Sacubitril/Valsartan in Pediatric Heart Failure (PANORAMA-HF): A Randomized, Multicenter, Double-Blind Trial.

BACKGROUND: Sacubitril/valsartan, an angiotensin receptor-neprilysin inhibitor (ARNI), is an established treatment for heart failure (HF) with reduced left ventricular ejection fraction. It has not been rigorously compared with angiotensin-converting enzyme inhibitors in children. PANORAMA-HF (Prospective Trial to Assess the Angiotensin Receptor Blocker Neprilysin Inhibitor LCZ696 Versus Angiotensin-Converting Enzyme Inhibitor for the Medical Treatment of Pediatric HF) is a randomized, double-blind trial that evaluated the pharmacokinetics and pharmacodynamics (PK/PD), safety, and efficacy of sacubitril/valsartan versus enalapril in children 1 month to <18 years of age with HF attributable to systemic left ventricular systolic dysfunction (LVSD). METHODS: Children with HF attributable to LVSD were randomized to sacubitril/valsartan versus enalapril to assess the efficacy and safety of sacubitril/valsartan at 52 weeks of follow-up. The primary end point of the study was to determine whether sacubitril/valsartan was superior to enalapril for the treatment of pediatric patients with HF attributable to systemic LVSD, assessed using a primary global rank end point consisting of ranking patients from worst to best on the basis of clinical events such as death, listing for urgent heart transplant, mechanical life support requirement, worsening HF, New York Heart Association (NYHA)/Ross class, Patient Global Impression of Severity (PGIS), and Pediatric Quality of Life Inventory physical functioning domain. The change from baseline to 52 weeks in NT-proBNP (N-terminal pro-B-type natriuretic peptide) was an exploratory end point. RESULTS: A total of 375 children (mean age, 8.1±5.6 years; 52% female) were randomized to sacubitril/valsartan (n=187) or enalapril (n=188). At week 52, no significant difference was observed between the 2 treatment arms in the global rank end point (Mann-Whitney probability, 0.52 [95% CI, 0.47-0.58]; Mann-Whitney odds, 0.91 [95% CI, 0.72-1.14]; P=0.42). At week 52, clinically meaningful reductions were observed in both treatment arms in NYHA/Ross, PGIS, Patient Global Impression of Change, and NT-proBNP, without significant differences between groups. Adverse events were similar between treatment arms (incidence: sacubitril/valsartan, 88.8%; enalapril, 87.8%), and the safety profile of sacubitril/valsartan was acceptable in children. CONCLUSIONS: In this study, sacubitril/valsartan did not show superiority over enalapril in the treatment of children with HF attributable to systemic LVSD using the prespecified global rank end point. However, both treatment arms showed clinically meaningful improvements over 52 weeks. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02678312.

Early hybrid cardiac rehabilitation in congenital heart disease: the QUALIREHAB trial.

BACKGROUND AND AIMS: Cardiopulmonary fitness in congenital heart disease (CHD) decreases faster than in the general population resulting in impaired health-related quality of life (HRQoL). As the standard of care seems insufficient to encourage and maintain fitness, an early hybrid cardiac rehabilitation programme could improve HRQoL in CHD. METHODS: The QUALIREHAB multicentre, randomized, controlled trial evaluated and implemented a 12-week centre- and home-based hybrid cardiac rehabilitation programme, including multidisciplinary care and physical activity sessions. Adolescent and young adult CHD patients with impaired cardiopulmonary fitness were randomly assigned to either the intervention (i.e. cardiac rehabilitation) or the standard of care. The primary outcome was the change in HRQoL from baseline to 12-month follow-up in an intention-to-treat analysis. The secondary outcomes were the change in cardiovascular parameters, cardiopulmonary fitness, and mental health. RESULTS: The expected number of 142 patients was enroled in the study (mean age 17.4 ± 3.4 years, 52% female). Patients assigned to the intervention had a significant positive change in HRQoL total score [mean difference 3.8; 95% confidence interval (CI) 0.2; 7.3; P = .038; effect size 0.34], body mass index [mean difference -0.7 kg/m2 (95% CI -1.3; -0.1); P = .022; effect size 0.41], level of physical activity [mean difference 2.5 (95% CI 0.1; 5); P = .044; effect size 0.39], and disease knowledge [mean difference 2.7 (95% CI 0.8; 4.6); P = .007; effect size 0.51]. The per-protocol analysis confirmed these results with a higher magnitude of differences. Acceptability, safety, and short-time effect of the intervention were good to excellent. CONCLUSIONS: This early hybrid cardiac rehabilitation programme improved HRQoL, body mass index, physical activity, and disease knowledge, in youth with CHD, opening up the possibility for the QUALIREHAB programme to be rolled out to the adult population of CHD and non-congenital cardiac disease.

Embracing the challenges of neonatal and paediatric pulmonary hypertension.

Paediatric pulmonary arterial hypertension (PAH) shares common features with adult disease, but is associated with several additional disorders and challenges that require unique approaches. This article discusses recent advances, ongoing challenges and distinct approaches for caring for infants and children with PAH, as presented by the paediatric task force of the 7th World Symposium on Pulmonary Hypertension. We provide updates on diagnosing, classifying, risk-stratifying and treating paediatric pulmonary hypertension (PH) and identify critical knowledge gaps. An updated risk stratification tool and treatment algorithm is provided, now also including strategies for patients with associated cardiopulmonary conditions. Treatment of paediatric PH continues to be hindered by the lack of randomised controlled clinical trials. The challenging management of children failing targeted PAH therapy is discussed, including balloon atrial septostomy, lung transplantation and pulmonary-to-systemic shunt (Potts). A novel strategy using a multimodal approach for the management of PAH associated with congenital heart diseases with borderline pulmonary vascular resistance is included. Advances in diagnosing neonatal PH, especially signs and interpretation of PH by echocardiography, are highlighted. A team approach to the rapidly changing physiology of neonatal PH is emphasised. Challenges in drug approval are discussed, particularly the challenges of designing accurate paediatric clinical trials with age-appropriate end-points and adequate enrolment.

Pulmonary vascular phenotype identified in patients with GDF2 (BMP9) or BMP10 variants: an international multicentre study.

BACKGROUND: Bone morphogenetic proteins 9 and 10 (BMP9 and BMP10), encoded by GDF2 and BMP10, respectively, play a pivotal role in pulmonary vascular regulation. GDF2 variants have been reported in pulmonary arterial hypertension (PAH) and hereditary haemorrhagic telangiectasia (HHT). However, the phenotype of GDF2 and BMP10 carriers remains largely unexplored. METHODS: We report the characteristics and outcomes of PAH patients in GDF2 and BMP10 carriers from the French and Dutch pulmonary hypertension registries. A literature review explored the phenotypic spectrum of these patients. RESULTS: 26 PAH patients were identified: 20 harbouring heterozygous GDF2 variants, one homozygous GDF2 variant, four heterozygous BMP10 variants, and one with both GDF2 and BMP10 variants. The prevalence of GDF2 and BMP10 variants was 1.3% and 0.4%, respectively. Median age at PAH diagnosis was 30 years, with a female/male ratio of 1.9. Congenital heart disease (CHD) was present in 15.4% of the patients. At diagnosis, most of the patients (61.5%) were in New York Heart Association Functional Class III or IV with severe haemodynamic compromise (median (range) pulmonary vascular resistance 9.0 (3.3-40.6) WU). Haemoptysis was reported in four patients; none met the HHT criteria. Two patients carrying BMP10 variants underwent lung transplantation, revealing typical PAH histopathology. The literature analysis showed that 7.6% of GDF2 carriers developed isolated HHT, and identified cardiomyopathy and developmental disorders in BMP10 carriers. CONCLUSIONS: GDF2 and BMP10 pathogenic variants are rare among PAH patients, and occasionally associated with CHD. HHT cases among GDF2 carriers are limited according to the literature. BMP10 full phenotypic ramifications warrant further investigation.

Immunodeficiency, autoinflammation and amylopectinosis in humans with inherited HOIL-1 and LUBAC deficiency.

We report the clinical description and molecular dissection of a new fatal human inherited disorder characterized by chronic autoinflammation, invasive bacterial infections and muscular amylopectinosis. Patients from two kindreds carried biallelic loss-of-expression and loss-of-function mutations in HOIL1 (RBCK1), a component of the linear ubiquitination chain assembly complex (LUBAC). These mutations resulted in impairment of LUBAC stability. NF-κB activation in response to interleukin 1ß (IL-1ß) was compromised in the patients' fibroblasts. By contrast, the patients' mononuclear leukocytes, particularly monocytes, were hyper-responsive to IL-1ß. The consequences of human HOIL-1 and LUBAC deficiencies for IL-1ß responses thus differed between cell types, consistent with the unique association of autoinflammation and immunodeficiency in these patients. These data suggest that LUBAC regulates NF-κB-dependent IL-1ß responses differently in different cell types.

Neurodevelopmental outcomes of preterm and growth-restricted neonate with congenital heart defect: a systematic review and meta-analysis.

The purpose of the study is to assess the risks of neurodevelopmental morbidity among preterm and growth restricted youth with congenital heart defects (CHD). This systematic review and meta-analysis included observational studies assessing neurodevelopmental outcomes among children with CHD born preterm (i.e., before 37 weeks of gestation) or growth restricted (small-for-gestational age (SGA) with a birthweight < the 10th percentile or with low birthweight (LBW) < 2500 g). Studies were identified in Medline and Embase databases from inception until May 2022, with data extracted by two blinded reviewers. Risk of bias was assessed using the Critical Appraisal Skills Programme cohort checklist. Meta-analysis involved the use of random-effects models. Main outcome measures were neurodevelopmental outcomes including overall cognitive impairment and intellectual disability, IQ, communication, and motor skills scores. From 3573 reports, we included 19 studies in qualitative synthesis and 6 meta-analysis studies. Risk of bias was low in 8/19 studies. Cognitive impairment and intellectual disability were found in 26% (95% CI 20-32, I2 = 0%) and 19% (95% CI 7-35, I2 = 82%) of preterm children with CHD, respectively. Two studies documented a lower IQ score for SGA children who underwent CHD operations in comparison to non-SGA children who also underwent CHD operations. Two studies have reported lower IQ, communication, and motor skills in children with hypoplastic left heart syndrome (HLHS) and low birth weight compared to those with HLHS and expected birth weight. CONCLUSIONS: Based on a low level of evidence, prematurity and/or growth retardation appear to accentuate specific neurodevelopmental outcomes in certain CHD subgroups. Further evidence is needed to confirm these findings. TRIAL REGISTRATION: PROSPERO [CRD42020201414]. WHAT IS KNOWN: • Children born with CHD, preterm birth, or growth restriction at birth are independently at higher risk for neurodevelopmental impairment. • The additional effect of preterm birth and/or growth restriction on neurodevelopmental outcomes in children with CHD remains unclear. WHAT IS NEW: • Prematurity and/or growth retardation appear to accentuate specific neurodevelopmental outcomes in certain CHD subgroups. • Children with CHD, particularly those born preterm or with growth restriction, should undergo lifelong systematic comprehensive neurodevelopmental assessment.

Renal function after ductus arteriosus transcatheter closure with or without angiography in very preterm infants.

AIM: Transcatheter closure of the patent ductus arteriosus (TCPDA) is increasingly used in preterm infants as an alternative to surgical ligation. However, clinically ill preterm infants are at risk of contrast nephropathy due to the angiography contrast agents used during the procedure. METHODS: We performed a single-centre before-and-after comparative study in VLBW infants to compare the kinetics of serum creatinine during the first 4 days after TCPDA with or without angiography. RESULTS: 69 patients were included and divided into two groups: TCPDA with (contrast+; n = 37) and without (contrast-, n = 32) use of contrast agent. The median dose [range] of contrast agent was 1.0 mL/kg [0.6-2.4 mL/kg]. The change in serum creatinine level between day 2 to 4 after TCPCA and baseline decreased in the contrast- group (-17% [-46%; 18%]), while it increased in the contrast+ group (7% [-24%; 202%] p = 0.002). Comparison of blood urea levels between groups showed similar significant differences. The change in serum creatinine between day 2 to 4 and baseline was significantly correlated with the dose of contrast agent (r2 = 0.682; p < 0.001). CONCLUSION: The use of contrast agents during TCPDA can potentially harm the renal function of very preterm infants. Therefore, we advise minimising or avoiding the use of contrast agents.

Aorta Without Coronary Arteries: Anatomic Variants of a Rare Malformation.

Absence of connection of both coronary arteries to the aorta is an extremely rare congenital malformation. Most cases reported are anatomic variants of anomalous left coronary artery to pulmonary artery, found in isolation or in association with other congenital heart defects. We describe here four cases of patients born without any coronary artery connected to the aorta, including two with an almost complete absence of epicardial coronary arteries, one with single coronary artery to the right pulmonary artery, and one with left ventricular connection of a single coronary artery. Those exceptional coronary malformations have a poor prognosis and are often diagnosed at autopsy. Total absence of epicardial coronary arteries, present in two of our patients and described only once in the literature, leads us to reconsider current knowledge of human coronary artery development.

Myocardial infarction in a 17-year-old patient diagnosed with MPOD II syndrome.

INTRODUCTION: Microcephalic osteodysplastic primordial dwarfism (MOPD) syndrome type 2, caused by a mutation in the PCNT gene (21q22.3), is a rare autosomal recessive disorder. Patients present with bone dysplasia, insulin resistance, kidney diseases, and cardiac malformations, making them prone to vascular diseases. Cardiomyopathy, hypertension, and coronary diseases are documented. The prognosis is associated with cerebrovascular complications. METHOD: We report a case of a patient with MOPD type II who suffered a myocardial infarction in our institution. Informed consent for publishing was obtained. RESULT: A 17-year-old female with MPOD II syndrome (20 kg and 86 cm) was referred for chest pain. Thoracic pains had been occurring for over a month, increasing in intensity, with an episode prompting emergency consultation. Initial tests revealed elevated troponin and an inflammatory response. Electrocardiogram (ECG) showed ST-segment depression and elevation. Echocardiography revealed hypokinetic inferior walls with moderate concentric hypertrophy. A coronary CT scan showed subendocardial hypodensity. Diagnostic coronary angiography revealed tri-branch lesions and almost complete stenoses or occlusions on the circumflex artery (Image). No indication for interventional treatment due to diffuse atheromatous lesions. Exclusive medical treatment was initiated. CONCLUSION: MPOD II syndrome is associated with cardiac malformations and neurovascular complications, including myocardial infarction. Regular ECG monitoring is advisable. Active surveillance for coronary diseases is necessary from adolescence. Recognising this complication allows for prompt intervention. This case highlights the need for specific monitoring and prompt management of chest pain in patients with MPOD II syndrome. Primary prevention could mitigate the occurrence of coronary events in this high-risk population.

Cerebral embolic protection during transcatheter stent expansion of restrictive extra-cardiac Fontan conduit.

We report a 20-year-old female patient (76 Kg/164 cm) with an extra-cardiac Fontan circulation who was referred to our institution for exertional dyspnoea and desaturation. The patient was diagnosed with a large calcified thrombus at the level of the Fontan fenestration, protruding inside the lumen of the conduit and reducing the diameter by half with a 3 mmHg pressure gradient. Transcatheter stent expansion of the obstructed extra-cardiac conduit was done with a 48 mm long XXL PTFE-covered Optimus-CVS® under temporary cerebral embolic protection with a TriGUARD-3™ deflection filter device (Keystone Heart). There was no procedural complication and the 3 months clinical outcomes are good.

Expanding the phenome and variome of the ROBO-SLIT pathway in congenital heart defects: toward improving the genetic testing yield of CHD.

BACKGROUND: Recent studies have shown the implication of the ROBO-SLIT pathway in heart development. Within this study, we aimed to further assess the implication of the ROBO and SLIT genes mainly in bicuspid aortic valve (BAV) and other human congenital heart defects (CHD). METHODS: We have analyzed a cohort of singleton exome sequencing data comprising 40 adult BAV patients, 20 pediatric BAV patients generated by the Pediatric Cardiac Genomics Consortium, 10 pediatric cases with tetralogy of Fallot (ToF), and one case with coarctation of the aorta. A gene-centered analysis of data was performed. To further advance the interpretation of the variants, we intended to combine more than 5 prediction tools comprising the assessment of protein structure and stability. RESULTS: A total of 24 variants were identified. Only 4 adult BAV patients (10%) had missense variants in the ROBO and SLIT genes. In contrast, 19 pediatric cases carried variants in ROBO or SLIT genes (61%). Three BAV patients with a severe phenotype were digenic. Segregation analysis was possible for two BAV patients. For the homozygous ROBO4: p.(Arg776Cys) variant, family segregation was consistent with an autosomal recessive pattern of inheritance. The ROBO4: c.3001 + 3G > A variant segregates with the affected family members. Interestingly, these variants were also found in two unrelated patients with ToF highlighting that the same variant in the ROBO4 gene may underlie different cardiac phenotypes affecting the outflow tract development. CONCLUSION: Our results further reinforce the implication of the ROBO4 gene not only in BAV but also in ToF hence the importance of its inclusion in clinical genetic testing. The remaining ROBO and SLIT genes may be screened in patients with negative or inconclusive genetic tests.

Transvenous retrograde thoracic duct embolization for effective treatment of recurrent plastic bronchitis after fontan palliation.

We report the case of a 5.5-year-old patient (16 kg/105 cm) who presented with plastic bronchitis (PB) refractory to conservative treatment 3 months after completion of Fontan palliation. Bi-inguinal transnodal fluoroscopy-guided lymphangiogram confirmed the chylous leak originating from the thoracic duct (TD) into the chest and did not opacify any central lymphatic vessel for direct transabdominal puncture. Retrograde transfemoral approach was adopted to catheterize the TD and selectively embolize its caudal portion using microcoils and liquid embolic adhesive. Recurrence of symptoms after 2 months indicated a redo catheterization to occlude the TD entirely using the same technique. The procedure was successful and the patient was discharged after 2 days with sustained clinical improvement at 24 months postoperative. In the context of refractory PB, end-to-end transvenous retrograde embolization of the TD appears to be an interesting alternative to more complex interventions such as transabdominal puncture, decompression, or surgical ligation of the TD.

Epicardial vs. transvenous implantable cardioverter defibrillators in children.

AIMS: The implantable cardioverter defibrillator (ICD) has been increasingly used in children. Both epicardial and transvenous approaches are used, with controversy regarding the best option with no specific recommendations. We aimed to compare outcomes associated with epicardial vs. transvenous ICDs in children. METHODS AND RESULTS: Data were analysed from a retrospective study including all patients <18-year-old implanted with an ICD in a tertiary centre from 2003 to 2021. Outcomes were compared between epicardial and transvenous ICDs. A total of 122 children with an ICD (mean age 11.5 ± 3.8 years, 57.4% males) were enrolled, with 84 (64.1%) epicardial ICDs and 38 (29.0%) transvenous ICDs. Early (<30 days) ICD-related complications were reported in 17 (20.2%) patients with an epicardial ICD vs. 0 (0.0%) with a transvenous ICD (P = 0.002). Over a mean follow-up of 4.8 ± 4.0 years, 25 (29.8%) patients with an epicardial ICD and 9 (23.7%) patients with a transvenous ICD experienced at least one late ICD-related complication [hazard ratio (HR) 1.8, 95% confidence interval (CI) 0.8-4.0]. Implantable cardioverter defibrillator lead dysfunction occurred in 19 (22.6%) patients with an epicardial ICD vs. 3 (7.9%) with a transvenous ICD (HR 5.7, 95% CI 1.3-24.5) and was associated with a higher incidence of ICD-related reintervention (HR 3.0, 95% CI 1.3-7.0). After considering potential confounders, especially age and weight at implantation, this association was no longer significant (P = 0.112). The freedom from ICD lead dysfunction was greater in patients with pleural coils than in those with epicardial coils (HR 0.38, 95% CI 0.15-0.96). CONCLUSION: In children, after a consideration of patient characteristics at implantation, the burden of complications and ICD lead dysfunction appears to be similar in patients with epicardial and transvenous devices. Pleural coils seem to be associated with better outcomes than epicardial coils in this population. CLINICAL TRIAL REGISTRATION: NCT05349162.

Catheter ablation of atrial tachyarrhythmias in patients with atrioventricular septal defect.

AIMS: The incidence of atrial tachyarrhythmias is high in patients with atrioventricular septal defect (AVSD). No specific data on catheter ablation have been reported so far in this population. We aimed to describe the main mechanisms of atrial tachyarrhythmias in patients with AVSD and to analyse outcomes after catheter ablation. METHODS AND RESULTS: This observational multi-centric cohort study enrolled all patients with AVSD referred for catheter ablation of an atrial tachyarrhythmia at six tertiary centres from 2004 to 2022. The mechanisms of the different tachyarrhythmias targeted were described and outcomes were analysed. Overall, 56 patients (38.1 ± 17.4 years, 55.4% females) were included. A total of 87 atrial tachyarrhythmias were targeted (mean number of 1.6 per patient). Regarding main circuits involved, a cavo-annular isthmus-dependent intra-atrial re-entrant tachycardia (IART) was observed in 41 (73.2%) patients and an IART involving the right lateral atriotomy in 10 (17.9%) patients. Other tachyarrhythmias with heterogeneous circuits were observed in 13 (23.2%) patients including 11 left-sided and 4 right-sided tachyarrhythmias. Overall, an acute success was achieved in 54 (96.4%) patients, and no complication was reported. During a mean follow-up of 2.8 ± 3.8 years, 22 (39.3%) patients had at least one recurrence. Freedom from atrial tachyarrhythmia recurrences was 77.5% at 1 year. Among 15 (26.8%) patients who underwent repeated ablation procedures, heterogeneous circuits including bi-atrial and left-sided tachyarrhythmias were more frequent. CONCLUSION: In patients with AVSD, most circuits involve the cavo-annular isthmus, but complex mechanisms are frequently encountered in patients with repeated procedures. The acute success rate is excellent, although recurrences remain common during follow-up.

Lympho-hematopoietic malignancies risk after exposure to low dose ionizing radiation during cardiac catheterization in childhood.

Pediatric patients with congenital heart disease (CHD) often undergo low dose ionizing radiation (LDIR) from cardiac catheterization (CC) for the diagnosis and/or treatment of their disease. Although radiation doses from a single CC are usually low, less is known about the long-term radiation associated cancer risks. We aimed to assess the risk of lympho-hematopoietic malignancies in pediatric CHD patients diagnosed or treated with CC. A French cohort of 17,104 children free of cancer who had undergone a first CC from 01/01/2000 to 31/12/2013, before the age of 16 was set up. The follow-up started at the date of the first recorded CC until the exit date, i.e., the date of death, the date of first cancer diagnosis, the date of the 18th birthday, or the 31/12/2015, whichever occurred first. Poisson regression was used to estimate the LDIR associated cancer risk. The median follow-up was 5.9 years, with 110,335 person-years. There were 22,227 CC procedures, yielding an individual active bone marrow (ABM) mean cumulative dose of 3.0 milligray (mGy). Thirty-eight incident lympho-hematopoietic malignancies were observed. When adjusting for attained age, gender and predisposing factors to cancer status, no increased risk was observed for lympho-hematopoietic malignancies RR/mGy = 1.00 (95% CI: 0.88; 1.10). In summary, the risk of lympho-hematopoietic malignancies and lymphoma was not associated to LDIR in pediatric patients with CHD who undergo CC. Further epidemiological studies with greater statistical power are needed to improve the assessment of the dose-risk relationship.

Failure to post-dilate BeSmooth peripheral stents to adult vessel size diameters during benchside tests.

BACKGROUND: Low-profile stent implantation remains a rescue treatment for aortic coarctation and branch pulmonary arteries stenosis in small children. Stent re-expansion to cope with vascular growth remains problematic. OBJECTIVES: To evaluate ex vivo feasibility and mechanical behaviour of over-dilating BeSmooth peripheral stents (Bentley InnoMed, Germany). METHODS: Three BeSmooth peripheral stents in diameters of 7, 8, and 10 mm were dilated to nominal pressure and then 13 atm. BeSmooth Ø7 × 23 mm was sequentially post-dilated using 12, 14, and 16 mm high-pressure balloons. BeSmooth Ø10 × 57 mm was post-dilated with a 14 mm balloon and then with a 48 mm bare-metal Optimus XXL stent hand-mounted on a 14 mm balloon (stent-in-stent). BeSmooth Ø8 × 57 mm was directly post-dilated with a 48 mm bare-metal Optimus XXL stent hand-mounted on a 16 mm balloon (stent-in-stent). The stents' diameter and length were measured. Digital inflation pressure was noted. Balloon rupture and stent fracture patterns were closely evaluated. RESULTS: At 20atm pressure, BeSmooth Ø7 × 23 mm shortened to 2 mm forming a 12 mm diameter solid ring circle and the woven balloon ruptured radially. At 10 atm pressure, BeSmooth Ø10 × 57 mm fractured longitudinally in various dispatched breaking points at a diameter of 13 mm without shortening and ruptured the balloon with multiple pinholes. At 10 atm pressure, BeSmooth Ø8 × 57 mm fractured centrally at three different points at a diameter of 11.5 mm without shortening and the balloon broke radially in half. CONCLUSIONS: In our benchmark tests, extreme shortening, severe balloon rupture, or unpredictable stent fracture patterns at small balloon diameters limits safe post-dilation of BeSmooth stents beyond 13 mm. BeSmooth stents are not ideal candidates for off-label stent interventions in smaller patients.

Early spontaneous closure of large arterial ducts in two term neonates with Ebstein anomaly after failed attempts of transcatheter closure.

In neonatal Ebstein's anomaly of the tricuspid valve, prolonged ductal patency in patients without anatomic pulmonary valve atresia can be deleterious. Circular shunts may develop in patients with different degrees of pulmonary and tricuspid insufficiency. Closure of the arterial duct may result in haemodynamic improvement in particular scenarios. The transcatheter approach is a valuable closure alternative despite some technical difficulties in large-sized arterial ducts and low birth weight neonates. Herein, we report on two consecutive term newborns with Ebstein's anomaly and large arterial ducts in whom mechanical stimulus of the arterial duct during failed attempts of transcatheter closure led after two days to definitive closure followed by good clinical outcomes.

An emerging phenotype of pulmonary arterial hypertension patients carrying SOX17 variants.

BACKGROUND: The phenotype of pulmonary arterial hypertension (PAH) patients carrying SOX17 pathogenic variants remains mostly unknown. METHODS: We report the genetic analysis findings, characteristics and outcomes of patients with heritable PAH carrying SOX17 variants from the French Pulmonary Hypertension Network. RESULTS: 20 patients and eight unaffected relatives were identified. The median (range) age at diagnosis was 17 (2-53) years, with a female:male ratio of 1.5. At diagnosis, most of the patients (74%) were in New York Heart Association Functional Class III or IV with severe haemodynamic compromise, including a median pulmonary vascular resistance of 14.0 (4.2-31.5) WU. An associated congenital heart disease (CHD) was found in seven PAH patients (35%). Patients with CHD-associated PAH were significantly younger at diagnosis than PAH patients without CHD. Four patients (20%) suffered from recurrent haemoptysis requiring repeated arterial embolisations. 13 out of 16 patients (81%) for whom imaging was available displayed chest computed tomography abnormalities, including dilated, tortuous pulmonary vessels, ground-glass opacities as well as anomalies of the bronchial and nonbronchial arteries. After a median (range) follow-up of 47 (1-591) months, 10 patients underwent lung transplantation and one patient benefited from a heart-lung transplantation due to associated CHD. Histopathological analysis of lung explants showed a congested lung architecture with severe pulmonary arterial remodelling, subpleural vessel dilation and numerous haemorrhagic foci. CONCLUSIONS: PAH due to SOX17 pathogenic variants is a severe phenotype, frequently associated with CHD, haemoptysis and radiological abnormalities. Pathological assessment reveals severe pulmonary arterial remodelling and malformations affecting pulmonary vessels and thoracic systemic arteries.

Quality of Life of Children Born with a Congenital Heart Defect.

OBJECTIVES: To identify subgroups with a congenital heart defect (CHD) at risk of health-related quality of life (QoL) impairment at 8 years of age according to their medical and surgical management. STUDY DESIGN: From a prospective population-based cohort study, 598 patients with CHD were subdivided according to their medical and surgical management: (1) CHD followed-up in an outpatient clinic, (2) complete repair before age 3 years, (3) complete repair after age 3 years, (4) palliative repair, or (5) CHD with spontaneous resolution (reference subgroup). Self-reported QoL and parent-reported QoL were measured using the Pediatric Quality of Life Inventory version 4.0 (score range, 0-100) at age 8 years. Multivariable regression analysis and Cohen effect size were used to compare outcomes across the CHD groups. RESULTS: Self-reported and parent-reported QoL scores for the palliative repair subgroup were lower (ß = -2.1 [95% CI, -3.9 to -0.2] and ß = -16.0 [95% CI, -22.4 to -9.5], respectively), with a large effect size (δ = -0.9 [95% CI, -1.4 to -0.4] and δ = -1.3 [95% CI, -1.8 to -0.7], respectively). Parent-reported QoL scores for the complete repair after age 3 years subgroup were lower (ß = -9.2; 95% CI, -15.0 to -3.5), with a large effect size (δ = -0.9; 95% CI, -1.4 to -0.5). Self-reported QoL scores for the complete repair before age 3 years subgroup was lower (ß = -1.3; 95% CI, -1.9 to -0.6), with a small effect size (δ = -0.4; 95% CI, -0.6 to -0.2). CONCLUSIONS: The QoL of children with CHD who experienced a hospital intervention is reduced at age 8 years. Patient age at the last cardiac intervention might influence QoL at 8 years.

Modified safety techniques for transcatheter repair of superior sinus venosus defects with partial anomalous pulmonary venous drainage using a 100-mm Optimus-CVS® covered XXL stent.

We report the first use of a single 100-mm long custom-made version of the Optimus-CVS® balloon-expandable PTFE-covered XXL (15-Zig) stent (AndraTec, GmbH) to eliminate sinus venosus defect left-to-right shunt and redirect anomalous right pulmonary veins blood flow through a new walled channel to the left atrium. Anatomical feasibility and strategy decision were guided by ex-vivo procedure simulation on the patient-specific 3D printed heart model and in-vivo balloon interrogation. Modified procedural and implantation techniques are detailed. Immediate and one-month follow-up showed excellent outcomes.