Introduction
Tetralogy of Fallot is one of the most common cyanotic CHDs, including ventricular septal defect, right ventricular outflow tract stenosis, aortic saddle and right ventricular hypertrophy. The incidence of tetralogy of Fallot is 0.3–0.6%, accounting for 5–7% of CHD. Reference Huishan and Shoujun1 The first repair of tetralogy of Fallot was completed in 1954, including closure of ventricular septal defect and relief of right ventricular outflow tract stenosis. Reference LILLEHEI, COHEN and WARDEN2 The risk of tetralogy of Fallot repair is low, and the long-term survival rate is satisfactory. The 10-year and 30-year survival rates were 97.7% and 94.5%, respectively. Freedom from reoperation at 10 and 20 years was 86.4 and 65.4%, respectively. Reference Ishigami, Ye and Buratto3 Transannular patch is the most common method to correct tetralogy of Fallot with hypoplastic pulmonary annulus. However, a serious disadvantage of transannular patch is loss of valve structural integrity and inducing chronic severe pulmonary regurgitation(PR), which has been proven to have long-term fatal disadvantages in tetralogy of Fallot patients. Transannular patch is related to postoperative pulmonary regurgitation and its progression. Severe postoperative pulmonary regurgitation leads to right ventricular volume overload, which in turn leads to postoperative right ventricular dilatation and dysfunction, and affects left ventricular function due to ventricular interaction. Reference Vanderlaan and Barron4 Due to dilatation of the right ventricle and atrium, it leads to deterioration of cardiac function and arrhythmias over time. Reference Mouws, de Groot and van de Woestijne5 Transannular patch is a risk factor for increased risk of early death. Reference Smith, McCracken and Thomas6 In propensity-score-matched analysis, freedom from pulmonary valve replacement at 15 years was higher in the valve-sparing group than in the transannular patch group. Freedom from reoperation for right ventricular outflow tract obstruction at 15 years was lower in the valve-sparing group than in the transannular patch group. Reference Ishigami, Ye and Buratto3 In view of the long-term adverse effects of transannular patch on tetralogy of Fallot children, the surgical method of tetralogy of Fallot repair has been changed from transannular patch to valve-sparing repair as much as possible in the past decade. 2020 Chinese expert consensus on surgical treatment of CHD (10) proposed that the purpose of surgical treatment of tetralogy of Fallot is to relieve right ventricular outflow tract stenosis, close the ventricular septal defect, preserve the pulmonary valve and maintain right ventricular function as much as possible. Reference Huishan and Shoujun1 The 2022 expert consensus of the American Association for Thoracic Surgery Reference Miller, Stephens and Goldstone8 also clearly points out that pulmonary valve function should be preserved as much as possible for tetralogy of Fallot patients undergoing radical repair, and pulmonary valve reconstruction can be considered if it cannot be salvaged. However, there are controversies about the application indications and surgical strategies of valve-sparing repair and lack of clear clinical guidelines. This article reviews the research progress of hot issues related to valve-sparing repair for tetralogy of Fallot, in order to provide evidence-based medical evidence for when to perform valve-sparing repair in tetralogy of Fallot patients, so as to better improve the quality of life of patients.
Advantages of valve-sparing repair
Compared with transannular patch, valve-sparing repair has better initial haemodynamic performance and earlier extubation time after surgery. Reference Sen, Najjar and Yimaz9 The increase of right ventricular end-diastolic diameter in patients with valve-sparing repair is significantly smaller than that in patients with transannular patch, and the right ventricular dilatation is less within 10 years. Therefore, the valve-sparing repair may be beneficial to the right ventricular geometry of TOF. Reference Hickey, Pham-Hung and Halvorsen10 valve-sparing repair can reduce right ventricular volume overload, preserve the dynamic motion of the pulmonary valve ring, and help to maintain the growth potential of the pulmonary valve. Reference Arafat, Elatafy, Elshedoudy, Zalat, Abdallah and Elmahrouk11 The survival rate of tetralogy of Fallot patients treated with valve-sparing repair is significantly higher than that of patients with TAP. Reference Mouws, de Groot and van de Woestijne5 A meta-analysis of 15 retrospective studies involving 1396 subjects also showed that the valve-sparing repair group had lower surgical mortality and lower reintervention rates 5 to 10 years after surgery than the transannular patch group. Reference Yi, Wang and Xu12 In addition, Bacha et al. Reference Bacha13 showed that valve-sparing repair significantly reduced the incidence of moderate to severe pulmonary regurgitation and other transannular patch repair-related complications compared with transannular patch. In addition, the long-term outcome of valve-sparing repair is excellent, with 20-year actuarial survival rate and reoperation-free rate of 98 and 95%, respectively. Reference Hoashi, Kagisaki and Meng14 It has been proposed that in the repair of tetralogy of Fallot, an acceptable residual stenosis of the right ventricular outflow tract is more beneficial than a full enlargement of the right ventricular outflow tract. Reference Lozano-Balseiro, Garcia-Vieites and Martinez-Bendayan15 Tetralogy of Fallot management has shifted from a strategy aimed at alleviating pulmonary stenosis to a strategy aimed at preserving the pulmonary valve, Reference Arafat, Elatafy, Elshedoudy, Zalat, Abdallah and Elmahrouk11 accepting a higher peak valve gradient in exchange for a lower degree of pulmonary regurgitation. Reference Sorabella and Si16 Therefore, it is beneficial and necessary to actively adopt the valve-sparing repair in the treatment of tetralogy of Fallot patients and should be the preferred strategy.
Indications for valve-sparing surgery
Surgical treatment should be considered in all tetralogy of Fallot patients once diagnosed. The valve-sparing repair indication is currently controversial. Indiscriminate valve-sparing repair may also have a negative impact on long-term prognosis, as the incidence of early pulmonary stenosis after valve-sparing repair is higher than that after transannular patch. Reference D’Udekem, Galati and Rolley17 Therefore, clarifying the indication of valve-sparing repair is crucial for selecting an appropriate surgical strategy. Several reference indicators for valve-sparing repair reported in previous literature are shown (Figure 1).
Tetralogy of Fallot surgery decision-making process. Abbreviations : TOF = tetralogy of Fallot; TAP = transannular patch; VS = valve-sparing repair; MDT = multi-disciplinary treatment; PVA = pulmonary valve annulus; GA = great aortic valve annulus; PAI = pulmonary valve annulus index; PAAI = pulmonary valve annulus area index; PVA prop = proportion of pulmonary valvular annulus; PGmax = peak systolic pressure gradient; PV Vmax = peak velocity across the pulmonary annulus; RV/LV ratio = right ventricle/left ventricle pressure ratio; MD = mechanical dilation; BPV = balloon pulmonary valvuloplasty; RSVP = reconstruction of a single cusp valve with a patch; SPA = valve-sparing repair with skeletonisation of the pulmonary annulus; NPV = neopulmonary valve creation using right atrial appendage tissue.
Pulmonary valve annulus Z score
Kirklin et al. Reference Kirklin, Kirklin and Pacifico18 proposed in 1990 that the pulmonary valve annulus diameter should be compared with the overall standard, that is, the pulmonary valve annulus Z score, as a method to determine whether transannular patch is needed. The data can be measured and calculated using echocardiography, computed tomography, and angiography. The advantage is that the Z score is a measurement that is reliable, objective, and easily reproducible on standard echocardiography. As for the determination of the cut-off value of Z score, it varies from −4 to −1 in different studies. Reference Choi, Kwon and Roh19 Awori et al. Reference Awori, Mehta, Mitema and Kebba20 proposed that transannular patch should be performed when pulmonary valve annulus Z value < −4. Sen et al. Reference Sen, Najjar and Yimaz9 proposed that transannular patch could be performed when the pulmonary valve annulus Z value was less than −1.3. Wang et al. Reference Wang, Li, Ding, Zhu, Li and Yi21 pointed out that the critical value of pulmonary valve annulus Z score was −1.96. Lyu et al. Reference Lyu, Jin and Yang22 pointed out that pulmonary valve Z score < −1.98 was feasible for transannular patch. Stellin et al. Reference Stellin, Guariento and Vida23 successfully performed pulmonary valve reconstruction in patients with Z scores between −4 and −3. Although the postoperative pulmonary valve was not anatomically satisfactory, its function was qualified, and the mid-term results were satisfactory, with no early death, late death, or need for reoperation. However, according to the study of Guariento et al. Reference Guariento, Schiena and Cattapan24 the risk of moderate to severe pulmonary regurgitation increased in patients with Z score ≤−2.85 during the 5-year follow-up of patients receiving valve-sparing repair, so Z score −2.85 was determined as the cut-off value of good surgical results and valve function without residual obstruction. Based on the current study, only patients with a Z score < −4 and the presence of highly hypoplastic valves must undergo transannular patch. However, a systematic review of pulmonary valve annulus Z score predicting the effectiveness of valve-sparing repair Reference Sinha, Gooty, Jang, Dodge-Khatami and Salazar7 showed that there was no correlation between the decrease of preoperative pulmonary valve annulus Z score and the increase of right ventricular outflow tract reintervention rate in quantitative terms. In observational studies, valve-sparing repair for tetralogy of Fallot was based on intraoperative assessment and pulmonary valve size after complete relief of right ventricular outflow tract obstruction at all levels, rather than pulmonary valve annulus Z score derived from preoperative echocardiography.
Great aortic valve annulus ratio(GA ratio, the ratio of pulmonary valve annulus diameter to aortic valve annulus diameter)
Although the pulmonary valve annulus Z score is widely used, the calculation of the Z score is very complex and is affected by height, weight, and body surface area. There are many formulas for the calculation of body surface area, and it also needs to be calculated separately for different populations, all of which increase the complexity of calculating pulmonary valve annulus Z score. Because the determination of the cut-off value of Z score has not been a recognised result, the great aortic valve annulus ratio has entered the field of view of researchers. Reference Pettersen, Du, Skeens and Humes25 According to the study of Choi et al. Reference Choi, Sung and Kim26 , compared with Z score, great aortic valve annulus ratio has higher sensitivity and specificity in predicting transannular patch demand, and it is also simpler and easier to implement in clinical practice. They performed a retrospective study of 122 children with tetralogy of Fallot and used a great aortic valve annulus ratio of 0.559 as a cut-off value to predict whether children should undergo valve-sparing repair, and patients with great aortic valve annulus ratio higher than 0.599 were suitable for valve-sparing repair. However, Wang et al. Reference Wang, Li, Ding, Zhu, Li and Yi21 believed that the critical value of great aortic valve annulus ratio was 0.64, and less than 0.64 could better predict transannular patch.
Pulmonary valve annulus index
Pulmonary valve annulus index is defined as the ratio of pulmonary valve annulus diameter to half of the sum of aortic valve annulus diameter and pulmonary valve annulus diameter. Kasturi et al. Reference Kasturi, Balaji and Sudhakar27 used pulmonary valve annulus index to predict whether tetralogy of Fallot children need valve-sparing repair. When pulmonary valve annulus index is greater than 0.73, valve-sparing repair can be considered. Lyu et al. Reference Lyu, Jin and Yang22 proposed that pulmonary valve annulus index < 0.53 is an effective indicator for predicting transannular patch. Wang et al. Reference Wang, Li, Ding, Zhu, Li and Yi21 pointed out that the cut-off value of pulmonary valve annulus index was 0.78.
Pulmonary valve annulus area index
In addition, pulmonary valve annulus area index seems to be a feasible indicator to predict transannular patch. Pulmonary valve annulus area index is defined as pulmonary valve annulus area to aortic valve annulus diameter area ratio. Zhao et al. Reference Zhao, Cai and Teng28 pointed out that pulmonary valve annulus area index is a useful and accessible indicator for predicting transannular patch, which is easy to be apply in clinical practice. The accuracy of prediction can be improved by incorporating transpulmonary valve velocity. The optimal cut-off for the pulmonary valve annulus area index for transannular patch placement was 0.23, with a sensitivity of 86.5% and a specificity of 69.1%. The area under the curve (AUC) of the pulmonary valve annulus area index tended to be better than that of the Z score, although this difference was not significant. The optimal cut-off for PV Vmax for transannular patch placement was 4.3 with a sensitivity of 36.5% and a specificity of 88.9%. Combination analysis of the pulmonary valve annulus area index and peak velocity across the pulmonary annulus (PV Vmax) showed better predictive value than the pulmonary valve annulus area index and PAV Z score. Lyu et al. Reference Lyu, Jin and Yang22 proposed that the pulmonary valve annulus area index cut-off value of transannular patch is 0.25, and Wang et al. Reference Wang, Li, Ding, Zhu, Li and Yi21 proposed that the pulmonary valve annulus area index cut-off value of transannular patch is 0.40.
Proportion of pulmonary valvular annulus
In the normal heart, the conus arteriosus septum divides the truncus arteriosus into two equal right ventricular outflow tracts and left ventricular outflow tracts. Correspondingly, the pulmonary annulus and the aortic annulus are nearly identical in size. However, in tetralogy of Fallot, the anterior displacement of the conus septum leads to the formation of one small pulmonary annulus and one large aortic annulus. The proportion of pulmonary valvular annulus was defined as the ratio of the diameter of pulmonary valvular annulus to the sum of the diameter of aortic annulus and pulmonary valve annulus. Cai et al. Reference Xiao-wei, Jun-fei and Xiao-bing29 retrospectively analysed the clinical data of 254 patients who underwent one-stage radical repair of tetralogy of Fallot in Guangdong Provincial People’s Hospital from January 2016 to January 2018, and found that pulmonary valve annulus proportion may better predict transannular patch. In the transannular patch and valve-sparing repair groups, the cut-off value of pulmonary valve annulus proportion was 0.353 (AUC 0.781, 95%CI 0.725−0.831), the sensitivity was 86.6%, and the specificity was 62.2%. The cut-off value of z score was −2.13 (AUC 0.766, 95%CI 0.709−0.817), the sensitivity was 85.4%, and the specificity was 56.7%. Although there was no significant difference in AUC between the two groups, the sensitivity and specificity of pulmonary valve annulus proportion were slightly higher than those of PAV Z value. Therefore, pulmonary valve annulus proportion has a certain guiding significance for the choice of transannular patch or not in tetralogy of Fallot radical repair, and in clinical practice, it has the advantages of being easy to obtain and convenient to calculate, which is conducive to clinical application. Wang et al. Reference Wang, Li, Ding, Zhu, Li and Yi21 obtained similar results, the cut-off value of pulmonary valve annulus proportion was 0.37.
Peak systolic pressure gradient(PGmax)/ peak velocity across the pulmonary annulus(;PV Vmax);
Siddiqi et al. Reference Siddiqi, Adewale and Pena30 found that there was a strong correlation between transvalvular pressure gradient measured by transesophageal echocardiography during surgery and the possibility of reintervention after valve-sparing repair. When PGmax was greater than 45 mmHg on intraoperative transesophageal echocardiography after valve-sparing repair, the risk of reintervention was about 4 times higher. Therefore, when PGmax is greater than 45 mmHg, the surgical strategy should be switched to transannular patch. However, Zhao et al. Reference Zhao, Cai and Teng28 found that the optimal cut-off for PV Vmax for transannular patch placement was 4.3 m/s. with a sensitivity of 36.5% and a specificity of 88.9%.
Right ventricle/left ventricle pressure ratio
Postoperative right ventricle/left ventricle pressure ratio(RV/LV ratio) is an indicator to evaluate surgical outcomes, and a ratio greater than 0.5 is associated with negative outcomes. Reference Sen, Najjar and Yimaz9 Satisfactory relief of right ventricular outflow tract stenosis was defined as RV/LV ratio <0.5, transpulmonary gradient <20 mmHg and right ventricular outflow tract velocity <3 m/s. If RV/LV ratio >0.8, transpulmonary pressure gradient >40 mmHg, right ventricular outflow tract velocity >3.5 m/s, the right ventricular outflow tract should be re-operated to relieve residual stenosis. In the study of Choi et al. Reference Choi, Kwon and Roh19 if it was necessary to switch from valve-sparing repair to transannular patch, the RV/LV ratio after valve-sparing repair was greater than 0.5, while the Z score was less than −2. These results suggest that RV/LV ratio may be useful in determining the need for conversion to transannular patch after valve-sparing repair.
Intraoperative examination of the pulmonary valve
The above indications do not consider the anatomical structure and characteristics of the pulmonary valve, and do not provide any information about the number of leaflets and the degree of hypoplasia, which are important data for valve repair and the key to ensure good repair duration and long-term valve function. Reference Lozano-Balseiro, Garcia-Vieites and Martinez-Bendayan15 Therefore, relying only on these indications in tetralogy of Fallot radical repair may lead to incorrect judgement or poor surgical results. Reference Choi, Kwon and Roh19 Pulmonary valve bicuspid malformation is one reason why predictive models fail to predict the possible avoidance of transannular patch. Reference Wang, Li, Ding, Zhu, Li and Yi21 Therefore, intraoperative examination of the valve is more important. During the operation, the specific repair strategy can be decided according to the pulmonary valve annulus and the shape of the pulmonary valve after dilatation by Hegar dilator. Reference Siddiqi, Adewale and Pena30
Different valve-sparing repair strategies
The valve-sparing repair strategy mainly includes: The ventricular septal defect was closed through the right atrium or pulmonary artery incision, and the hypertrophic muscle in the infundibulum was removed. A small right ventricular incision (<0.5 cm) or pulmonary artery incision was performed to completely relieve the stenosis of the junction between the pulmonary valve and the right ventricular infundibulum, and an appropriate width patch was used to widen the outflow tract incision and the distal main pulmonary artery longitudinal incision to avoid excessive resection of right ventricular muscle bundle, reduce postoperative pulmonary valve regurgitation and protect right ventricular function.
Pulmonary valvulotomy and mechanical dilation/balloon pulmonary valvuloplasty
Through the pulmonary artery wall incision, the incision was made along the junctional ridge of the fusion leaflets to the base of the valve, and then the pulmonary artery wall incision was sutured. The Hegar dilator can be used to measure the anterior and posterior orifice or to gently dilate the pulmonary valve under direct vision. Reference Bacha31 This surgical procedure exerts axial shear forces on the tissues surrounding the pulmonary annulus, potentially damaging both the valve and the pulmonary annulus. For patients with mild to moderate pulmonary valve stenosis, mechanical dilation is an appropriate surgical method. Reference Yi, Wang and Xu12 A Hegar dilator was used to determine the size of the effective valve orifice on the basis of a pulmonary valve commissure incision. It is generally started with a balloon 1 mm larger than the Hegar size, which easily slides across the valve and is inserted and inflated through the infundibular incision or via the right atrial path. Reference Hofferberth, Nathan and Marx32 Unlike mechanical dilation, the balloon can be introduced into the annulus with a diameter much smaller than the orifice, and stable dilation occurs in a stationary position. The radial transmission of stress expands and stretches the annulus, which has the potential to enable remodelling and growth of the pulmonary annulus. Reference Sluysmans, Neven and Rubay33,Reference Bautista-Hernandez, Cardenas, Martinez-Bendayan, Loyola, Rueda and Portela34 Balloon pulmonary valvuloplasty is generally used for moderate pulmonary valve stenosis or hypoplasia. Reference Bacha13
Reconstruction of a single cusp valve with a patch(RSVP)
Sharp division was used for fused commissures or leaflets tethered to the pulmonary wall. The pulmonary annulus was sized using Hegar dilators. If the pulmonary annulus was more than 2 standard deviations below the predicted mean diameter (z score < 2), the pulmonary annulus was divided. The appropriate patch material (based on surgeon’s preference) was selected. A triangular piece of the patch with a width twice the diameter of the predicted pulmonary annulus for the patient was prepared. The patch was sutured to the edges of the anterior pulmonary leaflet, and the suture line was then carried along the endocardial edge of the infundibulotomy (Figure 2, a). In patients with an anteroposterior orientation of the commissures, the patch was sutured to the edges of the divided commissure. Even where the commissure was eccentric, the patch was sutured to the free edge of the leaflets on either side. A second appropriately sized autologous or bovine pericardial patch was sutured to the epicardial edge of the infundibulotomy to create a neosinus over the augmented leaflet and the suture line was extended to close the pulmonary arteriotomy (Figure 2, b). RSVP can preserve the native valve to a great extent and effectively avoid postoperative pulmonary regurgitation. However, the disadvantages of patch calcification, thrombosis, endocarditis, and poor durability also limit its application in tetralogy of Fallot treatment. Reference Sen, Najjar and Yimaz9,Reference Patukale, Daley and Betts35
Reconstruction of a single cusp valve with a patch. ( a ) A triangular piece of e-PTFE patch with a width twice the diameter of the predicted pulmonary annulus is sutured to the edges of the anterior pulmonary leaflet. The suture line is then carried along the endocardial edge of the infundibulotomy. ( b ) A second appropriately sized autologous or bovine pericardial patch is sutured to the epicardial edge of the infundibulotomy to create a neosinus over the augmented leaflet. The suture line is extended to close the pulmonary arteriotomy.
Delamination technique
For patients with severe pulmonary artery stenosis, in addition to RSVP, pulmonary valve delamination technique based on BD has also been introduced as a valve-preservation strategy in recent years. Reference Dharmapuram, Ramadoss, Goutami, Verma, Pande and Devalaraja36 In severe pulmonary stenosis, the leaflet is insufficient to cover the new entire pulmonary annulus area after the balloon separates the pulmonary valve leaflet intersections. The delamination technique involves layering the base of each pulmonary valve with a scalpel, occasionally extending the layering into the right ventricular muscle to obtain more leaflet tissue for binding (Figure 3). Subsequently, the extended pulmonary valve is resuspended to create a new pulmonary valve commissure, thereby restoring pulmonary valve function. When leaflet tissue for pulmonary valve reconstruction is lacking, a small triangular prosthetic patch material can be added to lengthen the leaflet. This delamination increased the mobility and the free surface area. This is in addition to the small infundibular incision and aggressive resection of the sub-valvar tissue. Reference Vida, Angelini and Guariento37
Delamination technique. ( a ) Schematic illustration showing the fused cuspal apparatus to the pulmonary artery wall in longitudinal section. ( b ) Technique of delamination and release of the fused cuspal apparatus from the pulmonary artery wall. The arrows indicate the line of release of the fused apparatus and proceeding to the delamination of the bases.
Valve-sparing repair with skeletonisation of the pulmonary annulus(SPA)
Turkoz et al. Reference Turkoz, Dogan, Oktay and Saygili38 describe a novel valve-sparing technique for tetralogy of Fallot repair that primarily consists of skeletonisation of the anterior part of the pulmonary annulus and gentle dilatation by preserving the pulmonary valve and annulus integrity. With this technique, a scalpel is applied to completely dissect the surrounding tissue of the anterior pulmonary annulus, leaving only the annulus fibrosus of the anterior pulmonary annulus. After skeletonisation of the anterior part of the annulus, the pulmonary annulus was gently dilated using a Hegar dilator. Finally, the pulmonary valve annulus and pulmonary artery were reconstructed using the pericardial patch (Figure 4). Because there is no myocardial tissue on the anterior surface of the pulmonary annulus, it is assumed that dilation of the pulmonary annulus is more effective with less rebound effects than other techniques that preserve the thick myocardial tissue surrounding the pulmonary annulus. In addition, the use of interrupted sutures to attach a wider pericardial patch to the skeletonised pulmonary annulus may further increase the growth capacity of the pulmonary annulus.
Valve-sparing repair with skeletonisation of the pulmonary annulus. ( a ) Skeletonisated pulmonary valve annulus. ( b ) Dilatation of the pulmonary annulus with Hegar dilators. ( c ) Internal view of the attached pericardial patch to the pulmonary annulus. ( d ) Completed patch reconstruction.
Neopulmonary valve creation using right atrial appendage tissue(NPV)
RSVP has a high rate of postoperative reintervention due to the problem of patch materials, so it is imperative to find new patch materials or surgical methods. Linda J. Schulte et al. Reference Schulte, Miller and Bhat39 proposed a new reconstruction valve material, that is, to perform tetralogy of Fallot repair by constructing an autologous right atrial appendage valve. After the closure of the ventricular septal defect and the resection of the right ventricular outflow tract muscle, the autologous right atrial appendage valve was created and implanted, so as to play a pulmonary valve function (Figure 5). Neopulmonary valve offers an alternative option in patients with a small PV. It is a safe and effective method to prevent pulmonary regurgitation after tetralogy of Fallot repair, with good results in the short and medium term at least. Reference Amirghofran, Edraki and Edraki40 A longer follow-up period is needed to confirm whether this new valve can eliminate or significantly delay the need for pulmonary valve replacement in these patients. Reference Egunov, Kozhanov, Cetta and Krivoshchekov41
Neopulmonary valve creation using right atrial appendage tissue. ( a ) Right atrial appendage neopulmonary valve positioned in the native pulmonic valve position. ( b ) The anterior pulmonary homograft patch is attached to the main pulmonary artery opening beginning at the most distal aspect and brought inferiorly using continuous 6-0 polypropylene. The stitch is continued across the anterior neopulmonary valve annulus. ( c ) The anterior patch is completed inferiorly.
Outcomes of different valve-sparing surgical strategies
Studies have shown that the prognosis of tetralogy of Fallot patients without surgical treatment is significantly worse than that of those undergoing surgery. Reference Bertranou, Blackstone, Hazelrig, Turner and Kirklin42 The survival rates at 10, 20, 30 and 40 years after radical repair of tetralogy of Fallot were 98, 96, 92 and 86%, respectively. Reference Cuypers, Menting and Konings43
Mechanical dilation/balloon pulmonary valvuloplasty
Robinso et al. Reference Robinson, Rathod and Brown44 reviewed the retrospective analysis of 238 children younger than 180 days who underwent radical repair of tetralogy of Fallot (TAP group n = 111, commissurotomy group or mechanical dilation group n = 71, balloon pulmonary valvuloplasty n = 32, or no valvar intervention n = 24) found rates of valve growth did not differ across groups, but Z scores were 0.58 lower for the balloon pulmonary valvuloplasty group across all time points (P = .001). Freedom from reintervention was shorter for the balloon pulmonary valvuloplasty group than for the other groups (P < .001). In patients with tetralogy of Fallot and hypoplastic pulmonary valve, the longitudinal growth of the pulmonary annulus is obvious during intraoperative balloon pulmonary valvuloplasty with preservation of the pulmonary valve, and the size of the pulmonary annulus tends to be normal over time. Although balloon pulmonary valvuloplasty is used in more patients with hypoplastic valves, postoperative valve growth and pulmonary regurgitation are similar to conventional methods, but the rate of reintervention is higher. Although the precise role of this technique requires further refinement, it may be most appropriate for patients with moderate pulmonary valve stenosis and moderate pulmonary valve hypoplasia. Hofferberth et al. Reference Hofferberth, Nathan and Marx32 obtained similar results. They evaluated 162 consecutive patients with tetralogy of Fallot and pulmonary stenosis who underwent valve-sparing repair, with Balloon dilation (BD) under 1 year of age. Twenty-five patients (15.4%) required reintervention due to residual valvular stenosis. Multivariate analysis showed that preoperative annulus Z score less than 2.45 (P < 0.036) and younger age at surgery (P < 0.001) were independent risk factors for early reintervention of stenosis. The prevalence of freedom from at least moderate pulmonary regurgitation was 77% at 1 year, 61% at 3 years, and 43% at 5 years after repair. At mid-term follow-up, right ventricular diameter was not significantly different from that of a matched cohort of patients who underwent transannular patch. Studies have shown that this technique is associated with progressive pulmonary dysfunction and right ventricular dilatation. Balloon pulmonary valvuloplasty is not a long-term solution to preserve pulmonary valve function in tetralogy of Fallot patients.
Reconstruction of a single cusp valve with a patch
Patukale et al. Reference Patukale, Daley and Betts35 retrospectively analysed the clinical data of 120 patients with tetralogy of Fallot and 11 patients with double outlet right ventricle and pulmonary valve stenosis. Patch material was expanded polytetrafluoroethylene (n = 76), glutaraldehyde-treated autologous pericardium (n = 47) and bovine pericardium (n = 8). The 1 - and 5-year rates of freedom from severe pulmonary regurgitation were 85 and 76%, respectively. The 5-year and 10-year rates of freedom from moderate or higher pulmonary regurgitation were 69 and 30%, respectively. Three patients underwent pulmonary valve replacement, and 9 patients underwent balloon pulmonary valvuloplasty. Freedom from intervention for pulmonary stenosis at 1 and 5 years was 98 and 94%, respectively. The use of expanded polytetrafluoroethylene (PTFE) frees patients from moderate or higher pulmonary regurgitation. Studies have shown that the incidence of severe pulmonary regurgitation during mid-term follow-up is less than 50% for RSVP. The effect of expanded polytetrafluoroethylene patch is better than that of pericardium. A meta-analysis of 10 studies (including 8 retrospective cohort studies and 2 randomised controlled trials) involving 526 tetralogy of Fallot patients showed that, compared with transannular patch, RSVP had significant advantages in shortening the length of hospital stay and reducing the degree of pulmonary regurgitation in tetralogy of Fallot patients, but there was no significant difference in mortality. Reference Wei, Li and Ling45 Sen et al. Reference Sen, Najjar and Yimaz9 retrospectively analysed the clinical data of 80 children with tetralogy of Fallot from January 2010 to December 2014. The patients were divided into three groups according to different surgical methods: balloon pulmonary valvuloplasty/commissurotomy group (29 cases), RSVP group (19 cases) and transannular patch group (32 cases). The median follow-up time was 19 months (range, 1–59 months). The incidence of severe pulmonary regurgitation in the RSVP group was 100, 60 and 20% immediately after surgery, 6 months and 20 months after surgery, respectively, which was significantly lower than that in the transannular patch group (p < 0.05). There was no significant difference in pulmonary stenosis between RSVP and transannular patch at follow-up. Previous studies have shown that RSVP can be used to repair tetralogy of Fallot in patients with small PV, with good short- and medium-term results. Sasikumar et al. Reference Sasikumar, Sasidharan, Tharakan, Dharan, Mathew and Karunakaran46 conducted a prospective study on 30 tetralogy of Fallot patients who underwent RSVP, and the results showed that RSVP reduced pulmonary regurgitation immediately after surgery, but a large part of single-cusp valve function was lost, and pulmonary regurgitation progressed after 1 year. Bacha Reference Bacha13 specifically followed up patients with valve reconstruction and noted that pulmonary regurgitation progressed over time. At the last follow-up, about 80% of patients developed at least moderate pulmonary regurgitation, but none developed pulmonary stenosis or required reoperation. The above results suggest that despite the significant advantages of RSVP compared with transannular patch in preventing pulmonary regurgitation, pulmonary regurgitation will inevitably occur in most patients after a period of time. Fibrocollagen incorporation in the single cusp valve may be one of the reasons for the occurrence of progressive pulmonary regurgitation. Reference Turrentine, McCarthy, Vijay, McConnell and Brown47 The optimal size of the patch determines the efficacy of the valve, and poor patch size may also be one of the reasons for pulmonary regurgitation progression. Reference Vogt, Genoni, Kunzli and Turina48 In addition, the implantation of a single cusp valve does not have a supporting frame, and lack of support may also lead to early valve failure. Reference Sasikumar, Sasidharan, Tharakan, Dharan, Mathew and Karunakaran46 Therefore, how to better prevent the progression of pulmonary regurgitation and which factors affect the prognosis after RSVP still need to be further studied.
Delamination technique
Dharmapuram et al. Reference Dharmapuram, Ramadoss, Goutami, Verma, Pande and Devalaraja36 reported that the Z value of the repair can be extended to −3.5 by Delamination technique. They believed that the annulus could be adequately preserved by the Delamination technique. Vida et al. Reference Vida, Angelini and Guariento37 also found that none of the patients who applied the Delamination technique had pulmonary valve dysfunction, right ventricular muscle haematoma or other abnormal signs indicating failure of the Delamination technique during a two-year follow-up. This indicates that the prognosis of Delamination technique is satisfactory in the short term, but due to the short follow-up time and small sample size, the long-term results of this technique still need to be further studied.
Valve-sparing repair with skeletonisation of the pulmonary annulus
Turkoz et al. Reference Turkoz, Dogan, Oktay and Saygili38 found that 12 patients who underwent valve-sparing repair with skeletonisation of the pulmonary annulus were successfully discharged without complications. None of the patients required reintervention during the study. One month after surgery, 58% of patients had mild pulmonary regurgitation, and the remainder had moderate pulmonary regurgitation. At 6 months after surgery, 50% of the patients had mild pulmonary regurgitation, and the remaining patients had moderate pulmonary regurgitation. None of the patients had severe pulmonary regurgitation. We believe this technique can prevent severe pulmonary regurgitation and provide acceptable relief of pulmonary stenosis in patients with tetralogy of Fallot, and early results are encouraging. Nonetheless, further large-scale and medium - and long-term studies are needed to confirm the superiority of this technique.
Neopulmonary valve creation using right atrial appendage tissue
Amirghofran et al. Reference Amirghofran, Edraki and Edraki40 found that no death or related complications occurred in 21 tetralogy of Fallot patients repaired with RAA valves. There were 18 patients with mild or no pulmonary regurgitation early after surgery, and 3 patients with mild pulmonary regurgitation, one of whom progressed to moderate pulmonary regurgitation during a mean follow-up of 12 months. There were 15 patients with mild or no pulmonary artery stenosis, and 6 patients with moderate pulmonary artery stenosis. Compared with the other 10 patients who underwent transannular patch only, the patients who underwent neopulmonary valve had longer operative time and clamping time, but there was no difference in postoperative course and shorter hospital stay. Certainly, patients with RAA valves had a significantly less severe degree of pulmonary regurgitation, but the same degree of pulmonary valve stenosis. Schulte et al. Reference Schulte, Miller and Bhat39 found that neopulmonary valve was used in 8 patients and the median PV Z score was −4 (−4.7 to −3.9). At 6 months, 6 patients (75%) had mild or minimal pulmonary dysfunction. Oleg Anatolyevich Egunov et al. Reference Egunov, Kozhanov, Cetta and Krivoshchekov41 reported the results of five patients in their institution. The average follow-up time was 2.8 years, and the longest follow-up time was 4 years. All patients were in good physical condition and were not taking cardiac medications. Transthoracic echocardiography showed a mean right ventricular outflow tract gradient of less than 19 mm Hg, moderate pulmonary regurgitation in 2 cases and mild pulmonary regurgitation in 3 cases. The Z score of the new pulmonary valve was <0.91 in all patients. These results indicate that the neopulmonary valve is safe and effective in preventing pulmonary regurgitation after tetralogy of Fallot repair, at least in the short- and medium-term, but long-term results require further follow-up and study.
Perspectives
Application of tissue engineering technology in TOF patients with valve-sparing repair
Valve-sparing repair usually requires artificial materials, such as valves and patches to repair. However, existing artificial materials often face problems such as valve degradation and poor durability caused by the body’s immune response, inflammatory response, and calcification deposition. For paediatric patients, the biggest problem is the structural changes of the heart caused by the growth and development of the child, which leads to prosthetic valve-patient mismatch, and may cause postoperative cardiac dysfunction, ventricular remodelling and other serious complications. In the 1980s, Joseph Vacanti Reference Vacanti, Morse, Saltzman, Domb, Perez-Atayde and Langer49 and Robert Langer Reference Langer and Vacanti50 in the United States put forward the idea of trying to artificially fabricate human organs to cope with the shortage of organ grafts, and eventually developed into today’s tissue engineering. In 2018, the clinical application results of CardioCel, a new type of acellular bovine pericardial patch, were first reported by Leiden University Medical Center. Reference Tomsic, Bissessar, van Brakel, Marsan, Klautz and Palmen51 In the same year, Pavy et al. Reference Pavy, Michielon, Robertus, Lacour-Gayet and Ghez52 reviewed 101 children under 18 years old who were treated with CardioCel for congenital heart disease. The investigators found that the CardioCel was easy to implant during the procedure and performed well in the low-pressure region of the right heart system. The current concept of tissue engineering is to make tissue engineering grafts have certain growth and development potential after implantation in the human body, on the basis of solving the problems of anticoagulation, failure, and inflammatory reaction faced by existing grafts. Although this idea has not been fully realised in the clinical stage, the positive results obtained in animal experiments and the development potential in the field of paediatrics still attract many researchers to invest in tissue engineering.
Challenges of valve-sparing repair in TOF patients
Residual right ventricular outflow tract stenosis is a common postoperative complication and the most common reason for reintervention after surgery. Mild residual stenosis has been widely recognised and has a certain role in reducing pulmonary regurgitation. Reference D’Udekem, Galati, Konstantinov, Cheung and Brizard53 Previous studies have shown that Reference Park, Lee, Lim, Kim and Kim54 postoperative preservation of mild pulmonary valve stenosis (right ventricular systolic pressure of 60–70 mm Hg, transvalvular pressure gradient of 15–30 mm Hg) can significantly reduce long-term pulmonary regurgitation and the risk of later pulmonary valve replacement, while too high or too low right ventricular pressure will aggravation the decline of right ventricular function. However, severe residual stenosis requires reintervention. The RV/LV ratio is often used to evaluate the severity of the disease. RV/LV > 0.8 indicates the presence of significant stenosis. It is necessary to perform transannular patch in time for these patients with severe stenosis or highly hypoplastic pulmonary valve, as well as those patients with poor efficacy of valve-sparing repair. The RV/LV ratio will gradually decrease after partial tetralogy of Fallot repair, especially in infants and young children. The early residual pressure gradient will gradually decrease over time to avoid reintervention. There is still controversy about the timing of reintervention for residual stenosis that exists at a later stage. Although a large number of studies have shown that valve-sparing repair is superior to traditional transannular patch in preventing pulmonary regurgitation and improving long-term prognosis and survival rate, it has a higher risk of early pulmonary artery stenosis. In a series of studies, about 7% of tetralogy of Fallot patients required reintervention due to stenosis, and early stenosis in patients undergoing transannular patch was extremely rare. Reference Bacha13 Close follow-up is therefore necessary to ensure that pulmonary stenosis does not lead to long-term right ventricular hypertension.
Conclusions
In the past decades, long-term basic research and clinical practice of surgical treatment for tetralogy of Fallot have been carried out at home and abroad, and the treatment effect has been improved, the complications and mortality have been gradually decreased. Pulmonary regurgitation is a common complication after traditional radical repair of tetralogy of Fallot, which is an important factor leading to many adverse outcomes. Valve-sparing repair strategy has gradually become the first choice for the treatment of tetralogy of Fallot, which can effectively prevent the occurrence of postoperative pulmonary regurgitation, maintain right ventricular function, and improve the prognosis of children. However, surgical indications of valve-sparing repair remain controversial. At present, it is mainly based on the pulmonary valve annulus Z score, great aortic valve annulus ratio, pulmonary valve annulus index, pulmonary valve annulus area index, pulmonary valve annulus proportion, PGmax/ PV Vmax and RV/LV ratio should be used for evaluation. In addition, careful exploration of the morphology and quality of the pulmonary valve is more important. At present, the main surgical strategies for valve preservation include commissurotomy and mechanical dilation/balloon pulmonary valvuloplasty, RSVP, Delamination technique, SPA, and NPA. According to the surgeon’s preference and evaluation, the appropriate valve-preservation technique is selected to provide individualised treatment for patients. The prognosis is basically better than that of traditional transannular patch surgery, but there are still many problems that can not be solved, such as valve degeneration and poor durability. With the application of tissue engineering technology in valve-sparing repair of tetralogy of Fallot patients, some positive results have been achieved, and its development potential in the field of paediatrics can promote the development of this field and bring new hope to children with CHD. In addition, indiscriminate preservation of the pulmonary valve may face the aggravation of postoperative residual pulmonary valve stenosis. Therefore, close follow-up and timely intervention are necessary to protect the right ventricular function and improve the long-term quality of life of patients.
Data availability statement
All data are incorporated into the article, and the data underlying this article are available in the article.
Acknowledgements
We acknowledge the roles of our colleagues, perfusionists, nurses, and others involved in the care of the study participants.
Author contributions
Zhangwei Wang: Conceptualisation; Data curation; Formal analysis; Investigation; Methodology; Software; Validation; Visualisation; Writing—original draft. Honghao Fu: Writing—review and editing; Shoujun Li: Writing—review and editing.
Financial support
No funding was received for this work.
Competing interests
None declared.
Ethical standard
Not applicable.
Consent for publication
The manuscript is not currently under consideration elsewhere, and the work reported will not be submitted for publication elsewhere until a final decision has been made as to its acceptability by the journal.
