Role and Applications of Experimental Animal Models of Fontan Circulation.

Over the last four decades, the Fontan operation has been the treatment of choice for children born with complex congenital heart diseases and a single-ventricle physiology. However, therapeutic options remain limited and despite ongoing improvements in initial surgical repair, patients still experience a multiplicity of cardiovascular complications. The causes for cardiovascular failure are multifactorial and include systemic ventricular dysfunction, pulmonary vascular resistance, atrioventricular valve regurgitation, arrhythmia, development of collaterals, protein-losing enteropathy, hepatic dysfunction, and plastic bronchitis, among others. The mechanisms leading to these late complications remain to be fully elucidated. Experimental animal models have been developed as preclinical steps that enable a better understanding of the underlying pathophysiology. They furthermore play a key role in the evaluation of the efficacy and safety of new medical devices prior to their use in human clinical studies. However, these experimental models have several limitations. In this review, we aim to provide an overview of the evolution and progress of the various types of experimental animal models used in the Fontan procedure published to date in the literature. A special focus is placed on experimental studies performed on animal models of the Fontan procedure with or without mechanical circulatory support as well as a description of their impact in the evolution of the Fontan design. We also highlight the contribution of animal models to our understanding of the pathophysiology and assess forthcoming developments that may improve the contribution of animal models for the testing of new therapeutic solutions.

Risk of infective endocarditis after hybrid melody mitral valve replacement in infants: the French experience.

OBJECTIVES: Surgical management of mitral valve disease is challenging in infants <1 year old. We aimed at reviewing the French experience with Melody mitral valve replacement in critically ill infants. METHODS: A retrospective cohort study reporting the French experience with Melody mitral valve replacement. RESULTS: Seven symptomatic infants [complete atrioventricular septal defect (n = 4, Down syndrome: n = 3), hammock valve (n = 3)] underwent Melody mitral valve replacement [age: 3 months (28 days to 8 months), weight: 4.3 kg (3.2-6.4 kg)] because of severe mitral valve regurgitation (6) or mixed valve disease (1) and 14 mm (11-16 mm) mitral valve annulus. In 2 patients whose valve was felt irreparable, Melody mitral valve replacement was performed straightaway. The others underwent 2 (1-3) previous attempts of valve repair; 3 were on extracorporeal membrane oxygenation. Melody mitral valve replacement led to competent valve and low gradient [3 mmHg, (1-4 mmHg)]. One patient died 3 days post-implant from extracorporeal membrane oxygenation-related stroke. Of the 6 discharged home patients, 3 (50%) were readmitted for a definite diagnosis (1) or high suspicion (2) of infective endocarditis, of which 2 died. Over the follow-up, 1 underwent balloon expansions of the valve at 9- and 16-months post-implant, and mechanical mitral valve replacement at 2 years; another is currently planned for transcatheter Melody valve dilation. CONCLUSIONS: Melody mitral valve replacement may be considered in selected infants with small mitral valve annulus as an alternative to mechanical mitral valve replacement. Our experience highlights a high-risk of late infective endocarditis that deserves further consideration.

Adverse remodelling in tetralogy of Fallot: From risk factors to imaging analysis and future perspectives.

Although contemporary outcomes of initial surgical repair of tetralogy of Fallot (TOF) are excellent, the survival of adult patients remains significantly lower than that of the normal population due to the high incidence of heart failure, ventricular arrhythmias, and sudden cardiac death. The underlying mechanisms are only partially understood but involve an adverse biventricular response, so-called remodelling, to key stressors such as right ventricular (RV) pressure-and/or volume-overload, myocardial fibrosis, and electro-mechanical dyssynchrony. In this review, we explore risk factors and mechanisms of biventricular remodelling, from histological to electro-mechanical aspects, and the role of imaging in their assessment. We discuss unsolved challenges and future directions to better understand and treat the long-term sequelae of this complex congenital heart disease.

Outcomes of transcatheter pulmonary SAPIEN 3 valve implantation: an international registry.

BACKGROUND AND AIMS: Transcatheter pulmonary valve implantation (TPVI) is indicated to treat right-ventricular outflow tract (RVOT) dysfunction related to congenital heart disease (CHD). Outcomes of TPVI with the SAPIEN 3 valve that are insufficiently documented were investigated in the EUROPULMS3 registry of SAPIEN 3-TPVI. METHODS: Patient-related, procedural, and follow-up outcome data were retrospectively assessed in this observational cohort from 35 centres in 15 countries. RESULTS: Data for 840 consecutive patients treated in 2014-2021 at a median age of 29.2 (19.0-41.6) years were obtained. The most common diagnosis was conotruncal defect (70.5%), with a native or patched RVOT in 50.7% of all patients. Valve sizes were 20, 23, 26, and 29 mm in 0.4%, 25.5%, 32.1%, and 42.0% of patients, respectively. Valve implantation was successful in 98.5% [95% confidence interval (CI), 97.4%-99.2%] of patients. Median follow-up was 20.3 (7.1-38.4) months. Eight patients experienced infective endocarditis; 11 required pulmonary valve replacement, with a lower incidence for larger valves (P = .009), and four experienced pulmonary valve thrombosis, including one who died and three who recovered with anticoagulation. Cumulative incidences (95%CI) 1, 3, and 6 years after TPVI were as follows: infective endocarditis, 0.5% (0.0%-1.0%), 0.9% (0.2%-1.6%), and 3.8% (0.0%-8.4%); pulmonary valve replacement, 0.4% (0.0%-0.8%), 1.3% (0.2%-2.4%), and 8.0% (1.2%-14.8%); and pulmonary valve thrombosis, 0.4% (0.0%-0.9%), 0.7% (0.0%-1.3%), and 0.7% (0.0%-1.3%), respectively. CONCLUSIONS: Outcomes of SAPIEN 3 TPVI were favourable in patients with CHD, half of whom had native or patched RVOTs.

From Crafoord's End-to-End Anastomosis Approach to Percutaneous Interventions: Coarctation of the Aorta Management Strategies and Reinterventions.

First described in 1760 by the anatomist Morgagni, coarctation of the aorta (CoA) is a congenital heart defect characterized by narrowing the aorta, typically distal to the left subclavian artery. It accounts for approximately 5-8% of all congenital heart diseases, with an incidence estimated at 4 per 10,000 live births. In 1944, the Swedish surgeon Clarence Crafoord achieved the first successful surgical CoA repair by performing an aortic end-to-end anastomosis on two patients aged 12 and 27 years old. Presently, the most prevalent techniques for surgical repair, particularly in infants and neonates with isolated coarctation, involve resection with end-to-end anastomosis (EEA) and the modified Crafoord technique (extended resection with end-to-end anastomosis (EEEA)). Subclavian flap aortoplasty (SCAP) is an alternative surgical option for CoA repair in patients under two years of age. In cases where the stenosis extends beyond resection and end-to-end anastomosis feasibility, patch aortoplasty (PP) employing a prosthetic patch can augment the stenotic region, especially for older patients. Despite advances in pediatric cardiology and cardiac surgery, recoarctation remains a significant concern after surgical or interventional repair. This comprehensive review aims to provide a thorough analysis of coarctation management, covering the pioneering techniques introduced by Crafoord using end-to-end anastomosis and now extending to the contemporary era marked by percutaneous interventions as well as the recoarctation rate associated with each type.

Safety and efficacy of the Amplatzer™ Trevisio™ intravascular delivery system: Post-approval study results.

BACKGROUND: The Amplatzer™ Trevisio™ Intravascular Delivery System (Trevisio DS; Abbott Laboratories, Chicago, IL, USA) facilitates the delivery of Amplatzer™ Occluders and features an ultraflexible tip, which improves assessment of occluder position before release. AIMS: To assess the safety and efficacy of the Trevisio DS for transcatheter closure of patent foramen ovale and atrial septal defect. METHODS: The Amplatzer™ Trevisio™ Intravascular Delivery System Post-Approval Study was a prospective, postmarket, single-arm, multicentre, observational study of the Trevisio DS. Enrolled patients were indicated for transcatheter closure of patent foramen ovale or atrial septal defect. In all procedures, the Trevisio DS was used to deliver Amplatzer™ Occluders. Technical success was defined as successful deployment and release of at least one occluder. Device- or procedure-related serious adverse events were tracked until discharge or day 7, whichever occurred earlier. RESULTS: The study enrolled 144 patients with patent foramen ovale and 107 patients with atrial septal defect at 22 European sites; 53 patients with atrial septal defect (49.6%) were aged<18years. The rate of technical success was 98.4% (97.2% for atrial septal defect, 99.3% for patent foramen ovale). There was one serious adverse event (0.4%), an acute periprocedural device embolization that occurred after occluder release in a patient with atrial septal defect; the device was retrieved percutaneously. This was determined by the implanter to be unrelated to the performance of the Trevisio DS. CONCLUSIONS: The Trevisio DS exhibited a high rate of technical success and an excellent safety profile during transcatheter closure of patent foramen ovale and atrial septal defect.

Transcatheter Closure of Superior Sinus Venosus Defects.

Superior sinus venosus defect is a communication between the right and left atrium located above the upper margin of the oval fossa, immediately inferior to the junction of the superior vena cava and the right atrium. It is systematically associated with partial anomalous pulmonary venous drainage, especially of the right upper pulmonary vein. Surgical repair has been the gold standard approach to close that defect. Introduced in 2014, percutaneous closure has gradually become a safe and effective alternative to surgery in carefully selected patients, although worldwide experience remains limited. This article provides an appraisal of the patients' selection process and a step-by-step description of the procedure as well as a comprehensive review of its outcomes.

Electrophysiological study prior to planned pulmonary valve replacement in patients with repaired tetralogy of Fallot.

AIM: Ventricular arrhythmias (VAs) are the most common cause of death in patients with repaired Tetralogy of Fallot (rTOF). However, risk stratifying remains challenging. We examined outcomes following programmed ventricular stimulation (PVS) with or without subsequent ablation in patients with rTOF planned for pulmonary valve replacement (PVR). METHODS: We included all consecutive patients with rTOF referred to our institution from 2010 to 2018 aged ≥18 years for PVR. Right ventricular (RV) voltage maps were acquired and PVS was performed from two different sites at baseline, and if non-inducible under isoproterenol. Catheter and/or surgical ablation was performed when patients were inducible or when slow conduction was present in anatomical isthmuses (AIs). Postablation PVS was undertaken to guide implantable cardioverter-defibrillator (ICD) implantation. RESULTS: Seventy-seven patients (36.2 ± 14.3 years old, 71% male) were included. Eighteen were inducible. In 28 patients (17 inducible, 11 non-inducible but with slow conduction) ablation was performed. Five had catheter ablation, surgical cryoablation in 9, both techniques in 14. ICDs were implanted in five patients. During a follow-up of 74 ± 40 months, no sudden cardiac death occurred. Three patients experienced sustained VAs, all were inducible during the initial EP study. Two of them had an ICD (low ejection fraction for one and important risk factor for arrhythmia for the second). No VAs were reported in the non-inducible group (p < .001). CONCLUSION: Preoperative EPS can help identifying patients with rTOF at risk for VAs, providing an opportunity for targeted ablation and may improve decision-making regarding ICD implantation.

Exploring the Potential of Artificial Intelligence in Pediatric Echocardiography-Preliminary Results from the First Pediatric Study Using AI Software Developed for Adults.

(1) Background: Transthoracic echocardiography is the first-line non-invasive investigation for assessing pediatric patients' cardiac anatomy, physiology, and hemodynamics, based on its accessibility and portability, but complete anatomic and hemodynamic assessment is time-consuming. (2) Aim: This study aimed to determine whether an automated software developed for adults could be effectively used for the analysis of pediatric echocardiography studies without prior training. (3) Materials and Methods: The study was conducted at the University Hospital of Bordeaux between August and September 2022 and included 45 patients with normal or near normal heart architecture who underwent a 2D TTE. We performed Spearman correlation and Bland-Altman analysis. (4) Results: The mean age of our patients at the time of evaluation was 8.2 years ± 5.7, and the main reason for referral to our service was the presence of a heart murmur. Bland-Altman analysis showed good agreement between AI and the senior physician for two parameters (aortic annulus and E wave) regardless of the age of the children included in the study. A good agreement between AI and physicians was also achieved for two other features (STJ and EF) but only for patients older than 9 years. For other features, either a good agreement was found between physicians but not with the AI, or a poor agreement was established. In the first case, maybe proper training of the AI could improve the measurement, but in the latter case, for now, it seems unrealistic to expect to reach a satisfactory accuracy. (5) Conclusion: Based on this preliminary study on a small cohort group of pediatric patients, the AI soft originally developed for the adult population, had provided promising results in the evaluation of aortic annulus, STJ, and E wave.

Assessment of Nit-Occlud atrial septal defect occluder device healing process using micro-computed tomography imaging.

After percutaneous implantation of a cardiac occluder, a complex healing process leads to the device coverage within several months. An incomplete device coverage increases the risk of device related complications such as thrombosis or endocarditis. We aimed to assess the device coverage process of atrial septal defect (ASD) occluders in a chronic sheep model using micro-computed tomography (micro-CT). After percutaneous creation of an ASD, 8 ewes were implanted with a 16-mm Nit-Occlud ASD-R occluder (PFM medical, Cologne, Germany) and were followed for 1 month (N = 3) and 3 months (N = 5). After heart explant, the device coverage was assessed using micro-CT (resolution of 41.7 µm) and was compared to histological analysis. The micro-CT image reconstruction was performed in 2D and 3D allowing measurement of the coverage thickness and surface for each device. Macroscopic assessment of devices showed that the coverage was complete for the left-side disk in all cases. Yet incomplete coverage of the right-side disk was observed in 5 of the 8 cases. 2D and 3D micro-CT analysis allowed an accurate evaluation of device coverage of each disk and was overall well correlated to histology sections. Surface calculation from micro-CT images of the 8 cases showed that the median surface of coverage was 93±8% for the left-side disk and 55±31% for the right-side disk. The assessment of tissue reactions, including endothelialisation, after implantation of an ASD occluder can rely on in vitro micro-CT analysis. The translation to clinical practice is challenging but the potential for individual follow-up is shown, to avoid thrombotic or infective complications.

Correlation between three-dimensional echocardiography and cardiopulmonary fitness in patients with univentricular heart: A cross-sectional multicentre prospective study.

BACKGROUND: The prognosis of patients with a functional single ventricle has improved, with better cardiopulmonary fitness, health-related quality of life and survival. Conventional echocardiography remains the first-line technique in single ventricle follow-up. Three-dimensional (3D) echocardiography has shown recent value in congenital cardiology, but its ability to predict functional status in patients with a single ventricle remains unknown. AIM: To evaluate, in patients with a single ventricle, the association between 3D echocardiography variables and functional status determined by cardiopulmonary fitness. METHODS: Children and adults with a functional single ventricle were prospectively enrolled in this multicentre study. Cardiopulmonary fitness was assessed by cardiopulmonary exercise test, with measures of maximum oxygen uptake (VO2max) and ventilatory efficiency (VE/VCO2 slope). 3D echocardiography was performed with off-line reproducibility analyses, using TomTec Arena™ software. Health-related quality of life was assessed using the SF-36 questionnaire. RESULTS: A total of 33 patients were screened, and 3D echocardiography analyses were feasible in 22 subjects (mean age 28±9years). 3D echocardiography ejection fraction correlated with percent-predicted VO2max (r=0.64, P<0.01), VE/VCO2 slope (r=-0.41, P=0.05), two-dimensional echocardiography ejection fraction (r=0.55, P<0.01) and health-related quality of life physical functioning dimension (r=0.56, P=0.04). 3D echocardiography indexed end-systolic volume correlated with percent-predicted VO2max (r=-0.45, P=0.03) and VE/VCO2 slope (r=0.65, P<0.01). 3D echocardiography reproducibility was good. CONCLUSIONS: Single ventricle ejection fraction and volumes measured by 3D echocardiography correlated with cardiopulmonary fitness, as determined by two main prognostic cardiopulmonary exercise test variables: VO2max and VE/VCO2 slope. Despite good reproducibility, 3D echocardiography feasibility remained limited. 3D echocardiography may be of value in single ventricle follow-up, provided that the technique and analysis software are improved.

Multicentre experience with Optimus balloon-expandable cobalt-chromium stents in congenital heart disease interventions.

OBJECTIVES: To evaluate bare-metal Optimus and polytetrafluoroethylene (PTFE)-covered Optimus-CVS balloon-expandable, cobalt-chromium, hybrid cell-designed stents in congenital heart disease (CHD) interventions. METHODS: Retrospective multicentre review of patients with CHD receiving Optimus stents. Stent mechanical behaviour, clinical indications and outcomes were assessed. RESULTS: 183 stents (49.2% XXL/15-ZIG, 33.3% XL/12-ZIG, 17.5% L/9-ZIG) were implanted (98.9% success rate, 2.3% serious procedural complication rate) in 170 patients (57.6% men, 64.1% adults), median age 23.6 years (IQR, 15.2-39.2) and weight 63.5 kg (IQR, 47-75.7). Indications were right ventricular outflow tract stand-alone stenting or before revalvulation (62.4%), aortic coarctation treatment (15.3%), Fontan-circuit fenestration closure (12.4%) and miscellaneous (10%). 86/170 (50.6%) patients had PTFE-covered stenting (50% prophylactic). In 86/170 (50.6%) patients with stenotic lesions, median percentage of achieved stent expansion was 93.4% (IQR, 85.5%-97.7%), median gradient decreased from 28 mm Hg (IQR, 19-41) to 5 mm Hg (IQR, 1-9) (p<0.001), median vessel diameters increased from 13 mm (IQR, 7.9-17) to 18.9 mm (IQR, 15.2-22) (p<0.001) and percentage of vessel expansion was 45.2% (IQR, 19.8%-91.3%). In 30/36 (83.3%) patients with graft, median dilation of 2 mm (IQR, 2-5) above nominal diameter was achieved. Median stent shortening was 10.9% (IQR, 6.1-15.1) and was associated only with expansion diameter (OR: 0.66, 95% CI: 0.38 to 0.93). No clinically relevant fracture, stent embolisation or dysfunction occurred on a median follow-up of 9 (IQR, 4-14) months. CONCLUSIONS: Optimus stents are effective tools for transcatheter treatment of simple and complex CHD. Optimus stents' reliable mechanical behaviour and particular covering design can promote widespread use.

Feasibility and Diagnostic Value of Recording Smartwatch Electrocardiograms in Neonates and Children.

OBJECTIVE: The objective of this study was to evaluate the agreement of smartwatch-derived single-lead electrocardiogram (ECG) recordings with 12-lead ECGs for diagnosing electrocardiographic abnormalities. STUDY DESIGN: A 12-lead ECG and an ECG using Apple Watch were obtained in 110 children (aged 1 week to 16 years) with normal (n = 75) or abnormal (n = 35) 12-lead ECGs (atrioventricular block [7], supraventricular tachycardia [SVT] {5}, bundle branch block [12], ventricular preexcitation [6], long QT [5]). In children aged <6 years, the ECG recording was performed with the active participation of an adult who applied the neonate or child's finger to the crown of the watch. In older children, tracings were obtained after brief teaching without adult guidance. All 12-lead ECGs were independently evaluated by 2 blinded cardiologists. Apple Watch ECGs were independently evaluated by another blinded cardiologist. RESULTS: In 109 children (99.1%), the smartwatch tracing was of sufficient quality for evaluation. Smartwatch tracings were 84% sensitive and 100% specific for the detection of an abnormal ECG. All 75 normal tracings were correctly identified. Of the 35 children with abnormalities on 12-lead ECGs, 5 (14%) were missed, most often because of baseline wander and artifacts. Rhythm disorders (atrioventricular block or SVT) and bundle branch blocks were correctly detected in most cases (11 of 12 and 11 of 12, respectively); preexcitation and long QT was detected in 4 of 6 and 4 of 5, respectively. CONCLUSION: Smartwatch ECGs recorded with parental assistance in children aged up to 6 years and independently in older children have the potential to detect clinically relevant conditions.

Outcomes Following Closure of Secundum Atrial Septal Defect in Children ≤ 15 kg in a French Tertiary Centre.

Secundum atrial septal defects (sASDs) are common congenital cardiac defects mostly treated using a transcatheter approach. However, small children (<15 kg) are still undergoing surgical sASD closure in many centres. Although both options have been proved to have excellent results in children, comparative data of the two techniques are missing for patients ≤ 15 kg. The medical records of children ≤ 15 kg who underwent sASD surgical (group A) and transcatheter (group B) closure between 2010 and 2023 were reviewed retrospectively. Twenty-five children in group A and twenty-two in group B were included (mean weight 8.9 kg in group A and 10.3 kg in group B). The main indications for closure were right heart enlargement and failure to thrive. Major complications occurred in two patients in group A and none in group B. Minor complications occurred in eight patients in group A and one in group B. At last follow-up, symptoms resolved completely or improved significantly for all infants, with the exception of failure to thrive in the sub-population of children with extra-cardiac comorbidities. sASD closure can be performed safely in symptomatic infants ≤ 15 kg, even in the presence of comorbidity, and should not be postponed. However, in patients with extra-cardiac comorbidities, the only indication of growth retardation must be carefully evaluated.

Transcatheter interventions in patients with a Fontan circulation: Current practice and future developments.

The Fontan operation represents the last of multiple steps that are offered a wide range of congenital cardiac lesions with a single ventricle (SV) physiology. Nowadays this surgical program consists of a total cavopulmonary connection (TCPC), by anastomosing systemic veins to the pulmonary arteries (PAs), excluding the right-sided circulation from the heart. As a result of imaging, surgical, percutaneous, and critical care improvements, survival in this population has steadily increased. However, the Fontan physiology chronically increases systemic venous pressure causing systemic venous congestion and decreased cardiac output, exposing patients to the failure of the Fontan circulation (FC), which is associated with a wide variety of clinical complications such as liver disease, cyanosis, thromboembolism, protein-losing enteropathy (PLE), plastic bronchitis (PB), and renal dysfunction, ultimately resulting in an increased risk of exercise intolerance, arrhythmias, and premature death. The pathophysiology of the failing Fontan is complex and multifactorial; i.e., caused by the single ventricle dysfunction (diastolic/systolic failure, arrhythmias, AV valve regurgitation, etc.) or caused by the specific circulation (conduits, pulmonary vessels, etc.). The treatment is still challenging and may include multiple options and tools. Among the possible options, today, interventional catheterization is a reliable option, through which different procedures can target various failing elements of the FC. In this review, we aim to provide an overview of indications, techniques, and results of transcatheter options to treat cavopulmonary stenosis, collaterals, impaired lymphatic drainage, and the management of the fenestration, as well as to explore the recent advancements and clinical applications of transcatheter cavopulmonary connections, percutaneous valvular treatments, and to discuss the future perspectives of percutaneous therapies in the Fontan population.

Nuclear Imaging in Pediatric Cardiology: Principles and Applications.

Nuclear imaging plays a unique role within diagnostic imaging since it focuses on cellular and molecular processes. Using different radiotracers and detection techniques such as the single photon emission scintigraphy or the positron emission tomography, specific parameters can be assessed: myocardial perfusion and viability, pulmonary perfusion, ventricular function, flow and shunt quantification, and detection of inflammatory processes. In pediatric and congenital cardiology, nuclear imaging can add complementary information compared to other imaging modalities such as echocardiography or magnetic resonance imaging. In this state-of-the-art paper, we appraise the different techniques in pediatric nuclear imaging, evaluate their advantages and disadvantages, and discuss the current clinical applications.

Renaissance of Cardiac Imaging to Assist Percutaneous Interventions in Congenital Heart Diseases:The Role of Three-Dimensional Echocardiography and Multimodality Imaging.

Percutaneous interventions have completely refashioned the management of children with congenital heart diseases (CHD) and the use of non-invasive imaging has become the gold standard to plan and guide these procedures in the modern era. We are now facing a dual challenge to improve the standard of care in low-risk patients, and to shift our strategies from the classic open chest surgery to imaging-guided percutaneous interventions in high-risk patients. Such rapid evolution of ultrasound technologies over the last 20 years have permitted the integration of transthoracic, transesophageal and intracardiac echocardiography into the interventional workflow to improve image guidance and reduce radiation burden from fluoroscopy and angiography. Specifically, miniaturization of transesophageal probe and advances in three-dimensional (3D) imaging techniques have enabled real-time 3D image guidance during complex interventional procedure, In addition, multimodality and fusion imaging techniques harness the strengths of different modalities to enhance understanding of anatomical and spatial relationship between different structures, improving communication and coordination between interventionalists and imaging specialists. In this review, we aim to provide an overview of 3D imaging modalities and multimodal fusion in procedural planning and live guidance of percutaneous interventions. At the present times, 3D imaging can no longer be considered a luxury but a routine clinical tool to improve procedural success and patient outcomes.