Analysis of Risk Factors Associated with Early Mortality in Total Anomalous Pulmonary Venous Connection (TAPVC) Repairs Performed Over a Period of 10 Years – A Retrospective Observational Study

INTRODUCTION

Total anomalous pulmonary venous connection (TAPVC) is a congenital heart defect that occurs in 1–3% of children with cardiovascular malformations.^[1] It consists of an abnormally patent channel between the pulmonary circuit and systemic venous circuit formed during the fetal development. A right to left shunt in the form of either a patent foramen ovale or an atrial septal defect is necessary for the survival of the infant.^[2] It is a life-threatening congenital cardiac malformation that requires surgical therapy. It is classified into the following types, based on the location of the abnormal drainage of pulmonary veins into the systemic circulation: supracardiac, 45%; infracardiac, 25%; cardiac, 25%; and mixed, 5%.^[3]

Uncorrected TAPVC has a mortality rate of more than 78% in infancy.^[4] Although various published studies have documented early post-operative mortality varying from <10% to 50%, the mortality rates have become relatively better over the last couple of decades, mostly as a result of advancement of management strategies, both medical and surgical.^[5-7] Infants with complex TAPVC lesions with other associated severe cardiac abnormalities have poorer prognosis as compared with simple TAPVC with biventricular anatomy without any other severe cardiac malformation.^[5,6] Post-operative morbidities after TAPVC repair include arrhythmias, pulmonary hypertension, and residual stenosis in pulmonary veins or at the anastomosis.^[6,8]

MATERIAL AND METHODS

Eighty-eight patients who had undergone surgical treatment for TAPVC over the course of 10 years, beginning on June 1, 2009 and ending on May 31, 2019, and who had been operated on by a single surgeon, formed the basis of this study. The protocol for the study was checked out by the Institutional Ethics Committee. On April 23, 2020, the approval for the institute’s ethical clearance was granted (Reference Number: IECPG-113/April 23, 2020). For the purpose of publication of study data, informed consent was granted by the guardians of every participant. There was no conflict of interests.

All patients who underwent surgical treatment for TAPVC by a single surgeon during a period of 10 years, beginning on June 1, 2009 and ending on May 31, 2019, are being considered for inclusion in this study. There were no exclusion criteria.

The information regarding patient demographic details, pre-operative evaluation, surgical procedure, post-operative course, and follow-up after discharge was retrieved by searching O.T registries, medical record sections, and finally by patient follow-up in outpatient department/telephonic follow-up.

RESULTS

DISCUSSION

Recent reports of TAPVC repair have indicated that surgical outcomes have improved over the past three decades.^[5,12-14] This has largely been a result of better pre-operative management, minimization of invasive pre-operative work-up, operative advancements, and better post-operative care.

The median age of children with TAPVC undergoing surgery in our study was 3.5 months, which is comparable to most of the other similar studies.^[14-17] However, some studies had early presentation of cases for surgery.^[18-20] On the contrary, in some studies, the age of children undergoing surgery was found to be comparatively more.^[21,22] The reason for this delay is contemplated to be a lack of widespread prenatal diagnosis, delayed postnatal diagnosis, and referral and scarcity of tertiary care centers offering pediatric cardiac surgery services. The median weight of children with TAPVC undergoing surgery in our study was 4.05 kg, which is comparable to most of the other similar studies.^[6,14-23] The gender distribution in our study is also comparable to most of the other similar studies.^{[6,14,17,19,22,23]}

The TAPVC anatomy in our study was supracardiac in 41 (46.6%) cases, cardiac in 24 (27.3%), infracardiac in 14 (15.9%), and mixed in 9 (10.2%). This is comparable to the observations of some similar studies.^{[14,17,19,20]} However, certain other studies demonstrated much higher incidence of supracardiac type of TAPVC.^[6,15,18,22] This can be explained by relatively fewer number of cases being studied, leading to some amount of bias.

In our study, obstructed TAPVC cases being operated were 37.5%. This finding was comparable to that observed by other studies. For example, Lemaire et al. reported 45% obstructed TAPVCs in their study,^[14] while Choudhary et al.^[15] and Kelle et al.^[18] reported 49% and 29%, respectively. Hancock et al.,^[6] Yong et al.,^[19] and Harada et al.^[17] reported higher incidence of obstruction in their studies while Elamry et al.^[22] reported that only 15.7% obstructed TAPVC in their study.

About 33% of cases in our study had to be operated as emergency procedures. This was comparable to the findings of Harada et al.^[17] Choudhary et al.^[15] reported 20.5% as emergency procedure and Yong et al.^[19] reported it to be 19.1%. However, Hancock et al.^[6] had 53% of cases which were operated as emergency.

The need for pre-operative mechanical ventilation and pre-operative inotropes was not reported in most of the studies. In our study, 14.8% cases required pre-operative mechanical ventilation, while this data for Yong et al.^[19] and Harada et al.^[17] was 57% and 36.3%, respectively. In our study, 20.5% cases needed pre-operative inotropes, while 34% cases in the study by Harada et al.^[17] and 48% in that by Hancock et al.^[6] required pre-operative inotropes.

The average CPB time and aortic cross clamp time in our study was comparatively lesser than most of the studies.^[6,16,23]

The duration of mechanical ventilation, ICU stay, and hospital stay in our study was comparable to most of the similar studies.^{[15,18,19,22,23]}

The early mortality in our study has been found to be 12.5%, which is comparatively lesser than most of the similar studies. Sugano et al.^[20] reported an in-hospital mortality of 34%, while Choudhary et al.^[15] and Hancock et al.^[6] reported an early mortality of 23.3% and 24%, respectively. Lemaire et al.^[14] reported early mortality in their study to be 21.1%, while Domadia et al.^[24] and Sakamoto et al.^[21] reported early mortality to be 18% and 18.27%, respectively. Adzamli et al.^[23] reported that the in-hospital mortality in their study was only 7.5%. This can be attributed to the fact that they included only supracardiac type of TAPVC in their study, which has been known to have much lesser incidence of obstruction and better post-operative results. Similarly, Xiang et al.^[16] reported only 7.7% early mortality in their study. They included only mixed type of TAPVC, excluding infracardiac TAPVCs which are a known risk factor for poor post-operative outcome. Elamry et al.^[22] studied only those cases which were operated on an elective basis, excluding all the emergency cases. Consequently, the early mortality reported by them was only 5.7%. Kelle et al.,^[18] Yong et al.,^[19] and Harada et al.^[17] reported very good post-operative results in their studies, with early mortality of 12%, 7.9%, and 2.7%, respectively.

In our study, it has been found that age <1 month, low weight of the patient at the time of surgery, pre-operative obstructed pulmonary veins, pre-operative need of mechanical ventilation, pre-operative inotrope requirement, repair of TAPVC on an emergency basis, and post-operative PAH are statistically significant risk factors for early mortality. Gender, TAPVC type, pre-operative ventricular function, pre-operative PAH, associated cardiac lesions, CPB time, aortic cross clamp time, duration of ICU stay, duration of hospital stay, and post-operative ventricular function have not been found to have any statistically significant association with early mortality in our study.

This summation of correlations has been different from those observed in previously published literature. Yong et al.^[19] found increased CPB time and age <1 month as important risk factors for early deaths, while Sakamoto et al.^[21] demonstrated in their study that the risk factors are weight of the child <2 kg at the time of operation and post-operative pulmonary vein obstruction. Choudhary et al.^[15] found that the statistically significant risk factors for early mortality in TAPVC repair cases are post-operative PAH crisis, emergency repair of TAPVC, and weight of the child <25^th percentile. Hancock et al.^[6] reported obstructed TAPVC and single ventricle physiology to be risk factors for in-hospital mortality. Chowdhury et al.^[25] reported age <1 month, obstructed pulmonary vein preoperatively, hypoplastic pulmonary vein, post-operative PAH crisis, postoperative low cardiac output syndrome, and vertical vein ligation during surgery to be the significant risk factors for early mortality after TAPVC repair. Ricci et al.^[26] studied recurrent pulmonary vein obstruction after TAPVC repair and found the risk factors for early mortality to be age <6 months and persistent PAH after reoperation. Domadia et al.^[24] found that the presence of heterotaxy syndromes was significantly correlated with early mortality. St Louis et al.^[27] reported that only pre-operative obstruction of pulmonary vein is a significant risk factor for in-hospital mortality. Liufu et al.^[28] concluded that pre-operative pulmonary vein obstruction, increased duration of post-operative mechanical ventilation need, and TAPVC repair on an emergency basis are correlated significantly with early mortality.

Bayya et al. reported only 0.9% early mortality in their study. However, they included only isolated TAPVC patients without any associated lesion. Furthermore, it is not mentioned whether they included cases which were operated on emergency basis.^[29]

Shentu et al., in their study, reported overall, mortality of 25 patients (10%), at a median of 0.26 months. In their study, lower weight, greater last arterial lactate level before surgery, emergency surgery, non-cardiac connection type, long CPB, and cross-clamping time were associated with death.^[30]

Talwar et al. have reported no early or late deaths among 98 patients operated for TAPVC.^[31] However, a noteworthy difference is that they studied patients who presented and were operated after their first decade of life.

On the other hand, Tailor et al. reported a mortality of 5.4% in their study.^[32] However, only early mortality was mentioned.

Higher CPB time and obstructed TAPVC were reported by Beers et al. as risk factors for mortality. However, they found that cardiac type of TAPVC was protective, while our study does not demonstrate any significant correlation between type of TAPVC and mortality.^[33]

Wang et al. concluded in their study that higher CPB time was the only independent risk factor for the early post-operative mortality. However, it has not been mentioned whether obstructed TAPVC patients were taken into account.^[34]

Neonatal age group and preoperatively ventilated patients had significant risk of early mortality and bleeding in mixed cyanotic patients may also lead to early mortality in ICU.^[35-38]

CONCLUSION

Following conclusions can be drawn from the present study with regard to the association of risk factors with the early mortality:

1. Age <1 month, low weight at the time of surgery, pre-operative obstructed pulmonary veins, pre-operative need of mechanical ventilation, pre-operative inotrope requirement, repair of TAPVC on an emergency basis, and post-operative PAH were statistically significant risk factors for early mortality.

2. Although early mortality was highest in infracardiac type, the correlation of TAPVC sub-type with mortality was not found to be statistically significant.

3. Gender, TAPVC type, pre-operative ventricular function, pre-operative PAH, associated cardiac lesions, CPB time, aortic cross clamp time, duration of ICU stay, duration of hospital stay, and post-operative ventricular function have not been found to have any statistically significant association with the early mortality in our study.