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Simultaneous transthoracic intervention for multiple cardiac defects in children

Background Transthoracic intervention for isolated congenital heart disease (CHD) has been well tested for its technological feasibility and is increasingly used in clinical practice. We aimed to present our experience in simultaneous transthoracic intervention for multiple cardiac lesions in a series of pediatric patients. Methods Between March 2015 and December 2019, 20 patients with multiple CHD were referred to this study; mean age was 18.8±8.6 (range, 4–36) months. The transthoracic echocardiography (TTE) diagnosis was atrial septal defect (ASD) and perimembranous ventricular septal defect (pmVSD) in 7 patients, patent ductus arteriosus (PDA) and ASD in 6, pmVSD and PDA in 2, pmVSD and valvular pulmonary stenosis (PS) in 2, ASD and PS in 2, and doubly committed subarterial VSD (dcsVSD) and PS in 1 patient. These patients underwent simultaneous transthoracic interventions with transesophageal echocardiography guidance. The procedure sequence was PS→VSD→PDA→ASD. Electrocardiography and TTE were scheduled at discharge and follow-ups. Results All patients were occluded successfully without any thoracotomy conversion. Operation time was 56–120 (mean, 75±13) minutes. A 1.5–2.0-cm median sternum incision was performed in 6 ASD&PDAs, 2 ASD&PSs, and 1 dcsVSD&PS. In 11 other patients, a 1.5–2.0-cm incision in the inferior sternum was made and the chest closed with a drain. There were no serious complications before discharge and at follow-up. Conclusions Simultaneous transthoracic intervention for multiple cardiac defects in children is feasible with good short-term outcomes. For different lesions, the appropriate surgical incision and operational sequence can render the intervention minimally invasive and safer.

1. The value of the data are unfortunately extremely limited, as there is no comparison group of children with the same combinations of heart defects that have been treated with open heart surgery (according to the authors, only 15% received the intervention, so where and how are the results of the other 85% of infants?). A comparison in terms of perioperative management and outcome (including some statistical analyses) would be of great value to adequately assess the novel intervention.
Reply 1: Thank you very much for the suggestion. Between March 2015 and December 2019, 133 patients were admitted to our center with multiple CHD and were allocated to groups on the basis of the surgical method selected by the patient. A group consisted of 20 patients who underwent an attempt of simultaneous transthoracic intervention were referred to this study. These numbered 15 males and 5 females, with a mean age of 18.8 ± 8.6 (range, 4-36) months and a mean weight of 8.3±2.5 (range, 4.8-12.5) kg. Other 113 patients who refused device closure received conventional surgical repair with cardiopulmonary bypass (CPB).
Other 113 patients with multiple congenital cardiac defects were corrected by cardiac surgery. The anesthesia time and operation time were 150-360 (mean, 227 ± 47) minutes and 90-300 (mean, 181 ± 43) minutes respectively. The amount of intraoperative blood loss was 2.2-27.3 (mean, 10.1 ± 4.1) ml/kg. The length of postoperative ventilation ranged from 0.5 to 10 (mean, 3.3 ± 2.3) hours with postoperative hospital stay ranging from 3 to 13 (mean, 6.8 ± 2.4) days. Both time of CPB has been criticized because of operative trauma, an unsightly scar, and CPBassociated complications. Catheter-based closure is limited for infants because of small vascular diameters, and radiation exposure is still a disturbing problem for children. Transthoracic intervention for multiple cardiac defects, as a new technology that obviates the need for surgery or a multistaged interventional procedure with prolonged fluoroscopy time, has been reported in only a few studies. Therefore, we present our experience with simultaneous transthoracic interventions for multiple cardiac defects in a series of pediatric patients. Our study indicated that the procedure is technically feasible, with excellent short-term outcomes. For different lesions, the appropriate surgical incision can render the intervention minimally invasive and safer. And PS→VSD→PDA→ASD may be the most widely acceptable operational sequence.

2.
Methods should describe more the periprocedural monitoring: Which antibiotic was given periprocedural? What is the definition of "serious arrhythmia", which did not occur? Which types of arrhythmia occurred and how were they treated? With which examinations were arterial thromboses (cranial?) excluded? Is there a neurodevelopmental follow-up of the infants?
Reply 2: Thank you very much for the suggestion. All patients with device implantation received antibiotics during the operative procedure (cefuroxime sodium, 30 mg/kg) and the following day (cefuroxime sodium, 100 mg•kg -1 •d -1 , q8h). We have described antibiotic monitoring in the Procedures (see Page 8, line 125-127).
In this study, there was no arrhythmia observed in 20 patients during hospitalization and the post-operation period. Based on our experience with transthoracic intervention for isolated CHD, complete atrioventricular block occurred, defined as "serious arrhythmia", needed to be converted to conventional open-heart surgery.
Temporary arrhythmia that occurs in most cases did not require therapy and underwent spontaneous recovery. We have modified our text as advised in the

3.
To be able to better assess the interventions, following data should be added to

5.
Although the devices can be clearly seen, the image quality of Figure 2 (X-ray) should be improved.
Reply 5: As suggested, we have uploaded Figure 2 with higher image quality. Figure 4A (inferior sternum incision) should be referred to in the manuscript text.

6.
Reply 6: Thank you very much for the suggestion. In this study, a 1.5-2.0-cm inferior sternum incision ( Figure. 4A) was made in 11 patients as mentioned in Results.
Normally, the free wall of the RV is exposed via a minor inferior sternum incision for the closure of a perimembranous VSD, with a shorter distance and directional performance can vertically advance the delivery sheath across the VSD. We have Transthoracic intervention, a hybrid technique has been widely used in the past decades, associated with no age or weight limitation, shorter distance and directional performance, decreased surgical morbidity, shorter duration of hospital stay, and avoidance of radiation exposure and issues with satisfactory vascular access.
Moreover, with the real-time echocardiography monitor, the operative process can better observed and guided. Once the device fails or procedure unsuccessful, it can be easily converted to conventional surgery with CPB. Of course, the new technology still has its limitations. It must be performed under general anesthesia with tracheal intubation. And its minimally invasion has been questioned. As suggested, we have added discussion on advantages and disadvantages of this new technique include more up to date literature in the Discussion (see Page 10-11, line 177-186).

8.
Statistics: The presentation of variables and results in mean, range, average is incorrect (mean cannot be a range, presentation of average /SD?). 9. The authors should get advice by an English medical language expert for further language improvements.

Reply 9:
We had done the Language Editing and got the certification.