Discussion

Over the past years, cardiac surgery and postoperative management in the developed country have contributed to the excellent outcome of the totally corrected tetralogy of Fallot patients ^{Reference Bacha, Scheule and Zurakowski13} ; however, the results in developing country are still unknown ^{Reference Tanasan, Zanzani, Kocharian, Kiani and Navabi14} . A study on the outcomes of surgery in developing countries about the complications and mortality conducted by Murni et al. shows that the mortality of tetralogy of Fallot patients is 11%. Some factors associated with increased risk of mortality in developing countries after cardiac surgery are cyanotic CHD, longer cardiopulmonary bypass duration, high postoperative inotropes, and high blood lactate levels. ^{Reference Murni, Djer and Yanuarso15} Transannular patch during tetralogy of Fallot repair may result in pulmonary regurgitation, but this surgery has excellent long-term results. However, progressive right ventricular dysfunction requires continuous monitoring. ^{Reference Tornell, Lopez, Gonzales, Cerdan, Ojeda and Orozco2} To our knowledge, Indonesia has no studies describing mid-term outcomes, especially pulmonary regurgitation, in repaired tetralogy of Fallot. Therefore, this study proposes possible predictors for severe pulmonary regurgitation so that paediatric cardiologists, surgeons, and patients are well informed regarding further examinations related to pulmonary regurgitation and right ventricular function as well as other options in the follow-up.

Tetralogy of Fallot patients tend to have symptoms since early age; thus, they also have early corrective surgeries. This study shows that age at repair is not statistically significant for pulmonary regurgitation predictor. This result is in accordance with other studies. Cunningham et al. showed that surgeries in tetralogy of Fallot patients older than 55 days were safe. ^{Reference Cunningham, Donofrio, Peer, Zurakowski, Jonas and Sinha16} A study in Pakistan by Memon et al. showed that mean age 9.39 ± 2.3 months had good outcomes after tetralogy of Fallot repair. ^{Reference Memon, Akhtar, Mohsin, Ahmad, Arshad and Ahmed17} Baseline saturation <75% was an independent risk factor for low cardiac output syndrome and prolonged intubation. ^{Reference Memon, Akhtar, Mohsin, Ahmad, Arshad and Ahmed17} The optimum age for tetralogy of Fallot repair in our centre is 1 year, though our study population had a median age of 3.2 years in severe pulmonary regurgitation group and 3.4 years in mild-moderate pulmonary regurgitation group. A study in London by Johnson et al. showed that children with tetralogy of Fallot had their pulmonary arterial circulation and alveoli fail to develop normally. This study suggested for early correction because the potential for growth decreases with age. Lung growth and remodelling occur most rapidly in the first 2 years of life, so it is considered as the best time to do tetralogy of Fallot repair. ^{Reference Johnson and Haworth10}

All subjects in this study had transatrial-transpulmonary approach for tetralogy of Fallot repair. This is the most commonly used approach in most centres with excellent long-term results. ^{Reference Lutijen, Van den Bosch and Duppen18} Unfortunately, using transannular patch in this kind of surgery may lead to pulmonary regurgitation, and our study shows that severe pulmonary regurgitation tends to happen in patients with higher McGoon ratio and longer follow-up duration after having this surgery. This result is slightly different from those of Gao et al. in China which shows that McGoon ratio of more than 1.63 and Nakata index of more than 270.05 contribute to pulmonary regurgitation. Our study shows that McGoon ratio is a better predictor for severe pulmonary regurgitation compared to Nakata index. This is because tetralogy of Fallot has pulmonary stenosis, which influences the diameter ratio of main pulmonary trunk and the ascending aorta. Keep in mind that McGoon ratio is a ratio of diameters of the pulmonic annulus divided by the aortic annulus ^{Reference Chen, Chen, Wu, Li and Lue19} . In our opinion, Nakata index (the sum of cross-sectional area of both right and left pulmonary arteries divided by body surface area) is not suitable for pulmonary artery, considering its ovoid shape. ^{Reference Chen, Chen, Wu, Li and Lue19}

We also postulated that diameter of right pulmonary artery or left pulmonary artery could predict pulmonary regurgitation, but the study shows them to be insignificant for prediction. This difference with Gao’s study that has left pulmonary artery diameter as a better predictor than right pulmonary area might be explained by smaller left lung and its association with increased diastolic flow reversal in left pulmonary artery. ^{Reference Gao, Yang, Shi, Diao, Xu and Guo9,Reference Killner, Balossino and Dubini20} Lungs in tetralogy of Fallot are smaller in relation to body surface area and age, so the diameter of right pulmonary area or left pulmonary artery alone does not contribute to severe pulmonary regurgitation. ^{Reference Johnson and Haworth10}

In developed countries, pulmonary regurgitation and right ventricular diastolic dysfunction are the most important outcome following tetralogy of Fallot repair. Prolonged and severe pulmonary regurgitation affect right ventricular function and size, leading to right ventricular dysfunction. Pulmonary regurgitation induces right ventricular volume overload and often progressive right ventricular dilatation which may lead to tricuspid regurgitation and right ventricular dysfunction. ^{Reference Van der Ven, Van den Bosch, Bogers and Helbing21,Reference Redington22} There are studies measuring right ventricular function by myocardial performance index at mid-term and long-term follow-up. Pilla et al., Tanasan et al., and Shehata et al. measured right ventricular dysfunction in repaired tetralogy of Fallot with matching healthy subjects. All of them showed prolonged myocardial performance index and right ventricular dysfunction in the group with repaired tetralogy of Fallot. ^{Reference Tanasan, Zanzani, Kocharian, Kiani and Navabi14,Reference Pilla, Pereira and Fin23,Reference Shehata, El Nagar, Shara and Abu-Farag24} Their studies are in line with our results, which showed that all of our subjects had pulmonary regurgitation of varying degrees. All of our subjects had single assessment of pulmonary regurgitation using transthoracal echocardiography during their routine control. A higher myocardial performance index is indicative of reduced global right ventricular function. The prolonged right ventricular myocardial performance index is a reflection of reduced right ventricular function due to severity of pulmonary regurgitation.

For evaluation, follow-up duration in severe pulmonary regurgitation group was 2.7 years and mild-moderate group was followed up for 1.5 years. However, continuous right ventricle volume overload due to pulmonary regurgitation has been proven to accelerate the rate of progressive right ventricular systolic and diastolic dysfunction and size. ^{Reference Geva8.Reference Tanasan, Zanzani, Kocharian, Kiani and Navabi14,Reference Egbe, Mittnacht, Nguyen and Joshi25}

In conclusion, McGoon ratio of more than 1.8 and duration of follow-up of more than 1.9 years may be associated with severe pulmonary regurgitation. Further examinations for pulmonary regurgitation are needed to see its impact on right ventricular dysfunction in mid-term and long-term follow-up.

There were several limitations in this study. Follow-up duration for the patients varied greatly with 6 months at the earliest and 4 years at the longest. Another limitation was a wide variability of age at repair, with the youngest being 1 year old and the oldest at 17 years old. This may have impact on their preoperative hypoxaemia and cardiac function and therefore did not give the real distribution on pulmonary regurgitation severity after surgery. Location also played an important role, since most patients did routine follow-up after tetralogy of Fallot repair with their nearest paediatric cardiologists, thus influencing the variability in follow-up duration for subjects.