart disease in adult life . J Am Coll Cardiol 2001 ; 37 : 1170 – 5 . Google Scholar CrossRef Search ADS PubMed 10 Akins CW , Miller DC , Turina MI , Kouchoukos NT , Blackstone EH , Grunkemeier GL et al. Guidelines for reporting mortality and morbidity after cardiac valve interventions . Ann Thorac Surg 2008 ; 85 : 1490 – 5 . Google Scholar CrossRef Search ADS PubMed 11 Kwak JG , Lee JR , Kim WH , Kim YJ. Mid-term results of the Hancock II valve and Carpentier-Edward Perimount valve in the pulmonary portion in congenital heart disease . Heart Lung Circ 2010 ; 19 : 243 – 6 . Google Scholar CrossRef Search ADS PubMed 12 Lee C , Park CS , Lee CH , Kwak JG , Kim SJ , Shim WS et al. Durability of bioprosthetic valves in the pulmonary position: long-term follow-up of 181 implants in patients with congenital heart disease . J Thorac Cardiovasc Surg 2011 ; 142 : 351 – 8 . Google Scholar CrossRef Search ADS PubMed 13 Buchholz C , Mayr A , Purbojo A , Glockler M , Toka O , Cesnjevar RA et al. Performance of stented biological valves for right ventricular outflow tract reconstruction . Interact CardioVasc Thorac Surg 2016 ; 23 : 933 – 9 . Google Scholar CrossRef Search ADS PubMed 14 Nomoto R , Sleeper LA , Borisuk MJ , Bergerson L , Pigula FA , Emani S et al. Outcome and performance of bioprosthetic pulmonary valve replacement in patients with congenital heart disease . J Thorac Cardiovasc Surg 2016 ; 152 : 1333 – 42 . Google Scholar CrossRef Search ADS PubMed 15 Sarikouch S , Horke A , Tudorache I , Beerbaum P , Westhoff-Bleck M , Boethig D et al. Decellularized fresh homografts for pulmonary valve replacement: a decade of clinical experience . Eur J Cardiothorac Surg 2016 ; 50 : 281 – 90 . Google Scholar CrossRef Search ADS PubMed 16 Boethig D , Goerler H , Westhoff-Bleck M , Ono M , Daiber A , Haverich A et al. Evaluation of 188 consecutive homografts implanted in pulmonary position after 20 years . Eur J Cardiothorac Surg 2007 ; 32 : 133 – 42 . Google Scholar CrossRef Search ADS PubMed 17 Forbess JM , Shah AS , St. Louis JD , Jaggers JJ , Ungerleider RM. Cryopreserved homografts in the pulmonary position: determinants of durability . Ann Thorac Surg 2001 ; 71 : 54 – 9 . Google Scholar CrossRef Search ADS PubMed 18 Schorn K , Yankah AC , Alexi-Meskhishvili V , Weng Y , Lange PE , Hetzer R. Risk factors for early degeneration of allografts in pulmonary circulation . Eur J Cardiothorac Surg 1997 ; 11 : 62 – 9 . Google Scholar CrossRef Search ADS PubMed 19 Kanter KR , Budde JM , Parks WJ , Tam VKH , Sharma S , Williams WH et al. One hundred pulmonary valve replacements in children after relief of right ventricular outflow tract obstruction . Ann Thorac Surg 2002 ; 73 : 1801 – 7 . Google Scholar CrossRef Search ADS PubMed 20 Zubairi R , Malik S , Jaquiss RD , Imamura M , Gossett J , Morrow WR. Risk factors for prosthesis failure in pulmonary valve replacement . Ann Thorac Surg 2011 ; 91 : 561 – 5 . Google Scholar CrossRef Search ADS PubMed 21 Batlivala SP , Emani S , Mayer JE , McElhinney DB. Pulmonary valve replacement function in adolescents: a comparison of bioprosthetic valves and homograft conduits . Ann Thorac Surg 2012 ; 93 : 2007 – 16 . Google Scholar CrossRef Search ADS PubMed 22 Yankah AC , Alexi-Meskhishvili V , Weng Y , Berger F , Lange P , Hetzer R. Performance of pulmonary and aortic homografts in the right ventricular outflow tract in children . J Heart Valve Dis 1995 ; 4 : 392 – 5 . Google Scholar PubMed © The Author(s) 2018. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved. This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/about_us/legal/notices) http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png European Journal of Cardio-Thoracic Surgery Oxford University Press

Long-term performance of homografts versus stented bioprosthetic valves in the pulmonary position in patients aged 10–20 years

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Oxford University Press
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© The Author(s) 2018. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.
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1010-7940
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1873-734X
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10.1093/ejcts/ezy149
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Abstract

Abstract OBJECTIVES We aimed to compare the long-term performance of pulmonary homografts and stented bioprosthetic valves in the pulmonary position in patients aged 10–20 years. METHODS Between January 1995 and December 2015, 188 patients aged 10–20 years undergoing pulmonary valve replacement were identified retrospectively from hospital databases in both congenital cardiac centres in Brisbane. Valve performance was evaluated using previously described standard criteria. Propensity score matching was used to balance the 2 treatment groups. RESULTS Freedom from structural valve degeneration in homografts (n = 131) was 97%, 92% and 85% at 3, 5 and 10 years, respectively, and 91% and 53% at 3 and 5 years, respectively, in the bioprosthesis group (n = 57). Freedom from reintervention in homografts was 96%, 93% and 88% at 3, 5 and 10 years, respectively, and 93% and 68% at 3 and 5 years, respectively, in the bioprosthesis group. The unadjusted Cox regression analysis demonstrated that a bioprosthesis was at 5.64 times the risk of structural valve degeneration and 3.89 times the risk of reintervention. The Cox regression analysis performed on the propensity matched sample (45 pairs of patients) revealed that a bioprosthesis was at almost 10 times the risk of experiencing structural valve degeneration [hazard ratio (HR) = 9.18] and at more than 8 times the risk of undergoing a reintervention (HR = 8.34). CONCLUSIONS In our patient population, pulmonary homografts outperformed stented bioprosthetic valves within 5 years when implanted in the pulmonary position in patients aged 10–20 years. We recommend the use of a pulmonary homograft for pulmonary valve replacement in this age group in patients undergoing surgery for congenital heart disease. Pulmonary valve replacement, Homograft, Bioprosthetic valve INTRODUCTION In patients born with congenital heart disease, relief of right ventricular outflow tract obstruction often results in the development of pulmonary regurgitation (PR) later in life. Although initially this may be well tolerated, long-standing PR eventually results in dilation of the right ventricle with reduced exercise tolerance and increased risk of arrhythmias and sudden death [1]. Timely replacement of the pulmonary valve can mitigate or even reverse progression of right ventricle dilation [2, 3]. However, the optimal timing and the best prosthesis for pulmonary valve replacement (PVR) remain unclear [4, 5]. Older children and adolescents can often accommodate an adult-sized prosthesis greater than 19 mm in diameter in the pulmonary position. The commonest options include homografts (aortic or pulmonary), stented or stentless xenograft bioprosthesis, mechanical valves or bovine jugular conduits (Contegra®). Although all 4 have a comparable haemodynamic profile, each has unique advantages and disadvantages that influence selection. Historically, homografts have been the preferred choice for PVR. However, their biggest limitation is availability. Mechanical valves require anticoagulation with warfarin. The bovine jugular vein conduit (Contegra) is also available in diameters of 20 mm and 22 mm but is becoming increasingly difficult to obtain in these sizes in Brisbane. Stented xenograft bioprosthetic valves are readily available, have comparable haemodynamics to homografts and do not need anticoagulation. Increased use of the bioprosthesis began in the late 1990s and was first adopted in Brisbane around 2005. Heart donor shortage, lack of availability of the appropriate size, extended indications for surgery, availability of good long-term performance data in the aortic position and introduction of percutaneous valve-in-valve technology contributed to the change in practice. However, data on long-term durability are conflicting, and some evidence is available suggesting an accelerated rate of degeneration in the younger population [6–8]. To date, only limited direct comparative data exist between homografts and stented xenograft bioprosthetic valves in the pulmonary position and even less information on the performance of these valves in adolescents and young adults. As more information becomes available on the deleterious effects of PR on the right ventricle, there is a growing tendency to refer patients for valve implantation at an earlier age even in the absence of symptoms. This trend has been reflected internationally with an increasing number of adolescents being referred for PVR [9]. We aimed to directly compare the long-term performance of pulmonary homografts and stented xenograft bioprosthetic valves in the pulmonary position in patients aged 10–20 years. METHODS Sample All patients aged 10–20 years at the time of PVR between 1 January 1995 and 31 December 2015 were identified retrospectively from hospital databases. Patient data were collected from the only 2 congenital centres for the state of Queensland, both of which are located in Brisbane. Study patients had either a cryopreserved pulmonary homograft or a bovine or porcine pericardial bioprosthesis inserted in the pulmonary position. We have not implanted a mechanical valve in our unit since 2008, and they have been excluded from the study. Four patients received an aortic homograft in the pulmonary position throughout the study period and were also excluded from the analysis. End points Valve performance was evaluated using previously published criteria [10]. The primary end points were freedom from reintervention and structural valve degeneration (SVD; peak transpulmonary gradient ≥50 mmHg or more than moderate PR). Secondary end points are given in Table 1. Table 1: Differences in secondary end points by valve type Clinical outcomes Full sample % (n) Homograft % (n) Bioprosthesis % (n) P-value Non-structural valve degeneration 3.7 (7) 3.7 (5) 3.6 (2) 0.943 Valve thrombosis 0.0 (0) 0.0 (0) 0.0 (0) ** Embolism 2.7 (5) 3.8 (5) 0.0 (0) 0.140 Bleeding event 4.1 (6) 3.1 (4) 4.2 (2) 0.350 Operated valve endocarditis 1.1 (2) 0.8 (1) 1.8 (1) 0.530 Valve-related mortality 0.5 (1) 0.0 (0) 1.8 (1) 0.124 Sudden unexplained death 0.5 (1) 0.8 (1) 0.0 (0) 0.514 Cardiac death 0.5 (1) 0.8 (1) 0.0 (0) 0.514 All-cause mortality 1.1 (2) 0.8 (1) 1.8 (1) 0.530 Permanent valve-related impairment 2.7 (5) 2.3 (3) 3.6 (2) 0.613 Major adverse valve-related event 5.8 (11) 6.1 (8) 5.4 (3) 0.851 Clinical outcomes Full sample % (n) Homograft % (n) Bioprosthesis % (n) P-value Non-structural valve degeneration 3.7 (7) 3.7 (5) 3.6 (2) 0.943 Valve thrombosis 0.0 (0) 0.0 (0) 0.0 (0) ** Embolism 2.7 (5) 3.8 (5) 0.0 (0) 0.140 Bleeding event 4.1 (6) 3.1 (4) 4.2 (2) 0.350 Operated valve endocarditis 1.1 (2) 0.8 (1) 1.8 (1) 0.530 Valve-related mortality 0.5 (1) 0.0 (0) 1.8 (1) 0.124 Sudden unexplained death 0.5 (1) 0.8 (1) 0.0 (0) 0.514 Cardiac death 0.5 (1) 0.8 (1) 0.0 (0) 0.514 All-cause mortality 1.1 (2) 0.8 (1) 1.8 (1) 0.530 Permanent valve-related impairment 2.7 (5) 2.3 (3) 3.6 (2) 0.613 Major adverse valve-related event 5.8 (11) 6.1 (8) 5.4 (3) 0.851 Table 1: Differences in secondary end points by valve type Clinical outcomes Full sample % (n) Homograft % (n) Bioprosthesis % (n) P-value Non-structural valve degeneration 3.7 (7) 3.7 (5) 3.6 (2) 0.943 Valve thrombosis 0.0 (0) 0.0 (0) 0.0 (0) ** Embolism 2.7 (5) 3.8 (5) 0.0 (0) 0.140 Bleeding event 4.1 (6) 3.1 (4) 4.2 (2) 0.350 Operated valve endocarditis 1.1 (2) 0.8 (1) 1.8 (1) 0.530 Valve-related mortality 0.5 (1) 0.0 (0) 1.8 (1) 0.124 Sudden unexplained death 0.5 (1) 0.8 (1) 0.0 (0) 0.514 Cardiac death 0.5 (1) 0.8 (1) 0.0 (0) 0.514 All-cause mortality 1.1 (2) 0.8 (1) 1.8 (1) 0.530 Permanent valve-related impairment 2.7 (5) 2.3 (3) 3.6 (2) 0.613 Major adverse valve-related event 5.8 (11) 6.1 (8) 5.4 (3) 0.851 Clinical outcomes Full sample % (n) Homograft % (n) Bioprosthesis % (n) P-value Non-structural valve degeneration 3.7 (7) 3.7 (5) 3.6 (2) 0.943 Valve thrombosis 0.0 (0) 0.0 (0) 0.0 (0) ** Embolism 2.7 (5) 3.8 (5) 0.0 (0) 0.140 Bleeding event 4.1 (6) 3.1 (4) 4.2 (2) 0.350 Operated valve endocarditis 1.1 (2) 0.8 (1) 1.8 (1) 0.530 Valve-related mortality 0.5 (1) 0.0 (0) 1.8 (1) 0.124 Sudden unexplained death 0.5 (1) 0.8 (1) 0.0 (0) 0.514 Cardiac death 0.5 (1) 0.8 (1) 0.0 (0) 0.514 All-cause mortality 1.1 (2) 0.8 (1) 1.8 (1) 0.530 Permanent valve-related impairment 2.7 (5) 2.3 (3) 3.6 (2) 0.613 Major adverse valve-related event 5.8 (11) 6.1 (8) 5.4 (3) 0.851 Covariates Measured covariates included age, sex, height, weight, body surface area (BSA), valve size, z-score, prosthesis location (orthotopic or non-orthotopic), indication for surgery (PR, pulmonary stenosis and Ross procedure) and diagnosis. Orthotopic placement refers to placement of the valve within the native right ventricular outflow tract. The study was deemed low to negligible risk by the hospital’s ethics committee, and consent was waived. Statistical analysis The homograft and bioprosthesis groups were first examined for differences in covariates, using χ2 statistics for categorical covariates (or the Fisher’s exact tests for analyses with a cell count <10) and t-statistics for continuous covariates. Subsequently, the Kaplan–Meier curves and log-rank tests were used to compare time to SVD and freedom from reintervention separately between groups. The univariable Cox regression analysis was then used to calculate the unadjusted increased risk of SVD and reintervention in groups. Next, propensity scores were used to balance the 2 treatment groups (i.e. homograft and bioprosthesis) according to a number of baseline covariates selected a priori, including age, weight, height, BSA at surgery, sex, prosthesis size (mm), prosthesis location (1 = orthotopic; 2 = non-orthotopic) and diagnosis [1 = tetralogy of Fallot (TOF), 2 = all other diagnoses]. As PR was the indication for all patients receiving a bioprosthesis, we reran the final analysis among only patients indicated for PR as a means of controlling for this variable. The propensity score was estimated using a logistic regression model with 1:1 nearest neighbour matching without replacement based on an acceptable caliper width of 0.2 times the standard deviation of the logit of the propensity score. Balance diagnostics were then assessed by calculating the residual bias with values above 0.1 indicative of balance not having been achieved. Finally, the Cox regression analysis was used to calculate the increased risk of SVD and reintervention over the study period due to receiving a bioprosthesis among the sample of propensity score-matched pairs. The standard errors of these models were calculated with a clustered sandwich estimator to account for the lack of independence among the matched pairs. All analyses were undertaken in Stata version 14.2 (StataCorp LP, College Station, TX, USA). RESULTS Sample Between 1 January 1995 and 31 December 2015, 209 consecutive patients aged 10–20 years who underwent PVR and met the study inclusion criteria were identified from the hospital databases. Twenty-one patients had no recorded height or weight at surgery in the surgical database, and their hospital records at the Prince Charles Hospital were destroyed. We were unable to obtain follow-up data on these 21 patients. Complete demographic and follow-up data were obtained on 188 patients. A bioprosthesis was implanted in 30.3% of patients (n = 57, 38 bovine, 19 porcine), and a pulmonary homograft was implanted in 69.7% of patients (n = 131). The bioprostheses implanted included 13 EPIC (porcine; St Jude Medical, Saint Paul, MN, USA), 5 Magna Ease (bovine; Edwards, Irvine, CA, USA) and 38 Trifecta (bovine, St Jude Medical) valves. Baseline characteristics including sex, age, BSA, weight, height and prosthesis size were similar between the homograft and bioprosthesis groups (mean of 24.3 mm and 24.0 mm, respectively; Table 1); 43.2% (n = 57) of homografts were placed in the non-orthotopic position when compared with 23.2% (n = 13) of bioprostheses (P < 0.05). PR was the indication for surgery in 78.8% (n = 104) of homografts when compared with 100% (n = 57) of bioprostheses (P < 0.05). The original diagnosis was TOF in 45.5% (n = 60) of homografts and in 60.7% (n = 34) of bioprostheses (P < 0.05; Tables 2 and 3). The median follow-up in the homograft group was 9.11 years when compared with 3.02 years in the bioprosthesis group (P < 0.001). Table 2: Distribution of covariates Homograft Bioprosthesis (n = 131) (n = 57) Categorical covariates  Sex, % (n)   Male 61.4 (81) 46.4 (26)   Female 38.6 (51) 53.6 (30)  Prosthesis location, % (n)   Orthotopic 56.8 (75) 76.8 (43)   Non-orthotopic 43.2 (57) 23.2 (13)  Indication for surgery, % (n)   PR 78.8 (104) 100 (56)   PS 12.9 (17) 0 (0)   Non-structural 1.5 (2) 0 (0)   Ross procedure 6.8 (9) 0 (0)  Diagnosis (all), % (n)   TOF 45.5 (60) 60.7 (34)   PS 4.6 (6) 19.6 (11)   Pulmonary atresia 18.9 (25) 7.14 (4)   AS 6.1 (8) 0 (0)   Truncus 6.1 (8) 0 (0)   TGA 9.1 (12) 1.8 (1)   DORV 3.8 (5) 7.1 (4)   Other 6.1 (8) 3.6 (2)  Diagnosis (binary), % (n)   TOF 45.5 (60) 60.7 (34)   All others 54.6 (72) 39.3 (22) Quantitative covariates  Age (days), mean + SD 15.1 + 2.7 15.2 + 2.8  Height (cm), mean + SD 160.7 + 14.1 161.9 + 12.5  Weight (kg), mean + SD 54.5 + 16.4 53.4 + 16.2  Body surface area, mean + SD 1.5 + 0.3 1.5 + 0.3  Prosthesis size (mm), mean + SD 24.3 + 1.8 24.0 + 1.4 Homograft Bioprosthesis (n = 131) (n = 57) Categorical covariates  Sex, % (n)   Male 61.4 (81) 46.4 (26)   Female 38.6 (51) 53.6 (30)  Prosthesis location, % (n)   Orthotopic 56.8 (75) 76.8 (43)   Non-orthotopic 43.2 (57) 23.2 (13)  Indication for surgery, % (n)   PR 78.8 (104) 100 (56)   PS 12.9 (17) 0 (0)   Non-structural 1.5 (2) 0 (0)   Ross procedure 6.8 (9) 0 (0)  Diagnosis (all), % (n)   TOF 45.5 (60) 60.7 (34)   PS 4.6 (6) 19.6 (11)   Pulmonary atresia 18.9 (25) 7.14 (4)   AS 6.1 (8) 0 (0)   Truncus 6.1 (8) 0 (0)   TGA 9.1 (12) 1.8 (1)   DORV 3.8 (5) 7.1 (4)   Other 6.1 (8) 3.6 (2)  Diagnosis (binary), % (n)   TOF 45.5 (60) 60.7 (34)   All others 54.6 (72) 39.3 (22) Quantitative covariates  Age (days), mean + SD 15.1 + 2.7 15.2 + 2.8  Height (cm), mean + SD 160.7 + 14.1 161.9 + 12.5  Weight (kg), mean + SD 54.5 + 16.4 53.4 + 16.2  Body surface area, mean + SD 1.5 + 0.3 1.5 + 0.3  Prosthesis size (mm), mean + SD 24.3 + 1.8 24.0 + 1.4 Bold values indicate statistical significance >0.05. AS: aortic stenosis; DORV: double outlet right ventricle; PR: pulmonary regurgitation; PS: pulmonary stenosis; SD: standard deviation; TGA: transposition of the great arteries; TOF: tetralogy of Fallot. Table 2: Distribution of covariates Homograft Bioprosthesis (n = 131) (n = 57) Categorical covariates  Sex, % (n)   Male 61.4 (81) 46.4 (26)   Female 38.6 (51) 53.6 (30)  Prosthesis location, % (n)   Orthotopic 56.8 (75) 76.8 (43)   Non-orthotopic 43.2 (57) 23.2 (13)  Indication for surgery, % (n)   PR 78.8 (104) 100 (56)   PS 12.9 (17) 0 (0)   Non-structural 1.5 (2) 0 (0)   Ross procedure 6.8 (9) 0 (0)  Diagnosis (all), % (n)   TOF 45.5 (60) 60.7 (34)   PS 4.6 (6) 19.6 (11)   Pulmonary atresia 18.9 (25) 7.14 (4)   AS 6.1 (8) 0 (0)   Truncus 6.1 (8) 0 (0)   TGA 9.1 (12) 1.8 (1)   DORV 3.8 (5) 7.1 (4)   Other 6.1 (8) 3.6 (2)  Diagnosis (binary), % (n)   TOF 45.5 (60) 60.7 (34)   All others 54.6 (72) 39.3 (22) Quantitative covariates  Age (days), mean + SD 15.1 + 2.7 15.2 + 2.8  Height (cm), mean + SD 160.7 + 14.1 161.9 + 12.5  Weight (kg), mean + SD 54.5 + 16.4 53.4 + 16.2  Body surface area, mean + SD 1.5 + 0.3 1.5 + 0.3  Prosthesis size (mm), mean + SD 24.3 + 1.8 24.0 + 1.4 Homograft Bioprosthesis (n = 131) (n = 57) Categorical covariates  Sex, % (n)   Male 61.4 (81) 46.4 (26)   Female 38.6 (51) 53.6 (30)  Prosthesis location, % (n)   Orthotopic 56.8 (75) 76.8 (43)   Non-orthotopic 43.2 (57) 23.2 (13)  Indication for surgery, % (n)   PR 78.8 (104) 100 (56)   PS 12.9 (17) 0 (0)   Non-structural 1.5 (2) 0 (0)   Ross procedure 6.8 (9) 0 (0)  Diagnosis (all), % (n)   TOF 45.5 (60) 60.7 (34)   PS 4.6 (6) 19.6 (11)   Pulmonary atresia 18.9 (25) 7.14 (4)   AS 6.1 (8) 0 (0)   Truncus 6.1 (8) 0 (0)   TGA 9.1 (12) 1.8 (1)   DORV 3.8 (5) 7.1 (4)   Other 6.1 (8) 3.6 (2)  Diagnosis (binary), % (n)   TOF 45.5 (60) 60.7 (34)   All others 54.6 (72) 39.3 (22) Quantitative covariates  Age (days), mean + SD 15.1 + 2.7 15.2 + 2.8  Height (cm), mean + SD 160.7 + 14.1 161.9 + 12.5  Weight (kg), mean + SD 54.5 + 16.4 53.4 + 16.2  Body surface area, mean + SD 1.5 + 0.3 1.5 + 0.3  Prosthesis size (mm), mean + SD 24.3 + 1.8 24.0 + 1.4 Bold values indicate statistical significance >0.05. AS: aortic stenosis; DORV: double outlet right ventricle; PR: pulmonary regurgitation; PS: pulmonary stenosis; SD: standard deviation; TGA: transposition of the great arteries; TOF: tetralogy of Fallot. Table 3: Distribution of the covariates by structural valve degeneration and reintervention Structural valve degeneration Reintervention No Yes No Yes Categorical covariates  Sex, % (n)   Male 56.6 (90) 58.6 (17) 56.6 (94) 59.1 (13)   Female 43.4 (69) 41.4 (12) 43.4 (72) 40.9 (9)  Prosthesis location, % (n)   Orthotopic 66.7 (106) 41.4 (12) 65.1 (108) 45.45 (10)   Non-orthotopic 33.3 (53) 58.6 (17) 34.9 (58) 54.6 (12)  Indication for surgery, % (n)   PR 85.5 (136) 82.8 (24) 86.8 (144) 72.7 (16)   PS 10.1 (16) 3.5 (1) 9.0 (2) 9.1 (17)   Non-structural 1.3 (2) 0 (0) 1.2 (2) 0 (0)   Ross procedure 3.1 (5) 13.8 (4) 3.0 (5) 18.1 (4)  Diagnosis (all), % (n)   TOF 54.1 (86) 27.6 (8) 52.4 (87) 31.8 (7)   PS 8.8 (14) 10.3 (3) 9.0 (15) 9.1 (2)   Pulmonary atresia 13.8 (22) 24.1 (7) 15.1 (25) 18.2 (4)   AS 4.4 (7) 3.5 (1) 4.22 (7) 4.6 (1)   Truncus 3.8 (6) 6.9 (2) 3.61 (6) 9.1 (2)   TGA 5.7 (9) 13.8 (4) 4.8 (8) 22.7 (5)   DORV 5.0 (8) 3.5 (1) 4.8 (8) 4.6 (1)   Other 4.4 (7) 10.3 (3) 6.0 (10) 0 (0)  Diagnosis (binary), % (n)   TOF 54.1 (86) 27.6 (8) 52.4 (87) 31.8 (7)   All others 45.9 (73) 72.4 (21) 47.6 (79) 68.2 (15) Quantitative covariates  Age (years), mean + SD 15.11 + 2.7 14.3 + 2.3 15.3 + 2.7 14.1 + 2.7  Height (cm), mean + SD 161.5 + 13.3 158.6 + 15.4 161.4 + 13.1 158.8 + 17.6  Weight (kg), mean + SD 54.7 + 16.4 51.3 + 15.6 54.6 + 16.3 51.2 + 16.2  Body surface area, mean + SD 1.6 + 0.3 1.5 + 0.3 1.5 + 0.3 1.5 + 0.3  Prosthesis size (mm), mean + SD 24.4 + 1.7 23.3 + 1.7 24.4 + 1.7 23.1 + 1.7 Structural valve degeneration Reintervention No Yes No Yes Categorical covariates  Sex, % (n)   Male 56.6 (90) 58.6 (17) 56.6 (94) 59.1 (13)   Female 43.4 (69) 41.4 (12) 43.4 (72) 40.9 (9)  Prosthesis location, % (n)   Orthotopic 66.7 (106) 41.4 (12) 65.1 (108) 45.45 (10)   Non-orthotopic 33.3 (53) 58.6 (17) 34.9 (58) 54.6 (12)  Indication for surgery, % (n)   PR 85.5 (136) 82.8 (24) 86.8 (144) 72.7 (16)   PS 10.1 (16) 3.5 (1) 9.0 (2) 9.1 (17)   Non-structural 1.3 (2) 0 (0) 1.2 (2) 0 (0)   Ross procedure 3.1 (5) 13.8 (4) 3.0 (5) 18.1 (4)  Diagnosis (all), % (n)   TOF 54.1 (86) 27.6 (8) 52.4 (87) 31.8 (7)   PS 8.8 (14) 10.3 (3) 9.0 (15) 9.1 (2)   Pulmonary atresia 13.8 (22) 24.1 (7) 15.1 (25) 18.2 (4)   AS 4.4 (7) 3.5 (1) 4.22 (7) 4.6 (1)   Truncus 3.8 (6) 6.9 (2) 3.61 (6) 9.1 (2)   TGA 5.7 (9) 13.8 (4) 4.8 (8) 22.7 (5)   DORV 5.0 (8) 3.5 (1) 4.8 (8) 4.6 (1)   Other 4.4 (7) 10.3 (3) 6.0 (10) 0 (0)  Diagnosis (binary), % (n)   TOF 54.1 (86) 27.6 (8) 52.4 (87) 31.8 (7)   All others 45.9 (73) 72.4 (21) 47.6 (79) 68.2 (15) Quantitative covariates  Age (years), mean + SD 15.11 + 2.7 14.3 + 2.3 15.3 + 2.7 14.1 + 2.7  Height (cm), mean + SD 161.5 + 13.3 158.6 + 15.4 161.4 + 13.1 158.8 + 17.6  Weight (kg), mean + SD 54.7 + 16.4 51.3 + 15.6 54.6 + 16.3 51.2 + 16.2  Body surface area, mean + SD 1.6 + 0.3 1.5 + 0.3 1.5 + 0.3 1.5 + 0.3  Prosthesis size (mm), mean + SD 24.4 + 1.7 23.3 + 1.7 24.4 + 1.7 23.1 + 1.7 Bold values indicate significant associations. AS: aortic stenosis; DORV: double outlet right ventricle; PR: pulmonary regurgitation; PS: pulmonary stenosis; SD: standard deviation; TGA: transposition of the great arteries; TOF: tetralogy of Fallot. Table 3: Distribution of the covariates by structural valve degeneration and reintervention Structural valve degeneration Reintervention No Yes No Yes Categorical covariates  Sex, % (n)   Male 56.6 (90) 58.6 (17) 56.6 (94) 59.1 (13)   Female 43.4 (69) 41.4 (12) 43.4 (72) 40.9 (9)  Prosthesis location, % (n)   Orthotopic 66.7 (106) 41.4 (12) 65.1 (108) 45.45 (10)   Non-orthotopic 33.3 (53) 58.6 (17) 34.9 (58) 54.6 (12)  Indication for surgery, % (n)   PR 85.5 (136) 82.8 (24) 86.8 (144) 72.7 (16)   PS 10.1 (16) 3.5 (1) 9.0 (2) 9.1 (17)   Non-structural 1.3 (2) 0 (0) 1.2 (2) 0 (0)   Ross procedure 3.1 (5) 13.8 (4) 3.0 (5) 18.1 (4)  Diagnosis (all), % (n)   TOF 54.1 (86) 27.6 (8) 52.4 (87) 31.8 (7)   PS 8.8 (14) 10.3 (3) 9.0 (15) 9.1 (2)   Pulmonary atresia 13.8 (22) 24.1 (7) 15.1 (25) 18.2 (4)   AS 4.4 (7) 3.5 (1) 4.22 (7) 4.6 (1)   Truncus 3.8 (6) 6.9 (2) 3.61 (6) 9.1 (2)   TGA 5.7 (9) 13.8 (4) 4.8 (8) 22.7 (5)   DORV 5.0 (8) 3.5 (1) 4.8 (8) 4.6 (1)   Other 4.4 (7) 10.3 (3) 6.0 (10) 0 (0)  Diagnosis (binary), % (n)   TOF 54.1 (86) 27.6 (8) 52.4 (87) 31.8 (7)   All others 45.9 (73) 72.4 (21) 47.6 (79) 68.2 (15) Quantitative covariates  Age (years), mean + SD 15.11 + 2.7 14.3 + 2.3 15.3 + 2.7 14.1 + 2.7  Height (cm), mean + SD 161.5 + 13.3 158.6 + 15.4 161.4 + 13.1 158.8 + 17.6  Weight (kg), mean + SD 54.7 + 16.4 51.3 + 15.6 54.6 + 16.3 51.2 + 16.2  Body surface area, mean + SD 1.6 + 0.3 1.5 + 0.3 1.5 + 0.3 1.5 + 0.3  Prosthesis size (mm), mean + SD 24.4 + 1.7 23.3 + 1.7 24.4 + 1.7 23.1 + 1.7 Structural valve degeneration Reintervention No Yes No Yes Categorical covariates  Sex, % (n)   Male 56.6 (90) 58.6 (17) 56.6 (94) 59.1 (13)   Female 43.4 (69) 41.4 (12) 43.4 (72) 40.9 (9)  Prosthesis location, % (n)   Orthotopic 66.7 (106) 41.4 (12) 65.1 (108) 45.45 (10)   Non-orthotopic 33.3 (53) 58.6 (17) 34.9 (58) 54.6 (12)  Indication for surgery, % (n)   PR 85.5 (136) 82.8 (24) 86.8 (144) 72.7 (16)   PS 10.1 (16) 3.5 (1) 9.0 (2) 9.1 (17)   Non-structural 1.3 (2) 0 (0) 1.2 (2) 0 (0)   Ross procedure 3.1 (5) 13.8 (4) 3.0 (5) 18.1 (4)  Diagnosis (all), % (n)   TOF 54.1 (86) 27.6 (8) 52.4 (87) 31.8 (7)   PS 8.8 (14) 10.3 (3) 9.0 (15) 9.1 (2)   Pulmonary atresia 13.8 (22) 24.1 (7) 15.1 (25) 18.2 (4)   AS 4.4 (7) 3.5 (1) 4.22 (7) 4.6 (1)   Truncus 3.8 (6) 6.9 (2) 3.61 (6) 9.1 (2)   TGA 5.7 (9) 13.8 (4) 4.8 (8) 22.7 (5)   DORV 5.0 (8) 3.5 (1) 4.8 (8) 4.6 (1)   Other 4.4 (7) 10.3 (3) 6.0 (10) 0 (0)  Diagnosis (binary), % (n)   TOF 54.1 (86) 27.6 (8) 52.4 (87) 31.8 (7)   All others 45.9 (73) 72.4 (21) 47.6 (79) 68.2 (15) Quantitative covariates  Age (years), mean + SD 15.11 + 2.7 14.3 + 2.3 15.3 + 2.7 14.1 + 2.7  Height (cm), mean + SD 161.5 + 13.3 158.6 + 15.4 161.4 + 13.1 158.8 + 17.6  Weight (kg), mean + SD 54.7 + 16.4 51.3 + 15.6 54.6 + 16.3 51.2 + 16.2  Body surface area, mean + SD 1.6 + 0.3 1.5 + 0.3 1.5 + 0.3 1.5 + 0.3  Prosthesis size (mm), mean + SD 24.4 + 1.7 23.3 + 1.7 24.4 + 1.7 23.1 + 1.7 Bold values indicate significant associations. AS: aortic stenosis; DORV: double outlet right ventricle; PR: pulmonary regurgitation; PS: pulmonary stenosis; SD: standard deviation; TGA: transposition of the great arteries; TOF: tetralogy of Fallot. Primary end points The end points of SVD and reintervention were not associated with the covariates such as sex, age, height, weight or BSA. Non-orthotopic prosthesis location and a diagnosis other than TOF were associated with SVD but not reintervention. Tables 2 and 3 indicate that a larger proportion of bioprosthesis patients received a prosthesis in the orthotopic position than homograft patients. Patients who experienced SVD were less likely to have received a prosthesis in the orthotopic position, whereas no relationship between reintervention and prosthesis location was observed. SVD was associated with a smaller mean prosthesis size of 23.3 mm when compared with a mean of 24.4 mm in those who did not develop SVD (Table 3). In the bioprosthesis group, 16.1% (n = 9) and 12.5% (n = 7) experienced SVD and reintervention within the study period, respectively. In the homograft group, 15.2% (n = 20) and 11.4% (n = 15) experienced SVD and reintervention, respectively. Figure 1A and B show the Kaplan–Meier curves for SVD and reintervention by prosthesis type. Graphical differences evident in the survival curves for SVD and reintervention were found to be statistically significant (P < 0.001 and P = 0.006, respectively). Figure 1: View largeDownload slide (A)Kaplan–Meier curves showing freedom from SVD after surgery compared between homografts (blue) and bioprosthetic valves (red) (log-rank test, P-value <0.001). (B)Kaplan–Meier curves showing freedom from reintervention after surgery compared between homografts (blue) and bioprosthetic valves (red) (log-rank test, P-value = 0.006). SVD: structural valve degeneration. Figure 1: View largeDownload slide (A)Kaplan–Meier curves showing freedom from SVD after surgery compared between homografts (blue) and bioprosthetic valves (red) (log-rank test, P-value <0.001). (B)Kaplan–Meier curves showing freedom from reintervention after surgery compared between homografts (blue) and bioprosthetic valves (red) (log-rank test, P-value = 0.006). SVD: structural valve degeneration. The unadjusted Cox regression analysis among the full sample found that patients who received a bioprosthesis were at 5.64 (95% CI = 2.11, 15.07) times the risk of SVD and 3.89 (95% CI = 1.40, 10.82) times the risk of reintervention over the study period. Subgroup analysis demonstrated no statistical difference in the performance of bovine and porcine bioprosthesis though there appears to be a trend towards better performance of the bovine bioprosthesis (Fig. 2A and B). Figure 2: View largeDownload slide (A)Kaplan–Meier curves showing freedom from SVD after surgery compared between bovine (blue) and porcine (red) bioprosthetic valves (log-rank test, P-value <0.152). (B)Kaplan–Meier curves of days until reintervention after surgery compared between bovine (blue) and porcine (red) bioprosthesis (log-rank test, P-value = 0.063). SVD: structural valve degeneration. Figure 2: View largeDownload slide (A)Kaplan–Meier curves showing freedom from SVD after surgery compared between bovine (blue) and porcine (red) bioprosthetic valves (log-rank test, P-value <0.152). (B)Kaplan–Meier curves of days until reintervention after surgery compared between bovine (blue) and porcine (red) bioprosthesis (log-rank test, P-value = 0.063). SVD: structural valve degeneration. Accounting for confounding covariates using propensity score matching Propensity score matching resulted in a total of 45 pairs of patients (45 with each prosthesis type – total of 90 patients) with adequate balance achieved for all covariates included in the propensity score and a median residual bias of 0.045 (Table 4). The Cox regression analysis performed on the propensity matched sample revealed that patients receiving a bioprosthesis were at almost 10 times the risk of experiencing SVD [hazard ratio (HR) = 9.18; 95% CI = 1.28, 65.64] and at more than 8 times the risk of undergoing a reintervention (HR = 8.34; 95% CI = 1.02, 67.86) during the study period. Table 4: Propensity matching: distribution of covariates by matched sample Homograft (n = 45) Bioprosthesis (n = 45) Residual bias Categorical covariates  Sex, % (n)   Male 53 (24) 49 (22) 0.088  Prosthesis location, % (n)   Orthotopic 73 (33) 71 (32) 0.049  Diagnosis (binary), % (n)   TOF 42 (19) 40 (18) 0.045 Quantitative covariates  Age (days), mean + SD 5584 + 1005 5614 + 1057 0.029  Height (cm), mean + SD 162.2 + 14.4 162.2 + 13.2 0.005  Weight (kg), mean + SD 54.4 + 15.2 55.6 + 15.6 0.075  Body surface area, mean + SD 1.56 + 0.27 1.57 + 0.26 0.062  Prosthesis size (mm), mean + SD 24.3 + 1.9 24.2 + 1.5 0.026 Homograft (n = 45) Bioprosthesis (n = 45) Residual bias Categorical covariates  Sex, % (n)   Male 53 (24) 49 (22) 0.088  Prosthesis location, % (n)   Orthotopic 73 (33) 71 (32) 0.049  Diagnosis (binary), % (n)   TOF 42 (19) 40 (18) 0.045 Quantitative covariates  Age (days), mean + SD 5584 + 1005 5614 + 1057 0.029  Height (cm), mean + SD 162.2 + 14.4 162.2 + 13.2 0.005  Weight (kg), mean + SD 54.4 + 15.2 55.6 + 15.6 0.075  Body surface area, mean + SD 1.56 + 0.27 1.57 + 0.26 0.062  Prosthesis size (mm), mean + SD 24.3 + 1.9 24.2 + 1.5 0.026 Analysis based on 90 matched patients (45 with a homograft and 45 with a bioprosthesis). The median bias for all the covariates was 0.047. SD: standard deviation; TOF: tetralogy of Fallot. Table 4: Propensity matching: distribution of covariates by matched sample Homograft (n = 45) Bioprosthesis (n = 45) Residual bias Categorical covariates  Sex, % (n)   Male 53 (24) 49 (22) 0.088  Prosthesis location, % (n)   Orthotopic 73 (33) 71 (32) 0.049  Diagnosis (binary), % (n)   TOF 42 (19) 40 (18) 0.045 Quantitative covariates  Age (days), mean + SD 5584 + 1005 5614 + 1057 0.029  Height (cm), mean + SD 162.2 + 14.4 162.2 + 13.2 0.005  Weight (kg), mean + SD 54.4 + 15.2 55.6 + 15.6 0.075  Body surface area, mean + SD 1.56 + 0.27 1.57 + 0.26 0.062  Prosthesis size (mm), mean + SD 24.3 + 1.9 24.2 + 1.5 0.026 Homograft (n = 45) Bioprosthesis (n = 45) Residual bias Categorical covariates  Sex, % (n)   Male 53 (24) 49 (22) 0.088  Prosthesis location, % (n)   Orthotopic 73 (33) 71 (32) 0.049  Diagnosis (binary), % (n)   TOF 42 (19) 40 (18) 0.045 Quantitative covariates  Age (days), mean + SD 5584 + 1005 5614 + 1057 0.029  Height (cm), mean + SD 162.2 + 14.4 162.2 + 13.2 0.005  Weight (kg), mean + SD 54.4 + 15.2 55.6 + 15.6 0.075  Body surface area, mean + SD 1.56 + 0.27 1.57 + 0.26 0.062  Prosthesis size (mm), mean + SD 24.3 + 1.9 24.2 + 1.5 0.026 Analysis based on 90 matched patients (45 with a homograft and 45 with a bioprosthesis). The median bias for all the covariates was 0.047. SD: standard deviation; TOF: tetralogy of Fallot. Secondary end points Two deaths were recorded over the study period (homograft n = 1, bioprosthesis n = 1). No statistically significant differences were observed between the homograft and bioprosthesis groups for non-structural valve deterioration, thrombosis, embolism, endocarditis, valve-related mortality, sudden unexplained death, cardiac death, all-cause mortality, permanent valve-related impairment and major adverse valve-related events (Table 1). DISCUSSION Our study aimed to compare the long-term performance of pulmonary homografts and stented xenograft bioprosthetic valves in the pulmonary position in patients aged 10–20 years at the time of implantation. The unadjusted Cox regression analysis revealed that a bioprosthesis was associated with 5.64 times the risk of SVD and 3.89 times the risk of reintervention when compared with pulmonary homografts. This risk increased to 9.18 times for SVD and 8.34 times for reintervention when adjusted for covariates using propensity score matching. Xenograft bioprosthetic valves (bovine pericardial or porcine) in the pulmonary position in adolescents and young adults Kwak et al. [11] in their comparison of 63 Carpentier-Edwards bovine pericardial valves with 40 Hancock 2 porcine valves (mean age 12.8 years) noted a higher rate of failure in the bovine pericardial valve group with freedom from reoperation of 97%, 87% and 50% at 1, 3 and 5 years, respectively. The relatively poor performance of bioprosthetic valves in our series is similar, with freedom from SVD decreasing from 91% at 3 years to 53% at 5 years and freedom from reintervention decreasing from 93% at 3 years to 68% at 5 years. Lee et al. [12] in their series of 181 patients (mean age 14 years) reported freedom from reoperation of 93% and 51% and freedom from valve dysfunction of 92% and 20% at 5 and 10 years, respectively. Valve function was stable up to 5 years, but by 10 years, approximately 80% required reoperation or manifested with valve dysfunction. In the report from Chen et al. [7] involving 170 PVR patients (median follow-up 48 months), freedom from reintervention dropped from 94% at 5 years to 36% at 10 years. After 39 months of follow-up, SVD was significantly worse in patients who had undergone PVR at younger than 15 years with a significantly higher risk for reintervention (HR 19.54). Buchholz et al. [13] identified age <19 years as a risk factor with freedom from valve degeneration of 65% at 5 years and 40% at 10 years when compared with 95% and 80%, respectively, in patients older than 19 years. In the largest published series to date, Nomoto et al. reported their experience with 611 bioprosthetic valves (median age 17.8 years; 50% <18 years). The risk of reintervention was approximately 5 times greater for children than adults. The reintervention rate rose from 8% at 5 years to 46% by 10 years. However, their analysis also included patients younger than 12 years who had significantly worse outcomes than older patients [14]. Homografts in the pulmonary position in adolescents and young adults In our study, pulmonary homografts demonstrated freedom from SVD of 92%, 85% and 82% at 5, 10 and 15 years, respectively. The freedom from reintervention was 93%, 88% and 85% at 5, 10 and 15 years, respectively. Similar findings have been reported by other investigators. Sarikouch et al. [15] reported 84.2% freedom from reintervention for cryopreserved homografts at 10 years (mean age 5.2 years). Boethig et al. [16] in their analysis of 188 homografts reported 83% freedom from reoperation at 10 years in patients over the age of 10 years. Forbess et al. [17] reported 5-year freedom from reintervention of 81% for cryopreserved homografts in children older than 10 years. Their study included a significant number of aortic homografts that were found to have accelerated degeneration in the cohort older than 10 years. Aortic homografts have previously been shown to have accelerated degeneration secondary to calcification in the pulmonary position and were excluded from our study [18]. Comparison of homografts and bioprosthetic valves in the pulmonary position in adolescents and young adults In our study, the performance of bioprosthetic valves and homografts was comparable within the first 3 years following implantation. By 5 years, homografts significantly outperformed bioprosthetic valves. Little published data are available directly comparing the performance of bioprosthetic valves with homografts in the pulmonary position in adolescents and young adults with only 1 study with sufficiently large numbers to permit a meaningful interpretation. Kanter et al. [19] reported the outcome of 100 PVRs (62 homografts and 38 porcine bioprosthetic valves) in 93 children. The mean age and valve size in the homograft group was 9.3 years and 21 mm, respectively, and the mean age and valve size in the porcine group was 11.4 years and 26 mm, respectively. No significant difference was observed between the 2 groups with respect to pulmonary stenosis. Severe PR was more common in the homograft group. At a mean follow-up of 5 years, a small but definite early reoperation rate was observed in the homograft group. In contrast, reoperation was not performed in the porcine group until 8 years after valve replacement. However, on closer examination of the data, the authors noted that all 7 children with a homograft who required replacement had the original pulmonary valve placed at the of age ≤3 years. The freedom from reoperation at 8 years for children older than 3 years at the time of PVR with a homograft was 100%. In their cohort, the overall age was younger, and only 44% (n = 17 of 38) of patients in the bioprosthesis group received a stented bioprosthesis when compared with our own study. Zubairi et al. [20] compared the performance of 56 cryopreserved pulmonary homografts with 113 heterografts. No difference in reoperation was observed among the 4 heterograft valve types and between homografts and heterografts with freedom of reoperation of 93% at 5 years and 71% at 10 years. The multivariate analysis identified younger age as a risk factor for early (<3 years) and late failure. Homografts were an independent risk factor for early failure. However, a higher proportion of children younger than 10 years received a homograft, and in children older than 10 years, no difference in reoperation was observed between homografts and heterografts. We identified only 1 previous study with similar methodology to ours. Batlivala et al. [21] reported a retrospective, single-centre comparison in patients aged 10–21 years who underwent PVR from May 1990 to December 2009 (median follow-up 4.4 years): 84 cryopreserved homografts (aortic n = 50, pulmonary n = 34) and 170 bioprosthetic valves. At 5 years, freedom from moderate or severe pulmonary stenosis was 86% and freedom from moderate or severe PR was 84% with no difference between the 2 cohorts. Freedom from any reintervention was 90%, 67% and 47% at 3, 5 and 15 years, respectively. Freedom from PVR was 96%, 74% and 48% at 5, 10 and 15 years, respectively. The performance of bioprosthetic valves in their study mirrored the findings from our study. However, in contradistinction to our study, the authors found no difference between the homograft and bioprosthetic valve cohorts at all time points. The duration of follow-up was longer in our study (median 7.1 years vs 4.4 years). Additionally, the homograft group in this study contained 50 aortic homografts, which have previously been shown to deteriorate more rapidly in the pulmonary position [22]. Only 4 aortic homografts were available in our study population, and in the interest of consistency, we intentionally excluded them from the final analysis. Bovine versus porcine bioprosthetic valves Our subgroup analysis comparing the durability of bovine and porcine bioprosthesis demonstrated a trend towards higher reintervention rates in porcine valves. However, similar to other published reports, no statistically significant difference was observed in the performance of these 2 valve types [7]. Limitations Our findings must be interpreted in the light of several limitations. First, although we used propensity scores to match the comparison groups by important prognostic factors, this method was limited by the range of data collected, and our hospital records failed to account for factors such as donor homograft and recipient blood group compatibility. Second, patients receiving a bioprosthesis were more likely to have had their operations recently when compared with those receiving homografts resulting in unequal follow-up times and cohort effects by which bioprosthesis patients were likely to benefit from more recent advances in surgical and medical technologies. Importantly, however, both of these potential biases are likely to have attenuated our effect estimates, thus leaving our substantive conclusion unchanged. Third, the sample size among the bioprosthesis group is comparatively small as we approach 5 years. Finally, among the initial 209 participants, 21 were excluded from the analysis due to having no recorded height or weight at surgery. Although those lost to follow-up were more likely to be older, have valves inserted in an extra-anatomical position and were more likely to have a TOF diagnosis, having retained 90% of the sample, we believe it unlikely that this attrition would bias our results. CONCLUSION In our patient population, pulmonary homografts outperformed stented xenograft bioprosthetic valves when implanted in the pulmonary position in patients aged 10–20 years. The difference in performance was evident by 5 years. On the basis of these findings, we recommend the use of a pulmonary homograft for PVR in this age group in patients undergoing surgery for congenital heart disease. Conflict of interest: none declared. REFERENCES 1 Lee C , Kim YM , Lee CH , Kwak JG , Park CS , Song JY et al. Outcomes of pulmonary valve replacement in 170 patients with chronic pulmonary regurgitation after relief of right ventricular outflow tract obstruction: implications for optimal timing of pulmonary valve replacement . 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Risk factors for prosthesis failure in pulmonary valve replacement . Ann Thorac Surg 2011 ; 91 : 561 – 5 . Google Scholar CrossRef Search ADS PubMed 21 Batlivala SP , Emani S , Mayer JE , McElhinney DB. Pulmonary valve replacement function in adolescents: a comparison of bioprosthetic valves and homograft conduits . Ann Thorac Surg 2012 ; 93 : 2007 – 16 . Google Scholar CrossRef Search ADS PubMed 22 Yankah AC , Alexi-Meskhishvili V , Weng Y , Berger F , Lange P , Hetzer R. Performance of pulmonary and aortic homografts in the right ventricular outflow tract in children . J Heart Valve Dis 1995 ; 4 : 392 – 5 . Google Scholar PubMed © The Author(s) 2018. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved. This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/about_us/legal/notices)

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European Journal of Cardio-Thoracic SurgeryOxford University Press

Published: Apr 11, 2018

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