We conducted a retrospective cohort study in the Cardiac Intensive Care Unit (CICU) of the Heart Center at Shanghai Children’s Medical Center between January 2017 and December 2022. The hospital Institutional Review Board approved the study protocol.

This study included children aged under 6 months who underwent primary surgical repair for TAPVC. Exclusion criteria included secondary repair, functionally univentricular circulation, in-hospital death, or incomplete medical records. Participants were stratified into two groups based on the duration of postoperative ventilatory support. Children with ventilatory support durations exceeding the 75th percentile were classified into the delayed recovery group (group A). In contrast, the remaining children were assigned to the normal recovery group (group B) (Fig. 1). No changes were made to the devices used, the medical teams, or the surgical techniques employed throughout the study period.

Fig. 1.

Patient flowchart. TAPVC, total anomalous pulmonary venous connection. A total of 369 children received a TAPVC repair during the study period. A total of 323 children were included in the analysis.

“Prolonged recovery” was defined by the ventilation duration. Prolonged recovery was defined as ventilatory support exceeding the 75th percentile. A TAPVC was characterized by a failure of the pulmonary venous confluence (PVC) to empty into the left atrium (LA) in combination with a persistent connection to the systemic venous circulation. A diagnosis of preoperative PVO was made by echocardiography, with a non-phasic flow velocity $>$1.8 m/s [8]. The measurement is normally recorded at the sites of obstruction. The blood flow in the pulmonary vein obstruction was turbulent, which was characterized by a continuous spectrum and the disappearance of the negative phase. The velocity was measured at the confluence, at the individual pulmonary veins, or in the vertical vein, as shown in Fig. 2. Heart failure was caused by pulmonary vein obstruction, leading to pulmonary congestion and pulmonary edema, which is characterized by hypoxemia (PaO₂ 50 mmHg), metabolic acidosis, oliguria, circulatory failure, requiring mechanical ventilation with high positive end-expiratory pressure (PEEP) ($>$6 mmHg), and the use of catecholamine drugs. Surgery was performed when hypoxemia and heart failure could not be improved despite mechanical ventilation and pharmacotherapy.

Fig. 2.

Supracardiac TAPVC. (A) Diameter of the obstructed vertical vein: 0.283 cm. (B) Vertical venous flow velocity 2.49 cm/s.

A restrictive atrial septal defect (3 mm) [7] was present when there was an obstruction at the interatrial septum. Severe PH was diagnosed when the velocity of tricuspid regurgitation was $\ge$3.5 m/s on the echocardiography [9]. TAPVC was categorized into four types according to the classification by Shaw and Chen [10]. Postoperative PVO was present when the peak blood flow velocity at the anastomosis of the vein and the left atrium was $>$1.8 m/s on the echocardiography [7, 8].

Children with severe PH and heart failure before surgery were treated with oxygen supplementation, positive inotropic drugs, diuretics, and correction of acidosis. Appropriate antibiotics were administered in cases with positive sputum cultures, as determined by next-generation sequencing (NGS). Invasive ventilator therapy was instituted for children with respiratory and circulatory failure characterized by respiratory distress, hypoxemia, hypercapnia, metabolic acidosis, and oliguria.

Endotracheal intubation and central venous and arterial catheters were inserted by an anesthesiologist before the operation. TAPVC repair was performed through a median sternotomy under standard aorto-bicaval cardiopulmonary bypass (CPB). The ductus arteriosus was dissected and ligated before initiating the CPB. Senior surgeons performed all operations. A sutureless technique was used when possible. Briefly, an incision was made in the venous confluence and then extended to the individual PV stenosis. In situ pericardial flaps were anastomosed distally to the incised veins to create a neo-LA. Detailed information on sutureless and conventional repair techniques has been previously published [7, 8, 9, 10, 11, 12, 13]. No infants underwent balloon atrial septostomy before surgical correction. Seven patients had left atrial catheters, and three patients had pulmonary artery catheters. All patients underwent either transthoracic or transesophageal ultrasound. Most newborns received a transthoracic ultrasound. Postoperative ultrasound in the operating room revealed significant anastomotic stenosis in four patients who required reoperation under CPB. Meanwhile, other concurrent cardiac anatomical issues, such as atrial septal defect (ASD), ventricular septal defect (VSD), patent ductus arteriosus (PDA), and coarctation of the aorta (COA), were also addressed during the pulmonary vein stenosis repair.

All children were transferred to the CICU after surgery and were closely monitored for their heart rate, cardiac rhythm, blood pressure, central venous pressure, percutaneous oxygen saturation, body temperature, urine output, B-type natriuretic peptide (BNP), and blood–gas levels. Dopamine (5–7.5 µg$\cdot$kg$\cdot$min) and milrinone (0.25–0.75 µg$\cdot$kg$\cdot$min) were routinely used; meanwhile, epinephrine (0.05–0.1 µg$\cdot$kg$\cdot$min) or levosimendan (0.1–0.2 µg$\cdot$kg$\cdot$min for 24 hours) and norepinephrine (0.05–0.1 µg$\cdot$kg$\cdot$min) were used to improve cardiac output when necessary. Nitric oxide (NO) (5–20 ppm) inhalation, iloprost, bosentan, or phosphodiesterase-5 inhibitors were used alone or in combination for post-surgical management of reactive PH. For a mechanical ventilation time of 48 hours, midazolam (1–3 µg$\cdot$kg$\cdot$min) and dexmedetomidine (0.5–0.75 µg$\cdot$kg$\cdot$h) were administered; for a mechanical ventilation time of $>$48 hours, sedation and analgesia were provided with a combination of midazolam (2–4 µg$\cdot$kg$\cdot$min) and fentanyl (1–3 µg$\cdot$kg$\cdot$h, $\le$1 month) or sufentanil (0.3–0.75 µg$\cdot$kg$\cdot$h, 2–6 month).

Echocardiography was performed at the bedside to assess the cardiac function and any residual defects. Subsequently, for children who exhibited an intraoperative pulmonary venous flow velocity of around 1.8 m/s, a postoperative ultrasound examination was performed on two consecutive days to obtain the average values of the pulmonary venous flow velocity, ejection fraction (EF), and left ventricular end diastolic dimension (LVDD).

The protocol for extubation after surgery required that children successfully pass a spontaneous breathing trial (SBT), which included stable hemodynamics, spontaneous breathing, urine output $>$1 mL/kg/hour, minimal chest tube output, and complete sternal closure. Other parameters included warm extremities, normal skin color, and a capillary refill of 3 seconds, a normal heart rate, palpable peripheral pulses, no lactic acidosis, an inotropic score 20, PEEP 6 cmH₂O, FIO₂ 60%, SpO₂ target of $>$92% for all patients, a PaCO₂ 45 mmHg, PaO₂ $>$60 mmHg, and no acidosis. A total of 20 patients were re-intubated after a prior failed extubation.

When the hemodynamics of each patient were stable and ready for weaning, a bedside ultrasound examination of the diaphragm movement was performed. If one side of the diaphragm showed reduced movement, the patient was extubated, and non-invasive ventilation support was provided. For bilateral diaphragmatic weakness, neural-adjusted ventilator assist and potential monitoring were used. Ultimately, diaphragmatic plication was considered if the patient could not be weaned off non-invasive ventilation after extubation, had further elevation of the diaphragm or persistently low diaphragmatic potentials under neurally adjusted ventilatory assist (NAVA) monitoring, accompanied by atelectasis and weight loss caused by respiratory compromise.

A total of 18 children underwent diaphragmatic plication, and there were two cases of re-intubation due to arrhythmias after extubation.

All surgical patients who were discharged from the hospital were required to return for outpatient follow-up visits at 1, 3, and 6 months after the initial operation. Some patients were required to visit local hospitals for routine examinations and follow-up if the patients were unable to return to our hospital. Any abnormal examination findings or changes in cardiac function resulted in a return visit for further evaluation. Both echocardiography and electrocardiography were routinely performed during the follow-up period. If the echocardiography Doppler finding indicated recurrent PVO, computed tomography (CT) was performed to evaluate the obstruction. In this study, 31 children had pulmonary vein flow velocities $>$1.8 m/s. The follow-up results at six months are detailed in Fig. 3. Moderate symptoms of PVO were defined as the need for oxygen and diuretic therapy. Mild symptoms were defined as requiring only diuretic treatment.

Fig. 3.

Follow-up results in six months. The children whose pulmonary vein flow velocities are $>$1.8 m/s after the operation. PV, pulmonary venous flow; PVO, pulmonary venous obstruction.

A preoperative echocardiogram was performed for all patients. Computed tomography angiography (CTA) was performed in selected children, as determined by the primary treating physicians, in 98% of patients (317 of 323) before surgery. A six-month follow-up was performed. Early postoperative death was defined as death during hospitalization or death within 1 month after discharge. Intermediate death was applied to refer to death more than 1 month after discharge.

The preoperative PV $>$1.8m/s, PH (tricuspid regurgitation (TR) $\ge$3.5m/s), age, weight, length, weight-for-age Z score (WAZ), LVDD Z value, sex, anatomic type, associated cardiac lesion, metabolic acidosis, emergency operation, respiratory tract infection within 2 weeks, and invasive mechanical ventilation were recorded. The CPB and aortic cross-clamp (ACC) times, delayed sternal closure, low cardiac output syndrome (LCO) within 48 h after the operation, velocity of pulmonary venous flow/ejection fraction (PV/EF) ratio, and velocity of pulmonary venous flow/left ventricular end diastolic dimension (PV/LVDD) ratio, diaphragmatic plication, sepsis, duration of ventilation, postoperative ICU and hospital stay, postoperative severe PH and PVO were all documented.

Statistical analyses were performed using SPSS (version 22.0, IBM Corp, Armonk, NY, USA). Continuous data are presented as the median (range) or mean $\pm$ standard deviation (SD). Categorical data are presented as frequencies and percentages. The median and interquartile ranges of the postoperative mechanical ventilation period were calculated. Group A included children with a postoperative mechanical ventilation period longer than the 75th percentile of the postoperative mechanical ventilation period. Group B included the remaining children. A Student’s t-test or Wilcoxon–Mann–Whitney U test was used to compare the differences in the continuous data between the two groups. Categorical data were compared using the Pearson $\chi$² or Fisher’s exact test. A two-sided p-value 0.05 was considered significant. Multivariate logistic regression analysis was used to identify factors associated with the prolonged recovery periods.

A total of 369 children underwent TAPVC repair during the study period, of which 323 children were included in the analysis (Fig. 1). The median and interquartile ranges of the ventilation duration were 58 h and 120 h. During the operation, 311 (96.3%) children had moderate hypothermia, and 40 (12.4%) children required deep hypothermic circulatory arrest. The sutureless technique was used for 227 (70.3%) children. During the follow-up period, seven children required reoperation due to recurrent PVO. Among them, one child in group A refused reoperation and died two months after hospital discharge, while six children underwent reoperations, although recurrent PVO occurred during the 6-month follow-up period.

Table 1 summarizes the cohort characteristics. The median age at the time of surgery was 53.2 days (range: 0–180 days), and the median weight was 4.4 kg (range: 1.28–11.4 kg). Group A consisted of 66 children (38 males and 28 females) with a median age of 25.3 days, while group B included 257 children (156 males and 101 females) with a median age of 57.8 days. The preoperative, intraoperative, and postoperative characteristics were compared between the two groups (Tables 2,3,4).

In the preoperative analysis, the children in group A had significantly more intracardiac anatomic types, a higher WAZ –2 score, and more severe PH and emergency operation compared with the children in group B. Moreover, the children in group A had statistically significantly higher PV values $>$1.8 m/s, PV/EF, and PV/LVDD than the children in group B (Table 2).

In the intraoperative analysis, statistically significant differences were observed in CPB time and ACC time (Table 3). Conversely, there were no differences between the two groups in terms of other congenital heart defects, surgeon experience, surgical method, or the proportion of delayed chest closure postoperatively in the intraoperative analysis. The children in group A had longer CPB and ACC times than the children in group B.

Group A had a higher incidence of low cardiac output syndrome (LCOS) and required more diaphragmatic plications than Group B. LCOS was characterized by an elevated partial pressure of carbon dioxide (P(v–a)CO₂) between the artery and vein, decreased central venous oxygen saturation (ScvO₂), increased lactate levels, and a higher positive inotropic drug score (IS). Children in group A required longer durations of non-invasive ventilation (NIV) support than those in group B. The PV/LVDD ratio was significantly higher in group A, with a cutoff value of 0.624 identified for prolonged postoperative recovery (Fig. 4). Of the 11 children who died postoperatively, 10 died in the hospital, and one died two months after discharge. Four of these children had a PV of $>$1.8 m/s, and nine had a PV/LVDD ratio of $>$0.624. All infections listed in Table 4 were new-onset postoperative infections, detected through postoperative sputum culture, sputum NGS examination, or blood culture tests.

Fig. 4.

Receiver operating characteristic (ROC) curve for the PV/LVDD. ROC curve for the PV/LVDD on the first day after the operation. The area under the full ROC curve is 0.702, with a specificity of 0.789 and an estimated sensitivity of 0.579. The PV/LVDD cutoff value was 0.624.

The multivariate analysis revealed that a WAZ –2, preoperative PVO, emergency surgery, prolonged CPB and ACC times, postoperative diaphragmatic injury, and PV/LVDD were independent risk factors for a protracted recovery period (Table 5); however, intracardiac and LCOS were not statistically significant. A PV of $>$1.8 m/s, PV/EF, PV/LVDD, and preoperative PH before surgery were statistically significant between the two groups (Table 2); however, only PV/LVDD remained statistically significant after surgery.