Right ventricular outflow tract stent

Right ventricular outflow tract stenting is now seen as the first-line option for Tetralogy of Fallot palliation by leading centres globally in comparison to the modified Blalock-Taussig shunt alternative.^{Reference McGovern, Morgan and Oslizlok23–Reference Quandt, Ramchandani and Stickley25} It is preferred due to higher morbidity (such as pulmonary stenosis, pulmonary congestion requiring diuretic use, seroma formation, or Horner’s syndrome) associated with Blalock-Taussig shunt operation.^{Reference Ross, Costello and Backer26,Reference Gladman, McCrindle and Williams27} Quandt et al^{Reference Quandt, Ramchandani and Stickley25} also reported superior pulmonary artery growth in their right ventricular outflow tract stent patients in comparison to their Blalock-Taussig shunt patients.^{Reference Quandt, Ramchandani and Stickley25}

Carrying out a right ventricular outflow tract stent procedure can be difficult in patients with a short infundibulum, right ventricular outflow tract muscular atresia, or non-confluent central pulmonary arteries.^{Reference Sandoval, Chaturvedi and Benson24,Reference Quandt, Ramchandani and Stickley25} These patients require an alternative form of palliation such as a Blalock-Taussig shunt, or an early primary repair. Early primary repair is also preferred to right ventricular outflow tract stenting in patients with potential for pulmonary valve preservation.^{Reference Sandoval, Chaturvedi and Benson24} Outcomes of palliative intervention are summarised in Table 1.

Table 1. Outcomes of palliative intervention

PICU, Paediatric ICU; RVOT, right ventricular outflow tract; PS, Pulmonary Stenosis; PA, Pulmonary Atresia; LOS, length of stay; DS, Ductal stents; RV, right ventricle.

Right ventricular outflow tract stenting is an effective method of palliation for Tetralogy of Fallot patients, with reported success rates as high as 93.6%.^{Reference Ghaderian, Ahmadi and Sabri28} Oxygen saturations and pulmonary artery z-scores are consistently increased after right ventricular outflow tract stenting. Oxygen saturations increased by 20.1% across 10 studies,^{Reference Ghaderian, Ahmadi and Sabri28} and pulmonary artery z-score increased from −2.68 to −0.92 across one cohort.^{Reference McGovern, Morgan and Oslizlok23}

The procedural death rate of right ventricular outflow tract stenting is 3.7% across 10 studies.^{Reference Ghaderian, Ahmadi and Sabri28} Paediatric ICU length of stay ranges from 24 to 120 hours.^{Reference Ghaderian, Ahmadi and Sabri28} Re-intervention rates in right ventricular outflow tract stent patients are significant, with one trial reporting up to 54% of right ventricular outflow tract stent patients require a re-intervention before complete repair.^{Reference Sandoval, Chaturvedi and Benson24} Common re-interventions include repeat dilatation of the right ventricular outflow tract stent, or implantation of a second or third stent.^{Reference Sandoval, Chaturvedi and Benson24}

During the subsequent complete repair, 95/265 (36%) of right ventricular outflow tract patients require a transannular patch.^{Reference Ghaderian, Ahmadi and Sabri28} Fewer patients with staged repair require a transannular patch compared to primary repair.^{Reference Kanter, Kogon and Kirshbom29} Cardiopulmonary bypass time for complete repair ranges from 95 to 165 minutes in patients who first have right ventricular outflow tract stent palliation. One study found that average cardiopulmonary bypass time is longer in patients with right ventricular outflow tract stent palliation compared to those with primary repair;^{Reference Sandoval, Chaturvedi and Benson24} however, in another study, this difference lacked statistical significance.^{Reference Quandt, Ramchandani and Stickley25} Sandoval et al^{Reference Sandoval, Chaturvedi and Benson24} found that no patients with a right ventricular outflow tract stent had pulmonary valve preservation after complete repair, compared to 41% of early repair patients. Accordingly, right ventricular outflow tract stent palliation is usually not considered in patients with potential for pulmonary valve preservation.^{Reference Sandoval, Chaturvedi and Benson24}

One study found average post-operative Paediatric ICU length of stay after complete repair was an average of 5 days in right ventricular outflow tract stent palliation patients. This was slightly shorter than early repair groups (Pulmonary Stenosis = 6, Pulmonary Atresia = 7). Average post-operative hospital length of stay was reported as an average of 11 days for the stent group, also slightly shorter than early repair groups (Pulmonary Stenosis = 13, Pulmonary Atresia = 14).^{Reference Sandoval, Chaturvedi and Benson24}

There are varied medium-term outcomes reported for Tetralogy of Fallot patients with right ventricular outflow tract stent palliation before complete repair. One study found after 2.1 median years, 40% of patients have persistently elevated right ventricle pressures and 40% require multiple re-interventions such as left pulmonary artery dilatations to increase pulmonary blood flow.^{Reference Dohlen, Chaturvedi and Benson19} Another study similarly reports high re-intervention rates (25%), but no deaths by 3.2 median years.^{Reference Sandoval, Chaturvedi and Benson24} There is limited evidence describing long-term outcomes in Tetralogy of Fallot patients with stent palliation.

Ductal stent

Ductal stents are typically performed for duct-dependent lesions with compromised patency of right ventricular outflow tract.^{Reference Alwi17,Reference Sandoval, Chaturvedi and Benson24} There are various approaches to inserting this type of stent depending on the relationship of the patent ductus arteriosus to aorta.^{Reference Alwi17} An advantage of ductal stent is a reduction of complications commonly associated with the Blalock-Taussig shunts.^{Reference Alsagheir, Koziarz and Makhdoum30}

A meta-analysis^{Reference Alsagheir, Koziarz and Makhdoum30} comparing ductal stent to Blalock-Taussig shunt in neonates with duct-dependent lesions (not exclusively Tetralogy of Fallot) found ductal stent to be superior to Blalock-Taussig shunt in terms of risk for procedural-related complications. Ductal stent patients had complications such as arrhythmia (3.8%), vascular injury during access (9.4%), and ductal stent failure (15.7%).^{Reference Alsagheir, Koziarz and Makhdoum30} Median Paediatric ICU length of stay was 4.2 days, and hospital length of stay 12 days. There was no significant difference in 30-day mortality between patients who had a ductal stent and those who had a Blalock-Taussig shunt; however, ductal stent patients had better medium mortality rates.^{Reference Alsagheir, Koziarz and Makhdoum30} Forty-four percentage of patients who underwent ductal stent had re-interventions, including balloon angioplasty of ductal stent, re-stenting, and pulmonary valvuloplasty.^{Reference Alsagheir, Koziarz and Makhdoum30} Ductal stent can have negative impacts at time of complete repair, such as pulmonary artery distortion complicating surgery, and need for stent removal^{Reference Alsagheir, Koziarz and Makhdoum30} and should thus only be undertaken after careful consideration. Further studies looking at both short- and long-term outcomes of ductal stent in exclusive Tetralogy of Fallot cohorts would be beneficial.

Balloon pulmonary valvuloplasty

Balloon pulmonary valvuloplasty is best suited for patients with pulmonary artery valvular stenosis rather than infundibular obstruction.^{Reference Kim, Ban and Lee31} In this cohort, it can be used to delay early surgical repair in symptomatic neonates by enhancing blood flow through the pulmonary arteries, promoting pulmonary annulus growth and increasing oxygen saturations.^{Reference Kim, Ban and Lee31} However, balloon pulmonary valvuloplasty is less effective in cases with an hypertrophied infundibulum^{Reference Wu, Wang and Lee32}, and these patients often require early re-intervention with a Blalock-Taussig shunt before definitive repair.^{Reference Muneuchi, Watanabe and Sugitani33}

After balloon pulmonary valvuloplasty, studies report an increase in pulmonary artery z-scores and oxygen saturations. One recent study reports a z-score increase from −3.56 to −1.82 after balloon pulmonary valvuloplasty.^{Reference Muneuchi, Watanabe and Sugitani33} Another study states that the average oxygen saturations increased from 63 to 87% (+24%).^{Reference Wu, Wang and Lee32}

Transannular patching is required less often after balloon pulmonary valvuloplasty when compared to Blalock-Taussig shunt.^{Reference Kim, Ban and Lee31} One study reported only 29% of patients with balloon pulmonary valvuloplasty required transannular patch; this is compared to 90% with Blalock-Taussig shunt.^{Reference Kim, Ban and Lee31} This is because the balloon pulmonary valvuloplasty technique successfully promotes pulmonary annular growth in most patients.^{Reference Ducas, Harris and Labos34} Muneuchi et al^{Reference Muneuchi, Watanabe and Sugitani33} found that 48% (15/31) of patients who had a balloon pulmonary valvuloplasty still required another palliative surgical repair, an aortopulmonary shunt, before complete repair. The patients who required an aortopulmonary shunt before complete repair had greater infundibular obstruction.^{Reference Muneuchi, Watanabe and Sugitani33}

Transannular patch versus annulus preserving repair

Repair of the right ventricular outflow tract obstruction involves either a transannular patch or annulus-preserving repair.^{Reference Ducas, Harris and Labos34,Reference Sharkey and Sharma42,Reference Jeon, Kim and Kwon43} The optimum treatment for Tetralogy of Fallot involves limiting both residual post-operative pulmonary regurgitation and pulmonary stenosis, so selecting the correct procedure is imperative.^{Reference Jeon, Kim and Kwon43,Reference Yun44} Many valve-sparing surgical techniques have been described, such as balloon pulmonary valvuloplasty, pulmonary cusp patch reconstruction, pulmonary valve commissurotomy +/− rigid bougie dilatation, and complete resection of sub-valvular and supra-valvular areas of obstruction.^{Reference Bacha13} An annulus-preserving repair is preferable over a transannular patch due to reduced incidence of future valve replacement, lower rates of severe right ventricle dilation and pulmonary regurgitation, and better right ventricle function at first adult follow-up.^{Reference Ducas, Harris and Labos34} Annulus-preserving repairs are described as up to 6 times less likely than transannular patch to undergo pulmonary valve replacement indicating that transannular patch should only be done if necessary.^{Reference Ducas, Harris and Labos34}

A transannular patch procedure is commonly considered if the pulmonary annulus does not reach a threshold size,^{Reference Khan, Drury and Stickley45} a finding more frequent in neonatal repairs compared to later repairs. The long-term complications of arrhythmias and ventricular dysfunction mean that transannular patch are avoided when possible.^{Reference van der Ven, van den Bosch and Bogers46} Moreover, abnormal coronary arteries or a distinctly small pulmonary artery may require a conduit rather than a transannular patch.^{Reference Khan, Drury and Stickley45}

Due to anatomical variation of pulmonary valves in Tetralogy of Fallot, it is not always possible to preserve the pulmonary valve. One study discovered 10% of their patient cohort had monocuspid valves which are not suitable for pulmonary valve preservation.^{Reference Vida, Angelini and Guariento47} Promisingly, 90% of their patient cohort had bicuspid or tricuspid pulmonary valves. Of those 90%, in 48.7%, they were thickened and dysplastic and not able to be preserved, leaving 56% of the original cohort morphologically suitable for pulmonary valve preservation.^{Reference Vida, Angelini and Guariento47}

Pulmonary valve replacement

Pulmonary valve replacement is indicated in patients with significant pulmonary regurgitation; other indications include presence of heart failure or new arrhythmias due to right ventricle dilatation.^{Reference Weinberg and McElhinney48} Pulmonary valve replacement is usually given in adulthood (ranging from 12 to 31 years after complete repair).^{Reference Cocomello, Meloni and Rapetto49} Interestingly, recent evidence suggests that pulmonary valve replacement does not have significant clinical outcomes in comparison to conservative management of pulmonary regurgitation. Both a meta-analysis and multicentre observational study found that pulmonary valve replacement did not significantly impact right ventricle ejection fraction, atrial tachycardia, sustained ventricular tachycardia, heart failure, or death.^{Reference Mongeon, Ben Ali and Khairy50,Reference Bokma, Geva and Sleeper51} Instead, the meta-analysis only found significant impact on NYHA class and right ventricle volumes.^{Reference Mongeon, Ben Ali and Khairy50} Both studies highlighted a need for more evidence comparing outcomes of pulmonary valve replacement with conservative management.

Immediate post-operative outcomes

Evidence highlights that early repair increases ICU and hospital length of stay, and risk of post-operative cardiac events.^{Reference Jeon, Kim and Kwon43,Reference Bailey, Elci and Mascio52} Bailey et al^{Reference Bailey, Elci and Mascio52} report that ICU length of stay was increased by 90% to an average of 6 days in those having an early primary repair in comparison to a staged approach.^{Reference Bailey, Elci and Mascio52} One study reported infants >90 days old undergoing complete repair had both a lower rate of post-operative complications and a shorter hospital length of stay compared to neonates.^{Reference Yang, Wen and Tao53} Moreover, neonatal Tetralogy of Fallot repairs had the highest mortality rate (9.82%) compared to those >180 days old (0.85%) with the same open repair procedure.^{Reference Yang, Wen and Tao53}

In comparison to staged repair, a retrospective study analysing 2,363 patients noted a higher risk of mortality in those with complete neonatal repair during hospital stay, at 30-day follow-up, and 2-year follow-up.^{Reference Savla, Faerber and Huang54} Patients with neonatal repair had increased cardiac complications (ECMO, Pleural effusion, need for CPR) and longer hospital stay.^{Reference Savla, Faerber and Huang54} This study also adjusted for confounders, such as patient, hospital, and systematic factors.

There are common complications immediately following a complete neonatal Tetralogy of Fallot repair that require further intervention, investigation, and monitoring. These complications include: residual ventricular septal defect, residual and persistent right ventricular outflow tract obstruction, arrhythmias (ventricular tachycardia or atrial fibrillation/flutter), right bundle branch block, or sudden cardiac death.^{Reference Townsley, Windsor and Briston55} Other commonly reported immediate post-operative complications include pericardial effusion requiring draining, pleural effusion requiring drainage, chylothorax, bleeding requiring re-operation, superficial wound infection, and junctional ectopic tachycardia.^{Reference Mouws, de Groot and van de Woestijne56} In patients with transannular patch repair, right ventricle restrictive physiology is commonly reported due to poor diastolic relaxation, which can contribute to a low cardiac output state.^{Reference Norgård, Gatzoulis and Moraes57} This is commonly managed by optimising the ventricular preload through fluid resuscitation or by mechanical circulatory support if necessary.^{Reference Chandler and Kirsch58} While timing of the repair is a significant risk factor for increased mortality and morbidity in Tetralogy of Fallot patients, frequency of complications also depends largely on the severity of Tetralogy of Fallot. Important factors include pre-operative size of the pulmonary valve and pulmonary arteries, right ventricular – pulmonary artery pressure gradient, and oxygen saturation.^{Reference van der Ven, van den Bosch and Bogers46}

Long-term complications

Long-term survival after Tetralogy of Fallot repair is generally very good, with >90% of patients surviving after close to 30-year follow-up.^{Reference Luijten, Van den Bosch and Duppen35,Reference Smith, McCracken and Thomas59} While staged repair increased risk of mortality in the first 6 years following repair, there was no significant difference after this period.^{Reference Smith, McCracken and Thomas59} Pulmonary regurgitation is the most common long-term complication in patients who survive Tetralogy of Fallot repair; 20 years after complete repair, up to 64% of patients have pulmonary regurgitation.^{Reference Hoashi, Kagisaki and Meng60} Risk factors for pulmonary regurgitation include a larger transannular patch and prolonged post-operative ventilator support.^{Reference Kim, Sung and Kim61} Pulmonary regurgitation contributes to right ventricle dilatation in Tetralogy of Fallot patients, which reduces exercise tolerance and increases risk of right ventricle dysfunction, heart failure, and sudden cardiac death.^{Reference Hickey, Veldtman and Bradley62}

Smith et al^{Reference Smith, McCracken and Thomas59} also report the frequency of repaired Tetralogy of Fallot complications, such as arrhythmia (n = 12 [8.3%]), cardiac arrest (n = 34 [23.5%]), and congestive heart failure (n = 26 [17.9%]).^{Reference Smith, McCracken and Thomas59} Factors contributing to heart failure in repaired Tetralogy of Fallot include damage to the myocardium (due to multiple cardiac surgeries, insufficient myocardial protection during cardiopulmonary bypass, or long-standing palliative shunts), chronic volume overload (due to pulmonary regurgitation), and size of transannular patch (which can cause large segments of the right ventricular outflow tract to be akinetic or dyskinetic).^{Reference Wald, Marie Valente and Marelli63} Outcomes of early primary surgical repair are summarised in Table 3.

Table 3. Outcomes of early primary repair

PICU, Paediatric ICU; RVOTO, right ventricular outflow tract obstruction; RBBB, right bundle branch block; TOF, Tetralogy of Fallot; RV, right ventricle.