Long-term Consequences of Ventricular Septal Defect Closure Using Nit-Occlud Le VSD Coil Device: A Systematic Review and Meta-Analysis.

Background: The successful management of ventricular septal defect (VSD) has been possible through the development of advanced techniques. In this regard, percutaneous VSD closure by employing different types of occluders as an alternative for surgery can help to achieve the most desirable postprocedural consequences. However, the studies reported contradictory results on the use of different brands of VSD occluders. Herein, we performed a systematic review and meta-analysis of published studies to assess pooled long-term success rate and potential complications of using the Nit-Occlud Lê VSD coil for VSD closure. Materials and
Methods: Two reviewers began to deeply search the various databases for all eligible studies in accordance with the considered keywords. The inclusion criterion for retrieving the studies was to describe the mid-term or long-term consequences of VSD closing by the Nit-Occlud Lê VSD coil device. In the final, eight articles were eligible for the analysis. The follow-up time of the studies ranged from 6 months to 5 years.
Results: The success rate of the procedure ranged from 87.0% to 100% considering the weight of each study, the pooled success rate of VSDs closure by Nit-Occlud Lê VSD coil device was 93.1% (95% confidence interval [CI]: 89.9% to 95.5%). The pooled prevalence of postprocedural residual shunt was estimated to be 9.6% (95%CI: 6.8% to 13.4%). The corrected pooled prevalence of trivial mild aortic regurgitation (AR) was 2.9% (95%CI: 1.5% to 5.4%); however, moderate-to-severe AR and complete heart block or right bundle branch block were shown to be rare.
Conclusion: VSD closure using a Nit-Occlud Lê VSD coil device can lead to a high success rate with low rates of residual shunt, cardiac conductive or vascular disturbances. Copyright:

INTRODUCTION

The successful management of ventricular septal defect (VSD) as one of the most common congenital heart defects has been possible by the development of advanced techniques in the recent decade. The basis of almost all techniques is based on VSD percutaneous surgical closure which was initially described in 1988.[12] Thereafter, various types and generations of devices for closing VSD were commercially introduced but with different effectiveness and outcomes. Regardless of applying such modalities, surgical VSD closure may be accompanied by some potential concerns such as complete heart block or bundle branch blocks, myocardial defects, wound infection, electrolyte disturbances, valvular regurgitation, coagulopathies, and even renal insufficiency.[345] These risky situations may be also doubled by device-related complications including residual shunt early or long term after the procedure. It seems that appearing such complications depend potentially on both type or brand of the device (Nit-Occlud Lê VSD coil and Amplatzer™ occluders) and the characteristics of the closing device (size and length of occluder).[67] Although there has been considerable success in using these types of devices for VSD closure, varying incidence rates of postprocedural complications have been reported especially considering different types of devices.

The last decade has coincided with the introduction of the Nit-Occlud Lê VSD coil as a flexible VSD occluder for different types of VSDs particularly perimembranous (aneurysmatic) and muscular types.[8910] Some benefits of such devices include high effectiveness and safety due to using flexible polyester fibers, outstanding adaptation properties dependent on the aneurysmatic and muscular nature of the defect, low rate of atrioventricular blocks due to its flexible design, its broad range of different sizes suitable for various shapes and sizes of VSDs, and applying small delivery sheaths for its designing.[11] Despite all these benefits, studies have reported different consequences of using this tool, which requires a systematic look at the benefits of this tool. Herein, we performed a systematic review and meta-analysis of published studies to assess pooled long-term success rate and potential complications of using the Nit-Occlud Lê VSD coil for VSD closure.

MATERIALS AND METHODS

We performed the present systematic review and meta-analysis according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses statement. Two reviewers began to deeply search the various databases of the article published including MEDLINE, Web of Knowledge, Google Scholar, Scopus, and Cochrane Central Register of Controlled Trials in the Cochrane Library for all eligible studies in accordance with the considered keywords including “VSD,” “Nit-Occlud Lê VSD coil,” “outcome,” “complication,” and “occlude” based on the MeSH vocabulary. Disagreements were resolved through discussion and decided by a third reviewer. No limitation was considered for the country or date of articles published. All English language-based studies were included in the initial assessment. In this review, all cross-sectional, case–control, and clinical trials were included and thus the abstracts with unavailable full texts, case reports, or case series as well as reviews were excluded from the first step. We also tried to contact authors by letter writing to obtain unpublished data or full texts. The inclusion criterion for retrieving the studies was to describe the mid-term or long-term consequences of VSD closing by the Nit-Occlud Lê VSD coil device. In addition to patients, demographics, device-related characteristics (size), type of VSDs, operation time, time for following up, procedural success rate, and procedure-related complications were all considered for the endpoints. The study quality was evaluated based on the following criteria: (1) the systematic review and meta-analysis based on the questions primarily described and formulated, (2) inclusion and exclusion criteria predefined in the studies as eligibility criteria, (3) searching the literature performed on a systematic and comprehensive approach, (4) to minimize the bias, the full texts of the article were dually reviewed, (5) the quality of included studies were rated independently by the reviewers for appraising internal validity, (6) studies' characteristics and findings were comprehensively listed, (7) the publication and risk of bias were listed, and (8) heterogeneity was also assessed. The risk of bias for each study was assessed using the criteria outlined in the Cochrane Handbook for Systematic Reviews of Interventions and also according to the QUADAS-2 tool.

For statistical analysis, the Comprehensive Meta-Analysis Software (CMA, version 3.0) was employed. The address is 14 North Dean Street, Englewood, NJ 07631 USA was employed. We presented dichotomous data related to pooled prevalence of each procedural complication as prevalence rate and its 95% confidence interval (CI). Data were assessed by both fixed effects and random effect models; however, the random effect analyses were reported if the heterogeneity was significantly evaluated by the I2 statistic. Reported values were two-tailed, and hypothesis testing results were considered statistically significant at P = 0.05. The publication bias was assessed by drawing the funnel plot.

RESULTS

The flow diagram of the study selection is summarized in Figure 1. Primarily, 70 articles were collected by database searching and other sources. After removing six articles due to evidence of duplication, 64 records were primarily underscreened. Based on the titles and abstracts, 53 records were excluded and the remaining 15 citations were assessed for further eligibility. Of those, seven were also excluded due to the incompleteness of the data and contents. In the final, eight articles were eligible for the final analysis[1112131415161718] [Table 1].

Figure 1

The flowchart of screening the eligible studies

Table 1

The assessment of the risk of bias

	Patient selection	Index test	Outcomes measuring	Flow and timing
Chungsomprasong, 2011	+	?	?	+
Durongpisitkul, 2017	?	?	?	+
El Shedoudy, 2018	?	+	+	+
Haas, 2016	+	+	+	+
Houeijeh, 2020	?	+	+	+
Nguyen 2018	+	+	+	+
Nogi, 2008	?	?	?	+
Odemis, 2014	+	?	+	+

: + Low,

: ? Unclear,

: - High

The studies included were assessed qualitatively by the QUADAS-2 tool. According to our risk of bias assessment, all seven studies yielded good quality and none of the citations was determined to have a high risk of bias therefore the pooled results should be persuasive [Table 1].

In total, eight studies including 455 patients with a median age ranged 1–16.8 years suffering VSDs with the different types that underwent VSD closure by Nit-Occlud Lê VSD coil were finally evaluated in terms of mid- and long-term sequels of the procedure. The details of patients' characteristics and device-related parameters are shown in Table 2. The operation time ranged from 84 to 105 min. The follow-up time of the studies also ranged from 6 months to 5 years. As shown in Table 3, the success rate of the procedure ranged from 87.0% to 100% considering the weight of each study, the pooled success rate of VSDs closure by the Nit-Occlud Lê VSD coil device was 93.1% (95% CI: 89.9% to 95.5%). The heterogeneity across the studies was insignificant for the assessment of overall success rate (I2 = 32.796, P = 0.166) [Figure 2a] with no publication of bias according to the funnel plot drawn (P = 0.556) [Figure 3a]. Regarding the prevalence of residual shunt, the pooled prevalence was estimated to be 9.6% (95% CI: 6.8% to 13.4%) that was reliable due to low heterogeneity between studies (I2 = 35.341, P = 0.155) [Figure 2b] and insignificant publication of bias (P = 0.216) lFigure 2b]. Regarding heart blocks, four studies reported no evidence of right bundle branch block (RBBB) and four studies reported no evidence of complete atrioventricular block (AVB) with the overall prevalence rate ranging from 0.0% to 5.9% for RBBB and 0.0% to 19.4% for AVB. The coil removal certainly for hemolysis was reported in three studies leading the device removal rate ranged 0.0%–10.0%.

Table 2

The details of studies included in the meta-analysis

Author, year	Number of patients	Male/female	Median age	Type of VSD	Median VSD size	Procedure time
Chungsomprasong, 2011	33	20/13	9.8	Pm: 6 Pm with inlet: 5 Outlet and DCSA VSD: 22	10.3	88.2
Durongpisitkul, 2017	53	27/26	1.0	Pm: 39.6% Pm with inlet: 11.3% DCSA: 49.1%	5.0	84.9
El Shedoudy, 2018	80	30/50	5.0	Pm: 77 Muscular: 2 Gerbode: 1	Left: 8.3 Right: 4.5	105
Haas, 2016	111	45/66	5.1	Pm: 81 Aneurismal: 48 Muscular: 30 Multiple: 20 Midmuscular: 24 Apical: 6	Left: 8.6 Right: 4.4	121
Houeijeh, 2020	46	28/18	13.9	Pm: 46	Left: 8.0 Right: 5.0	88
Nguyen 2018	71	31/40	16.8	Pm: 71	Left: 4.4 Right: 4.1	92.7
Nogi, 2008	41		13.0	Pm: 41	-	-
Odemis, 2014	20	10/10	7.3	Pm: 20	Left: 8.2 Right: 5.1	88.5

VSD: Ventricular septal defect, DCSA: Doubly committed subarterial

Table 3

The details of the outcome of ventricular septal defect closure

Author, year	Follow-up time (months)	Success rate	RBBB	AVB	Device removal	Residual shunt	AR (mild)	AR (moderate-severe)
Chungsomprasong, 2011[12]	6	31/33	0	6	0	5	11	0
Durongpisitkul, 2017[13]	60	53/53	2	1	0	8	22	0
El Shedoudy, 2018[14]	24	79/80	1	1	0	2	1	0
Haas, 2016[15]	24	102/111	6	0	1	4	3	0
Houeijeh, 2020[16]	27	40/46	0	0	4	8	2	3
Nguyen, 2018[11]	24	69/71	0	1	0	1	1	0
Nogi, 2008[17]	6	38/41	1	0	0	1	2	0
Odemis, 2014[18]	12	20/20	0	0	1	2	0	0

RBBB: Right bundle branch block, AVB: Atrioventricular block, AR: Aortic regurgitation

Figure 2

Forest plots of pooled relative prevalence for long-term outcome of VSD using Nit-Occlud Lê VSD coil. (a) Success rate, (b) residual shunt, (c) mild aortic regurgitation. VSD: ventricular septal defects

Figure 3

Funnel plot with pseudo 95% confidence limits for estimating the publication bias in the assessment of the long-term outcome of VSD using Nit-Occlud Lê VSD coil (a): success rate, (b): residual shunt; (c): mild aortic regurgitation. VSD: ventricular septal defects

Concerning the occurrence of aortic regurgitation (AR), the pooled prevalence of trivial-to-mild AR was assessed to be 19.4% (14.4%–25.7%), but with notable heterogeneity between studies (I2 = 88.604 and P = 0.001) [Figure 2c] and also with high publication bias (P = 0.002). In the sub-assessment of the studies, we found that the rate of mild AR was reported to be very high in two of eight studies assessed according to the judgment of our authors, it might be due to a higher proportion of doubly committed subarterial VSD or perhaps for the double-disc device design of VSD device. By excluding two pointed articles from the analysis, the corrected pooled prevalence of mild AR was 2.9% (95% CI: 1.5% to 5.4%) with low heterogeneity (I2 = 0.001, P = 0.822) and consequently without publication of bias (P = 0.577) [Figure 3C]. In this regard, moderate-to-severe AR was only reported by a study with a prevalence rate of 7.5%.

DISCUSSION

For years, surgery had remained the gold standard for repairing VSD defects; however, this approach was associated with high-postoperative complications, requiring a prolonged hospital stay, need for sternotomy, and therefore patients' dissatisfaction concerning esthetics as well as psychological disturbances. Since percutaneous VSD closure by different occluders was developed, not only the pointed sequels were considerably minimized but also the long-term outcome of the repairing procedure has been significantly improved. However, various factors could affect the procedural outcome such as the patients' baseline clinical comorbidities and procedure-related parameters. In this regard, the types of deployment techniques and devices were at the forefront of these factors. Thus, recent efforts focused on the selection of the best devices with good performance and minimized complications and limitations. In this regard, applying VSD occluders with higher flexibility, lower residual shunt, and also lower cardiac complications was considered by the designers and manufacturers. By introducing the VSD coil, many of these goals were achieved. As shown systematically in the present study, a minority of published interventional studies pointed to postoperative complications following the use of the Nit-Occlud Lê VSD coil for VSD closure. In other words, the likelihood of cardiac arrhythmias, valvular insufficiencies, and even residual shunts was reported rarely in the studies or was so light that they were improved after a while. As systematically shown, VSD closure using a Nit-Occlud Lê VSD coil device led to a high procedural success rate, ranging from 87.0% to 100%. More interestingly, almost all studies acknowledge the high effectiveness of this device to achieve long-term safety as well as low long-term complication rate and therefore low rate of reoperation. It seems that by manufacturing VSD coil, the compression to the defect wall and conduction system was minimized.

Despite the advantages and high success of VSD closure by Nit-Occlud Lê VSD coil, the risk of postprocedural complications has been also assessed in some studies. In this regard, it seems that the likelihood of such complications may increase by lowering the patient's age,[1920] and therefore for minimizing this risk, the use of low-profile devices with a small delivery system is recommended. Furthermore, a larger defect size in addition to an undersized device could affect the procedural outcome concerning a higher risk for residual shunt or device embolization, while an oversized device may result in a higher risk for valvular injuries or ventricular outflow tract obstruction.[2122] Thus, it is not commendable that for a better assessment of the effectiveness of such VSD occluders, considering such variables in subsequent studies is essential.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.