# Outcomes of transcatheter patent ductus arteriosus closure in infants weighing 2 to 6 kg

Sophie Malekzadeh-Milani, Paul Padovani, Kothandam Sivakumar, Thomas Goronflot, Mathilde Méot, Matthew I Jones, Naychi Lwin, Caroline Ovaert, Sébastien Hascoët, Zakaria Jalal, et al.

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## To cite this version:

Sophie Malekzadeh-Milani, Paul Padovani, Kothandam Sivakumar, Thomas Goronflot, Mathilde Méot, et al. Outcomes of transcatheter patent ductus arteriosus closure in infants weighing 2 to 6 kg. Revista Española de Cardiología (English version), 2025, pp.1885-5857. 10.1016/j.rec.2025.09.011. hal-05380921

HAL Id: hal-05380921

https://hal.science/hal-05380921v1

Submitted on 25 Nov 2025

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Original article

Outcomes of transcatheter patent ductus arteriosus closure in infants weighing 2 to 6 kg

Sophie Malekzadeh-Milani,ᵃ,¹ Paul Padovani,ᵇ,ᶜ,¹ Kothandam Sivakumar,ᵈ Thomas Goronflot,ᵉ

Mathilde Méot,ᵃ Matthew I. Jones,ᵇ Naychi Lwin,ᵇ Caroline Ovaert,ᵉ Sébastien Hascoët,ᵇ,¹ Zakaria Jalal,¹

Carles Bautista-Rodriguez,⁴ Marc Gewillig,¹ Hugues Lucron,⁵ Konstantin Averin,⁵ Béatrice Susanne Kahl,⁰

Janus Freyr Gudnason,⁵ Alejandro J. Torres,⁵ Bruno Lefort, r Zakhia Saliba, s Ali Houeijeh, t

Michal Galeczka, u Hasri Samion, v Sonia El Saiedi, w Juan Manuel Lange, x Nurit Yaakobi-Simhayoff, y

Alessia Callegari, a,z Anders Haugom Christensen, aa Martin B. Ystgaard, aa Jean-Bernard Selly, ab

Hélène Bouvaist, ac Deborah Neil, ad Domenico Sirico, ae Clément Karsenty, af Catalina Vargas-Acevedo, ag

Ernesto Mejia, ag Eric Rosenthal, f Céline Grunenwald, b Nadir Benbrik, b Oscar Werner, b,c

Anne Chauvire-Drouard, c Marine Gloanec, g Antoine Moktadir, h Jean-Benoit Thambo, j Mélanie Brard, ah

Gérald Laforest, ab Pramod Sagar, d Anu Joseph, d Thejaswi Puthiyedath, d Henrik Holmstrom, aa

Roland Fiszer, u Håkan Wåhlander, p,ai Ina Michel-Behnke, o Damien Bonnet, a Pierre-Antoine Gourraud, e

Gianfranco Butera, aj Shakeel A. Qureshi, f Alain Fraisse, k Gareth J. Morgan, ag

and Alban-Elouen Baruteauᵇ,ᶜ,ak,al,2,*

<footnote>ᵃ M3C-Necker, Department of Pediatric and Congenital Cardiology, Hôpital Necker-Enfants Malades, Assistance Publique-Hôpitaux de Paris (AP-HP), University of Paris Cité, Paris, France</footnote>

<footnote>ᵇ Nantes Université, CHU Nantes, Department of Pediatric Cardiology and Pediatric Cardiac Surgery, FHU PreciCare, Nantes, France</footnote>

<footnote>ᶜ Nantes Université, CHU Nantes, INSERM, CIC FEA 1413, Nantes, France</footnote>

<footnote>ᵈ Department of Pediatric Cardiology, Institute of Cardio Vascular Diseases, Madras Medical Mission, Chennai, Tamil Nadu, India</footnote>

<footnote>ᵉ Nantes Université, CHU Nantes, Pôle Hospitalo-Universitaire 11, Santé Publique, Clinique des Données, INSERM, CIC 1413, Nantes, France</footnote>

<footnote>f Department of Congenital Cardiology, Evelina London Children's Hospital, Guy's and St Thomas' NHS Foundation Trust, London, United Kingdom</footnote>

<footnote>g Department of Pediatric Cardiology, AP-HM Timone Enfants, Marseille, France</footnote>

<footnote>h Department of Pediatric and Congenital Cardiology, M3C-Marie-Lannelongue, Groupe Hospitalier Paris Saint-Joseph, Paris, France</footnote>

<footnote>i BME Lab, Université Paris-Saclay, Le Plessis-Robinson, France</footnote>

<footnote>j Department of Paediatric and Adult Congenital Cardiology, CHU de Bordeaux, Centre Constitutif Réseau Maladies Rares Cardiopathies Congénitales Complexes (M3C), Bordeaux, France</footnote>

<footnote>k Paediatric Cardiology, Royal Brompton and Harefield Hospitals, Guy's and St Thomas' NHS Foundation Trust, London, United Kingdom</footnote>

<footnote>l Department of Pediatric Cardiology, University Hospitals Leuven, Leuven, Belgium</footnote>

<footnote>m Pediatric Cardiology Unit, Children's University Hospital of Geneva, Switzerland</footnote>

<footnote>n Northwell, New Hyde Park, NY, Cohen Children's Medical Center, Cohen Children's Heart Center, New York, United States</footnote>

<footnote>o Division of Pediatric Cardiology, University Hospital for Children and Adolescent Medicine, Paediatric Heart Centre, Medical University Vienna, Vienna, Austria</footnote>

<footnote>p Department of Cardiology, Paediatric Heart Centre, Queen Silvia's Children's Hospital, Gothenburg, Sweden</footnote>

<footnote>q Division of Pediatric Cardiology, Department of Pediatrics, Columbia University Irving Medical Center, Morgan Stanley Children's Hospital, New York, United States</footnote>

<footnote>r Department of Pediatric Cardiology and Pediatric Cardiac Surgery, Clocheville Hospital, CHRU Tours, Tours, France</footnote>

<footnote>s Department of Pediatric Cardiology, Hotel Dieu de France University Medical Center, Saint Joseph University, Alfred Naccache Boulevard, Achrafieh, Beirut, Lebanon</footnote>

<footnote>t Pediatric Cardiology Department, Institut Cœur Poumon, CHRU Lille, Lille, France</footnote>

<footnote>u Department of Pediatric Cardiology and Congenital Heart Defects, Faculty of Medical Sciences in Zabrze, Medical University of Silesia, Silesian Center for Heart Diseases, Zabrze, Poland</footnote>

<footnote>v PCHC Department, Institut Jantung Negara, 145, Jalan Tun Razak, Kuala Lumpur, Malaysia</footnote>

<footnote>w Pediatric Department, Division of Pediatric Cardiology, Cairo University, Giza, Egypt</footnote>

<footnote>x Department of Pediatric Cardiology and Congenital Cardiology, Instituto Cardiovascular Chaco, Chaco, Argentina</footnote>

<footnote>y Department of Pediatric Cardiology, Hadassah Medical Center, Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel</footnote>

<footnote>z Pediatric Heart Center and Children's Research Center, University Children's Hospital Zurich, Zurich, Switzerland</footnote>

<footnote>aa Department of Paediatric Cardiology, Oslo University Hospital, Oslo, Norway</footnote>

<footnote>ab Department of Pediatric Cardiology, University Hospital, Saint-Denis, France</footnote>

<footnote>ac Cardiology Unit, Grenoble Alpes University Hospital, Grenoble, France</footnote>

<footnote>ad Instituto Nacional de Cardiologia, Rio de Janeiro, Brazil</footnote>

<footnote>ae Pediatric and Congenital Cardiology Unit, Department for Women's and Children's Health, University Hospital of Padova, Padova, Italy</footnote>

<footnote>af Pediatric Cardiology Department, CHU Toulouse, Toulouse, France</footnote>

<footnote>ag Department of Pediatric Cardiology, University of Colorado, The Heart Institute, Children's Hospital Colorado, Aurora, Colorado, United States</footnote>

<footnote>ah M3C Antilles-Guyane Pediatric Cardiology Center, University Hospital of Martinique, Martinique, France</footnote>

<footnote>ai Department of Paediatrics, Institution of Clinical Sciences, University of Gothenburg, Gothenburg, Sweden</footnote>

<footnote>a) Bambino Gesù Children's Hospital, IRCCS, Rome, Italy</footnote>

<footnote>ak Nantes Université, CHU Nantes, CNRS, INSERM, l'institut du thorax, Nantes, France</footnote>

<footnote>al Nantes Université, INRAE, UMR 1280, PhAN, Nantes, France</footnote>

<footnote>* Corresponding author.
E-mail address: albanelouen.baruteau@chu-nantes.fr (A.-E. Baruteau).</footnote>

<footnote>These authors contributed equally to this work.</footnote>

<footnote n="2">² This author has senior authorship.</footnote>
**Article history:**
Received 6 June 2025
Accepted 10 September 2025

**Keywords:**
Congenital heart disease
Cardiac catheterization
Infant
Low birth weight
Ductus arteriosus
Patent

**Palabras clave:**
Cardiopatía congénita
Catheterismo cardiaco
Lactante
Bajo peso al nacer
Ductus arterioso
Persistente

## Abbreviations

CHD: congenital heart disease

LPA: left pulmonary artery

PDA: patent ductus arteriosus

VSD: ventricular septal defect

## ABSTRACT

**Introduction and objectives:** Transcatheter patent ductus arteriosus (PDA) closure is safe in < 2-kg infants and in ≥ 6-kg patients, but major safety concerns remain when applied to the intermediate weight range. We aimed to assess outcomes of transcatheter PDA closure in 2- to 6-kg infants.

**Methods:** An international, multicenter, retrospective cohort study was conducted in 31 tertiary hospitals in 17 countries between 2000 and 2023, investigating all infants who underwent attempted transcatheter PDA closure with a procedural weight of 2-to-6 kg.

**Results:** Attempted transcatheter PDA closure was performed in 1231 infants (median [Q1-Q3] weight, 4747 [3700-5300] g; median age, 132 [83-194] days; ex-preterm, n = 581 [56.8%]) with a 95.0% success rate. A composite outcome of procedural failure or major adverse events was observed in 173 (14%) patients, including device embolization in 64 (3.7%), device-induced left pulmonary artery stenosis in 47 (2.7%), and procedural death in 2 (0.2%). Logistic regression model analysis identified a 2- to 3.9-kg procedural weight, increased pulmonary artery pressure, and window-type or tubular ductal morphologies as independent predictors of the composite outcome. Based on propensity score matching analysis, 2- to 3.9-kg infants had a risk ratio of 2.19 (95%CI, 1.25-3.83) for experiencing the composite outcome, compared with 4- to 5.9-kg infants.

**Conclusions:** Transcatheter PDA closure in 2- to 6-kg infants was feasible in most patients. Procedural failure or major adverse events occurred in 14% and several independent risk factors were identified, including the 2- to 3.9-kg weight range identified as a higher-risk subgroup. These findings may improve risk stratification and the decision-making process.

© 2025 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

## Resultados del cierre percutáneo del ductus arterioso persistente en lactantes de 2-6 kg

## RESUMEN

**Introducción y objetivos:** El cierre percutáneo del ductus arterioso persistente (DAP) ha demostrado ser seguro en lactantes de < 2 kg y aquellos con ≥ 6 kg; sin embargo, persiste una importante preocupación acerca de su seguridad en el grupo de peso intermedio. El objetivo de este estudio fue evaluar los resultados del cierre percutáneo del DAP en lactantes de 2-6 kg.

**Métodos:** Se llevó a cabo un estudio de cohorte retrospectivo, internacional y multicéntrico en 31 hospitales terciarios de 17 países, entre los años 2000 y 2023. Se incluyó a todos los lactantes con un peso procedimental de 2-6 kg que se sometieron a un intento de cierre percutáneo del DAP.

**Resultados:** Se intentó el cierre percutáneo del DAP en 1.231 lactantes (peso mediano: 4.747 gramos; Q1-Q3 [3.700-5.300]; edad mediana: 132 días; Q1-Q3 [83-194]; prematuros: n = 581 [56,8%]), con una tasa de éxito del 95,0%. Se observó un desenlace compuesto de fracaso del procedimiento o eventos adversos mayores en 173 pacientes (14%), que incluyó la embolización del dispositivo en 64 (3,7%), la estenosis inducida de la arteria pulmonar izquierda en 47 (2,7%) y la muerte procedimental en 2 (0,2%). El análisis multivariable identificó como predictores independientes del desenlace compuesto un peso procedimental de 2-3,9 kg, una presión pulmonar elevada y morfologías ductales tipo ventana o tubular. Según el análisis emparejado por puntuación de propensión, los lactantes de 2-3,9 kg tuvieron un riesgo relativo de 2,19 (IC95%, 1,25-3,83) para presentar el desenlace compuesto, en comparación con aquellos de 4-5,9 kg.

**Conclusiones:** El cierre percutáneo del DAP en lactantes de 2-6 kg fue factible en la mayoría de los casos. El 14% presentaron un fracaso procedimental o eventos adversos mayores, identificándose varios factores de riesgo independientes, entre ellos el grupo de 2-3,9 kg, considerado de mayor riesgo. Estos hallazgos pueden contribuir a una mejor estratificación del riesgo y a la toma de decisiones clínicas.

© 2025 Sociedad Española de Cardiología. Publicado por Elsevier España, S.L.U. Este es un artículo Open Access bajo la licencia CC BY (http://creativecommons.org/licenses/by/4.0/).

## INTRODUCTION

Patent ductus arteriosus (PDA) closure is indicated in any patient with a left-to-right shunt resulting in congestive heart failure, failure to thrive, pulmonary overcirculation with or without pulmonary hypertension, and/or left ventricular volume overload.¹,² Transcatheter PDA closure has become the standard of care in most cases, provided the anatomy and patient size are suitable. Transcatheter PDA closure has proved safe in ≥ 6-kg
patients with various devices,² and in < 2-kg infants, in whom a 98% success rate with a 4% to 5% rate of major adverse events has been reported in recent large-scale series using the Amplatzer Piccolo Occluder device (Abbott, USA).³ However, major safety concerns remain in 2- to 6-kg infants, an intermediate weight range in which there is no dedicated Food and Drug Administration-approved and/or CE-marked device.

Therefore, challenging questions in clinical practice remain unanswered, and risk stratification is inadequate. This study aimed to assess the outcomes and risk factors of transcatheter PDA closure in a large, international cohort of 2- to 6-kg infants, to improve their management and better define the decision-making process.

# METHODS

## Study design and data source

An international, multicenter, retrospective cohort study was conducted in 31 tertiary hospitals in 17 countries from January 2000 to December 2023. All infants who underwent attempted transcatheter PDA closure with a procedural weight > 2 kg and < 6 kg were eligible for the study. In accordance with the Transparency and Openness Promotion Guidelines, the data that support the findings of this study are available from the corresponding author upon reasonable request. Institutional review board approval was obtained from Nantes University Hospital (GNEDS n°22-10-240) and from all participating institutions. The research study complies with the Declaration of Helsinki.

## Study variables

Study variables are detailed in the methods of the supplementary data.

## Procedural outcomes

### Primary endpoint

The primary endpoint was procedural success, serving as a direct measure of feasibility, and was defined as successful coil or device release within the PDA by the end of the procedure.⁴ Instances in which a device embolized during the procedure, but was subsequently percutaneously retrieved, followed by successful PDA closure using another device during the same procedure, were still considered procedural success. However, device embolization was also categorized as a major adverse event, as detailed below (figure 1).

### Secondary endpoints

Secondary endpoints included: a) the type, frequency, and severity of adverse events; b) a composite endpoint comprising procedural failure and/or the occurrence of predefined,⁵,⁶ periprocedural and/or in-hospital procedure-related major adverse events. Further methodological details and stratified analyses are provided in the methods section of the supplementary data.

### Late outcomes

Prospective follow-up was achieved until June 2024 and relevant data were recorded (methods section of the supplementary data).

## Statistical analysis

Categorical variables are described as numbers and percentages, whereas continuous variables are summarized by the

<figure><img src="image_3.png" /><figcaption>**Figure 1.** Study flowchart. Main outcomes of all procedures. The flow chart outlines the selection process of this retrospective cohort study, including participant identification, inclusion and exclusion criteria, and outcomes throughout the study period. PDA, patent ductus arteriosus.</figcaption></figure>
mean ± standard deviation when normally distributed or by the median [Q1-Q3] otherwise. Missing values were systematically reported, with no imputation performed due to the inability to assume the type of missing data. Patient-, procedural-, and hospital-level factors that could bias the estimated association between the exposure of interest and the outcome were identified based on expertise in the field and the bibliography. A directed acyclic graph was constructed to summarize our causal reasoning and identify the factors on which we conditioned the analysis to limit bias (figure 2). Logistic regression model analysis and propensity score matching analysis were performed (methods section of the supplemental data).

RESULTS

A total of 1272 infants fulfilled the study inclusion criteria. Patients were enrolled from Europe (n = 776: France, Switzerland, Austria, Italy, Belgium, Sweden, Norway, Poland), United Kingdom (n = 117), United States of America (n = 176), Asia (n = 137: India, Malaysia), South America (n = 13: Brazil, Argentina), and North Africa and the Middle East (n = 58: Egypt, Lebanon, Israel). We subsequently excluded: a) 23 patients because of missing or incorrect procedural weight, b) 16 patients in whom transcatheter PDA closure was not attempted after the initial angiogram, c) 2 patients with unknown procedural success, leaving 1231 patients (35.6% male) in the final analysis (figure 1).

<figure><img src="image_4.png" /><figcaption>**Figure 2.** Directed acyclic graph summarizing causal reasoning and identifying the factors for which we adjusted the analysis to limit bias. A directed acyclic graph is a graphical representation of causal relationships, where edges indicate directionality. To interpret a directed acyclic graph, follow the arrows from one node to another to understand the assumed causal pathways and potential confounders. In epidemiology, directed acyclic graphs are crucial for identifying confounding variables and informing appropriate statistical adjustments to estimate causal effects accurately. CHD, congenital heart disease. a suspected or proved; b Krichenko classification; c narrowest ductal diameter.</figcaption></figure>
## Baseline characteristics

Attempted transcatheter PDA closure was performed at a median procedural weight of 4747 [3700-5300] g and a median procedural age of 132 [83-194] days. A genetic syndrome was identified in 254 (20.6%) infants, as were associated cardiac malformations in 489 (39.7%), lung disease in 271 (22.0%), and major nonrespiratory, extracardiac comorbidities in 255 (20.7%) (table S1). Of the 1181 infants whose prematurity status was known, 599 (50.7%) were born preterm (< 28 weeks of gestation: 210 [17.8%], 28-31 + 6 weeks: 133 [11.3%], 32-36 weeks: 238 [20.2%], gestational age < 36 weeks without further precision: 18 infants), with a median birth weight of 1265 [832-1980] g and a median gestational age of 30 [26-34] weeks.

## Preprocedural characteristics

All patients were symptomatic and diuretics were required in 472 (38.3%), respiratory support in 420 (34.1%), nutritional support in 399 (32.4%), and hemodynamic support with catecholamines in 41 (3.3%). Compared with term infants, preterm infants had fewer genetic syndromes (28.2% vs 12.2%; *P* < .0001) and less associated congenital heart disease (43.1% vs 35.4%; *P* = .0078), but they had a more hemodynamically significant PDA with higher pulmonary artery pressure (52.7% vs 58.9%; *P* = .0375) and a greater need for respiratory support (14.3% vs 55.4%; *P* < .0001), nutritional support (18.9% vs 48.1%; *P* < .0001), and hemodynamic support with catecholamines (1.4% vs 5.5%; *P* = .0002) (table 1). A previous medical treatment with cyclo-oxygenase inhibitors and/or paracetamol had failed to close the PDA in 205 (34.2%) ex-preterm infants.

Based on preprocedural echocardiography, 683/1231 (55.5%) infants had increased pulmonary artery pressure, and 440/639 (68.9%) exhibited left ventricular volume overload (moderate left ventricular dilation with + 2 to + 3 standard deviation (SD) z-score: 26.3%; severe left ventricular dilation with > + 3 SD z-score: 43.0%); 217 (22.5%) infants also had at least grade II mitral regurgitation.

## Procedural characteristics

Ductal morphology was mainly conical (A type, 443 [43.6%]) or tubular (C type, 424 [41.7%]), whereas B, D, and E types were noted in 2.7%, 2.9%, and 9.1% of cases, respectively. In preterm infants, tubular PDA was the most prevalent morphology (C type, 270 [53.7%]). Angiographic minimal ductal diameter was 3.5 mm [2.7-4.8], with a minimal ductal diameter/ductal length ratio of 0.40 [0.29-0.62]. PDA was short in length in 58/556 (10.4%) infants (missing data: 677 infants).

All procedures were performed in the catheterization laboratory with fluoroscopy and echocardiographic guidance, either under general anesthesia in mechanically ventilated patients (n = 1028, 83.5%) or under deep sedation in spontaneously breathing infants (n = 205, 16.7%). Prophylactic antibiotics and heparin were administered in all patients. PDA closure was contrast-free in 62 (5.0%), whereas iodine contrast agent (mean volume, 25 mL [12-26]) was used in 1171 (95.1%). Both arterial and venous access were used in 858/1144 (75%) infants, whereas 224 (19.6%) had venous access only and 62 (5.4%) had arterial access only. Neither pulmonary vasoreactivity testing nor transient balloon test occlusion was performed, as pulmonary arterial hypertension was always considered proportionate to the importance of the shunt. PDA occlusion was achieved with a median fluoroscopy time of 9.1 [5.6-12.6] minutes, a median radiation dose of 15.9 [0.5-27] mGy, and a median dose-area product of 179.1 [118.1-292.5] cGy cm². Devices used were licensed ductus

arteriosus occluders in 904 patients (73.4%; Amplatzer Duct Occluder-I [Abbott, USA] and similar devices in 542 [44.0%]; Amplatzer Duct Occluder-II [Abbott, USA] in 57 [4.6%]; Amplatzer Piccolo Occluder in 305 [24.7%]), but also vascular plugs in 229 (18.6%; Amplatzer Vascular Plug-II in 191 [15.5%]; Amplatzer Vascular Plug-IV in 12 [1.0%]; Medtronic Micro Vascular Plug [Medtronic, USA] in 26 [2.1%]), ventricular septal defect occluders in 33 (2.7%; muscular VSD occluder [mVSD, Abbott, USA] in 12 [1.0%]; Lifetech KONAR-MF VSD occluder [Lifetech, China] in 21 [1.7%]), atrial septal defect occluders in 2 (0.2%), and coils in 65 (5.3%).

## Procedural outcomes

### Procedural success

Of the 1231 infants, 1170 (95.0%) met the primary endpoint, including 20 (1.6%) patients with immediate device embolization, percutaneous device retrieval, and successful placement and delivery of a new device during the same procedure. Device closure was achieved at first attempt in 923 (74.9%) patients.

The procedure failed in 61 (5.0%) infants. At least 1 device was deployed but not released in 52 cases, in which the duct was considered too large to be closed without device-related left pulmonary artery (LPA) and/or descending aorta obstruction, and withdrawn without incident. Acute device migration with unsuccessful percutaneous device retrieval occurred in 9 cases (0.7%), including 2 (0.2%) procedural deaths due to device embolization to the aorta.

There was no statistically significant difference in procedural success according to baseline characteristics, including prematurity and procedural age or weight. Procedural failure was statistically more frequent with increased pulmonary artery pressure, a larger PDA, and an increased minimal ductal diameter/ductal length ratio. Shorter PDAs were not associated with poorer outcomes. The success rate also varied according to PDA morphology, with a higher failure rate in B-type and C-type PDAs (figure 3).

### Adverse events

Reported adverse events were minor in 92 (7.5%) patients, moderate in 62 (5.0%), major in 76 (6.2%), and catastrophic in 2 (0.2%), indicating a major adverse event rate of 11.4% (140 patients) (table 2). The total adverse event rate was 16.6% (n = 204). Adverse events were more commonly observed in the 2- to -3.9 kg weight range, regardless of prematurity.

Device embolization occurred in 64 (5.2%) patients: immediate in 31 and delayed in 33. The occluder embolized to the pulmonary artery in 57/64 cases (89.1%; LPA, 29; right pulmonary artery [RPA], 28) and to the aorta in 7 cases. In 38/64 patients (59.4%), percutaneous device retrieval was achieved with successful transcatheter PDA closure using a different device during the same procedure, while 24 were referred for surgical device extraction and PDA ligation. Two patients died following device embolization to the aorta.

Device-related LPA or descending aorta stenosis was reported in 47 (3.8%) and 25 (2.0%) patients, respectively. Of these, 28/47 (59.6%) LPA stenoses and 18/25 (72.0%) descending aorta obstructions resolved with time without intervention, but 22 patients were referred for surgery (LPA stenosis, 16/47 [34.0%]; descending aorta obstruction, 6/25 [24.0%]) and 4 for percutaneous balloon dilation or stenting (LPA stenosis, 3/47 [6.4%]; descending aorta obstruction, 1/25 [4.0%]).
<caption>**Table 1**</caption>

Demographic-, procedural-, and hospital-level patient characteristics in relation to the composite outcome (n = 1231)

<table><thead><tr><th>Variables</th><th>No composite outcome (n = 1058)</th><th>Composite outcome (n = 173)</th><th>P</th><th>Missing values (%)</th></tr></thead><tbody><tr><td><strong>Patient characteristics</strong></td><td></td><td></td><td></td><td></td></tr><tr><td>Gestational age at birth, WG</td><td>36.00 [28.00-38.00]</td><td>36.00 [30.00-39.00]</td><td>.2779</td><td>17.0</td></tr><tr><td>Female sex</td><td>678 (64.4)</td><td>112 (64.7)</td><td>.9968</td><td>0.4</td></tr><tr><td>Birth weight, g</td><td>2160.00 [1110.00-2885.00]</td><td>2300.00 [1317.50-3000.00]</td><td>.1223</td><td>24.7</td></tr><tr><td>Severity of prematurity</td><td></td><td></td><td>.1289</td><td>17.0</td></tr><tr><td>32-36 WG</td><td>196 (22.6)</td><td>42 (27.5)</td><td></td><td></td></tr><tr><td>28-31 + 6 WG</td><td>109 (12.6)</td><td>24 (15.7)</td><td></td><td></td></tr><tr><td>&lt; 28 WG</td><td>188 (21.7)</td><td>22 (14.4)</td><td></td><td></td></tr><tr><td>Genetic syndrome</td><td>216 (20.4)</td><td>37 (21.4)</td><td>.8480</td><td>0.0</td></tr><tr><td>Associated CHD</td><td>412 (38.9)</td><td>68 (39.3)</td><td>.9943</td><td>0.0</td></tr><tr><td>Previous hospitalization for heart failure</td><td>416 (39.3)</td><td>84 (48.6)</td><td>.0271</td><td>0.0</td></tr><tr><td>Diuretics</td><td>392 (37.1)</td><td>79 (45.7)</td><td>.0378</td><td>0.0</td></tr><tr><td>Respiratory support</td><td>348 (32.9)</td><td>73 (42.2)</td><td>.0212</td><td>0.0</td></tr><tr><td>Nutritional support</td><td>216 (20.4)</td><td>37 (21.4)</td><td>.8480</td><td>0.0</td></tr><tr><td>Catecholamine use</td><td>31 (2.9)</td><td>10 (5.8)</td><td>.0876</td><td>0.0</td></tr><tr><td><strong>Preprocedural characteristics</strong></td><td></td><td></td><td></td><td></td></tr><tr><td>Left ventricular volume overload</td><td></td><td></td><td>.0277</td><td>47.4</td></tr><tr><td>No LV dilatation</td><td>180 (32.4)</td><td>19 (20.4)</td><td></td><td></td></tr><tr><td>Moderate LV dilatation (Z-score: +2 to +3 SD)</td><td>138 (24.9)</td><td>33 (35.5)</td><td></td><td></td></tr><tr><td>Severe LV dilatation (Z-score &gt; +3 SD)</td><td>237 (42.7)</td><td>41 (44.1)</td><td></td><td></td></tr><tr><td>Increased pulmonary artery pressure</td><td>561 (53.0)</td><td>120 (69.4)</td><td>.0001</td><td>0.0</td></tr><tr><td><strong>Procedural characteristics</strong></td><td></td><td></td><td></td><td></td></tr><tr><td>Age (at time of procedure), d</td><td>137.00 [86.00-199.50]</td><td>105.00 [70.00-156.00]</td><td>&lt;.0001</td><td>9.3</td></tr><tr><td>PDA closure attempt after 2010</td><td>862 (89.6)</td><td>153 (95.0)</td><td>.0437</td><td>8.8</td></tr><tr><td>Average number of PDA closure attempt per center/y</td><td>3.50 [1.90-7.80]</td><td>3.50 [2.00-7.80]</td><td>.2685</td><td>8.1</td></tr><tr><td>Weight (at time of procedure), g</td><td>4771.50 [3840.00-5300.00]</td><td>4000.00 [3200.00-5000.00]</td><td>&lt;.0001</td><td>0.0</td></tr><tr><td>Narrowest PDA diameter, mm</td><td>3.78 (1.71)</td><td>4.03 (1.62)</td><td>.1360</td><td>28.8</td></tr><tr><td>Short duct</td><td>50 (4.7)</td><td>8 (4.6)</td><td>.8805</td><td>54.9</td></tr><tr><td>PDA narrowest diameter/PDA length ratio</td><td>0.40 [0.28-0.61]</td><td>0.45 [0.33-0.71]</td><td>.1719</td><td>57.7</td></tr><tr><td>PDA narrowest diameter (mm)/weight (kg)</td><td>0.80 [0.56-1.16]</td><td>1.03 [0.75-1.38]</td><td>&lt;.0001</td><td>28.8</td></tr><tr><td>PDA narrowest diameter/body surface index ratio</td><td>14.68 [10.45-20.46]</td><td>17.27 [13.83-20.38]</td><td>.0253</td><td>53.0</td></tr><tr><td>Morphology</td><td></td><td></td><td>&lt;.0001</td><td>17.5</td></tr><tr><td>Type A (conical)</td><td>408 (47.0)</td><td>35 (23.8)</td><td></td><td></td></tr><tr><td>Type B (window-type)</td><td>19 (2.2)</td><td>8 (5.4)</td><td></td><td></td></tr><tr><td>Type C (tubular)</td><td>330 (38.0)</td><td>93 (63.3)</td><td></td><td></td></tr><tr><td>Type D (complex)</td><td>28 (3.2)</td><td>2 (1.4)</td><td></td><td></td></tr><tr><td>Type E (elongated)</td><td>84 (9.7)</td><td>9 (6.1)</td><td></td><td></td></tr><tr><td>Type of device used</td><td></td><td></td><td>.0012</td><td>0</td></tr><tr><td>Coils</td><td>63 (6.0)</td><td>2 (1.2)</td><td></td><td></td></tr><tr><td>Duct occluder</td><td>784 (74.2)</td><td>118 (68.2)</td><td></td><td></td></tr><tr><td>Vascular plug</td><td>184 (17.4)</td><td>45 (26.0)</td><td></td><td></td></tr><tr><td>VSD occluder</td><td>25 (2.4)</td><td>8 (4.6)</td><td></td><td></td></tr><tr><td>Atrial septal defect occluder</td><td>2 (0.2)</td><td>0 (0.0)</td><td></td><td></td></tr><tr><td>Use of an alternative device compared to ADO 1</td><td>567 (53.6)</td><td>124 (71.7)</td><td>&lt;.0001</td><td>0</td></tr></tbody></table>

ADO, Amplatzer Duct Occluder; CHD, congenital heart disease; IQR, interquartile range; LV, left ventricular; PDA, patent ductus arteriosus; SD, standard deviation; VSD, ventricular septal defect; WG, weeks of gestation.

The data are presented as No. (%), mean ± standard deviation, or median [Q1, Q3].

Composite outcome

The composite outcome occurred in 173 (14.1%) patients (table 2, figure 4). The more symptomatic and hemodynamically significant the PDA, the greater the risk of the composite outcome,

including previous hospitalization for heart failure, need for respiratory support, left ventricular volume overload, and increased pulmonary artery pressure. The occurrence of the composite outcome was also associated with younger procedural age, lower procedural weight, a greater minimal ductal diameter/
<figure><img src="image_5.png" /><figcaption>**Figure 3.** Propensity score matching for the estimation of relative risk of composite outcome. Density plots of propensity scores in both groups regarding exposure of interest (ie, procedural weight), before and after matching (A). Standardized mean differences in variables to be balanced between groups before and after matching (B). Distribution of propensity scores for treated (ie, exposed) and control (ie, unexposed) subjects according to whether they were in the matched sample or not (C). CHD, congenital heart disease.</figcaption></figure>
<table><caption>**Table 2**
Adverse event rates according to prematurity and procedural weight (n = 1181)</caption><thead><tr><th rowspan="2">Severity level</th><th rowspan="2">Total<br>(n = 1181*)</th><th colspan="2">Full-term birth</th><th colspan="2">Ex preterm</th><th rowspan="2">P</th></tr><tr><th>Procedural<br>weight 2-4 kg<br>(n = 114)</th><th>Procedural<br>weight 4-6 kg<br>(n = 468)</th><th>Procedural<br>weight 2-4 kg<br>(n = 283)</th><th>Procedural<br>weight 4-6 kg<br>(n = 316)</th></tr></thead><tbody><tr><td>Minor adverse events</td><td>92 (7.8)</td><td>12 (10.5)</td><td>33 (7.1)</td><td>28 (9.9)</td><td>19 (6.0)</td><td>.1886</td></tr><tr><td>Moderate adverse events</td><td>62 (5.2)</td><td>7 (6.1)</td><td>18 (3.8)</td><td>23 (8.1)</td><td>14 (4.4)</td><td>.0730</td></tr><tr><td>Major adverse events</td><td>76 (6.4)</td><td>14 (12.3)</td><td>22 (4.7)</td><td>29 (10.2)</td><td>11 (3.5)</td><td>.0002</td></tr><tr><td>Catastrophic A adverse events E</td><td>2 (0.2)</td><td>-</td><td>1 (0.2)</td><td>1 (0.4)</td><td>-</td><td>.7876</td></tr><tr><td>All adverse events</td><td>204 (17.3)</td><td>29 (25.4)</td><td>62 (13.2)</td><td>74 (26.1)</td><td>39 (12.3)</td><td>&lt;.0001</td></tr></tbody></table>

The data are presented as No. (%).

* There were 52 missing values for preterm birth status. P-values refer to Fisher exact test results. P < .005 indicates that at least 1 of the 4 distributions differs from the others.

body surface index ratio, and ductal morphology (table 2). Logistic regression model analysis indicated that independent predictors of the composite outcome were lower procedural weight in term infants, increased pulmonary artery pressure, and B- and C-type ductal morphology, but not prematurity (table 3).

A 2-group comparison between 2- to 3.9-kg infants at procedure (exposed group, n = 212) and 4- to 5.9-kg infants (unexposed group, n = 212) was performed to compare the incidence of the composite outcome according to procedural weight (figure 3, table S2). In the 2- to 3.9-kg group, 35 occurrences (16.5%) of the composite outcome were observed, compared with 16 occurrences (7.5%) in the 4- to 5.9-kg matched group, indicating a relative risk ratio of 2.19 (95%CI, 1.25-3.83). The relative risk ratio of a composite outcome for < 4-kg patients was 4.5 (95%CI, 1.02-19.9; P = .0301; n = 54 matched pairs) during the 2000 to 2017 period, and 1.6 (95%CI, 0.76-3.35; P = .2162; n = 99 matched pairs) during the 2018 to 2023 period. Infants with a 2- to 3.9-kg

procedural weight had a higher ductal diameter/body surface area ratio and displayed more nontype A PDAs, requiring more non-Amplatzer Duct Occluder-I devices for closure compared with the 4- to 5.9-kg group (table 4).

## Late outcomes

Patients were discharged home after a median hospital stay of 1 [1-4] day postprocedure. One-month follow-up data were available for 1164 (94.6%) patients, of whom 1126 (96.7%) were asymptomatic. Four patients experienced delayed major adverse events, consisting of surgical revision for hemodynamically significant residual shunt in symptomatic infants (n = 3) and for severe, new-onset tricuspid regurgitation (n = 1). At last review, 28 (2.3%) had mild device-related LPA stenosis, 18 (1.5%) mild device-related descending aorta stenosis, and 37 (5.6%) stable, mild tricuspid regurgitation.

<figure><img src="image_6.png" /><figcaption>**Figure 4.** Central illustration. Major safety concerns remain regarding transcatheter patent ductus arteriosus (PDA) closure in 2 to 5.9-kg infants, which are mostly performed off-label. Such PDAs may otherwise require surgical intervention. In the largest international cohort reported to date, transcatheter PDA closure in 2- to 6-kg infants was feasible in most patients. Procedural failure or major adverse events occurred in 14.0% and several independent risk factors were identified, including the 2-to-3.9 kg weight range as a higher-risk subgroup.</figcaption></figure>
<table><caption>**Table 3**
Logistic regression model for the composite outcome</caption><thead><tr><th>Variable</th><th>Unadjusted OR [95%CI]</th><th>Adjusted OR</th><th>95%CI</th><th>P</th></tr></thead><tbody><tr><td>Intercept</td><td></td><td>0.03</td><td>0.014-0.077</td><td>&lt;.0001</td></tr><tr><td>Full-term birth, procedural weight: 4-5.9 kg</td><td>1.00</td><td>1.00</td><td>-</td><td>-</td></tr><tr><td>Full-term birth, procedural weight: 2-3.9 kg</td><td>2.40 [1.26-4.50]</td><td>2.17</td><td>1.08-4.31</td><td>.028</td></tr><tr><td>Preterm birth, procedural weight: 4-5.9 kg</td><td>0.82 [0.43-1.53]</td><td>0.62</td><td>0.29-1.28</td><td>.207</td></tr><tr><td>Preterm birth, procedural weight: 2-3.9 kg</td><td>2.41 [1.45-4.06]</td><td>1.55</td><td>0.81-2.98</td><td>.188</td></tr><tr><td>Genetic syndrome</td><td>0.96 [0.57-1.56]</td><td>1.08</td><td>0.60-1.89</td><td>.802</td></tr><tr><td>Associated CHD</td><td>0.82 [0.53-1.25]</td><td>0.73</td><td>0.45-1.17</td><td>.196</td></tr><tr><td>Respiratory support</td><td>1.58 [1.05-2.38]</td><td>1.06</td><td>0.62-1.84</td><td>.826</td></tr><tr><td>Nutritional support</td><td>1.48 [0.98-2.23]</td><td>0.88</td><td>0.52-1.46</td><td>.615</td></tr><tr><td>Increased pulmonary artery pressure</td><td>2.41 [1.51-3.97]</td><td>2.22</td><td>1.36-3.76</td><td>.002</td></tr><tr><td>Minimal ductal diameter</td><td>1.09 [0.97-1.22]</td><td>1.04</td><td>0.91-1.19</td><td>.532</td></tr><tr><td>Ductal morphology*</td><td>1.09 [0.97-1.22]</td><td></td><td></td><td></td></tr><tr><td>Type A (conical)</td><td></td><td>1.00</td><td>-</td><td>-</td></tr><tr><td>Type B (window-type)</td><td>1.00</td><td>5.34</td><td>1.69-15.5</td><td>.002</td></tr><tr><td>Type C (tubular)</td><td>6.13 [2.00-17.1]</td><td>3.57</td><td>2.01-6.57</td><td>&lt;.0001</td></tr><tr><td>Type D (complex)</td><td>4.23 [2.54-7.38]</td><td>1.53</td><td>0.23-6.13</td><td>.597</td></tr><tr><td>Type E (elongated)</td><td>1.18 [0.18-4.37]</td><td>1.33</td><td>0.46-3.39</td><td>.569</td></tr><tr><td></td><td>1.28 [0.45-3.14]</td><td></td><td></td><td></td></tr></tbody></table>

95%CI, 95% confidence interval; CHD, congenital heart disease; OR, odds ratio.

Model built using 779 observations (454 excluded because of missing values).

* Krichenko classification.

<table><caption>**Table 4**
Comparison of patient characteristics according to procedural weight (n = 1231)</caption><thead><tr><th rowspan="2">Variables</th><th colspan="2">Procedural weight<br>between 2 and 3.9 kg (n = 403)</th><th colspan="2">Procedural weight<br>between 4 and 5.9 kg (n = 828)</th><th rowspan="2">P</th><th rowspan="2">Missing<br>values (%)</th></tr><tr><th>Composite<br>outcome<br>(n = 89)</th><th>No composite<br>outcome<br>(n = 314)</th><th>Composite<br>outcome<br>(n = 84)</th><th>No composite<br>outcome<br>(n = 744)</th></tr></thead><tbody><tr><td colspan="7"><strong>Patient characteristics</strong></td></tr><tr><td>Gestational age at birth, WG</td><td>33.00 [28.00, 37.00]</td><td>33.00 [27.00, 36.00]</td><td>38.00 [34.00, 39.00]</td><td>37.00 [30.00, 39.00]</td><td>&lt;.0001</td><td>17.1</td></tr><tr><td>Birth weight, g</td><td>1740.00 [1075.00,<br>2600.00]</td><td>1590.00 [900.00,<br>2326.25]</td><td>2740.00 [1930.00,<br>3287.50]</td><td>2480.00 [1372.50,<br>3000.00]</td><td>&lt;.0001</td><td>24.8</td></tr><tr><td>Full term birth</td><td>21 (26.2)</td><td>70 (24.7)</td><td>44 (60.3)</td><td>305 (52.1)</td><td>&lt;.0001</td><td>17.1</td></tr><tr><td>Severity of prematurity</td><td></td><td></td><td></td><td></td><td>&lt;.0001</td><td>17.1</td></tr><tr><td>32-36 WG</td><td>26 (32.5)</td><td>86 (30.4)</td><td>16 (21.9)</td><td>110 (18.8)</td><td></td><td></td></tr><tr><td>28-31 + 6 WG</td><td>16 (20.0)</td><td>42 (14.8)</td><td>8 (11.0)</td><td>67 (11.5)</td><td></td><td></td></tr><tr><td>&lt; 28 WG</td><td>17 (21.2)</td><td>85 (30.0)</td><td>5 (6.8)</td><td>103 (17.6)</td><td></td><td></td></tr><tr><td>Genetic syndrome</td><td>15 (16.9)</td><td>64 (20.4)</td><td>22 (26.2)</td><td>152 (20.4)</td><td>.4949</td><td>0</td></tr><tr><td>Associated CHD</td><td>29 (32.6)</td><td>138 (43.9)</td><td>39 (46.4)</td><td>274 (36.8)</td><td>.0421</td><td>0</td></tr><tr><td>Previous hospitalization for<br>heart failure</td><td>49 (55.1)</td><td>150 (47.8)</td><td>35 (41.7)</td><td>266 (35.8)</td><td>.0001</td><td>0</td></tr><tr><td>Diuretics</td><td>46 (51.7)</td><td>141 (44.9)</td><td>33 (39.3)</td><td>251 (33.7)</td><td>.0003</td><td>0</td></tr><tr><td>Respiratory support</td><td>49 (55.1)</td><td>165 (52.5)</td><td>24 (28.6)</td><td>183 (24.6)</td><td>&lt;.0001</td><td>0</td></tr><tr><td>CPAP</td><td>31 (59.6)</td><td>109 (66.5)</td><td>13 (32.5)</td><td>111 (37.4)</td><td>&lt;.0001</td><td>55.2</td></tr><tr><td>HFO</td><td>7 (15.2)</td><td>30 (23.4)</td><td>1 (3.3)</td><td>23 (9.2)</td><td>.0005</td><td>63.1</td></tr><tr><td>Nutritional support</td><td>49 (55.1)</td><td>149 (47.5)</td><td>21 (25.0)</td><td>179 (24.1)</td><td>&lt;.0001</td><td>0</td></tr><tr><td>Use of catecholamine</td><td>9 (10.1)</td><td>23 (7.3)</td><td>1 (1.2)</td><td>8 (1.1)</td><td>&lt;.0001</td><td>0</td></tr><tr><td colspan="7"><strong>Pre-procedural characteristics</strong></td></tr><tr><td>Left ventricular volume overload</td><td>36 (100.0)</td><td>94 (100.0)</td><td>36 (85.7)</td><td>273 (84.8)</td><td>.0001</td><td>59.9</td></tr><tr><td>No LV dilatation</td><td>12 (25.5)</td><td>48 (33.8)</td><td>7 (15.2)</td><td>132 (32.0)</td><td></td><td></td></tr><tr><td>Moderate LV dilatation<br>(Z-score: +2 to +3 SD)</td><td>17 (36.2)</td><td>39 (27.5)</td><td>16 (34.8)</td><td>99 (24.0)</td><td></td><td></td></tr><tr><td>Severe LV dilatation<br>(Z-score > +3 SD)</td><td>18 (38.3)</td><td>55 (38.7)</td><td>23 (50.0)</td><td>182 (44.1)</td><td></td><td></td></tr></tbody></table>
<caption>**Table 4 (Continued)**</caption>

Comparison of patient characteristics according to procedural weight (n = 1231)

<table><thead><tr><th rowspan="2">Variables</th><th colspan="2">Procedural weight between 2 and 3.9 kg (n = 403)</th><th colspan="2">Procedural weight between 4 and 5.9 kg (n = 828)</th><th rowspan="2">P</th><th rowspan="2">Missing values (%)</th></tr><tr><th>Composite outcome (n = 89)</th><th>No composite outcome (n = 314)</th><th>Composite outcome (n = 84)</th><th>No composite outcome (n = 744)</th></tr></thead><tbody><tr><td>Increased pulmonary artery pressure</td><td>68 (76.4)</td><td>177 (56.4)</td><td>52 (61.9)</td><td>384 (51.6)</td><td>.0001</td><td>0</td></tr><tr><td>Mitral regurgitation grade II, III or IV</td><td>36 (48.6)</td><td>58 (27.4)</td><td>13 (16.9)</td><td>110 (18.3)</td><td>&lt;.0001</td><td>21.7</td></tr><tr><td colspan="7"><strong>Procedural characteristics</strong></td></tr><tr><td>Age (at time of procedure), d</td><td>77.00 [54.00-113.50]</td><td>80.00 [53.00-120.00]</td><td>150.00 [108.00-196.50]</td><td>165.00 [121.00-228.00]</td><td>&lt;.0001</td><td>9.3</td></tr><tr><td>Weight (at time of procedure), g</td><td>3200.00 [2600.00-3900.00]</td><td>3000.00 [2500.00-3700.00]</td><td>5000.00 [4735.50-5505.00]</td><td>5000.00 [4742.75-5600.00]</td><td>&lt;.0001</td><td>0</td></tr><tr><td>Narrowest PDA diameter, mm</td><td>4.00 (1.58)</td><td>3.48 (1.39)</td><td>4.07 (1.68)</td><td>3.91 (1.82)</td><td>.0046</td><td>28.8</td></tr><tr><td>Short duct</td><td>3 (6.2)</td><td>18 (11.2)</td><td>5 (15.2)</td><td>32 (10.2)</td><td>.6095</td><td>54.9</td></tr><tr><td>PDA narrowest diameter/PDA length ratio</td><td>0.37 [0.31-0.55]</td><td>0.40 [0.29-0.58]</td><td>0.50 [0.39-0.72]</td><td>0.40 [0.27-0.62]</td><td>.112</td><td>57.7</td></tr><tr><td>PDA narrowest diameter (mm)/weight (kg)</td><td>1.25 [1.00-1.50]</td><td>1.12 [0.81-1.50]</td><td>0.80 [0.60-1.06]</td><td>0.70 [0.51-1.00]</td><td>&lt;.0001</td><td>28.8</td></tr><tr><td>PDA narrowest diameter/body surface index ratio</td><td>18.63 [15.35-21.07]</td><td>17.84 [13.58-23.82]</td><td>15.51 [12.41-19.33]</td><td>13.09 [9.67-18.04]</td><td>&lt;.0001</td><td>53</td></tr><tr><td>Morphology*</td><td></td><td></td><td></td><td></td><td>&lt;.0001</td><td>17.5</td></tr><tr><td>Type A (conical)</td><td>11 (13.4)</td><td>86 (31.5)</td><td>24 (36.9)</td><td>322 (54.0)</td><td></td><td></td></tr><tr><td>Type B (window-type)</td><td>2 (2.4)</td><td>7 (2.6)</td><td>6 (9.2)</td><td>12 (2.0)</td><td></td><td></td></tr><tr><td>Type C (tubular)</td><td>53 (64.6)</td><td>96 (35.2)</td><td>26 (40.0)</td><td>152 (25.5)</td><td></td><td></td></tr><tr><td>Type D (complex)</td><td>1 (1.2)</td><td>6 (2.2)</td><td>1 (1.5)</td><td>22 (3.7)</td><td></td><td></td></tr><tr><td>Type E (elongated)</td><td>3 (3.7)</td><td>27 (9.9)</td><td>6 (9.2)</td><td>57 (9.6)</td><td></td><td></td></tr><tr><td>Type of device used</td><td></td><td></td><td></td><td></td><td>.0087</td><td>0.2</td></tr><tr><td>Coils</td><td>1 (1.1)</td><td>14 (4.5)</td><td>1 (1.2)</td><td>49 (6.6)</td><td></td><td></td></tr><tr><td>Duct occluder</td><td>59 (66.3)</td><td>227 (72.5)</td><td>59 (70.2)</td><td>557 (75.0)</td><td></td><td></td></tr><tr><td>Vascular plug</td><td>24 (27.0)</td><td>61 (19.5)</td><td>21 (25.0)</td><td>123 (16.6)</td><td></td><td></td></tr><tr><td>VSD occluder</td><td>5 (5.6)</td><td>11 (3.5)</td><td>3 (3.6)</td><td>14 (1.9)</td><td></td><td></td></tr><tr><td>Atrial septal defect occluder</td><td>0 (0.0)</td><td>1 (0.3)</td><td>0 (0.0)</td><td>1 (0.1)</td><td></td><td></td></tr><tr><td>Use of an alternative device compared to ADO 1</td><td>74 (83.1)</td><td>248 (79.0)</td><td>50 (59.5)</td><td>319 (42.9)</td><td>&lt;.0001</td><td>0</td></tr><tr><td colspan="7"><strong>Procedural outcomes</strong></td></tr><tr><td>Procedural success</td><td>65 (73.0)</td><td>314 (100.0)</td><td>47 (56.0)</td><td>744 (100.0)</td><td>&lt;.0001</td><td>0.2</td></tr><tr><td>All adverse events</td><td>73 (82.0)</td><td>33 (10.5)</td><td>61 (72.6)</td><td>44 (5.9)</td><td>&lt;.0001</td><td>0</td></tr><tr><td>Minor AE</td><td>8 (9.0)</td><td>33 (10.5)</td><td>12 (14.3)</td><td>44 (5.9)</td><td>.0079</td><td>0</td></tr><tr><td>Moderate AE</td><td>31 (34.8)</td><td>0 (0.0)</td><td>32 (38.1)</td><td>0 (0.0)</td><td>&lt;.0001</td><td>0</td></tr><tr><td>Major AE</td><td>45 (50.6)</td><td>0 (0.0)</td><td>33 (39.3)</td><td>0 (0.0)</td><td>&lt;.0001</td><td>0</td></tr><tr><td>Catastrophic AE</td><td>1 (1.1)</td><td>0 (0.0)</td><td>1 (1.2)</td><td>0 (0.0)</td><td>.0065</td><td>0</td></tr></tbody></table>

ADO, Amplatzer duct occlude; CHD, congenital heart disease; CPAP, continuous positive airway pressure; HFO, high frequency oscillation; IQR, interquartile range; LV, left ventricular; PDA, patent ductus arteriosus; SD, standard deviation; VSD, ventricular septal defect; WG: weeks of gestation.

The data are presented as No. (%), mean ± standard deviation, or median [Q1, Q3].

There were 52 missing values for preterm birth status.

* Krichenko classification.

## DISCUSSION

In the largest cohort of 2- to 6-kg infants undergoing attempted transcatheter PDA closure reported to date, the procedural success rate was high, at the expense of a higher failure rate and a higher major adverse event rate compared with device PDA closure in < 2-kg infants and in ≥ 6-kg patients.

### Procedural outcomes

Few studies have reported outcomes of device PDA closure in patients < 6 kg and the results have been inconsistent. In 2008,

Sivakumar et al.⁷ first reported a 92.9% success rate but a 14.3% major adverse event rate in a monocenter series of 28 infants weighing < 6 kg. Abadir et al.⁸ subsequently reported a French multicenter experience on 58 infants weighing < 6 kg, with a poorer success rate of 89.7%, and procedural mortality, major adverse events, and minor adverse event rates of 1.7%, 6.9%, and 31.0%, respectively, which prompted the authors to recommend surgery as first-line treatment in small infants. A better procedural success rate of 94.0% was later reported in 2 small series, although associated with 7.5% to 10.0% major adverse events and 2.0% mortality.⁹,¹⁰

Data from 2 larger series were reported in 2017, based on: a) 747 infants weighing < 6 kg from 73 hospitals in the North
American IMPACT registry, showing a 94.3% success rate but a 12.6% major adverse event rate, including a 3.5% mortality rate⁴; and b) 408 infants weighing < 6 kg from 14 hospitals in the United Kingdom and Ireland, with a 92.0% procedural success rate and a 10.0% major adverse event rate, with no deaths.⁵ To compare these results with previously published series, we considered technical success rather than true procedural success, whose definition would also have accounted for in-hospital complications.

Transcatheter PDA closure with the Amplatzer Piccolo Occluder has gained widespread acceptance as a safe and effective alternative to surgical ligation in extremely low-birth-weight infants weighing > 700 g.³ Simultaneously, there has been an exponential increase in the uptake of device closure among 2- to 6-kg infants worldwide. Our study presents real-world data on the success rates and complications that can be expected with the percutaneous approach in this challenging procedural weight range, including the learning curve in multiple institutions using a variety of devices.

In the absence of randomized comparisons between transcath-
eter PDA occlusion and surgical ligation in 2- to 6-kg infants, our
study was not designed to compare transcatheter vs surgical
approaches. Only a small proportion of hemodynamically signifi-
cant PDAs in 2- to 6-kg infants remain unsuitable for percutaneous
closure despite the wide range of available device sizes and shapes.
Unsuitable PDAs are often short and unrestricted (types B and C).
In such patients, a large device is needed. When retention disks are
present, the likelihood of protrusion or obstruction of surrounding
structures such as the LPA and/or descending aorta is very high
because the retention disks are usually larger than the central
waist. Consequently, in a minority of cases, surgery may remain the
only option. Surgical PDA ligation provides excellent success rates
of 94% to 100% and low mortality rates of 0% to 2%,¹¹ but it carries
significant postoperative morbidity, including postligation cardiac
syndrome in 15% to 30% cases,¹²,¹³ vocal cord paralysis in up to 10%
to 30% cases,¹²,¹⁴,¹⁵ prolonged mechanical ventilation, bleeding,
pneumothorax, infection, chylothorax, hemodynamic instability
and thoracic scoliosis. Our results encourage wider uptake with
prospective evaluation and comparison with surgical repair and
appropriate regulation.

Predictors of procedural failure or composite outcome

In their multivariate model, Backes et al.⁴ identified a
procedural age < 30 days as the sole independent predictor of
composite failure. In the present study, we selected procedural
weight as a primary variable of interest based on its stronger
clinical and technical relevance. This choice was supported by a
priori causal modeling using a directed acyclic graph, in which
procedural age was identified as a potential confounder reflecting
prematurity and nutritional status, rather than an independent
determinant of procedural outcome.

In our logistic regression analysis, lower procedural weight in
term infants, increased pulmonary artery pressures, and B- and
C-type ductal morphologies were independent predictors of the
composite outcome. Disparities may reflect differences in sample
sizes, our analysis benefiting from higher statistical power. We also
analyzed a higher proportion of ex-preterm infants, which may
have contributed to identifying C-type ductal morphology as a
significant risk predictor. Former preterm infants often have ductal
morphologies that evolve from type F to type C, with a significantly
different distribution compared with term infants.¹⁶ In 376 unse-
lected patients of all ages undergoing device PDA closure, device
embolization occurred in 4%, especially in larger ducts with high

pulmonary artery pressures in younger and smaller infants and in
tubular ducts,¹⁷ which is consistent with our findings.

We found no differences regarding the success rate or
composite outcome rate between ex-preterm infants and term
infants. This indicates that ex-preterm infants who underwent
attempted device PDA closure between 2 and 6 kg had a lower
success rate and a higher major adverse event rate compared with
those reported in series of < 2-kg premature infants.³,¹⁸,¹⁹ This
should encourage offering device PDA closure earlier in these
premature infants when indicated, ideally below a procedural
weight of 2 kg, for safety reasons.

Devices used

Devices were used off-label for PDA closure in 2- to 6-kg infants, as manufacturers' instructions for use recommend a minimum weight limit of 6 kg for most ductal occluders. Our study presents a wide variety of devices used, whether designed for duct occlusion (73.4%) or not, including vascular plugs, multifunctional occluders, mVSD occluders, and atrial septal defect occluders, to accommodate various PDA shapes and hemodynamic conditions. Successful use of the Amplatzer Vascular Plug IV for tubular PDA closure has been reported in a monocenter series of 47 patients,²⁰ and in a case report in a 2.2-kg preterm infant.²¹ PDA closure using VSD occluders in small infants is uncommon. Use of a muscular VSD device for PDA occlusion was effective and safe, with encouraging late outcomes in an international series of 8 infants < 10 kg.²² However, mVSD occluders are rigid, exposing patients to a greater risk of LPA and/or descending aorta obstruction in low-body-weight infants, and making percutaneous device retrieval more difficult in case of embolization. This encouraged Grunenwald et al.²³ to close large and short PDAs in < 6-kg infants with the KONAR-MF VSD occluder, a low-profile, symmetric, shorter, more easily retrievable, and softer VSD device. Promising results in handling complex PDA cases, including large PDAs, PDAs with increased pulmonary artery pressures, and atypical PDA anomalies, have been reported in a pilot study of 7 infants weighing 2 to 6 kg.²³

Study limitations

The retrospective data collection over 23 years at multiple
centers may have underestimated the incidence of adverse events
during follow-up. However, the vast majority of adverse events
occur in the early postoperative period, which limits the likelihood
of underreporting clinically significant events. Second, clinical
practice evolved during the study period with the development of
transcatheter PDA closure in extremely low-birth-weight infants
at selected centers. Moreover, variability in procedural techniques
and postprocedural care among different centers may have
influenced the outcomes. However, we did not find any difference
in outcomes according to the study period or center volume. The
retrospective nature of the study also carries a risk of missing data;
we decided not to impute missing data to maintain the integrity
and robustness of the study findings.

CONCLUSIONS

In this large international cohort, transcatheter PDA closure in
2- to 6-kg infants was feasible in most patients, providing a 14.0%
rate of procedural failure or major adverse events, including an
11.4% rate of major adverse events, with 5.2% embolization and
0.2% procedural mortality. Transcatheter PDA closure may be a viable alternative to surgical ligation in selected patients. Duct morphology and device retrievability require careful consideration before deciding whether transcatheter therapy or surgical ligation is the better treatment. Independent risk factors for composite failure were lowest procedural weight (2- to 3.9-kg infants), younger procedural age, a greater minimal ductal diameter/body surface index ratio, and ductal morphology. These findings may improve risk stratification and the decision-making process.

## FUNDING

This study was supported by a research grant from the French Federation of Cardiology (to P. Padovani). A.-E. Baruteau is supported by the French Government as part of the "Investments of the Future" program managed by the National Research Agency (grant reference ANR-16-IDEX-0007). A.-E. Baruteau is also a recipient of an I-SITE NExT Health of the Future Junior Talent Chair, France.

## ETHICAL CONSIDERATIONS

This work was approved by the Ethics Committee of Nantes University Hospital (GNEDS No. 22-10-240), and institutional review board approval was obtained from all participating institutions with a consent waiver. In this work, the possible variables of sex and gender were taken into account in accordance with the SAGER guidelines.

## STATEMENT ON THE USE OF ARTIFICIAL INTELLIGENCE

No artificial intelligence was used in the preparation of this article.

## AUTHORS' CONTRIBUTIONS

S. Malekzadeh-Milani and P. Padovani contributed equally. A.-E. Baruteau has senior authorship. A.-E. Baruteau: methodology conception, data curation, interpretation of data, formal analysis, writing-original draft, writing-review and editing, supervision, and final approval; S. Malekzadeh-Milani: data curation, formal analysis, writing-original draft, writing-review, statistics and editing, and final approval; P. Padovani: data curation, formal analysis, writing-original draft, writing-review, statistics and editing, and final approval; T. Goronflot: data curation and statistics; K. Sivakumar, M. Méot, M.I. Jones, N. Lwin, C. Ovaert, S. Hascoët, Z. Jalal, C. Bautista-Rodriguez, M. Gewillig, H. Lucron, K. Averin, B.S. Kahl, J.F. Gudnason, A.J. Torres, B. Lefort, Z. Saliba, A. Houeijeh, M. Galeczka, H. Samion, S. El Saiedi, J.M. Lange, N. Yaakobi-Simhayoff, A. Callegari, A. Haugom Christensen, M.B. Ystgaard, J.-B. Selly, H. Bouvaist, D. Neil, D. Sirico, C. Karsenty, C. Vargas-Acevedo, E. Mejia, E. Rosenthal, C. Grunenwald, N. Benbrik, O. Werner, A. Chauvire Drouard, M. Gloanec, A. Moktadir, J.-B. Thambo, M. Brard, G. Laforest, P. Sagar, A. Joseph, T. Puthiyedath, H. Holmstrom, R. Fiszer, H. Wählander, I. Michel-Behnke, D. Bonnet, P.-A. Gourraud, G. Butera, S.A. Qureshi, A. Fraisse, G.J. Morgan: investigation and data curation. A.-E. Baruteau had full access to, and verified, all the data in the study. All authors contributed to the literature search and subsequent drafting, reading, and approval of the final version

of the manuscript. The corresponding author was responsible for the final decision to submit for publication and had full access to all study data.

## CONFLICTS OF INTEREST

S. Hascoët is a consultant and proctor for Abbott; G. Butera is a consultant and proctor for Abbott and Occlutech; S.A. Qureshi is a consultant and proctor for Occlutech; A. Fraisse is a consultant and proctor for Abbott and Occlutech; G.J. Morgan is a consultant and proctor for Abbott and Occlutech; A.-E. Baruteau is a consultant and proctor for Abbott and Occlutech. The other authors have no disclosures relevant to this article.

## ACKNOWLEDGMENTS

We gratefully acknowledge GCS HUGO, AVIESAN, and FHU PRECICARE.

## APPENDIX, SUPPLEMENTARY DATA

Supplementary data associated with this article can be found in the online version, at https://doi.org/10.1016/j.rec.2025.09.011

## APPENDIX C. PRINCIPAL INVESTIGATORS AND PARTICIPATING CENTERS

The authors guarantee that the following researchers are responsible for the data published in this study: M3C-Necker, Paris, France (Sophie Malekzadeh-Milani), CHU Nantes, Nantes, France (Alban-Elouen Baruteau), Madras Medical Mission, Chennai, India (Kothandam Sivakumar), Evelina London Children's Hospital, London, United Kingdom (Matthew I. Jones), CHU Marseille, Marseille, France (Caroline Ovaert), M3C-Marie Lannelongue, Paris, France (Sébastien Hascoët), CHU Bordeaux, Bordeaux, France (Zakaria Jalal), Royal Brompton Hospital, London, United Kingdom (Alain Fraisse), University Hospitals Leuven, Leuven, Belgium (Marc Gewillig), Children's University Hospital of Geneva, Switzerland (Hugues Lucron), Cohen Children's Heart Center, NY, USA (Konstantin Averin), Medical University Vienna, Vienna, Austria (Ina Michel-Behnke), Queen Silvia's Children's Hospital, Gothenburg, Sweden (Janus Freyr Gudnason), Columbia University Medical Center, New York, NY, USA (Alejandro J. Torres), CHU Tours, Tours, France (Bruno Lefort), Hotel Dieu de France University Medical Center, Beirut, Lebanon (Zakhia Saliba), CHU Lille, Lille, France (Ali Houeijeh), Silesian Center for Heart Diseases, Zabrze, Poland (Michal Galeczka), Institut Jantung Negara, Kuala Lumpur, Malaysia (Hasri Samion), Cairo University, Giza, Egypt (Sonia El Saiedi), Instituto Cardiovascular Chaco, Chaco, Argentina (Juan Manuel Lange), Hebrew University of Jerusalem, Israel (Nurit Yaakobi-Simhayoff), University Children's Hospital Zurich, Zurich, Switzerland (Alessia Callegari), Oslo University Hospital, Oslo, Norway (Henrik Holmstrom), CHU La Réunion, France (Jean-Bernard Selly), CHU Grenoble, Grenoble, France (Hélène Bouvaist), Instituto Nacional de Cardiologia, Rio de Janeiro, Brazil (Deborah Neil), University Hospital of Padova, Padova, Italy (Domenico Sirico), CHU Toulouse, Toulouse, France (Clément Karsenty), Children's Hospital Colorado, Aurora, CO, USA (Gareth J. Morgan), Bambino Gesù Children's Hospital, Rome, Italy (Gianfranco Butera).
## WHAT IS KNOWN ABOUT THE TOPIC?

- Major safety concerns remain regarding transcatheter PDA closure in 2 to 5.9-kg infants, which are mostly performed off-label. Such PDAs may otherwise require surgical intervention.

## WHAT DOES THIS STUDY ADD?

- In the largest international cohort reported to date, the procedural success rate was 95.0%, although the complication rate was 14.0%, with a higher risk in < 4-kg infants and/or in cases of elevated pulmonary artery pressure and window-type or tubular ductal morphologies.

- Transcatheter PDA closure is feasible, effective and safe in infants with a procedural weight between 2 and 5.9 kg, although it may carry a risk of procedural complications, especially in the 2- to 3.9-kg weight group and in some challenging ductal anatomies.

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