Abstract
Background: Complications arising from transcatheter closure of perimembranous ventricular septal defects (pmVSD) in children, such as residual shunts and aortic regurgitation (AR), have been observed. However, the associated risk factors remain unclear. This study identified risk factors linked with residual shunts and AR following transcatheter closure of pmVSD in children aged 2–12 years.
Methods and Results: The medical records of 63 children with pmVSD and a pulmonary-to-systemic blood flow ratio <2.0 who underwent transcatheter closure between 2011 and 2018 were analyzed with a minimum 3-year follow-up. The success rate of transcatheter closure was 98.4%, with no emergency surgery, permanent high-degree atrioventricular block, or mortality. Defects ≥4.5 mm had significantly higher odds of persistent residual shunt (odds ratio [OR] 6.85; P=0.03). The use of an oversize device (≥1.5 mm) showed a trend towards reducing residual shunts (OR 0.23; P=0.06). Age <4 years (OR 27.38; 95% confidence interval [CI] 2.33–321.68) and perimembranous outlet-type VSD (OR 11.94, 95% CI 1.10–129.81) were independent risk factors for AR progression after closure.
Conclusions: Careful attention is crucial for pmVSDs ≥4.5 mm to prevent persistent residual shunts in transcatheter closure. Assessing AR risk, particularly in children aged <4 years, is essential while considering the benefits of pmVSD closure.
Ventricular septal defect (VSD) is the most common congenital heart disease in children. Perimembranous VSD (pmVSD) can close spontaneously by aneurysmal transformation of the tricuspid valve.1 For persistent pmVSD, transcatheter closure may be used as an alternative to surgical repair. Transcatheter closure of VSD was first described in late 1980s.2 Previous studies have reported that the success rate of transcatheter VSD closure is as high as 98%.3,4 However, specific minor complications,5 such as aortic regurgitation (AR) and residual shunts, persisted and should not be ignored. Carminati et al documented that age and weight demonstrated associations with early complications, such as mortality, vascular complications, hemolysis attributed to residual shunts, infections, device embolization, and arrhythmias, following transcatheter closure of pmVSD.6 Shrestha et al demonstrated that the use of a Produkte für die Medizin AG (PFM) coil was borderline (P=0.14) associated with the development of AR within 1 year after transcatheter pmVSD closure.7 However, there is limited discussion on the risk factors associated with the development of residual shunts and the onset of new-onset AR within 3 years after transcatheter closure of pmVSD in young children who undergo such interventions. Therefore, the aim of the present retrospective study, conducted at a tertiary medical center, was to identify and clarify these factors.
Methods
Patients
We retrospectively reviewed the medical records of 63 children aged 2–12 years with pmVSD whose pulmonary-to-systemic blood flow (Qp/Qs) ratio was <2.0 and who had undergone transcatheter closure in National Taiwan University Children’s Hospital between August 2011 and February 2018.
The indications for transcatheter closure in these patients included: (1) heart failure symptoms, including failure to thrive; (2) a cardiothoracic ratio >0.5 on chest plain film; (3) a z-score of M-mode left ventricular end-diastolic diameter (LVEDD) >2; (4) prolapse of the coronary cusp with or without AR on transthoracic echocardiography (TTE); and (5) a Qp/Qs ratio ≥1.5.
The perimembranous inlet-type VSD was excluded from transcatheter closure due to concerns about the proximity of the conduction system along the posterior-inferior rim, which may raise the risk of heart block, as reported by Yip et al.8 We analyzed patients’ baseline characteristics, cardiac catheterization-related hemodynamic data, transcatheter closure complications, and echocardiography before and after (during follow-up) the intervention. The z-score of M-mode LVEDD was calculated according to the Boston Children’s Hospital z-score system (URL: https://zscore.chboston.org). The severity of the residual shunt after pmVSD closure was classified as trivial, mild, moderate, or severe (color jet width <1, 1–2, 2–4, and ≥4 mm, respectively).6 To assess the degree of AR, we measured the proximal jet width from the long-axis views and its ratio to the left ventricular outflow tract (LVOT) diameter (mild, <25%; moderate, 25–64%; severe, ≥65%) and the width of the vena contracta (mild, <0.3 cm; moderate, 0.3–0.6 cm; severe, ≥0.6 cm).9 AR progression was defined as an increase in AR severity after pmVSD closure.
Cardiac Catheterization Protocol
Hemodynamic data were assessed before the intervention, and the Qp/Qs ratio was calculated according to Fick’s principle. We selected the AmplatzerTM
duct occluder (ADO) and AmplatzerTM
duct occluder II (ADO II; Abbott Structural Heart, Plymouth, MN, USA) or HeartR pmVSD occluder (Lifetech Scientific, Shenzhen, China) based on both angiography and transesophageal echocardiography (TEE). We crossed the defect retrograde, snaring and establishing an arteriovenous rail through the pmVSD according to the procedure detailed elsewhere,10 and an antegrade approach was used to implant all 3 types of occluders (ADO, ADO II and HeartR pmVSD Occluder). TEE and a left ventriculogram were performed to check the residual shunt and cardiac valvular function. The device was released under TEE and fluoroscope guidance. A left ventriculogram, aortogram, and TEE were also used to evaluate the adequacy of device position, residual shunt, and AR after device implantation. Patients were administered aspirin (3–5 mg/kg/day, orally) for 6 months after discharge.
TTE Follow-up
Echocardiographic follow-up for possible complications after transcatheter closure of the pmVSD11 was arranged at 0–3, 3–6, 6–12, and 12 months after discharge, and every 6–12 months thereafter. The device position, residual shunts, LVEDD, and cardiac valvular function, such as AR, were documented. Follow-up data were collected until September 2021. We also calculated patient survival after the date of transcatheter closure of pmVSD.
Statistical Analysis
Categorical variables are presented as percentages and were analyzed using the Chi-squared. Continuous variables are presented as the mean±SD or median with interquartile range (IQR), and were compared using Student’s t-test, paired t-test, or the Mann-Whitney U test. The following independent variables were included in the analysis: age at intervention, weight percentile at the time of the procedure, sex, defect type (perimembranous trabecular [PT] or perimembranous outlet [PO]), the presence of aneurysmal transformation, defect diameter (TTE or TEE), LVEDD z-score, Qp/Qs ratio, device type (ADO, ADO II, or HeartR), device diameter, and difference in device diameter and defect diameter measured by TEE. Risk factors for residual shunts and AR progression were analyzed using multiple logistic regression. Independent variables with P<0.2 in the univariate analysis were included in the receiver operating characteristic (ROC) curve analysis and multivariate model (odds ratios [OR] and 95% confidence intervals [CIs] were calculated). The duration of follow-up covered the time from Day 1 after transcatheter closure to the last echocardiographic assessment of the patients. The probability of persistent residual shunt- and AR progression-free survival was estimated using the Kaplan-Meier method; the log-rank test was used for univariate comparison. Persistent residual shunt- and AR progression-free survival after pmVSD closure were evaluated using Cox proportional hazards regression. All analyses were conducted using SPSS software, version 25.0 (SPSS Inc., Chicago, IL, USA). Two-tailed P<0.05 was considered statistically significant.
Results
General Characteristics and Interventional Data
In all, 63 patients with pmVSD underwent transcatheter closure, of whom 34 (54.0%) were male. Table 1 summarizes patients’ baseline demographic and hemodynamic data. The median age of patients was 6.8 years (IQR 5.1–9.0 years), and the median weight was 22.4 kg (IQR 16.6–29.0 kg). Of the 63 patients, 50 had PT-type VSD and 13 had PO-type VSD. The median diameter of the pmVSD measured by TTE within 4 months before catheterization in 59 patients was 3.5 mm (IQR 2.9–4.6 mm). The median LVEDD measured in 61 patients was 3.9 cm (IQR 3.6–4.3 cm), with a median z-score of +0.9 (IQR −0.3, +1.9). LVEDD z-scores were significantly higher for patients with a Qp/Qs ratio ≥1.3 than for those with a Qp/Qs ratio <1.3 (1.48±1.67 vs. 0.47±1.24, respectively; P=0.009). Aneurysmal transformation was detected in 59 patients through methods such as TTE, TEE, or left ventricular angiography. AR was found in 17 patients. In addition, 19 (30.2%) patients had associated cardiac abnormalities including mild LVOT obstruction (n=4), patent ductus arteriosus status after transcatheter closure (n=3), subaortic ridge without LVOT obstruction (n=2) or with mild LVOT obstruction (n=2), patent foramen ovale (n=2), atrial septal defect (n=2), mitral valve prolapse (n=2), left ventricular (LV) non-compaction (n=1), small coronary arteriovenous fistula (n=1), and persistent left superior vena cava (n=1).
Table 1.
Baseline Characteristics
| Characteristic |
Values |
| Age (years) |
6.8 [5.1~9.0] |
| Male sex |
34 (54.0) |
| Height (cm) |
119.0 [106.0~135.0] |
| Weight (kg) |
22.4 [16.6~29.0] |
| Weight percentile |
49.4 [22.6~73.0] |
| BSA (m2) |
0.9 [0.7~1.0] |
| NYHA functional class |
| I |
53 (84.1) |
| II |
9 (14.3) |
| III |
1 (1.6) |
| Precatheterization echocardiography |
| PO-type of VSD |
13 (20.6) |
| Defect diameter on TTE (mm) |
3.5 [2.9~4.6] |
| LVEDD (cm) |
3.9 [3.6~4.3] |
| Total (z-score) |
0.9 [−0.3~2.0] |
| Qp/Qs ratio ≥1.3 (z-score) |
1.3 [0.2~2.8] |
| Qp/Qs ratio <1.3 (z-score) |
0.4 [−0.4~1.4] |
| Defect diameter on TEE (mm) |
4.0 [3.5~5.0] |
| Aneurysmal transformation |
59 (93.7) |
| Hemodynamic data |
| Qp/Qs ratio |
1.3 [1.1~1.5] |
| mPAP (mmHg) |
17.0 [14.0~20.0] |
| Indications for VSD closure |
| Symptoms or signs of heart failure |
12 (19.0) |
| Failure to thrive |
6 (9.5) |
| C/T ratio ≥0.5 |
42 (66.7) |
| LVEDD z-score ≥2.0 |
14 (22.2) |
| RCC prolapse |
42 (66.7) |
| AR |
17 (27.0) |
| Qp/Qs ratio ≥1.5 |
16 (25.4) |
Values are presented as n (%) or median [interquartile range]. AR, aortic regurgitation; BSA, body surface area; C/T ratio, cardiothoracic ratio; LVEDD, left ventricular end-diastolic diameter; mPAP, mean pulmonary arterial pressure; NYHA, New York Heart Association; PO, perimembranous outlet; Qp/Qs ratio, pulmonary-to-systemic blood flow ratio; RCC, right coronary cusp; TEE, transesophageal echocardiography; TTE, transthoracic echocardiography; VSD, ventricular septal defect.
Regarding the hemodynamic data of catheterization, the median Qp/Qs ratio was 1.3 (IQR 1.1–1.5). The median mean pulmonary arterial pressure was 17.0 mmHg (IQR 14.0–20.0 mmHg), and >25 mmHg in 5 patients. The median defect diameter measured by TEE was 4.0 mm (IQR 3.5–5.0 mm). The median difference in defect diameter measured by TEE and TTE was 0.6 mm (IQR −0.4–1.5 mm). The indications for pmVSD closure in the study cohort are presented in Table 1; 42 patients had 2 or more indications.
Device implantation for pmVSD closure was successful in 62 (98.4%) patients. ADO and ADO II were properly deployed in 23 and 24 patients, respectively. Fifteen patients were implanted with a HeartR pmVSD occluder. Transcatheter closure failed in one 3-year-old female because she developed significant AR and residual shunts after we deployed a 4-mm ADO II device.
Early Complications
One female aged 4 years and 10 months experienced device (ADO 8/6 mm) dislodgement during the procedure. Nonetheless, we successfully retrieved it and deployed a new 8-mm ADO device (Model number: 9-PDA-006).
No atrioventricular block was detected during or 1 day after the procedure. Other early events within 1 day after pmVSD closure (Table 2) were the onset of transient arrhythmic or conductive events (n=13), anesthesia-related complications such as nausea or vomiting (n=5), and fever (n=2). Those who had fever received empirical intravenous antibiotics until it subsided. The median duration of stay in the intensive care unit was 1 day, and the median hospitalization duration was 3 days.
Table 2.
Early Complications After pmVSD Closure
| Complication |
n (%) |
| Device dislodgement |
1 (1.6) |
| Arrhythmic events |
| Short-run VT |
2 (3.2) |
| AV block |
0 (0) |
| Transient junctional rhythm |
1 (1.6) |
| Complete RBBB |
1 (1.6) |
| Incomplete RBBB |
9 (14.3) |
| Residual shunt |
27 (43.5) |
| New AR |
21 (45.7) |
| Fever |
2 (3.2) |
| Nausea/vomiting |
5 (7.9) |
AR, aortic regurgitation; AV, atrioventricular; pmVSD, perimembranous ventricular septal defect; RBBB, right bundle branch block; VT, ventricular tachycardia.
Postintervention Follow-up
The median follow-up time after discharge in 62 patients was 46.1 months (IQR 36.8–62.3 months). However, 4 patients were lost to follow-up after 1 year. Five patients had persistent conduction problems 1 year after the intervention (1 had right bundle branch block [RBBB] and 4 had incomplete RBBB). None of the patients experienced complete atrioventricular block (cAVB) during the follow-up period.
Residual Shunts
From Day 1 after pmVSD closure, 27 (43.5%) patients had trivial or small residual shunts. The median follow-up time was 47.9 months (IQR 37.3–65.0 months). At 1, 6, and 12 months after transcatheter closure, 81.5%, 50%, and 44.4% of these 27 patients, respectively, had a persistent residual shunt. Nine (14.5%) patients had trivial or small residual shunts for >3 years after pmVSD closure. Hence, univariate analysis was conducted to explore the potential risk factors for persistent (>3 years) residual shunts (Table 3). The results showed that the median diameter of the pmVSD (on TEE) in those with residual shunts after the procedure was 5.5 mm, which was significantly larger than that of patients without a residual shunt (4 mm; P=0.002). The defect diameters in all patients with residual shunts were ≥4.5 mm. However, of the 53 patients without a residual shunt, only 18 (34.6%) had a VSD ≥4.5 mm (P<0.001). In patients without residual shunts, the median difference between the diameter of the device and the diameter of the pmVSD on TEE was 2.0 mm (IQR 1.0–3.0 mm), compared with 1.0 mm (IQR 0.5–2.5 mm) in those with residual shunts. The number of patients with and without residual shunts in whom the difference exceeded 1.5 mm was 33 (63.5%) and 3 (33.3%), respectively (P=0.142). ROC curve analysis demonstrated an area under curve (AUC) of 0.82 (95% CI 0.72–0.93) with a cut-off value of 4.52 mm for VSD diameter on TEE, and an AUC of 0.62 and a cut-off value of 1.48 mm for the difference between the diameter of the device and the diameter of pmVSD on TEE, as detailed in Supplementary Table 1.
Table 3.
Persistent Residual Shunts 3 Years After pmVSD Closure
| Variable |
No residual shunt
(n=53) |
Residual shunt
(n=9) |
P value |
| Age (years) |
6.8 [5.2~9.2] |
6.5 [5.2~9.7] |
0.7A |
| Male sex |
30 (56.6) |
4 (44.4) |
0.719 |
| Weight percentile |
49.0 [22.6~72.7] |
53.9 [39.0~80.9] |
0.337A |
| PO type of VSD |
10 (18.9) |
2 (22.2) |
1 |
| Aneurysmal transformation |
50 (94.3) |
8 (88.9) |
0.475 |
| LVEDD z-score |
0.8 [−0.4~2.0] |
1.2 [0.4~2.0] |
0.425A |
| Qp/Qs ratio |
1.3 [1.1~1.5] |
1.4 [1.2~1.6] |
0.498A |
| VSD diameter on TTE (mm) |
3.5 [2.9~4.6] |
3.4 [3.0~5.1] |
0.765A |
| VSD diameter on TEE (mm) |
4.0 [3.3~5.0] |
5.5 [5.0~6.0] |
0.002A |
| Diameter ≥3.5 mm |
37 (71.2) |
9 (100) |
0.097 |
| Diameter ≥4.0 mm |
29 (55.8) |
9 (100) |
0.011 |
| Diameter ≥4.5 mm |
18 (34.6) |
9 (100) |
<0.001 |
| Diameter ≥5.0 mm |
14 (26.9) |
7 (77.8) |
0.006 |
| Device type |
|
|
0.610 |
| ADO |
19 (35.8) |
4 (44.4) |
|
| ADO II |
20 (37.7) |
4 (44.4) |
|
| HeartR |
14 (26.4) |
1 (11.1) |
|
| Device diameter minus VSD diameter on TEE |
| Difference (mm)* |
2.0 [1.0~3.0] |
1.0 [0.5~2.5] |
0.241A |
| Difference ≥0.5 mm |
45 (86.5) |
7 (77.8) |
0.609 |
| Difference ≥1.0 mm |
42 (80.8) |
6 (66.7) |
0.386 |
| Difference ≥1.5 mm |
33 (63.5) |
3 (33.3) |
0.142 |
| Difference ≥2.0 mm |
28 (53.8) |
3 (33.3) |
0.301 |
Values are presented as n (%) or median [interquartile range]. AMann-Whitney U test. ADO, Amplatzer duct occluder; ADO II, Amplatzer duct occluder II; HeartR, HeartR perimembranous ventricular septal defect (pmVSD) occluder; LVEDD, left ventricular end-diastolic diameter; PO, perimembranous outlet; Qp/Qs, pulmonary-to-systemic blood flow ratio; TEE, transesophageal echocardiography; TTE, transthoracic echocardiography; VSD, ventricular septal defect.
Multivariate logistic regression analysis showed that the only independent risk factor for a residual shunt lasting for 3 years after the procedure was a diameter of the pmVSD ≥4.5 mm on TEE (OR 6.85; 95% CI 1.28–36.71; P=0.025). A difference between the diameter of the device and the diameter of the pmVSD on TEE ≥1.5 mm, while lacking statistical significance, may suggest a potential trend towards a reduction in residual shunts (OR 0.23; 95% CI 0.05–1.08; P=0.062).
Throughout the period from immediately after the procedure up to 3 years, the probability of persistent residual shunt was higher in patients with than without a pmVSD diameter ≥4.5 mm (log-rank test, P<0.001; Figure 1A). However, the probability of a persistent residual shunt was significantly lower among patients in whom the difference between the diameter of the device and the diameter of the pmVSD on TEE was ≥1.5 mm compared with those with a difference <1.5 mm (log-rank test P=0.042; Figure 1B).
To avoid interactions among potential risk factors, we conducted Cox regression to identify independent risk factors for persistent residual shunt after transcatheter VSD closure. We found that VSD diameter (≥4.5 mm) on TEE was the only independent risk factor for persistent residual shunt 3 years after transcatheter VSD closure (hazard ratio [HR] 0.49; 95% CI 0.04–0.70; P=0.038). The diameter of the device minus the diameter of pmVSD on TEE ≥1.5 mm had an OR of 1.78 (95% CI 0.73–4.33; P=0.203); analysis on the remaining variables yielded no significant results (Supplementary Table 2).
AR
New onset or progression of AR severity was observed in 23 (37.1%) patients just 1 day after the procedure (Supplementary Figure). Among the 8 patients who had mild or more severe AR prior to their transcatheter closure of VSD, no further progression in AR severity was detected. Within the cohort, 21 patients exhibited new-onset trivial or mild AR, whereas 2 patients showed a progression from trivial to mild AR. The condition persisted in 5 patients 6 months after the procedure (Supplementary Figure). Even after a minimum follow-up period of 3 years, 6 patients continued to display this AR progression compared with their pre-intervention state, although without further deterioration. Analysis of the data (Table 4) highlighted that of patients with persistently progressing AR severity, 50% (3/6) were aged <4 years, a notably higher percentage than among those without such progression (4/56 [7%]; P=0.016, Fisher’s exact test).
Table 4.
Progression of AR 3 Years After pmVSD Closure
| Variable |
No progression of AR
(n=56) |
Progression of AR
(n=6) |
P value |
| Age (years) |
6.8 [5.3~9.2] |
5.0 [3.1~8.4] |
0.216A |
| Age <4 years |
4 (7.1) |
3 (50) |
0.016 |
| Male sex |
29 (51.8) |
5 (83.3) |
0.209 |
| BSA (m2) |
0.9 [0.7~1.0] |
0.8 [0.6~1.1] |
0.344A |
| Weight percentile |
49.8 [22.8~72.6] |
48.4 [16.8~81.4] |
0.949A |
| Severity of AR |
| Trivial or no AR |
48 (85.7) |
6 (100) |
1.0 |
| RCC prolapse |
36 (64.3) |
5 (83.3) |
0.654 |
| PO-type VSD |
9 (16.1) |
3 (50.0) |
0.081 |
| VSD diameter on TEE (mm) |
4.0 [3.5~5.0] |
4.6 [3.3~5.8] |
0.617A |
| Device diameter/measured diameter |
1.5 [1.3~1.7] |
1.2 [1.0~1.9] |
0.276A |
| LVEDD z-score |
0.8 [−0.4~1.9] |
1.9 [0.2~2.9] |
0.315A |
| Qp/Qs ratio |
1.3 [1.1~1.5] |
1.3 [1.2~1.6] |
0.841A |
| Device type |
|
|
0.269 |
| ADO |
22 (39.3) |
1 (16.7) |
|
| ADO II |
22 (39.3) |
2 (33.3) |
|
| HeartR |
12 (21.4) |
3 (50) |
|
Values are presented as n (%), or median [interquartile range]. AMann-Whitney U test. Abbreviations as in Tables 1,3.
Multivariate logistic regression analysis showed that younger age (<4 years; OR 27.38; 95% CI 2.33–321.68; P=0.008) and PO-type VSD (OR 11.94; 95% CI 1.10–129.81; P=0.042) were both independent risk factors of AR progression 3 years after transcatheter closure.
We also conducted person–time data analysis for AR after VSD closure (Figure 2). None of the enrolled patients experienced new-onset AR deterioration 11.9 months after the procedure. Analysis using the Cox proportional hazards model to evaluate potential risk factors for AR progression (Supplementary Table 3) revealed that younger age (<4 years; HR 3.10; 95% CI 1.08–8.86) was an independent risk factor for AR progression after the procedure. The HRs for the use of ADO (HR 3.01; 95% CI 0.99–9.12; P=0.051), PO-type VSD, and a difference between the diameter of the device and the diameter of the pmVSD on TEE ≥1.5 mm were not statistically significant.
LV Volume
The mean LVEDD z-score was 1.01±1.56 before transcatheter closure and –0.34±0.97 at 1 year after the procedure (P<0.001). A significant reduction in LVEDD was detected (Figure 3A,D). In subgroup analysis, a reduction in LVEDD was detected not only in patients with a Qp/Qs ratio ≥1.3 (Figure 3B,E), but also in those with a Qp/Qs ratio <1.3 (Figure 3E,F), although the percentage of patients with an improvement in LVEDD differed between the 2 subgroups (96% vs. 72%, respectively; P=0.024).
During the first 3 months after the procedure, the LVEDD z-score decreased significantly in 29 patients with a Qp/Qs ratio ≥1.3 (z-score difference −1.28±1.31 [P<0.001]; Figure 3B). For those with a Qp/Qs ratio <1.3, the reduction in the LVEDD z-score was not significant until after 1 year (z-score difference −0.76±1.15 [P=0.004]; Figure 3F).
Discussion
We made several important observations in our cohort. First, using a closure device with a diameter 1.5 mm larger than the VSD diameter resulted in a reduced likelihood of a persistent residual shunt. Second, we observed that 37.1% of patients experienced new or progressive AR after VSD closure. We identified age <4 years and the use of ADO as risk factors for the development or progression of AR in these patients. Third, we found a significant decrease in the LVEDD z-score after closure of small-to-moderate pmVSD, even in patients with a Qp/Qs ratio <1.3, in whom the reduction in LVEDD z-score was not significant until after 1 year following the procedure.
Previous studies reported that new-onset AR following transcatheter closure developed in approximately 3.3–4.5% of patients with pmVSD.6,12 The incidence of new-onset AR, even when categorized as trivial or mild, was notably higher in the present cohort, reaching 37.1% (23/62) within the first day after the procedure and 9.7% (6/62) at the 3-year mark. This discrepancy could potentially be attributed to the substantial proportion (up to 66.7%) of the present cohort having right coronary cusp prolapse prior to the intervention. In contrast, in the study of Jiang et al, only 3.2% of the analyzed cohort exhibited pre-existing coronary cusp prolapse.12 Furthermore, prior studies have established an association between the presence of coronary cusp prolapse13 and advanced age14 in relation to the progression of AR in patients diagnosed with VSD. These findings have led to recommendations for expedited intervention in patients exhibiting these factors. Based on the findings from both the aforementioned and present studies, it may be advisable to recommend that patients with pmVSD and coronary cusp prolapse, yet without concurrent AR, undergo transcatheter closure after reaching the age of 4 years. Using this targeted subgrouping approach may have the potential to effectively mitigate the risk of new-onset AR associated with the procedure while also helping to halt the progression of the disease. This could ultimately result in substantial benefits for patients.
Although transcatheter closure is safe and uncomplicated in most patients with pmVSD, previous large cohort studies still noted some patients experienced cAVB.4,6,12,15 Risk factors for the development of cAVB after transcatheter VSD closure included age, weight, VSD location and device type. Jiang et al reported that up to 25% of patients with transcatheter closure of pmVSD experienced rhythm or conduction abnormalities early after the procedure.12 However, in the present study, with a median cohort age of 6.8 years, no cAVB was detected, and 10 (10.8%) patients had minor rhythm disturbance (complete RBBB in 1 patient and incomplete RBBB in 9). The relatively lower occurrence of rhythm disturbance may be due to conservative use of devices only 1–2 mm larger than the measured diameter of the defects and the deployment of relatively soft devices in our patients. A multicenter registry is needed to clarify the real risk factors for rhythm disturbance.
Several studies have demonstrated the incidence of and longitudinal changes in residual shunts after transcatheter pmVSD closure.3,5,7,12,16 The incidence of residual shunt after transcatheter closure has been reported to range from 8.3% to 30.8%,5,7,12,16 and one-third of the residual shunts diminished gradually during follow-up.12,17 Similar results were obtained in the present study, and we clarified the risk factors for persistent residual shunts. Our study revealed that the defect diameter and device size were strongly related to residual shunts. In logistic regression analysis, a pmVSD diameter ≥4.5 mm on TEE significantly increased the risk of residual shunts (OR 6.85; 95% CI 1.28–36.71; P=0.03). Choosing a device with a diameter 1.5 mm greater than the pmVSD diameter on TEE, the risk of residual shunts decreased, although the result was only borderline significant (P=0.06). In cases of residual shunt, the probability of the disappearance of the residual shunt in patients with a pmVSD diameter ≥4.5 mm on TEE (HR 0.49; 95% CI 0.04–0.7) was half that in patients with a pmVSD diameter <4.5 mm. Hence, we could consider choosing a device size that is at least 1.5 mm larger than the pmVSD diameter on TEE to minimize the risk of residual shunts, and we should regularly follow up cases of residual shunt after closure in patients with a pmVSD diameter ≥4.5 mm.
Most patients with small unrepaired VSDs and no LV volume overload on their echocardiography remain symptom-free and do not require surgery.18 However, in a randomized controlled trial of adult VSD, LVEDD normalized after transcatheter closure and surgical repair of VSD at the 2-year follow-up.19 Children with pmVSD also exhibited a significant decrease in LVEDD 1 day after transcatheter closure.12 In the present study, we further demonstrated a reduction in LVEDD not only in patients with a Qp/Qs ratio ≥1.3, but also in those with a Qp/Qs ratio <1.3. The indications for pmVSD closure varied among the 29 patients in the present study with a Qp/Qs ratio <1.3. Five of these patients underwent pmVSD closure due to heart failure symptoms, 18 underwent the procedure due to a cardiothoracic ratio >0.5, 3 underwent the procedure because of LV enlargement (LVEDD z-score >2.0), 21 had a right coronary cusp prolapse, 8 had AR, and 14 had multiple of the reasons mentioned for pmVSD closure. A significant reduction in LVEDD was not observed until 1 year after the procedure, and the underlying mechanisms behind this phenomenon remain unclear. Prior studies have indicated that regardless of the size of the shunt, a persistent VSD over an extended period may result in impaired systolic function and an increase in the compliance of both ventricles due to chronic pressure and volume overload.20,21 Abnormal increases in pulmonary vascular resistance and LV end-diastolic pressure, particularly during exercise, were observed, and these may be attributed to the presence of dysplastic cardiac muscle.22 Collectively, the elimination of the mechanisms mentioned above may contribute to LV remodeling, even over an extended period of time.
Our study has some limitations, such as being a single-center study with a retrospective study design, enrolling a small sample size, and failing to compare transcatheter closure with surgical repair in similar patients. Hence, prospective, comparative studies with a longer follow-up time are needed.
Conclusions
We identified risk factors associated with the development of residual shunts (VSD size ≥4.5 mm) and AR (age <4 years) subsequent to transcatheter closure of pmVSD in young children. It is essential to examine the potential benefits and risks of transcatheter pmVSD closure in this vulnerable subgroup of patients in future investigations.
Sources of Funding
This study did not receive any specific funding.
Disclosures
The authors have no conflicts of interest to disclose.
IRB Information
This study was approved by the Ethics Committee from the National Taiwan University Hospital Ethics Center Research Ethics Section (Reference no. 201703133RINB).
Data Availability
Deidentified participant data will not be shared, except for the data presented in the paper.
Supplementary Files
Please find supplementary file(s);
https://doi.org/10.1253/circj.CJ-23-0891
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