Continuous development of new techniques and material has made catheter treatment of congenital vascular malformation or congenital heart disease (CHD) possible in children and infants [
In this observational multicenter study, a retrospective chart review of all children aged less than 10 years, having undergone a cardiac, vascular, or conduit occlusion procedure using AVP II or IV between January 2007 and March 2020, was conducted in 6 academic centers from the same European country. All cardiovascular abnormalities were potential candidates for AVP II or IV implantation. All patients were treated and followed-up through a dedicated nationwide network. All vascular abnormalities were potential candidates for AVP device implantation whenever another “on-label” device could not be selected, such as the one used during some PDA closures. All procedures contributing to this work comply with the ethical standards of the relevant national guidelines on human experimentation, and with the Helsinki Declaration of 1975, as revised in 2008. Informed consent was obtained from each study participant’s parents or legal guardians, and the Institutional Review Board of one of the study centers approved all study procedures (IRB 2020/053).
The tri-lobe AVP II (4 to 22 mm, 5 to 9 Fr delivery catheter) was first delivered in 2007. A few years later
Each device was chosen by the interventional paediatric cardiologists in order to obtain adequate occlusion without abnormal protrusion into nearby structures. Device selection was based on multiple parameters such as lesion anatomy (type, size, length), blood flow crossing the defect, vascular access, best technical approach, and finally, the availability of an appropriate landing zone. Due to its property of rapid occlusion and wide availability of sizes, AVP II was selected more frequently for the occlusion of large vessels (diameter > 6 mm), even in very young children. AVP IV was more often selected for closing smaller but longer and tortuous vessels, as well as small surgical conduits.
Overall, AVP was usually chosen 20% to 50% larger than the arterial native vessel size measured on initial angiography [
Following parent/legal guardian consent, interventions were performed in a digital catheterization laboratory under conscious sedation or general anesthesia, according to age, procedure type, and team practice. All patients received IV heparin and standard antibiotic prophylaxis. Anterograde and retrograde route were used according either to the choice of the operators, the lesion to occlude, type and size of the selected device, findings during the procedures, or requested size of the delivery sheath. A few patients with either venous fistulae, partial cavo-pulmonary connection, single ventricle circulation, or interruption of the inferior vena cava, requested exclusive internal jugular vein access. All devices were deployed through a delivery sheath (AVP II) or a diagnostic catheter (AVP IV) using previously described techniques [
Demographic data and procedure characteristics such as vascular access, occlusion type, and implanted AVP types and number were recorded. PDA morphologies were defined according to Krinchenko’s classification [
Immediate technical success was defined as successful plug delivery in an adequate position with no more than mild intra-prosthetic residual shunt and without residual para-prosthetic shunt around the device or compression of nearby structures. Occlusion rate was monitored immediately after the procedure, at day 1 and 6 months later using echocardiography or CT scan whenever indicated. Adverse events (severity level ≥3) were defined according to the previously published CHARM (Catheterization for congenital Heart Disease Adjustment for Risk Method) model (
Baseline patient and procedure characteristics were described and compared according to AVP type and MAE occurrence. Quantitative variables were described using mean ± standard deviation or median (minimum-maximum range). Categorical variables were presented as absolute values and percentages. Group comparisons were conducted with Student
Over a 14 year-period, 125 children under 10 years (57.6% female, mean age: 2.8 ± 3.1 years, mean weight 13.9 ± 13.7 kg) underwent 136 procedures using either AVP II and/or AVP IV for the percutaneous treatment of 147 different lesions. Overall, 169 plugs (60 AVP II and 109 AVP IV) were successfully implanted out of the 171 initially engaged. As such, two procedures failed due to poor patient tolerance requiring withdrawal before release. The first procedure failure involved an infant who developed immediate left pulmonary artery (LPA) stenosis (
A wide variety of procedures were carried out throughout the study period (
Overall, 55 PDA occlusions were performed with a minimal diameter of 5.5 ± 1.6 mm and different morphologies [
Furthermore, 80% of PDA closure procedures included both arterial and venous femoral access with arterio-venous loop, while 7 AVP II were implanted into PDA by venous route only, and 4 plugs (3 AVP II) by a pure arterial approach. Five AVP II, as well as 2 AVP IV, were implanted to replace “on-label” PDA devices. Patient and procedure characteristics according to AVP II and IV “Off-label” use in children are further summarized in
Characteristics | Overall sample |
AVPII* |
AVP IV* |
|
---|---|---|---|---|
Age, years | 1.0 (0.01–9.98) | 0.8 (0.05–9.98) | 1.3 (0.01–9.56) | 0.08 |
Age ≤ 1 year | 62 (49.6) | 31 (53.5) | 29 (45.3) | 0.37 |
Male gender | 53 (42.4) | 19 (32.8) | 34 (53.1) | 0.02 |
Weight, Kg | 8.4 (1.0–69.0) | 6.9 (1.0–69.0) | 10.3 (2.1–60.0) | 0.03 |
Weight ≤ 5 kg | 34 (27.2)) | 22 (37.9) | 11 (17.2) | 0.01 |
Arterial access | 112 (82.4) | 49 (83.1) | 61 (82.4) | 0.93 |
Venous route for delivery | 81 (59.6) | 49 (83.1) | 32 (43.3) | <0.001 |
Minimal vessel diameter, mm | 5.4 (2.8–17.0) | 6.0 (3.0–17.0) | 5.0 (2.8–7.0) | <0.001 |
PDA minimal diameter, mm | 5.4 (3.0–10.5) | 5.8 (3.0–10.5) | 4.2 (3.5–6.2) | 0.02 |
AVP diameter | 8.0 (4.0–20.0) | 8.0 (4.0–20.0) | 6.0 (4.0–8.0) | <0.001 |
Oversizing | ||||
Ratio AVP diameter to minimal vessel diameter | 1.3 (0.0–2.0) | 1.4 (0.0–2.0) | 1.3 (1.1–1.7) | <0.001 |
Ratio AVP diameter to patient weight | 0.9 (0.0–6.0) | 1.3 (0.0–6.0) | 0.5 (0.1–2.9) | <0.001 |
PDA | 55 (40.4) | 42 (71.2) | 11 (14.9) | <0.001 |
Type of PDA** | ||||
A | 4 (2.9) | 3 (5.1) | 1 (1.4) | - |
C | 26 (19.1) | 23 (39.0) | 2 (2.7) | <0.001 |
D | 12 (8.8) | 8 (13.6) | 4 (5.4) | - |
D/E | 2 (1.5) | 0 (0.0) | 2 (2.7) | - |
E | 11 (8.1) | 8 (13.6) | 2 (2.7) | - |
AP collateral | 23 (16.9) | 2 (3.4) | 19 (25.7) | <0.001 |
Sequestration and/or Scimitar Syndrome | 18 (13.2) | 0 (0.0) | 16 (21.6) | <0.001 |
Arteriovenous fistula | 8 (5.9) | 1 (1.7) | 7 (9.5) | 0.08 |
Veno-venous fistula | 8 (5.9) | 2 (3.4) | 6 (8.1) | 0.30 |
Coronary fistula | 6 (4.4) | 0 (0.0) | 6 (8.1) | 0.03 |
Surgical conduit | 6 (4.4) | 1 (1.7) | 5 (6.8) | 0.23 |
Left vertical vein | 6 (4.4) | 5 (8.5) | 1 (1.4) | 0.09 |
VSD | 5 (3.7) | 2 (3.4) | 3 (4.1) | 1.00 |
Bronchial or parietal-bronchial collaterals | 5 (3.7) | 1 (1.7) | 4 (5.4) | 0.38 |
Miscellaneous*** | 6 (4.4) | 3 (5.1) | 2 (2.7) | 0.65 |
Note: Values represent mean ± standard deviation, median (min-max) or number (%). A two-tailed
Successful closures of anomalous or aberrant systemic arterial supply to a lung segment was achieved using 18 AVP IV and 2 AVP II. Six uncomplicated closures of single or multiple congenital artery fistulae (CAF) using 6 to 8 mm AVP IV in infants and neonates were also completed, for which delayed post-procedure angiograms demonstrated the absence of residual shunt or coronary thrombosis. The effective closures of 2 peri-membranous Ventricular Septal Defects (VSD) with aneurysm (AVP II) as well as 1 postoperative VSD (AVP IV) and 2 muscular VSDs (AVP IV,
Overall, the median oversizing of devices was 130%, but was higher with AVP II than with AVP IV (1.4
In contrast, AVP IV was more widely used for the occlusion of single or multiple AP collaterals (25.7%
The positioning and release of at least one device was possible in 134 procedures, accounting for an immediate procedure success rate of 98.5%. Full occlusion rate observed at day 1 and 6-month post procedure were 94.8% and 98.5%, respectively. No difference was observed according to AVP type. Procedure efficacy and safety of AVP II and IV are detailed in
Characteristics |
Overall sample |
AVPII* |
AVP IV* |
|
---|---|---|---|---|
Immediate successful procedure | 134 (98.5) | 57 (96.6) | 74 (100.0) | 0.19 |
Occlusion rate |
||||
24-hours post procedure | 127 (94.8) | 54 (94.7) | 70 (94.6) | 1.00 |
6 months post-procedure | 132 (98.5) | 56 (98.3) | 73 (98.7) | 1.00 |
SAE (grade ≥ 3) ** |
11 (8.1) |
10 (17.0) |
1 (1.4) |
0.002 |
• No PDA | 0 (0.0) | 0 (0.0) | 0 (0.0) | |
• PDA | 7 (5.2) | 7 (11.9) | 0 (0.0) | |
Plug embolization | 4 (2.9) | 4 (6.8) | 0 (0.0) | 0.04 |
Mild to severe PA stenosis | 5 (3.7) | 4 (6.8) | 1 (1.4) | 0.17 |
Surgical device removal | 4 (2.9) | 4 (6.8) | 0 (0) | 0.04 |
30-day in-hospital mortality | 1 (0.7) | 1 (1.7) *** | 0 (0.0) | 0.44 |
Note: Values represent number (%). A two-tailed
There was no procedure related death. Thirty-day in-hospital mortality occurred only in one patient who died due to hypoxemic pneumonia complicating a severe bronchiolitis, unrelated to procedure. Significant adverse events of severity level ≥3 (including 4-transient femoral artery thrombosis) occurred in a total of 8.1% of procedures. Patient and procedure characteristics according to occurrence of Major Adverse Events (MAE, grade ≥ 4) in children are summarized in
In total, 5.2% of patients underwent MAE, solely observed during catheter closure of large PDAs using AVP II. Observed MAE were predominantly device embolization or the need for urgent or delayed surgery. MAE occurred more frequently in younger patients (mean age 1.6 ± 3.5 years,
In all, there were a total of 4 device embolization, always observed within the first 24 h (
Additional surgical procedures were performed in 2 patients presenting delayed severe LPA stenosis. The latter were documented 2 weeks after PDA closure in a 3.2 kg baby (10 mm AVP II) and 8 weeks after the procedure in another infant weighing 4.9 kg (10 mm PDA, 14 mm AVP II). This patient presented with a device “attraction” of the descending aorta and severe plication of the LPA. The last MAE involved a 3.6 kg infant already on inotropic support at the entrance to the catheterization room who presented a cardiac arrest during the first aortography. He was successfully resuscitated. There was no EKG modification, with unremarkable immediate coronary angiogram. PDA closure was successfully achieved using a 6 mm AVP II. Three other mild LPA stenosis did not require treatment, with uneventful follow-ups. There was no haemolysis, severe bleeding, cardiac arrhythmia, or late embolization.
Using univariate logistic regression analysis (
Characteristics at procedure | Univariate analysis | Multivariate analysis | ||
---|---|---|---|---|
Odds-ratio (95% CI) | Odds-ratio (95% CI) | |||
Age, years | 0.85 (0.60–1.19) | 0.34 | ||
Age ≤ 1 year | 6.90 (0.81–58.94) | 0.08 | ||
Weight, kg | 0.96 (0.88–1.05) | 0.37 | ||
Weight ≤ 5 kg | 7.90 (1.46–42.78) | 0.02 | ||
Female gender | 4.32 (0.51–36.93) | 0.18 | ||
Pulmonary hypertension | 3.32 (0.71–15.54) | 0.13 | ||
Urgent procedure | 4.09 (0.85–19.67) | 0.08 | ||
PDA, type C | 6.49 (1.36–31.04) | 0.02 | 5.35 (0.99–28.97) | 0.052 |
PDA minimal diameter, mm | 1.41 (0.88–2.26) | 0.15 | ||
AVP diameter, mm | 1.12 (0.93–1.35) | 0.25 | ||
Ratio AVP diameter to patient weight | 2.32 (1.33–4.04) | 0.003 | 2.33 (1.31–4.13) | 0.003 |
Ratio ≥ 1.45 | 9.02 (1.67–48.99) | 0.01 | ||
Ratio AVP diameter to minimal vessel diameter | 19.78 (0.42–923.59) | 0.13 | ||
Ratio ≥ 1.38 | 5.56 (1.04–29.90) | 0.046 | ||
Ratio AVP diameter to PDA minimal diameter | 1.07 (0.08–13.63) | 0.96 | ||
Ratio PDA minimal diameter to patient weight | 2.41 (1.01–5.76) | 0.048 |
Note: * Variables with significant association in univariate analysis (
Multivariate analysis (
The cohort reported in this paper is the largest paediatric series describing multiple indications of AVP II and IV use, with a total of 169 implanted devices (55.6% of AVP IV). In this multicenter experience, the off-label utilization of such devices appears effective in children and infants (median age: 1 year). The overall rate of successful AVP implantation (98.5%) constitutes a major indicator of efficacy which compares favourably with previous reports on use of AVPs and other devices formally developed for PDA or vascular occlusions [
The instruction manual of the manufacturer recommends an AVP II or IV oversizing of 30%–50%, which is underlined by our study results (median oversizing percentage 130%). We report several occlusions of large vessels (median > 5 mm) which is remarkable and rarely reported in infants till now. Off-label use of AVPs with even greater oversizing (150%–160%) could sometimes be indicated in cases of high blood flow (CAF, large arterial collaterals, VSD, large PDAs), severe pulmonary hypertension, surgical conduits, as well as very large, short or even slightly elastic lesions in infants and young children [
In our study, the higher number of AVP IV implanted per procedure compared to AVP II reflects the concomitant treatment of several lesions, such as multiple collaterals or multiple feeding vessels. Thus, using an oversizing of 120%–160%, and with the exception of a few complex arterio-venous malformations that cannot be treated exclusively with plugs, the achievement of selective or supra-selective occlusions does not require any additional occluders or coils implantations [
This compares very favourably with the use of more recent devices such as the microvascular plug (MVP, Medtronic™, Minneapolis, MN, USA), for which implantation may require significant oversizing (30% to 60% for venous occlusions, 40% to 70% for arterial occlusions) and the complementary use (20%) of coils or other occluders at the same site to obtain a similar occlusion rate [
Moreover, to the best of our knowledge, we report the largest patient series in which AVP II and IV are used to occlude several anatomical shunt varieties including large malformations [
Furthermore, although recent plugs such as the smallest MVP types [
AVP II could prove to be a potential alternative, as underlined by our study results. AVP II is also a relatively “low-cost device” which requires most often 5 to 6 Fr standard delivery catheters [
Pertaining to the safety of “off-label” AVP use, we did not experience any major complications using AVP IV, as reported by several authors [
Finally, an overall AVP II or IV oversizing of more than 140% compared to vessel diameter is probably not recommended in low-weight children, except in certain particular cases. This is consistent with general manufacturer recommendations for the use of these two devices in adults.
Our retrospective study design might have introduced potential interpretation bias. Firstly, we did not take into account center heterogeneity among the 6 participating institutions, in terms of patient volume, procedure type, and operator-biased device selection. Secondly, large tubular PDAs in infants of low weight were not considered for AVP catheter occlusion in half of the participating centers, which preferred surgical procedures for this high-risk patient group [
This multi-institutional study reports the largest and youngest group of catheter-treated children (50% infants <1 year), with AVP II or IV “off-label” use for the occlusion of heterogeneous congenital cardiovascular malformations. For a wide range of indications, we demonstrate that both devices are perfectly safe and effective in children under 10 years. Despite some MAEs that were solely related to PDA closure in infants, AVP II might still represent an alternative for the closure of well-selected atypical or large tubular PDAs. New plugs with a small profile and an adapted design are required to further improve the management of very large vessels in small infants. In the meantime, effective paediatric labelling of AVP II and IV seems essential and will contribute to the optimization of future catheter techniques in children.
The authors would like to acknowledge Ms. Mélanne Ghahraman and Mrs. Maria Minassian, for their assistance with manuscript proofreading.
Severity level | Definition |
---|---|
1-None | No harm. No change in condition. May have required monitoring to assess for potential change in condition with no intervention indicated. |
2-Minor | Transient change in condition. Not life–threatening. Condition returns to baseline. Required monitoring. Required minor intervention such as maintaining medication or obtaining laboratory tests. |
3-Moderate | Transient change in condition. May be life–threatening if not treated. Condition returns to baseline. Required monitoring. Required intervention such as reversal agent, additional medication, transfer to the intensive care unit for monitoring, or moderate trans-catheter intervention to correct condition. |
4-Major | Change in condition. Life-threatening if not treated. Change in condition may be permanent. May have required an intensive care unit admission or emergent readmission to hospital. May have required invasive monitoring. May have required interventions such as electrical cardioversion or unanticipated intubation, or required major invasive procedures or trans-catheter interventions to correct condition. |
5-Catastrophic | Any death or emergent surgery or heart lung bypass support (ECMO) to prevent death. |
Abbreviations: CHARM: Catheterization for congenital Heart Disease Adjustment for Risk Method [
Characteristics at procedure | Overall sample (N = 125 Pts; 136 procedures) | No MAE* (N = 118 Pts; 129 procedures) | MAE* (N = 7 Pts; 7 procedures) | |
---|---|---|---|---|
Age, years | 1.0 (0.01–9.98) | 1.1 (0.01–9.98) | 0.3 (0.05–9.5) | 0.03 |
Age ≤ 1 year | 62 (49.6%) | 56 (47.5%) | 6 (85.7%) | 0.06 |
Weight, kg | 8.4 (1.0–69) | 9.4 (1.0–69) | 4.0 (1.4–43.0) | 0.05 |
PDA closure | 55 (40.4%) | 48 (37.2%) | 7 (100%) | 0.001 |
PDA type C | 26 (19.1%) | 22 (17.1%) | 4 (57.1%) | 0.03 |
PDA minimal diameter, mmn = 55 | 5.4 (3.0–10.5) | 5.0 (3.0–10.5) | 6.0 (5.0–9.0) | 0.09 |
AVP II | 59 (44.4%) | 52 (41.3%) | 7 (100%) | 0.003 |
AVP diameter, mm | 8.0 (4.0–20.0) | 8.0 (4.0–20.0) | 8.0 (4.0–14.0) | 0.03 |
Ratio AVP diameter to patient weight | 1.1 ± 1.0 0.9 (0.0–6.0) | 1.0 ± 0.8 0.8 (0.0–6.0) | 2.4 ± 1.7 2.0 (0.2–5.7) | 0.01 |
Ratio AVP diameter to minimal vessel diameter (%) | 1.3 (0.0–2.0) | 1.3 (0.0–2.0) | 1.4 (1.3–1.6) | 0.03 |
Ratio AVP diameter to PDA minimal diameter n = 55 | 1.4 ± 0.3 1.5 (0.0–2.0) | 1.4 ± 0.3 1.5 (0.0–2.0) | 1.4 ± 0.1 1.4 (1.3–1.6) | 0.60 |
Ratio PDA minimal diameter to patient weight n = 55 | 1.1 ± 0.8 1.0 (0.1–4.3) | 1.0 ± 0.6 0.9 (0.1–4.0) | 1.7 ± 1.3 1.4 (0.1–4.3) | 0.048 |
Plug embolization | 4 (2.9%) | 0 | 4 (57.1%) | <0.001 |
Need for surgery | 4 (2.9%) | 0 | 4 (57.1%) | <0.001 |
Note: Values represent mean ± standard deviation, median (min-max) or number (%). *MAE: Major adverse events (grade ≥ 4)30. A two-tailed