Transcatheter Device Closure of Perimembranous Ventricular Septal Defect in Pediatric Patients: Long-Term Outcomes.

AIMS: The aim of this study is to evaluate the safety and efficacy of transcatheter device closure of perimembranous ventricular septal defects in pediatric patients at long-term follow-up.
MATERIALS AND METHODS: We prospectively studied 376 patients with perimembranous VSDs between September 2008 and December 2015 who underwent percutaneous closure at our center. Transthoracic echocardiography (TTE) and electrocardiogram were done before and after the procedure in all the patients. All patients were subjected to follow-up evaluation at 1, 3, 6, 12 months, and annually thereafter with TTE and electrocardiogram.
RESULTS: A total of 376 patients (210 males and 166 females) underwent transcatheter closure of perimembranous VSD. Mean age of patients was 8.67 ± 3.02 (range 3-18 years) and mean weight was 21.15 ± 8.31 (range 8-65 kg). The procedure was carried out successfully in 98.93% of patients with no reported mortality. Rhythm disturbances occurred in 8.5% of patients after the procedure which included three cases of complete atrioventricular block.
CONCLUSION: This study shows that in experienced hands transcatheter closure of perimembrnous VSD is safe and effective at long-term follow-up. With minimal morbidity and no mortality, the transcatheter is an effective alternative to surgical closure in selected patients. Copyright:

INTRODUCTION

Ventricular septal defects (VSDs) are the most common congenital heart problems accounting for almost one-third of all cases. The perimembranous VSD (pmVSD) accounting for majority of cases involves membranous septum and part of adjacent muscular septum.[1] Surgical closure of VSD is still widely a performed procedure across the globe but involves potential risks such as complete atrioventricular block (cAVB), infection, postpericardiotomy syndrome, chylothorax, and neurologic sequelae after cardiopulmonary bypass.[234567] Catheter-based interventions are showing promising results compared to surgery ever since the first reported case in 1988.[8910111213141516] Data for transcatheter closure of pmVSD are scarce and without long-term results.[1718192021222324]

MATERIALS AND METHODS

Patients

A total of 376 children with pmVSDs underwent percutaneous closure between September 2008 and December 2015. There were 210 male and 166 female children ranging ranging in age between 3 and 18 years. A complete preprocedural evaluation which included clinical examination, X-rays, electrocardiograms, and transthoracic echocardiogram (TTE) was done in all the patients.

Inclusion criteria used in the study were as follows: (i) congenital pmVSD on TTE, (ii) body weight >8 kg and age >2 years, (iii) maximum defect diameter <14 mm on TTE, (iv) defect in 9–11 o'clock position on parasternal short-axis view on TTE, (v) subaortic rim >4 mm, (vi) significant left-to-right shunt, (vii) <60 mm Hg of pulmonary pressure on TTE, and (viii) history of infective endocarditis related to VSD.

Findings suggestive of significant left-to-right shunting were as follows: (1) cardiomegaly on chest X-ray defined as cardiothoracic ratio >0.55, (2) left atrial enlargement defined as left atrial to aortic diameter ratio >1.5 on TTE, (3) left ventricular volume overload defined as left ventricular end diastolic diameter > +2 SD above mean for patients age, and (4) frequent respiratory infections defined as >6 events/year.

The exclusion criteria were as follows: (i) pmVSD associated with other congenital cardiac defects requiring surgery, (ii) body weight <8 kg and age <2 years, (iii) aortic regurgitation, (iv) severe aortic valve prolapse, (v) bidirectional or right-to-left shunt through VSD, (vi) sepsis, (vii) contraindication to antiplatelet therapy, and (viii) subaortic rim <2 mm. A detailed and informed written consent was taken from all the eligible patients or parents before the procedure.

Procedure

The procedure was performed under general anesthesia with TTE and fluoroscopic guidance. The defect diameter was measured on TTE using two-dimensional imaging and color flow in short- and long-axis views. The vertical diameter of the defect was measured during left ventricular angiography. 100 U/kg heparin and intravenous antibiotics were given in all the patients. The right femoral vein and artery were used for access during the procedure.

All the patients underwent standard right and left heart catheterization, left ventriculography, and ascending aortic angiography. VSD defect diameter and its relation to aorta were studied in all cases. A device 2 mm larger than the measured diameter was selected during the procedure. The defect was negotiated from left ventricle using right coronary artery catheter (Cordis Corp., Miami, FL, USA) or an Amplatzer right coronary catheter (Cordis Corp.) and exchange length straight tipped Terumo Guidewire (Terumo Medical Corp., US) which was parked in the pulmonary artery or superior or inferior vena cava. It was then snared (EV3, Plymouth, Minnesota, USA) forming an arteriovenous loop. A long sheath (6–12 Fr) was then advanced over looped wire from venous end into the left ventricle. The device occluder was then deployed under fluoroscopic and echocardiographic guidance.

Postdeployment left ventriculography, and aortic root angiogram was done to verify complete closure and to detect any new onset of aortic regurgitation.

All the procedures in this study were approved by Institutional Ethics Committee and were in accordance with guidelines provided by the World Medical Association Declaration of Helsinki on Ethical Principles for Medical research involving human beings. All procedures were in accordance with Helsinki Declaration of 1975, as revised in 2000.

Follow-up

All patients underwent complete clinical examination, electrocardiography, X-ray chest, and TTE before discharge, at 1, 6, 12 months after the procedure, and yearly thereafter. Aspirin 5 mg/kg/day orally was prescribed for 6 months along with oral steroids (tablet prednisolone 1–2 mg/kg) in tapered doses over 2 weeks. Treatment with steroids was extended in patients with conduction disturbances.

Data analysis

All data were expressed as a frequency or percentage for nominal variable, as median for categorical variables and mean ± standard deviation for continuous variables. SPSS software version 25.0 ((IBM Corp., Armonk, NY, USA) was used for statistical analysis. P < 0.05 was considered statistical significance.

RESULTS

Patient-related variables

Transcatheter pmVSD closure was attempted in 376 children which was successful in (371/376) 98.93% patients. There were 166 female and 210 male patients [Table 1]. The weight of children varied between 8 and 65 kg (21.15 ± 8.31). The size of the defect on TTE varied between 2.5 mm up to 12 mm (5.02 ± 1.42) [Table 1].

Table 1

General characteristics

n	376
Gender
Female	166
Male	210
Age (years)	8.67±3.02 (3-18)
<6	125 patients
6-12	180 patients
12-18	71 patients
Weight (kg)	21.15±8.31 (8-65)

Catheterization data

Cardi-O-Fix VSD occluder (Starway Medical Technology Inc., Beijing) was the most frequently used device (52%) followed by Shanghai symmetrical VSD occluder (Shape Memory Alloy Ltd., Shanghai) in 26% of patients and Amplatzer duct occluder (St. Jude Medical Inc., MN, USA) in 22% of patients [Table 2]. The fluoroscopy time of procedure ranged between 3 min and 72 min (13.01 ± 8.71) while device/defect ratio varied between 110 and 290 in percentage (135 ± 35) [Table 2].

Table 2

Procedural data and devices used

Fluoroscopy time (min)	13.01±8.71 (3-72)
Qp/Qs	2.1±0.5 (1.4-4.5)
Mean PA pressures (mmHg)	22±5 (15-30)
VSD diameter on TTE (mm)	5.02±1.42 (2.5-12)
Device diameter/VSD diameter on TTE (%)	135±35 (110-290)
Type of device used (%)
Cardi-O-Fix VSD occluder	52
Shanghai shape memory alloy occluder	26
Amplatzer duct occluder	22

VSD: Ventricular septal defects, TTE: Transthoracic echocardiogram, PA: Pulmonary artery, Qp: Pulmonary flow, Qs: Systemic flow

Adverse events and follow-up evaluation

The follow-up period of patients varied between 28 months and 121 months with a median follow-up of 78 months. There were a total of 87 adverse events (23.13%) reported in patients who underwent attempted pmVSD device closure [Table 3]. Residual shunting immediately after the procedure was detected in 14 patients which decreased significantly during the follow-up evaluation of patients.

Table 3

Adverse events

Events	n
Major adverse events	4
cAVB that required surgery	1
New-onset valvular regurgitation that required surgery	1
Device embolization that required surgical removal	1
Hemolysis required surgical removal	1
Minor adverse events	83
Hematoma of groin	5
Blood transfusion due to blood loss	3
Junctional rhythm	27
Transient cAVB	2
RBBB	3
LBBB	2
Hemolysis required medication	2
Residual shunt immediately after procedure	7
Others (fever >38.5°C, rash, loss of peripheral pulse)	32

cAVB: Complete atrioventricular block, RBBB: Right bundle branch block, LBBB: Left bundle branch block

Overall four major adverse events were reported in our study. There was no mortality observed during the procedure and hospital stay. There was one case of device embolization into descending abdominal aorta during the procedure which was immediately retrieved, and defect was closed surgically. The second patient has persistent gross hematuria and anemia which was tackled with device removal surgically and defect closure. The third patient developed cAVB during the procedure, and so the defect was tackled by surgical approach. Another patient developed severe new-onset aortic regurgitation during device deployment with transient asystole and bradycardia. The device was retrieved, and defect required surgical closure.

Cardiac conduction abnormalities were seen in 8.5% of patients with transient cAVB occurring in two patients. Conduction disturbances noted were junctional rhythm (27 patients), right bundle branch block (3 patients), and left bundle branch block (2 patients). Except for mentioned adverse events, there were no cases of deaths, cardiac perforations, infective endocarditis, device malposition, thrombus formations, late cAVB, or significant arrhythmias during the median follow-up period of 78 months.

DISCUSSION

This study depicts a large single-center experience in percutaneous device closure of pmVSD with excellent procedural success rates (98.93%) which is in line with previously published data.[141719202526] In addition, transcatheter approach is superior in terms of psychological impact, hospital stay, procedural discomfort, and faster recovery.

Among different percutaneous devices available to occlude pmVSD,[8272829] Amplatzer occluders and other similar devices provide exceptionally good results with minimal comorbidities.[111417193031] This study is unique because it depicts the safety and efficacy of transcatheter closure of pmVSD at long-term follow-up in contrast to previous studies where data at long-term follow-up is glaringly lacking. The present study depicts an excellent immediate outcome and follow-up results of pmVSD device closure.

Knowledge of technical complexities of pmVSD device occlusion is vital because of variations of anatomical associations of perimembranous defect with aortic valve, tricuspid chordae tendineae, atrioventricular node, and conduction bundle. Certain anatomic and physiologic parameters such as severe aortic valve prolapse, abnormal tricuspid chordae insertion, VSD with pulmonary hypertension, and small babies with low-body weight are not amenable to device therapy and so should be excluded beforehand for transcatheter closure.

Different diagnostic catheters such as three dimensional right coronary (3DRC), Amplatzer right 1 (AR 1), Judkins right, and partly cut pigtail catheter can help during the passage of guide wire across the defect. After snaring of guide wire, the arteriovenous loop should be met with no resistance and should be straight without any kinks. In case of any kinks in the arteriovenous circuit, the entire procedure should be repeated due to the risk of damage to tricuspid chordae and acute valvular regurgitation.

Before releasing the device aortic root angiography is must to document the absence of aortic regurgitation. If new-onset aortic valvular insufficiency is detected, either asymmetric devices or culmination of procedure should be considered.

Although transesophageal echocardiography is the modality of choice to guide pmVSD device closure as depicted in studies,[12141920] TTE provides excellent guidance along with reduced procedural time and increased patient compliance.

We observed that window, tubular, and infundibular types of pmVSD were technically easier to occlude percutaneously compared to aneurysmal type of defect. Due to the resemblance of aneurysmal type of pmVSD to patent ductus arteriosus, Amplatzer duct occluder I (St. Jude Medical, MN, US) is a device of choice for such defects.[32]

In our study, the most common cardiac conduction disturbance was junctional rhythm (7.18%), bundle branch block (1.32%), and transient cAVB (0.6%) which recovered with steroids. cAVB is the most significant arrhythmia leading to complications in both early phase and follow-up period, with an incidence ranging from 3.5% to 8.6%.[183334] Certain patient and procedural variables directly related to a higher incidence of cAVB are namely young age, low body weight, type of device, oversized device, position of defects, and repeated maneuvers.[12162534] Myocardial edema due to immature myocardium with higher water content and tender structure in young patients is the predisposing factor leading to a higher incidence of cAVB in younger patients.[35]

Our study also showed that the incidence of postprocedure heart blocks (PPHBs) was more in patients where defect is in proximity to tricuspid valve and farther from aortic valve. This may be due to the conduction system crossing in proximity to the tricuspid valve which is susceptible to direct traumatic compression due to the device. Moreover, the device may lead to inflammatory reaction and fibrosis of the conduction system.

The occurrence of cAVB after surgery is in the early postoperative period in contrast to cAVB arising after percutaneous closure, where it is quite unpredictable and usually a late problem. In most of the cases, PPHBs are transient and recovers spontaneously or with hydrocortisone and a temporary pacemaker.[1423243637] PPHBs including high-degree atrioventricular block (AVB) occurs mostly 2–7 days after procedure,[131617253336373839] but sometimes occur at 2–4 weeks or even later (12–36 months).[253336373839404142]

There is less chance of recovery in PPHBs especially high-degree AVB developing during or immediately after the procedure due to the immediate effect of device-related traumatic compression of the conduction system. This necessitates close monitoring for at least 5 days in the hospital and during the follow-up evaluation.

CONCLUSION

This study shows that the transcatheter closure of pmVSD is safe and effective in experienced hands compared to surgery at longer-term follow-up. However, close monitoring is recommended for early detection of potentially life-threatening complications like PPHBs during the hospital stay and follow-up visits. Careful attention should be paid to appropriate device selection and meticulous delineation of defect anatomy in young patients.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.