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.

Clinical course and follow-up of pediatric patients with COVID-19 vaccine-associated myocarditis compared to non-vaccine-associated myocarditis within the prospective multicenter registry-"MYKKE".

BACKGROUND: Since the onset of widespread COVID-19 vaccination, increased incidence of COVID-19 vaccine-associated myocarditis (VA-myocarditis) has been noted, particularly in male adolescents. METHODS: Patients <18 years with suspected myocarditis following COVID-19 vaccination within 21 days were enrolled in the PedMYCVAC cohort, a substudy within the prospective multicenter registry for pediatric myocarditis "MYKKE." Clinical data at initial admission, 3- and 9-months follow-up were monitored and compared to pediatric patients with confirmed non-vaccine-associated myocarditis (NVA-myocarditis) adjusting for various baseline characteristics. RESULTS: From July 2021 to December 2022, 56 patients with VA-myocarditis across 15 centers were enrolled (median age 16.3 years, 91% male). Initially, 11 patients (20%) had mildly reduced left ventricular ejection fraction (LVEF; 45%-54%). No incidents of severe heart failure, transplantation or death were observed. Of 49 patients at 3-months follow-up (median (IQR) 94 (63-118) days), residual symptoms were registered in 14 patients (29%), most commonly atypical intermittent chest pain and fatigue. Diagnostic abnormalities remained in 23 patients (47%). Of 21 patients at 9-months follow-up (259 (218-319) days), all were free of symptoms and diagnostic abnormalities remained in 9 patients (43%). These residuals were mostly residual late gadolinium enhancement in magnetic resonance imaging. Patients with NVA-myocarditis (n=108) more often had symptoms of heart failure (P = .003), arrhythmias (P = .031), left ventricular dilatation (P = .045), lower LVEF (P < .001) and major cardiac adverse events (P = .102). CONCLUSIONS: Course of COVID-19 vaccine-associated myocarditis in pediatric patients seems to be mild and differs from non-vaccine-associated myocarditis. Due to a considerable number of residual symptoms and diagnostic abnormalities at follow-up, further studies are needed to define its long-term implications.

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.

Myocarditis and sports in the young: data from a nationwide registry on myocarditis-"MYKKE-Sport".

Background: Myocarditis represents one of the most common causes of Sudden Cardiac Death in children. Myocardial involvement during a viral infection is believed to be higher as a consequence of intensive exertion. Recommendations for return to sports are based on cohort and case studies only. This study aims to investigate the relationship between physical activity and myocarditis in the young. Patient: Every patient in the MYKKE registry fulfilling criteria for suspicion of myocarditis was sent a questionnaire regarding the physical activity before, during and after the onset of myocarditis. Method: This study is a subproject within the MYKKE registry, a multicenter registry for children and adolescents with suspected myocarditis. The observation period for this analysis was 93 months (September 2013-June 2021). Anamnestic, cardiac magnetic resonance images, echocardiography, biopsy and laboratory records from every patient were retrieved from the MYKKE registry database. Results: 58 patients (mean age 14.6 years) were enrolled from 10 centers. Most patients participated in curricular physical activity and 36% in competitive sports before the onset of myocarditis. There was no significant difference of heart function at admission between the physically active and inactive subjects (ejection fraction of 51.8 ± 8.6% for the active group vs. 54.4 ± 7.7% for the inactive group). The recommendations regarding the return to sports varied widely and followed current guidelines in 45%. Most patients did not receive an exercise test before returning to sports. Conclusion: Sports before the onset of myocarditis was not associated with a more severe outcome. There is still a discrepancy between current literature and actual recommendations given by health care providers. The fact that most participants did not receive an exercise test before being cleared for sports represents a serious omission.

Cardiac Muscle Training-A New Way of Recognizing and Supporting Recovery for LVAD Patients in the Pediatric Population.

Patients with refractory heart failure due to chronic progressive cardiac myopathy (CM) may require mechanical circulatory support as a bridge to transplantation. A few patients can be weaned from support devices if recovery can be achieved. The identification of these patients is of great importance as recovery may be missed if the heart is unloaded by the ventricular assist device (VAD). Testing the load-bearing capacity of the supported left ventricle (LV) by temporarily and gradually reducing mechanical support during cardiac exercise can help identify responders and potentially aid the recovery process. An exercise training protocol was used in 3 patients (8 months, 18 months and 8 years old) with histological CM findings and myocarditis. They were monitored regularly using clinical information and functional imaging with VAD support. Echocardiographic examination included both conventional real-time 3D echocardiography (RT3DE) and speckle tracking (ST). A daily temporary reduction in pump rate (phase A) was followed by a permanent reduction in rate (phase B). Finally, pump stops of up to 30 min were performed once a week (phase C). The final decision on explantation was based on at least three pump stops. Two patients were weaned and successfully removed from the VAD. One of them was diagnosed with acute viral myocarditis. The other had chronic myocarditis with dilated myopathy and mild interstitial fibrosis. The noninvasive assessment of cardiac output and strain under different loading conditions during VAD therapy is feasible and helps identify candidates for weaning despite severe histological findings. The presented protocol, which incorporates new echocardiographic techniques for determining volume and deformation, can be of great help in positively guiding the process of individual recovery, which may be essential for selecting and increasing the number of patients to be weaned from VAD.

Cerebrovascular accidents in paediatric patients supported by the Berlin Heart EXCOR.

OBJECTIVES: Ventricular assist device support as a bridge to transplant or recovery is a well-established therapy in children on the cardiac transplant waiting list. The goal of this study was to investigate the incidence of and the associated factors for cerebrovascular accidents in paediatric patients supported by a Berlin Heart EXCOR. METHODS: All patients <19 years of age supported by a Berlin Heart EXCOR between January 2011 and January 2021 from the European Registry for Patients with Mechanical Circulatory Support were included. RESULTS: In total, 230 patients were included. A total of 140 (60.9%) patients had a diagnosis of dilated cardiomyopathy. 46 patients (20.0%) sustained 55 cerebrovascular accidents, with 70.9% of the episodes within 90 days after the ventricular assist device was implanted. The event rate of cerebrovascular accidents was highest in the first era (0.75). Pump thrombosis and secondary need for a right ventricular assist device were found to be associated with a cerebrovascular accident (hazard ratio 1.998, P = 0.040; hazard ratio 11.300, P = 0.037). At the 1-year follow-up, 44.4% of the patients had received a transplant, 13.1% were weaned after recovery and 24.5% had died. Event rates for mortality showed a significantly decreasing trend. CONCLUSIONS: Paediatric ventricular assist device support is associated with important adverse events, especially in the early phase after the device is implanted. Pump thrombosis and the need for a secondary right ventricular assist device are associated with cerebrovascular accidents. Furthermore, an encouragingly high rate of recovery in this patient population was shown, and death rates declined. More complete input of data into the registry, especially concerning anticoagulation protocols, would improve the data.

Pathogenic Variants in Cardiomyopathy Disorder Genes Underlie Pediatric Myocarditis-Further Impact of Heterozygous Immune Disorder Gene Variants?

Myocarditis is an inflammatory disease of the heart. Pediatric myocarditis with the dilated cardiomyopathy (DCM) phenotype may be caused by likely pathogenic or pathogenic genetic variants [(L)P] in cardiomyopathy (CMP) genes. Systematic analysis of immune disorder gene defects has not been performed so far. We analyzed 12 patients with biopsy-proven myocarditis and the DCM phenotype together with their parents using whole-exome sequencing (WES). The WES data were filtered for rare pathogenic variants in CMP (n = 89) and immune disorder genes (n = 631). Twelve children with a median age of 2.9 (1.0-6.8) years had a mean left ventricular ejection fraction of 28% (22-32%) and myocarditis was confirmed by endomyocardial biopsy. Patients with primary immunodeficiency were excluded from the study. Four patients underwent implantation of a ventricular assist device and subsequent heart transplantation. Genetic analysis of the 12 families revealed an (L)P variant in the CMP gene in 8/12 index patients explaining DCM. Screening of recessive immune disorder genes identified a heterozygous (L)P variant in 3/12 index patients. This study supports the genetic impact of CMP genes for pediatric myocarditis with the DCM phenotype. Piloting the idea that additional immune-related genetic defects promote myocarditis suggests that the presence of heterozygous variants in these genes needs further investigation. Altered cilium function might play an additional role in inducing inflammation in the context of CMP.

Compensatory Upregulation of Anti-Beta-Adrenergic Receptor Antibody Levels Might Prevent Heart Failure Presentation in Pediatric Myocarditis.

Background: Myocarditis can be associated with severe heart failure and is caused by different inflammatory and autoimmune responses. The aim of this study was to describe the immunological response in children with myocarditis by analyzing anti-beta-adrenergic receptor antibodies (anti-ß-AR Abs). Methods: Sera of children who were hospitalized with biopsy-proven myocarditis were prospectively collected between April 2017 and March 2019. Anti-ß1-AR Ab, anti-ß2-AR Ab, and anti-ß3-AR Ab were quantified by a CE-certified ELISA kit. According to normal values for immunoglobulin G (IgG), three age groups, <1, 1-5, and >5-17 years, were defined. Children without inflammatory cardiac pathology and no heart failure signs were served as a control group. Results: We compared 22 patients with biopsy-proven myocarditis and 28 controls. The median age (interquartile range) of the myocarditis group (MYC) was 12.1 (2.7-16.4) years, 13 men, left ventricular ejection fraction (LVEF) 51% and for control group, the median age was 5.0 (3.0-6.8) years, nine men, LVEF 64%. Myocarditis patients in the age group >5-17 years showed significantly higher anti-ß3-AR Ab levels as compared to controls (p = 0.014). Lower anti-ß2-AR Ab and anti-ß3-AR Ab levels were significantly correlated with higher left ventricular diameters in myocarditis patients. The event-free survival using a combined endpoint (mechanical circulatory support [MCS], transplantation, and/or death) was significantly lower in myocarditis patients with antibody levels below the median as compared to myocarditis patients with antibody levels ≥ the median. Conclusion: Anti-ß-AR Ab levels are increased in children with myocarditis and >5 years of age. These antibodies might be upregulated compensatory to prevent further cardiac deterioration. A worse event-free survival in patients with lower anti-ß-AR Ab levels might be a therapeutic target for immunoglobulin substitution.

Revascularization of Left Subclavian to Common Carotid Artery Prepares for Covered Stent Implantation in Patients With Complex Aortic Coarctation.

Seven adult patients underwent a two-stage treatment of complex coarctation (CoA), including surgical revascularization of the left subclavian artery (LSA) to left common carotid artery (LCCA), followed by transcatheter covered stent implantation. The majority of patients (5 of 7, 71%) received 1 covered stent (covered Cheatham Platinum stent: 8 zig/45 mm [n = 2], 10 zig/60 mm [n = 1], 10 zig/65 mm [n = 1]; BeGraft: 24/48 mm [n = 2]). In 1 patient (14%), the implantation of 2 covered stents (BeGraft 20/48 mm) was necessary. During a median follow-up of 2.4 years (interquartile range, 0.1 to 4.9 years), complications occurred in 3 of 7 patients (43%), including an asymptomatic but severe stenosis of the LSA bypass (n = 1), a recoarctation with a mild endoleak (n = 1), and a severe endoleak (n = 1). Surgical revascularization of the LSA to the LCCA can successfully prepare for covered stent implantation in complex CoA in adult patients. This two-stage approach was feasible and safe with complications occurring in 3 of 7 patients (43%). All complications were managed by catheter reintervention only.

Clinical characteristics and outcome of biopsy-proven myocarditis in children - Results of the German prospective multicentre registry "MYKKE".

BACKGROUND: Heart failure (HF) due to myocarditis might not respond in the same way to standard therapy as HF due to other aetiologies. The aim of this study was to investigate the value of endomyocardial biopsies (EMB) for clinical decision-making and its relation to the outcome of paediatric patients with myocarditis. METHODS: Clinical and EMB data of children with myocarditis collected for the MYKKE-registry between 2013 and 2020 from 23 centres were analysed. EMB studies included histology, immunohistology, and molecular pathology. The occurrence of major adverse cardiac events (MACE) including mechanical circulatory support (MCS), heart transplantation, and/or death was defined as a combined endpoint. RESULTS: Myocarditis was diagnosed in 209/260 patients: 64% healing/chronic lymphocytic myocarditis, 23% acute lymphocytic myocarditis (AM), 14% healed myocarditis, no giant cell myocarditis. The median age was 12.8 (1.4-15.9) years. Time from symptom-onset to EMB was 11.0 (4.0-29.0) days. Children with AM and high amounts of mononuclear cell infiltrates were significantly younger with signs of HF compared to those with healing/chronic or healed myocarditis. Myocardial viral DNA/RNA detection had no significant effect on outcome. The worst event-free survival was seen in patients with healing/chronic myocarditis (24%), followed by acute (31%) and healed myocarditis (58%, p = 0.294). A weaning rate of 64% from MCS was found in AM. CONCLUSIONS: EMB provides important information on the type and stage of myocardial inflammation and supports further decision-making. Children with fulminant clinical presentation, high amounts of mononuclear cell infiltrates or healing/chronic inflammation and young age have the highest risk for MACE.

Nationwide Registry-Based Analysis of Infective Endocarditis Risk After Pulmonary Valve Replacement.

Background Infective endocarditis (IE) after pulmonary valve replacements in congenital heart disease is a significant concern. This study aimed to identify specific long-term risk factors for IE after percutaneous pulmonary valve implantation or surgical pulmonary valve replacement. Methods and Results All patients with congenital heart disease from the National Register for Congenital Heart Defects with at least 1 pulmonary valve replacement before January 2018 were included. A total of 1170 patients (56.3% men, median age at study inclusion 12 [interquartile range {Q1-Q3} 5-20 years]) received 1598 pulmonary valve replacements. IE occurred in 4.8% of patients during a follow-up of total 9397 patient-years (median 10 [Q1-Q3, 6-10] years per patient). After homograft implantation 7 of 558 (1.3%) patients developed IE, after heterograft implantation 31 of 723 (4.3%) patients, and after Melody valve implantation 18 of 241 (7.5%) patients. Edwards Sapien and mechanical valves were used less frequently and remained without IE. The incidence of IE in heterografts excluding Contegra valves was 7 of 278 (2.5%), whereas the incidence of IE in Contegra valves was 24 of 445 (5.4%). The risk of IE was not increased compared with homografts if Contegra valves were excluded from the heterografts (hazard ratio [HR], 2.60; P=0.075). The risk of IE was increased for bovine jugular vein valves, Contegra valves (HR, 6.72; P<0.001), and Melody valves (HR, 5.49; P<0.001), but did not differ between Melody valves and Contegra valves (HR, 1.01; P=0.978). Conclusions Bovine jugular vein valves have the highest risk of IE, irrespective of the mode of deployment, either surgical or percutaneous.

Prospective multicenter study of the breakable babystent for treatment of aortic coarctation in newborns and infants.

To assess the efficacy and safety of a breakable BabyStent to treat complex aortic coarctation (CoA) in early childhood. Although recommended in several guidelines, there is no approved aortic stent for young infants, because of the dilemma between two mandatory requirements: expandable up to adult size on the one hand, and small enough to fit through a baby's femoral artery on the other. Prospective interventional, multi-center clinical trial with the breakable Osypka BabyStent® (OBS). The OBS is a low-profile, 15-mm long cobalt-chromium stent, pre-mounted on a 6 mm balloon and inserted via a 4 Fr sheath. After implantation, its diameter is adjustable from 6 to 12 mm by balloon dilation. Further dilation opens predefined joints enabling unrestricted growth. Nineteen patients (9 male), median age 112 days (range: 7-539), median body weight 5.6 kg (range: 2.4-8.4) were deemed high risk and underwent stent implantation. Of those, 74% suffered from re-CoA following surgery, 53% had additional cardiac and 21% noncardiac malformations. Our primary combined endpoint was fulfilled: All stents were implanted in the desired region, and a >50% intrastenotic diameter-extension was achieved in 15 patients (78.9%, 80% confidence interval [62.2; 90.5], 95% confidence interval [54.4; 93.9]). Secondary endpoint confirmed that the OBS fits the baby's femoral vessel diameter. All children survived the procedure and 12-month follow-up. This stent enables percutaneous stenting of complex aortic coarctation to treat high-risk newborns and infants.

Patterns of Early Coronary Artery Changes in Pediatric Heart Transplant Recipients Detected Using Optical Coherence Tomography.

BACKGROUND: Cardiac allograft vasculopathy, the leading cause of graft failure in pediatric heart transplant recipients, is characterized by diffuse and concentric coronary intimal thickening. Early treatment yields better outcomes. While coronary angiography is the standard for cardiac allograft vasculopathy screening and diagnosis, it only identifies luminal narrowing, which occurs in more severe disease. Coronary optical coherence tomography (OCT) is a high-definition intravascular imaging modality that may offer earlier diagnosis. We used OCT to investigate coronary intimal thickening in pediatric transplant recipients and examined its (1) location (ie, vessel type and location) and (2) nature (ie, characteristics of cross-sectional and longitudinal thickening). METHODS: Sites collected coronary angiography and OCT data from participants (N=258 vessel segments from 73 individuals; median age: 11.5 years [8.4-15.3]; 55% male). Images were collected from the left anterior descending, left circumflex, and right coronary arteries, and location (ie, proximal, middle, and distal) were classified using coronary angiography. RESULTS: OCT identified 32 vessel segments meeting criteria for significant thickening, 88% of which were angiographically silent. Longitudinal thickening was segmental rather than global in 88%, and cross-sectional thickening was 48% eccentric and 52% concentric. Intimal thickening prevalence and severity measures did not consistently differ between coronary artery type (P=1.000) or location (P=0.248) but increased with time since transplant and age at transplant and OCT procedure. CONCLUSIONS: In pediatric transplant recipients, we observed a surprisingly high prevalence of segmental and eccentric intimal thickening. Insights from intravascular imaging suggest these patterns of coronary vascular changes may precede overt cardiac allograft vasculopathy. Identifying early changes may offer opportunity for enhanced surveillance and earlier intervention.

Cardiovascular magnetic resonance in children with suspected myocarditis: current practice and applicability of adult protocols.

BACKGROUND: Cardiovascular magnetic resonance serves as a useful tool in diagnosing myocarditis. Current adult protocols are yet to be validated for children; thus, it remains unclear if the methods used can be applied with sufficient image quality in children. This study assesses the use of cardiovascular magnetic resonance in children with suspected myocarditis. METHODS: Image data from clinical cardiovascular magnetic resonance studies performed in children enrolled in Mykke between June 2014 and April 2019 were collected and analysed. The quality of the data sets was evaluated using a four-point quality scale (4: excellent, 3: good, 2: moderate, 1: non-diagnostic). RESULTS: A total of 102 patients from 9 centres were included with a median age (interquartile range) of 15.4(10.7-16.6) years, 137 cardiovascular magnetic resonance studies were analysed. Diagnostic image quality was found in 95%. Examination protocols were consistent with the original Lake Louise criteria in 58% and with the revised criteria in 35%. Older patients presented with better image quality, with the best picture quality in the oldest age group (13-18 years). Sedation showed a negative impact on image quality in late gadolinium enhancement and oedema sequences. No such correlation was seen in cardiac function assessment sequences. In contrast to initial scans, in follow-up examinations, the use of parametric mapping increased while late gadolinium enhancement and oedema sequences decreased. CONCLUSION: Cardiovascular magnetic resonance protocols for the assessment of adult myocarditis can be applied to children without significant constraints in image quality. Given the lack of specific recommendations for children, cardiovascular magnetic resonance protocols should follow recent recommendations for adult cardiovascular magnetic resonance.

Reintervention and Survival After Transcatheter Pulmonary Valve Replacement.

BACKGROUND: Transcatheter pulmonary valve (TPV) replacement (TPVR) has become the standard therapy for postoperative pulmonary outflow tract dysfunction in patients with a prosthetic conduit/valve, but there is limited information about risk factors for death or reintervention after this procedure. OBJECTIVES: This study sought to evaluate mid- and long-term outcomes after TPVR in a large multicenter cohort. METHODS: International registry focused on time-related outcomes after TPVR. RESULTS: Investigators submitted data for 2,476 patients who underwent TPVR and were followed up for 8,475 patient-years. A total of 95 patients died after TPVR, most commonly from heart failure (n = 24). The cumulative incidence of death was 8.9% (95% CI: 6.9%-11.5%) 8 years after TPVR. On multivariable analysis, age at TPVR (HR: 1.04 per year; 95% CI: 1.03-1.06 per year; P < 0.001), a prosthetic valve in other positions (HR: 2.1; 95% CI: 1.2-3.7; P = 0.014), and an existing transvenous pacemaker/implantable cardioverter-defibrillator (HR: 2.1; 95% CI: 1.3-3.4; P = 0.004) were associated with death. A total of 258 patients underwent TPV reintervention. At 8 years, the cumulative incidence of any TPV reintervention was 25.1% (95% CI: 21.8%-28.5%) and of surgical TPV reintervention was 14.4% (95% CI: 11.9%-17.2%). Risk factors for surgical reintervention included age (0.95 per year [95% CI: 0.93-0.97 per year]; P < 0.001), prior endocarditis (2.5 [95% CI: 1.4-4.3]; P = 0.001), TPVR into a stented bioprosthetic valve (1.7 [95% CI: 1.2-2.5]; P = 0.007), and postimplant gradient (1.4 per 10 mm Hg [95% CI: 1.2-1.7 per 10 mm Hg]: P < 0.001). CONCLUSIONS: These findings support the conclusion that survival and freedom from reintervention or surgery after TPVR are generally comparable to outcomes of surgical conduit/valve replacement across a wide age range.

Pulmonary valve prostheses: patient's lifetime procedure load and durability. Evaluation of the German National Register for Congenital Heart Defects.

OBJECTIVES: We evaluated 4384 procedures performed between 1957 and 2018, collected in the National Register for Congenital Heart Defects, conducted on 997 patients with 1823 pulmonary valve replacements (PVRs), including 226 implanted via catheter [transcatheter valve (TCV)]. Main study targets are as follows: TCV benefit, valve type durability, decade-wise treatment changes and procedure frequencies over the lifetime of a PVR patient. METHODS: We studied TCV impact on surgical valve replacement (via Kaplan-Meier); pulmonary valve type-specific performance (Kaplan-Meier and Cox regressions with age group as stratification or ordinary variable); procedure interval changes over the decades (Kaplan-Meier); procedure load, i.e. frequency of any procedure/surgical PVR/interventional or surgical PVR by patient age (multistate analyses). RESULTS: TCV performance was equivalent to surgical PVRs and extended durability significantly. Homografts were most durable; Contegras lasted comparably less in older; and Hancock devices lasted less in younger patients. Matrix P-valves showed poorer performance. Age group stratification improves the precision of valve-specific explantation hazard estimations. The current median interval between procedures is 2.6 years; it became significantly shorter in most age groups below 40 years. At 30 years, 80% of patients had undergone ≥3 procedures, 20% ≥3 surgical PVRs and 42% ≥3 surgical or interventional PVRs. CONCLUSIONS: TCVs doubled freedom from explantation of conventional valves. Homografts' age group-specific explantation hazard ratio was lowest; Matrix P's hazard ratio was highest. Age-stratified Cox regressions improve the precision of prosthesis durability evaluations. The median time between procedures for PVR patients shortened significantly to 2.6 years. At 30 years, 42% had ≥3 PVRs.

Coronary Interventions in Pediatric Congenital Heart Disease.

Coronary artery lesions represent rare conditions in pediatric congenital heart disease and mainly include coronary artery stenoses (CAS) or coronary artery fistulae (CAF). Due to the small vessel size, pediatric percutaneous coronary interventions (PCI) are demanding and studies concerning long-term results are missing. In this retrospective study, we analyzed indications, procedural details, and post-procedural outcomes in pediatric patients who underwent PCI in our institution. For CAS treatment, procedural success was defined as efficient coronary revascularization with a significant improvement of coronary perfusion. CAF treatment was considered successful, when no residual shunt was detectable. From 1995 to 2020, 32 pediatric patients aged ≤ 18 years received interventional treatment for CAS (n = 24/32) or CAF (n = 8/32). Reasons for CAS were post-surgical (n = 15/24) or post-transplant (n = 9/24). Interventional treatment strategies included coronary angioplasty (20/43), stent placement (10/43), and a combination of both (13/43). In-hospital mortality occurred in 6/24 patients and late mortality in 5/24 patients leading to an overall 5-year survival of 62.5%. Early mortality mainly occurred due to post-ischemic myocardial failure. CAF occlusion was performed using coil embolization (n = 3), placement of vascular plugs (n = 3), a combination of both (n = 1), or a combination of coil embolization and a covered stent (n = 1). Treatment of coronary fistulae was successful in all patients with excellent post-procedural results and no follow-up death. PCI in pediatric patients with congenital heart disease can be performed safely and effectively. However, the overall 5-year survival probability of patients with CAS is reduced due to severe ischemic myocardial damage.

Common Genetic Variants Contribute to Risk of Transposition of the Great Arteries.

RATIONALE: Dextro-transposition of the great arteries (D-TGA) is a severe congenital heart defect which affects approximately 1 in 4,000 live births. While there are several reports of D-TGA patients with rare variants in individual genes, the majority of D-TGA cases remain genetically elusive. Familial recurrence patterns and the observation that most cases with D-TGA are sporadic suggest a polygenic inheritance for the disorder, yet this remains unexplored. OBJECTIVE: We sought to study the role of common single nucleotide polymorphisms (SNPs) in risk for D-TGA. METHODS AND RESULTS: We conducted a genome-wide association study in an international set of 1,237 patients with D-TGA and identified a genome-wide significant susceptibility locus on chromosome 3p14.3, which was subsequently replicated in an independent case-control set (rs56219800, meta-analysis P=8.6x10-10, OR=0.69 per C allele). SNP-based heritability analysis showed that 25% of variance in susceptibility to D-TGA may be explained by common variants. A genome-wide polygenic risk score derived from the discovery set was significantly associated to D-TGA in the replication set (P=4x10-5). The genome-wide significant locus (3p14.3) co-localizes with a putative regulatory element that interacts with the promoter of WNT5A, which encodes the Wnt Family Member 5A protein known for its role in cardiac development in mice. We show that this element drives reporter gene activity in the developing heart of mice and zebrafish and is bound by the developmental transcription factor TBX20. We further demonstrate that TBX20 attenuates Wnt5a expression levels in the developing mouse heart. CONCLUSIONS: This work provides support for a polygenic architecture in D-TGA and identifies a susceptibility locus on chromosome 3p14.3 near WNT5A. Genomic and functional data support a causal role of WNT5A at the locus.