Essay: Compare the clinical outcome of transcatheter device closure of ventricular septal defect

Evolving technology in the interventional techniques has now made the transcatheter closure of anatomically selected ventricular septal defects feasible with satisfactory results and low morbidity rates10. In most centers, the procedure is approached using antegrade or transvenous method by creating an arteriovenous guide wire loop; which is the standard technique for transcatheter VSD device closure. Some studies have described that retrograde method and transarterial approach cannot be performed due to technical difficulties, mostly in adult patients. Recent studies of using variety of Amplatzer occluder devices had been successful with retrograde technique in adolescents and children with congenital VSD. Retrograde technique involves fewer steps and possesses the potential to significantly reduce fluoroscopy and total procedure time in comparison with the conventional methods. In a case series of Pekel et al. presented their experience of the transcatheter VSD closure using transarterial retrograde approach and concluded that it simplifies the procedure, decreases the radiation exposure, and shortens the procedure time.13 After a thorough literature search, no local study on transcatheter device closure of VSD comparing the two techniques was published.
Early in this institution, most patients with ventricular septal defect that undergo transcatheter technique still use the conventional method (transvenous antegrade approach). Only ten years ago, transcatheter closure using implantable devices has been introduced and is recently gaining popularity. When explaining the therapeutic options to the patients or the parents with VSD, outcome goals and complications or adverse events should be fully discussed. Since transcatheter device closure of VSD is an evolving technology, data on effectiveness, cost and mid-term outcome comparing these two techniques in transcathether closure of ventricular septal defect are currently lacking; hence this research was formulated.
OBJECTIVES
The general objective is to compare the clinical outcome of transcatheter device closure of ventricular septal defect using Antegrade and Retrograde approaches among patients of this institution.
The specific objectives are:
1. To compare clinical characteristics of patients underwent antegrade and retrograde group.
2. To compare procedural data of patients underwent antegrade and retrograde group.
3. To determine clinical outcome of antegrade technique on VSD closure.
4. To determine clinical outcome of retrograde technique on VSD closure.
METHODS
Patients
From January 2013 to July 2018, we retrospectively collected data on 81 patients who underwent transcatheter device closure of VSD at our institution. Seventy-two of these 72 subjects were diagnosed with isolated VSD that underwent transcatheter closure. Patients were assessed by the standard transthoracic echocardiographic protocol. The study was conducted in compliance with the ethical principle set forth in the Declaration of Helsinki. The study was also reviewed and approved by the Institutional Ethics Review Board (IERB).
Sample Size Calculation
Sample size computed for this study was n = 72 at 95% confidence level, maximum tolerable error of 5% and assumed prevalence of 31 cases who underwent transcatheter closure of VSDs among children in the paper of Valdez et al12.
Inclusion and exclusion criteria
The criteria for inclusion in this study were:
1. Age >1 year old and weight > 7kg
2. Pre and post-procedure Transthoracic Echocardiography done at our institution
3. Pre and post-procedure Chest radiography and 15 Lead ECG done at our institution
4. Fulfill all the echocardiography criteria:
a. Presence of ventricular septal defect in 2 different views
b. Defect diameter on the left ventricular side <12mm.
c. Aortic rim > 5mm
d. No significant aortic valve prolapsed nor regurgitation.
The criteria for exclusion in this study were:
1. Pelvic vein or inferior vena cava thrombosis.
2. Other cardiac anomaly that require surgical or transcatheter intervention.
3. Patients who have pulmonary vascular resistance >8woods unit.
Subjects were labeled into 2 groups: those who underwent transcatheter VSD closure using Antegrade or arteriovenous (AV) loop and Retrograde or transarterial approach.
Occluder Devices
Two local brands of device are available in our institution: Lifetech Scientific and Cocoon. The availability of the devices at operation day will be the main factor in the choice of devices.
Procedures
Percutaneous closure of a VSD is performed under general anesthesia with sedation. Patients are given heparin 100 IU/kg, hydrocortisone 5mg/kg and antibiotic intravenously. The procedure is performed under fluoroscopic control.
Procedures for apical VSD (Figure 1) using antegrade technique; and perimembranous VSD (Figure 2) using retrograde technique have been previously reported in detailed.13,14
Study Maneuver
a. A retrospective review of the charts of all pediatric patients who underwent transcatheter device closure of VSD from January 2014 to July 2018 was done. Data were extracted from Medical Records of the hospital; and patients were identified by discharge diagnosis from the CV laboratory databases. Patients who underwent transcatheter VSD closure were grouped according to the approach used during the procedure.
b. Charts were reviewed and the following information were obtained:
i. Demographic Information
1. Age of the patient
2. Gender
3. Weight
4. Modified Ross Classification
Modified Ross Heart Failure Classification in Children
I Asymptomatic
II Mild tachypnea or diaphoresis with feeding in infants
Dyspnea on exertion in older children
III Marked tachypnea or diaphoresis with feeding in infants
Marked dyspnea on exertion
Prolonged feeding times with growth failure
IV Symptoms such as tachypnea, retractions, grunting, or diaphoresis at rest
ii. Electrocardiographic Data
1. Heart rate
2. PR interval
3. Rhythm
4. ST-T wave (normal, elevation, depression)
iii. Echocardiographic Data
1. Maximum diameter Ventricular septal defect (mm)
2. Presence of Left Ventricular enlargement
3. Presence of Left Atrial enlargement
4. Pulmonary artery pressure (mmHg)
iv. Procedural Data
1. Fluoroscopy time
2. Procedure time
3. Mean pulmonary artery pressure (mmHg)
4. VSD size (mm)
5. Device used
c. Charts were reviewed for the outcome.
1. Principal Efficacy
i. Acute procedure success: the number of patients where the two techniques were attempted, those who successfully close the ventricular septal defect.
ii. Pre-discharge efficacy (24-hrs efficacy): complete closure at pre-discharge (maximum 24 hours)
iii. Hospital stay
iv. Follow-up Periods:
1. 2D echo follow-up (Complete closure of VSD)
a. 1-month efficacy: complete closure at 1-month follow-up
b. 3-month efficacy: complete closure at 3-month follow-up
2. Principal Safety
i. Serious adverse event: any event causing death
ii. Major adverse event: any event causing organ failure or dysfunction (e.g. stroke emboli) or any damage to other structure inside the heart, device embolization required surgical removal, and complete heart block during follow-up.
iii. Minor adverse event: device embolization required percutaneous removal, mild to moderate regurgitation of the valve (especially tricuspid and aorta) related to the procedures, hemolysis, hematoma of the groin, loss of peripheral pulse, cardiac arrhythmia requiring cardioversion or medication during procedures, blood loss required transfusion and residual shunt.
iv. Any adverse event: any event not classified above.
Follow-up Period
The follow up variables includes clinical examination; electrocardiography and echocardiography at 1 month and 3-month follow up.
DATA ANALYSIS
We used SPSS 16.0 for Windows (SPSS, Inc., Chicago, IL, USA) for the statistical analysis. The quantitative variables were summarized and presented as mean and standard deviation, while qualitative variables will be tabulated and presented as frequency and percent distribution. Homogeneity of characteristics between the 2 groups was tested using the t test for the quantitative variables and Fisher’s exact test for qualitative variables. Comparison of outcome between the 2 groups was determined and tested using independent t-test for the fluoroscopic time, procedure time and length of hospital stay while Fisher’s exact test for specific outcomes. A p-value less that or equal to 0.05 was considered significant. Furthermore, logistic regression analysis was used to compare the two techniques of transcatheter VSD closure in terms of developing at least 1 complication.
RESULTS
Patients
A total of 81 patients who underwent successful transcatheter closure of VSD were reviewed in our institution. Based on the inclusion criteria only 72 patients (88.9%) were included in this study. There were 37 whom underwent antergrade or transvenous (Group A) approach (Figure 1) and 35 whom underwent retrograde or transarterial (Group B) approach (Figure 2). The mean age of patient in Group A was 9.89 years + 4.68 and in Group B was 12.03 years + 5.03; which was not statistically significant. There were 37 male and 35 female patients. The weight and height of the patients between the two groups were statistically significant (p-value 0.001 and <0.001); group A had 25% with z-score of -2 (wasted and stunted) while group B had 100% with z-score of -1 to 0 (normal). In this study, group B had higher body surface area (BSA) at 1.19 + 0.37 compared with group A with BSA of 1.00 + 0.39 (p-value 0.041). Functional Class using Modified Ross Classification was not significant with p-value 0.061. Diagnostic data such as types and sizes of VSD as well as presence of LA enlargement and pulmonary arterial hypertension were not significant for both groups with p-values above 0.05. The most common VSD type for both groups was the perimembranous type with 28 (77%) patients in Group A and 33 (94%) patients in Group B. Twenty-seven (72.97%) of patients from Group A manifested with LV enlargement compared with Group B with 11 (31.43%); which was statistically significant (p-value 0.000). Significant shunting (QpQs ratio) was also observed more with Group A (1-1.6:1) compared with Group B (1-1.2:1). Electrocardiograhic data such as PR interval and rhythm were not statistically significant (p-values >0.05). Heart rate of group B (74.37 + 13.9) was noted to be lower in comparison with Group A (84 + 14.85) with p-value of 0.004. Demographic and diagnostic data are summarized in Table 1.
Table 1. Baseline demographic and diagnostic of the patients underwent transcatheter procedure according to technique used.
Antegrade
(n=37) Retrograde
(n=35) P-value
Frequency (%); Mean + SD; Median (IQR)
Demographic Profile
Age 9.89 + 4.68 12.03 + 5.03 0.066
Sex
Male
Female
22 (59.46)
15 (40.54)
18 (51.43)
17 (48.57) 0.493
Weight
z-score
-1 (-2 to 0)
0 (-1 to 0)
0.001
Height
z-score
-1 (-2 to 0)
0 (0 to 0)
<0.001
BSA 1.00 + 0.39 1.19 + 0.37 0.041
Modified Ross Functional Class
I
II
31 (83.78)
6 (16.22)
33 (97.06)
1 (2.94) 0.061
Echocardiographic Parameters
VSD, type
Muscular
Perimembranous
Apical
Multiple
7 (18.92)
28 (75.68)
1 (2.70)
1 (2.70)
2 (5.71)
33 (94.29)
0 (0)
0 (0) 0.051
VSD Size cm 0.5 (0.40 to 0.70) 0.45 (0.38 to 0.50) 0.062
LV enlargement
Yes
27 (72.97)
11 (31.43) <0.001
LA enlargement
Yes
17 (45.95)
12 (34.29) 0.313
PA Pressure
Normal
Mild
Moderate
Severe
30 (81.08)
2 (5.41)
4 (10.81)
1 (2.70)
33 (94.29)
2 (5.71)
0 (0)
0(0) 0.165
QpQs Ratio 1.2:1 (1 to 1.6:1) 1:1 (1 to 1.2:1) 0.002
Electrocardiographic Parameters
HR 84 + 14.85 74.37 + 13.9 0.004
PR interval 0.12 + 0.02 0.12 + 0.02 0.723
Rhythm
Sinus
Abnormal
36 (97.30)
1 (2.70)
35 (100)
0 (0) 0.959
Procedural details
The median fluoroscopic time was 21.3 minutes (13.43–27.3 minutes) in Group A and 15.34 minutes (10.87–24.07 minutes) in Group B; which was not significant (p-value 0.086). The mean procedure time was 38.6 minutes (26.9–45.6 minutes) in Group A and 25.7 minutes (18.6–33.7 minutes) in Group B; which was significant (p-value 0.000). Most of the pulmonary arterial (PA) pressure measured were normal for both groups and was not significant (p-value 0.079). According to ventriculography, the median measured of VSD size for Group A was 0.6cm (0.4–1.5cm) and Group B was 0.4cm (0.3–0.5cm), which was significant (p-value 0.001). There were several device occluders used during the study period with Lifetech Multi-functional occluder (MFO) (Group A 2, 5.41% and Group B 35,100%) as the majority device used. Procedural data was summarized in Table 2.
Table 2. Procedural Data
Antegrade
(n=37) Retrograde
(n=35) P-value
Frequency (%); Median (IQR)
Fluoroscopic time (min) 21.3 (13.43 to 27.3) 15.34 (10.87 to 24.07) 0.086
Procedure time (min) 38.6 (26.9 to 45.6) 25.7 (18.6 to 33.7) <0.001
VSD Size cm 0.6 (0.4 to 1.5) 0.4 (0.3 to 0.5) 0.001
PA Pressure
Normal
Mild
Moderate
32 (86.49)
4 (10.81)
1 (2.70)
35 (100)
0 (0)
0 (0) 0.079
VSD Device Size cm 0.6 (0.6 to 1.8) 0.6 (0.5 to 0.8) 0.123
Device Occluder Used
PDA ductal
Lifetech
Cocoon
VSD symmetrical
Lifetech
Cocoon
VSD muscular
Lifetech
Lifetech MFO
2 (5.41)
1 (2.70)
18 (48.65)
5 (13.51)
9 (24.32)
2 (5.41)
0 (0)
0 (0)
0 (0)
0 (0)
0 (0)
35 (100) <0.001
Adverse events and follow-up evaluation
The median follow-up was 24 months (4 – 55.3 months). Acute procedure success was not significant. Antegrade technique had 100% success rate while retrograde technique had 97% success rate (34 out of 35). This case was a 6-year-old male diagnosed case of VSD perimembranous who had embolization and was retrieved percutaneously. His technique was converted to antegrade approach and was successfully occluded. Pre-discharge complete closure was seen in 27 (73%) patients for Group A and 8% of residual shunts diminished 3 months after the intervention. In comparison with Group B, immediate closure was seen in 27 (77%) patients and all residual shunts diminished 3 months after the intervention. Comparison of immediate or pre-dischareg complete closure of the defect was not significant (p value 0.683). The median hospital stay for both group were at 3 days (Group A, 3-4days and Group, B 3-3days). Most of the patients on Group A had stayed more than 3 days while Group B patients had stayed 3 days at the hospital. Comparison of hospital stay between two groups was significant at p value of <0.001. In our study, residual shunt was considered with a presence of left-to-right shunt across the interventricular septum on color Doppler flow mapping. On a 3-month follow-up, it was noted that 89%n (33 out of 37 cases) on Group A had residual shunts while Group B had 100% complete closure; which was significant (p-value 0.012). Comparison of principal efficacy for both groups was summarized in Table 3.
In pre-procedure echo, there were 53% of patients with left ventricular (LV) enlargement and 40% with left atrial (LA) enlargement. Noted a significant improvement (p-value <0.001) with chamber sizes post-transcatheter closure of VSD (Table 4). Two patients whom still with LV enlargement still had residual shunt after transcatheter closure via antegrade approach.
Table 3. Principal Efficacy
Antegrade
(n=37) Retrograde
(n=35) P-value
Frequency (%); Mean + SD; Median (IQR)
Acute Procedure success 37 (100) 34 (97.14) 0.486
Pre-discharge complete closure 27 (72.97) 27 (77.14) 0.683
Hospital Stay 3 (3 to 4) 3 (3 to 3) <0.001
Complete Closure on 2D Echo
1 month follow-up
3 month follow-up
29 (78.38)
33 (89.12)
30 (85.71)
35 (100)
0.419
0.012
Table 4. LV and LA enlargement in 2D Echo (n=72)
Pre procedure Post procedure P-value
Frequency (%)
With LV enlargement 38 (52.78) 2 (2.78) <0.001
With LA enlargement 29 (40.28) 1 (1.39) <0.001
Complications
A total of 12 adverse events (16.7%) were reported in patients who underwent VSD device closure. No serious and major adverse events were observed in this study. In Group A, 10 minor adverse events were observed: Device embolization (n = 1), new or increased valve regurgitation (n = 3), hematoma of the groin (n = 1), cardiac arrhythmia (n = 1); and residual shunt (n = 4). In Group B, 2 minor adverse events were observed: embolization and cardiac arrhythmia. Complications were summarized in Table 5. Odds ratio was used and showed that patients in Group A had 6.11 times more likely to have complication compared to Group B (Table 6).
Table 5. Complications after VSD device closure according to technique
COMPLICATIONS Antegrade
n = 10 Retrograde
n = 2
Serious adverse event (Death) 0 0
Major adverse events
Thromboembolism 0 0
Device Embolization
required surgical removal 0
Complete Heart Block
New onset valvular
regurgitation that
required surgical repair 0
0 0
Minor adverse event
Device Embolization
required percutaneous
removal
New or increased (mild to
moderate) regurgitation
of the valve 1
3
1
Hemolysis
Hematoma of the groin
Loss of peripheral pulse
Cardiac arrhythmia (LBBB,
RBBB)
Blood transfusion because
of blood loss
Residual shunt 0
1
1
4 0
1
Others (fever, rash) 0 0
Table 6. Comparison of the outcome according to technique used (n=72)
With complication
(n=12) Without complication
(n=60) Odds ratio
(95% CI) P-value
Frequency (%)
Antegrade 10 (83.33) 27 (45) 6.11 (1.23 to 30.3) 0.027
Retrograde 2 (16.67) 33 (55) 0.16 (0.03 to 0.81)
DISCUSSION
Ventricular septal defect represents the most common type of congenital heart malformation, accounting for up to 40% of congenital heart defects and it is more frequent in Asian countries.8 Our previous local study and literature from other countries showed that both surgery closure, and transcatheter closure using the antegrade technique have excellent results in closing VSDs. Meanwhile, this local study also showed that transcatheter closure has the advantage of reduced psychological impact, less pain, and discomfort due to the procedure, shorter hospital stay, no need for admission to an intensive care unit, faster time to normal activities.12 Different devices had been used to close ventricular septal defects, and with evolving technology improved devices made it possible to use it on transcatheter closure using the retrograde technique. However, studies with transcatheter closure of VSD using retrograde technique have been lacking. This study was designed to compare the clinical outcome of transcatheter device closure of ventricular septal defect using antegrade and retrograde techniques.
Demographic profile and Diagnostic data of patients
Based on WHO child growth assessment, it was observed in this study that more patients in Group A (p value 0.001) were wasted at below Z score -1. Stunted growth for Group A was also noted (Z-score -2 to 0, p-value <0.001). This observation may be explained by the larger ventricular septal defect size on echocardiography (0.4cm to 0.7cm) in younger patients for group A (9.89 years + 4.68); although age and defect size were not significant in these study. In added effect of large VSD defect in group A, expected LV enlargement and shunt significance (Qp:Qs ratio) were observed with Group A compared with Group B. In Group A, faster heart rate was also observed due to younger population and significance of shunt (Qp:qs ratio) in this group. In this study, it was observed that Group A patients belong to a younger group with significant shunt and weighed less compared to Group B. This may be explained that in able to successfully perform transcather closure of ventricular septal defect, weight, age and size of the defect of the patient were factors on selecting the technique to be used. With the large ventricular septal defect, expected larger devices and sheath to be used hence antegrade approach will be a better technique for younger and wasted patients to avoid vascular injury with retrograde technique.
Efficacy of transcather device closure of ventricular septal defect
We have presented 72 patients who underwent transcather VSD closure with 37 patients via antegrade approach and 35 patients via retrograde approach. The meadian follow-up was 24 months. In this study, we considered effectiveness in terms of procedural success, complete defect closure (pre-discharge, 1-month and 3-month follow-up) and hospital stay. Transcatheter closure of VSD via retrograde approach shows a shorter hospital stay and 100% complete closure of the defect in 3-month follow-up. However, the present study also demonstrates an excellent immediate outcome and follow-up results for both techniques; supported by the significant improvement on chamber sizes.
Safety of transcatheter device closure of ventricular septal defect
In our study, complications of transcatheter closure of VSD using both techniques were rare. Among all 12 complications (16.7% of the study population), no serious and major adverse event occurred. In our retrospective study suggested that complications (10 of 12) are 6.11 times more likely to occur with patients undergoing antegrade technique. Most cases of minor adverse events: residual shunts (4 of 12) and new or increased valve regurgitation (3 of 12) were observed with antegrade technique. The creation of arteriovenous loop with antegrade technique might explain the new tricuspid regurgitation in 3 cases, in the early period of the study. Other minor adverse events observed in this study include device embolization, hematoma of the groin and cardiac arrhythmia. Both cases of cardiac arrhythmia were resolved within 24 hours and no recurrence during follow-up. Outcome from this study is rather diverse from earlier studies.2,6,8 Generally, in this study manageable adverse events were recorded and did not outweigh the benefits of transcatheter closure of VSD using both techniques.
Technical consideration of transcatheter closure of ventricular septal defect
Transcatheter closure of ventricular septal defect has many important technical considerations due to the involvement of adjacent structures (aortic valve, tricuspid tendineae, AV node, conduction bundle) and variations of VSD type (tubular, conical, window and aneurysmal type). First, the inclusion criteria for transcatheter closure of muscular and perimembranous VSD should be strict. Large VSD defined as more than 2/3 the size of the aortic valve annulus, VSD with severe pulmonary hypertension, severe aortic valve regurgitation and small infants with weight less than 7 kg should be referred to open heart surgery and excluded from transcatheter intervention. Due to this strict criteria that the success rate of transcatheter VSD closure in both groups were high. As previously discussed, VSD size determined during angiography was crucial in selecting the appropriate approach in transcatheter closure of VSD. Most of patients underwent VSD device closure with antegrade approach was observed with a larger median ventricular septal defect size of 0.6 cm (0.4–1.5cm).
Second, the most crucial step on transcatheter VSD device closure is passing of the guide-wire catheter across the defect. In our study, we had used two types of guide catheters that were useful in passing the defect: Judkins right and cut pigtail catheter with the use of hydrophilic 0.032” or 0.035”x260cm Terumo long guidewire.
Third, the technique selection in this study was one of the important technical considerations. Antegrade technique requires a creation of arteriovenous wire loop for line stabilization through which the device can be advanced. Unlike retrograde technique that directly advanced the delivery system without AV loop to the defect from the LV side and deployed the RV disc of the occlude first. This technique simplifies the step compared to the antegrade technique; hence also avoids the factors associated with the advancement failure of the device via the venous route. It was observed in this study that retrograde approach shortened the procedural time, high rate of successful deployment (97.1%), and lower rate of complications (5.7%). This outcome is similar with the previous reported series and case reports.13,14,15
Fourth, device selection was another important technical consideration. Multiple devices were used during this study, however the availability of the device was the main decisive factor on which device to be used; in early study period. The availability of the Multifunctional occluder device (MFO) LifetechTM heralded the transcatheter closure of VSD via retrograde technique. In our study, most perimembranous VSD could be successfully closed with retrograde approach using Multifunctional occluder device (MFO) LifetechTM requiring a French 5–7mm delivery sheath.
Lastly, in previous studies2,4,6,7 transesophageal echocardiography (TEE) is the imaging modality that is mostly used for guidance on transcatheter VSD closure. During the early years of the study period, angiography was the sole imaging modality that guide us through the transcatheter closure because TEE extends the procedural time. However in the later years of the study period, usage of transthoracic echo (TTE) combined with angiography remarkably guide us on device closure of VSD.
STUDY LIMITATION
Although our study demonstrated a significant advantage of transcatheter VSD closure using retrograde approach, it nevertheless had some limitation. First, this was a single-center, non-randomized study and our experience may not be universally representative. Secondly, these techniques can only be carried out safely and complications managed in the proper way by very experienced hands. Third, although both of the techniques of VSD closure appear to be safe in the mid-term follow-up, it is not known whether they are safe in the very long-term, whereas the long-term safety and efficacy of surgical closure are well documented.
CONCLUSION
The transcatheter VSD closure using both approaches were immediately safe and effective. In the presence of favorable characteristic of patients and anatomic considerations, retrograde technique is less likely to have complications; and shortened procedure time compared to antegrade technique. The only limitation in pediatric patients is the size of the delivery sheath. Smaller size of delivery sheath is required for the safe placement of the device using the retrograde technique to avoid vascular injury.
The results of this study suggest that retrograde approach may be implemented successfully in transcatheter closure of VSD. This study suggests that transcatheter VSD closure must be initiated using the retrograde approach; and may switched to antegrade approach if with unfavourable anatomic conditions.